A mutation (C677T) in the gene, MTHFR, is known to increase susceptibility to various multifactorial disorders. In order to assess this single nucleotide polymorphism (SNP) as risk factor for idiopathic male infertility, a case-control study was done on an Indian population. DNA from 151 cases of non-obstruction, idiopathic oligo-/azoospermia and 200 fertile males (controls) was polymerase chain reaction amplified using site-specific primers, and analysed for the mutation following HinfI-digestion. Our results show a significantly increased frequency of CT heterozygotes among infertile patients (p value <0.04). More importantly, while there were no T homozygotes in the control population, six of 151 infertile cases were T homozygous. Considering that T allele occurs in very low frequency in the control population, 677T is clearly a risk factor for infertility in the Indian population. We contend that the same could also be true for African and Southeast Asian populations where the frequency of 677T is very low. The lack of similar association in western populations could be because of the overall dietary enrichment of folates, which could nullify or minimize the effect of this polymorphism.

The aim of this study was to detect, isolate and characterize the nanobacteria from human renal stones from a north Indian population, and to determine their role in biomineralization. Renal stones retrieved from the kidneys of 65 patients were processed and subjected to mammalian cell culture conditions. The isolated bacteria were examined using scanning (SEM) and transmission electron microscopy (TEM). They were characterized for the presence of DNA, proteins and antigenicity. The role of these bacteria in biomineralization was studied by using the (14)C-oxalate based calcium oxalate monohydrate (COM) crystallization assay. We observed the presence of apatite forming, ultrafilterable gram negative, coccoid microorganisms in 62% of the renal stones. SEM studies revealed 60-200 nm sized organisms with a distinct cell wall and a capsule. TEM images showed needle like apatite structures both within and surrounding them. They were heat sensitive, showed antibiotic resistance and accelerated COM crystallization. A potent signal corresponding to the presence of DNA was observed in demineralized nanobacterial cells by flow cytometry. The protein profile showed the presence of several peptide bands of which those of 18 kDa and 39kDa were prominent. Apatite forming nanosized bacteria are present in human renal stones and may play a role in the pathophysiology of renal stone formation by facilitating crystallization and biomineralization. However, further studies are required to establish the exact mechanism by which nanobacteria are involved in the causation of renal stones.

Key words human leukocyte antigen B; human leukocyte antigen-DRB1; interferon-g; interleukin-6; interleukin-10; single nucleotide polymorphisms; transforming growth factorb; tumor necrosis factor-a; type 1 diabetes AbstractType 1 diabetes (T1D) is a multifactorial autoimmune disorder where major histocompatibility complex (MHC) genes and the insulin-linked polymorphic region have been shown to play major roles. We report here an integrated effect of tumor necrosis factor (TNF) a with other cytokine genes. The TNF-a 2308 GA and AA (high secretor) polymorphisms were significantly increased in the patients with T1D (n ¼ 235) [P < 7 Â 10 C) did not show a significant difference between patients and controls. However, simultaneous presence of TNFa 2308 GA1AA along with both high and low secretor genotypes of IFN-g (P < 0.003) was significantly increased in patients. Simultaneous presence of TNF-a 2308 GA 1 AA along with high secretor genotypes of IL-6 (P < 0.0001, OR ¼ 2.61, 95% CI ¼ 1.5-4.56), IL-10 (P < 0.0001, OR ¼ 4.26, 95% CI ¼ 1.9-10.1) and TGFb1 (P < 0.00004, OR ¼ 2.8, 95% CI ¼ 1.6-4.86) was also significantly increased in patients with T1D. Low secretor genotype of TNF-a 2308 GG along with low secretor genotypes of IFN-g (P < 0.001, OR ¼ 0.465, 95% CI ¼ 0.28-0.77), high secretor genotypes of IL-6 (P < 0.000004, OR ¼ 0.76, 95% CI ¼ 0.227-0.621) and TGF-b1 (P < 0.000006, OR ¼ 0.336, 95% CI ¼ 0.198-0.568) was protective. The TNF-a 2308 G allele was in linkage disequilibrium (LD) with the human leukocyte antigen (HLA)-B*0801-DRB1*0301 haplotype, while TNF-a 2308 A allele was in LD with the HLA-B*5001-DRB1*0301 and B*5801-DRB1*0301 haplotypes, suggesting that the effect of TNF-a 2308 A allele is not because of its being in LD with any HLA alleles, but because of its functional role and its integrated effect with other cytokines.

Genitourinary tuberculosis contributes to 10-14% of extrapulmonary tuberculosis and is a major health problem in India. Prostate tuberculosis is uncommon and is usually found incidentally following transurethral resection. The most common mode of involvement is hematogenous, though descending infection and direct intracanalicular extension is known. Predisposing factors include prior tubercular infection, immuno-compromised status, previous BCG therapy. The presentation is diffuse caseating epitheloid cell granulomas, which can be confirmed by prostate biopsy. Urine PCR has good sensitivity (95.5%) and specificity ( 98.12%) in diagnosis. Imaging techniques like TRUS and CT/MRI also allow good visualization of the lesion and its extension. Urethral tuberculosis is very rare and is usually secondary to upper tract or genital tuberculosis. The presentation may be acute urethritis or chronic stricture or fistulae. The treatment of choice is chemotherapy with 3-4 anti tubercular drugs for initial 6-12 weeks and later 2 drugs for additional 3-6 months. Surgery is usually reserved for cases where chemotherapy fails and is done after 4-6 weeks of ATT. With a high index of suspicion it may be possible to diagnose a larger number of cases of prostatic and urethral tuberculosis especially in this country where tuberculosis is almost endemic.