Somatostatin analogs: angiogenesis inhibitors with novel mechanisms of action.
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Amino Acid Sequence↗
Biomedical subjects
C Sharma
Publications and source records attributed to C Sharma.
Molecular characterization of Vibrio cholerae O1 biotype El Tor strains isolated between 1992 and 1995 in Calcutta, India: evidence for the emergence of a new clone of the El Tor biotype.
Sixty-one clinical strains of Vibrio cholerae O1 El Tor isolated in Calcutta before, during, and after the V. cholerae O139 Bengal outbreak were examined to see if the O1 strains of the post-O139 period were different from those in existence before. Comparison of the restriction fragment length polymorphism of the rRNA genes (ribotyping) and the CTX genetic element revealed that all "before" strains except 1 belonged to a single known ribotype, whereas all "after" strains except 2 belonged to a hitherto undescribed ribotype. Also, 23 of 25 "before" strains harbored two or more copies of CTX in tandem and also a "free" RS1 element away from CTX, whereas 19 of 21 "after" strains had a single copy of CTX and no free RS1 element. CTX occupied different chromosomal locations in "before" and "after" strains. These studies clearly showed that El Tor O1 strains, which displaced V. cholerae O139 in Calcutta, belonged to a new clone and suggested that there is a continuous genetic reassortment among El Tor strains of V. cholerae O1.
Blotting, Southern↗
Unique organization of the CTX genetic element in Vibrio cholerae O139 strains which reemerged in Calcutta, India, in September 1996.
We studied the restriction fragment length polymorphism of the rRNA gene and CTX genetic element in Vibrio cholerae O139 Bengal, which resurged in Calcutta in September 1996 after a gap of 32 months. While the strains from this resurgence were indistinguishable from the earlier strains by ribotyping, the structure of the CTX genetic element present in the current O139 strains was found to be unconventional.
Cholera↗
Studies on the genesis of Vibrio cholerae O139: identification of probable progenitor strains.
Four lines of evidence suggest that the recent outbreak strains of Vibrio cholerae O139 could have emerged from serogroup O1 strains typified by isolates M01 and M0477 described in this paper, which are neither truly classical nor truly E1 Tor in their biotype attributes. Firstly, like all O139 isolates, these O1 strains, isolated in Madras during and before the O139 outbreak, were resistant not only to polymyxin B but also to all biotype-specific choleraphages, i.e. classical phage phi 149 and E1 Tor phages e4 and e5. Secondly, the restriction fragment pattern (RFP) polymorphism displayed by these strains for the cholera toxin (ctx) gene, were identical with those produced by O139 isolates but were different from those of O1 type strains, namely V. cholerae 569B (classical) and V. cholerae MAK757 (E1 Tor). Thirdly, all the O139 isolates and the two O1 isolates carried an identical large number of copies of cholera toxin gene in their chromosomes. Finally, the outer-membrane protein profiles of strains M01 and M0477 were identical to those of O139 isolates but were different from those displayed by strains 569B and MAK757.
Bacterial Outer Membrane Proteins↗
A computer-based instrumentation system for measurement of breath-by-breath oxygen consumption and carbon dioxide production.
Improvements are implemented (Version 4) in a Computer-Based Respiratory Measurement System (CBRMS) identified as Version 3. The programming language has been changed from Pascal to C. A Gateway 2000 desktop computer with 486 DX2/50MHz CPU and a plug-in data I/O board (KEITHLEY METRABYTE/ASYST/DAC's DAS-HRES 16-bit Analog and Digital I/O board) replaces an HP 9836 system used in Version 3. The breath-by-breath system consists of a mass spectrometer for measuring fractional concentrations of oxygen and carbon dioxide and the accommodation of a turbine or pneumotachometer for measuring inspiratory and expiratory flows. The temperature of the inspiratory and expiratory gases can be monitored if temperature corrections are necessary for the flow measurement device. These signals are presented to the PC via the data acquisition module. To compare the two Versions, ten significant respiratory parameters were investigated and compared for physiological resting states and steady states obtained during an exercise forcing. Both graphical and statistical (analysis of variance, regression, and correlation) tests were carried out on the data. The results from the two versions compared well for all ten parameters. Also, no evidence of a statistically significant difference was found between the resting and steady-state results of the present CBRMS (Version 4) and the previous CBRMS (Version 3). This evidence suggests that Version 3 (Pascal) has been successfully converted to Version 4 (C). Implementation of the CBRMS in C on a PC has several advantages.(ABSTRACT TRUNCATED AT 250 WORDS)
Carbon Dioxide↗
Tandem repeats of cholera toxin gene in Vibrio cholerae O139.
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Cholera Toxin↗
Fibronectin synthesis by aorta explants from rabbits fed high cholesterol diets.
Fibronectin synthesis was studied in aorta explants in culture from rabbits fed a high fat-high cholesterol diet. [3H]Mannose and [14C]leucine were used to label oligosaccharide side chains and the protein core, respectively. The synthesis was followed by monitoring immunoprecipitable fibronectin from the culture medium using polyclonal goat anti-rabbit fibronectin antibody. Synthesis of fibronectin increased by [14C]leucine (81%) and [3H]mannose (29%) incorporation over controls. On gel filtration, fibronectin synthesized by controls and cholesterol-fed rabbit resolved into four fractions. Pulse-chase experiment with [3H]glucosamine or [3H]leucine showed that fibronectin secreted by the aorta explants from rabbits fed high fat-high cholesterol diets incorporated an increased amount of radioactivity. Pulsing with [3H]mannose showed decreased incorporation of the label. During the chase period, the rate of secretion of fibronectin into the media by the hypercholesterolemic rabbit aorta explants was increased. The fibronectin that bound to the gelatin or heparin columns from cholesterol-fed rabbit aorta media had lower levels of [3H]mannose incorporated into the glycoprotein than the control. These results indicate that there is an alteration in carbohydrate composition of the fibronectin synthesized by the aorta explants from rabbits fed a high cholesterol diet. High fat-cholesterol intake could play a causative role in matrix dysfunction during atherogenesis by altering glycoprotein synthesis.
Animals↗
Therapeutic and diagnostic role of bronchoscopy in pediatric age group.
Two hundred and seventy five cases were evaluated bronchoscopically for various respiratory conditions. In 140 cases, a foreign body and in 30 cases mucus plug was removed. In 47 cases there was inflammation of the tracheobronchial tree. Forty patients with empyema thoracis were evaluated bronchoscopically because of persistence of bronchopleural fistula or continued pus discharge from intercostal tubes not responding to the routine treatment. The purpose of the article is to stress the therapeutic as well as diagnostic aspect of bronchoscopy for various respiratory conditions in pediatric age group.
Bronchoscopy↗
Temperature induced changes in microsomal (Na+,K+)-ATPase and lipid composition of Candida kefyr.
Growth temperature affected both the membrane lipid composition and microsoma (Na+, K+)-ATPase activity of Candida kefyr. Higher growth, temperature (37 degrees C) increased the amount of total lipids, phospholipids and free sterol. Ratios of phosphatidylcholine to phosphatidylethanolamine as well saturated to unsaturated fatty acids increased with a rise in growth temperature. Km of the ATPase isolated from the yeast grown at 27 degrees C was minimum, suggesting that the membranes of C. kefyr grown at optimal growth temperature provide the most suitable environment for the activity of ATPase.
Candida↗
Activation of dolichol-phosphate mannosyltransferase by dibutryl cyclic AMP in rat liver.
Radiolabeled mannose incorporation into secretory glycoproteins and immunoprecipitable fibronectin in the incubation media significantly increased (105 and 32 percent respectively) with a corresponding increase in the levels of dolichol-phosphate mannose, dolichol-diphosphate oligosaccharides and dolichol-phosphate mannosyltransferase activity in the rat liver slices when incubated with dibutryl cAMP and ATP. Dibutryl cAMP activated maximally this enzyme in the presence of ATP in the incubation medium. The activation of the enzyme resulted in a two fold increase in Vmax with no apparent change in the Km for GDP mannose. Phosphorylation the rat liver microsomes with catalytic subunit of cAMP dependent protein kinase, resulted in the activation of dolichol-phosphate mannosyltransferase. These results suggest that cAMP modulates protein glycosylation by activating dolicholphosphate mannosyltransferase activity. The activation of this enzyme could be through phosphorylation/dephosphorylation mechanism involving a cAMP dependent protein kinase.
Adenosine Triphosphate↗
Use of 86Rb and 22Na in assaying active and cotransport activities in human erythrocytes in a biracial population.
A defect in Na+-K+ transport across the red cell membrane has been shown to be associated with essential hypertension. A sensitive assay system to measure active, co- and countertransport systems in erythrocytes from normotensive adults was developed. Active, co- and countertransport systems in the erythrocytes were assayed by measuring the influx of radioactive 22Na+ and 86Rb+. In the biracial (black-white) population group studied, analysis of variance of the active transport showed a significant race effect (p = 0.003). Cotransport activity showed age by race interaction (p = 0.001) and age by sex (p = 0.02). Cotransport activity was significantly higher in whites than blacks (p = 0.0001). Countertransport activity did not vary either by sex or race. Of the Spearman correlation coefficients for transport activities and blood pressure, white males showed a strong positive correlation with countertransport, whereas in black males, blood pressures showed a strong interaction with active transport. Among the transport activities, active transport showed significant interaction with countertransport activity in black males, whereas cotransport activity in whites showed a strong interaction with countertransport. The results suggest a subtle difference in Na+-K+ transport systems between blacks and whites, and these variations may be related to differences for susceptibility to essential hypertension.
Adult↗
Composition of proteoglycans synthesized by rabbit aortic explants in culture and the effect of experimental atherosclerosis.
The synthesis of proteoglycans by aorta explants from rabbits with diet-induced atherosclerosis and controls was studied by 35S-incorporation. Proteoglycans were isolated under dissociative conditions from incubation medium and from arterial explants. Additionally, the tissue proteoglycans that were not extracted by 4 M guanidine-HCl were solubilized by digestion of the tissue by elastase in the presence of proteinase inhibitors. The residual tissue was hydrolyzed by papain and glycosaminoglycans were isolated. The atherosclerotic aorta tissue incorporated twice the amount of 35S into proteoglycans than observed for controls; in both groups about 70% of the label incorporated into the tissue was noted in the proteoglycans extracted by guanidine-HC;, while about 30% of the total 35S-labeled proteoglycans synthesized by the explants were found in the media. Atherosclerotic tissue incorporated 35S predominantly into chondroitin sulfate proteoglycans when compared to control tissue. The chondroitinase ABC-digestable proteoglycans that were extracted by guanidine-HCl from atherosclerotic tissues were of larger molecular size than those from control tissue, but the core proteins from these preparations were similar. The heparan sulfate proteoglycan that was obtained by dissociative extraction from atherosclerotic tissue had greater amounts of N-acetyl and lesser amounts of N-sulfate ester groups than the preparation from control tissue. Digestion of the tissue by elastase yielded heparan sulfate proteoglycan as the major constituent in both groups, although atherosclerotic tissue contained relatively small amounts of this proteoglycan. The residual tissue from both groups contained chondroitin sulfate and heparan sulfate as the major glycosaminoglycans with the latter showing a decrease with atherosclerosis. Atherosclerotic tissue secreted into the medium about two-fold more 35S-labeled proteoglycans with larger molecular size than control tissue; proteoglycans of the heparan sulfate and chondroitin sulfate types were the major constituents in the culture medium of both tissues. Thus, proteoglycans undergo both quantitative and qualitative changes in atherosclerosis, reflecting the enhanced smooth muscle cell activity. These changes are potentially important in modulating lipoprotein binding and hemostatic properties, as well as fibrillogenesis of the arterial wall.
Animals↗
Metabolic epidemiology of colon cancer: effect of dietary fiber on fecal mutagens and bile acids in healthy subjects.
Because of potential significance of fecal mutagens and secondary bile acids in the pathogenesis of colonic cancer and of inverse association between dietary fiber and colonic cancer risk, the effect of dietary wheat and rye fiber on fecal mutagenic activity and bile acid levels was studied in 15 healthy men and women who were consuming high fat/moderately low fiber diets and excreting high levels of fecal mutagens and bile acids. Each participant provided two 24-h stool specimens and a 3-day diet record while consuming their normal diet (control). All subjects were then asked to consume their normal diet plus 11 g of supplemental fiber per day in the form of whole grain bread for 4 weeks. During the last week of diet intervention, each subject provided two 24-h stool specimens and a 3-day dietary record. Fecal samples collected from both periods were analyzed for bile acids and for mutagens using Salmonella typhimurium strains TA98 and TA100 with and without microsomal activation. The concentration of fecal secondary bile acids was significantly lower during the fiber supplemental period in all subjects. Fiber supplementation also inhibited the fecal mutagenic activity in TA100 and TA98 with and without microsomal activation. Thus, the increased fiber intake in the form of whole wheat and rye bread may reduce the production and/or excretion of fecal mutagens and decrease the concentration of fecal secondary bile acids in humans.
Bile Acids and Salts↗
Dolichol synthesis in liver slices of streptozotocin diabetic rats.
The rate of dolichol synthesis in normal and diabetic liver slices in the presence or absence of insulin was investigated with radiolabeled acetate and mevalonate as substrates. Cholesterol and dolichol syntheses were found low in diabetic rat liver slices when incubated either with 1-14C-acetate or 2-3H-mevalonate. In the presence of insulin, cholesterol and dolichol synthesis in diabetic rat liver slices returned to normal in nine hours when incubated with 1-14C-acetate; however, with 2-3H-mevalonate, synthesis of cholesterol and dolichol normalized in about three hours. These studies show that dolichol synthesis in rat liver slices is dependent on insulin.
Acetates↗
Hepatic glycoprotein synthesis in streptozotocin diabetic rats.
In vitro incorporation of 3H-mannose into dolichol phosphate mannose, dolichol pyrophosphate oligosaccharides, and secretory and membrane glycoproteins was investigated in liver slices from streptozotocin diabetic rats. In addition, 14C-leucine incorporation into glycoproteins was studied. 3H-mannose incorporation was significantly less in secretory glycoproteins from diabetic rat liver slices than from control tissues, but 14C-leucine incorporation in these proteins was similar in both groups. Dolichol-phosphate mannose and dolichol-phosphate oligosaccharide synthesis were significantly down-regulated in diabetes. When incubated with insulin, mannosylation of secretory proteins, dolichol-phosphate mannose and dolichol-phosphate oligosaccharides reached control levels in three hours. Dolichol-phosphate mannosyltransferase activity was significantly less in diabetes, while in the presence of insulin, the enzyme activity reached control levels in three hours. These results indicate that key intermediates in glycoprotein biosynthesis are regulated by insulin.
Animals↗
Nonenzymatic glycosylation of proteins and protease activities in granulation tissues in experimental diabetes.
Serum proteins and hemoglobins show increased nonenzymatic glycosylation in diabetes mellitus. The measure of glycosylated proteins, particularly hemoglobin, is considered to be a preferred indicator in the control of diabetes. In a study of diabetes and inflammation, we assessed the extent of nonenzymatic glycosylation of proteins of granulation tissue from diabetic rats. Five, seven, and ten days after carrageenan injection, the granuloma proteins were extracted. Nonenzymatic glycosylation was measured in soluble and insoluble granuloma proteins by thiobarbituric acid assay. Protease activities and free amino groups were assayed in soluble extracts. Nonenzymatic glycosylation in soluble proteins of both groups reached a maximum on the seventh day. However, nonenzymatic glycosylation in soluble proteins of the diabetic granulomas was significantly greater than the controls on days five and seven. During the days after granuloma induction, nonenzymatic glycosylation in the insoluble granuloma tissue proteins gradually decreased without any significant differences between controls and diabetics. Significant decreases in the free amino groups in soluble proteins of the diabetic tissues were noted. Greater activities of cathepsins B and D were noted in diabetic tissues over controls. These observations suggest that, in addition to increased proteolysis, increased nonenzymatic glycosylation of tissue proteins could be associated with the impaired process of wound healing in diabetics.
Animals↗
Studies of chemical and biologic properties of a fraction of sulodexide, a heparin-like glycosaminoglycan.
The chemical composition and biologic properties of a fraction (f) of Sulodexide, a heparin-like GAG, were studied and compared with those of two sulfated GAG preparations and heparin from intestinal mucosa. f-Sulodexide and the sulfated GAG preparations were fractionated on a Dowex-1Cl- column and subsequently on an antithrombin III affinity column. Low affinity and high affinity fractions had similar chemical composition and lipoprotein lipase releasing ability, but they varied in anticoagulant activity. Low affinity fractions from f-Sulodexide had negligible anticoagulant activity while high affinity fractions had one-half the activity of mucosal heparin. When compared to heparin, both fractions had one third amount of lipoprotein lipase releasing activity. The low anticoagulant activity of f-Sulodexide suggests a suitability for long-term use as an antiatherogenic agent.
Animals↗