The study replicates the findings of decreased GABA concentrations in the occipital cortex of subjects with MDD. It also demonstrates that there is a change in the ratio of excitatory-inhibitory neurotransmitter levels in the cortex of depressed subjects that may be related to altered brain function. Last, the combined data set suggests that magnetic resonance spectroscopy GABA measures may serve as a biological marker for a subtype of MDD.

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Combined treatment with allogeneic small lymphocytes or T-depleted small lymphocytes plus a blocking antibody to CD40 ligand (CD40L) permitted indefinite pancreatic islet allograft survival in 37 of 40 recipients that differed from islet donors at major and minor histocompatibility loci.

Multiple small injections of streptozotocin produce a delayed, progressive increase in plasma-glucose in mice within 5-6 days after the injections, in association with pronounced insulitis and induction of type C viruses within beta cells. Multiple subdiabetogenic doses of streptozotocin in rats and multiple injections of another beta cell toxin, alloxan, in mice did not induce insulitis although hyperglycemia followed the injection of larger quantities of both agents. In mice, the prior injection of 3-O-methyl-D-glucose (3-OMG) or nicotinamide attenuated the diabetic syndrome produced by streptozotocin; however, 3-OMG was more protective. Rabbit antimouse lymphocyte serum, alone, provided partial protection but, when given together with either 3-OMG or nicotinamide, effectively prevented the streptozotocin-induced diabetic syndrome. Cessation of these preventive treatments was followed by the appearance of insulitis and diabetes. These findings suggest that multiple injections of streptozotocin induce, in susceptible hosts, the triad of direct beta cell cytotoxicity, virus induction within beta cells, and cell-mediated autoimmune reaction. These factors, acting separately or in concert, appear to induce a destructive insulitis and severe diabetes. The relative importance of each component and the factors governing host susceptibility remain to be clarified. Streptozotocin [SZ; 2-deoxy-2(3-methyl-3-nitrosoureido)-Dglucopyranose] is a broad-spectrum antibiotic with oncolytic, oncogenic, and diabetogenic properties (1-4). The diabetogenic action is mediated by selective destruction of pancreatic beta cells and has been widely utilized as a method for inducing diabetes mellitus in experimental animals and for treatment of malignant beta cell tumors and other neoplasms in humans. To produce diabetes, SZ is conventionally administered as a single injection. SZ is cleared from the bloodstream rapidly (serum half-life, 15 min) (5); beta cell necrosis can be detected by electron microscopy within hours after SZ injection (6-8). Elevated blood glucose levels are demonstrable within 1-2 days, and dissolution and phagocytosis of necrotic cells are observed histologically after 3 days (3, 6). In rats and mice, the administration of a single subdiabetogenic dose produces only mild histologic alterations without evidence of significant hyperglycemia when compared with buffer-injected control animals (9, 10).We have recently reported (10) that the administration of multiple (five) subdiabetogenic doses of SZ to Charles River Laboratory (CD-1) mice, either intravenously or intraperitoneally, produced a delayed but progressive increase in blood glucose with levels of 350450 mg/100 ml within 5-6 days after the last injection. Morphologically, the pancreatic islets revealed pronounced insulitis with infiltrating lymphocytes and macrophages, architectural distortion, and beta cell necrosis. There was a subsequent decrease in inflammation within the remaining islets which were small and composed almost exclusively of non-bet...