Physiatrists, Pain Management Specialist
17 years of experience

Accepting new patients
Cal Young
Rehabilitation Medicine Associates
242 Country Club Rd
Eugene, OR 97401
541-683-4242
Locations and availability (1)

Education ?

Medical School Score Rankings
University of California at San Francisco (1993)
  • Currently 4 of 4 apples
Top 25%

Awards & Distinctions ?

Associations
American Board of Physical Medicine and Rehabilitation
Depuymitek.com (knee Osteoarthritis)- Orthovisc.com

Affiliations ?

Dr. Lin is affiliated with 8 hospitals.

Hospital Affilations

Score

Rankings

  • Sacred Heart Medical Center
    1255 Hilyard St, Eugene, OR 97401
    • Currently 4 of 4 crosses
    Top 25%
  • Cottage Grove Hospital
    1515 Village Dr, Cottage Grove, OR 97424
    • Currently 4 of 4 crosses
    Top 25%
  • Peace Harbor Hospital
    400 9th St, Florence, OR 97439
    • Currently 3 of 4 crosses
    Top 50%
  • McKenzie - Willamette Medical Center
    1460 G St, Springfield, OR 97477
    • Currently 2 of 4 crosses
  • St. Joseph's Hospital
  • Sacred Heart Medical Center At Riverbend
    3333 Riverbend Dr, Springfield, OR 97477
  • St John's Medical Center
  • Sacred Heart Medical Center - Riverbend 7/23/1997 Active Current Phys Med & Rehab
  • Publications & Research

    Dr. Lin has contributed to 19 publications.
    Title A Comprehensive Approach Toward Novel Serum Biomarkers for Benign Prostatic Hyperplasia: the Mpsa Consortium.
    Date March 2008
    Journal The Journal of Urology
    Excerpt

    PURPOSE: Clinical benign prostatic hyperplasia is primarily diagnosed based on a diverse array of progressive lower urinary tract symptoms and is likely distinct from histological benign prostatic hyperplasia, which is detected by the presence of nonmalignant proliferation of prostate cells but may or may not be associated with symptoms. Pharmacological management of lower urinary tract symptoms has emerged as an effective initial treatment for clinical benign prostatic hyperplasia due to the introduction of new drug therapies shown to be effective in recent large clinical trials. Despite advances in symptom management and research into disease pathology, diagnostic strategies for the prediction of benign prostatic hyperplasia progression and response to drug modalities are lacking, and questions remain as to the molecular differences underlying clinical (symptomatic) vs histological (nonsymptomatic) benign prostatic hyperplasia. MATERIALS AND METHODS: As part of the Medical Therapy of Prostatic Symptoms (MTOPS) clinical trial, which demonstrated the effectiveness of combination drug therapy in slowing benign prostatic hyperplasia progression, an archive of biological specimens linked to clinical data was collected for future profiling of disease pathology and changes associated with response to drug therapy. The MTOPS Prostatic Samples Analysis (MPSA) Consortium was established to identify and validate molecular markers that may better define benign prostatic hyperplasia related pathologies, identify risk of progression of lower urinary tract symptoms, and predict response to drug therapy using the MTOPS archive. The cooperating MPSA Biomarker Discovery Sites and Pathology Coordinating Center use diverse methodologies and scientific approaches as well as unique expertise to address the goals of the Consortium. RESULTS: To date the MPSA has identified a number of promising biomarkers as well as other molecular and cellular changes associated with benign prostatic hyperplasia. CONCLUSIONS: These findings and ongoing Consortium discovery efforts have the potential to provide a greater understanding of the defects underlying disease pathology, and may lead to the development of early and more effective pharmacological treatment strategies for benign prostatic hyperplasia.

    Title Elastin Expression and Elastic Fibre Width in the Anterior Vaginal Wall of Postmenopausal Women with and Without Prolapse.
    Date September 2007
    Journal Bju International
    Excerpt

    OBJECTIVES: To compare elastin expression and elastic fibre width in the anterior vaginal wall of postmenopausal women with and with no bladder prolapse. PATIENTS AND METHODS: Full-thickness specimens were obtained from the upper lateral anterior vaginal wall of women having a large cystocele repaired (stage III or IV; prolapse group, 33) and the same location in patients with no prolapse having radical cystectomy (control group, 10). The percentage of elastin-positive tissue and elastic fibre width were measured by immunohistochemistry on 6 microm thick tissue sections from 10 random field readings per sample using image analysis software. The examiner was unaware of sample identity and the patients' clinical history. RESULTS: The age was comparable between the control and prolapse groups (median 70.5 years), and the parity, vaginal deliveries, hormone replacement use, cigarette smokers and body mass index were no different between the groups. Immunohistochemical staining and morphometric analysis indicated that elastin expression in the prolapse group was 10.6%, vs 14.4% in the control group (P = 0.049). The median width of elastic fibres was 0.9 microm in the prolapse and 1.8 microm in the control groups (P < 0.001). Elastin expression and elastic fibre width appeared to be stable with increasing age in the prolapse group. CONCLUSIONS: In this case-control study investigating elastin changes in postmenopausal women with prolapse, the elastin expression and fibre width were significantly lower in the vaginal wall of patients with a large cystocele than in controls of a similar age.

    Title Alpha(2) Macroglobulin, a Psa Binding Protein, is Expressed in Human Prostate Stroma.
    Date May 2005
    Journal The Prostate
    Excerpt

    BACKGROUND: Benign prostatic hyperplasia (BPH) is characterized as a stromal process. The stroma smooth muscle (SM) may alter its phenotype during the progression of BPH. We have identified gene transcripts that may be differentially expressed in BPH using a differential display method. Among the fragments isolated, alpha(2) macroglobulin (alpha(2)-M) is one of the most interesting. alpha(2)-M is a binding protein of a variety of proteinases, including prostatic specific antigen (PSA). It also plays roles in molecular trapping and targeting. In this study, we characterized alpha(2)-M expression in the human prostate. METHODS: Differential display was used to identify and isolate the differentially expressed transcripts between normal prostate and BPH tissues. RT-PCR, Western blot, in situ hybridization, and immunohistochemistry were utilized to confirm and characterize alpha(2)-M expression in the prostate. RESULTS: Real-time RT-PCR results revealed that a 3.2-fold increase in alpha(2)-M mRNA expression is observed in BPH compared with normal prostate tissue. A 1.9-fold increase at protein level was also observed. In situ hybridization and immunohistochemistry showed that alpha(2)-M expression is primarily localized to the stromal compartment. Cultured primary stroma cells maintained alpha(2)-M expression, while prostate epithelial cells had a significantly lower level of alpha(2)-M expression. Furthermore, stromal cells in culture produce and secrete alpha(2)-M in the medium. CONCLUSIONS: We identified alpha(2)-M expression in the human prostate. An increased alpha(2)-M expression appears to be associated with BPH. Considering the unique features of its protein binding and targeting properties, alpha(2)-M expressed in the prostate may play an important role in regulating benign and malignant prostatic growth.

    Title Changes in Detrusor Smooth Muscle Myosin Heavy Chain Mrna Expression Following Spinal Cord Injury in the Mouse.
    Date February 2005
    Journal Neurourology and Urodynamics
    Excerpt

    AIMS: Smooth muscle myosin heavy chain (SMMHC) isoform composition has been shown to be developmentally regulated and to be associated with functional changes in smooth muscle activity. In this study, we sought to determine expression patterns of SMMHC isoforms in a murine model of spinal cord injury (SCI) and to compare these expression patterns to neurologic, cytometric, and morphometric findings. MATERIALS AND METHODS: Baseline cystometry was performed on adult, female mice followed by either thoracic spinal cord transection (SCI) or sham operation (Sham). At 1, 3, or 6 weeks postoperatively neurologic evaluation and cystometry were performed, bladders were harvested, and expression patterns of SMMHC isoforms (SM1 vs. SM2 and SMA vs. SMB) were assessed by RT-PCR. Morphometrics utilizing computer-assisted color image analysis was also performed on all bladders. RESULTS: There was a significant increase in bladder weight and capacity 1 week following SCI which normalized over time, however, morphometric analysis did not reveal an alteration in tissue composition amongst the three groups. One week following SCI, SM1 was predominantly expressed over SM2 and began to normalize at 3 weeks. This coincided with the emergence of reflex voiding and detrusor overactivity. SMA was expressed following SCI only, and the number of bladders found to express SMA decreased with increasing duration since SCI. CONCLUSIONS: Smooth muscle myosin heavy chain mRNA expression patterns appear to be affected by SCI. We believe the induction of SMA may be a factor in altered bladder function following injury.

    Title Heterogeneity of 5 Alpha-reductase Gene Expression in Benign Prostatic Hyperplasia.
    Date February 2003
    Journal The Journal of Urology
    Excerpt

    PURPOSE: The search for molecular markers of benign prostatic hyperplasia in general is based on an analysis of a limited number of biopsy samples. Little is known about the homogeneity of the expression of key genes in different zones of the prostate. We studied the intraprostatic (that is within the same gland) and inter-prostatic (that is between glands) variability of 5 alpha-reductase 2 (5aR2) gene expression. MATERIALS AND METHODS: Ten tissue samples removed by open prostatectomy were the source of tissue specimens. Two frozen sections were generated from each of several random biopsies taken from each adenoma immediately after enucleation, 1 of which was used for 5aR2 gene expression analysis and 1 for morphometric analysis. Results among biopsies were compared using the 5 alpha-reductase index (ratio of 5 alpha-reductase expression to an internal standard measured as electrophoretic band intensity). Morphometric composition was determined for smooth muscle, collagen, epithelium and glandular lumens. Statistical comparisons were performed with ANOVA by pairwise multiple comparison (Dunn) and Spearman's rank correlation procedure. RESULTS: For the 71 biopsies analyzed mean 5 alpha-reductase index was 0.23 +/- 0.16 and overall tissue distribution was smooth muscle 34%, collagen 35%, epithelium 14% and glandular lumens 17%. Inter-prostate and intraprostate variability in 5 alpha-reductase index was statistically significant (p = 0.004) as was the variability in stromal-to-epithelial ratio (p = 0.012). The 5 alpha-reductase index showed strong correlation with stroma (%) and negative correlation with epithelium (%). CONCLUSIONS: Benign prostatic hyperplasia is heterogeneous in terms of tissue morphometry and expression of single important genes. This finding limits the use of single biopsy based markers to predict biological behavior, and has significant impact on the ability of distinguishing longitudinal changes in tissue composition from sampling artifacts.

    Title Up-regulation of a Gene Homologous to the Human Tumor Necrosis Factor Receptor Associated Factor 6 Gene in the Obstructed Rabbit Bladder Determined by Differential Display Polymerase Chain Reaction.
    Date May 2001
    Journal The Journal of Urology
    Excerpt

    PURPOSE: We identified differentially expressed genes in the rabbit bladder after partial outlet obstruction. MATERIALS AND METHODS: Differential display polymerase chain reaction (PCR) was performed on smooth muscle tissue from normal, 2 and 6-week obstructed rabbit bladders. Semiquantitative reverse transcriptase PCR, Western and RNA blot analysis were done to confirm messenger RNA and protein up-regulation. RESULTS: A signal transducing protein human tumor necrosis factor receptor associated factor 6 (TRAF6)-like protein was identified on differential display PCR. TRAF6-like protein was up-regulated in rabbit bladders after 2 weeks of partial outlet obstruction. Reverse transcriptase PCR demonstrated TRAF6-like protein in bladder muscle tissue and semiquantitative analysis confirmed up-regulation in 2-week obstructed tissue. These findings were confirmed by RNA and Western blot analysis. CONCLUSIONS: TRAF6-like protein is up-regulated during the early phase of bladder outlet obstruction in rabbits. To our knowledge involvement of this gene in bladder outlet obstruction has not been described previously. TRAF6 may have a role in the regulation of molecular changes during the early bladder response to outlet obstruction, such as the up-regulation of growth factors and proto-oncogenes. Further understanding of this signaling pathway and its role in bladder outlet obstruction may open new avenues for treating detrusor dysfunction.

    Title Contractile Protein Expression in Bladder Smooth Muscle is a Marker of Phenotypic Modulation After Outlet Obstruction in the Rabbit Model.
    Date May 2001
    Journal The Journal of Urology
    Excerpt

    PURPOSE: We determined changes in contractile protein expression before and after the relief of partial bladder outlet obstruction in the rabbit model and assessed their potential role as predictors of recovery. MATERIALS AND METHODS: We examined the ratio of the smooth muscle myosin heavy chain isoforms SM2-to-SM1, caldesmon isoform expression and bladder function in obstructed and unobstructed adult rabbit bladders. Cystometry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis were done to determine changes in bladder function and contractile protein expression. RESULTS: Overall we observed significant correlation of bladder weight with the SM2-to-SM1 ratio (p <0.05). Regardless of the duration of obstruction (up to 10 weeks) the ratio appeared to stabilize around a value comparable to that in fetal rabbit smooth muscle cells, suggesting a reversal of SM2 and SM1 expression to a level similar to that at the fetal stage. The pattern of h and l-caldesmon isoform expression showed an increase in l-caldesmon expression in obstructed bladders. Except for decreased leak point pressure in the obstructed group we noted no statistically significant urodynamic changes in bladder capacity or compliance. CONCLUSIONS: There is significant correlation of bladder weight, which is the best known marker of obstruction, with the SM2-to-SM1 ratio. The myosin heavy chain isoform expression ratio appears to be an indicator of phenotypic modulation in bladder smooth muscle before and after the relief of bladder outlet obstruction. Thus, it may be useful as a marker of bladder dysfunction and predictor of functional recovery. Regression to a fetal pattern of protein expression may suggest irreversible damage to smooth muscle cells, possibly limiting recovery.

    Title Alpha-blockade Downregulates Myosin Heavy Chain Gene Expression in Human Benign Prostatic Hyperplasia.
    Date April 2001
    Journal Urology
    Excerpt

    OBJECTIVES: Smooth muscle (SM), a major component of prostate stroma, plays an important role in the pathogenesis of benign prostatic hyperplasia. In many muscle systems, steroid hormones and alpha(1)-adrenergic neurotransmitters tightly regulate expression of contractile proteins. In this study, SM content and the expression of myosin heavy chain (MHC) in tissues from patients with benign prostatic hyperplasia treated with androgen ablation or alpha-blockade were compared with untreated controls. METHODS: Prostatic periurethral tissue specimens from patients receiving luteinizing hormone-releasing hormone analogues (n = 12), alpha-blocking agents (n = 12), and no treatment (n = 13) were examined. The samples were analyzed for SM MHC mRNA expression using competitive reverse transcription-polymerase chain reaction. SM content was measured by morphometric analysis of trichrome-stained sections. RESULTS: Stromal SM constituted 45.4% +/- 8.6%, 48.1% +/- 18.4%, and 45.9% +/- 10.8% of the total tissue in androgen ablated, alpha-blocked, and untreated tissues, respectively. No significant difference was observed among these three groups (P = 0.84, analysis of variance). However, SM MHC mRNA expression was markedly decreased in the alpha-blockade group (0.15 +/- 0.02 attomole/mg tissue) compared with the androgen-ablated (0.58 +/- 0.15 attomole/mg tissue) or control (0.44 +/- 0.10 attomole/mg tissue) groups. The relationship between SM content and expression of SM MHC significantly differed among the groups (P = 0.02, analysis of variance). CONCLUSIONS: Androgen ablation and alpha-blockade do not appear to alter the histologic characteristics of prostate stroma in men with symptomatic benign prostatic hyperplasia. However, contractile protein gene expression in stromal SM cells is significantly altered after alpha-blockade. These data suggest that, in addition to the simple relaxation of muscle tone, alpha-blocking agents may affect the phenotypic expression of contractile proteins in prostate SM cells.

    Title Smooth Muscle Myosin Heavy Chains Are Developmentally Regulated in the Rabbit Bladder.
    Date October 2000
    Journal The Journal of Urology
    Excerpt

    PURPOSE: In smooth muscle (SM), myosin heavy chain (MHC) is expressed predominantly as two isoforms, SM1 and SM2, which are encoded by a single gene and expressed by alternative splicing mechanisms. Although functional differences of these isoforms are unknown, changes in SM1/SM2 ratio have been reported in various pathophysiologic conditions. We analyzed MHC composition of bladder detrusor SM from rabbits of different ages to determine whether SM1 and SM2 isoform expressions are developmentally regulated. MATERIALS AND METHODS: Rabbit bladders on the -11, -4, 1, 7, 14, 21, and 90th days of life were analyzed for SM MHC isoform expression at protein and mRNA levels. Porous sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), S1 protection assay, and histological analysis were employed. RESULTS: The predominant MHC isoform in fetal and neonatal bladders was SM1. In the third postnatal week, the SM1/SM2 ratio decreased from 2.3 to 1.0. A stable SM1/SM2 ratio of 0.6 was observed in the adult animal. Although expression of SM1 mRNA was 2.6-fold greater than that of SM2 in the fetus, the relative amount of SM2 mRNA increased rapidly after birth and remained the predominant isoform throughout adult life. Developmental changes in relative amounts of SM1 and SM2 protein in bladder tissues were virtually identical to those of SM1 and SM2 mRNA. SM cell growth and disappearance of primitive mesenchyme from the bladder occurred concomitantly with the MHC isoform shift. CONCLUSIONS: The parallel temporal course of MHC mRNA and protein isoform levels suggests detrusor SM MHC expression may be developmentally regulated at the mRNA level.

    Title Myosin Heavy Chain Gene Expression in Normal and Hyperplastic Human Prostate Tissue.
    Date August 2000
    Journal The Prostate
    Excerpt

    BACKGROUND: Benign prostatic hyperplasia (BPH) is common among aging men. Over 80% of males 50-60 years and older have various degrees of bladder outlet obstruction secondary to BPH. Despite the tremendous medical impact of BPH, its molecular pathophysiology remains unclear. Current BPH research focuses on steroid hormonal effects, stromal-epithelial cell interaction, and oncogenes and growth factors. But little is known about the potential prostatic smooth muscle (SM) alterations that may occur during stromal hyperplasia. METHODS: To study SM phenotypic modulation in hyperplastic prostatic growth, we isolated and characterized the 3' end of human SM myosin heavy chain (SMMHC) cDNA as a molecular probe. Expression of SMMHC and nonmuscle myosin heavy chain (NMMHC) in human prostates was analyzed using Western blot, Northern blot, and in situ hybridization to determine if BPH tissue expresses significantly less SMMHC and more NMMHC than a normal prostate. In addition, a competitive, reverse transcription (RT) polymerase chain reaction (PCR) method was adapted to quantify SMMHC and NMMHC mRNA expression at the sensitivity level of 10(-21) mole per mg of wet tissue. RESULTS: Western blot, Northern blot, and in situ hybridization results reveal that both SMMHC and NMMHC are expressed in the human prostate, while SMMHC is the predominant form found in normal prostate stroma. Results from competitive RT-PCR analysis indicate that NMMHC mRNA expression is approximately 10(-20) mole/mg of tissue. The SMMHC mRNA expressed is approximately 10(-18) mole/mg. No significant difference was found when NMMHC mRNA expression was compared between normal and BPH periurethral tissues. However, SMMHC expression was reduced almost fivefold in BPH compared to normal prostate, despite an increase in prostatic stromal mass. CONCLUSIONS: Our results suggest the pathogenesis of BPH is associated with a unique type of SM proliferation. Such proliferation is characterized by downregulation of SMMHC mRNA expression but without upregulation of NMMHC mRNA expression, the pattern seen in proliferating SM cells in culture and in other pathologic forms of SM hyperplasia (e.g., atherosclerosis). These findings support a model of BPH typified by active smooth muscle proliferation early in the disease process, and supports clinical observations that suggest ongoing prostate growth of the prostate is minimal in older men. Therapeutic strategies to prevent disease progression should therefore focus on early phases of prostatic growth.

    Title Altered Response to Partial Bladder Outlet Obstruction in Mice Lacking Inducible Nitric Oxide Synthase.
    Date June 2000
    Journal The Journal of Urology
    Excerpt

    INTRODUCTION: Following prolonged partial bladder outlet obstruction (BOO) in the mouse, cholinergic mediated detrusor contractility decreases. Previous work has demonstrated an increase in the inducible form of nitric oxide synthase (iNOS) at the mRNA and protein levels soon after obstruction. Since nitric oxide (NO), the product of the action of iNOS on molecular oxygen and l-arginine, produces vasodilation and decreases platelet aggregation, we believe it is an integral part of the initial detrusor response to obstruction. These experiments evaluated the detrusor response in mice incapable of producing iNOS. MATERIALS AND METHODS: Wild type and knockout mice were partially obstructed for 1, 3, and 5 weeks. Physiologic evaluation consisted of cystometric analyses, and muscle strip studies in response to cholinergic and electrical stimulation. Strips were also relaxed with L-arginine, sodium nitroprusside, and 8-bromoguanosine 3' - 5' cyclic GMP, after precontraction. RESULTS: After 5 weeks of obstruction, both wild type (WT) and knockout (KO) mouse bladders increased significantly in weight. WT bladders obstructed for 5 weeks had the greatest capacity (increase of 42%, p = 0.022), and a decreased contractile response to carbachol (decrease of 32% at 10-5 M, p = 0.018). No differences were noted at 1 and 3 weeks of obstruction. In contrast, KO mice had a significantly larger bladder capacity at 1 week of obstruction compared with WT, and had significantly lower responses to electrical stimulation than WT at the same time (p = 0.03). Additionally, after 5 weeks of obstruction, bladder capacity and contractility returned to baseline levels in KO mice, at a time when WT mice had significantly larger capacity and decreased contractility. CONCLUSIONS: Bladder function following partial BOO in mice incapable of producing iNOS differed significantly from the normal response. Our data suggest that generation of iNOS soon after obstruction is necessary to prevent detrusor dysfunction at that time. Moreover, the enhanced function seen in KO bladders after longer periods of obstruction (5 weeks) in comparison to WT bladders suggests that reactive nitrogen species-induced protein nitrosylation may be involved in the loss of contractile function observed after more prolonged periods of obstruction.

    Title Physiologic Sequelae of Partial Infravesical Obstruction in the Mouse: Role of Inducible Nitric Oxide Synthase.
    Date March 1999
    Journal The Journal of Urology
    Excerpt

    PURPOSE: To develop a mouse model for partial infravesical obstruction, and determine the resultant changes in bladder function, with particular emphasis on the role of inducible nitric oxide synthase (iNOS) in the bladder response. MATERIALS AND METHODS: Wild type mice were subjected to no intervention, sham operation, and varying durations of partial outlet obstruction (1, 3, and 5 weeks). They then underwent cystometric evaluation, bladder strip stimulation studies using carbachol, and relaxation studies using l-arginine, sodium nitroprusside, and 8-bromoguanosine 3'-5' cyclic guanosine monophosphate. Bladder tissue was subjected to RT-PCR and Western analysis for iNOS. Bladders were also studied histologically using morphometric analysis. RESULTS: Bladders from mice obstructed for 5 weeks were heavier (weight increased by 110%), larger (capacity increased by 73%), and had a higher frequency of abnormal appearing cystometric curves than normal bladders. Tissue bath studies demonstrated decreased contractility in response to cholinergic stimulation at 5 weeks of obstruction (decreased by 55% at maximal stimulation). RT-PCR demonstrated iNOS in approximately 70% of bladders obstructed for 1 and 3 weeks, while the iNOS protein was apparent in 50% of the bladders from the same groups. CONCLUSIONS: This new animal model of infravesical obstruction is reliable and reproducible. Moreover, the physiologic changes noted are comparable to other models, but an added advantage is the relevance of this model with regard to studying new transgenic or knockout mice. Enhanced expression of iNOS seen early after obstruction may serve to improve oxygenation during obstruction-induced ischemia.

    Title Type Iii Collagen Messenger Rna is Modulated in Non-compliant Human Bladder Tissue.
    Date June 1997
    Journal The Journal of Urology
    Excerpt

    PURPOSE: Previous studies have demonstrated that the non-compliant bladder is characterized histologically by an increased deposition of extracellular matrix protein, especially type III collagen, in the muscle wall. We sought to determine if an increased tissue level of type III collagen messenger RNA (mRNA) parallels the observed increase in protein expression. MATERIALS AND METHODS: Using a reverse transcription-polymerase chain reaction (RT-PCR) quantitative technique we measured and compared the bladder tissue concentration of type III collagen mRNA between an experimental group of patients (n = 7) with urodynamically proven non-compliant bladders (< 12 cc/cm. H2O) and a control group (n = 8) with normal bladder compliance (> 20 cc/cm. H2O). RESULTS: The mean (+/-S.E.M.) of type III collagen mRNA level in the non-compliant group was 11.72 +/- 2.56 attomole/milligram (amol/mg.) which was almost threefold higher than the level 4.26 +/- 0.74 amol/mg measured in the control group. This difference was statistically significant (p = 0.027). CONCLUSIONS: Type III collagen mRNA levels are increased in the human non-compliant bladder. Therefore the accumulation of type III collagen protein is, in part, transcriptionally regulated.

    Title Smooth-muscle Myosin Heavy-chain Isoform Expression in Bladder-outlet Obstruction.
    Date February 1997
    Journal World Journal of Urology
    Excerpt

    Bladder-outlet obstruction leads to detrusor smooth-muscle hypertrophy/hyperplasia. Despite this overall increase in muscle mass, smooth-muscle contractility decreases and bladder emptying is impaired. The goal of this study was to determine whether smooth-muscle myosin heavy-chain (MHC) alterations occur in conjunction with partial obstruction of the rabbit bladder. Total MHC and MHC-isoform protein concentrations were determined by quantitative gel electrophoresis in rabbit bladders partially obstructed for 1-4 weeks. MHC gene expression was assessed by Northern and nuclease protection assays. Two MHC isoforms (SM1/SM2) were identified in the normal rabbit bladder. After 2 weeks of obstruction the ratio of SM1/SM2 changed from 0.4:0.6 to 0.5:0.5 (P < 0.01). As compared with sham-operated values, the level of MHC mRNA decreased significantly as of 1 day after obstruction. Quantitation of MHC-isoform mRNA levels revealed a nearly 3-fold increase in the SM1/SM2 ratio. In this animal model of bladder-outlet obstruction, early changes in MHC isoforms as well as an overall decrease of MHC mRNA expression were demonstrated, suggesting that obstruction induces significant alterations in myofilament gene expression.

    Title Smooth-muscle Physiology.
    Date July 1996
    Journal The Urologic Clinics of North America
    Excerpt

    In the last several years, significant advances have been made in the understanding of bladder smooth muscle physiology. This article provides a summary for the clinician of current knowledge about the detrusor smooth muscle cell structure, function, and the relationship of structure to function in terms of bladder storage and physical properties such as compliance. The integration of this basic science knowledge into clinical practice is illustrated in discussion of two common disorders: detrusor instability, and outflow obstruction.

    Title Molecular Aspects of Bladder Outlet Obstruction.
    Date March 1996
    Journal Advances in Experimental Medicine and Biology
    Excerpt

    In an animal model of obstruction, increasing load induces significant smooth muscle hypertrophy which is associated with a down-regulation of myosin heavy chain expression. This undoubtedly contributes to the decreased smooth muscle contractility seen in this model. Moreover, obstruction-induced hypertrophy leads to the development of a dedifferentiated smooth muscle phenotype, as evidenced by a revision of the cell to fetal (of non-muscle) gene expression patterns. Similar alterations are seen in atherosclerotic vessels and other pathologic smooth muscle systems. In these systems, dedifferentiation is also associated with significant alterations in extracellular matrix expression. It seems likely that obstruction in the bladder induces dedifferentiation of the smooth muscle cell which alters contractility as well as extracellular matrix expression, leading to altered bladder performance and decreased compliance.

    Title Effects of Obstruction on Bladder Contractile Proteins.
    Date January 1995
    Journal Progress in Clinical and Biological Research
    Excerpt

    In an animal model of obstruction, increasing load induces significant smooth muscle hypertrophy which is associated with a down-regulation of myosin heavy chain expression. This undoubtedly contributes to the decreased smooth muscle contractility seen in this model. Moreover, obstruction-induced hypertrophy leads to the development of a dedifferentiated smooth muscle phenotype. Similar alterations are seen in atherosclerotic vessels and other pathologic smooth muscle systems. In these systems, dedifferentiation is also associated with significant alterations in extracellular matrix expression. It seems likely that obstruction in the bladder induces dedifferentiation of the smooth muscle cell which alters contractility as well as extracellular matrix expression, leading to altered bladder performance and decreased compliance.

    Title Fabrication of a Nano-cone Array on a P-gan Surface for Enhanced Light Extraction Efficiency from Gan-based Tunable Wavelength Leds.
    Date
    Journal Nanotechnology
    Excerpt

    We report on the fabrication of a nano-cone structured p-GaN surface for enhanced light extraction from tunable wavelength light emitting diodes (LEDs). Prior to p-contact metallization, self-assembled colloidal particles are deposited and used as a mask for plasma etching to create nano-cone structures on the p-GaN layer of LEDs. A well-defined periodic nano-cone array, with an average cone diameter of 300 nm and height of 150 nm, is generated on the p-GaN surface. The photoluminescence emission intensity recorded from the regions with the nano-cone array is increased by two times as compared to LEDs without surface patterning. The light output power from the LEDs with surface nano-cones shows significantly higher electroluminescence intensity at an injection current of 70 mA. This is due to the internal multiple scattering of light from the nano-cone sidewalls. Furthermore, we have shown that with an incorporation of InGaN nanostructures in the quantum well, the wavelength of these surface-patterned LEDs can be tuned from 517 to 488 nm with an increase in the injection current. This methodology may serve as a practical approach to increase the light extraction efficiency from wavelength tunable LEDs.

    Title The Use of Chemokine-releasing Tissue Engineering Scaffolds in a Model of Inflammatory Response-mediated Melanoma Cancer Metastasis.
    Date
    Journal Biomaterials
    Excerpt

    Inflammatory responses and associated products have been implicated in cancer metastasis. However, the relationship between these two processes is uncertain due to the lack of a suitable model. Taking advantage of localized and controllable inflammatory responses induced by biomaterial implantation and the capability of tissue scaffolds to release a wide variety of chemokines, we report a novel system for studying the molecular mechanisms of inflammation-mediated cancer metastasis. The animal model is comprised of an initial subcutaneous implantation of biomaterial microspheres which prompt localized inflammatory responses, followed by the transplantation of metastatic cancer cells into the peritoneal cavity or blood circulation. Histological results demonstrated that substantial numbers of B16F10 cells were recruited to the site nearby biomaterial implants. There was a strong correlation between the degree of biomaterial-mediated inflammatory responses and number of recruited cancer cells. Inflammation-mediated cancer cell migration was inhibited by small molecule inhibitors of CXCR4 but not by neutralizing antibody against CCL21. Using chemokine-releasing scaffolds, further studies were carried out to explore the possibility of enhancing cancer cell recruitment. Interestingly, erythropoietin (EPO) releasing scaffolds, but not stromal cell-derived factor-1α-releasing scaffolds, were found to accumulate substantially more melanoma cells than controls. Rather unexpectedly, perhaps by indirectly reducing circulating cancer cells, mice implanted with EPO-releasing scaffolds had ~30% longer life span than other groups. These results suggest that chemokine-releasing scaffolds may potentially function as implantable cancer traps and serve as powerful tools for studying cancer distraction and even selective annihilation of circulating metastatic cancer cells.


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