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Biomedical subjects

B Das

Publications and source records attributed to B Das.

At least 127 records · Page 7Linked to original sources

Synthesis and biological activities of novel 5-(2-acylethynyl)uracils.

5-(2-Acylethynyl)-2,4-dimethoxypyrimidines (3-6) were synthesized in excellent yields from 2,4-dimethoxy-5-[2-(trimethylsilyl)ethynyl]pyrimidine (2) by treatment with acid chlorides in the presence of anhydrous aluminum chloride. Compounds 3-6 were deblocked with chlorotrimethylsilane and sodium iodide in acetonitrile to the corresponding 5-[(2-acyl-1-iodo)vinyl]uracils (7-10), which on treatment with potassium hydroxide in dioxane yielded the corresponding 5-(2-acylethynyl)uracils (11-14). The 5-(2-acylethynyl)uracils were found to be active against Ehrlich ascites carcinoma (EAC) cells in vivo, the most active compounds being 5-(2-benzoylethynyl)uracil (11) and 5-(2-p-toluoylethynyl)uracil (12). The T/C values of 281 and 300 were obtained for compounds 11 and 12, respectively, in the case of mice bearing EAC cells. The 5-(2-acylethynyl)uracils have also shown in vitro activity against CCRF-CEM and L1210/0 tumor cell lines. The lead compound 5-(2-p-toluoylethynyl)uracil effectively inhibited thymidylate synthetase.

Animals↗

Cardiac injuries--a clinical and autopsy profile.

One hundred two patients sustaining cardiac injuries over a 4-year period were analysed to highlight the natural history of the cardiac injuries. There were 45 blunt, 36 stab, and 21 gunshot injuries. The injury involved the ventricle in 85, atrium in seven, pulmonary artery in five cases, and resulted in crush injury to the heart in the remaining five cases. Thirty-three patients (32.3%) died on the scene and 58 (56.9%) died during the transportation. Only 11 patients (10.8%) reached the hospital alive, and ten of these patients survived following thoracotomy and repair of the cardiac injury. The factors influencing the natural course of cardiac injury were analysed: 2.2% of patients with blunt cardiac trauma reached the hospital alive compared to 19.4% with stab and 14.3% with gunshot injuries; ventricular injuries had a greater prehospital mortality compared to atrial or pulmonary artery injuries; 11.3% of patients sustaining injury to right ventricle reached the hospital alive compared to 3% of those with left ventricular injuries. These data emphasize the need for rapid transport, immediate recognition, and aggressive surgical management, to make a favourable impact on the natural history of cardiac injuries.

Adolescent↗

Comparison of the regulation of carboxypeptidase E and prolactin in GH4C1 cells, a rat pituitary cell line.

The treatment of GH4C1 cells, a prolactin-producing rat anterior pituitary cell line, with estradiol (1 nM), insulin (300 nM) and epidermal growth factor (10 nM) has been previously shown to substantially increase both the intracellular level of prolactin, as well as the number of secretory granules. In this study, we examined the effect of this treatment on levels of carboxypeptidase E (CPE), a prohormone-processing enzyme. GH4C1 cells contain CPE mRNA and enzymatic activity. The secretion of both prolactin and CPE activity from GH4C1 cells is stimulated 10-fold by 50 mM KCl and 2- to 3-fold by 100 nM thyrotropin-releasing hormone, suggesting that these two proteins are contained in secretory granules. Treatment of GH4C1 cells with estradiol, insulin, and epidermal growth factor causes an increase in the intracellular level of CPE to approximately 2-fold of control values. This change is much smaller than the change in the level of prolactin: intracellular prolactin is increased 140-fold by the treatment. Kinetic analysis of the CPE activity indicates that the treatment does not alter the Km of substrate hydrolysis, with the change in activity the result of an increase in apparent Vmax. Northern blot analysis indicates that the level of CPE mRNA is not influenced (less than 10%) by the treatment, whereas the level of prolactin mRNA is increased 9-fold. These results indicate that CPE is not coordinately regulated with prolactin in the GH4C1 cell line, although some regulation of CPE activity does occur.

Animals↗

Maternal mortality.

Maternal mortality in Chittaranjan Seva Sadan, Calcutta, in 1983, 1985 and 1986 was 2.45, 3.01 and 2.8 per thousand respectively. Abortion contributed a little in 1983 and 1985, whereas it was 15.7% in 1986. Haemorrhage was the commonest single cause of death in 1983 (28%) and 1985 (21.4%) as opposed to eclampsia in 1986 (28.9%). Infective hepatitis during pregnancy and labour was the commonest indirect cause of maternal mortality followed by anaemia. Usual difficulties like lack of antenatal care, multiparity, low socio-economical status, illiteracy, etc, in populated developing countries are responsible for this sad state of affairs in this country as well.

Female↗

Functional cysteinyl residues in human placental aldose reductase.

Incubation of human placental aldose reductase (EC 1.1.1.21) with the sulfhydryl oxidizing reagents 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) and N-ethylmaleimide (NEM) results in a biexponential loss of catalytic activity. Inactivation by DTNB or NEM is prevented by saturating concentrations of NADPH. ATP-ribose offers partial protection against inactivation by DTNB, whereas NADP, nicotinamide mononucleotide (NMN), and the substrates glyceraldehyde and glucose offer little or no protection. The inactivation by DTNB was reversed by dithiothreitol and partially by 2-mercaptoethanol but not by KCN. When the release of 2-nitro-5-mercaptobenzoic acid was measured, 3 mol of sulfhydryl residues was found to be modified per mole of the enzyme by DTNB. Correlation of the fractional activity remaining with the extent of modification by the statistical method of C.-L. Tsou (1962, Sci. Sin. 11, 1535-1558) indicates that of the three reactive residues, one reacts at a faster rate than the other two, and that two residues are essential for the catalytic activity of the enzyme. Labeling of the total sulfhydryl by [14C]NEM and quantification of DTNB-reactive residues in the enzyme denatured by 6 M urea indicates that a total of seven sulfhydryl residues are present in the protein. The modification of the enzyme did not affect Km glyceraldehyde, but the modified enzyme had a lower Km NADPH. Kinetic analysis of the data suggests that a biexponential nature of inactivation could be due to the formation of a dissociable E:DTNB complex and the presence of a partially active enzyme species.

Aldehyde Reductase↗

Surgical experience with diseases of the tricuspid valve. Cross-sectional and Doppler echocardiographic evaluation following DeVega's repair.

Seventy-eight patients undergoing mitral valve surgery with or without replacement of the aortic valve also underwent procedures on the tricuspid valve over a period of 10 years. All patients were in functional class III or IV preoperatively. The procedures were performed in all patients with organic disease of the tricuspid valve (N = 44) and in those with moderate or severe functional tricuspid valvar regurgitation (N = 34). Seventy-one patients underwent DeVega's annuloplasty with or without commissurotomy. The overall mortality was 11.5%. 65 long-term survivors were followed up for a period of 6 months to 10 years (mean 5.3 years). Sixty-three patients were in functional class I or II at the last follow-up. Six patients had clinical evidence of mild to moderate tricuspid regurgitation. Regression of cardiomegaly (as judged by the chest radiograph and right ventricular hypertrophy seen in the electrocardiogram) was evident in most cases. Fifty-one of 54 patients evaluated by cross-sectional echocardiography were reported to have a functionally normal tricuspid valve. Doppler echocardiography in 28 patients showed no significant tricuspid regurgitation or stenosis in 26 patients. Eleven consecutive patients undergoing DeVega's annuloplasty were studied prospectively with pre- and postoperative Doppler echocardiography. Good correlation existed between right ventricular systolic pressures predicted by Doppler with those obtained preoperatively at cardiac catheterization. Postoperative Doppler echocardiography in these 11 patients showed complete restoration of competence of the tricuspid valve as well as normalisation of the right ventricular systolic pressure in 10 patients.

Adult↗

Cultured astrocytes and neurons synthesize and secrete carboxypeptidase E, a neuropeptide-processing enzyme.

Carboxypeptidase E (EC 3.4.17.10) is a carboxypeptidase B-like enzyme associated with the biosynthesis of many peptide hormones and neurotransmitters. Media collected from cultured astrocytes contain a carboxypeptidase E-like activity. Cultured astrocytes secrete approximately 73% of their cellular level of carboxypeptidase E per hour, and secretion is not substantially influenced by 35 mM KCl. In contrast, neurons secrete only 29% of their cellular carboxypeptidase E per hour, but secretion increases to 86% on stimulation with 35 mM KCl. Secretion of carboxypeptidase E activity from both neuronal and astrocyte cultures is relatively selective; neither acid phosphatase or acetylglucosaminidase is secreted in appreciable amounts. Cultured neurons and astrocytes express a carboxypeptidase E mRNA of a similar size. The levels of this mRNA differ in astrocytes cultured from different brain regions, with high levels in striatal, cortical, hippocampal, and hypothalamic astrocytes and low levels in cerebellar astrocytes. The level of carboxypeptidase E mRNA in hypothalamic astrocyte cultures is four- to fivefold higher than the level in hypothalamic neuronal cultures. These results indicate that cultured astrocytes express carboxypeptidase E mRNA and enzymatic activity and thus contain one of the enzymes required in the biosynthesis of many peptide hormones and neurotransmitters.

Animals↗

Activation of aldose reductase by nonenzymatic glycosylation.

Incubation of human erythrocyte with 50 mM glucose results in glycosylation of aldose reductase besides hemoglobin A and other proteins. The glycosylation of aldose reductase is established by adsorption of the enzyme on phenyl boronate (PBA-60) column. Furthermore, the enzyme was purified to an apparent homogeneity from the erythrocytes incubated with 50 mM glucose and the glycosylation was quantitated by reduction with tritiated sodium borohydride. The glycosylated aldose reductase exhibits lower Km for glucose and NADPH as compared to unglycosylated enzyme and is not inhibited by phosphorylated intermediates such as ADP, 1,3-DPG, 2,3-DPG and 3-PGA, whereas physiological concentrations of these intermediates almost completely inhibit the unglycosylated enzyme. In addition, the glycosylated enzyme is less susceptible to aldose reductase inhibitors such as sorbinil and alrestatin. In hyperglycemia, blood glucose higher than 11 mM, almost all the aldose reductase is glycosylated.

Aldehyde Reductase↗

Spectral properties of human placental aldose reductase and aldehyde reductase II.

Circular dichroism and fluorescence spectra of aldose reductase (E.C.1.1.1.21) and aldehyde reductase II (E.C.1.1.1.19) purified to homogeneity from human placenta have been studied. The alpha helical content of aldose reductase and aldehyde reductase II was 51% and 56%, respectively, whereas no beta helical structure was found in either case. In the case of aldose reductase, the secondary structure was unaffected at alkaline pH (9.5), whereas a drastic alteration in the structure was observed at 58 degrees C. The secondary structure of aldehyde reductase II, on the other hand, remained unaffected at higher pH and temperature.

Aldehyde Reductase↗

Involvement of sulfhydryl residues in aldose reductase-inhibitor interaction.

Purification and storage of aldose reductase isolated from human placenta or kidney in beta-mercaptoethanol-containing buffers causes a time-dependent decrease in its catalytic activity, as well as in its sensitivity to inhibition by aldose reductase inhibitors such as sorbinil. Dithiothreitol (DTT) slowly regenerated the enzyme activity, as well as reversed the alterations in the sensitivity of the enzyme to sorbinil. In contrast to sorbinil, the inhibition of aldose reductase by tolrestat was less affected by purification and/or storage in beta-mercaptoethanol-containing buffers. Kinetic analysis of the rate of increase in sensitivity of the enzyme to sorbinil on incubation with DTT reveals that the reaction follows two kinetically distinct rate constants. Also, sorbinil protected the enzyme from inactivation with sulfhydryl-modifying reagents 5,5'-dithiobis(2-nitrobenzoic acid) and glutathione disulfide. The enzyme stored in beta-mercaptoethanol migrates as two distinct bands, one corresponding to molecular weight 36,000 and the other to molecular weight 33,000, on nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis, whereas under reducing conditions the protein migrates as a single discrete band corresponding to molecular weight 36,000. Moreover, the molecular weight 33,000 form of the enzyme could be converted to the molecular weight 36,000 form on reduction with DTT, indicating that the molecular weight 33,000 form of the enzyme is due to intramolecular disulfide bond(s) formed, which presumably cause the protein to assume a more folded conformation and migrate faster through the gel, and not due to proteolysis. These studies indicate that oxidation of sulfhydryl residues, including disulfide bond formation, during purification and storage in beta-mercaptoethanol-containing buffers alters the sensitivity of the enzyme to some inhibitors.

Aldehyde Reductase↗

The distribution of aldose reductase and aldehyde reductase II in different regions of bovine lens.

The distribution of aldose reductase and aldehyde reductase II in the epithelium, cortex and nuclear regions of the bovine lens has been studied. The levels of the two enzymes in different regions of the bovine lens were determined after partial purification by DEAE-cellulose (DE-52) column chromatography. Aldose reductase was present in all the three regions of the lens, whereas aldehyde reductase II was present mainly in the epithelium and cortex. The activity of the enzymes, expressed per mg protein, was 10-15 fold higher in lens epithelium as compared to cortex and when expressed per g tissue wet weight, was approximately 2 fold higher. Substrate specificity of aldose reductase purified from all three regions of the lens was comparable, but the susceptibility to inhibition by various aldose reductase inhibitors was significantly different. As compared to the enzyme of cortex and nucleus, the epithelial aldose reductase was less (30-40%) susceptible to inhibition by aldose reductase inhibitors such as sorbinil, tolrestat, statil and tetramethylene glutaric acid. The substrate specificity and characteristics of inhibition of aldehyde reductase II purified from epithelium and cortex were similar.

Alcohol Dehydrogenase↗

Assigned and participative production standards and feedback affecting worker productivity in a repetitive production task.

The main objective of this research was to determine the effects of assigned and participative standards in conjunction with feedback on worker productivity in a repetitive production task. An assigned hard standard and feedback was significantly better than a participative standard and feedback in terms of quality output but no significant difference in quantity output was found between them. Thus from the overall worker productivity viewpoint, the former condition was superior to the latter condition. Both conditions provided a significant improvement in worker productivity. The percentage increases in quantity and quality output for the assigned hard standard and feedback condition were 12% and 7%, respectively, compared to the control group. The assigned normal standard and feedback had a significant positive impact on quantity output but no significant effect was found in terms of quality output.

Efficiency↗

The moderating effects of production feedback and standards on the relationship between worker job attitudes and productivity.

An experimental study was performed to investigate the impact of production feedback and standards, singly as well as jointly, as moderators of the worker job attitudes-productivity relationship in a repetitive production task. There was no substantial or consistent correlation between worker job attitudes and productivity and the correlation coefficient values in general were not statistically significant. The provision of production feedback and standards affected worker job attitudes and productivity differently and this in turn had an effect on the job attitudes-productivity relationship.

Adolescent↗

Detection of a new focus of Brugia malayi infection in Orissa.

526 people were surveyed in a village called Chudamani, in Balasore district of Orissa, for detection of asymptomatic microfilaria (mf) carriers. Of these 36 (6.8 per cent) were cases found to harbour mf; 19 cases had Brugia malayi, 4 Wuchereria bancrofti and 5 cases had mixed infection. In 8 cases, species could not be ascertained. For the first time after 1955, a focus of B. malayi has been detected in Orissa.

Animals↗