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Credentials

Education ?

Medical School Score
The University of Texas at San Antonio (1988)
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Awards & Distinctions ?

Associations
American Board of Surgery

Affiliations ?

Dr. Kim is affiliated with 9 hospitals.

Hospital Affiliations

Score

Rankings

  • Odessa Regional Hospital
    520 E 6th St, Odessa, TX 79761
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    Top 25%
  • Midland Memorial Hospital
    2200 W Illinois Ave, Midland, TX 79701
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    Top 25%
  • Medical Center Hospital
    500 W 4th St, Odessa, TX 79761
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    Top 50%
  • Regency Hospital - Odessa
    500 W 4th St, Odessa, TX 79761
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  • U-Mass Memorial Medical Center
  • Healthalliance Hospitals
  • Odessa Regional Medical Center
  • Umass Memorial Medical Center
  • Permian Regional Medical Center
    720 Hospital Dr, Andrews, TX 79714
  • Publications & Research

    Dr. Kim has contributed to 313 publications.
    Title Laminar Closure After Classic Hirabayashi Open-door Laminoplasty.
    Date March 2012
    Journal Spine
    Excerpt

    Prospective analysis of preoperative and postoperative radiological data.

    Title The Association of Albuminuria, Arterial Stiffness, and Blood Pressure Status in Nondiabetic, Nonhypertensive Individuals.
    Date March 2012
    Journal Journal of Hypertension
    Excerpt

    Although several studies have reported an association between microalbuminuria and pulse wave velocity in patients with hypertension or diabetes, there have been no reports of their significance in apparently healthy individuals.

    Title Inflammatory Mammary Carcinoma with Metastasis to the Brain and Distant Organs in a Spayed Shih Tzu Dog.
    Date March 2012
    Journal Journal of Veterinary Diagnostic Investigation : Official Publication of the American Association of Veterinary Laboratory Diagnosticians, Inc
    Excerpt

    Inflammatory mammary carcinoma (IMC) is a specific type of rare, very aggressive, and highly metastatic mammary cancer in both human beings and dogs. A 10-year-old female spayed Shih Tzu dog was diagnosed with secondary IMC. At necropsy, brain metastasis of mammary neoplastic cells was observed in tissues of the cerebrum and cerebellum. Metastases were also found in other distant organs such as heart, lung, liver, spleen, and inguinal lymph node. There is limited data about the metastasis of IMC and its pattern. The current report of IMC with brain metastases contributes to the understanding of metastatic IMC.

    Title Skeletal Muscle Mass to Visceral Fat Area Ratio is Associated with Metabolic Syndrome and Arterial Stiffness: The Korean Sarcopenic Obesity Study (ksos).
    Date February 2012
    Journal Diabetes Research and Clinical Practice
    Excerpt

    Sarcopenia measured as appendicular skeletal muscle mass (ASM), and central obesity measured as visceral fat area (VFA) may act synergistically to influence metabolic syndrome and atherosclerosis. However, several previous studies reported that metabolic risk is higher in non-sarcopenic obesity groups than in sarcopenic obesity groups because of the close relationship between muscle mass and body fat. We investigated the association of the ASM to VFA ratio, which we have termed the muscle-to-fat ratio (MFR), with metabolic syndrome and arterial stiffness.

    Title Expression of Her-2 and Nuclear Localization of Her-3 Protein in Canine Mammary Tumors: Histopathological and Immunohistochemical Study.
    Date February 2012
    Journal Veterinary Journal (london, England : 1997)
    Excerpt

    HER-2 and HER-3 are transmembrane receptor proteins that are considered to be important but poorly understood biomarkers in canine tumors. In this study, the expression and the localization of HER-2 and HER-3 were evaluated immunohistochemically in canine mammary tumors (n=64; 12 benign, 52 malignant). HER-2 overexpression was identified in 2/12 (16.7%) benign and in 18/51 (35.3%) malignant cases. HER-3 was expressed in a non-nuclear localization in 11/12 (91.7%) benign and 18/52 (34.6%) malignant tumors. In contrast, HER-3 was expressed in the nucleus of neoplastic cells in 0/12 (0%) benign and 22/52 (42.3%) malignant tumors. Nuclear HER-3 expression was higher in neoplastic epithelial cells compared to myoepithelial cells, and positively correlated with high histological grade and lymphatic vessel invasion. These results suggest that nuclear HER-3 expression is significantly associated with tumor progression and metastasis and may serve as a useful prognostic biomarker in canine malignant mammary tumors.

    Title 3-hydroxyflavone Improves the in Vitro Development of Cloned Porcine Embryos by Inhibiting Ros Production.
    Date January 2012
    Journal Cellular Reprogramming
    Excerpt

    UV-irradiation of oocytes during enucleation and serum starvation of donor cells during cell cycle synchronization may compromise the development competence of cloned embryos through excessive generation of reactive oxygen species (ROS). Here, we show that 3-hyroxyflavone (a flavonoid having hydroxyl group at 3 carbon position) inhibits UV- and serum starvation-induced ROS production in oocytes and donor cells, respectively, and thereby improves the in vitro development of cloned porcine embryos (p<0.05). In a parthenogenetic model, UV-irradiation for 5 sec or more was found to reduce the in vitro development and quality of the embryo, which could be rescued by their culture in the presence of 3-hydroxyflavone. The rescuing effect of 3-hydroxyflavone was associated with significant reduction in ROS level (14.4±1.0 vs. 47.1±6.7), increase in ERK signaling molecules by 2.1-fold, and decrease in Caspase3 expression by 3.2-fold. Culture of donor cells (18.5±1.4 vs. 13.0±1.7%) or cloned embryos (20.6±1.1 vs. 12.2±1.1%) in the presence of 3-hydroxflavone also increased (p<0.05) the rates of blastocyst formation in cloned embryos produced by the nuclear transfer of serum-starved donor cells into recipient cytoplasts exposed to UV-irradiation during the enucleation step. Importantly, both parthenotes and cloned embryos cultured in the presence of 3-hydroxyflavone had significantly increased ability to expand, and contained a higher number of cells than those of the control group (p<0.05). These results suggest that 3-hydroxyflavone may be useful for improving the in vitro developmental potential of cloned embryos through inhibition of ROS production induced by the UV-irradiation of oocyte and/or the serum starvation of donor cells.

    Title Preparation of Non-covalently Functionalized Graphene Using 9-anthracene Carboxylic Acid.
    Date January 2012
    Journal Nanotechnology
    Excerpt

    A simple way of achieving stable aqueous dispersion of graphene by non-covalent functionalization using 9-anthracene carboxylic acid has been successfully accomplished. Unlike in chemically reduced graphene, the C-sp(2) network of the graphene remains undistorted and therefore of superior quality. The non-covalent functionalization facilitates the exfoliation of graphite layers in a polarity controlled combination of media. A detailed exfoliation mechanism is proposed based on the controlled experiment and is supported by the data from UV-vis spectroscopy, transmission electron microscopy, and x-ray diffraction studies. Formation of monolayer graphene has been confirmed from Raman spectroscopy. The graphene based ultracapacitor shows a high value of specific capacitance (148 F g(-1)).

    Title A P53/mirna-34 Axis Regulates Snail1-dependent Cancer Cell Epithelial-mesenchymal Transition.
    Date January 2012
    Journal The Journal of Cell Biology
    Excerpt

    Snail1 is a zinc finger transcriptional repressor whose pathological expression has been linked to cancer cell epithelial-mesenchymal transition (EMT) programs and the induction of tissue-invasive activity, but pro-oncogenic events capable of regulating Snail1 activity remain largely uncharacterized. Herein, we demonstrate that p53 loss-of-function or mutation promotes cancer cell EMT by de-repressing Snail1 protein expression and activity. In the absence of wild-type p53 function, Snail1-dependent EMT is activated in colon, breast, and lung carcinoma cells as a consequence of a decrease in miRNA-34 levels, which suppress Snail1 activity by binding to highly conserved 3' untranslated regions in Snail1 itself as well as those of key Snail1 regulatory molecules, including β-catenin, LEF1, and Axin2. Although p53 activity can impact cell cycle regulation, apoptosis, and DNA repair pathways, the EMT and invasion programs initiated by p53 loss of function or mutation are completely dependent on Snail1 expression. These results identify a new link between p53, miR-34, and Snail1 in the regulation of cancer cell EMT programs.

    Title Reversible Tuning of Sers Hot Spots with Aptamers.
    Date January 2012
    Journal Advanced Materials (deerfield Beach, Fla.)
    Title Gm130: New Insights into Oocyte Asymmetric Division.
    Date December 2011
    Journal Cell Cycle (georgetown, Tex.)
    Title Pro- and Anti-inflammatory Cytokine Expression and Histopathological Characteristics in Canine Brain with Traumatic Brain Injury.
    Date December 2011
    Journal Journal of Veterinary Science
    Excerpt

    We analyzed the expression level and cellular localization of pro- and anti-inflammatory cytokines and histopathologically characterized canine traumatic brain injury (TBI). Canine TBI brains revealed subarachnoid and cerebral cortical hemorrhage, neutrophilic infiltration, neuronal necrosis, astrocytosis, and vasogenic edema. Immunohistochemical evaluations suggested that both pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, and tumor necrosis factor-α] and anti-inflammatory cytokines [IL-10 and transforming growth factor-beta (TGF-β)] were highly expressed in neurons and neutrophils. In particular, the highest magnitude of expression was identified for IL-1β and TGF-β. This data helps describe the pathologic characteristics of canine TBI, and may help in the design of potential therapeutic approaches to control secondary damage by inflammatory cytokines.

    Title Wave2 Regulates Meiotic Spindle Stability, Peripheral Positioning and Polar Body Emission in Mouse Oocytes.
    Date November 2011
    Journal Cell Cycle (georgetown, Tex.)
    Excerpt

    During oocyte meiotic maturation, meiotic spindles form in the central cytoplasm and then migrate to the cortex to extrude a small polar body, forming a highly polarized cell through a process involving actin and actin-related molecules. The mechanisms underlying oocyte polarization are still unclear. The Arp2/3 complex regulates oocyte polarization but it is not known whether the WASP family of proteins, a known regulator of the Arp2/3 complex, is involved in this context. In the present study, the role of WASP family member WAVE2 in mouse oocyte asymmetric division was investigated. (1) WAVE2 mRNA and protein were detected during mouse oocyte meiosis. (2) siRNA-mediated and antibody-mediated disruption of WAVE2 resulted in the failure of chromosome congression, spindle formation, spindle positioning and polar body extrusion. (3) WAVE2 regulated actin-driven chromosome migration since chromosomes were arrested in the central cytoplasm by WAVE2 RNAi in the absence of microtubules. (4) Localization of γ-tubulin and MAPK was disrupted after RNAi, confirming the effect of WAVE2 on spindle formation. (5) Actin cap and cortical granule-free domain (CGFD) formation was also disrupted, further confirming the failure of oocyte polarization. Our data suggest that WAVE2 regulates oocyte polarization by regulating meiotic spindle, peripheral positioning, probably via an actin-mediated pathway, and is involved in polar body emission during mouse oocyte meiotic maturation.

    Title Characterisation of Mouse Interferon-induced Transmembrane Protein-1 Gene Expression in the Mouse Uterus During the Oestrous Cycle and Pregnancy.
    Date November 2011
    Journal Reproduction, Fertility, and Development
    Excerpt

    During the oestrous cycle, pregnancy and parturition, the uterus undergoes marked morphological, physiological and functional changes. Amid these changes, the Wnt/β-catenin signalling pathway has been identified as having a crucial role in regulating associated biological events. Recently, based on results from a mouse embryo study, interferon-induced transmembrane protein 1 (Ifitm1) was reported as a downstream molecule of the Wnt/β-catenin signalling pathway. Differential expression patterns of the Ifitm1 gene during the oestrous cycle, pregnancy and parturition were identified in the present study. Quantitative real-time polymerase chain reaction data from uterine samples of mice induced start the oestrous cycle by injection of human chorionic gonadotropin (hCG) and revealed that Ifitm1 mRNA expression increased from late pro-oestrus to metoestrus, and decreased during dioestrus and early pro-oestrus. During pregnancy, Ifitm1 gene expression was minimal until parturition, but increased markedly 2 days after parturition. This significant elevation in Ifitm1 gene expression at post partum stage was identical to Ifitm1 expression after the induction of abortion by injection of prostaglandin F(2α). Interestingly, pregnant mare serum gonadotropin (PMSG) and oestrogen are also facilitates changes in Ifitm1 gene expression in an ovariectomised (OVX) mouse model. Expression of Ifitm1 mRNA was higher in response to PMSG than other hormones investigated. These results suggest that Ifitm1 may be involved in uteri physiology, although the mechanisms involved in the regulation of this gene expression and function in the uterus remain unknown. In the present study, differential expression patterns of the Ifitm1 gene were identified in the uteri of mice and the correlation between the patterns of Ifitm1 gene expression and Wnt/β-catenin signalling discussed.

    Title Ct Scan Assessment of the Pathway of the True Lateral Approach for Transforaminal Endoscopic Lumbar Discectomy: is It Possible?
    Date November 2011
    Journal The Journal of Bone and Joint Surgery. British Volume
    Excerpt

    We performed a prospective study to examine the influence of the patient's position on the location of the abdominal organs, to investigate the possibility of a true lateral approach for transforaminal endoscopic lumbar discectomy. Pre-operative abdominal CT scans were taken in 20 patients who underwent endoscopic lumbar discectomy. Axial images in parallel planes of each intervertebral disc from L1 to L5 were achieved in both supine and prone positions. The most horizontal approach angles possible to avoid injury to the abdominal organs were measured. The results demonstrated that the safe approach angles were significantly less (i.e., more horizontal) in the prone than in the supine position. Obstacles to a more lateral approach were mainly the liver, the spleen and the kidneys at L1/2 (39 of 40, 97.5%) and L2/3 (28 of 40, 70.0%), and the intestines at L3/4 (33 of 40, 82.5%) and L4/5 (30 of 30, 100%). A true lateral approach from each side was possible for 30 of the 40 discs at L3/4 (75%) and 23 of the 30 discs at L4/5 (76.7%). We concluded that a more horizontal approach for transforaminal endoscopic lumbar discectomy is possible in the prone position but not in the supine. Prone abdominal CT is more helpful in determining the trajectory of the endoscope. While a true lateral approach is feasible in many patients, our study shows it is not universally applicable.

    Title Combined Effect of High-normal Blood Pressure and Low Hdl Cholesterol on Mortality in an Elderly Korean Population: the South-west Seoul (sws) Study.
    Date November 2011
    Journal American Journal of Hypertension
    Excerpt

    It is unclear whether prehypertension by the seventh Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) criteria (systolic blood pressure (SBP) 120-139 or diastolic blood pressure (DBP) 80-89 mm Hg) or high-normal blood pressure (HNBP) by the European Society of Hypertension and European Society of Cardiology (ESH/ESC) criteria (SBP 130-139 or DBP 85-89 mm Hg) predicts mortality in elderly Koreans. We compared the mortality risk between those with prehypertension and HNBP and evaluated whether the presence of components of metabolic syndrome (MetS) can improve the prediction of mortality in subjects with HNBP.

    Title Large-scale Genome-wide Association Studies in East Asians Identify New Genetic Loci Influencing Metabolic Traits.
    Date November 2011
    Journal Nature Genetics
    Excerpt

    To identify the genetic bases for nine metabolic traits, we conducted a meta-analysis combining Korean genome-wide association results from the KARE project (n = 8,842) and the HEXA shared control study (n = 3,703). We verified the associations of the loci selected from the discovery meta-analysis in the replication stage (30,395 individuals from the BioBank Japan genome-wide association study and individuals comprising the Health2 and Shanghai Jiao Tong University Diabetes cohorts). We identified ten genome-wide significant signals newly associated with traits from an overall meta-analysis. The most compelling associations involved 12q24.11 (near MYL2) and 12q24.13 (in C12orf51) for high-density lipoprotein cholesterol, 2p21 (near SIX2-SIX3) for fasting plasma glucose, 19q13.33 (in RPS11) and 6q22.33 (in RSPO3) for renal traits, and 12q24.11 (near MYL2), 12q24.13 (in C12orf51 and near OAS1), 4q31.22 (in ZNF827) and 7q11.23 (near TBL2-BCL7B) for hepatic traits. These findings highlight previously unknown biological pathways for metabolic traits investigated in this study.

    Title Recent Advances in Reproductive Technologies.
    Date November 2011
    Journal Veterinary Medicine International
    Title Ubiquitous-severance Hospital Project: Implementation and Results.
    Date November 2011
    Journal Healthcare Informatics Research
    Excerpt

    The purpose of this study was to review an implementation of u-Severance information system with focus on electronic hospital records (EHR) and to suggest future improvements.

    Title Percutaneous Endoscopic Gastrostomy Prevents Gastroesophageal Reflux in Patients with Nasogastric Tube Feeding: A Prospective Study with 24-hour Ph Monitoring.
    Date November 2011
    Journal Gut and Liver
    Excerpt

    Percutaneous endoscopic gastrostomy (PEG) has been widely used for patients with swallowing dysfunction. However, its beneficial effects in the treatment of gastroesophageal reflux (GER) are controversial. The aim of this study was to evaluate the effect of PEG on the prevention of GER in patients with nasogastric tube (NGT) feeding.

    Title Effect of Previous Statin Therapy in Patients with Acute Coronary Syndrome and Percutaneous Coronary Intervention.
    Date November 2011
    Journal Korean Circulation Journal
    Excerpt

    Statin therapy after percutaneous coronary intervention (PCI) has been associated with reduced major adverse cardiovascular events (MACE). However, it has been less clear as to whether statin therapy before acute coronary syndrome (ACS) is beneficial. We studied the effect of previous statin therapy, initiated ≥1 month before PCI, on the outcome of patients with ACS who had undergone early invasive strategies.

    Title Lysophosphatidic Acid Induces Neurite Retraction in Differentiated Neuroblastoma Cells Via Gsk-3β Activation.
    Date November 2011
    Journal Molecules and Cells
    Excerpt

    Lysophosphatidic acid (LPA) is a lipid growth factor that exerts diverse biological effects, including rapid neurite retraction and cell migration. Alterations in cell morphology, including neurite retraction, in neurodegenerative disorders such as Alzheimer's disease involve hyperphosphorylation of the cytoskeletal protein tau. Since LPA has been shown to induce neurite retraction in various cultured neural cells and the detailed underlying molecular mechanisms have not yet been elucidated, we investigated whether LPA induced neurite retraction through taumediated signaling pathways in differentiated neuroblastoma cells. When Neuro2a cells differentiated with retinoic acid (RA) were exposed to LPA, cells exhibited neurite retraction in a time-dependent manner. The retraction of neurites was accompanied by the phosphorylation of tau. The LPA-induced neurite retraction and tau phosphorylation in differentiated Neuro2a cells were significantly abolished by the glycogen synthase kinase-3β (GSK-3β) inhibitor lithium chloride. Interestingly, the LPA-stimulated tau phosphorylation and neurite retraction were markedly prevented by the administration of H89, an inhibitor of both cyclic-AMP dependent protein kinase (PKA) and cyclic-AMP response element-binding protein (CREB). Transfection of the dominant-negative CREBs, K-CREB and A-CREB, failed to prevent LPA-induced tau phosphorylation and neurite retraction in differentiated Neuro2a cells. Taken together, these results suggest that GSK-3β and PKA, rather than CREB, play important roles in tau phosphorylation and neurite retraction in LPA-stimulated differentiated Neuro2a cells.

    Title Preparation of Water-dispersible Graphene by Facile Surface Modification of Graphite Oxide.
    Date November 2011
    Journal Nanotechnology
    Excerpt

    Water-dispersible graphene was prepared by reacting graphite oxide and 6-amino-4-hydroxy-2-naphthalenesulfonic acid (ANS). X-ray diffraction study showed that the basal reflection (002) peak of graphite oxide was absent in the ANS-functionalized graphene (ANS-G), indicating crystal layer delamination. Ultraviolet-visible spectral data were recorded to assess the solubility of the ANS-G in water. Fourier transform infrared spectral analysis suggested the attachment of ANS molecules to the surface of graphene. Raman and x-ray photoelectron spectroscopy revealed that oxygen functionality in the graphite oxide had been removed during reduction. Atomic force microscopy found that the thickness of ANS-G in water was about 1.8 nm, much higher than that of single layer graphene. Thermal stability measurements also indicated successful removal of oxygen functionality from the graphite oxide and the attachment of thermally unstable ANS to the graphene surfaces. The electrical conductivity of ANS-G, determined by a four-point probe, was 145 S m(-1) at room temperature.

    Title Antidepressant-like Effect of Altered Korean Red Ginseng in Mice.
    Date October 2011
    Journal Behavioral Medicine (washington, D.c.)
    Excerpt

    Altered Korean red ginseng has been used as a treatment for patients suffering from anxiety. We assessed whether red ginseng hydrolyzed by malted barley (HRG) and acetate-fermented red ginseng (ARG) would improve brain activity, by using forced swimming test (FST) in mice. The effect of the fluoxetine (a classical antidepressant), ginsenoside Rg3 (Rg3), red ginseng (RG), HRG, and the ARG groups for two weeks on the immobility time was significantly decreased in comparison with the control group (p<0.05). The immobility time of HRG and ARG in FST was lower than that of RG. The plasma level of glucose and total protein was significantly increased in the HRG and ARG group compared with the control group (p<0.05), whereas albumin, lactate dehydrogenase, creatine kinase, and blood urea nitrogen levels were not changed. In conclusion, altered Korean red ginsengs, HRG, and ARG therapy appeared to be effective in improving depression.

    Title Prominent Apoptosis in Pautrier Microabscesses: a Distinctive Finding in Adult T-cell Leukemia/lymphoma?
    Date October 2011
    Journal The American Journal of Dermatopathology
    Title Dna Synthesis and Epigenetic Modification During Mouse Oocyte Fertilization by Human or Hamster Sperm Injection.
    Date October 2011
    Journal Journal of Assisted Reproduction and Genetics
    Excerpt

    To evaluate DNA synthesis and epigenetic modification in mouse oocytes during the first cell cycle following the injection of human or hamster sperm.

    Title Serum Selenoprotein P Levels in Patients with Type 2 Diabetes and Prediabetes: Implications for Insulin Resistance, Inflammation, and Atherosclerosis.
    Date October 2011
    Journal The Journal of Clinical Endocrinology and Metabolism
    Excerpt

    The dysregulation of hepatokines may be associated with the pathogenesis of insulin resistance and type 2 diabetes. A recent study has suggested that selenoprotein P (SeP), a novel hepatokine, may play a role in the regulation of glucose metabolism and insulin sensitivity. We examined the relationship between circulating SeP levels and clinical parameters associated with insulin resistance in humans.

    Title Electrochemical Performance of a Graphene-polypyrrole Nanocomposite As a Supercapacitor Electrode.
    Date October 2011
    Journal Nanotechnology
    Excerpt

    A unique nanoarchitecture has been established involving polypyrrole (PPy) and graphene nanosheets by in situ polymerization. The structural aspect of the nanocomposite has been determined by Raman spectroscopy. Atomic force microscopy reveals that the thickness of the synthesized graphene is ∼ 2 nm. The dispersion of the nanometer-sized PPy has been demonstrated through transmission electron microscopy and the electrochemical performance of the nanocomposite has been illustrated by cyclic voltammetry measurements. Graphene nanosheet serves as a support material for the electrochemical utilization of PPy and also provides the path for electron transfer. The specific capacitance value of the nanocomposite has been determined to be 267 F g(-1) at a scan rate of 100 mV s(-1) compared to 137 mV s(-1) for PPy, suggesting the possible use of the nanocomposite as a supercapacitor electrode. After 500 cycles, only 10% decrease in specific capacitance as compared to initial value justifies the improved electrochemical cyclic stability of the nanocomposite.

    Title Cross Species Fertilization and Development Investigated by Cat Sperm Injection into Mouse Oocytes.
    Date September 2011
    Journal Journal of Experimental Zoology. Part A, Ecological Genetics and Physiology
    Excerpt

    The use of intracytoplasmic sperm injection (ICSI) in model animals is a powerful approach for the study of species-specific fertilization processes and multiploidy embryogenesis. In this study, we examined the fertilization process in mouse oocytes following injection of a single mouse or cat sperm, two mouse spermatozoa or mouse and cat spermatozoa. These treatments did not affect histone H3K9 acetylation or methylation, although the pattern of DNA methylation differed following the injection of cat sperm. Immunocytochemical staining revealed that sperm chromatin was normally incorporated with female mouse chromatin following any of the four injection scenarios. Furthermore, metaphase was successfully entered to reach a normal two-cell stage, and cell division could even persist to produce blastocyst stage embryos. In addition, both mouse and cat Pou5l and Nanog mRNA were expressed in the hybrid embryos. These results suggest that, although epigenetic modification of DNA is affected by the sperm injection treatment, fertilization and cleavage occur in a non-species-specific manner. In addition, despite abnormal division of the chromosomes, intra- and inter-species ICSI produced embryos that could develop into blastocysts.

    Title [a Case of Autoimmune Hepatitis Following Acute Hepatitis A].
    Date September 2011
    Journal The Korean Journal of Gastroenterology = Taehan Sohwagi Hakhoe Chi
    Excerpt

    The pathogenesis of autoimmune hepatitis (AIH) is unclear, but viral infections have been proposed as a potential trigger in patients with genetic predisposition. We report a case of AIH following acute hepatitis A (AHA). A 57-year-old woman presented with fatigue and pitting edema for last 3 months. She had been diagnosed as an AHA 15 months ago based on clinical features, biochemical tests and positive HAV IgM antibody at a local clinic. Her biochemical tests was normalized one month after AHA diagnosis, but the serum levels of aminotransferase started to rise four months after AHA diagnosis. Antinuclear antibody was positive at a titer of 1:40, and anti-smooth muscle antibody was also positive. Hypergammaglobulinemia and liver pathology were typical for AIH. The patients had a score of 17 according to the International Autoimmune Hepatitis Group's system. She was given prednisolone and azathioprine and showed complete response to immunosuppressive therapy. The present case is the first report on AIH triggered by AHA in Korea.

    Title Optimal Entry Points and Trajectories for Cervical Pedicle Screw Placement into Subaxial Cervical Vertebrae.
    Date September 2011
    Journal European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society
    Excerpt

    The present study was performed to determine the optimal entry points and trajectories for cervical pedicle screw insertion into C3-7. The study involved 40 patients (M:F = 20:20) with various cervical diseases. A surgical simulation program was used to construct three-dimensional spine models from cervical spine axial CT images. Axial, sagittal, and coronal plane data were simultaneously processed to determine the ideal pedicle trajectory (a line passing through the center of the pedicle on coronal, sagittal, and transverse CT images). The optimal entry points on the lateral masses were then identified. Horizontal offsets and vertical offsets of the optimal entry points were measured from three different anatomical landmarks: the lateral notch, the center of the superior edge and the center of lateral mass. The transverse angle and sagittal angles of the ideal pedicle trajectory were measured. Using those entry points and trajectory results, virtual screws were placed into the pedicles using the simulation program, and the outcomes were evaluated. We found that at C3-6, the optimal entry point was located 2.0-2.4 mm medial and 0-0.8 mm inferior to the lateral notch. Since the difference of 1 mm is difficult to discern intra-operatively, for ease of remembrance, we recommend rounding off our findings to arrive at a starting point for the C3-6 pedicle screws to be 2 mm directly medial to the lateral notch. At C7, by contrast, the optimal entry point was 1.6 mm lateral and 2.5 mm superior to the center of lateral mass. Again, for ease of remembrance, we recommend rounding off these numbers to use a starting point for the C7 pedicle screws to be 2 mm lateral and 2 mm superior to the center of lateral mass. The average transverse angles were 45° at C3-5, 38° at C6, and 28° at C7. The entry points for each vertebra should be adjusted according to the transverse angles of pedicles. The mean sagittal angles were 7° upward at C3, and parallel to the upper end plate at C4-7. The simulation study showed that the entry point and ideal pedicle trajectory led to screw placements that were safer than those used in other studies.

    Title Ndc80 Regulates Meiotic Spindle Organization, Chromosome Alignment, and Cell Cycle Progression in Mouse Oocytes.
    Date September 2011
    Journal Microscopy and Microanalysis : the Official Journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada
    Excerpt

    Ndc80 (called Hec1 in human), the core component of the Ndc80 complex, is involved in regulation of both kinetochore-microtubule interactions and the spindle assembly checkpoint in mitosis; however, its role in meiosis remains unclear. Here, we report Ndc80 expression, localization, and possible functions in mouse oocyte meiosis. Ndc80 mRNA levels gradually increased during meiosis. Immunofluorescent staining showed that Ndc80 was restricted to the germinal vesicle and associated with spindle microtubules from the Pro-MI to MII stages. Ndc80 was localized on microtubules and asters in the cytoplasm after taxol treatment, while Ndc80 staining was diffuse after disruption of microtubules by nocodazole treatment, confirming its microtubule localization. Disruption of Ndc80 function by either siRNA injection or antibody injection resulted in severe chromosome misalignment, spindle disruption, and precocious polar body extrusion. Our data show a unique localization pattern of Ndc80 in mouse oocytes and suggest that Ndc80 may be required for chromosome alignment and spindle organization, and may regulate spindle checkpoint activity during mouse oocyte meiosis.

    Title Nf-at5 is a Critical Regulator of Inflammatory Arthritis.
    Date August 2011
    Journal Arthritis and Rheumatism
    Excerpt

    To investigate the role of NF-AT5, an osmoprotective transcription factor, in synovial hyperplasia and angiogenesis in patients with rheumatoid arthritis (RA).

    Title Dbc-1 Mediates Endocrine Resistant Breast Cancer Cell Survival.
    Date August 2011
    Journal Cell Cycle (georgetown, Tex.)
    Title Chronic Thromboembolic Pulmonary Hypertension.
    Date August 2011
    Journal American Journal of Respiratory and Critical Care Medicine
    Excerpt

    Over the past 4 decades, chronic thromboembolic pulmonary hypertension has evolved from an autopsy curiosity to a potentially correctable form of pulmonary hypertension. Advances in surgical techniques along with the introduction of pulmonary hypertension disease-modifying therapies provide a therapeutic option for the majority of patients afflicted with the disease. Approximately 5,000 thromboendarterectomy procedures have now been performed worldwide with mortality rates reported by established programs experienced in the management of this disease process falling to a range of 4 to 7%. A mortality rate of 1.3% has been reported in patients at low risk based on their preoperative hemodynamic profile. After a successful pulmonary thromboendarterectomy, substantial improvement and often normalization can be achieved in right ventricular function, gas exchange, exercise capacity, and quality of life. For patients not candidates for thromboendarterectomy, or for those with persistent post-thromboendarterectomy pulmonary hypertension, disease-modifying medical therapies have been demonstrated to stabilize and improve pulmonary hemodynamics, albeit not to the same extent as primary thromboendarterectomy. The current review focuses on the diagnostic approach to chronic thromboembolic pulmonary hypertension and the available surgical and medical therapeutic options. Additional research is necessary to more accurately predict postoperative hemodynamic outcome and to define the optimal therapeutic approach, especially in patients with involvement of the distal vasculature.

    Title Src Family Kinase Potentiates the Activity of Nicotinic Acetylcholine Receptor in Rat Autonomic Ganglion Innervating Urinary Bladder.
    Date August 2011
    Journal Neuroscience Letters
    Excerpt

    Src family kinases (SFKs), one of the tyrosine kinase groups, are primary regulators of signal transductions that control cellular functions such as cell proliferation, differentiation, survival, metabolism, and other important roles of the cell. One of the crucial functions of SFKs is to regulate the activities of various neuronal channels. In this study, we investigated the modulatory action of SFK on nicotinic acetylcholine receptors (nAChRs) expressed in rat major pelvic ganglion (MPG) neurons innervating the urinary bladder. PP1 and PP2 (5 μM), selective Src-kinase inhibitors, attenuated ACh-induced ionic currents and [Ca²+](i) transients in MPG neurons, whereas PP3, an inactive analogue, had no effect. Blocking the tyrosine kinase activity of Src kinase by pp60 c-src inhibitory peptide also reduced the ACh-induced currents. Conversely, sodium orthovanadate (200 μM), a tyrosine phosphatase inhibitor, significantly augmented the ACh-induced currents. In the kinase assay, the activities of SFKs in MPG neurons were also inhibited by PP2, but not by PP3. These data suggests that SFKs may have a facilitative role on the synaptic transmission in rat pelvic autonomic ganglion.

    Title Arp2/3 Complex Regulates Asymmetric Division and Cytokinesis in Mouse Oocytes.
    Date August 2011
    Journal Plos One
    Excerpt

    Mammalian oocyte meiotic maturation involves oocyte polarization and a unique asymmetric division, but until now, the underlying mechanisms have been poorly understood. Arp2/3 complex has been shown to regulate actin nucleation and is widely involved in a diverse range of processes such as cell locomotion, phagocytosis and the establishment of cell polarity. Whether Arp2/3 complex participates in oocyte polarization and asymmetric division is unknown. The present study investigated the expression and functions of Arp2/3 complex during mouse oocyte meiotic maturation. Immunofluorescent staining showed that the Arp2/3 complex was restricted to the cortex, with a thickened cap above the meiotic apparatus, and that this localization pattern was depended on actin. Disruption of Arp2/3 complex by a newly-found specific inhibitor CK666, as well as by Arpc2 and Arpc3 RNAi, resulted in a range of effects. These included the failure of asymmetric division, spindle migration, and the formation and completion of oocyte cytokinesis. The formation of the actin cap and cortical granule-free domain (CGFD) was also disrupted, which further confirmed the disruption of spindle migration. Our data suggest that the Arp2/3 complex probably regulates oocyte polarization through its effect on spindle migration, asymmetric division and cytokinesis during mouse oocyte meiotic maturation.

    Title Mitochondrial Dysfunction Influences Apoptosis and Autophagy in Porcine Parthenotes Developing in Vitro.
    Date August 2011
    Journal The Journal of Reproduction and Development
    Excerpt

    Mitochondria are important regulators of both apoptosis and autophagy. One of the triggers for mitochondrial-mediated apoptosis is the production of reactive oxygen species (ROS), which include hydrogen peroxide, superoxide, hydroxyl radical, nitric oxide and peroxynitrite. Recently, several studies have indicated that ROS may also be involved in the induction of autophagy. In the present study, we used H(2)O(2) to induce mitochondrial stress, examined apoptotic- and autophagic-related gene expression and observed LC3 protein (autophagosome presence marker) expression in porcine parthenotes developing in vitro. In porcine four-cell parthenotes cultured for 5 days in NCSU37 medium containing 0.4% BSA, the developmental rate and mitochondrial distribution did not differ from that of the group supplemented with 100 µM H(2)O(2) but was significantly decreased in the group supplemented with 500 µM H(2)O(2) (P<0.05). Transmission electron microscopy (TEM) indicated that whereas normal shaped mitochondria were observed in blastocysts from the control group, abnormal mitochondria (mitophagy) and autophagic vacuoles were observed in blastocysts from the group that received 500 µM H(2)O(2). Furthermore, addition of H(2)O(2) (100 µM and 500 µM) decreased cell numbers (P<0.05) and increased both apoptosis (P<0.05) and LC3 protein expression in the blastocysts. Real-time RT-PCR showed that H(2)O(2) significantly decreased mRNA expression of anti-apoptotic gene Bcl-xL but increased pro-apoptotic genes, Caspase 3 (Casp3) and Bak, and autophagy-related genes, microtubule-associated protein 1 light chain 3 (Map1lc3b) and lysosomal-associated membrane protein 2 (Lamp2). However, the addition of H(2)O(2) had no effect on mRNA expression levels in nuclear DNA-encoded mitochondrial-related genes, cytochrome oxidase (Cox) 5a, Cox5b and Cox6b1, in blastocysts. These results suggest that H(2)O(2) leads to mitochondrial dysfunction that results in apoptosis and autophagy, which is possibly related to porcine early embryo development.

    Title Trichostatin A Modulates Apoptotic-related Gene Expression and Improves Embryo Viability in Cloned Bovine Embryos.
    Date July 2011
    Journal Cellular Reprogramming
    Excerpt

    Low efficiency of somatic cell nuclear transfer (SCNT) is attributed to incomplete reprogramming of transferred nuclei into oocytes. Trichostatin A (TSA), a histone deacetylase inhibitor, has been used to enhance nuclear reprogramming following SCNT. However, the molecular mechanism of TSA for the improvement of the preimplantation embryo and fetal development following SCNT is not known. The present study investigates embryo viability and gene expression of cloned bovine preimplantation embryos in the presence and absence of TSA compared to embryos produced by in vitro fertilization or parthenogenetic activation. Our results indicated that TSA treatment significantly improved total and inner cell mass (ICM) cell number and ratio of ICM:trophectoderm (TE) and also decreased the apoptotic index including total, ICM, and ratio of ICM:TE. Four apoptotic-related genes, Bcl-xL, survivin, Bcl2-associated X protein (Bax), and caspase 3 (Casp3), and four pluripotency/differentiation related genes, Oct4, SRY (sex determining region Y)-box 2 (Sox2), Cdx2, and colony-stimulating factor 1 receptor (Csf1r), were measured by real-time RT-PCR. TSA treatment resulted in the high expression of antiapoptotic gene Bcl-xL and low expression of pro-apoptotic gene Bax compared to untreated NT embryos, fertilized embryos, or parthenotes. Furthermore, mRNA expression of Cdx2 was higher in NT-TSA embryos than in NT and in vitro fertilization (IVF) counterparts. Additionally, low expression of microRNA (mir)-21 in NT embryos was enhanced following TSA treatment. These results suggest that TSA positively regulates nuclear reprogramming, and TSA may increased resistance or reduced signal for induction of apoptosis.

    Title Switching-on of Serotonergic Calcium Signaling in Activated Hepatic Stellate Cells.
    Date July 2011
    Journal World Journal of Gastroenterology : Wjg
    Excerpt

    To investigate serotonergic Ca²+ signaling and the expression of 5-hydroxytryptamine (5-HT) receptors, as well as Ca²+ transporting proteins, in hepatic stellate cells (HSCs).

    Title Efficacy of a New Navigable Percutaneous Disc Decompression Device (l'disq) in Patients with Herniated Nucleus Pulposus Related to Radicular Pain.
    Date July 2011
    Journal Pain Medicine (malden, Mass.)
    Excerpt

    An institutional, prospective clinical data analysis.

    Title Otogenic Pneumocephalus Associated with a Ventriculoperitoneal Shunt.
    Date July 2011
    Journal Clinical and Experimental Otorhinolaryngology
    Excerpt

    Otogenic pneumocephalus is a condition of intracranial air originating from the middle ear or mastoid air cells. This communication between the intracranial cavity and the pneumatic cavities is usually associated with trauma after cranial fractures or iatrogenic trauma. We present a rare case of otogenic pneumocephalus arising in the left posterior fossa from wellpneumatized mastoid air cells. The patient complained of roaring tinnitus that developed 29 months after ventriculoperitoneal shunt insertion due to brain tumor surgery. High resolution computed tomography scan of the temporal bones revealed a large pneumocephalus below the left tentorium, and a bony dehiscent route was clearly identified in a sagittal view. A left mastoidectomy with preservation of the posterior wall of the external auditory canal was performed, and the expected bony dehiscent site was identified in the posterior fossa dura plate, just posterior to the posterior semicircular canal, below the Donaldson's line. This communication was sealed with a temporalis muscle plug from the deep temporalis muscle fascia and bone dust. Pneumocephalus may be caused by negative intracranial pressure in a patient with very well-pneumatized mastoid bone, and it can be a possible cause of 'wind-like' sound in the ear.

    Title Occipital Neuralgia As the Only Presenting Symptom of Foramen Magnum Meningioma.
    Date July 2011
    Journal Journal of Clinical Neurology (seoul, Korea)
    Excerpt

    Occipital neuralgia (ON) is a condition characterized by a paroxysmal stabbing pain in the area of the greater or lesser occipital nerves; it is usually regarded by clinicians as idiopathic. Some have suggested that ON can be induced by trauma or injury of the occipital nerves or their roots, but tumor has rarely been reported as a cause of ON.

    Title 20-year-follow Up of Treatment Using Spine Osteotomy and Halo-pelvic Traction for Tuberculous Kyphosis - A Case Report -.
    Date July 2011
    Journal Asian Spine Journal
    Excerpt

    A 23-year-old male whose medical history included tuberculous spondylitis presented with a kyphotic deformity and incomplete paraplegia of twenty days duration. Preoperative radiographs demonstrated a T12-L4 kyphotic Cobb's angle of 100 degrees with a complete block showing on the lumbar myelogram at L4-5. The patient underwent anterior osteotomy and release. After the operation, a halo-pelvic apparatus was fit onto the patient, and distraction was begun. After distraction for 2 months, posterior osteotomy and release was performed for final correction, and distraction was maintained for another three weeks. Finally, the kyphotic deformity was corrected to a Cobb's angle of 62 degrees from T12 to L4. Supplementary anterior fusion was done, and the apparatus was removed after consolidation of the fusion mass.Even twenty years after correction of a tuberculous kyphosis, he had no neurological deterioration, and could work as a farmer using agricultural machines. Correction angle and sagittal balance were well maintained.

    Title Renal Dysfunction Induced by Bacterial Infection Other Than Spontaneous Bacterial Peritonitis in Patients with Cirrhosis: Incidence and Risk Factor.
    Date July 2011
    Journal Gut and Liver
    Excerpt

    Deterioration of renal function in cirrhotic patients with spontaneous bacterial peritonitis (SBP) is a predictor for in-hospital mortality; however, the clinical significance of renal dysfunction during bacterial infection other than SBP is unknown. The aim of this study was to investigate the prevalence and clinical significance of renal dysfunction due to bacterial infections other than SBP in patients with liver cirrhosis.

    Title Apoptosis in Cardiovascular Diseases: Mechanism and Clinical Implications.
    Date July 2011
    Journal Korean Circulation Journal
    Excerpt

    Apoptosis is a tightly regulated, cell deletion process that plays an important role in various cardiovascular diseases, such as myocardial infarction, reperfusion injury, and heart failure. Since cardiomyocyte loss is the most important determinant of patient morbidity and mortality, fully understanding the regulatory mechanisms of apoptotic signaling is crucial. In fact, the inhibition of cardiac apoptosis holds promise as an effective therapeutic strategy for cardiovascular diseases. Caspase, a critical enzyme in the induction and execution of apoptosis, has been the main potential target for achieving anti-apoptotic therapy. Studies suggest, however, that a caspase-independent pathway may also play an important role in cardiac apoptosis, although the mechanism and potential significance of caspase-independent apoptosis in the heart remain poorly understood. Herein we discuss the role of apoptosis in various cardiovascular diseases, provide an update on current knowledge about the molecular mechanisms that govern apoptosis, and discuss the clinical implications of anti-apoptotic therapies.

    Title Mitogen-activated Protein Kinases and Reactive Oxygen Species: How Can Ros Activate Mapk Pathways?
    Date July 2011
    Journal Journal of Signal Transduction
    Excerpt

    Mitogen-activated protein kinases (MAPKs) are serine-threonine protein kinases that play the major role in signal transduction from the cell surface to the nucleus. MAPKs, which consist of growth factor-regulated extracellular signal-related kinases (ERKs), and the stress-activated MAPKs, c-jun NH(2)-terminal kinases (JNKs) and p38 MAPKs, are part of a three-kinase signaling module composed of the MAPK, an MAPK kinase (MAP2K) and an MAPK kinase (MAP3K). MAP3Ks phosphorylate MAP2Ks, which in turn activate MAPKs. MAPK phosphatases (MKPs), which recognize the TXY amino acid motif present in MAPKs, dephosphorylate and deactivate MAPKs. MAPK pathways are known to be influenced not only by receptor ligand interactions, but also by different stressors placed on the cell. One type of stress that induces potential activation of MAPK pathways is the oxidative stress caused by reactive oxygen species (ROS). Generally, increased ROS production in a cell leads to the activation of ERKs, JNKs, or p38 MAPKs, but the mechanisms by which ROS can activate these kinases are unclear. Oxidative modifications of MAPK signaling proteins and inactivation and/or degradation of MKPs may provide the plausible mechanisms for activation of MAPK pathways by ROS, which will be reviewed in this paper.

    Title Increase of Lycopene Production by Supplementing Auxiliary Carbon Sources in Metabolically Engineered Escherichia Coli.
    Date June 2011
    Journal Applied Microbiology and Biotechnology
    Excerpt

    In the fed-batch culture of glycerol using a metabolically engineered strain of Escherichia coli, supplementation with glucose as an auxiliary carbon source increased lycopene production due to a significant increase in cell mass, despite a reduction in specific lycopene content. L-Arabinose supplementation increased lycopene production due to increases in cell mass and specific lycopene content. Supplementation with both glucose and L-arabinose increased lycopene production significantly due to the synergistic effect of the two sugars. Cell growth by the consumption of carbon sources was related to endogenous metabolism in the host E. coli. Supplementation with L-arabinose stimulated only the mevalonate pathway for lycopene biosynthesis and supplementation with both glucose and L-arabinose stimulated synergistically only the mevalonate pathway. In the fed-batch culture of glycerol with 10 gl(-1) glucose and 7.5 gl(-1) L-arabinose, the cell mass, lycopene concentration, specific lycopene content, and lycopene productivity after 34 h were 42 gl(-1), 1,350 mgl(-1), 32 mg g cells(-1), and 40 mgl(-1)h(-1), respectively. These values were 3.9-, 7.1-, 1.9-, and 11.7-fold higher than those without the auxiliary carbon sources, respectively. This is the highest reported concentration and productivity of lycopene.

    Title Surface Reaction of Licoo2/li System Under High-voltage Conditions by X-ray Spectroscopy and Two-dimensional Correlation Spectroscopy (2d-cos).
    Date May 2011
    Journal Applied Spectroscopy
    Excerpt

    We studied the surface reactions of a LiCoO(2)/Li cell under high-voltage conditions using X-ray photoelectron spectroscopy (XPS), X-ray absorption spectroscopy (XAS), and two-dimensional correlation spectroscopy (2D-COS). 2D XPS correlation spectra show that Li(2)CO(3) is formed first by decomposition of the organic solvents, and then polycarbonate, which is formed by polymerization of the electrolytes, is produced on the cathode surface of the LiCoO(2)/Li system under high-voltage conditions. XAS measurements also confirm that the solid electrolyte interface (SEI) layer is formed on the LiCoO(2) electrode by decomposition of the organic solvents. The thickness of the SEI layer is less than 100 Å.

    Title Tryptase-positive Mast Cells Correlate with Angiogenesis in Canine Mammary Carcinoma.
    Date May 2011
    Journal Journal of Comparative Pathology
    Excerpt

    Angiogenesis plays a crucial role in tumour growth, invasion and metastasis. Mast cells (MCs) release angiogenic factors that promote endothelial proliferation and differentiation. Previous studies have suggested that MCs are involved in tumour angiogenesis due to the release of various pro-angiogenic factors. This study evaluated samples from 40 canine mammary carcinomas and eight healthy non-neoplastic canine mammary glands. Toluidine blue staining was performed to characterize the MCs. Immunohistochemical labelling was performed to detect the number of tryptase-positive MCs and microvessels. MCs accumulated in tumour tissue and were closely associated with blood or lymphatic vessels in the tumour microenvironment. Angiogenesis, as measured by microvessel density, increased in direct proportion to the number of MCs. The correlation coefficient was significantly higher for tryptase-positive MCs than for toluidine blue-stained MCs. These results suggest that MCs are involved in tumour angiogenesis, which in turn influences tumour growth, invasion and metastasis. In particular, MC tryptase may be influential in mediating this function of MCs.

    Title Association of Adiponectin, Resistin, and Vascular Inflammation: Analysis with 18f-fluorodeoxyglucose Positron Emission Tomography.
    Date May 2011
    Journal Arteriosclerosis, Thrombosis, and Vascular Biology
    Excerpt

    Adiponectin and resistin are adipokines that are linked to obesity, inflammation, and atherosclerosis. (18)F-Fluorodeoxyglucose (FDG) positron emission tomography is a promising imaging technique that can be used to evaluate vascular inflammation.

    Title Hypoxia-inducible Factor-1alpha Enhances Haptoglobin Gene Expression by Improving Binding of Stat3 to the Promoter.
    Date May 2011
    Journal The Journal of Biological Chemistry
    Excerpt

    Haptoglobin (Hp) is known to play a role in angiogenesis as well as in anti-inflammation. STAT3 is a major transcription factor for expression of human Hp. We investigated whether hypoxia-inducible factor-1α (HIF-1α), a key mediator of angiogenesis, participates in Hp gene expression. HIF-1α overexpression by gene transfection or hypoxia augmented Hp transcription in HepG2 human hepatoma cells. Conversely, knockdown of HIF-1α by specific siRNA transfection diminished Hp expression, although the level of STAT3 phosphorylation remained unchanged. A luciferase reporter assay using mutant Hp promoters demonstrated that two adjacent DNA elements, a STAT3-binding element (SBE) and a cAMP-response element (CRE)-like site in human Hp promoter -120/-97, were required for HIF-1α-stimulated transactivation of the Hp gene. HIF-1α, STAT3, and p300/CBP were simultaneously bound to the SBE/CRE as a complex form. When HIF-1α was knocked down, STAT3 binding to the SBE in the Hp promoter was attenuated. Our findings suggest that HIF-1α assists STAT3 in strong binding to the proximal SBE in the Hp promoter. The CRE-like site located near the SBE may contribute to the formation of a stable complex of STAT3, HIF-1α, and p300/CBP, which leads to maximum transcription of the Hp gene.

    Title Myelopathy Due to Intracranial Dural Arteriovenous Fistula: a Potential Diagnostic Pitfall. Case Report.
    Date April 2011
    Journal Journal of Neurosurgery
    Excerpt

    Intracranial dural arteriovenous fistula (DAVF) is rare and potentially life-threatening disease often presenting as vascular myelopathy. The early and proper diagnosis is challenging because the clinical manifestations are related to the distribution of the draining vein, not the fistula site, and imaging findings are similar to demyelinating disease of the spinal cord. The authors present the case of a 45-year-old man who developed acute progressive quadriplegia and respiratory difficulty with an enhancing, longitudinally extensive cervical cord lesion. These symptoms were highly suspicious for transverse myelitis but were caused by an intracranial DAVF. Intracranial DAVF with venous reflux to the brainstem and spinal cord is a rare but important differential diagnosis of progressive worsening myelopathy that is treatment resistant and gives the diagnostic impression of transverse myelitis.

    Title Chronic Thromboembolic Pulmonary Hypertension in Pediatric Patients.
    Date April 2011
    Journal The Journal of Thoracic and Cardiovascular Surgery
    Excerpt

    Chronic thromboembolic pulmonary hypertension is a rare form of pulmonary hypertension that can lead to progressive right heart failure and death. Pulmonary thromboendarterectomy surgery is the treatment of choice resulting in significant improvements in functional status, cardiopulmonary hemodynamics, and survival. This study reports the largest case series of pediatric patients with chronic thromboembolic pulmonary hypertension who underwent pulmonary thromboendarterectomy surgery at one institution.

    Title Perturbation of Spc25 Expression Affects Meiotic Spindle Organization, Chromosome Alignment and Spindle Assembly Checkpoint in Mouse Oocytes.
    Date March 2011
    Journal Cell Cycle (georgetown, Tex.)
    Excerpt

    Spc25 is a component of the Ndc80 complex which consists of Ndc80, Nuf2, Spc24, and Spc25. Previous work has shown that Spc25 is involved in regulation of kinetochore microtubule attachment and the spindle assembly checkpoint in mitosis. The roles of Spc25 in meiosis remain unknown. Here, we report its expression, localization and functions in mouse oocyte meiosis. The Spc25 mRNA level gradually increased from the GV to MI stage, but decreased by MII during mouse oocyte meiotic maturation. Immunofluorescent staining showed that Spc25 was restricted to the germinal vesicle, and associated with chromosomes during all stages after GVBD. Overexpression of Spc25 by mRNA injection resulted in oocyte meiotic arrest, chromosome misalignment and spindle disruption. Conversely, Spc25 RNAi by siRNA injection resulted in precocious polar body extrusion and caused severe chromosome misalignment and aberrant spindle formation. Our data suggest that Spc25 is required for chromosome alignment, spindle formation, and proper spindle checkpoint signaling during meiosis.

    Title Chronic Thromboembolic Pulmonary Hypertension.
    Date February 2011
    Journal Clinics in Chest Medicine
    Excerpt

    Chronic thromboembolic pulmonary hypertension is one of the few forms of pulmonary hypertension that is surgically curable. It is likely underdiagnosed and must be considered in every patient presenting with pulmonary hypertension to avoid missing the opportunity to cure these patients. This article discusses the epidemiology, risk factors, natural history, diagnosis, and preoperative evaluation of patients with this disorder. Also covered are putative mechanisms for the conversion of acute emboli into fibrosed thrombembolic residua. Mechanical obstruction of the central pulmonary vasculature is rarely the sole cause of the pulmonary hypertension, and a discussion of the small vessel arteriopathy present in these patients is offered. Technical aspects of pulmonary endartectomy and the data supporting its role are discussed, as are the limited data on pulmonary arterial hypertension specific medical therapies for patients deemed noncandidates for the operation.

    Title Incidence of Atazanavir-associated Hyperbilirubinemia in Korean Hiv Patients: 30 Months Follow-up Results in a Population with Low Udp-glucuronosyltransferase1a1*28 Allele Frequency.
    Date February 2011
    Journal Journal of Korean Medical Science
    Excerpt

    Hyperbilirubinemia is frequently observed in Caucasian HIV patients treated with atazanavir. UDP-glucuronosyltransferase 1A1 polymorphism, UGT1A1*28, which is associated with atazanavir-induced hyperbilirubinemia, is less common in Asians than in Caucasians. However, little is known about the incidence of atazanavir-associated hyperbilirubinemia in Asian populations. Our objective was to investigate the incidence of and tolerability of atazanavir-associated hyperbilirubinemia in Korean HIV patients. The prevalence and cumulative incidence of atazanavir-associated hyperbilirubinemia and UGT1A1*28 allele frequency was investigated in 190 Korean HIV-infected patients treated with atazanavir 400 mg per day. The UGT1A1*28 were examined by direct sequencing of DNA from peripheral whole blood. The UGT1A1*28 allele frequency was 11%. The cumulative incidence of any grade of hyperbilirubinemia was 77%, 89%, 98%, and 100%, at 3, 12, 24, and 30 months, respectively. The cumulative incidence of severe (grade 3-4) hyperbilirubinemia was 21%, 41%, 66%, and 75%, at 3, 12, 24, and 30 months, respectively. However, the point prevalence of severe hyperbilirubinemia did not increase with time and remained around 25%. Our data suggest that atazanavir-associated hyperbilirubinemia is common but transient in a population with low UGT1A1*28 allele frequency.

    Title Scopoletin from the Flower Buds of Magnolia Fargesii Inhibits Protein Glycation, Aldose Reductase, and Cataractogenesis Ex Vivo.
    Date February 2011
    Journal Archives of Pharmacal Research
    Excerpt

    Five compounds previously known structures, scopoletin (1), northalifoline (2), stigmast-4-en-3-one (3), tiliroside (4), and oplopanone (5) were obtained from the flower buds of Magnolia fargesii using chromatographic separation methods. The structures of 1-5 were identified by the interpretation of their spectroscopic data including 1D- and 2D-NMR as well as by comparison with reported values. Three compounds 1-3 were found from M. fargesii for the first time in this study. All the isolates (1-5) were subjected to in vitro bioassays to evaluate the inhibitory activity on advanced glycation end products formation and rat lens aldose reductase (RLAR). Compound 1 showed a remarkable inhibitory activity on advanced glycation end products formation with IC(50) value of 2.93 μM (aminoguanidine: 961 μM), and showed a significant RLAR inhibitory activity with IC(50) value of 22.5 μM (3.3-tetramethyleneglutaric acid: 28.7 μM). Compound 4 exhibited potent inhibitory activity against RLAR (IC(50) = 14.9 μM). In the further experiment ex vivo, cataractogenesis of rat lenses induced with xylose was significantly inhibited by compound 1 treatment.

    Title Role of Heme Oxygenase in Preserving Vascular Bioactive No.
    Date February 2011
    Journal Nitric Oxide : Biology and Chemistry / Official Journal of the Nitric Oxide Society
    Excerpt

    Beyond its vasodilator role, vascular nitric oxide (NO), which is synthesized by endothelial NO synthase (eNOS) via its activation, has been shown to play a number of other beneficial roles in the vascular system; it inhibits proliferation of vascular smooth muscle cells, prevents platelet aggregation, and regulates endothelial apoptosis. Such beneficial roles have been shown to be implicated in the regulation of endothelial functions. A loss of NO bioavailability that may result either from decreased eNOS expression and activity or from increased NO degradation is associated with endothelial dysfunction, a key factor in the development of vascular diseases. Heme oxygenase-1 (HO-1), an inducible enzyme, catalyzes the oxidative degradation of heme to free iron, carbon monoxide, and biliverdin, the latter being subsequently converted into bilirubin. In the vascular system, HO-1 and heme degradation products perform important physiological functions, which are ultimately linked to the protection of vascular cells. Studies have shown that HO-1 and heme degradation products exert vasodilatory, antioxidant, anti-inflammatory, antiproliferative and anti-apoptotic effects on vascular cells. Interestingly, these effects of HO-1 and its by-products are similar, at least in part, to those of eNOS-derived NO; this similarity may prompt investigators to study a possible relationship between eNOS-derived NO and HO-1 pathways. Many studies have been reported, and accumulating evidence suggests that HO-1 and heme degradation products can improve vascular function, at least in part, by compensating for the loss of NO bioavailability. This paper will provide the possible pathway explaining how HO-1 and heme degradation products can preserve vascular NO.

    Title Oncogenic Ras-mediated Downregulation of Clast1/lr8 is Involved in Ras-mediated Neoplastic Transformation and Tumorigenesis in Nih3t3 Cells.
    Date February 2011
    Journal Cancer Science
    Excerpt

    Oncogenic Ras proteins transform cells by way of multiple downstream signaling pathways that promote the genesis of human cancers. However, the exact cellular mechanisms by which downstream targets are regulated are not fully understood. Here, we show that oncogenic Ras reduced Clast1/LR8 transcript levels in mouse NIH3T3 fibroblasts and human WI38 fibroblasts. Clast1/LR8 transcript was undetectable in H460, A549, and H1299 cells showing high Ras activity, but was relatively abundant in DMS53 cells displaying low Ras activity. We also showed that K-Ras siRNA restored Clast1/LR8 expression in H460 and A549 cells, and that inhibitors of DNA methylation and histone deacetylation reversed oncogenic H-Ras-mediated suppression of Clast1/LR8 transcription. Additionally, ectopic expression of Clast1/LR8 inhibited serum-stimulated phosphorylation of ERK1/2 and Akt in H-RasV12-transformed NIH3T3 cells. We further showed that the expression of Clast1/LR8 interfered with oncogenic Ras-induced NIH3T3 cell transformation and invasion. Finally, our results showed that Clast1/LR8 inhibited Ras-induced proliferation of, and tumor formation by, oncogenic H-RasV12-transformed NIH3T3 cells in vivo. This study identifies the downregulation of Clast1/LR8 as a potentially important mechanism by which oncogenic Ras-mediated neoplastic transformation occurs.

    Title Vascular Inflammation Stratified by C-reactive Protein and Low-density Lipoprotein Cholesterol Levels: Analysis with 18f-fdg Pet.
    Date February 2011
    Journal Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
    Excerpt

    We examined the severity of vascular inflammation in healthy individuals without hyperlipidemia but with elevated high-sensitivity C-reactive protein (hsCRP) using 18F-FDG PET, which is a promising imaging technique for the assessment of vascular inflammation within atherosclerotic plaques. Methods: Vascular inflammation in the carotid arterial wall, represented as the target-to-background ratio (TBR), was measured using 18F-FDG PET in 120 healthy subjects without a history of cardiovascular diseases. RESULTS: Subjects with high hsCRP (≥2 mg/L) and low low-density lipoprotein cholesterol (LDL-C) (<130 mg/dL) levels had a significantly higher maximum TBR than did those with low hsCRP (<2 mg/L) and low LDL-C levels (<130 mg/dL) or low hsCRP (<2 mg/L) and high LDL-C levels (≥130 mg/dL) (1.29±0.13, 1.12±0.10, and 1.16±0.05, respectively), even though there were no significant differences in the carotid intima-media thickness. The maximum TBR values had the strongest positive correlation with hsCRP level among the various cardiovascular risk factors (r=0.68, P<0.01). However, other emerging inflammatory markers such as lipoprotein-associated phospholipase A(2) or monocyte chemoattractant protein-1 were not coherently associated with TBR values. Multiple stepwise regression analyses showed that hsCRP and diastolic blood pressure were independent decisive factors for maximum TBR, whereas age, diastolic blood pressure, and LDL-C were factors that determined the maximum intima-media thickness. CONCLUSION: Vascular inflammation measured using 18F-FDG PET was increased in healthy individuals without hyperlipidemia but with elevated hsCRP.

    Title Aptamer-mediated Surface-enhanced Raman Spectroscopy Intensity Amplification.
    Date January 2011
    Journal Nano Letters
    Excerpt

    A bifunctional adenosine-sensitive double-stranded DNA aptamer was used to create and control a surface-enhanced Raman spectroscopy (SERS) hot spot between a bulk Au surface and a gold nanoparticle (Au NP) attached to the aptamer via a biotin-avidin linkage. The Au NP was decorated with 4-aminobenzenethiol (4-ABT), a Raman reporter molecule. In the presence of adenosine, the target molecule, the SERS spectrum of 4-ABT increased in intensity by (concentration-dependent) factors as large as ∼4; in situ, atomic force microscopy imaging showed the mean height of the Au NP-bearing aptamer to decrease by ∼5 nm consistent with the observed SERS intensity change. Because the aptamer's geometrical change is induced by one or two molecules, while the resulting SERS intensity changes involve many reporter molecules residing in the modified hot spot, the aptamer amplifies the SERS effect.

    Title Riociguat: an Upcoming Therapy in Chronic Thromboembolic Pulmonary Hypertension?
    Date January 2011
    Journal European Respiratory Review : an Official Journal of the European Respiratory Society
    Excerpt

    Although pulmonary endarterectomy remains the treatment of choice for patients with chronic thromboembolic pulmonary hypertension (CTEPH), not all patients will benefit from or receive this highly specialised surgery. Patients whose CTEPH is deemed inoperable by an experienced centre and patients with persistent pulmonary hypertension after surgery are candidates for trial of pulmonary arterial hypertension (PAH) specific pharmacotherapies. However, the currently available PAH specific pharmacotherapies have not demonstrated a clear benefit in either of these patient groups. Accordingly, PAH therapies remain off-label for use in CTEPH. Riociguat (BAY 63-2521) is a stimulator of soluble guanylate cyclase, and may represent a novel agent in the treatment of select patients with CTEPH. Pre-clinical and human phase II studies with riociguat have reported promising results, and a multinational, randomised, controlled, double-blinded phase III study is currently underway to investigate the effect of riociguat in patients with inoperable CTEPH and those with persistent or recurrent pulmonary hypertension following pulmonary endarterectomy.

    Title Candidate Genes of Cerebrovascular Disease and Sudden Sensorineural Hearing Loss.
    Date January 2011
    Journal Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/hemostasis
    Excerpt

    Auditory dysfunction is related to large/small vessel occlusions and hemorrhage. Sudden sensorineural hearing loss (SSNHL) frequently occurs with anterior inferior cerebellar artery occlusion proximal to the internal auditory artery. Moreover, SSNHL has various pathogenetic mechanisms, the main proposed mechanisms being vascular disease, membrane ruptures, infection, and autoimmunity. Tumor necrosis factor (TNF) is an important cytokine in the inflammation process of cerebrovascular diseases. In the current study, the possible effects of polymorphisms in TNF-alpha and TNF-beta genes on SSNHL are evaluated. Two genetic polymorphisms in the TNF locus (TNF-alpha -308 G - ->A and TNF-beta +252 A - ->G) were investigated as risk factors for SSNHL by determining their prevalence in 97 SSNHL patients and in 587 controls. A significant increase was found for the TNF-beta allele 1 in SSNHL patients compared with the controls (chi( 2) = 7.251, P = .007, odds ratio [OR] = 1.534, confidence interval [CI] = 1.12-2.10). These findings suggest that the TNF-beta +252 locus plays an important role in the etiopathogenesis of SSNHL.

    Title Snail1 is Stabilized by O-glcnac Modification in Hyperglycaemic Condition.
    Date January 2011
    Journal The Embo Journal
    Excerpt

    Protein O-phosphorylation often occurs reciprocally with O-GlcNAc modification and represents a regulatory principle for proteins. O-phosphorylation of serine by glycogen synthase kinase-3β on Snail1, a transcriptional repressor of E-cadherin and a key regulator of the epithelial-mesenchymal transition (EMT) programme, results in its proteasomal degradation. We show that by suppressing O-phosphorylation-mediated degradation, O-GlcNAc at serine112 stabilizes Snail1 and thus increases its repressor function, which in turn attenuates E-cadherin mRNA expression. Hyperglycaemic condition enhances O-GlcNAc modification and initiates EMT by transcriptional suppression of E-cadherin through Snail1. Thus, dynamic reciprocal O-phosphorylation and O-GlcNAc modification of Snail1 constitute a molecular link between cellular glucose metabolism and the control of EMT.

    Title Afterhyperpolarization Induced by the Activation of Nicotinic Acetylcholine Receptors in Pelvic Ganglion Neurons of Male Rats.
    Date December 2010
    Journal Neuroscience Letters
    Excerpt

    The electrophysiological mechanism underlying afterhyperpolarization induced by the activation of the nicotinic acetylcholine receptor (nAChR) in male rat major pelvic ganglion neurons (MPG) was investigated using a gramicidin-perforated patch clamp and microscopic fluorescence measurement system. Acetylcholine (ACh) induced fast depolarization through the activation of nAChR, followed by a sustained hyperpolarization after the removal of ACh in a dose-dependent manner (10 microM to 1mM). ACh increased both intracellular Ca(2+) ([Ca(2+)](i)) and Na(+) concentrations ([Na(+)](i)) in MPG neurons. The recovery of [Na(+)](i) after the removal of ACh was markedly delayed by ouabain (100 microM), an inhibitor of Na(+)/K(+) ATPase. Pretreatment with ouabain blocked ACh-induced hyperpolarization by 67.2+/-5.4% (n=7). ACh-induced hyperpolarization was partially attenuated by either the chelation of [Ca(2+)](i) with BAPTA/AM (20 microM) or the blockade of small-conductance Ca(2+)-activated K(+) channels by apamin (500 nM). Taken together, the activation of nAChR increases [Na(+)](i) and [Ca(2+)](i), which activates Na(+)/K(+) ATPase and Ca(2+)-activated K(+) channels, respectively. Consequently, hyperpolarization occurs after the activation of nAChR in the autonomic pelvic ganglia.

    Title Effects of Tau on the Activity of Triose Phosphate Isomerase (tpi) in Brain Cells.
    Date November 2010
    Journal Neurochemistry International
    Excerpt

    Tau is a main component of the aberrant paired helical filaments (PHF) found in Alzheimer's disease (AD). It has also been reported to enhance oxidative stress, which is a major factor in the pathogenesis of neurodegenerative diseases. However, protective functions of Tau have recently been reported, including antagonizing apoptosis, in addition to its role in stabilizing microtubules. In this study, the interaction between Tau and triose phosphate isomerase (TPI) in a normal, nondisease state as well as in a neurodegeneration state was examined and demonstrated for the first time. More importantly, we also showed that Tau protects TPI against oxidative damage. An oxidative stress-induced decrease in the activity of TPI was attenuated in Tau-overexpressing cells, indicating that Tau protects TPI against oxidative damage. By contrast, the activity of TPI was decreased in Tau-transgenic (Tg) mice compared to non-Tg (NTg) mice even though protein levels were not changed in both groups. Some TPIs were found on the PHF in Tg mice, which explains the decrease in the activity of TPI. Taken together, we concluded that while Tau binds and protects TPI in normal cells, and conversely, the formation of PHF induced by Tau phosphorylation trap some TPI and trigger the functional loss of TPI in the development of neurodegenerative diseases. Our results provide new insights into understanding the in-depth involvement of Tau in the development of neurodegenerative disorders.

    Title Prevalence of Multiple Sclerosis in Korea.
    Date November 2010
    Journal Neurology
    Excerpt

    The aim of this study was to estimate the prevalence of multiple sclerosis (MS) in Korea through a nationwide survey.

    Title Extract of Cassiae Semen and Its Major Compound Inhibit S100b-induced Tgf-beta1 and Fibronectin Expression in Mouse Glomerular Mesangial Cells.
    Date October 2010
    Journal European Journal of Pharmacology
    Excerpt

    Non-enzymatic glycation reactions between reducing sugar and free reactive amino groups of protein lead to the formation of advanced glycation end products, which increase under conditions of aging or diabetes. A previous study showed that extracts of Cassiae Semen (CS), the seed of Cassia tora, had inhibitory activity on advanced glycation end products formation in vitro. To examine the pharmacological effects of a butanol-soluble extract of CS under conditions of diabetic nephropathy, we evaluated the expression of transforming growth factor-beta1 (TGF-beta1) and fibronectin, key mediators of diabetic nephropathy, in mouse glomerular mesangial cells cultured in the presence of S100b (a specific ligand for receptor of advanced glycation end products). CS inhibited S100b-induced TGF-beta1 and fibronectin expression in mouse mesangial cells by suppressing activation of Smad2/3, extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK), and oxidative stress. Moreover, CS suppressed nuclear factor-kappa B (NF-kappaB) activation in S100b-stimulated mouse mesangial cells. To identify the active compounds of CS, three major compounds, rubrofusarin-6-O-beta-d-gentiobioside (CS-A), toralactone-9-O-beta-d-gentiobioside (CS-B), and cassiaside (CS-C), were tested in cells. Of these compounds, CS-A significantly decreased the expression of TGF-beta1 and fibronectin and NF-kappaB DNA binding activity. These findings suggest that CS, especially CS-A, has potential as a preventive agent for advanced glycation end products-related diabetic complications.

    Title Prevalence of Sarcopenia and Sarcopenic Obesity in Korean Adults: the Korean Sarcopenic Obesity Study.
    Date October 2010
    Journal International Journal of Obesity (2005)
    Excerpt

    To examine the prevalence of sarcopenia and sarcopenic obesity (SO) as defined by different indices, including appendicular skeletal muscle mass (ASM)/height(2), skeletal muscle mass index (SMI) and residuals for Korean adults, and to explore the association between SO and metabolic syndrome.

    Title Prevalence and Determinant Factors of Sarcopenia in Patients with Type 2 Diabetes: the Korean Sarcopenic Obesity Study (ksos).
    Date October 2010
    Journal Diabetes Care
    Excerpt

    We examined prevalence of sarcopenia in Korean patients with type 2 diabetes and compared body compositional parameters between subjects with and without type 2 diabetes.

    Title Scrophularia Buergeriana Regulates Cytokine Production in Vitro.
    Date October 2010
    Journal Immunopharmacology and Immunotoxicology
    Excerpt

    The Scrophularia buergeriana (SB) has long been used to treat various diseases an account of its antimicrobial and anti-virus activity. However, it is unclear how SB regulates the immune responses. This study investigated the effect of SB on the production of cytokines in a human T-cell line, MOLT-4 cells, and mouse peritoneal macrophages. The MOLT-4 cells were cultured for 24 h in the presence or absence of SB plus concanavalin (con) A. SB plus con A significantly increased the level of interleukin (IL)-2, IL-4 and interferon (IFN)-gamma production compared with that of con A alone (approximately 1.79-fold for IL-2, 2-fold for IL-4, and 1.85-fold for IFN-gamma, p < 0.05). SB plus recombinant IFN-gamma (rIFN-gamma) increased the level of IL-12 and NO production compared with rIFN-gamma alone. In addition, SB plus rIFN-gamma increased the level the iNOS expression on mouse peritoneal macrophages. Overall, SB may have an immune-enhancement effect through cytokine production.

    Title Effects of Hydrolyzed Chlorella Vulgaris by Malted Barley on the Immunomodulatory Response in Icr Mice and in Molt-4 Cells.
    Date October 2010
    Journal Journal of the Science of Food and Agriculture
    Excerpt

    Chlorella vulgaris is a unicellular and microscopic algae that is currently used in a variety of forms of tablets, capsules and liquid as a biological response modifier. The aim of this study was to investigate the effects of hydrolyzed Chlorella vulgaris by malted barley for its potential reduction of the immobility time in ICR mice and on the cytokine regulation in human T cell line, Molt-4.

    Title Simultaneous Diagnostic Method for Phenylketonuria and Galactosemia from Dried Blood Spots Using High-performance Liquid Chromatography-pulsed Amperometric Detection.
    Date October 2010
    Journal Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
    Excerpt

    We developed a simultaneous diagnostic method for phenylketonuria (PKU) and galactosemia through simultaneous determination of phenylalanine (Phe) and galactose (Gal) by high-performance liquid chromatography (HPLC) with pulsed amperometric detection (PAD). The intra- and inter-day precisions were <5.8%, with satisfactory mean recoveries (98.2-105%). For all PKU-positive samples, Phe levels were above the cut-off value (>30.0 mg/L), but Gal levels were nearly zero. For 77% of galactosemia-positive samples, Phe levels were above the cut-off value, but Gal levels were above the cut-off value (>80.0 mg/L) for all samples. Our HPLC-PAD method can reduce the false-positive rate of misdiagnosis for PKU and galactosemia.

    Title Borealin Regulates Bipolar Spindle Formation but May Not Act As Chromosomal Passenger During Mouse Oocyte Meiosis.
    Date October 2010
    Journal Frontiers in Bioscience (elite Edition)
    Excerpt

    In mitosis, Borealin is a member of the chromosomal passenger complex (CPC), which plays interaction roles with INCENP and survivin in the complex. Its roles in mammalian meiosis are unknown. Here, we report the expression, localization, and function of Borealin and its relation with survivin in mouse oocyte meiosis. Borealin expression was gradually increased from GV stage to MII. Immunofluorescence results revealed that Borealin accumulated near chromosomes after GVBD, localized at the spindle poles in MI, AI and MII, and at the midbody in TI stage. Taxol and nocodazole treatment showed that the localization of Borealin was dependent on microtubule dynamics, whereas survivin was independent of this. Disruption of Borealin function by antibody injection resulted in severe spindle assembly defects, but did not affect PBE. We also found that depletion of survivin by MO injection had no effect on the localization of Borealin. In conclusion, our data suggest that Borealin is required for bipolar spindle formation, but may not regulate spindle checkpoint activity as a component of the CPC during mouse oocyte meiosis.

    Title Cytotoxic Role of Methylglyoxal in Rat Retinal Pericytes: Involvement of a Nuclear Factor-kappab and Inducible Nitric Oxide Synthase Pathway.
    Date October 2010
    Journal Chemico-biological Interactions
    Excerpt

    Methylglyoxal (MGO), a cytotoxic metabolite, is produced from glycolysis. Elevated levels of MGO are observed in a number of diabetic complications, including retinopathy, nephropathy and cardiomyopathy. Loss of retinal pericyte, a hallmark of early diabetic retinal changes, leads to the development of formation of microaneurysms, retinal hemorrhages and neovasculization. Herein, we evaluated the cytotoxic role of MGO in retinal pericytes and further investigated the signaling pathway leading to cell death. Rat primary retinal pericytes were exposed to 400muM MGO for 6h. Retinal vessels were prepared from intravitreally MGO-injected rat eyes. We demonstrated apoptosis, nuclear factor-kappaB (NF-kappaB) activation and inducible nitric oxide synthase (iNOS) induction in cultured pericytes treated with MGO and MGO-injected retinal vessels. In MGO-treated pericytes, TUNEL-positive nuclei were markedly increased, and NF-kappaB was translocalized into the nuclei of pericytes, which paralleled the expression of iNOS. The treatment of pyrrolidine dithiocarbamate (an NF-kappaB inhibitor) or l-N6-(1-iminoethyl)-lysine (an iNOS inhibitor) prevented apoptosis of MGO-treated pericytes. In addition, in intravitreally MGO-injected rat eyes, TUNEL and caspase-3-positive pericytes were significantly increased, and activated NF-kappaB and iNOS were highly expressed. These results suggest that the increased expression of NF-kappaB and iNOS caused by MGO is involved in rat retinal pericyte apoptosis.

    Title Tetracycline-dependent Expression of the Human Erythropoietin Gene in Transgenic Chickens.
    Date September 2010
    Journal Transgenic Research
    Excerpt

    A critical problem in the production of transgenic animals is the uncontrolled constitutive expression of the foreign gene, which occasionally results in serious physiological disorders in the transgenic animal. In this study, we report successful production of transgenic chickens that express the human erythropoietin (hEPO) gene under the control of a tetracycline-inducible promoter. A recombinant Moloney murine leukemia virus (MoMLV)-based retrovirus vector encapsidated with vesicular stomatitis virus G glycoprotein (VSV-G) was injected beneath the blastoderm of unincubated chicken embryos (stage X). Out of 198 injected eggs, 15 chicks hatched after 21 days of incubation and 14 hatched chicks expressed the vector-encoded hEPO gene when fed doxycycline, a tetracycline derivative, without any significant physiological dysfunctions. The expression of hEPO reverted to the pre-induction state by removing doxycycline from the diet. The biological activity of the hEPO produced in the transgenic chickens was comparable to commercially available CHO cell-derived hEPO. Successful germline transmission of the transgene was also confirmed in G1 transgenic chicks produced from crossing G0 transgenic roosters with non-transgenic hens. Tetracycline-inducible expression of the hEPO gene was also confirmed in the blood and eggs of the transgenic chickens.

    Title Reduced Aquaporin3 Expression and Survival of Keratinocytes in the Depigmented Epidermis of Vitiligo.
    Date September 2010
    Journal The Journal of Investigative Dermatology
    Excerpt

    Activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway is critical for the survival of differentiating cells and depends on the E-cadherin-catenin complex. In an earlier study we showed impaired PI3K/AKT activation in vitiliginous keratinocytes (KCs). Recently, aquaporin3 (AQP3) has been reported to co-accumulate with E-cadherin in forming cell-to-cell contacts. Therefore, we examined the expression of AQP3 in vitiliginous KCs and the role of AQP3 in KC survival and differentiation by comparing downstream signaling molecules. AQP3 protein expression was significantly decreased in the depigmented epidermis compared with the normally pigmented epidermis of patients with vitiligo. Transfection of cultured normal human KCs with AQP3 small interfering RNA (siRNA) reduced the expression levels of phosphorylated PI3K, E-cadherin, beta-catenin, and gamma-catenin, regardless of the calcium concentration. These downstream signaling molecules were also decreased in the depigmented epidermis. The results of immunoprecipitation and double staining confirmed colocalization of AQP3 with E-cadherin, as well as an active role of AQP3 in E-cadherin expression of cell-to-cell contacts. Moreover, AQP3 knockdown induced no increase in differentiating markers at high calcium concentrations and reduced survival of KCs, suggesting that reduced AQP3 in vitiliginous KCs might be responsible for their reduced survival.

    Title Dilinoleoylphosphatidylcholine Induces the Expression of the Anti-inflammatory Heme Oxygenase-1 in Raw264.7 Macrophages.
    Date September 2010
    Journal Biofactors (oxford, England)
    Excerpt

    1,2-Dilinoleoyl-sn-glycero-3-phosphocholine (DLPC), the main and active component of soybean lecithin, has been reported to exert anti-inflammatory effects, but the underlying mechanisms remain to be established. It was found that DLPC could induce the expression of the anti-inflammatory heme oxygenase-1 (HO-1) through the activation of nuclear erythroid 2-related factor 2 (Nrf2) in RAW264.7 macrophages. Pretreatment with DLPC suppressed the expression of inducible nitric oxide (NO) synthase (iNOS), one of proinflammatory enzymes, and reduced NO production in lipopolysaccharide (LPS)-stimulated macrophages. Similarly, DLPC also diminished the production of tumor necrosis factor-alpha (TNF-alpha), one of proinflammatory cytokines. Interestingly, the inhibitory effects of DLPC on LPS-induced iNOS expression and TNF-alpha production were reversed by tin protoporphyrin, a HO-1 inhibitor. Thus, HO-1 expression via Nrf2 activation may be one of the possible mechanisms explaining the anti-inflammatory effects of DLPC.

    Title Xanthomonas Campestris Pv. Vesicatoria Effector Avrbst Induces Cell Death in Pepper, but Suppresses Defense Responses in Tomato.
    Date September 2010
    Journal Molecular Plant-microbe Interactions : Mpmi
    Excerpt

    A type III effector protein, AvrBsT, is secreted into plant cells from Xanthomonas campestris pv. vesicatoria Bv5-4a, which causes bacterial spot disease on pepper (Capsicum annuum) and tomato (Solanum lycopersicum). To define the function and recognition of AvrBsT in the two host plants, avrBsT was introduced into the virulent pepper strain X. campestris pv. vesicatoria Ds1. Expression of AvrBsT in Ds1 rendered the strain avirulent to pepper plants. Infection of pepper leaves with Ds1 (avrBsT) expressing AvrBsT but not with near-isogenic control strains triggered a hypersensitive response (HR) accompanied by strong H(2)O(2) generation, callose deposition, and defense-marker gene expressions. Mutation of avrBsT, however, compromised HR induction by X. campestris pv. vesicatoria Bv5-4a, suggesting its avirulence function in pepper plants. In contrast, AvrBsT acted as a virulence factor in tomato plants. Growth of strains Ds1 (avrBsT) and Bv5-4a DeltaavrBsT was significantly enhanced and reduced, respectively, in tomato leaves. X. campestris pv. vesicatoria-expressed AvrBsT also significantly compromised callose deposition and defense-marker gene expression in tomato plants. Together, these results suggest that the X. campestris pv. vesicatoria type III effector AvrBsT is differentially recognized by pepper and tomato plants.

    Title Dietary Polyphenols Affect Muc5ac Expression and Ciliary Movement in Respiratory Cells and Nasal Mucosa.
    Date September 2010
    Journal American Journal of Rhinology & Allergy
    Excerpt

    Dietary polyphenols have been widely consumed in food, and their anti-inflammatory and anticancer activities have been recently studied. Although the effects of dietary polyphenols on mucin hypersecretion have been studied to some extent, the effects of mucociliary movement have not been elucidated thus far. Therefore, we investigated whether dietary polyphenols inhibit MUC5AC gene expression in NCI-H292 cells, and, if so, whether they would have an effect on ciliary beat frequency (CBF) of human nasal mucosa.

    Title 3,5-di-o-caffeoyl-epi-quinic Acid from the Leaves and Stems of Erigeron Annuus Inhibits Protein Glycation, Aldose Reductase, and Cataractogenesis.
    Date September 2010
    Journal Biological & Pharmaceutical Bulletin
    Excerpt

    In our ongoing project directed toward the discovery of novel treatments for diabetic complications from herbal medicines, sixteen compounds including three caffeoylquinic acids and four flavonoids were isolated from an EtOAc-soluble extract of the stems and leaves of Erigeron annuus. All the isolates were evaluated in vitro for inhibitory activity on the formation of advanced glycation end products (AGEs) and rat lens aldose reductase (RLAR). Of these, 3,5-di-O-caffeoyl-epi-quinic acid (3) exhibited the most potent inhibitory activity in both the AGEs and aldose reductase (AR) assays. Compound 3 markedly reduced AGEs-bovin serum albumin (BSA) cross-linking in a dose-dependent manner. Furthermore, opacity of lenses was significantly prevented when they were treated with 3 in an ex vivo experiment.

    Title Libanoridin Inhibits the Mast Cell-mediated Allergic Inflammatory Reaction.
    Date August 2010
    Journal Immunopharmacology and Immunotoxicology
    Excerpt

    Corydalis heterocarpa is a biennial herb in South Korea, with spikes of yellow flowers. It has been used for as a folk medicine to cure travail and spasm. However, studies on this herb and its secondary metabolites have rarely been reported. In the present study, we isolated secondary metabolite libanlibanoridin from Corydalis heterocarpa. We have also examined the effect of libanoridin on the inflammatory cytokines production in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore, A2318 stimulated human mast cell line, HMC-1. PMA plus A23187 significantly increased interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha production compared to media control (P < 0.05).

    Title Canine Classical Seminoma: a Specific Malignant Type with Human Classifications is Highly Correlated with Tumor Angiogenesis.
    Date August 2010
    Journal Bmc Cancer
    Excerpt

    Human seminoma is classified as classical seminoma (SE) and spermatocytic seminoma (SS). Human SE is known to be more malignant and metastasizing more frequently than SS. Tumor angiogenesis is highly related with tumor progression and metastasis, with microvessel density (MVD) being an important parameter of metastatic potential. Canine seminoma is not yet well-established as SE or SS type including correlation with angiogenesis. We classified canine SE and SS, and then compared them to tumor associated vessels.

    Title Utility of the Cutaneous Silent Period in Patients with Diabetes Mellitus.
    Date August 2010
    Journal Journal of the Neurological Sciences
    Excerpt

    We performed this study to evaluate whether or not the cutaneous silent period (CSP) is a useful metric to identify small-fiber neuropathy in diabetic patients. The CSP was measured from the abductor pollicis brevis muscle in 30 healthy controls and 110 diabetic patients, who in turn were divided into 3 subgroups (patients with large-fiber neuropathy, patients with small-fiber neuropathy, and asymptomatic patients). The measured CSP and clinical characteristics were compared among the groups. The power of the CSP in discriminating patients from controls and any correlation with other clinical variables were analyzed. Each patient subgroup had a significantly delayed CSP latency compared to the controls. The latency of patients with large-fiber neuropathy was also significantly prolonged compared to the other subgroups of patients. The CSP latency was the only variable to discriminate patients. The latency showed a significant correlation with the late responses in nerve conduction studies. Thus, the CSP latency may be a useful tool in evaluating small neural fiber function in diabetic patients.

    Title Cut-off Value for Needle Washout Thyroglobulin in Athyrotropic Patients.
    Date July 2010
    Journal The Laryngoscope
    Excerpt

    The purpose of this study was to determine the appropriate cut-off value for fine needle aspiration-thyroglobulin (FNA-Tg) associated with postoperative recurrences and validate the diagnostic efficacy of FNA-Tg in patients after total thyroidectomy compared with concomitant cytology (C).

    Title Role of Ck1 in Gsk3beta-mediated Phosphorylation and Degradation of Snail.
    Date July 2010
    Journal Oncogene
    Excerpt

    The epithelial to mesenchymal transition (EMT) that occurs during embryonic development has begun to attract attention as a potential mechanism for tumor cell metastasis. Snail is a well-known Zn-finger transcription factor that promotes EMT by repressing E-cadherin expression. It is known that Snail is phosphorylated by GSK3beta and degraded by beta-TrCP-mediated ubiquitination. Here we described another protein kinase, CK1, whose phosphorylation of Snail is required for the subsequent GSK3beta phosphorylation. Specific inhibition or depletion of CK1varepsilon inhibits the phosphorylation and degradation of Snail and promotes cell migration, suggesting a central role of CK1varepsilon in the EMT process. Furthermore, our study uncovered distinct roles and steps of Snail phosphorylation by CK1varepsilon and GSK3beta. Taken together, we identified CK1varepsilon as a new component of the Snail-mediated EMT process, providing insight into the mechanism of human cancer metastasis.

    Title Double Reversing Z-plasty with Inferiorly Widening Stomaplasty for the Management of Tracheostomal Stenosis.
    Date June 2010
    Journal Auris, Nasus, Larynx
    Excerpt

    To present a surgical technique for the management of tracheostomal stenosis: double reversing Z-plasty with inferiorly widening stomaplasty.

    Title Molecular Characterization of Pig Alpha2,3-gal-beta1,3-galnac-alpha2,6-sialyltransferase (pst6galnac Iv) Gene Specific for Neu5acalpha2-3galbeta1-3galnac Trisaccharide Structure.
    Date June 2010
    Journal Glycoconjugate Journal
    Excerpt

    Sialic acids of glycoconjugates play crucial roles in various biological processes, such as cell-cell communication and cell-substrate interaction. A sisalyltransferase, ST6GalNAc IV (Neu5Ac-alpha2,3-Gal-beta1,3-GalNAc-alpha2,6-sialyltransferase), catalyzes the formation of alpha2-6-linkages onto GalNAc residues of O-glycosidically linked Ser/Thr of proteins. In this study, we cloned the pig ST6GalNAc IV (pST6GalNAc IV) and investigated its functional characterization. pST6GalNAc IV cDNA has been isolated from pig liver tissues and it contains an entire open reading frame (ORF, 906 bp) coding for 302 amino acid residues. Entire ORF of pST6GalNAc IV containing sialylmotif 'L'-(Large), 'S'-(Small) and '-VS' (Very small) has a high degree of sequence similarity with Homo sapiens (90%), Pan troglodytes (91%) and Mus musculus (87%). Expression of pST6GalNAc IV mRNA in various pig tissues was identified by reverse transcription polymerase chain reaction (RT-PCR) analysis. pST6GalNAc IV mRNA was highly expressed in tongue, muscle and heart, whereas it was not expressed in pancreas. For functional characterization of pST6GalNAc IV gene in pig kidney PK15 cells, we have also established pST6GalNAc IV-transfected PK15 cells, which are stably expressing the pST6GalNAc IV gene. The glycosylation pattern of pST6GalNAc IV-transfected PK15 cells was detected by flow cytometry and immunofluorescence analysis with Maackia amurensis agglutinin (MAA), Maackia amurensis hemagglutinin (MAL II), Sambucus nigra agglutinin (SNA) and peanut agglutinin (PNA) lectins. The specific carbohydrate structures of Neu5Acalpha2-3Galbeta1-3(Neu5Acalpha2-6)GalNAc tetrasaccharide or Neu5Acalpha2-6GalNAc disaccharide recognized by MAL-II and SNA were revealed to be newly synthesized by pST6GalNAc IV. From the results, it was suggested that the pig pST6GalNAc IV gene is capable of synthesizing Neu5Acalpha2-3Galbeta1-3(Neu5Acalpha2-6)GalNAc tetrasaccharide structures on O-glycoproteins.

    Title The Separate and Joint Effects of Prolonged Qt Interval and Heart Rate on Mortality.
    Date June 2010
    Journal Atherosclerosis
    Excerpt

    Understanding why prolonged Bazett-corrected QT interval (QTc) is a risk factor for mortality is difficult, because QTc is positively correlated with heart rate. To optimally distinguish the effects of QT interval and heart rate on mortality, QT interval and heart rate were modeled separately and jointly in Pima Indians.

    Title Lack of Association Between Antisperm Antibodies and Language Dysfunction in Alzheimer's Disease.
    Date June 2010
    Journal Archives of Gerontology and Geriatrics
    Excerpt

    Alzheimer's disease (AD) is the single most common cause of primary dementia. Language-based frontotemporal dementia, another type of primary dementia, is known as primary progressive aphasia (PPA). Although the cardinal feature of AD is a progressive loss of memory, many patients with AD also present with language impairment. Moreover AD and PPA have partially shared pathophysiology. Recently, it was suggested that a history of vasectomy might be a risk factor for PPA, by immune responses to sperm or antisperm antibody (ASA), which has long been known to have antigenic property. As ASAs could develop naturally in both men and women, we studied the relation between the presence of ASAs and cognitive function in AD. A total of 86 elderly were selected (46 patient with AD, 20 with mild cognitive impairment, and 20 without cognitive dysfunction) and were assessed for the presence of ASAs with neuropsychological evaluation. However, there were no significant differences in the distribution of ASAs according to cognitive status or language function status. Thus, the current study does not support the association between the immune responses and language dysfunction in AD.

    Title Low Levels of Plasma Agmatine in the Metabolic Syndrome.
    Date May 2010
    Journal Metabolic Syndrome and Related Disorders
    Excerpt

    The biophysiology of the amino acid l-arginine has been a field of active research. Agmatine, which is a metabolite of l-arginine, is known to participate in many biophysical reactions, including those in the cardiovascular system. We sought to investigate plasma agmatine levels in human subjects as a potential biomarker for the metabolic syndrome.

    Title Papillary Thyroid Carcinoma Arising in a Branchial Cleft Cyst.
    Date May 2010
    Journal Thyroid : Official Journal of the American Thyroid Association
    Title Fabrication of Highly Uniform Conductive Polypyrrole Nanowires with Dna Template.
    Date May 2010
    Journal Journal of Nanoscience and Nanotechnology
    Excerpt

    Deoxyribonucleic acid (DNA) is considered as one of the alternative materials for electronic device applications; however, DNA has critical limitation to electronic device applications due to its low electrical conductivity and unreliability. Therefore, it is required for electronic devices to prepare the well defined conductive polymer nanowires with DNA as a template. Polypyrrole (PPy) is an attractive polymer due to its high conductivity and environmental stability in bulk; although it is well known that ammonium persulfate (APS) used for the polymerization of pyrrole causes the deformation of DNA molecules. We minimized the damage of immobilized DNA strands on (3-aminopropyl) triethoxysilane (APTES) modified silicon wafer during APS polymerization. Atomic force microscopy (AFM) images from different APS treatment times and from using the vortex process obviously showed the effect on the synthesis of individual and continuous polypyrrole nanowires (PPy NWs). The PPy NWs at various pyrrole concentrations had similar height; however, the higher concentration gave more residues. Fourier transform-infrared spectroscopy (FT-IR) spectroscopy provided the strong evidence that PPy NWs were successfully synthesized on the DNA strands.

    Title Electrical Characteristics and Doping Mechanism of Dna Molecules Doped with Iodine Solutions.
    Date May 2010
    Journal Journal of Nanoscience and Nanotechnology
    Excerpt

    This study examined the electrical characteristics of deoxyribonucleic acid (DNA) molecules doped with iodine solution and their chemical state changes before and after doping. The experiments were progressed in each lambda (A), poly(dA)-poly(dT) and poly(dG)-poly(dC) DNA under the same conditions. The authors prepared 20 nm gap Au/Ti electrodes fabricated by e-beam lithography. DNA solutions were dropped on the nano gap of the electrodes and DNA films were formed by drying in a vacuum. DNA films were doped with an iodine solution dissolved in methanol. The authors measured the electrical conductivity of DNA molecules as the number of iodine doping times in 10(-2) torr vacuum. As increase of the iodine solution doping number, the electrical conductivity of three sorts of DNA molecules was remarkably improved respectively. X-ray photoelectron spectroscopy (XPS) was performed to inspect the electrical conduction mechanism that holes on DNA nitrogen region were generated by transferring electrons to iodine molecules.

    Title Vascular Inflammation in Patients with Impaired Glucose Tolerance and Type 2 Diabetes: Analysis with 18f-fluorodeoxyglucose Positron Emission Tomography.
    Date May 2010
    Journal Circulation. Cardiovascular Imaging
    Excerpt

    Type 2 diabetes mellitus (T2DM) is associated with an increased risk of atherosclerotic cardiovascular disease. Vascular inflammation is a key factor in both the pathogenesis and outcome of atherosclerosis. (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a promising tool for indentifying and quantifying vascular inflammation within atherosclerotic plaques. This study was designed to examine the vascular inflammation measured using FDG-PET in patients with impaired glucose tolerance and T2DM, in comparison with age- and sex-matched control subjects with normal glucose tolerance.

    Title Dokhwaljihwang-tang Inhibits Lps-induced Inflammatory Cytokine Production in Peripheral Blood Mononuclear Cells.
    Date April 2010
    Journal Neurological Research
    Excerpt

    Dokhwaljihwang-tang, one of the prescriptions in Four Constitution medicine, has been used to treat neurological disorders. This work was aimed to examine the effect of Dokhwaljihwang-tang on lipopolysaccharide-induced inflammatory cytokine production in peripheral blood mononuclear cells from the lesser yang subjects.

    Title Predictive Value of Albuminuria in American Indian Youth with or Without Type 2 Diabetes.
    Date April 2010
    Journal Pediatrics
    Excerpt

    To examine the prognostic significance of elevated albuminuria in youth with type 2 diabetes.

    Title Cloning and Functional Characterization of Pig Cmp-n-acetylneuraminic Acid Hydroxylase for the Synthesis of N-glycolylneuraminic Acid As the Xenoantigenic Determinant in Pig-human Xenotransplantation.
    Date April 2010
    Journal The Biochemical Journal
    Excerpt

    In the present study, the pig CMP-N-acetylneuraminic acid hydroxylase gene (pcmah), a key enzyme for the synthesis of NeuGc (N-glycolylneuraminic acid), was cloned from pig small intestine and characterized. The ORF (open reading frame) of pcmah was 1734 bp, encoding 577 amino acids and consisting of 14 exons. Organ expression pattern analysis reveals that pcmah mRNA is mainly expressed in pig rectum, tongue, spleen and colon tissues, being the most highly expressed in small intestine. In the ectopic expression of pcmah, when pig kidney PK15 cells and human vascular endothelial ECV304 cells were transfected with the cloned pcmah, the NeuGc contents of these transfectants were greater in comparison with vector transfectants used as controls. In addition, in the functional analysis of NeuGc, HSMC (human-serum-mediated cytotoxicity) was elevated in the ectopic NeuGc-expressing pcmah-transfected cells compared with controls. Moreover, binding of human IgM to the pcmah-transfected cells was significantly increased, whereas binding of IgG was slightly increased, indicating that the human IgM type was a major anti-NeuGc antibody. Furthermore, pcmah silencing by shRNA (short hairpin RNA) resulted in a decrease in NeuGc content and xenoantigenicity in PK15. From the results, it was concluded that the pcmah gene was capable of synthesizing the NeuGc acting as a xenoantigen in humans, confirming the NeuGc-mediated rejection response in pig-human xenotransplantation.

    Title Effects of Omeprazole on the Antiplatelet Activity of Clopidogrel.
    Date March 2010
    Journal International Heart Journal
    Excerpt

    Clopidogrel is used with aspirin as a standard combined treatment in patients with acute coronary syndrome. A proton pump inhibitor (PPI) is often administered to patients receiving antiplatelet therapy. However, PPI use with clopidogrel was recently shown to result in increased risk of major cardiovascular events when compared to clopidogrel use alone. Therefore, the aim of the present study was to evaluate the effects of omeprazole, a PPI, on the antiplatelet effect of clopidogrel.We divided 20 healthy volunteers into 2 groups (n = 10 each). Twenty-four hours after a 300 mg loading dose of clopidogrel, one group received a dosage of 75 mg/day of clopidogrel and a placebo for 14 days, followed 3 weeks later by the same protocol but with coadministration of 75 mg/day clopidogrel and 20 mg/day omeprazole instead. The other group received the same treatment but in reverse order. Antiplatelet activity was assessed in terms of the P2Y12 reaction unit (PRU) and percentage inhibition using a VerifyNow P2Y12 assay system.The PRU of the omeprazole-treated subjects was significantly higher than that of the omeprazole-untreated subjects on day 14 (281.3 +/- 54.0 versus 240.0 +/- 72.2, P = 0.048). The percentage inhibition showed a decrease after the 14-day omeprazole treatment (22.7 +/- 29.9% versus 35.1 +/- 18.7%, P = 0.014). Consequently, omeprazole reduces the antiplatelet effect of clopidogrel, suggesting that careful treatment planning is required when administering omeprazole to patients on clopidogrel therapy.

    Title Lysophosphatidic Acid Induces Upregulation of Mcl-1 and Protects Apoptosis in a Ptx-dependent Manner in H19-7 Cells.
    Date March 2010
    Journal Cellular Signalling
    Excerpt

    Lysophosphatidic acid (LPA) is a lipid growth factor known to regulate diverse cell functions, including cell proliferation, survival, and apoptosis. Tight regulation of cell survival in neuronal precursor is essential during neurogenesis in both developing and adult brain. Increasing data show that diverse external factors including LPA play roles in controlling cell survival and apoptosis in early developing neurons. However, the underlying control mechanism remains unclear. To explore how LPA regulates cell survival or apoptosis in a developing neuron, mechanisms for cell survival and signaling cascades by LPA were investigated in H19-7 hippocampal progenitor cells. Here, we showed that LPA promotes cell survival by protection from apoptosis. Mcl-1 was demonstrated to be crucial in LPA-induced cell survival by transfection of the siRNA specific for Mcl-1 and overexpression of Mcl-1. LPA-induced cell survival was critically mediated by the upregulation of Mcl-1 which was regulated not only through a post-translational control but a transcriptional control. Mcl-1 stabilization by LPA-induced inhibitory phosphorylation of GSK-3 contributed predominantly to the Mcl-1 upregulation. Both LPA-induced cell survival and the GSK-3 phosphorylation were attenuated by PTX and by siRNA specific for LPA1 or LPA2 receptor. Taken together, these results showed that Mcl-1 stabilization by inhibitory phosphorylation of GSK-3 through Gi/o coupling of the LPA1 and LPA2 receptors following Mcl-1 upregulation plays a critical role in LPA-induced survival of H19-7 cells. In developing neurons, modulation of Mcl-1 levels may constitute a crucial mechanism for controlling their fates.

    Title Molecular Characterization and Polyadenylation-regulated Expression of Cyclin B1 and Cdc2 in Porcine Oocytes and Early Parthenotes.
    Date February 2010
    Journal Molecular Reproduction and Development
    Excerpt

    Meiotic maturation of mammalian oocytes is controlled by the maturation/M-phase promotion factor (MPF), a complex of Cdc2 kinase and cyclin B protein. To better understand the molecular mechanism of oocyte maturation, we characterized porcine cyclin B1 and Cdc2 genes, both of which are widely expressed in pig tissues. We further analyzed their expression profiles during in vitro maturation of pig oocyte and early embryonic development at both the mRNA and protein level. Two isoforms of cyclin B1, comprising the same open reading frame but differing in 3'-UTR length, were identified. Cyclin B1 transcripts was up-regulated after 30 hr of maturation, while Cdc2 mRNA levels were unchanged during maturation except for a sharp decline at 44 hr. Cyclin B1 protein synthesis increased with oocyte maturation. Cdc2 protein expression was relatively low during 0-18 hr, followed by a higher level of expression up to 44 hr of maturation. Poly(A)-test PCR clearly revealed that both cyclin B1 isoforms underwent cytoplasmic polyadenylation starting around 18-24 hr during maturation, while a substantial de-adenylation and degradation of Cdc2 isoforms were observed in metaphase II oocytes and during embryo development after parthenogenetic activation. Porcine MII oocytes derived from small follicles (< or = 3 mm) and bad quality 2-cell parthenotes showed lower developmental competence and lower levels of cyclin B1 protein, and Cdc2 mRNA or both gene mRNAs, respectively, compared to their control counterparts. These results suggested that cyclin B1 was regulated posttranscriptionally by cytoplasmic polyadenylation during porcine oocyte maturation. Further, the decreased expression of maternal cyclin B1 and Cdc2 at the mRNA or protein level in developmentally incompetent oocytes and embryos was responsible for, at least in part, a profound defect in further embryonic development.

    Title A Pooled Analysis of 29 Patients with Fulminant Type 1 Diabetes in Korea: a Comparison with a Nationwide Survey in Japan.
    Date January 2010
    Journal Diabetes Research and Clinical Practice
    Excerpt

    We performed a retrospective pooled analysis of 29 patients who had been diagnosed with fulminant type 1 diabetes in Korea and compared the results with 161 patients' data from a nationwide survey in Japan. Fulminant type 1 diabetic patients in Korea have a similar phenotype compared with Japanese patients.

    Title Nodular Lymphoid Hyperplasia and Histologic Changes Mimicking Celiac Disease, Collagenous Sprue, and Lymphocytic Colitis in a Patient with Selective Iga Deficiency.
    Date January 2010
    Journal Pathology, Research and Practice
    Excerpt

    Selective IgA deficiency is the most common primary immunoglobulin deficiency. The clinical manifestations of selective IgA deficiency, including gastrointestinal (GI) complications, are rare and typically milder than those seen with common variable immunodeficiency or X-linked agammaglobulinemia. We present a rare case of selective IgA deficiency that shows a number of interesting histological features in the GI tract, including diffuse nodular lymphoid hyperplasia involving the entire small and large intestine, celiac disease-like and collagenous sprue-like changes in the small intestine, as well as lymphocytic colitis pattern. However, this patient had no particular GI symptoms suggestive of celiac sprue or microscopic colitis. These findings suggest that the GI tract in patients with selective IgA deficiency can show peculiar histologic changes that mimic celiac disease, collagenous sprue, or lymphocytic colitis, which may be a pattern of injury related to infection or immunoglobulin immunodeficiency-associated autoimmune phenomena.

    Title Colonic Mucosal Necrosis Following Administration of Calcium Polystryrene Sulfonate (kalimate) in a Uremic Patient.
    Date January 2010
    Journal Journal of Korean Medical Science
    Excerpt

    Colonic necrosis is known as a rare complication following the administration of Kayexalate (sodium polystryrene sulfonate) in sorbitol. We report a rare case of colonic mucosal necrosis following Kalimate (calcium polystryrene sulfonate), an analogue of Kayexalate without sorbitol in a 34-yr-old man. He had a history of hypertension and uremia. During the management of intracranial hemorrhage, hyperkalemia developed. Kalimate was administered orally and as an enema suspended in 20% dextrose water to treat hyperkalemia. Two days after administration of Kalimate enema, he had profuse hematochezia, and a sigmoidoscopy showed diffuse colonic mucosal necrosis in the rectum and sigmoid colon. Microscopic examination of random colonic biopsies by two consecutive sigmoidoscopies revealed angulated crystals with a characteristic crystalline mosaic pattern on the ulcerated mucosa, which were consistent with Kayexalate crystals. Hematochezia subsided with conservative treatment after a discontinuance of Kalimate administration.

    Title [efficacy of 48-week Clevudine Therapy for Chronic Hepatitis B].
    Date January 2010
    Journal The Korean Journal of Hepatology
    Excerpt

    Clevudine is a nucleoside analogue that exhibits potent and sustained antiviral effects as a 24-week therapy for chronic hepatitis B (CHB). This study evaluated the efficacy and viral resistance of a 48-week course of clevudine treatment for CHB.

    Title The Cutoff Values of Visceral Fat Area and Waist Circumference for Identifying Subjects at Risk for Metabolic Syndrome in Elderly Korean: Ansan Geriatric (age) Cohort Study.
    Date January 2010
    Journal Bmc Public Health
    Excerpt

    In Korea, the cutoff values of waist circumference (WC) for the identification of metabolic syndrome (MetS) were suggested to be 90 cm for men and 85 cm for women based on the analysis mainly in middle-aged adults. As aging is associated with increased fat, especially abdominal visceral fat, the cutoff value of WC may differ according to age. In addition, the usefulness of visceral abdominal fat area (VFA) to predict MetS in the elderly has not been studied yet. We aimed to suggest WC and VFA criteria and to compare the predictability of WC and VFA to identify people at risk for MetS.

    Title Hypersensitivity to Rf Fields Emitted from Cdma Cellular Phones: a Provocation Study.
    Date January 2010
    Journal Bioelectromagnetics
    Excerpt

    With the number of cellular phone users rapidly increasing, there is a considerable amount of public concern regarding the effects that electromagnetic fields (EMFs) from cellular phones have on health. People with self-attributed electromagnetic hypersensitivity (EHS) complain of subjective symptoms such as headaches, insomnia, and memory loss, and attribute these symptoms to radio frequency (RF) radiation from cellular phones and/or base stations. However, EHS is difficult to diagnose because it relies on a person's subjective judgment. Various provocation studies have been conducted on EHS caused by Global System for Mobile Communications (GSM) phones in which heart rate and blood pressure or subjective symptoms were investigated. However, there have been few sham-controlled provocation studies on EHS with Code Division Multiple Access (CDMA) phones where physiological parameters, subjective symptoms, and perception of RF radiation for EHS and non-EHS groups were simultaneously investigated. In this study, two volunteer groups of 18 self-reported EHS and 19 non-EHS persons were tested for both sham and real RF exposure from CDMA cellular phones with a 300 mW maximum exposure that lasted half an hour. We investigated not only the physiological parameters such as heart rate, respiration rate, and heart rate variability (HRV), but also various subjective symptoms and the perception of EMF. In conclusion, RF exposure did not have any effects on physiological parameters or subjective symptoms in either group. As for EMF perception, there was no evidence that the EHS group better perceived EMF than the non-EHS group.

    Title Clinical Significance of On-treatment Triglyceride Level in Patients Treated by Percutaneous Coronary Intervention for Non-st-segment Elevation Acute Coronary Syndrome.
    Date January 2010
    Journal The Korean Journal of Internal Medicine
    Excerpt

    The use of statins in patients with acute coronary syndrome (ACS) has increased, and reduced levels of low-density lipoprotein cholesterol (LDL-C) lead to lower coronary event rates. We studied the effect of lipid levels during statin treatment on prognosis in patients with ACS and percutaneous coronary intervention (PCI).

    Title Hyperglycemia Reduces Mitochondrial Content and Glucose Transporter Expression in Mouse Embryos Developing in Vitro.
    Date December 2009
    Journal The Journal of Reproduction and Development
    Excerpt

    The objective of this research was to examine the effects of high concentrations of glucose on mouse embryos developing in vitro by studying embryo viability, mitochondrial content and expression of glucose transporters. Addition of 55 mM glucose to the culture medium of two-cell stage embryos significantly reduced the formation of morulae and blastocysts, resulting in fewer cells in the blastocyst stage embryos and increased levels of apoptosis. Quantitative reverse transcriptase (RT) PCR analysis revealed that the expression levels of the pro-apoptotic genes Bax and Casp3 at the blastocyst stage were increased significantly by the addition of either 25 or 55 mM glucose to the culture medium. However, addition of 25 or 55 mM glucose to the culture medium did not change the copy numbers of the apoptosis-related miRNAs mmu-mir-15a, mmu-mir-16 and mmu-mir-21. MitoTracker Green fluorescence revealed a decrease in the mitochondrial mass. The expression levels of the mitochondrial DNA-encoded genes Cox1 and Cox2 decreased sharply with the addition of 25 or 55 mM glucose to the culture medium. Both transcripts and protein synthesis of the glucose transporters Glut1 and Glut3 were reduced in blastocysts cultured in the presence of either 25 or 55 mM glucose. These results suggest that hyperglycemia reduces both mitochondrial content and expression levels of glucose transporters in mouse embryos developing in vitro and that this may result in apoptosis in these embryos.

    Title Perturbation of Survivin Expression Affects Chromosome Alignment and Spindle Checkpoint in Mouse Oocyte Meiotic Maturation.
    Date December 2009
    Journal Cell Cycle (georgetown, Tex.)
    Excerpt

    Survivin is a member of inhibitors of apoptosis proteins (IAPs), which have multiple regulatory functions in mitosis, but its roles in meiosis remain unknown. Here, we report its expression, localization and functions in mouse oocyte meiosis. Survivin displayed a maximal expression level in GV stage, and then gradually decreased from Pro-MI to MII stages. Immunofluorescent staining showed that survivin was restricted to the germinal vesicle, associated with centromeres from pro-metaphase I to metaphase I stages, distributed at the midzone and midbody of anaphase and telophase spindles, and located to centromeres at metaphase II stages. Depletion of survivin by antibody injection and morpholino injection resulted in severe chromosome misalignment, precocious polar body extrusion, and larger-than-normal polar bodies. Overexpression of survivin resulted in severe chromosome misalignment and prometaphase I or metaphase I arrest in a large proportion of oocytes. Our data suggest that survivin is required for chromosome alignment and that it may regulate spindle checkpoint activity during mouse oocyte meiosis.

    Title The Effectiveness of Simethicone in Improving Visibility During Colonoscopy.
    Date December 2009
    Journal Hepato-gastroenterology
    Excerpt

    In colonoscopy examination, luminal visibility is frequently limited due to intraluminal bubbles. In present study was evaluated factors affecting bubble formation and the effects of simethicone in preventing bubble formation during colonoscopy.

    Title Enhancement of Angiogenic and Vasculogenic Potential of Endothelial Progenitor Cells by Haptoglobin.
    Date November 2009
    Journal Febs Letters
    Excerpt

    Endothelial progenitor cells (EPCs) were transfected with the haptoglobin (Hp) gene to investigate the effect of Hp on cell function. Hp potentiated the gene expression of various pro-angiogenic factors in the EPCs. The Hp-modified EPCs also increased in vitro tube formation on Matrigel compared with control cells. In hindlimb ischaemia models, Hp-EPCs showed a greater ability for improving blood perfusion and recovery from ischaemic injury. These results indicate that Hp improves EPC function in neovasculogenesis, which suggests that ex vivo modification of EPCs with the Hp gene can be applied to the treatment of vascular damage.

    Title Pulmonary Hypertensive Medical Therapy in Chronic Thromboembolic Pulmonary Hypertension Before Pulmonary Thromboendarterectomy.
    Date October 2009
    Journal Circulation
    Excerpt

    The currently recommended treatment for chronic thromboembolic pulmonary hypertension is pulmonary thromboendarterectomy (PTE). No convincing evidence for the use of pulmonary hypertensive medical therapy (PHT) exists in operable candidates. We sought to determine the prevalence of the use of PHT on referral for PTE and the effects on pre-PTE hemodynamics and post-PTE outcomes/hemodynamics.

    Title A Link Between the Interleukin-6/stat3 Anti-apoptotic Pathway and Microrna-21 in Preimplantation Mouse Embryos.
    Date October 2009
    Journal Molecular Reproduction and Development
    Excerpt

    Signal transducers and activators of transcription-3 (Stat3) plays a central role in interleukin-6 (IL-6)-mediated cell proliferation by inhibiting apoptosis in a variety of cell types. MicroRNA-21 (miRNA-21), a ubiquitous miRNA, acts as an anti-apoptotic factor that seems to be indirectly but strictly linked to Stat3. In order to determine whether the IL-6 induced Stat3 anti-apoptosis pathway is linked with miRNA-21, we first determined the effects of recombinant mouse IL-6 on Stat3 expression, mouse embryo viability, and the mRNA levels of apoptosis related genes and miRNA-21 during mouse embryo development in vitro. Addition of 10 or 100 ng/ml of recombinant IL-6 to the culture medium did not affect the developmental ability of 2-cell stage embryos into blastocysts. However, total cell number was significantly increased and apoptosis was reduced in blastocyst stage embryos cultured in the presence of 100 ng/ml of recombinant IL-6. Furthermore, addition of recombinant IL-6 to the culture medium significantly increased the copy numbers of anti-apoptotic miRNA-21, up-regulated Bcl2l1, and down-regulated casp3. Similarly, the injection of mature miRNA-21 into cells up-regulated Bcl2l1 and down-regulated casp3. These results suggest that the induction of the Stat3 anti-apoptotic pathway by IL-6 is linked to miRNA-21 expression, which possibly results in the regulation of cell apoptosis in early mouse embryo development.

    Title Adiposity Parameters and Cognitive Function in the Elderly: Application of "jolly Fat" Hypothesis to Cognition.
    Date October 2009
    Journal Archives of Gerontology and Geriatrics
    Excerpt

    Obesity has a strong association with cardiovascular and metabolic diseases, which have also been linked with dementia. While recent studies have reported an association between mid-life obesity and dementia, the role that later-life obesity may have is less clear. A total of 721 community-dwelling elderly (60-85 years old) were selected. Obesity parameters, like body mass index (BMI), waist-hip ratio (WHR), waist circumference (WC), and percent body fat (PBF), as well as cognitive functions were measured over a period of approximately 2 years, and then the relationships between these variables were assessed. The change in cognitive function in the elderly was associated with the baseline assessment of BMI (linearly, beta=0.092), WC (quadratic, beta=1.333), and PBF (linearly, beta=0.097). Using multiple regression analyses, the differences exist in the change of cognitive function over time according to the sex. For men, increased obesity over time when obese in the baseline assessment (BMI, WHR, WC) were associated with a positive change in cognitive function. For women, a decreased obesity over time when obese in the baseline assessment (WHR) and an increased obesity over time when they had a normal adiposity in the baseline assessment (WC) were both associated with cognitive decline. The relationship between obesity and cognitive decline in the elderly is complex and some differences exist between the sexes. The application of the "Jolly Fat" hypothesis to cognitive function can only be applied to elderly men and not to elderly women.

    Title Response of High-sensitivity C-reactive Protein to Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome.
    Date October 2009
    Journal Heart and Vessels
    Excerpt

    Percutaneous coronary intervention (PCI) provokes an inflammatory reaction, as shown by increased concentrations of plasma C-reactive protein (CRP) after PCI. However, the changes of CRP levels after PCI in patients with acute coronary syndrome (ACS) have not been well evaluated. We evaluated the characteristics of the patients with elevated CRP response after PCI and whether an increase in CRP after PCI predicts long-term prognosis in patients with ACS. We studied consecutive 360 patients with ACS who underwent elective coronary stenting. Inflammatory response to PCI was calculated as the difference between the peak postprocedural hsCRP level and the preprocedural hsCRP level (DeltaCRP). Twelve months follow-up data were obtained and clinical outcomes were compared with DeltaCRP. In receiver operating characteristics analyses, the cutoff point of DeltaCRP for major adverse cardiac events (MACE) was 3.0 mg/l, which yielded sensitivity of 61.7% and specificity of 69.7%. The patients with DeltaCRP > 3 mg/l revealed higher incidence of myocardial infarction (37.7 vs 14.6%, P < 0.001), and ACC/AHA type B2/C lesion (81.5 vs 68.7%, P = 0.006) than in patients with low DeltaCRP. White blood cell count, low-density lipoprotein cholesterol, peak creatinine kinase-MB, and peak troponin T were significantly elevated in patients with DeltaCRP > 3 mg/l than in those with < or =3 mg/l. There was significant correlation between DeltaCRP and the changes in troponin T after PCI (r = 0.210, P < 0.001). An increase in hsCRP > 3 mg/l after PCI had a higher predictive value for the occurrence of MACE than low hsCRP elevation (hazard ratio 2.1, P = 0.005). In multivariate analysis, DeltaCRP and peak troponin T were independent predictors of MACE (P < 0.001 and P = 0.013, respectively). In conclusion, postprocedural hsCRP elevation >3 mg/l was associated with higher incidence of MACE in patients with ACS. DeltaCRP determinations may be of value for risk stratification after PCI.

    Title Substrate Specificity of a Mannose-6-phosphate Isomerase from Bacillus Subtilis and Its Application in the Production of L-ribose.
    Date September 2009
    Journal Applied and Environmental Microbiology
    Excerpt

    The uncharacterized gene previously proposed as a mannose-6-phosphate isomerase from Bacillus subtilis was cloned and expressed in Escherichia coli. The maximal activity of the recombinant enzyme was observed at pH 7.5 and 40 degrees C in the presence of 0.5 mM Co(2+). The isomerization activity was specific for aldose substrates possessing hydroxyl groups oriented in the same direction at the C-2 and C-3 positions, such as the d and l forms of ribose, lyxose, talose, mannose, and allose. The enzyme exhibited the highest activity for l-ribulose among all pentoses and hexoses. Thus, L-ribose, as a potential starting material for many L-nucleoside-based pharmaceutical compounds, was produced at 213 g/liter from 300-g/liter L-ribulose by mannose-6-phosphate isomerase at 40 degrees C for 3 h, with a conversion yield of 71% and a volumetric productivity of 71 g liter(-1) h(-1).

    Title Endothelial Function in Lacunar Infarction: a Comparison of Lacunar Infarction, Cerebral Atherosclerosis and Control Group.
    Date September 2009
    Journal Cerebrovascular Diseases (basel, Switzerland)
    Excerpt

    There are conflicting evidences on endothelial function in lacunar infarction. This may be attributed to the effects of risk factors on the vascular smooth muscle. To test endothelial function only in patients with lacunar infarction, we evaluated the endothelium-dependent and -independent vasodilatation of the brachial artery.

    Title New Class of Microrna Targets Containing Simultaneous 5'-utr and 3'-utr Interaction Sites.
    Date September 2009
    Journal Genome Research
    Excerpt

    MicroRNAs (miRNAs) are known to post-transcriptionally regulate target mRNAs through the 3'-UTR, which interacts mainly with the 5'-end of miRNA in animals. Here we identify many endogenous motifs within human 5'-UTRs specific to the 3'-ends of miRNAs. The 3'-end of conserved miRNAs in particular has significant interaction sites in the human-enriched, less conserved 5'-UTR miRNA motifs, while human-specific miRNAs have significant interaction sites only in the conserved 5'-UTR motifs, implying both miRNA and 5'-UTR are actively evolving in response to each other. Additionally, many miRNAs with their 3'-end interaction sites in the 5'-UTRs turn out to simultaneously contain 5'-end interaction sites in the 3'-UTRs. Based on these findings we demonstrate combinatory interactions between a single miRNA and both end regions of an mRNA using model systems. We further show that genes exhibiting large-scale protein changes due to miRNA overexpression or deletion contain both UTR interaction sites predicted. We provide the predicted targets of this new miRNA target class, miBridge, as an efficient way to screen potential targets, especially for nonconserved miRNAs, since the target search space is reduced by an order of magnitude compared with the 3'-UTR alone. Efficacy is confirmed by showing SEC24D regulation with hsa-miR-605, a miRNA identified only in primate, opening the door to the study of nonconserved miRNAs. Finally, miRNAs (and associated proteins) involved in this new targeting class may prevent 40S ribosome scanning through the 5'-UTR and keep it from reaching the start-codon, preventing 60S association.

    Title Comparison of Cytological Results Obtained by Repeated Us-guided Fine-needle Aspiration Biopsies of Thyroid Nodules: Focus on the Rate of Malignancy and Diagnostic Concordance.
    Date September 2009
    Journal Diagnostic Cytopathology
    Excerpt

    The debate still continues on the repeated fine-needle aspiration biopsies (FNABs) for thyroid nodule in clinical practice. In this study, we determined the rate of cytological change to malignancy and the diagnostic concordance of repeated FNABs when the same nodules were targeted under US-guidance. We retrospectively reviewed data for 187 thyroid nodules (173: twice, 14: three times) from 160 patients who underwent repeated US-guided FNABs, which were performed by one skillful radiologist targeting for the same nodules at a mean interval of 7.5 months. Their initial cytological findings were compared with second or third results and histopathologic follow-up. The initial FNABs findings of 187 nodules were unsatisfactory, benign, and indeterminate in 56, 52, and 79 cases, respectively. The rate of a second cytological diagnosis changed to malignancy was significantly higher in the unsatisfactory aspirates (10.7%; 6/56), when compared with those of the benign (0.0%; 0/52) or of indeterminate aspirates (3.8%; 3/79) (P = 0.022). However, there was no change to malignancy at third cytological findings of all 14 nodules. After the second US-guided FNABs, 30.8% (16/52) of the initially diagnosed as benign aspirates were reclassified as indeterminate, while 26.6% (21/79) of the initially diagnosed as indeterminate were reclassified as benign. In conclusion, to identify malignancies, repeated US-guided FNABs are recommended for thyroid nodules initially classified as unsatisfactory aspirates. However, although US-guidance is applied, a discrepancy might be unavoidable in the cytological interpretation of the nodules classified as benign or as indeterminate aspirates because of overlapping cytological criteria.

    Title Reduction of Prion Infectivity and Levels of Scrapie Prion Protein by Lithium Aluminum Hydride: Implications for Rna in Prion Diseases.
    Date August 2009
    Journal Journal of Neuropathology and Experimental Neurology
    Excerpt

    Previous studies indicate that RNA may be required for proteinase-resistant prion protein (PrP) amplification and for infectious prion formation in vitro, suggesting that RNA molecules may function as cellular cofactors for abnormal PrP (PrPSc) formation and become part of the structure of the infectious agent. To address this question, we used chemicals that can cleave phosphodiester bonds of RNA and assessed their effects on the infectious agent. Lithium aluminum hydride, a reducing agent that can induce reductive cleavage of oxidized molecules such as carbonyls, carboxyl acids, esters, and phosphodiester bonds, did not affect cellular PrP degradation; however, it destroyed PrPSc, extended the scrapie incubation period, and markedly reduced total RNA concentrations. These results prompted us to investigate whether RNA molecules are cofactors for PrPSc propagation. RNase A treatment of partially purified PrP and of 263K scrapie brain homogenates was sufficient to increase the sensitivity of PrPSc to proteinase K degradation. This is the first evidence that suggests that RNA molecules are a component of PrPSc. Treatment with RNase A alone and PrP degradation by RNase A plus proteinase K in vitro, however, did not result in loss of scrapie infectivity compared with the effects of lithium aluminum hydride. Together, these data suggest that RNA molecules may be important for maintaining the structure of PrPSc and that oxidized molecules can be important in scrapie agent replication and prion infectivity.

    Title Interstitial Tissue-specific Gene Expression in Mouse Testis by Intra-tunica Albuguineal Injection of Recombinant Baculovirus.
    Date August 2009
    Journal Asian Journal of Andrology
    Excerpt

    The purpose of this study is to establish a gene delivery system for interstitial tissue-specific protein expression in mice testes using modified recombinant baculovirus. Green fluorescent protein (GFP)-expressing recombinant baculovirus (GFP-baculovirus), in which the insect cell-specific polyhedron promoter was replaced by the cytomegalovirus (CMV)-IE promoter, was used to transfect testicular cells in vitro, and for intra-tunica albuguineal injection of the interstitial tissue of the testis. GFP expression was monitored in frozen testes sections by fluorescence microscopy. Expression of GFP in testicular tissues was also assessed by reverse transcription polymerase chain reaction (RT-PCR), and protein expression was assessed by Western blot. Testicular cells in vitro were infected efficiently by modified recombinant GFP-baculovirus. Intra-tunica albuguineal injection of GFP-baculovirus into the mouse testis resulted in a high level of GFP expression in the interstitial tissues. RT-PCR analysis clearly showed GFP gene expression in the testis, particularly interstitial tissues. Intra-tunica albuguineal injection of a modified baculovirus that encoded recombinant rat insulin-like growth factor binding protein (IGFBP)-5 resulted in an increase in IGFBP-5 in testis and semen. In conclusion, we have developed an efficient delivery system for gene expression in vivo in testicular cells, particularly cells of the interstitial tissue using intra-tunica albuguineal injection of a modified recombinant baculovirus. This method will be particularly relevant for application that requires gene delivery and protein expression in the testicular cells of the outer seminiferous tubule of the testis.

    Title Expression of Inducible Nitric Oxide Synthase by Corydalis Turtschaninovii on Interferon-gamma Stimulated Macrophages.
    Date August 2009
    Journal Journal of Ethnopharmacology
    Excerpt

    Corydalis turtschaninovii (CT) has been used for tumor therapy. However, it is still unclear how this herb prevents the diseases in experimental models. Nitric oxide (NO) as a potent macrophage-derived effector molecule against a variety of tumors has received increasing attention.

    Title Interventional and Surgical Modalities of Treatment in Pulmonary Hypertension.
    Date July 2009
    Journal Journal of the American College of Cardiology
    Excerpt

    Most patients with chronic thromboembolic pulmonary hypertension are operable, and pulmonary endarterectomy is the treatment of choice. Pulmonary endarterectomy should not be delayed for medical therapy, and risk stratification helps to define patients likely to achieve the best outcome. Inoperable patients should be referred for trials of medical agents. Atrial septostomy is promising but underutilized, although better ways of ensuring an adequate, lasting septostomy still need to be determined. Indications for the procedure are unchanged, and it should be considered more frequently. Bilateral sequential lung or heart-lung transplantation is an important option for selected patients, and potential candidates who are class IV or III but not improving should be referred early to a transplantation center. Currently, there is a need for right ventricular assist devices with flow characteristics suited to the circulation of patients with pulmonary arterial hypertension. Right ventricular synchronization therapy has not yet been tested. Novel shunts (e.g., Potts anastomosis) also hold promise. All surgery for pulmonary hypertension should be performed in centers with experience in these techniques.

    Title End Points and Clinical Trial Design in Pulmonary Arterial Hypertension.
    Date July 2009
    Journal Journal of the American College of Cardiology
    Excerpt

    New and emerging therapies might provide benefit in patients with pulmonary arterial hypertension. Their efficacy and safety will be compared with existing combination therapies in randomized clinical trials. Appropriate end points for these trials need to be identified: these will include exercise testing, the composite end point of time to clinical worsening, and hemodynamic markers, including advanced imaging modalities and biomarkers. Quality-of-life questionnaires are useful and important secondary end points; pulmonary arterial hypertension-specific questionnaires are currently being developed. Advantages and disadvantages of various trial designs, including placebo-controlled monotherapy or add-on trials, noninferiority studies, and withdrawal trials are also discussed.

    Title 7-diethylamino-3(2'-benzoxazolyl)-coumarin is a Novel Microtubule Inhibitor with Antimitotic Activity in Multidrug Resistant Cancer Cells.
    Date June 2009
    Journal Biochemical Pharmacology
    Excerpt

    Microtubules are a proven target for anticancer drug development because they are critical for mitotic spindle formation and the separation of chromosomes at mitosis. We here report a novel synthetic microtubule inhibitor 7-diethylamino-3(2'-benzoxazolyl)-coumarin (DBC). DBC causes destabilization of microtubules, leading to a cell cycle arrest at G(2)/M stage. In addition, human cancer cells are more sensitive to DBC (IC(50) 44.8-475.2nM) than human normal fibroblast (IC(50) 7.9microM), and DBC induces apoptotic cell death of cancer cells. Furthermore, our data show that DBC is a poor substrate of drug efflux pumps and effective against multidrug resistant (MDR) cancer cells. Taken together, these results describe a novel pharmacological property of DBC as a microtubule inhibitor, which may make it an attractive new agent for treatment of MDR cancer.

    Title A Simple Hplc Method for Doxorubicin in Plasma and Tissues of Nude Mice.
    Date May 2009
    Journal Archives of Pharmacal Research
    Excerpt

    Doxorubicin is a cytotoxic anthracycline that has been used for the treatment of several malignancies. Several HPLC methods have been reported for the quantification of doxorubicin in biological samples. Tissue matrix effect and sample size requirements, however, have been remaining issues for simple and easy-to-adapt analytical methods in small animal experiments. The present study established a simple HPLC method for doxorubicin in plasma and tissues (tumor, heart, spleen, liver, gastrointestinal tract, brain, lung, and kidney) of nude mice. Our method required a small sample volume (100 microL plasma and 10 mg tissue), which made it possible to use each blank tissue for calibration curves. The limit of quantification was 25 ng/mL in plasma and 0.1 to 0.4 microg/mg in other tissues with recovery rates ranging from 52.4 to 95.2%. The linearity, accuracy and precision in all tissues, except gastrointestinal tract (GIT), were found to be acceptable in the range of 25-2000 ng/mL plasma and 0.1-4 ng/mg tissue. This method was used successfully to determine the drug concentration in plasma and tissues of human tumor xenograft-bearing nude mice given intratumoral doxorubicin in a polymeric drug delivery system designed for sustained release. In conclusion, the present method may be useful as a simple and easy-to-adapt, yet, sensitive analytical method of doxorubicin for plasma and tissue pharmacokinetic studies in small animals such as nude mice.

    Title Fabrication of Aspherical Polymer Lenses Using a Tunable Liquid-filled Mold.
    Date May 2009
    Journal Optics Letters
    Excerpt

    We demonstrated a tunable molding process to fabricate aspherical polymer lenses that can reduce aberrations and the total length of an optical system. Radius of curvature and conic constant are shown to be the key parameters to characterize the lens profile. The good agreement between the measured profiles and the simulated profiles allows us to design and fabricate lenses of a wide range of user-specified properties. Compared to the conventional aspherical lens fabrication method using injection molding with a diamond-turned mold, the proposed method may yield savings in time and cost.

    Title Respiratory Rate Detection Algorithms by Photoplethysmography Signal Processing.
    Date May 2009
    Journal Conference Proceedings : ... Annual International Conference of the Ieee Engineering in Medicine and Biology Society. Ieee Engineering in Medicine and Biology Society. Conference
    Excerpt

    Photoplethysmography (PPG) offers the clinically meaningful parameters, such as, heart rate, and respiratory rate. In this study, we presented three respiratory signal detection algorithms using photoplethysmography raw data generated from commercial PPG sensor: (1)Min-Max (2)Peak-to-Peak (3)Pulse Shape. As reference signal, nasal sensor signal was acquired simultaneously and compared and analyzed. We used two types of moving average filtering technique to process three PPG parameters. In laboratory experiment, 6 subjects' PPG signals were measured when they respire ten and fifteen, and arbitrary times per minute. From the results, following conclusions were drawn. Min-Max and Peak-to-Peak algorithms perform better than Pulse shape algorithm. They can be used to detect respiratory rate. But, Pulse Shape algorithm was accurate for subject 4 only. More experimental data is necessary to improve the accuracy and reliability.

    Title A Patient with Micropapillary Thyroid Carcinoma and Macronodular Lung Metastasis: Stable Disease for Eight Years Without Treatment.
    Date May 2009
    Journal Thyroid : Official Journal of the American Thyroid Association
    Excerpt

    In this report, we described a very rare type of patient with micropapillary thyroid carcinoma with macronodular lung metastasis that had prolonged growth arrest for more than 8 years without any treatment. Unlike previous reports with stable metastasis, the patient presented here was older than prior cases and had a smaller size of the primary carcinoma.

    Title Phosphorylation of Creb, a Cyclic Amp Responsive Element Binding Protein, Contributes Partially to Lysophosphatidic Acid-induced Fibroblast Cell Proliferation.
    Date April 2009
    Journal Biochemical and Biophysical Research Communications
    Excerpt

    Lysophospholipids regulate a wide array of biological processes including cell survival and proliferation. In our previous studies, we found that in addition to SRE, CRE is required for maximal c-fos promoter activation triggered by lysophosphatidic acid (LPA). c-fos is an early indicator of various cells into the cell cycle after mitogenic stimulation. However, role of CREB activation in LPA-stimulated proliferation has not been elucidated yet. Here, we investigate how LPA induces proliferation in Rat-2 fibroblast cell via CREB activation. We found that total cell number and BrdU-positive cells were increased by LPA. Moreover, levels of c-fos mRNA and cyclin D1 protein were increased via LPA-induced CREB phosphorylation. Furthermore, LPA-induced Rat-2 cell proliferation was decreased markedly by ERK inhibitor (U0126) and partially by MSK inhibitor (H89). Taken together, these results suggest that CREB activation could partially up-regulate accumulation of cyclin D1 protein level and proliferation of LPA-stimulated Rat-2 fibroblast cells.

    Title The Effect of Residual Renal Function at the Initiation of Dialysis on Patient Survival.
    Date April 2009
    Journal The Korean Journal of Internal Medicine
    Excerpt

    The optimal time point for initiating renal replacement therapy in patients with end-stage renal disease remains controversial. The primary objective of our study was to determine the effects of residual renal function at the beginning of renal replacement therapy on the mortality of patients with end-stage renal disease.

    Title Study Design and Methods of the Ansan Geriatric Study (age Study).
    Date April 2009
    Journal Bmc Neurology
    Excerpt

    The overall objective of the Ansan Geriatric Study (AGE study) was to describe the prevalence, incidence, and related risk factors for geriatric diseases in elderly Koreans.

    Title Anti-inflammatory Activity of Schizonepeta Tenuifolia Through the Inhibition of Mapk Phosphorylation in Mouse Peritoneal Macrophages.
    Date March 2009
    Journal The American Journal of Chinese Medicine
    Excerpt

    Schizonepeta tenuifolia (ST) is a well-known herb to treat the cold and its associated headache. However, the anti-inflammatory mechanism of ST in mouse peritoneal macrophages is not clear. In this study, we demonstrated that ST inhibited lipopolysaccaride (LPS)-induced tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 production. The maximal inhibition rate of TNF-alpha and IL-6 production by ST (2 mg/ml) was 48.01 +/- 2.8% and 56.45 +/- 2.8%, respectively. During the inflammatory process, cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) were increased in mouse peritoneal macrophages. However, treated with ST decreased the protein level of COX-2 and iNOS, as well as the production of PGE(2) and NO in LPS-stimulated mouse peritoneal macrophages. In addition, ST inhibited the phosphorylation of MAPK. Taken together, the results of this study suggest an important molecular mechanism by which ST reduces inflammation, which may explain its beneficial effect in the regulation of inflammatory reactions.

    Title Hwanggunchungyitang Prevents Cadmium-induced Ototoxicity Through Suppression of the Activation of Caspase-9 and Extracellular Signal-related Kinase in Auditory Hei-oc1 Cells.
    Date March 2009
    Journal Biological & Pharmaceutical Bulletin
    Excerpt

    Hwanggunchungyitang (HGCYT) is a newly designed herbal drug formula for the purpose of treating auditory diseases. A number of heavy metals have been associated with toxic effects to the peripheral or central auditory system. Cadmium (Cd(2+)) is a heavy metal and a potent carcinogen implicated in tumor development through occupational and environmental exposure. However, the auditory effect of Cd(2+) is not poorly understood. The purpose of the present study was to investigate whether HGCYT prevent the ototoxic effects induced by Cd(2+) in auditory cell line, HEI-OC1. HGCYT inhibited the cell death, reactive oxygen species generation (ROS), activation of caspase-9, and extracellular signal-related kinase (ERK) induced by Cd(2+). In addition, we observed that cochlear hair cells in middle turn were damaged by Cd(2+). However, HGCYT prevented the destruction of hair cell arrays of the rat primary organ of Corti explants in the presence of Cd(2+). These results support the notion that ROS are involved in Cd(2+) ototoxicity and suggest HGCYT therapeutic usefulness, against Cd(2+)-induced activation of caspase-9 and ERK.

    Title Leonurus Sibiricus Induces Nitric Oxide and Tumor Necrosis Factor-alpha in Mouse Peritoneal Macrophages.
    Date February 2009
    Journal Canadian Journal of Physiology and Pharmacology
    Excerpt

    Using mouse peritoneal macrophages, we have examined the mechanism by which Leonurus sibiricus (LS) regulates nitric oxide (NO) production. When LS was used in combination with recombinant interferon-gamma (rIFN-gamma), there was a marked cooperative induction of NO production; however, LS by itself had no effect on NO production. The increased production of NO from rIFN-gamma plus LS-stimulated cells was almost completely inhibited by pretreatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor kappaB. Furthermore, treatment of peritoneal macrophages with rIFN-gamma plus LS caused a significant increase in tumor necrosis factor-alpha (TNF-alpha) production. PDTC also decreased the effect of LS on TNF-alpha production significantly. Because NO and TNF-alpha play an important role in immune function and host defense, LS treatment could modulate several aspects of host defense mechanisms as a result of stimulation of the inducible nitric oxide synthase.

    Title Hemodynamics and Epoprostenol Use Are Associated with Thrombocytopenia in Pulmonary Arterial Hypertension.
    Date January 2009
    Journal Chest
    Excerpt

    Thrombocytopenia develops in some patients with advanced pulmonary arterial hypertension (PAH) while receiving IV epoprostenol therapy. In this study, we evaluate whether epoprostenol use, other PAH medication use, hemodynamics, or PAH etiology are associated with thrombocytopenia in PAH.

    Title The Effect of Hydrolyzed Spirulina by Malted Barley on Forced Swimming Test in Icr Mice.
    Date January 2009
    Journal The International Journal of Neuroscience
    Excerpt

    Spirulina is a true puree of a filamentous, spiral-shaped blue alga and exerts the useful properties as a source of many biochemicals. This study investigated the antidepressant-like effect of hydrolyzed Spirulina by malted barley on the forced swimming test in mice. After the forced swimming test, we examined the levels of several blood biochemical parameters in mice. The effect of the hydrolyzed Spirulina by malted barley-treated group for 2 weeks on the immobility time was significantly reduced in comparison with the control group (p < .05). Plasma level of blood urea nitrogen and lactate dehydrogenase was significantly decreased in the hydrolyzed Spirulina by malted barley-treated group compared with the control group (p < .05). It had no effect on the variation of creatine kinase, glucose, total protein, and albumin levels. Therefore, these results suggest that hydrolyzed Spirulina by malted barley might be a candidate among antidepressant agents.

    Title Dermoscopic-histopathologic Correlation of Cutaneous Lymphangioma Circumscriptum.
    Date December 2008
    Journal Archives of Dermatology
    Title [a Case of Primary Neuroendocrine Carcinoma of Liver Presenting with Liver Abscess].
    Date September 2008
    Journal The Korean Journal of Gastroenterology = Taehan Sohwagi Hakhoe Chi
    Excerpt

    Primary hepatic neuroendocrine cell carcinoma is a very rare tumor. We experienced a 75-year-old woman with primary hepatic neuroendocrine carcinoma presenting with pyogenic liver abscess. Abdominal CT scan revealed a multiseptated liver abscess and an enlarged lymph node in portocaval portion. We performed percutaneous drainage of the liver abscess, but the amount of drained pus did not decrease after 20 days. The follow-up abdominal CT scan showed that the cystic portion of liver abscess had been replaced by the solid tumor. Microscopic examination of the tumor tissue showed nests of epithelial cells with uniform round hyperchromatic nuclei and high nuclear to cytoplasmic ratio. Immunohistochemical staining was strongly positive for synaptophysin and chromogranin A.

    Title Effect of Serum Starvation on the Efficiency of Nuclear Transfer Using Odd-eyed White Cat Fibroblasts.
    Date September 2008
    Journal Theriogenology
    Excerpt

    In the present study, we compared in vitro and in vivo development of nuclear transfer (NT) embryos derived from serum-starved or non-serum-starved odd-eyed cat skin fibroblast cells. Flow cytometry analyses revealed that a higher percentage of cells were in the G0/G1 phase after serum starvation (89.3%) as compared with non-serum-starved cells (73.8%, P<0.05). Frequency of cleavage and development to the blastocyst stage was not different between the serum-starved or non-serum-starved treatment group, 67.9 and 12.5% versus 73.0 and 10.2%, respectively (P>0.05). After transfer of two to four-cell NT embryos derived from starved and non-starved fibroblasts, three of nine (33%) and one of nine (11%) recipients delivered three live male (plus, one dead) and two live male kittens, respectively. Of the five live-cloned kittens, one died from diarrhea at 3 weeks of age and the other four kittens are growing at a normal rate. The cloned kittens are blue-eyed and have functional auditory systems, including clones of the odd-eyed deaf Turkish Angora cat. Subsequent DNA analysis of nine-cat specific microsatellite loci confirmed that all of the cloned kittens were identical to the odd-eyed donor male, but a point mutation occurred in the dead fetus at the FCA 290 marker.

    Title The Dermoscopic Differential Diagnosis of Yellow Lobularlike Structures.
    Date August 2008
    Journal Archives of Dermatology
    Title Generation of Transgenic Chickens That Produce Bioactive Human Granulocyte-colony Stimulating Factor.
    Date August 2008
    Journal Molecular Reproduction and Development
    Excerpt

    We report here the generation of transgenic chickens that produce human granulocyte-colony stimulating factor (hG-CSF) using replication-defective Moloney murine leukemia virus (MoMLV)-based vectors packaged with vesicular stomatitis virus G glycoprotein (VSV-G). The recombinant retrovirus was injected beneath the blastoderm of nonincubated chicken embryos (stage X). Out of 140 injected eggs, 17 chicks hatched after 21 days of incubation and all hatched chicks were found to express vector-encoded hG-GSF gene. The biological activity of the recombinant hG-CSF was significantly higher than its commercially derived E. coli-derived counterpart. Successful germline transmission of the transgene was also confirmed in G(1) transgenic chicks produced from the cross of Go transgenic roosters with nontransgenic hens, but most of the G(1) progeny were dead within 1 month of hatching.

    Title A Report on the Diagnosis of Intermediate Hyperglycemia in Korea: A Pooled Analysis of Four Community-based Cohort Studies.
    Date August 2008
    Journal Diabetes Research and Clinical Practice
    Excerpt

    Many studies show poor agreement between fasting plasma glucose (FPG)-based and 2-h postchallenge glucose (2-h PG)-based criteria to assess glucose metabolism. We examined the rate of agreement between FPG- and 2-h PG-based criteria in the diagnosis of intermediate hyperglycemia in four representative cohort studies in South Korea and compared the clinical characteristics and biochemical parameters in subjects with impaired fasting glucose (IFG) according to their FPG values. Of 6234 subjects from four population-based studies performed from 1993 to 2000, 4610 individuals with data from a 75g oral glucose tolerance test (OGTT) and no previous history of diabetes were selected. We examined the concordance rate between the FPG and 2-h PG-based criteria. We also investigated the differences in the clinical characteristics and biochemical parameters between individuals with IFG according to their FPG values. The fasting and 2-h PG criteria had large discordance rates in the diagnosis of diabetes and impaired glucose tolerance (IGT) in Korean adults. When individuals with IFG were classified into stage 1 [5.6-6.1mmol/L (100-109mg/dL)] and stage 2 [6.1-7.0mmol/L (110-125mg/dL)] IFG, individuals with stage 2 IFG are more obese and had higher blood pressure and total cholesterol and triglycerides concentrations compared with those with stage 1 IFG. In addition, more individuals with stage 2 IFG were with diabetes as determined by a 2-h PG>or=11.1mmol/L (14.1% vs. 1.9%) (P<0.05). Considering the poorer metabolic profile and higher percentage of people with diabetes by OGTT, these data indicate that, in the Korean population, individuals with stage 2 IFG should be treated differently from those with stage 1 IFG. To detect more cases of diabetes, the OGTT is recommended for all individuals with stage 2 IFG and cases with stage 1 IFG with some additional risk factors for diabetes.

    Title A Mapk Pathway is Involved in the Control of Cortical Granule Reaction and Mitosis During Bovine Fertilization.
    Date August 2008
    Journal Molecular Reproduction and Development
    Excerpt

    In order to understand the mechanism by which mitogen-activated protein kinase (MAPK) regulates fertilization, we examined the effect of the MAPK pathway inhibitor U0126 on polyspermy, cortical granule reaction and mitosis in bovine oocytes during and after fertilization. Oocytes were treated with 30 microM U0126 for 30 min prior to insemination, or from 15 to 27 hr following insemination. Western blotting with antibodies that detect active, phosphorylated MAPK revealed that MAPK activity was decreased in U0126 treated oocytes. Oocytes that were treated with U0126 before insemination displayed a significantly higher incidence of polyspermic penetration and incomplete cortical granule reaction than that observed in untreated oocytes (P < 0.05). Exposure of oocytes to 30microM U0126 15-27 hr after insemination induced aberrant microtubule assembly and cell division, often resulting in the formation of two or three daughter cells with altered shapes and sizes. These results suggest that an ERK-like cascade is part of a mechanism that controls cortical granule reaction and the formation of the mitotic spindle following sperm penetration in the bovine.

    Title Plasma Glucose Regulation and Mortality in Pima Indians.
    Date June 2008
    Journal Diabetes Care
    Excerpt

    OBJECTIVE: To evaluate whether impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) are associated with increased risk of mortality and prevalent ischemic heart disease (IHD) and to analyze if the increased risk of death is dependent on subsequent development of diabetes in Pima Indians. RESEARCH DESIGN AND METHODS: A total of 2,993 Pima Indians aged >or=35 years were included. Prevalent IHD, defined by major ischemic electrocardiogram changes, was evaluated according to the following glucose/diabetes categories: normal glucose regulation (NGR), IFG and/or IGT, and diabetic groups by duration. During a median follow-up of 10.4 years, 780 subjects died from natural causes and 156 of these died from IHD. Mortality was analyzed according to the same glucose/diabetes categories at baseline and then as time-dependent variables. RESULTS: Only subjects with diabetes >or=15 years of duration have a higher prevalence of IHD (odds ratio 1.9 [95% CI 1.4-2.5]) relative to NGR. In baseline and time-dependent models, age- and sex-adjusted death rates from natural causes and from IHD were similar among the nondiabetic groups. Among diabetic subjects, natural mortality was higher in those with >or=15 years diabetes duration (death rate ratio [DRR] relative to NGR = 2.6 [95% CI 2.1-3.3]). IHD mortality was higher in subjects with long diabetes duration (DRR for diabetes 10-15 years = 3.8 [1.5-9.5]; DRR for diabetes >or=15 years = 8.6 [3.8-19.4]) in the time-dependent model. CONCLUSIONS: Natural and IHD mortality are not increased in Pima Indians with IFG and/or IGT. Only after the onset of diabetes do the rates of these events increase relative to NGR.

    Title Generation of Cloned Transgenic Cats Expressing Red Fluorescence Protein.
    Date May 2008
    Journal Biology of Reproduction
    Excerpt

    A method for engineering and producing genetically modified cats is important for generating biomedical models of human diseases. Here we describe the use of somatic cell nuclear transfer to produce cloned transgenic cats that systemically express red fluorescent protein. Immature oocytes were collected from superovulating cat ovaries. Donor fibroblasts were obtained from an ear skin biopsy of a white male Turkish Angora cat, cultured for one to two passages, and subjected to transduction with a retrovirus vector designed to transfer and express the red fluorescent protein (RFP) gene. A total of 176 RFP cloned embryos were transferred into 11 surrogate mothers (mean = 16 +/- 7.5 per recipient). Three surrogate mothers were successfully impregnated (27.3%) and delivered two liveborn and one stillborn kitten at 65 to 66 days of gestation. Analysis of nine feline-specific microsatellite loci confirmed that the cloned cats were genetically identical to the donor cat. Presence of the RFP gene in the transgenic cat genome was confirmed by PCR and Southern blot analyses. Whole-body red fluorescence was detected 60 days after birth in the liveborn transgenic (TG) cat but not in the surrogate mother cat. Red fluorescence was detected in tissue samples, including hair, muscle, brain, heart, liver, kidney, spleen, bronchus, lung, stomach, intestine, tongue, and even excrement of the stillborn TG cat. These results suggest that this nuclear transfer procedure using genetically modified somatic cells could be useful for the efficient production of transgenic cats.

    Title Preoperative Plasma N-terminal Pro-brain Natriuretic Peptide Concentration and Perioperative Cardiovascular Risk in Elderly Patients.
    Date May 2008
    Journal Circulation Journal : Official Journal of the Japanese Circulation Society
    Excerpt

    BACKGROUND: The prediction of perioperative cardiovascular complications is important in the medical management of patients undergoing noncardiac surgery. Several indices have been developed, but a simpler, more practical and accurate method is needed. The purpose of this study was to determine whether the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration before operation can be used to predict perioperative cardiovascular complications in elderly patients undergoing noncardiac surgery. METHODS AND RESULTS: The study group comprised 279 patients older than 60 years who were scheduled for elective surgery. The plasma NT-proBNP concentration, clinical cardiac indices and left ventricular ejection fraction were measured prior to operation. The postoperative cardiac outcomes were followed and predictors for postoperative cardiac risk were identified. Cardiovascular complications occurred in 25 patients (9.0%). Age, the incidence of prior ischemic heart disease or congestive heart failure, and the plasma NT-proBNP concentration were significantly higher in patients with perioperative cardiovascular complications than in those without. Using receiver operating characteristic analysis to predict perioperative cardiovascular events, a cut-off value of 201 pg/ml was identified as the optimal predictor of perioperative complications, showing a sensitivity of 80.0% and specificity of 81.1%. Multivariate analysis revealed that NT-proBNP >201 pg/ml (odds ratio (OR) 7.6, 95% confidence interval (CI) 2.2-26.6, p=0.003) and revised cardiac index > or =2 (OR 6.3, 95% CI 1.7-23.8, p=0.007) were independent predictors for perioperative cardiovascular complications. CONCLUSIONS: Elevated NT-proBNP levels are independently associated with an increase in the risk of perioperative cardiovascular complications in elderly patients undergoing noncardiac and nonvascular operations.

    Title Histone Deacetylase Inhibitor Apicidin-mediated Drug Resistance: Involvement of P-glycoprotein.
    Date March 2008
    Journal Biochemical and Biophysical Research Communications
    Excerpt

    Multidrug resistance (MDR), which is a significant impediment to the success of cancer chemotherapy, is attributable to the overexpression of membrane transport proteins, such as P-glycoprotein (P-gp), resulting in an increased drug efflux. In this study, we show that the histone deacetylase (HDAC) inhibitor apicidin leads to resistance of HeLa cells to paclitaxel through the induction of P-gp expression. Furthermore, apicidin dramatically increases the release of a fluorescent P-gp substrate, rhodamine 123, from cells. In parallel, apicidin resistance to the apoptotic potential of paclitaxel is associated with induction of P-gp expression in HeLa cells, as evidenced by specific inhibition of P-gp function using either the pharmacological inhibitor verapamil or RNA silencing. We also demonstrate the contribution of apicidin-induced functional P-gp expression to drug resistance using KB cells. Failure of P-gp induction by apicidin does not reverse paclitaxel-induced cytotoxicity in the cells. Although HDAC inhibitors are widely appreciated as a new class of anti-tumor agent, our findings clearly demonstrate that apicidin treatment may lead to P-gp-mediated resistance to other anti-tumor agents, suggesting a need for careful design of clinical applications using HDAC inhibitors.

    Title Antibody Response in Endemic Pemphigus Foliaceus.
    Date March 2008
    Journal The Journal of Investigative Dermatology
    Title Plasma Visfatin Levels Are Positively Associated with Circulating Interleukin-6 in Apparently Healthy Korean Women.
    Date March 2008
    Journal Diabetes Research and Clinical Practice
    Excerpt

    Even though visfatin has been suggested as a proinflammatory adipokine, there are few studies of the relationship between plasma visfatin concentrations and proinflammatory markers in the nondiabetic population. We showed that plasma visfatin concentrations were positively associated with circulating interleukin-6 levels and diastolic blood pressure independent of obesity in nondiabetic healthy Korean women. These results suggest that circulating visfatin may be related with some proinflammatory condition even in a nondiabetic state.

    Title Effects of Alpha-lipoic Acid on Ischemia-reperfusion-induced Renal Dysfunction in Rats.
    Date March 2008
    Journal American Journal of Physiology. Renal Physiology
    Excerpt

    We investigated whether alpha-lipoic acid (alpha-LA), an antioxidant, attenuates the ischemia-reperfusion (I/R)-induced dysregulation of these transporters. Both renal pedicles of male Sprague-Dawley rats were clamped for 40 min. alpha-LA (80 mg/kg) was administered intraperitoneally before and immediately after induction of ischemia. After 2 days, the expression of aquaporins (AQPs), sodium transporters, and nitric oxide synthases (NOS) was determined in the kidney by immunoblotting and immunohistochemistry. The expression of endothelin-1 (ET-1) mRNA was determined by real-time PCR. Activities of adenylyl cyclase and guanylyl cyclase were measured by stimulated generation of cAMP and cGMP, respectively. The expression of AQP1-3 as well as that of the alpha(1)-subunit of Na-K-ATPase, type 3 Na/H exchanger, Na-K-2Cl cotransporter, and Na-Cl cotransporter was markedly decreased in response to I/R. The expression of type VI adenylyl cyclase was decreased in I/R-injured rats, which was counteracted by the treatment of alpha-LA. AVP-stimulated cAMP generation was blunted in I/R rats and was then ameliorated by alpha-LA treatment. alpha-LA treatment attenuated the downregulation of AQPs and sodium transporters. The expression of endothelial NOS was decreased in I/R rats, which was prevented by alpha-LA. The cGMP generation in response to sodium nitroprusside was blunted in I/R rats, which was also significantly prevented by alpha-LA. The mRNA expression of ET-1 was increased, which was recovered to the control level by alpha-LA treatment. In conclusion, alpha-LA treatment prevents I/R-induced dysregulation of AQPs and sodium transporters in the kidney, possibly through preserving normal activities of local AVP/cAMP, nitric oxide/cGMP, and ET systems.

    Title Successful Extracorporeal Life Support After Potentially Fatal Pulmonary Oedema Caused by Inhalation of Nitric and Hydrofluoric Acid Fumes.
    Date February 2008
    Journal Resuscitation
    Excerpt

    Two patients presented with potentially fatal pulmonary oedema after accidental exposure to nitric and hydrofluoric acid fumes during electroplating. Despite aggressive respiratory support, one succumbed to respiratory failure 3.5h after inhalation. The other patient also rapidly progressed to respiratory failure. Extracorporeal life support (ECLS) was started 5h after exposure at the ED. During ECLS, hypoxia improved, but pulmonary oedema shown by chest radiography became aggravated. N-Acetyl cysteine and calcium gluconate were given i.v. on the first day of admission and nebulised for 48 h after exposure. Pulmonary secretions were significantly reduced 24 h after the nebulising therapy began. Ultimately, the patient was discharged without serious pulmonary or neurological complications after 28 days of hospitalisation. In this case, early ECLS, nebulised antioxidant and antidote were available to treat potentially fatal pulmonary oedema after exposure to nitric and hydrofluoric acid fumes.

    Title Effects of Atmospheric Temperature and Humidity on Outbreak of Diseases.
    Date February 2008
    Journal Emergency Medicine Australasia : Ema
    Excerpt

    OBJECTIVE: The present study aimed to determine the plausibility of forecasting the outbreak of diseases based on the weather by analysing the impact of atmospheric temperature and humidity on the occurrence of different diseases. METHODS: The subjects of the present study were the 30,434 patients who visited the ED in 1 year from 1 February 2005 to 3 February 2006. The present study analysed the correlation between the daily number of patients who suffered from 22 types of traumatic and non-traumatic diseases and the data on atmospheric temperature and humidity provided by the Korea Meteorological Administration. RESULTS: With traumatic disease, the occurrence tended to increase in proportion to the rise in temperature and humidity; whereas with non-traumatic disease, the occurrence tended to increase according to the rise in temperature, irrespective of humidity changes. The research on the impact of atmospheric temperature and humidity on different diseases revealed a high level of distribution of most diseases in an environment with high temperature and humidity. However, in the case of pulmonary diseases and trauma to multiple body regions, the occurrence increased in environments with low temperature and high humidity for pulmonary diseases, and with low temperature and low humidity for trauma to multiple body regions. CONCLUSION: Most diseases tend to increase in proportion to the rise in atmospheric temperature whereas being less affected by humidity. However, an increase in humidity in an optimum range of atmospheric temperature (12 degrees C or higher) triggers an increase in the occurrence of diseases.

    Title Effect of Follicle Stimulation Hormone and Luteinizing Hormone on Cumulus Cell Expansion and in Vitro Nuclear Maturation of Canine Oocytes.
    Date January 2008
    Journal Reproduction in Domestic Animals = Zuchthygiene
    Excerpt

    In general, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) play important roles in the regulation of cumulus cell expansion and oocyte maturation. We investigated the effects of supplementation of FSH or LH in in vitro maturation (IVM) medium on the incidence of cumulus cell expansion and nuclear maturation in canine oocytes. Cumulus-oocyte complexes (COCs) were cultured in TCM-199 supplemented with 10% foetal bovine serum (FBS), 1 mg/ml cysteine, 0.2 mm pyruvic acid and different concentrations of FSH or LH (control, 0.5, 5 or 50 microg/ml) at 38.5 degrees C, 5% CO(2) in air for 72 h. The cumulus cell expansion was measured by microscopic visualization, and nuclear maturation of denuded oocytes was determined by staining with 10 microg/ml Hoechst33342 for 30 min. The cumulus cell expansion in the 5 microg/ml FSH group (397.2 +/- 64.3 microm) was significantly higher than those in the control, 0.5, and 50 microg/ml FSH groups (168.3 +/- 19.1, 286.0 +/- 69.7 and 300.0 +/- 84.3 microm, respectively; p < 0.05). However, there was no difference in cumulus cell expansion among the control, 0.5, 5 and 50 microg/ml LH groups (165.6 +/- 20.2, 160 +/- 26.5, 172 +/- 20.5 and 168 +/- 23.1 microm, respectively; p > 0.05). After 72 h of IVM, the proportion of nuclear development to the MI-MII stage in the 0.5 microg/ml FSH group (15.1%) was higher than those in the control, 0.5 and 50 microg/ml FSH groups (0.9%, 6.5% and 8.0%, respectively; p < 0.05). However, there was no significant difference in nuclear maturation to the MI-MII stage among control, 0.5, 5 and 50 microg/ml LH groups (4.6%, 2.3%, 5.4% and 8.6%, respectively; p > 0.05). This study indicated that a FSH supplement in IVM medium can increase cumulus cell expansion and nuclear maturation, while the nuclear maturation rate remained low. Further studies are required to improve the nuclear development to the MI-MII stages in canine oocytes.

    Title Photolithographic Fabrication of Poly(ethylene Glycol) Microstructures for Hydrogel-based Microreactors and Spatially Addressed Microarrays.
    Date January 2008
    Journal Journal of Microbiology and Biotechnology
    Excerpt

    We describe the fabrication of poly(ethylene glycol) diacrylate (PEG-DA) hydrogel microstructures with a high aspect ratio and the use of hydrogel microstructures containing the enzyme beta-galactosidase (beta-Gal) or glucose oxidase (GOx)/horseradish peroxidase (HRP) as biosensing components for the simultaneous detection of multiple analytes. The diameters of the hydrogel microstructures were almost the same at the top and at the bottom, indicating that no differential curing occurred through the thickness of the hydrogel microstructure. Using the hydrogel microstructures as microreactors, beta-Gal or GOx/HRP was trapped in the hydrogel array, and the time-dependent fluorescence intensities of the hydrogel array were investigated to determine the dynamic uptake of substrates into the PEG-DA hydrogel. The time required to reach steady-state fluorescence by glucose diffusing into the hydrogel and its enzymatic reactions with GOx and HRP was half the time required for resorufin beta-D-galactopyranoside (RGB) when used as the substrate for beta-Gal. Spatially addressed hydrogel microarrays containing different enzymes were micropatterned for the simultaneous detection of multiple analytes, and glucose and RGB solutions were incubated as substrates. These results indicate that there was no cross-talk between the beta-Gal-immobilizing hydrogel micropatches and the GOx/HRP-immobilizing micropatches.

    Title Induction of Apoptosis by the Licochalcone E in Endothelial Cells Via Modulation of Nf-kappab and Bcl-2 Family.
    Date January 2008
    Journal Biological & Pharmaceutical Bulletin
    Excerpt

    Licochalcones have a variety of biological properties including anti-tumor, anti-parasitic and anti-bacterial activities. Recently, a new retrochalcone (licochalcone E, Lico-E) was isolated from the roots of Glycyrrhiza inflata (Chem. Pharm. Bull., 53, 2005, Yoon et al.) by cytotoxicity-guided fractionation. This study examined whether or not Lico-E-induced endothelial cell death occurs through apoptosis, and investigated molecular mechanisms involved in this process. Lico-E was found to suppress ECV304 cell growth and induce apoptosis. The induction of apoptosis by Lico-E was confirmed by the ladder-patterned DNA fragmentation, the presence of cleaved and condensed nuclear chromatin and the increased number of annexin V-positive cells. Lico-E could effectively inhibit the constitutive NF-kappaB activation, as revealed by the electrophoretic mobility shift assay and NF-kappaB-dependent luciferase reporter study. In addition, the Lico-E treatment caused a change in the Bax/Bcl-2 ratio that favored apoptosis. These results suggest that Lico-E induces endothelial cell apoptosis by modulating NF-kappaB and the Bcl-2 family.

    Title Relationship of Thyroid Stimulating Hormone with Coronary Atherosclerosis in Angina Patients.
    Date December 2007
    Journal International Journal of Cardiology
    Excerpt

    BACKGROUND: In the previous recent reports, subclinical hypothyroidism is an independent risk factor for acute myocardial infarction in elderly women. It was not established whether a normal range of thyroid stimulating hormone (TSH) influences the presence of coronary atherosclerosis. We postulated that the level of TSH is risk factor of coronary atherosclerosis in angina patients who have normal thyroid function. METHODS: We studied 344 angina patients (62.5+/-9.72 years, male 50%) who underwent elective coronary angiography. TSH, free thyroxine, serum lipid levels and high-sensitivity C-reactive protein levels were measured and compared to the severity of coronary artery disease. RESULTS: In patients with high level of TSH (> or =2.1 microIU/mL), age (p=0.016), the levels of serum creatinine (p=0.004) and Gensini's score (p=0.016) were significantly higher than those in patients with low TSH levels. The incidence of multi-vessel disease was higher in patients with high TSH level (p=0.026). TSH level showed a significant correlation with age (r=0.109, p=0.044) and Gensini's score (r=0.117, p=0.045). The multivariate analysis revealed that age (OR 2.39, p=0.001), diabetes (OR 3.74, p=0.001), creatinine (OR 2.06, p=0.008), and smoking (OR 1.85, p=0.045) were independent predictors for significant coronary artery disease, but TSH level did not predict coronary artery stenosis. CONCLUSIONS: Although the high level of serum TSH is associated with multi-vessel disease, it was not the determinant of coronary artery disease in patients with normal range of thyroid function.

    Title A Liquid Chromatographic Method for the Determination of Histamine in Immunoglobulin Preparation Using Solid Phase Extraction and Pre-column Derivatization.
    Date December 2007
    Journal Archives of Pharmacal Research
    Excerpt

    An immunoglobulin (IgG) preparation with micro-amount of histamine fixed on the active protein fraction has been used to increase the resistance to allergic reactions. However, excessive histamine may cause hypo- or hypertension, headache, or anaphylactic shock and so the histamine content of the drug is strictly controlled by a regulation: 0.15 microg of histamine dihydrochloride is allowed for 12 mg of immunoglobulin. In this study, a liquid chromatographic method to determine micro-amount of histamine in the pharmaceutical was developed and validated. This method include a sample cleanup by a solid phase extraction (SPE) using a polystyrene-divinyl benzene (PS-DVB) polymeric sorbent and high-performance liquid chromatography after precolumn fluorescent labeling of the histamine with o-phthaldialdehyde. The drug sample was loaded to the SPE cartridge after adjusting to pH 9.5. After successive washings of the cartridge with water and 30% aqueous methanol, histamine was then eluted with 100 mM sodium acetate (pH 9.5)-methanol (20:80, v/v). An aliquot from the eluate was labeled with o-phthaldialdehyde-mercaptoethanol (OPA-ME) for fluorescence detection at the excitation maximum of 340 nm and emission maximum of 450 nm. HPLC analysis was performed on a phenyl-hexyl column with an acetonitrile-phosphate buffer (pH 6.8; 50 microM) (35:65, v/v) as the mobile phase. The retention times of histamine and 3-methylhistamine (IS) were approximately 7.2 and 9.5 min, respectively. The quantitation range was between 0.01-0.2 mg/mL of histamine showing good linearity (r=0.9996). This analytical method would provide a potential mean for the strict control of histamine content in the pharmaceutical product.

    Title Comparison of Polymerase Chain Reaction and the Indirect Particle Agglutination Antibody Test for the Diagnosis of Mycoplasma Pneumoniae Pneumonia in Children During Two Outbreaks.
    Date November 2007
    Journal The Pediatric Infectious Disease Journal
    Excerpt

    BACKGROUND: Diagnosis of Mycoplasma pneumoniae pneumonia is challenging because of the lack of standardized rapid tests. Many serologic tests and polymerase chain reaction (PCR) based methods are used with different diagnostic criteria. METHODS: This retrospective study was conducted to compare the diagnostic values of the indirect particle agglutination test and nested PCR of nasopharyngeal aspirates for the diagnosis of M. pneumoniae pneumonia in children. These assays were evaluated in 234 hospitalized children with community-acquired lower respiratory tract infections during 2 outbreaks of M. pneumoniae pneumonia in 2000 and 2003. RESULTS: The cumulative PCR positive rate was 26.7% in patients with maximum antibody titers of < or =1:320 and 78.2% in those with titers of > or =1:640. Based on these data, a positive PCR, a 4-fold increase in antibody titer, or a single titer > or =1:640 were considered to indicate acute M. pneumoniae infection. Overall, 152 children were diagnosed to have M. pneumoniae pneumonia; 27 (18%) by serology only, 26 (17%) by PCR only, and 99 (65%) by both methods. Children who were diagnosed by PCR only were significantly younger (P = 0.003) and were more often immunocompromised (P = 0.019) than those that were PCR negative. Duration of cough before PCR diagnosis was shorter in cases diagnosed by PCR only than those that were PCR negative (P = 0.045). CONCLUSIONS: In conclusion, during the 2 outbreaks of M. pneumoniae infection, we found that the PCR test may be useful for the rapid diagnosis of M. pneumoniae pneumonia, particularly in young children and in immunocompromised patients and in early stage disease.

    Title Determination of Eperisone in Human Plasma by Liquid Chromatography-esi-tandem Mass Spectrometry.
    Date November 2007
    Journal Archives of Pharmacal Research
    Excerpt

    A sensitive and selective method for the determination of 4'-ethyl-3-methyl-3-piperidinopropiophenone hydrochloride (eperisone hydrochloride) in human plasma was developed and validated. The procedure employed an internal standard and a solvent extraction step followed by chromatography on a Xterra C18 minibore column. Detection was by electrospray ionization tandem mass spectrometry with multiple reaction monitoring. The mass transitions of eperisone and tolperisone (IS) were m/z 260 --> 98 and m/z 246 --> 98, respectively. The method has a limit of detection of 0.1 pg/mL for eperisone based on the three times signal-to-noise value with a linear range from 0.01 to 10.0 ng/mL for the analyte. Extraction recovery was on average 98.6 +/- 7.2% (SD) for eperisone. The Intra- and inter-day assay accuracy ranged from 93 to 114% and precision (RSD) was better than 8.5%. The method was successfully employed to analyze plasma samples and evaluate pharmacokinetics of eperisone in healthy male volunteers.

    Title Arterial Minus End-tidal Co2 As a Prognostic Factor of Hospital Survival in Patients Resuscitated from Cardiac Arrest.
    Date November 2007
    Journal Resuscitation
    Excerpt

    The purpose of this study was to determine the clinical value of arterial minus end-tidal CO(2) [P(a-et)CO(2)] and alveolar dead space ventilation ratio (V(dA)/V(t)) as indicators of hospital mortality in patients that have been resuscitated from cardiac arrest at emergency department.

    Title Reproductive Fertility of Cloned Male Cats Derived from Adult Somatic Cell Nuclear Transfer.
    Date October 2007
    Journal Cloning and Stem Cells
    Excerpt

    This study was designed to investigate the reproductive fertility by the natural breeding of cloned male cats with domestic female cats, and to measure endocrine hormone concentration related to male reproduction such as testosterone, leutinizing hormone (LH), and follicle stimulating hormone (FSH). Cloned A, B, C, and D cats produced three, two, four, and five kittens after natural mating with four domestic female cats, respectively, despite later puberty of the cloned D cat than those of the other cloned male cats. Three of the 14 kittens expressed an odd eye color, which was produced by 1 and 2 from cloned A and B cats. The eye color of the other F1 kittens varied from nine brown to two blue. Body weight at birth ranged from 72.9 to 134.0 g. Although clone D had a poorer libido and entered puberty later than those of the other cloned male cats, he produced gonadal hormones within the average range. Four of the cloned male cats had normal fertility. The concentration of gonadal hormones in cloned male cats was similar to two control and donor cats. The concentration of testosterone was not significantly different among clones A, B, C, D, and control cats (5.99 +/- 5.68; 3.46 +/- 2.81; 6.41 +/- 2.17; 3.75 +/- 0.34; 4.0 +/- 3.63 ng/mL, p < 0.05). The concentrations of LH and FSH were not significantly different among the cloned cats (p < 0.05). Seven male and seven female (in total 14) kittens were produced by the natural breeding with four domestic female cats. These results indicated that cloned male cats have normal reproductive fertility and lie within the normal range of gonadal hormone production. All F1 kittens were produced by natural breeding and delivery, and are still alive and have normal growth health (27 months age).

    Title Central Venous Blood Oxygen Saturation Monitoring in Patients with Chronic Pulmonary Arterial Hypertension Treated with Continuous Iv Epoprostenol: Correlation with Measurements of Hemodynamics and Plasma Brain Natriuretic Peptide Levels.
    Date October 2007
    Journal Chest
    Excerpt

    BACKGROUND: IV epoprostenol is a highly effective therapy for pulmonary arterial hypertension (PAH). However, monitoring the efficacy and adjusting the dose of epoprostenol often requires serial invasive hemodynamic measurements. This study investigated whether superior vena cava (SVC) oxygen saturation measured from the indwelling catheter and brain natriuretic peptide (BNP) level would predict right heart catheterization markers associated with lower survival rates (right atrial pressure [RAP], > 10 mm Hg; pulmonary artery [PA] oxygen saturation, < 62%) in epoprostenol-treated patients with PAH. METHODS: Twenty-seven epoprostenol-treated PAH patients had a BNP level and SVC oxygen saturation measured from their indwelling central venous catheters. The results were compared with cardiac catheterization results. RESULTS: SVC oxygen saturation and BNP level both showed significant correlation with hemodynamic variables. BNP level correlated best with RAP (r = 0.66; p < 0.001), while SVC oxygen saturation correlated most closely with PA oxygen saturation (r = 0.91; p < 0.001). All patients with a BNP level of >or= 117 pg/mL had an elevated RAP (specificity, 100% [defined as a RAP of > 10 mm Hg]), but sensitivity was only 65%. An SVC oxygen saturation of < 64% showed a sensitivity of 89% and a specificity of 78% in predicting a PA oxygen saturation of < 62%. CONCLUSIONS: SVC oxygen saturation and BNP level predict hemodynamics associated with lower survival rates and may be useful as "noninvasive" markers of prognosis in epoprostenol-treated PAH patients. BNP levels have a lower sensitivity relative to specificity, and a normal BNP level did not exclude a high RAP or low PA oxygen saturation.

    Title Alteration of Iron Regulatory Proteins (irp1 and Irp2) and Ferritin in the Brains of Scrapie-infected Mice.
    Date October 2007
    Journal Neuroscience Letters
    Excerpt

    Considerable evidence suggests that oxidative stress may be involved in the pathogenesis of Transmissible Spongiform Encephalopathies (TSEs). To investigate the involvement of iron metabolism in TSEs, we examined the expression levels of iron regulatory proteins (IRPs), ferritins, and binding activities of IRPs to iron-responsive element (IRE) in scrapie-infected mice. We found that the IRPs-IRE-binding activities and ferritins were increased in the astrocytes of hippocampus and cerebral cortex in the brains of scrapie-infected mice. These results suggest that alteration of iron metabolism contributes to development of neurodegeneration and that some protective mechanisms against iron-induced oxidative damage may occur during the pathogenesis of TSEs.

    Title Chronic Atrial Fibrillation Associated with Somatic Mitochondrial Dna Mutations in Human Atrial Tissue.
    Date September 2007
    Journal Journal of Clinical Pathology
    Title Reversine Stimulates Adipocyte Differentiation and Downregulates Akt and P70(s6k) Signaling Pathways in 3t3-l1 Cells.
    Date July 2007
    Journal Biochemical and Biophysical Research Communications
    Excerpt

    In this study, we investigate the ability of reversine to stimulate adipocyte differentiation and its effect on cellular signaling pathways associated with adipocyte differentiation. Our data show that reversine treatment of 3T3-L1 cells under differentiation conditions synergistically enhances adipocyte differentiation and the expression of adipogenic marker genes such as aP2, PPAR-gamma, resistin, C/EBPalpha, and adiponectin. In parallel, reversine treatment leads to a selective downregulation of Akt and p70(s6k) signaling pathways, but not the ERK pathway. Furthermore, reversine stimulation of adipocyte differentiation seems to be quite different from troglitazone's action, because reversine treatment does not induce the transcriptional activation of PPAR-gamma and troglitazone does not affect the Akt and p70(s6k) signaling pathways. Taken together, our data clearly demonstrate the ability of reversine to stimulate adipocyte differentiation, which is independent of the Akt and p70(s6k) signaling pathways.

    Title The Diagnosis of Diabetes Mellitus in Korea: a Pooled Analysis of Four Community-based Cohort Studies.
    Date June 2007
    Journal Diabetic Medicine : a Journal of the British Diabetic Association
    Title Effects of Extracellular Potassium Concentrations on Acrosome Reaction and Polyspermy During in Vitro Fertilization and Subsequent Development in Vitro in the Pig.
    Date June 2007
    Journal Theriogenology
    Excerpt

    Potassium (K(+)) concentration in the mammalian oviduct and uterus is particularly interesting due to its unusually high concentration (12 to 25 mM) compared with that in the blood stream (3 to 6 mM). In this study we examined the effects of various K(+) concentrations in the fertilization medium on polyspermy and subsequent in vitro development of porcine oocytes. In the absence of K(+) in the fertilization medium, sperm penetration was not observed. The incidence of polyspermy was significantly higher in the fertilization medium that contained 6 or 12 mM K(+) as compared with 3 mM K(+). The mean number of sperm penetrated in oocytes in medium with 6 and 12 mM K(+) was higher than in medium with 3 mM K(+). The addition of 3, 6 or 12 mM K(+) to the fertilization medium did not significantly affect the proportion of zygotes that developed to the blastocyst stage (14.1, 12.4 and 15.0%, respectively). Chlorotetracycline (CTC) analysis was used to determine the capacitation and acrosome reaction of spermatozoa incubated for 3 h with various concentrations of K(+). The number of acrosome reacted spermatozoa decreased with increasing K(+) concentration. These results suggest that extracellular K(+) in the fertilization medium affects sperm acrosome reaction which may be related to the sperm penetration.

    Title Comparison of in Vitro Development and Gene Expression of in Vivo- and Ivm/ivf-derived Porcine Embryos After Microinjection of Foreign Dna.
    Date June 2007
    Journal Theriogenology
    Excerpt

    We compared the developmental ability and gene expression of in vivo- and IVM/IVF-derived porcine embryos following microinjection with SV40-LacZ. A total of 412 IVM/IVF-derived and 129 in vivo-collected zygotes was used to examine developmental ability and gene expression following DNA microinjection. When either DNA injected or noninjected zygotes were cultured for 4 d in NCSU 23 followed by 5 d in Eagle's minimal essential medium (EMEM), the percentages of zygotes developing to blastocysts and hatched blastocysts were higher (P < 0.05) compared with groups cultured in NCSU 23 alone. The percentages of injected embryos reaching the morula and blastocyst stages were significantly lower (P < 0.05) than that of noninjected control embryos whether in vivo or IVM/IVF derived. The percentages of morula and blastocyst stage embryos expressing the gene were higher in the in vivo-derived embryos than in IVM/IVF-derived embryos. A lower proportion of (67 to 77%) mosaicism was observed in the in vivo-derived embryos than in IVM/IVF (90 to 100%) derived embryos. The total cell number of blastocysts cultured in both NCSU 23 and EMEM media was significantly higher than that of blastocysts cultured continuously in NCSU 23. Our results suggest that this dual culture system enhanced embryo viability following microinjection of foreign DNA.

    Title Design of Multimedia Telemedicine System for Inter-hospital Consultation.
    Date June 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

    The telemedicine systems for the decision of patient transfer, and the direction of patient treatment through remote consultation are necessarily required for better patient care in emergency situation. In this paper, the prototype emergency telemedicine system has been designed and implemented. The unified integration of multimedia components, including full-quality video, vital sign signals, radiological images and video conferencing in a single computer, provides an efficient means to investigate the accurate status of emergency patient at the remote location. The software implementation of needed functionality without any externally attached hardware CODEC units enables the compact design with low cost, and ease of operation at the emergency room. Experimental tests at the local networks analyze the technical aspects of implemented systems, and optimize the parameters subjectively to run telemedicine systems with affordable error. Inter-hospital experiments demonstrate the possibility to be effectively used at emergency situation.

    Title Echocardiographic Epicardial Fat Thickness and Coronary Artery Disease.
    Date June 2007
    Journal Circulation Journal : Official Journal of the Japanese Circulation Society
    Excerpt

    BACKGROUND: The association between epicardial fat and coronary artery disease has not been evaluated. The objective of the present study was to evaluate the relationship of echocardiographic epicardial fat to the presence and severity of coronary artery disease in a clinical setting. METHODS AND RESULTS: Two hundred and three consecutive patients who underwent echocardiography and diagnostic coronary angiography were studied. The epicardial fat thickness on the free wall of the right ventricle was measured at end-diastole from the parasternal long-axis views of 3 cardiac cycles. Coronary angiograms were analyzed for the extent and severity of coronary artery disease using Gensini's score. The patients were divided into 2 groups according to the fourth quartile of epicardial fat thickness (Group I <7.6 mm; Group II > or =7.6 mm). There were no significant differences in the baseline characteristics except for waist circumference (p=0.023). Significant correlations were demonstrated between epicardial fat thickness and age (r=0.332, p<0.001), C-reactive protein (r=0.182, p=0.009), body mass index (r=0.142, p=0.044) and waist circumference (r=0.229, p=0.001). The patients with a higher epicardial fat thickness were associated with a high Gensini's score (p=0.014). Multivariate analysis showed that age (odds ratio (OR) 5.29, p=0.003), epicardial fat thickness (OR 10.53, p=0.004), diabetes (OR 8.06, p=0.006) and smoking (OR 14.65, p=0.015) were independent factors affecting significant coronary artery stenosis. CONCLUSIONS: Epicardial fat thickness was significantly correlated with the severity of coronary artery disease in patients with known coronary artery disease.

    Title A Case of Malignant Otitis Externa Caused by Candida Glabrata in a Patient Receiving Haemodialysis.
    Date May 2007
    Journal Scandinavian Journal of Infectious Diseases
    Excerpt

    A 74-y-old male receiving haemodialysis presented with right-sided otalgia, otorrhoea and diffuse swelling on the right external auditory canal. Following an initial successful treatment with prolonged intravenous antibiotics, the patient relapsed with a secondary infection in the same site due to Candida glabrata. We report an unusual case of malignant otitis externa caused by the fungus C. glabrata.

    Title Chronic Thromboembolic Pulmonary Hypertension.
    Date May 2007
    Journal Clinics in Chest Medicine
    Excerpt

    The description of organized thrombus in major pulmonary arteries can be found in autopsy reports dating back to the late nineteenth and early twentieth centuries. Not until the 1950s was the antemortem diagnosis and clinical syndrome of chronic thrombotic obstruction of the major pulmonary arteries better characterized. The first surgical attempt to remove the adherent thrombus from the vessel wall occurred in 1958. This operation provided the conceptual foundation for the distinction between acute and chronic thromboembolic disease of the pulmonary vascular bed, and established that an endarterectomy, and not an embolectomy, would be necessary if a surgical remedy for this disease was to be successful.

    Title A Specific and Rapid Hplc Assay for the Determination of Cefroxadine in Human Plasma and Its Application to Pharmacokinetic Study in Korean.
    Date March 2007
    Journal Journal of Pharmaceutical and Biomedical Analysis
    Excerpt

    A specific and rapid high performance liquid chromatographic (HPLC) method with UV detection (254 nm) was developed for the determination of cefroxadine in human plasma. The sample extraction was performed by a simple procedure, vortexing and centrifugation of sample following addition of 60% trichloroacetic acid. Cephalexin was used as an internal standard (I.S.). The HPLC analysis was carried out on a Capcell Pak C18 analytical column with a mobile phase of 50 mM ammonium formate buffer/pH 3.5 and acetonitrile (90:10, v/v). No interference was observed near the peaks of cefroxadine and I.S. The calibration curve was linear over the range of 0.5-40 microg/mL and the lower limit of quantification (LLOQ) was 0.5 microg/mL. The method was validated with excellent sensitivity, accuracy, precision and stability. This assay was successfully applied to determine the pharmacokinetic parameters of cefroxadine in Korean healthy volunteers after an oral administration of two 250 mg cefroxadine capsules. As a result, the plasma half-life was 1.00+/-0.26 h and the mean AUC(0-6 h) was 46.25+/-6.41microgh/mL. The maximum plasma concentration (C(max)) of 17.62+/-4.87 microg/mL reached 1.44+/-0.39 h after administration.

    Title Serum Adiponectin, Interleukin-10 Levels and Inflammatory Markers in the Metabolic Syndrome.
    Date March 2007
    Journal Diabetes Research and Clinical Practice
    Excerpt

    We examined the association between interleukin-10 (IL-10), adiponectin levels and inflammatory markers such as interleukin-6 (IL-6) and high-sensitive C-reactive protein (hsCRP). Furthermore, the association of these anti-/pro-inflammatory cytokine levels with the metabolic syndrome was investigated. The study subjects were composed of 312 Korean individuals without diabetes. Serum adiponectin level was associated with hsCRP (r=-0.21, P<0.001), IL-6 (r=-0.13, P<0.05) and IL-10 (r=-0.22, P<0.001) levels. Subjects without the metabolic syndrome showed higher adiponectin (17.03 microg/ml versus 13.85 microg/ml, P<0.001) and IL-10 (4.74 pg/ml versus 4.34 pg/ml, P=0.014) levels, and lower serum hsCRP (0.38 microg/ml versus 0.66 microg/ml, P=0.001) and IL-6 (0.94 pg/ml versus 1.32 pg/ml, P=0.009) levels compared to those with the metabolic syndrome. In multiple logistic regression analysis, the metabolic syndrome was associated with sex, age, waist circumference, systolic blood pressure, HDL cholesterol, triglyceride, fasting blood glucose and interleukin-10. Furthermore, serum adiponectin levels are associated with serum hsCRP, IL-6 and IL-10 levels. These results suggest that adiponectin might be associated with the metabolic syndrome through regulation of pro-/anti-inflammatory cytokines.

    Title Abnormally Sialylated Fibrinogen Gamma-chains in a Patient with Chronic Thromboembolic Pulmonary Hypertension.
    Date March 2007
    Journal Thrombosis Research
    Title A Wnt-axin2-gsk3beta Cascade Regulates Snail1 Activity in Breast Cancer Cells.
    Date January 2007
    Journal Nature Cell Biology
    Excerpt

    Accumulating evidence indicates that hyperactive Wnt signalling occurs in association with the development and progression of human breast cancer. As a consequence of engaging the canonical Wnt pathway, a beta-catenin-T-cell factor (TCF) transcriptional complex is generated, which has been postulated to trigger the epithelial-mesenchymal transition (EMT) that characterizes the tissue-invasive phenotype. However, the molecular mechanisms by which the beta-catenin-TCF complex induces EMT-like programmes remain undefined. Here, we demonstrate that canonical Wnt signalling engages tumour cell dedifferentiation and tissue-invasive activity through an Axin2-dependent pathway that stabilizes the Snail1 zinc-transcription factor, a key regulator of normal and neoplastic EMT programmes. Axin2 regulates EMT by acting as a nucleocytoplasmic chaperone for GSK3beta, the dominant kinase responsible for controlling Snail1 protein turnover and activity. As dysregulated Wnt signalling marks a diverse array of cancerous tissue types, the identification of a beta-catenin-TCF-regulated Axin2-GSK3beta-Snail1 axis provides new mechanistic insights into cancer-associated EMT programmes.

    Title The Application of a Digital Solution for Completing Emr Consent.
    Date December 2006
    Journal Studies in Health Technology and Informatics
    Excerpt

    There are several crucial obstacles to change such as user resistance and the time it takes to type data. So there is a significant need for an easy and user-friendly migration tool toward EMR. The purpose of this study was to develop a digital pen solution to support electronic medical recording. A digital pen is not only good for saving images quickly but also useful in digitalizing text by applying a text recognition engine. Therefore, we expect the digital pen solution to be the most helpful and easiest migration tool in the successful adaptation of EMR.

    Title Clinical Significance of Aortic Knob Width and Calcification in Unstable Angina.
    Date November 2006
    Journal Circulation Journal : Official Journal of the Japanese Circulation Society
    Excerpt

    Chest radiography is a routine examination evaluating those patients with chest pain. There are few data about the correlation between aortic knob width, calcification and coronary atherosclerosis.

    Title [a Case of Idiopathic Colitis Developed After Barium Enema].
    Date October 2006
    Journal The Korean Journal of Gastroenterology = Taehan Sohwagi Hakhoe Chi
    Excerpt

    It has been reported that colitis may be associated with intrarectally administered drugs or chemicals. Colonotoxicity may results from conventional medical therapy, herbal or other illicit drugs, contrast materials, and detergents. Clues that a colitis may be due to an intrarectally administered agent include perianal excoriation, segmental distal colitis due to a concentration gradient from enema administration, and recent diagnostic or therapeutic administration of high risk solutions such as hypertonic contrast agents or detergent enemas. Barium is a highly viscous contrast agent that is insoluble in water. Barium enemas are usually very safe. Also, no case report of barium-induced chemical colitis has been reported yet. We report a case of chemical colitis with colonic stricture occurring after the barium enema for diagnostic purpose.

    Title [the Role of Smoking As a Risk Factor in Inflammatory Bowel Diseases: Single Center Study in Korea].
    Date October 2006
    Journal The Korean Journal of Gastroenterology = Taehan Sohwagi Hakhoe Chi
    Excerpt

    Cigarette smoking is the most significant environmental factor identified in inflammatory bowel disease (IBD). Smoking has a beneficial effect on ulcerative colitis (UC) patients. In contrast, Crohn's disease (CD) is associated with smoking, and a detrimental effect of smoking on the course of CD has been demonstrated. The aim of this study was to explore the prevalence in smoking in CD and UC at the time of diagnosis compared with the general population in a single center study.

    Title [a Case of Stump Malt Lymphoma After Partial Gastrectomy]
    Date October 2006
    Journal The Korean Journal of Gastroenterology = Taehan Sohwagi Hakhoe Chi
    Excerpt

    Gastrectomy is known to be a risk factor for adenocarcinoma in remnant stomach. It is suggested that reflux of bile juice or duodenal secretion to remnant stomach induces atrophic gastritis, intestinal metaplasia, and gastric adenocarcinoma. Malignant lymphoma in remnant stomach after gastrectomy is very rare. Only about thirty cases are reported in the world, and there is no case report in Korea. Gastric MALT (mucosa-associated lymphoid tissue) lymphoma is associated with Helicobacter pylori infection but the mechanism of lymphoma development in remnant stomach is still unknown. We report a case of low grade gastric MALT lymphoma of gastric stump after 10 years from partial gastrectomy.

    Title Anti-inflammatory Effect of Jeongshintang Through Suppression of P38 Activation in Human Astrocytoma, U373mg Cells.
    Date September 2006
    Journal Experimental and Molecular Pathology
    Excerpt

    Jeongshintang (JST) is a Korean herbal prescription, which has been successfully used for cerebral diseases. However, the anti-inflammatory effect of JST on Alzheimer's disease (AD) is still not fully understood. In this study, we investigated the effects of JST in attenuating the inflammatory response induced by interleukin (IL)-1beta plus beta-amyloid [1-42] fragment (A beta) in the human astrocyte cell line, U373MG. The production of IL-6, IL-8, and prostaglandin (PG)E2 was significantly increased by IL-1beta plus A beta (1-42) in a time-dependent manner (P < 0.05). JST significantly inhibited the IL-1beta plus A beta (1-42)-induced IL-6, IL-8, and PGE2 production at 24 h (P < 0.05). Maximal inhibition rate of IL-6, IL-8, and PGE2 production by JST was about 54.40%, 56.01%, and 44.06% respectively. JST (0.01-1 mg/ml) also attenuated the expression of cyclooxygenase (COX)-2 and activation of p38 MAPK induced by IL-1beta and A beta (1-42). These results demonstrated that JST has an anti-inflammatory effect, which might explain its beneficial effect in the treatment of various neurodegenerative diseases such as AD.

    Title An Increased Monocyte Count Predicts Coronary Artery Spasm in Patients with Resting Chest Pain and Insignificant Coronary Artery Stenosis.
    Date September 2006
    Journal The Korean Journal of Internal Medicine
    Excerpt

    Coronary atherosclerosis with inflammation gives rise to coronary vasospasm in the patients with coronary vasospastic angina. We have postulated that the peripheral leukocyte count and the differential count are associated with vasospastic angina.

    Title [saccharomyces Boulardii Activates Expression of Peroxisome Proliferator-activated Receptor-gamma in Ht-29 Cells].
    Date September 2006
    Journal The Korean Journal of Gastroenterology = Taehan Sohwagi Hakhoe Chi
    Excerpt

    Saccharomyces boulardii (S. boulardii) has been reported to be beneficial in the treatment of inflammatory bowel disease, however, little is known about its mechanism of action. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is recently found to regulate inflammation in intestinal epithelial cells. We hypothesized that the anti-inflammatory effects of S. boulardii are mediated, in part, through PPAR-gamma. To test this hypothesis, we examined the ability of S. boulardii to modulate the expression of PPAR-gamma in human colon cells.

    Title Association of Sporadic Creutzfeldt-jakob Disease with Homozygous Genotypes at Prnp Codons 129 and 219 in the Korean Population.
    Date August 2006
    Journal Neurogenetics
    Excerpt

    Human prion protein gene (PRNP) is considered an important gene in determining the incidence of human transmissible spongiform encephalopathies or prion diseases. Polymorphisms of PRNP at codon 129 in Europeans and codon 219 in Japanese may play an important role in the susceptibility to sporadic Creutzfeldt-Jakob disease (CJD); data regarding codon 129 in the Japanese population have led to divergent interpretations. In order to determine which, if any, of the PRNP genotypes in Korean people are associated with sporadic CJD, we examined the genotype and allelic distributions of human PRNP polymorphisms in 150 patients with sporadic CJD. All Korean sporadic CJD patients were Met/Met at codon 129, Glu/Glu at codon 219 and undeleted at the octarepeat region of PRNP. Our study showed significant differences in genotype frequency of PRNP at codon 129 (chi 2=8.8998, P=0.0117) or 219 (chi 2=12.6945, P=0.0004) between sporadic CJD and normal controls. Furthermore, the genotype frequency of the heterozygotes for codons 129 and/or 219 showed a significant difference between the normal population and sporadic CJD patients (chi 2=21.0780, P<0.0001).

    Title Annealing Control Primer System Identifies Differentially Expressed Genes in Blastocyst-stage Porcine Parthenotes.
    Date August 2006
    Journal Zygote (cambridge, England)
    Excerpt

    There is very little information available on stage-specific gene expression during early embryo development, particularly in the pig. Here, we accurately identified the genes that are specifically or prominently expressed in parthenogenetic porcine blastocysts as compared with 2-cell stage embryos. We accomplished this by using a PCR technology regulated by annealing control primers (ACPs). By utilizing 120 ACPs, a total of 46 expressed sequence tags (ESTs) of genes that are differentially expressed in blastocysts as compared with 2-cell stage embryos were cloned and sequenced. The cloned genes or ESTs all exhibited significant sequence similarity with known genes or ESTs of other species. Of the known genes, six genes [renin-binding protein (RNBP), BMDP, solute carrier family 25 (SLC25A6), MTHFD1, TRK-fused gene (TFG), spermidine synthase (SRM)] were selected and their stage-specific expression levels in porcine parthenotes were determined by real-time quantitative polymerase chain reaction at the 1-, 2-, 4-cell, morula and blastocyst stages. While RNBP, BMDP, SLC25A6, MTGFD1 and SRM were highly expressed only at the blastocyst stage, TFG was highly expressed at the 1-cell stage, then declined after genomic activation, high levels of expression being again detected at the morula and blastocyst stages. This analysis suggests that the ACP system is an effective tool for use in the identification of stage-specific genes in small numbers of porcine parthenotes. Examination of the genes differentially expressed in the blastocyst, which we have identified here, will provide insight into the molecular basis of preimplantation development.

    Title Effects of Green Tea Consumption on Inflammation, Insulin Resistance and Pulse Wave Velocity in Type 2 Diabetes Patients.
    Date July 2006
    Journal Diabetes Research and Clinical Practice
    Excerpt

    In this study, we examined the effects of green tea on inflammation and arterial stiffness in type 2 diabetes patients. As results, inflammatory markers, such as hsCRP and IL-6, were unchanged after green tea consumption, and neither were blood glucose, lipid profiles, insulin resistance, or serum adiponectin levels. Furthermore, tea consumption did not improve baPWV. These results suggest that the above-described mechanisms are unlikely to explain the cardiovascular risk reduction by tea consumption observed in epidemiological studies.

    Title The Effect of Insulin Resistance on Prognosis of Non-diabetic Patients Who Underwent Percutaneous Coronary Intervention.
    Date June 2006
    Journal Journal of Korean Medical Science
    Excerpt

    Insulin resistance is an important risk factor for coronary artery disease. However, there has been no data regarding its clinical effect on the outcomes of percutaneous coronary intervention (PCI) in non-diabetic patients. We analyzed 98 non-diabetic consecutive patients (59+/-11.5 yr, male:female=63:35) who underwent elective coronary angiography. The patients were divided into two groups: Group I (n=71; the value of HOMA-IR [homeostasis model assessment of insulin resistance] <2.6) and Group II (n=27; the value of HOMA-IR > or = 2.6). In-hospital and 30-day major adverse cardiac events (MACE) were compared between the two groups. The concentrations of fasting insulin and triglyceride were significantly higher in Group II than in Group I. Significant correlations were observed between the value of HOMA-IR and body mass index (r=0.489, p<0.001), levels of total cholesterol (r=0.204, p=0.045), triglyceride (r=0.334, p=0.001) and apolipoprotein B (r=0.212, p=0.038). PCI was performed in 59 patients (60.2%). In-hospital and 30-day MACE were higher in Group II than Group I (2.4% vs. 27.8%, p=0.008; 2.4% vs. 27.8%, p=0.008). Multivariate analysis revealed that the value of HOMA-IR > or = 2.6 was an independent predictor of MACE. Increased HOMA-IR level is an important prognostic indicator in non-diabetic patients underwent PCI.

    Title A Case of Santorinicele Without Pancreas Divisum: Diagnosis with Multi-detector Row Computed Tomography.
    Date June 2006
    Journal Journal of Korean Medical Science
    Excerpt

    A santorinicele is defined as a focal cystic dilatation of the terminal portion of the dorsal pancreatic duct at the minor papilla. Most cases reported previously were associated with pancreas divisum and a santorinicele without pancreas divisum is known to be rare. We recently experienced a typical case of a santorinicele without pancreas divisum in a 67-yr-old woman with abdominal pain and hematochezia, subsequently proven to be the result of an ischemic colitis. The santorinicele was diagnosed incidentally with multi-detector row computed tomography using a minimum intensity projection technique, which clearly showed a cystic dilatation of the terminal portion of the dorsal pancreatic duct and a communication between the ventral and dorsal pancreatic ducts. This finding was also confirmed by a magnetic resonance cholangiopancreatography.

    Title Delayed Puberty Due to Pituitary Stalk Dysgenesis and Ectopic Neurohypophysis.
    Date June 2006
    Journal The Korean Journal of Internal Medicine
    Excerpt

    Hypopituitarism is not a common cause of delayed puberty. A 22 year old man was referred to our clinic because of the absence of the development of secondary sexual characteristics. The patient had no complaints of physical discomfort. Random serum testosterone and luteinizing hormone level were obtained and found to be low. The combined pituitary function stimulation test revealed a partial hypopituitarism. A pituitary magnetic resonance imaging (MRI) was obtained and showed decreased pituitary stalk enhancement and ectopic neurohypophysis. Therefore, we conclude that the delayed puberty was a result of hypopituitarism due to pituitary stalk dysgenesis and ectopic neurohypophysis. The patient was started on hormone replacement therapy and gradually developed secondary sexual characteristics.

    Title Clinical Study of Adrenal Incidentaloma in Korea.
    Date April 2006
    Journal The Korean Journal of Internal Medicine
    Excerpt

    This study was designed to evaluate the clinical, endocrinological and histological characteristics of adrenal incidentalomas.

    Title Effect of Rosiglitazone on Plasma Adiponectin Levels and Arterial Stiffness in Subjects with Prediabetes or Non-diabetic Metabolic Syndrome.
    Date April 2006
    Journal European Journal of Endocrinology / European Federation of Endocrine Societies
    Excerpt

    Thiazolidinediones have favorable influences on surrogate markers of atherosclerosis such as adiponectin, and arterial stiffness in diabetic patients. However, it is not well known whether these beneficial effects occur in subjects without diabetes, such as prediabetes or the non-diabetic metabolic syndrome (MetS). The present study was therefore designed to evaluate the effectiveness of the insulin-sensitizing agent rosiglitazone on circulating adipocytokine levels and brachial-ankle pulse wave velocity (baPWV) in non-diabetics.

    Title Redox Dependence of Glomerular Epithelial Cell Hypertrophy in Response to Glucose.
    Date April 2006
    Journal American Journal of Physiology. Renal Physiology
    Excerpt

    Podocytes or glomerular epithelial cells (GECs) are important targets of the diabetic microenvironment. Podocyte foot process effacement and widening, loss of GECs and hypertrophy are pathological features of this disease. ANG II and oxidative stress are key mediators of renal hypertrophy in diabetes. The cellular mechanisms responsible for GEC hypertrophy in diabetes are incompletely characterized. We investigated the effect of high glucose on protein synthesis and GEC hypertrophy. Exposure of GECs to high glucose dose dependently stimulated [(3)H]leucine incorporation, but not [(3)H]thymidine incorporation. High glucose resulted in the activation of ERK1/2 and Akt/PKB. ERK1/2 pathway inhibitor or the dominant negative mutant of Akt/PKB inhibited high glucose-induced protein synthesis. High glucose elicited a rapid generation of reactive oxygen species (ROS). The stimulatory effect of high glucose on ROS production, ERK1/2, and Akt/PKB activation was prevented by the antioxidants catalase, diphenylene iodonium, and N-acetylcysteine. Exposure of the cells to hydrogen peroxide mimicked the effects of high glucose. In addition, ANG II resulted in the activation of ERK1/2 and Akt/PKB and GEC hypertrophy. Moreover, high glucose and ANG II exhibited additive effects on ERK1/2 and Akt/PKB activation as well as protein synthesis. These additive responses were abolished by treatment of the cells with the antioxidants. These data demonstrate that high glucose stimulates GEC hypertrophy through a ROS-dependent activation of ERK1/2 and Akt/PKB. Enhanced ROS generation accounts for the additive effects of high glucose and ANG II, suggesting that this signaling cascade contributes to GEC injury in diabetes.

    Title Micropatterning of Biomolecules on Glass Surfaces Modified with Various Functional Groups Using Photoactivatable Biotin.
    Date April 2006
    Journal Analytical Biochemistry
    Excerpt

    Biomolecule patterning by photolithographic methods has considerable advantages because a large number of different biomolecules can be assembled on a spatial area by a combinatorial method and complex biomolecule patterning can be created in situ in closed environments such as microfluidic channels. Here, a photobiotin was used as the photoactivatable reagent to create patterned arrays of biomolecules. The variability of photobiotin deposition on glass substrates modified with a variety of materials having carboxyl, lysine, aldehyde, amine groups, and BSA (bovine serum albumin) was characterized by subsequent derivatization with Cy3-labeled streptavidin. The fluorescence images of the photobiotin patterned glass surfaces showed that the BSA/aldehyde-coated glass could be considered as the most appropriate substrate to immobilize photobiotin, in view of the homogeneous immobilization of biomolecules with high density in defined regions and the reduction of nonspecific binding to the surface. In streptavidin equilibrium adsorption assays, the maximum amount of streptavidin-Cy3 bound to the BSA/aldehyde-coated glass surface continued to rise with increasing streptavidin-Cy3 concentration until 12.0 microg/mL was reached and the surface then became saturated. Also, a line array of biotin-labeled single-strand probe DNAs was created on the BSA/aldehyde-coated glass by photolysis of photobiotin through a slit-type mask and biotin/streptavidin/biotin chemistry, extended to a quantitative measurement of the concentrations of target DNA. The results of target DNA analysis showed linearity over a wide range from 0.5 ng/mL to 5 microg/mL and were reproducible.

    Title [positive Predictability and Predictive Factors of the Third Generation Anti-hepatitis C Virus (hcv) Elisa Test for Hcv Infection].
    Date March 2006
    Journal The Korean Journal of Gastroenterology = Taehan Sohwagi Hakhoe Chi
    Excerpt

    Anti-HCV positivity suggests past or present infection of HCV, or false positivity. The positive predictability of this test can differ according to the subjects. This study examines the positive predictability of the third generation anti-HCV ELISA and factors predicting HCV infection with special emphasis on the significance of the anti-HCV sample/cut-off (S/CO) ratio.

    Title [frequent Epigenetic Inactivation of Xaf1 by Promotor Hypermethylation in Human Colon Cancers].
    Date March 2006
    Journal The Korean Journal of Gastroenterology = Taehan Sohwagi Hakhoe Chi
    Excerpt

    X-linked inhibitor of apoptosis (XIAP) is the most potent member of the IAP family that exerts antiapoptotic effects. Recently, XIAP-associated factor 1 (XAF1) and two mitochondrial proteins, Smac/ DIABLO and HtrA2, have been identified to negatively regulate the caspase-inhibiting activity of XIAP. We explored the candidacy of XAF1, Smac/DIABLO and HtrA2 as a tumor suppressor in colonic carcinogenesis.

    Title [the Incidence and Clinical Significance of Paraneoplastic Syndromes in Patients with Hepatocellular Carcinoma].
    Date March 2006
    Journal The Korean Journal of Hepatology
    Excerpt

    Patients with hepatocellular carcinoma (HCC) may manifest paraneoplastic syndromes such as hypercholesterolemia, hypoglycemia, hypercalcemia and erythrocytosis. This study was aimed at evaluating the incidence and clinical significance of paraneoplastic syndromes in Korean HCC patients.

    Title Polymorphisms of the Prion Protein Gene (prnp) in Hanwoo (bos Taurus Coreanae) and Holstein Cattle.
    Date March 2006
    Journal Genes & Genetic Systems
    Excerpt

    Polymorphisms in the prion protein gene (PRNP) in humans and sheep correlate with susceptibility to transmissible spongiform encephalopathies (TSEs). Bovine spongiform encephalopathy (BSE) has been reported in British and Japanese cattle; it has occurred thus far in Holstein cattle. BSE in Hanwoo (Bos taurus coreanae) cattle has not been diagnosed up to now. To characterize the bovine PRNP polymorphisms in Korean cattle, we analyzed the open reading frame (ORF) of PRNP in 120 Hanwoo (beef) cattle and 53 Holstein (dairy) cattle. Three polymorphisms were found, the third position of codon 78 (G-->A), the third position of codon 192 (C-->T), and the deletion of a single octa-repeat. An analysis of codon 78 revealed no difference in the genotype (P = 0.2026) or allele (P = 0.7180) frequencies between Hanwoo and Holstein animals. However, there were significant differences in the genotype (P < 0.0001) and allele (P < 0.0001) frequencies at PRNP codon 192 between Hanwoo and Holstein animals. The rate of Holstein animals with deletion of a single octa-repeat was 91.5% undeleted homozygotes, 8.5% heterozygotes (with R3 deletion), and 0% deleted homozygotes. However, none of the 120 Hanwoo animals had any octa-repeat deletions. The genotype (P < 0.0001) and allele (P < 0.0001) frequencies of a single octa-repeat-deletion were also significantly different between Hanwoo and Holstein animals.

    Title Serum Osteoprotegerin Levels Are Associated with Inflammation and Pulse Wave Velocity.
    Date February 2006
    Journal Clinical Endocrinology
    Excerpt

    We examined the association between serum osteoprotegerin (OPG) levels, systemic inflammation and arterial stiffness in normal and diabetic patients.

    Title Association Among Serum Ferritin, Alanine Aminotransferase Levels, and Metabolic Syndrome in Korean Postmenopausal Women.
    Date December 2005
    Journal Metabolism: Clinical and Experimental
    Excerpt

    We examined the relationships among serum ferritin, alanine aminotransferase (ALT) levels, and cardiovascular risk factors of metabolic syndrome in Korean postmenopausal women. We conducted a cross-sectional study of 959 postmenopausal women without an apparent cause of liver disease. Metabolic syndrome was defined as the presence of at least 3 of the following: elevated blood pressure, low high-density lipoprotein cholesterol, elevated serum triglycerides, elevated plasma glucose, and abdominal obesity. Serum ferritin and ALT levels were found to be correlated (r=0.374, P<.001) and to be associated with the components of metabolic syndrome. Subjects with metabolic syndrome showed significantly higher serum ferritin (74.7+/- 2.0 vs 59.6+/- 2.0 ng/mL, P<.001) and ALT levels (21.3+/-1.6 vs 18.7+/-1.5 IU/L, P<.001). Moreover, the greater the number of metabolic syndrome components present, the higher were the serum ferritin and ALT levels (P<.001). Multiple regression analysis showed that serum ALT levels are significantly associated with serum ferritin levels, waist circumference, fasting blood glucose, age, and white blood cell count (adjusted R(2)=0.147). Elevated iron stores were positively associated with serum ALT levels and metabolic syndrome in Korean postmenopausal women.

    Title Effect of Transition Metals (mn, Cu, Fe) and Deoxycholic Acid (da) on the Conversion of Prpc to Prpres.
    Date December 2005
    Journal The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology
    Excerpt

    The PMCA (protein misfolding cyclic amplification) technique has been shown to drive the amplification of misfolded prion protein by PrP(Sc) seeds during several cycles of incubation-sonication. Here, we report that cyclic amplification of normal hamster brain homogenates treated with a number of transition metals (manganese [Mn], copper [Cu], and iron [Fe]) leads to conversion of PrP(C) into protease-resistant PrP(res). The efficiency of PrP(res) formation and the glycoforms induced by Mn were different from those obtained by Cu and Fe. Previous results have shown higher Mn and lower Cu levels in the affinity-purified PrP(Sc) from the brain of prion diseases compared with normal hamster brain homogenates. We focused on Mn because we observed higher levels of Mn in whole brain, mitochondria, and scrapie-associated fibril-enriched fractions from the brains of animals with prion disease. In the presence of minute quantities of Mn-induced PrP(res) template with a large amount of PrP(C), PrP(res) amplification is observed. A metal chelater, EDTA reverses the effect of Mn on PrP(res) amplification, suggesting that Mn may play a role in the formation of PrP(res). It has been proposed that metal-catalyzed oxidation of PrP leads to the oxidation of amino acids and extensive aggregation of oxidized PrP. Carboxyl acids such as deoxycholic acid (DA) are oxidized molecules produced by 3' oxidation pathway. In in vitro studies, the potent effect of Mn on PrP(res) amplification is augmented by DA in a dose-dependent manner. On the basis of the evidence of the elevated Mn levels in scrapie-associated fibril (SAF)-enriched preparations from the brains of animals with prion disease, Mn-loaded PrP and oxidized molecules such as carboxyl acids may contribute to the formation of the scrapie isoform of PrP in prion diseases.

    Title Management Following Pulmonary Thromboendarterectomy: Experience Versus Evidence.
    Date November 2005
    Journal Critical Care Medicine
    Title Effect of Ppar-alpha and -gamma Agonist on the Expression of Visfatin, Adiponectin, and Tnf-alpha in Visceral Fat of Oletf Rats.
    Date October 2005
    Journal Biochemical and Biophysical Research Communications
    Excerpt

    A variety of adipocytokines and peptides secreted from adipocytes have been considered to play a crucial role in obesity, insulin resistance, and type 2 diabetes. Recently, visfatin, a new adipocytokine, known as a pre-B cell colony-enhancing factor, has been isolated from visceral fat deposits. It has been shown to activate insulin receptors in a manner different from insulin. To understand the role of adipocytokines in improving insulin sensitivity via activation of the nuclear receptor peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and -gamma (PPAR-gamma), we examined the expression of visfatin, adiponectin, and TNF-alpha in visceral fat depots of Otsuka Long-Evans Tokushima fatty (OLETF) rats from early to advanced diabetic stage (from 28 to 40 weeks of age). Serum glucose and insulin concentrations significantly (P<0.05) decreased in rosiglitazone or fenofibrate-treated OLETF rats compared to untreated OLETF rats. Rosiglitazone significantly increased serum adiponectin concentration from 20 to 40 weeks of age (P<0.05), whereas fenofibrate reduced TNF-alpha concentration. The expression of visfatin and adiponectin mRNA in visceral fat deposits was elevated by rosiglitazone or fenofibrate treatments when compared to untreated OLETF rats (P<0.05), whereas, TNF-alpha mRNA was down-regulated by these drugs (P<0.05). These results suggest that rosiglitazone and fenofibrate may prevent type 2 diabetes by regulating adipocytokines including visfatin, adiponectin, and TNF-alpha.

    Title Polymorphism at 3' Utr +28 of the Prion-like Protein Gene is Associated with Sporadic Creutzfeldt-jakob Disease.
    Date October 2005
    Journal European Journal of Human Genetics : Ejhg
    Excerpt

    The downstream prion-like protein (doppel or Dpl) shares significant biochemical and structural homology with the cellular prion protein, PrP(C), which is considered as a responsible protein for the transmissible spongiform encephalopathies (TSEs) or prion diseases. Recently, polymorphisms in open reading frame (ORF) of the prion-like protein gene (PRND) have been analysed in relation to the occurrence of prion diseases and other neurodegenerative disorders. We examined the role of a single-nucleotide polymorphism (SNP) at 3' untranslated region (UTR) +28 of PRND. We analysed this polymorphism in 110 Korean patients with sporadic Creutzfeldt-Jakob disease (CJD) and 102 healthy control subjects. Significant differences in genotype (P=0.005) and allele (P=0.032) frequencies at 3' UTR +28 were observed between sporadic CJD and normal controls. This result suggests that the PRND polymorphism at 3' UTR +28 might be associated with the occurrence of sporadic CJD.

    Title Altered Patterns of Gene Expression in Response to Chronic Atrial Fibrillation.
    Date October 2005
    Journal International Heart Journal
    Excerpt

    To obtain greater insight into atrial remodeling at the molecular level we analyzed the changes in gene expression in human atrial tissue between patients with chronic atrial fibrillation (AF) and those with normal sinus rhythm (NSR). cDNA microarray analysis was used to identify genes differentially expressed during sustained AF of more than 6 months (n = 9, mean age, 45 +/- 12, 6 males and 3 females) as compared to those with NSR (n = 9, mean age, 47 +/- 13, 6 males and 3 females). Western blot analysis was performed to confirm the altered gene expression and to establish the changes in protein expression. DNA gel electrophoresis to establish DNA ladder formation, which was associated with apoptosis in response to chronic AF, was performed. Microscopic findings were observed via electron microscopy. In the microarray analysis, out of 8,167 candidate genes, 66 genes showed a significant change in the expression level in the patients with chronic AF, which was in contrast to those with NSR. Among those, 31 genes were consistently down-regulated and 35 up-regulated more than 2-fold. The relative amounts of the Bcl-2 and p27 in the atrial tissue were decreased and angiotensin II type 2 (AT2) receptor and p21 were increased in the patients with chronic AF as compared to those with NSR. The atrial cardiomyocytes in chronic AF showed a prominent DNA ladder, which is a biochemical hallmark of apoptosis. The expression of Bcl-2, AT2 receptor, p21, and p27 were consistent with a significant role in the apoptosis of cardiac myocytes in the patients with chronic AF.

    Title Chronic Thromboembolic Pulmonary Hypertension.
    Date October 2005
    Journal Seminars in Respiratory and Critical Care Medicine
    Excerpt

    Over the past 4 decades, chronic thromboembolic pulmonary hypertension has evolved from an autopsy curiosity to a potentially correctable form of pulmonary hypertension. Approximately 2500 thromboendarterectomy procedures have now been performed worldwide with mortality rates reported by established programs experienced in the management of this disease process falling to a range of 4 to 8%. Following a successful pulmonary thromboendarterectomy, substantial improvement, and at times normalization, can be achieved in right ventricular function, gas exchange, exercise capacity, and quality of life. Reperfusion lung injury and residual postoperative pulmonary hypertension remain the major causes of mortality in patients undergoing the procedure.

    Title Polymorphisms at Codons 56 and 174 of the Prion-like Protein Gene (prnd) Are Not Associated with Sporadic Creutzfeldt-jakob Disease.
    Date October 2005
    Journal Journal of Human Genetics
    Excerpt

    Association between sporadic Creutzfeldt-Jakob disease (CJD) and the prion-like protein gene (PRND) has been reported in the German population. To investigate whether the PRND polymorphisms are associated with an increased risk for developing sporadic CJD in the Korean population, we compared the genotype and allele frequencies of PRND polymorphisms in 110 sporadic CJD patients with those in 102 healthy Koreans. Two polymorphisms (P56L, T174 M) in Koreans were found in the open reading frame (ORF) of PRND. One heterozygote of P56L was observed in normal controls but not in sporadic CJD patients. A strong significant difference of PRND genotype frequency at codon 174 was found between the normal Korean population and various European populations. In contrast to results in the German population, our study did not show a significant difference in PRND genotype or allele frequency at codon 174 between sporadic CJD and normal controls. This was the first genetic association study of the ORF of PRND in an Asian CJD population.

    Title Clinical Features of Hbsag-negative but Anti-hbc-positive Hepatocellular Carcinoma in a Hepatitis B Virus Endemic Area.
    Date September 2005
    Journal Journal of Gastroenterology and Hepatology
    Excerpt

    The presence of antibody to the hepatitis B core antigen (anti-HBc) IgG in serum usually means a past infection of the hepatitis B virus (HBV). The clinical characteristics of patients with hepatocellular carcinoma (HCC), who have only a marker for past HBV infection, were investigated.

    Title The Effects of Qrs Duration and Pacing Sites on the Acute Hemodynamic Changes During Right Ventricular Pacing.
    Date July 2005
    Journal The Korean Journal of Internal Medicine
    Excerpt

    BACKGROUND: Has been reported that patients exhibiting prolonged paced QRS duration tend to have more serious heart disease, and the paced QRS duration can be an effective indicator of impaired left ventricular function. However, the acute and chronic hemodynamic effects of paced QRS duration and pacing sites during right ventricular (RV) pacing remain unknown. METHODS: A total of 14 patients who underwent electrophysiologic study for paroxysmal supraventricular tachycardia were examined. RV pacing was performed at 10 different sites with cycle lengths of 600 ms and 500 ms utilizing a 6-7F deflectable quadripolar electrode catheter. Systolic, diastolic, and mean blood pressures during pacing were measured once the blood pressure was stabilized. RESULTS: During RV pacing, blood pressures (systolic/diastolic/mean) decreased. The change of post-pacing QRS duration and pre-pacing the systolic blood pressure (SBP) were greater in the group with paced QRS duration. The differences overall were greater than 140 ms. The SBP decrease during pacing was larger in the group exhibiting paced QRS duration of greater than 140 ms. The SBP decrease during pacing showed relation to QRS duration during pacing (r = 0.500, p = 0.001), the change of QRS duration post-pacing (r = 0.426, p = 0.001), and SBP during sinus rhythm (r = 0.342, p = 0.001) on linear correlation analysis. The pacing site, on the other hand, did not affect acute hemodynamic changes during pacing. CONCLUSION: Ventricular pacing of less than 40 ms at the area of paced QRS duration is recommended.

    Title The Right Ventricle in Pulmonary Hypertension.
    Date June 2005
    Journal Coronary Artery Disease
    Excerpt

    Pulmonary arterial hypertension (PAH) is a term used to classify a variety of conditions that share in common an injury to the pulmonary vasculature that produces elevations in pulmonary arterial pressure. However, it is the integrity of right ventricular function, rather than the degree of vascular injury, that is the major determinant of symptoms and survival in PAH. The article will review the normal structure and function of the right ventricle and summarize the impact of PAH and its treatments on right ventricular function.

    Title Increased Expression of Phospholipase D1 in the Brains of Scrapie-infected Mice.
    Date June 2005
    Journal Journal of Neurochemistry
    Excerpt

    Mitochondrial dysfunction and free radical-induced oxidative damage are critical factors in the pathogenesis of neurodegenerative diseases. Recently, phospholipid breakdown by phospholipase D (PLD) has been recognized as an important signalling pathway in the nervous system. Here, we examined the expression of PLD and alteration of membrane phospholipid in scrapie brain. We have found that protein expression and enzyme activity of PLD1 were increased in scrapie brains compared with controls; in particular, there was an increase in the mitochondrial fraction. PLD1 in mitochondrial membranes from scrapie brains, but not from control brains, was tyrosine phosphorylated. Furthermore, the concentration of mitochondrial phospholipids such as phosphatidylcholine and phosphatidylethanolamine was increased and the content of phosphatidic acid, a product of PLD activity, was up-regulated in the mitochondrial membrane fractions. Immunohistochemically, PLD1 immunoreactivity was significantly increased in activated astrocytes in both cerebral cortex and hippocampus of scrapie brains. Taken together, these results suggest that PLD activation might induce alterations in mitochondrial lipids and, in turn, mediate mitochondrial dysfunction in the brains of scrapie-infected mice.

    Title Vascular Endothelial Growth Factor (vegf) and Soluble Vegf Receptor Flt-1 in Diabetic Nephropathy.
    Date June 2005
    Journal Kidney International
    Excerpt

    BACKGROUND: Vascular endothelial growth factor (VEGF) and its receptors have been implicated in the pathogenesis of diabetic nephropathy. The objective of this study was to determine whether alterations of the plasma and urinary VEGF and sFLT-1 levels were related to the stages and risk factors of diabetic nephropathy. In addition, we also examined the regulation of the VEGF/sFLT-1 expression by various stimuli in cultured human proximal tubule cells (HPTC). METHODS: A total of 107 type 2 diabetic patients and 47 healthy control subjects were studied. The expression and protein levels of VEGF and sFLT-1 were measured by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: The urinary VEGF and sFLT-1 excretions were significantly increased in the microalbuminuric and proteinuric diabetic patients. The urinary VEGF levels were positively correlated with the urinary albumin to creatinine ratio (ACR), urinary sFLT-1 levels, and negatively correlated with creatinine clearance. The urinary sFLT-1 levels also showed a positive relationship with the urinary ACR. In cultured HPTC, high glucose stimuli rapidly up-regulated VEGF synthesis without having any effect on sFLT-1 synthesis. Interestingly, angiotensin II (Ang II) induced a dose-dependent increase in the synthesis of both VEGF and sFLT-1, which was significantly blocked by losartan. CONCLUSION: The urinary excretion of VEGF and sFLT-1 increased at a relatively early stage in diabetic nephropathy associated with urinary albumin excretion. A marked increase in both VEGF/sFLT-1 synthesis in response to Ang II was observed in HPTC, which was different from the response to glucose stimuli. These findings may imply that VEGF and sFLT-1 can actively take part in the pathogenesis of diabetic nephropathy.

    Title Less Keratinocyte-derived Factors Related to More Keratinocyte Apoptosis in Depigmented Than Normally Pigmented Suction-blistered Epidermis May Cause Passive Melanocyte Death in Vitiligo.
    Date June 2005
    Journal The Journal of Investigative Dermatology
    Excerpt

    Stem cell factor (SCF) of keratinocyte origin regulates melanocyte growth and survival. Deprivation of survival factors causes the apoptosis of melanocytes. Vitiligo often develops following physical trauma, even if this is minor. The exact mechanism of the Koebner phenomenon in vitiligo is unclear. Apoptosis of keratinocytes, which occurs more in depigmented suction-blistered epidermis than in the normally pigmented counterpart, could reduce levels of keratinocyte-derived factors such as SCF and basic fibroblast growth factor (bFGF). Levels of SCF expression were examined in the depigmented and normally pigmented paired epidermis of 19 patients with vitiligo, and bFGF expression in six patients. The expression of SCF (p<0.001) and bFGF was usually reduced in the depigmented compared with the normally pigmented epidermis. Apoptosis of cultured normal human keratinocytes, which was induced by staurosporine, resulted in a concentration-dependent decrease in levels of SCF mRNA and protein. Normal human melanocytes proliferated more in medium containing SCF or keratinocyte (XB-2) feeder than in medium with neither. Deprivation of SCF or keratinocyte feeder in the culture medium induced a marked decrease in melanocytes as a result of apoptosis. Therefore, lower expression of keratinocyte-derived factors, including SCF, in vitiliginous keratinocytes, which could result from keratinocyte apoptosis, might be responsible for passive melanocyte death and may explain the Koebner phenomenon.

    Title Urinary Concentration of Transforming Growth Factor-beta-inducible Gene-h3(beta Ig-h3) in Patients with Type 2 Diabetes Mellitus.
    Date April 2005
    Journal Diabetic Medicine : a Journal of the British Diabetic Association
    Excerpt

    AIMS: The expression of TGF beta-inducible gene h3(beta ig-h3) has been used to assess the biological activity of TGF beta in the kidney. In this study, we investigated whether the urinary concentration of beta ig-h3 is associated with diabetic nephropathy in patients with Type 2 diabetes mellitus. We also evaluated the relationship between the urinary concentration of beta ig-3 and proteinuria and microalbuminuria (AER) in a normal healthy population and in Type 2 diabetes patients. METHODS: Four hundred and seventy-nine Type 2 diabetic patients without non-diabetic kidney diseases and 528 healthy control subjects were enrolled. The study subjects were divided into five groups: a non-diabetic healthy control group with normal ACR (n = 443), a non-diabetic healthy control group with microalbuminuria (n = 85), a normoalbuminuric diabetic group (n = 198), a microalbuminuric diabetic group (n = 155) and an overt proteinuria group (n = 126). Urinary levels of beta ig-h3 were measured by enzyme-linked immunosorbent assay. RESULTS: (i) Urinary excretion of beta ig-h3 was significantly higher in the diabetic groups than in the controls, even in the normoalbuminuric stage (25.02 +/- 8.84 vs. 18.67 +/- 6.56, P = 0.03). In diabetic patients, urinary beta ig-h3 levels increased significantly as diabetic nephropathy advanced (25.02 +/- 8.84 vs. 34.06 +/- 24.55 vs. 169.63 +/- 57.33, P < 0.001). (ii) Proteinuria was found to be significantly correlated with urinary beta ig-h3 (healthy control; r = 0.137, P = 0.019, diabetic patients; r = 0.604, P < 0.001). ACR was also found to be significantly related with urinary beta ig-h3 in diabetic patients (r = 0.383, P = 0.006). (iii) In diabetic patients, urinary beta ig-h3 was significantly related with systolic and diastolic blood pressure (systolic blood pressure: r = 0.436, P = 0.024; diastolic blood pressure, r = 0.365, P = 0.042), total cholesterol and HbA(1c) (cholesterol: r = 0.169, P = 0.03, HbA(1c); r = 0.387, P = 0.044). Logistic regression analyses showed that urinary beta ig-h3 was associated with a significant increase in the risk of microalbuminuria and proteinuria in diabetic patients. CONCLUSIONS: Longitudinal monitoring of urinary beta ig-h3 may improve the likelihood of detecting diabetic nephropathy at an earlier stage and beta ig-h3 could be a sensitive marker of diabetic kidney disease progression.

    Title [the Changes of Ammonia and Epidermal Growth Factor Concentration in Gastric Juice Before and After the Helicobacter Pylori Eradication].
    Date April 2005
    Journal The Korean Journal of Gastroenterology = Taehan Sohwagi Hakhoe Chi
    Excerpt

    Helicobacter pylori (H. pylori) infection is the cause of peptic ulcer diseases, and gastric cancer. Hydrolysis of urea generating ammonia may cause cytotoxic effects on the gastric epithelium. The ammonia may induce the synthesis of epidermal growth factor (EGF) in gastric epithelium as an adaptive cytoprotective mechanism. The first aim was to examine the concentration of ammonia and EGF in gastric juice before and after H. pylori eradication in functional dyspepsia patients. The second aim was to examine the correlation among ammonia concentration, EGF concentration, and inflammatory score of gastritis.

    Title Retrovirus-mediated Gene Transfer and Expression of Egfp in Chicken.
    Date April 2005
    Journal Molecular Reproduction and Development
    Excerpt

    Here, we successfully demonstrate expression of the EGFP (enhanced green fluorescence protein) gene in chickens using replication-defective MLV (murine leukemia virus)-based retrovirus vectors encapsidated with VSV-G (vesicular stomatitis virus G glycoprotein). The recombinant retrovirus was injected beneath the blastoderm of non-incubated chicken embryos (stage X). After 12 days incubation, all of the eight living embryos assayed were found to express this vector-encoded EGFP gene, which was under the control of the RSV (Rous Sarcoma Virus) promoter, in diverse organ tissues, including head, beak, neck, wing, hock, tail, toes, heart, amnion, and yolk sac. Surprisingly, despite the presumed cytotoxicity of EGFP, some embryos hatched and survived and these had prominent green fluorescent spots, both in internal organs and externally.

    Title [a Case of Non-traumatic Hemobilia Due to Warfarin Therapy].
    Date April 2005
    Journal The Korean Journal of Gastroenterology = Taehan Sohwagi Hakhoe Chi
    Excerpt

    Hemobilia is a hemorrhage into the biliary tract that may follow surgical trauma, liver biopsy, aneurysms, extra- or intra-hepatic tumors of the biliary tract, gallstones, and inflammatory lesion of liver, especially helminthic or pyogenic. Sometimes, it is associated with primary liver cancer. An 84 year-old woman was admitted because of continuous right upper quadrant pain 4 days before admission. Physical examination revealed decreased skin turgor, icteric sclerae and severe tenderness on right upper quadrant abdomen. She had no hepatosplenomegaly, and no rebound tenderness. She has been taking warfarin for 3 weeks before admission because of atrial fibrillation. On admission, serum bilirubin and transaminase were elevated. The level of hemoglobin and hematocrit were 11.3 g/dL and 37.4%, respectively. HBsAg was negative, but IgG anti-HBc and anti-HBs were positive and anti-HCV was negative. Parasite skin test and stool ova count demonstrated non-specific findings. Stool occult blood was strongly positive, and prothrombin time was markedly prolonged. According to endoscopic retrograde cholangiopancreatography, common bile duct was dilated, and filled with blood clot but there was no stone in bile tree. After two weeks, serum transaminase, bilirubin, hemoglobin, hematocrit, and CA19-9 were normalized. We report a case of hemobilia, occurring in a patient with continuous warfarin use.

    Title [etiology and Clinical Consequence of Spontaneous Acute Exacerbation of Chronic Hepatitis B].
    Date April 2005
    Journal The Korean Journal of Hepatology
    Excerpt

    Acute exacerbation (AE) of chronic hepatitis B (CHB) can occur spontaneously, and may be followed by HBeAg clearance. HBeAg seroconversion often coincides with the normalization of liver biochemical tests and clinical remission. The purpose of this study was to identify the etiology and the clinical consequence of severe AE in Korean patients with CHB.

    Title Relationship Between Brachial-ankle Pulse Wave Velocity and Cardiovascular Risk Factors of the Metabolic Syndrome.
    Date April 2005
    Journal Diabetes Research and Clinical Practice
    Excerpt

    In this study, we investigated the association between brachial-ankle pulse wave velocity (baPWV), a novel non-invasive means of measuring atherosclerosis, and the cardiovascular risk factors of the metabolic syndrome. The study group comprised of 368 Koreans without history of diabetes or hypertension. Anthropometric parameters, blood pressure, fasting blood glucose (FBG), lipid profiles, ankle-brachial pressure index (ABI), and baPWV were measured in each subject. ABI and baPWV levels were higher in men than in women. ABI and baPWV levels were not correlated with each other. In women, baPWV was closely associated with the cardiovascular risk factors of the metabolic syndrome. Women with the metabolic syndrome showed higher baPWV levels compared to those without the metabolic syndrome (1540 +/- 281 versus 1312 +/- 223, P < 0.001). Multiple regression analysis showed that baPWV was significantly associated with systolic blood pressure, age, sex, waist circumference, and FBG (adjusted R2 = 0.548). The present study shows that baPWV is significantly associated with the features of the metabolic syndrome in Korean women.

    Title Relationship Between Serum Adiponectin Concentration, Pulse Wave Velocity and Nonalcoholic Fatty Liver Disease.
    Date April 2005
    Journal European Journal of Endocrinology / European Federation of Endocrine Societies
    Excerpt

    OBJECTIVES: We aimed to investigate the relationship between nonalcoholic fatty liver disease (NAFLD), serum adiponectin concentration and brachial-ankle pulse wave velocity (baPWV) as a risk marker for atherosclerosis. METHODS: A total of 213 nonalcoholic subjects (67 males, 146 females) participated in this study. Division of subjects into the NAFLD group or the normal group was based on the existence of fatty liver detected by sonography. RESULTS: Serum adiponectin levels in the NAFLD group were significantly lower than those in the normal group. After adjusting for age, body-mass index (BMI) and the homeostasis model of assessment (HOMA), there was a significant negative correlation between NAFLD and serum adiponectin level only in females (r = -0.22, P = 0.008). Multiple logistic regression analysis showed a tendency of inverse correlation between NAFLD and serum adiponectin level in females (P = 0.055). After adjustment for age, BMI and HOMA value, serum adiponectin levels were inversely correlated with serum alanine aminotransferase (ALT) and gamma-glutamyltranspeptidase (GGT) levels (r = -0.199 (P = 0.004) and r = -0.282 (P < 0.001)). On the other hand, baPWV in the NAFLD group was also significantly higher than that in the normal group in females (P = 0.005). Individual levels of serum ALT, aspatate aminotransferase (AST), alkaline phosphatase (ALP) and GGT were positively correlated with baPWV after adjusting for age, sex, BMI, HOMA and systolic blood pressure (P < 0.05). CONCLUSION: Serum adiponectin level and baPWV were significantly associated with NAFLD and various liver enzymes, especially in females.

    Title Keratinocytes in the Depigmented Epidermis of Vitiligo Are More Vulnerable to Trauma (suction) Than Keratinocytes in the Normally Pigmented Epidermis, Resulting in Their Apoptosis.
    Date March 2005
    Journal The British Journal of Dermatology
    Excerpt

    Vitiligo may develop following minor physical trauma. However, in autologous epidermal grafting, depigmentation of the donor (normally pigmented) site from a suction blister is rare, even in cases displaying failure of repigmentation at the recipient (depigmented) site.

    Title Interleukin-1b (il-1b) Polymorphisms and Gastric Mucosal Levels of Il-1beta Cytokine in Korean Patients with Gastric Cancer.
    Date March 2005
    Journal International Journal of Cancer. Journal International Du Cancer
    Excerpt

    Interleukin-1B and IL-1 receptor antagonist gene polymorphisms are associated with an increased risk of gastric cancer (GC) in Caucasian populations. However, recent studies could not find any association between IL-1B-511T polymorphism and the risk of GC in Asians. We tested for an association between IL-1 loci polymorphisms with increased gastric mucosal levels of IL-1beta and an increased risk of developing GC in a Korean population. Polymorphisms of IL-1A-889, IL-1B-31, IL-1B-511 and IL-1RN were genotyped in 434 controls and 234 patients with GC. Mucosal IL-1beta cytokine was measured using an ELISA. The frequencies of IL-1A, IL-1B-511, IL-1B-31 and IL-1RN were not statistically different between controls and all patients with GC. After subclassification of GC, only patients with intestinal-type GC showed a higher frequency of IL-1B-31T homozygotes (OR = 2.2; 95% CI = 1.1-4.3) compared with controls. Risk was also significantly increased in these patients for IL-1B-31T homozygotes compared with patients with diffuse-type GC (OR = 3.4; 95% CI = 1.5-7.7). As in Caucasian populations, linkage disequilibrium between IL-1B-31 and IL-1B-511 was nearly complete, but the pattern of haplotype related to the risk of GC (IL-1B-31T/IL-1B-511C) was opposite (IL-1B-511T/IL-1B-31C). Mucosal IL-1beta levels in H. pylori-infected GC patients were higher in patients homozygous for IL-1B-31T compared with IL-1B-31C/T and IL-1B-31C/C. Thus, the combined effects of H. pylori infection and IL-1B-31T/IL-1B-511C polymorphisms with enhanced mucosal IL-1beta production contributed to the development of intestinal-type GC in this Korean population.

    Title Fibronectin Induces Ureteric Bud Cells Branching and Cellular Cord and Tubule Formation.
    Date February 2005
    Journal Kidney International
    Excerpt

    BACKGROUND: The extracellular matrix (ECM) protein fibronectin is involved in several stages of embryogenesis. Fibronectin exerts its effect through interaction with cellular integrin and nonintegrin receptors. METHODS: We investigated the effect of fibronectin on branching and tubulogenesis of ureteric bud cells in a three-dimensional gel culture system. Primary ureteric bud cells from mouse embryos at gestation 11 days (E11) were isolated and established in culture. Fibronectin and integrin subunits were localized using immunoperoxidase staining. RESULTS: In three-dimensional collagen type I gel culture of ureteric bud cell, fibronectin dose dependently induces cord and tubule formation. Both ureteric bud cells and ureteric bud branches in embryonic kidney express the same multiple integrin subunits that include beta(1), beta(3), alpha(3), alpha(4) and alpha(v). Embryonic kidneys examined at E12, E14, and E16 days of gestation express fibronectin in the undifferentiated mesenchyme especially next to ureteric bud branches and in the interstitium around glomerulotubular structures and blood vessels. Fibronectin expression was similar at the tips and stalks of branching ureteric bud. Fibronectin expression is maximum at E12 and decreases with advanced gestation. Cultured ureteric bud cells also express fibronectin. RGD peptides inhibit cord and tubular formation in the three-dimensional gel. Anti-alpha(3)beta(1) antibody partially inhibits fibronectin-induced cord and tubule formation. Hepatocyte growth factor (HGF), fibroblast growth factor (FGF), and glial cell line-derived neurotrophic factor (GDNF) induce ureteric bud cell cord formation in three-dimensional gel. The effects of growth factors are delayed and quantitatively less compared to the effect of fibronectin. CONCLUSION: Fibronectin induces ureteric bud cells branching and tubulogenesis through interaction with multiple integrin receptors. Cultured ureteric bud cells express fibronectin and the origin of fibronectin at mesenchyme-ureteric bud interface is likely both the metanephric mesenchyme and ureteric bud epithelium. Addition of individual neutralizing antibodies to beta(1), beta(3), alpha(3), alpha(4,)alpha(6) and alpha(v) integrin subunits does not block the effect of fibronectin. Only an antibody to alpha(3)beta(1) integrin substantially blocks the effect of fibronectin. Other mechanisms, including unidentified integrins, are likely involved in fibronectin-induced cord and tubule formation.

    Title Inflammation, Insulin Resistance, and Glucose Intolerance in Acute Myocardial Infarction Patients Without a Previous Diagnosis of Diabetes Mellitus.
    Date February 2005
    Journal The Journal of Clinical Endocrinology and Metabolism
    Excerpt

    We examined the prevalence of impaired glucose metabolism and its association with inflammation and insulin resistance (IR) in acute myocardial infarction (AMI) patients without a previous diagnosis of diabetes. This prospective study enrolled 52 AMI patients, and 75-g oral glucose tolerance testing was performed on 30 patients at discharge and again 3 months later. We also measured serum adiponectin, high sensitive C-reactive protein, and IL-6 on both occasions. Data were compared with those of 30 type 2 diabetic patients without a history of AMI. Forty percent and 36.7% of AMI patients had impaired glucose tolerance (IGT) at discharge and at 3 months, respectively. The corresponding proportions for newly diagnosed diabetes are 33.0% and 30.0%. At discharge, AMI patients with IGT or diabetes showed higher high sensitive C-reactive protein and IL-6 levels compared with AMI patients with normal glucose tolerance or control type 2 diabetic patients. Furthermore, AMI patients with IGT or diabetes exhibited higher IR and lower serum adiponectin levels than AMI patients with normal glucose tolerance at 3 months after discharge. Previously undiagnosed diabetes and IGT are common in Korean patients with AMI. These glycometabolic abnormalities are associated with inflammation, IR, and serum adiponectin levels.

    Title Vascular Endothelial Growth Factor is Increased During Early Stage of Diabetic Nephropathy in Type Ii Diabetic Rats.
    Date December 2004
    Journal The Journal of Endocrinology
    Excerpt

    Vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of diabetic nephropathy. We investigated serial changes of VEGF in the kidney and assessed whether glomerular and urinary VEGF levels are related to the severity of diabetic nephropathy. Furthermore, we examined the relationship between urinary VEGF levels and the urinary albumin excretion (UAE) rate in Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats. Glomerular VEGF mRNA expression and protein synthesis were evaluated by the reverse transcription-polymerase chain reaction, immunohistochemical staining and in situ hybridization. Urinary levels of VEGF were determined by enzyme-linked immunosorbent assay. UAE was significantly higher in OLETF rats than in control Long-Evans-Tokushima-Fatty (LETO) rats throughout the study period. Urinary VEGF levels were significantly higher from 25 to 37 weeks, and then gradually reduced until 55 weeks, although the levels were still higher than those in control rats. Urinary VEGF levels also showed a significant positive correlation with UAE (r=0.262, P=0.045) and serum creatinine (r=0.398, P=0.044), and were found to be independently correlated with UAE by Spearman's rank correlation. By immunohistochemical staining and in situ hybridization, VEGF was mainly detected in the podocytes in the glomeruli. Interestingly, a significant increase in VEGF mRNA expression was observed in the early period of diabetic nephropathy, and this was associated with increased urinary VEGF excretion. Thus, the overproduction of VEGF in the diabetic kidney may participate in the pathogenesis of early-stage diabetic nephropathy.

    Title Comparison of Serum Concentrations of C-reactive Protein, Tnf-alpha, and Interleukin 6 Between Elderly Korean Women with Normal and Impaired Glucose Tolerance.
    Date November 2004
    Journal Diabetes Research and Clinical Practice
    Excerpt

    This study was performed to compare concentrations of pro-inflammatory cytokines, such as interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha) as well as acute-phase protein, such as C-reactive protein (CRP) between subjects with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT). The purpose of this study was to verify whether the pro-inflammatory cytokine-induced acute-phase response is a pathogenic mechanism in type 2 diabetes in elderly Korean women. A total of 1737 elderly subjects aged over 60 years participated in a population based study in Seoul, Korea (SWS Study 1999). Amongst them, a total of 232 non-smoking and non-diabetic female subjects aged 60-89 years was randomly selected and compared with each other. Higher serum high-sensitivity CRP (hs-CRP) concentrations were shown in subjects with IGT than those with normal glucose tolerance (median 1.2 versus 0.9, P < 0.05). Moreover, a relationship between serum hs-CRP concentrations and many components of the metabolic syndrome were detected. Serum pro-inflammatory cytokine IL-6 or TNF-alpha concentrations, however, were neither increased in subjects with IGT nor closely correlated with the components of the metabolic syndrome. In multiple regression analysis with stepwise selection method using hs-CRP as a dependent variable, it was found that white blood cell (WBC) counts, body mass index (BMI), fasting insulin, post-load 2h glucose, hematocrit and LDL cholesterol were significant independent variables. Our study confirms that increased acute-phase reaction is associated with impaired glucose tolerance and the metabolic syndrome in elderly Korean women. However, the hypothesis that pro-inflammatory cytokine-induced systemic inflammation is an early metabolic defect prior to onset of type 2 diabetes, is not supported in our study of elderly Korean women.

    Title Preoperative Partitioning of Pulmonary Vascular Resistance Correlates with Early Outcome After Thromboendarterectomy for Chronic Thromboembolic Pulmonary Hypertension.
    Date November 2004
    Journal Circulation
    Excerpt

    BACKGROUND: Pulmonary thromboendarterectomy (PTE) is the preferred treatment for chronic thromboembolic pulmonary hypertension (CTEPH), but persistent pulmonary hypertension after PTE, as a result of either inaccessible distal thrombotic material or coexistent intrinsic small-vessel disease, remains a major determinant of poor outcome. Conventional preoperative evaluation is unreliable in identifying patients at risk for persistent pulmonary hypertension or predicting postoperative hemodynamic outcome. We postulated that pulmonary arterial occlusion pressure waveform analysis, a technique that has been used for partitioning pulmonary vascular resistance, might identify CTEPH patients with significant distal, small-vessel disease. METHODS AND RESULTS: Twenty-six patients underwent preoperative right heart catheterization before PTE. Pulmonary artery occlusion waveform recordings were performed in triplicate. Postoperative hemodynamics after PTE were compared with preoperative partitioning of pulmonary vascular resistance derived from the occlusion data. Preoperative assessment of upstream resistance (Rup) correlated with both postoperative total pulmonary resistance index (R2=0.79, P<0.001) and postoperative mean pulmonary artery pressure (R2=0.75, P<0.001). All 4 postoperative deaths occurred in patients with a preoperative Rup <60%. CONCLUSIONS: Pulmonary arterial occlusion pressure waveform analysis may identify CTEPH patients at risk for persistent pulmonary hypertension and poor outcome after PTE. Patients with CTEPH and Rup value <60% appear to be at highest risk.

    Title Angiotensin Ii-induced Erk1/erk2 Activation and Protein Synthesis Are Redox-dependent in Glomerular Mesangial Cells.
    Date November 2004
    Journal The Biochemical Journal
    Excerpt

    Angiotensin II (Ang II) stimulates hypertrophy of glomerular mesangial cells. The signalling mechanism by which Ang II exerts this effect is not precisely known. Downstream potential targets of Ang II are the extracellular-signal-regulated kinases 1 and 2 (ERK1/ERK2). We demonstrate that Ang II activates ERK1/ERK2 via the AT1 receptor. Arachidonic acid (AA) mimics the action of Ang II on ERK1/ERK2 and phospholipase A2 inhibitors blocked Ang II-induced ERK1/ERK2 activation. The antioxidant N-acetylcysteine as well as the NAD(P)H oxidase inhibitors diphenylene iodonium and phenylarsine oxide abolished both Ang II- and AA-induced ERK1/ERK2 activation. Moreover, dominant-negative Rac1 (N17Rac1) blocks activation of ERK1/ERK2 in response to Ang II and AA, whereas constitutively active Rac1 resulted in an increase in ERK1/ERK2 activity. Antisense oligonucleotides for Nox4 NAD(P)H oxidase significantly reduce activation of ERK1/ERK2 by Ang II and AA. We also show that protein synthesis in response to Ang II and AA is inhibited by N17Rac1 or MEK (mitogen-activated protein kinase/ERK kinase) inhibitor. These results demonstrate that Ang II stimulates ERK1/ERK2 by AA and Nox4-derived reactive oxygen species, suggesting that these molecules act as downstream signal transducers of Ang II in the signalling pathway linking the Ang II receptor AT1 to ERK1/ERK2 activation. This pathway involving AA, Rac1, Nox4, reactive oxygen species and ERK1/ERK2 may play an important role in Ang II-induced mesangial cell hypertrophy.

    Title Chronic Thromboembolic Pulmonary Hypertension.
    Date November 2004
    Journal Cardiology Clinics
    Excerpt

    During the past 2 decades, there has been a steady rise in the number of patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing surgery and in the number of programs worldwide dedicated to the diagnosis and management of this patient population. This article discusses the natural history and clinical presentation of CTEPH, the evaluation of patients for pulmonary thromboendarterectomy, and the outcomes following surgery, along with a brief review of the procedure as performed at the University of California, San Diego.

    Title Serum Adiponectin Concentrations Predict the Developments of Type 2 Diabetes and the Metabolic Syndrome in Elderly Koreans.
    Date September 2004
    Journal Clinical Endocrinology
    Excerpt

    OBJECTIVE: To determine whether low serum adiponectin concentrations are able to predict the future developments of type 2 diabetes and the metabolic syndrome using the National Cholesterol Education Programme (NCEP) criteria. We also investigated the stability of adiponectin levels and the relationships between baseline adiponectin levels and changes in the parameters related to the metabolic syndrome over a period of 3 years. PATIENTS AND MEASUREMENTS: This prospective cohort study included 372 elderly Koreans who participate in the SWS (South-West Seoul) study, which was conducted in 1999 and 2002 in Seoul, Korea. Fasting and postchallenge 2-h plasma glucose, body mass index (BMI), waist-to-hip ratio (WHR), blood pressure, lipid profiles and serum adiponectin data obtained in 1999 and 2002 were examined. RESULTS: The within-person variation between 1999 and 2002 of serum adiponectin was not significant (P = 0.61). Serum adiponectin was closely correlated with the risks factors of cardiovascular disease (CVD), that is negatively with BMI, WHR, blood pressure, triglyceride and blood glucose levels, and positively with high density lipoprotein (HDL)-cholesterol levels. Subjects with the metabolic syndrome showed lower serum adiponectin concentrations than those without the metabolic syndrome (P < 0.0001). Baseline adiponectin levels were found to be correlated with subsequent changes in WHR, low density lipoprotein (LDL)-cholesterol, fasting and postload 2-h glucose over the 3-year period, after adjusting for baseline values. Multiple logistic regression analysis showed that lower baseline serum adiponectin concentrations were significantly associated with the developments of type 2 diabetes and the metabolic syndrome after adjusting for age, sex, obesity, history of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), hypertension and dyslipidaemia. CONCLUSIONS: Reduced concentrations of adiponectin were found to be independently associated with increased risk of both type 2 diabetes and the metabolic syndrome in elderly Koreans.

    Title Real-time Emergency Telemedicine System: Prototype Design and Functional Evaluation.
    Date September 2004
    Journal Yonsei Medical Journal
    Excerpt

    In this paper, an emergency telemedicine system was designed for the transmission of real-time multimedia for remote consultation, including radiological images, patient records, video-conferencing, full-quality video, ECG, BP, respiration, temperature, SpO(2), systolic and diastolic pressures and heart rate. The standardized, modular, software-based design architecture, without resorting to external hardware compression boards, enables the low-cost implementation of the telemedicine system, using the unified, systematic and compact integration of multimedia on general personal computers. Experimental tests on local networks analyze the technical aspects of designed systems, and inter-hospital experiments demonstrate its clinical usefulness.

    Title Plasma and Urinary Vascular Endothelial Growth Factor and Diabetic Nephropathy in Type 2 Diabetes Mellitus.
    Date August 2004
    Journal Diabetic Medicine : a Journal of the British Diabetic Association
    Excerpt

    AIMS: Vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of diabetes mellitus. We determined whether alterations of plasma and urinary VEGF levels are related to diabetic nephropathy in Type 2 diabetic patients. METHODS: One hundred and seven patients and 47 healthy controls were studied. Study subjects were divided into four groups using urinary albumin-to-creatinine ratio (ACR): a non-diabetic healthy control group (n = 47), a normoalbuminuric diabetic group (n = 37), a microalbuminuric diabetic group (n = 37) and an overt proteinuric diabetic group (n = 33). VEGF levels were measured by enzyme-linked immunosorbent assay. RESULTS: (i) Urinary VEGF concentrations were significantly higher in the diabetic groups, even at the normoalbuminuric stage (log VEGF/Cr, normoalbuminuria; 4.33 +/- 1.06 vs. control; 3.53 +/- 0.79, P = 0.009). Urinary VEGF excretions increased as diabetic nephropathy advanced. (ii) Plasma and urinary VEGF levels were higher in hypertensive diabetic patients than in the normotensive individuals with diabetes. (iii) In those with diabetes, plasma VEGF levels were found to be positively correlated with plasma urea (r = 0.398, P = 0.039) and urinary ACR (r = 0.251, P = 0.044), and urinary VEGF to be positively correlated with urinary ACR (r = 0.645, P < 0.001), and creatinine (r = 0.336, P = 0.009), and to be negatively correlated with serum albumin (r = -0.557, P < 0.001). Urinary VEGF and serum creatinine were independently correlated with urinary ACR. CONCLUSIONS: Urinary excretion of VEGF increased during the earlier stage of diabetic nephropathy and was significantly correlated with urinary albumin excretion. This suggests that urinary VEGF might be used as a sensitive marker of diabetic nephropathy and for predicting disease progression.

    Title Development of Transgenic Chickens Expressing Enhanced Green Fluorescent Protein.
    Date August 2004
    Journal Biochemical and Biophysical Research Communications
    Excerpt

    In this work we demonstrated the successful production of transgenic chickens expressing the enhanced green fluorescence protein (EGFP) gene. Replication-defective recombinant retroviruses produced from vesicular stomatitis virus G glycoprotein pseudotyped retrovirus vector system were injected beneath the blastoderm of non-incubated chicken embryos (stage X). From 129 injected eggs, 13 chicks hatched after 21 days of incubation. All hatched chicks were found to express vector-encoded EGFP gene, which was under the control of the Rous sarcoma virus promoter and boosted post-transcriptionally by woodchuck hepatitis virus post-transcriptional regulatory element sequence. Green fluorescent signals, indicative of the EGFP gene expression, were detected in various body parts, including head, limb, eye, toe, and several internal organs. Genomic incorporation of the transgene was also proven by Southern blot assay. Our results show the exceptional versatile effectiveness of the EGFP gene as a marker in the gene expression-related studies which therefore would be very helpful in establishing a useful transgenic chicken model system for studies on embryo development and for efficient production of transgenic chickens as bioreactors.

    Title Pacemaker Lead Endocarditis Caused by Achromobacter Xylosoxidans.
    Date July 2004
    Journal Journal of Korean Medical Science
    Excerpt

    We report the case of a 35-yr-old patient who presented with high fever and chills. He had undergone a patch closure of the ventricular septal defect 18 yr before. One year later, a VVI pacemaker was implanted via the right subclavian vein because of complete heart block. Nine years after that, a new VVI pacemaker with another right ventricular electrode was inserted controlaterally and the old pacing lead was abandoned. Trans-thoracic and trans-esophageal echocardiogram identified the pacemaker lead in the right ventricle (RV) attaching hyperechoic materials and also a fluttering round hyperechoic mass with a stalk in the RV outflow tract. Cultures in blood and pus from pacemaker lead grew Achromobacter xylosoxidans. A diagnosis of pacemaker lead endocarditis due to Achromobacter xylosoxidans was made. In this regards, the best treatment is an immediate removal of the entire pacing system and antimicrobial therapy.

    Title The Associations Between Plasma Adiponectin, Ghrelin Levels and Cardiovascular Risk Factors.
    Date June 2004
    Journal European Journal of Endocrinology / European Federation of Endocrine Societies
    Excerpt

    OBJECTIVE: Ghrelin is a recently discovered peptide, which is produced primarily in the stomach. This orexigenic peptide participates not only in the induction of mealtime hunger but also in long-term body weight regulation and energy homeostasis. Adiponectin is a protein secreted by adipocytes, and has been proposed to mediate obesity-related insulin resistance. Moreover, concentrations of adiponectin are reduced in individuals with obesity, insulin resistance and cardiovascular disease. However, human data are sparse about the direct relationship between adiponectin, ghrelin and cardiovascular risk factors including insulin resistance. DESIGN: Three hundred and thirty-eight elderly Korean women (mean age+/-s.d., 72.3+/-5.5 years) were included in the present study. METHODS: Plasma ghrelin and adiponectin levels were measured by RIA. Anthropometric measurements were taken and a 75 g oral glucose tolerance test performed. Fasting insulin and lipid profile were measured and insulin resistance was determined using the homeostasis model assessment insulin resistance index (HOMA-R) and the quantitative insulin sensitivity check index. RESULTS: Plasma adiponectin levels were negatively correlated with central obesity indices such as waist circumference (r=-0.27, P<0.001) and waist-to-hip ratio (WHR) (r=-0.32, P<0.001), and with insulin resistance indices such as fasting insulin (r=-0.17, P=0.004) and HOMA-R (r=-0.13, P=0.035). Plasma ghrelin levels were negatively correlated with WHR (r=-0.12, P=0.03), but plasma adiponectin and ghrelin levels were not correlated (r=0.03, P=0.66). Multiple regression analysis showed that adiponectin was associated with WHR, fasting insulin and fasting glucose levels. When ghrelin was used as a dependent variable, only WHR remained in the final fitted model. CONCLUSION: Fasting plasma adiponectin and ghrelin levels were found to be associated with central obesity or insulin resistance. However, plasma adiponectin and ghrelin concentrations were not associated with each other in elderly Korean women.

    Title Three-dimensional Localization of Cochlear Implant Electrodes Using Epipolar Stereophotogrammetry.
    Date June 2004
    Journal Ieee Transactions on Bio-medical Engineering
    Excerpt

    Three-dimensional (3-D) localization of individual cochlear implant electrodes within the inner ear is of importance for modeling the electrical field of the cochlea, designing the electrode array, and programming the associated speech processor. A 3-D reconstruction method of cochlear implant electrodes is proposed to localize individual electrodes from two X-ray views in combination with the spiral computed tomography technique. By adapting epipolar geometry to the configuration of an X-ray imaging system, we estimate individual electrode locations in the least square sense without using a patient attachment required by an existing stereophotogrammetry technique. Furthermore, our method does not require any knowledge of the intrinsic and extrinsic parameters of the imaging system. The performance of our method is studied in numerical simulation and with patient data and is found to be sufficiently accurate for clinical use. The maximum root mean-square errors measured are 0.0445 and 0.214 mm for numerical simulation and patient data, respectively.

    Title A Case of Primary Pericardial Undifferentiated Sarcoma.
    Date June 2004
    Journal Journal of Korean Medical Science
    Excerpt

    Primary pericardial sarcomas are extremely rare. The authors report a case of a 46-yr-old woman in whom a large mediastinal mass was discovered. The patient presented with cough, dyspnea, and orthopnea. Diagnostic investigations, such as echocardiography, computed tomography, and exploratory thoracotomy provided the evidence of a large mass in the mediastinum, attached by a broad base to the superior portion of the pericardium. A excisional biopsy was performed, and histologic examination of a biopsy specimen showed undifferentiated sarcoma. However, the complete removal of the mass was impossible due to adhesion to the adjacent great vessels. After the completion of the chemotherapy the patient was completely asymptomatic. However, follow-up transesophageal echocardiography showed a residual 3 x 4 cm-sized mass. The patient received the radiotherapy with a total dose of 55 Gy over 6 weeks. At present, there is no evidence of disease progression.

    Title Alignment of Ct Images of Skull Dysmorphology Using Anatomy-based Perpendicular Axes.
    Date May 2004
    Journal Physics in Medicine and Biology
    Excerpt

    Rigid body registration of 3D CT scans, based on manual identification of homologous landmarks, is useful for the visual analysis of skull dysmorphology. In this paper, a robust and simple alignment method was proposed to allow for the comparison of skull morphologies, within and between individuals with craniofacial anomalies, based on 3D CT scans, and the minimum number of anatomical landmarks, under rigidity and uniqueness constraints. Three perpendicular axes, extracted from anatomical landmarks, define the absolute coordinate system, through a rigid body transformation, to align multiple CT images for different patients and acquisition times. The accuracy of the alignment method depends on the accuracy of the localized landmarks and target points. The numerical simulation generalizes the accuracy requirements of the alignment method. Experiments using a human dried skull specimen, and ten sets of skull CT images (the pre- and post-operative CT scans of four plagiocephaly, and one fibrous dysplasia patients), demonstrated the feasibility of the technique in clinical practice.

    Title Nuclear Remodelling and the Developmental Potential of Nuclear Transferred Porcine Oocytes Under Delayed-activated Conditions.
    Date February 2004
    Journal Zygote (cambridge, England)
    Excerpt

    It is still unclear whether nuclear envelope breakdown and premature chromosome condensation are essential for the reprogramming of the donor nucleus following somatic nuclear transfer. To address this, we determined the ability of delayed-activated or simultaneously activated porcine oocytes to undergo nuclear remodelling and development following somatic cell nuclear transfer. A small microtubule aster was observed in association with decondensed chromatin following nuclear transfer, suggesting the introduction of a somatic cell centrosome. In the delayed-activated condition, most fibroblast nuclei divided into two chromosome masses and two pronuclear-like structures following transfer into oocytes. In contrast, fibroblast nuclei in the simultaneously activated condition formed a large, swollen, pronuclear-like structure. Microtubule asters were organised in the vicinity of the nucleus regardless of the number of nuclei. More reconstructed oocytes developed to the blastocyst stage in the delayed-activated condition than in the simultaneously activated condition (p < 0.05). Nine piglets were born from two recipient sows following transfer of delayed-activated reconstructed oocytes, while none developed to full term in the simultaneously activated condition. Fingerprint analysis showed that the PCR-RFLP patterns of the nine offspring were identical to that of the donor pig. These results suggest that the activation of recipient oocytes during nuclear transfer probably relates to the nuclear remodelling process, which can affect the ability of embryos created by somatic cell nuclear transfer to develop.

    Title Relation Between Insulin Resistance and Hematological Parameters in Elderly Koreans-southwest Seoul (sws) Study.
    Date January 2004
    Journal Diabetes Research and Clinical Practice
    Excerpt

    In this study, we investigated the relation between insulin resistance and hematological parameters in elderly Koreans. This study included 1314 non-diabetic subjects over the age of 60, selected from a cross-sectional study, which was conducted in 1999 in Seoul, Korea. We measured fasting and post-load 2 h plasma glucose, insulin levels, lipid profiles, anthropometric measures, and hematological parameters. The degree of insulin resistance was assessed using the homeostasis model assessment (HOMA). We found a correlation between insulin resistance and hemoglobin concentrations in non-smoking men (r=0.20, P=0.0186). In non-smoking women, insulin resistance correlated with hemoglobin (r=0.10, P=0.0017) and with white blood cell (WBC) count (r=0.15, P=0.001). Hemoglobin concentrations and WBC counts were also associated with other components of the insulin resistance syndrome such as body mass index, blood pressure, lipid profiles and fasting plasma insulin levels (surrogate for insulin resistance). Furthermore, the group in the upper quartile for insulin resistance showed higher hemoglobin concentrations and WBC counts than the lower quartile, independent of smoking status and serum iron concentrations. Using HOMA-IR as a dependent variable in a multiple regression analysis, age, body mass index (BMI), waist-to-hip ratio (WHR), systolic blood pressure, HDL cholesterol, triglyceride, WBC count, hemoglobin, hematocrit and serum TIBC were significant. Our results provide support for a relation between insulin resistance/hyperinsulinemia and hematological parameters such as hemoglobin concentrations and WBC counts in elderly Koreans. This suggests that increased erythropoiesis and subclinical inflammation could be part of the metabolic syndrome in elderly Koreans.

    Title Genetic Analysis of Phosphomannomutase/phosphoglucomutase from Vibrio Furnissii and Characterization of Its Role in Virulence.
    Date January 2004
    Journal Archives of Microbiology
    Excerpt

    The pmm gene from Vibrio furnissii, which encodes phosphomannomutase (PMM), was cloned and sequenced. The open reading frame consisted of 1,434 bp, encoding a polypeptide of 477 amino acids with a molecular mass of 53,325 Da. The predicted amino acid sequence of V. furnissii PMM showed high similarity with PMMs from other enteric bacteria, such as V. cholerae, Salmonella sp. and Escherichia coli. The PMM protein was overexpressed in E. coli as a His(6)-tagged recombinant protein. The estimated apparent K(m )and k(cat) values of the purified recombinant protein for mannose 1-phosphate were about 60 microM and 800 min(-1), respectively. To investigate the biochemical functions and the role of pmm in the virulence of V. furnissii, a pmm knock-out mutant was constructed by homologous recombination mutation. Under the various physical conditions, cell numbers of the wild-type and the mutant did not differ. Oral introduction of bacterial suspensions to a mouse model showed that the pmm-deficient mutant decreased in viability at the intestine. Microscopy of the isolated intestines from mice revealed significant damage after 3 days in intestinal mucosa infected with the wild-type as compared with the mutant. The pmm-deficient mutant caused a reduction of virulence in mice and the loss of O-antigen polysaccharide, and showed low resistance relative to the wild-type when incubated with normal human serum.

    Title Successful Withdrawal of Long-term Epoprostenol Therapy for Pulmonary Arterial Hypertension.
    Date November 2003
    Journal Chest
    Excerpt

    BACKGROUND: IV epoprostenol treatment of pulmonary arterial hypertension (PAH) has been believed to require an indefinite duration of therapy OBJECTIVE: To describe the successful discontinuation of long-term epoprostenol therapy in four patients DESIGN: Case reports SETTING: Outpatient clinic, tertiary-care hospital PATIENTS: Four patients with acutely nonvasoreactive, World Health Organization (WHO) functional class IV PAH received long-term epoprostenol therapy. All patients subsequently demonstrated normalization of pulmonary arterial pressures on epoprostenol treatment. These patients were selected for epoprostenol withdrawal INTERVENTION: Down-titration and discontinuation of epoprostenol RESULTS: All four patients were safely transitioned from epoprostenol to oral therapies and have maintained WHO functional class I-II for a mean of 11 months (range, 8 to 16 months). The duration of epoprostenol therapy prior to discontinuation averaged 5.7 years (range, 2.4 to 13.5 years) CONCLUSION: Epoprostenol may sufficiently reverse the pathogenic process in select patients with PAH to allow a transition to less complex and less invasive treatment modalities.

    Title Nox4 Mediates Angiotensin Ii-induced Activation of Akt/protein Kinase B in Mesangial Cells.
    Date August 2003
    Journal American Journal of Physiology. Renal Physiology
    Excerpt

    ANG II induces protein synthesis through the serine-threonine kinase Akt/protein kinase B (PKB) in mesangial cells (MCs). The mechanism(s) of activation of Akt/PKB particularly by G protein-coupled receptors, however, is not well characterized. We explored the role of the small GTPase Rac1, a component of the phagocyte NADPH oxidase, and the gp91phox homologue Nox4/Renox in this signaling pathway. ANG II causes rapid activation of Rac1, an effect abrogated by phospholipase A2 inhibition and mimicked by arachidonic acid (AA). Northern blot analysis revealed high levels of Nox4 transcript in MCs and transfection with antisense (AS) oligonucleotides for Nox4 markedly decreased NADPH-dependent reactive oxygen species (ROS)-producing activity. Dominant negative Rac1 (N17Rac1) as well as AS Nox4 inhibited ROS generation in response to ANG II and AA, whereas constitutively active Rac1 stimulated ROS formation. Moreover, N17Rac1 blocked stimulation of NADPH oxidase activity by AA. N17Rac1 or AS Nox4 abolished ANG II- or AA-induced activation of the hypertrophic kinase Akt/PKB. In addition, AS Nox4 inhibited ANG II-induced protein synthesis. These data provide the first evidence that activation by AA of a Rac1-regulated, Nox4-based NAD(P)H oxidase and subsequent generation of ROS mediate the effect of ANG II on Akt/PKB activation and protein synthesis in MCs.

    Title Lysophosphatidic Acid Stimulates Creb Through Mitogen- and Stress-activated Protein Kinase-1.
    Date July 2003
    Journal Biochemical and Biophysical Research Communications
    Excerpt

    Lysophosphatidic acid (LPA) is a growth factor-like phospholipid that elicits a variety of cellular responses in numerous cell types, including neurons, immune cells, and fibroblasts. In this report, we investigated the possibility that LPA activates the transcription factor cAMP response element-binding protein, CREB, in Rat-2 fibroblast cells. CREB is activated in many cells downstream of signaling events, such as growth factor and neurotrophin stimulation. We found that LPA rapidly stimulated phosphorylation of CREB at Ser133 in a time- and dose-dependent manner, as revealed by immunoblot analysis with a phospho-specific antibody recognizing CREB on Ser133. LPA-induced phosphorylation of CREB was dependent on the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK). Inhibition of ERK1/2 with PD98059 and of p38 MAPK with SB203580 efficiently blocked LPA-mediated phosphorylation of CREB. The LPA-induced CREB phosphorylation was abolished by H89, an inhibitor of mitogen- and stress-activated protein kinase-1 (MSK1). Together, these data suggest that LPA stimulates nuclear transcription factor CREB via mitogen-activated protein kinase signaling components, ERK1/2, p38 MAPK, and MSK1 in Rat-2 fibroblast cells.

    Title Factor Analysis of the Metabolic Syndrome Among Elderly Koreans--the South-west Seoul Study.
    Date March 2003
    Journal Diabetic Medicine : a Journal of the British Diabetic Association
    Excerpt

    AIMS: To examine the relationship between the components of the metabolic syndrome and to explore whether insulin resistance unifies the clustering of components of the metabolic syndrome among urban elderly Koreans using exploratory factor analysis. METHODS: We included 1314 non-diabetic subjects over the age of 60 years, selected from a cross-sectional study, which was conducted in 1999 in Seoul, Korea. Factor analysis was carried out using the principle components analysis with Varimax orthogonal rotation of the components of the metabolic syndrome. RESULTS: We found four major factors of cardiovascular disease risk variables in our study subjects. Impaired glucose tolerance, dyslipidaemia, hypertension and obesity aggregated as the major domain. Obesity and dyslipidaemia variables were closely related and loaded on the same factor. However, hypertension was not linked closely with other factors of the metabolic syndrome. CONCLUSIONS: Insulin resistance is not the only contributor to the metabolic syndrome among urban elderly Koreans. Although the components of the metabolic syndrome were closely related, the finding of more than one factor suggests that more than one pathophysiological mechanism underlies full expression of the metabolic syndrome among elderly Koreans.

    Title Chronic Thromboembolic Pulmonary Hypertension.
    Date January 2003
    Journal Progress in Cardiovascular Diseases
    Excerpt

    Chronic thromboembolic pulmonary hypertension (CTEPH) should be differentiated from other etiologies of pulmonary hypertension since surgical intervention may be potentially curative. The presentation of this illness is nonspecific and may mimic other cardiopulmonary disease states. Without treatment, progressive pulmonary hypertension, right heart failure, and death will ensue. Echocardiography, lung ventilation-perfusion scan, right heart catheterization, and angiography are required for proper diagnosis and preoperative assessment. Definitive treatment requires surgical resection of thromboembolic material. The role of medical therapy remains to be defined.

    Title Comparison of Ada and Who Criteria for the Diagnosis of Diabetes in Elderly Koreans.
    Date January 2003
    Journal Diabetic Medicine : a Journal of the British Diabetic Association
    Excerpt

    This study was conducted to compare the prevalence and cardiovascular risk factors of different categories of glucose tolerance in the elderly Korean population using World Health Organization (WHO) and American Diabetes Association (ADA) criteria.

    Title Improvement of Multi-channel Isolated Bio-potential Amplifiers Using Multiplexing.
    Date November 2002
    Journal Physiological Measurement
    Excerpt

    We propose a simple isolated link circuit for a multi-channel bio-potential amplifier, by adapting the multiplexing/demultiplexing technique that is generally used in digital circuit design. The reduced number of isolation amplifiers, due to the multiplexing technique, results in an increase in the amount of isolation, as well as a reduction in manufacturing cost. The simple incorporation of a dead-zone in multiplexed timing, and a pull-down resistor in the multiplexed signal line, enables a multiple isolated bio-signal transmission over the shared isolation amplifier, with an affordable inter-channel cross talk.

    Title Endothelin in Health and Disease: Endothelin Receptor Antagonists in the Management of Pulmonary Artery Hypertension.
    Date September 2002
    Journal Journal of Cardiovascular Pharmacology and Therapeutics
    Excerpt

    Endothelin (ET) has been identified as playing a fundamental role in many disease processes. Therapeutic efforts at interrupting ET's pathologic effects have focused on endothelin receptor antagonists (ERAs), of which two, bosentan and sitaxsentan, have been evaluated for the treatment of both primary and secondary pulmonary arterial hypertension (PAH). We discuss the multiple actions of ET, its role in various disease states, and the effects of ET receptor stimulation and blockade. Current classification and management of PAH are reviewed, along with the promise of greatly improved treatment generated by recent and ongoing clinical trials using ERAs.

    Title A Case of Adrenocortical Tumor Coexisted with Paragangliomas.
    Date February 2002
    Journal Endocrine Journal
    Excerpt

    We report a case of adrenocortical tumor that coexisted with paragangliomas. A 35-year-old woman was admitted to the hospital because of left upper abdominal pain. A palm-sized mass was palpated at left upper quadrant. Hormonal studies revealed the features of pheochromocytoma. An emergency operation was performed because hemorrhage of the tumor was suspected. A 10 cm diameter ruptured mass was found in the left adrenal area and other tumors were also noted adjacent to inferior vena cava (IVC). The pathologic report revealed that the adrenal mass was an adrenocortical tumor with hemorrhagic necrosis and that the tumors adjacent to IVC were paragangliomas. This was the first case of adrenocortical tumor with paragangliomas in our Medline search result, hence we report the case with a review of the literature.

    Title A Case of Successful Primary Coronary Intervention for the Total Occlusion of Left Main Stem with the Aid of Abciximab.
    Date October 2001
    Journal Journal of Korean Medical Science
    Excerpt

    A 61-yr-old male patient presented with severe chest pain with cardiogenic shock due to an extensive anterolateral myocardial infarction. Two-dimensional echocardiogram showed severe left ventricular systolic dysfunction (ejection fraction=17%). Emergent coronary angiogram obtained immediately after placing temporary pacing electrode revealed total thrombotic occlusion in the left main stem. We performed direct coronary intervention using kissing balloon technique with the aid of Abciximab (ReoPro) infusion. Residual stenosis with thrombus remained even after high pressure balloon dilatations, therefore we placed two stents, one in the ostia of left anterior descending (LAD) and the other in left circumflex artery (LCX). Coronary angiogram after kissing stents showed improved LAD and LCX flows without residual stenosis. Chest pain resolved and blood pressure normalized after coronary intervention. The whole procedure time was 15 min. Follow-up coronary angiogram taken one week later showed patent previous stented arteries, and echocardiography demonstrated 40% of left ventricular ejection fraction. The clinical course for one-year follow-up was uneventful.

    Title A Case of Torsade De Pointes Associated with Hypopituitarism Due to Hemorrhagic Fever with Renal Syndrome.
    Date October 2001
    Journal Journal of Korean Medical Science
    Excerpt

    We describe a 51-yr-old man presenting with syncope due to torsade de pointes. The torsade de pointes was refractory to conventional medical therapy, including infusion of isoproterenol, MgSO4, potassium, lidocaine, and amiodarone. His past history, physical findings, and hormone study confirmed that QT prolongation was caused by anterior hypopituitarism that developed as a sequela of hemorrhagic fever with renal syndrome. The long QT interval with deep inverted T wave was completely normalized 4 weeks after starting steroid and thyroid hormone replacement. Hormonal disorders should be considered as a cause of torsade de pointes, because this life-threatening arrhythmia can be treated by replacing the missing hormone.

    Title Fra-1 Expression in Malignant and Benign Thyroid Tumor.
    Date October 2001
    Journal The Korean Journal of Internal Medicine
    Excerpt

    BACKGROUND: The differential diagnosis of thyroid nodules is very important in deciding the treatment modality and the fine needle aspiration is the best diagnostic method. But, there are some limitations in use because of inadequate test materials and difficulty in interpreting. According to the study of oncogene and tumor suppressor gene about the origin of thyroid tumor, expression of Fra-1, one of AP-1 complex, is increased in thyroid neoplasm, though not present in the normal tissue. So, there is a possibility that it will be used as a method for the differential diagnosis of thyroid nodules. We tried to know whether presence or absence of Fra-1 expression can be used as a diagnostic method in differential diagnosis of thyroid nodules using the immunohistochemical (IHC) staining method. METHODS: In 4 types of thyroid tumor that were confirmed by histologic diagnosis after operation (18 cases of adenomatous goiter, 16 cases of follicular adenoma, 30 cases of papillary cancer, 10 cases of follicular cancer), IHC staining method was performed to evaluate the expression of Fra-1. RESULTS: In papillary and follicular thyroid cancers, the expression of Fra-1 was stronger than in benign thyroid tumor, but there was no difference in Fra-1 expression between the two types of carcinoma. Weak expression of Fra-1 was observed in all cases of follicular adenoma, though it was weaker than in carcinoma, and it was also weakly expressed only in some cases (33%) of adenomatous goiter. CONCLUSION: The expression of Fra-1 was stronger in thyroid cancer than in benign thyroid tumor, but it was impossible to differentiate thyroid cancer from benign thyroid tumor by presence or absence of Fra-1 expression using IHC staining method.

    Title In Vitro and in Vivo Evaluation of Albumin Synthesis Rate of Porcine Hepatocytes in a Flat-plate Bioreactor.
    Date October 2001
    Journal Artificial Organs
    Excerpt

    Several configurations of extracorporeal bioartificial liver devices have been developed for the potential treatment of fulminant hepatic failure or as a bridge to liver transplantation. Recently, we developed a microchannel flat-plate bioreactor with an internal membrane oxygenator in which porcine hepatocytes are cultured as a monolayer on the bottom glass surface. In the present study, we investigated synthetic function of porcine hepatocytes in the bioreactor in both in vitro and in vivo flow circuit models. In vitro, albumin synthesis was stable in the bioreactor for up to 4 days of perfusion. In vivo, with the extracorporeal connection of the bioreactor to rat vasculature, porcine albumin was detectable for 24 h in the rat plasma. We also developed a simple mathematical model to predict the in vivo porcine albumin concentration in rat plasma. These results indicate that this configuration of a microchannel flat-plate bioreactor has potential as a liver support device and warrants further investigation.

    Title Angiotensin Ii Activates Akt/protein Kinase B by an Arachidonic Acid/redox-dependent Pathway and Independent of Phosphoinositide 3-kinase.
    Date October 2001
    Journal The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology
    Excerpt

    Angiotensin II (Ang II) exerts contractile and trophic effects in glomerular mesangial cells (MCs). One potential downstream target of Ang II is the protein kinase Akt/protein kinase B (PKB). We investigated the effect of Ang II on Akt/PKB activity in MCs. Ang II causes rapid activation of Akt/PKB (5-10 min) but delayed activation of phosphoinositide 3-kinase (PI3-K) (30 min). Activation of Akt/PKB by Ang II was not abrogated by the PI3-K inhibitors or by the introduction of a dominant negative PI3-K, indicating that in MCs, PI3-K is not an upstream mediator of Akt/PKB activation by Ang II. Incubation of MCs with phospholipase A2 inhibitors also blocked Akt/PKB activation by Ang II. AA mimicked the effect of Ang II. Inhibitors of cyclooxygenase-, lipoxyogenase-, and cytochrome P450-dependent metabolism did not influence AA-induced Akt/PKB activation. However, the antioxidants N-acetylcysteine and diphenylene iodonium inhibited both AA- and Ang II-induced Akt/PKB activation. Dominant negative mutant of Akt/PKB or antioxidants, but not the dominant negative form of PI3-K, inhibited Ang II-induced protein synthesis and cell hypertrophy. These data provide the first evidence that Ang II induces protein synthesis and hypertrophy in MCs through AA/redox-dependent pathway and Akt/PKB activation independent of PI3-K.

    Title Design of a Pc-based Multimedia Telemedicine System for Brain Function Teleconsultation.
    Date June 2001
    Journal International Journal of Medical Informatics
    Excerpt

    During time-critical brain surgery, the detection of developing cerebral ischemia is particularly important because early therapeutic intervention may reduce the mortality of the patient. The purpose of this system is to provide an efficient means of remote teleconsultation for the early detection of ischemia, particularly when subspecialists are unavailable. The hardware and software design architecture for the multimedia brain function teleconsultation system including the dedicated brain function monitoring system is described. In order to comprehensively support remote teleconsultation, multi-media resources needed for ischemia interpretation were included: EEG signals, CSA, CD-CSA, radiological images, surgical microscope video images and video conferencing. PC-based system integration with standard interfaces and the operability over the Ethernet meet the cost-effectiveness while the modular software was customized with a diverse range of data manipulations and control functions necessary for shared workspace and standard interfaces.

    Title Clinical Characteristics of Unexplained Sudden Cardiac Death in Korea.
    Date May 2001
    Journal Japanese Circulation Journal
    Excerpt

    In Western countries, sudden cardiac death (SCD) is closely related to coronary artery disease, but in Korea the clinical characteristics of SCD are not well determined. Over a 4-year period (June 1995 to May 1999), 186 cases of SCD, ranging in age from 16 to 75 years, were admitted to the Chonnam National University Hospital. In 82 (44.1%) of these, neither symptoms nor evidence of structural heart disease was found and so their clinical characteristics were investigated. There were 66 (80.5%) men and 16 (19.5%) women (male/female ratio = 4.1:1). The mean age was 50 +/- 14 years: 19 (23.2%) were in their 40s, 21 (25.6%) in their 50s, and 17 (20.7%) in their 60s. The time of circulatory collapse witnessed in 68 cases of SCD showed 2 peaks: between midnight and 03.00h (n=16, 23.5%) and between 09.00h and midday (n=15, 22.1%). Unexplained SCD occurred at home in 48 (64.9%) cases and on the street in 12 (16.2%); it occurred during normal daily routine activity in 23 (39.6%) and during sleep in 15 (25.9%). Thirty-three patients (40.2%) experienced various prodromal symptoms, including chest discomfort (n=13, 15.9%) and dyspnea (n=8, 9.8%). The electrocardiogram taken on arrival recorded asystole in 65 (79.3%) and ventricular fibrillation in 17 (20.7%). Idiopathic ventricular fibrillation was diagnosed in 14 (10 men, 4 women; 45 +/- 11 years) of 21 patients who recovered spontaneous circulation. Five (6.1%) patients were discharged alive, and an implantable cardioverter-defibrillator was implanted in 2. Unexplained SCD is common in Korea and develops predominantly in middle-aged males around midnight or in the late morning usually with no prodromal symptoms (59.8%). Idiopathic ventricular fibrillation is thought to be one of the important causes.

    Title Successful Management of Intractable Coronary Spasm with a Coronary Stent.
    Date March 2001
    Journal Japanese Circulation Journal
    Excerpt

    Although the long-term survival of patients suffering from coronary spasm is usually excellent, serious complications can develop, such as disabling pain, myocardial infarction, ventricular tachyarrhythmias, atrioventricular block and sudden cardiac death. A 40-year-old man who had intractable chest pain from coronary artery spasm suffered ventricular fibrillation and an acute anterior myocardial infarction upon first admission. The patient underwent a coronary angiogram, which revealed a spontaneous focal spasm at the proximal left anterior descending coronary artery (LAD). He was treated by the combination of nitrate and calcium channel blocker, but continued to complain of severe chest pain despite intensive medical therapy and he had to be treated in the emergency room 5 times during an 8-month follow-up period. An ergonovine coronary angiogram was performed and an intracoronary ultrasound examination, which revealed a focal spasm at the same site of the proximal LAD with a small amount of localized eccentric atheromatous plaque. A coronary artery stent was placed in the proximal LAD and his symptoms resolved. A follow-up coronary angiogram was performed 3 years after stenting and the stent remained patent without any in-stent restenosis or spasm.

    Title Serum Insulin, Proinsulin and Proinsulin/insulin Ratio in Type 2 Diabetic Patients: As an Index of Beta-cell Function or Insulin Resistance.
    Date March 2001
    Journal The Korean Journal of Internal Medicine
    Excerpt

    Although insulin resistance and decreased insulin secretion are characteristics of established type 2 DM, which of these metabolic abnormalities is the primary determinant of type 2 DM is controversial. It is also not well known how insulin resistance and beta cell dysfunction influence serum insulin, proinsulin, proinsulin/insulin ratio in type 2 DM.

    Title Role of Vascular Endothelial Growth Factor in Diabetic Nephropathy.
    Date January 2001
    Journal Kidney International. Supplement
    Excerpt

    Vascular endothelial growth factor (VEGF) is a potent cytokine that is considered to be an important mediator in the pathogenesis of endothelial dysfunction in diabetes.

    Title Expression of Enhanced Green Fluorescent Protein (egfp) and Neomycin Resistant (neo(r)) Genes in Porcine Embryos Following Nuclear Transfer with Porcine Fetal Fibroblasts Transfected by Retrovirus Vector.
    Date December 2000
    Journal Molecular Reproduction and Development
    Excerpt

    In this study, we demonstrated expression of enhanced green fluorescent protein (EGFP) and neomycin resistant (Neo(R)) genes in porcine embryos following nuclear transfer from porcine fetal fibroblasts (PFFs) transduced with the EGFP and Neo(R) genes by retrovirus-mediated infection. Nuclear transfer of the nonstarved transfected PFF into enucleated oocytes was accomplished by cell to cell fusion. Out of 188 porcine eggs reconstructed by nuclear transfer, 116 (61.7%) eggs cleaved and 25 (13.3%) developed to morula and blastocyst stages. Of these 25 morulae and blastocysts, 25 (100%) embryos emitted green fluorescence. Expression of the both EGFP and Neo(R) genes was detected as early as the 2-cell stage. As determined by EGFP gene expression, mosaicism was not observed in any embryo. These results suggest that porcine oocytes reconstructed by nuclear transfer with transfected PFFs can successfully develop to the blastocyst stage. In addition, this approach might be applicable to the production of transgenic pigs with complex genetic modifications.

    Title Simultaneous Determination of Fenfluramine and Phentermine in Urine Using Gas Chromatography Mass Spectrometry with Pentafluoropropionic Anhydride Derivatization.
    Date November 2000
    Journal Therapeutic Drug Monitoring
    Excerpt

    Fenfluramine and phentermine ('fen-phen') are stimulants used primarily for weight loss that have a causative association with serious health problems. Though voluntarily removed from the market by their manufacturers and the FDA in September of 1997, both drugs occasionally reappear in the clinical and forensic setting from individuals who retained old prescriptions, transported the drugs from foreign countries, or 'stockpiled' the medications immediately before their removal from the market. The authors describe an analytical method for simultaneous detection of fenfluramine, phentermine, and the internal standard, N-propylamphetamine, in urine using pentafluoropropionic anhydride derivatization. Detection using and mass spectrometry is described. Baseline resolution of the analytes was achieved in the presence of four other common sympathomimetic amines. The increased molecular weights, better peak profiles, and characteristic fragments containing portions of both derivatizing agent and parent compound aid in the unambiguous identification of these analytes.

    Title Serum Ferritin in Healthy Subjects and Type 2 Diabetic Patients.
    Date September 2000
    Journal Yonsei Medical Journal
    Excerpt

    In order to study the relationship between the serum ferritin level and the components of the insulin resistance syndrome in type 2 diabetic patients, we evaluated fifty type 2 diabetic patients who were selected according to NDDG/WHO criteria from those patients attending Korea University Hospital from 1997 to 1998. Twenty-five healthy non-diabetic subjects of comparable age and sex distribution acted as a control group. The results showed that the value of log ferritin was higher in the type 2 diabetes patients than the control subjects, but not at a statistically significant level (p = 0.09). Log ferritin was correlated with fasting blood sugar level (r = 0.235, p = 0.048) and body mass index (BMI) (r = 0.285, p = 0.05). In the type 2 diabetic patients, log ferritin was correlated with fasting C-peptide (r = 0.478, p = 0.009). In the control subjects, log ferritin was correlated only with BMI (r = 0.477, p = 0.012). In a stepwise multiple regression analysis, the diabetic group showed a significant correlation between fasting C-peptide and log ferritin (p = 0.001). In the control group, the fasting sugar level was significantly correlated with log ferritin (p = 0.034). These results suggest that serum ferritin can be employed as a marker of not only glucose homeostasis but also insulin resistance both in type 2 diabetic and control subjects.

    Title Expression of Vascular Endothelial Growth Factor in Response to High Glucose in Rat Mesangial Cells.
    Date August 2000
    Journal The Journal of Endocrinology
    Excerpt

    Diabetic nephropathy associated with hyperglycemia is characterized by glomerular hyperfiltration and endothelial dysfunction. Vascular endothelial growth factor (VEGF) is known to be primarily involved in neoangiogenesis and increased endothelial permeability. The purpose of this study was to investigate VEGF expression in response to high glucose in rat cultured mesangial cells and to identify its signal pathway via protein kinase C (PKC). Rat mesangial cells were cultured with different concentrations of glucose: normal (5 mM d-glucose), medium (15 mM d-glucose) and high (30 mm d-glucose). Calphostin-C as a PKC inhibitor and phorbol myristate acetate (PMA) as a PKC downregulator were instillated into culture media to evaluate the role of PKC in mediating the glucose-induced increase in VEGF expression. High glucose increased expression of VEGF at the mRNA and protein levels, identified by semi-quantitative RT-PCR and western blotting, within 3 h and in a time- and glucose concentration-dependent manner. Calphostin-C and PMA inhibited glucose-induced increases in VEGF expression at the mRNA and protein levels. In conclusion, high glucose can directly increase VEGF expression in rat mesangial cells via a PKC-dependent mechanism. These results suggest that VEGF could be a potential mediator of glomerular hyperfiltration and proteinuria in diabetic nephropathy.

    Title Erythropoietin Does Not Affect Nitric Oxide System in Rats with Chronic Renal Failure.
    Date July 2000
    Journal Journal of Korean Medical Science
    Excerpt

    We investigated to see whether an altered role of nitric oxide (NO) system is involved in erythropoietin (EPO)-induced hypertension in chronic renal failure (CRF). Male Sprague-Dawley rats were five-sixths nephrectomized to induce CRF. Six weeks after the operation, EPO or vehicle was injected for another 6 weeks. Plasma and urine nitrite/nitrate (NOx) levels were determined. Expression of NO synthase (NOS) proteins in the aortae and kidneys were also determined. In addition, the isometric tension of isolated aorta in response to acetylcholine and nitroprusside was examined. Blood pressure progressively rose in CRF groups, the degree of which was augmented by EPO treatment. Plasma NOx levels did not differ among the groups, while urine NOx levels were lower in CRF groups. Endothelial NOS expression was lower in the kidney and aorta in CRF rats, which was not further affected by EPO-treatment. The inducible NOS expression in the kidney and aorta was not different among the groups. Acetylcholine and sodium nitroprusside caused dose-dependent relaxations of aortic rings, the degree of which was not altered by EPO-treatment. Taken together, EPO-treatment aggravates hypertension in CRF, but altered role of NO system may not be involved.

    Title Diminished Adenylate Cyclase Activity and Aquaporin 2 Expression in Acute Renal Failure Rats.
    Date May 2000
    Journal Kidney International
    Excerpt

    The present study was aimed at investigating the changes of aquaporin 2 (AQP2) expression and its underlying mechanisms in ischemic acute renal failure (ARF).

    Title Fertilization and in Vitro Development of Porcine Oocytes Following Intracytoplasmic Injection of Round Spermatid or Round Spermatid Nuclei.
    Date April 2000
    Journal Theriogenology
    Excerpt

    The objective of this study was to determine fertilization rates and developmental ability of porcine oocytes following injection of round spermatid and round spermatid nucleus with artificial activation either 2 h before or immediately after injection. Electrical stimulation at 2 h before spermatid injection significantly increased the incidence of normal fertilization compared with that following injection without stimulation or with stimulation immediately after injection. Incidences of formation of 2 pronuclei and of apposition were not different in oocytes following intracytoplasmic spermatid and spermatid nucleus injection. Chromosome analysis revealed that most oocytes were diploid either following round spermatid or round spermatid nucleus injection. There was no diploid set of chromatin in oocytes at 20 h following sham injection. At 6 d following injection blastocoele formation was seen in the oocytes following round spermatid (25%) and round spermatid nucleus injection (27%). However, none of the oocytes developed to the blastocyst stage 6 d following sham injection. The average cell numbers of blastocysts 8 d after injection of spermatid and spermatid nucleus were 99 and 87, respectively. These results suggest that electrical stimulation before injection enhances the incidence of fertilization following round spermatid injection in the pig. Our study also indicates that either the round spermatid or it's nucleus can be used to produce viable embryos by injection into unfertilized porcine oocytes.

    Title Bcg Vaccine Prevents Insulitis in Low Dose Streptozotocin-induced Diabetic Mice.
    Date March 2000
    Journal Diabetes Research and Clinical Practice
    Excerpt

    Autoimmune type 1 diabetes mellitus is caused by the immunologic destruction of pancreatic beta-cells; therefore, there have been many attempts at immunologic modulation as a block or prevention of the underlying process. The aim of this study is to investigate the effect of BCG vaccination on low dose streptozotocin-induced diabetic (LDSD) mice. The mice were pretreated with BCG 7 days before starting low dose streptozotocin (STZ), observed body weight and blood glucose for 2 months, then analyzed the severity of the STZ-induced insulitis after the animals were sacrificed. In this experiment, the mean body weights in the BCG-STZ group on days 1, 19, 33, 47, and 61 of the experiment were 37.5 +/- 3.6, 37.3 +/- 3.6, 37.5 +/- 3.5, 39.4 +/- 3.9, and 39.3 +/- 4.5 (g), respectively. Those in the STZ group were 37.7 +/- 3.5, 38.3 +/- 4.5, 38.4 +/- 3.9, 36.2 +/- 4.5, and 36.3 +/- 4.0 (g), respectively (P < 0.05). The mean blood glucose levels in the BCG-STZ group on days 1, 19, 33, 47, and 61 were 106.5 +/- 8, 150 +/- 37, 147 +/- 54, 143 +/- 60, and 142 +/- 66 (mg/dl), respectively. Those in the STZ group were 103 +/- 12, 196 +/- 90, 261 +/- 236, 236 +/- 91, and 224 +/- 89 (mg/dl), respectively (P < 0.05). The numbers developing grade 0, I, II, III, and IV insulitis in the BCG-treated group were 63, 48, 33, 4, and 2, respectively, and in the control group were 16, 23, 31, 45, and 35, respectively. This study indicates that BCG vaccination reduces the development of insulitis and overt diabetes in LDSD mice.

    Title A Case of Prominent Epicardial Fat Mimicking a Tumor on Echocardiography.
    Date January 2000
    Journal Journal of Korean Medical Science
    Excerpt

    Epicardial fat may anteriorly produce an echo-free space that can be mistaken for pericardial fluid. We recently experienced a 67-year-old woman with prominent epicardial fat which was presented as an echogenic tumor-like mass. She underwent open pericardiostomy to relieve large amount of pericardial effusion. Operative findings revealed only prominent epicardial fat. Biopsy of the pericardial and fat tissues revealed an inflammation and normal fat cells without any malignant cell infiltration.

    Title Implementation of a Low-cost Pacs/cr for Clinical Use in Yonsei Cardiovascular Center.
    Date September 1999
    Journal Studies in Health Technology and Informatics
    Excerpt

    The PACS/CR for clinical use in Yonsei Cardiovascular Center has been designed and implemented. Our system is open architecture to comply with emerging standards such as DICOM. database SQL, TCP/IP and to reduce operational and maintenance costs, PC-based low cost workstations running Microsoft Windows, database as Microsoft SQL based on Client/Server, Long-term storage using CD-ROM Jukebox are developed. Also, auto routing and image pre-fetching are implemented.

    Title Intracytoplasmic Injection of Porcine, Bovine, Mouse, or Human Spermatozoon into Porcine Oocytes.
    Date July 1999
    Journal Molecular Reproduction and Development
    Excerpt

    We determined the incidence of activation, male pronuclear formation, and apposition of pronuclei in porcine oocytes following intracytoplasmic injection of various porcine sperm components and foreign species spermatozoa, such as that of cattle, mouse or human. The porcine oocytes were activated by injection of a spermatozoon or an isolated sperm head. In contrast, injection of either sperm tail or a trypsin- or NaOH-treated sperm head failed to induce oocyte activation. Because injection of mouse, bovine, or human spermatozoon activated porcine oocytes, the sperm-borne activation factor(s) is not strictly species-specific. Male pronuclear formation and pronuclear apposition were observed in porcine oocytes following injection of porcine, bovine, mouse or human spermatozoa. Electrical stimulation following sperm cell injection did not enhance the incidence of male pronuclear formation or pronuclear apposition compared with sperm cell injection alone (P > 0.1). Following porcine sperm injection, the microtubular aster was organized from the neck of the spermatozoon, and filled the whole cytoplasm. In contrast, following injection of bovine, mouse, or human spermatozoon, the maternal-derived microtubules were organized from the cortex to the center of the oocytes, which seems to move both pronuclei to the center of oocytes. Cleavage to the two-cell stage was observed at 19-21 hr after injection of porcine spermatozoon. However, none of the oocytes following injection of mouse, bovine, or human spermatozoa developed to the mitotic metaphase or the two-cell stage. These results suggested that the oocyte activating factor(s) is present in the perinuclear material and that it is not species-specific for the porcine oocyte. Self-organized microtubules seemed to move the pronuclei into center of oocytes when foreign species spermatozoa were injected into porcine oocytes.

    Title The Effects of Antiplatelet Agents in the Prevention of Ventricular Tachyarrhythmias During Acute Myocardial Ischemia in Rats.
    Date June 1999
    Journal Japanese Heart Journal
    Excerpt

    Experiments were performed in rat models to study the effectiveness of various antiplatelet agents in the prevention of ventricular tachyarrhythmias during acute myocardial ischemia. The time to the onset of ST-segment elevation and initiating ventricular arrhythmias, frequency and incidence of ventricular arrhythmias, and mortality rates were observed during acute myocardial ischemia (20 minutes) induced by ligation of the proximal left anterior descending coronary artery (LAD) in anesthetized rats. Four groups were studied: Control group (n = 10, not pretreated); Aspirin pretreated group (n = 10, 300 mg/kg p.o. for 1 wk); Ticlopidine pretreated group (n = 10, 200 mg/kg p.o. for 1 wk); and Abciximab (Platelet glycoprotein IIb/IIIa receptor antagonist) pretreated group (n = 10, 2 mg/kg i.v. 10-20 minutes before an experiment). No significant difference was observed in the time to the onset of ST-segment elevation and ventricular arrhythmias between the groups. The incidence of ventricular tachycardia (VT) in the abciximab group was significantly lower than in the control group (p < 0.05) and ventricular fibrillation (VF) in the aspirin and ticlopidine group was significantly lower than in the control group (p < 0.05). The mortality rate in the ticlopidine group was significantly lower than in the control group (p < 0.01). This study suggests aspirin, ticlopidine, and abciximab can effectively prevent VT or VF during acute myocardial ischemia induced by nonthrombotic occlusion and its antiarrhythmic effect may lead to prolonged survival.

    Title Altered Renal Expression of Nitric Oxide Synthase Isozymes in Spontaneously Hypertensive Rats.
    Date April 1999
    Journal The Korean Journal of Internal Medicine
    Excerpt

    The present study was aimed at exploring whether the pathogenesis of hypertension is related with an altered expression of nitric oxide synthase (NOS) isozymes, i.e., bNOS, iNOS and ecNOS.

    Title Fertilization of Porcine Oocytes Following Intracytoplasmic Spermatozoon or Isolated Sperm Head Injection.
    Date February 1999
    Journal Molecular Reproduction and Development
    Excerpt

    We demonstrated normal fertilization processes (as determined by pronuclear formation, pronuclear apposition and syngamy) in porcine oocytes either following intracytoplasmic spermatozoon (ICSI) or isolated sperm head injection. Microtubule organization and chromatin configuration were investigated in these oocytes during the first cell cycle. Following ICSI, the microtubular aster was organized from the neck of the spermatozoon and filled the whole cytoplasm. These male-derived microtubules appear to move both pronuclei to the center of oocytes. These cytoskeletal changes are analogous to those seen following conventional fertilization. In contrast, following isolated sperm head injection, the sperm aster was not seen. Instead, the microtubule matrix was organized from the cortex and then filled the whole cytoplasm in all cases in normally fertilized oocytes following injection (n=35). This organization is similar to what has been shown in the parthenogenetically activated oocytes. Chromosome analysis revealed that the oocytes injected with isolated sperm heads were fertilized normally. At 7 days following injection, the incidence of blastocoele formation following ICSI (38%) and isolated sperm head injection (22%) was higher than that following sham injection (2%). These results suggested that successful fertilization and preimplantation development occurred in porcine oocytes following either ICSI or isolated sperm head injection. Our results also indicated that fertilization processes can occur by self-assembled microtubules within cytoplasm in the absence of a sperm centrosome.

    Title Effect of Cytochalasin B and Cycloheximide on the Activation Rate, Chromosome Constituent and in Vitro Development of Porcine Oocytes Following Parthenogenetic Stimulation.
    Date January 1998
    Journal Reproduction, Fertility, and Development
    Excerpt

    Activation rate, chromosome constituent and developmental pattern of porcine oocytes was examined in the presence and absence of cytochalasin B and cycloheximide following parthenogenetic stimulation. Treatment with cycloheximide after ethanol or Ca2+ ionophore treatment increased the incidence of activation. The percentage of oocytes with two or more female pronuclei was higher (P < 0.05) in oocytes treated with cytochalasin B than in control or cycloheximide-treated oocytes. Treatment with both electrical stimulation and cytochalasin B increased the incidence of diploid chromosome spreads, and accelerated development to the morula and blastocyst stage compared with the control and cycloheximide-treated groups, suggesting a role of ploidy in the development of parthenote.

    Title A K-ras Oncogene Increases Resistance to Sulindac-induced Apoptosis in Rat Enterocytes.
    Date January 1998
    Journal Gastroenterology
    Excerpt

    BACKGROUND & AIMS: Mutations of c-K-ras occur commonly in colonic neoplasms. The aim of this study was to determine how c-K-ras mutations alter the responses to the chemopreventive agent sulindac. METHODS: The parental rat intestinal cell line IEC-18 and c-K-ras-transformed derivatives were treated with sulindac sulfide. Cell cycle distribution was determined by flow-cytometric analysis (fluorescence-activated cell sorter), apoptosis by DNA fragmentation (laddering), flow cytometry, and microscopy, and changes in gene expression by immunoblotting. RESULTS: Sulindac sulfide inhibited cell growth and induced apoptosis in a time- and dose-dependent manner more rapidly in and at lower concentrations in parental cells than ras-transformed cells. Expression of the sulindac sulfide arrested cells in G0/G1, but cells entered apoptosis throughout the cell cycle. Proapoptotic protein Bak was relatively high in untreated parental cells and increased markedly after sulindac sulfide but was low in untreated ras-transformed cells and did not increase after sulindac sulfide. Expression of other Bcl-2 family members was unchanged after sulindac sulfide. However, sulindac sulfide reduced levels of cyclin D1 protein and cyclin E- and cyclin D1-associated kinase activity. CONCLUSIONS: c-K-ras-transformed enterocytes are relatively resistant to sulindac sulfide-induced growth inhibition and apoptosis, which may result from specific reduction of bak expression.

    Title Design of a Medical Image Processing Software for Clinical-pacs.
    Date November 1997
    Journal Yonsei Medical Journal
    Excerpt

    Software modules for interactive display, manipulation and retrieval of medical images have been designed for a Picture Archiving and Communications System (PACS). The target of these modules is not for a high-end diagnostic workstation for radiologists, but for a PC-based low cost clinical workstation for a referring physician. This software is constructed based on a concept of an object-oriented language which is designed to be modular and expandable. It consists of several functional modules: (a) a communication module for image retrieval, (b) a standard module for the interpretation of the DICOM images, (c) a user interface module for the non-computer oriented clinicians and (d) a tool module for viewing and manipulating images as well as editing the annotation.

    Title Alterations of Intrarenal Renin-angiotensin and Nitric Oxide Systems in Streptozotocin-induced Diabetic Rats.
    Date October 1997
    Journal Kidney International. Supplement
    Title Effects of Oviductal Fluid and Heparin on Fertility and Characteristics of Porcine Spermatozoa.
    Date August 1997
    Journal Zygote (cambridge, England)
    Excerpt

    The objective of this study was to determine the effects of oviductal fluid and heparin on sperm penetration and the characteristics of spermatozoa. The addition of oviductal fluid and heparin to the fertilisation medium decreased sperm penetration and the mean number of spermatozoa in penetrated eggs. The number of spermatozoa firmly bound to zona pellucida was also decreased in the presence of oviductal fluid and heparin. Chlortetracycline (CTC) fluorescence patterns were used to determine the incidence of capacitation and the acrosome reaction. The proportion of capacitated and acrosome-free spermatozoa increased when spermatozoa were exposed for 1.5 and 3 h to oviductal fluid and heparin. In contrast heparin alone did not increase the number of capacitated spermatozoa at these time points. These results suggest that factor(s) in oviductal secretions reduce polyspermic fertilisation and the number of spermatozoa that will penetrate porcine oocytes. The reduction of polyspermic penetration by oviductal secretions may be due to a reduced number of spermatozoa in the fertilisation medium with an intact acrosome.

    Title Antisense to Cyclin D1 Inhibits the Growth and Tumorigenicity of Human Colon Cancer Cells.
    Date April 1997
    Journal Cancer Research
    Excerpt

    Cyclin D1 plays an important role in regulating the progression of cells through the G1 phase of the cell cycle. This gene is frequently overexpressed in human colon cancer. To address the role of cyclin D1 in growth control and tumorigenesis in this disease, we have overexpressed an antisense cyclin D1 cDNA construct in the human colon cancer cell line SW480E8, which expresses high levels of cyclin D1. The integration and expression of the antisense construct was verified by Southern and Northern blot analyses, respectively, and resulted in decreased expression of the cyclin D1 protein. This was associated with decreased levels of the Rb and p27Kip1 proteins. In addition, the hypophosphorylated form of Rb was increased in these cells. The SW480E8 antisense cyclin D1 cells displayed an increased doubling time, a decrease in saturation density, decreased plating efficiency and anchorage-independent growth, and a loss of tumorigenicity in nude mice. These findings provide direct evidence that increased expression of cyclin D1 in colon tumor cells contributes to their abnormal growth and tumorigenicity. The ability to revert the transformed phenotype of these cells with antisense cyclin D1 suggests that cyclin D1 or its associated cyclin-dependent kinase 4 may be useful targets in the therapy of colon cancer.

    Title Iatrogenic Aorto-coronary Venous Fistula As a Complication of Coronary Artery Bypass Surgery: Patient Report and Review of the Literature.
    Date September 1996
    Journal Catheterization and Cardiovascular Diagnosis
    Excerpt

    We report a patient and review the literature of an unusual complication of coronary artery bypass graft surgery, an acquired aorto-coronary venous fistula. This report reviews the clinical presentation, physical findings, and management of this rare finding.

    Title Use of a 64 Channel Computerized Cardiac Mapping System in Arrhythmia Surgery.
    Date December 1995
    Journal Yonsei Medical Journal
    Excerpt

    A multipoint and computerized intraoperative mapping system has been known to be of value in improving the results of surgery for cardiac arrhythmia. It shows great potential as a new tool in the surgical intervention of the more common and lethal types of supraventricular tachyarrhythmias such as atrial flutter and atrial fibrillation. In addition, it also enhances the ability of the investigators to map and ablate the sometimes fleeting automatic atrial tachycardia. The authors developed a 64 channel computerized cardiac mapping system using a microcomputer (Macintosh IIx) and this has been used for basic research in cardiac electrophysiology as well as in arrhythmia surgery. In this system, bipolar electrograms are obtained from 64 different cardiac sites simultaneously at a sampling rate of 1 Ksample/sec and with a continuous and total data storage of up to 30 seconds. When the reference electrode is selected, delay time from the reference point is displayed on a two dimensional diagram of the heart. This system was used in one patient who underwent a surgical ablation of a ventricular tachycardia in whom we observed a ventricular activation sequence involving a variety of rhythms over several minutes. The system design permits easy expansion to a simultaneous sampling from 256 sites. This 64-channel mapping appeared to have the potential to be of great help in our understanding of cardiac arrhythmia as well as in its diagnosis and surgical treatment.

    Title Pulmonary Vein Thrombosis.
    Date September 1993
    Journal Chest
    Excerpt

    Pulmonary vein thrombosis is difficult to diagnose clinically and requires a combination of conventional diagnostic modalities. Transesophageal echocardiography was used in the present case to readily diagnose this entity and follow thrombus regression on anticoagulant therapy. This limited experience suggests that transesophageal echocardiography may be the initial diagnostic study of choice for pulmonary vein thrombosis.

    Title Serum Retinol-binding Protein 4 Levels Are Elevated in Non-alcoholic Fatty Liver Disease.
    Date
    Journal Clinical Endocrinology
    Excerpt

    OBJECTIVE: Retinol-binding protein 4 (RBP4) is a recently identified adipokine that is elevated in the serum in several insulin-resistant states. We investigated the relationship between non-alcoholic fatty liver disease (NAFLD) and serum RBP4 in nondiabetic adults. METHODS: One hundred and fifty-nine nondiabetic, non-alcoholic subjects (95 males and 64 females) participated in this study. Division of subjects into a NAFLD group (n = 73; 45 males and 28 females) or a normal group (n = 86; 50 males and 36 females) was based on the presence of fatty liver disease determined by sonography. RESULTS: Serum RBP4 levels in the NAFLD group were significantly higher than those in the normal group (62.8 +/- 16.0 mg/l vs. 51.7 +/- 14.6 mg/l, P < 0.0001). Multiple logistic regression analysis revealed that the RBP4 level was an independent factor associated with NAFLD (P = 0.0042). In addition, serum RBP4 levels were positively correlated with serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltranspeptidase (GGT) levels. The significant association between serum RBP4 and GGT levels remained even after adjusting for age, gender, body mass index, the homeostasis model of assessment (HOMA) value and the presence of NAFLD (r = 0.3097, P = 0.0002). CONCLUSION: Serum RBP4 levels are significantly associated with NAFLD and liver enzymes.

    Title Association Between Endogenous Secretory Rage, Inflammatory Markers and Arterial Stiffness.
    Date
    Journal International Journal of Cardiology
    Excerpt

    BACKGROUND: Advanced glycation end products (AGEs) and its receptor (RAGE) were known to play a pivotal role in the development of cardiovascular complications of diabetes. We investigated the association between circulating endogenous secretory RAGE (esRAGE) levels, inflammatory markers and arterial stiffness measured using brachial-ankle pulse wave velocity (baPWV). METHODS: The study subjects were composed of 76 type 2 diabetic patients and 78 age- and sex-matched non-diabetic subjects. RESULTS: Circulating esRAGE levels were significantly lower in subjects with type 2 diabetes (0.237+/-0.123 ng/ml vs. 0.307+/-0.177 ng/ml, p=0.005), and those levels were inversely correlated with body mass index (BMI), waist circumference, blood pressure, triglyceride, fasting glucose level and insulin resistance. Furthermore, esRAGE levels were significantly associated with adiponectin (r=0.164, p=0.044), interleukin-6 (IL-6) (r=-0.242, p=0.009) levels and baPWV (r=-0.296, p<0.001). Multiple regression analysis showed that fasting insulin, IL-6, glucose level and insulin resistance are major factor determining esRAGE (R(2)=0.186). Moreover, baPWV was found to be associated with age, systolic blood pressure, triglyceride, sex, BMI, fasting insulin and esRAGE level (R(2)=0.583). CONCLUSIONS: Circulating esRAGE levels were significantly lower in type 2 diabetic patients, and were associated with inflammation and arterial stiffness. These results suggest that esRAGE may play an important role on ligand-RAGE interaction propagated inflammation and atherosclerosis.

    Title A Role for a Menthone Reductase in Resistance Against Microbial Pathogens in Plants.
    Date
    Journal Plant Physiology
    Excerpt

    Plants elaborate a vast array of enzymes that synthesize defensive secondary metabolites in response to pathogen attack. Here, we isolated the pathogen-responsive CaMNR1 [menthone: (+)-(3S)-neomenthol reductase] gene, a member of the short-chain dehydrogenase/reductase (SDR) superfamily, from pepper (Capsicum annuum) plants. Gas chromatography-mass spectrometry analysis revealed that purified CaMNR1 and its ortholog AtSDR1 from Arabidopsis (Arabidopsis thaliana) catalyze a menthone reduction with reduced nicotinamide adenine dinucleotide phosphate as a cofactor to produce neomenthol with antimicrobial activity. CaMNR1 and AtSDR1 also possess a significant catalytic activity for neomenthol oxidation. We examined the cellular function of the CaMNR1 gene by virus-induced gene silencing and ectopic overexpression in pepper and Arabidopsis plants, respectively. CaMNR1-silenced pepper plants were significantly more susceptible to Xanthomonas campestris pv vesicatoria and Colletotrichum coccodes infection and expressed lower levels of salicylic acid-responsive CaBPR1 and CaPR10 and jasmonic acid-responsive CaDEF1. CaMNR1-overexpressing Arabidopsis plants exhibited enhanced resistance to the hemibiotrophic pathogen Pseudomonas syringae pv tomato DC3000 and the biotrophic pathogen Hyaloperonospora parasitica isolate Noco2, accompanied by the induction of AtPR1 and AtPDF1.2. In contrast, mutation in the CaMNR1 ortholog AtSDR1 significantly enhanced susceptibility to both pathogens. Together, these results indicate that the novel menthone reductase gene CaMNR1 and its ortholog AtSDR1 positively regulate plant defenses against a broad spectrum of pathogens.

    Title Green Tea Seed Oil Reduces Weight Gain in C57bl/6j Mice and Influences Adipocyte Differentiation by Suppressing Peroxisome Proliferator-activated Receptor-gamma.
    Date
    Journal Pflugers Archiv : European Journal of Physiology
    Excerpt

    Given that tea contains a number of chemical constituents possessing medicinal and pharmacological properties, green tea seed is also believed to contain many biologically active compounds such as saponin, flavonoids, vitamins, and oil materials. However, little is known about the physiologic functions of green tea seed oil. The aim of this study is to investigate the anti-obesity effects of green tea seed oil in C57BL/6J mice and in preadipocyte 3T3L-1 cell lines. In vivo, three groups of mice were fed with a standard diet, a high-fat diet containing 30% shortening, or 30% of green tea seed oil based on a standard diet for 85 days. The levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, glucose, and alanine aminotransferase in blood were analyzed at the end of the study. The mice given green tea seed oil gained less weight compared to mice given the shortening diet (p < 0.01). The plasma level of total cholesterol was decreased by a significant level of 32.4% in mice given the green tea seed oil compared to the mice given the shortening diet (p < 0.01). In addition, 3T3-L1 cells were treated for 2 days to evaluate effects of green tea seed oil on adipocyte differentiation. Green tea seed oil inhibited expression of peroxisome proliferator-activated receptor-gamma(2) and CCAAT/enhancer binding protein-alpha in adipocytes and adipose tissue from the experimental animals. These results indicate that the anti-obesity effects of green tea seed oil might be, in part, through suppression of transcription factors related to adipocyte differentiation.

    Title The Beneficial Effect of High Loading Dose of Rosuvastatin Before Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome.
    Date
    Journal International Journal of Cardiology
    Excerpt

    BACKGROUND: Statin therapy prior to percutaneous coronary intervention (PCI) is associated with reduced mortality and periprocedural myocardial injury after PCI. We studied whether single high dose statin loading is beneficial on the outcome of patients with acute coronary syndrome (ACS) underwent PCI. METHODS: Consecutive 445 patients with ACS who underwent PCI were randomly assigned to either the group of no statin treatment before PCI (Control group: n=220, 63+/-11 years, male 62%) or the group of 40 mg rosuvastatin loading before PCI (Rosuvastatin group: n=225, 64+/-10 years, male 60%). Incidence of periprocedural myocardial injury was assessed by analysis of creatinine kinase-MB (CK-MB) and cardiac troponin T before PCI, at 6 h and the next morning after PCI. RESULT: There were no significant differences in clinical characteristics between the two groups. After PCI, incidence of periprocedural myocardial injury was higher in control than in rosuvastatin group (11.4% versus 5.8%, p=0.035). Mean preprocedural CK-MB and high sensitivity C-reactive protein were similar between the two groups, whereas after PCI, peak values of both markers were elevated significantly higher in control than in rosuvastatin group. Multivariate analysis revealed that no prior use of statin (OR=2.2; 95% CI=1.1-4.6; p=0.029), procedural complication (OR=3.1; 95% CI=1.4-6.9; p=0.007) and multi-vessel disease (OR=2.6; 95% CI=1.0-6.6; p=0.039) were the independent predictors for periprocedural myocardial infarction. CONCLUSION: Single high dose of rosuvastatin prior to PCI reduces periprocedural myocardial injury in patients with ACS.

    Title The Effect of Fenton Reaction on Protease-resistant Prion Protein (prpsc) Degradation and Scrapie Infectivity.
    Date
    Journal Brain Research
    Excerpt

    In prion diseases, metal imbalances in brain and/or metal substitutions for copper in prion protein suggest that metal-catalyzed oxidation (MCO) and oxidative stress may affect cellular function and accumulation of protease-resistant prion protein (PrP(Sc)). We examined the effect of metal-induced oxidative stress by Fenton reaction on prion protein with regard to its degradation, insolubility, and infectivity. Precipitation and insolubility of prion protein were induced by Fenton reaction in scrapie-infected brain homogenate. Results showed an increase in hydroxylation products (thiobarbituric acid reactive substances; TBARS) and a decrease of ferrous ion (Fe(2+)) levels after Fenton reaction. Efficiency of metal-induced oxidation was higher for Fe(2+) than Mn(2+). Compared to untreated samples, there was increased susceptibility to proteolytic degradation of PrP(Sc) after treatment with 3.12-12.5 mM Fe(2+)-Mn(2+)/H(2)O(2). Interestingly, we observed that Fenton reaction could extend incubation periods, indicating a decrease in scrapie infectivity. These results suggest that PrP(Sc) hydroxylation and degradation may affect PrP conversion and the pathogenesis of prion diseases.

    Title Triptolide Inhibits the Proliferation of Immortalized Ht22 Hippocampal Cells Via Persistent Activation of Extracellular Signal-regulated Kinase-1/2 by Down-regulating Mitogen-activated Protein Kinase Phosphatase-1 Expression.
    Date
    Journal Journal of Korean Neurosurgical Society
    Excerpt

    Triptolide (TP) has been reported to suppress the expression of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), of which main function is to inactivate the extracellular signal-regulated kinase-1/2 (ERK-1/2), the p38 MAPK and the c-Jun N-terminal kinase-1/2 (JNK-1/2), and to exert antiproliferative and pro-apoptotic activities. However, the mechanisms underlying antiproliferative and pro-apoptotic activities of TP are not fully understood. The purpose of this study was to examine whether the down-regulation of MKP-1 expression by TP would account for antiproliferative activity of TP in immortalized HT22 hippocampal cells.

    Title Cardioprotective Effects of Alpha-lipoic Acid on Myocardial Reperfusion Injury: Suppression of Reactive Oxygen Species Generation and Activation of Mitogen-activated Protein Kinase.
    Date
    Journal Korean Circulation Journal
    Excerpt

    Reactive oxygen species (ROS) and mitogen-activated protein (MAP) kinase play an important role in the development of myocardial reperfusion injury. In this study, we examined whether treatment with alpha-lipoic acid (ALA) before reperfusion could prevent myocardial reperfusion injury in vivo.

    Title Alteration of Ventricular Repolarization by Intracoronary Infusion of Normal Saline in Patients with Variant Angina.
    Date
    Journal Korean Circulation Journal
    Excerpt

    During coronary angiography and interventional procedures, catheters that are engaged in a coronary ostium are routinely flushed, typically with normal saline, to expel blood from the catheter or to inject a pharmacologic agent. Saline contains sodium and chloride ions. Such injections may affect the electrophysiologic properties of the myocardium; however, the effect of normal saline on ventricular repolarization has not been established in patients with variant angina.

    Title Tetrahydroabietic Acid, a Reduced Abietic Acid, Inhibits the Production of Inflammatory Mediators in Raw264.7 Macrophages Activated with Lipopolysaccharide.
    Date
    Journal Journal of Clinical Biochemistry and Nutrition
    Excerpt

    Abietic acid (AA), the main component of the rosin fraction of oleoresin synthesized by conifer species, has been reported to have anti-inflammatory effects. AA is a weak contact allergen; however, compounds resulting from its oxidation by air elicit stronger allergic response. Hydrogenation of the conjugated double bonds of AA, as in tetrahydroabietic acid (THAA), decreases its susceptibility to air oxidation and would thus reduce the allergenicity of AA. The aim of this study was to investigate whether THAA could exert anti-inflammatory effects to the same extent as AA in RAW264.7 macrophages activated with the endotoxin lipopolysaccharide (LPS). THAA and AA inhibited the production of nitric oxide (NO) and prostaglandin E(2) by suppressing the expression of inducible NO synthase and cyclooxygenase-2, respectively, in LPS-activated RAW264.7 macrophages. They also inhibited the LPS-induced production of interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha. Both THAA and AA prevented the LPS-induced nuclear translocation of the nuclear factor-kappaB/p65 subunit, suggesting that THAA may inhibit the production of pro-inflammatory mediators through the same mechanism as AA. In comparison, the anti-inflammatory effects of THAA and AA were almost identical, indicating that THAA retains the anti-inflammatory activity of AA at least in LPS-activated RAW264.7 macrophages.

    Title 12-month Follow-up Results of High Dose Rosuvastatin Loading Before Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome.
    Date
    Journal International Journal of Cardiology
    Excerpt

    Statin pretreatment before percutaneous coronary intervention (PCI) is associated with a reduced incidence of short-term adverse events and periprocedural myocardial infarction (MI). However, the long-term effects of statin pretreatment have not been evaluated.

    Title Heme Oxygenase in the Regulation of Vascular Biology: from Molecular Mechanisms to Therapeutic Opportunities.
    Date
    Journal Antioxidants & Redox Signaling
    Excerpt

    Heme oxygenases (HOs) are the rate-limiting enzymes in the catabolism of heme into biliverdin, free iron, and carbon monoxide. Two genetically distinct isoforms of HO have been characterized: an inducible form, HO-1, and a constitutively expressed form, HO-2. HO-1 is a kind of stress protein, and thus regarded as a sensitive and reliable indicator of cellular oxidative stress. The HO system acts as potent antioxidants, protects endothelial cells from apoptosis, is involved in regulating vascular tone, attenuates inflammatory response in the vessel wall, and participates in angiogenesis and vasculogenesis. Endothelial integrity and activity are thought to occupy the central position in the pathogenesis of cardiovascular diseases. Cardiovascular disease risk conditions converge in the contribution to oxidative stress. The oxidative stress leads to endothelial and vascular smooth muscle cell dysfunction with increases in vessel tone, cell growth, and gene expression that create a pro-thrombotic/pro-inflammatory environment. Subsequent formation, progression, and obstruction of atherosclerotic plaque may result in myocardial infarction, stroke, and cardiovascular death. This background provides the rationale for exploring the potential therapeutic role for HO system in the amelioration of vascular inflammation and prevention of adverse cardiovascular outcomes.

    Title Relationship Between the Echocardiographic Epicardial Adipose Tissue Thickness and Serum Adiponectin in Patients with Angina.
    Date
    Journal Journal of Cardiovascular Ultrasound
    Excerpt

    It is still unknown whether increased cardiac adiposity is related to the risk factors of coronary artery disease (CAD). We measured epicaridal adopose tissue (EAT) and mediastinal adipose tissue (MAT) using echocardiography and examined their correlations with CAD and serum adiponectin.

    Title Inhibition of Aldose Reductase and Xylose-induced Lens Opacity by Puerariafuran from the Roots of Pueraria Lobata.
    Date
    Journal Biological & Pharmaceutical Bulletin
    Excerpt

    High sugar levels found in diabetic cataract cause the opacification of lenses by osmotic changes induced via the aldose reductase (AR)-mediated polyol pathway. In this study, puerariafuran, a 2-arylbenzofuran from Pueraria lobata, investigated the inhibitory effects upon AR, antioxidant contents and enzyme activities in the lens. The effect of puerariafuran on xylose-induced lens opacity was also examined. Puerariafuran showed potential inhibitory activity with an IC50 value of 22.34 microM against rat lens AR. The xylose-induced opacity of lenses was significantly improved when treated with puerariafuran. Xylose exposure of rat lenses significantly decreased the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, superoxide dismutase (SOD), and catalase (CAT) activity and treatment with puerariafuran significantly increased these factors. These results suggest that puerariafuran may provide a potential therapeutic approach for prevention of diabetic complications, such as cataracts.

    Title Trichostatin A Promotes the Development of Bovine Somatic Cell Nuclear Transfer Embryos.
    Date
    Journal The Journal of Reproduction and Development
    Excerpt

    We studied the effects of trichostatin A (TSA), a histone deacetylase inhibitor, on the development of bovine somatic cell nuclear transfer (SCNT) embryos by investigating (1) the optimal concentration and treatment time of TSA for development of bovine SCNT embryos, (2) the status of histone acetylation in TSA-treated and control SCNT embryos and (3) the expression of histone acetylation- and deacetylation-related genes in TSA-treated and control SCNT embryos. We observed that 50 nM TSA-treatment for 20 h following fusion resulted in more efficient in vitro development of bovine SCNT embryos to the blastocyst stage. In regard to histone H4K5 acetylation, half of the control SCNT embryos faintly displayed histone H4K5 signals 30 min after electrofusion, while most of the TSA-treated SCNT embryos displayed histone H4K5 signals within 30 min after electrofusion. Furthermore, the expressions of HDAC1 and HDAC2 in the blastocysts were significantly lower (P<0.05) in the TSA-treated SCNT than in the control SCNT. However, the expression of GCN5 and HAT1 did not differ between the TSA-treated and control SCNT. In conclusion, we demonstrated that TSA-treatment after SCNT in bovine embryos can dramatically improve the practical applications of current cloning techniques.

    Title Schwannoma in Head and Neck: Preoperative Imaging Study and Intracapsular Enucleation for Functional Nerve Preservation.
    Date
    Journal Yonsei Medical Journal
    Excerpt

    In treating schwannoma patients, it is critical to determine the origin of the tumor to preserve nerve function. We evaluated the validity of preoperative imaging studies in distinguishing the neurological origin of the schwannomas of the head and neck, and the efficacy of intracapsular enucleation in preserving nerve function.

    Title Sacroiliitis is Common in Crohn's Disease Patients with Perianal or Upper Gastrointestinal Involvement.
    Date
    Journal Gut and Liver
    Excerpt

    Sacroiliitis (SI) is one of the most frequent extraintestinal manifestations in inflammatory bowel disease (IBD) patients, but the exact prevalence has not been evaluated in Asia. There are few data on the association between SI and other clinical features of IBD. The prevalence of SI was evaluated using computed tomography (CT) and the phenotypic parameters associated with SI in Korean IBD patients were determined.

    Title [a Case of Psoriasis Induced by Infliximab Treatment for Crohn's Disease].
    Date
    Journal The Korean Journal of Gastroenterology = Taehan Sohwagi Hakhoe Chi
    Excerpt

    Infliximab, the monoclonal antibody to tumor necrosis factor, is indicated for refractory luminal and fistulizing Crohn's disease and rheumatoid arthritis. Infliximab treatment has adverse events including infusion reactions, opportunistic infections, and the potential for the event such as reactivation of latent tuberculosis. Cutaneous adverse reactions of TNF-α agents include skin rash, urticaria, pruritus, lupus-like eruption, and injection site reactions. Most of all, psoriasis or psoriasiform dermatitis induced by infliximab treatment for Crohn's disease is rarely reported in Korea. We report a case of psoriasis induced by infliximab treatment for Crohn's disease with a review of world literature.

    Title 4 X 4 Vertical-cavity Surface-emitting Laser (vcsel) and Metal-semiconductor-metal (msm) Optical Backplane Demonstrator System.
    Date
    Journal Applied Optics
    Excerpt

    We describe a system demonstrator based on vertical-cavity surface-emitting lasers, metal-semiconductor-metal detectors, printed circuit board (PCB) level optoelectronic device packaging, a compact bulk optical relay, and novel barrel/PCB optomechanics. The entire system was constructed in a standard VME electrical backplane chassis and was capable of operating at >1.7 Gbit/s of aggregate data capacity. In addition to the component technologies developed, we describe operational testing and characterization of the demonstrator.

    Title Serum Adipocyte Fatty Acid-binding Protein Is Associated Independently with Vascular Inflammation: Analysis with 18f-fluorodeoxyglucose Positron Emission Tomography.
    Date
    Journal The Journal of Clinical Endocrinology and Metabolism
    Excerpt

    Context: The inflammatory status of atherosclerotic lesions is a major factor triggering acute cardiovascular events. Growing evidence has shown that adipocyte fatty acid-binding protein (A-FABP) has an important role in the development of atherosclerosis. Objective: The objective of the study was to determine the association between circulating A-FABP levels with vascular inflammation as measured using [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography (PET), which is a novel imaging technique for noninvasive measurement of atherosclerotic inflammation. Design: This was a cross-sectional study. Participants: Eighty-seven men without previously diagnosed cardiovascular disease or diabetes participated in the study. Main Outcome Measure: We measured the serum A-FABP, adiponectin, and leptin levels as well as other cardiovascular risk factors. Vascular inflammation in the carotid arterial wall, as indicated by the target to background ratio (TBR), was analyzed using FDG-PET. Results: The circulating A-FABP and leptin levels had positive correlations with maximum TBR values (r = 0.38, P < 0.001; and r = 0.28, P = 0.010, respectively), whereas the adiponectin levels had a negative correlation (r = -0.31, P = 0.004). The maximum TBR levels exhibited an additive linear increment according to the rise in tertiles of the A-FABP levels in subjects with and without metabolic syndrome. Multiple regression analysis showed that serum A-FABP levels were independently associated with maximum TBR after adjustment for other cardiovascular risk factors (P = 0.006). Conclusions: Circulating A-FABP, adiponectin, and leptin levels were shown to be associated with vascular inflammation, as measured using FDG-PET. Specifically, the A-FABP level was an independent risk factor for vascular inflammation in Korean men without cardiovascular disease or diabetes.

    Title Hdac Inhibitors Downregulate Mrp2 Expression in Multidrug Resistant Cancer Cells: Implication for Chemosensitization.
    Date
    Journal International Journal of Oncology
    Excerpt

    Although histone deacetylase (HDAC) inhibitors are emerging as a promising class of cancer chemotherapeutic agents, their effects on multidrug resistance (MDR) are poorly understood. In this study, we investigated whether HDAC inhibitors overcome MDR phenotype. HDAC inhibitors suppress the growth of both MDR positive cancer cells KBV20C and its parental cells KB with similar potencies. In parallel, histone acetylation and p21WAF1 expression by the HDAC inhibitors were similarly increased in both cell types, indicating that these HDAC inhibitors are poor substrates of ABC drug transporters and effective in MDR cancer cells. In addition, multidrug resistance protein 2 (MRP2) expression is selectively attenuated by HDAC inhibitors, especially SAHA and TSA, in KBV20C cells, whereas MDR1 and BCRP expressions are not affected. This downregulation of MRP2 contributes to increase in paclitaxel-induced G2/M arrest and apoptosis, which might be due to intracellular accumulation of paclitaxel. Collectively, our data provide a molecular rationale for the application of HDAC inhibitors to overcome MDR in cancer cells.

    Title Involvement of Hdac1 in E-cadherin Expression in Prostate Cancer Cells; Its Implication for Cell Motility and Invasion.
    Date
    Journal Biochemical and Biophysical Research Communications
    Excerpt

    In this study, we investigate the molecular mechanism by which histone deacetylase (HDAC) inhibitors exert anti-invasiveness effect against prostate cancer cells. We first evaluate the growth inhibition effect of HDAC inhibitors in prostate cancer cells, which is accompanied by induction of p21(WAF1) expression and accumulation of acetylated histones. And we found that the migration and invasion of prostate cancer cells is strongly inhibited by treatment with HDAC inhibitors. In parallel, E-cadherin level is highly up-regulated in HDAC inhibitor-treated prostate cancer cells. And siRNA knockdown of E-cadherin significantly diminishes the anti-invasion effect of HDAC inhibitors, indicating that E-cadherin overexpression is one of possible mechanism for anti-invasion effect of HDAC inhibitors. Furthermore, specific downregulation of HDAC1, but not HDAC2, causes E-cadherin expression and subsequent inhibition of cell motility and invasion. Collectively, our data demonstrate that HDAC1 is a major repressive enzyme for E-cadherin expression as well as HDAC inhibitor-mediated anti-invasiveness.

    Title Nfat5 is a Critical Regulator of Inflammatory Arthritis.
    Date
    Journal Arthritis and Rheumatism
    Excerpt

    OBJECTIVE.: To investigate the role of nuclear factor of activated T cells 5 (NFAT5), which is known as an osmoprotective transcription factor, in synovial hyperplasia and angiogenesis in rheumatoid arthritis (RA) METHODS.: Expression of NFAT5 was examined in the synovial tissues and synoviocytes of RA patients using immunohistochemistry and Western blot analysis, respectively. The mRNAs of RA synoviocytes and human umbilical vein endothelial cells (HUVEC) transfected with dummy siRNA or NFAT5 siRNA were profiled using microarray technology. Assays to determine synoviocyte apoptosis and proliferation were performed in the presence of NFAT5 siRNA.VEGF(165)-induced angiogenesis was assessed by measuring the proliferation, tube formation, and wounding migration of HUVEC. Experimental arthritis was induced in mice by injection of anti-type II collagen antibody. RESULTS.: NFAT5 was highly expressed in the rheumatoid synovium and its activity was increased by proinflammatory cytokines, such as IL-1β and TNF-α. The mRNA profiling of synoviocytes and HUVEC transfected with NFAT5-targeted siRNA revealed three major changes in cellular processes associated with the pathogenesis of RA: cell cycle and survival, angiogenesis, and cell migration. Consistent with these results, NFAT5 knock-down in RA synoviocytes and HUVEC inhibited their proliferation/survival and impeded angiogenic processes in HUVEC. Mice with NFAT5 haplo-insufficiency (NFAT5(+/-)) developed very limited degree of synovial proliferation in histological analysis, decreased angiogenesis, and exhibited a nearly complete suppression of experimentally induced arthritis. CONCLUSION.: NFAT5 regulates synovial proliferation and angiogenesis in chronic arthritis.

    Title Jmy is Required for Asymmetric Division and Cytokinesis in Mouse Oocytes.
    Date
    Journal Molecular Human Reproduction
    Excerpt

    JMY is a transcriptional co-factor of p53. Latest work has revealed that JMY is also a actin nucleation factor which regulates new filament assembly and activates Arp2/3 complex in somatic cells, however, roles of JMY in mouse oocyte are unknown. Here we showed the expression and functions of JMY during mouse oocyte meiotic maturation. JMY mRNA is expressed largely from germinal vesicle (GV) to metaphase I (MI) stage, and gradually decreased during anaphase I, telophase I (TI) and metaphase II (MII) stages. Immunostaining results showed that JMY localized at the spindle and cytoplasm of oocytes. Depletion of JMY by RNAi resulted in symmetric division, failure of spindle migration and cytokinesis during oocyte meiotic maturation, showing 2 cell-like MII oocyte and TI stage arrest. Actin cap and cortical granules-free domain formation were also disrupted after JMY RNAi, indicating the failure of spindle migration. JMY antibody injection results were consistent with those of JMY RNAi, further confirming the involvement of JMY in oocyte polarity. Our data indicate that JMY is required for spindle migration, asymmetric division and cytokinesis during mouse oocyte maturation.

    Title Theanine is a Candidate Amino Acid for Pharmacological Stabilization of Mast Cells.
    Date
    Journal Amino Acids
    Excerpt

    The increasing occurrences of allergic disorders may be attributed to exposure to environmental factors that contribute to the pathogenesis of allergy. The health benefits of green tea have been widely reported but are largely unsubstantiated. Theanine is the major amino acid present in green tea. In this study, we investigated the role of theanine in both IgE- and non- IgE-induced allergic response. Theanine inhibited compound 48/80-induced systemic anaphylactic shock and ear swelling responses. IgE-mediated passive cutaneous anaphylaxis was inhibited by the oral administration or pharmaceutical acupuncture of theanine. Histamine release from mast cells was decreased with the treatment of theanine. Theanine also repressed phorbol 12-myristate 13-acetate and calcium ionophore A23187-induced TNF-α, IL-1β, IL-6, and IL-8 secretion by suppressing NF-κB activation. Furthermore, theanine suppressed the activation of caspase-1 and the expression of receptor interacting protein-2. The current study demonstrates for the first time that theanine might possess mast cell-stabilizing capabilities.

    Title The Dynamics of Vein Graft Remodeling Induced by Hemodynamic Forces: a Mathematical Model.
    Date
    Journal Biomechanics and Modeling in Mechanobiology
    Excerpt

    Although vein bypass grafting is one of the primary options for the treatment of arterial occlusive disease and provides satisfactory results at an early stage of the treatment, the patency is limited to a few months in many patients. When the vein is implanted in the arterial system, it adapts to the high flow rate and high pressure of the arterial environment by changing the sizes of its layers, and this remodeling is believed to be a precursor of future graft failure. Hemodynamic forces, such as wall shear stress (WSS) and wall tension, have been recognized as major factors impacting vein graft remodeling. Although a wide range of experimental evidence relating hemodynamic forces to vein graft remodeling has been reported, a comprehensive mathematical model describing the relationship among WSS, wall tension, and the structural adaptation of each individual layer of the vein graft wall is lacking. The current manuscript presents a comprehensive and robust framework for treating the complex interaction between the WSS, wall tension, and the structural adaptation of each individual layer of the vein graft wall. We modeled the intimal and medial area and the radius of external elastic lamina, which in combination dictate luminal narrowing and the propensity for graft occlusion. Central to our model is a logistic relationship between independent and dependent variables to describe the initial increase and later decrease in the growth rate. The detailed understanding of the temporal changes in vein graft morphology that can be extracted from the current model is critical in identifying the dominant contributions to vein graft failure and the further development of strategies to improve their longevity.

    Title Cat Fertilization by Mouse Sperm Injection.
    Date
    Journal Zygote (cambridge, England)
    Excerpt

    SummaryInterspecies intracytoplasmic sperm injection has been carried out to understand species-specific differences in oocyte environments and sperm components during fertilization. While sperm aster organization during cat fertilization requires a paternally derived centriole, mouse and hamster fertilization occur within the maternal centrosomal components. To address the questions of where sperm aster assembly occurs and whether complete fertilization is achieved in cat oocytes by interspecies sperm, we studied the fertilization processes of cat oocytes following the injection of cat, mouse, or hamster sperm. Male and female pronuclear formations were not different in the cat oocytes at 6 h following cat, mouse or hamster sperm injection. Microtubule asters were seen in all oocytes following intracytoplasmic injection of cat, mouse or hamster sperm. Immunocytochemical staining with a histone H3-m2K9 antibody revealed that mouse sperm chromatin is incorporated normally with cat egg chromatin, and that the cat eggs fertilized with mouse sperm enter metaphase and become normal 2-cell stage embryos. These results suggest that sperm aster formation is maternally dependent, and that fertilization processes and cleavage occur in a non-species specific manner in cat oocytes.

    Title Response to Primary and Booster Vaccination with 10-valent Pneumococcal Nontypeable Haemophilus Influenzae Protein D Conjugate Vaccine in Korean Infants.
    Date
    Journal The Pediatric Infectious Disease Journal
    Excerpt

    This randomized single-blind study in Korea evaluated noninferiority of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) versus the 7-valent pneumococcal conjugate vaccine (7vCRM) when both were coadministered with H. influenzae type b (Hib) conjugate vaccine, as opposed to coadministration with diphtheria-tetanus-acellular pertussis-based combination vaccines in previous studies.

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