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Biomedical subjects

S Khare

Publications and source records attributed to S Khare.

At least 73 records · Page 4Linked to original sources
PubMed1994

Guanylin activates rat colonic particulate guanylate cyclase.

The polypeptide guanylin is an endogenous activator of small intestinal guanylate cyclase. In rat, guanylin mRNA is found predominantly in intestinal tissues, with its highest abundance in the colon. To date, the effect of guanylin on rat colonic particulate guanylate cyclase, however, has not been examined. It was, therefore, of interest to determine whether the addition of guanylin to intact rat colonocytes, or directly to isolated crude colonic membranes, stimulated guanylate cyclase activity. These studies demonstrated that: 1) rat guanylin, in a concentration-dependent manner, rapidly (within min), but transiently, stimulated particulate guanylate cyclase activity when added to intact colonocytes; 2) guanylin also stimulated guanylate cyclase activity when added directly to isolated colonic membranes; and 3) this latter effect of guanylin on guanylate cyclase activity was increased by ATP or ADP and markedly accentuated by ATP gamma S. Taken together, these results demonstrate that guanylin rapidly stimulates rat colonic particulate guanylate cyclase activity and, moreover, that this effect can be modulated by adenine nucleotides.

Adenosine Triphosphate↗
PubMed1994

Vitamin D status modulates rat colonic M3 muscarinic receptor characteristics and coupling to guanylate cyclase.

The present studies were conducted to determine whether [3H]quinuclidinyl benzilate binding in rat colonic membranes and/or carbachol-mediated stimulation of particulate guanylate cyclase were altered by changes in vitamin D status. EC50 values for the stimulation of colonic guanylate cyclase by carbachol were found to be significantly greater in vitamin D-deficient rats compared to their D-sufficient counterparts. Concomitantly, the density of receptors (Bmax) were significantly lower, and dissociation constants (Kd) were significantly higher in D-deficient colonic membranes. In vitamin D-repleted animals, moreover, all of these aforementioned alterations were at least partially corrected.

Animals↗
PubMed1994

Protein kinase C mediates the calcium-induced activation of rat colonic particulate guanylate cyclase.

Calcium can influence the cGMP/guanylate cyclase system in many tissues, including rat colon. The mechanisms involved in this phenomenon, however, are unclear. To further elucidate the mechanisms involved in the Ca(2+)-induced activation of rat colonic particulate guanylate cyclase, isolated colonocytes were incubated with Ca2+ or other agents, and crude membrane prepared and analyzed for particulate guanylate cyclase activity. Alternatively, the test agents were directly added to the guanylate cyclase reaction mixture containing isolated membranes. The results of these studies demonstrated: (i) extracellular Ca2+ (1 and 2 mM) increased basal particulate guanylate cyclase activity; (ii) increases in intracellular Ca2+ induced by 10 microM thapsigargin activated this enzyme; (iii) preincubation of the cells with 50 nM staurosporine, a broad-spectrum inhibitor of protein kinases, including protein kinase C (PKC), or 5 microM U73122, a specific inhibitor of phosphoinositide-phospholipase C-dependent processes, blocked the Ca(2+)-induced increase in particulate guanylate cyclase activity; (iv) incubation of cells with 1 microM 12-O-tetradecanoyl phorbol 13-acetate (TPA), an activator of PKC, stimulated guanylate cyclase; (v) no additivity in stimulation of this enzyme was observed when cells were concomitantly incubated with 1 microM TPA and 2 mM extracellular Ca2+; (vi) incubation of membranes with 250 nM TPA, in the presence of 0.2 mM Ca2+, 6 mM Mg2+, and 1 mM ATP, activated guanylate cyclase; and (vii) incubation of membranes with purified rat brain PKC further augmented this stimulation. These results indicate that Ca2+ activates rat colonic particulate guanylate cyclase, at least in part, via a PKC-dependent mechanism.

Alkaloids↗
PubMed1994

Subacute sclerosing panencephalitis in Delhi.

Between 1989 and 1992 (to October), 65 patients of subacute sclerosing panencephalitis were referred to the Virology Laboratory of the National Institute of Communicable Diseases, Delhi, from the major hospitals of Delhi. The cases were mainly residents of Delhi, but a few were from states bordering Delhi. The age group of affected cases ranged from 2 to 24 years. The disease (SSPE) was six times more common in males than in females. All but four patients below 3 years of age gave a past history of measles. No patient had history of measles vaccination. The titres of haemagglutination inhibition antibodies (HAI) to measles virus in serum of SSPE patients ranged from 1:8 to 1:2048 and in CSF it ranged from 1:4 to 1:64, while in the control group it ranged from 1:2 to 1:256 in serum and nil in CSF. The geometric mean titres in serum was 10-fold higher in serum and four-fold higher in CSF from SSPE cases as compared to control.

Adolescent↗
PubMed1994

The role of protein kinase-C alpha in the activation of particulate guanylate cyclase by 1 alpha,25-dihydroxyvitamin D3 in CaCo-2 cells.

Recent studies have implicated protein kinase-C (PKC) in the regulation of guanylate cyclase in several cell types. In view of prior experiments by our laboratory which have demonstrated that 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3] can activate PKC in CaCo-2 cells, it was of interest to determine whether this secosteroid influenced particulate guanylate cyclase and, if so, to determine which isoforms of PKC were involved. To address these issues, CaCo-2 cells were treated with 1 alpha,25-(OH)2D3 or other agents (see below), and crude membranes prepared from these cells were assayed for guanylate cyclase activity. In several experiments, agents were added directly to isolated membranes, and guanylate cyclase activity was then assayed. These studies demonstrated that 1) the addition of 1 alpha,25-(OH)2D3 or 12-O-tetradecanoyl phorbol 13-acetate (TPA), a known activator of PKC, to intact CaCo-2 cells stimulated particulate guanylate cyclase activity in a time- and concentration-dependent manner; 2) these agents induced the translocation of PKC alpha, but not PKC zeta, from the cytosolic to the membrane fraction of these cells; 3) preincubation of cells with staurosporine (50 nM), a PKC inhibitor, or U73122 (10 microM), an inhibitor of phospholipase-C-dependent processes, significantly reduced (P < 0.05) the stimulatory effect of 1 alpha,25-(OH)2D3 (3 nM) on guanylate cyclase; 4) preincubation of isolated membranes with TPA, calcium, and Mg(2+)-ATP increased guanylate cyclase activity, an affect that was augmented by purified rat brain PKC and inhibited by the PKC inhibitor peptide, PKC-(19-36); and 5) selective down-regulation of PKC alpha by treatment of cells with TPA (200 nM) for 24 h concomitantly abolished the activation of guanylate cyclase by 1 alpha,25-(OH)2D3. Taken together, these studies demonstrate that 1 alpha,25-(OH)2D3 activates particulate guanylate cyclase at least in part via a PKC alpha-dependent mechanism.

Bacterial Toxins↗
PubMed1994

An outbreak of influenza A (H3N2) in Delhi, 1993.

An outbreak of Influenza A, subtype H3N2 occurred in Delhi during July-August, 1993. Both urban and rural areas were affected. Attack rates in children and adults were found to be similar; the mean age of patients from whom the virus was isolated was found to be 21 years. The disease was of acute onset, mild in nature and about one week in duration. Main symptoms included fever, chills, cough, sore throat, bodyaches, backache and headache. Complications were absent. About 82 per cent of the affected house-holds had only a single case. Influenza A subtype H3N2 virus was isolated from 12 of 15 throat swabs collected from PUO cases.

Adolescent↗
PubMed1993

M3 muscarinic receptors on rat colonocytes are coupled to particulate guanylate cyclase activation.

The ability of muscarinic receptor antagonists to compete with (-)-[3H]quinuclidinyl benzilate ([3H]QNB) binding was compared with their ability to block carbachol-mediated stimulation of particulate guanylate cyclase activity in rat colonocytes. The binding of [3H]QNB to membranes was inhibited by antagonists with the following rank order of potencies (inhibitory constants, nM): atropine (2.5) approximately 4-diphenylacetoxy-N-methylpiperidine iodide (4-DAMP) [4.6] >> pirenzepine (121) > methoctramine (385). 4-DAMP (IC50 = approximately 10 nM) was also more potent in blocking carbachol-induced stimulation of guanylate cyclase activity than either pirenzepine (IC50 = approximately 700 nM) or methoctramine (IC50 = approximately 1500 nM).

Animals↗
PubMed1993

1,25-Dihydroxycholecalciferol rapidly activates rat colonic particulate guanylate cyclase via a protein kinase C-dependent mechanism.

The present studies were performed to determine whether the major biologically active metabolite of vitamin D3, 1,25-dihydroxycholecalciferol [1,25(OH)2D3], could influence the activities of rat colonic particulate guanylate cyclase and adenylate cyclase. To address these issues, colonocytes were harvested from Sprague-Dawley rats and suspended in Krebs-Ringer bicarbonate buffer. The cells were then treated with 1,25(OH)2D3 or other agents (see below) and crude membranes were prepared and analyzed for particulate guanylate cyclase and adenylate cyclase activities. The results of these studies demonstrated that: 1) 1,25(OH)2D3, in a concentration-dependent manner, rapidly (within minutes) stimulated guanylate, but not adenylate cyclase activity; 2) preincubation of the cells with staurosporine, a protein kinase inhibitor, or U73122, an inhibitor of phosphoinositide-phospholipase C-dependent processes, blocked the increase in guanylate cyclase activity induced by 1,25(OH)2D3; and 3) 12-O-tetradecanoyl phorbol 13-acetate and 1,2-dioctanoyl-sn-glycerol, known activators of protein kinase C, also rapidly stimulated rat colonic particulate guanylate cyclase activity. Taken together, these results demonstrate that 1,25(OH)2D3 rapidly stimulates together, these results demonstrate that 1,25(OH)2D3 rapidly stimulates rat colonic particulate guanylate cyclase, at least in part, via a protein kinase C-dependent mechanism.

Adenylyl Cyclases↗
PubMed1993

Modulation of peripheral blood derived monocytes/macrophages from leprosy patients using 'tuftsin' for production of reactive oxygen intermediates.

Phagocytic cells respond to a variety of membrane stimulants by producing reactive oxygen intermediates (ROI), i.e. O2-, H2O2 and OH.metabolites. Plasma membrane activation is associated with superoxide generating NADPH oxidase, thereby causing the production of these toxic species. Stimulation of phagocytic cells also results in activation of purine catabolism, which directs the metabolic flux through xanthine oxidase to produce the superoxide anion. We previously observed that BL/LL macrophages (M phi) exhibited a premature inability to undergo tuftsin stimulated phagocytosis and microbicidal activity. The present study was undertaken to measure ROI levels in the absence and presence of 'tuftsin' pulsing as a function of in vitro culture age and also correlated these levels with adenosine deaminase (ADA) activity. The latter is known to be a contributor of O2- generation and is also involved in the maturation of the monocyte/macrophage system. The behaviour of normal and tuberculoid monocytes/macrophages were more or less the same, either in the presence or absence of tuftsin, i.e. they showed a progressive increase in ROI production until day 3, then tapered off in older cultures by day 7. In contrast, after day 1, the lepromatous macrophages were unable to undergo tuftsin mediated stimulation for the production of ROI and ADA activity. These findings indicate a defective M phi function in lepromatous patients towards tuftsin pulsing, thereby supporting our earlier observations. Thus BL/LL M phi behaved as if they were aged after 1 day of in vitro culture, which may account for an inability to handle Mycobacterium leprae for efficient killing.

Adenosine Deaminase↗
PubMed1992

Immunogenicity of enhanced potency inactivated polio vaccine.

Fifty two children were immunized with two doses of enhanced potency inactivated polio vaccine in order to determine its efficacy. The vaccine was very efficacious with 92.3, 92.3 and 88.3% of the children seroconverting to the three poliovirus types, respectively. The vaccine was equally efficacious whether the two doses were given at 4-week or 8-week intervals or when immunization was started at 6-7 weeks of age or later. The presence of maternal antibodies did not interfere significantly with the seroresponse to two doses of IPV-E. The study recommends that two doses of IPV-E give satisfactory seroconversion rates. Immunization can be started as early as 6 weeks age and the two doses can be given at 4 weeks interval to complete primary immunization against poliomyelitis.

Antibodies, Viral↗
PubMed1991

Cyclic AMP level in red blood cells of Plasmodium berghei-infected Mastomys natalensis.

The present report describes the changes in cyclic AMP level which occur upon parasitization of red cells by Plasmodium berghei. Parasitized erythrocytes were separated from the non-parasitized population by percoll density-gradient centrifugation. An increase in the cyclic AMP content of both non-parasitized and parasitized erythrocytes of infected animals compared with that of uninfected animals was observed. The patterns of physiological response to isoproterenol in normal, parasitized and non-parasitized erythrocytes were identical.

Animals↗
PubMed1991

Sero-epidemiological study of severe forms of paralytic poliomyelitis.

Poliomyelitis has assumed immense public health importance owing to the magnitude of problem. The present study describes clinical, epidemiological and virological profile of seventy four cases of severe forms of acute paralytic poliomyelitis admitted to Kalawati Saran Children Hospital, New Delhi, during the period from August, 1986 to May, 1987. Thirty two per cent of total paralytic poliomyelitis cases were diagnosed as severe cases. Highest incidence (45.95%) of the cases were in the age group of 6-12 months and male to female ratio was 2.08:1. There was preponderance of cases from urban area. Among all the cases, 12.2% had received three or more doses of oral poliovaccine. Fever and respiratory involvement were the commonest symptoms. Sixty seven patients (90.5%) were virologically or serologically confirmed as an acute poliomyelitis due to any of the three poliovirus type. On follow up of the cases, complete recovery could be seen only in 4.2% of cases with varying degree of residual paralysis in 95.8% cases.

Age Factors↗
PubMed1991

Antibody response to three doses of standard and double dose of trivalent oral polio vaccine.

The study was undertaken to compare the antibody response of 6-12 weeks old infants after three doses of standard trivalent oral polio vaccine (TOPV) (Groups A; (n = 42) with three doses of double the amount of TOPV (Group B; n = 35). Seroconversions in Group A were 64.2, 80.9% and 57.1% for Types I, II and III polioviruses, respectively. The corresponding figures for Group B were 77.7, 80.0 and 60.6%, respectively, the differences being insignificant. Differences in feeding practices and presence of maternal antibodies did not affect seroconversion. This suggests that increasing the amount of vaccine virus in each dose is not an alternative to present strategy. Breast feeding and presence of maternal antibodies are not responsible for poor seroconversion.

Antibodies, Viral↗
PubMed1991

Enzyme immunoassay of phagocytosis stimulating tetrapeptide "tuftsin" in normal and leprosy sera.

The serum concentrations of the phagocytosis stimulating the tetrapeptide, tuftsin, were determined by competitive enzyme immunoassay in borderline tuberculoid/tuberculoid (BT/TT, 16 cases), borderline lepromatous/lepromatous (BL/LL, 16 cases), and in healthy controls (20 cases). Using checkerboard titration, 10 ng/well of diphtheria toxoid-p-aminophenylacetyl tuftsin (DTPT) conjugate when incubated with tuftsin antisera at 1:15,000 dilution with a preincubation time of 60 min with the competitor (tuftsin) followed by a further 60-min incubation onto the DTPT-coated wells gave consistent results with a sensitivity of 5 ng/well tuftsin. The mean serum tuftsin concentration was significantly lower in BL/LL patients (134.42 +/- 48.7 ng/ml, p less than 0.01) than in healthy controls (262.86 +/- 59.8 ng/ml), while BT/TT sera (210.94 +/- 75.5 ng/ml) showed slightly decreased levels than did normals, which was not statistically significant. The mean serum IgG levels in BL/LL and BT/TT patients (37.26 +/- 10.99 mg/ml; 28.08 +/- 6.57 mg/ml, respectively) showed significantly (p less than 0.001) higher concentrations than did healthy controls (12.3 +/- 3.6 mg/ml). These observations on the serum concentrations of tuftsin and IgG in leprosy individuals suggest that there is splenic dysfunction in BL/LL patients in terms of the processing of leukokinin to release the free, active molecule tuftsin.

Binding, Competitive↗
PubMed1990

The effect of food on gastrointestinal (GI) transit of sustained-release ibuprofen tablets as evaluated by gamma scintigraphy.

The GI transit of radiolabeled sustained-release ibuprofen 800-mg tablets in eight healthy, fed volunteers was monitored using external gamma scintigraphy. Ibuprofen serum concentrations were determined from blood samples drawn over 36 hr following dosing. Sustained-release ibuprofen tablets containing 0.18% of 170Er2O3 (greater than 96% 170Er) in the bulk formulation were manufactured under pilot-scale conditions and were radiolabeled utilizing a neutron activation procedure which converted stable 170Er to radioactive 171Er (t1/2 = 7.5 hr). At the time of dosing, each tablet contained 50 mu Ci of 171Er. Dosage form position were reported at various time intervals. In five subjects the sustained-release tablet remained in the stomach and eroded slowly over 7-12 hr, resulting in gradual increases in small bowel radioactivity. In the remaining three subjects, the intact tablet was ejected from the stomach and a gastric residence time of approximately 4 hr was measured. This is in marked contrast to a previous study conducted in fasted volunteers in which gastric retention time ranged from 10 to 60 min. Differences in GI transit between fed and fasted volunteers had little effect on ibuprofen bioavailability. AUC and Tmax were unaltered and Cmax was increased by 24%, which is in agreement with results from a previous, crossover-design food effect study.

Adult↗
PubMed1990

Field evaluation of measles vaccine efficacy in New Seemapuri, Shahdara Zone-Delhi during 1990.

A field evaluation of measles vaccine efficacy was undertaken in resettlement colonies in New Seemapuri, Shahdara Zone, Delhi, having an estimated population of 20,500 by case-reference method. The standard 30 cluster sampling technique was adopted and 261 measles vaccinated children were matched with 545 measles non-vaccinated children. The attack rate of measles was found to be 4.2 and 30.3 per cent in measles vaccinated and non-vaccinated children respectively, which is statistically highly significant (P less than 0.001). The relative risk of developing measles in non-vaccinated child is seven times more as compared to a vaccinated child. Vaccine efficacy (V.E.) evaluated by different epidemiological and laboratory methods was found to be 86.1 per cent +/- 11 at P = 0.05. Further, a large scale study on measles V.E. is recommended in different parts of the country by case-reference method, as it is found to be simple, reproducible and easy to undertake in a field situation.

Antibodies, Viral↗
PubMed1990

Sero-epidemiology of measles--a three years prospective study in a rural population of Rajasthan.

A community based prospective study on measles was undertaken during 1986 to 1988 in Ramgarh village of Alwar district (Rajasthan) to elucidate epidemiological features of measles. The initial population of the village was 5258 with 2018 children (0-14 years) which rose to total population of 5923 with 2200 children in 1988. During the entire period of study, all the children (0-14 years) were covered regularly through monthly domicilliary visits by trained paramedical personnel under direct supervision of Medical Officers. A total of 208 measles cases were detected which gave an overall incidence rate of 31.5 per 1000 children (0-14 years) per year. Incidence rate was highest in children of 2-5 years of age group and lowest (4.6 per 1000) in 10-14 years of age group. The maximum number (86.5 per cent) of cases occurred during the first six months of year. The Kolmogrov-Smirnov statistical method validated the seasonal character of the disease (Vn = 5.36, p less than 0.01). A significant (P less than 0.005) rise in seropositivity with increase in age was observed in children (6-36 months) who had no previous history of measles and measles immunization during their life time. A higher rate of sero-conversion was observed in children vaccinated after 10-months of age than those before. No significant relationship of seroconversion following vaccination could be seen with age of vaccination (p greater than 0.50), sex and nutritional status (p greater than 0.10).

Child↗