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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sera from 30 newly diagnosed diabetic BB/OK rats were analyzed cross-sectionally for complement-dependent antibody-mediated cytotoxicity (C'AMC) to pancreatic islet cells using different 51Cr release test systems. The sera contained enough active complement to lyse either sheep erythrocytes or 51Cr-labelled rat islet cells that had been sensitized with specific rabbit antibodies, but, in the presence of BB/OK rat islet cell antibody they released significant amounts of islet cell-bound 51Cr only after addition of rabbit complement. In a one-step assay, 19 out of the 30 sera produced lysis significantly above that by sera from the non-diabetes-prone WOK strain. This was increased 2.5-fold (p less than 0.01) by briefly washing the serum-treated cells before adding complement (two-step assay), indicating that C'AMC inhibitory activity was present in the diabetic sera. Some inhibitory activity could still be detected in heated sera but only when they were added to the cells immediately before the rabbit complement. Islet cell lysis was still substantial after preferential inactivation of factor B of the alternative complement activation pathway (by heating at 50 degrees C), and thus mainly depended on the classical pathway. From these findings it is concluded that (a) islet cell surface antibodies in diabetic rats activate heterologous complement via the classical pathway, (b) anti-islet C'AMC is sensitive both to species-restricted interference in interactions between homologous antibody and homologous complement in the target cell membrane, and to a distinct serum inhibitor that impairs the ability of membrane-fixed BB/OK rat antibody to interact with rabbit complement.
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PMID:Complement-dependent antibody-mediated cytotoxicity (C'AMC) to pancreatic islet cells in the spontaneously diabetic BB/OK rat: interference from cell-bound and soluble inhibitors. 166 61

One hundred consecutive patients with diabetic ulcers were studied in an 8-month-period. There were 58 females. The mean age was 59.9 years. Eighty three patients had non-insulin dependent diabetes mellitus. The mean duration of diabetes mellitus was 11.6 years. The mean duration of the ulcer was 8.5 months. Sixty nine of the ulcers were gangrenous. Over 50% of the ulcers involved the big toes. Neuropathic ulcers were found mainly in the sole of the feet. Roentgenograms showed evidence of osteomyelitis in 44 patients. There were 356 bacterial isolates (340 aerobes and 16 anaerobes) from the ulcers. There were 3.6 infecting organisms per ulcer in gangrenous ulcers, while in neuropathic ulcers, there were 3.4 infecting organisms per ulcer. In both types of ulcer Staphylococcus aureus and Escherichia coli were the commonest infecting organisms each being isolated in 88 of the 100 ulcers studied. In repeat bacterial cultures at 4 weeks there were 116 bacterial isolates. Staphylococcus aureus persisted in 63 ulcers despite therapy, while Escherichia coli persisted in 35. There were no new organisms isolated at repeat cultures and no ulcer was completely sterile. The Staphylococcus aureus was 100% sensitive to Augmentin (Amoxicillin plus clavulinic acid), Clindamycin, Novobiocin, and Amikacin while the gram negative bacilli were sensitive to Cefotaxime, Piperacillin, Amikacin and augmentin, Clindamycin, Chloramphenicol and Lincomycin inhibited the growth of anaerobes to a varying degree.
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PMID:Diabetic ulcers--a clinical and bacteriological study. 207 Jul 56

Neonatal rat pancreatic islets can be affected in vitro by ADCC mediated by serum and mononuclear cells from diabetic BB/OK rats or complement-dependent antibody-mediated cytotoxicity (C'AMC) of BB rat serum as revealed by enhanced 51Cr-release. Using a syngeneic islet transplantation system in BB/OK rats this study addressed the question whether the destruction of islets of Langerhans in vivo is reflected by the appearance of ADCC or C'AMC in vitro. The frequency of the appearance of enhanced anti-islet ADCC in newly diagnosed diabetic BB/OK rats amounted to 33% whereas ADCC was not detectable in long-term diabetic rats with a diabetes duration in a range between 50 and 90 days. After transplantation of syngeneic islets beneath the kidney capsule of long-term diabetic BB/OK rats held without immunosuppression the destruction of the islet graft and the persistence of hyperglycaemia was accompanied by an increase of anti-islet ADCC in 66.6% of the animals. While only 18.7% of the long-term diabetic BB/OK rats showed C'AMC against islet cells before transplantation this frequency raised after transplantation and 62.8% of the animals exhibited increased C'AMC within a period of 21 days but with a pronounced individual variability of the time-course. Increased anti-islet cytotoxicity (ADCC or C'AMC) parallels newly initiated or reactivated beta-cell destruction after transplantation and thus seems to reflect this process.
Diabetes Res 1990 Sep
PMID:Beta cell destruction of pancreatic islets transplanted into diabetic BB/OK rats may be reflected by increased antibody-mediated anti-islet cytotoxicity. 213 97

The present study examines the ability of serum from BB rats below the age of 33 days to mediate cytotoxicity to islet cells in vitro. Serum activities of complement-dependent antibody mediated cytotoxicity (C'AMC) were cross-sectionally analyzed in diabetes-prone BB/OK rats at 10 (n = 14), 20 (n = 14) and 30 (n = 10) days of age and were compared with those in non-diabetic, diabetes-prone BB/OK rats studied at 50 (n = 10) and 100 (n = 10) days of age. Exposure of 51Cr-labeled neonatal rat islet cells to sera from diabetes-prone BB/OK rats and rabbit complement revealed C'AMC activities above the mean + 2 SD of that of control Wistar rats in only two (14%) cases at day 10. This percentage increased to 79% at day 20 with all animals being C'AMC-positive at day 30. The means of the specific 51Cr-release were 3.6 +/- 1.7% at day 10, 10.4 +/- 2.2% at day 20, and 16.1 +/- 1.8% at day 30. Also, 90% of BB/OK rats investigated at 50 or 100 days of age were C'AMC-positive. In contrast, when 51Cr-labeled splenic lymphocytes were substituted for islet cells, isotope release did not exceed spontaneous release with any of the serum samples tested. Taken together, the present findings indicate that anti-islet but not anti-lymphocyte serum C'AMC activity usually appears in diabetes-prone BB/OK rats after day 10 with all animals being affected at day 30. The absence of cytolytic activity in 86% of BB/OK rats studied at 10 days of age strongly suggests, however, that anti-islet C'AMC is neither an inborn abnormality of humoral immunity in the BB rat nor does it seem to be passively acquired by transplacental passage.
Diabetes Res 1990 Apr
PMID:Early appearance of complement-dependent antibody mediated cytotoxicity (C'AMC) to islet cells in serum of diabetes-prone BB/OK rats. 213 10

The present study examined in the spontaneously diabetic BB/OK rat whether a relationship exists between the appearance of complement-dependent antibody-mediated cytotoxicity (C'AMC) in serum and the relative beta cell volume density determined in pancreatic biopsies. C'AMC was estimated by 51Cr release from prelabeled major histocompatibility complex-compatible neonatal rat islet cells after exposure to rat serum and rabbit complement. Fifty-one percent (72/141) of sera from BB/OK rats with newly diagnosed diabetes were positive for C'AMC. At onset of hyperglycemia, insulin-immunoreactive beta cells were only detectable in pancreas biopsies of 25% (10/40) of the BB/OK rats who displayed mild hyperglycemia (plasma glucose 8.3-13.0 mmol/l) and low serum C'AMC. A twofold increase (p less than 0.01) of C'AMC and loss of the remaining beta cells was evident in untreated animals upon their reexamination within 1 week after diagnosis of hyperglycemia. Initiation of insulin therapy prevented neither the increase in C'AMC activity nor the decrease in the beta cell volume density. In contrast, three out of four mildly hyperglycemic BB/OK rats treated with cyclosporin A maintained both their initial C'AMC levels and relative beta cell volume density not only throughout the treatment period (4 weeks) but also for at least 4 weeks thereafter. In one additional animal receiving cyclosporin A no protection of the remaining beta cells could be achieved and C'AMC levels were markedly increased. It is concluded that the appearance of increased C'AMC in serum may reflect autoimmune reactions against the islet beta cells of spontaneously diabetic BB/OK rats. The increase of C'AMC seen in untreated as well as insulin-treated BB/OK rats, which were even devoid of beta cells, suggests that C'AMC activity appears secondary to the loss of beta cells. These results do not support the hypothesis of a direct beta cell destruction via intrainsular complement activation.
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PMID:Complement-dependent antibody-mediated cytotoxicity in the spontaneously diabetic BB/OK rat: association with beta cell volume density. 219 2

Sera were obtained from 24 patients with newly-diagnosed insulin-dependent diabetes mellitus (IDDM) and 14 children with a high risk of diabetes. The influence of the decomplementated sera on basal and stimulated insulin secretion was studied in a mixed culture of newborn rat islet cells. In addition, complement-dependent antibody-mediated cytotoxicity (C'AMC) was measured by 51Cr-release from pre-labelled islet cells. Incubation of the islet cells with sera from ten IDDM patients did not affect the basal insulin release. Sera from other children with IDDM (n = 14) either significantly increased (n = 7) or inhibited (n = 7) basal IRI secretion was compared with the sera of control donors. Nearly half of the sera from the high-risk children was found to be insulin-stimulating. Preincubation of islet cells with sera from IDDM children caused a significant decrease of insulin response to 16.5 mM glucose plus 5 mM theophylline (P less than 0.001). Sera from the high-risk children did influence the response of pancreatic cells to secretagogues. C'AMC was found in 45% of the patients with IDDM and in 33% of the high-risk children, however, there was no correlation between C'AMC and serum effect upon basal insulin secretion. These results suggest the presence of B-cytotropic factors in serum from children with IDDM or with a risk of diabetes. Opposite effects of different sera on insulin secretion may reflect the variety of pathogenetic mechanisms involved in islet cell destruction.
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PMID:The effects of sera obtained from children with insulin-dependent diabetes mellitus on cultivated islet cells: cytotoxicity and insulin release. 267 10

In a cross-sectional study comprising of 56 patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM) serum was examined for the presence of complement-dependent antibody mediated cytotoxicity (C'AMC) by an improved assay measuring the release of 51Cr from freshly isolated normal rat islet cells prelabeled with the isotope. In the presence of complement, 35 (63%) IDDM sera specifically mediated cytotoxicity against islet cells. The degree of cell specificity was tested using prelabeled exocrine cells, but this cell type did not reveal any differences between the lytic effects of IDDM and control serum. At the time of clinical onset of IDDM the age of the patients, fasting and stimulated C-peptide levels, insulin requirement, HLA antigens, antibodies to Coxsackie B1-6 viruses, diabetes heredity, and, surprisingly, islet cell surface antibodies (ICSA) were not associated with C'AMC. It is concluded that the mere presence of C'AMC against rat islet cells at the time of diagnosis of IDDM is not indicative of a low residual B cell function and HLA-linked susceptibility to diabetes does not necessarily include enhancement of humoral anti-islet cell autoimmunity. More elaborate methods for quantitative detection of C'AMC and ICSA (e.g. in terms of titres) together with autoantibody subclass determination are needed to reveal possible associations between C'AMC and the clinical characteristics of IDDM.
Diabetes Res 1987 Feb
PMID:Cytotoxic islet cell autoantibodies in newly diagnosed insulin-dependent diabetes mellitus: lack of correlation to age, residual beta cell function, HLA antigens and Coxsackie B virus antibodies. 303 75

We have produced a monoclonal antibody 3A4 to the surface of islet cells by fusing spleen lymphocytes from nonobese diabetic (NOD) mice. To identify the molecular weight of specific target antigens reacting with 3A4, 125I-surface-labeled In-111 insulinoma cells were solubilized and extracts were absorbed with 3A4, and immunoprecipitates were followed by polyacrylamide gel electrophoresis and autoradiography. 3A4 recognized two major polypeptides with apparent molecular weights of radioactive 64K and inactive 28K. In order to evaluate the antibody-mediated cytotoxic mechanisms of 3A4, complement-dependent antibody-mediated cytotoxicity (C'-AMC) and antibody-dependent cellular cytotoxicity (ADCC) were tested using a method of specific 51Cr release. In the study for C'-AMC, even over wide ranges of concentration of antibody and rabbit complement, purified 3A4 had no apparent cytotoxic effects on In-111 cells. On the other hand, significant ADCC was observed at an antibody concentration of 10 micrograms/ml and a target:effector cell ratio of 1:40 (P less than 0.01). Finally, the effects of 3A4 on glucose-stimulated insulin release were examined in isolated rat islets. At a glucose concentration of 16.7 mM, 3A4 significantly inhibited the insulin release either in the presence or absence of complement (P less than 0.01). In conclusion, 3A4 could not only bind but also be active to the target cells. Therefore, this monoclonal antibody should be a useful tool to permit a detailed analysis of the pathogenesis of type I diabetes mellitus.
Diabetes 1986 May
PMID:Immunochemical characterization of anti-islet cell surface monoclonal antibody from nonobese diabetic mice. 351 30

Serum activities of complement-dependent antibody mediated cytotoxicity (C'AMC) were determined in 36 consecutive patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM). The sequential exposure of 51Cr labeled neonatal rat islet cells to patient serum and rabbit complement revealed the presence of C'AMC in 28 IDDM subjects. The C'AMC titres ranged between 1:4 and 1:512 and were not related to the C'AMC activity of a given sample as measured at a standard dilution (1:4). In comparison to the clinical characteristics of 21 IDDM patients with negative C'AMC, higher C'AMC titres (greater than or equal to 1:32) were associated with a lower mean age at diagnosis of IDDM (12.2 +/- 2.1 vs. 19.0 +/- 2.3 years; p less than 0.05), with a higher frequency of infections up to 6 months prior to diagnosis (6 out of 11 vs. 3 out of 21 patients; p less than 0.05) and, although statistically not significant, a preponderance of female sex together with a decreased frequency of HLA-DR4. In contrast, fasting C-peptides levels, HLA-DR3 antigen frequency and Coxsackie B1-6 virus antibody titres were not related to the C'AMC titres. It is concluded that (1) C'AMC titration is superior to the detection of initial C'AMC levels for evaluating the strength of the complement-dependent humoral immune response towards islet cell surface (auto)antigen(s), and (2) infectious agents may be involved in eliciting a C'AMC response.
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PMID:Complement-dependent antibody mediated cytotoxicity (C'AMC) in patients with newly diagnosed insulin-dependent diabetes mellitus. 366 52

Plasma levels of islet cell cytoplasmic and cytotoxic antibodies were determined in 10 children with insulin-dependent diabetes mellitus (IDDM) treated with plasmapheresis shortly after diagnosis, and in 9 children with IDDM treated by conventional means alone. Islet cell cytoplasmic antibody (ICA) titers were determined by indirect immunofluorescence using unfixed sections of human pancreas, and islet cell cytotoxic antibody levels were determined in a complement-dependent antibody-mediated cytotoxicity (C'AMC) assay using a human fetal cloned insulin-producing cell line (JHPI-1) as target. Before plasmapheresis, ICA was present in 7 out of 10 children and C'AMC was positive in 4. Four successive treatments with plasmapheresis did not consistently decrease plasma levels of ICA or C'AMC. ICA was present in 15 out of the total 19 children at diagnosis, and titers of ICA decreased in 12 out of 15 subjects by at least 1 degree of dilution (1:3) at 18-30 months follow-up, whether or not they had been treated with plasmapheresis; C'AMC was positive in 6 out of the 18 children at diagnosis and decreased in 2 out of 6. Plasma levels of C-peptide did not differ at diagnosis but remained higher in the plasmapheresis treated diabetic children at 3 and 18-30 months follow-up. Neither ICA titers nor C'AMC levels correlated with plasma C-peptide responses at 18-30 months. It is concluded that plasmapheresis decreases ICA and C'AMC but is followed rapidly by a rebound effect, and does not affect the rates at which these islet cell antibodies decrease with increasing duration of IDDM.
Diabetes Res 1985 Sep
PMID:Islet cell antibodies in insulin-dependent (type 1) diabetic children treated with plasmapheresis. 390 87


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