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Biomedical subjects

S Naik

Publications and source records attributed to S Naik.

At least 91 records · Page 5Linked to original sources
PubMed1995

Gene regulation and genetic defects in the pyruvate dehydrogenase complex.

The mammalian pyruvate dehydrogenase complex (PDC) is subject to both short-term (product inhibition and covalent modification) and long-term (increases in total activity and protein mass) regulation mediated by dietary and hormonal treatments. Recent advances in the isolation and characterization of the complementary DNAs as well as genes encoding several components of mammalian PDC have facilitated studies concerning long-term regulation of PDC. Analyses of the promoter-regulatory regions of the two human PDC genes show characteristics of both facultative and housekeeping gene promoters, indicating complex transcriptional regulation. Deficiency of PDC activity causes a wide range of neurological disabilities. A spectrum of genetic defects in PDC components has been reported; however, the most frequent defects are associated with the pyruvate dehydrogenase component. Heterogeneity in pyruvate dehydrogenase deficiency has been shown to occur at both protein and messenger RNA levels, and several mutations in pyruvate dehydrogenase have been identified. Dietary treatments such as ketogenic diets and vitamin supplements as well as dichloroacetate treatment have been utilized to treat PDC deficiency, but their efficacy requires further evaluation.

Gene Expression Regulation, Enzymologic↗
PubMed1995

Compound heterozygosity of HLA-DR4 and DR1 antigens in Asian Indians increases the risk of extra-articular features in rheumatoid arthritis.

The relationship of HLA-DR antigens in rheumatoid arthritis (RA) patients with the presence of rheumatoid factor (RF), extra-articular features, joint erosions, functional status and response to disease modifying anti-rheumatic drugs (DMARDs) was studied. Seventy-four patients with RA were serologically typed for class II antigens. Clinical features were recorded before starting DMARDs and during follow-up to assess response and side-effects. HLA-DR1 and DR4 antigens were present more frequently in patients with RA than in the general population. The presence of DR4 correlated with RF seropositivity (P < 0.001) while DR1 was associated with seronegativity (P < 0.02). Ten of the 11 patients with extra-articular features had DR1 and/or DR4. Patients with both DR4 and DR1 had a significantly higher frequency of extra-articular features compared with those with only one of these (P < 0.01). HLA-DR4 and DR1 had no relation with the presence of subcutaneous nodules, erosive changes, deformities, response to drugs and side-effects of DMARDs.

Adult↗
PubMed1995

Effectiveness of mandatory transmissible diseases screening in Indian blood donors.

This study was undertaken to determine the prevalence of transfusion transmitted diseases (TTDs) among local blood donors, the safety offered by the four mandatory tests (for HIV, HBsAg, syphilis and malaria) and to assess alanine aminotransferase (ALT) as a surrogate test. A total of 313 blood donors were tested for HBsAg, hepatitis B core (HBc) antibody, hepatitis C (HCV) antibody, HIV antibody, and IgM antibody to cytomegalovirus (CMV-IgM). The serum alanine aminotransferase levels were also done on each unit of blood. The prevalence of various markers was 7(2.2%) for HBsAg, 57 (18.2%) for anti HBc (total), 1 (0.3%) for anti HCV, 16 (5.1%) for anti CMV. None of the donors were positive for HIV, VDRL or malaria. ALT level was raised in 16.5 per cent of donors and showed no correlation with hepatitis markers. ALT was not found to be useful as a surrogate marker for routine screening of donors. Sensitive tests like ELISA and immunofluoresence for malaria antigen should be applied for screening for malaria. VDRL test may be used to detect high risk donors rather than detection of syphilis when stored blood is used. HBsAg and HIV tests should be routinely done on every unit of blood and anti HCV tests should be done regularly, if possible.

Adult↗
PubMed1995

In vivo evaluation of a hollow fiber liver assist device.

Orthotopic liver transplantation is the only effective form of therapy currently available for patients with fulminant hepatic failure (FHF). The use of an extracorporeal (EC) liver assist device (LAD) may result in improved presurgical clinical management. Alternatively, patients treated with LADs could avoid the transplantation procedure if they are able to regenerate a critical mass of hepatocytes that will sustain functional viability. In this study, the efficacy of a prototype hollow fiber LAD seeded with rabbit hepatocytes was assessed in vivo by the use of two different animal models: (1) normal rabbits injected with diazepam or lidocaine, and (2) a galactosamine (Gal)-intoxicated rabbit model of FHF. The EC LAD clearly decreased the blood levels of the two drugs and significantly generated diazepam and lidocaine metabolites indicating the maintenance of active P450 forms in the cellular component of the devices. A 6-hour EC treatment significantly increased the survival time and delayed the onset of hepatic encephalopathy (HE) in the Gal-intoxicated rabbits. Histological evaluations of postmortem livers showed greater hepatocyte regenerative activity in the animals treated with hepatocyte-seeded LADs than in the two control groups, e.g., rabbits not treated or treated with unseeded devices. These findings support the concept that a microporous hollow fiber LAD seeded with rabbit hepatocytes is able to sustain drug detoxification in vivo as well as to modify the course of FHF in a well-characterized animal model.

Animals↗
PubMed1995

Defective lymphoproliferative responses & interleukin-2 production in chronic renal failure patients.

Cellular immune responses were evaluated in 12 early renal failure (ERF) patients who were not on maintenance haemodialysis, 43 end stage renal disease (ESRD) patients on haemodialysis (HD) and 25 healthy volunteers. Peripheral blood mononuclear cells (PBMC) of ERF and ESRD patients on HD had a significantly diminished lymphoproliferative responses to phytohaemagglutinin and a monoclonal antibody to the CD3 (anti-CD3) receptor on T-cells as compared to normals. The interleukin-2 (IL-2) production by the PBMC was also significantly reduced in renal failure patients as compared to normals. These data suggest that both IL-2 dependent and IL-2 independent T-cell functions are defective in renal failure patients.

Adult↗
PubMed1994

Serum IgM rheumatoid factor by enzyme-linked immunosorbent assay (ELISA) delineates a subset of patients with deforming joint disease in seronegative juvenile rheumatoid arthritis.

Using human IgG as an antigen in an enzyme-linked immunosorbent assay (ELISA), we looked for the presence of IgM rheumatoid factor (RF) in the sera of 74 children with juvenile rheumatoid arthritis (JRA). Nine children had RF detectable by both latex agglutination and ELISA. Forty-five percent (26 of 65) of the children who were seronegative by latex agglutination were found to be positive for IgM RF by ELISA. The prevalence of IgM RF was higher in patients with polyarticular onset disease (57.4%) than in those with pauciarticular onset (38.5%) or systemic onset (27.2%) disease. The prevalence of RF was higher in sera from patients with deforming joint disease than those without deformities (P < 0.01).

Adolescent↗
PubMed1994

Primary cultures of rat hepatocytes in hollow fiber chambers.

Hepatocyte culture may represent an alternative to the use of animals to study drug detoxification by the liver. An ideal in vitro system should closely mimic the in vivo environment by providing continuous media perfusion and oxygenation, and should facilitate sampling of cells and culture media. To meet these criteria, a hollow fiber bioreactor seeded with isolated rat hepatocytes was developed and tested by measuring the formation of three products of the oxidative metabolism of diazepam and the glucuronidation of phenolsulfonphthalein (PSP). To compare the performance of conventional monolayer culture to that of the bioreactor system, diazepam metabolism was studied for 45 days in both systems. The oxygen dependency of diazepam metabolism was evaluated by perfusing the bioreactor in an oxygen-rich atmosphere (30%). Total diazepam metabolism was twofold higher in the O2-rich perfused hollow fiber cultures than in the cultures perfused under normal conditions, reflecting an increase in temazepam and oxazepam production. Diazepam detoxification activity was significantly enhanced by oxygen (P < or = 0.001) over the life of the perfused cultures. PSP metabolism was similar in all three culture systems. By Day 10, diazepam metabolism in the oxygenated bioreactor system was 44% of the in vivo activity of rat hepatocytes. This activity dropped to 30% by Day 25 of culture. These results justify the use of perfused culture systems for in vitro detoxification studies as an alternative to animal use and emphasize the capacity of a culture device perfused under O2-enriched conditions to maintain long-term P450 activity of rat hepatocytes.

Animals↗
PubMed1994

High prevalence of HBV infectivity in blood donors detected by the dot blot hybridisation assay.

Hepatitis B virus (HBV) continues to be a significant cause for post-transfusion hepatitis in India, in spite of the introduction of compulsory hepatitis B surface antigen (HBsAg) screening. To understand the true HBV-infective pool in the blood donor population, HBV DNA was detected by a 32P-labelled dot blot hybridisation assay in 605 donor units that were negative for HBsAg by a third-generation Elisa. Serum alanine aminotransferase (ALT) was estimated in all these samples and correlated with DNA positivity. The frequency of HBV DNA positivity in HBsAg-negative units was very high (9.91%) and correlated well with the elevation in ALT (p < 0.00005). However, the frequency of elevated ALT was high (11.9%), using the locally determined upper limit of normal, and half of the DNA-positive samples had a normal ALT. Thus, ALT is a poor surrogate marker for HBV infectivity and efforts should be made to apply DNA detection systems in blood banks.

Adult↗
PubMed1993

Multiple protein-binding domains and functional cis-elements in the 5'-flanking region of the human pyruvate dehydrogenase alpha-subunit gene.

We have characterized the 5'-flanking region of the alpha-subunit gene of the human pyruvate dehydrogenase (E1). DNase I footprinting with rat liver nuclear extracts identified 7 major protein-binding domains termed P1 through P7 in a 796 base pair DNA fragment (base pairs -763 to +33). P1 through P4 are clustered in the -221/+33 region. These protein-binding domains contain several known consensus sequences such as a TATA box, CAAT box, Sp1, and CRE, which all have previously been implicated in the constitutive transcription of several genes. Oligonucleotide competition studies indicate that oligonucleotides specific for CTF/NF-1 and Sp1 displaced the nuclear proteins bound to the CAAT box (within P3) and an Sp1 site (within P4), respectively. Several other well-characterized and purified transactivators (c-Fos, c-Jun, C/EBP, AP-2, and Sp1) have been shown to bind to the -221/+33 region. Other elements located upstream of the -221/+33 region, which includes nuclease protection domains P5-P7, are required for enhanced promoter activity of the 796 bp sequence. Promoter activity was measured by transient expression of a chloramphenicol acetyltransferase gene ligated to deletion fragments of the 5'-flanking region. Crucial element(s) for promoter activity and complex DNA-nuclear protein interactions were confined within a region spanning -221/+33. This region also retained more than 75% of the promoter activity of the 796 bp sequence. Additionally, this promoter region shows characteristics of both facultative and housekeeping gene promoters, suggesting complex transcriptional regulation.

Base Sequence↗
PubMed1993

Audit in the management of gliomas.

A retrospective study of 139 glioma patients was conducted in an effort to audit management. Factors affecting survival were studied using a Cox Proportional Hazard Model. These factors included age, sex, location, grade, type of surgery, use of radiotherapy, presenting symptoms, Karnofsky score on admission and Karnofsky score 3 months following surgery. Lower grade, high Karnofsky score on admission, radiotherapy and frontal location were associated with better survival. There was statistically insignificant evidence that the other factors had an influence on survival. Patients presenting with a poor neurological score were treated with burrhole biopsy alone. Only 10% of these patients survived more than 6 months. On the other hand, 26% of patients who had craniotomy on the basis of reasonable clinical status lived less than 6 months. Sixty-six per cent of patients in this craniotomy group were aged 60 years or over, and 66% of those aged over 60 had a Karnofsky score of less than 70. We conclude that careful judgement is required before subjecting patients aged over 60, especially those with a low Karnofsky score, to radical therapy.

Adolescent↗
PubMed1993

Interleukin-8 release and neutrophil degranulation after pediatric cardiopulmonary bypass.

Capillary leak after cardiopulmonary bypass operations for correction of congenital heart defects is universally seen in children and often causes significant morbidity and mortality. Since neutrophil-mediated endothelial injury has been implicated as a pathogenetic mechanism, a prospective controlled descriptive study was performed to investigate possible activation pathways during and after the bypass procedure. Eighteen children undergoing operations, nine with cardiopulmonary bypass and nine neurosurgical craniotomy (i.e., operations without bypass), had samples of arterial blood collected at intervals before, during, and after operations. In six of nine cardiac patients circulating interleukin-8 concentrations rose from less than 30 pg/ml to very high concentrations (> 500 pg/ml); in the remaining three patients small rises (peak 57 to 81 pg/ml) were also seen. In all nine, the rise commenced at the time of rewarming, toward the end of bypass, and peaked 1 to 3 hours thereafter. Interleukin-8 release correlated significantly with length of bypass. Interleukin-1 alpha and interleukin-1 beta were not found, and traces of tumor necrosis factor-alpha were detected in one patient only. Circulating elastase alpha 1-antitrypsin concentrations rose simultaneously and correlated significantly with interleukin-8 (p < 0.001) in patients with cardiac disease, as did absolute neutrophil counts (p < 0.001). In contrast, only one of nine patients with neurosurgical disease (undergoing an unusually long operation and exchange transfusion) had a rise in circulating interleukin-8 to levels greater than 500 pg/ml (p < 0.01). The two samples from this patient with elevated interleukin-8 were the only neurosurgical samples with elevated elastase. This study demonstrates the release of interleukin-8 into the circulation after pediatric hypothermic cardiopulmonary bypass and supports the suggestion that this cytokine plays a role in the pathophysiology of capillary leak through neutrophil degranulation.

Cardiopulmonary Bypass↗