Interleukin-1 gene cluster variants in hemodialysis patients with end stage renal disease: An association and meta-analysis.

We evaluated whether polymorphisms in interleukin (IL-1) gene cluster (IL-1 alpha [IL-1A], IL-1 beta [IL-1B], and IL-1 receptor antagonist [IL-1RN]) are associated with end stage renal disease (ESRD). A total of 258 ESRD patients and 569 ethnicity matched controls were examined for IL-1 gene cluster. These were genotyped for five single-nucleotide gene polymorphisms in the IL-1A, IL-1B and IL-1RN genes and a variable number of tandem repeats (VNTR) in the IL-1RN. The IL-1B - 3953 and IL-1RN + 8006 polymorphism frequencies were significantly different between the two groups. At IL-1B, the T allele of - 3953C/T was increased among ESRD (P = 0.0001). A logistic regression model demonstrated that two repeat (240 base pair [bp]) of the IL-1Ra VNTR polymorphism was associated with ESRD (P = 0.0001). The C/C/C/C/C/1 haplotype was more prevalent in ESRD = 0.007). No linkage disequilibrium (LD) was observed between six loci of IL-1 gene. We further conducted a meta-analysis of existing studies and found that there is a strong association of IL-1 RN VNTR 86 bp repeat polymorphism with susceptibility to ESRD (odds ratio = 2.04, 95% confidence interval = 1.48-2.82; P = 0.000). IL-1B - 5887, +8006 and the IL-1RN VNTR polymorphisms have been implicated as potential risk factors for ESRD. The meta-analysis showed a strong association of IL-1RN 86 bp VNTR polymorphism with susceptibility to ESRD.

Genetic affinities of north and northeastern populations of India: inference from HLA-based study.

India is like a microcosm of the world in terms of its diversity; religion, climate and ethnicity which leads to genetic variations in the populations. As a highly polymorphic marker, the human leukocyte antigen (HLA) system plays an important role in the genetic differentiation studies. To assess the genetic diversity of HLA class II loci, we studied a total of 1336 individuals from north India using DNA-based techniques. The study included four endogamous castes (Kayastha, Mathurs, Rastogies and Vaishyas), two inbreeding Muslim populations (Shias and Sunnis) from north India and three northeast Indian populations (Lachung, Mech and Rajbanshi). A total of 36 alleles were observed at DRB1 locus in both Hindu castes and Muslims from north, while 21 alleles were seen in northeast Indians. At the DQA1 locus, the number of alleles ranged from 11 to 17 in the studied populations. The total number of alleles at DQB1 was 19, 12 and 20 in the studied castes, Muslims and northeastern populations, respectively. The most frequent haplotypes observed in all the studied populations were DRB1*0701-DQA1*0201-DQB1*0201 and DRB1*1501-DQA1*0103-DQB1*0601. Upon comparing our results with other world populations, we observed the presence of Caucasoid element in north Indian population. However, differential admixturing among Sunnis and Shias with the other north Indians was evident. Northeastern populations showed genetic affinity with Mongoloids from southeast Asia. When genetic distances were calculated, we found the north Indians and northeastern populations to be markedly unrelated.

Fine structure of prolactin cell of female albino rat as affected by some antifertility drugs--a comparative electron microscopic study.

One antioestrogenic compound as well as some antifertility drugs have been administered to female albino rats over a period of six months to study their long term effects on fine structures in PRL cell. Almost in all the cases, the dynamics of hormone synthesis and secretion have been affected. Fine structure is suggestive of activation of synthetic machinery of the cell. The cell picture under the estradiol valerate regimen presents a transitional stage progressing towards involution due to accelerated cell cycle. Sparse granulation, frequent granule extrusion and misplaced exocytosis under the influence of tamoxifen citrate or levonorgestrel + ethinyloestradiol are similar to those observed in adenomatous PRL cell. Fine structural correlates of stepped up synthesis are also observed following chronic progesterogenic influences of progesterone and norethisterone heptanoate, but the magnitude of the change is on a lower scale. All the fine structural changes have been discussed in the context of ultrastructural pathology.

Regulation of hsp90 and hsp70 genes during antheridiol-induced hyphal branching in the oomycete Achlya ambisexualis.

When mycelia of Achlya ambisexualis J. Raper strain E87 were undergoing antheridial branching, a marked increase was observed in the levels of transcript populations encoding the heat shock protein chaperone Hsp90 and transcript populations encoding three different Hsp70-family heat shock protein chaperones, respectively. Although up to 90% of hyphae in the hormone-treated thalli were undergoing antheridial branching, no similar increase in the level of transcripts encoding actin was observed. Nuclear run-on assays demonstrated that the observed antheridiol-induced increases in the levels of the chaperone RNAs resulted from increased transcription. Although not tested for function, the nucleotide sequence of the 5' flanking region of each of the two A. ambisexualis hsp90 genes revealed a diversity of sequences and motifs similar or identical to the sequences of known transcription factor response elements. Among these potential response element sequences observed in the A. ambisexualis genes were motifs observed also in animal steroid hormone response elements. Surrounding the primer-extension determined transcription start site of each A. ambisexualis hsp90 gene was a 16-nucleotide sequence that matched in 14 out of 16 nucleotides a sequence found in the transcription initiation region of many different oomycete genes.

Regulation of two different hsp70 transcript populations in steroid hormone-induced fungal development.

In the filamentous oomycete fungus Achlya, the differentiation of gamete bearing structures on vegetative hyphae of the male mating type, is induced by the Achlya steroid hormone, antheridiol. Among the several metabolically labeled intracellular proteins whose synthesis or accumulation is altered by hormone treatment are steroid-induced 85-kDa and 68- to 78-kDa proteins. The 85-kDa protein was previously shown to be the Achlya heat shock protein hsp85 [Brunt et al., 1990; Brunt and Silver, 1991], a component of the putative Achlya steroid hormone receptor. It was of interest to determine if the antheridiol-induced "70-kDa" proteins were hsp70-family heat shock proteins and if hormone treatment-induced changes in the level of hsp70 transcripts. Two different Achlya hsp70 genomic sequences were cloned and used to investigate these questions. The two hsp70 sequences recognized two different mycelial transcript populations, one of which was regulated also by decreased glucose. Of note, both of the two hsp70 transcript populations were found to be regulated by antheridiol. The hormone-induced changes in hsp70 transcript levels were temporally correlated with the onset of massive lateral hyphal branching and alterations in the pattern of secreted N-linked glycoproteins which occur in hormone-treated mycelia. To our knowledge, this represents one of the first reports on changes in hsp70 proteins and transcripts during fungal differentiation. Our results may have implications for the role of heat shock proteins in hyphal branching and secretion in filamentous fungi and perhaps other cell types.