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Biomedical subjects

S Bhattacharya

Publications and source records attributed to S Bhattacharya.

At least 361 records · Page 20Linked to original sources

Abetalipoproteinemia is caused by defects of the gene encoding the 97 kDa subunit of a microsomal triglyceride transfer protein.

Abetalipoproteinemia is an inherited disorder of lipoprotein metabolism. Affected individuals produce virtually no circulating apolipoprotein B-containing lipoproteins (chylomicrons, very low density lipoprotein, low density lipoprotein and lipoprotein (a)). Malabsorption of the antioxidant vitamin E occurs, leading to spinocerebellar and retinal degeneration. Biochemical and genetic studies show that abetalipoproteinemia is not a defect of lipid biosynthesis or of the apolipoprotein B gene. Instead a microsomal triglyceride transfer protein, which exists as a complex with protein disulphide isomerase in the endoplasmic reticulum, has been implicated. We have cloned and sequenced the human cDNA encoding microsomal triglyceride transfer protein. The predicted amino acid sequence shows extensive homology to vitellogenin, the precursor of the lipovitellin complex, which has been shown by X-ray crystallography to contain a large lipid storage cavity. Microsomal triglyceride transfer protein is expressed in ovary, testis and kidney, in addition to liver and small intestine. A homozygous mutation that disrupts splicing has been identified in affected siblings with classical abetalipoproteinemia. These results elucidate a key process in the packaging of apolipoprotein B with lipid, and should increase our understanding of the processes regulating the production of atherogenic lipoproteins.

Abetalipoproteinemia↗

Exclusion of the involvement of all known retinitis pigmentosa loci in the disease present in a family of Irish origin provides evidence for a sixth autosomal dominant locus (RP8).

Retinitis Pigmentosa (RP) is the most prevalent degenerative retinal disease of mendelian origin, currently affecting approximately 1.5 million people worldwide. To date it has been established that a minimum of five different genes maybe involved in the pathogenesis of autosomal dominant forms of RP (adRP). The genes encoding two retinal specific proteins, rhodopsin and peripherin/RDS, have been implicated in causing adRP due to the observation of many different mutations in these genes in patients suffering from RP. The three remaining adRP genes have been mapped to specific regions of human chromosomes but as yet are uncharacterized. We have investigated if there is evidence for the presence of another locus in the genome which when mutated causes adRP. We have utilised polymorphic genetic markers which have previously been mapped to each of the regions known to harbour adRP genes, to test for the exclusion or linkage of the disease gene segregating in a pedigree of Irish origin and find no evidence for linkage. Hence we provide definitive evidence for the involvement of yet another locus. The implications of high levels of genetic heterogeneity inherent in adRP are discussed in relation to diagnosis, prognosis and future therapies.

Chromosome Mapping↗

IFN-gamma is directly cytostatic to the extracellular form (promastigote) of Leishmania donovani.

We investigated the effect of various human cytokines on the in vitro growth of Leishmania donovani (L. donovani) promastigotes. rhIFN-alpha, rhIFN-beta, rhIL-1, rhIL-2, rhIL-3, rhIL-4, rhIL-6 and rhM-CSF had no effect. By contrast, rhIFN-gamma was directly growth inhibitory to L. donovani promastigotes in a dose-dependent manner. Anti-IFN-gamma antibody, but neither anti-IFN-alpha nor anti-IFN-beta antibody, abolished this promastigote growth inhibitory effect of rhIFN-gamma. L. donovani promastigotes were not lysed by rhIFN-gamma as determined by 51Cr-release assay. These data indicate that rhIFN-gamma is cytostatic, not cytotoxic, to L. donovani promastigotes.

Animals↗

Impairment of natural killer cell activity in Indian kala-azar: restoration of activity by interleukin 2 but not by alpha or gamma interferon.

Indian kala-azar patients have normal numbers of peripheral blood NK cells but impaired functional activity due to decreased binding and lysis of target cells. This impairment of NK activity could not be corrected by exogenous recombinant human alpha or gamma interferon. However, recombinant human interleukin 2 was able to restore this activity by augmenting conjugate formation and lysis of target cells.

Adolescent↗

Rate of change of left ventricular ejection fraction during exercise is superior to the peak ejection fraction for predicting functionally significant coronary artery disease.

OBJECTIVE: To detect and characterise rapid temporal changes in the left ventricular response to exercise in patients with ischaemic heart disease and to relate these changes to the functional severity of coronary artery disease. BACKGROUND: The gamma camera does not allow the detection of rapid changes in cardiac function during exercise radionuclide ventriculography, the monitoring of which may improve the assessment of patients with ischaemic heart disease. METHODS: A miniature nuclear probe (Cardioscint) was used to monitor continuously left ventricular function during exercise in 31 patients who had coronary angiography for suspected coronary artery disease. A coronary angiographic jeopardy score was calculated for each patient. RESULTS: The coronary jeopardy score ranged from 0 to 12 (median 4). Ejection fraction fell significantly during exercise from 46% to 34%. Patients were divided into two groups based on the response of their ejection fraction to exercise. In 14 patients (group I), the peak change in ejection fraction coincided with the end of exercise, whereas in the other 17 patients (group II) the peak change in ejection fraction occurred before the end of exercise, resulting in a brief plateau. The peak change in ejection fraction and the time to its occurrence were independent predictors of coronary jeopardy (r = -0.59, p < 0.001 for peak change and r = -0.69, p < 0.001 for time to that change). The rate of change in ejection fraction was the strongest predictor of coronary jeopardy (r = -0.81, p < 0.001). In group I the peak change in ejection fraction was a poor predictor severity of coronary disease (r = -0.28, NS), whereas the time to peak and the rate of change in ejection fraction were good predictors (r = -0.65 and r = -0.73, p < 0.01). In group II the peak, the time to the peak, and the rate of change in ejection fraction were good predictors of coronary jeopardy (r = -0.75, r = -0.61, and r = -0.83, p < 0.01). CONCLUSION: The rate of change of ejection fraction during exercise can be assessed by continuous monitoring of left ventricular function with the nuclear probe, and is the best predictor of functionally significant coronary artery disease.

Adult↗

Human chorionic gonadotropin binding sites in the human endometrium.

The existence of high-affinity and low-capacity specific binding sites for luteinizing hormone (LH)/human chorionic gonadotropin (hCG) has been reported in porcine, rabbit and rat uteri. We have identified hCG binding sites in the human endometrium collected from 35-42-year-old ovulatory and anovulatory women. The binding characteristics of hCG to endometrial tissue preparations from ovulatory and anovulatory women showed saturability with high affinity and low capacity. Scatchard plot analysis showed the dissociation constant of specific binding sites in the ovulatory women to be 3.5 x 10(-10) mol/l and in anovulatory women to be 3.1 x 10(-10) mol/l. The maximum binding capacity varied considerably between ovulatory (3.85 nmol/kg protein) and anovulatory (6.12 nmol/kg protein) endometrium. Among the divalent metal ions tested (Zn2+, Mg2+, Mn2+, Ca(2+)--4 mol/l), Zn2+ effected a remarkable increase in [125I]hCG binding to the endometrium (p < 0.005) whereas Mn2+ showed a marginal increase and other metal ions did not have any effect. Data obtained with human endometrium indicate an influence of the functional state of the ovary on [125I]hCG binding to endometrium.

Adult↗

Time dependent distribution of [203Hg] mercuric nitrate in the subcellular fractions of rat and fish liver.

Cytotoxicity of inorganic mercury to the liver of two species, Anabas testudineus and Sprague Dawley male rat was evaluated. Distribution kinetics of this metal in the different hepatic subcellular fractions were followed for 48 h after a single injection of [203Hg] mercuric nitrate at a dose of 4mg/kg b.w. Interaction of this metal with protein, DNA and RNA was also studied. In rat, nuclear and lysosomal fractions showed a significant increase in the protein content, while in fish, the amount of protein increased in all fractions except microsome. Comparatively more mercury was bound to protein in fish during the later phase of treatment. Retention of mercury in nuclear DNA of rat gradually declined from 15 min to 48 h of treatment, while, mitochondrial DNA binding to mercury increased from 15 min to 2 h of post injection and then declined in the later phase of the experiment. Such a biphasic binding pattern of mercury was shown by both the nuclear and mitochondrial DNA of the fish. The nuclear RNA of rat and mitochondrial and cytosolic RNA of both test species also showed a biphasic pattern of mercury binding, however, with a higher rate of binding in fish at the later phase of the experiment. The present study thus highlights that (a) mercury follows a definite distribution pattern in the subcellular fractions of the liver in both animal species, (b) cytosol is the major site of mercury accumulation.

Animals↗

Infusions of a novel calcitonin gene-related peptide (CGRP) derivative at the time of reperfusion to salvage ischaemic rabbit skin flaps.

Rabbit epigastric skin flaps were subjected to 21 h of ischaemia at 25 degrees C. In the first 40 min of reperfusion the flaps were infused intraarterially with either Hanks' balanced salt solution (controls), chicken CGRP or a derivative DADA-CGRP. Skin biopsies and blood specimens were taken immediately before and after 1-h reperfusion. The aim was to observe the effect of CGRP derivatives on compromised skin-flap survival and to help elucidate the critical biochemical mechanisms. It was found that chicken CGRP and DADA-CGRP produced a dose-dependent increase in blood flow, significant at and above 0.1 microgram/kg, but only the 0.1 microgram/kg DADA-CGRP infusion produced a statistically significant increase in flap survival (75.1%) as compared with controls (41.6%). CGRP infusions caused significantly more rapid restoration of tissue ATP levels and resulted in a smaller rise in blood thromboxane as compared with controls. However, CGRP caused no significant change in the tissue levels of myeloperoxidase, a measure of neutrophil infiltration, and lipid peroxidation, an indicator of free-radical activity. It is concluded that intraarterial CGRP infusions to ischaemic flaps at the time of reperfusion are indicated. However, an ideal infusion solution would also need to counteract free radicals and neutrophils which are believed to also play a major role in the inflammatory response leading to flap failure.

Animals↗

Tuberculous endometritis in hills of Darjeeling: a clinicopathological and bacteriological study.

Combined histological and bacteriological investigations of 800 specimens of nonpregnant endometrial curettings of 15 to 60 years age group of hill women of Darjeeling District were carried out for detection of tuberculous endometritis. The principal complaints were infertility (47.5 per cent), abnormal uterine bleeding (30.75 per cent), amenorrhoea (11.25 per cent), leucorrhoea (6.25 per cent), and miscellaneous conditions (pelvic pain and pyometra) (4.25 per cent) cases. By histological examination alone, only 10.9 per cent cases could be diagnosed while by combined study the incidence rate was 11.8 percent, an increase in the diagnostic acumen by more than 10.3 per cent. Bacteriological study was of greater value in doubtful cases where there was absence of tuberculous granuloma or epithelioid cell but presence of nonspecific inflammatory cells along with variable degree of necrosis of glandular epithelia. The incidence of M.tuberculosis was 97.7 percent while that of atypical mycobacteria was 2.3 per cent. Thus simultaneous use of culture and biopsy yielded better results. Our prevalence is a little higher than other reports from India. In cold weather at a high altitude, the tubercle bacilli survive longer in fomites which serve as important sources of infection in Darjeeling. Women of third decade are more frequently affected (43.2 per cent).

Adolescent↗

The calcium binding protein of Entamoeba histolytica: expression in Escherichia coli and immunochemical characterization.

The gene encoding calcium binding protein (CaBP) of Entamoeba histolytica is single-copy and transcribes a single class of mRNA. The coding region of the gene, amplified from a genomic clone of CaBP by polymerase chain reaction, was cloned into the Escherichia coli expression vector pET-3c. The expressed protein was 15 kD in size, which agreed with the predicted size from the open reading frame. The recombinant protein showed altered mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) after binding calcium and was found to be resistant to boiling, a property shared by many calcium binding proteins. A polyclonal antibody raised against the recombinant CaBP recognized a 15 kD protein in lysates from E. histolytica pathogenic strain HM-1:IMSS. The amebic protein could compete with the recombinant protein in binding to the antibody. While the antibody recognized lysates from a number of E. histolytica strains, it failed to cross-react with other Entamoeba species, e.g., E. invadens and E. moshkovskii. Moreover, no homologue of the CaBP gene could be detected in these species by using a set of degenerate primers for amplification by polymerase chain reaction (PCR). Our data demonstrate that amebic CaBP can be expressed in E. coli and that this protein is detectable only in E. histolytica but not in other Entamoeba.

Animals↗

Early diagnosis of acute myocardial infarction with use of a rapid immunochemical assay of creatine kinase MB isoenzyme.

In 195 patients presenting with chest pain and referred acutely for cardiological assessment, blood was taken immediately for assay of creatine kinase (CK; EC 2.7.3.2) MB isoenzyme by an immunochemical method and results [mass units of enzyme per liter of plasma (microgram/L)] were obtained within 30 min of sampling. Diagnosis of acute myocardial infarction in the patients was made independently, based on electrocardiograms and conventional cardiac enzyme profiles. The administration of any thrombolytic therapy in response to the CK-MB concentration result was also noted, allowing assessment of the assay's potential influence on patient management in addition to the diagnostic efficiency evaluation. The study demonstrated that, when blood samples were collected on admission to hospital and the decision level suggested by the manufacturers was utilized, the assay had an immediate sensitivity of 52% and a specificity of 97%. Of the 81 patients who were shown by conventional means to have had acute myocardial infarction, 8 (10%) had equivocal electrocardiograms but positive CK-MB concentration results. In four of these patients (5%), thrombolytic therapy was given on the basis of the clinical features and a positive CK-MB concentration result alone.

Creatine Kinase↗

Acute phase response of rabbit to HgCl2 and CdCl2.

A variety of changes occur in the rabbit under metal stress which include the appearance of the acute phase protein, C-reactive protein in the serum and significant reduction in the serum titres of albumin and acetylcholinesterase. The phospholipid profile is positively correlated with the higher degree of tissue necrosis encountered in mercury treated rabbit. Cadmium and mercury treatments evoke a similar response pattern in rabbit differing only in the degree of change.

Acetylcholinesterase↗