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Biomedical subjects

Hongwei Wang

Publications and source records attributed to Hongwei Wang.

At least 37 records · Page 2Linked to original sources
PubMed2005

Assessing quality of diabetes care by measuring longitudinal changes in hemoglobin A1c in the Veterans Health Administration.

CONTEXT: A1c levels are widely used to assess quality of diabetes care provided by health care systems. Currently, cross-sectional measures are commonly used for such assessments. OBJECTIVE: To study within-patient longitudinal changes in A1c levels at Veterans Health Administration (VHA) facilities as an alternative to cross-sectional measures of quality of diabetes care. DESIGN: Longitudinal study using institutional data on individual patient A1c level over time (October 1, 1998-September 30, 2000) with time variant and invariant covariates. SETTING: One hundred and twenty-five VHA facilities nationwide, October 1, 1998-September 30, 2000. PATIENTS: Diabetic veteran users with A1c measurement performed using National Glycosylated Hemoglobin Standardization Project certified A1c lab assay methods. EXPOSURES: Characteristics unlikely to reflect quality of care, but known to influence A1c levels, demographics, and baseline illness severity. MAIN OUTCOME MEASURE: Monthly change in A1c for average patient cared for at each facility. RESULTS: The preponderance of facilities showed monthly declines in within-patient A1c over the study period (mean change of -0.0148 A1c units per month, range -0.074 to 0.042). Individual facilities varied in their monthly change, with 105 facilities showing monthly declines (70 significant at .05 level) and 20 showing monthly increases (5 significant at .05 level). Case-mix adjustment resulted in modest changes (mean change of -0.0131 case-mix adjusted A1c units per month, range -0.079 to 0.043). Facilities were ranked from worst to best, with attached 90 percent confidence intervals. Among the bottom 10 ranked facilities, four remained within the bottom decile with 90 percent confidence. CONCLUSIONS: There is substantial variation in facility-level longitudinal changes in A1c levels. We propose that evaluation of change in A1c levels over time can be used as a new measure to reflect quality of care provided to populations of individuals with chronic disease.

Aged↗
PubMed2005

The secreted glycoprotein lubricin protects cartilage surfaces and inhibits synovial cell overgrowth.

The long-term integrity of an articulating joint is dependent upon the nourishment of its cartilage component and the protection of the cartilage surface from friction-induced wear. Loss-of-function mutations in lubricin (a secreted glycoprotein encoded by the gene PRG4) cause the human autosomal recessive disorder camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP). A major feature of CACP is precocious joint failure. In order to delineate the mechanism by which lubricin protects joints, we studied the expression of Prg4 mRNA during mouse joint development, and we created lubricin-mutant mice. Prg4 began to be expressed in surface chondrocytes and synoviocytes after joint cavitation had occurred and remained strongly expressed by these cells postnatally. Mice lacking lubricin were viable and fertile. In the newborn period, their joints appeared normal. As the mice aged, we observed abnormal protein deposits on the cartilage surface and disappearance of underlying superficial zone chondrocytes. In addition to cartilage surface changes and subsequent cartilage deterioration, intimal cells in the synovium surrounding the joint space became hyperplastic, which further contributed to joint failure. Purified or recombinant lubricin inhibited the growth of these synoviocytes in vitro. Tendon and tendon sheath involvement was present in the ankle joints, where morphologic changes and abnormal calcification of these structures were observed. We conclude that lubricin has multiple functions in articulating joints and tendons that include the protection of surfaces and the control of synovial cell growth.

Animals↗
PubMed2004

Imatinib mesylate (STI-571) enhances antigen-presenting cell function and overcomes tumor-induced CD4+ T-cell tolerance.

Tumor antigen-specific T-cell tolerance imposes a significant barrier to the development of effective therapeutic cancer vaccines. Bone marrow-derived antigen-presenting cells (APCs) are critical in the induction of this unresponsive state. Here we show that in vitro treatment of APCs with the tyrosine kinase inhibitor, imatinib mesylate (STI-571), enhances the activation of naive antigen-specific T cells and restores the responsiveness of tolerant T cells from tumor-bearing hosts. Furthermore, in vivo treatment with STI-571 not only prevented the induction of tolerance in tumor-specific CD4(+) T cells, preserving their responsiveness to a subsequent immunization, but also resulted in enhanced vaccine efficacy. These findings demonstrate that tolerance to tumor antigens is not an insurmountable obstacle and points to modulation of APC function as a promising strategy in the immunotherapy of cancer.

Amino Acid Sequence↗
PubMed2004

Strain distribution pattern of susceptibility to immune-mediated nephritis.

The genetic basis of immune-mediated nephritis is poorly understood. Recent studies have demonstrated that the NZW mouse strain is more prone to immune-mediated nephritis compared with C57BL/6 and BALB/c strains. The present study extends these findings by challenging 12 additional inbred strains of mice with rabbit anti-mouse glomerular basement membrane (GBM) reactive sera. Compared with control sera-injected mice and anti-GBM-injected A/J, AKR/J, C3H/HeJ, DBA/2J, MRL/MpJ, NOD/LtJ, P/J, SJL/J, and SWR/J mice, the anti-GBM-injected BUB/BnJ, DBA/1J, and 129/svJ mice developed severe proteinuria and azotemia. Their kidneys exhibited pronounced glomerulonephritis, with crescent formation, as well as tubulointerstitial disease, with these phenotypes being particularly profound in 129/svJ mice. However, these strains did not appear to differ in the nature of their xenogeneic immune response to the administered rabbit sera, either quantitatively or qualitatively. Collectively, these findings allude to the presence of genetic elements in the BUB/BnJ, DBA/1J, and 129/svJ genomes that may potentially confer susceptibility to immune-mediated nephritis. Detailed studies to dissect out the immunological and genetic basis of renal disease in these three strains are clearly warranted.

Animals↗
PubMed2004

Th1/Th2 cytokine profiles and their relationship to clinical features in patients following nonmyeloablative allogeneic stem cell transplantation.

An imbalance in helper T-cell type 1 (Th1) and type 2 (Th2) cytokines is suggested to play an important role in the pathogenesis of acute graft-versus-host disease (aGVHD). The aim of this study was to investigate the cytokine bias acquired by T cells after transplantation and its possible influence on relapse of original malignancy. Cytokine levels by peripheral CD4 and CD8 T cells were tested at various pre- and post-transplant time points with fluorescein isothiocyanate-based intracellular cytokine assay after short-term in vitro mitogenic stimulation (phorbol myristate acetate + ionomycin). In both CD4+ and CD8+ cells, interferon (IFN)-gamma-producing cell populations increased, indicating a shift to a Th1 cytokine profile with aGVHD. IFN-gamma-producing T cells was significantly lower in patients who experienced relapse of original disease compared to those who showed no signs of relapse and compared to normal controls. Our studies demonstrate that aGVHD correlates with a Th1 bias and that Th1 response may potentiate an effective immune surveillance.

Adolescent↗
PubMed2004

Effect of all-trans retinoic acid on airway inflammation in asthmatic rats and its mechanism.

The inhibitive effects of all-trans retinoic acid (ARTA) on airway inflammation in asthmatic rats and its mechanism on the basis of the regulation of nuclear factor kappaB (NF-kappaB) were explored. Thirty-two SD rats were randomly divided into 4 groups: control group, asthma group, dexamethasone treatment group and retinotic acid treatment group. The total and differential cell counts in the collected bronchoalveolar lavage fluid (BALF) were measured. The pathological changes in lung tissues were estimated by scoring. The expression of NF-kappaB inhibitor (IkappaBa), NF-kappaB, intercellular adhering molecule-1 (ICAM-1) in lung tissue was detected by immunohistochemical method. The results showed that in the two treatment groups, the total cell counts and proportion of inflammatory cells in BALF were significantly reduced, but there was no significant difference in differential cell counts in BALF between them. The pathological changes in lung tissues in the treatment groups were significantly attenuated as compared with asthma group. Except the epithelial injury in retinotic acid treatment group was milder than in dexamethasone treatment group, the remaining lesions showed no significant difference between them. In the two treatment groups, the expression of IkappaBa was increased, while the expression of NF-kappaB and ICAM-1 decreased with the difference between the two groups being not significant. It was concluded that the similar anti-inflammatory effects and mechanism of ATRA on airway in asthmatic rats to those of dexamethasone were contributed to the increase of cytoplasmic IkappaBa content and suppression of NF-kappaB activation and expression.

Animals↗
PubMed2004

[Effects of the combined use of benazepril and valsartan on apoptosis in the kidney of rats with adriamycin-induced nephritic glomerulosclerosis].

The effects of the combined use of angiotensin converting enzyme inhibitor (ACEI) benazepril and angiotensin II type 1 receptor antagonist (AT1RA) valsartan on apoptosis and the expression of apoptosis-related proteins Fas and FasL in the kidney of rats with adriamycin-induced nephritic glomerulosclerosis was investigated. Uninephrectomy and the injection of adriamycin induced the rat model of glomerulosclerosis. Benazepril (6 mg/kg), valsantan (20 mg/kg), or benazepril (3 mg/kg) plus valsantan (20 mg/kg) was respectively delivered daily by gavage to the rats in three treatment groups for 12 weeks. Apoptosis was examined by means of terminal-deoxynucleotidyl transferase mediated d-UTP nick end labeling (TUNEL). Immunohistochemistry was adopted to detect the expression of Fas and FasL. Software of pathological analysis quantitated the levels of Fas and FasL. The results showed that as compared with those in the control group, the kidneys in the model group had more severe glomerulosclerosis, much more apoptotic cells and higher levels of expression of Fas and FasL. The degree of glomerulosclerosis, the number of apoptotic cells and the levels of expression of Fas and FasL were reduced by benazepril and valsartan. The combined use of benazepril and valsartan had the best therapeutic effect. It was concluded that benazepril and valsartan could suppress the excessive apoptosis of kidney cells by lowering the expression of the apoptosis-related proteins Fas and FasL, so as to postpone the process of glomerulosclerosis. The combined use of benazepril and valsartan has better therapeutic effect.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2004

Electrophysiologic effects of nicorandil on the guinea pig long QT1 syndrome model.

INTRODUCTION: The slow component of the delayed rectifier K+ current IKs modulates repolarization of the cardiac action potential (AP), and the loss of IKs is known to cause long QT1 (LQT1) syndrome by prolonging action potential duration (APD). In this study, we generated a guinea pig LQT1 syndrome model using the IKs blocker chromanol 293B and then assayed the electrophysiologic effects of the ATP-sensitive potassium channel IK,ATP opener nicorandil on this model. METHODS AND RESULTS: Transmembrane action potentials of perfused right ventricular papillary muscle preparations and both in vitro and in vivo ECGs of guinea pigs were recorded. Blockade of IKs by chromanol 293B (30 microM) prolonged the action potential duration at 90% repolarization (APD90) by 8.5% and QT interval by 16.5% of control values. In addition, proarrhythmic early afterdepolarizations (EADs) and ventricular fibrillation were observed. Venoinjection of chromanol 293B (1 mg/kg) revealed 10.9% QT prolongation. Nicorandil (5-30 microM) dose-dependently shortened APD90 under the control condition, whereas it reversed the AP prolongation effect of chromanol 293B by 7.4% at the 30 microM concentration. Moreover, nicorandil shortened QT intervals both in vitro and in vivo and displayed an inhibitory effect on EADs and ventricular fibrillation. CONCLUSION: The ATP-sensitive potassium channel opener nicorandil may be an effective drug in the therapy of LQT1 syndrome by shortening APD and the QT interval.

Action Potentials↗
PubMed2004

Molecular therapeutics: promise and challenges.

The ability to analyze the genetic and epigenetic aberrations present in a particular patient's tumor on a global basis is rapidly maturing. The emerging fields of functional genomics and functional proteomics offer the opportunity to translate these advances into a full comprehension of the pathophysiology of cancer. Linking these approaches to chemical genomics and molecular therapeutics should provide an expanding repertoire of targeted therapeutics for clinical evaluation. Novel clinical trial designs that can determine the efficacy of targeted therapeutics in patients selected for aberrations in the target are needed to evaluate the wealth of new drugs becoming available. The promise of these technologies and advances in our understanding of cancer is immense, making it our responsibility to see them to fruition. These technologies should lead to a new era of individualized molecular medicine, wherein we will treat each patient with a "prescription" based on the genetic changes in each patient's tumor and their own genetic make-up, resulting in more effective and less toxic therapy.

Animals↗
PubMed2003

Extra-lymphatic solid tumor growth is not immunologically ignored and results in early induction of antigen-specific T-cell anergy: dominant role of cross-tolerance to tumor antigens.

A better understanding of how solid malignancies arise in an immunocompetent host, avoid immune recognition, and ultimately progress to widely disseminated cancer is essential to effectively harness the immune system against solid tumors. Because of their extra-lymphatic localization, it has been proposed that solid malignancies are just ignored by the immune system, thereby allowing their uncontrolled growth and dissemination. Alternatively, as most of the solid tumors are unable to express costimulatory molecules, the "signal one without signal two" model of tolerance induction has been frequently evoked to account for the failure of the immune system to reject antigenic tumors in vivo. In this study, we showed, however, that the extra-lymphatic growth of solid tumors is not immunologically ignored by the lymphoid compartment, resulting instead in the early induction of antigen-specific CD4(+) T-cell tolerance. Furthermore, analysis of parent-into-F1 bone marrow (BM) chimeras demonstrates that presentation of tumor antigens by BM-derived antigen-presenting cells represents the dominant mechanism in solid tumor-induced CD4(+) T-cell tolerance. Our findings of early development of antigen-specific T-cell unresponsiveness mediated by BM-derived antigen-presenting cells, not only provides a plausible explanation for the failure of the immune system to reject antigenic solid tumors in vivo, but more importantly, they have identified a barrier that, if appropriately manipulated, may lead to approaches to effectively harness the immune system against solid malignancies.

Animals↗
PubMed2003

Proportion of treatment effect (PTE) explained by a surrogate marker.

In time-varying covariate analysis of clinical survival data, it is often of interest to estimate the proportion of treatment effect (PTE), along with its confidence intervals, explained by a surrogate marker. The conventional procedure for such an analysis fits data into two working models separately to estimate the treatment effects before and after adjustment of the covariate. The construction of confidence intervals for the PTE under the conventional procedure lacks support by standard statistical software such as SAS, and could be very computationally demanding even after the support is available in the future. To overcome this problem, we propose a new procedure to simplify the computation. Under the new procedure, the treatment effects before and after adjustment of the covariate are simultaneously estimated from a single model. More important than saving computational effort, the new procedure can also be effectively applied to multiple-covariate models for the decomposition of overall treatment effect and for the comparison of PTE among several surrogate markers. The new procedure is applied to the motivating data example from the LIFE study, and demonstrates flexibility that the conventional procedure currently lacks.

Antihypertensive Agents↗
PubMed2003

Src family protein-tyrosine kinases alter the function of PTEN to regulate phosphatidylinositol 3-kinase/AKT cascades.

Src family protein-tyrosine kinases, which play an important role in signal integration, have been implicated in tumorigenesis in multiple lineages, including breast cancer. We demonstrate, herein, that Src kinases regulate the phosphatidylinositol 3-kinase (PI3K) signaling cascade via altering the function of the PTEN tumor suppressor. Overexpression of activated Src protein-tyrosine kinases in PTEN-deficient breast cancer cells does not alter AKT phosphorylation, an indicator of signal transduction through the PI3K pathway. However, in the presence of functional PTEN, Src reverses the activity of PTEN, resulting in an increase in AKT phosphorylation. Activated Src reduces the ability of PTEN to dephosphorylate phosphatidylinositols in micelles and promotes AKT translocation to cellular plasma membranes but does not alter PTEN activity toward water-soluble phosphatidylinositols. Thus, Src may alter the capacity of the PTEN C2 domain to bind cellular membranes rather than directly interfering with PTEN enzymatic activity. Tyrosine phosphorylation of PTEN is increased in breast cancer cells treated with pervanadate, suggesting that PTEN contains sites for tyrosine phosphorylation. Src kinase inhibitors markedly decreased pervanadate-mediated tyrosine phosphorylation of PTEN. Further, expression of activated Src results in marked tyrosine phosphorylation of PTEN. SHP-1, a SH2 domain-containing protein-tyrosine phosphatase, selectively binds and dephosphorylates PTEN in Src transfected cells. Both Src inhibitors and SHP-1 overexpression reverse Src-induced loss of PTEN function. Coexpression of PTEN with activated Src reduces the stability of PTEN. Taken together, the data indicate that activated Src inhibits PTEN function leading to alterations in signaling through the PI3K/AKT pathway.

Animals↗
PubMed2003

[The induction of apoptosis and reactive oxygen species in human skin fibroblast by ultraviolet A].

OBJECTIVE: To analyse the induction of apoptosis and reactive oxygen species (ROS) in human skin fibroblast by ultraviolet A (UVA). METHODS: Human skin fibroblasts were irradiated with UVA, apoptosis was determined with flowcytometry and fluorescent microscopy, the intracellular ROS production was measured with a spectrofluorometer, and the free radicals were determined with electron spin resonance. RESULTS: A significant increase of apoptosis was observed in human skin fibroblast after exposure to UVA with a dosage at 110-120 kJ.m-2, mannitol could counteract apoptosis; a higher level of intracellular ROS and the hydroxyl free radical was detected in the irradiated samples. CONCLUSION: A lower dose of irradiation of UVA(0.6 mW.cm-2) can induce apoptosis in human skin fibroblast, and ROS might play a role in the induction of apoptosis.

Annexin A5↗
PubMed2003

Amphetamine-induced dopamine efflux. A voltage-sensitive and intracellular Na+-dependent mechanism.

Amphetamine (AMPH) elicits its behavioral effects by acting on the dopamine (DA) transporter (DAT) to induce DA overflow into the synaptic cleft. Facilitated exchange diffusion is the classical model used to describe AMPH-induced DA efflux. This model hypothesizes that AMPH-induced DA efflux is mediated by DAT and results from the transport of AMPH into the cell followed by a counter movement of DA out to the extracellular compartment. To further characterize the action of AMPH, we used the patch clamp technique in the whole-cell configuration combined with amperometry on human embryonic kidney HEK-293 cells stably transfected with the human DAT (DAT cells). In DAT cells, AMPH-induced DAT-mediated currents were blocked by cocaine. We demonstrate that DA efflux mediated by DAT is voltage-dependent, electrogenic, and dependent on intracellular Na(+) concentration in the recording electrode. Intracellular Na(+) fluorescence, as measured by confocal microscopy using a Na(+)-sensitive dye, was enhanced by AMPH application. Furthermore, the ability of AMPH to induce DA efflux was regulated by intracellular Na(+) concentration and correlated with the size of the DAT-mediated, AMPH-induced ion flux across the plasma membrane. In the absence of intracellular Na(+) but the presence of high intracellular Cl(-), AMPH-induced inward currents elicited DA efflux proportionally to their dimension and duration. Thus, we propose that AMPH-induced DA efflux depends on two correlated transporter processes. First, AMPH binds to the DAT and is transported, thereby causing an inward current. Second, because of this AMPH-induced inward current, Na(+) becomes more available intracellularly to the DAT, thereby enhancing DAT-mediated reverse transport of DA.

Amphetamine↗
PubMed2003

Flavonoids: promising anticancer agents.

Flavonoids are polyphenolic compounds that are ubiquitously in plants. They have been shown to possess a variety of biological activities at nontoxic concentrations in organisms. The role of dietary flavonoids in cancer prevention is widely discussed. Compelling data from laboratory studies, epidemiological investigations, and human clinical trials indicate that flavonoids have important effects on cancer chemoprevention and chemotherapy. Many mechanisms of action have been identified, including carcinogen inactivation, antiproliferation, cell cycle arrest, induction of apoptosis and differentiation, inhibition of angiogenesis, antioxidation and reversal of multidrug resistance or a combination of these mechanisms. Based on these results, flavonoids may be promising anticancer agents.

Anticarcinogenic Agents↗
PubMed2003

Role of adrenomedullin in congenital heart disease associated with pulmonary hypertension.

The changes of adrenomedullin (ADM), endothelin-1 (ET-1) and nitric oxide (NO) levels before and after operation in congenital heart disease (CHD) associated with pulmonary hypertension (PH) were observed in order to investigate their role in CHD with PH and their clinical significance. The CHD patients were divided into 3 groups according to pulmonary artery systolic pressure (PASP): Non-PH group: PASP < or = 30 mmHg (n = 11); mild-PH group: PASP 31-49 mmHg (n = 10); moderate or severe-PH group: PASP > or = 50 mmHg (n = 12). The control group consisted of 15 health children. Plasma ADM, ET-1 and NO levels were determined by radioimmunoassay and colorimetry methods. The correlation between ADM and ET-1, NO, PASP was analyzed. The changes in plasma ADM, ET-1 and plasma NO on the 7th day after operation among the groups were compared. The results showed that plasma ADM levels in non-PH group were significantly higher than that in control group (P < 0.05), but there was no significant difference in ET-1 and NO levels between the two groups (P > 0.05). ADM and ET-1 levels in mild-PH group were significantly elevated as compared with those in non-PH group (both P < 0.05), but NO levels were decreased (P < 0.05). ADM and ET-1 levels in moderate or severe-PH groups were increased as compared with those in mild-PH group (both P < 0.01), but NO level significantly declined (P < 0.05). On the 7th day after operation, plasma ADM and ET-1 levels in PH group were significantly decreased (P < 0.05, P < 0.01) as compared with those before operation, but there was no significant difference in NO levels (P > 0.05). But NO levels in non-PH group were significantly increased (P < 0.05). Plasma ADM levels in CHD were positively correlated with PASP and ET-1 (r = 0.77, P < 0.01; r = 0.82, P < 0.01), negatively correlated with NO (r = -0.56, P < 0.05). It was concluded that during the progression of PH in the cases of CHD, plasma ADM, ET-1 and NO might play an important role in the development of PH. The increased ADM may represent a compensatory mechanism. It can interact with NO and ET-1 to regulate pulmonary circulation in the pathophysiology of PH with CHD. ADM may be involved in the defence mechanism against further increase of pulmonary arterial pressure. ADM could be used as a reliable indicator of the severity of CHD associated PH.

Adolescent↗