NRAMP1 (SLC11A1): A plausible candidate gene for systemic sclerosis (SSc) with interstitial lung involvement

Systemic sclerosis (SSc), also termed "scleroderma," is a progressive, systemic disease of unknown origin characterized by excessive fibrosis, vascular abnormalities and immune dysfunction. Nramp 1 gene has multiple pleiotropic effects on macrophage activation pathways, including up-regulation of the chemokine/cytokine genes KC, tumor necrosis factor alpha, interleukin-1 b, inducible nitric oxide syntase, and major histocompatibility complex class II expression, as well as tumoricial activity and antimicrobial activity. All of these pleiotropic effects are important for resistance to infection, but they may also be involved in the induction and maintenance of autoimmune diseases. We analyzed four natural resistance associated macrophage protein 1 (NRAMP1) gene polymorphisms including 5' promoter (GT)n microsatellite, INT4 (469+14G/C), 3'UTR (1729+55del4), and D543N (codon 543, Asp to Asn) in 52 systemic sclerosis patients with interstitial lung involvement and 136 healthy controls. We found a significant association between INT4, (GT)n polymorphisms (p=0.006 and 0.027, respectively), and SSc. Our findings suggest that NRAMP1 is a plausible candidate gene for SSc

Interleukin-10 and tumor necrosis factor-alpha gene polymorphisms in tuberculosis

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is an infectious disease in humans killing nearly three million people and eight million cases annually. The cytokines TNF-alpha and IL-10 have been implicated in the pathogenesis of TB. Certain single nucleotide polymorphisms within the promoter region of the IL10 and TNF genes have been associated with altered levels of circulating IL10 and TNF-alpha. We analyzed TNF-a (-308 G/A, -238 G/A, -376 G/A) and IL10 (-1,082 G/A, -819 C/T, -592 C/A) polymorphisms in 128 patients with TB and 80 healthy subjects using by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). A significant association was found between TB and -1,082 G allele (Pc: 0.000, OR 2.22, 95% CI 1.45-3.4 1). Significant difference was observed in IL10 GCC and ACC haplotypes distribution between TB and control subjects (Pc: 0.000, OR 2.22, 95% CI 1.45-3.41; Pc: 0.004, OR 0.53, 95% CI 0.35-0.81). No statistically significant association was found between IL-10 -819 C/T, TNF-alpha 308 G/A, -238 G/A, -376 G/A polymorphisms, functional TNF alpha/IL-10 genotypes and TB. Our findings suggest that IL-10 108 2G/A alleles or haplotypes containing these alleles may influence the Th1/Th2 balance and hence may play a role in TB susceptibility and increase risk of developing disease. This polymorphism may be one of the many genetic factors affecting disease outcome

Association between 'interleukin' 10 gene (IL10) polymorphisms and systemic sclerosis with interstitial lung involvement

Systemic sclerosis (SSc), also termed as "scleroderma", is a progressive, systemic disease of unknown origin characterized by excessive fibrosis, vascular abnormalities and immune dysfunction. Extracellular matrix (ECM) production by fibroblasts in SSc is modulated and regulated by cytokines. Since IL10 has antiinflamatory properties and, contributes to the fibrotic processes in SSc, we analyzed IL-10 gene polymorphisms including -1082 G/A, -819 C/T and -592C/A in 45 systemic sclerosis patients with lung involvement and 150 healthy control using ARMS-PCR. While no association was found between SSc and -819C/T, -592C/A polymorphism, -1082 G/A allele frequency in SSc patients was higher than that in control and significant association was found between SSc and -1082 G/A (Pc: < 0.000, OR: 2.85 95% CI: 1.74-4.63). In addition significant difference was found between the frequencies of the IL-10 GCC, ACC haplotypes (Pc: < 0.000, OR: 2.85, 95% CI: 1.74-4.63; Pc: 0.012, O.R: 1.56, 95% CI: 1.09-2.23, respectively), GCC(+)/GCC(+), GCC(-)/GCC(-) genotypes (Pc: 0.002, OR: 5.07, 95% CI: 1.82-14.21; Pc: < 0.000, O.R: 4.00, 95% CI: 1.87-8.98, respectively) and SSc. Our findings suggest that IL-10 1082 G/A alleles or haplotypes containing these alleles may play role in SSc susceptibility

A rapid technique for the determination of furfural in the fission yeast culture media

A simple and rapid technique for the determination of furfural in the culture medium, which contains this compound as a degradation product of xylose at autoclave conditions, was evaluated. Besides, the growth and the furfural metabolism of the fission yeast Schizosaccharomyces pombe has been monitored using spectral methods

Concentrations of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS) in cerebrospinal of patients with severe head injuries

There is growing evidence that nitric oxide (NO) produced by isoforms of nitric oxide synthase (NOS), namely, inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS), plays a role in neuronal damage after neurotrauma. NO is a powerful universal mediator of many biologic reactions, including the mechanisms of injury during head trauma. Understanding of the organization and function of NO and NOS has led to new concepts in the treatment modalities of neuronal damage after head injury. In the current study, nine consecutive patients with a severe head injury who were admitted to Cerrahpasa Medical School Hospital at the University of Istanbul between January 2001 and July 2001 were evaluated. Cerebrospinal fluid (CSF) samples were withdrawn from the intraventricular catheter at admission (4-8 hours after trauma) and on each of the next 3 days. The iNOS and nNOS concentrations were assayed in 72 samples of ventricular CSF. CSF concentrations of iNOS and nNOS were increased after severe closed-head injury and peaked at 64 to 72 hours and 20 to 24 hours after trauma, respectively. These results suggest that maximal neuronal damage may occur between 20 and 24 hours after injury as a result of increased nNOS activity, which may contribute to the concomitant excitotoxic neuronal death after traumatic brain injury

The association between BsmI variant of vitamin D receptor gene and susceptibility to tuberculosis

Vitamin D receptor (VDR) gene variants may play a key role in the susceptibility to tuberculosis (TB). We have investigated the association BsmI, TaqI, FokI polymorphisms in the VDR gene with susceptibility to tuberculosis. This study included 128 patients with TB (pulmonary and extrapulmonary TB) and 80 healthy subjects living in Istanbul, Turkey. Genetic polymorphisms were studied by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques at genomic DNA isolated from whole blood-EDTA. The present study results indicate that the genotype and allele frequencies for patient group (BB:22, Bb:53, bb:25; B allele:48%, b allele:52%) was significantly different from the control group (BB:6, Bb:48, bb: 46; B allele:30 b allele:70) due to an overrepresentation of B allele (P: 0.000 OR: 1.61 95% 1.23-2.11). However there were no significant differences in distribution of allele/genotype frequencies of FokI, TaqI variants between TB and healthy controls. This study results suggest that BsmI variant of VDR gene may play an important role in susceptibility to tuberculosis