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Browse Health

Credentials

Education ?

Medical School Score Rankings
Northwestern University (1997)
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Top 50%

Awards & Distinctions ?

Awards  
Patients' Choice Award (2012)
Compassionate Doctor Recognition (2012)
Associations
American Urological Association
Society of Urologic Oncology
American Society of Clinical Oncology
American Board of Urology

Affiliations ?

Dr. Kim is affiliated with 5 hospitals.

Hospital Affiliations

Score

Rankings

  • Virtua Memorial Hospital Of Burlington County
    Urology
    175 Madison Ave, Mount Holly, NJ 08060
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  • Robert Wood Johnson Univ Hosp
    Urology
    1 Robert Wood Johnson Pl, New Brunswick, NJ 08901
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  • University Medical Center At Princeton
    Urology
    253 Witherspoon St, Princeton, NJ 08540
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  • Rwj University Hospital
  • Princeton House Behavorial Healthcare
    905 Herrontown Rd, Princeton, NJ 08540
  • Publications & Research

    Dr. Kim has contributed to 282 publications.
    Title Double Primary Malignancies Associated with Colon Cancer in Patients with Situs Inversus Totalis: Two Case Reports.
    Date February 2012
    Journal World Journal of Surgical Oncology
    Excerpt

    Situs inversus totalis (SIT) is not itself a premalignant condition, however, rare synchronous or metachronous multiple primary malignancies have been reported. Herein we present a case of synchronous transverse and sigmoid colon cancers and a case of metachronous rectosigmoid colon and gastric cancers in patients with SIT.A 66-year-old male with SIT was referred for a two-month history of hematochezia. Synchronous colonic tumors were found on the proximal transverse and sigmoid colon. The patient underwent open total colectomy and was discharged without incident. A 71-year-old female with rectosigmoid colon cancer and SIT underwent laparoscopy-assisted low anterior resection. Fourteen months after the surgery, the patient developed a single hepatic metastasis and underwent hepatic segmentectomy (S6). Forty-six months after laparoscopy-assisted low anterior resection, the patient developed metachronous early gastric cancer on the antrum and underwent radical subtotal gastrectomy with gastroduodenostomy. The patient is doing well without recurrence for 28 months.

    Title A Four-gene Signature Predicts Disease Progression in Muscle Invasive Bladder Cancer.
    Date October 2011
    Journal Molecular Medicine (cambridge, Mass.)
    Excerpt

    There are no reliable criteria to handle disease progression of muscle invasive bladder cancer (MIBC), which strongly influences patient survival. Therefore, an accurate predicting method to identify progressive MIBC patients is greatly needed. The aim of this study was to identify a genetic signature associated with disease progression in MIBC. To address this issue, we analyzed three independent cohorts (a training set, test set 1 and test set 2) comprising a total of 128 MIBC patients. Microarray gene expression profiling, including gene network analysis, was performed in the training set to identify a gene expression signature associated with disease progression. The prognostic value of the signature was validated in test set 1 and test set 2 by microarray and real-time reverse transcriptase polymerase chain reaction (RT-PCR), respectively. The determination of gene expression patterns by microarray data analysis identified 1,320 genes associated with disease progression. Gene network analysis of the 1,320 genes suggested that IL1B, S100A8, S100A9 and EGFR were important mediators of MIBC progression. We validated this putative four-gene signature in two independent cohorts (log-rank test, P < 0.05 each, respectively) and estimated the predictive value of the signature by multivariate Cox regression analysis (hazard ratio [HR], 6.24; 95% confidence interval [CI], 1.58-24.61; P = 0.009). Finally, signature-based stratification demonstrated that the four-gene signature was an independent predictor of MIBC progression. In conclusion, a molecular signature defined by four genes represents a promising diagnostic tool for the identification of MIBC patients at high risk of progression.

    Title Prognosis of Oligodendroglial Tumor with Ring Enhancement Showing Central Necrotic Portion.
    Date September 2011
    Journal Journal of Neuro-oncology
    Excerpt

    Oligodendroglial tumors sometimes show heterogeneous ring enhancement with a central necrotic portion. We aimed to reveal the prognosis of such tumors based on such radiologic findings and compare them to other prognostic factors. Participants were 32 patients with oligodendroglioma (17 oligodendrogliomas, 15 anaplastic oligodendrogliomas) who underwent surgery from 2004 to 2008. We investigated tumor radiologic findings, locations, calcification, whether localized or diffuse type, and enhancement patterns. Of other prognostic factors, we analyzed age, sex, pathology, extent of removal, adjuvant therapy, genetic change in 1p and 19q, and MGMT methylation status. We checked for genetic abnormality in 1p and 19q using the FISH method. To investigate MGMT methylation, we performed methylation-specific PCR (MSP). Mean follow-up duration was 3.2 years. Median age was 42.4 years, and the male:female ratio was 21:11. Out of 17 oligodendrogliomas, 14 (82.4%) showed combined 1p/19q deletion, and 14 (82.4%), methylated MGMT. Among 15 anaplastic oligodendrogliomas, there were 7 (46.6%) with combined 1p/19q deletion and 11 (73.3%) with methylated MGMT. The 4-year recurrence-free survival and overall survival were 77.6 and 100% in oligodendrogliomas and 59.1 and 71.6% in anaplastic oligodendrogliomas, respectively. On univariate analysis, radiologic variable of ring enhancement pattern was statistically significant related with recurrence-free survival (P = 0.003). Variables such as sex (P = 0.03), combined 1p/19q loss (P = 0.04), tumor location (P = 0.02), and anaplastic pathology (P = 0.04) were significantly correlated with overall survival. Cox's regression model revealed that ring enhancement pattern was associated with frequent recurrence (ring enhancement, hazard ratio = 8.281, P = 0.04), and these showed 1p deletion only. Anaplastic oligodendrogliomas with ring enhancement like glioblastomas and without combined 1p/19q loss should receive close follow-up after treatment because of frequent recurrences.

    Title Technical Considerations to Prevent Postoperative Endocrine Dysfunction After the Fenestration of Suprasellar Arachnoid Cyst.
    Date July 2011
    Journal Journal of Korean Neurosurgical Society
    Excerpt

    The endocrine dysfunction after the operation for suprasellar arachnoid cysts is not rare. The careful operation to prevent structures can prevent this complication, but it is not enough and effective to prevent it. Authors present technical surgical considerations to prevent this complication with a review of our suprasellar arachnoid cyst patients who had postoperative endocrine dysfunction.

    Title Identification of C16orf74 As a Marker of Progression in Primary Non-muscle Invasive Bladder Cancer.
    Date July 2011
    Journal Plos One
    Excerpt

    Methylation-induced silencing of PRSS3 has been shown to be significantly associated with invasive bladder cancer, and expression of the C16orf74 gene locus has been shown to correlate positively with PRSS3. The aim of the current study was to evaluate the relationship between C16orf74 expression level and progression in non-muscle invasive bladder cancer (NMIBC).

    Title Tribological Behavior of Aluminum-cnt Coated Metal Composite Under Dry and Water Lubricated Conditions.
    Date May 2011
    Journal Journal of Nanoscience and Nanotechnology
    Excerpt

    Carbon nanotubes are considered the best material in the field of composites because of their mechanical and tribological properties. In this study, carbon nanotubes coated metal was dispersed in aluminum, the base metal, to improve the wettability between aluminum and carbon nanotubes. The friction and wear behaviors of the aluminum-carbon nanotube coated metal, which is a nickel and copper composite, were investigated using a pin-on-disk wear tester under dry sliding and water lubricated conditions and evaluated using SEM and EDX analysis. All the results demonstrated that the addition of the carbon nanotubes coated metal significantly improved the wettability of CNTs in the aluminum. And the distribution of CNTs prevented the propagation of micro cracks on the surface of the aluminum base metal sample, resulting in enhanced friction characteristics and wear resistance of the nano composite. The composite exhibited lower friction coefficient and wear resistance under the water lubricated condition than the dry sliding condition. Although the lubrication and cooling effect of water contributed to the reduction of the friction coefficient of the composite, the separation of wear particles from the sliding surface changed the wear type from three-body to two-body, resulting in very high wear rate. Also the concentration of oxide under water lubricated condition contributed to the increase of the wear rate because the amount of oxide film removed in terms of thickness exceeded the critical thickness of real contact area.

    Title Hmox1 is an Important Prognostic Indicator of Nonmuscle Invasive Bladder Cancer Recurrence and Progression.
    Date February 2011
    Journal The Journal of Urology
    Excerpt

    HMOX1, which is highly expressed in various solid tumors, has an important role in rapid tumor growth. We investigated the relationship between HMOX1 expression and clinicopathological parameters in patients with NMIBC.

    Title Transcriptional Regulation of Selenoprotein W by Myod During Early Skeletal Muscle Differentiation.
    Date January 2011
    Journal The Journal of Biological Chemistry
    Excerpt

    Selenoprotein W (SelW) is expressed in various tissues, but it is especially high in the skeletal muscle of mammals. Such tissue-specific protein expression implies regulation by a tissue-specific factor. In this study, we investigated SelW expression during myogenic C2C12 cell differentiation using RT-PCR, quantitative PCR, and Western blot analysis. Both the protein and mRNA levels of SelW were increased during C2C12 cell differentiation, particularly during the early stage. Sequence analysis of the SelW promoter revealed four putative E-boxes, E1, E2, E3, and E4, which are known binding sites for MyoD, a myogenic transcriptional factor. Luciferase reporter assay showed that E1 and E4 were crucial for MyoD-dependent promoter activity. Using EMSA analysis, we observed that MyoD bound directly to E1 but not to E4, even though E4 mutation reduced SelW promoter activity in the luciferase reporter assay. Binding of MyoD to E1 was further investigated by ChIP assay. These results suggest that the SelW gene was activated by the binding of MyoD to a specific E-box during early skeletal muscle differentiation.

    Title 1h Nmr-based Metabolomic Study on Resistance to Diet-induced Obesity in Ahnak Knock-out Mice.
    Date January 2011
    Journal Biochemical and Biophysical Research Communications
    Excerpt

    AHNAK is a giant protein of approximately 700 kDa identified in human neuroblastomas and skin epithelial cells. Recently, we found that AHNAK knock-out (AHNAK(-/-)) mice have a strong resistance to high-fat diet-induced obesity. In this study, we applied (1)H NMR-based metabolomics with multivariate statistical analysis to compare the altered metabolic patterns detected in urine from high-fat diet (HFD) fed wild-type and AHNAK(-/-) mice and investigate the mechanisms underlying the resistance to high-fat diet-induced obesity in AHNAK(-/-) mice. In global profiling, principal components analysis showed a clear separation between the chow diet and HFD groups; wild-type and AHNAK(-/-) mice were more distinctly separated in the HFD group compared to the chow diet group. Based on target profiling, the urinary metabolites of HFD-fed AHNAK(-/-) mice gave higher levels of methionine, putrescine, tartrate, urocanate, sucrose, glucose, threonine, and 3-hydroxyisovalerate. Furthermore, two-way ANOVAs indicated that diet type, genetic type, and their interaction (gene × diet) affect the metabolite changes differently. Most metabolites were affected by diet type, and putrescine, threonine, urocanate, and tartrate were also affected by genetic type. In addition, cis-aconitate, succinate, glycine, histidine, methylamine (MA), phenylacetylglycine (PAG), methionine, putrescine, uroconate, and tartrate showed interaction effects. Through the pattern changes in urinary metabolites of HFD-fed AHNAK(-/-) mice, our data suggest that the strong resistance to HFD-induced obesity in AHNAK(-/-) mice comes from perturbations of amino acids, such as methionine, putrescine, threonine, and histidine, which are related to fat metabolism. The changes in metabolites affected by microflora such as PAG and MA were also observed. In addition, resistance to obesity in HFD-fed AHNAK(-/-) mice was not related to an activated tricarboxylic acid cycle. These findings demonstrate that (1)H NMR-based metabolic profiling of urine is suitable for elucidating possible biological pathways perturbed by functional loss of AHNAK on HFD feeding and could elucidate the mechanism underlying the resistance to high-fat diet-induced obesity in AHNAK(-/-) mice.

    Title Reactive Oxygen Species Generated by Nadph Oxidase 2 and 4 Are Required for Chondrogenic Differentiation.
    Date January 2011
    Journal The Journal of Biological Chemistry
    Excerpt

    Although generation of reactive oxygen species (ROS) by NADPH oxidases (Nox) is thought to be important for signal transduction in nonphagocytic cells, little is known of the role ROS plays in chondrogenesis. We therefore examined the possible contribution of ROS generation to chondrogenesis using both ATDC5 cells and primary chondrocytes derived from mouse embryos. The intracellular level of ROS was increased during the differentiation process, which was then blocked by treatment with the ROS scavenger N-acetylcysteine. Expression of Nox1 and Nox2 was increased upon differentiation of ATDC5 cells and primary mouse chondrocytes, whereas that of Nox4, which was relatively high initially, was decreased gradually during chondrogenesis. In developing limb, Nox1 and Nox2 were highly expressed in prehypertrophic and hypertrophic chondrocytes. However, Nox4 was highly expressed in proliferating chondrocytes and prehypertrophic chondrocytes. Depletion of Nox2 or Nox4 expression by RNA interference blocked both ROS generation and differentiation of ATDC5 cells, whereas depletion of Nox1 had no such effect. We also found that ATDC5 cells depleted of Nox2 or Nox4 underwent apoptosis. Further, inhibition of Akt phosphorylation along with subsequent activation of ERK was observed in the cells. Finally, depletion of Nox2 or Nox4 inhibited the accumulation of proteoglycan in primary chondrocytes. Taken together, our data suggest that ROS generated by Nox2 or Nox4 are essential for survival and differentiation in the early stage of chondrogenesis.

    Title Induction of Interleukin-6 Expression by Bone Morphogenetic Protein-6 in Macrophages Requires Both Smad and P38 Signaling Pathways.
    Date January 2011
    Journal The Journal of Biological Chemistry
    Excerpt

    Unlike the prototype transforming growth factor-β (TGF-β), bone morphogenetic protein-6 (BMP-6) activates macrophages. Here, we report that BMP-6 induces the expression of IL-6 in macrophages. Using overexpression and knockdown experiments, we demonstrate that BMP receptor type II and activin-like kinase-2 are necessary for IL-6 induction by BMP-6. At the intracellular level, both Smad and p38 signaling pathways are required for the induction of IL-6. The cross-talk between the two pathways occurs at the level of transcription factor GATA4 and Smad 1/4. These results, taken together, demonstrate a novel BMP-6 signaling mechanism in which both the Smad and non-Smad pathways directly interact to activate the transcription of a target gene.

    Title Renal Hilar Control During Laparoscopic Partial Nephrectomy: to Clamp or Not to Clamp.
    Date November 2010
    Journal Journal of Endourology / Endourological Society
    Excerpt

    To decrease intraoperative and perioperative morbidity that is associated with laparoscopic partial nephrectomy (LPN), clamping of the renal hilum has been advocated. It has been suggested, however, that renal hilar control is not necessary in all patients. We compared the perioperative and pathologic results of 21 consecutive patients who underwent LPN with or without renal hilar clamping at our institution.

    Title Regulatory Mechanism of Hypothalamo-pituitary-adrenal (hpa) Axis and Neuronal Changes After Adrenalectomy in Type 2 Diabetes.
    Date October 2010
    Journal Journal of Chemical Neuroanatomy
    Excerpt

    Diabetes, especially type 2, is closely associated with hypothalamo-pituitary-adrenal (HPA) axis regulation. Short-term effects of adrenalectomy (ADX) in type 2 diabetes are well characterized; however, there have been few reports on the long-term effects of ADX in genetically engineered type 2 diabetes and the neuroendocrine system. We performed bilateral ADX in Zucker Lean Control rats (ZLC; ADX-ZLC), Zucker Diabetic Fatty rats (ZDF; ADX-ZDF), and sham control rats to evaluate how the HPA axis would be regulated in long-term corticosterone deficient type 2 diabetic animals. We evaluated arginine vasopressin (AVP), glucocorticoid receptor (GR), and corticotropin-releasing hormone (CRH) expression with immunohistochemistry (IHC), immunofluorescence, real-time PCR, and Western blot analysis in each treatment group 7 weeks post ADX to assess HPA axis regulatory patterns in connection with type 2 diabetes. Additionally, mRNA expression of AVP and CRH receptors (V1aR, V1bR, CRHR1, and CRHR2) was also measured and adrenocorticotropin hormone (ACTH) immunoreactivity was surveyed by IHC to add to data regarding the regulatory mechanism. AVP and CRH protein expression levels increased after ADX in the hypothalamus of diabetic rats based on IHC results; however, we found that the subtypes of each receptor may be regulated differently in ADX groups compared to sham groups. Immunoreactivity of ACTH in the pituitary gland was enhanced in ADX groups and GR expression levels in the hypothalamic paraventricular nuclei (PVN) remained high, as determined by IHC as well as Western blot analysis. Without the negative feedback system of corticosterone, CRH is highly enhanced and may primarily combine with CRHR1 to stimulate negative feedback through ACTH in the pituitary gland in type 2 diabetic rats with long-term ADX. Although the negative feedback signal was not transmitted appropriately following long-term ADX with type 2 diabetes, a high GR protein level was maintained as in type 2 diabetes. The long-termed lack of corticosterone in the blood stream is a very important factor for normal regulation of the HPA axis even in diabetic animals. From the data, we can conclude that the stimulated HPA axis regulation in the developing type 2 diabetic animals following long-term adrenalectomy has remained elevated rather than diminished. Therefore, the current study may provide useful information to better understand patients suffering from both type 2 diabetes and Addison's disease.

    Title Diffuse Pattern of Transient Hepatic Attenuation Differences in Viral Hepatitis: a Sign of Acute Hepatic Injury in Patients Without Cirrhosis.
    Date October 2010
    Journal Journal of Computer Assisted Tomography
    Excerpt

    Our objective was to describe the transient hepatic attenuation differences (THADs) on dynamic computed tomography in patients with viral hepatitis who had no evidence of cirrhosis.

    Title Is There a Role for a Strict Incision Length Criterion for Determining Conversions During Laparoscopic Colorectal Resection?
    Date September 2010
    Journal Surgical Innovation
    Excerpt

    There's no consensus about what defines a conversion for laparoscopic-assisted colorectal resection (LACR). This study's goal was to assess the utility of a strict incision length (IL) definition of conversion (incision > 7 cm) and compare it with results obtained when the surgeon determined (SD) if a LACR had been successfully completed.

    Title Development of Intraoperative Electrochemical Detection: Wireless Instantaneous Neurochemical Concentration Sensor for Deep Brain Stimulation Feedback.
    Date September 2010
    Journal Neurosurgical Focus
    Excerpt

    Deep brain stimulation (DBS) is effective when there appears to be a distortion in the complex neurochemical circuitry of the brain. Currently, the mechanism of DBS is incompletely understood; however, it has been hypothesized that DBS evokes release of neurochemicals. Well-established chemical detection systems such as microdialysis and mass spectrometry are impractical if one is assessing changes that are happening on a second-to-second time scale or for chronically used implanted recordings, as would be required for DBS feedback. Electrochemical detection techniques such as fast-scan cyclic voltammetry (FSCV) and amperometry have until recently remained in the realm of basic science; however, it is enticing to apply these powerful recording technologies to clinical and translational applications. The Wireless Instantaneous Neurochemical Concentration Sensor (WINCS) currently is a research device designed for human use capable of in vivo FSCV and amperometry, sampling at subsecond time resolution. In this paper, the authors review recent advances in this electrochemical application to DBS technologies. The WINCS can detect dopamine, adenosine, and serotonin by FSCV. For example, FSCV is capable of detecting dopamine in the caudate evoked by stimulation of the subthalamic nucleus/substantia nigra in pig and rat models of DBS. It is further capable of detecting dopamine by amperometry and, when used with enzyme linked sensors, both glutamate and adenosine. In conclusion, WINCS is a highly versatile instrument that allows near real-time (millisecond) detection of neurochemicals important to DBS research. In the future, the neurochemical changes detected using WINCS may be important as surrogate markers for proper DBS placement as well as the sensor component for a "smart" DBS system with electrochemical feedback that allows automatic modulation of stimulation parameters. Current work is under way to establish WINCS use in humans.

    Title Radiosurgery for Brain Metastases from Unknown Primary Cancers.
    Date August 2010
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    We evaluated the role of Gamma Knife stereotactic radiosurgery in the multidisciplinary management of brain metastases from an undiagnosed primary cancer.

    Title Metformin Normalizes Type 2 Diabetes-induced Decrease in Cell Proliferation and Neuroblast Differentiation in the Rat Dentate Gyrus.
    Date August 2010
    Journal Neurochemical Research
    Excerpt

    In this study, we observed the effects of metformin, one of the most widely prescribed drugs for the treatment of type 2 diabetes, on cell proliferation and neuroblast differentiation in the subgranular zone of the hippocampal dentate gyrus (SZDG) in Zucker diabetic fatty (ZDF) rats, which are a model for type 2 diabetes. For this, metformin was administered orally once a day to 14-week-old ZDF rats for 2 weeks and the animals were sacrificed at 16 weeks of age. During this period, blood glucose levels were higher in the vehicle-treated ZDF rats than in the Zucker lean control (ZLC) rats. Metformin treatment significantly decreased the blood glucose levels from 15.5 weeks of age. In the SZDG, Ki67 (a marker for cell proliferation)- and doublecortin (DCX, a marker for differentiated neuroblasts)-immunoreactive cells were much lower in the vehicle-treated ZDF rats than in the ZLC rats. In the metformin-treated ZDF group, Ki67- and DCX-immunoreactive cells were significantly increased in the SZDG compared to those in the vehicle-treated ZDF group. These results suggest that diabetes significantly reduces cell proliferation and neuroblast differentiation in the SZDG and that metformin treatment normalizes the reduction of cell proliferation and neuroblast differentiation in the SZDG in diabetic rats.

    Title Impact of Posterior Urethral Plate Repair on Continence Following Robot-assisted Laparoscopic Radical Prostatectomy.
    Date July 2010
    Journal Yonsei Medical Journal
    Excerpt

    The objective of this study is to evaluate the continence rate following reconstruction of the posterior urethral plate in robot-assisted laparoscopic radical prostatectomy (RLRP).

    Title High Frequency Stimulation of the Subthalamic Nucleus Evokes Striatal Dopamine Release in a Large Animal Model of Human Dbs Neurosurgery.
    Date June 2010
    Journal Neuroscience Letters
    Excerpt

    Subthalamic nucleus deep brain stimulation (STN DBS) ameliorates motor symptoms of Parkinson's disease, but the precise mechanism is still unknown. Here, using a large animal (pig) model of human STN DBS neurosurgery, we utilized fast-scan cyclic voltammetry in combination with a carbon-fiber microelectrode (CFM) implanted into the striatum to monitor dopamine release evoked by electrical stimulation at a human DBS electrode (Medtronic 3389) that was stereotactically implanted into the STN using MRI and electrophysiological guidance. STN electrical stimulation elicited a stimulus time-locked increase in striatal dopamine release that was both stimulus intensity- and frequency-dependent. Intensity-dependent (1-7V) increases in evoked dopamine release exhibited a sigmoidal pattern attaining a plateau between 5 and 7V of stimulation, while frequency-dependent dopamine release exhibited a linear increase from 60 to 120Hz and attained a plateau thereafter (120-240Hz). Unlike previous rodent models of STN DBS, optimal dopamine release in the striatum of the pig was obtained with stimulation frequencies that fell well within the therapeutically effective frequency range of human DBS (120-180Hz). These results highlight the critical importance of utilizing a large animal model that more closely represents implanted DBS electrode configurations and human neuroanatomy to study neurotransmission evoked by STN DBS. Taken together, these results support a dopamine neuronal activation hypothesis suggesting that STN DBS evokes striatal dopamine release by stimulation of nigrostriatal dopaminergic neurons.

    Title Ct Findings of Colonic Complications Associated with Colon Cancer.
    Date May 2010
    Journal Korean Journal of Radiology : Official Journal of the Korean Radiological Society
    Excerpt

    A broad spectrum of colonic complications can occur in patients with colon cancer. Clinically, some of these complications can obscure the presence of underlying malignancies in the colon and these complications may require emergency surgical management. The complications of the colon that can be associated with colon cancer include obstruction, perforation, abscess formation, acute appendicitis, ischemic colitis and intussusception. Although the majority of these complications only rarely occur, familiarity with the various manifestations of colon cancer complications will facilitate making an accurate diagnosis and administering prompt management in these situations. The purpose of this pictorial essay is to review the CT appearance of the colonic complications associated with colon cancer.

    Title Mouse Phenogenomics, Toolbox for Functional Annotation of Human Genome.
    Date May 2010
    Journal Bmb Reports
    Excerpt

    Mouse models are crucial for the functional annotation of human genome. Gene modification techniques including gene targeting and gene trap in mouse have provided powerful tools in the form of genetically engineered mice (GEM) for understanding the molecular pathogenesis of human diseases. Several international consortium and programs are under way to deliver mutations in every gene in mouse genome. The information from studying these GEM can be shared through international collaboration. However, there are many limitations in utility because not all human genes are knocked out in mouse and they are not yet phenotypically characterized by standardized ways which is required for sharing and evaluating data from GEM. The recent improvement in mouse genetics has now moved the bottleneck in mouse functional genomics from the production of GEM to the systematic mouse phenotype analysis of GEM. Enhanced, reproducible and comprehensive mouse phenotype analysis has thus emerged as a prerequisite for effectively engaging the phenotyping bottleneck. In this review, current information on systematic mouse phenotype analysis and an issue-oriented perspective will be provided.

    Title Anticancer Activity of Pegylated Matrix Metalloproteinase Cleavable Peptide-conjugated Adriamycin Against Malignant Glioma Cells.
    Date May 2010
    Journal International Journal of Pharmaceutics
    Excerpt

    Although matrix metalloproteinases (MMPs) play a crucial role in the invasion and growth of malignant gliomas, their increased activity in tumor environment can be used as a specific target for chemotherapy. We investigated whether polymer-drug conjugates formed via MMP-cleavable peptide linkages could provide MMP-responsive tumor targeting and cytotoxicity for malignant glioma cells. One end of an MMP-cleavable peptide was attached to the end of methoxy polyethylene glycol (MPEG) while the other end was attached to adriamycin (ADR). The release of drugs in the presence of conditioned media of U87MG cells was investigated. The cytotoxicities of the MMP-cleavable MPEG-peptide-ADR (PPA) conjugates and non-cleavable MPEG-ADR (PA) conjugates were investigated using U87MG cells. The (1)H nuclear magnetic resonance (NMR) spectra confirmed the conjugation of the two ends of the peptide to the ends of MPEG and ADR, respectively. Gelatin zymography showed that MMP-2 was strongly expressed in the media of U87MG cells. The PA conjugate did not release ADR either in the phosphate buffered saline (PBS) or conditioned media of U87MG cells. The PPA conjugate released ADR in the presence of the conditioned media of U87MG cells, but not in PBS only. In the cytotoxicity test using U87MG cells, ADR and PPA conjugate showed similar anti-proliferative activities, while the cytotoxicity of PA conjugate was lower than that of ADR. Considering that the cytotoxicity of the PPA conjugate was similar to that of ADR, MMP-cleavable polymer-drug conjugates can be used as targeting carriers for the purpose of inhibiting the proliferation of malignant glioma cells.

    Title Assessment of Post-stroke Extrapersonal Neglect Using a Three-dimensional Immersive Virtual Street Crossing Program.
    Date April 2010
    Journal Acta Neurologica Scandinavica
    Excerpt

    To investigate the potential of our newly developed three-dimensional immersive virtual reality (VR) program modeled on a real street crossing as an assessment tool for extrapersonal neglect in stroke patients.

    Title Erbb2-enhanced Invasiveness of H-ras Mcf10a Breast Cells Requires Mmp-13 and Upa Upregulation Via P38 Mapk Signaling.
    Date March 2010
    Journal International Journal of Oncology
    Excerpt

    Overexpression of ErbB2 has been frequently found in mammary carcinoma. We have previously shown that the aberrant activation of H-Ras induces human breast cell invasion and migration. The present study was aimed at investigating the effect of ErbB2 overexpression on H-Ras-induced breast cell invasion and to elucidate the underlying mechanisms. Herein, we show that overexpression of ErbB2 promotes invasive and migratory abilities of H-Ras-activated MCF10A human breast epithelial cells through upregulation of matrix metalloproteinase (MMP)-13 and urokinase-type plasminogen activator (uPA). We also demonstrate that the p38 MAPK is an important signaling molecule in the ErbB2-induced upregulation of MMP-13 and uPA and invasion/migration of H-Ras MCF10A cells overexpressing ErbB2. The present study elucidating the molecular mechanism underlying ErbB2-induced promotion of H-Ras MCF10A cell invasion may provide invaluable information for understanding breast cancer progression and establishing therapeutic interventions for breast cancer.

    Title Sex Differences in the Temporal Lobe White Matter and the Corpus Callosum: a Diffusion Tensor Tractography Study.
    Date February 2010
    Journal Neuroreport
    Excerpt

    We assessed sex differences in fractional anisotropy (FA) and mean diffusion (MD) of temporal lobe white matter (TLWMFA, TLWMMD), TLWM asymmetry, and the relationship between TLWM asymmetry and FA and MD of the corpus callosum (CCFA, CCMD) using diffusion tensor tractography. We found sex differences in the MD of both inferior longitudinal fasciculus (ILF); however, it disappeared after statistical adjustments for intracranial volume and CCMD variability. FA of the superior longitudinal fasciculus (SLFFA) and FA and MD of the ILF (ILFFA, ILFMD) showed leftward asymmetry. In females, the asymmetry indices of SLFFA and the MD of the SLF were significantly correlated with CCFA and CCMD, respectively, which may be related to sex differences in the hemispheric specialization for language.

    Title Bone Morphogenetic Protein-6 Induces the Expression of Inducible Nitric Oxide Synthase in Macrophages.
    Date January 2010
    Journal Immunology
    Excerpt

    Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta (TGF-beta) superfamily. In the present study, we investigated the effect of BMPs on the production of inducible nitric oxide synthase (iNOS) in the murine macrophage cell line, RAW 264.7, and in mouse peritoneal macrophages. Among the BMPs, only BMP-6 induced iNOS expression in a time-dependent and dose-dependent manner in both cell types. Induction of iNOS was inhibited by both cycloheximide and actinomycin D, indicating that the induction of iNOS expression by BMP-6 requires new protein synthesis. Mechanistic studies revealed that the BMP-6-induced iNOS expression requires both Smads and nuclear factor-kappa B (NF-kappaB) signalling pathways. Furthermore, induction of interleukin-1beta (IL-1beta) was necessary for iNOS induction by BMP-6. These observations suggest that BMP-6 stimulates macrophages to produce iNOS through IL-1beta via Smad and NF-kappaB signalling pathways and that BMP-6 may be an important regulator of macrophages.

    Title Antioxidative Role of Selenoprotein W in Oxidant-induced Mouse Embryonic Neuronal Cell Death.
    Date December 2009
    Journal Molecules and Cells
    Excerpt

    It has been reported that selenoprotein W (SelW) mRNA is highly expressed in the developing central nerve system of rats, and its expression is maintained until the early postnatal stage. We here found that SelW protein significantly increased in mouse brains of postnatal day 8 and 20 relative to embryonic day 15. This was accompanied by increased expression of SOD1 and SOD2. When the expression of SelW in primary cultured cells derived from embryonic cerebral cortex was knocked down with small interfering RNAs (siRNAs), SelW siRNA-transfected neuronal cells were more sensitive to the oxidative stress induced by treatment of H2O2 than control cells. TUNEL assays revealed that H2O2-induced apoptotic cell death occurred at a higher frequency in the siRNA-transfected cells than in the control cells. Taken together, our findings suggest that SelW plays an important role in protection of neurons from oxidative stress during neuronal development.

    Title Antitumor Activity of Egfr Targeted Ph-sensitive Immunoliposomes Encapsulating Gemcitabine in A549 Xenograft Nude Mice.
    Date December 2009
    Journal Journal of Controlled Release : Official Journal of the Controlled Release Society
    Excerpt

    Immunoliposomes directed by monoclonal antibodies are promising vehicles for tumor targeted drug delivery. Development of a long-circulating formulation of pH-sensitive liposomes (PSLs) with epidermal growth factor receptor (EGFR) antibody attached was designed and tested using A549 cells and BALB/c-nu/nu mouse tumor model. PSL formulation was prepared using small unilamellar vesicles of DOPE and CHEMS (6:4 molar ratio) by REV method. The average size and zeta-potential of the formulation measured by dynamic laser-light scattering were approximately 146+/-43.9 nm (PDI=0.09+/-0.02) and -1.77+/-0.03 mV, respectively. A549 cells were xenotransplanted into BALB/c-nu/nu mice and various formulations of gemcitabine (gem), such as in its free form, PSLs or Ab-PSLs, were injected intravenously via a tail vein. The rate of tumor volume increment in Ab-PSLs with gem-treated group was remarkably slower than that of other drug-treated group. The tumor from Ab-PSLs with gem 160 mg/kg-injected group exhibited a markedly lowest account of PCNA labeled cells and had highest TUNEL-positive cells among tested. This suggests that treatment of Ab-PSLs with gem resulted in an increased apoptosis of tumor cells, leading to tumor growth inhibition. These results demonstrate that PSLs provide an efficient and targeted delivery of gemcitabine and may represent a useful new treatment approach for tumors which overexpress the EGFR.

    Title Mri of Gastric Carcinoma: Results of T and N-staging in an in Vitro Study.
    Date December 2009
    Journal World Journal of Gastroenterology : Wjg
    Excerpt

    To determine the accuracy of 1.5-T magnetic resonance imaging (MRI) in the evaluation of gastric wall invasion and perigastric lymph node metastasis in gastric adenocarcinoma.

    Title Elevation of Glutamine Level by Selenophosphate Synthetase 1 Knockdown Induces Megamitochondrial Formation in Drosophila Cells.
    Date December 2009
    Journal The Journal of Biological Chemistry
    Excerpt

    Although selenophosphate synthetase 1 (SPS1/SelD) is an essential gene in Drosophila, its function has not been determined. To elucidate its intracellular role, we targeted the removal of SPS1/SelD mRNA in Drosophila SL2 cells using RNA interference technology that led to the formation of vacuole-like globular structures. Surprisingly, these structures were identified as megamitochondria, and only depolarized mitochondria developed into megamitochondria. The mRNA levels of l(2)01810 and glutamine synthetase 1 (GS1) were increased by SPS1/SelD knockdown. Blocking the expression of GS1 and l(2)01810 completely inhibited the formation of megamitochondria induced by loss of SPS1/SelD activity and decreased the intracellular levels of glutamine to those of control cells suggesting that the elevated level of glutamine is responsible for megamitochondrial formation. Overexpression of GS1 and l(2)01810 had a synergistic effect on the induction of megamitochondrial formation and on the synthesis of glutamine suggesting that l(2)01810 is involved in glutamine synthesis presumably by activating GS1. Our results indicate that, in Drosophila, SPS1/SelD regulates the intracellular glutamine by inhibiting GS1 and l(2)01810 expression and that elevated levels of glutamine lead to a nutritional stress that provides a signal for megamitochondrial formation.

    Title Increased Personal Space of Patients with Schizophrenia in a Virtual Social Environment.
    Date November 2009
    Journal Psychiatry Research
    Excerpt

    Virtual reality may be a good alternative method for measuring personal space and overcoming some limitations in previous studies on the social aspects of schizophrenia. Using this technology, we aimed to investigate the characteristics of personal space in patients with schizophrenia and evaluate the relationship between their social behaviors and schizophrenic symptoms. The distance from a virtual person and the angle of head orientation while talking to a virtual person in a virtual environment were measured in 30 patients with schizophrenia and 30 normal controls. It was found that patients with schizophrenia had longer distances and larger angles than did normal controls. The severity of the negative syndrome had significant inverse correlations with the distance from the angry and neutral virtual persons and with the angle of head orientation toward the happy and angry virtual persons, suggesting that negative symptoms may have a close relationship with personal space, including distancing and eye gaze. The larger personal space of patients may reflect their discomfort in close situations or cognitive deficits. Showing these profiles to patients could help them realize the amount of personal space they need.

    Title Label-free Electrochemical Detection of Adenosine Based on Electron Transfer from Guanine Bases in an Adenosine-sensitive Aptamer.
    Date November 2009
    Journal Chemical Communications (cambridge, England)
    Excerpt

    The selective recognition of adenosine with an adenosine-sensitive oligonucleotide is studied via the electrochemical oxidation of guanine bases of the aptamer in solution, leading to a label-free voltammetric aptasensor based on the difference in the oxidative electron transfer rate.

    Title Multiple Gastrointestinal Stromal Tumours Presenting As a Haemoperitoneum in a Patient with Type 1 Neurofibromatosis: Mdct Findings.
    Date August 2009
    Journal The British Journal of Radiology
    Excerpt

    We report multidetector row CT images of multiple gastrointestinal tumours in a patient with Type 1 neurofibromatosis who presented with haemoperitoneum. The use of CT demonstrated multiple, variably sized, ovoid, relatively well-enhancing masses in the intramural or subserosal location of the jejunum. The largest mass that showed a haemorrhagic necrosis caused haemoperitoneum. These imaging features are unique and differ from previous imaging features that have been reported in the radiological literature.

    Title Effects of High Cholesterol Diet on Newly Generated Cells in the Dentate Gyrus of C57bl/6n and C3h/hen Mice.
    Date August 2009
    Journal The Journal of Veterinary Medical Science / the Japanese Society of Veterinary Science
    Excerpt

    In this study, we observed and compared the effects of a high cholesterol diet (HCD) on cell proliferation and differentiation in the subgranular zone of the dentate gyrus of C57BL/6N (B6, susceptible strain) and C3H/HeN (C3H, resistant strain) mice. Ki67 (a marker for cell proliferation) positive cells) were significantly decreased in HCD-fed B6 mice compared to those in B6 (49.7%) and C3H mice fed a low cholesterol diet (LCD). In addition, doublecortin (DCX, a marker for cell differentiation or neuroblasts)-immunoreactive cells in HCD-fed B6 mice were significantly decreased compared to those in LCD-fed B6 and C3H mice. These results suggest that B6 strains are sensitive to HCD, which impairs cell proliferation and differentiation.

    Title Foreign Body Granulomas Simulating Recurrent Tumors in Patients Following Colorectal Surgery for Carcinoma: a Report of Two Cases.
    Date August 2009
    Journal Korean Journal of Radiology : Official Journal of the Korean Radiological Society
    Excerpt

    We report here two cases of foreign body granulomas that arose from the pelvic wall and liver, respectively, and simulated recurrent colorectal carcinomas in patients with a history of surgery. On contrast-enhanced CT and MR images, a pelvic wall mass appeared as a well-enhancing mass that had invaded the distal ureter, resulting in the development of hydronephrosis. In addition, a liver mass had a hypointense rim that corresponded to the fibrous wall on a T2-weighted MR image, and showed persistent peripheral enhancement that corresponded to the granulation tissues and fibrous wall on dynamic MR images. These lesions also displayed very intense homogeneous FDG uptake on PET/CT.

    Title Gamma Knife Radiosurgery for Metastatic Brain Tumors from Thyroid Cancer.
    Date July 2009
    Journal Journal of Neuro-oncology
    Excerpt

    We report our experience using gamma knife radiosurgery (GKR) for brain metastasis from thyroid cancer, which is extremely rare.

    Title Characteristics of Social Anxiety from Virtual Interpersonal Interactions in Patients with Schizophrenia.
    Date June 2009
    Journal Psychiatry
    Excerpt

    Dysfunctional emotional processing affects social functioning in patients with schizophrenia. However, the relationship between emotional perception and response in social interaction has not been elucidated. Twenty-seven patients with schizophrenia and 27 normal controls performed a virtual reality social encounter task in which they introduced themselves to avatars expressing happy, neutral, or angry emotions while verbal response duration and onset time were measured and perception of emotional valence and arousal, and state anxiety were rated afterwards. Self-reported trait-affective scale scores and the Positive and Negative Syndrome Scale (PANSS) ratings were also obtained. Patient group significantly underestimated the valence and arousal of angry emotions expressed by an avatar. While valence and arousal ratings of happy avatars were comparable between groups, patient group reported significantly higher state anxiety in response to happy avatars. State anxiety ratings significantly decreased from encounters with neutral to happy avatars in normal controls while no significant decrease was observed in the patient group. The Social Anhedonia Scale and PANSS negative symptom subscale scores (blunted affect, emotional withdrawal, and passive/ apathetic social withdrawal items) were significantly correlated with state anxiety ratings of the encounters with happy avatars. These results suggest that patients with schizophrenia have interference with the experience of pleasure in social interactions which may be associated with negative symptoms.

    Title Expression of Tissue-type Transglutaminase (ttg) and the Effect of Ttg Inhibitor on the Hippocampal Ca1 Region After Transient Ischemia in Gerbils.
    Date June 2009
    Journal Brain Research
    Excerpt

    Chronological changes of tissue-type transglutaminase (tTG) were observed in the hippocampal CA1 region after transient forebrain ischemia in gerbils. In the sham-operated group, tTG immunoreactivity was weakly detected in blood vessels which were immunostained with platelet endothelial cell adhesion molecule-1 (PECAM-1), and tTG immunoreactivity in blood vessels was highest 5 days after ischemia/reperfusion. In addition, tTG immunoreaction was expressed in microglia which were immunostained with Iba-1 at 4 days post-ischemia, and tTG immunoreactivity in the microglia was also highest at 5 days post-ischemia. In Western blot analysis, tTG protein levels in the CA1 region after ischemia/reperfusion began to increase 3 days after ischemia/reperfusion and peaked 5 days after ischemia/reperfusion. The expression of tTG in PECAM-1-immunoreactive blood vessels may be associated with integrin regulation or transendothelial migration of leukocytes in the ischemic CA1 region. In this study, we also observed the effect of cystamine, a tTG inhibitor, against ischemic damage. Administration of cystamine protected in certain degree neuronal damage from ischemic damage in the CA1 region. These results suggest that tTG may be associated with neuronal death in the hippocampal CA1 region induced by ischemia/reperfusion.

    Title Transient Arterial Enhancement of the Hepatic Parenchyma in Patients with Acute Cholangitis.
    Date June 2009
    Journal Journal of Computer Assisted Tomography
    Excerpt

    Our objectives were to determine the clinical significance of transient arterial enhancement (TAE) of the hepatic parenchyma in patients with suspected biliary disease and to investigate the relationship between the pattern and extent of TAE and acute cholangitis.

    Title Gamma Knife Radiosurgery for Intraventricular Meningiomas.
    Date May 2009
    Journal Acta Neurochirurgica
    Excerpt

    Intraventricular meningiomas are relatively rare tumors that may benefit from stereotactic radiosurgery as a minimally invasive treatment strategy. We report our experience using gamma knife radiosurgery (GKR) for intraventricular meningiomas.

    Title Effects of Methimazole on the Onset of Type 2 Diabetes in Leptin Receptor-deficient Rats.
    Date May 2009
    Journal The Journal of Veterinary Medical Science / the Japanese Society of Veterinary Science
    Excerpt

    We investigated the effects of methimazole, an anti-thyroid drug, on the onset of type 2 diabetes in Zucker diabetic fatty (ZDF) rats. For this, 0.03% methimazole was administered to 7-week-old, pre-diabetic ZDF rats in drinking water for 5 weeks and the animals were sacrificed at 12 weeks of age. Methimazole treatment to ZDF rats significantly reduced blood glucose levels, food intake, body weight, and serum T3 levels. Hepatocytes in ZDF-methi rats were more densely stained with eosin than those in ZDF rats because of low fat accumulation in ZDF-methi hepatocytes. The pancreatic islet in ZDF-methi rats was normal compared to that in ZDF rats. Glucagon, not insulin, immunoreactivity in ZDF-methi rats was significantly higher than that in ZDF-methi rats. These suggest that methimazole treatment may delay the onset of type 2 diabetes in leptin receptor-deficient rats and also suggests that thyroid hormones may be necessary for the onset of diabetes.

    Title Virtual Reality Prototype for Measurement of Expression Characteristics in Emotional Situations.
    Date April 2009
    Journal Computers in Biology and Medicine
    Excerpt

    Expressions are a basic necessity for daily living, as they are required for managing relationships with other people. Conventional expression training has difficulty achieving an objective measurement, because their assessment depends on the therapist's ability to assess a patient's state or training effectiveness. In addition, it is difficult to provide emotional and social situations in the same manner for each training or assessment session. Virtual reality techniques can overcome shortcomings occurring in conventional studies by providing exact and objective measurements and emotional and social situations. In this study, we developed a virtual reality prototype that could present emotional situation and measure expression characteristics. Although this is a preliminary study, it could be considered that this study shows the potential of virtual reality as an assessment tool.

    Title Duplication of the Spleen with a Short Pancreas.
    Date March 2009
    Journal The British Journal of Radiology
    Excerpt

    The most common form of splenic anomaly with a concurrent short pancreas is polysplenia, which has been described in various studies in the radiological literature. However, splenic duplication has never been reported. We report here a case of splenic duplication associated with a short pancreas and pre-duodenal portal vein. This extremely rare case of splenic anomaly shows unique multidetector CT findings that are distinguishable from a splenic lobulation or cleft.

    Title Superparamagnetic Iron Oxide Nanoparticles Coated with Mannan for Macrophage Targeting.
    Date March 2009
    Journal Journal of Nanoscience and Nanotechnology
    Excerpt

    To develop the functionalized superparamagnetic iron oxide nanoparticles (SPIONs) demonstrating the capacities to be delivered in antigen presenting cells specifically and to be dispersed in physiological environment stably, the nanoparticle surface was coated with mannan that induces receptor-mediated endocytosis. Mannan is a water-soluble polysaccharide having high content of D-mannose residues to be recognized by mannose receptors on immunate macrophages. Mannan-coated SPIONs (mannan-SPIONs) were prepared by traditional coprecipitation method, followed by a thermochemical treatment and post-coating with mannan solution. Poly(vinyl alcohol)-coated SPIONs (PVA-SPIONs) were also prepared as a control. Upon characterization, mannan-SPIONs were proven to be suitable for MR imaging due to small size, excellent stability in ferrofluid, and low cytotoxicity. In addition mannan-SPIONs exhibited enhanced targeted delivery efficiency to macrophages than PVA-SPIONs in vitro and in vivo. Therefore, mannan as a coating material not only prevented the aggregation of SPIONs in physiological medium but also provided a capacity to be delivered in antigen presenting cells specifically, suggesting of the potential utility of mannan-SPIONs as a macrophage-targeting MRI contrast agent.

    Title Gamma Knife Surgery for Schwannomas Originating from Cranial Nerves Iii, Iv, and Vi.
    Date January 2009
    Journal Journal of Neurosurgery
    Excerpt

    Schwannomas from the motor cranial nerves controlling eye movement are rare. The authors evaluated the role of Gamma Knife surgery (GKS) in the management of schwannomas originating from cranial nerves III, IV, and VI.

    Title Gamma Knife Radiosurgery for Treatment Resistant Choroid Plexus Papillomas.
    Date November 2008
    Journal Journal of Neuro-oncology
    Excerpt

    OBJECTIVE: To report the results of gamma knife radiosurgery (GKR) for treatment resistant choroid plexus papillomas. METHODS: Six patients (median age 55 years; range 29-75) with residual (n = 2) or recurrent (n = 4) choroid plexus papillomas underwent GKR. All failed prior surgery and one failed prior proton beam radiation therapy. These six patients had a total of 11 locally or distant recurrent intracranial tumors. The median and mean tumor volumes were 2.7 and 3.9 cc (range, 0.23-21.1). A median margin dose of 12.0 Gy (range, 11.5-15) was prescribed to the tumor margin. RESULTS: The progression-free periods varied from 7 to 108 months (mean: 36.9). Four tumors were stable after GKR but seven showed progression. Four recurrent tumors in two patients were managed with repeat radiosurgery and three were observed. At the second GKR, the tumor volume varied from 1.3 to 12.4 cc, and the marginal radiation dose varied from 11 to 14 Gy. The overall survival after the first GKR varied from 15 to 120 months. Four patients were alive at the end of the study period. CONCLUSIONS: Radiosurgery represents an additional management strategy for patients who progress despite surgical removal. It may especially be useful for patients with small deep seated residual choroid plexus papillomas, and for tumors that recur at a site distant from their origin.

    Title Laparoscopic Partial Nephrectomy Without Hilar Control.
    Date November 2008
    Journal Journal of Endourology / Endourological Society
    Title Characterization of the Insp6-dependent Interaction Between Ck2 and Nopp140.
    Date November 2008
    Journal Biochemical and Biophysical Research Communications
    Excerpt

    Nopp140, a highly phosphorylated nucleolar protein, negatively regulates CK2, a kinase essential for cell proliferation. We quantitatively analyzed the interaction between two subunits of CK2 and Nopp140 and characterized the mechanism by which InsP(6) inhibits the interaction. Nopp140 specifically binds to the catalytic subunit of CK2 (CK2alpha) with a dissociation constant of (K(d)) of 4nM, which interferes with the catalytic activity of CK2. The C-terminal region of Nopp140 is determined as CK2alpha-binding region by a yeast two-hybrid method as well as a direct measurement of the interaction between CK2alpha and deletion mutants of Nopp140. InsP(6) specifically binds to CK2alpha and disrupts the interaction between CK2alpha and Nopp140 with an IC(50) value of 25 microM, thereby attenuating the Nopp140-mediated repression of CK2 activity.

    Title Primary Central Nervous System Lymphoma Presenting As an Acute Massive Intracerebral Hemorrhage: Case Report with Immunohistochemical Study.
    Date October 2008
    Journal Surgical Neurology
    Excerpt

    BACKGROUND: Hemorrhage at presentation in primary CNS lymphoma is extremely rare and only 2 studies have reported it. We experienced a case of hemorrhage in primary CNS lymphoma, but the feature was different from those in the 2 studies mentioned. We report a case of primary CNS lymphoma presenting as an acute massive ICH causing catastrophic mental deterioration, along with immunohistochemical profiles. CASE DESCRIPTION: A 49-year-old woman was admitted with sudden deterioration of mental status. Immediate CT scan showed a massive ICH in the left frontal lobe with perilesional edema and midline shifting. Emergency operation was performed and the hematoma was removed gross totally, including the abnormal lesions distinguished from adjacent normal brain. The histopathologic diagnosis was non-Hodgkin lymphoma, diffuse, large, B cell type with acute hemorrhage, and immunohistochemistry results showed high VEGF immunoreactivity and intermediate CD34 immunoreactivity. CONCLUSION: Primary CNS lymphoma can present as an acute massive ICH, and immunohistochemistry in the present study strengthened the suggestion that VEGF activity is related to the hemorrhage in primary CNS lymphoma.

    Title Computational Study of Wolff's Law with Trabecular Architecture in the Human Proximal Femur Using Topology Optimization.
    Date October 2008
    Journal Journal of Biomechanics
    Excerpt

    In the field of bone adaptation, it is believed that the morphology of bone is affected by its mechanical loads, and bone has self-optimizing capability; this phenomenon is well known as Wolff's law of the transformation of bone. In this paper, we simulated trabecular bone adaptation in the human proximal femur using topology optimization and quantitatively investigated the validity of Wolff's law. Topology optimization iteratively distributes material in a design domain producing optimal layout or configuration, and it has been widely and successfully used in many engineering fields. We used a two-dimensional micro-FE model with 50 microm pixel resolution to represent the full trabecular architecture in the proximal femur, and performed topology optimization to study the trabecular morphological changes under three loading cases in daily activities. The simulation results were compared to the actual trabecular architecture in previous experimental studies. We discovered that there are strong similarities in trabecular patterns between the computational results and observed data in the literature. The results showed that the strain energy distribution of the trabecular architecture became more uniform during the optimization; from the viewpoint of structural topology optimization, this bone morphology may be considered as an optimal structure. We also showed that the non-orthogonal intersections were constructed to support daily activity loadings in the sense of optimization, as opposed to Wolff's drawing.

    Title Mannosylated Polyethylenimine Coupled Mesoporous Silica Nanoparticles for Receptor-mediated Gene Delivery.
    Date September 2008
    Journal International Journal of Pharmaceutics
    Excerpt

    Organic-inorganic nanohybrids have been studied for their use as non-viral transfection agents. The purpose of this study was to examine the ability of mesoporous silica nanoparticles (MSN) coupled with mannosylated polyethylenimine (MP) to transfect plasmid DNA in vitro. Although MSN is biocompatible and has low cytotoxicity, it is not easily transfected into a variety of cell types. To overcome this barrier, MP was coupled to MSN (abbreviated as MPS) to target macrophage cells with mannose receptors and enhance transfection efficiency. The DNA conveyance ability of MPS was examined by evaluating properties such as particle size, zeta potential, complex formation, protection of plasmid DNA against DNase-I, and the release of DNA upon cell entry. Particle sizes of the MPS/DNA complexes decreased with increasing weight ratio of MPS to DNA, while the zeta potential increased. Complete MPS/DNA complexes were formed at a weight ratio of five, and their resistance to DNase-I was evaluated. Cytotoxicity studies showed that MPS/DNA complexes resulted in a high percentage of cell viability, compared with PEI 25K as a vector. The transfection efficiency of MPS/DNA complexes was evaluated on Raw 264.7 and HeLa cell lines. It was found that MPS/DNA complexes showed enhanced transfection efficiency through receptor-mediated endocytosis via mannose receptors. These results indicate that MPS can be employed in the future as a potential gene carrier to antigen presenting cells.

    Title Role of Galectin-1 in Migration and Invasion of Human Glioblastoma Multiforme Cell Lines.
    Date September 2008
    Journal Journal of Neurosurgery
    Excerpt

    OBJECT: Galectin-1 is highly expressed in motile cell lines. The authors investigated whether galectin-1 actually modulates the migration and invasion of human glioblastoma multiforme (GBM) cell lines, and whether its expression with respect to invasion and prognosis is attributable to certain glioma subgroups. METHODS: In the human GBM cell lines U343MG-A, U87MG, and U87MG-10', the RNA differential display was evaluated using Genefishing technology. The results were validated by reverse transcription polymerase chain reaction and Northern blot analysis to detect possible genetic changes as the determining factors for the motility of the malignant glioma. The migration and invasion abilities were investigated in human GBM cell lines and galectin-1 transfectant using an in vitro brain slice invasion model and a simple scratch technique. The morphological and cytoskeletal (such as the development of actin and vimentin) changes were examined under light and confocal microscopy. Galectin-1 expression was assessed on immunohistochemical tests and Western blot analysis. RESULTS: Endogenous galectin-1 expression in the human GBM cell lines was statistically correlated with migratory abilities and invasiveness. The U87-G-AS cells became more round than the U87MG cells and lacked lamellipodia. On immunohistochemical staining, galectin-1 expression was increased in higher-grade glioma subgroups (p = 0.027). CONCLUSIONS: Diffuse gliomas demonstrated higher expression levels than pilocytic astrocytoma in the Western blot. Galectin-1 appears to modulate migration and invasion in human glioma cell lines and may play a role in tumor progression and invasiveness in human gliomas.

    Title Development and Verification of an Alcohol Craving-induction Tool Using Virtual Reality: Craving Characteristics in Social Pressure Situation.
    Date September 2008
    Journal Cyberpsychology & Behavior : the Impact of the Internet, Multimedia and Virtual Reality on Behavior and Society
    Excerpt

    Alcoholism is a disease that affects parts of the brain that control emotion, decisions, and behavior. Therapy for people with alcoholism must address coping skills for facing high-risk situations. Therefore, it is important to develop tools to mimic such conditions. Cue exposure therapy (CET) provides high-risk situations during treatment, which raises the individual's ability to recognize that alcohol craving is being induced. Using CET, it is hard to simulate situations that induce alcohol craving. By contrast, virtual reality (VR) approaches can present realistic situations that cannot be experienced directly in CET. Therefore, we hypothesized that is possible to model social pressure situations using VR. We developed a VR system for inducing alcohol craving under social pressure situations and measured both the induced alcohol craving and head gaze of participants. A 2 x 2 experimental model (alcohol-related locality vs. social pressure) was designed. In situations without an avatar (no social pressure), more alcohol craving was induced if alcohol was present than if it was not. And more alcohol craving was induced in situations with an avatar (social pressure) than in situations without an avatar (no social pressure). The difference of angle between the direction of head gazing and the direction of alcohol or avatar was smaller in situations with an avatar alone (social pressure) than in situations with alcohol alone. In situations with both alcohol and an avatar, the angle between the direction of head gaze and the direction of the avatar was smaller than between the direction of head gaze and the direction of the alcohol. Considering the results, this VR system induces alcohol craving using an avatar that can express various social pressure situations.

    Title Prognostic Factors of Postoperative Visual Outcomes in Tuberculum Sellae Meningioma.
    Date August 2008
    Journal British Journal of Neurosurgery
    Excerpt

    Tuberculum sellae meningiomas usually present optic pathway related symptoms, such as decreased visual acuity and/or visual field defect. In this report, the authors retrospectively analysed 27 patients with tuberculum sellae meningioma who underwent surgical treatment and then sought to identify prognostic factors of the postoperative visual outcomes. From April 1998 to June 2006, the authors treated 27 patients diagnosed with tuberculum sellae meningioma. Age, gender, duration of symptoms, tumour size, tumour consistency on intraoperative and T2WI findings, and resectability were analysed as potential prognostic factors of postoperative visual outcomes. Pre- and postoperative ophthalmological examinations were performed in all patients. Of the 27 patients who presented with visual dysfunction before operation, 12 were improved (44.4%), nine were unchanged (33.3%) and six worsened (22.2%). Those patients with a symptom duration of less than 1 year had a greater likelihood of visual improvement than those with a symptom duration of more than 1 year and those with a soft tumour had a greater likelihood of visual improvement than those with a hard tumour, though this was without statistical significance. Moreover, patients with high signal intensity lesion on T2-weighted images had a greater likelihood of visual improvement than those with an iso or low signal intensity with statistical significance. An excellent correlation was found between tumour consistency and appearance on T2-weighted images (p = 0.001). The results of this study indicate that MRI-T2WI can be used to estimate tumour hardness preoperatively and that this is an important prognostic factor of the visual impairments caused by intrasellar meningioma.

    Title Enhanced Expressions of Arginine Vasopressin (avp) in the Hypothalamic Paraventricular and Supraoptic Nuclei of Type 2 Diabetic Rats.
    Date August 2008
    Journal Neurochemical Research
    Excerpt

    Arginine vasopressin (AVP) is known to a neuropeptide that plays important roles in water conservation, sodium homeostasis, and in the regulation of serum osmolality. Several studies have reported that the elevated AVP level is related with diabetes mellitus as an acute or chronic stressor using type 1 diabetes mellitus animal models. However, it is unclear as to how the immunoreactivity and protein level of AVP in the brain is regulated in animal models of type 2 diabetes mellitus. In the present study, Zucker diabetic fatty (ZDF) rats were employed as a type 2 diabetes mellitus model and were compared with Zucker lean control (ZLC) rats with respect to AVP protein expression. Furthermore, in order to verify the regulation of AVP expression before and after the onset of diabetes mellitus, pre-diabetic rats (4 week-old) and obese-diabetic rats (12 week-old) were used. Blood glucose levels and water consumption were also measured and the results showed significantly high in 12 week-old ZDF than any other groups. AVP expression levels in the paraventricular nucleus and supraoptic nucleus were found to be significantly higher in 12 week-old ZDF rats than in 12 week-old ZLC rats and than in 4 week-old rats by immunostaining and western blotting. Enhanced expression of AVP in these animals may be associated with type 2 diabetes mellitus.

    Title Cortical Thickness Abnormality in Juvenile Myoclonic Epilepsy.
    Date June 2008
    Journal Journal of Neurology
    Excerpt

    Previous studies on gray matter concentration changes in patients with juvenile myoclonic epilepsy (JME) are inconsistent. To investigate cortical abnormality in JME differently, we measured the cortical thickness in 19 JME patients and 18 normal controls. Results showed that the cortical thicknesses of superior/middle/medial frontal gyri, and superior/middle/ inferior temporal gyri were decreased in JME patients. Moreover, cortical thicknesses of precentral gyrus and medial orbital gyrus of right hemispheres were negatively correlated with disease duration. These findings suggest that JME brains have cortical gray matter atrophy in the frontal and temporal lobes.

    Title Chitosan and Its Derivatives for Tissue Engineering Applications.
    Date June 2008
    Journal Biotechnology Advances
    Excerpt

    Tissue engineering is an important therapeutic strategy for present and future medicine. Recently, functional biomaterial researches have been directed towards the development of improved scaffolds for regenerative medicine. Chitosan is a natural polymer from renewable resources, obtained from shell of shellfish, and the wastes of the seafood industry. It has novel properties such as biocompatibility, biodegradability, antibacterial, and wound-healing activity. Furthermore, recent studies suggested that chitosan and its derivatives are promising candidates as a supporting material for tissue engineering applications owing to their porous structure, gel forming properties, ease of chemical modification, high affinity to in vivo macromolecules, and so on. In this review, we focus on the various types of chitosan derivatives and their use in various tissue engineering applications namely, skin, bone, cartilage, liver, nerve and blood vessel.

    Title Quantification of Thalamocortical Tracts in Schizophrenia on Probabilistic Maps.
    Date June 2008
    Journal Neuroreport
    Excerpt

    Diffusion properties of the thalamocortical pathways were compared between 30 schizophrenic patients and 22 healthy age-matched and sex-matched volunteers. T1-weighted and diffusion tensor images were used for cortical parcellation and probabilistic tractography to generate population-based thalamocortical pathway maps. The weighted fractional anisotropy and the longitudinal and transversal diffusivity of each pathway were calculated for individual participants. Patients with schizophrenia demonstrated decreased anisotropy and increased longitudinal and transversal diffusivity within the pathways from the mediodorsal nucleus and the pulvinar to the orbitofrontal and parietal-occipital-temporal lobes. Anisotropy decreases and diffusivity increases were correlated with positive and negative syndrome scale scores. Alterations in global diffusion properties within the thalamocortical pathways imply the disruption of brain circuitry in schizophrenic patients.

    Title Traumatic Rupture of an Intracranial Dermoid Cyst.
    Date June 2008
    Journal Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia
    Excerpt

    This paper reports the first case in which an intracranial dermoid cyst that underwent traumatic rupture was treated surgically and discusses the importance of the preoperative radiological identification and management of the rupture. For adequate management of a ruptured intracranial dermoid cyst, in addition to early surgery, we emphasize the importance of expeditious identification of the rupture with MRI, including an additional fat-suppression sequence, and prompt management of the accompanying chemical meningitis with intravenous steroid therapy beginning from the pre-operative period.

    Title Preparation of Ph-sensitive, Long-circulating and Egfr-targeted Immunoliposomes.
    Date June 2008
    Journal Archives of Pharmacal Research
    Excerpt

    A long-circulating formulation of pH-sensitive liposomes (PSLs) with antibodies against epidermal growth factor receptor (EGFR) attached was designed, expecting an increase in binding and delivery of liposomes to the target cells including non-small cell lung cancer (NSCLC) cells. Physicochemical properties of the PSLs were measured by SEM and DLS. Leakage of a self-quenching fluorescent probe, calcein, from the liposome was studied for the evaluation of pH-sensitivity. Encapsulation efficiency of gemcitabine (an anti-cancer drug) in PSLs was about 67%. Average size of liposomes was 88 nm in diameter. The PSL of DOPE/CHEMS (6:4 molar ratio) formulation showed a dramatic pH-sensitivity at/around pH 5.5, whereas non-PSL of DPPC/Chol or PC/CHEMS formulation did not. Anti-proliferation effect of gemcitabine-encapsulating PSLs & Ab-PSLs in A549 cells was 2-fold higher than the free drug, which was further elucidated by the apoptosis of the cells by gemcitabine (approximately 10% apoptosis for PSL or Ab-PSL formulation vs. approximately 1% for free drug or non-PSL formulation) using FACS analysis. These data demonstrate delivery of gemcitabine to tumor cells can be improved by long-circulating PSLs or Ab-PSLs formulations in vitro.

    Title Application of Irregular and Unbalanced Data to Predict Diabetic Nephropathy Using Visualization and Feature Selection Methods.
    Date June 2008
    Journal Artificial Intelligence in Medicine
    Excerpt

    OBJECTIVE: Diabetic nephropathy is damage to the kidney caused by diabetes mellitus. It is a common complication and a leading cause of death in people with diabetes. However, the decline in kidney function varies considerably between patients and the determinants of diabetic nephropathy have not been clearly identified. Therefore, it is very difficult to predict the onset of diabetic nephropathy accurately with simple statistical approaches such as t-test or chi(2)-test. To accurately predict the onset of diabetic nephropathy, we applied various machine learning techniques to irregular and unbalanced diabetes dataset, such as support vector machine (SVM) classification and feature selection methods. Visualization of the risk factors was another important objective to give physicians intuitive information on each patient's clinical pattern. METHODS AND MATERIALS: We collected medical data from 292 patients with diabetes and performed preprocessing to extract 184 features from the irregular data. To predict the onset of diabetic nephropathy, we compared several classification methods such as logistic regression, SVM, and SVM with a cost sensitive learning method. We also applied several feature selection methods to remove redundant features and improve the classification performance. For risk factor analysis with SVM classifiers, we have developed a new visualization system which uses a nomogram approach. RESULTS: Linear SVM classifiers combined with wrapper or embedded feature selection methods showed the best results. Among the 184 features, the classifiers selected the same 39 features and gave 0.969 of the area under the curve by receiver operating characteristics analysis. The visualization tool was able to present the effect of each feature on the decision via graphical output. CONCLUSIONS: Our proposed method can predict the onset of diabetic nephropathy about 2-3 months before the actual diagnosis with high prediction performance from an irregular and unbalanced dataset, which statistical methods such as t-test and logistic regression could not achieve. Additionally, the visualization system provides physicians with intuitive information for risk factor analysis. Therefore, physicians can benefit from the automatic early warning of each patient and visualize risk factors, which facilitate planning of effective and proper treatment strategies.

    Title Effects of a Tetracycline Blended Polylactic and Polyglycolic Acid Membrane on the Healing of One-wall Intrabony Defects in Beagle Dogs.
    Date June 2008
    Journal Biomedical Materials (bristol, England)
    Excerpt

    The purpose of this study was to evaluate the regenerative effects of a tetracycline blended polylactic and polyglycolic acid (TC-PLGA) and non-blended polylactic and polyglycolic acid (PLGA) barrier membrane on one-wall intrabony defects in beagle dogs. It can be concluded that when used for guided tissue regeneration TC-PLGA membranes show a beneficial effect on one-wall intrabony defects in beagle dogs.

    Title Redox-mediated Modification of Plzf by Sumo-1 and Ubiquitin.
    Date May 2008
    Journal Biochemical and Biophysical Research Communications
    Excerpt

    Earlier, we reported that the transcriptional repressor promyelocytic leukemia zinc-finger protein (PLZF) is sumoylated at position K242, and the sumoylation regulated its biological function. Here, we show that the sumoylation site can be modified by ubiquitin. The stability and nuclear localization of PLZF were regulated by the antagonistic relationship between sumoylation and ubiquitination. We observed the antagonistic effects of ubiquitin and SUMO-1 on PLZF under oxidative stress induced by serum deprivation. Thus, the choice between modification of PLZF by SUMO or ubiquitin was determined by the intracellular level of ROS, which was generated by serum deprivation that inactivated the SUMO-conjugating enzymes Uba2 and Ubc9, and resulted in decrease of sumoylation. The ubiquitination was increased under these conditions. The expression of BID, a known transcriptional target protein of PLZF, was decreased, and the consequent apoptosis was induced by the ROS generated during serum starvation. On the basis of these results, we propose that PLZF post-translational modification is controlled by intracellular ROS, and the biological function of PLZF is regulated by sumoylation and ubiquitination.

    Title Nonlinear Support Vector Machine Visualization for Risk Factor Analysis Using Nomograms and Localized Radial Basis Function Kernels.
    Date May 2008
    Journal Ieee Transactions on Information Technology in Biomedicine : a Publication of the Ieee Engineering in Medicine and Biology Society
    Excerpt

    Nonlinear classifiers, e.g., support vector machines (SVMs) with radial basis function (RBF) kernels, have been used widely for automatic diagnosis of diseases because of their high accuracies. However, it is difficult to visualize the classifiers, and thus difficult to provide intuitive interpretation of results to physicians. We developed a new nonlinear kernel, the localized radial basis function (LRBF) kernel, and new visualization system visualization for risk factor analysis (VRIFA) that applies a nomogram and LRBF kernel to visualize the results of nonlinear SVMs and improve the interpretability of results while maintaining high prediction accuracy. Three representative medical datasets from the University of California, Irvine repository and Statlog dataset-breast cancer, diabetes, and heart disease datasets-were used to evaluate the system. The results showed that the classification performance of the LRBF is comparable with that of the RBF, and the LRBF is easy to visualize via a nomogram. Our study also showed that the LRBF kernel is less sensitive to noise features than the RBF kernel, whereas the LRBF kernel degrades the prediction accuracy more when important features are eliminated. We demonstrated the VRIFA system, which visualizes the results of linear and nonlinear SVMs with LRBF kernels, on the three datasets.

    Title Conjugated Linoleic Acids Produced by Lactobacillus Dissociates Ikk-gamma and Hsp90 Complex in Helicobacter Pylori-infected Gastric Epithelial Cells.
    Date May 2008
    Journal Laboratory Investigation; a Journal of Technical Methods and Pathology
    Excerpt

    Although probiotics have been reported to reduce the gastric inflammatory response to Helicobacter pylori infection, little information is available regarding the molecular mechanisms behind this reduction. This study investigates the role of conjugated linoleic acids (CLA) produced by probiotics in interactions of IkappaB kinase (IKK) and heat shock protein 90 (Hsp90) to activate the nuclear factor-kappaB (NF-kappaB) signaling pathway in human gastric epithelial cells infected with H. pylori. Conditioned medium (CM) containing Lactobacillus acidophilus-producing CLA significantly inhibited the activated NF-kappaB signals and the upregulated expression of interleukin-8 (IL-8) in MKN-45 cells infected with H. pylori. Pretreatment with CM with CLA attenuated the increased IKK activity induced by H. pylori. Transfection of siRNA for IKK-beta dramatically reduced H. pylori-induced IkappaBalpha phosphorylation, but siRNA for IKK-alpha had little effect on IkappaBalpha phosphorylation, although the siRNA for IKK-alpha significantly decreased IL-8 production. Furthermore, Hsp90 was associated with IKK-alpha and IKK-gamma in H. pylori-infected cells, and CM with CLA dissociated the complex between Hsp90 and IKK-gamma. These results suggest that CLA produced by probiotics has anti-inflammatory activity in gastric epithelial cells infected with H. pylori via dissociation of the IKK-gamma and Hsp90 complex.

    Title Reduced Hippocampal Cell Differentiation in the Subgranular Zone of the Dentate Gyrus in a Rat Model of Type Ii Diabetes.
    Date May 2008
    Journal Neurochemical Research
    Excerpt

    It has recently been reported that diabetes mellitus is strongly associated with neurodegenerative and functional disorders of the central nervous system. In the present study, we investigated the changes in proliferating neurons in the dentate gyrus of type II diabetic rats using doublecortin (DCX), a marker of progenitors differentiating into neurons. At 4 weeks after birth, there were no differences in the blood glucose levels of Zucker diabetic fatty (ZDF) rats or Zucker lean control (ZLC) rats. DCX-immunoreactive neurons were detectable in the subgranular zone of the dentate gyrus in both the ZDF and ZLC rats; however, DCX immunoreactivity was higher in the ZLC rats than in the ZDF rats. At 12 weeks after birth, the blood glucose level was significantly increased by 400 mg/dl in the ZDF rats, but the blood glucose level in the ZLC rats was only slightly increased by 152.3 mg/dl. DCX immunoreactivity was significantly decreased in 12-week-old rats in comparison to 4-week-old rats. Some DCX-immunoreactive neurons were detectable in the subgranular zone of the dentate gyrus in the ZLC rats. However, only a few DCX-immunoreactive neurons were observed in the ZDF rats, and the DCX-immunoreactive neurons in the ZDF rats did not show fully developed processes. These results suggest that DCX-immunoreactive neurons were significantly decreased in an age-dependent manner and that DCX-immunoreactive neurons were also reduced in diabetic rats. In addition, the reduction in DCX-immunoreactive neurons in age matched rats may be associated with type II diabetes.

    Title Cisplatin-incorporated Hyaluronic Acid Nanoparticles Based on Ion-complex Formation.
    Date May 2008
    Journal Journal of Pharmaceutical Sciences
    Excerpt

    The aim of this study is to prepare cisplatin-incorporated nanoparticles based on ion complex formation between hyaluronic acid (HA) and cisplatin for antitumor drug delivery. To prepare nanoparticles using HA, bulk HA was degraded by hyaluronidases (HAses). Cisplatin-incorporated HA nanoparticles were prepared by mixing cisplatin with an aqueous solution of HA and then the nanoparticle solution was dialyzed to remove trace elements. Since glioma tumor cell lines are able to secrete HAse, extracts from U343MG and U87MG cell lines were used to test the release of cisplatin from the nanoparticles. The morphological observation of the cisplatin-incorporated nanoparticles showed that they had spherical shapes with a particle size around 100-200 nm. The loading efficiency of cisplatin in the nanoparticles was about 67-81% (w/w) and cisplatin was continuously released from the nanoparticles for 4 days. Especially, the release rate of cisplatin from the nanoparticles increased when HAse was added to the release medium. In the results of the HA zymography, the U343MG cell line secreted HAse, while the U87MG cell line did not. When the extracts from U343MG were added to the release medium, the release rate of cisplatin was slightly increased, while the extracts from U87MG did not significantly affect the release rate of cisplatin. In conclusion, cisplatin-incorporated nanoparticles have sufficiently small particle sizes to use as a drug targeting system. The release of cisplatin from the nanoparticles was responsive to the secretion of HAse. These nanoparticles are suitable vehicles for an antitumor drug targeting system.

    Title Voxel-based Morphometry Study of Gray Matter Abnormalities in Obsessive-compulsive Disorder.
    Date April 2008
    Journal Journal of Korean Medical Science
    Excerpt

    To examine regional abnormalities in the brains of patients with obsessive-compulsive disorder (OCD), we assessed the gray matter (GM) density using voxel-based morphometry (VBM). We compared magnetic resonance images (MRIs) acquired from 71 OCD patients and 71 age- and gender-matched normal controls and examined the relationship between GM density and various clinical variables in OCD patients. We also investigated whether GM density differs among the subtypes of OCD compared to healthy controls. We detected significant reduction of GM in the inferior frontal gyrus, the medial frontal gyrus, the insula, the cingulate gyrus, and the superior temporal gyrus of OCD patients. A significant increase in GM density was observed in the postcentral gyrus, the thalamus, and the putamen. Some of these regions, including the insular and postcentral gyrus, were also associated with the severity of obsessive- compulsive symptoms. These findings indicate that the frontal-subcortical circuitry is dysfunctional in OCD, and suggest that the parietal cortex may play a role in the pathophysiology of this disease.

    Title Enhanced Detectability of Recurrent Brain Tumor Using Glucose-loading F-18 Fdg Pet.
    Date March 2008
    Journal Clinical Nuclear Medicine
    Excerpt

    A 43-year-old man with a history of lung cancer, brain metastasis, and gamma knife radiosurgery underwent FDG PET/CT to differentiate recurrence from radiation necrosis. Basal PET/CT scan showed equivocal uptake in the margin of necrotic tumor. After glucose loading (10% glucose 50 mL for 5 minutes), marginal FDG uptake was more easily depicted. Proton magnetic resonance spectroscopy (1H-MRS) showed increased Cho/Cr ratio (1.7), which was consistent with tumor recurrence. The patient underwent whole brain radiotherapy thereafter. It is implicated that hyperglycemia-induced reduction of glucose uptake in recurrent brain tumors was less than in a normal brain, resulting in higher tumor-to-gray matter ratio.

    Title The Relationship Between Brain Morphometry and Neuropsychological Performance in Alcohol Dependence.
    Date February 2008
    Journal Neuroscience Letters
    Excerpt

    The aim of this study was to explore local brain atrophy of patients with alcohol dependence using a voxel-based analysis of magnetic resonance images and to investigate the relationship of those atrophic regions with drinking history and neuropsychological performances. Statistical parametric mapping was applied for the global and regional comparison of segmented gray matter and white matter images from 20 patients with alcohol dependence and with those from 20 controls. The Rey auditory-verbal learning test, Rey-Osterrieth complex figure test, Stroop test, trail-making test, and Wisconsin card sorting test were conducted as neuropsychological evaluations. There was a significant decrease in both gray matter and white matter globally in alcohol dependence. Bilateral parahippocampal white matter areas were reduced in particular. Perseverative responses and perseverative errors in the Wisconsin card sorting test had significant correlation with the decrease of gray matter decrease including the left superior temporal gyri and right postcentral region. The psychological performance measures correlated with gray matter rather than white matter, whereas right temporal white matter correlated with drinking amount for last 4 weeks. This may imply that alcohol consumption in heavy amounts damages both gray matter and white matter, and gray matter atrophy mainly leads to cognitive impairment, whereas white matter is related to drinking history.

    Title Moyamoya Disease with Repeated Intracranial Haemorrhage in Two Consecutive Pregnancies.
    Date January 2008
    Journal Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia
    Excerpt

    A 26-year-old woman presented with an intraventricular haemorrhage during the 27th week of gestation in July 1996, and recovered without general or neurological complications after external ventricular drainage. The fetus was delivered spontaneously through the vagina at the 30th week of gestation, but eventually died. Cerebral angiography demonstrated typical appearances of moyamoya disease with occlusion of the supraclinoid portion of both internal carotid arteries and presence of abnormal collateral vessels. Five years later the second haemorrhage, an intracerebral haematoma in the right temporoparietooccipital area, occurred during the 28th week of pregnancy. Emergency craniotomy was performed and the intracerebral haematoma was removed totally. It is still unknown whether repeated pregnancy increases the risk of cerebrovascular accident in moyamoya disease. A long-term follow up study of several patients with haemorrhagic moyamoya disease is needed to clarify risk factors for rebleeding.

    Title A Highly Efficient Non-heme Manganese Complex in Oxygenation Reactions.
    Date January 2008
    Journal Chemical Communications (cambridge, England)
    Excerpt

    A non-heme manganese(II) complex shows a high catalytic activity in the epoxidation of olefins by iodosyl benzene and in the oxidation of olefins, alcohols and alkanes by peracetic acid; a mechanism involving metal-based oxidants is proposed for the oxidation reactions.

    Title Association Analysis of G72/g30 Polymorphisms with Schizophrenia in the Korean Population.
    Date January 2008
    Journal Schizophrenia Research
    Excerpt

    Several studies examining the association between G72/G30 polymorphisms and schizophrenia in cohorts of various ethnic origins have recently been reported. The aim of the current study was to examine the genetic influence of the G72/G30 polymorphisms in the Korean population. Nine G72/G30 single-nucleotide polymorphisms (SNPs) were genotyped in 388 patients with schizophrenia and 367 normal controls from the Korean population. Based on statistical analyses, the positive associations of previous studies of other populations were not replicated in the present study. However, 2 of the 9 tested SNPs, rs778294 and rs947267, were found to be associated with the risk of schizophrenia after correction for multiple testing (P(cor)=0.03 and P(cor)=0.04, respectively). The rs778294 SNP, taken singly, had not been found to be associated with schizophrenia in previous studies, and the second SNP, rs947267, showed an opposite direction of genetic effect on schizophrenia risk here than in a previous study. Our association results were not consistent with those found in other populations, and, thus could be chance findings. Therefore, further studies with larger sample sizes are needed to confirm a risk allele for this gene if it exists.

    Title Multiple Intracranial Tuberculomas Mimicking Granulocytic Sarcomas in Acute Myeloid Leukemia.
    Date January 2008
    Journal Journal of Korean Medical Science
    Excerpt

    The diagnosis of incracranial tuberculoma in immune-compromised hosts is often difficult because conventional magnetic resonance (MR) imaging of tuberculoma reveals various findings and neurologic symptoms are not typical. Here, we report a case of a 54-yr old man with multiple intracranial tuberculoma who was treated for acute myeloid leukemia. He complained of right-side paresthesia after the third consolidation chemotherapy without leukemic relapse and fever. MR imaging of the brain showed multiple ring-enhanced lesions in the cerebrum, cerebellar hemisphere, and pons. The lesions appeared to mimic a metastatic tumor or abscess. Cerebrospinal fluid analysis showed no abnormal cells, but the level of adenosine deaminase was elevated (28.8 IU/L, normal 0-8). Stereotactic brain biopsy was performed, but only reactive gliosis was observed. To confirm diagnosis, an open brain biopsy was performed. The histopathology demonstrated chronic granulomatous inflammation with caseous necrosis. Tuberculous-polymerase chain reaction of the biopsy showed a positive result. He was treated with anti-tuberculosis medication and a high dose of steroid. Paresthesia improved, and follow-up brain MR imaging showed the decreased size and numbers of ring-enhanced lesions and improvement of perilesional edema 1 month after treatment. Here, we report on an interesting case of intracranial tuberculoma in acute myeloid leukemia.

    Title Mechanics of the Passive Knee Joint. Part 2: Interaction Between the Ligaments and the Articular Surfaces in Guiding the Joint Motion.
    Date January 2008
    Journal Proceedings of the Institution of Mechanical Engineers. Part H, Journal of Engineering in Medicine
    Excerpt

    The aim of this study was to examine how the interaction between ligament tensions and contact forces guides the knee joint through its specific pattern of passive motion. A computer model was built based on cadaver data. The passive motion and the ligament lengthening and force patterns predicted by the model were verified with data from the literature. The contribution of each ligament and contact force was measured in terms of the rotational moment that it produced about the tibial medial plateau and the anterior-posterior (AP) force that it exerted on the tibia. The high tension of the anterior cruciate ligament (ACL) and the geometric constraints of the anterior horns of the menisci were found to be key features that stabilized the knee at full extension. The mutual effect of the cruciates was found as the reason for the screw-home mechanism at early flexion. Past 300, the AP component of contact force on the convex geometry of the lateral tibial plateau and tension of the lateral collateral ligament (LCL) were identified as elements that control the joint motion. From 60 degrees to 90 degrees, reduction in the tension of the ACL was determined as a reason for continuation of the tibial anterior translation. From 90 degrees to 120 degrees, increase in the tension of the posterior cruciate ligament and the AP component of the contact force on the convex geometry of the lateral tibial plateau pushed the tibia more anteriorly. This anterior translation was limited by the constraining effects of the ACL tension and the AP component of the contact force on the medial meniscus. The important guiding role observed for the LCL suggests that it should not be overlooked in knee models.

    Title Evaluation of Practice Efficiency with a Novel Sheathed Flexible Cystoscope: a Randomized Controlled Trial.
    Date January 2008
    Journal Urology
    Excerpt

    OBJECTIVES: The processing of standard flexible cystoscopes is time-consuming and potentially hazardous to healthcare staff. We evaluated a novel flexible cystoscope system containing a disposable sheath, which obviates the need for chemical processing. METHODS: A total of 100 patients undergoing office cystoscopy were randomized into a "sheath" or a control group (n = 50 for each group). Disposable Slide-On sheaths and the CST-2000 Flexible Cystoscope System were used in the former group. A standard 16F flexible cystoscope, manually cleaned and disinfected with Cidex OPA or Rapicide, was used in the control group and the preparation times were recorded. Questionnaires to assess cystoscope setup, handling, optical quality, and patient comfort were completed by the physician, nursing staff, and patients. RESULTS: Data were available for 97 patients. The mean total time required for preparation of the cystoscopes was 10.7, 14.7, and 42.2 minutes for the sheath (n = 49), Rapicide (n = 21), and Cidex OPA (n = 27), respectively (P <0.01 for all comparisons). The control group scored better than the sheath group with regard to ease of cystoscope insertion (9.1 versus 7.7), cystoscope handling (8.8 versus 8.1), and irrigation setup (8.8 versus 8.2; all P < or = 0.01). No statistically significant difference was found between groups for procedure time, optical quality, or patient comfort, either during or after the procedure. CONCLUSIONS: The EndoSheath System can save 4 to 31 minutes of processing time while avoiding exposure to irritants found in conventional soaking methods. Although maneuvering of the sheathed cystoscope was slightly more difficult, the optical quality and patient comfort were similar to those of standard flexible cystoscopy.

    Title Type I Collagen-induced Pro-mmp-2 Activation is Differentially Regulated by H-ras and N-ras in Human Breast Epithelial Cells.
    Date January 2008
    Journal Journal of Biochemistry and Molecular Biology
    Excerpt

    Tumor cell invasion and metastasis are often associated with matrix metalloproteinases (MMPs), among which MMP-2 and MMP-9 are of central importance. We previously showed that H-Ras, but not N-Ras, induced invasion of MCF10A human breast epithelial cells in which the enhanced expression of MMP-2 was involved. MMP-2 is produced as a latent pro-MMP-2 (72 kDa) to be activated resulting the 62 kDa active MMP-2. The present study investigated if H-Ras and/or N-Ras induces pro-MMP-2 activation of MCF10A cells when cultured in two-dimensional gel of type I collagen. Type I collagen induced activation of pro-MMP-2 only in H-Ras MCF10A cells but not in N-Ras MCF10A cells. Induction of active MMP-2 by type I collagen was suppressed by blocking integrin alpha2, indicating the involvement of integrin signaling in pro-MMP-2 activation. Membrane-type (MT)1-MMP and tissue inhibitor of metalloproteinase (TIMP)-2 were up-regulated by H-Ras but not by N-Ras in the type I collagen-coated gel, suggesting that H-Ras-specific up-regulation of MT1-MMP and TIMP-2 may lead to the activation of pro-MMP-2. Since acquisition of pro-MMP-2 activation can be associated with increased malignant progression, these results may help understanding the mechanisms for the cell surface matrix-degrading potential which will be crucial to the prognosis and therapy of breast cancer metastasis.

    Title Cortical Thinning in Obsessive Compulsive Disorder.
    Date January 2008
    Journal Human Brain Mapping
    Excerpt

    Although studies of obsessive-compulsive disorder (OCD) over the last 20 years have suggested abnormalities in frontal-subcortical circuitry, evidences of structural abnormalities in those areas are still imperfect and contradictory. With recent advances in neuroimaging technology, it is now possible to study cortical thickness based on cortical surfaces, which offers a direct quantitative index of cortical mass. Using the constrained Laplacian-based automated segmentation with proximities (CLASP) algorithm, we measured cortical thickness of 55 patients with OCD (33 men and 22 women) and 52 age- and sex-matched healthy volunteers (32 men and 20 women). We found multiple regions of cortical thinning in OCD patients compared to the normal control group. Patients with OCD had thinner left inferior frontal, left middle frontal, left precentral, left superior temporal, left parahippocampal, left orbitofrontal, and left lingual cortices. Most thinned regions were located in the left ventral cortex system, providing a new perspective that this ventral cortical system may be involved in the pathophysiology of OCD.

    Title Increased Expression of Intracystic Matrix Metalloproteinases in Brain Tumors: Relationship to the Pathogenesis of Brain Tumor-associated Cysts and Peritumoral Edema.
    Date January 2008
    Journal Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia
    Excerpt

    Although several types of brain tumors are commonly associated with cyst formation, the pathogenesis of tumor-associated cysts (TAC) is unknown. We investigated the matrix metalloproteinase (MMP) expression of cyst fluids to elucidate the pathogenesis of TAC in brain tumors. We also examined the relationship between the severity of peritumoral edema and the expression of intracystic MMP. We collected 40 cyst fluid samples from 34 patients with TAC and studied the expression of MMP-2 and -9 in the cyst fluid using gelatin zymography. Radiological studies were used to estimate the severity of the peritumoral edema and to determine the presence of TAC. Although gelatin zymography of the cyst fluid showed high levels of MMPs, there was no correlation between the expression of MMPs in the cyst fluid and that in the tumor tissue. The level of MMP expression in the cyst fluid did not reflect the pathologic grade of the individual tumors. However, the total and activated MMP-9 levels were significantly associated with the severity of the peritumoral edema (p<0.05). These results suggest that MMPs may be partly involved in the pathogenesis of TAC and peritumoral edema in brain tumors.

    Title Lipolysis is Stimulated by Pegylated Conjugated Linoleic Acid Through the Cyclic Adenosine Monophosphate-independent Signaling Pathway in 3t3-l1 Cells: Activation of Mek/erk Mapk Signaling Pathway and Hyper-secretion of Adipo-cytokines.
    Date December 2007
    Journal Journal of Cellular Physiology
    Excerpt

    We previously reported that PEGylated conjugated linoleic acid (PCLA) as a pro-drug treatment of cultures of 3T3-L1 cells containing differentiated adipocytes caused de-differentiation by downregulation of PPARgamma2-induced adipogenesis, and cell apoptosis induced by PCLA was lower than that induced by conjugated linoleic acid (CLA) owing to the biocompatible and hydrophilic properties of poly(ethylene glycol) (PEG). To further investigate our previous observations, the present study is designed to evaluate the lipolytic action of PCLA and its role in biochemical signaling pathways of 3T3-L1 cells when compared to the CLA itself. Although both CLA and PCLA stimulated lipolysis, our results indicated a sensitivity difference between CLA and PCLA treatment: a time-dependent effect on lipolysis and p-extracellular signal-related kinases (ERK) expression was observed for PCLA-treated, but not for CLA-treated cultures. Also, the induction by PCLA of mitogen-activated protein kinase kinase (MEK)/ERK mitogen-activated protein kinase (MAPK) activation was linked to secretion of adipo-cytokines, interleukin-6 (IL-6), and interleukin-8 (IL-8), in time-dependent manners. Interestingly, adenylyl cyclase inhibitor, 2', 5'-dideoxyadenosine (DDA), pre-treatment did not prevent PCLA-stimulated lipolysis. In fact, isoproterenol, but not PCLA, caused a significant increase in cyclic adenosine monophosphate (cAMP) levels, suggesting that the PCLA-induced lipolysis was not mediated in the conventional cAMP-dependent pathway and the cAMP was the intracellular mediator for isoproterenol-induced lipolysis. Overall, our findings provide support for a role for PCLA as a pro-drug in the regulation of metabolism in adipose tissue.

    Title Contralateral Migration of Cerebral Sparganosis Through the Splenium.
    Date December 2007
    Journal Clinical Neurology and Neurosurgery
    Excerpt

    Even though it has been known for some time that the cerebral sparganosis could migrate to the contralateral hemisphere, there have been no reports which described the route of migration. This paper reports a case of cerebral sparganosis which migrated from the right temporo-occipital lobe to the contralateral temporo-occipital lobe though the splenium over a period of 3 years. A 24-year-old man visited our hospital complaining of headache for about a month. Three years ago, non-contrast MRI had been performed in a local hospital, and the major finding was cortical atrophy and ventricular dilatation in the right temporo-occipital lobe area, which were compatible with cerebral sparganosis. After admission to our hospital, we performed MRI which showed a 2 cm-sized well-enhanced mass in the left temporo-occipital area. The findings of the right side were similar to the MRI checked 3 years ago. The presence of multiple calcifications and small enhanced lesions on the right side also indicated that the old lesion had been a cerebral sparganosis. The most important finding was that the FLAIR image showed that the entire splenium had high signal intensity which linked the high signal areas of both hemispheres. The patient underwent surgery with the guidance of neuronavigation. The mass was well-capsulated, and removed totally in an en bloc fashion. After opening the capsule, we found a long worm which showed the shape of a whole lava but no movement. The histopathological diagnosis was sparganosis.

    Title Alteration of Brain Metabolites in Young Alcoholics Without Structural Changes.
    Date December 2007
    Journal Neuroreport
    Excerpt

    Using proton magnetic resonance spectroscopy and magnetic resonance imaging, we investigated concentrations of various brain metabolites, including glutamate, and measured brain volumes and neuropsychological performances in 13 recently abstinent young alcoholic men compared with 18 controls. No differences were found in volumetric variables between groups (intracranial volume, white matter, grey matter, anterior cingulate, insula, hippocampus, and amygdala). For the anterior cingulate, choline and creatine levels in the patient group were significantly lower than controls, and the glutamate to creatine ratio was significantly increased. These were correlated with altered short-term memory functions. Thus, neurochemical changes can occur even in the brains of young alcoholic men lacking brain atrophy.

    Title Hippocampal Shape Deformity Analysis in Obsessive-compulsive Disorder.
    Date November 2007
    Journal European Archives of Psychiatry and Clinical Neuroscience
    Excerpt

    Abnormalities of orbital prefrontal cortex and caudate nuclei have, thus far, been the main findings regarding the pathophysiology of obsessive-compulsive disorder (OCD). On the other hand, neuroimaging studies have failed to reach a consensus with regard to the issue of hippocampal abnormalities in OCD patients. Shape analysis may facilitate a resolution of the discordance among these former studies by detecting local structural changes, thus enhancing power to discriminate structural differences. It has been suggested that neural circuitry interconnecting brain areas may critically influence the shape of neuroanatomical structures, serving as a rationale for better sensitivity of shape analysis compared to volume analysis, especially in detecting abnormalities of neural circuitry. Shape analysis of the hippocampus was performed in 22 matched pairs of OCD patients and normal control subjects. As a result, we observed a bilateral hippocampal shape deformity including the most prominent characteristic of downward displacement of the head. The hippocampal structural alteration observed in this study indicates that this structure may play a role in the pathophysiology of OCD. Also, further considering the hippocampal neural connections specific to its surface topography, these surface deformities may reflect developmental alterations in these patients with regard to the neural circuitry involving hippocampus.

    Title Approximated Affine Projection Algorithm for Feedback Cancellation in Hearing Aids.
    Date November 2007
    Journal Computer Methods and Programs in Biomedicine
    Excerpt

    We propose an approximated affine projection (AP) algorithm for feedback cancellation in hearing aids. It is based on the conventional approach using the Gauss-Seidel (GS) iteration, but provides more stable convergence behaviour even with small step sizes. In the proposed algorithm, a residue of the weighted error vector, instead of the current error sample, is used to provide stable convergence. A new learning rate control scheme is also applied to the proposed algorithm to prevent signal cancellation and system instability. The new scheme determines step size in proportion to the prediction factor of the input, so that adaptation is inhibited whenever tone-like signals are present in the input. Simulation results verified the efficiency of the proposed algorithm.

    Title Multiplanar Reformations and Minimum Intensity Projections Using Multi-detector Row Ct for Assessing Anomalies and Disorders of the Pancreaticobiliary Tree.
    Date November 2007
    Journal World Journal of Gastroenterology : Wjg
    Excerpt

    CT scan is regarded as the imaging modality of choice in patients with pancreaticobiliary ductal abnormalities. However, the axial orientation of the CT images provides only limited anatomical view of pancreaticobiliary ductal abnormalities. The technological advances of multi-detector row CT and three-dimensional image processing in workstations allows rapid image acquisition and a short postprocessing time. In particular, multiplanar reformations (MPR) and minimum intensity projections (MinIP) offer rapid and accurate images of the anatomy and abnormalities of the pancreaticobiliary tree. Moreover, MPR and MinIP help determine the relationship between the pancreaticobiliary ductal anatomy and the surrounding structures. This pictorial review illustrates the wide spectrum of images obtained by the MPR and MinIP of the anomalies and disorders of the pancreaticobiliary tree.

    Title White Matter Abnormalities in Drug-naïve Patients with Obsessive-compulsive Disorder: a Diffusion Tensor Study Before and After Citalopram Treatment.
    Date October 2007
    Journal Acta Psychiatrica Scandinavica
    Excerpt

    OBJECTIVE: The aim was to investigate the white matter abnormalities of drug-naïve patients with obsessive-compulsive disorder (OCD) using diffusion tensor-imaging and the white matter changes in the patients after pharmacotherapy. METHOD: Thirteen drug-naïve OCD patients and 13 age- and sex-matched healthy comparison subjects were examined using diffusion tensor-imaging and structural magnetic resonance imaging. Measurements were made in OCD patients before and after 12 weeks of citalopram treatment. RESULTS: Compared with controls, the drug-naïve OCD patients showed significant increases in fractional anisotropy (FA) in the corpus callosum, the internal capsule and white matter in the area superolateral to the right caudate. The increases in FA were mostly no longer observed in patients after 12 weeks of treatment compared with controls. CONCLUSION: Our findings suggest that white matter alterations are associated with the pathophysiology of OCD, and the abnormalities may be partly reversible with pharmacotherapy.

    Title Shape Deformity of the Corpus Striatum in Obsessive-compulsive Disorder.
    Date October 2007
    Journal Psychiatry Research
    Excerpt

    Volumetric changes of striatal structures based on magnetic resonance imaging (MRI) have been inconsistent in patients with obsessive-compulsive disorder (OCD) due to methodological limitations. The purpose of this study was to investigate shape deformities of the corpus striatum in patients with OCD. We performed 3-D shape deformation analysis of the caudate nucleus, the putamen, and the globus pallidus in 36 patients with OCD and 36 healthy normal subjects. Shape analysis showed deformity of the striatal structures, especially the caudate nucleus. Outward deformities in the superior, anterior portion of the bilateral caudate were observed in patients with OCD. In addition, an outward deformity in the inferior, lateral portion of the left putamen was also detected. These results suggest that patients with OCD have shape deformities of the corpus striatum, especially the caudate nucleus, compared with healthy normal subjects, and that shape analysis may provide an important complement to volumetric MRI studies in investigating the pathophysiology of OCD.

    Title Vr-based Conversation Training Program for Patients with Schizophrenia: a Preliminary Clinical Trial.
    Date October 2007
    Journal Cyberpsychology & Behavior : the Impact of the Internet, Multimedia and Virtual Reality on Behavior and Society
    Excerpt

    Schizophrenia is a devastating mental illness and is characterized by hallucinations and delusions as well as social skills deficits. Generally, social skills training designed to help patients develop social skills includes role-playing, but this form of training has typical shortcomings, which are largely due to a trainer's difficulties to project emotion. Virtual reality (VR)-based techniques have the potential to solve these difficulties, because they provide a computer-generated but realistic three-dimensional world and humanlike avatars that can provide emotional stimuli. In this paper, we report on a method of implementing virtual environments (VEs) in order to train people with schizophrenia to develop conversational skills in specific situations, which could overcome the shortcomings of or complement conventional role-playing techniques. The paper reports the efficacy of the proposed approach in a preliminary clinical trial with 10 patients with schizophrenia.

    Title Prevention of Postoperative Subdural Fluid Collections Following Transcortical Transventricular Approach.
    Date October 2007
    Journal Surgical Neurology
    Excerpt

    BACKGROUND: Subdural fluid collections appear in about 39% of patients after the removal of intra- and paraventricular tumors. This extracerebral fluid collection requires surgical intervention when progressive fluid accumulation takes place. The authors retrospectively and prospectively studied the efficacy of gelfoam and fibrin adhesive in closing cortical and ependymal defects after intraventricular and/or paraventricular lesion resection to prevent the development of SFCs. METHODS: From 1999 to 2004, we used gelfoam and fibrin adhesive on the cortical and ependymal defects of 28 patients who underwent the resection of intraventricular and/or paraventricular lesions via the transcortical approach associated with the communicated ventricle. We investigated the percentage of symptomatic and asymptomatic SFC. RESULTS: The patients median age was 59.5 years (range, 30-76 years), and the male/female ratio was 16:12. A frontal approach was performed in 18 patients, an occipital approach in 2, a parietal approach in 4, and a temporal approach in 4. The incidence of SFCs was 7% (2 patients). Of the 2 patients with SFCs, 1 required temporary drainage. The other patient was asymptomatic, and the SFCs were spontaneously absorbed 2 months later. CONCLUSIONS: The use of gelfoam and fibrin adhesive to seal cortical and ependymal defects after a transcortical procedure might be a viable method of preventing the development of SFC.

    Title Expression of Bone Morphogenetic Proteins, the Subfamily of the Transforming Growth Factor-beta Superfamily, in Renal Cell Carcinoma.
    Date October 2007
    Journal The Journal of Urology
    Excerpt

    PURPOSE: We investigated the potential expression of bone morphogenetic proteins, including bone morphogenetic protein-4, 6 and 7, the largest subfamily of the transforming growth factor-beta superfamily, in patients with renal cell carcinoma and identified its potential prognostic value in terms of clinical outcome. MATERIALS AND METHODS: Immunohistochemical staining of paraffin sections for bone morphogenetic protein was performed in 185 cases of renal cell carcinoma using a streptavidin-peroxidase procedure. Relationships between bone morphogenetic protein expression, and clinicopathological characteristics and clinical outcome were analyzed. RESULTS: The positive rate of bone morphogenetic protein-4, 6 and 7 expression in renal cell carcinoma was 44.3%, 20.0% and 34.1%, respectively. No statistically significant association was observed between bone morphogenetic protein immunoreactivity and age, Eastern Cooperative Oncology Group performance status and T stage. However, bone morphogenetic protein-4 expression correlated with Fuhrman grade (p = 0.034). The bone morphogenetic protein-7 expression rate was higher in female than in male patients (p = 0.007). The bone morphogenetic protein expression rate in nonclear types including chromophobe or papillary type was higher than that in the clear cell type (each p <0.001). Disease-free survival was higher in patients with bone morphogenetic protein-7 expression than in those without expression (log rank test for trend p = 0.0273). CONCLUSIONS: In the current study, the correlation between the expression of bone morphogenetic proteins and histological subtype was found. In addition, our findings suggest that bone morphogenetic protein-7 expression may be considered a new prognostic factor in renal cell carcinoma.

    Title Evaluation of Semi-interpenetrating Polymer Networks Composed of Chitosan and Poloxamer for Wound Dressing Application.
    Date September 2007
    Journal International Journal of Pharmaceutics
    Excerpt

    We have elsewhere reported the work on the preparation of semi-interpenetrating polymer networks (SIPNs) composed of chitosan (CS) and poloxamer to improve the mechanical strength of CS sponge. This study focuses on evaluation of the CS/poloxamer SIPNs to intend for wound dressing application and the efficacy of dehydroepiandrosterone (DHEA)-loaded CS/poloxamer SIPNs in the wound model studies. The properties required for ideal wound dressing, such as equilibrium water content (EWC), water absorption (A(w)), water vapor transmission rate (WVTR), and evaporative water loss, were examined. The CS/poloxamer SIPNs were found to have a water content of 90% of their weight which could prevent the wound bed from accumulation of exudates and also have excellent water adsorption. The WVTR of CS/poloxamer SIPNs was found to be 2,508.2+/-65.7gm(-2)day(-1), indicating that the SIPNs can maintain a moist environment over wound bed in moderate to heavily exuding wound which enhances epithelial cell migration during the healing process. Also, the CS/poloxamer SIPNs in vitro assessment showed proper biodegradation and low cytotoxicity for wound dressing application. The wound healing efficacy of CS/poloxamer SIPNs as a wound dressing was evaluated on experimental full thickness wounds in a mouse model. It was found that the wounds covered with CS/poloxamer SIPNs or DHEA-loaded CS/poloxamer SIPNs were completely filled with new epithelium without any significant adverse reactions after 3 weeks. The results thus indicate that CS/poloxamer SIPNs could be employed in the future as potential wound dressing materials.

    Title Effects of Commonly Used Hemostatic Agents on the Porcine Collecting System.
    Date September 2007
    Journal Journal of Endourology / Endourological Society
    Excerpt

    PURPOSE: Topical hemostatic agents have been particularly useful for preventing bleeding in tubeless percutaneous nephrolithotomy. In the present study, we investigated the effect of gelatin matrix hemostatic sealant (FloSeal), fibrin glue (Tisseel,), polyethylene glycol polymers (CoSeal), and bovine serum albumin/ glutaraldehyde (BioGlue) in the pig urinary collecting system after injection through a percutaneous nephrostomy (PCN) tract. MATERIALS AND METHODS: Percutaneous nephrostomy was performed in 40 kidneys in 24 domestic pigs. Animals were divided into four groups of six each: (1) FloSeal; (2) Tisseel; (3) CoSeal; and (4) BioGlue. In 16 animals that tolerated the procedure, the contralateral kidney was used as a control for PCN only. All tracts were dilated to 30F with the Amplatz dilator, and 2 mL of the hemostatic agent was injected into the collecting system before pulling back to seal the puncture. RESULTS: Among the control PCN kidneys, no obstruction was detected at the end of a 5-day period. However, three of six kidneys injected with FloSeal, Tisseel, or CoSeal and four of six kidneys injected with BioGlue were obstructed. In each of these cases, there was an associated retroperitoneal urinoma. CONCLUSION: FloSeal, Tisseel, CoSeal, and BioGlue, if injected directly into the porcine collecting system, can result in significant obstruction that does not resolve over a 5-day period. Until there are clinical data to the contrary, we believe that when using one of these hemostatic agents in association with a tubeless percutaneous procedure, a retrograde occlusion balloon catheter should be considered to prevent inadvertent injection of these materials into the collecting system.

    Title Repeated 28-day Oral Toxicity Study of Ketoconazole in Rats Based on the Draft Protocol for the "enhanced Oecd Test Guideline No. 407" to Detect Endocrine Effects.
    Date August 2007
    Journal Archives of Toxicology
    Excerpt

    We performed a 28-day repeated-dose toxicity study of ketoconazole, a widely used an antimycotic drug, based on the draft protocol of the "Enhanced OECD Test Guideline 407" (Enhanced TG407) to investigate whether ketoconazole has endocrine-mediated properties according to this assay. Seven-week-old SD rats were administered with ketoconazole daily by oral gavage at doses of 0, 6.25, 25 or 100 mg kg(-1) day(-1) for at least 28 days. The ketoconazole-treated male rats showed reduction of epididymis and accessory sex organ weights, spermatid retention in the seminiferous tubules, decrease of testosterone and increases of estradiol, luteinizing hormone (LH) and follicular stimulating hormone (FSH). A prolongation of the estrous cycle and increases of estradiol, LH and FSH were observed in the treated female rats. Thyroxin and triiodothyronine were decreased and thyroid-stimulating hormone was increased in both sexes; however, there were no compound-related microscopic lesions in the thyroid gland or changes in the thyroid weight. The endocrine-related effects of ketoconazole could be detected by the parameters examined in the present study based on the Organization for Economic Cooperation and Development (OECD) protocol, suggesting that the Enhanced TG407 protocol should be a suitable screening test for detection of endocrine-mediated effects of chemicals.

    Title Effect of Dominant Negative Transforming Growth Factor-beta Receptor Type Ii on Cytotoxic Activity of Raw 264.7, a Murine Macrophage Cell Line.
    Date August 2007
    Journal Cancer Research
    Excerpt

    Transforming growth factor-beta (TGF-beta) is a potent suppressor of the immune system. In the present study, we investigated the effect of TGF-beta resistance on a murine macrophage cell line, RAW 264.7, by overexpressing a dominant negative TGF-beta receptor type II (TbetaRIIDN) construct. As expected, TbetaRIIDN-expressing RAW cells, designated as RAW-TbetaRIIDN, were resistant to TGF-beta signaling. When these cells were cocultured with the murine renal cell carcinoma cell line, Renca, a dramatic increase in apoptosis of Renca cells was observed. Simultaneously, elevated levels of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) in association with IFN-gamma were detected in RAW-TbetaRIIDN cells. When the effects of TNF-alpha and iNOS were neutralized through the use of neutralizing antibody and N(G)-methyl-L-arginine, respectively, the enhanced cytotoxicity of TbetaRIIDN-RAW cells was partially reversed. Taken together, these results show that TGF-beta-resistant RAW 264.7 murine macrophage cells have increased cytotoxic activity that is in part mediated by iNOS and TNF-alpha.

    Title Vacuolating Cytotoxin in Helicobacter Pylori Water-soluble Proteins Upregulates Chemokine Expression in Human Eosinophils Via Ca2+ Influx, Mitochondrial Reactive Oxygen Intermediates, and Nf-kappab Activation.
    Date August 2007
    Journal Infection and Immunity
    Excerpt

    Helicobacter pylori-infected gastric mucosa is characterized by infiltration of inflammatory cells such as neutrophils and eosinophils. However, little information is available on the relationship between H. pylori virulence factors and chemokine expression in eosinophils. This study investigates the role of vacuolating cytotoxin (VacA) in chemokine expression from human eosinophils. Eosinophils were isolated from the peripheral blood of healthy volunteers using a magnetic cell separation system. VacA(+) H. pylori water-soluble proteins (WSP) induced higher expression of interleukin-8, growth-related oncogene alpha, monocyte chemotactic protein 1, and RANTES (regulated on activation, normal, T-cell expressed and secreted) than Vac(-) WSP in human eosinophils, as assessed by quantitative reverse transcription-PCR and enzyme-linked immunosorbent assay. Purified VacA not only increased chemokine expression but also activated p65/p50 NF-kappaB heterodimers and phosphorylated IkappaB kinase (IKK) alpha/beta signals in human eosinophils. Inhibition of NF-kappaB and IKK significantly decreased the chemokine expression in VacA-stimulated eosinophils. Furthermore, VacA-induced NF-kappaB activation and chemokine release from eosinophils were dependent on Ca(2+) influx and mitochondrial generation of reactive oxygen intermediates (ROI). These results suggest that NF-kappaB and IKK signals via Ca(2+) influx and mitochondrial ROI play a role in the up-regulation of chemokine expression in eosinophils stimulated with H. pylori VacA.

    Title Cytoplasmic Localization and Ubiquitination of P21(cip1) by Reactive Oxygen Species.
    Date July 2007
    Journal Biochemical and Biophysical Research Communications
    Excerpt

    Reactive oxygen species were previously shown to trigger p21(Cip1) protein degradation through a proteasome-dependent pathway, however the detailed mechanism of degradation remains to be elucidated. In this report, we showed that p21(Cip1) was degraded at an early phase after low dose H(2)O(2) treatment of a variety of cell types and that preincubation of cells with the antioxidant, N-acetylcysteine, prolonged p21(Cip1) half-life. A mutant p21(Cip1) in which all six lysines were changed to arginines was protected against H(2)O(2) treatment. Direct interaction between p21(Cip1) and Skp2 was elevated in the H(2)O(2)-treated cells. Disruption of the two nuclear export signal (NES) sequences in p21(Cip1), or treatment with leptomycin B blocked H(2)O(2)-induced p21(Cip1) degradation. Altogether, these results demonstrate that reactive oxygen species induce p21(Cip1) degradation through an NES-, Skp2-, and ubiquitin-dependent pathway.

    Title Effect of Di(n-butyl) Phthalate on Testicular Oxidative Damage and Antioxidant Enzymes in Hyperthyroid Rats.
    Date July 2007
    Journal Environmental Toxicology
    Excerpt

    This study compared the effects of di(n-butyl) phthalate (DBP) on the oxidative damage and antioxidant enzymes activity in testes of hyperthyroid rats. Hyperthyroidism was induced in pubertal male rats by intraperitoneal injection of triiodothyronine (T3, 10 microg/kg body weight) for 30 days. An oral dose of DBP (750 mg/kg) was administered simultaneously to normal or hyperthyroid (T3) rats over a 30-day period. No changes in body weight were observed in the hyperthyroid groups (T3, T3 + DBP) compared with controls. There were significantly higher serum T3 levels observed in the hyperthyroid rats than in the control, but the serum thyroid stimulating hormone levels were markedly lower in the hyperthyroid rats. DBP significantly decreased the weight of the testes in the normal (DBP) and hyperthyroid (T3 + DBP) groups. The serum testosterone concentrations were significantly lower in only DBP group. DBP significantly increased the 8-hydroxy-2-deoxyguanosine (8-OHdG) level in the testes, whereas the DBP-induced 8-OHdG levels were slightly higher in T3 + DBP group. Superoxide dismutase and glutathione peroxidase activities were significantly higher in the testes of the DBP or T3 + DBP groups. Catalase (CAT) activity was significantly higher in the DBP treatment group, but the T3 + DBP group showed slightly lower DBP-induced CAT activity. The testicular expression of thyroid hormone receptor alpha-1 (TRalpha-1) was significantly higher in the DBP groups, and androgen receptor (AR) expression was not detected in the DBP treatment group. In addition, DBP significantly increased the peroxisome proliferator-activated receptor-r (PPAR-r) levels in the testis. These results suggest that hyperthyroidism can cause a change in the expression level of PPAR-r in testes, and may increase the levels of oxidative damage induced by the metabolic activation of DBP.

    Title Regulation of Adipocyte Differentiation by Pegylated All-trans Retinoic Acid: Reduced Cytotoxicity and Attenuated Lipid Accumulation.
    Date July 2007
    Journal The Journal of Nutritional Biochemistry
    Excerpt

    Obesity is major risk factor for many disorders, including diabetes, hypertension and heart disease. Unfortunately, there is a dearth of therapeutic agents available to clinicians for the treatment of obesity. The principal aim of this study was to investigate whether PEGylated all-trans retinoic acid (PRA) can have favorable stability and biological activity in 3T3-L1 preadipocytes as an antiobesity drug. Here, we found that PRA inhibits the process of adipogenesis, including survival of adipocytes and differentiation to mature adipocytes. The results showed that RA nanoparticles (NPs) were prepared by PEGylation; below 200 nm, PRA-NPs were obtained. Moreover, PRA decreased glycerol-3-phosphate dehydrogenase activity in 3T3-L1 preadipocytes by acting with major adipocyte marker proteins such as PPARgamma2, C/EBPalpha and aP2 modulators. Apoptosis, in addition, increased as the level of RA increased from 10 to 20 microM, whereas PRA reduced apoptosis with increasing concentrations. Our data suggest that PRA-NP has potential as an antiobesity drug carrier due to its small particle size and PEGylated core-shell structure. In addition, our results suggest that PRA inhibits the process of adipogenesis and may be developed to treat obesity. Based on these results, PRA is suitable for adipocyte studies, and an enhanced effect of PRA with adipocyte differentiation offers a challenging approach for pharmaceutical applications.

    Title Solitary Intracranial Subdural Osteoma: Intraoperative Findings and Primary Anastomosis of an Involved Cortical Vein.
    Date July 2007
    Journal Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia
    Excerpt

    We report a patient with a intracranial subdural osteoma with a large cortical vein passing through the subdural calcified mass. A 60-year-old man presented with an approximately 3-year history of persistent headache. Computerized tomography (CT) scanning showed a homogeneous high-density nodule attached to the inner surface of the right frontal skull. Intraoperatively, the hard mass was found to be located in the intradural subarachnoid space. A large cortical vein passed through the subdural mass and was anastomosed in an end-to-end fashion after the excision of the segment involved by the tumor. The histopathologic examination showed lamellated bony trabeculae lined by osteoblasts and the underlying dura was uninvolved by the tumor cells.

    Title Characteristics of Social Perception Assessed in Schizophrenia Using Virtual Reality.
    Date July 2007
    Journal Cyberpsychology & Behavior : the Impact of the Internet, Multimedia and Virtual Reality on Behavior and Society
    Excerpt

    Impairment in social skills is one of the few criteria that all individuals diagnosed with schizophrenia must meet. Successful social skills require the coordination of many abilities, including social perception, which involves the decoding and interpretation of social cues from others. In this study, we examined the potential for virtual reality (VR) in social skill training. We attempted to determine if VR can be used to measure social skills and social perception, and to determine which VR parameters are related to schizophrenic symptoms. Some of these results have clear clinical relevance, while other observations need further study. The VR system appears to be useful in assessing the social perception of schizophrenics and normal people, and could be more widely used in the future for social training and in the assessment of social problem-solving abilities, assertiveness skills, and general social skills.

    Title Cystic Vestibular Schwannomas: a Possible Role of Matrix Metalloproteinase-2 in Cyst Development and Unfavorable Surgical Outcome.
    Date June 2007
    Journal Journal of Neurosurgery
    Excerpt

    OBJECT: The authors evaluated the clinical manifestations and surgical results in patients with cystic vestibular schwannoma (VS), and investigated the matrix metalloproteinase (MMP) expression of the cyst fluid and wall in an attempt to elucidate the pathogenesis and characteristics of this disease. METHODS: The clinical and neuroimaging features, perioperative findings, and surgical outcomes in 24 cases of cystic VS and 82 cases of solid VS, all of which were treated using the suboccipital approach, were retrospectively compared. To evaluate the role of MMP in cystic VS, gelatin zymography and immunohistochemical studies of the cyst fluid, wall, and solid portion were performed in nine cases of this disease. The mean duration of symptoms was shorter (14.0 months compared with 26.1 months; p = 0.04) and the mean size of the tumor was larger (43.8 mm compared with 34.2 mm; p = 0.048) in the cystic than the solid VS group. Although gross-total resection was easier to accomplish in this group (100% compared with 84.1%), adhesion to the facial nerve was more frequent (62.5% compared with 48.8%; p = 0.042). On gelatin zymography studies, MMP-2 expression was ubiquitously observed in all cyst fluids. Immunohistochemical analysis of the cyst wall showed that MMP-2 was apparently localized to the tumor cells on the luminal inner surface, adjacent to the cyst cavity. CONCLUSIONS: Resection of cystic VS is complicated by severe adhesion of the tumor capsule to the facial nerve and the large size of the lesion. The authors believe that MMP-2 may be involved in the pathogenesis of cyst formation or in its enlargement and may aggravate adhesion to the facial nerve, either by promoting the enlargement of the tumor or engendering the degradation of the tumor-nerve barrier proteolytically.

    Title A Giant Intradiploic Epidermoid Cyst with Perforation of the Dura and Brain Parenchymal Involvement.
    Date June 2007
    Journal Clinical Neurology and Neurosurgery
    Excerpt

    A patient with a long-standing intradiploic epidermoid cyst with perforation of the dura and brain parenchymal involvement is reported. A 69-year-old man, who had previously presented with a subcutaneous mass on the left frontoparietal scalp, developed a sudden grand mal seizure. Magnetic resonance imaging showed a well-defined mass in the frontoparietal scalp with destruction of the skull. Penetration of the dura allowed for communication with the intracranial structures. Surgical resection and cranioplasty were performed. There were no well-defined margins in the deep portion and the mass was subtotally removed. Histological examination showed that the cystic structure was lined by squamous epithelium containing laminated keratin material. The pathologic findings were consistent with the diagnosis of an epidermoid cyst.

    Title Screening for Motility-associated Genes in Malignant Astrocytoma Cell Lines.
    Date May 2007
    Journal Journal of Neuro-oncology
    Excerpt

    The most characteristic feature of a malignant astrocytoma is its early and extensive infiltration into adjacent parenchymal structures. We focused on detecting the possible expression changes as the determining factors for malignant astrocytoma's motile ability. We confirmed that four of 39 genes showed different expression on DD-PCR by RT-PCR and Northern blot analysis. These findings suggest that the genes identified may be important for determining high motility in astrocytoma cell lines. These findings may help us understand the molecular invasion mechanism in astrocytomas.

    Title Pattern Classification Using Principal Components of Cortical Thickness and Its Discriminative Pattern in Schizophrenia.
    Date May 2007
    Journal Neuroimage
    Excerpt

    We proposed pattern classification based on principal components of cortical thickness between schizophrenic patients and healthy controls, which was trained using a leave-one-out cross-validation. The cortical thickness was measured by calculating the Euclidean distance between linked vertices on the inner and outer cortical surfaces. Principal component analysis was applied to each lobe for practical computational issues and stability of principal components. And, discriminative patterns derived at every vertex in the original feature space with respect to support vector machine were analyzed with definitive findings of brain abnormalities in schizophrenia for establishing practical confidence. It was simulated with 50 randomly selected validation set for the generalization and the average accuracy of classification was reported. This study showed that some principal components might be more useful than others for classification, but not necessarily matching the ordering of the variance amounts they explained. In particular, 40-70 principal components rearranged by a simple two-sample t-test which ranked the effectiveness of features were used for the best mean accuracy of simulated classification (frontal: (left(%)|right(%))=91.07|88.80, parietal: 91.40|91.53, temporal: 93.60|91.47, occipital: 88.80|91.60). And, discriminative power appeared more spatially diffused bilaterally in the several regions, especially precentral, postcentral, superior frontal and temporal, cingulate and parahippocampal gyri. Since our results of discriminative patterns derived from classifier were consistent with a previous morphological analysis of schizophrenia, it can be said that the cortical thickness is a reliable feature for pattern classification and the potential benefits of such diagnostic tools are enhanced by our finding.

    Title New Idea of Hearing Aid Algorithm to Enhance Speech Discrimination in a Noisy Environment and Its Experimental Results.
    Date May 2007
    Journal Conference Proceedings : ... Annual International Conference of the Ieee Engineering in Medicine and Biology Society. Ieee Engineering in Medicine and Biology Society. Conference
    Excerpt

    A hearing aid can help the hearing impaired to listen to speech by amplifying its sound. However, amplification cannot always improve speech perception. To improve speech perception in a noisy environment, we proposed a new hearing aid algorithm that combines independent component analysis (ICA) with multiband loudness compensation. The proposed method was applied to a behind-the-ear type (BTE) dual microphone hearing aid. The proposed method successfully separated a target speech signal from background noise such as babble, car noise, factory noise. This method may help hearing aid users to hear the speech that he or she wishes to hear clearly in noisy conditions.

    Title Virtual Environment Training System for Rehabilitation of Stroke Patients with Unilateral Neglect: Crossing the Virtual Street.
    Date April 2007
    Journal Cyberpsychology & Behavior : the Impact of the Internet, Multimedia and Virtual Reality on Behavior and Society
    Excerpt

    In this paper, we propose a system for training of stroke patients with unilateral neglect by using technology of virtual reality (VR). The proposed system is designed to compensate for unilateral neglect. This system contains the calibration of unilateral neglect and the training of this disease. The calibration procedure is implemented by aligning the virtual object at a subjective middle line. The training procedure is implemented by completing the missions that are used to keep the virtual avatar safe during crossing the street in a virtual environment. The results of this study show that the proposed system is effective to train unilateral neglect. The left to right ratio scores extracted from this system gradually decrease as the sessions of training are repeated. To validate the VR system parameters, the parameters are analyzed by correlation with those of traditional unilateral neglect assessment methods (such as the line bisection test and the cancellation test).

    Title A Novel Quantitative Validation of the Cortical Surface Reconstruction Algorithm Using Mri Phantom: Issues on Local Geometric Accuracy and Cortical Thickness.
    Date April 2007
    Journal Medical Image Computing and Computer-assisted Intervention : Miccai ... International Conference on Medical Image Computing and Computer-assisted Intervention
    Excerpt

    Cortical surface reconstruction is important for functional brain mapping and morphometric analysis of the brain cortex. Several methods have been developed for the faithful reconstruction of surface models which describe the true cortical surface in both geometry and topology. However there has been no explicit method for the quantitative evaluation of the whole-cortical-surface models. In this study, we present a novel phantom-based evaluation method of the cortical surface reconstruction algorithm and quantitatively validated the local morphometric accuracy of CLASP which is one of the well-established reconstruction methods. The evaluation included local geometrical accuracy and performance of cortical thickness measure. The validation study revealed that there were some underestimations of cortical thickness measure using CLASP in the ventral and sulcal areas of the cortex and overestimations in the gyral areas and inferior temporal lobe. This study could present a generic metric for the quantitative evaluation of cortical surface reconstruction algorithm.

    Title Traumatic Acute Spinal Subarachnoid Hematoma.
    Date March 2007
    Journal Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia
    Excerpt

    This report describes a 66-year-old man who presented with progressive paraparesis after a fall. Magnetic resonance imaging showed an acute spinal hematoma at T11-12 with spinal cord compression. The patient underwent an emergency left T11-12 hemilaminectomy. The hematoma was subarachnoid and the source of bleeding was an injured radicular vein. To the best of our knowledge, this is the first reported case of traumatic spinal subarachnoid hematoma. We discuss the possible mechanism and our case illustrates an injured radicular vein can be a source of traumatic spinal subarachnoid hematoma.

    Title Intracisternal Schwannoma of the Spinal Accessory Nerve: a Case Report.
    Date March 2007
    Journal Skull Base : Official Journal of North American Skull Base Society ... [et Al.]
    Excerpt

    We report the details of a patient with an intracisternal schwannoma that developed from the spinal accessory nerve. The patient, a 70-year-old women, presented with a 5-year history of intermittent headache and neck pain. A 3.2 x 2.5 cm partially cystic mass was found in the right cervicomedullary cistern. It was removed through a far-lateral inferior suboccipital craniotomy using image-guidance. The tumor arose from one rootlet of the right accessory nerve and histological examination confirmed the diagnosis of a schwannoma. Removal of the schwannoma did not result in a significant neurological deficit.

    Title How Does Distortion Correction Correlate with Anisotropic Indices? A Diffusion Tensor Imaging Study.
    Date March 2007
    Journal Magnetic Resonance Imaging
    Excerpt

    PURPOSE: The purpose of this study was to determine a suitable registration algorithm for diffusion tensor imaging (DTI) using conventional preprocessing tools [statistical parametric mapping (SPM) and automated image registration (AIR)] and to investigate how anisotropic indices for clinical assessments are affected by these distortion corrections. MATERIALS AND METHODS: Brain DTI data from 15 normal healthy volunteers were used to evaluate four spatial registration schemes within subjects to correct image distortions: noncorrection, SPM-based affine registration, AIR-based affine registration and AIR-based nonlinear polynomial warping. The performance of each distortion correction was assessed using: (a) quantitative parameters: tensor-fitting error (Ef), mean dispersion index (MDI), mean fractional anisotropy (MFA) and mean variance (MV) within 11 regions of interest (ROI) defined from homogeneous fiber bundles; and (b) fiber tractography through the uncinate fasciculus and the corpus callosum. Fractional anisotropy (FA) and mean diffusivity (MD) were calculated to demonstrate the effects of distortion correction. Repeated-measures analysis of variance was used to investigate differences among the four registration paradigms. RESULTS: AIR-based nonlinear registration showed the best performance for reducing image distortions with respect to smaller Ef (P<.02), MDI (P<.01) and MV (P<.01) with larger MFA (P<.01). FA was decreased to correct distortions (P<.0001) whether the applied registration was linear or nonlinear and was lowest after nonlinear correction (P<.001). No significant differences were found in MD. CONCLUSION: In conventional DTI processing, anisotropic indices of FA can be misestimated by noncorrection or inappropriate distortion correction, which leads to an erroneous increase in FA. AIR-based nonlinear distortion correction would be required for a more accurate measurement of this diffusion parameter.

    Title Mechanics of the Passive Knee Joint. Part 1: The Role of the Tibial Articular Surfaces in Guiding the Passive Motion.
    Date February 2007
    Journal Proceedings of the Institution of Mechanical Engineers. Part H, Journal of Engineering in Medicine
    Excerpt

    The motion of the unloaded knee is associated with tibial internal rotation and femoral posterior translation. Although it is known that the passive motion is the result of the interaction between the articular surfaces and the ligaments, the mechanism through which the particular pattern of motion is guided is not completely understood. The goal of this study was to focus on the tibial geometry and to identify the roles that its geometric features have in guiding the passive knee motion. The method used in this study simplified the geometry of the tibial plateaux and the menisci into basic features that could be eliminated individually. The generated tibial geometry was implemented in a computer model to simulate the passive motion. Different parts of the geometry were eliminated individually and the comparison between the simulation results was used to identify the role that each part of the geometry had in guiding the passive motion. The medial meniscus was found as the feature that promoted the tibial internal rotation and restrained the femoral posterior translation. The lateral meniscus and the medial aspect of the tibial eminence, on the other hand, were found as the elements that confined the tibial internal rotation.

    Title Spatial Accuracy of Fmri Activation Influenced by Volume- and Surface-based Spatial Smoothing Techniques.
    Date February 2007
    Journal Neuroimage
    Excerpt

    As improvements in cortical surface modeling allowed accurate cortical topology in brain imaging studies, surface-based methods for the analysis of functional magnetic resonance imaging (fMRI) were introduced to overcome the topological deficiency of commonly used volume-based methods. The difference between the two methods is mainly due to the smoothing techniques applied. For practical applications, the surface-based methods need to quantitatively validate the accuracy of localizing activation. In this study, we evaluated the spatial accuracy of activation detected by the volume- and surface-based methods using simulated blood oxygenation level-dependent (BOLD) signals and MRI phantoms focusing on the influence of their smoothing techniques. T1- and T2-weighted phantoms were acquired from BrainWeb () and used to extract cortical surfaces and to generate echo planar imaging (EPI) data. Simulated BOLD signals as the gold standard of activation in our experiment were applied to the surfaces and projected to the volume space with random noise. Three-dimensional isotropic Gaussian kernel smoothing and two-dimensional heat kernel smoothing were applied to the volume- and surface-based methods. Sensitivity and 1-specificity, which are truly and falsely detected activations, and similarity measures, which are spatially and statistically similar for the gold standard and detected activations, were calculated. In the results, the surface-based method showed the sensitivity and similarity scores of about 12% higher than the volume-based method. In conclusion, the surface-based method guarantees better spatial accuracy for the localization of BOLD signal sources within the cortex than the volume-based method.

    Title Pilot Study for Assessing the Behaviors of Patients with Schizophrenia Towards a Virtual Avatar.
    Date February 2007
    Journal Cyberpsychology & Behavior : the Impact of the Internet, Multimedia and Virtual Reality on Behavior and Society
    Excerpt

    This study examined whether a virtual avatar could be perceived as a real human by patients with mental disease, especially schizophrenia, as well as whether a virtual avatar could be applied to acquiring patients' behavior characteristics in a short conversation situation. The virtual avatar has been used for various applications which need to communicate with other person or to train or educate by showing humanlike behavior. Recently, many researches have shown that the virtual avatar technology has been enhanced and the avatar could be perceived like real human. A virtual avatar, standing in a virtual room, was designed for this study. Tasks to approach, initiate a talk, and answer to avatar's questions was assigned to the 11 patients with schizophrenia. As behavioral parameters in the virtual environment, the interpersonal distance and the verbal response time were acquired. In addition, the Positive and Negative Syndrome Scale (PANSS) for patients was administered in order to investigate the relationship between patients' symptomatic characteristics and behavior parameters. The interpersonal distance was negatively correlated with the negative syndrome scale, a subscale of PANSS, which is consistent with previous research reporting the relationship between interpersonal distance and a real person's image. The verbal response time, however, was not correlated with any other subscale of PANSS. After analyzing subitems of the negative syndrome of PANSS, two positive correlations were found: one was with blunted affect and the other was with poor rapport. We concluded that the virtual avatar could be perceived as a real human by schizophrenic patients and the avatar could draw the schizophrenic patients' behavior characteristics.

    Title Down-regulation of Ppargamma2-induced Adipogenesis by Pegylated Conjugated Linoleic Acid As the Pro-drug: Attenuation of Lipid Accumulation and Reduction of Apoptosis.
    Date February 2007
    Journal Archives of Biochemistry and Biophysics
    Excerpt

    This study is designed to evaluate whether the PEGylated conjugated linoleic acid (PCLA) as the pro-drug can have favorable stability, bioavailability, and anti-adipogenic activity in 3T3-L1 cells for anti-obesity when compared with conjugated linoleic acid (CLA) itself. The CLA was simply coupled to poly(ethylene glycol) (PEG) at the melting state without solvents or catalysts through ester linkages between the carboxylic group of CLA and the hydroxyl group of PEG. To confirm of PCLA as the pro-drug, CLA release from PCLA was investigated by using high-performance liquid chromatographic (HPLC), showing that CLA release from PCLA was almost 90% in a nearly continuous fashion over the next 75h. Apoptosis was promoted by both CLA- and PCLA-treatments with increasing concentrations. However, the level of cell apoptosis induced by PCLA was lower than that induced by CLA owing to the biocompatible and hydrophilic properties of PEG. Moreover, the PCLA decreased glycerol-3-phosphate dehydrogenase (GPDH) activity in 3T3-L1 cells by acting upon major adipocyte marker proteins such as PPARgamma2, C/EBPalpha, and aP2 modulators. Furthermore, either CLA or PCLA stimulated basal, but not isoproterenol-sensitive, lipolysis in our cell model, suggesting that both CLA and PCLA may stimulate lipolysis via hormone sensitive lipase (HSL)-independent mechanisms. These results suggest that the PCLA may prove to be a stable pro-drug to control the deposition of fat in the human body, and that the anti-adipogenic effect of the PCLA on 3T3-L1 cells will offer a challenging approach for anti-obesity.

    Title Fractal Dimension in Human Cortical Surface: Multiple Regression Analysis with Cortical Thickness, Sulcal Depth, and Folding Area.
    Date January 2007
    Journal Human Brain Mapping
    Excerpt

    Fractal dimension (FD) has been widely used to provide a quantitative description of structural complexity in the cerebral cortex. FD is an extremely compact measure of shape complexity, condensing all details into a single numeric value. We interpreted the variation of the FD in the cortical surface of normal controls through multiple regression analysis with cortical thickness, sulcal depth, and folding area related to cortical complexity. We used a cortical surface showing a reliable representation of folded gyri and manually parcellated it into frontal, parietal, temporal, and occipital regions for regional analysis. In both hemispheres the mean cortical thickness and folding area showed significant combination effects on cortical complexity and accounted for about 50% of its variance. The folding area was significant in accounting for the FD of the cortical surface, with positive coefficients in both hemispheres and several lobe regions, while sulcal depth was significant only in the left temporal region. The results may suggest that human cortex develops a complex structure through the thinning of cortical thickness and by increasing the frequency of folds and the convolution of gyral shape rather than by deepening sulcal regions. Through correlation analysis of FD with IQ and the number of years of education, the results showed that a complex shape of the cortical surface has a significant relationship with intelligence and education. Our findings may indicate the structural characteristics that are revealed in the cerebral cortex when the FD in human brain is increased, and provide important information about brain development.

    Title Application of Neuronavigation System to Brain Tumor Surgery with Clinical Experience of 420 Cases.
    Date January 2007
    Journal Minimally Invasive Neurosurgery : Min
    Excerpt

    A new era of neurosurgery has recently been unveiled with the advent of image-guided surgery. The use of neuronavigation is beginning to have a significant impact on a variety of intracranial procedures. Herein, we report our clinical experience using a neuronavigation system with different surgical applications and techniques for a variety of brain tumors. We used the BrainLab VectorVision neuronavigation system, which is a frameless and image-guided system. We operated on 420 cases having various types of brain tumor with the help of this system. The mean target localizing accuracy and mean volume were 1.15 mm and 30.8 mL (0.2-216.4 mL), respectively. We utilized this system to effectively make bone flaps, to detect critically located, deep-seated, subcortical, skull-base and skull bone tumors, and to operate on intraparenchymal lesions with grossly unclear margins, such as gliomas. We also performed tumor biopsy using the combination of a conventional stereotactic biopsy instrument and an endoscope. The application of the neuronavigation system not only revealed benefits for operative planning, appreciation of anatomy, lesion location and the safety of surgery, but also greatly enhanced surgical confidence.

    Title Polyion Complex Micelles Composed of All-trans Retinoic Acid and Poly (ethylene Glycol)-grafted-chitosan.
    Date January 2007
    Journal Journal of Pharmaceutical Sciences
    Excerpt

    The goal of this study is to develop novel types of polyion complex micelles for the drug delivery to brain tumor. Methoxy poly(ethylene glycol) (mPEG)-grafted chitosan (CP) was synthesized in order to make polymeric micelles encapsulating all-trans retinoic acid (ATRA) based on polyion complex formation. Polyion complex micelles were found to have spherical shapes with sizes of about 50 approximately 200 nm. The loading efficiency of micelle was higher than 80% (w/w) for all formulations. 1H nuclear magnetic resonance (NMR) spectra confirmed the formation of polymeric micelles. The CP graft copolymer and ATRA have distinguishing peaks in their 1H NMR spectra. The specific peaks of ATRA disappeared in D2O or DMSO while it appeared at mixtures of D2O/DMSO, indicating that ATRA and chitosan formed ion complex inner-core. In the cell cytotoxicity study using U87MG cells in vitro, polyion complex micelles showed similar cytotoxicity to that of free ATRA. A migration test was performed to investigate the inhibition of tumor cell invasion in vitro. The results suggested that the polyion complex micelles was more effective at inhibiting tumor cell migration than free ATRA.

    Title Structural Brain Abnormalities in Juvenile Myoclonic Epilepsy Patients: Volumetry and Voxel-based Morphometry.
    Date December 2006
    Journal Korean Journal of Radiology : Official Journal of the Korean Radiological Society
    Excerpt

    OBJECTIVE: We aimed to find structural brain abnormalities in juvenile myoclonic epilepsy (JME) patients. MATERIALS AND METHODS: The volumes of the cerebrum, hippocampus and frontal lobe and the area of the corpus callosum's subdivisions were all semiautomatically measured, and then optimized voxel-based morphometry (VBM) was performed in 19 JME patients and 19 age/gender matched normal controls. RESULTS: The rostrum and rostral body of the corpus callosum and the left hippocampus were significantly smaller than those of the normal controls, whereas the volume of the JME's left frontal lobe was significantly larger than that of the controls. The area of the rostral body had a significant positive correlation with the age of seizure onset (r = 0.56, p = 0.012), and the volume of the right frontal lobe had a significant negative correlation with the duration of disease (r = -0.51, p = 0.025). On the VBM, the gray matter concentration of the prefrontal lobe (bilateral gyri rectus, anterior orbital gyri, left anterior middle frontal gyrus and right anterior superior frontal gyrus) was decreased in the JME group (corrected p < 0.05). CONCLUSION: The JME patients showed complex structural abnormalities in the corpus callosum, frontal lobe and hippocampus, and also a decreased gray matter concentration of the prefrontal region, which all suggests there is an abnormal neural network in the JME brain.

    Title Improved Noise Reduction in Single Fiber Auditory Neural Responses Using Template Subtraction.
    Date December 2006
    Journal Journal of Neuroscience Methods
    Excerpt

    When recording single-unit responses from neural systems, a common problem is the accurate detection of spikes (action potentials) in the presence of competing unwanted (noise) signals. While some sources of noise can be readily dealt with through filtering or established "template subtraction" techniques, other sources present a more difficult problem. In particular, noise components introduced by power supplies, which contain harmonics of the power-line frequency, can be particularly troublesome in that they can mimic the shape of the desired spikes. The aforementioned standard techniques typically fail to effectively deal with such "noise". In this study, we propose the use of a novel template-subtraction scheme that involves estimating the power-line noise waveform and using cross-correlation techniques to subtract it from the recordings. This technique requires two key steps: (1) cross-correlation analysis of each recorded waveform to extract a robust representation of the power-line noise waveform and (2) a second level of cross-correlation to successfully subtract that representation from each recorded waveform. This paper describes this algorithm and provides examples of its implementation using actual recorded waveforms that were contaminated with these power-line noise signals. An improvement (reduction) in the noise level is reported, as are suggestions for future implementation of this strategy.

    Title Bimodal Actions of Reactive Oxygen Species in the Differentiation and Bone-resorbing Functions of Osteoclasts.
    Date December 2006
    Journal Febs Letters
    Excerpt

    In order to demonstrate that cellular redox status undergoes decreased reduction during osteoclast differentiation and further decreased reduction during osteoclastic bone resorption, we analyzed gamma-glutamylcysteinyl synthetase activity, a glutathione synthesis rate-limiting enzyme, and total glutathione and thiol groups. Moderate and severe redox shifts towards a more oxidizing environment induced gradual increases and decreases in osteoclastogenesis. Moreover, while severe glutathione depletion inhibited bone resorption, moderate glutathione repletion enhanced bone resorption. In summary, our observations suggest that there is a threshold for redox status, representing biphasic patterns in osteoclast differentiation and function.

    Title Role of Bone Morphogenetic Proteins in Transitional Cell Carcinoma Cells.
    Date November 2006
    Journal Cancer Letters
    Excerpt

    Bone morphogenetic proteins (BMPs) are pleiotropic growth factors that signal through an interaction with the membrane receptors-type--IA, -IB, and -II (BMP-RIA, -RIB, and -RII, respectively). Although the prototypical members of this group of growth factors were isolated as osteoinductive factors, recently accumulated data have suggested that these factors regulate malignant cells. Herein, we review the data concerning BMPs in transitional cell carcinoma cells.

    Title Comparative Evaluation of the Alkaline Comet Assay with the Micronucleus Test for Genotoxicity Monitoring Using Aquatic Organisms.
    Date October 2006
    Journal Ecotoxicology and Environmental Safety
    Excerpt

    A comparative analysis between the in vivo comet assay and the in vivo micronucleus test (MNT) was carried out in three aquatic organisms suitable for genotoxicity monitoring, carp (Cyprinus carpio), rainbow trout (Oncorhynchus mykiss), and clam (Spisula sachalinensis), using a direct-acting mutagen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and an indirect mutagen, benzo[a]pyrene (B[a]P). By optimizing the conditions for cell isolation, gill and liver (or digestive glands) were selected as test tissues of the comet assay for MNNG and B[a]P. The MNT employed the erythrocytes (or hemocytes), the most universal cell type for the assay. The analysis of DNA strand breaks using the comet assay and the micronucleus frequencies using the MNT revealed dose- and time-dependent increases between animals exposed to several concentrations of mutagens. But the statistical significance (P<0.05) obtained was higher by the comet assay than by the MNT. When the time profiles of genotoxic signals resulting from B[a]P exposure to carp were plotted representatively, clear distinctions between all concentrations were made in the comet assay, but not in the MNT. The correlation index defined in this study also showed a higher correlation between concentration and signal in the comet assay than in the MNT. It is suggested that the standardization of the comet assay is necessary for its methodological evaluation and use as a genotoxicity biomarker. We conclude that the comet assay has an excellent suitability for aquatic genotoxicity monitoring because of its high and reliable sensitivity.

    Title Osteochondroma of the Cervical Spine Extending Multiple Segments with Cord Compression.
    Date October 2006
    Journal Pediatric Neurosurgery
    Excerpt

    Involvement of the cervical spinal cord by a solitary osteochondroma is rare. We describe a case of cervical osteochondroma extending from C5 to C7 in a 16-year-old male. The tumor, arising from the inner aspect of the C6 spinous process, projected longitudinally into the spinal canal and compressed the spinal cord; this caused clinical symptoms associated with myelopathy and radiculopathy. Total excision of the tumor by C5-C7 hemilaminectomy resulted in a good functional recovery.

    Title Dumbbell-shaped Middle Cranial Fossa Meningioma with Interdural Cavernous Sinus Extension: Report of Two Cases with Complete Removal.
    Date October 2006
    Journal Surgical Neurology
    Excerpt

    BACKGROUND: Surgery for meningiomas involving the cavernous sinus remains controversial. Interdural cavernous sinus is called the lateral dural wall in the cavernous sinus, which is composed of two layers, the outer dural layer and the inner membranous layer. We encountered two cases of dumbbell-shaped middle cranial fossa meningioma with interdural cavernous sinus extension, which were successfully removed by surgical means. CASE DESCRIPTION: A 57-year-old woman presented with headache and decreased visual acuity. Neurological assessment was normal. Computed tomography and magnetic resonance imaging showed the presence of a dumbbell-shaped, smooth-contoured, well-enhanced mass in the right mesial temporal area. The lateral wall of the cavernous sinus was exposed via frontotemporal craniotomy and the tumor originating in the lateral wall was totally removed. A 41-year-old man presented with seizure attacks and drowsy mental status. Magnetic resonance imaging showed the presence of a multilobulated, well-enhanced mass in the left parasellar area. The tumor was totally resected via a transsylvian temporopolar approach. The mass originated from tentorial edge and extended into the cavernous sinus by dural penetration. CONCLUSION: Middle cranial fossa meningioma with interdural cavernous sinus extension can be removed more easily than other tumors with intracavernous sinus extension and, consequently, can be safely resected without any resulting cranial nerve deficit.

    Title Increased Water Diffusivity in the Frontal and Temporal Cortices of Schizophrenic Patients.
    Date October 2006
    Journal Neuroimage
    Excerpt

    Schizophrenia has been suggested to be the result of both macroscopic and microscopic abnormalities in the brain. Although no definitive clinico-pathological correlations have been found to reconcile the many facets inherent in this disorder, the recent development of the magnetic resonance diffusion tensor imaging (DTI) has allowed us to gather useful information regarding the microcircuitry of the brain. Specifically, the apparent diffusion coefficient (ADC) reflects the degree of diffusion barriers and heterosynaptic communication for the brain neurotransmitter. Nineteen patients with DSM-IV schizophrenia and 21 age- and sex-matched control subjects participated in DTI, and the severity of the patients' symptoms was evaluated according to the Positive and Negative Syndrome Scale (PANSS). The ADC values were determined and compared between patients and control subjects via voxel-based morphometry. The results show an increased ADC in the bilateral fronto-temporal regions of the schizophrenic patients, as compared with those of the control subjects. In addition, the ADC values in the area of the right insular were correlated with the negative syndromes from the PANSS. Our findings of increased water diffusivity in the fronto-temporal regions of schizophrenic patients and the correlation between negative symptom scales and the ADC in the right insular region indicate that damaged brain microcircuitry might contribute to the pathophysiology of schizophrenia. These findings contribute towards integrating micro and macrostructural abnormalities and syndromes of schizophrenia.

    Title Gender Difference Analysis of Cortical Thickness in Healthy Young Adults with Surface-based Methods.
    Date September 2006
    Journal Neuroimage
    Excerpt

    We have examined gender differences of cortical thickness using a 3-D surface-based method that enables more accurate measurement in deep sulci and localized regional mapping compared to volumetric analyses. Cortical thickness was measured using a direct method for calculating the distance between corresponding vertices from inner and outer cortical surfaces. We normalized cortical surfaces using 2-D surface registration and performed diffusion smoothing to reduce the variability of folding patterns and to increase the power of the statistical analysis. In stereotaxic space, significant localized cortical thickening in women was found extensively in frontal, parietal and occipital lobes, including the superior frontal gyrus (SFG), superior parietal gyrus (SPG), inferior frontal gyrus (IFG) and postcentral gyrus (PoCG) in the left hemisphere and mostly in the parietal lobe, including the SPG in the right hemisphere. In the temporal lobe, small regions of the left and right caudal superior temporal gyrus (STG) and the left temporal pole showed significantly greater cortical thickness in women. The temporal lobe shows relatively less significant thickening than other lobes in both hemispheres. In native space, significantly greater cortical thickness in women was detected in left parietal region, including SPG and PoCG. No significant local increases of cortical thickness were observed in men in both spaces. These findings suggest statistically significant cortical thickening in women in localized anatomical regions, which is consistent with several previous studies and may support a hypothesis of sexual dimorphism.

    Title Shape Deformation of the Insula in Schizophrenia.
    Date September 2006
    Journal Neuroimage
    Excerpt

    Schizophrenia has been conceptualized to be a neurodevelopmental disorder. Neuroimaging evidence was generally findings of volumetric reductions in various brain structures. The shape analysis of the insula can uncover unique structural deformity in the neurodevelopmental disorder, which cannot be revealed from a simple volume measurement. The objective of this study was to demonstrate a subtle change of the insula in schizophrenia using our special shape analysis technique. Subjects were 23 patients with schizophrenia and 23 normal healthy subjects. A landmark-based structural and surface shape analysis of the insula was performed using high-spatial resolution magnetic resonance imaging. A characteristic finding was that the frontotemporal sides of the right insula were deformed in the patients with schizophrenia compared with normal controls. This deformation can be associated with abnormal development of the frontal and temporal lobes in schizophrenia.

    Title Primary Endodermal Sinus Tumor of the Cerebellar Hemisphere: a Case Report with Review of the Literature.
    Date August 2006
    Journal Journal of Neuro-oncology
    Excerpt

    Primary intracranial endodermal sinus tumors, which have been regarded as a rare histologic subtype, usually arise in the pineal and suprasellar regions and are often associated with components of other germ cell tumors. We report an extremely rare case of pure primary endodermal sinus tumor found in the cerebellar hemisphere. A 3-year-old boy was admitted to our institution because of gait disturbance, vomiting and deteriorated mental state. MR imaging revealed the presence of a round mass with heterogeneous enhancement in the left cerebellar hemisphere. Radical surgical removal of the tumor was performed, followed by adjuvant chemotherapy, consisting of etoposide, carboplatin and bleomycin. The patient has since attended regular follow-ups, without any neurological deficit or signs of recurrence in the 4 years since diagnosis.

    Title A Novel Quantitative Cross-validation of Different Cortical Surface Reconstruction Algorithms Using Mri Phantom.
    Date August 2006
    Journal Neuroimage
    Excerpt

    Cortical surface reconstruction is important for functional brain mapping and morphometric analysis of the brain cortex. Several methods have been developed for the faithful reconstruction of surface models which represent the true cortical surface in both geometry and topology. However, there has been no explicit comparison study among those methods because each method has its own procedures, file formats, coordinate systems, and use of the reconstructed surface. There has also been no explicit evaluation method except visual inspection to validate the whole-cortical surface models quantitatively. In this study, we presented a novel phantom-based validation method of the cortical surface reconstruction algorithm and quantitatively cross-validated the three most prominent cortical surface reconstruction algorithms which are used in Freesurfer, BrainVISA, and CLASP, respectively. The validation included geometrical accuracy and mesh characteristics such as Euler number, fractal dimension (FD), total surface area, and local density of points. CLASP showed the best geometric/topologic accuracy and mesh characteristics such as FD and total surface area compared to Freesurfer and BrainVISA. In the validation of local density of points, Freesurfer and BrainVISA showed more even distribution of points on the cortical surface compared to CLASP.

    Title A Proton Mrsi Study of Brain N-acetylaspartate Level After 12 Weeks of Citalopram Treatment in Drug-naive Patients with Obsessive-compulsive Disorder.
    Date August 2006
    Journal The American Journal of Psychiatry
    Excerpt

    OBJECTIVE: Reductions in the level of N-acetylaspartate within subcortical structures of patients with obsessive-compulsive disorder (OCD) have been reported in several studies. However, there have been, as yet, no reports regarding N-acetylaspartate levels in the prefrontal cortex of adult drug-naive OCD patients. The authors used proton magnetic resonance spectroscopic imaging ((1)H-MRSI) to investigate regional N-acetylaspartate level abnormalities and changes after 12 weeks of pharmacotherapy with citalopram in drug-naive OCD patients. METHOD: Thirteen drug-naive OCD patients and 13 age- and sex-matched healthy comparison subjects were included in this study. N-acetylaspartate levels (obtained from ratios of N-acetylaspartate with creatine, choline, and creatine plus choline) in the prefrontal cortex, parietal cortex, anterior cingulate, posterior cingulate, frontal white matter, and parietal white matter were measured by (1)H-MRSI. In OCD patients, measurements were taken before and after 12 weeks of citalopram treatment. Correlations between N-acetylaspartate concentrations in regions of interest and clinical measures were also assessed. RESULTS: Drug-naive OCD patients exhibited significantly lower N-acetylaspartate levels in the prefrontal cortex, frontal white matter, and anterior cingulate at baseline than did comparison subjects. Significant increases in N-acetylaspartate level were detected in the prefrontal cortex and frontal white matter in OCD patients after 12 weeks of citalopram treatment. CONCLUSIONS: These data suggest that reductions in neuronal viability occur in the frontal region of OCD patients and that these reductions may be partly reversible.

    Title Expression of Estrogen Receptors-alpha and -beta in Bladder Cancer Cell Lines and Human Bladder Tumor Tissue.
    Date July 2006
    Journal Cancer
    Excerpt

    BACKGROUND: Estrogen receptors (ERs) are known to mediate important physiologic responses as well as the growth of some tumors in response to estradiol stimulation. In a previous study the selective ER modulator raloxifene was shown to induce apoptosis in an ERbeta-positive bladder cancer cell line. However, the expression of ERbeta in human bladder cancer has not been thoroughly investigated. METHODS: ERalpha and ERbeta expression in 224 bladder tumor samples was evaluated using tissue microarray and immunohistochemistry. Levels of ERalpha and ERbeta protein and mRNA expression were determined in several bladder cancer cell lines using quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis. The effect of estradiol and antiestrogen treatments on RT4 bladder cancer cell growth was determined by cell proliferation assays. RESULTS: Analyses revealed that only 2 human bladder cancers weakly expressed ERalpha. In contrast, the expression of ERbeta was detected in 141 tumors (63%). ERbeta was expressed in 58% of WHO Grade 1 and 2 tumors, whereas 70% of Grade 3 tumors demonstrated expression (P = .085). Importantly, although only 53% and 55% of Ta and T1 tumors demonstrated ERbeta expression, 80% of T2, 81% of T3, and 75% of T4 tumors showed ERbeta expression. The differences in ERbeta expression between Ta/T1 and T2/T3/T4 tumors were found to be highly significant (P < .001). Metastatic transitional cell carcinomas had ERbeta expression (80%) comparable to that of muscle invasive bladder cancers. Western blot analysis detected ERbeta protein expression in each of the 5 bladder cancer cell lines tested, whereas no or very low levels of ERalpha were found. Quantitative RT-PCR revealed that higher levels of ERbeta than ERalpha mRNA were present in 5637, T-24, TSU-Pr1, and TCC-Sup bladder cancer cells, whereas ER-alpha mRNA levels were greater than ERbeta in RT4 cells. Treatment with 17beta-estradiol modestly increased RT4 cell growth, whereas the antiestrogens, 4-hydroxtamoxifen, raloxifene, or ICI 182,780 inhibited the growth of RT4 cells. CONCLUSIONS: ERbeta is the dominant receptor expressed in bladder cancer cell lines and in the majority of human bladder tumors. Moreover, the degree of ERbeta expression increases with increasing stage and grade of differentiation. Antiestrogens have an inhibitory effect on the growth of bladder cancer cells in vitro.

    Title Effects of Lactate Dehydrogenase Suppression and Glycerol-3-phosphate Dehydrogenase Overexpression on Cellular Metabolism.
    Date July 2006
    Journal Molecular and Cellular Biochemistry
    Excerpt

    In order to conduct a physiological functional study of lactate dehydrogenase (LDH) and glycerol-3-phosphate dehydrogenase (GPDH), we engineered a CHO dhfr(-) cell, by overexpressing either the anti-sense LDH-A RNA (anti-LDH cells) or GPDH (GP3 cells), or both (GP3/anti-LDH cells). LDH activity in the cell cytosol, and lactate content and pHe change in the growth media were found to decrease according to the order: cell lines GP3/anti-LDH > anti-LDH > GP3 > CHO. Intracellular ATP contents, representing the extent of respiration rate, also decreased, according to a rank order as follows: GP3 > CHO > GP3/anti-LDH > anti-LDH. We also attempted to identify and characterize any physiological changes occurring in the cells which harbored diverse metabolic pathways. First, anti-LDH cells with heightened respiration rates were found to display a higher degree of sensitivity to the prooxidant tert-butyl hydroperoxide (tBOOH), and the mitochondrial complex III inhibitor, antimycin A, than the GPDH-expressing cells (GP3 and GP3/anti-LDH), which have a lower respiration rate. Second, the anti-sense LDH-A RNA-expressing cells (anti-LDH and GP3/anti-LDH) evidenced a higher degree of resistance to apoptosis by cell-cell contact inhibition, and a faster doubling time ( approximately 19 h compared with approximately 26 h) than the CHO and GP3 cells. Additionally, cell growth in an extended culture under HCO(3) (-)-free conditions to induce a steep acidification could be maintained with the anti-sense LDH-A RNA-expressing cells, but could not be maintained with the CHO and GP3 cells. Third, we observed that the most appropriate cell line for the optical production of a certain therapeutic protein (Tissue-Plasminogen Activator) was the GP3/anti-LDH cells. Collectively, our data indicate a variety of physiological roles for LDH and GPDH, including cellular acidosis, oxidoresistance, apoptosis by both acidosis and cell-cell contact inhibition, cell growth, and the generation of recombinant proteins.

    Title Possible Pathophysiological Role of Vascular Endothelial Growth Factor (vegf) and Matrix Metalloproteinases (mmps) in Metastatic Brain Tumor-associated Intracerebral Hemorrhage.
    Date June 2006
    Journal Journal of Neuro-oncology
    Excerpt

    BACKGROUND: Intratumoral hemorrhage, as one of the cerebrovascular complications in various tumor-related conditions, occurs mainly in malignant brain tumors. Recent studies have shown that the overexpression of vascular endothelial growth factor (VEGF) and metalloproteinase (MMP) may play a role for the loss of vascular integrity and the subsequent hemorrhage in several instances, in addition to their well-known properties in tumor development and metastasis. METHODS: To investigate the potential role of VEGF and MMP in hemorrhagic complication of metastatic brain tumor, we estimated the expression of VEGF, MMP-2 & -9 by immunohistochemical studies in pathological specimens of metastatic brain tumors obtained from 16 patients, 7 in hemorrhagic and 9 in non-hemorrhagic group. We also examined the expression of collagen type IV, CD34, Factor VIII in order to evaluate the status of tumor vasculature. RESULTS: Patients in hemorrhagic group showed a higher VEGF expression with neovascularization than those in non-hemorrhagic group. The basement membranes of newly formed vessels were disrupted in cases with high expression in both MMP-2 and -9. These results indicate that rapid growing nascent blood vessels, responding vigorously to VEGF, are concentrated around the hemorrhagic tumors. Besides, these results suggest a possibility that the basement membranes of these nascent vessels could be disrupted proteolytically by MMP. CONCLUSION: We conclude that overexpression of VEGF and MMP may play a role in metastatic brain tumor-associated hemorrhage. Presumably, the underlying pathophysiological mechanisms are through rapid growth and breakdown of vessels around the tumors caused by overexpression of VEGF and MMP of tumor cells.

    Title Benign Osteoblastoma of the Occipital Bone: Case Report and Literature Review.
    Date June 2006
    Journal Neuropathology : Official Journal of the Japanese Society of Neuropathology
    Excerpt

    We present a case of benign osteoblastoma of the occipital bone. Benign osteoblastoma is an uncommon primary bone tumor, which usually involves the vertebrae and the long bones. This tumor rarely develops in the calvaria, showing a preference for the temporal and frontal bones when it does. To the best of our knowledge, this case is only the eighth reported case of benign osteoblastoma confined to the occipital bone. A 20-year-old male presented with a mild tender mass lesion of the occipital area, just below the lambda. Plain X-ray films and CT scans demonstrated an osteolytic mass surrounded by the sclerotic rim within the diploic space. MRI proved to be effective for the evaluation of the intracranial and intraosseous extensions of the tumor. However, it was very difficult to formulate a differential diagnosis against other osteoblastic tumors, or osteoid osteoma, in view of its radiological appearance. The final diagnosis was obtained by careful consideration of the histopathological characteristics of the tumor combined with its clinical and radiological features. Although generally regarded as benign, a complete resection is preferred over conventional curettage as this can guard against possible recurrence and malignant transformation.

    Title An Mri Study of Structural Variations in Schizophrenia Using Deformation Field Morphometry.
    Date June 2006
    Journal Psychiatry Research
    Excerpt

    Magnetic resonance imaging (MRI) has an important role in investigating the changes in brain structure that are associated with schizophrenia. In this study, MRI scans of patients diagnosed with schizophrenia (37 males; 19 females; 17-42 years of age) were compared with those of an age- and sex-matched group of normal subjects (37 males; 19 females; 18-40 years of age). Based on the images of the healthy control subjects, we constructed a representative average brain template. Automated image analysis techniques were used to measure differences in the regional nonlinear deformation fields between the two groups. A deformation field, which measures the spatial transformation to deform a template of brain anatomy to each individual data, was obtained as a three-dimensional displacement vector in each voxel. There was a significantly greater magnitude of the deformation fields in the superior frontal and parietal lobes as well as in the cingulate gyrus connecting both lobes of the patients with schizophrenia than in those of healthy controls, suggesting that these cerebral regions have a significantly higher structural variability in schizophrenia.

    Title Preparation of Semi-interpenetrating Polymer Networks Composed of Chitosan and Poloxamer.
    Date June 2006
    Journal International Journal of Biological Macromolecules
    Excerpt

    Through semi-interpenetration of polymer networks with poloxamer, mechanical properties of chitosan (CS) sponge were increased for wound dressing application. Synthesis of poloxamer macromer was confirmed by proton nuclear magnetic resonance (1H NMR) spectra. Possible interactions between CS and poloxamer in semi-interpenetrating polymer networks (SIPNs), and changes in crystalline structures of both polymers were evaluated by Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD), respectively. Swelling behavior, thermal analysis, mechanical properties, and morphology of SIPNs were studied by thermal gravimetric analysis, differential scanning calorimetry (DSC), compressive modulus measurement, and scanning electron microscopy (SEM), respectively. Preparation of poloxamer macromer, and intermolecular hydrogen bonding between CS and poloxamer were confirmed by NMR and FTIR, respectively. Melting temperature of poloxamer in SIPNs decreased due to prevention of crystallization by incorporation of CS. Formation of SIPNs with poloxamer and increasing poloxamer content in CS/poloxamer SIPNs increased mechanical strength of CS sponge compared with CS/poloxamer blend. Formation of SIPNs with poloxamer remarkably increased water content of CS due to hydrophilicity of CS and poloxamer. These results suggest CS/poloxamer sponges prepared by SIPNs method have good possibility for wound dressing application owing to rapid water adsorption, high mechanical strength, and interconnected cross-sectional morphology of SIPNs.

    Title Papillary Endothelial Hyperplasia Associated with Repeated Bleeding.
    Date May 2006
    Journal British Journal of Neurosurgery
    Excerpt

    We report a case of intracranial papillary endothelial hyperplasia (PEH) with subsequent haemorrhage and the possible pathogenesis of bleeding. PEH is a slow growing tumour and for rapid enlargement the process of haemorrhage may be necessary.

    Title Rapid Spontaneous Resolution of a Traumatic Cervical Epidural Haematoma.
    Date May 2006
    Journal British Journal of Neurosurgery
    Title Clinical and Histopathological Analysis of Cystic Meningiomas.
    Date May 2006
    Journal Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia
    Excerpt

    Between 1993 and 2003, we treated 21 patients with cystic meningioma (of 365 with meningioma, 5.5%). We grouped these patients according to classifications by Nauta and Rengachary and analyzed them by gender, age, tumor location, clinical manifestations, MRI features and histopathology. The mean duration of symptoms was relatively short at 1.6 months. There were five atypical and 16 benign meningiomas on histopathology. In type I and II cystic meningiomas, with intratumoral cysts, all cyst walls enhanced on MRI and had tumor cells in the cyst wall on histopathology. In type III and IV cystic meningiomas, with peritumoral cysts, the cyst wall did not enhance on MRI and only one case (type III) had tumor cells in the cyst wall on histopathology. We suggest that when the cyst wall shows contrast enhancement on imaging, the cyst wall should be completely removed at surgery. If there is no contrast enhancement, multiple biopsies of the cyst wall should be taken to assess the presence of tumor cells in the cyst wall.

    Title Inflammatory Aneurysm Due to Neurocysticercosis.
    Date May 2006
    Journal Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia
    Excerpt

    A 69-year old man presented with a subarachnoid hemorrhage associated with a large intracerebral hematoma in the right temporal lobe. The oblique views of cranio-orbital computerized tomographic angiography (CTA) were suspicious for an aneurysm on a middle cerebral artery branch. At surgery, a cystic mass was found in the Sylvian fissure, associated with an aneurysm on a distal branch of the anterior temporal artery. The aneurysm was not situated at a bifurcation of the artery and was located beneath the cyst. It was secured by trapping. Pathological examination revealed that the cystic lesion was neurocysticercosis and that the aneurysm was inflammatory. We report a ruptured inflammatory aneurysm of a distal branch of the anterior temporal artery associated with neurocysticercosis, and present the histological findings. We believe this is the first report of such an inflammatory aneurysm with histological confirmation.

    Title Representative Brain Selection Using a Group-specific Tissue Probability Map.
    Date May 2006
    Journal Magnetic Resonance Imaging
    Excerpt

    PURPOSE: To determine the anatomy of a standard brain reflecting well-defined group characteristics based on probabilistic information from group-specific anatomical variations. MATERIALS AND METHODS: We constructed a group-specific tissue probabilistic map for 20 subjects and used it to extract voxel-wise probabilistic information for each subject through regional spatial normalization using Automated Image Registration software (AIR 5.2.5). Extracted probabilistic information was then used to determine standard properties of the subjects. For comparison, we employed an empirical scoring function - a measure of entropy - in ordering the data set. A brain with minimum entropy was then selected for a group standard. The evaluation of our proposed method was performed using two different selection schemes: deformation analysis and similarity index measurements. RESULTS: This method showed highly correlated result with previous method by Kochunov et al., with fewer computational tasks. CONCLUSION: This method can thus be used to determine an appropriate standard model to compare with disease-affected brains.

    Title Two Cases of Pineal Germinoma with Granulomatous Inflammation.
    Date April 2006
    Journal Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia
    Excerpt

    We report two cases of pineal germinoma with remarkable chronic granulomatous inflammation. In the first case, the pineal mass was totally removed via an occipital transtentorial approach as symptoms were due to direct mass effect. In the second case, endoscopic third ventriculostomy and tissue biopsy was performed to alleviate worsening hydrocephalus. Pathological examination of specimens of both cases showed chronic granulomatous inflammation associated with a few germ cell tumor nests, which demonstrated positive staining for placental alkaline phosphatase. Both patients received post-operative craniospinal irradiation with no subsequent neurological deficits. Follow-up magnetic resonance imaging (MRI) of the second case showed an asymptomatic, shrunken residual tumor mass. MRI of the first case showed no residual or recurrent disease. Thus, a pineal mass with unusual features on MRI and chronic granulomatous inflammation on histopathology, should raise the suspicion of germinoma. In cases with symptomatic mass effect, open resection can be considered. In cases with lesser mass effect, conventional therapeutic modalities without resection can achieve a good outcome, as for other germinomas.

    Title Hemorrhagic Intracranial Inflammatory Pseudotumor Originating from the Trigeminal Nerve: a Case Report.
    Date April 2006
    Journal Journal of Neuro-oncology
    Excerpt

    We report here on a case of intracranial inflammatory pseudotumor arising from the trigeminal nerve. A 52-year-old man presented with sudden onset severe headache. He had had facial numbness several months earlier and no signs indicating infection. On the computerized tomography scan, intracranial hemorrhage was detected at the cerebellopontine angle. Magnetic resonance imaging demonstrated a 2.7-cm-sized, homogenously enhancing mass. A provisional diagnosis of trigeminal schwannoma was made, and suboccipital craniotomy was then performed. The mass was encapsulated and had multiple capsular veins. There was a evidence of intratumoral bleeding. It originated from the trigeminal root and was adhered to the 4th cranial nerve. Pathologic examination showed fibrovascular tissue with dense infiltrates of plasma cells and lymphocytes, some histiocytes, and occasional neutrophils and eosinophils. It showed immunopositivity for leukocyte common antigen (LCA) and immunonegativity for S-100 and lysozyme. It was also immunopositive for EBV antigen. Intracranial inflammatory pseudotumors mostly arise from dural/meningeal structures in the intracranial location. This case is the first to describe an intracranial inflammatory pseudotumor originating from a cranial nerve. The pathologic examination supported the postinfection hypothesis out of several possible pathologic mechanisms.

    Title Third Prize: Comparison of Radical Nephrectomy, Laparoscopic Microwave Thermotherapy, Cryotherapy, and Radiofrequency Ablation for Destruction of Experimental Vx-2 Renal Tumors in Rabbits.
    Date March 2006
    Journal Journal of Endourology / Endourological Society
    Excerpt

    BACKGROUND AND PURPOSE: Currently available minimally invasive renal tumor-ablation procedures include cryotherapy, radiofrequency ablation, and microwave thermotherapy. In this study, we investigated the ability of these three approaches to destroy experimental renal tumors in rabbits. The mechanism of potential tumor metastasis was also explored. MATERIALS AND METHODS: The VX-2 tumor line is an aggressive rabbit epidermoid tumor with a high metastatic potential. An initial experiment comparing cooled-tip microwave thermotherapy with cryotherapy and radical nephrectomy for treatment of small VX-2 tumors revealed that all microwave-treated rabbits had local recurrence and that several also had diffuse intraperitoneal carcinomatosis. In view of these results, a second experiment was performed in which 45 New Zealand White rabbits were implanted laparoscopically with VX-2 xenografts underneath the kidney capsule and divided into five groups of 9 each. The test groups were microwave thermotherapy with a 3.5-mm cooled-tip probe, microwave thermotherapy with a 3.5-mm noncooled- tip probe, radiofrequency ablation with a 1.5-mm cooled-tip probe, radiofrequency ablation with a 1.5- mm non-cooled tip probe, and cryotherapy with a 2.3-mm cryoprobe. The control groups were five rabbits that were not treated, five rabbits with tumors that had the tumor pierced with a probe but were untreated, and five rabbits that underwent nephrectomy after piercing of the tumor. Treatment was initiated 5 days after tumor implantation. One month later, all animals were euthanized and autopsied. RESULTS: At 5 days after tumor implantation, laparoscopic inspection revealed no visible peritoneal metastases. At 1 month, in the cooled and non-cooled microwave-thermotherapy groups, carcinomatosis occurred in five and six of nine animals, respectively. In comparison, carcinomatosis was detected in two of nine animals in the cryotherapy group at autopsy. With respect to cooled and non-cooled radiofrequency ablation, carcinomatosis was observed in four of nine rabbits in each group. In the control groups, none of the animals with unpierced tumors exhibited carcinomatosis, while carcinomatosis was seen in two of the five rabbits with tumor violated by piercing and in three of the five rabbits that underwent immediate nephrectomy after piercing of the tumor. CONCLUSION: Carcinomatosis occurred most frequently in animals treated with microwave thermotherapy, followed by radiofrequency ablation, and lastly cryoablation. The simple act of piercing a highly aggressive tumor can result in local spread. More disconcerting, and less well understood, is why certain ablative modalities appear to increase the rate of intraperitoneal spread.

    Title Enhanced Liver Functions of Hepatocytes Cocultured with Nih 3t3 in the Alginate/galactosylated Chitosan Scaffold.
    Date March 2006
    Journal Biomaterials
    Excerpt

    Formation of primary hepatocyte spheroids in the hydrogel scaffold is a promising approach for enhancing liver-specific functions in liver tissue engineering as well as for developing bioartificial liver (BAL) devices. In the present study, a highly porous hydrogel scaffold composed of alginate (AL) and galactosylated chitosan (GC) as a synthetic extracellular matrix (ECM) for hepatocytes was fabricated with 150-200 microm pore size in diameter. Cell adhesion onto AL/GC and AL/chitosan film was 72.7 and 45% at 1 wt% of GC (or chitosan) to AL content whereas cell adhesion onto AL film was 28.5%. The optimal concentration of GC in AL/GC sponge was 1 wt% to AL content by the measurement of albumin secretion. Cell viabilities performed on AL and AL/GC sponges were 72.2+/-3.6 and 81.3+/-3.5% of control, respectively, after 10 days incubation. Hepatocytes were aggregated to form multicellular spheroids in AL/GC sponge with diameter enlarged up to about 100 microm, 36 h postseeding, whereas most of them in the AL sponge remained as single cells and only a few cells began to form aggregates. Intercellular molecules such as connexin32 and E-cadherin genes related with cell-cell contact were expressed in hepatocytes within AL/GC sponge at 36 h after incubation, but not in AL sponge. Treatment with a gap junctional intercellular communication (GJIC) inhibitor, 18beta-glycyrrhetinic acid, resulted in a 1.5-fold marked decrease in albumin secretion levels in AL/GC sponge. Specially, coculture of hepatocytes in AL and AL/GC sponges with NIH3T3 in a transwell insert resulted in enhanced increase of liver-specific functions, such as albumin secretion rates, ammonia elimination rates, and ethoxyresorufin-O-deethylase activity by cytochrome P4501A1, compared to those in hepatocyte monoculture. The results suggest that formation of hepatocyte spheroids in coculture system enhances liver-specific functions for the AL/GC sponge as a new synthetic ECM to design developed BAL devices.

    Title Pancreatic Carcinoid Tumor with Obstructive Pancreatitis: Multislice Helical Ct Appearance: Case Report.
    Date February 2006
    Journal Abdominal Imaging
    Excerpt

    Carcinoid tumor of the pancreas is rare. Moreover, obstructive pancreatitis secondary to a pancreatic carcinoid tumor is extremely rare. We report a case of pancreatic carcinoid tumor in a 50-year-old male who presented with pancreatitis. On multislice helical computed tomography, the main pancreatic duct was obstructed by a small round tumor, and the main pancreatic duct proximal to the tumor was dilated. The correlation between the main pancreatic duct and the tumor was well depicted on minimum intensity projection image. This is the first report of multislice helical computed tomorgraphic and minimum intensity projection image findings of a pancreatic carcinoid tumor presenting with pancreatitis.

    Title Experimental Results of Affective Valence and Arousal to Avatar's Facial Expressions.
    Date February 2006
    Journal Cyberpsychology & Behavior : the Impact of the Internet, Multimedia and Virtual Reality on Behavior and Society
    Excerpt

    The objectives of this study were to propose a method of presenting dynamic facial expressions to experimental subjects, in order to investigate human perception of avatar's facial expressions of different levels of emotional intensity. The investigation concerned how perception varies according to the strength of facial expression, as well as according to an avatar's gender. To accomplish these goals, we generated a male and a female virtual avatar with five levels of intensity of happiness and anger using a morphing technique. We then recruited 16 normal healthy subjects and measured each subject's emotional reaction by scoring affective arousal and valence after showing them the avatar's face. Through this study, we were able to investigate human perceptual characteristics evoked by male and female avatars' graduated facial expressions of happiness and anger. In addition, we were able to identify that a virtual avatar's facial expression could affect human emotion in different ways according to the avatar's gender and the intensity of its facial expressions. However, we could also see that virtual faces have some limitations because they are not real, so subjects recognized the expressions well, but were not influenced to the same extent. Although a virtual avatar has some limitations in conveying its emotion using facial expressions, this study is significant in that it shows that a new potential exists to use or manipulate emotional intensity by controlling a virtual avatar's facial expression linearly using a morphing technique. Therefore, it is predicted that this technique may be used for assessing emotional characteristics of humans, and may be of particular benefit for work with people with emotional disorders through a presentation of dynamic expression of various emotional intensities.

    Title Tyrosine 740 Phosphorylation of Discoidin Domain Receptor 2 by Src Stimulates Intramolecular Autophosphorylation and Shc Signaling Complex Formation.
    Date February 2006
    Journal The Journal of Biological Chemistry
    Excerpt

    DDR2 is a receptor tyrosine kinase whose activating ligands are various collagens. DDR2-mediated cellular signaling has been shown to require Src activity. However, the precise mechanism underlying the Src dependence of DDR2 signaling is unknown. Here, using baculoviral co-expression of the DDR2 cytosolic domain and Src, we show that Src targets three tyrosine residues (Tyr-736, Tyr-740, and Tyr-741) in the activation loop of DDR2 for phosphorylation. This phosphorylation by Src stimulates DDR2 cis-autophosphorylation of additional tyrosine residues. In vitro Shc binding assays demonstrate that phosphotyrosines resulting from DDR2 autophosphorylation are involved in Shc binding to the DDR2 cytosolic domain. Mutating tyrosine 740 of DDR2 to phenylalanine stimulates autophosphorylation of DDR2 to an extent similar to that resulting from Src phosphorylation of DDR2. In addition, the DDR2 Y740F mutant protein displays collagen-independent, constitutively activated signaling. These findings suggest that tyrosine 740 inhibits DDR2 autophosphorylation. Collectively, our findings are consistent with the following mechanism for Src-dependent DDR2 activation and signaling: 1) ligand binding promotes phosphorylation of Tyr-740 in the DDR2 activation loop by Src; 2) Tyr-740 phosphorylation stimulates intramolecular autophosphorylation of DDR2; 3) DDR2 autophosphorylation generates cytosolic domain phosphotyrosines that promote the formation of DDR2 cytosolic domain-Shc signaling complexes.

    Title Pyrethroid Insecticides, Fenvalerate and Permethrin, Inhibit Progesterone-induced Alkaline Phosphatase Activity in T47d Human Breast Cancer Cells.
    Date January 2006
    Journal Journal of Toxicology and Environmental Health. Part A
    Excerpt

    Pyrethroid insecticides exhibited a weak estrogenic activity by stimulation of MCF-7 cell proliferation and induction of alkaline phosphatase (AlkP) enzyme activity in cultured Ishikawa cells. Previously it was reported that fenvalerate and permethrin significantly inhibited the 17beta-estradiol-induced MCF-7 BUS cell proliferation. Although certain pyrethroid insecticides exert estrogenic or antiestrogenic activities, it is not clear whether pyrethroid insecticides act as progesterone agonists or antagonists. Therefore, the aim of this study was to evaluate the effects of fenvalerate and permethrin on AlkP activity as a progesterone-specific response in T47D cells. In the present study, the stimulation of AlkP activity was concentration dependent with addition of progesterone, and maximum activity was observed at concentration of 1 x 10(-8) M. Both fenvalerate (1 x 10(-6) M) and permethrin (1 x 10(-6) M) did not stimulate the AlkP activity, but progesterone (1 x 10(-8) M)-induced AlkP activity was significantly inhibited at 1 x 10(-6) M concentration of fenvalerate and permethrin, respectively. Progesterone receptor (PR) levels in cytosolic protein of T47D cells were studied to determine the relationship between cellular PR expression and AlkP activity. Similar to AlkP activity, progesterone (1 x 10(-8) M) significantly increased PR protein levels compared to control. However, PR protein levels were not affected in T47D cells cultured with fenvalerate and permethrin alone, whereas fenvalerate and permethrin significantly decreased progesterone-induced PR protein levels. Our data indicate that fenvalerate and permethrin exhibit antiprogestagenic activity in T47D human breast cancer cells.

    Title Validation Study of Oecd Rodent Uterotrophic Assay for the Assessment of Estrogenic Activity in Sprague-dawley Immature Female Rats.
    Date January 2006
    Journal Journal of Toxicology and Environmental Health. Part A
    Excerpt

    The Organization for Economic Cooperation and Development (OECD) is developing a screening and testing method to identify estrogenic/antiestrogenic compounds. Based on these demands, phase 1 study for OECD uterotrophic assay was undertaken. The OECD is in the process of validating the assay results from international participating laboratories, which carried out this study with established environmental estrogenic compounds using designed protocols. The aim of this study was to provide data for validating the OECD uterotrophic assay using Sprague-Dawley immature female rats when testing with weak or partial estrogenic compounds. Ethinyl estradiol (EE) at 0.3 or 1 microg/kg/d, a positive control used in the present study, significantly increased both uterine wet and blotted weights. In the case of weak estrogenic compounds, the uterine wet weights were significantly increased by bisphenol A (BPA) at 300 mg/kg/d, nonylphenol (NP) at 80 mg/kg/d, genistein (GN) at 35 mg/kg/d, and methoxychlor (MXC) at 500 mg/kg/d. In addition, the increase in uterine blotted weights also showed a similar pattern to that of uterine wet weights. However, both 1,1,1-trichloro-2,2-bis(p-chlorphenyl)ethane (o,p-DDT) and dibutyl phthalate (DBP) did not affect uterus (wet and blotted) weights at doses of 100 and 500 mg/kg/d. These results suggest that the increase in uterine weights should be considered useful as a sensitive endpoint for detecting weak estrogenic compounds in 3-d rodent uterotrophic assay. However, further combination studies using surrogate biomarkers may be needed to improve the sensitivity of this assay for the detection of weak estrogenic compounds, such as o,p-DDT.

    Title Selenite-induced Apoptosis of Osteoclasts Mediated by the Mitochondrial Pathway.
    Date January 2006
    Journal Toxicology Letters
    Excerpt

    The possible effects of sodium selenite on mature osteoclasts were investigated. Incubation of osteoclast-like cells differentiated from RAW 264.7 cells with sodium selenite induced apoptosis as revealed by morphological changes, internucleosomal DNA fragmentation, and activation of caspase-3. Selenite also induced generation of the superoxide anion and reduced the number of free thiol groups in the osteoclast-like cells, suggestive of a shift to a more oxidizing intracellular environment. In addition, selenite induced protein aggregation by thiol cross-linking, loss of the mitochondrial membrane potential, and cytochrome c release in mitochondria isolated from the osteoclast-like cells. Finally, selenite-induced DNA fragmentation in osteoclasts was inhibited both by cyclosporin A, a blocker of the mitochondrial permeability transition pore, and by DEVD-CHO, a cell-permeable inhibitor of caspase-3. These results thus suggest that selenite induces apoptosis mediated by the mitochondrial pathway in mature osteoclasts.

    Title Asymmetry Analysis of Deformable Hippocampal Model Using the Principal Component in Schizophrenia.
    Date September 2005
    Journal Human Brain Mapping
    Excerpt

    The hippocampus is thought to play an important role in learning and memory processing, and impairments in memory, attention, and decision making are found commonly in schizophrenia. Although many studies have reported decreases in hippocampal volume in the left hemisphere in schizophrenia, regionally specific hippocampal volume loss has not been revealed consistently using volume analysis. Recently, many studies have analyzed shape asymmetry using 3-D models; however, inconsistent results have been reported, mainly due to methodologic differences. We therefore used an active, flexible, deformable shape model for surface parameterization, and compared shape asymmetry based on principal component analysis (PCA) in the hippocampi of schizophrenic patients with those of the normal controls. Although the overall pattern of the statistical results did not change according to the number of principal components, the reconstructed results based on six major components were much more distinguishable. Although the left hemispheric hippocampal volume was larger than the right hemispheric was in this study, the difference was not significant. In shape asymmetry analysis, the right hemisphere hippocampus was bilaterally larger than the left hemisphere hippocampus was in the head of the superior CA1 and smaller in the tail and head of the inferior CA1. The asymmetry in the schizophrenia group was statistically smaller than that in the control group through reduction of the left hemisphere hippocampus volume.

    Title Preoperative Evaluation of Venous Systems with 3-dimensional Contrast-enhanced Magnetic Resonance Venography in Brain Tumors: Comparison with Time-of-flight Magnetic Resonance Venography and Digital Subtraction Angiography.
    Date August 2005
    Journal Surgical Neurology
    Excerpt

    BACKGROUND: Recent developments in magnetic resonance (MR) technology now enable the use of MR venography, providing 3-dimensional (3D) images of intracranial venous structures. The purpose of this study was to assess the usefulness of 3D contrast-enhanced MR venography (CE MRV) in the evaluation of intracranial venous system for surgical planning of brain tumors. METHODS: Forty patients underwent 3D CE MRV, as well as 25 patients, 2-dimensional (2D) time-of-flight (TOF) MR venography in axial and sagittal planes; and 10 patients, digital subtraction angiography. We determined the number of visualized sinuses and cortical veins. Degree of visualization of the intracranial venous system on 3D CE MRV was compared with that of 2D TOF MR venography and digital subtraction angiography as a standard. We also assessed the value of 3D CE MRV in the investigation of sinus occlusion or localization of cortical draining veins preoperatively. RESULTS: Superficial cortical veins and the dural sinus were better visualized on 3D CE MRV than on 2D TOF MR venography. Both MR venographic techniques visualized superior sagittal sinus, lateral sinus, sigmoid sinus, straight sinus, and internal cerebral vein and provided more detailed information by showing obstructed sinuses in brain tumors. Only 3D CE MRV showed superficial cortical draining veins. However, it was difficult to accurately evaluate the presence of cortical collateral venous drainage. CONCLUSION: Although we do not yet advocate MR venography to replace conventional angiography as the imaging standard for brain tumors, 3D CE MRV can be regarded as a valuable diagnostic method just in evaluating the status of major sinuses and localization of the cortical draining veins.

    Title Fractal Dimension of Cerebral Cortical Surface in Schizophrenia and Obsessive-compulsive Disorder.
    Date August 2005
    Journal Neuroscience Letters
    Excerpt

    Schizophrenia and obsessive-compulsive disorder (OCD) are assumed to be neurodevelopmental disorders. To examine the cortical patterns in the two disorders, three-dimensional fractal dimension (FD) of skeletonized cerebral cortical surface was estimated from magnetic resonance (MR) images of 50 patients with schizophrenia, 45 patients with OCD and 26 healthy normal controls. The schizophrenic group had a significantly smaller mean FD than OCD group, and the OCD group than normal controls. The FD revealed a significant interaction effect of group-by-hemisphere, and the FD asymmetry index distinguished the schizophrenic group from normal controls. In logistic regression models, the FD and CSF volume correctly classified 95.6% of the schizophrenics from the controls and 88.0% of the patients with OCD from the controls. In the control and schizophrenic groups, the FD was not associated with any of tissue volume measures. In the OCD group, however, the FD was significantly correlated with gray matter tissue volume and intracranial volume (ICV). The results of the present study suggest that three-dimensional FD of cortical surface may be a sensitive indicator for investigation of the structural brain abnormalities in mental disorders, especially those developmentally disturbed. Further studies to explore regional FD changes in mental disorders and clinical implications of the FD including diagnostic value should be performed in the future.

    Title Sex Differences in the Human Corpus Callosum: Diffusion Tensor Imaging Study.
    Date August 2005
    Journal Neuroreport
    Excerpt

    In order to assess underlying structural differences between the male and female corpus callosum, the fractional anisotropy and volume of the corpus callosum, and also its T1 signal intensity, were measured. The corpus callosum of the 15 normal women and 15 normal men was drawn on the mid-sagittal T1-weighted image, for determining its volume and signal intensity, and this region of interest was projected onto the coregistered fractional anisotropy image, in order to obtain the value for the corpus callosum. We found increased T1 signal intensity and decreased fractional anisotropy in the female corpus callosum, as compared with that of the male. Despite the long-standing debates, the corpus callosum remains a region of sex differences.

    Title Quantitative Analysis of Group-specific Brain Tissue Probability Map for Schizophrenic Patients.
    Date August 2005
    Journal Neuroimage
    Excerpt

    We developed group-specific tissue probability map (TPM) for gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF) on the common spatial coordinates of an averaged brain atlas derived from normal controls (NC) and from schizophrenic patients (SZ). To identify differences in group-specific TPMs, we used quantitative evaluation methods based on differences in probabilistic distribution as a global criterion, and the mean probability and the similarity index (SI) by lobe as regional criteria. The SZ group showed more spatial variation with a lower mean probability than NC subjects. And, for the right temporal and left parietal lobes, the SI between each group was lower than the other lobes. It can be said that there were significant differences in spatial distribution between controls and schizophrenic patients at those areas. In case of female group, although group differences in the volumes of GM and WM were not significant, global difference in the probabilistic distribution of GM was more prominent and the SI was lower and its descent rate was greater in all lobes, compared with the male group. If these morphological differences caused by disease or group-specific features were not considered in TPM, the accuracy and certainty of specific group studies would be greatly reduced. Therefore, suitable TPM is required as a common framework for functional neuroimaging studies and an a priori knowledge of tissue classification.

    Title Transforming Growth Factor-beta : Biology and Clinical Relevance.
    Date July 2005
    Journal Journal of Biochemistry and Molecular Biology
    Excerpt

    Transforming growth factor-beta is a pleiotropic growth factor that has enthralled many investigators for approximately two decades. In addition to many reports that have clarified the basic mechanism of transforming growth factor-beta signal transduction, numerous laboratories have published on the clinical implication/application of transforming growth factor-beta . To name a few, dysregulation of transforming growth factor-beta signaling plays a role in carcinogenesis, autoimmunity, angiogenesis, and wound healing. In this report, we will review these clinical implications of transforming growth factor-beta .

    Title Interindividual Reproducibility of Glutamate Quantification Using 1.5-t Proton Magnetic Resonance Spectroscopy.
    Date June 2005
    Journal Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine
    Excerpt

    The goal of this study was to measure the interindividual reproducibility of glutamate quantification in 1.5-T (1)H MRS of human brains. To determine the effective echo time (TE) for glutamate quantification, spectra from a phantom and 12 participants were obtained with TE = 30, 35, 40, and 144 ms (repetition time (TR) = 2000 ms and volume of interest = 4 cm(3)). The average Cramer-Rao lower bounds for glutamate quantification using LCModel was lowest in two experiments when TE = 40 ms.Twenty-one subjects participated in experiments that measured interindividual reproducibility of glutamate quantification. Spectra were acquired with TR = 6000 ms and TE = 40 ms. Results showed that the coefficients of variance were 11.0 and 13.1% in the anterior cingulate cortex and insula, respectively. This suggests that glutamate can be reproducibly measured from 1.5-T (1)H MRS with long TR, effective TE, and the LCModel.

    Title Multislice Ct Cholangiography Using Thin-slab Minimum Intensity Projection and Multiplanar Reformation in the Evaluation of Patients with Suspected Biliary Obstruction: Preliminary Experience.
    Date May 2005
    Journal Clinical Imaging
    Excerpt

    Thirty-three patients with suspected biliary obstruction were prospectively evaluated with multislice CT cholangiography using thin-slab minimum intensity projection (MinIP) and multiplanar reformation (MPR) to determine its usefulness and to compare with the comparative studies of endoscopic retrograde cholangiography (ERC), magnetic resonance cholangiography (MRC), or percutaneous transhepatic cholangiography (PTC). CT cholangiography made correct diagnoses in all biliary obstructions except in two patients with common bile duct stones. The correspondence with the comparative study was 93.9%. Multislice CT cholangiography may be favorable in noninvasive evaluation of biliary obstructions.

    Title Nicotine Craving and Cue Exposure Therapy by Using Virtual Environments.
    Date May 2005
    Journal Cyberpsychology & Behavior : the Impact of the Internet, Multimedia and Virtual Reality on Behavior and Society
    Excerpt

    Smokers who are exposed to cues associated with smoking show cardiovascular reactivity and an increase in smoking urges as compared to when they are presented with neutral cues. Cue exposure therapy (CET), which refers to the repeated exposure to drug-related cues in order to extinguish this learned association, has increasingly been proposed as a potential treatment of addictive behaviors, including tobacco smoking. The result of our pilot study suggests that a cue elicited using a virtual environment (VE) is more effective than other cue exposure devices. The VE was composed of craving environments (virtual bar) and objects (an alcoholic drink, a packet of cigarettes, a lighter, an ashtray, a glass of beer, and advertising posters) that are likely to trigger craving, a smoking avatar, and an audio environment that included the noisy sound and music of a restaurant. Sixteen late-adolescent males who smoked at least 10 cigarettes a day were recruited to participate in the VE-CET study. The CET virtual bar program consisted of six sessions, and the participants were exposed repeatedly to each session using different questions and procedures. Although the effects of CET did not yield significant reductions in all of the dependent variables, the craving for cigarettes was gradually decreased during the course of the sessions. This tendency was closely related to the reduction in the smoking count between the morning before the experiment and the start of the experiment. Based on these preliminary results, it appears that VE-CET maybe a useful tool to use in treatment programs to help reduce craving in those who are nicotine dependent.

    Title A Virtual Reality Assessment and Training System for Unilateral Neglect.
    Date May 2005
    Journal Cyberpsychology & Behavior : the Impact of the Internet, Multimedia and Virtual Reality on Behavior and Society
    Excerpt

    Patients with unilateral neglect have problems reporting, responding, or orienting to novel or meaningful stimuli that is presented to the side opposite to that of a brain lesion. This creates a serous problem in regards to daily living activities. However, the established methods for assessing and training of unilateral neglect patients have several deficits. Recently, virtual reality (VR) technologies have been used as an assessment and treatment tool for rehabilitation. Hence, this study designed a VR system to assess and train unilateral neglect patients. In addition, the suitability and feasibility of our VR system for unilateral neglect patients was verified.

    Title Neuronavigation-guided Endoscopic Surgery for Pineal Tumors with Hydrocephalus.
    Date April 2005
    Journal Minimally Invasive Neurosurgery : Min
    Excerpt

    We have applied the neuronavigation system to endoscopic biopsy and third ventriculostomy in the management of patients with a pineal tumor with hydrocephalus. With the guidance of neuronavigation, the two optimal sites of burr hole and trajectories were planned preoperatively, and the advancing endoscopic device was monitored in real time during the procedure. In our five patients, the diameters of the tumors were 2-3 cm, and the mean systemic accuracy of registration with neuronavigation was 1.2 mm. The biopsy and third ventriculostomy were performed successfully via the respective optimal burr hole and the trajectory determined using preoperative neuronavigation. There were no procedure-related complications, and none of the patients needed another procedure for CSF diversion during the follow-up periods. We present our technique which includes the application of the neuronavigation system to the biopsy and third ventriculostomy in pineal tumor with associated hydrocephalus. This technique can be performed using a simple rigid endoscope via the determined optimal entries and trajectories. The optimal preoperative planning and the intraoperative guidance by neuronavigation are thought to be able to give more chances to minimize the brain injury related to movements or deviation of endoscopic device.

    Title Small Cell Carcinoma of the Colon: Barium Study and Ct Findings.
    Date April 2005
    Journal The British Journal of Radiology
    Excerpt

    Extrapulmonary small cell carcinoma is a rare neoplasm. It is an aggressive malignant tumour characterized by rapid local progression and early metastasis. We report a case of small cell carcinoma arising in the transverse colon in a 34-year-old man who presented with epigastric pain. On CT, a poorly enhancing bulky mass encircling the transverse colon with extensive regional lymph node metastases was observed. A segmental annular narrowing with thick interhaustral folds of the transverse colon was found by barium enema examination. This is the first report of barium study and CT findings of extrapulmonary small cell carcinoma of the colon.

    Title Nonlinear-analysis of Human Sleep Eeg Using Detrended Fluctuation Analysis.
    Date April 2005
    Journal Medical Engineering & Physics
    Excerpt

    Quantification of the fractal scaling properties of human sleep EEG dynamics was sought and each normal sleep stage was compared with that of sleep apnea. The fractal scaling exponents that quantify power-law correlations were computed using detrended fluctuation analysis. Six healthy subjects, aged 30-35 years, participated and six recordings of the apnea were acquired from MIT/BIH polysomnography database. The data were 8-h baseline recordings (23:00-07:00 h). The EEG signals from the C4-A1 derivation were acquired with a resolution of 250 Hz. The sleep stages were visually scored for 30 s epochs, according to the criteria of Rechtschaffen and Kales. The mean scaling exponents increased from the awake stage to stages 1, 2 and 3-4, but decreased during rapid eye movement (REM) sleep. The scaling exponents of the apnea were lower than those of the healthy subject for all the stages. The scaling exponents could be attributed to the fractal nature of EEG, which would be more appropriate for describing the complexity of EEG due to its assumption of non-stationarity.

    Title Metastatic Glioblastoma in Cervical Lymph Node After Repeated Craniotomies: Report of a Case with Diagnosis by Fine Needle Aspiration.
    Date April 2005
    Journal Journal of Korean Medical Science
    Excerpt

    Head and neck metastasis from glioblastoma is rare event usually seen in patients with previous and repeated surgery. We present the case of a 35 yr-old-female suffering from metastatic glioblastoma in cervical lymph node that was diagnosed by fine needle aspiration. During the last 4 yr, she had four separate craniotomies for the recurrent brain tumors. Cytological diagnosis was made by light microscopy with immunostaining with glial fibrillay acid protein. Chemotherapy with vincristine and procarbazine was performed. The cervical masses were decreased in size and some disappeared while the intracranial glioblastoma continued to grow during chemotherapy. We discuss possible explanations for these different courses after chemotherapy in extraneural metastatic glioblastoma and primary intracranial glioblastoma.

    Title Allergen-induced Proteolytic Cleavage of Annexin-1 and Activation of Cytosolic Phospholipase A2 in the Lungs of a Mouse Model of Asthma.
    Date April 2005
    Journal Proteomics
    Excerpt

    To identify proteins that might play an important role in allergen-induced asthma, we analyzed lung extracts prepared from allergen (ovalbumin)-challenged animals in a mouse model of this condition. The combination of two-dimensional gel electrophoresis and mass spectrometry revealed that annexin-1, a 37 kDa anti-inflammatory protein that inhibits the activity of cytosolic phospholipase A(2) (cPLA(2)), was down-regulated by allergen challenge in the lungs of ovalbumin-sensitized mice. Immunoblot analysis showed that this effect of ovalbumin challenge was attributable to proteolytic cleavage of annexin-1. The ovalbumin-induced degradation of annexin-1 was blocked by pretreatment of mice with the antioxidant N-acetylcysteine (NAC) or with sodium selenite, both of which have previously been shown to exert anti-inflammatory effects in this asthma model. Ovalbumin challenge also both increased the expression of cPLA(2) in lung tissue and reduced the extent of the interaction between cPLA(2) and annexin-1, and these effects were inhibited by NAC or selenite. Moreover, the concentrations of cysteinyl leukotrienes in bronchoalveolar lavage fluid and of leukotriene B(4) in lung tissue were increased by ovalbumin challenge in a NAC- or selenite-sensitive manner. Together, these results suggest that allergen-induced oxidative stress results in proteolysis of annexin-1 and consequent up-regulation of cPLA(2) activity and leukotriene production in this mouse model of asthma, and that the anti-inflammatory effects of selenite may provide a basis for the development of new antiasthmatic drugs.

    Title Gray Matter Abnormalities in Paranoid Schizophrenia and Their Clinical Correlations.
    Date March 2005
    Journal Psychiatry Research
    Excerpt

    Numerous imaging studies have shown structural brain abnormalities in schizophrenia. Recently, voxel-based morphometry enabled whole brain analysis beyond the regions of interest (ROI). Regional gray matter concentrations of magnetic resonance (MR) images from 35 patients with paranoid schizophrenia were compared with those from 35 age- and sex-matched controls, and their clinical correlations were explored using voxel-based morphometry. Gray matter concentrations in the patients were significantly reduced in the left insular and dorsolateral prefrontal regions, and bilaterally in the medial frontal, anterior cingulate, inferior frontal and superior temporal regions. On the other hand, gray matter concentrations in the bilateral cerebellum and right striatum were significantly increased in the patients compared with controls. A negative correlation between the score for the severity of 'lack of insight and judgment' and gray matter concentrations in the left posterior and right anterior cingulate and bilateral inferior temporal regions including the lateral fusiform gyri was found. These results suggest the important roles of the paralimbic structures in the pathophysiology of schizophrenia and the involvement of the perceptual and monitoring systems in the mechanism of insight.

    Title Soluble Fibroin Enhances Insulin Sensitivity and Glucose Metabolism in 3t3-l1 Adipocytes.
    Date March 2005
    Journal The Journal of Nutrition
    Excerpt

    Type 2 diabetes is characterized by hyperglycemia and hyperinsulinemia, features of insulin resistance. In vivo treatment of ob/ob mice with hydrolyzed fibroin reverses these pathological attributes. To explore the mechanism underlying this effect, we used the murine, 3T3-L1 adipocyte cell line, which has been used extensively to model adipocyte function. Chronic exposure of 3T3-L1 adipocytes to insulin leads to a 50% loss of insulin-stimulated glucose uptake. Chronic exposure to different preparations of fibroin partially blocked the response to insulin but also increased the sensitivity of control cells to the acute action of insulin. The latter effect was most robust at physiologic concentrations of insulin. Fibroin did not prevent the insulin-induced downregulation of the insulin receptor or the tyrosine kinase activity associated with the receptor. Further, fibroin had no effect on the activity of the insulin-sensitive downstream kinase, Akt. Interestingly, fibroin accelerated glucose metabolism and glycogen turnover independent of insulin action. In addition, fibroin upregulated glucose transporter (GLUT)1, which increased its expression at the cell surface and enhanced GLUT4 translocation. Together, these phenomena may underlie the improvement in diabetic hyperglycemia noted in vivo in response to fibroin.

    Title Neurofeedback Training with Virtual Reality for Inattention and Impulsiveness.
    Date February 2005
    Journal Cyberpsychology & Behavior : the Impact of the Internet, Multimedia and Virtual Reality on Behavior and Society
    Excerpt

    In this research, the effectiveness of neurofeedback, along with virtual reality (VR), in reducing the level of inattention and impulsiveness was investigated. Twenty-eight male participants, aged 14-18, with social problems, took part in this study. They were separated into three groups: a control group, a VR group, and a non-VR group. The VR and non-VR groups underwent eight sessions of neurofeedback training over 2 weeks, while the control group just waited during the same period. The VR group used a head-mounted display (HMD) and a head tracker, which let them look around the virtual world. Conversely, the non-VR group used only a computer monitor with a fixed viewpoint. All participants performed a continuous performance task (CPT) before and after the complete training session. The results showed that both the VR and non-VR groups achieved better scores in the CPT after the training session, while the control group showed no significant difference. Compared with the other groups, the VR group presented a tendency to get better results, suggesting that immersive VR is applicable to neurofeedback for the rehabilitation of inattention and impulsiveness.

    Title Traumatic Bowel Perforation: Analysis of Ct Findings According to the Perforation Site and the Elapsed Time Since Accident.
    Date January 2005
    Journal Clinical Imaging
    Excerpt

    Abdominal CTs of 57 patients with bowel perforation after blunt abdominal trauma were retrospectively analyzed to determine: the diagnostic accuracy of the perforation site, and the differential findings according to the elapsed time from the trauma. Diagnostic accuracy of the perforation site was as follows: duodenum (100%), jejunum (81%), jejunoileal junction (100%), ileum (93%), and colon (20%). Extraluminal air was the only significant differential findings according to the elapsed time, and was seen more commonly on late stage of bowel perforation (P<.05).

    Title Phthalates Inhibit Tamoxifen-induced Apoptosis in Mcf-7 Human Breast Cancer Cells.
    Date January 2005
    Journal Journal of Toxicology and Environmental Health. Part A
    Excerpt

    Environmental estrogens represent a class of compounds that can mimic the function or activity of the endogenous estrogen 17 -estradiol (E2). Phthalates including butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), and di(2-ethylhexyl) phthalate (DEHP) are used as plasticizers, and also widely used in food wraps and cosmetic formulations. Phthalates have been shown to mimic estrogen and are capable of binding to the estrogen receptor (ER). It has been demonstrated that estrogen promotes drug resistance to tamoxifen (TAM) in breast cancer. In order to further evaluate the potential role of the phthalates as environmental estrogens, the effect of phthalates was investigated on TAM-induced apoptosis in MCF-7 human breast cancer cells. Our results show that phthalates, BBP (100 M), DBP (10 M), and DEHP (10 M), significantly increased cell proliferation in MCF-7, but not in MDA-MB-231 cells. In addition, BBP, DBP, and DEHP mimicked estrogen in the inhibition of TAM-induced apoptosis in MCF-7 cells. Our data suggest that the inhibitory effect of phthalates on TAM-induced apoptosis involves an increase in intracellular Bcl-2 to Bax ratio. Given that the phthalates are widely used in cosmetics mainly for women, our findings that revealed the promoting effect of BBP, DBP, and DEHP on chemotherapeutic drug resistance to TAM in breast cancer may be of biological relevance.

    Title Neonatal Exposure to Di(n-butyl) Phthalate (dbp) Alters Male Reproductive-tract Development.
    Date January 2005
    Journal Journal of Toxicology and Environmental Health. Part A
    Excerpt

    The purpose of this study was to evaluate male reproductive-organ development in early postnatal male rats following neonatal exposure to di(n-butyl) phthalate (DBP) and identify a mechanism of action. Neonatal male rats were injected subcutaneously from d 5 to 14 after birth with corn oil (control) and DBP (5, 10, or 20 mg/animal). Animals were killed at postnatal day (PND) 31 and PND 42, respectively, and testes, epididymis, seminal vesicles, ventral prostate, levator ani plus bulbocavernosus muscles (LABC), and Cowper's glands were weighed. In addition, the expressions of androgen receptor (AR), estrogen receptors (ERs), and steroidogenic factor-1 (SF-1) were also examined in the testes. Total body weights gains were significantly reduced at PND 29-31, but gradually recovered on PND 42. However, DBP (20 mg/animal) significantly reduced the weights of testes and accessory sex organs (seminal vesicles, LABC, and Cowper's glands), but not of the epididymis. These adverse effects persisted through puberty at PND 42. Serum testosterone levels did not show any significant changes in the control and DBP treatment groups. Histomorphological examination showed mild diffuse Leydig-cell hyperplasia in the interstitium of severely affected tubules on PND 31. Only a few multinuclear germ cells were observed. DBP (20 mg/animal) significantly decreased the expression of AR, whereas ER expression and SF-1 expression were increased in a dose-dependent manner on PND 31 in the rat testes. On PND 42, DBP (20 mg/animal) significantly inhibited ER expression in the testes, but not AR, ER, and SF-1. These results demonstrate that neonatal exposure to DBP produces permanent changes in the endocrine system and leads to abnormal male reproductive-tract development until puberty. Thus our data suggest that DBP is likely to exert its antiandrogenic actions through disruption of AR or ER expression during the early neonatal stage.

    Title The Development of a Vr System for the Cognitive & Behavioral Assessment of Schizophrenia.
    Date December 2004
    Journal Studies in Health Technology and Informatics
    Excerpt

    Patients with schizophrenia have many trouble in their life due to their thinking disorders such as delusion or hallucination. It is because they have a deficit in the ability which to systematize and integrate information. Therefore, they cannot integrate or systematize properly the integrated stimuli occurring frequently in a real situation. In this study, we suggest a virtual reality system for the assessment of their ability to integrate, memorize and react to integrated stimuli. The virtual reality system we developed provided multimodal stimuli, such as visual and auditory stimuli or visuo-spatial integration, and the patients was assessed and compared their thought flexibility and working memory abilities based on multi-modal manner by making the patient experience and react to multimodal stimuli. From this study, we could conclude that the VR could provide a patient with various stimuli in an immersive environment and allow the assessment of cognitive ability, and the identification of the relationships between cognitive functions.

    Title Three-dimensional Reconstructed Images Using Multidetector Computed Tomography in Evaluation of the Biliary Tract.
    Date December 2004
    Journal Abdominal Imaging
    Excerpt

    The recent development of multidetector computed tomography (MDCT) and the parallel escalation in the capabilities of the workstation allow the use of high-quality multiplanar and three-dimensional reconstruction images. As a noninvasive technique, MDCT dedicated to the biliary tract represents an alternative to magnetic resonance cholangiography. The usefulness of three-dimensional reconstructed images using MDCT in evaluating biliary tract abnormality is illustrated.

    Title Restoration of Bone Morphogenetic Protein Receptor Type Ii Expression Leads to a Decreased Rate of Tumor Growth in Bladder Transitional Cell Carcinoma Cell Line Tsu-pr1.
    Date December 2004
    Journal Cancer Research
    Excerpt

    Bone morphogenetic proteins (BMPs), potential regulators of cellular growth and metastasis that signal through an interaction with plasma membrane receptors, have been suggested to be important regulators of malignant cells. The present study was carried out to evaluate the potential role of BMP receptor (BMP-R) types IA, IB, and II in bladder transitional cell carcinoma (TCC) cells. Initially, we investigated the expression of these BMP-Rs in 30 archival tissues of human bladder TCC using immunohistochemistry; 10 benign bladder specimens were used for comparison. The results demonstrated that the expression of BMP-Rs is localized preferentially to the transitional epithelium and that there was a significant association between loss of BMP-RII expression and tumor grade. To find a cell line that can serve as a model system for clinical observation, we subsequently examined sensitivity to BMP-4 and expression of BMP-RII, BMP-RIA, and BMP-RIB in three human bladder cancer cell lines, TCC-Sup, RT4, and TSU-Pr1. Of the three cell lines, TSU-Pr1 exhibited a decreased level of BMP-RII expression and was resistant to the growth-inhibitory effect of BMP-4. Overexpression of BMP-RII in TSU-Pr1 cells not only restored BMP-4 responsiveness but also significantly decreased tumorigenicity in vivo. Taken together, these results demonstrate that human bladder TCC tissues have a frequent loss of BMP-RII expression and that overexpression of BMP-RII leads to restoration of BMP signaling and decreased tumor growth in the human bladder TCC cell line TSU-Pr1.

    Title Loss of Expression of Bone Morphogenetic Protein Receptor Type Ii in Human Prostate Cancer Cells.
    Date November 2004
    Journal Oncogene
    Excerpt

    Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta superfamily and signal through a number of membrane receptors. We have previously demonstrated that the loss of expression of BMP receptors (BMPRs) type IA, -IB, and -II (BMP-RIA, -RIB, and -RII) correlates with Gleason score in prostate cancer patients. To evaluate the prognostic value of this observation, we used immunohistochemistry to investigate the expression of BMPRs in association with disease progression in 60 patients. The results demonstrated a significant association between the loss of expression of the three BMPRs and Gleason score and clinical stage. However, only the loss of expression of BMP-RII showed a statistically significant association with 5-year survival rate (P<0.05) and biochemical recurrence-free rate following radical prostatectomy (P<0.005). To elucidate the effect of an abnormal BMP signaling in prostate cancer cells, we transfected dominant-negative BMP-RII (BMP-RIIDN) into the human prostate cancer cell line, PC3M. When a stable clone overexpressing BMP-RIIDN was inoculated subcutaneously into nude mice, the tumor growth rate was approximately 10 times that of control and parental cell line. These observations, taken together, indicate that the loss of BMP-RII expression as measured by immunohistochemistry may be a prognostic marker in prostate cancer patients, and that the loss of BMP-RII function may result in increased tumorigenicity in human prostate cancer cells.

    Title Assessing Estrogenic Activity of Pyrethroid Insecticides Using in Vitro Combination Assays.
    Date November 2004
    Journal The Journal of Reproduction and Development
    Excerpt

    Pyrethroid insecticides are among the most commonly used classes of insecticides worldwide, but their endocrine disrupting activities remain unclear. Therefore, in the present study, we examined the estrogenic activities of pyrethroid insecticides in E-screen and competition binding assays. In addition, we measured estrogen receptor (ER) protein and pS2 mRNA levels in human breast cancer cells (MCF-7 BUS) to clarify the mechanism of their estrogenicity. Seven pyrethroid insecticides (bioallethrine, cypermethrin, deltamethrin, fenvalerate, permethrin, sumithrin, and tetramethrin) were tested because of their worldwide usage. In addition, 17beta-estradiol was tested as a positive control. As expected, 17beta-estradiol significantly increased MCF-7 BUS cell proliferation at concentrations of 10(-11) M and above. Of the pyrethroid insecticides tested, only sumithrin increased MCF-7 BUS cell proliferation in a dose-dependent manner; the maximum induction of cell proliferation was observed at a dose of 10(-5) M. In the anti-estrogenic activity test, bioallethrin, fenvalerate, and permethrin significantly inhibited 17beta-estradiol-induced MCF-7 BUS cell proliferation at 10(-6) M, a concentration comparable to the effective dose (10(-9) M) of ICI 182,780, a pure ER antagonist. However, none of the pyrethroid insecticides competitively inhibited the binding of [(3)H]estradiol to rat uterus ERs in competition binding assays. Both 17beta-estradiol (10(-10) M) and sumithrin (10(-5) M) decreased the levels of cytosolic ERalpha and ERbeta protein expression significantly as compared with the vehicle control. In addition, 17beta-estradiol (10(-10) M) increased pS2 mRNA expression markedly, and sumithrin significantly increased pS2 mRNA levels in a dose-dependent manner. The other six compounds tested in the present study did not affect ER protein levels or pS2 mRNA levels. These results suggest that certain pyrethroid insecticides may be considered to be estrogen-like chemicals that act through pathways other than direct ER binding, and may function as endocrine modulators in both wildlife and humans.

    Title An Investigation of Immersiveness in Virtual Reality Exposure Using Physiological Data.
    Date November 2004
    Journal Studies in Health Technology and Informatics
    Excerpt

    As virtual reality technology is increasingly attracting significant attention in clinical psychology, especially in the treatment of phobias, physiological monitoring is increasingly considered as an objective measuring tool for studying participants. However, there are few studies of the normal individual's physiological response to virtual environments, or their reactions to different virtual environments. The goal of this study is to analyze non-phobic participants' physiological reaction to two virtual environments: driving and flying and to investigate the usefulness of heart rate variability. Eleven non-phobic participants were exposed to each virtual environment for 15 minutes. Heart rate, skin resistance, and skin temperature measurements were taken for physiological monitoring and Presence and Simulator Sickness Questionnaires were obtained after each exposure. This study found that skin resistance and heart rate variability can be used to show arousal of participant exposed to virtual environments experience and that such measures generally returned to normal as time went by. The Study showed that skin resistance and heart rate can be used as objective measures in monitoring the reaction of non-phobic participants to virtual environments. Significantly, heart rate variability analysis in virtual environments showed that it could be useful for assessing the emotional states of participants.

    Title The Development and Clinical Trial of a Driving Simulator for the Handicapped.
    Date November 2004
    Journal Studies in Health Technology and Informatics
    Excerpt

    We developed a Virtual Reality Driving Simulator in order to safely evaluate and improve the driving ability of the handicapped. The Virtual Environment consists of 18 sections (e.g. a speed limited road, a strait road, a curved road, a left turn course, etc) and each section is linked naturally. For the interface of our driving simulator, an actual car was adapted for realism and then connected to a computer. We also equipped it with hand control driving devices especially adapted for the handicapped. A beam projector was used so that the subjects could see the virtual scene on a large screen which was set in front of them. The subjects selected for this trial were 10 normal drivers with valid driving licenses and 15 patients with thoracicor lumber cord injuries who had prior driving experience. For evaluation, 5 driving skills were measured including average speed, steering stability, centerline violations, traffic signal violations, and driving time in various road conditions such as strait and curved roads. The normal subjects manipulated the gas pedal and the brake with their feet while the patients manipulated a hand control with their hands. After they finished driving the whole course, the participants answered the questions such as "How realistic did the Virtual Reality Driving Simulator seeme to you?" and "How much was your fear reduced". The five driving skills measured between the two groups (normal vs. handicapped) did not show any significant differences (p > 0.05). And in the three kinds of road conditions (a speed limited road and roads with a sharp curve and left-hand turn), the average speed of the handicapped group was 45.6 Km, less than 61.2 Km (p<0.05) of the normal group. In all, 11 patients (73%) reported that their fear of driving was reduced. Furthermore, their average score on the degree of realism question was 51.5%.

    Title Development of a Virtual Speaking Simulator Using Image Based Rendering.
    Date November 2004
    Journal Studies in Health Technology and Informatics
    Excerpt

    The fear of speaking is often cited as the world's most common social phobia. The rapid growth of computer technology has enabled the use of virtual reality (VR) for the treatment of the fear of public speaking. There are two techniques for building virtual environments for the treatment of this fear: a model-based and a movie-based method. Both methods have the weakness that they are unrealistic and not controllable individually. To understand these disadvantages, this paper presents a virtual environment produced with Image Based Rendering (IBR) and a chroma-key simultaneously. IBR enables the creation of realistic virtual environments where the images are stitched panoramically with the photos taken from a digital camera. And the use of chroma-keys puts virtual audience members under individual control in the environment. In addition, real time capture technique is used in constructing the virtual environments enabling spoken interaction between the subject and a therapist or another subject.

    Title Different Distributions of Selenoprotein W and Thioredoxin During Postnatal Brain Development and Embryogenesis.
    Date October 2004
    Journal Molecules and Cells
    Excerpt

    Whereas the levels of other selenoproteins in the brain decrease when selenium is deficient, the level of selenoprotein W (Se-W) is maintained, suggesting that it has a critical role in the brain. Previously, we reported that Se-W is a GSH-dependent antioxidant [Jeong et al. (2002)]. In this study, the expression of Se-W and thioredoxin (Trx) in the brain and during embrynic development was analyzed by an in situ hybridization technique. Se-W mRNA was highly expressed in the cortex, dentate gyrus, and hippocampus of postnatal rat brains, and in the spinal cord and brain of developing embryos. In contrast, Trx mRNA was highly expressed in the cerebellum, olfactory bulb, and dentate gyrus of postnatal rat brains, and in the liver, telencephalon, and back muscle of developing embryos. Thus these two antioxidant proteins have different and non-overlapping expression patterns. The distribution of Se-W suggests that it plays an important role as an antioxidant in the developing brain and embryo.

    Title Tissue Expression of Transforming Growth Factor-beta1 and Its Receptors: Correlation with Pathologic Features and Biochemical Progression in Patients Undergoing Radical Prostatectomy.
    Date October 2004
    Journal Urology
    Excerpt

    OBJECTIVES: To determine whether the abnormal expression of transforming growth factor-beta1 (TGF-beta1) and/or its receptors (TGFbeta-RI and TGFbeta-RII) is associated with prostate cancer features and progression; and to investigate the relationship between tissue expression of TGFs and blood levels of TGF-beta1. METHODS: Immunohistochemical staining for TGF-beta1, TGFbeta-RI, and TGFbeta-RII was carried out on archival specimens from 118 consecutive patients who underwent radical prostatectomy for clinically localized disease (median follow-up 57.5 months). Preoperative plasma TGF-beta1 levels were also measured. RESULTS: TGF-beta1 was overexpressed in 71 (60%) of 118 patients, and TGFbeta-RI and TGFbeta-RII expression was decreased in 34 (29%) and 39 (33%) of 118 patients, respectively. Of the 118 patients, 82 (70%) had abnormal expression of at least one of the three TGFs and 22 (19%) had abnormal expression of all three. The concordance rates between the expression of TGF-beta1 and its receptors were 54% and 62%. Abnormal expression of all three TGFs was significantly associated with extracapsular disease. However, only decreased expression of TGFbeta-RI and TGFbeta-RII was significantly associated with seminal vesicle involvement and greater pathologic Gleason score. Preoperative plasma TGF-beta1 levels were significantly elevated in patients with abnormal expression of TGFs. TGFbeta-RI expression and surgical margin status were independently associated with biochemical progression. CONCLUSIONS: Our results showed that abnormal expression of TGF-beta1 and its receptors is common in prostate cancer. TGF-beta1 overexpression is moderately but significantly associated with a loss of expression of TGFbeta-RI and TGFbeta-RII. Loss of TGFbeta-RI expression is a prognostic marker in patients with prostate cancer.

    Title Analysis of the Hemispheric Asymmetry Using Fractal Dimension of a Skeletonized Cerebral Surface.
    Date September 2004
    Journal Ieee Transactions on Bio-medical Engineering
    Excerpt

    We investigated hemispheric asymmetry using the fractal dimension (FD) of the skeletonized cerebral surface. Sixty-two T1-weighted magnetic resonance imaging volumes from normal Korean adults were used. The skeletonization of binary volume data, which corresponded to the union of the gray matter and cerebrospinal flow classified by fuzzy clustering, was performed slice by slice in the sagittal direction, and then skeletonized slices were integrated into the three-dimensional (3-D) hemisphere. Finally, the FD of the 3-D skeletonized cerebral surface was calculated using the box-counting method. We measured the FD of the skeletonized cerebral surface and the volumes of intracranial gray matter and white matter for the whole hemispheres and obtained the hemispheric asymmetries of each measurement. The FD, the gray matter, and the white matter volumes for the whole hemispheres decreased in the old group. The asymmetry of the FD revealed a significant right-greater-than-left asymmetry showed rightward, but did not change according to age and gender. None of the intracranial gray matter or white matter volumes showed any significant asymmetric changes. It could be said that the FD of the skeletonized cerebral surface is a novel measure of cerebral asymmetry.

    Title Deformable Model with Surface Registration for Hippocampal Shape Deformity Analysis in Schizophrenia.
    Date August 2004
    Journal Neuroimage
    Excerpt

    Changes to the hippocampal structure have been reported as consistent structural abnormalities in schizophrenic patients and have been related to the learning and memory deficits in such patients. Although many magnetic resonance (MR) imaging studies have focused on the hippocampal volume, local structural changes were difficult to discriminate from normal neuroanatomical variations. 3D shape deformation analysis of the brain structure may reflect localized schizophrenic abnormalities. A deformable model, evolved from the ellipsoid to hippocampal surface, with 2562 vertexes, was developed to analyze the left and right hippocampus shapes in 22 schizophrenic patients and 22 healthy age and gender matched controls. One of the most critical issues in the shape analysis is the determination of homologous points between two objects. To determine more accurate corresponding points, an alignment procedure, consisting of coarse and fine steps, following a deformation process, was applied. The performance of the alignment process was tested using artificial data, to get the alignment error to within 3 degrees for each angle. A volume analysis indicated the hippocampal volume to be bilaterally reduced in schizophrenic patients compared to the normal controls, with a shape analysis showing a deformity pattern of the hippocampal surface. Bilateral inward deformities in the anterior and posterior hippocampus and a unilateral outward deformity in the right anterior hippocampus were observed, respectively.

    Title Decreased Expression of Bone Morphogenetic Protein (bmp) Receptor Type Ii Correlates with Insensitivity to Bmp-6 in Human Renal Cell Carcinoma Cells.
    Date July 2004
    Journal Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
    Excerpt

    PURPOSE: Bone morphogenetic proteins (BMPs) are members of a family of pleiotropic growth factors that play a critical role during renal development as well as maintaining kidney homeostasis. In the present study, we investigated the potential role of BMP receptors (BMPRs) in renal cell carcinoma (RCC) cells. EXPERIMENTAL DESIGN: Immunohistochemistry was used to investigate the expression of BMPRs in human RCC tissues. As an in vitro model of RCC, three cell lines were used: 112, 117, and 181. Northern blot, immunoblot, and reverse transcription-PCR were used to study the expression of BMPRs in the cell lines. Finally, cells were transfected using LipofectAMINE. RESULTS: Normal human kidney tissues express the three BMPRs: types RIA, RIB, and RII. In contrast, human RCC cells frequently exhibit a loss of expression of BMP-RII. In tissue culture, BMP-6 inhibits in a dose-dependent manner the proliferation of 112 cells but not of 117 and 181 cells. Assays for BMPRs demonstrated that 117 and 181 cells express low levels of BMP-RII RNA. When these two BMP-6 resistant cell lines were infected with the adenovirus containing the constitutively active form of BMP-RIA or -RIB in combination with a BMP-6-responsive luciferase reporter construct, luciferase activity increased. Finally, when these cell lines were transfected with BMP-RII, BMP-6-sensitivity was restored. CONCLUSIONS: These results demonstrate that human RCC tissues frequently have decreased levels of expression of BMP-RII and that the human RCC cell lines 117 and 181 are resistant to the growth-inhibitory effect of BMP-6 because they have decreased levels of expression of BMP-RII.

    Title Comparison of Anti-androgenic Activity of Flutamide, Vinclozolin, Procymidone, Linuron, and P, P'-dde in Rodent 10-day Hershberger Assay.
    Date July 2004
    Journal Toxicology
    Excerpt

    The rodent Hershberger assay proposed by the Organization for Economic Co-operation and Development (OECD) is in the process of the validating a test method to detecting the androgenic or anti-androgenic compounds. The aim of this study was to compare the anti-androgenic properties of flutamide, vinclozolin, procymidone, linuron, and p,p'-DDE in a 10-day Hershberger assay. In the present study, we used immature Sprague-Dawley male rats castrated at 6 weeks of age. Testosterone propionate (TP) was subcutaneously injected for 10 consecutive days at doses of 0.1, 0.2, 0.4, 0.8, or 1.6 mg/kg per day. To compare the anti-androgenic activity of test compounds, flutamide (1, 5, 10, or 20 mg/kg per day), a pure androgen antagonist was used as a positive control, and administered by oral gavage after TP (0.4 mg/kg per day) treatment. In addition, vinclozolin (25, 50, or 100 mg/kg per day), procymidone (25, 50, or 100 mg/kg per day), linuron (25, 50, or 100 mg/kg per day), and p,p '-DDE (25, 50, or 100 mg/kg per day) were also administered by oral gavage after TP (0.4 mg/kg per day) treatment. As expected, TP dose-dependently increased accessory sex organ weights, and statistically significant effects were observed at doses of 0.1 (only seminal vesicles) or 0.2mg/kg per day and above. Serum testosterone levels increased significantly at 0.4 mg/kg per day and above, while serum LH levels were decreased in a dose-dependent manner. Flutamide significantly inhibited the TP-induced re-growth of seminal vesicles, ventral prostate, and Levator ani plus bulbocavernosus muscles (LABC) at 1mg/kg per day and above, and Cowper's glands and glans penis at 5mg/kg per day and above. In contrast to accessory sex organ weights, flutamide did not affect the serum testosterone levels compared to the control at any concentration, but serum LH levels were significantly increased at doses of 10 and 20 mg/kg per day. Similar to flutamide, vinclozolin caused a statistically significant decrease in the weights of seminal vesicles (to 65 and 40% of the control), ventral prostate (to 66 and 51% of the control), LABC (to 81 and 66% of the control), and Cowper's glands (to 81 and 65% of the control) at 50 and 100 mg/kg per day, respectively. Glans penis weight was also significantly reduced (to 79% of the control), but only at 100 mg/kg per day. The most pronounced effects were observed in the procymidone treatment groups. Procymidone significantly inhibited TP-induced re-growth of accessory sex organs at 25mg/kg per day and above, whereas glans penis weight significantly decreased (to 69% of the control), but only at 100 mg/kg per day. Linuron also inhibited TP-induced re-growth of the seminal vesicles (to 72 and 53% of the control), ventral prostate (to 75 and 62% of the control), Cowper's glands (to 74 and 61% of the control) at 50 and 100 mg/kg per day, respectively. LABC (to 65% of the control) and glans penis (to 80% of the control) weights were significantly reduced, but only at 100 mg/kg per day. In case of p,p'-DDE, seminal vesicle weights were significantly decreased at 50 (to 66% of the control) and 100 mg/kg per day (to 58% of the control). In addition, ventral prostate (to 79% of the control), LABC (to 75% of the control), and Cowper's gland (to 82% of the control) weights were reduced, but only at 100 mg/kg per day. On the contrary, no statistically significant differences in serum testosterone or LH levels were observed versus the control. p,p'-DDE significantly increased liver weight in a dose-dependent manner, without affecting on body weights. Our results indicate that procymidone may act as a stronger androgen receptor (AR) antagonist than vinclozolin, linuron, or p,p'-DDE. We conclude that the 10-day Hershberger assay is a sensitive method for detecting potential anti-androgenic compounds.

    Title Left Anterior Subregion of Orbitofrontal Cortex Volume Reduction and Impaired Organizational Strategies in Obsessive-compulsive Disorder.
    Date May 2004
    Journal Journal of Psychiatric Research
    Excerpt

    The orbitofrontal cortex (OFC) may be involved in the clinical and cognitive expressions of obsessive-compulsive disorder (OCD) and is a heterogenous region with respect to its cytoarchitecture, function and connectivity. This study was designed to examine the morphological abnormality of the anterior subregion of OFC and its relationship to clinical symptoms and cognitive performance in patients with OCD. We divided the OFC into anterior and posterior subregions using an external landmark and measured the gray matter volumes of each by three-dimensional magnetic resonance imaging in age- and sex-matched groups, which consisted of 34 OCD and 34 normal volunteers. Clinical and cognitive evaluations were completed using Yale-Brown Obsessive Compulsive Scale (YBOCS) and four sets of neuropsychological tests that assessed executive functions and visual memory. Volume reduction of the left anterior OFC was observed in patients with OCD versus normal controls. Also, a significant positive correlation was found between left anterior OFC gray matter volume and the copy score of the Rey-Osterrieth Complex Figure Test in patients with OCD. These results suggest that left anterior subregion volume reduction of the OFC may be related to impaired organizational strategies in patients with OCD.

    Title A Data Glove with Tactile Feedback for Fmri of Virtual Reality Experiments.
    Date April 2004
    Journal Cyberpsychology & Behavior : the Impact of the Internet, Multimedia and Virtual Reality on Behavior and Society
    Excerpt

    Virtual reality (VR) technology is increasingly recognized as a useful tool for the assessment and rehabilitation of neurologic and psychiatric disorders. The hope that VR can accurately mimic real-life events is also of great interest in basic neuroscience, to identify the brain activity that underlies complex behavior by combining VR with techniques such as functional magnetic resonance imaging (fMRI). Toward these applications, in this study we designed and validated an fMRI-compatible data glove with a built-in vibratory stimulus device for tactile feedback during VR experiments. A simple VR-fMRI experiment was performed at 3.0 Tesla on four young healthy adults involving touching a virtual object with and without tactile feedback. The usefulness of the data glove was subsequently assessed using a series of questionnaires, behavioral performance, and the resulting activation images. Questionnaire scores indicated positive opinions with respect to the data glove, the tactile feedback, and the experimental paradigm. All subjects felt comfortable in the scanner during the VR experiment and were able to perform all aspects of the tasks successfully and with reasonable accuracy. In addition, activation maps showed the anticipated modulations in motor, somatosensory, and parietal cortex. These results support that tactile feedback enhances the realism of virtual hand-object interactions, and that the tactile data glove is suitable for use in other VR-fMRI research applications (e.g., VR physical therapy for stroke recovery).

    Title Web-based Remote Monitoring of Infant Incubators in the Icu.
    Date March 2004
    Journal International Journal of Medical Informatics
    Excerpt

    A web-based real-time operating, management, and monitoring system for checking temperature and humidity within infant incubators using the Intranet has been developed and installed in the infant Intensive Care Unit (ICU). We have created a pilot system which has a temperature and humidity sensor and a measuring module in each incubator, which is connected to a web-server board via an RS485 port. The system transmits signals using standard web-based TCP/IP so that users can access the system from any Internet-connected personal computer in the hospital. Using this method, the system gathers temperature and humidity data transmitted from the measuring modules via the RS485 port on the web-server board and creates a web document containing these data. The system manager can maintain centralized supervisory monitoring of the situations in all incubators while sitting within the infant ICU at a work space equipped with a personal computer. The system can be set to monitor unusual circumstances and to emit an alarm signal expressed as a sound or a light on a measuring module connected to the related incubator. If the system is configured with a large number of incubators connected to a centralized supervisory monitoring station, it will improve convenience and assure meaningful improvement in response to incidents that require intervention.

    Title Modification of Glycolysis Affects Cell Sensitivity to Apoptosis Induced by Oxidative Stress and Mediated by Mitochondria.
    Date March 2004
    Journal Biochemical and Biophysical Research Communications
    Excerpt

    The effect of alteration of the glycolytic pathway on cell damage induced by oxidative stress was investigated with dihydrofolate reductase-deficient Chinese hamster ovary (CHO) cells that either overexpress cytosolic glycerol-3-phosphate dehydrogenase (CHO/cGPDH cells) or are depleted of the A subunit of lactate dehydrogenase as a result of anti-sense RNA expression (CHO/anti-LDH cells). The extent of oxidative phosphorylation in CHO/anti-LDH and CHO/cGPDH cells was increased and decreased, respectively, relative to that in parental CHO cells, as revealed by measurement of the intracellular content of ATP, the rate of cellular O(2) consumption, the mitochondrial membrane potential (DeltaPsi(m)), and the generation of reactive oxygen species. The sensitivity of these cell lines to cell death induced by the exogenous oxidant tert-butyl hydroperoxide decreased according to the rank order CHO/anti-LDH>CHO>CHO/cGPDH. Exogenous pyruvate markedly increased the sensitivity of CHO/cGPDH cells to oxidant-induced death. The differences among the three cell lines in susceptibility to oxidant-induced death were reflected in the proportion of oxidant-treated cells with a subdiploid DNA content, with a collapsed DeltaPsi(m), and with cytochrome c in the cytosol, indicating that death was mediated by apoptosis. These results demonstrate that the influx of respiratory substrate into mitochondria is an important determinant of cell sensitivity to oxidant-induced apoptosis.

    Title Evaluation of Automated and Semi-automated Skull-stripping Algorithms Using Similarity Index and Segmentation Error.
    Date February 2004
    Journal Computers in Biology and Medicine
    Excerpt

    The skull-stripping in the MR brain image appears to be a key issue in neuroimage analysis. In this paper, we evaluated the accuracy and efficiency of both automated and semi-automated skull-stripping methods. The evaluation was performed on both simulated and real data with the ground truth in skull-stripping. Although automated method showed better efficient results, it should require additional intervention. In contrast to that, semi-automated method showed better accurate results, but it was time consuming and prone to operator bias. Therefore, it might be practical that the semi-automated method was used as the post-processing of the automated one.

    Title Modification of Promyelocytic Leukemia Zinc Finger Protein (plzf) by Sumo-1 Conjugation Regulates Its Transcriptional Repressor Activity.
    Date January 2004
    Journal The Journal of Biological Chemistry
    Excerpt

    Promyelocytic leukemia zinc finger (PLZF) protein is a sequence-specific DNA-binding protein that represses the transcriptional activity of target genes such as those for cyclin A and the interleukin-3 receptor alpha chain. The PLZF gene becomes fused to the retinoic acid receptor alpha gene as a result of the t(11, 17)(q23;q21) chromosomal translocation that is associated with acute promyelocytic leukemia. We now show that endogenous PLZF in human promyelocytic leukemia HL-60 cells is modified by conjugation with SUMO-1 (small ubiquitin-related modifier-1) and that PLZF colocalizes with SUMO-1 in the nucleus of transfected human embryonic kidney 293T cells. Site-directed mutagenesis identified lysine 242 in the RD2 domain of human PLZF as the sumoylation site. A luciferase reporter gene assay suggested that SUMO-1 modification of this residue is required for transcriptional repression by PLZF, and an electrophoretic mobility shift assay showed that this modification increases the DNA binding activity of PLZF. PLZF-mediated regulation of the cell cycle and transcriptional repression of the cyclin A2 gene were also dependent on sumoylation of PLZF on lysine 242. These results demonstrate that PLZF is modified by SUMO-1 conjugation and that this modification regulates the biological functions of PLZF.

    Title A Virtual Reality System for the Assessment and Rehabilitation of the Activities of Daily Living.
    Date January 2004
    Journal Cyberpsychology & Behavior : the Impact of the Internet, Multimedia and Virtual Reality on Behavior and Society
    Excerpt

    Successful rehabilitation with respect to the activities of daily living (ADL) requires accurate and effective assessment and training. A number of studies have emphasized the requirement for rehabilitation methods that are both relevant to the patient's real world environment, and that can also be transferred to other daily living tasks. Virtual reality (VR) has many advantages over other ADL rehabilitation techniques, and offers the potential to develop a human performance testing and training environment. Therefore, in this study, the virtual supermarket was developed and the possibility of using a VR system to assess and train cognitive ability in ADL investigated. This study demonstrates that VR technology offers great promise in the field of ADL training.

    Title A Virtual Environment for Investigating Schizophrenic Patients' Characteristics: Assessment of Cognitive and Navigation Ability.
    Date January 2004
    Journal Cyberpsychology & Behavior : the Impact of the Internet, Multimedia and Virtual Reality on Behavior and Society
    Excerpt

    Patients with schizophrenia have thinking disorders such as delusions or hallucinations because they have a deficit in the ability to systematize and integrate information. Therefore, they cannot integrate or systematize visual, auditory, and tactile stimuli. The multimodal integration model of the brain can provide a theoretical background from which one can approach multimodal stimulus integration. In this study, we suggest a virtual reality system for the multi-modal assessment of cognitive ability of schizophrenia patients. The virtual reality system can provide multimodal stimuli, such as visual and auditory stimuli, to the patient and can evaluate the patient's multimodal integration and working memory integration abilities by making the patient interpret and react to multimodal stimuli, which must be remembered for a given period of time. The clinical study showed that the virtual reality program developed is comparable to those of the Wisconsin Card Sorting Test (WCST) and the Standard Progressive Matrices (SPM), and it provides some information related to the schizophrenic patients' behavior in 3D virtual environment.

    Title Induction of the Mitochondrial Permeability Transition by Selenium Compounds Mediated by Oxidation of the Protein Thiol Groups and Generation of the Superoxide.
    Date January 2004
    Journal Biochemical Pharmacology
    Excerpt

    The cancer chemopreventive effect of selenium compounds cannot be fully explained by the role of selenium as a component of antioxidant enzymes, suggesting that other mechanisms, such as thiol oxidation or free radical generation, also underlie this effect. The toxicities of six different selenium compounds (selenite, selenate, selenocystine, selenocystamine, selenodioxide, and selenomethionine) have now been compared in HepG2 human hepatoma cells and isolated rat liver mitochondria. Selenite, selenocystine, and selenodioxide induced apoptosis in HepG2 cells and mediated oxidation of protein thiol groups in both HepG2 cells and isolated mitochondria. Selenocystamine oxidized protein thiol groups in isolated mitochondria and crude extracts of HepG2 cells but not in intact HepG2 cells, suggesting that this compound is not able to cross the cell membrane. The selenium compounds capable of oxidizing thiol groups also induced the mitochondrial permeability transition (MPT) in isolated mitochondria. Furthermore, they generated the superoxide (O(2) .-) on reaction with glutathione in the presence of mitochondria, and an O(2) .-) scavenger inhibited their induction of the MPT. These results suggest that the pro-apoptotic action of selenium compounds is mediated by both thiol oxidation and the generation of O(2) .-), both of which contribute to opening of the MPT pore.

    Title Experimental Application of Virtual Reality for Nicotine Craving Through Cue Exposure.
    Date November 2003
    Journal Cyberpsychology & Behavior : the Impact of the Internet, Multimedia and Virtual Reality on Behavior and Society
    Excerpt

    Research has shown that many smokers experience an increase in the desire to smoke when exposed to smoking-related cues. Cue exposure treatment (CET) refers to the manualized, repeated exposure to smoking-related cues, aimed at the reducing cue reactivity by extinction. In this study, we constructed a virtual reality system for evoking a desire of nicotine, which was based on the results of a Questionnaire of Nicotine-craving. And we investigated the effectiveness of the virtual reality system as compared to classical device (pictures). As a result, we reached the conclusion that virtual reality elicits more craving symptoms than the classical devices.

    Title A Pc-based High-quality and Interactive Virtual Endoscopy Navigating System Using 3d Texture Based Volume Rendering.
    Date September 2003
    Journal Computer Methods and Programs in Biomedicine
    Excerpt

    As an alternative method to optical endoscopy, visual quality and interactivity are crucial for virtual endoscopy. One solution is to use the 3D texture map based volume rendering method that offers high rendering speed without reducing visual quality. However, it is difficult to apply the method to virtual endoscopy. First, 3D texture mapping requires a high-end graphic workstation. Second, texture memory limits reduce the frame-rate. Third, lack of shading reduces visual quality significantly. As 3D texture mapping has become available on personal computers recently, we developed an interactive navigation system using 3D texture mapping on a personal computer. We divided the volume data into small cubes and tested whether the cubes had meaningful data. Only the cubes that passed the test were loaded into the texture memory and rendered. With the amount of data to be rendered minimized, rendering speed increased remarkably. We also improved visual quality by implementing full Phong shading based on the iso-surface shading method without sacrificing interactivity. With the developed navigation system, 256 x 256 x 256 sized brain MRA data was interactively explored with good image quality.

    Title Oxidative Stimuli Affect Polyglutamine Aggregation and Cell Death in Human Mutant Ataxin-1-expressing Cells.
    Date September 2003
    Journal Neuroscience Letters
    Excerpt

    Spinocerebellar ataxia 1 (SCA1), one of the inherited polyglutamine neurodegenerative diseases, is associated with intracellular aggregates. However, the process of aggregate formation and the factors that influence aggregation remain unclear. Here, we show that oxidative stimuli and alteration of the cellular redox state significantly affect aggregation and cell death in cells expressing mutant ataxin-1, the SCA gene product. Treatment of cells with buthionine sulfoximine, hydrogen peroxide or t-butylhydroperoxide increased the formation of mutant ataxin-1 aggregates, but treatment with the anti-oxidant, N-acetylcysteine (NAC), decreased aggregate formation. Oxidative damage of mutant ataxin-1 protein increased its recruitment in nuclear aggregates and increased cell death. However, NAC treatments reduced cell death and the number of cells with abnormal morphology. Our results might give insight into the mechanism whereby polyglutamine proteins aggregate and suggest that treatment of appropriate antioxidant reagents might prevent progression of SCA1 and other polyglutamine diseases.

    Title Laparoscopic Duodenojejunostomy for Management of Superior Mesenteric Artery Syndrome: Two Cases Report and a Review of the Literature.
    Date September 2003
    Journal Yonsei Medical Journal
    Excerpt

    Superior mesenteric artery(SMA) syndrome is rare disorder, which is caused by a reduction in the aortomesenteric angle causing a duodenal obstruction. It is usually occurs after a period of weight loss, nausea, and vomiting by a partial obstruction of the third portion of the duodenum. If conservative management fails then a laparotomy with a duodenojejunostomy is indicated. Recently, a minimally invasive or laparoscopic approach to the retroperitoneum or duodenal detachment was introduced. Although the role of a laparoscopy in managing SMA syndrome is not clearly defined, a laparoscopic duodenojejunostomy may be an alternative approach to the surgical treatment of SMA syndrome cases. Two cases of superior mesenteric artery syndrome that were treated laparoscopically after medical therapy failure are described. The 4-port procedure was performed. A dilated bowel on the third portion of the duodenum was observed below the transverse mesocolon and to right of the superior mesenteric artery. A proximal loop of the jejunum was anastomosed to the duodenum using an endoscopic GIA stapler. The surgery time and hospital length of stay were acceptable. No complications were encountered in this study. A laparoscopic duodenojejunostomy is a feasible alternative option for treating SMA syndrome. It provides the benefits of being a definitive and minimally invasive surgical technique in a duodenal obstruction.

    Title Polyglutamine-expanded Ataxin-1 Recruits Cu/zn-superoxide Dismutase into the Nucleus of Hela Cells.
    Date September 2003
    Journal Biochemical and Biophysical Research Communications
    Excerpt

    Spinocerebellar ataxia 1 (SCA1) is an inherited neurodegenerative disorder caused by expansion of the polyglutamine stretch in ataxin-1, the SCA1 gene product. Polyglutamine expansion leads to the aggregation of ataxin-1 proteins. Superoxide dismutases (SODs) are involved in the pathogenesis of other aggregate-forming neurodegenerative diseases and are known to localize in the cytoplasm. Here, we show that Cu/Zn-SOD is translocated into the nucleus of HeLa cells in the presence of expanded ataxin-1, whereas Mn-SOD is localized in the cytoplasm: the longer the expansion of polyglutamine, the higher the level of translocation of Cu/Zn-SOD. In addition, the oxidation of intracellular proteins occurs with higher frequency in the presence of mutant ataxin-1 (82Q), suggesting that the functional activity of Cu/Zn-SOD might be decreased by mutant ataxin-1. We demonstrate that mutant ataxin-1-expressing cells encounter mitochondrial dysfunction in the conditions of oxidative stress. Our results suggest that polyglutamine-expanded ataxin-1 increases the levels of reactive oxygen species in HeLa cells.

    Title Modified Magnetic Resonance Image Based Parcellation Method for Cerebral Cortex Using Successive Fuzzy Clustering and Boundary Detection.
    Date August 2003
    Journal Annals of Biomedical Engineering
    Excerpt

    Development of the accurate and reproducible parcellation of the human brain can be used to resolve the complex structure-functional relationships in the brain. We propose a modified parcellation method that provides the reliable and reproducible regions of interest using successive fuzzy c-means (sFCM) and boundary-detection algorithm. This method displays simultaneously both original brain image for identifying the sulcal landmarks and its tissue-classified image for referring to patterns of sulci. The whole cerebral region is extracted by the semiautomated region growing method and then classified to gray matter, white matter, and cerebrospinal fluid by sFCM. Referred to the other previous researches, the volume ratio of gray matter to white matter was shown to find that the efficiency of classification was improved (conventional FCM: 0.80 +/- 0.12 vs. sFCM: 1.57 +/- 0.18). Inter-rater reliability, estimated by the regression analysis, demonstrated that the proposed method was more reliable and reproducible than conventional methods [ANALYZE: correlation coefficient (CC)=0.341, Sig.=0.335 vs. proposed method: CC=0.816, Sig.=0.004]. The volume ratio of the whole cerebrum to the parceled object can be used to investigate structural abnormalities for the pathological detection of the various mental diseases such as schizophrenia, obsessive-compulsive disorder.

    Title Morphometric Abnormality of the Insula in Schizophrenia: a Comparison with Obsessive-compulsive Disorder and Normal Control Using Mri.
    Date June 2003
    Journal Schizophrenia Research
    Excerpt

    The insula is increasingly the subject of great interest in psychiatric disorders of neurodevelopmental origin because of its anatomical location, wide interconnectivity, and variety of functions. This study explores the possible morphometric change of the insula in schizophrenia and obsessive-compulsive disorder (OCD), and its potential relationship to clinical symptoms. The insula was traced on all coronal slices of magnetic resonance images of three age- and sex-matched diagnostic groups, which consisted of 21 patients with schizophrenia, 21 patients with OCD and 21 normal volunteers. The volumetric measures of the insula were compared among the three groups, and their relationships to the symptom severity were investigated. Volumetric reduction of the left insula was observed in the schizophrenia group, but not in the OCD group. These results confirm the involvement of deficient insular function in the pathophysiology of schizophrenia.

    Title Comparative Estrogenic Effects of P-nonylphenol by 3-day Uterotrophic Assay and Female Pubertal Onset Assay.
    Date February 2003
    Journal Reproductive Toxicology (elmsford, N.y.)
    Excerpt

    Nonylphenol (NP) is widely used as a component of detergents, paints, pesticides, and many other formulated products. Several studies have demonstrated that NP is estrogenic in fish, avian, and mammalian cells. NP also competitively inhibits the binding of 17 beta-estradiol (E2) to the estrogen receptor (ER). However, there are relatively few in vivo data related to this issue in mammals. The aim of this study was to investigate the estrogenic activity of NP in animal models. We performed a 3-day uterotrophic assay using immature female rats for comparison with other endpoints of Tier I screening including vaginal opening (VO) in prepubertal intact female rats. For the uterotrophic assay, diethylstilbestrol (DES) (0.2 and 1.0 microg/kg) and p-NP (10, 25, 50, 100, and 200 mg/kg) were administered subcutaneously to immature Sprague-Dawley female rats for 3 consecutive days (postnatal days (PND) 20, 21, and 22). For the female pubertal onset assay, DES (0.2, 1.0, and 5.0 microg/kg) and p-NP (10, 50, and 100 mg/kg) were administered daily by oral gavage from 21 days of age for 20 days. In the uterotrophic assay, statistically significant increases in uterine wet weight were observed at doses of 100 and 200 mg/kg p-NP. DES (0.2 and 1.0 microg/kg) also significantly increased uterine weight compared to the vehicle control. In the female pubertal onset assay, the age of VO was advanced following oral exposure to DES (1.0 and 5.0 microg/kg) and p-NP (50 and 100 mg/kg). Estrous cyclicity was monitored in prepubertal rats from the day of VO to the day of necropsy. Irregular estrous cycles were observed in the groups treated with DES (5.0 microg/kg) and p-NP (50 and 100 mg/kg). High-dose DES (5.0 microg/kg) produced a persistent estrus state, whereas p-NP (50 and 100 mg/kg) increased the number of days in diestrus. Serum thyroxine (T(4)) concentrations were decreased in a dose-dependent manner by DES and p-NP treatment. A significant decrease in serum T(4) level was observed at high-dose DES (5.0 microg/kg) and p-NP (100 mg/kg). Serum TSH level was significantly increased by DES (5.0 microg/kg) treatment. Statistically significant decreases in ovarian weight were observed in female rats treated with DES (5.0 microg/kg) and p-NP (100 mg/kg). Our data demonstrate that p-NP can accelerate the onset of puberty and alter estrous cyclicity in prepubertal female rats at oral doses lower than the subcutaneous doses typically used in the uterotrophic assay. We therefore suggest that the female pubertal onset assay may be used as a sensitive testing method to detect environmental agents with weak estrogenic activity, but requires further research.

    Title Virtual Reality System for Treatment of the Fear of Public Speaking Using Image-based Rendering and Moving Pictures.
    Date January 2003
    Journal Cyberpsychology & Behavior : the Impact of the Internet, Multimedia and Virtual Reality on Behavior and Society
    Excerpt

    The fear of speaking is often cited as the world's most common social phobia. The rapid growth of computer technology enabled us to use virtual reality (VR) for the treatment of the fear of public speaking. There have been two techniques used to construct a virtual environment for the treatment of the fear of public speaking: model-based and movie-based. Virtual audiences and virtual environments made by model-based technique are unrealistic and unnatural. The movie-based technique has a disadvantage in that each virtual audience cannot be controlled respectively, because all virtual audiences are included in one moving picture file. To address this disadvantage, this paper presents a virtual environment made by using image-based rendering (IBR) and chroma keying simultaneously. IBR enables us to make the virtual environment realistic because the images are stitched panoramically with the photos taken from a digital camera. And the use of chroma keying allows a virtual audience to be controlled individually. In addition, a real-time capture technique was applied in constructing the virtual environment to give the subjects more interaction, in that they can talk with a therapist or another subject.

    Title The Development of Virtual Reality Therapy (vrt) System for the Treatment of Acrophobia and Therapeutic Case.
    Date November 2002
    Journal Ieee Transactions on Information Technology in Biomedicine : a Publication of the Ieee Engineering in Medicine and Biology Society
    Excerpt

    Virtual reality therapy (VRT), based on this sophisticated technology, has been recently used in the treatment of subjects diagnosed with acrophobia, a disorder that is characterized by marked anxiety upon exposure to heights and avoidance of heights. Conventional VR systems for the treatment of acrophobia have limitations, over-costly devices or somewhat unrealistic graphic scenes. The goal of this study was to develop an inexpensive and more realistic virtual environment (VE) in which to perform exposure therapy for acrophobia. It is based on a personal computer, and a virtual scene of a bunge-jump tower in the middle of a large city. The virtual scenario includes an open lift surrounded by props beside a tower, which allows the patient to feel a sense of heights. The effectiveness of the VE was evaluated through the clinical treatment of a subject who was suffering from the fear of heights. As a result, it was proved that this VR environment was effective and realistic at overcoming acrophobia according not only to the comparison results of a variety of questionnaires before and after treatment but also to the subject's comments that the VE seemed to evoke more fearful feelings than the real situation.

    Title The Treatment of Fear of Flying: a Controlled Study of Imaginal and Virtual Reality Graded Exposure Therapy.
    Date November 2002
    Journal Ieee Transactions on Information Technology in Biomedicine : a Publication of the Ieee Engineering in Medicine and Biology Society
    Excerpt

    The goal of this study was to determine if virtual reality graded exposure therapy (VRGET) was equally efficacious, more efficacious, or less efficacious, than imaginal exposure therapy in the treatment of fear of flying. Thirty participants (Age = 39.8 +/- 9.7) with confirmed DSM-IV diagnosis of specific phobia fear of flying were randomly assigned to one of three groups: VRGET with no physiological feedback (VRGETno), VRGET with physiological feedback (VRGETpm), or systematic desensitization with imaginal exposure therapy (IET). Eight sessions were conducted once a week. During each session, physiology was measured to give an objective measurement of improvement over the course of exposure therapy. In addition, self-report questionnaires, subjective ratings of anxiety (SUDs), and behavioral observations (included here as flying behavior before beginning treatment and at a three-month posttreatment followup) were included. In the analysis of results, the Chi-square test of behavioral observations based on a three-month posttreatment followup revealed a statistically significant difference in flying behavior between the groups [chi(2) (4) = 19.41, p < 0.001]. Only one participant (10%) who received IET, eight of the ten participants (80%) who received VRGETno, and ten out of the ten participants (100%) who received VRGETpm reported an ability to fly without medication or alcohol at three-month followup. Although this study included small sample sizes for the three groups, the results showed VRGET was more effective than IET in the treatment of flying. It also suggests that physiological feedback may add to the efficacy of VR treatment.

    Title The Human Papilloma Virus E7 Oncoprotein Inhibits Transforming Growth Factor-beta Signaling by Blocking Binding of the Smad Complex to Its Target Sequence.
    Date November 2002
    Journal The Journal of Biological Chemistry
    Excerpt

    The human papillomavirus (HPV) oncoprotein E7 is implicated in the etiology of cervical cancer associated with infection by HPV. HPV-positive cells develop resistance to TGF-beta growth inhibitory activity through the inhibition of hypophosphorylation of pRb by papillomavirus type 16 E7 oncoprotein. In this study, we examined whether E7, in addition to its well known effects on pRb, might directly target the Smad proteins that mediate TGF-beta signaling. Here, we show that E7 significantly blocks both Smad transcriptional activity and the ability of TGF-beta to inhibit DNA synthesis. We found that E7 interacts constitutively with Smad2, Smad3, and Smad4. Confocal microscopic studies confirm that E7 and Smads co-localize in vivo. Using a canonical Smad DNA binding sequence, we found that E7 blocks Smad3 binding to its target sequence on DNA. These results suggest that suppression of Smad-mediated signaling by E7 may contribute to HPV-associated carcinogenesis.

    Title The Effect of Virtual Reality Cognitive Training for Attention Enhancement.
    Date November 2002
    Journal Cyberpsychology & Behavior : the Impact of the Internet, Multimedia and Virtual Reality on Behavior and Society
    Excerpt

    Our main goal in this research was to validate the possibility of virtual reality (VR) for attention enhancement in cognitive training program. Then, we developed some cognitive training tasks using VR technology. Thirty subjects who had little behavioral problems and social problems were randomly assigned into three groups: VR group, non-VR group, and control group. Only the VR group used the head-mounted display (HMD) and position sensor. While the VR group and non-VR group performed cognitive training, the control group received no special treatment. All participants took their eight session tasks over 2 weeks. Participants executed a continuous performance task (CPT) before and after training sessions. We found that immersive VR with cognitive training is effective for attention enhancement. Also, we confirmed that our cognitive training can improve the attention span of children and adolescents with behavioral problems and help them learn to focus on some tasks.

    Title Development and Validation of Virtual Driving Simulator for the Spinal Injury Patient.
    Date November 2002
    Journal Cyberpsychology & Behavior : the Impact of the Internet, Multimedia and Virtual Reality on Behavior and Society
    Excerpt

    We developed a virtual reality (VR) driving simulator in order to safely evaluate and improve the driving ability of spinal injury patients. The simulator is composed of an actual car, a beam projector, and a large screen. For the interface of our driving simulator, an actual car was adapted and then connected to a computer. We equipped the car with hand control driving devices especially adapted for spinal injury patients. A beam projector was used so that the subjects could see the virtual scene on a large screen set up in front of them. The virtual environment (VE) consisted of 18 sections (e.g., a speed-limited road, a straight road, a curved road, a left turn) and each section was linked naturally to the next. The subjects selected for this trial were 10 normal drivers with valid driving licenses and 15 patients with thoracic or lumbar cord injuries who had prior driving experience. For evaluation, five driving skills were measured, including average speed, steering stability, centerline violations, traffic signal violations, and driving time in various road conditions such as straight and curved roads. The normal subjects manipulated the gas pedal and the brake with their feet, while the patients manipulated a hand control with their hands. After they finished driving the whole course, the participants answered the questions such as "How realistic did the virtual reality driving simulator seem to you?" and "How much was your fear reduced?" In this study, we found that the difference in manipulation method (i.e., the patient group's hand control versus the normal driver's foot controls) does not seem to influence relative performance in the VR driving simulator, though training to improve the use of hand controls in the VR driving simulator would be useful to reduce the fear that the patients feel while driving.

    Title No Androgenic/anti-androgenic Effects of Bisphenol-a in Hershberger Assay Using Immature Castrated Rats.
    Date November 2002
    Journal Toxicology Letters
    Excerpt

    Several studies have demonstrated that bisphenol A (BPA) exhibited weak estrogenic activity in the 3-day uterotrophic assay using ovariectomized (OVX) and immature rats (Toxicol. Lett. 115 (2000) 231; Regul. Toxicol. Pharmacol. 32 (2000) 118; J. Toxicol. Sci. 26 (2001) 111) and BPA also possessed anti-androgenic activity in in vitro yeast based assays (J. Endocrinol. 158 (1998) 327). To investigate anti-androgenic effects of BPA. a rodent Hershberger assay was carried out using immature Sprague-Dawley male rats. An androgen agonist, testosterone (0.4 mg/kg per day), was administered for 7 consecutive days by subcutaneous (s.c.) injection as a positive control. Additionally, a pure androgen antagonist, flutamide (1, 5. 10 mg/kg per day. oral) was co-administered with testosterone (0.4 mg/kg per day s.c.). BPA was also administered orally with or without testosterone (0.4 mg/kg per day, s.c.) for 7 consecutive days. In the testosterone treated groups, glans penis, seminal vesicles, ventral prostate, and levator ani plus bulbocavernosus muscles (LABC) weights were significantly increased compared with control. However. flulamide dose-dependently inhibited the testosterone-induced re-growth of seminal vesicles, ventral prostate, and LABC, with a significant decrease at flutamide 1.0 mg/kg and above (P<0.05). Serum LH levels were also significantly increased (5 mg/kg and above, P<0.05), but no changes in serum testosterone levels. In contrast, BPA had no effects on the re-growth of seminal vesicles, ventral prostate and LABC induced by testosterone, and no significant differences were observed in serum LH and testosterone levels. In summary, the Hershberger assay could be a sensitive method for detecting androgenic or anti-androgenic chemicals, but BPA did not exhibit any androgenic or anti-androgenic activities in Hershberger assay.

    Title Analysis of Physiological Response to Two Virtual Environments: Driving and Flying Simulation.
    Date October 2002
    Journal Cyberpsychology & Behavior : the Impact of the Internet, Multimedia and Virtual Reality on Behavior and Society
    Excerpt

    As virtual reality technology continues to attract significant attention in clinical psychology, especially in the treatment of phobias, physiological monitoring is increasingly considered as an objective measurement tool for studying participants. There are few studies, however, of the normal physiological response to virtual environments or reactions to different virtual environments. The goal of this study is to analyze nonphobic participants' physiological reactions to two virtual environments: driving and flying. Eleven nonphobic participants were exposed to each virtual environment for 15 min. Heart rate, skin resistance, and skin temperature were measured during physiological monitoring, and the Presence and Simulator Sickness Questionnaire scores were obtained after each exposure. This study found that skin resistance and heart rate variability can be used to show arousal of participants exposed to the virtual environment experience and that such measures generally returned to normal over time. The data suggest that skin resistance and heart rate can be used as objective measures in monitoring the reaction of non-phobic participants to virtual environments. We also noted that heart rate variability could be useful for assessing the emotional states of participants.

    Title Raloxifene, a Mixed Estrogen Agonist/antagonist, Induces Apoptosis Through Cleavage of Bad in Tsu-pr1 Human Cancer Cells.
    Date October 2002
    Journal The Journal of Biological Chemistry
    Excerpt

    Selective estrogen receptor modulator is a proven agent for chemoprevention and chemotherapy of cancer. Raloxifene, a mixed estrogen agonist/antagonist, was developed to prevent osteoporosis and potentially reduce the risk of breast cancer. In this study, we examined the effect of raloxifene on the TSU-PR1 cell line. This cell line was originally reported to be a prostate cancer cell line, but recently it has been shown to be a human bladder transitional cell carcinoma cell line. The TSU-PR1 cell line contains high levels of estrogen receptor beta. Following treatment with raloxifene, evidence of apoptosis, including change in nuclear morphology, DNA fragmentation, and cytochrome c release, was observed in a dose-dependent manner in the TSU-PR1 cells (10(-9) to 10(-6) m range). We observed no detectable change in the steady-state levels of Bax, Bcl-2, and Bcl-X(L) following raloxifene treatment. However, raloxifene induced caspase-dependent cleavage of BAD to generate a 15-kDa truncated protein. Overexpression of a double mutant BAD resistant to caspase 3 cleavage blocked raloxifene-induced apoptosis. These results demonstrate that raloxifene induces apoptosis through the cleavage of BAD in TSU-PR1 cells. This molecular mechanism of apoptosis suggests that raloxifene may be a therapeutic agent for human bladder cancer.

    Title Intensity Based Affine Registration Including Feature Similarity for Spatial Normalization.
    Date October 2002
    Journal Computers in Biology and Medicine
    Excerpt

    This paper presents a new spatial normalization with affine transformation. The quantitative comparison of brain architecture across different subjects requires a common coordinate system. For the analysis of a specific brain area, it is required to normalize and compare a region of interest and global brain. Intensity based registration method matches the global brain well. But a region of interest may not be locally normalized compared to feature based method. The method of this paper uses feature similarities of local region as well as intensity similarities. The lateral ventricle and the central gray nuclei of brain including the corpus callosum, which is used for features in Schizophrenia detection, is appropriately normalized. In the results section, our method reduces the difference of feature area such as corpus callosum (7.7%, 2.4%) and lateral ventricle (8.2%, 13.5%) compared with mutual information and Talairach methods.

    Title Raloxifene, a Mixed Estrogen Agonist/antagonist, Induces Apoptosis in Androgen-independent Human Prostate Cancer Cell Lines.
    Date October 2002
    Journal Cancer Research
    Excerpt

    Raloxifene, a selective estrogen receptor (ER) modulator, is a mixed estrogen agonist/antagonist that has been shown to prevent osteoporosis and breast cancer in women. Because the prostate contains high levels of ER-beta, the present study investigated the effect of raloxifene in three well-characterized, androgen-independent human prostate cancer cell lines: (a) PC3; (b) PC3M; and (c) DU145. Reverse transcriptase-PCR and Western blot analysis for ER-alpha and ER-beta demonstrated that all three cell lines express ER-beta, whereas only PC3 and PC3M cells were positive for ER-alpha. After the treatment with raloxifene, a dramatic increase in cell death was observed in a dose-dependent manner in the three prostate cancer cell lines (10(-9) to 10(-6) M range). Because the three prostate cancer cell lines demonstrated similar morphological changes after the raloxifene treatment, PC3 (ER-alpha/ER-beta+) and DU145 (ER-beta+ only) cells were selected to further characterize the raloxifene-induced cell death. Using the nucleus-specific stain 4',6-diamidino-2-phenylindole, nuclear fragmentation was observed in a time-dependent manner in both cell lines after exposure to 10(-6) M raloxifene. Using the terminal deoxynucleotidyl transferase-mediated nick end labeling apoptotic assay, it was demonstrated that the nuclear fragmentation was caused by apoptosis. To investigate the possibility that caspase activation is involved in raloxifene-induced apoptosis, cells were treated with the pan-caspase inhibitor ZVAD. The results demonstrated that the dramatic change in cellular morphology after treatment with raloxifene was no longer observed when cells were pretreated with ZVAD. Immunoblot demonstrated activation of caspases 8 and 9 in PC3 and DU145 cells, respectively. Taken together, these results demonstrate that the mixed estrogen agonist/antagonist, raloxifene, induces apoptosis in androgen-independent human prostate cancer cell lines.

    Title Raloxifene, a Selective Estrogen Receptor Modulator, Induces Apoptosis in Androgen-responsive Human Prostate Cancer Cell Line Lncap Through an Androgen-independent Pathway.
    Date August 2002
    Journal Cancer Research
    Excerpt

    Raloxifene, a selective estrogen receptor (ER) modulator, is a mixed estrogen agonist/antagonist that has been shown to prevent osteoporosis and breast cancer in women. Because the prostate contains a high level of ER-beta, the present study investigated the effect of raloxifene in the androgen-sensitive human prostate cancer cell line LNCaP. Previously, it has been demonstrated that LNCaP cells express ER-beta but not ER-alpha and that tamoxifene induces apoptosis in these cells. After treatment with raloxifene, a dramatic increase in cell death occurred in a dose-dependent manner (10(-9) to 10(-6) M range). Using the terminal deoxynucleotidyl transferase-mediated nick end labeling apoptotic assay, we demonstrated that the nuclear fragmentation was due to apoptosis. The dramatic change in cellular morphology after treatment with raloxifene was no longer observed when cells were pretreated with a pan-caspase inhibitor, Z-VAD-FMK, and a specific caspase-9 inhibitor, Z-LEHD-FMK. Furthermore, immunoblot demonstrated an activation of caspase-9 in LNCaP cells. Because LNCaP cells contain a mutated androgen receptor that allows cellular proliferation in the presence of antiandrogens, prostate-specific antigen assay and transfection with a reporter construct containing luciferase gene under the control of androgen response element (pARE) were carried out. The results demonstrated that raloxifene does not significantly alter androgen receptor activity in LNCaP cells. Taken together, these results demonstrate that raloxifene, a selective ER modulator, induces apoptosis in the androgen-sensitive human prostate cancer cell line LNCaP through an androgen-independent pathway.

    Title Metastatic Spinal Cord Compression of Testicular Yolk Sac Tumor.
    Date July 2002
    Journal Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery
    Excerpt

    INTRODUCTION: Pediatric testicular tumors are rare. Spinal metastasis of testicular yolk sac tumor (YST) is extremely rare, with only one reported case. CASE REPORT: We report a rare case of metastatic spinal cord compression of testicular YST in a 14-month-old boy who presented with progressive paraparesis and neurological bladder dysfunction. Two months prior to admission, he underwent a left radical orchiectomy for YST of the testis. Magnetic resonance imaging revealed severe spinal cord compression by the ventral epidural mass from T-9 to T-11 and at S-3. Emergency surgical resection was performed for tissue diagnosis and spinal decompression. Histopathological features of the epidural mass indicated metastasis of the testicular YST. CONCLUSION: Although spinal involvement with metastatic YST is rare, it must be considered in children with testicular YST exhibiting evidence of pain or weakness, and surgical decompression followed by adjuvant chemotherapy should not be delayed.

    Title Evaluation of the 20-day Pubertal Female Assay in Sprague-dawley Rats Treated with Des, Tamoxifen, Testosterone, and Flutamide.
    Date July 2002
    Journal Toxicological Sciences : an Official Journal of the Society of Toxicology
    Excerpt

    The Endocrine Disrupter Screening and Testing Advisory Committee (EDSTAC) has recommended the rodent pubertal female assay as a Tier I test to detect potential endocrine disrupters (EDs). This assay is designed to screen estrogenic activity in immature rats exposed to chemicals during sexual maturation. The aim of this study was to evaluate whether this assay can detect the EDs with effects brought about through various mechanisms. Immature Sprague-Dawley female rats (21 days of age) were dosed daily for 20 days by oral gavage (DES, tamoxifen, and flutamide) or sc injection (testosterone). The mean age at vaginal opening (VO) was 32.3 +/- 0.5 days in control rats. Although VO was unaffected by DES at doses of 0.2 and 1.0 microg/kg, a high dose of DES (5.0 microg/kg) significantly advanced the age at VO to 24 days. Both tamoxifen (50 and 200 microg/kg) and flutamide (25 mg/kg) also significantly accelerated VO to 27.8 +/- 0.5, 25.1 +/- 0.1, and 26.1 +/- 0.1, respectively. However, testosterone dose-dependently delayed VO (exposure to 1.0 mg/kg extended VO to 37.3 +/- 0.8 days, and VO did not occur in 2 of 10 animals by the time of necropsy at 41 days of age). Estrous cyclicity was monitored in rats from VO to necropsy. Irregular cycles were observed in the groups treated with DES (5.0 microg/kg), tamoxifen (200 microg/kg), testosterone (1.0 mg/kg), and flutamide (25 mg/kg). High dose of DES showed a persistent estrus state throughout the entire observation period. In addition, the number of days in diestrus was increased by tamoxifen (200 microg/kg) and flutamide (25 mg/kg) treatments. Significant decreases in ovarian weight were observed in 5.0 microg/kg DES (64% of control), 25 mg/kg flutamide (76% of control), and 200 microg/kg tamoxifen (47% of control). Testosterone also significantly decreased the ovarian weights in all treatment groups. Uterine weights were also decreased significantly at high doses of tamoxifen (200 microg/kg, 39% of control) or testosterone (1.0 mg/kg, 47% of control). In hormone analysis, tamoxifen significantly increased serum E(2) levels at 50 microg/kg. The mean serum levels of TSH were significantly increased in tamoxifen (10 and 50 microg/kg), testosterone (0.2 mg/kg), and flutamide (1.0 and 25 mg/kg) treatment groups compared with the control. However, serum T(4) levels were significantly reduced by testosterone. Furthermore, serum T(3) levels were significantly increased in DES, tamoxifen (10 and 50 microg/kg), testosterone (1.0 mg/kg), and flutamide (1.0 and 5 mg/kg). Our data demonstrate that the rodent pubertal female assay is useful for identifying potential EDs having not only estrogenic/antiestrogenic but also androgenic/antiandrogenic activities. However, further validation study is necessary to identify chemicals that operate through other action mechanisms, including steroid biosynthesis inhibitors and thyroid inhibitors. Moreover, additional data on other compounds with weak endocrine disrupting activity will be required to further characterize the sensitivity of the female pubertal assay.

    Title Dysfunction of Rat Liver Mitochondria by Selenite: Induction of Mitochondrial Permeability Transition Through Thiol-oxidation.
    Date July 2002
    Journal Biochemical and Biophysical Research Communications
    Excerpt

    Selenium is an essential trace element in mammals and is thought to play a chemopreventive role in human cancer, possibly by inducing tumor cell apoptosis. Mitochondria play a pivotal role in the induction of apoptosis in many cell types. The effects of selenite on mitochondrial function were therefore investigated. Selenite induced the oxidation and cross-linking of protein thiol groups, mitochondrial permeability transition (MPT), a decrease in the mitochondrial membrane potential, and the release of cytochrome c in mitochondria isolated from rat liver. Induction of the MPT by selenite was prevented by cyclosporin A, EGTA, or N-ethylmaleimide. These results thus indicate that selenite induces the MPT as a result of direct modification of protein thiol groups, resulting in the release of cytochrome c and a loss of mitochondrial membrane potential.

    Title Selenoprotein W is a Glutathione-dependent Antioxidant in Vivo.
    Date July 2002
    Journal Febs Letters
    Excerpt

    The function of selenoprotein W (Se-W) was investigated by cloning the corresponding cDNA from mouse brain and expressing it in CHO cells and H1299 human lung cancer cells. Overexpression of Se-W markedly reduced the sensitivity of both cell lines to H2O2 cytotoxicity. The intracellular peroxide concentration of the transfected cells was lower than that of the parental cells in the absence or presence of extracellular H2O2. The resistance to oxidative stress conferred by Se-W was dependent on glutathione. Expression of Se-W mutants in which selenocysteine-13 or cysteine-37 was replaced by serine did not confer resistance to H2O2, implicating these residues in the antioxidant activity of Se-W in vivo.

    Title Laparoscopic Nephrectomy for Renal Cell Carcinoma.
    Date July 2002
    Journal Current Urology Reports
    Excerpt

    Since the first reported case of laparoscopic nephrectomy by Clayman et al. in 1991, laparoscopy is gaining acceptance as a viable alternative to open surgery for renal cell carcinoma. The benefits of laparoscopy include improved quality of life and lower incidence of perioperative morbidity. The perceived risks of laparoscopic nephrectomy for renal cell carcinoma include port-site metastasis, increased operative time, and the concern for inadequate surgical resection. The preliminary data concerning laparoscopy in renal cell carcinoma, however, indicate that rates of tumor recurrence are equivalent to open surgery while resulting in better cosmesis, decreased level of perioperative analgesic use, and decreased length of time to full convalescence.

    Title Protection of Mice from Allergen-induced Asthma by Selenite: Prevention of Eosinophil Infiltration by Inhibition of Nf-kappa B Activation.
    Date July 2002
    Journal The Journal of Biological Chemistry
    Excerpt

    The potential anti-inflammatory effect of sodium selenite in a mouse model of asthma was investigated. Selenite was injected into the peritoneum of allergen (ovalbumin)-sensitized mice before allergen challenge. Ovalbumin challenge resulted in activation of the transcription factor NF-kappaB and an increase in the expression of cell adhesion molecules (intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin, which are encoded by NF-kappaB-dependent genes) in lung tissue as well as in the recruitment of eosinophils to lung airways. These effects of ovalbumin challenge were all inhibited by pretreatment of mice with selenite. Selenite administration also increased the activity of selenium-dependent glutathione peroxidase in lung tissue. Furthermore, supplementation of A549 human airway epithelial cell cultures with selenite increased glutathione peroxidase activity as well as inhibited both the generation of hydrogen peroxide and the activation of NF-kappaB induced by tumor necrosis factor alpha in these cells. Selenite also reversed in vitro the activation of NF-kappaB induced by this cytokine in intact A549 cells. These results suggest that selenite regulates the activity of NF-kappaB by increasing the activity of glutathione peroxidase, thereby removing potential activators of NF-kappaB, and possibly also by direct oxidation of critical sulfhydryl groups of this transcription factor. These effects of selenite likely underlie its anti-inflammatory action in asthma.

    Title H(2)o(2)-induced Ap-1 Activation and Its Effect on P21(waf1/cip1)-mediated G2/m Arrest in a P53-deficient Human Lung Cancer Cell.
    Date June 2002
    Journal Biochemical and Biophysical Research Communications
    Excerpt

    Cellular response to oxidative stress is a complex process that is often connected to cell cycle regulation. The present study examines the effect of H(2)O(2) on cell cycle regulation and involvement of reactive oxygen species (ROS) in these H(2)O(2)-induced responses in a p53-deficient human lung carcinoma cell line, H1299. Treatment of the cells with H(2)O(2) caused a G2/M phase arrest. Among the redox-sensitive transcription factors, NF-kappaB and AP-1, we found that only AP-1 was activated by 200 microM H(2)O(2) in human lung cells. Furthermore, electrophoretic mobility shift assays revealed that H(2)O(2) enhanced the DNA binding of AP-1 to a putative AP-1 binding element (TGAGGAA) in the p21(WAF1/CIP1) promoter region (between -2203 and -2197 nucleotides upstream of the transcription initiation site). An increase in c-Jun phosphorylation by ERK was also found to accompany the increased AP-1 activity as detected by Western blot. PD98059, a specific inhibitor of MEK, diminished H(2)O(2)-induced phosphorylation of c-Jun and DNA binding activity of AP-1, decreased expression of p21(WAF1/CIP1), and released the cells from G2/M arrest. Taken together, these results revealed a novel AP-1 binding site in the promoter region of p21(WAF1/CIP1) and a possible cell cycle regulation mechanism mediated by activation of a redox-dependent ERK signaling pathway.

    Title Effects of Flutamide on Puberty in Male Rats: an Evaluation of the Protocol for the Assessment of Pubertal Development and Thyroid Function.
    Date April 2002
    Journal Journal of Toxicology and Environmental Health. Part A
    Excerpt

    To establish a test protocol for the rodent 20-d thyroid/pubertal assay, flutamide, a non-steroidal androgen antagonist, was administered to intact male Sprague-Dawley rats from postnatal d 33 for 20 d, and several reproductive endpoints were examined to assess the sensitivity of a number of parameters with respect to the detection of endocrine-related effects. Immature male rats were divided into 4 groups and given flutamide once daily by oral gavage at doses of 0, 1, 5, or 25 mg/kg/d. Prepuce separation was significantly delayed in flutamide-treated rats (5 and 25 mg/kg/d). One day after the last dose, the rats were sacrificed. Flutamide treatment resulted in a significant reduction in the weights of epididymides, ventral prostate, seminal vesicles plus coagulating glands and fluid, levator ani plus bulbocavernosus muscles, Cowper's glands, and glans penis. The weight of adrenal glands decreased at 25 mg/kg/d, while testes and any other organ weights were unaffected. No microscopic changes were observed in the thyroid glands. Serum levels of testosterone were significantly increased in the flutamide-treated groups (5 and 25 mg/ kg/d) and serum levels of estradiol were also increased (25 mg/kg/d). No differences were observed in the serum thyroxine levels. These results indicate that flutamide delays puberty in the male rat, and its mode of action appears to be via altered secretion of steroids, which subsequently affect the development of the reproductive tract. Thus, this assay might be used as an alternative for screening antiandrogenic activities of chemicals.

    Title Preoperative Plasma Levels of Transforming Growth Factor Beta(1) Strongly Predict Clinical Outcome in Patients with Bladder Carcinoma.
    Date January 2002
    Journal Cancer
    Excerpt

    BACKGROUND: Elevated local and circulating levels of transforming growth factor (TGF)-beta(1) have been associated with cancer invasion, progression, and metastasis. The authors tested the hypothesis that preoperative plasma TGF-beta(1) levels would independently predict cancer stage and prognosis in patients with transitional cell carcinoma (TCC) of the urinary bladder. METHODS: The study group consisted of 51 patients who underwent radical cystectomy for muscle-invasive or intravesical immuno- and/or chemotherapy refractory Tis, Ta, or T1 TCC (median follow-up, 45.7 months). Preoperative plasma levels of TGF-beta(1) were measured and correlated with pathologic features and clinical outcome. Transforming growth factor-beta(1) levels also were measured in 44 healthy men without any cancer. RESULTS: The mean preoperative plasma TGF-beta(1) level in patients who eventually developed metastases to distant (11.9 +/- 0.9 ng/mL) or regional (9.6 +/- 2.4 ng/mL) lymph nodes was significantly higher than that in patients with nonmetastatic muscle-invasive TCC (5.4 +/- 1.1 ng/mL), which, in turn, was significantly higher than that in patients with nonmetastatic Tis, Ta, or T1 TCC (4.5 +/- 1.2 ng/mL) and healthy subjects (4.5 +/- 1.2 ng/mL; P < 0.001). Preoperative plasma TGF-beta(1) level was an independent predictor of lymphovascular invasion (P = 0.002), metastases to lymph nodes (P = 0.030), disease recurrence (P = 0.009), and disease specific survival (P = 0.015). In a subgroup of patients with muscle-invasive TCC, TGF-beta(1) level was associated with disease recurrence (P = 0.005) and death from bladder carcinoma (P = 0.001). CONCLUSIONS: The authors confirm that plasma TGF-beta(1) levels are elevated in patients with muscle-invasive TCC before cystectomy. Transforming growth factor-beta(1) levels are highest in patients with bladder carcinoma metastatic to lymph nodes and are a strong independent predictor of disease recurrence and disease specific mortality.

    Title Predictive Value of Expression of Transforming Growth Factor-beta(1) and Its Receptors in Transitional Cell Carcinoma of the Urinary Bladder.
    Date January 2002
    Journal Cancer
    Excerpt

    BACKGROUND: The purpose of this study was to describe the expression patterns of transforming growth factor (TGF)-beta(1) and its receptors in transitional cell carcinoma (TCC) of the bladder, to investigate the relation between the TGF-beta(1) and its receptors, and to determine whether altered expression of TGF-beta or its receptors is associated with disease progression and survival in patients with TCC of the bladder. METHODS: Immunohistochemical staining for TGF-beta(1) and its receptors I and II was conducted on formalin fixed paraffin embedded archival cystectomy specimens of 80 patients with bladder TCC. Immunoreactivity was categorized as either positive or negative in a blinded fashion. RESULTS: Expression of TGF-beta(1), TGF-beta-RI, and TGF-beta-RII was altered in 51 (64%), 34 (43%), and 38 (48%) specimens, respectively. Sixty (75%) specimens had altered expression of at least 1 of the 3 TGF-betas, and 26 (33%) had altered expression of all 3. Expression of the three TGF-betas was highly concordant (P < 0.018). Loss of expression of TGF-beta-RI or TGF-beta-RII was associated with invasive tumor stage (P < 0.001), high grade (P < 0.006), and lymphovascular invasion (P < 0.030). Overexpression of TGF-beta(1) was associated with invasive tumor stage only (P = 0.024). With a median follow-up of 101 months, TGF-beta-RI was an independent predictor of both disease progression (P = 0.007) and disease specific survival (P = 0.006) whereas TGF-beta(1) was an independent predictor of disease progression only (P = 0.050). Transforming growth factor-beta-RII was not independently associated with either disease progression or survival. CONCLUSIONS: Altered expression of TGF-beta(1) and its receptors is common in TCC of the bladder. Overexpression of TGF-beta(1) is associated with the loss of expression of its receptors. Transforming growth factor-beta(1) and TGF-beta-RI are independently associated with clinical outcome in patients with bladder TCC treated by radical cystectomy.

    Title Real-time Volume Rendering of Four-dimensional Images Based on Three-dimensional Texture Mapping.
    Date December 2001
    Journal Journal of Digital Imaging : the Official Journal of the Society for Computer Applications in Radiology
    Excerpt

    A four-dimensional (4-D) image consists of three-dimensional (3-D) volume data that varies with time. It is used to express a deforming or moving object in virtual surgery or 4-D ultrasound. It is difficult to obtain 4-D images by conventional ray-casting or shear-warp factorization methods because of their time-consuming rendering process and the pre-processing stage necessary whenever the volume data are changed. Even when 3-D texture mapping is used, repeated volume loading is time-consuming in 4-D image rendering. In this study, we propose a method to reduce data loading time using coherence between currently loaded volume and previously loaded volume in order to achieve real-time rendering based on 3-D texture mapping. Volume data are divided into small bricks and each brick being loaded is tested for similarity to one that was already loaded in memory. If the brick passes the test, it is defined as 3-D texture by OpenGL functions. Later, the texture slices of the brick are mapped into polygons and blended by OpenGL blending functions. All bricks undergo this test. Using continuous deforming, 50 volumes are rendered in interactive time with SGI ONYX. Realtime volume rendering based on 3-D texture mapping is currently available for personal computers.

    Title Grey Matter Abnormalities in Obsessive-compulsive Disorder: Statistical Parametric Mapping of Segmented Magnetic Resonance Images.
    Date October 2001
    Journal The British Journal of Psychiatry : the Journal of Mental Science
    Excerpt

    BACKGROUND: Although a number of functional imaging studies are in agreement in suggesting orbitofrontal and subcortical hyperfunction in the pathophysiology of obsessive-compulsive disorder (OCD), the structural findings have been contradictory. AIMS: To investigate grey matter abnormalities in patients with OCD by employing a novel voxel-based analysis of magnetic resonance images. METHOD: Statistical parametric mapping was utilised to compare segmented grey matter images from 25 patients with OCD with those from 25 matched controls. RESULTS: Increased regional grey matter density was found in multiple cortical areas, including the left orbitofrontal cortex, and in subcortical areas, including the thalamus. On the other hand, regions of reduction were confined to posterior parts of the brain, such as the left cuneus and the left cerebellum. CONCLUSIONS: Increased grey matter density of frontal-subcortical circuits, consonant with the hypermetabolic findings from functional imaging studies, seems to exist in patients with OCD, and cerebellar dysfunction may be involved in the pathophysiology of OCD.

    Title Heterozygous Mice for the Transforming Growth Factor-beta Type Ii Receptor Gene Have Increased Susceptibility to Hepatocellular Carcinogenesis.
    Date October 2001
    Journal Cancer Research
    Excerpt

    The transforming growth factor-beta (TGF-beta) receptor complex and its downstream signaling intermediates constitute a tumor suppressor pathway. In many cancers, expression of TGF-beta type II receptor (TbetaR-II) is markedly decreased. In the present study, we show that the hepatocytes isolated from 15-day-old, but not 9-month-old, mice heterozygous for the deletion of the TbetaR-II gene are slightly less sensitive to the growth-inhibitory effect of TGF-beta when compared with wild-type littermates of same age. In addition, the proliferation index of hepatocytes as indicated by bromodeoxyuridine incorporation is mildly increased in the heterozygous mice. These subtle changes in cellular phenotype did not result in either gross or microscopic abnormality of the liver. The treatment of these mice with the chemical carcinogen, diethylnitrosamine, results in a significantly enhanced tumorigenesis in the liver when compared with the wild-type littermates. Our results demonstrate the gene-dosage effect of TbetaR-II and indicate that the reduced expression of TbetaR-II in mice increases susceptibility to tumorigenesis in the liver.

    Title Preoperative Plasma Levels of Transforming Growth Factor Beta(1) (tgf-beta(1)) Strongly Predict Progression in Patients Undergoing Radical Prostatectomy.
    Date July 2001
    Journal Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
    Excerpt

    PURPOSE: Elevated local and circulating levels of transforming growth factor beta(1) (TGF-beta(1)) have been associated with prostate cancer invasion and metastasis. We tested the hypothesis that preoperative plasma TGF-beta(1) levels would independently predict cancer stage and prognosis in patients who undergo radical prostatectomy. PATIENTS AND METHODS: The study group consisted of 120 consecutive patients who underwent radical prostatectomy for clinically localized prostate cancer (median follow-up, 53.8 months). Preoperative plasma levels of TGF-beta(1) were measured and correlated with pathologic parameters and clinical outcomes. TGF-beta(1) levels also were measured in 44 healthy men without cancer, in 19 men with prostate cancer metastatic to regional lymph nodes, and in 10 men with prostate cancer metastatic to bone. RESULTS: Plasma TGF-beta(1) levels in patients with lymph node metastases (14.2 +/- 2.6 ng/mL) and bone metastases (15.5 +/- 2.4 ng/mL) were higher than those in radical prostatectomy patients (5.2 +/- 1.3 ng/mL) and healthy subjects (4.5 +/- 1.2 ng/mL) (P <.001). In a preoperative analysis, preoperative plasma TGF-beta(1) level and biopsy Gleason sum both were predictors of organ-confined disease (P =.006 and P =.006, respectively) and PSA progression (P <.001 and P =.021, respectively). In a postoperative multivariate analysis, preoperative plasma TGF-beta(1) level, pathologic Gleason sum, and surgical margin status were predictors of PSA progression (P =.020,P =.020, and P =.022, respectively). In patients who progressed, preoperative plasma TGF-beta(1) levels were higher in those with presumed distant compared with local-only failure (P =.019). CONCLUSION: Plasma TGF-beta(1) levels are markedly elevated in men with prostate cancer metastatic to regional lymph nodes and bone. In men without clinical or pathologic evidence of metastases, the preoperative plasma TGF-beta(1) level is a strong predictor of biochemical progression after surgery, presumably because of an association with occult metastatic disease present at the time of radical prostatectomy.

    Title Changes in Dead Space/tidal Volume Ratio and Pulmonary Mechanics After Surfactant Replacement Therapy in Respiratory Distress Syndrome of the Newborn Infants.
    Date May 2001
    Journal Journal of Korean Medical Science
    Excerpt

    This study was performed to elucidate the mechanism of improved oxygenation after surfactant replacement therapy in respiratory distress syndrome (RDS) of the newborn infants. In 26 newborns with RDS, end tidal-CO2 tension (PetCO2), arterial blood gas analysis and pulmonary function tests were measured at baseline, 30 min, 2 hr and 6 hr after surfactant administration. The changes in dead space/tidal volume ratio (VD/VT ratio=(PaCO2-PetCO2)/PaCO2), oxygenation index and arterial-alveolar partial pressure difference for oxygen ((A-a)DO2) were elucidated and correlated with pulmonary mechanics. Oxygenation index and (A-a)DO2 improved, and VD/VT ratio decreased progressively after surfactant administration, becoming significantly different from the baseline at 30 min and thereafter with administration of surfactant. Pulmonary mechanics did not change significantly during the observation period. VD/VT ratio showed close correlation with OI and (A-a)DO2, but not with pulmonary mechanics. These results suggest that decreased physiologic dead space resulting from the recruitment of atelectatic alveoli rather than improvement in pulmonary mechanics is primarily responsible for the improved oxygenation after surfactant therapy in the RDS of newborn.

    Title An Unusual Presenting Symptom of Sarcoidosis: Neurogenic Bladder Dysfunction.
    Date May 2001
    Journal The Journal of Urology
    Title Measurement of Femoral Neck Anteversion in 3d. Part 1: 3d Imaging Method.
    Date February 2001
    Journal Medical & Biological Engineering & Computing
    Excerpt

    Femoral neck anteversion is the torsion of the femoral head with reference to the distal femur. Conventional methods that use cross-sectional computed tomography (CT), magnetic resonance or ultrasound images to estimate femoral anteversion have met with several problems owing to the complex, three-dimensional (3D) structure of the femur. These problems include not only the difficulty of defining the direction of the femoral neck axis and condylar line but also the dependency upon patient positioning. In particular, the femoral neck axis, the direction of the femoral head, known as the major source of error, is difficult to determine from either a single or several two-dimensional (2D) cross-sectional images. A new method has been devised for the measurement of femoral anteversion using the 3D imaging technique. 3D reconstructed CT images from the femoral head and trochanter to the distal femur are used to measure the anteversion. It is necessary to remove the soft tissue from the CT images and extract just the bone part. Then, the femoral anteversion is measured from a computer-rendered femur image. The 3D imaging method is compared with both the conventional 2D method and the physical method using 20 dried femurs. For the physical method, which is used as a reference value, a special apparatus is devised. The average difference between the results of the physical method and those of the 2D CT method is 5.33 degrees. The average difference between the results of the physical method and those of the 3D imaging method is 0.45 degrees. Seventy-four patients, who suffer from toe-in-gait disease, are tested to compare the 3D imaging method with the conventional 2D CT method. The average difference between the 2D and 3D methods is 8.6 degrees, and the standard is 7.43 degrees. This method provides a very accurate and reliable measurement of femoral anteversion, as it is virtually equivalent to the direct measurement of bisected dried femur in vitro.

    Title Measurement of Femoral Neck Anteversion in 3d. Part 2: 3d Modelling Method.
    Date February 2001
    Journal Medical & Biological Engineering & Computing
    Excerpt

    Femoral neck anteversion is the torsion of the femoral head with reference to the distal femur. Conventional methods that use cross-sectional computed tomography (CT), magnetic resonance or ultrasound images to estimate femoral anteversion have met with several problems owing to the complex three-dimensional (3D) structure of the femur. A 3D imaging method has been developed that virtually measures femoral anteversion on the 3D computer space with continuous CT slices; this 3D method provides more accurate and reliable results than conventional 2D CT measurements. A 3D modelling method is devised for the measurement of femoral neck anteversion. This method has advantages over the 3D imaging method, such as shorter processing time, reduced number of slices and an objective result compared with the 3D imaging method. The results of the 3D modelling method are compared with the conventional CT methods (2D CT method and 3D imaging method) using 20 dried femurs.

    Title Expression of Bone Morphogenetic Protein Receptors Type-ia, -ib and -ii Correlates with Tumor Grade in Human Prostate Cancer Tissues.
    Date June 2000
    Journal Cancer Research
    Excerpt

    Bone morphogenetic proteins (BMPs) are potential regulators of prostate cancer cell growth and metastasis that signal through an interaction with BMP membrane receptors (BMPRs) type I and type II. In the present study, Western blot and immunohistochemical analysis of BMPRs were carried out in benign and malignant human prostate tissues to explain the loss of BMP response in human prostate cancer cells. The results demonstrated that the benign prostate specimens expressed high levels of all three BMPRs. In normal prostate, BMPRs were localized predominantly to epithelial cells. Among prostate cancer specimens, well-differentiated cancers were positive for the expression of BMPR-II, BMPR-IA, and BMPR-IB, for the most part. In contrast, only 1 of 10 poorly differentiated prostate cancer cases was positive for each of the three BMPRs (P < 0.005 for all three receptors). Taken together, these results indicate that human prostate cancer cells frequently exhibit loss of expression of BMPRs and suggest that loss of BMPRs may play an important role during the progression of prostate cancer.

    Title Absence of Proximal Duct Apoptosis in the Ventral Prostate of Transgenic Mice Carrying the C3(1)-tgf-beta Type Ii Dominant Negative Receptor.
    Date May 2000
    Journal The Prostate
    Excerpt

    BACKGROUND: Prostatic epithelial cells are sensitive to the inhibitory effects of TGF-beta. However, TGF-beta signaling in the prostate is dependent on androgenic status. Under the in vivo conditions, it is difficult to dissociate the effect of TGF-beta from that of androgen on the prostate. METHODS: The objective of the present study was to create and verify a transgenic mouse system in which epithelial cells of the ventral prostate are insensitive to the actions of TGF-beta. By using a modified prostate-specific promoter, C3(1), the TGF-beta dominant negative receptor is only expressed in the epithelial cells of the ventral prostate, and these cells are resistant to TGF-beta. Morphology of transgenic animal prostates was compared to wild-type animal prostates by immunohistochemistry and microscopy. RESULTS: The prostate of transgenic mice exhibited an abnormal morphology with multiple layers of epithelial cells lining the proximal ducts, in contrast to the simple cuboidal monolayer of cells seen in the normal prostate. This observation was accompanied by a loss of apoptosis in this region, as seen by TUNEL assay. There was no significant difference in serum levels of testosterone between the wild-type and transgenic animals. CONCLUSIONS: These results demonstrated that a loss of sensitivity to TGF-beta results in the accumulation of multiple layers of epithelial cells in the proximal region of the ventral prostate. This abnormal growth illustrates that TGF-beta plays an important role in regulating prostate growth. The current transgenic system can be used as an experimental model to study the functional role of TGF-beta in prostatic growth and function.

    Title Bacillus Calmette-guerin Induced Peritonitis in a Patient on Dialysis.
    Date January 2000
    Journal The Journal of Urology
    Title Decreased Expression of Transforming Growth Factor Beta Receptor Type I is Associated with Poor Prognosis in Bladder Transitional Cell Carcinoma Patients.
    Date November 1999
    Journal Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
    Excerpt

    Transforming growth factor (TGF) beta, a potent growth inhibitor of proliferation in most cells, usually exerts its effects through an interaction with membrane receptors, type I (TbetaR-I) and type II (TbetaR-II). In the present study, the expression of TGF-beta receptors was correlated with tumor grade, pathological stage, and probability of progression and survival in patients with bladder transitional cell carcinoma (TCC). To this end, immunohistochemistry was carried out in specimens obtained from 59 patients who underwent either radical cystectomy or transurethral resection of bladder tumor. Among these patients, 18 (30.5 %) had loss of TbetaR-I expression, whereas 27 (44.0%) had loss of TbetaR-II expression. There was a correlation between the loss of expression of TbetaR-I and TbetaR-II and the tumor grade (P = 0.041 and P = 0.026, respectively). In addition, both pathological and lymph node status also were associated with the loss of TbetaR-I and TbetaR-II expression (P = 0.025 and P = 0.004, respectively). Interestingly though, only the loss of expression of TbetaR-I was associated with an increased probability of tumor progression and a decreased probability of survival (P = 0.0046 and P = 0.0022, respectively). These results suggest that the status of TbetaR-I expression may be a potential prognostic marker in patients with bladder TCC.

    Title The Loss of Expression of Transforming Growth Factor-beta Receptors Correlates with the Histopathologic Tumor Grade in Bladder Transitional Cell Carcinoma Patients.
    Date June 1999
    Journal Yonsei Medical Journal
    Excerpt

    Transforming growth factor-beta (TGF-beta), a pleiotropic growth factor, is a potent inhibitor of cellular proliferation in cells of epithelial origin. Recently, it has been suggested that a loss of sensitivity to TGF-beta through a loss of expression of TGF-beta receptors T beta R-I and T beta R-II--is associated with tumor initiation and progression. Therefore, to investigate the relationship between TGF-beta receptors expression and carcinogenesis of bladder TCC, this study examined the expression of T beta R-I and T beta R-II in 46 bladder TCC patients using immunohistochemistry. Since histopathological grade is a widely accepted marker of prognosis, the results were compared in relation to the three grades of bladder TCC. The results demonstrated that the loss of TGF-beta receptors expression is associated with increasing histopathological grades of bladder TCC. Specifically, both T beta R-I and T beta R-II were readily detected in all 10 normal bladder mucosa specimens. Likewise, all 6 specimens of grade I TCC samples expressed high levels of both TGF-beta receptors. However, among grade II TCC samples, T beta R-I and T beta R-II were detected in 78% and 89%, respectively: among grade III TCC samples, T beta R-I and T beta R-II were detected in 45% and 41%, respectively. These results suggested that loss of sensitivity to TGF-beta may play a role in the progression of TCC from low to high grade disease.

    Title Loss of Expression of Transforming Growth Factor Beta Type I and Type Ii Receptors Correlates with Tumor Grade in Human Prostate Cancer Tissues.
    Date February 1999
    Journal Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
    Excerpt

    Transforming growth factor beta1 (TGF-beta1) is a potential regulator of prostate cancer cell growth that signals through a heteromeric complex composed of type I and type II receptors. In the present study, an attempt was made to establish a correlation between expression of TGF-beta receptors and tumor grade in archival human prostate cancer tissues. To this end, immunohistochemical studies for TGF-beta receptors were carried out on 32 cases of human prostate cancer and 8 samples of benign human prostate. In both benign and malignant human prostate tissues, immunoreactivity for both type I and type II receptors was detected predominantly in epithelial cells. In addition, there was an inverse correlation between the loss of expression of TGF-beta1 type I and type II receptors and the tumor grade. Of the 32 prostate cancer cases screened, staining was completely absent in four samples for type II receptor (P < 0.05) and eight samples for type I receptor (P < 0.025). In contrast, all eight samples of benign prostate tissues investigated in this study showed strong staining for both type I and type II receptors. These results, taken together, indicate that human prostate cancer cells frequently have loss of expression of TGF-beta type I and/or type II receptors. Furthermore, these observations provide a potential mechanism for prostate cancer cells to escape the growth-inhibitory effect of TGF-beta.

    Title Absence of Expression of Transforming Growth Factor-beta Type Ii Receptor is Associated with an Aggressive Growth Pattern in a Murine Renal Carcinoma Cell Line, Renca.
    Date November 1998
    Journal The Journal of Urology
    Excerpt

    Transforming growth factor-beta1 (TGF-beta1) inhibits the proliferation of many cancer cells. However, tumor cells frequently become resistant to this inhibitory effect due to the absence of TGF-beta receptor (TbetaR) expression. This study reports the nature of TGF-beta sensitivity in an aggressive murine renal carcinoma cell line, Renca, investigated in a series of experiments. The growth of Renca cells, in tissue culture, was not sensitive to the inhibitory effect of TGF-beta1 with doses ranging from 0.1 to 10 ng./ml., nor was this cell line sensitive to the effect of TGF-beta1 in inducing the expression of plasminogen activator inhibitor-I. Renca cells expressed TGF-beta1 mRNA and protein, as determined by RT-PCR and ELISA, respectively. The level of TGF-beta1 production by Renca cells was moderate, thus eliminating the possibility that endogenous TGF-beta1 production might be masking the effect of TGF-beta sensitivity. Furthermore, Renca cells expressed TbetaR-I mRNA, but did not express TbetaR-II mRNA, suggesting that the absence of this receptor may be the cause of TGF-beta insensitivity. Additionally, a vector containing the TbetaR-II cDNA was transiently transfected into Renca cells. The inhibitory effect of TGF-beta1 was introduced in Renca cells after transfection with this receptor. At the same time, the growth rate of these cells diminished significantly when compared with that of the wild type Renca cells, as judged by the rate of [3H]-thymidine incorporation in the absence of any exogenous TGF-beta1. These observations demonstrated that Renca cells lack the functional TbetaR-II and suggest that their aggressive growth pattern is due, at least in part, to their insensitivity to TGF-beta.

    Title Loss of Expression of Transforming Growth Factor-beta Receptors is Associated with Poor Prognosis in Prostate Cancer Patients.
    Date September 1998
    Journal Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
    Excerpt

    Transforming growth factor beta (TGF-beta) is a potent inhibitor of proliferation in most cells and exerts its effects through an interaction with membrane receptors type I (TGF-betaRI) and type II (TGF-betaRII). Recently, we have demonstrated a correlation between the loss of expression of TGF-betaRI and TGF-betaRII and increasing Gleason score in archival human prostate cancer tissues. To evaluate the potential prognostic value of this observation, the present study investigated the expression of TGF-beta receptors in association with disease progression after the initial diagnosis in 52 archival human prostate cancer tissues. The expression of both TGF-betaRI and TGF-betaRII was correlated with the Gleason score, clinical tumor stage, 4-year survival rate, and serological recurrence rate after radical prostatectomy. Results revealed that there was a significant association between the Gleason score and the loss of expression of TGF-betaRI (P < 0.025) and TGF-betaRII (P < 0.01). However, only the loss of TGF-betaRI expression showed a statistically significant association with the clinical tumor stage (P < 0.05), 4-year survival rate (P < 0.05), and serological recurrence rate after radical prostatectomy (P < 0.025). Therefore, these data indicate that the loss of TGF-betaRI expression as measured by immunohistochemical staining may be a potential prognostic marker in prostate cancer patients.

    Title Prostate Cancer Cell Growth Inhibition by Tamoxifen is Associated with Inhibition of Protein Kinase C and Induction of P21(waf1/cip1).
    Date September 1998
    Journal The Prostate
    Excerpt

    BACKGROUND: Inhibition of protein kinase C (PKC) and modulation of transforming growth factor-beta (TGF-beta) are both associated with tamoxifen treatment, and both appear to be important in the regulation of prostate cancer cell growth. Investigations were performed which sought to measure the efficacy, and to elucidate the mechanism of growth inhibition by tamoxifen, in hormone-refractory prostate cancer. METHODS: Growth assays were performed on PC3, PC3-M, and DU145 prostate cancer cells. TGF-beta was measured by ELISA; p21(waf1/cip1) and retinoblastoma (Rb) protein levels were measured by Western blot; PKC activity was measured by kinase assay; and effects upon cell cycle were measured by flow cytometric analysis. RESULTS: IC50s for growth inhibition ranged from 5.5-10 microM, and were not affected by estrogen. Tamoxifen-mediated growth inhibition was not associated with induction of TGF-beta. However, tamoxifen treatment was associated with inhibition of PKC, which was followed by induction of p21(waf1/cip1), Rb dephosphorylation, and G1/S phase cell cycle arrest. Similar effects were observed with the known PKC inhibitor, Ro31-8220. CONCLUSIONS: These data suggest that micromolar concentrations of tamoxifen inhibit prostate cancer cell growth by inhibition of PKC, resulting in induction of the p21(waf1/cip1) protein.

    Title Telomerase: a Potential Marker of Bladder Transitional Cell Carcinoma in Bladder Washes.
    Date May 1998
    Journal Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
    Excerpt

    Telomerase is an enzyme that immortalizes cells by maintaining a constant telomere length. Here, telomerase activity in bladder washes was analyzed and compared with the final pathological diagnosis in 23 patients with bladder transitional cell carcinoma (TCC). Bladder washes and normal tissues were obtained from each patient prior to transurethral resection of bladder tumor. Telomerase activity was detected using telomeric repeat amplification protocol assay based on PCR. Cytological diagnosis of centrifuged cells from bladder washes was made using Papanicolau's stain. Results demonstrated that telomerase activity was detected in 95.7% of both cancer tissues and bladder washes. In normal tissues, telomerase activity was not detected in 22 of 23 samples. Regarding cytological diagnosis, only 69.6% of bladder wash samples had positive cytology. Moreover, in five cases of grade 1 TCC, only 20% of the cytological specimens were positive for malignancy, whereas 80% showed positive telomerase activity. These results demonstrate that telomerase activity is detectable in a majority of human bladder cancer tissues and bladder washes obtained from patients with TCC. In addition, results of this study suggest that the presence of telomerase in bladder washes may be a specific marker of bladder cancer, especially in low-grade tumors.

    Title Prostatic Ductal System in Rats: Tissue-specific Expression and Regional Variation in Stromal Distribution of Transforming Growth Factor-beta 1.
    Date October 1997
    Journal The Prostate
    Excerpt

    BACKGROUND: Regional variations in stromal-epithelial interactions, mediated through soluble growth factors, may be responsible for differences in epithelial growth and death observed between regions of the rat prostatic ductal system. Since transforming growth factor-beta 1 (TGF-beta 1) can induce prostatic epithelial cell death in vitro and in vivo, we examined the localization and production of TGF-beta 1 with respect to the functional regions of the rat prostatic ductal system. METHODS: The distribution of TGF-beta 1 in the rat ventral prostate was examined by immunohistochemistry. Cell type-specific expression of TGF-beta 1 was determined using RT-PCR analysis of prostate epithelial and stromal cell fractions separated by Percoll gradient centrifugation. RESULTS: Immunohistochemical staining of normal prostate revealed regional variations in stromal TGF-beta 1 protein, which was most abundant in the stroma surrounding the degenerative proximal ducts. TGF-beta 1 staining was also tightly associated with the prostatic smooth muscle. Results of RT-PCR experiments confirmed the major source of TGF-beta 1 mRNA in normal rat prostate to be the stroma, with lesser expression by the epithelium. CONCLUSIONS: Stromal TGF-beta 1 was associated with cell death in the adjacent epithelial cell compartment in the prostatic ductal system, and alpha-smooth muscle actin-positive stromal cells may play a negative growth-regulatory role in the rat ventral prostate through production of TGF-beta 1.

    Title Telomerase Activity: a Potential Marker of Bladder Transitional Cell Carcinoma in Bladder Washes.
    Date September 1997
    Journal Yonsei Medical Journal
    Excerpt

    The enzyme telomerase maintains a constant telomere length in immortalized cells, allowing unlimited cell proliferation. Almost all cancer cells express telomerase activity. However, little data is available regarding the role of telomerase activity in the detection of bladder cancer with a bladder wash specimen. We detected telomerase activity in a bladder wash specimen of bladder cancer and normal tissues, and compared them with final pathologic diagnosis. Twenty-three patients with transitional cell carcinoma (TCC) of the bladder were enrolled in our study. A bladder wash specimen was obtained before transurethral resection of the bladder (TURB) and normal and cancer tissues from the same patients during TURB. Telomerase activity was analyzed in each specimen a using telomeric repeat amplification protocol (TRAP) assay based on polymerase chain reaction (PCR) technique. Cytologic diagnosis was performed using Papanicolaou's stain with cytocentrifuged cytology preparation. We observed telomerase activity in 95.7% (22/23) of bath cancer tissues and bladder wash specimens; only one case did not express telomerase activity. Telomerase activity was undetected in all normal tissues except one, which was obtained from a patient with carcinoma in situ. A total of 69.6% (16/23) of wash specimens were positive in cytopathologic diagnosis. The accuracy of cytopathologic diagnosis in pathologic grade 2 or 3 was relatively high (83.3%, 15/18). However, in five cases of grade 1 TCC only 20% (1/5) of cytologic diagnosis was positive whereas the telomerase activity of wash specimens was detected in 80% (4/5). Our data demonstrates that not only the majority of human bladder cancer tissues, but also the bladder wash specimens obtained from patients with TCC, expressed telomerase activity. It indicates that telomerase activity may be a reliable marker in detecting bladder cancer especially in cases with a low grade that bladder wash cytology can miss.

    Title Fetal Mouse Selenophosphate Synthetase 2 (sps2): Characterization of the Cysteine Mutant Form Overproduced in a Baculovirus-insect Cell System.
    Date March 1997
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    A novel gene detected in mouse embryonic sites of hematopoiesis was cloned and shown to be a eukaryotic analog of the Escherichia coli selenophosphate synthetase gene. Unlike the E. coli enzyme, which is not a selenoprotein, the presence of selenocysteine in the mouse enzyme is indicated by a TGA codon in the open reading frame of the gene in a position corresponding to the essential cysteine of the E. coli enzyme. An ionized selenol group in place of a cysteine sulfhydryl group could render this mammalian selenocysteine-containing enzyme a more active catalyst. The native cDNA clone and also a mutant form containing a TGC (cysteine) codon in place of TGA were expressed in a baculovirus-insect cell system. Based on recovery of purified proteins, expression of the mutant enzyme was about 40 times higher than wild-type enzyme. The cysteine mutant enzyme exhibited selenophosphate synthetase activity in the assay that measures selenide-dependent AMP formation from ATP. Although expression of wild-type enzyme has not been optimized, the mutant form of the fetal mouse enzyme can be produced in amounts sufficient for isolation in homogeneous form and precise physicochemical and mechanistic studies allowing direct comparison with the analogous cysteine-containing prokaryotic enzyme.

    Title Molecular Cloning and Characterization of the 78-kilodalton Glucose-regulated Protein of Trypanosoma Cruzi.
    Date June 1994
    Journal Infection and Immunity
    Excerpt

    The protozoan Trypanosoma cruzi is the etiologic agent of Chagas' disease, an illness responsible for morbidity and death among millions of Latin Americans. Mice also develop this disease when infected with T. cruzi and are a useful model organism for the study of parasite-specific immune responses. To identify immunogenic T. cruzi antigens, serum from an infected mouse was used to isolate clones from a T. cruzi epimastigote cDNA expression library. One of these clones was found to encode the 78-kDa glucose-regulated protein (grp78), the endoplasmic reticular member of the 70-kDa heat shock protein (hsp70) family. Like the mammalian and yeast grp78s, the T. cruzi protein contains an endoplasmic reticular leader peptide and a carboxyl-terminal endoplasmic reticular retention sequence. T. cruzi grp78 is encoded by a tandemly arranged family of three genes located on a chromosome of 1.6 Mb. The effects on grp78 expression of heat shock and tunicamycin treatment, the latter of which specifically stimulates mammalian grp78, were investigated. While the level of the grp78 protein remained constant under all circumstances, grp78 mRNA was unaffected by heat shock but induced fivefold by tunicamycin. Finally, we found that grp78 is the most immunogenic of the T. cruzi heat shock proteins we have characterized, reacting strongly in immunoblots with sera from infected mice.

    Title Selenophosphate Synthetase. Enzyme Properties and Catalytic Reaction.
    Date May 1994
    Journal The Journal of Biological Chemistry
    Excerpt

    Selenophosphate synthetase, the product of the selD gene, produces the biologically active selenium donor compound, monoselenophosphate, from ATP and selenide. Isolation of the enzyme and characterization of some of its physical and catalytic properties are described. Magnesium ion and a monovalent cation, K+, NH4+, or Rb+, are required for catalytic activity. Polyphosphates and other common nucleotide triphosphates do not replace ATP as substrate. The stoichiometry of the catalytic reaction (Reaction 1) was established using 31P NMR, anaerobic molecular sieve chromatography, and radiochemical labeling procedures. ATP+selenide+H2O-->selenophosphate+Pi+AMP. In the absence of selenide, ATP is converted completely to AMP and orthophosphate upon prolonged incubation with elevated levels of enzyme. AMP is a competitive inhibitor of ATP, Ki = 170 microM, whereas selenophosphate and orthophosphate are weak inhibitors indicating a multistep reaction. Attempts to obtain direct evidence for a postulated enzyme-pyrophosphate intermediate using several experimental approaches are described. No exchange of [14C]AMP with ATP could be detected after the enzyme was freed of traces of contaminating adenylate kinase by chromatography on phenyl-Sepharose.

    Title Mr Imaging of Hepatic Iron Overload in Rat.
    Date March 1993
    Journal Journal of Magnetic Resonance Imaging : Jmri
    Excerpt

    To investigate the relationship of hepatic signal intensity and T2 with histologic grading in an animal model of oral iron overload and to determine the duration of feeding necessary to produce abnormalities detectable on magnetic resonance (MR) images, hepatic iron overload was induced in 12 rats by feeding them a diet supplemented with 4% carbonyl iron for 2-11 weeks. Iron overload seen on MR images was graded independently and blindly by two radiologists as normal, mild, moderate, or severe. The rats were killed, and histologic findings were graded blindly by four pathologists using a similar subjective scale. Hepatic T2 values were estimated from spin-echo images. In the rats with iron overload, intracellular iron deposition was noted on histologic studies. On MR images, hepatic signal intensity and T2 decreased after only 2 weeks of dietary iron overload, and both continued to decrease with longer duration of feeding. There was significant correlation between iron overload duration and changes on MR images and between MR images and histologic grading (r = .92, P = .0001 for both). The mean T2 of hepatic iron overload decreased with longer duration of feeding.

    Title Inactivation of S-adenosylhomocysteine Hydrolase by Nucleosides.
    Date July 1985
    Journal Biochimica Et Biophysica Acta
    Excerpt

    The irreversible inactivation of S-adenosylhomocysteine hydrolase purified from hamster and bovine liver by adenosine analogs substituted in the 5' and 2 positions has been investigated in detail. 5'-Cyano-5'-deoxyadenosine inactivates as potently as 9-beta-D-arabinofuranosyladenine (Ara-A). Substitution of the Ara-A at the 2 position by halogens or deleting N at the 3 position decreases its potency. Although weak, 2',3'-dideoxyadenosine can also inactivate the enzyme. The irreversible inactivation of the hydrolase in rat hepatocytes incubated with 2-chloroadenosine or 3-deaza-Ara-A could be demonstrated, concomitant with increases in 35S-labeled S-adenosylhomocysteine and S-adenosylmethionine in the hepatocytes.

    Title Dyspareunia: an Unusual Presentation of Leiomyoma of the Bladder.
    Date
    Journal Reviews in Urology
    Excerpt

    Leiomyoma is a rare, benign tumor of the bladder. It frequently has an unusual presentation and its treatment options remain controversial. We describe a case of a leiomyoma of the bladder in a young female whose chief complaint was dyspareunia, and we review the management options.

    Title An Efficient Adaptive Feedback Cancellation Using by Independent Component Analysis for Hearing Aids.
    Date
    Journal Conference Proceedings : ... Annual International Conference of the Ieee Engineering in Medicine and Biology Society. Ieee Engineering in Medicine and Biology Society. Conference
    Excerpt

    In this paper, we proposed a feedback cancellation algorithm based on independent component analysis (ICA) for digital hearing aids. In conventional adaptive feedback cancelling systems, the normalized least mean squares (NLMS) algorithm used to reduce acoustic feedback in which hearing aids occurs, generally at high gains. But primary input signal depend on the acoustic feedback signal in higher-order statistics, proposed algorithm was better acoustic feedback cancelling performance than the conventional NLMS algorithm when the input signal has a Laplacian distribution with high-order processing in real-time simulation of TMS320C 6711 DSK.

    Title Superparamagnetic Iron Oxide Nanoparticles Coated with Galactose-carrying Polymer for Hepatocyte Targeting.
    Date
    Journal Journal of Biomedicine & Biotechnology
    Excerpt

    Our goal is to develop the functionalized superparamagnetic iron oxide nanoparticles (SPIONs) demonstrating the capacities to be delivered in liver specifically and to be dispersed in physiological environment stably. For this purpose, SPIONs were coated with polyvinylbenzyl-O-beta-D-galactopyranosyl-D-gluconamide (PVLA) having galactose moieties to be recognized by asialoglycoprotein receptors (ASGP-R) on hepatocytes. For use as a control, we also prepared SPIONs coordinated with 2-pyrrolidone. The sizes, size distribution, structure, and coating of the nanoparticles were characterized by transmission electron microscopy (TEM), electrophoretic light scattering spectrophotometer (ELS), X-ray diffractometer (XRD), and Fourier transform infrared (FT-IR), respectively. Intracellular uptake of the PVLA-coated SPIONs was visualized by confocal laser scanning microscopy, and their hepatocyte-specific delivery was also investigated through magnetic resonance (MR) images of rat liver. MRI experimental results indicated that the PVLA-coated SPIONs possess the more specific accumulation property in liver compared with control, which suggests their potential utility as liver-targeting MRI contrast agent.

    Title Pegylated Conjugated Linoleic Acid Stimulation of Apoptosis Via a P53-mediated Signaling Pathway in Mcf-7 Breast Cancer Cells.
    Date
    Journal European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.v
    Excerpt

    The objective of this study was to investigate whether PEGylated conjugated linoleic acid (PCLA), as compared with conjugated linoleic acid (CLA) alone, displays anti-cancer properties in MCF-7 breast cancer cells. To generate PCLA, CLA was simply coupled to poly(ethylene glycol) (PEG) at the melting state of PEG without a solvent or a catalyst. The coupling reaction generated an ester linkage between the carboxyl group of CLA and hydroxyl one of PEG. The half-life of the generated PCLA was 52h at pH 7.4 at 37 degrees C, indicating that PCLA potentially acts as a pro-drug. Apoptosis of MCF-7 breast cancer cells treated with PCLA showed a dose response to PCLA concentration during treatment. In addition, pro-apoptotic proteins such as Bax were up-regulated, whereas anti-apoptotic proteins, such as Bcl-2, were down-regulated by treatment with both CLA and PCLA. The tumor suppressor gene p53 was significantly up-regulated by treatment with increasing concentrations of PCLA, suggesting that PCLA-induced apoptosis is regulated by a p53-mediated signaling pathway. Overall, the anti-cancer effects of PCLA on MCF-7 breast cancer cells may have therapeutic significance.

    Title Intracranial Tuberculoma with Adjacent Inflammatory Aneurysms.
    Date
    Journal Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia
    Excerpt

    We describe for the first time a case of intracranial tuberculoma with adjacent intracerebral inflammatory aneurysms, and include a brief discussion of the developmental mechanism of these pathologies. A 28-year-old woman presented with a history of intermittent seizure attacks. She had been diagnosed as having pulmonary tuberculosis 1 year previously, and had been treated with antituberculosis medications for 9 months. Her brain MRI revealed a 1-cm-diameter round subcortical mass lesion on the left parietal lobe, which showed gadolinium enhancement. At surgery, we were surprised to find multiple small aneurysms in the distal middle cerebral arteries surrounding the mass. The mass was totally removed, and the aneurysms were secured by wrapping and fibrin tissue adhesive. The mass was diagnosed as a tuberculoma, and the aneurysms were suspected of being inflammatory in nature and associated with the patient's tuberculosis.

    Title Primary Glioblastoma in the Pineal Region: a Case Report and Review of the Literature.
    Date
    Journal Journal of Medical Case Reports
    Excerpt

    ABSTRACT: INTRODUCTION: Glioblastoma in the pineal region is extremely rare with only a few cases reported in the literature. CASE PRESENTATION: A 68-year-old man presented with a sudden deterioration manifesting as a headache, vomiting and gait disturbance. A magnetic resonance imaging study revealed a heterogeneously ring-enhanced mass in the pineal region. The mass was subtotally removed through the occipital transtentorial approach, and diagnosed as a glioblastoma. CONCLUSION: We discuss the clinical course, radiological findings and treatment strategies of pineal glioblastoma with a review of the relevant literature.

    Title Bioactive Composites Consisting of Peek and Calcium Silicate Powders.
    Date
    Journal Journal of Biomaterials Applications
    Excerpt

    Bioactive bone-repairing materials with mechanical properties analogous to those of natural bone can be obtained through the combination of bioactive ceramic fillers with organic polymers. Previously, we developed novel bioactive microspheres in a binary CaO-SiO2 system produced through a sol-gel process as filler for the fabrication of composites. In this study, we fabricate bioactive composites in which polyetheretherketone is reinforced with 0-50 vol% 30CaO c 70SiO2 (CS) microspheres. The prepared composites reinforced with CS particles form hydroxyapatite on their surfaces in simulated body fluid. The induction periods of hydroxyapatite formation on the composites decrease with increasing amount of CS particles. The mechanical properties of the composites are evaluated by three-point bending test. The composites reinforced with 20 vol% CS particles show 123.5 MPa and 6.43 GPa in bending strength and Young's modulus, respectively.

    Title Glucocorticoid Receptor Changes Associate with Age in the Paraventricular Nucleus of Type Ii Diabetic Rat Model.
    Date
    Journal Neurochemical Research
    Excerpt

    Diabetes is a metabolic disorder that is associated with the dysregulation of a number of systems within the body. In the present study, we investigated glucocorticoid receptor (GR) immunoreactivity and its protein levels in the paraventricular nuclei of 4-, 12-, 20- and 30-week-old Zucker diabetic fatty (fa/fa, ZDF) and in Zucker lean control (fa/+ or +/+, ZLC) rats, because the progressive induction of diabetes is detectable in this model after 7 weeks of age and chronic diabetic conditions are maintained after 12 weeks of age. GR immunoreactivity was detected in parvocellular paraventricular nuclei and this and GR protein levels were exponentially increased according to the ages. In particular, GR immunoreactivities and protein levels were markedly more increased in 30-week-old ZDF rats than in age-matched ZLC group and in younger ZDF group. The present study suggests that GR immunoreactivity and its protein level is associated with a degenerative phenotype in the hypothalamus of from 12-weeks old in the ZDF rat type II diabetes model.

    Title Strain-specific Differences in Cell Proliferation and Differentiation in the Dentate Gyrus of C57bl/6n and C3h/hen Mice Fed a High Fat Diet.
    Date
    Journal Brain Research
    Excerpt

    The authors investigated strain-specific cell proliferation and differentiation differences in the dentate gyri of C57BL/6N (susceptible strain to obesity) and C3H/HeN (resistant strain to obesity) mice. In addition, the influences of a high fat diet (HD) on neuronal differentiation in C57BL/6N and C3H/HeN mice fed a low-fat diet (LD) or HD for 4 or 12 weeks were investigated. Body weight and body weight gains were significantly higher in HD-fed C57BL/6N and C3H/HeN mice than in LD-fed C57BL/6N and C3H/HeN mice. In particular, body weight gains were significantly higher in C57BL/6N mice than in C3H/HeN mice. In both of HD- and LD-fed C57BL/6N and C3H/HeN mice for 4 weeks, some Ki67 and many DCX immunoreactive cells were detected in the subgranular zone of the dentate gyrus. In HD-fed C57BL/6N and C3H/HeN mice, the number of Ki67 immunoreactive cells and DCX immunoreactivities in the dentate gyri were significantly lower than in LD-fed C57BL/6N and C3H/HeN mice. However, the number of Ki67 immunoreactive cells and DCX immunoreactivities in HD-fed C57BL/6N mice were significantly lower than in HD-fed C3H/HeN mice. These results suggest that C57BL/6N mice are more vulnerable to HD induced obesity than C3H/HeN mice. In addition, the feeding of HD was found to exacerbate reduced cell proliferation and differentiation in the dentate gyri of C57BL/6N mice as compared with that in C3H/HeN mice.

    Title Brain Mechanisms Involved in Processing Unreal Perceptions.
    Date
    Journal Neuroimage
    Excerpt

    Individuals sometimes experience an illusory or hallucinatory perception. This unreal perception is usually resolved after the individual recognizes that the perception was not real. In this study, we investigated the brain mechanisms involved in the process to an illusory or hallucinatory perception through 'obtaining insight into unreality'. We used a novel and intuitive paradigm designed by combining functional magnetic resonance imaging and augmented reality technology to simulate visual illusory stimuli that mimic hallucinations during brain scanning. The results showed various brain activations, predominantly in the amygdala in the early phase, the medial frontal cortex and the occipitotemporal junction in the middle phase, and the thalamus in the late phase, which correlated with a subject's proneness to hallucinating. These activations may correspond to a 'responding stage' for a perception-based immediate emotional reaction, a 'monitoring stage' for integration and recalibration to ascertain that the perception was not real, and a 'resolving stage' for controlling the information and finally settling it, respectively. Our paradigm and findings may be useful in understanding the mechanisms for discriminating and coping with hallucinatory perceptions.

    Title Colorectal Resection, Both Open and Laparoscopic-assisted, in Patients with Benign Indications is Associated with Proangiogenic Changes in Plasma Angiopoietin 1 and 2 Levels.
    Date
    Journal Surgical Endoscopy
    Excerpt

    INTRODUCTION: Plasma vascular endothelial growth factor (VEGF) levels are increased after surgery and may stimulate tumor growth after cancer resection. Angiopoietin 1 (Ang 1) and Ang 2 are proteins that impact VEGF-related angiogenesis (VRA). Ang 1 stabilizes mature vessels and inhibits VRA, whereas Ang 2 destabilizes vessels and promotes VRA. The ratio of Ang 1 to Ang 2 reflects the net effect; a low ratio promotes VRA. This study's purpose was to determine the impact of open and minimally invasive (MIS) colorectal resection (CR) for benign indications on plasma Ang 1 and 2 levels. METHODS: A total of 30 patients operated by MIS and 26 operated by open procedure were studied. Plasma was obtained preoperatively (PO) and on postoperative days (POD) 1 and 3. Plasma Ang 1 and Ang 2 levels were assessed via enzyme-linked immunosorbent assay (ELISA) in duplicate. Data were compared using Wilcoxon's matched-pair test and the Mann-Whitney U-test (significance p < 0.05). RESULTS: Indications, types of resection, and morbidity for the groups were similar. The mean MIS incision length was 4.7 +/- 1.6 cm while it was 16.8 +/- 7.1 cm for the open group (p = 0.0001). For both groups Ang 2 levels were significantly higher and the Ang 1 to Ang 2 ratio was significantly lower on POD 1 and 3 compared with preoperative results. Ang 1 levels were significantly decreased on POD 1 and 3 in the MIS group but only on POD 1 in the open group. For unclear reasons, preoperative Ang 1 levels and Ang 1 to Ang 2 ratios were significantly different between the groups, which precludes comparison of the postoperative results between groups. CONCLUSION: CR for benign pathology results in higher Ang 2 levels, lower Ang 1 levels, and lower Ang 1 to Ang 2 ratios early after surgery. These alterations are proangiogenic. These results, plus the already noted VEGF increases, suggest that surgery results in proangiogenic plasma protein changes that may stimulate tumor growth early after surgery. The duration of the Ang 1 and 2 changes needs to be determined.

    Title Comparative Study on High Fat Diet-induced 4-hydroxy-2e-nonenal Adducts in the Hippocampal Ca1 Region of C57bl/6n and C3h/hen Mice.
    Date
    Journal Neurochemical Research
    Excerpt

    In the present study, we investigated the influences of a high fat diet (HD) fed for 12 weeks, on lipid peroxidation and antioxidant enzyme using 4-hydroxy-2E-nonenal (HNE)-modified proteins (HNE-mp) and Cu,Zn-superoxide dismutase (SOD1) in the hippocampal CA1 region (CA1) in C57BL/6N and C3H/HeN mice. Body weights and body weight gains were significantly higher in HD fed C57BL/6N mice than in low fat diet (LD) fed C57BL/6N and LD or HD fed C3H/HeN mice. In the HD fed C57BL/6N and C3H/HeN mice, HNE-mp immunoreactivity and protein levels were much higher than in the LD fed C57BL/6N or C3H/HeN mice. In particular, HNE-mp immunoreactivity and protein levels in HD fed C57BL/6N mice was higher than that in the HD fed C3H/HeN mice. SOD1 immunoreaction was detected in the non-pyramidal cells of C57BL/6N mice, while in the C3H/HeN mice SOD1 immunoreaction was observed in CA1 pyramidal cells. The SOD1 immunoreactivity in the LD fed C57BL/6N and C3H/HeN mice was slightly, but not significantly decreased compared to that in the HD fed C57BL/6N and C3H/HeN mice, respectively. In addition, ionized calcium-binding adapter molecule 1 (Iba-1) immunoreactive microglia in the HD fed C57BL/6N showed hypertrophy of cytoplasm, which is the characteristics of activated microglia. These results suggest that HD fed C57BL/6N mice are more susceptible to lipid peroxidation in the CA1 than in LD fed C57BL/6N and LD or HD fed C3H/HeN mice without any differences of SOD1 expression.

    Title Gene Mutations of 23s Rrna Associated with Clarithromycin Resistance in Helicobacter Pylori Strains Isolated from Korean Patients.
    Date
    Journal Journal of Microbiology and Biotechnology
    Excerpt

    Although resistance of Helicobacter pylori to clarithromycin is a major cause of failure of eradication therapies, little information is available regarding gene mutations of clarithromycin-resistant primary and secondary H. pylori isolates in Korea. In the present study, we examined gene mutations of H. pylori 23S rRNA responsible for resistance to clarithromycin. DNA sequences of the 23S rRNA gene in 21 primary clarithromycin-resistant and 64 secondary clarithromycin-resistant strains were determined by PCR amplification and nucleotide sequence analyses. Two mutations of the 23S rRNA gene, A2143G and T2182C, were observed in primary clarithromycin-resistant isolates. In secondary isolates, dual mutation of A2143G+T2182C was frequently observed. In addition, A2143G+T2182C+ T2190C, A2143G+T2182C+C2195T, and A2143G+T2182C +A2223G were observed in secondary isolates. Furthermore, macrolide binding was tested on purified ribosomes isolated from T2182C or A2143C mutant strains with [14C]erythromycin. Erythromycin binding increased in a dose-dependent manner for the susceptible strain but not for the mutant strains. These results indicate that secondary isolates show a greater variety of 23S rRNA gene mutation types than primary isolates, and triple mutations of secondary isolates are associated with A2143G+T2182C in H. pylori isolated from Korean patients.

    Title Effect of In-1130, a Small Molecule Inhibitor of Transforming Growth Factor-beta Type I Receptor/activin Receptor-like Kinase-5, on Prostate Cancer Cells.
    Date
    Journal The Journal of Urology
    Excerpt

    PURPOSE: Transforming growth factor-beta is a potent immune suppressor that is over expressed by most malignant cells to evade the host immune response. Thus, a potential anticancer therapeutic strategy is the inhibition of transforming growth factor-beta signaling. MATERIALS AND METHODS: We investigated the specificity and the antitumor effect of IN-1130, a novel small molecule inhibitor of the transforming growth factor-beta type I receptor ALK-5. RESULTS: IN-1130 inhibited transforming growth factor-beta induced cell death and gene transcriptional activity in a concentration dependent manner in the human hepatoma cell line HepG2. Simultaneously immunoblot analysis demonstrated that IN-1130 inhibited the Smad2 phosphorylation induced by transforming growth factor-beta. To determine the specificity of IN-1130 for transforming growth factor-beta signaling the effect on active and bone morphogenic protein signaling was subsequently investigated. Results demonstrated that IN-1130 did not inhibit bone morphogenic protein signaling. However, active signaling was blocked by IN-1130 in a concentration dependent manner. Furthermore, immunoblot analysis for phospho-Smad2 following transfection with constitutively active ALK-1 to 7 demonstrated that IN-1130 inhibited ALK-4 (active receptor type IB), 5 (TbetaRI) and 7 (nodal type I receptor). To investigate the antitumor effect of IN-1130 WT mice were injected subcutaneously with the murine prostate cancer cell line Tramp C2. Seven days later IN-1130 was administered intraperitoneally daily for 30 days. Results demonstrated a dramatic decrease in tumor volume in association with an enhanced immune response in the treatment group. CONCLUSIONS: Taken together these results demonstrate that IN-1130 is a relatively nontoxic inhibitor of ALK-4/5/7 that may potentially treat prostate cancer.

    Title Neurenteric Cyst with Xanthomatous Changes in the Prepontine Area: Unusual Radiological Findings.
    Date
    Journal Journal of Neurosurgery. Pediatrics
    Excerpt

    Preoperative diagnosis of neurenteric cysts can be difficult because the imaging findings of a neurenteric cyst may be similar to those of an arachnoid cyst. The authors report a case of a neurenteric cyst with xanthomatous changes in the prepontine area. This 4-year-old girl was admitted to their institution with intermittent neck pain and vomiting. Computed tomography showed a hypodense mass in the prepontine area. Magnetic resonance imaging showed a cystic lesion measuring approximately 4 x 3 cm. The brainstem was displaced posteriorly, and the cisterns in both cerebellopontine angles were widened. The signal intensity of the cyst was similar to that of cerebrospinal fluid. Adjacent to the basilar artery there was a solid component of the mass that enhanced after administration of Gd. Intraoperatively, the authors found a cystic mass containing clear fluid with a yellowish solid nodule. On the basis of histopathological findings, the lesion was diagnosed as a neurenteric cyst with xanthomatous changes.

    Title Effects of Treadmill Exercise on Cell Proliferation and Differentiation in the Subgranular Zone of the Dentate Gyrus in a Rat Model of Type Ii Diabetes.
    Date
    Journal Neurochemical Research
    Excerpt

    In the present study, we investigated the effects of a treadmill exercise on serum glucose levels and Ki67 and doublecortin (DCX) immunoreactivity, which is a marker of cell proliferation expressed during cell cycles except G0 and early G1 and a marker of progenitors differentiating into neurons, respectively, in the subgranular zone of the dentate gyrus (SZDG) using a type II diabetic model. At 6 weeks of age, Zucker lean control (ZLC) and Zucker diabetic fatty (ZDF) rats were put on a treadmill with or without running for 1 h/day/5 consecutive days at 22 m/min for 5 weeks. Body weight was significantly increased in the control (without running)-ZDF rats compared to that in the other groups. In the control groups blood glucose levels were increased by 392.7 mg/dl in the control-ZDF rats and by 143.3 mg/dl in the control-ZLC rats. However, in the exercise groups, blood glucose levels were similar between the exercise-ZLC and ZDF rats: The blood glucose levels were 110.0 and 118.2 mg/dl, respectively. Ki67 positive nuclei were detected in the SZDG in control and exercise groups. The number of Ki67 positive nuclei was significantly high in exercise groups compared to that in the control groups. In addition, Ki67 positive cells were abundant in ZLC groups compared to those in ZDF groups. DCX-immunoreactive structures in the control-ZDF rats were lower than that in the control-ZLC rats. In the exercise groups, DCX-immunoreactive structures (somata and processes with tertiary dendrites) and DCX protein levels were markedly increased in both the exercise-ZLC and ZDF rats compared to that in the control groups. These results suggest that a treadmill exercise reduces blood glucose levels in ZDF rats and increases cell proliferation and differentiation in the SZDG in ZLC and ZDF rats compared to those in control groups.

    Title Overexpression of Erbb2 Induces Invasion of Mcf10a Human Breast Epithelial Cells Via Mmp-9.
    Date
    Journal Cancer Letters
    Excerpt

    Metastasis is the principal cause of death from breast cancer. ErbB2 (HER-2/neu) has been identified as an important regulator of metastatic potential of breast cancer. The present study investigated the molecular mechanism underlying the role of ErbB2 in malignant phenotypic conversion of MCF10A human breast epithelial cells which originally have 'normal' cell character. Here we report that ErbB2 induces invasion and migration of MCF10A cells though up-regulation of matrix metalloproteinase (MMP)-9. We also observed a marked reduction of an epithelial cell marker, E-cadherin, and an induction of vimentin in ErbB2-MCF10A cells, suggesting that epithelial-mesenchymal transition may play a role in the ErbB2-induced invasion and migration of MCF10A cells. Overexpression of ErbB2 significantly activated p38 MAPK and Akt, while Raf-1/MEK/ERK pathway was not activated by ErbB2. Using pharmacological inhibitors, we further show that p38 MAPK and Akt signaling pathways are crucial for the ErbB2-induced MMP-9 up-regulation, invasion and migration of MCF10A cells. Given that ErbB2 is one of the most important oncogenes in human breast cancer and thus is an attractive therapeutic target, our findings may provide a molecular basis for the promoting role of ErbB2 in breast cancer progression.

    Title Colorectal Resection, Both Open and Laparoscopic-assisted, in Patients with Benign Indications is Associated with Proangiogenic Changes in Plasma Angiopoietin 1 and 2 Levels.
    Date
    Journal Surgical Endoscopy
    Title Duplication of the Extrahepatic Bile Duct in Association with Choledocholithiasis As Depicted by Mdct.
    Date
    Journal Korean Journal of Radiology : Official Journal of the Korean Radiological Society
    Excerpt

    We report here on an extremely rare case of duplicated extrahepatic bile ducts that was associated with choledocholithiasis, and this malady was visualized by employing the minimum intensity projection images with using multi-detector row CT. The presence of duplicated extrahepatic bile ducts with a proximal communication, and the ducts were joined distally and they subsequently formed a single common bile duct, has not been previously reported.

    Title Analogy of Strain Energy Density Based Bone-remodeling Algorithm and Structural Topology Optimization.
    Date
    Journal Journal of Biomechanical Engineering
    Excerpt

    In bone-remodeling studies, it is believed that the morphology of bone is affected by its internal mechanical loads. From the 1970s, high computing power enabled quantitative studies in the simulation of bone remodeling or bone adaptation. Among them, Huiskes et al. (1987, "Adaptive Bone Remodeling Theory Applied to Prosthetic Design Analysis," J. Biomech. Eng., 20, pp. 1135-1150) proposed a strain energy density based approach to bone remodeling and used the apparent density for the characterization of internal bone morphology. The fundamental idea was that bone density would increase when strain (or strain energy density) is higher than a certain value and bone resorption would occur when the strain (or strain energy density) quantities are lower than the threshold. Several advanced algorithms were developed based on these studies in an attempt to more accurately simulate physiological bone-remodeling processes. As another approach, topology optimization originally devised in structural optimization has been also used in the computational simulation of the bone-remodeling process. The topology optimization method systematically and iteratively distributes material in a design domain, determining an optimal structure that minimizes an objective function. In this paper, we compared two seemingly different approaches in different fields-the strain energy density based bone-remodeling algorithm (biomechanical approach) and the compliance based structural topology optimization method (mechanical approach)-in terms of mathematical formulations, numerical difficulties, and behavior of their numerical solutions. Two numerical case studies were conducted to demonstrate their similarity and difference, and then the solution convergences were discussed quantitatively.

    Title Social Pressure-induced Craving in Patients with Alcohol Dependence: Application of Virtual Reality to Coping Skill Training.
    Date
    Journal Psychiatry Investigation
    Excerpt

    This study was conducted to assess the interaction between alcohol cues and social pressure in the induction of alcohol craving.

    Title Polybrominated Diphenyl Ethers Orally Administration to Mice Were Tansferred to Offspring During Gestation and Lactation with Disruptions on the Immune System.
    Date
    Journal Immune Network
    Excerpt

    The present study was undertaken to examine the immunological effects of pentabrominated diphenyl ether (penta-BDE) and decabrominated diphenyl ether (deca-BDE) on the immune system of the dams and the developmental immune system of the offsprings.

    Title Increasing Incidence of Inflammatory Bowel Disease Among Young Men in Korea Between 2003 and 2008.
    Date
    Journal Digestive Diseases and Sciences
    Excerpt

    BACKGROUND AND AIMS: Temporal trends in incidence rates of Crohn's disease (CD) and ulcerative colitis (UC) can provide valuable clues about etiology. Korea has a draft system, and every male must fulfill his military service. However, according to military rules, patients with CD and UC are not conscripted into the army, and when the disease is diagnosed during military service, patients are relieved from military duties. Such policies provide a unique opportunity to determine the incidence of CD and UC among young men in Korea. We studied the incidence of CD and UC over time in Korea, a rapidly developing country. METHODS: The Armed Forces Medical Command of the Republic of Korea Army provided lists of members who were relieved from military duties due to diagnoses of CD and UC between 2003 and 2008. RESULTS: During this 6-year period, there were 96 incident cases of CD and 104 incident cases of UC. For the 6-year period, the adjusted mean annual incidence rates of CD and UC per 100,000 persons were 3.2 and 3.5, respectively. When analyzed by 2-year intervals, the mean annual incidence of CD and UC increased, from 1.8 and 1.7 per 100,000 persons in 2003-2004, to 2.7 and 3.3 per 100,000 persons in 2005-2006, and to 5.1 and 5.4 per 100,000 persons in 2007-2008, respectively. CONCLUSIONS: Incidence of CD and UC among young men is rapidly increasing in Korea, which strongly suggests an environmental contribution to the disease.

    Title Epstein-barr Virus-associated Lymphoepithelioma-like Gastric Carcinoma Presenting As a Submucosal Mass: Ct Findings with Pathologic Correlation.
    Date
    Journal Korean Journal of Radiology : Official Journal of the Korean Radiological Society
    Excerpt

    A lymphoepithelioma-like carcinoma, characterized by a carcinoma with heavy lymphocyte infiltration, is one of the histological patterns observed in patients with Epstein-Barr virus (EBV)-associated gastric carcinoma. Less than half of invasive carcinomas with lymphoepithelioma-like histology can grow to make a submucosal mass. These tumors generally have a better prognosis than conventional adenocarcinomas. We report a case of an EBV-associated lymphoepithelioma-like gastric carcinoma that presented as a submucosal mass on multi-detector (MD) CT and correlate them with the pathology.

    Title Paxilline Enhances Trail-mediated Apoptosis of Glioma Cells Via Modulation of C-flip, Survivin and Dr5.
    Date
    Journal Experimental & Molecular Medicine
    Excerpt

    Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) induces apoptosis selectively in cancer cells while sparing normal cells. However, many cancer cells are resistant to TRAIL-induced cell death. Here, we report that paxilline, an indole alkaloid from Penicillium paxilli, can sensitize various glioma cells to TRAIL-mediated apoptosis. While treatment with TRAIL alone caused partial processing of caspase-3 to its p20 intermediate in TRAIL-resistant glioma cell lines, co-treatment with TRAIL and subtoxic doses of paxilline caused complete processing of caspase-3 into its active subunits. Paxilline treatment markedly upregulated DR5, a receptor of TRAIL, through a CHOP/GADD153-mediated process. In addition, paxilline treatment markedly downregulated the protein levels of the short form of the cellular FLICE-inhibitory protein (c-FLIPs) and the caspase inhibitor, survivin, through proteasome-mediated degradation. Taken together, these results show that paxilline effectively sensitizes glioma cells to TRAIL-mediated apoptosis by modulating multiple components of the death receptor-mediated apoptotic pathway. Interestingly, paxilline/TRAIL co-treatment did not induce apoptosis in normal astrocytes, nor did it affect the protein levels of CHOP, DR5 or survivin in these cells. Thus, combined treatment regimens involving paxilline and TRAIL may offer an attractive strategy for safely treating resistant gliomas.

    Title Tissue Hogg1 Genotype Predicts Bladder Cancer Prognosis: A Novel Approach Using a Peptide Nucleic Acid Clamping Method.
    Date
    Journal Annals of Surgical Oncology
    Excerpt

    BACKGROUND: Tissue genotyping is a more useful approach than using blood genomic DNA, because the tumor tissues can reflect the effects of somatic mutations in cancer. We investigated the value of the human oxoguanine glycosylase (hOGG1) genotype determined in tumor tissues as a prognostic indicator for bladder cancer (BC) using a novel technological approach. METHODS: A total of 335 DNA samples from patients with primary BC were analyzed by peptide nucleic acid (PNA)-mediated real-time polymerase chain reaction (PCR) clamping to characterize the association between genetic polymorphisms within hOGG1 codon 326 and the clinicopathological characteristics of primary BC patients. RESULTS: Tumor stage and number were significantly associated with the hOGG1 codon 326 genotype in nonmuscle invasive bladder cancer (NMIBC) patients. Compared with Cys326Ser and Ser326Ser, the Cys326Cys genotype had a greater progression-free survival benefit in patients with muscle invasive bladder cancer (MIBC). Univariate and multivariate Cox regression analyses indicated that the hOGG1 Cys326Cys genotype has a protective effect against progression in MIBC (hazard ratio, 0.360 and 0.314, respectively). CONCLUSIONS: The hOGG1 tissue genotype is associated with aggressive clinicopathological features in NMIBC and with progression in patients with MIBC. Results suggest that the hOGG1 tissue genotype represents a promising marker for assessing BC prognosis in the clinical setting.

    Title Cpg Odn, Toll Like Receptor (tlr)-9 Agonist, Inhibits Metastatic Colon Adenocarcinoma in a Murine Hepatic Tumor Model.
    Date
    Journal The Journal of Surgical Research
    Excerpt

    Colorectal liver metastases (mets) are often refractory to conventional therapies. CpG oligodeoxynucleotide 1826 (CpG), a Toll like receptor (TLR)-9 agonist, inhibits murine tumor growth by augmenting Th1 immunity. The impact of CpG on metastatic colon tumors is unknown. The purpose of this study was to determine the effect of CpG on the growth of hepatic colon cancer mets.

    Title Macrophages Induce Neuroendocrine Differentiation of Prostate Cancer Cells Via Bmp6-il6 Loop.
    Date
    Journal The Prostate
    Excerpt

    BACKGROUND: Frequently associated with hormone refractory prostate cancer are neuroendocrine cells. Because these cells do not express androgen receptors and are castration-resistant, further understanding the mechanism of neuroendocrine differentiation (NED) of prostate cancer cells may yield novel intervention methods in hormone refractory prostate cancer. In this regard, the present study investigated the effect of macrophages on prostate cancer NED. METHODS: THP-1 and LNCaP or RAW264.7 and TRAMP-C2 cell line co-cultures were used to investigate NED-macrophage interactions. Also interleukin-6 (IL-6) knockout mice and macrophage-depleted mice were used to test NED in vivo. RESULTS: We found that co-culturing with THP-1 human monocytic cell line and RAW 264.7 murine macrophage cell line led to the NED of LNCaP and TRAMP-C2 prostate cancer cells, respectively. Specifically, the conditioned media of activated macrophages stimulated the expression of parathyroid hormone-related peptide (PTHrP), a marker of NED, in both LNCaP and TRAMP-C2 cells. Mechanistically, bone morphogenetic protein-6 (BMP-6) derived from prostate cancer cells increased the expression of IL-6 in macrophages. Subsequently, IL-6 induced the NED of prostate cancer cells. When this feedback loop was disrupted with neutralizing antibodies to either BMP-6 or IL-6, NED was no longer observed. In human prostate cancer tissues, neuroendocrine cells frequently co-localized with macrophages and BMP-6. In mice, the removal of IL-6 or macrophages blocked the BMP-6-induced NED of prostate cancer cells. CONCLUSIONS: Therefore, we propose that BMP-6 secreted by prostate cancer cells induces IL-6 expression in macrophages; IL-6, in turn, stimulates the NED of prostate cancer cells. Prostate © 2011 Wiley-Liss, Inc.

    Title Pathologic Implications of Prostatic Anterior Fat Pad.
    Date
    Journal Urologic Oncology
    Excerpt

    OBJECTIVE:: Lymph node status has significant pathologic implications in patients with prostate cancer. In this study, we have performed pathologic analysis of prostatic anterior fat pad (PAFP) excised during robot-assisted radical prostatectomy (RARP) to investigate the potential role of AFP on pathologic staging of prostate cancer. METHODS:: A total of 258 consecutive patients underwent PAFP excision during RARP between July 2007 and June 2009. PAFP was removed and submitted en bloc to the pathology department and evaluated for the presence of lymphoid tissue and metastatic prostate cancer. Retrospective chart review was performed for all patients. RESULTS:: Of the 258 patients, 30 (11.6%) had 1 or 2 PAFP lymph nodes and 228 (88.4%) men showed no lymphoid tissue in their PAFPs. Preoperatively, mean PSA level was higher in the former group. There were no significant pathologic differences between the 2 groups. Among the 30 patients with PAFP lymph nodes, 3 were positive for metastatic prostate cancer. All 3 of these patients had high-risk features preoperatively. In 1 patient, the pelvic lymph nodes were negative for metastatic prostate cancer. At 2-year follow-up, PSA level of this patient was undetectable. CONCLUSIONS:: Herein, we demonstrated that the PAFP contained lymph nodes in over 11% of the patients undergoing RARP at our institution. Prostate cancer was upstaged in 1 patient as a result of PAFP excision. Since this patient is free of biochemical recurrence at 2 years, routine excision and pathologic analysis of PAFP should be considered in prostate cancer patients undergoing radical prostatectomy.

    Title The Hogg1 Mutant Genotype is Associated with Prostate Cancer Susceptibility and Aggressive Clinicopathological Characteristics in the Korean Population.
    Date
    Journal Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo
    Excerpt

    The gene encoding human 8-oxoguanine glycosylase 1 (hOGG1) is involved in DNA base excision repair from oxidatively damaged DNA. A case-control study was conducted to evaluate the correlation between the susceptibility and clinicopathological outcomes of prostate cancer (CaP) and hOGG1 genotype.

    Title Pathologic Analysis of Glioblastoma Via Multiple Stereotactic Biopsies of Active Tumor and Necrosis.
    Date
    Journal Oncology Reports
    Excerpt

    To obtain more representative biopsy specimens in glioblastoma, we performed multiple stereotactic biopsies of active tumor and necrosis. We investigated their pathologic differences of diagnosis and also examined the pathologic features that varied with 11C-methionine uptake on PET. From December 2009 to October 2010, we performed stereotactic biopsies in 12 patients with radiologically heterogeneous, ring-enhanced lesions. We biopsied the MR enhanced lesions for active tumor and the MR non-enhanced lesions for necrosis and analyzed differences of pathologic diagnoses between them. As correlating factors of the degree of 11C-methionine uptake (T/N ratio), the pathologic findings, including cell density, Ki‑67 LI, microvessel density, number of endothelial proliferations, the immunopositivity for L-amino acid transporter 1 (LAT1) were analyzed. The final diagnosis of each specimen was glio-blastoma. The diagnostic failure rate was 33.3% (4/12 patients) when we selected only active tumors and 40% (4/10 patients) when we selected necrotic lesions. The T/N ratio showed a statistical correlation with cell density depending on the degree of necrosis and LAT1 immunopositivity (P=0.002 and 0.032). LAT1 was localized in the tumor cells, vascular endothelium, and the vicinity of endothelial proliferation. Multiple stereotactic biopsies of active tumor and necrosis could provide the diagnostic yield in glioblastoma. The 11C-methionine uptake mostly reflected cell densities depending on the degree of necrosis.

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