Biomedical subjects

Henry Wu

Publications and source records attributed to Henry Wu.

5 recordsLinked to original sources

PubMed2006

Oral CD3-specific antibody suppresses autoimmune encephalomyelitis by inducing CD4+ CD25- LAP+ T cells.

A major goal of immunotherapy for autoimmune diseases and transplantation is induction of regulatory T cells that mediate immunologic tolerance. The mucosal immune system is unique, as tolerance is preferentially induced after exposure to antigen, and induction of regulatory T cells is a primary mechanism of oral tolerance. Parenteral administration of CD3-specific monoclonal antibody is an approved therapy for transplantation in humans and is effective in autoimmune diabetes. We found that orally administered CD3-specific antibody is biologically active in the gut and suppresses autoimmune encephalomyelitis both before induction of disease and at the height of disease. Orally administered CD3-specific antibody induces CD4+ CD25- LAP+ regulatory T cells that contain latency-associated peptide (LAP) on their surface and that function in vitro and in vivo through a TGF-beta-dependent mechanism. These findings identify a new immunologic approach that is widely applicable for the treatment of human autoimmune conditions.

Administration, Oral↗

PubMed2006

Effectiveness of an enhanced peer assessment program: introducing education into regulatory assessment.

INTRODUCTION: The College of Physicians and Surgeons of Ontario developed an enhanced peer assessment (EPA), the goal of which was to provide participating physicians educational value by helping them identify specific learning needs and aligning the assessment process with the principles of continuing education and professional development. In this article, we examine the educational value of the EPA and whether physicians will change their practice as a result of the recommendations received during the assessment. METHODS: A group of 41 randomly selected physicians (23 general or family practitioners, 7 obstetrician-gynecologists, and 11 general surgeons) agreed to participate in the EPA pilot. Nine experienced peer assessors were trained in the principles of knowledge translation and the use of practice resources (tool kits) and clinical practice guidelines. The EPA was evaluated through the use of a postassessment questionnaire and focus groups. RESULTS: The physicians felt that the EPA was fair and educationally valuable. Most focus group participants indicated that they implemented recommendations made by the assessor and made changes to some aspect of their practice. The physicians' suggestions for improvement included expanding the assessment beyond the current medical record review and interview format (eg, to include multisource feedback), having assessments occur at regular intervals (eg, every 5 to 10 years), and improving the administrative process by which physicians apply for educational credit for EPA activities. CONCLUSIONS: The EPA pilot study has demonstrated that providing detailed individualized feedback and optimizing the one-to-one interaction between assessors and physicians is a promising method for changing physician behavior. The college has started the process of aligning all its peer assessments with the principles of continuing professional development outlined in the EPA model.

Attitude of Health Personnel↗

PubMed2006

Lipoprotein glomerulopathy: a new apolipoprotein E mutation with enhanced glomerular binding.

We describe a case of lipoprotein glomerulopathy, the second ever reported from the United States, in a Mexican man with a hitherto undescribed mutation in the apolipoprotein E gene (substitution of proline for arginine at position 147 [Arg147Pro]). In this patient, glomerular basement membranes showed double contours and circumferential mesangial extensions, suggesting that deposition of lipids could be injurious to endothelial cells. Immunofluorescence staining of thrombi was positive for apolipoprotein E and B. To study the reason for lipid deposition in glomeruli, we incubated normal human kidney sections with serum from the patient and a healthy control. Apolipoprotein E from the patient's serum showed binding to the glomerular capillary wall, but the control did not, suggesting enhanced binding of the mutated apolipoprotein E to glomerular capillaries. Apolipoprotein E genotyping by means of restriction endonuclease digestion of polymerase chain reaction-amplified genomic DNA showed it to be of the wild-type E3/E3.

Adult↗

PubMed2005

Antagonism of vascular endothelial growth factor results in microvessel attrition and disorganization of wound tissue.

Vascular endothelial growth factor (VEGF) is a potent growth factor that is indispensable for the development of blood vessels in the fetus and for wound healing in adults. VEGF likely plays a role in maintaining the blood vessels once they have been formed. It is not clear, however, whether a low tissue VEGF (caused either by disease or by systemic administration of VEGF antagonists) can cause abnormalities in preexisting blood vessels, especially of wound tissue that requires high local levels of VEGF for healing. The present study investigated the effect of VEGF antagonism on blood vessels of foreign-body granulomas (a model of wound-healing tissue). Granulomas were induced by implanting perforated polyvinyl tubes into the subcutaneous tissue of rats and allowed to develop for 14 days, at which time the implanted tubes were completely encapsulated by the subcutaneous tissue. The encapsulated granulomas consisted of 3 distinct histological layers, of which the middle layer was well perfused by a rich supply of microvessels. Morphologically, the granuloma remained "stable" after developing for 14 days. At 1 week, VEGF levels in the granuloma fluid, which is in equilibrium with the interstitial fluid, were 25 times higher than in the plasma. VEGF levels in the granuloma fluid continued to increase for up to 3 weeks, reflecting the high dependence of the wound tissue on ambient VEGF levels. After injection of the VEGF receptor antagonist in the fully formed granuloma, the preexisting blood vessels in the middle layer regressed and underwent apoptosis, accompanied by expansion of the extracellular matrix (predominately collagen I) into areas normally devoid of matrix. We conclude that wound tissue is sensitive to ambient VEGF levels, and that a low VEGF condition resulting from VEGF receptor antagonism can disrupt the healing of wound tissue.

Animals↗

PubMed2004

Evolvable social agents for bacterial systems modeling.

We present two approaches to the individual-based modeling (IbM) of bacterial ecologies and evolution using computational tools. The IbM approach is introduced, and its important complementary role to biosystems modeling is discussed. A fine-grained model of bacterial evolution is then presented that is based on networks of interactivity between computational objects representing genes and proteins. This is followed by a coarser grained agent-based model, which is designed to explore the evolvability of adaptive behavioral strategies in artificial bacteria represented by learning classifier systems. The structure and implementation of the two proposed individual-based bacterial models are discussed, and some results from simulation experiments are presented, illustrating their adaptive properties.

Adaptation, Physiological↗