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Biomedical subjects

Y Shechter

Publications and source records attributed to Y Shechter.

At least 91 records · Page 5Linked to original sources
PubMed1985

Impaired immune function in hemophilia patients treated exclusively with cryoprecipitate: relation to duration of treatment.

Recently, abnormalities of cell-mediated immunity were found in hemophiliac patients receiving factor VIII concentrate therapy. Contradictory results were reported concerning cellular immune functions in hemophiliacs treated only with cryoprecipitate or fresh frozen plasma. Therefore, we evaluated the immunological status of 15 Israeli patients with severe classic hemophilia-A who were treated only with cryoprecipitate and never exposed to factor VIII concentrate whether of commercial source or blood bank prepared. As a group, only mildly depressed cellular immune functions and slight reduction in the helper to suppressor cell ratio were found. However, when patients treated more than 15 years were analyzed separately, a significant reduction in proportion of T cells, T-helper cells, helper to suppressor ratio, and proliferative response to phytohemaglutinin and pokeweed mitogen were observed compared to patients treated for less than 15 years and normal controls. Proportion of T-suppressor cells, Con A-activated suppressor activity, and IgG and IgA levels were significantly elevated in patients treated for more than 15 years. These results may support the view that derangement of immune function in hemophiliacs results from infusion of foreign proteins or an ubiquitous virus rather than contracting AIDS infectious agent.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Significance of multiple types of antibodies on red blood cells of patients with positive direct antiglobulin test: a study of monospecific antiglobulin reactions in 85 patients.

Blood samples from 85 patients with a positive direct antiglobulin test were tested with monospecific antiglobulin reagents: anti-IgG, anti-IgM, anti-IgA, and anti-C3. No typical pattern of antiglobulin reaction could be correlated with specific diseases except for the patients with methyldopa-induced positive direct antiglobulin test, all of whom had only IgG on their red blood cells. The presence of more than 1 type of antibody on red blood cells was associated with severe haemolysis. These patients responded less frequently to steroids, and in most of them no underlying disease could be found. Most patients with complement alone on red blood cells had no evidence of haemolysis, and when present it was never severe.

Antibodies, Anti-Idiotypic↗
PubMed1984

Cis-unsaturated fatty acids induce both lipogenesis and calcium binding in adipocytes.

The addition of 0.4-3 mM of cis-unsaturated fatty acids such as oleic acid (18:1) or linoleic acid (18:2) to intact rat adipocytes stimulated lipogenesis at 37 degrees C. Saturated or trans-unsaturated fatty acids were ineffective. Fluorescence photobleaching recovery studies performed under similar conditions indicated that the cis-unsaturated fatty acids do not alter lateral mobility of either a lipid probe or a general protein marker in the plasma membrane. A high concentration (7 mM) of Ca2+, which by itself has some stimulatory effect on lipogenesis, significantly potentiated the effect of oleic acid on this insulin-like activity. Measurement of 45Ca2+ binding by fat cells has indicated that cis-unsaturated (but not saturated) fatty acids increased 12- to 20-fold the amount of Ca2+ associated with the cells. The dependence of this effect on the fatty acid concentration correlates well with the effect of the fatty acid on the induction of lipogenesis. Our results suggest that cis-unsaturated fatty acids affect membrane organization in a manner which induces a significant increase in membrane associated or intracellular Ca2+. This increase may be responsible for inducing exocytotic-like processes which facilitate translocation of glucose transport activity from storage sites to the plasma membrane and thus produce an insulin-like effect.

Adipose Tissue↗
PubMed1984

Mouse antibodies to the insulin receptor developing spontaneously as anti-idiotypes. I. Characterization of the antibodies.

Mice immunized to ungulate insulins were found to develop antibodies of two specificities: insulin antibodies that were mostly IgG1 and IgG2 antibodies that acted both as anti-idiotypes to specific mouse insulin antibodies and as antibodies to the insulin receptor. There was a negative association between the presence of anti-idiotypic receptor antibodies and insulin antibodies bearing the specific idiotype; the specific idiotypic antibodies were confined to the early phase of the primary response while the anti-idiotypic receptor antibodies were detected only after the idiotypic antibodies had disappeared. To map the insulin epitope that triggered the specific idiotypic response, we chemically altered the insulin molecule so as to inhibit its interaction with the insulin receptor. The altered insulins triggered high titers of antibodies binding to antigenic determinants on native insulin, but no anti-idiotypic receptor antibodies. Thus, the epitope responsible for the specific idiotypic-anti-idiotypic network was probably the part of the insulin molecule whose conformation is recognized by the insulin receptor.

Adipose Tissue↗
PubMed1984

Trifluoperazine inhibits insulin action on glucose metabolism in fat cells without affecting inhibition of lipolysis.

One of the specific inhibitors of calmodulin action, trifluoperazine, blocked the stimulating action of insulin on 2-deoxyglucose uptake and glucose metabolism. The inhibitory effect of insulin on lipolysis was not altered by the drug. The active (insulin-stimulated) state and the basal state of lipogenesis were inhibited half-maximally at 80 and 550 microM trifluoperazine, respectively. 2-Deoxyglucose uptake was inhibited half-maximally at a trifluoperazine concentration of 70 microM. Other less potent calmodulin inhibitors also inhibited glucose metabolism in fat cells but in a nonspecific manner. The inhibition was noncompetitive and was not altered in Ca2+- free medium. The stimulating activity of wheat germ agglutinin and of sodium vanadate were also inhibited by trifluoperazine. The dose-dependent inhibitions were indistinguishable whether the active (stimulated) state was produced by insulin, wheat germ agglutinin, or vanadate. The data indicate that a late event in the sequence that ultimately leads to enhanced glucose transport activity in fat cells is specifically inhibited by trifluoperazine. The possible involvement of calmodulin or another related Ca2+-dependent regulatory protein in the exocytic (fusion) reaction that recruits glucose-transport activity from storage sites to the plasma membranes is discussed.

Adipose Tissue↗
PubMed1984

Differential effects of two phosphodiesterase inhibitors on fat cell metabolism.

The various effects of the phosphodiesterase inhibitor D-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (RO-20-1724) on fat cell metabolism were examined and compared to those obtained with 1-methyl-3-isobutylxanthine (IBMX). Like IBMX, RO-20-1724 increased the rate of lipolysis, suppressed the incorporation of glucose into fat, did not increase the basal rate of cAMP production, but induced fast linear accumulation of the nucleotide when combined with a lipolytic agent. The time scale and the effective concentrations of both reagents in exerting these effects were similar. Both inhibitors were also equally potent in inhibiting the low Michaelis-Menten constant (Km) cAMP phosphodiesterase activity in fat cell homogenate. A fundamental difference between both inhibitors however did exist. Whereas the addition of IBMX abolished the ability of insulin to inhibit lipolysis as previously reported, insulin is fully functional in inhibiting the increased rate of lipolysis in the presence of RO-20-1724. Also, RO-20-1724 does not interfere with the ability of insulin to inhibit fully cholera toxin-mediated lipolysis. It is concluded that under these conditions the antilipolytic effect of insulin may be produced without demonstrable activation of cAMP phosphodiesterase. The effects of the methylxanthines in abolishing insulin action probably relates to interference with insulin-dependent intracellular enzymic activity other than cAMP phosphodiesterase.

1-Methyl-3-isobutylxanthine↗
PubMed1983

Autoantibodies to the insulin receptor in juvenile onset insulin-dependent diabetes.

Insulin-dependent diabetes mellitus (IDDM) usually begins in childhood or early adulthood, and its aetiology is thought to involve autoimmune damage to the islet cells that secrete insulin. To investigate an additional target of autoimmunity in IDDM we examined sera for antibodies to insulin receptors. Such antibodies were defined by their ability to compete with insulin for binding to insulin receptors and by their capacity to behave like insulin in activating lipogenesis in adipocytes. We now report the occurrence of anti-insulin receptor antibodies of the IgM class in the sera of 10 of 22 IDDM patients obtained before their treatment with exogenous insulin. Furthermore, two of five IDDM patients who were initially negative developed anti-insulin receptor antibodies during treatment with human or pork insulin. These findings suggest that autoimmunity to the insulin receptor may contribute to the pathophysiology of IDDM.

Autoantibodies↗
PubMed1983

Mice immunized to insulin develop antibody to the insulin receptor.

We immunized mice with insulin and found that those strains that develop insulin antibodies subsequently produce insulin-like activity in amount equivalent to 300-400 ng insulin per ml serum. The activity was due exclusively to IgG2 antibodies. Bioactivity could be blocked efficiently by insulin antibodies from guinea pigs and from mice. The active IgG2 also displaced labeled insulin from fat cells. Preliminary in vivo studies have indicated that the appearance of insulin-like antibodies in the mouse resulted in abnormal glucose homeostasis and "down regulation" of insulin receptors. These results indicate that immunization to insulin can initiate an idiotype-anti-idiotype network resulting in antibodies to the hormone receptor.

Animals↗
PubMed1983

Bound lectins that mimic insulin produce persistent insulin-like activities.

Short preincubation of rat adipocytes with wheat germ agglutinin, followed by removal of unbound lectin, resulted in persistent activation of lipogenesis, which lasted at least 3 h. The bound lectin also inhibited lipolysis initiated by isoproterenol 1 or 2 h after the removal of the free lectin. This property was also shared by other insulinomimetic lectins, such as Concanavalin A and wax bean agglutinin. Persistent bioactivation is the consequence of lectin adsorbed to external cell surface determinants in a permanent fashion. This fraction is not internalized, processed, or appreciably dissociated from the cells, since the addition of N-acetyl-D-glucosamine at any time after the onset of wheat germ agglutinin-induced persistent lipogenesis leads to termination. The property of producing persistent bioactivation is not shared by insulin itself, since removal of the unbound hormone results in termination of bioactivation. This study indicates the existence of externally located fat cell surface determinants, which, upon being occupied continuously, produce persistent insulin-like activities. The study also strongly supports the notion that the initial perturbation is sufficient to activate the insulin machinery system, and that internalization and processing of hormone-receptor complexes are the sole pathway for termination.

Acetylglucosamine↗
PubMed1982

Autoantibodies to insulin receptor spontaneously develop as anti-idiotypes in mice immunized with insulin.

Mice immunized with insulin developed antibodies to both insulin and the insulin receptor. The antibodies to insulin receptor displaced labeled insulin from insulin receptors and mimicked the actions of insulin in stimulating the oxidation of glucose and its incorporation into lipids, and in inhibiting lipolysis. The antibodies to insulin receptor could be blocked by or bound to the antibodies to insulin, and therefore were identified as anti-idiotypes. Thus, immunization against a hormone may activate spontaneously an idiotype-anti-idiotype network resulting in antibodies to the hormone receptor.

Animals↗
PubMed1982

Evaluation of adenosine or related nucleosides as physiological regulators of lipolysis in adipose tissue.

The removal of extracellular, endogenously produced adenosine in isolated rat adipocytes by treatment with adenosine deaminase enhanced their responsiveness to various lipolytic agents, i.e. the response to catecholamines, glucagon, LH, TSH, and cholera toxin was elicited at concentrations that were 10-500 times lower than those required for the stimulation of lipolysis in untreated cells in vitro. The removal of adenosine from intact fat cells largely potentiated the isoproterenol-stimulated increase in cAmP level. However, a similar treatment of undissociated segments of adipose tissue failed to influence further the response to isoproterenol. These results strongly suggest that in the intact adipose tissue, adenosine and related nucleosides are absent and do not function as modulators of adenylate cyclase or lipolysis. Under these circumstances the estimated "low" physiological concentrations of the neurotransmitters in the adipose tissue are able to modulate lipid mobilization. Previous studies have shown that insulin failed to inhibit lipolysis, induced by micromolar norepinephrine concentrations, in adenosine-free adipocytes. The present study demonstrates that at physiological catecholamine concentrations, insulin is a potent antilipolytic agent.

Adenosine↗
PubMed1981

Suppression of lymphocyte reactivity in vitro by a soluble factor secreted by explants of human decidua.

The immunologic mechanisms that protect the fetus from rejection were the subject of numerous investigations. Reports showing the uterus as a favorable site of implantation focused our attention to the decidua which is the maternal tissue intimately attached to fetal structures. Explants of human decidua were cultured for periods of 24 h and incubation media tested for their immunosuppressive activity. The incubation medium of human decidua when added to cultures of human lymphocytes suppressed both their reactivity to lectins and their activity in the mixed lymphocyte reaction. The results of these experiments suggest that decidual tissue releases a soluble factor which is a potent inhibitor of cell-mediated immunity.

Amnion↗