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Biomedical subjects

R Gupta

Publications and source records attributed to R Gupta.

At least 505 records · Page 28Linked to original sources
PubMed1995

Prevalence and determinants of hypertension in the urban population of Jaipur in western India.

OBJECTIVES: To determine age-specific blood pressure levels and prevalence of hypertension in an urban Indian population. DESIGN AND SETTING: A cross-sectional survey in six randomly selected municipal blocks in Jaipur city, India. SUBJECTS AND METHODS: There were 2122 subjects (1415 male, 797 female) aged 20 years or more. Evaluation was by physician-administered questionnaire, physical examination and electrocardiography. Diagnosis of hypertension used World Health Organization (WHO) and USA Fifth Joint National Committee (JNC-V) guidelines. Hypertension was subclassified according to the Framingham Study criteria. RESULTS: The mean +/- SD blood pressures (mmHg) were 125 +/- 19 systolic and 81 +/- 24 diastolic in men and 126 +/- 20 systolic and 81 +/- 12 diastolic in women. A significant correlation of blood pressure with increasing age groups was seen. The prevalence of hypertension according to the JNC-V criteria was 30% in men and 33% in women; by WHO criteria it was 11% in men and 12% in women and increased with age in all subjects. In the JNC-V hypertensive group borderline isolated systolic hypertension was present in 13% of men and 17% of women, definite isolated systolic hypertension was present in 7% of men and 2% of women, isolated diastolic hypertension was present in 65% of men and 57% of women and definite hypertension was present in 16% of men and 24% of women. Multivariate analysis revealed that age, smoking and higher body mass index were independently associated with higher prevalence of hypertension both in men and in women. CONCLUSIONS: A high prevalence of JNC-V-defined hypertension was found in an Indian urban population. Isolated diastolic hypertension was the commonest subtype. Significant determinants of hypertension were age, smoking and body mass index.

Adult↗
PubMed1995

An ascending non-obstructive model for chronic pyelonephritis in BALB/c mice.

Chronic pyelonephritis was successfully produced in female BALB/c mice with Escherichia coli after introduction of the bacterial inoculum by the ascending route. E. coli strain 31-B, a nalidixic acid-resistant derivative of strain TN675 expressing type-1 pili, and E. coli strain BH-5, a mutant of 31-B, not expressing type-1 pili, were used in the model. Both the strains were able to induce chronic renal inflammation in the experimental animals. Whereas the initial colonisation was greater with strain 31-B, its non-pilate mutant BH-5 caused a significantly greater inflammatory response and also caused renal scarring observable 5 months after the infection.

Animals↗
PubMed1995

Chitinase production by Streptomyces viridificans: its potential in fungal cell wall lysis.

Streptomyces viridificans was found to be a good chitinase producer among nine species of Streptomyces screened. Minimum levels of constitutive enzyme were observed with both simple and complex carbon substrate. Arabinose doubled the enzyme production amongst the various pentoses and hexoses used with chitin. However, with glucose end-product inhibition and catabolite repression were observed. The enzyme tolerated a wide range of temperature (30-55 degrees C) and pH (3-7.5). Among various divalent cations Mn2+ and Hg2+ completely inhibited the purified enzyme while beta-mercaptoethanol stimulated its activity. Crude and purified enzyme had potential for cell wall lysis of many fungal pathogens tested.

Antifungal Agents↗
PubMed1995

Differential inhibition of signaling pathways by dominant-negative SH2/SH3 adapter proteins.

SH2/SH3 adapters are thought to function in signal transduction pathways by coupling inputs from tyrosine kinases to downstream effectors such as Ras. Members of the mitogen-activated protein kinase family are known to be activated by a variety of mitogenic stimuli, including tyrosine kinases such as Abl and the epidermal growth factor (EGF) receptor. We have used activation of the mitogen-activated protein kinase Erk-1 as a model system with which to examine whether various dominant-negative SH2/SH3 adapters (Grb2, Crk, and Nck) could block signaling pathways leading to Erk activation. Activation of Erk-1 by oncogenic Abl was effectively inhibited by Grb2 with mutations in either its SH2 or SH3 domain or by Crk-1 with an SH3 domain mutation. The Crk-1 SH2 mutant was less effective, while Nck SH2 and SH3 mutants had little or no effect on Erk activation. These results suggest that both Crk and Grb2 may contribute to the activation of Erk by oncogenic Abl, whereas Nck is unlikely to participate in this pathway. Next we examined whether combinations of these dominant-negative adapters could inhibit Erk activation more effectively than each mutant alone. When combinations of Crk-1 and Grb2 mutants were analyzed, the combination of the Crk-1 SH3 mutant plus the Grb2 SH3 mutant gave a striking synergistic effect. This finding suggests that in Abl-transformed cells, more than one class of tyrosine-phosphorylated sites (those that bind the Grb2 SH2 domain and those that bind the Crk SH2 domain) can lead to Ras activation. In contrast to results with Abl, Erk activation by EGF was strongly inhibited only by Grb2 mutants; Crk and Nck mutants had little or no effect. This finding suggests that Grb2 is the only adapter involved in the activation of Erk by EGF. Dominant-negative adaptors provide a novel means to identify binding interactions important in vivo for signaling in response to a variety of stimuli.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Design, synthesis, DNA sequence preferential alkylation and biological evaluation of N-mustard derivatives of Hoechst 33258 analogues.

The design, synthesis and biological evaluation of a series of bis-benzimidazole analogues of Hoechst 33258 bearing nitrogen mustard moieties is described. The novel compounds show clear evidence of interstrand cross-linking of linear lambda DNA, in contrast to their distamycin nitrogen mustard counterparts. Interference of the cross-linking reaction by the minor groove-selective distamycin suggests that this process takes place in the minor groove of DNA. Sequence preferential alkylation is revealed by high-resolution polyacrylamide gel electrophoresis and autoradiography. Alkylation occurs predominantly at the 5'-A or 5'-G termini of mixed sequences, determined largely by the sequence-recognizing properties of the bis-benzimidazole carrier moiety. An analysis of the frequency of bases around the alkylation sites reveals marked individual base preferences, especially for A at -3 and +3 positions. All of the compounds tested showed cytotoxic properties against the human tumor cell line KB in culture.

Alkylation↗
PubMed1995

DNA alkylation by minor groove-binding N1-alkoxyalkyl-bis-benzimidazoles.

Two groups of isomeric N1-alkoxyalkyl-bis-benzimidazoles differing in the orientation of the N-alkoxyalkyl group (R) with respect to the DNA minor groove have been examined as to their reaction with DNA. Agarose gel mobility shift assay demonstrates that the 'R-inward' isomers alkylate and cause thermally induced strand breakage, in contrast to a much weaker reaction of the 'R-outward' isomers. Complementary studies using high-resolution polyacrylamide gel electrophoresis confirmed relatively weak but definite alkylation-induced thermal cleavage at all available G base sites, but at selected A sites. The alkylation reaction is interpreted in terms of an SN2 displacement of the alkoxy group by nucleophiles within the groove, in contrast to the complete lack of such nucleophilic displacement of these drugs in bulk solution. Reaction with all available Gs is interpreted in terms of nucleophilic strength within the DNA minor groove whereas, in contrast, reaction at the A residues appears to be determined primarily by initial molecular recognition of a DNA site by the drug, followed by an SN2 displacement. The relative cytotoxic potencies of these drugs against KB human tumor cells may be explained on the basis of this mechanism.

Alkylation↗
PubMed1995

MR imaging of central nervous system tuberculosis.

TB involving the CNS and its coverings is a complex and potentially devastating disease. The increasing incidence of this disease in both immunologically normal as well as immunologically incompetent populations makes the subject of TB one of universal concern. Although its appearance on MR is not specific, it is important in the proper clinical setting to recognize the range of possible patterns that can be observed on images. The inclusion of TB in the differential diagnosis on the basis of the patient's region of origin, the socioeconomic background of the patient, and the presence of underlying predisposing disease may potentially promote timely initiation of appropriate therapy.

Brain↗
PubMed1995

Design, synthesis, DNA sequence preferential alkylation and biological evaluation of N-mustard derivatives of distamycin and netropsin analogues.

The design and synthesis of certain oligopeptides structurally related to distamycin and netropsin, but bearing mixed heterocyclic moieties capable of recognizing alternative base sites and nitrogen mustard moieties capable of covalent binding to DNA, are described. The binding and thermally induced DNA cleavage, covalent interstrand cross-linking, DNA preferential alkylation and anticancer cytotoxicities of the new agents are described. In contrast to the mustard derivative derived directly from distamycin, the new agents give evidence of extensive DNA alkylation and interstrand cross-linking. In general, strong alkylation is observed at A residues for this class of agents, while the G residues that are alkylated appear to be more characteristic of individual compounds. Densitometric analysis of the frequency of bases adjacent to the alkylation sites (-3 to +3) revealed that the preferred bases are exclusively A/T with little preference shown for G bases and none for C sites. Further insight into the DNA alkylation processes afforded by the drugs was provided by an independent assay whereby heating the drug-DNA adduct with 10% aqueous piperidine only yielded strand breaks specifically at G-N7 sites in the major groove.

Alkylation↗
PubMed1995

Biliary ascariasis associated with periampullary carcinoma.

A 65 year old man presented with obstructive jaundice, biliary colics and recurrent cholangitis. Sonography revealed dilated intrahepatic biliary radicles and common bile duct. Bile duct also showed linear parallel intraluminal structures suggesting biliary ascariasis. The lower end of common bile duct and pancreatic region showed a mass which proved to be a coexistent periampullary carcinoma.

Adenocarcinoma↗
PubMed1995

Smoking and alcohol intake in a rural Indian population and correlation with hypertension and coronary heart disease prevalence.

3148 persons (1982 males and 1166 females) aged more than 20 years in a cluster of three villages were examined. The overall prevalence of smoking was 51% in males (n = 1006) and 5% in females (n = 54). Among male smokers there were 26% light smokers (< or = 5 bidis/day), 51% moderate smokers (6-20/day) and 17% heavy smokers (> 20 day) and in females there were 54% light smokers, 41% moderate smokers and 5% heavy smokers. Smokers were less educated and had higher prevalence of work-related physical activity and alcohol intake. There was a higher prevalence of hypertension and of ECG Q-waves in male smokers. Regular alcohol intake was seen in 19% males (n = 377) and in 2% females (n = 26). Among males there were 43% light drinkers (< or = 28 gm ethanol/day), 32% moderate drinkers (28-56 gm ethanol/day) and 5% heavy drinkers (> 56 gm ethanol/day). Although this group had a higher prevalence of hypertension there was an insignificant difference in CHD prevalence and a significantly lower prevalence of ECG Q-waves. Subgroup analysis has also been performed taking non-smoker-non-alcohol consuming group as controls. It was found that group which comprised of smokers-non-alcohol consumers had a significantly higher prevalence of hypertension and of ECG Q-waves. Alcohol intake-smoker group had a significantly higher prevalence of hypertension. The habits of smoking and alcohol consumption are widely prevalent among males in this rural community. Smoking and alcohol-intake, both individually and collectively, are related to higher prevalence of hypertension as well as CHD. While the prevalence of hypertension is more among the alcohol consumers, smokers have a higher prevalence of CHD.

Adult↗
PubMed1995

Ascitic fluid cholesterol in malignant and tubercular ascites.

Cholesterol was estimated in ascitic fluid of 44 patients (29 malignant and 15 tubercular). Mean ascitic cholesterol level was significantly higher in malignant ascites (89.52 mg/dl) as compared to tubercular ascites (35.07 mg/dl). At a cut off value of 54.5 mg/dl (mean in tubercular ascites + 2SD), the sensitivity, specificity, positive and negative predictive value and overall diagnostic accuracy for differentiating malignant from tubercular ascites was found to be 89.65%, 100%, 100%, 83.33% and 93.18% respectively. Ascitic fluid cholesterol estimation is a reliable and simple test for differentiating malignant ascites from tubercular ascites.

Adult↗
PubMed1994

Differential effects of protein phosphatase 2A on distinguishable intracellular signals initiated by v-Src and mediated by HaRas.

v-Src activates gene expression mediated by serum response elements (SREs) and TPA response elements (TREs). v-Src-induced SRE- and TRE-mediated gene expressions are both dependent upon HaRas. Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase that has been implicated in v-Src-initiated signals. We report here that expression of the catalytic subunit of PP2A upregulates v-Src- and v-HaRas-induced TRE-mediated gene expression, whereas PP2A downregulates v-Src- and v-HaRas-induced SRE-mediated gene expression. These data suggest that intracellular signals activated by v-Src and mediated by HaRas are differentially regulated by PP2A.

3T3 Cells↗