HLA-DR alleles are associated with IDDM, but not with impaired neutrophil chemotaxis in IDDM.

Insulin-dependent diabetes mellitus (IDDM) is a risk factor for periodontitis. Depressed neutrophil chemotaxis has been demonstrated in IDDM and in early-onset periodontitis (EOP). HLA-DR antigens are associated with both IDDM and periodontitis. This investigation sought to determine an association of HLA-DR3, -DR4, and -DR53 with impaired neutrophil chemotaxis in an IDDM sample. The neutrophil chemotaxis index of 41 diabetics and 27 controls was determined by a modified Boyden chamber method, and certain class II HLA genotypes were determined by polymerase chain-reaction amplification of genomic DNA by means of sequence-specific primers (PCR-SSP). The mean chemotaxis index of the diabetics was significantly less than that of the controls (p < or = 0.02). HLA-DR3 (p < or = 0.002), -DR4 (p < 0.003), and -DR53 (p < or = 0.001) were associated with IDDM. Neutrophil chemotaxis and glucose metabolism were not significantly correlated. None of the HLA-DR alleles was associated with impaired neutrophil chemotaxis. Therefore, the neutrophil chemotaxis defect of IDDM appears to be independent of these HLA-DR-associated genes.

Interleukin-10 promotes anti-collagen antibody production in type I diabetic peripheral B lymphocytes.

Previous studies have shown that type I diabetes (IDDM) increases the risk of developing periodontitis by 2-3-fold. IDDM patients exhibit destruction of the pancreatic beta cells, most probably caused by an autoimmune reaction. Evidence is accumulating to support the role of the autoimmune response in periodontal pathogenesis. A cytokine, interleukin (IL)-10, has been reported to selectively promote the expansion of a B lymphocyte lineage (CD5/LY1/B1) which has the propensity for secreting high levels of autoantibody. Therefore, the purpose of this project was to evaluate IL-10 production, percentage of CD5 B cells and the frequency of anti-collagen secreting cells in peripheral blood mononuclear cells of age, gender and race matched IDDM patients and controls. IL-10 production was evaluated by an ELISA using the supernatant of adherent peripheral blood cells cultured for 24 h in the presence of Porphyromonas gingivalis lipopolysaccharide (LPS). In 8 of 31 patients, IL-10 levels were significantly increased in IDDM compared to controls and a higher percentage of CD5 B cells was also observed by flow cytometry. In addition, these patients exhibited a higher frequency of anti-collagen secreting cells as elucidated by an ELISPOT. Moreover, treatment with a neutralizing anti-IL-10 antibody diminished the anti-collagen antibody response by 70%. These findings support the concept that a subset of IDDM patients possess an extremely robust IL-10 response following exposure to Gram-negative LPS, which could predispose them to the development of periodontitis through a heightened autoimmune mechanism.

Paternal inheritance of egg traits in mice: a case of genomic imprinting.

Eggs from reciprocal hybrids between the C57BL/6By and BALB/cBy strains were tested for their susceptibility to attack by hyaluronidase and pronase. There were significant reciprocal differences between the F1 females in the responses of their unfertilized eggs to both enzymes. The F1 hybrids from BALB mothers showed the increased susceptibility characteristic of C57BL whilst the F1 hybrids with C57BL mothers were more resistant to both enzymes, like BALB mice. Eggs from the four kinds of reciprocal F2 hybrid females also showed patroclinous patterns of susceptibility. A patroclinous difference was found between reciprocal crosses of the CXBD and CXBE recombinant inbred strains but not in crosses between recombinant inbred strains with similar phenotypes. Cross fostering did not alter the phenotypes of the C57BL and BALB females or those of their reciprocal F1 hybrids. The findings are interpreted in terms of differential genomic imprinting of paternally inherited information. The possible general usefulness of patroclinous differences between reciprocal F1 females in revealing differences in imprinting is noted.

Genetic differences in periovum sensitivity to hyaluronidase and protease between C57BL/6, BALB and CXB recombinant mice.

The cumulus oophorus surrounding eggs from C57BL/6 mice was digested by bovine or leech hyaluronidase significantly more rapidly than that surrounding eggs from BALB/c mice. The zona pellucida of C57BL/6 eggs was also more rapidly attacked by pronase. Three other sublines of C57BL showed the same characteristics. Measurements of susceptibility to hyaluronidase and pronase on eggs from the CXB recombinant inbred strains indicated that variation at a minimum of 2 loci affected each character. The lack of correlation between susceptibilities to the 2 enzymes across the recombinant strains implied that these differences separately affect the substrates of the enzymes, rather than reflecting a common difference in the process of oocyte maturation. The variation in susceptibility was unrelated to differences, controlled by the Ped and Qa-2 loci, in the rate of later embryonic cleavage. However, pronase susceptibility was significantly correlated with the early onset of the first cleavage.

Reduced estradiol production by a substituted triazole results in delayed ovulation in rats.

Ovulation in the rat is delayed by a single administration of the substituted triazole R151885 (1,1-di(4-fluorophenyl)-2-(1,2,4-triazol-1-yl)-ethanol). This delay results from a 24-hr shift in the preovulatory luteinizing hormone (LH) surge since administration of chorionic gonadotrophin on proestrus restores ovulation. Plasma levels of estradiol are markedly reduced (42-45%) 6-12 hr after administration of R151885. The restoration of ovulation in R151885-pretreated rats, by administration of exogenous estradiol benzoate, indicates that the reduced estradiol levels play a pivotal role in the delay of ovulation. Granulosa cells isolated from rat ovaries produce estradiol and progesterone in vitro in the presence of both follicle-stimulating hormone and testosterone. The addition of R151885 to such cultures results in a dose-dependent inhibition of estradiol production (69% by 1 microM) without a significant effect on progesterone production. This inhibition occurs at concentrations of R151885 similar to those measured in vivo. R151885 is a competitive inhibitor of human placental aromatase (apparent Ki with androstenedione substrate of 410 nM) and produces a type II spectral perturbation of cytochrome P-450 from placental microsomes. Pituitaries isolated from R151885-treated rats have reduced LH output in response to gonadotrophin-releasing hormone stimulation compared with those of controls. It is proposed that R151885 competitively inhibits aromatase activity in developing ovarian follicles. The resultant temporary reduction of plasma estradiol levels at a critical time in the estrous cycle, and consequent inadequate pituitary sensitization, produces a 24-hr delay in the preovulatory LH surge and hence ovulation is delayed by 24 hr.

Lactate dehydrogenase isozymes in human cardiac transplantation.

Lactate dehydrogenase (LDH) isozyme activities have been followed in 17 human cardiac allografts. A pattern of abnormality associated with cardiac rejection during the first month after operation has been determined: (i) LDH-1 activity is greater than LDH-2 activity; (ii) LDH-1 activity is greater than 35 percent of total LDH activity; and (iii) LDH-1 activity is greater than 100 international units. The LDH-1 abnormality helps to meet the need for an index of cardiac rejection during the early weeks after operation when the electro-cardiogram is least reliable.