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Biomedical subjects

S Basu

Publications and source records attributed to S Basu.

At least 109 records · Page 6Linked to original sources

Effects of melagatran, a novel direct thrombin inhibitor, during experimental septic shock.

Sepsis and endotoxaemia initiate the generation of thrombin, which is responsible for the conversion of fibrinogen to fibrin, platelet aggregation and acts as an inflammatory mediator affecting numerous types of cells, including myocardial, smooth muscle and endothelial cells. Human Gram-negative septic shock, frequently seen in intensive care units, is a condition with high mortality. This condition can be replicated in the endotoxaemic pig. As many of the toxic effects of sepsis are due to thrombin generation, it was of interest to study, using this porcine experimental septic shock model, whether inhibition of thrombin could alleviate the effects of endotoxaemia. For this purpose melagatran, a direct synthetic thrombin inhibitor with a molecular weight of 429 Da, was employed. Melagatran does not significantly interact with any other enzymes in the coagulation cascade or fibrinolytic enzymes aside from thrombin. Furthermore, melagatran does not require endogenous co-factors such as antithrombin or heparin co-Factor II for its antithrombin effect, which is important, as these inhibitors are often consumed in septic patients. We have shown that melagatran exerts a beneficial effect on renal function, as evaluated by plasma creatinine and urinary output, during experimental septic shock. These effects were most pronounced during the later phase of the experimental period, after the infusion of melagatran had been discontinued. Prevention of intrarenal coagulation may be attributable to this finding. In addition, melagatran had beneficial effects on systemic haemodynamics (left ventricular stroke work index, pulmonary capillary wedge pressure and systemic vascular resistance index) in endotoxaemic pigs. This result may be explained by the ability of melagatran to inhibit thrombin, thereby counteracting thrombin's cellular effects. Thus, it can be seen, using this experimental model of septic shock, that melagatran may help to alleviate some of the damaging effects of endotoxaemia, although more research is required to test this further.

Animals↗

Cloning and cellular localization of the rat mast cell 78-kDa protein phosphorylated in response to the mast cell "stabilizer" cromolyn.

Disodium cromoglycate (cromolyn) inhibits mast cell secretion, but its mechanism has not been elucidated. One possibility is the phosphorylation of a 78-kDa mast cell protein, two fragments of which are homologous to moesin, a member of the ezrin, radixin, moesin family. These proteins appear to be involved in signal transduction by regulating functional associations between the cell surface and the cytoskeleton. Moesin cDNA was cloned from rat basophil leukemia cells, which are similar to mucosal mast cells, and polyclonal antiserum was prepared against recombinant moesin expressed in Escherichia coli. Moesin phosphorylated in mast cells treated with cromolyn shifted from the soluble to the precipitable fraction and associated with Sepharose-linked beta-actin. Recombinant moesin also associated with Sepharose-linked beta-actin, and so did purified RBL moesin, but only if the latter was first denatured. Moesin thus appears to have actin binding sites that are not exposed under normal conditions but may become available by in vivo phosphorylation or by denaturation. Immunocytochemistry using confocal microscopy showed moesin to be primarily localized on the inner aspect of the plasma membrane and around secretory granules. Double immunocytochemistry for moesin and actin colocalized them in most areas. Ultracryoimmunoelectron microscopy to preserve the antigenicity of moesin identified the protein close to the plasma and secretory granule membranes. Cromolyn appeared to induce clustering of moesin around secretory granules. It is hypothesized that conformational changes of moesin, regulated by phosphorylation/dephosphorylation, may lead to positional rearrangements with respect to the membrane/cytoskeleton that could possibly regulate mast cell secretion.

Actins↗

An epidemiological survey of carcinoma cervix in north Bengal zone.

Correlation between various epidemiological factors and carcinoma cervix patients in North Bengal zone has been studied for the first time. Significant correlation between elderly women (41-50 years age group), low socio-economic status (SES), first coitus before 17 years of age, low literacy rate and this illness has been established. Suggestion has been made for improvement of the picture. Oncology and radiotherapy department of North Bengal Medical College and Hospital should be utilised as the centre for National Cancer Registration Project in North Bengal zone.

Adolescent↗

The impact of aspirin therapy and anticoagulation on the prevalence of spontaneous subdural haematoma.

A retrospective analysis was performed of all patients who received operative intervention for subdural haematoma at the Beaumont neurosurgical unit between 1994 and 1997 inclusive. There were 123 spontaneous (mean age 74 +/- 5 years) and 77 traumatic haematomas (mean age 43 +/- 23 years) in the series. Ninety three patients (76%) in the spontaneous group were on antiplatelet agents or anticoagulants (78 aspirin, 15 warfarin) and the indication for their use was unknown in twenty four patients (19%). The re-operation rate in the group on aspirin and anticoagulants was twice that in the non aspirin / non anticoagulant group. These results highlight a significant medical problem and emphasise the need for cautious use of antiplatelet and anticoagulant agents, particularly in the elderly.

Adult↗

Sporadic paroxysmal exercise induced dystonia: report of a case and review of the literature.

Sporadic paroxysmal exercise induced dystonia (PEID) is a rare condition. So far only fifteen cases have been reported in the world literature. It is characterised by dystonic posture on prolonged exercise, which gets relieved with rest. In general, these are refractory to medical treatment. We report one such case, along with review of the literature. The lower limbs were spared and only right shoulder was tucked up with the head turning to right side. The duration of exercise necessary to bring out the dystonic posture gradually diminished with time, a feature not reported previously.

Dystonic Disorders↗

Evaluation of vitamin A status during pregnancy.

Adequate maternal vitamin A nutrition is essential for successful pregnancy outcome and estimation of serum retinol among pregnant women enables a precise and objective assessment of vitamin A status, during pregnancy, even in subclinical state. In order to evaluate vitamin A status during pregnancy, and its relationship with personal and pregnancy related variables of the mother, 300 antenatal clinic attenders were interviewed at RG Kar Medical College and Hospital, Calcutta and tested for serum retinol, using Carr-Price test. Serum retinol values less than 30 microg/dl and 20 microg/dl, in this study, were considered as poor and severe vitamin A deficiency respectively. According to this 14.7% and 4% pregnant women were found to be suffering from poor and severe vitamin A deficiency respectively. Clinical signs of vitamin A deficiency (eg, nightblindness) were reported only among 60% cases of the deficient population. The problems of vitamin A deficiency were associated with low literacy and poor nutritional status of the mother, advanced gestational age of current pregnancy,increased number of pregnancies, shorter interval between births and poor dietary intake of vitamin A rich foods during pregnancy. The study thus raises the question of supplementation of vitamin A, during pregnancy, in Indian context where habitual diets are either inadequate or deficient in vitamin A.

Adolescent↗

Aluminium related changes in brain histology: protection by calcium and nifedipine.

Aluminium (Al; 50 mg AlCl3/kg body wt/day) treatment caused a marked change in histological picture of normal brain as indicated by an increased number of vacuolated spaces. These changes returned to normal partially by simultaneous treatment with nifedipine (0.7 mg/kg body wt/day) and completely by similar treatment with 50 ppm calcium (CaCl2; 12.5 mg/kg body wt./day). Neither nifedipine nor calcium treatment alone altered the normal histological condition. The histological changes could not be correlated with the decrease in calcineurin activities in brain as nifedipine decreases calcineurin activity without any histological changes. Hence the histological changes may be considered as specific for Al and not due to a general decrease in calcineurin activity.

Aluminum Chloride↗

Chemical and immunochemical studies of the O-antigen from enteropathogenic Escherichia coli O158 lipopolysaccharide.

The O-specific polysaccharide isolated from Escherichia coli O158 smooth lipopolysaccharide contains L-rhamnose, D-glucose and 2-acetamido-2-deoxy-D-galactose in the molar ratios 1:2:2. Studies on composition, methylation analysis and specific degradations together with a 1H and 13C NMR spectral study established that the O-antigen is built up from a pentasaccharide repeating unit having the following structure: [formula: see text] The most effective inhibitory part of the oligosaccharide from E. coli O158 lipopolysaccharide has been serologically characterized by an ELISA-inhibition study using different sugars. The results showed that methyl alpha- and beta-D-GalpNAc are the most effective inhibitors among the monosaccharides tested, while the main antibody specificity lies on the main-chain trisaccharide repeating unit.

Carbohydrate Sequence↗

Genetic studies of autistic disorder and chromosome 7.

Genome-wide scans have suggested that a locus on 7q is involved in the etiology of autistic disorder (AD). We have identified an AD family in which three sibs inherited from their mother a paracentric inversion in the chromosome 7 candidate region (inv(7)(q22-q31.2)). Clinically, the two male sibs have AD, while the female sib has expressive language disorder. The mother carries the inversion, but does not express AD. Haplotype data on the family suggest that the chromosomal origin of the inversion was from the children's maternal grandfather. Based on these data, we have genotyped 76 multiplex (>/=2 AD affecteds/family) families for markers in this region of 7q. Two-point linkage analysis yielded a maximum heterogeneity lod score of 1.47 and maximum lod score (MLS) of 1.03 at D7S495. Multipoint MLS and NPL analyses resulted in peak scores of 1.77 at D7S2527 and 2.01 at D7S640. Examination of affected sibpairs revealed significant paternal (P = 0.007), but not maternal (P = 0. 75), identity-by-descent sharing at D7S640. Significant linkage disequilibrium was detected with paternal (P = 0.02), but not maternal (P = 0.15), transmissions at D7S1824 in multiplex and singleton families. There was also evidence for an increase in recombination in the region (D7S1817 to D7S1824) in the AD families versus non-AD families (P = 0.03, sex-averaged; and P = 0.01, sex-specific). These results provide further evidence for the presence of an AD locus on chromosome 7q, as well as provide evidence suggesting that this locus may be paternally expressed.

Adult↗

Ca2+ and phorbol ester effect on the mast cell phosphoprotein induced by cromolyn.

Several phosphoproteins are involved in stimulus-secretion coupling. The beta and gamma subunits of immunoglobulin E binding protein (FC epsilonRI) and three other protein bands get phosphorylated during stimulation of mast cell secretion. These additional proteins of 42, 59 and 68 kDa are also phosphorylated when secretion is stimulated by compound 48/80 (C48/80). A 78 kDa band, however, is phosphorylated as secretion wanes after stimulation with C48/80 and by the anti-allergic drug disodium cromoglycate (cromolyn). Phosphorylation was blocked by protein kinase C inhibitors. We investigated the isozyme involved by first showing that a cation ionophore prevented the phosphorylation of the 78 kDa protein, while a Ca2+ chelator did not affect phosphorylation even though it enhanced the inhibitory effect of cromolyn. This protein was identified as moesin by immunoprecipitation. Protein kinase C activators had no effect on 78 kDa protein phosphorylation either in the presence or absence of Ca2+ ions, but prevented its phosphorylation by cromolyn. Protein phosphatase inhibitors prolonged the duration, but not the amount of phosphate incorporated in the 78 kDa protein band while cromolyn had no effect on protein phosphatase action in vitro. The insensitivity of the 78 kDa protein phosphorylation to calcium and protein kinase C activators suggests that an atypical protein kinase C isozyme may be involved. Western blot analysis identified the presence of isozymes alpha, beta, delta and zeta, of which only the latter fits the profile suggested by the present findings.

Animals↗

The Electrochemistry of Nonaqueous Copper Phthalocyanine Dispersions in the Presence of a Metal Soap Surfactant: A Simple Equilibrium Site Binding Model.

The electrophoretic mobilities of copper phthalocyanine particles, dispersed in isoparaffin solutions containing zirconium octanoate, have been determined using phase-analysis light scattering. All the samples studied contained trace concentrations of water. The mobility values were converted to zeta potentials using the Hückel equation. All the systems studied exhibited a pronounced maximum in zeta potential as the zirconium octanoate concentration increased. The maximum occurred at a bulk zirconium octanoate concentration equivalent to that required for complete coverage of the particles. The zeta potential data were converted to surface charge density values through the use of the Poisson-Boltzmann equation. The latter were in the range 0.4 to 2.5 µC m-2. A simple two equation site binding theory, which considered the dissociation of zirconium octanoate and the subsequent adsorption of ions at a generic surface site, was successfully applied to the surface charge data. It is proposed that the maximum in the zeta potential and surface charge as a function of zirconium octanoate concentration was observed due to the preferential location of ZrO2+ ions at the particle surface, followed by charge neutralization with octanoate anions. It is suggested that water facilitates the dissociation process of the zirconium octanoate, although it does not directly contribute to the surface charge itself. Two plausible qualitative mechanisms are described. The first involves the presence of water at the particle-solution interface, whilst the second considers the formation of micelles in the bulk isoparaffin phase. Copyright 1999 Academic Press.

Journal Article↗

Calreticulin, a peptide-binding chaperone of the endoplasmic reticulum, elicits tumor- and peptide-specific immunity.

Calreticulin (CRT), a peptide-binding heat shock protein (HSP) of the endoplasmic reticulum (ER), has been shown previously to associate with peptides transported into the ER by transporter associated with antigen processing (Spee, P., and J. Neefjes. 1997. Eur. J. Immunol. 27: 2441-2449). Our studies show that CRT preparations purified from tumors elicit specific immunity to the tumor used as the source of CRT but not to an antigenically distinct tumor. The immunogenicity is attributed to the peptides associated with the CRT molecule and not to the CRT molecule per se. It is further shown that CRT molecules can be complexed in vitro to unglycosylated peptides and used to elicit peptide-specific CD8(+) T cell response in spite of exogenous administration. These characteristics of CRT closely resemble those of HSPs gp96, hsp90, and hsp70, although CRT has no apparent structural homologies to them.

Animals↗

Oxidative injury induced cyclooxygenase activation in experimental hepatotoxicity.

This report investigates the plasma and/or urinary levels of 8-iso-PGF2alpha, a nonenzymatic, and 15-keto-dihydro-PGF2alpha, a cyclooxygenase catalyzed oxidation product of arachidonic acid in experimental hepatotoxicity in rats. The study was undertaken to evaluate oxidative injury-induced inflammation as a consequence of cyclooxygenase induction. A significant and immediate increase of 8-iso-PGF2alpha in both plasma and urine after CCl4 administration indicates an oxidative injury during acute hepatotoxicity in rats. The inflammatory response index was determined by measuring 15-keto-dihydro-PGF2alpha levels in plasma which increased significantly 9-fold at 4 h after the administration of CCl4. The oxidative injury index, 8-iso-PGF2alpha, in both plasma and urine increased 17- and 53-fold, respectively. Six hours later the levels of 15-keto-dihydro-PGF2alpha in plasma remained high (5-fold increase) when 8-iso-PGF2alpha levels in plasma and urine elevated to 7- and 87-fold, respectively. Thus, cyclooxygenase and free radical-catalyzed oxidation of arachidonic acid are well involved during CCl4-induced hepatotoxicity. Cyclooxygenase-dependent inflammatory response through PGF2alpha formation in CCl4-induced hepatotoxicity may possibly be a secondary effect to oxidative injury and a conceivable link between inflammatory response and oxidative injury.

Animals↗