Biomedical subjects

Fred Finkelman

Publications and source records attributed to Fred Finkelman.

4 recordsLinked to original sources

PubMed2006

Advances in basic and clinical immunology.

This review comments on basic and clinical immunology articles that were published in 2005, with a focus on those that appeared in the Journal of Allergy and Clinical Immunology. In the area of basic immunology, mechanisms of the innate immune system and its interaction with the adaptive immune system were described, with special consideration to applications in biodefense strategies. T regulatory cells were further characterized in their role for the control of allergic, autoimmune, and neoplastic disorders. The function of the thymus Hassall's corpuscles was reported to be the generation of T regulatory cells. Flavonoid molecules obtained from medicinal herbs, including astilbin and epigallocatechin gallate, were discovered to have immunomodulatory properties. Advances in clinical immunology resulted from efforts to develop a newborn screening test for severe combined immunodeficiency and the elucidation of the crystal structure of the IL-2 receptor gamma chain. Mutations in the membrane receptor transmembrane activator and calcium modulator and cyclophilin ligand interactor were found in patients with common variable immunodeficiency. New therapeutic options are described, such as the use of infliximab for granulomas and GM-CSF for chronic ulcers in patients with common variable immunodeficiency. The importance of mucosal immunity in acute HIV infection is cited, as is the role of CD8+ T-cell activation in HIV disease progression in children.

Allergy and Immunology↗

PubMed2005

Deficiencies in selenium and/or vitamin E lower the resistance of mice to Heligmosomoides polygyrus infections.

Previous studies have shown that deficiencies in selenium (Se) and/or vitamin E (VE) can exacerbate the infectivity and pathogenesis of coxsackievirus B3 and influenza. Both Se and VE play a role in immune function and antioxidant defense. To determine whether these deficiencies would affect the normal course of infection with a metazoan parasite, mice were made deficient in Se and/or VE and inoculated with the gastrointestinal nematode parasite Heligmosomoides polygyrus. Both primary and secondary infections were assessed. Although the course of a primary infection with H. polygyrus was unaffected by diet, diets deficient in Se, VE, and both Se and VE (Se/VE double-deficiency) all caused delayed adult worm expulsion and increased fecundity during a secondary infection; suggesting an impaired intestinal response. H. polygyrus-induced IL-4 levels were diet-independent; but Se/VE double-deficiency blocked the H. polygyrus-induced IL-4 receptor-associated decrease in sodium-dependent glucose absorption in the jejunum that contributes to worm expulsion. In contrast, Se/VE double-deficiency had no effect on the infection-induced, IL-4R-associated increase in epithelial cell permeability that accompanies the infection. These results suggest that both Se and VE are required for specific IL-4-related changes in intestinal physiology that promote host protection against H. polygyrus.

Animals↗

PubMed2004

Transgenic expression of insulin receptor substrate 2 in murine B cells alters the cell density-dependence of IgE production in vitro and enhances IgE production in vivo.

Previous studies have shown that insulin receptor substrate (IRS)1 and IRS2 mediate proliferative and antiapoptotic signaling through the IL-4R in 32D cells; however their role in regulating normal B cell responses is not clear. To investigate the role of IRS2 in normal B cell function, we developed IRS2 transgenic (Tg) mice on the C57BL/6 background. Western blot analysis revealed a 2-fold elevation in IRS2 protein levels in Tg(+) mice compared with littermate controls and a 3-fold increase in basal tyrosine phosphorylated IRS2 in the absence of IL-4 stimulation. IL-4-induced tyrosine phosphorylation of IRS2 was elevated in Tg(+) B cells, whereas IL-4-induced phosphorylation of STAT6 was similar between Tg(+) and Tg(-) B cells. Tg expression of IRS2 had little effect on IL-4-mediated proliferation and no effect on protection from apoptosis. However, production of IgE and IgG1 by Tg(+) B cells using standard in vitro conditions was diminished 50-60%. Because Ig production in vitro is known to be highly cell concentration-dependent, we performed experiments at different cell concentrations. Interestingly, at very low B cell concentrations (1000-5000 B cells/well), IgE and IgG1 production by Tg(+) B cells was greater than that of controls, whereas at higher cell concentrations (10,000-20,000 cells/well) Ig production by Tg(+) B cells was less than controls. Furthermore, in vivo immunization with OVA-alum or goat anti-IgD resulted in elevated serum IgE levels in the Tg(+) mice. These results indicate that overexpression of IRS2 alters the B cell intrinsic density-dependence of IgE and IgG1 production in vitro and enhances IgE responses in vivo.

Adjuvants, Immunologic↗

PubMed2004

Veterans Administration support for medical research: opinions of the endangered species of physician-scientists.

Over the past three decades the Veterans Affairs (VA) Research program has evolved into a powerful, peer-reviewed funding mechanism for basic and translational research that has resulted in numerous important contributions to medical science and improvements in patient care. Continuity in VA Merit Review funding has fostered and nurtured the scientific careers of a large number of physician-scientists who have remained devoted to the mission of performing creative and innovative research that affects the patient care mission of the VA. VA medical research policies have undergone a major overhaul in the past year. Although many of these changes (de-emphasizing bench research and revamping the peer review process) have recently been reversed, the future direction of VA research remains in flux. The goal of this manuscript is to demonstrate the importance of the Merit Review medical research funding mechanism not just to the VA, but to the entire nation's health care system. To achieve this goal, the opinions of 65 established VA medical investigators were obtained regarding the past success and future direction of VA research. The conclusions reached include the following. 1) Merit Review research funding has been essential to the training, recruitment, and retention of productive VA physician-scientists. 2) The VA research program has contributed both basic and clinical innovations that have led to improvements in medical care. Contributions of VA researchers to excellence in many aspects of patient care at VA hospitals have been extraordinary. 3) Development of initiatives that entice outstanding Ph.D.'s to develop their careers in the VA has been crucial to the success of the program. 4) The VA research program has fostered a mutually beneficial relationship with affiliated medical schools. 5) Better methods to quantify VA research contributions and outcomes are essential for future program development.

Biomedical Research↗