Association of fulminant type 1 diabetes with pregnancy.

It has been reported that fulminant type 1 diabetes is a novel subtype of type 1B diabetes. However, whether the etiology of fulminant type 1 diabetes is associated with an autoimmune or nonautoimmune process remains to be solved. In order to further characterize fulminant type 1 diabetes, we compared the clinical, immunological and genetic characteristics with those of acute-onset type 1A diabetes. Nine patients with fulminant diabetes and nine patients with acute-onset type 1A diabetes, who had been newly diagnosed during 1998-2001, were analyzed. In female patients of child-bearing age, the onset of diabetes occurred during pregnancy or after delivery in three cases of six fulminant cases, but not in any of seven type 1A diabetes. Eight of nine fulminant patients had fever immediately prior to the onset of hyperglycemic symptoms, whereas only one of nine type 1A patients had this (P=0.002). In Japanese type 1 susceptible HLA haplotypes, DRB1*0901-DQB1*0303 was more frequent in type 1A diabetes than fulminant diabetes (7/18 vs. 0/18, P=0.004), whereas the frequency of DRB1*0405-DQB1*0401 was similar (type 1A 4/18 vs. fulminant 6/18). Therefore, pregnancy, possible viral infection, or HLADRB1*0405-DQB1*0401 may contribute to the onset of fulminant type 1 diabetes.

[Effectiveness of synthetic calcitonin derivative (elcatonin) on the bone pain and serum calcium concentration in multiple myeloma].

Fifteen patients (8 male and 7 female) with multiple myeloma, who were admitted to our hospital between July 1986 and August 1988 and suffering from pain and hypercalcemia, were treated with synthetic calcitonin derivative (elcatonin: ECT). ECT was administered intravenously at a dose of 10-640 units twice daily. Seven patients were treated with ECT (ECT group), and eight patients received combination treatment with ECT and other form of chemotherapy (combination group). With regard to the pain score (PS), significant analgesic effects in both groups were observed during 1-4 week treatments (p less than 0.05). There were no significant differences in PS between two groups. Serum calcium levels in the combination group at 1 and 4 weeks were significantly lower than the initial value (p less than 0.05). Hypocalcemia was not seen in any of the patients. Urinary excretion of calcium at 1 week in ECT group was higher than the initial value (p less than 0.05). The observed toxicities of ECT were slight nausea and vomiting in only 2 patients. These findings suggest that ECT is an useful agent for the treatment of pain and hypercalcemia accompanied with multiple myeloma.

Immunohistochemical study of insulitis induced by multiple low doses of streptozocin in CD-1 mice.

In an attempt to characterize insulitis induced by multiple low doses of streptozocin (SZ), we immunohistochemically examined sequential changes of the subsets of lymphocytes infiltrating the pancreatic islets in CD-1 mice. Daily intraperitoneal injections of 30 mg/kg body wt of SZ for five consecutive days led to lymphocytic infiltration around the islets. Most of the infiltrated cells were initially CD4 positive (helper/inducer) T-lymphocytes and no immunoglobulin-bearing cells were detected. The number of helper/inducer T-lymphocytes increased with progression of the insulitis, then surface immunoglobulin-positive cells (B-lymphocytes) accumulated around the area of CD4 positive T-lymphocytes. CD8 positive (suppressor/cytotoxic) T-lymphocytes were seen scattered throughout the study and only a few asialo GM1 positive (natural killer) cells existed in the area of insulitis. Subsequently, the pancreatic insulin contents were considerably decreased and diabetes occurred on day 21. These observations suggest that CD4 positive T-lymphocyte-dependent B-lymphocyte infiltration in and around islet cells may be associated with islet cell destruction and the development of diabetes in CD-1 mice treated with multiple low doses of streptozocin.

Encephalomyocarditis (EMC) virus-induced diabetes mellitus prevented by Corynebacterium parvum in mice.

Corynebacterium parvum prevented the development of encephalomyocarditis virus-induced diabetes in mice, when it was given 3-14 days before the virus infection. This treatment inhibited virus replication in the pancreas of the infected mice at an early stage of the infection.

Cyclosporin A enhances streptozocin-induced diabetes in CD-1 mice.

Cyclosporin A (CYA), when administered to CD-1 mice treated with a subdiabetogenic dose of Streptozocin (STZ), exacerbated the STZ-induced insulitis and elevated the plasma glucose levels, parallel to a reduction of the insulin content of the pancreas. The possible mechanisms of CYA-mediated aggravation of STZ-induced diabetes are discussed.

Identification and partial purification of a low-molecular-weight growth inhibitor formed by density-inhibited, tumorigenic V79 Chinese hamster cells.

Medium conditioned by exposure to density-inhibited, tumorigenic V79 Chinese hamster cell cultures reversibly inhibited the growth and DNA synthesis of sparse, proliferating cultures, not only of the same cell line but also of the BALB/c 3T3 A31 murine cell line. This species nonspecific inhibitory activity was found to be mediated by the soluble inhibitor produced endogenously by V79 cells at the time of density inhibition. The molecular weight of this inhibitor is approximately 2000, and production of this compound seems to be serum dependent. Partial purification was done by reverse-phase fast protein liquid chromatography. The inhibitory activity was linearly dependent on the concentration in the inhibitory fraction. This partially purified inhibitor did not include lactic acid, a growth-inhibitory metabolite. These data indicate that a growth-regulatory factor is also operant in tumorigenic V79 cells and suggest that growth of neoplastic cells cannot only be explained by an enhanced positive growth potential but rather by the balance between a positive and negative growth potential.

The relationship between molecular and cellular repair from potentially lethal damage induced by N-methyl-N'-nitro-N-nitrosoguanidine in Chinese hamster V79 cells.

The relationship between molecular and cellular repair from potentially lethal damage (PLD) induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was investigated in exponentially growing V79 Chinese hamster cells. We compared the repair processes by an alkaline sucrose sedimentation analysis and a colony formation assay. MNNG-treated cells were exposed to the conditioned medium (CM) from density-inhibited plateau-phase V79 cell cultures, as a post-treatment for the induction of PLD repair. When MNNG-treated cells were postincubated in CM, cell survival continuously increased for 18 h, and during this period, DNA replication was substantially suppressed. CM did not inhibit the rejoining of the single-strand breaks of parental DNA. Rather, parental DNA fragments sedimented more rapidly when postincubated in CM than in fresh medium. These data indicate that cellular recovery from MNNG-induced PLD increases in proportion to the resealing of MNNG-induced single-strand breaks of DNA during the suppression of DNA replication, suggesting that excision repair is involved in the PLD repair process.