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Biomedical subjects

B S Handwerger

Publications and source records attributed to B S Handwerger.

At least 55 records · Page 3Linked to original sources
PubMed1985

Characterization of murine T cell activation signals produced by B lymphoma cells.

The activation requirements of alloreactive and antigen reactive murine T cells were examined by stimulating class II restricted T cell clones with monoclonal B lymphoma cells. One B lymphoma cell line (T27A) was found to stimulate IL 2 release from some alloreactive T cell clones without stimulating any significant T cell proliferation response. The same B lymphoma cells are capable of stimulating IL 2 release and proliferative responses from other T cell clones. Evidence is presented suggesting that B lymphoma cell stimulation of these T cell clones is largely IL 1 independent and that at least some T cell clones may require activation signals other than Ia, antigen, and IL 1. The addition of exogenous, purified IL 1 to the T cell activation assays was found to have a wide range of stimulatory effects on the proliferative responses of different T cell clones. The absence of comparable IL 1-induced stimulation of IL 2 secretion suggests that IL 1 primarily enhances antigen specific T cell proliferation through mechanisms other than acting as a co-stimulant for IL 2 release.

Animals↗
PubMed1985

Pathologically defined neuro-, vasculo-, entero-Behçet's disease.

Behçet's disease is characterized clinically by the presence of a diagnostic triad of stomatitis, genital ulceration and uveitis. Multiple other organ systems may be involved. Prognosis is related to the presence of central nervous system, vascular or intestinal involvement. This report describes the pathology of neuro-, vasculo- and entero-Behçet's disease in a single patient.

Adult↗
PubMed1984

Polyglandular autoimmune syndromes.

One of the basic caveats in endocrinology is that glandular abnormalities tend to occur together. Continued suspicion of other glandular hypofunction should be maintained in following patients with any type of endocrine gland hypofunction, since the risk of multiple glandular involvement is significant. Family members should be alerted to the high prevalence of endocrinopathies especially among first-degree relatives of patients with polyglandular autoimmune disease. Parameters such as antiorgan antibodies, although occasionally helpful, have not been shown to be consistently useful in predicting the future development of clinical organ-specific autoimmune disease. HLA typing remains a research tool at this time, as does evaluation of humoral and cell-mediated immunity.

Adult↗
PubMed1984

Alterations in immunological function in streptozotocin-induced murine diabetes mellitus: correction by islet cell transplantation.

Cell-mediated and humoral immune responses of streptozotocin-induced diabetic mice were evaluated using in vivo and in vitro immunological assays. C57BL/6 mice were rendered diabetic by a single intraperitoneal injection of 125-200 mg/kg of streptozotocin. Immunological studies were performed after the mice were diabetic (mean +/- SEM serum glucose 537 +/- 14 mg/dl) for a minimum of 4 weeks. Spleen cells from streptozotocin-induced diabetic mice exhibited significantly diminished direct IgM plaque-forming cell (PFC) responses following either in vivo or in vitro immunization with sheep erythrocytes, markedly impaired cytotoxic cell responses following in vivo or in vitro allogeneic stimulation, and diminished blastogenic response to the T-cell mitogens phytohemagglutinin and concanavalin A. In contrast the blastogenic response of diabetic spleen cells to lipopolysaccharide, a B-cell mitogen, was normal. The defects in in vivo PFC responses and in vivo cytotoxic cell responses were corrected by islet cell transplantation, suggesting that the abnormalities in immunological function of streptozotocin-induced diabetic mice are a consequence of the diabetic state and not of direct streptozotocin toxicity to lymphoid cells.

Animals↗
PubMed1984

Separate influences of insulin and hyperglycemia on hepatic drug metabolism in mice with genetic and chemically induced diabetes mellitus.

Numerous investigators have reported abnormalities of hepatic drug metabolism in hypoinsulinemic animal models with chemically induced diabetes mellitus, but there has been little assessment of hepatic drug metabolism in recently described animal models with genetic diabetes mellitus characterized by hyperinsulinemia and insulin resistance rather than insulin deficiency. Hepatic microsomal cytochrome P-450 content and drug metabolizing activity in obese, diabetic C57BL/KsJ mice homozygous for the diabetes gene mutation (db/db) have been compared with levels found in livers of 1) lean, nondiabetic control mice with the same C57BL/KsJ genetic background and 2) lean C57BL/6J animals made diabetic by streptozotocin treatment. No changes in specific enzyme content or activity were seen in young db/db mice, but microsomal protein and total hepatic cytochrome P-450 content and meperidine demethylation and pentobarbital hydroxylation activity were markedly increased compared to controls. In hyperglycemic, hypoinsulinemic mice with streptozotocin-induced diabetes mellitus, the amount of microsomal protein did not change, but hepatic cytochrome P-450 content and enzyme activity were significantly increased whether expressed per milligram of microsomal protein or as totals per liver. In old db/db animals, hyperglycemia persisted but plasma insulin levels fell into the normal range so that the insulin-glucose profile of these animals resembled that seen in the streptozotocin treatment group. In association with these changes, hepatic enzyme specific activities in the old db/db mice approximated values found in the streptozotocin group rather than in the young db/db animals. These differences in hepatic microsomal enzymes between hyperinsulinemic and hypoinsulinemic mice with diabetes mellitus suggest that both hyperglycemia and insulin separately and significantly influence cytochrome P-450 turnover and mixed function oxidase activity.

Animals↗
PubMed1984

Monoclonal antibody-induced murine hemolytic anemia.

A panel of 11 IgG monoclonal antierythrocyte antibodies was generated by fusing spleen and bone marrow cells from unimmunized New Zealand black mice with the nonsecreting murine plasmacytoma cell line P3.X63.NS1. The monoclonal antibodies were detected by indirect hemagglutination of unaltered erythrocytes from several strains of mice. Seven of the antibodies cross-reacted with rat erythrocytes, but none of the antibodies agglutinated erythrocytes from any other species tested. Seven of the monoclonal antibodies were also capable of fixing rabbit complement. In vivo studies utilizing these 11 IgG-secreting hybridomas were performed in syngeneic BALB/c mice. Mice injected with nine of the hybridomas showed positive direct antiglobulin test results but did not become anemic. In contrast, hybridoma 114, secreting an IgG3 antibody, and hybridoma 245, secreting an IgG1 antibody, were both capable of mediating an acute, rapidly fatal hemolytic anemia. Intraperitoneal injection of hybridomas 114 and 245 resulted in positive direct and indirect antiglobulin test results, decreased hematocrit level, and reticulocytosis 3 to 6 days after cell injection. The mice survived a mean of 8 days, and death was associated with severe anemia and spontaneous erythrocyte agglutination. Autopsy studies revealed hepatosplenomegaly, small mesenteric tumor (hybridoma) mass, and no ascites. The liver and spleens were characterized histologically by erythrophagocytosis, extramedullary hematopoiesis, and hemosiderin deposition. Acute hemolytic anemia in BALB/c mice mediated by hybridomas 114 and 245 represents a new animal model that can be used to further define the mechanisms of immune hemolytic disease.

Anemia, Hemolytic, Autoimmune↗
PubMed1983

Effect of low-level lead exposure on antibody-dependent and natural killer cell-mediated cytotoxicity.

Splenic antibody-dependent, cell-mediated cytotoxicity against chicken red blood cell targets [ADCC (CRBC)] and natural killer cell-mediated cytotoxicity (NKMC) were determined in C57BL/6 mice given 1300 ppm lead acetate (827 ppm lead) in their drinking water for 8 weeks. ADCC in lead exposed mice was significantly lower than controls at effector to target cell ratios of 100:1, 50:1, and 25:1. In contrast, no significant difference in unstimulated NKMC was seen in lead exposed mice and control mice at effector to target cell ratios of 200:1, 100:1, and 50:1. Moreover, in vivo poly I:C-enhanced NKMC in lead-treated mice was similar to controls at an effector to target cell ratio of 200:1. Blood lead levels averaged 40.5 +/- 1.2 micrograms% in lead-exposed mice and 1.9 +/- 0.3 micrograms% in controls. These findings suggest that chronic low-level lead exposure in mice results in significant suppression of ADCC (CRBC) but does not alter natural killer activity.

Animals↗
PubMed1983

Hepatic and intestinal 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in genetically diabetic mice.

Cholesterol synthesis rate, as determined by 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, is characterized in the major organs of genetically diabetic mice. Both C57BL/Ks db+/db+ and C57BL/6 ob+/ob+ mice are hyperinsulinemic and insulin-resistant. These animals demonstrate loss of the circadian rhythm of hepatic reductase activity and a tendency for increased intestinal activity. As a result, proportionally more endogenous cholesterol synthesis occurs in intestinal mucosa than liver in genetically diabetic animals. Thus, the alterations in activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase which are observed in animal models of diabetes are the result of diminished insulin effect rather than insulin level.

Animals↗
PubMed1983

Tissue zinc status of genetically diabetic and streptozotocin-induced diabetic mice.

A structural and functional relationship exists between zinc and insulin. In the present study zinc concentrations of various tissues from genetically diabetic and streptozotocin-induced diabetic mice and their appropriate control mice were determined. The zinc concentrations were depressed in serum and femur of C57BL/Ks-db+/db+ mice (db/db) when compared with their nondiabetic heterozygote controls (db/m) and homozygous controls (m/m). No differences were noted in the hepatic or renal Zn concentration of the db/db, db/m, or m/m mice. Zinc supplementation in the drinking water for a 4-wk period had no effect on serum or tissue zinc concentration. Hyperzincuria was noted in the db/db mice. No differences were noted in the Zn concentration of serum or tissue in streptozotocin-induced diabetic mice compared to their controls. These data suggest that zinc deficiency may play a role in the pathogenesis of the insulin resistance present in type II (insulin independent) diabetics.

Animals↗
PubMed1982

Tail pinch behavior and analgesia in diabetic mice.

Mild tail pinch induced "consummatory" behaviors in mice. The major tail pinch behavior appeared to be chewing with food ingestion occurring possibly as an epiphenomenon. All tail pinch behaviors were obliterated by the dopamine antagonist haloperidol; and the opiate antagonist, naltrexone, decreased eating without altering chewing. The combination of dopamine blockade and tail pinch induced jumping behavior in mice. Diabetic mice showed increased tail flick latencies to radiant heat and to the induction of tail pinch behaviors, displaying these behaviors less commonly than their homozygote and heterozygote littermate controls.

Animals↗
PubMed1980

Immune and autoimmune aspects of diabetes mellitus.

The immune and autoimmune aspects of diabetes mellitus are reviewed. Emphasis is given to the clinical association of diabetes with other autoimmune disease; the increased incidence of organ-specific autoimmunity in diabetic patients; the occurrence of humoral and cell-mediated antipancreas (islet) autoimmunity in diabetes; the association of HLA with juvenile-onset, insulin-dependent diabetes mellitus and with certain specific subpopulations of diabetic patients; the possible role of viruses in the etiology of diabetes; and the occurrence of alterations in humoral and cell-mediated immunity, granulocyte function, and the host defense against infectious agents in human diabetics and in animals with experimental diabetes.

Animals↗
PubMed1980

Decreased T cell function in mice exposed to chronic, low levels of lead.

The immune responsiveness of mice given low levels of lead acetate (1300 p.p.m.) in their drinking water for 8 weeks was determined. Mean percentages of splenic T and B lymphocytes in lead-exposed mice were slightly lower than in controls. Mean mitogen response to phytohaemmaglutinin and concanavalin A in mice exposed to lead was significantly decreased compared to controls. The response to lipopolysaccharide on the other hand was not significantly mitogenic response to phytohaemagglutinin and concanavalin A is impaired in mice exposed chronically to low concentrations of lead.

Animals↗
PubMed1978

Lymphocyte-mediated antibody-dependent cytolysis: role in immune hemolysis.

Peripheral blood lymphocytes obtained from normal volunteers were capable of lysing Rh(D)-positive human erythrocytes in the presence of IgG anti-Rh(D) antibodies. The percent cytotoxicity produced by peripheral blood lymphocytes was approximately equivalent to that produced by unfractionated peripheral blood mononuclear cells. Neither peripheral blood mononuclear cells nor peripheral blood lymphocytes lysed Rh(D)-negative human erythrocytes in the presence of IgG anti-Rh(D) antibody.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1978

Immune response in the mutant diabetic C57BL/Ks-dt+ mouse. Discrepancies between in vitro and in vivo immunological assays.

Cell-mediated and humoral immune responses of mutant diabetic db+/db+ mice were evaluated using in vivo and in vitro immunological assays. When compared to lean, nondiabetic db+/m+ or m+/m+ mice, db+/db+ mice demonstrated markedly altered in vivo immune responses characterized by a significantly diminished ability to reject allogeneic skin grafts, a markedly diminished capacity to generate cytotoxic cells after sensitization with allogeneic EL-4 lymphoma cells and a significantly enhanced plaque-forming cell response to sheep erythrocytes. In contrast, spleen cells from db+/db+ mice demonstrated only minimal alterations in in vitro responses to mitogens and allogeneic cells and no alteration in their capacity to generate an in vitro plaque-forming cell response. The spleens and thymuses of db+/db+ mice weighed significantly less than organs from db+/db+ mice. In addition, thymuses from db+/db+ mice demonstrated a marked deficiency in in vivo [125I]UdR uptake. These data suggest that the altered metabolic status of the diabetic host influences immune function in vivo possibly due to abnormal function of lymphocyte subpopulations.

Animals↗