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Biomedical subjects

Peter Lin

Publications and source records attributed to Peter Lin.

At least 19 recordsLinked to original sources

Awareness and attitudes regarding microbicides and Nonoxynol-9 use in a probability sample of gay men.

A household probability sample of 879 adult gay and other men who have sex with men in San Francisco underwent phone interviews. Approximately, half reported recent unprotected anal intercourse (UAI). Yet, lubricant use was high, a behavior that may facilitate future adoption of topical microbicide delivered by a lubricant gel. Despite warnings against Nonoxynol-9 (N-9), 26% of respondents reported still using it. Microbicide awareness was higher among men reporting UAI than among consistent condom users. Scenarios presenting microbicides "as effective as condoms," "nearly as effective," or "less effective but better than nothing" produced wide variability in willingness to use them, which may have implications for microbicide acceptability. HIV-infected men and those who reported UAI showed greater microbicide acceptance.

Adolescent↗

Rectal microbicide acceptability: results of a volume escalation trial.

OBJECTIVES: The objectives of this study were to determine what volume of a microbicide placebo gel is acceptable when applied intrarectally before receptive anal intercourse (RAI); and to evaluate responses to properties of the gel, its application, and its use. STUDY DESIGN: HIV-uninfected men who reported unprotected RAI with serodiscordant or unknown-status partners were enrolled in a volume escalation trial. RESULTS: Up to 35 mL of gel with the physical properties of Femglide (transparent and odorless) was acceptable to the majority of participants. Choice of different levels of viscosity may be needed. For some men, volumes judged acceptable when tried without intercourse were not acceptable when used during sex. Overall, participants reported high intentions to use microbicides when available. Condom use was inconsistent despite advice to use condoms. CONCLUSIONS: Microbicides that would require up to 35 mL of volume to be effective would be acceptable to men who engage in high-risk RAI.

Administration, Rectal↗

2-Aminoquinoline melanin-concentrating hormone (MCH)1R antagonists.

A series of 2-aminoquinoline compounds was prepared and evaluated in MCH1R binding and functional antagonist assays. Small dialkyl, methylalkyl, methylcycloalkyl, and cyclic amines were tolerated at the quinoline 2-position. The in vivo efficacy of compound 12 was explored and compared to that of a related inactive analog to determine their effects on food intake and body weight in rodents.

Animals↗

4-Aminoquinoline melanin-concentrating hormone 1-receptor (MCH1R) antagonists.

Structure-activity relationships of a 4-aminoquinoline MCH1R antagonist lead series were explored by synthesis of analogs with modifications at the 2-, 4-, and 6-positions of the original HTS hit. Improvements to the original screening lead included lipophilic groups at the 2-position and biphenyl, cyclohexyl phenyl, and hydrocinnamyl carboxamides at the 6-position. Modifications of the 4-amino group were not well tolerated.

Aminoquinolines↗

Adipokine resistin promotes in vitro angiogenesis of human endothelial cells.

OBJECTIVE: Resistin may be associated with obesity and cardiovascular diseases. However, it is unknown whether resistin directly contributes to angiogenesis. In the present study, we evaluated the effects of resistin on angiogenic potential, including endothelial cell proliferation, migration, and capillary-like tube formation. METHODS: Human coronary artery endothelial cells (HCAECs) were treated with resistin. Cell proliferation was evaluated by [3H]thymidine incorporation and MTS assays. Cell migration was assessed by a modified Boyden chamber assay. Capillary-like tube formation was studied with a Matrigel model. Several gene expression levels were determined by real-time PCR. Activation of mitogen-activated protein kinases (MAPKs) was determined by Bio-Plex luminex analyzer. Basic fibroblast growth factor (bFGF) was used as a control. Human umbilical vein endothelial cells (HUVECs) and human lung microvascular endothelial cells (HMVEC-L) were also included. RESULTS: Resistin induced both endothelial proliferation and migration in a dose- and time-dependent manner with the maximal effect at 40 ng/ml. Both resistin-induced cell proliferation and migration could be effectively blocked by a resistin-neutralization antibody. In addition, resistin promoted capillary-like tube formation of HCAECs on Matrigel. Resistin also significantly upregulated the mRNA expression of vascular endothelial growth factor receptors (VEGFR-1 and VEGFR-2) and matrix metalloproteinases (MMP-1 and MMP-2) at both mRNA and protein levels. Furthermore, transient phosphorylation of ERK1/2 and p38 was observed after the addition of resistin to HCAECs. The resistin-induced cell proliferation and migration were both completely blocked by specific ERK1/2 and p38 inhibitors. CONCLUSIONS: Resistin induces human endothelial cell proliferation and migration, promotes capillary-like tube formation, upregulates the expression of VEGFRs and MMPs, and activates ERK1/2 and p38 pathways. Thus, resistin may play an important role in angiogenesis-associated vascular disorders.

Antibodies, Monoclonal↗

Thymosin beta10 inhibits cell migration and capillary-like tube formation of human coronary artery endothelial cells.

Thymosin beta10 is a cytoplasm G-actin sequestering protein whose functions are largely unknown. To determine the direct effects of exogenous thymosin beta10 on angiogenic potentials as endothelial cell migration and capillary-like tube formation, human coronary artery endothelial cells (HCAECs) were incubated with increasing doses of thymosin beta10 (25-100 ng/ml). By using a modified Boyden chamber assay, thymosin beta10 inhibited cell migration in a dose- and time-dependent manner with the maximal effect being a 36% reduction at 100 ng/ml as compared to controls (P < 0.01). In addition, thymosin beta10 (100 ng/ml) significantly inhibited the capillary-like tube-formation of HCAECs on Matrigel, showing a 21% reduction of the total tube length as compared to negative controls (P < 0.01). Furthermore, by using real time PCR analysis, thymosin beta10 significantly decreased mRNA levels of vascular endothelial growth factor (VEGF), VEGF receptor-1 (VEGFR-1) and integrin alphaV after 24 h treatment in HCAECs. By contrast, thymosin beta4 significantly increased HCAEC migration. These results indicate that thymosin beta10, but not thymosin beta4, have direct inhibitive effects on endothelial migration and tube formation that might be mediated via downregulation of VEGF, VEGFR-1 and integrin alphaV in HCAECs. This study suggests a potential therapeutic application of thymosin beta10 to the diseases with excessive angiogenesis such as cancer.

Capillaries↗

Endovascular occlusion of right to left arteriovenous shunt associated with persistent left superior vena cava.

Left-sided superior vena cava (SVC) as the result of persistence of the left superior cardinal vein in postnatal life is a rare congenital anomaly, is usually associated with other cardiac defects, and can cause symptoms of right to left shunt. We report the case of a 58-year-old Asian man with a history of end-stage renal disease and Ebstein anomaly that was corrected surgically who presented with progressively worsening disabling dyspnea. An echocardiogram with concomitant intravenous saline injection raised the suspicion of right to left shunt, a finding that was confirmed with contrast injection of the left SVC that rapidly filled the left heart chambers and subsequently the aortic arch. To treat this anomaly, we accessed the left basilic vein under ultrasound guidance and inserted a 14F sheath into the left subclavian vein. A covered stent was then prepared at the back table with three Prolene 4-0 sutures that were wrapped around the middle portion of the graft to achieve a controlled area of stenosis after deployment. The stent graft was placed along the proximal innominate vein and the contiguous part of the left SVC. Coil embolization was then performed with coils that were positioned at the stenotic area of the covered stent. An immediate venogram demonstrated residual flow into the left SVC; however, a delayed venogram 2 weeks after the procedure showed occlusion of the left SVC and the development of collaterals to the right innominate vein that was draining to a normal right SVC. The patient remained marginally hypotensive after surgery, but he soon noted a substantial improvement in his symptoms. A repeat echocardiogram with intravenous saline injection confirmed the correction of the right to left shunt. Endovascular repair of persistent left SVC is feasible and safe and can be performed with minimal morbidity.

Arteriovenous Shunt, Surgical↗

Cybercartography of popular internet sites used by New York City men who have sex with men interested in bareback sex.

A systematic method was used to elicit the names of the six most popular free Internet sites used by gay men and other men who have sex with men in New York City, to meet partners for "bareback" sex. An analysis of the sites characteristics shows that men can use mainstream Internet sites, gay-specific sites, and sex-focused sites free of charge to search for bareback sex partners, selecting by location, physical attributes, sexual mode, HIV-serostatus, and other characteristics. Many individuals use these sites, producing the impression that bareback sex is not an oddity confined to just a few. The official language of the bareback sites associates bareback sex with masculinity and courage, prioritizing pleasure, freedom, choice, and intimacy over HIV-transmission prevention. The sites facilitate sexual experimentation and the expansion of bareback networks. Although some consider bareback sex to represent a failure of HIV prevention, this study suggests that harm reduction strategies may be viable within bareback networks.

Adult↗

Effect of lysophosphatidylcholine on vasomotor functions of porcine coronary arteries.

BACKGROUND: Lysophosphatidylcholine (LPC) is a product of phosphatidylcholine hydrolysis by phospholipase A(2) and a mediator of the lipid-induced atherosclerotic changes. In this study, we determined the effects of LPC on vasomotor functions, oxidative stress, and endothelial nitric oxide synthase (eNOS) expression in porcine coronary arteries. METHODS: Porcine coronary arteries were cut into 5-mm rings and were treated with LPC or antioxidant selenomethionine (SeMet). For the vasomotor studies, we used a myograph tension system. Levels of superoxide anion (O(2)(-)) were detected by the lucigenin-enhanced chemiluminescence method. The eNOS protein level was studied by immunohistochemistry with avidin-biotin complex immunoperoxidase procedure. RESULTS: Endothelium-dependent relaxation in response to bradykinin was reduced by 36% and 81% for the rings treated with 12.5 and 25 mum of LPC, respectively, as compared with controls (P < 0.05). Endothelium-independent relaxation in response to sodium nitroprusside also was reduced by 63% after treatment with 25 mum LPC (P < 0.05). The O(2)(-) level was increased in the porcine arteries treated with 25 mum of LPC by 41% as compared with controls (P < 0.05). The antioxidant SeMet reversed the effects of LPC on vascular relaxation and O(2)(-) production. Immunoreactivity of eNOS in LPC-treated vessel rings also was reduced substantially. CONCLUSIONS: LPC impairs endothelium-dependent and endothelium-independent vasorelaxation. This effect is associated with increased superoxide radical production and decreased eNOS activity and is practically reversed with the use of the antioxidant SeMet.

Animals↗

Ginsenosides block HIV protease inhibitor ritonavir-induced vascular dysfunction of porcine coronary arteries.

Human immunodeficiency virus (HIV) protease inhibitor ritonavir (RTV) may induce vascular dysfunction through oxidative stress. Ginsenosides have been shown to have potential benefits on the cardiovascular system through diverse mechanisms, including antioxidative property. The objective of this study was to determine whether ginsenosides could prevent coronary arteries from RTV-induced dysfunction. Porcine coronary artery rings were incubated with RTV and ginsenosides Rb1, Rc, and Re for 24 h. Vasomotor function was recorded by a myograph tension system. In response to the thromboxane A(2) analog U-46619, the contraction of the vessel rings was significantly reduced. When cocultured with Rb1, Rc, and Re, the contractility significantly increased. In response to bradykinin at 10(-5) M, the endothelium-dependent relaxation of vessel rings was significantly reduced by 59% for RTV compared with controls (P < 0.05). When cocultured with Rb1, Rc, and Re, the relaxation significantly increased 100%, 90%, and 134%, respectively, compared with the RTV-alone groups (P > 0.05). In response to sodium nitroprusside, RTV significantly reduced vasorelaxation. In addition, the endothelial nitric oxide synthase (eNOS) mRNA levels were significantly reduced by 78% for RTV group (P < 0.05) by real-time PCR analysis. The eNOS protein levels measured by Western blot analysis and nitrite concentrations measured by Griess assay were also decreased, whereas O(2)(-) production by lucigenin-enhanced chemiluminescence was significantly increased in the RTV-treated group. These effects of RTV were effectively blocked by ginsenosides. Thus HIV protease inhibitor RTV significantly impaired the vasomotor function of porcine coronary arteries. This effect may be mediated by the downregulation of eNOS and overproduction of O(2)(-). These results suggest that ginsenosides can effectively block RTV-induced vascular dysfunction.

Animals↗

Curcumin blocks HIV protease inhibitor ritonavir-induced vascular dysfunction in porcine coronary arteries.

BACKGROUND: HIV protease inhibitor ritonavir (RTV) is associated with many cardiovascular complications and causes vascular dysfunction through oxidative stress. In the present study, we determined the effects of RTV and curcumin (a pigment derived from turmeric) on porcine coronary arteries. STUDY DESIGN: Artery rings were incubated with 15 microM concentration of RTV and curcumin (5 or 10 microM) for 24 hours. Vasomotor function was studied with a myograph tension system. Endothelial nitric oxide synthase (eNOS) mRNA and protein levels were studied using real-time polymerase chain reaction, Western blot, and immunohistochemistry. Nitric oxide was measured using Griess assay. Superoxide anion levels were determined by lucigenin enhanced chemiluminescence. RESULTS: RTV considerably reduced vessel contraction by 71%, endothelium-dependent relaxation by 59%, and endothelium-independent relaxation by 52%, as compared with controls. Curcumin effectively blocked RTV-induced vasomotor dysfunction. RTV-treated arteries showed substantial reductions of eNOS mRNA by 77%, eNOS protein by 72%, and nitric oxide release by 37% as compared with controls. The RTV plus curcumin-treated vessels showed substantial increases of eNOS and nitric oxide levels as compared with the RTV-treated vessels. Finally, there was a 47% increase of superoxide anion production in the RTV-treated vessels as compared with controls. Again, curcumin effectively reversed this effect of RTV. CONCLUSIONS: HIV protease inhibitor RTV impairs vasomotor functions, reduces eNOS expression and nitric oxide release, and increases oxidative stress in porcine coronary arteries. Curcumin effectively blocks these detrimental effects of RTV.

Animals↗

Effects of cyclophilin A on cell proliferation and gene expressions in human vascular smooth muscle cells and endothelial cells.

BACKGROUND: Cyclophilin A (CypA) is a cytosolic protein which involves many biological functions including immune modulation, cell growth, tumorigenesis, and vascular disease. The objective of this study was to determine the effect of CypA on cell proliferation and several gene expressions in human endothelial cells and vascular smooth muscle cells. METHODS: Human coronary artery endothelial cells (HCAEC), human lung microvascular endothelial cells (HMVEC-L), and human aorta smooth muscle cells (HAoSMC) were used in this study. Cells were treated with 10 nM CypA for 24 h. The cell proliferation was determined by [3H]thymidine incorporation. The mRNA levels of 13 genes including CD147 (receptor for CypA), PDGF-BB, endothelin-1 (ET-1), vascular endothelial growth factor receptor-1 (VEGFR-1), VEGFR-2, VEGFR-3, neuropilin-1 (NRP-1), NRP-2, eNOS, iNOS, nNOS, ICAM-1, and PECAM-1 were semiquantitatively determined by real time RT-PCR as standardized with a house keeping gene beta-actin. RESULTS: CypA significantly increased cell proliferation of HAoSMC and HMVEC-L by 31% and 45%, respectively, as compared to controls, but had no effect on HCAEC. Blocking CD147 did not affect the mitogenic action of CypA. In addition, CypA also significantly increased the mRNA expression of CD147 by 43% and VEGFR-2 by 65% in HAoSMCs (P < 0.05, t test). HAoSMCs expressed much higher CD147 and neuropilin-1 (NRP-1) mRNA than HMVECs-L and HCAECs (P < 0.017, ANOVA). Furthermore, CypA increased ET-1 mRNA by 22% and VEGFR-1 mRNA by 23% in HMVECs-L, but had limited effects on HCAECs. HMVECs-L had much higher expressions of PDGF-BB, ET-1, VEGFR-2, VEGFR-1, VEGFR-3, and NRP-2 than HAoSMCs and HCAECs (P < 0.017, ANOVA). By contrast, HCAECs had much higher ICAM-1 mRNA levels than HMVECs-L and HAoSMCs (P < 0.017, ANOVA). CONCLUSIONS: These data demonstrate that CypA has a mitogenic effect on HAoSMCs and HMVECs-L, but not HCAECs. CD147 may not mediate the action of CypA. In addition, CypA substantially alters the mRNA levels of several key genes in human vascular cells, indicating potential multifunctional roles of CypA in vascular system. Furthermore, this study provides several new aspects of gene expressions in vascular cells.

Aorta↗

Cellular and molecular mechanisms of coronary vessel development.

Development of coronary vessels is a complex process in developmental biology and it may have clinical implications. Although coronary vessels develop as a form of vasculogenesis followed by angiogenesis, the cells of the entire coronary system do not arise from the developing heart. The key events of the coronary system formation include the generation of primordium and proepicardial organ; formation of epicardium; generation of subepicardial mesenchymal cells, and the formation, remodeling and maturation of the final vascular plexus. These events represent a complex regulation of the cell fate determination, cellular migration, epicardial/ mesenchymal transformation, and patterning of vasculatures. Recent studies suggest that several transcription factors, adhesion molecules, growth factors and signaling molecules play essential roles in these events. This article reviews the literature on the development of coronary vessels, and discusses current advances and controversies of molecular and cellular mechanisms, thereby directing future investigations.

Acetyltransferases↗

A web-based system for managing and co-ordinating multiple multisite studies.

Efficient and secure collection and management of information is essential in any modern biomedical study. Data management and coordination of multisite studies is a complex process. It involves development of systems for data collection, data cleaning with quality assurance checks, and specimen tracking, as well as development of procedures for conducting the study, training clinical sites, and communicating with sites to answer study questions and resolve and track data inquiries and resolutions. We developed a secure web-based system that is designed to automate evaluation of eligibility criteria and data collection, track specimens, serve as a resource for study-specific information, facilitate communication across sites in multisite studies, track data queries and resolutions, and allow administrative management of studies. The system combines a common framework across studies that defines the internal structure for all the web pages, with a study-specific one that defines the content of each page via a relational database. This combination creates a flexible and efficient environment enabling several multisite studies to be simultaneously or consecutively implemented and managed in a timely manner. We describe the development process, the system and its evaluation, current status, lessons learned, and future development plans.

Biomarkers, Tumor↗

The health belief model, sexual behaviors, and HIV risk among Taiwanese immigrants.

In this first investigation of Taiwanese sexual behaviors in the United States, 144 Taiwanese students completed an online anonymous survey. Demographics, health belief model (HBM) constructs, and acculturation were examined as predictors of sexual behaviors over the last year. Analyses indicated that participants who reported a higher number of sexual partners and more frequent sexual intercourse tended to be more educated and more likely to be nonheterosexual. The HBM constructs, as a set, reliably predicted participants' sexual behaviors. Self-efficacy was the strongest predictor within the HBM. Furthermore, acculturation moderated the predictive power of the HBM with respect to intercourse frequency. The main limitation of the study is that the measure of HBM, which was not designed to target Asian immigrants, was psychometrically poor. The results suggest self-efficacy is a target for behavioral change, acculturation may need to be incorporated into the HBM, and more culturally sensitive measures need to be developed.

Acculturation↗

Laparoscopic distal pancreatic resection.

Laparoscopic resection is not an established treatment for pancreatic tumors. Previous reports, mainly in Europe and Japan, have demonstrated the potential utility of laparoscopic distal pancreatectomy (LDP). However, few reports have been published from the United States. We instituted a pilot program to assess LDP. A total of 11 patients were included from December 2003 to December 2004. All patients were staged with preoperative endoscopic ultrasound and received vaccinations for possible splenectomy. The indications for surgery were as follows: neuroendocrine tumor (n = 7), unspecified tumor (n = 1), and cystic neoplasm (n = 3). All procedures began with diagnostic laparoscopy and intraoperative ultrasound. Three patients underwent laparoscopic enucleation of a discrete pancreatic nodule. In eight patients, LDP was attempted. One patient required conversion to an open procedure. In the other seven patients, the procedure was completed laparoscopically, two with hand-assist. The average operative time was 5 hours and 3 minutes; average length of stay was 5 days; and the splenectomy rate was 57 per cent (n = 4). There was one complication of an infected hematoma. There were no pancreatic leaks, deaths, nor readmissions. LDP with or without splenectomy is feasible and can be performed with minimum morbidity and only slightly increased operative time.

Adult↗

Effects of TNF-alpha and curcumin on the expression of thrombomodulin and endothelial protein C receptor in human endothelial cells.

The objective of this study was to elucidate the effects of tumor necrosis factor-alpha (TNF-alpha) on the expression of thrombomodulin (TM) and endothelial protein C receptor (EPCR) in human endothelial cells as well as the effect of curcumin, a spice and coloring food compound, as a potential therapeutic agent. Human umbilical vein endothelial cells (HUVECs) treated with TNF-alpha (2.0 ng/ml) showed reduced TM mRNA levels by 80%, 97%, 94%, and 97% at 3, 6, 12, and 24 h, respectively (P<0.05), by real-time PCR analysis. Dose-dependent study showed that TM mRNA levels of HUVECs were decreased by 86%, 89%, 91%, and 94% after treatment of TNF-alpha (0, 0.25, 0.5, 1, and 2 ng/ml) for 6 h, respectively (P<0.05). TM protein levels in HUVECs were significantly reduced by 69% in TNF-alpha-treated cells as compared to controls (P<0.05) by Western blot analysis. Secreted protein and activity of TM of HUVEC cultures were also significantly reduced in TNF-alpha-treated cells. In addition, EPCR mRNA levels of HUVECs were significantly reduced in TNF-alpha-treated group as compared to controls (P<0.05). Furthermore, these effects were observed in other types of endothelial cells from human coronary arteries, lung, and skin. Curcumin effectively blocked these effects of TNF-alpha on downregulation of TM and EPCR. These data demonstrate that TNF-alpha significantly decreases expression of TM and EPCR at both mRNA and protein levels in several human endothelial cells. Curcumin can effectively block TNF-alpha-induced endothelial dysfunction. This study suggests a new molecular mechanism of inflammation-induced thrombosis and a new therapeutic strategy to prevent this clinical problem.

Antigens, CD↗