Multiple low doses of streptozotocin (LDS) induce low-incidence diabetes mellitus in Balb/cHan and high-incidence diabetes in CD-1 mice. We studied offspring of diabetic parents in both strains. Group 1 consisted of litters from control mice with no streptozotocin treatment. Group 2 litters had an LDS diabetic mother and a control father, group 3 litters had control mother with LDS diabetic father, and group 4 litters had both, LDS diabetic mother and father. Diabetes was induced by 5 x 40 mg streptozotocin per kg on five consecutive days. Progeny of diabetic mothers showed a state of reduced glucose tolerance associated with reduced glucose disappearance during intravenous glucose tolerance test and increased insulin secretion of isolated islets of Langerhans. These metabolic abnormalities predominated in the male litters of both strains of mice. Amniotic insulin was increased in diabetic mothers during pregnancy. No histologic abnormalities were observed in group 2 progeny. Pancreases in male offspring of LDS diabetic CD-1 fathers (group 3) were studied for insulitis. Insulitis was found in 40% of mice with normal glucose tolerance. A single subdiabetogenic dose of streptozotocin (40 mg/kg) induced insulitis in 90% of pancreases accompanied by reduced insulin release of isolated islets. By contrast, male Balb/cHan progeny of diabetic fathers failed to develop insulitis. In conclusion, we found (1) parental LDS diabetes was transmitted more often to male offspring, (2) maternal LDS diabetes was associated with hyperinsulin secretion and glucose intolerance in the offspring and (3) paternal LDS diabetes was accompanied by insulitis and insulin secretion deficiency in CD-1 progeny.

Aging↗

PubMed1993

Lymphoid activation by micro- and macroencapsulated islets during mixed lymphocyte islet culture.

We have recently demonstrated long-lasting normoglycaemia after transplantation of barium alginate microencapsulated rat and porcine islets. Nevertheless the transplantation results obtained with different microencapsulation techniques have been controversial. Little is known about possible immune interactions between host and encapsulated islet. This study demonstrates in vitro stimulation of lymphoid cells by encapsulated islets that is similar to that of unencapsulated islets. This stimulation was reduced by a 4-day culture with unencapsulated islets only. After macroencapsulation of islets in hollow fibres a stimulatory effect was also observed, but this was less pronounced than after microencapsulation. Empty microcapsules as well as macrocapsules induced lymphoid proliferation as a result of mitogenic impurities in the encapsulation materials themselves. In the same donor-recipient combination in which we have shown successful transplantation, we found activation of the sensibilization arm of the immune system. This suggests that microencapsulation results in protection of the transplanted islets from the action of the effector arm. This lymphoid activation could be triggered by the mitogeniticity of the encapsulation material itself. In the case of alginates these mitogenic factors could not be abolished by culture (i.e. dialysis).

Alginates↗

PubMed1993

Rat pancreatic islet pretreatment with anti-MHC class II monoclonal antibodies and culture: in vitro MLIC test response does not predict islet allograft survival.

Antigen presenting cells (APC) expressing MHC class II antigens have been attributed with stimulatory capacity for initiating islet allograft rejection (direct pathway). Therefore, we evaluated the effect of pretreating isolated islets with different monoclonal antibodies against MHC class II antigens and complement, with and without culture at 22 degrees C or 37 degrees C, on MHC class II antigen expression, on the allogeneic proliferative response in the mixed lymphocyte islet culture (MLIC) and on islet allograft survival in adult rats. Experiments were performed in two different strain combinations incompatible for MHC class II antigens and either incompatible or compatible for MHC class I antigens, in order to elucidate further the impact of class I antigens on islet allograft rejection. In terms of class II antigen suppression, pretreatment with anti-MHC class II antibodies together with complement and a 5-day (37 degrees C) culture period proved most effective. After this procedure 92.7% of the islets of LEW rats and 91.1% of the islets of LEW.1WR2 rats were negative for MHC class II antigens, as demonstrated by indirect immunofluorescence. Transfer of successfully pretreated islets to a MLIC in vitro test system provoked a significantly reduced allogeneic T-cell proliferative response in the case of additional MHC class I disparity (ratio 1.3 vs 4.7) and a response as low as that of a syngeneic setting when stimulator islets and allogeneic responder lymphocytes shared MHC class I antigens (ratio 1.0 vs 1.6).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Evidence of ex vivo and in vitro impaired neutrophil oxidative burst and phagocytic capacity in type 1 diabetes mellitus.

In this study neutrophil (PMN) oxidative burst activity was investigated ex vivo and in vitro in comparison to the PMN-phagocytic functions ingestion and bacterial killing in poorly-controlled type 1 diabetic patients. Luminol enhanced chemiluminescence in response to phorbolesters as a measure of oxidative burst was assessed in a parallel detecting microtiterplate luminometer in 40 poorly-controlled type 1 diabetic subjects. PMN ingestion was measured with [3H]thymidine-labelled Staphylococcus aureus in a kinetic radiometric assay. Microbicidal activity was determined by pure plate counting of surviving bacteria (colony forming units, cfu) after defined pmn challenge. PMNs of type 1 diabetic subjects showed a highly significant reduction of peak CL response in response to PMA compared to nondiabetic controls (P < 0.001) and PMN ingestion (51.8 +/- 4.6%) and bacterial killing (28.6 +/- 3.2%) were reduced as well (78.2 +/- 5.2% (IN) and 18.4 +/- 4.1% (BK), P < 0.01, respectively). The in vitro data displayed impaired PMN oxidative burst activity at glucose concentrations > or = 13.8 mmol/l whereas PMN IN and BK were significantly reduced at glucose levels > or = 27.75 mmol/l. In the control group there was a positive correlation of peak CL response and IN as well as BK (P < 0.05); in type 1 diabetic patients this was also true, but did not reach statistical significance. The data obtained in this study clearly demonstrated impaired PMN oxidative burst activity and markedly reduced ingestion and bacterial killing in type 1 diabetic patients ex vivo and in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

BGP serum levels in patients with thyroid carcinoma before and 4-14 weeks after radioiodine therapy.

In the present short paper we compared the BGP and AP levels of 26 patients with thyroid carcinoma during radio-iodine therapy. BGP values reflect the bone turnover before and after radio-iodine therapy. There were no significant AP changes during this period. These results suggest that thyroid hormone has a direct effect on osteoblast function and that this effect can be best monitored by determination of BGP levels.

Adolescent↗

PubMed1993

[Chronic heat stress modulates the immune system in the preclinical phase of murine lupus erythematosus].

Repetitive thermal stress induces a reduction in the characteristic Thy1.2+B220+ lymphocyte subpopulation in lupus mice which were studied before the onset of disease. The immunomodulating effect was systemic, and alterations were not related to corticosterone serum levels.

Animals↗

PubMed1993

[Immunologic isolation of transplanted islets of Langerhans: microcapsules with defined molecular limits].

Immunoisolated transplantation of islets of Langerhans in barium alginate microcapsules is a promising therapeutic approach to cure diabetes. An improved membrane for the coating of barium alginate microcapsules has been developed. Chemically stable barium alginate microcapsules with a controlled molecular weight cutoff between 9400 and 40,500 D were obtained after coating of barium alginate capsules in Polybrene solutions. Microcapsules prepared by this new method were still freely permeable to low molecular weight substances.

Alginates↗

PubMed1993

Is the allograft response to islet transplantation antigens MHC restricted?

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Animals↗