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Biomedical subjects

R Bhatnagar

Publications and source records attributed to R Bhatnagar.

At least 55 records · Page 3Linked to original sources
PubMed1991

Growth suppression of human breast carcinoma cells in culture by N-(4-hydroxyphenyl)retinamide and its glucuronide and through synergism with glucarate.

The inhibitory effects of N-(4-hydroxyphenyl)retinamide (HPR) and its glucuronide derivative on the growth of MCF-7 human breast cancer cells in vitro were compared. The results indicate that the glucuronide had slightly greater potency and much less cytotoxicity than the free retinoid. At a concentration of 10(-6) M, HPR inhibited MCF-7 cell growth by approximately 25%, whereas an equimolar concentration of the glucuronide caused a 40% growth inhibition. Higher concentrations of HPR were highly cytotoxic. At a 10(-5) M concentration of the glucuronide, cell viability was 77%, and 65% of the cells were able to resume growth. On the other hand, at 10(-5) M HPR, cell viability dropped to 49%, and only 15% of the cells were capable of resuming growth. The lower cytotoxicity and higher potency of the retinoid glucuronide compared to the parent retinamide suggest that the conjugate may have a chemotherapeutic advantage over the parent compound. The apparent higher efficacy of HPR in combination with glucarate (GT) compared to the single agents could be due to increased net formation of HPR glucuronide conjugate following conversion of GT to the beta-glucuronidase inhibitor, D-glucaro-1,4-lactone. However, HPLC analysis of the cell metabolites did not show any detectable levels of the retinoid glucuronide upon treatment of MCF-7 cells with HPR and GT.

Breast Neoplasms↗
PubMed1991

Risk of cataract and history of severe diarrheal disease in southern India.

A case-control study was carried out in the state of Tamil Nadu, southern India, to examine the association between the risk of visually disabling cataract and a lifetime history of severe diarrhea (including cholera). A series of 421 subjects, aged 35 to 65 years, meeting case (n = 181) and control (n = 240) eligibility criteria were enrolled from 19 rural cataract-screening camps. Ninety case-control pairs were postmatched for (reported) age (+/- 2 years), sex, and area of residence. A history of diarrhea was obtained by using an algorithm developed by other investigators in India who have reported a strong association between cataract and diarrhea. An odds ratio of 0.8 (95% confidence limits: 0.0, 3.2) was obtained from matched pairs analysis, and an odds ratio of 1.3 (95% confidence limit: 0.6, 2.7) was obtained among all subjects (n = 392) from a logistic analysis that adjusted for age, sex, occupation, area of residence, and caste. Findings of this study do not support the hypothesis of an increased risk of visually disabling cataract in persons with a positive history of severe diarrhea.

Adult↗
PubMed1991

Diffuse infiltrating retinoblastoma.

The authors describe two children who presented with atypical posterior uveitis and who were subsequently diagnosed as having diffuse infiltrating retinoblastoma. A review of these two cases and 26 previously published cases was performed to assess the epidemiology, presenting signs, and usefulness of diagnostic tests. In contrast to typical retinoblastoma, results of histologic analysis showed that only 4 of the 28 cases with infiltrating lesions contained calcium. Computed tomography scans and ultrasonography were not particularly helpful and many eyes required an anterior chamber paracentesis to establish the correct diagnosis. A systematic approach to the diagnosis of diffuse infiltrating retinoblastoma is presented.

Child↗
PubMed1991

Protection of the reperfused heart by L-propionylcarnitine.

The effects of L-propionylcarnitine on mechanical function, creatine phosphate and ATP content, and lactate dehydrogenase leakage were studied in isolated perfused rat hearts exposed to global no-flow ischemia for 30 min followed by reperfusion for 20 min. Five and 10 mM L-propionylcarnitine resulted in a 100% recovery of left ventricular-developed pressure, whereas the recovery was only 40% in the hearts perfused without this agent. Ischemia-reperfusion caused a 85% loss of creatine phosphate and a 77% loss of ATP, which was prevented by 10 mM L-propionylcarnitine. Five millimolar L-propionylcarnitine protected the heart from the loss of creatine phosphate but not from the loss of ATP. Ten millimolar L-propionylcarnitine failed to improve the postischemic left ventricular-developed pressure, when it was added to the perfusate only after ischemia. L-propionylcarnitine alleviated the decrease of coronary flow in the reperfused hearts. Lactate dehydrogenase leakage was aggravated in the beginning of the reperfusion period by 10 mM L-propionylcarnitine. This adverse effect was, however, transient. L-Propionylcarnitine provides protection for the postischemic reperfused heart in a dose-dependent manner. The optimal time for administration is before the ischemic insult. High doses of this compound may perturb cell membrane integrity. Moreover, the present data point to an intracellular, metabolic, and perhaps anaplerotic mechanism of action of L-propionylcarnitine in cardiac ischemia-reperfusion injury.

Animals↗
PubMed1991

Propranolol ameliorates the development of portal-systemic shunting in a chronic murine schistosomiasis model of portal hypertension.

We investigated the role of early portal hypotensive pharmacotherapy in preventing the development of portal-systemic shunting in a portal hypertensive model of chronic murine schistosomiasis induced by infecting C3H mice with 60 cercariae of Schistosoma mansoni. Propranolol was administered in drinking water to 20 animals for a period of 6 wk at a dose of 10 mg.kg-1d-1, starting at 5 wk of schistosomal infection. 32 age-matched mice with chronic schistosomal infection served as controls. All animals were studied 11 wk after the infection. Compared with controls the portal pressure (10.8 +/- 0.40 mmHg) was significantly lower (P less than 0.001) in the propranolol-treated animals (7.9 +/- 0.80 mmHg). Portal-systemic shunting was decreased by 79%, from 12.2 +/- 3.34% in controls to 2.5 +/- 0.99% in the propranolol group (P less than 0.05). Portal venous inflow was reduced by 38% in the propranolol treated animals (2.50 +/- 0.73 ml/min; n = 6) compared with controls (4.00 +/- 0.34 ml/min; n = 8; P less than 0.05). The worm burden, the granulomatous reaction, the collagen content of the liver, and the serum bile acid levels were not significantly different between the two groups of animals. These results demonstrate that in chronic liver disease induced by schistosomiasis, the development of portal-systemic shunting can be decreased or prevented by the reduction of flow and pressure in the portal system.

Animals↗
PubMed1989

Internalization and processing of Bacillus anthracis lethal toxin by toxin-sensitive and -resistant cells.

Anthrax lethal toxin consists of two separate proteins, protective antigen and lethal factor (LF). Certain macrophages and a mouse macrophage-like cell line, J774A.1, are lysed by low concentrations of lethal toxin. In contrast, another macrophage cell line, IC-21, and all other cell types tested were resistant to this toxin. To discover the basis for this difference, each step in the intoxication process was examined. No differences between sensitive and resistant cells were found in receptor binding or proteolytic activation of protective antigen, steps that are required prior to LF binding. To determine whether resistance results from a defect in translocation to the cytosol, we introduced LF into J774A.1 and IC-21 cells and a nonmacrophage cell line (L6 myoblast) by osmotic lysis of pinocytic vesicles. Only J774A.1 cells were lysed; no effect was observed in IC-21 and L6 cells. These results suggest that resistant cells either lack the intracellular target of LF or fail to process LF to an active form. The relatively low potency of LF introduced into J774A.1 cells by osmotic lysis suggests that protective antigen may also be required at a stage subsequent to endocytosis.

Animals↗
PubMed1989

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine inhibits proton motive force in energized liver mitochondria.

It is known that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which induces Parkinson's-like disease in primates and humans, depletes hepatocytes of ATP and subsequently causes cell death. Incubation of rat liver mitochondria with MPTP and 1-methyl-4-phenyl pyridinium ion (MPP+) significantly inhibited incorporation of 32Pi into ATP.MPTP and MPP+ inhibited the development of membrane potential and pH gradient in energized rat liver mitochondria, suggesting that reduction of the proton motive force may have reduced ATP synthesis. Since deprenyl, an inhibitor of monoamine oxidase, prevented the formation of MPP+ and inhibited the decrease in membrane potential caused by MPTP, but not that caused by MPP+, these effects of MPTP, as well as cell death, probably were mediated by MPP+. This mechanism may play a role in the specific loss of dopaminergic neurons resulting in MPTP-induced Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1989

Transport of nutrients into the renal brush border membrane vesicles as marker in evaluating the role of antipili antibodies in modulation of ascending pyelonephritis in rats.

The uptake of D-glucose, L-aspartate, L-lysine and L-proline was investigated in renal brush border membrane (BBM) vesicles prepared from control, infected or passively-immunized-infected rats. Except L-aspartate, a progressive decrease in the uptake of these nutrients in both infected and immunized-infected groups during the course of infection was observed, but the changes were less apparent in immunized-infected rats than in non-immunized ones. The uptake of L-aspartate was increased in vesicles from early stages of infection but decreased in those from later stages. Also in L-aspartate uptake, the changes were smaller in immunized animals. The uptake of nutrients was detectable earlier than were histopathological alterations of both kidneys. The observations demonstrated that uptake of D-glucose and amino acids in the kidneys is disturbed prior to appearance of histopathological lesions and thus can be used for early detection of the disease. The data also demonstrate that antipili antibodies afford partial protection against ascending pyelonephritis.

Animals↗
PubMed1989

Does milk have a cataractogenic effect? Weighing of clinical evidence.

We undertook a prospective study to test Simoons' hypothesis that in certain susceptible races milk exerts a cataractogenic effect. Overall milk intake in low lactase deficiency areas did not correlate with cataract occurrence. Subgrouping of cataract patients revealed that greater milk intake did show positive correlation with cortical cataracts. Cortical cataracts were also markedly more common in females. Analysis of data from three different regions showed greater milk intake in cortical cataract patients only. Our data indicate the importance of specifying cataract type in cataract studies and highlight the problem this approach brings forth. We noted no different trends in subjects from northwest and southeast India, although the number of subjects from the southeast was considerably less. Patients with early cortical cataracts may be advised to restrict milk intake.

Adult↗
PubMed1989

Calcium is required for the expression of anthrax lethal toxin activity in the macrophagelike cell line J774A.1.

Anthrax lethal toxin, which consists of two separate proteins, protective antigen (Mr, 82,700) and lethal factor (Mr, approximately 83,000), is cytotoxic to the macrophagelike cell line J774A.1. Removal of calcium from the culture medium protected cells against the action of lethal toxin. Calcium depletion during the binding phase of intoxication afforded only partial protection. Further analysis showed that calcium removal caused some inhibition of protective antigen binding but that it had minimal effect on proteolytic conversion of protective antigen to the active 63-kilodalton fragment and that it had no effect on lethal factor binding. Cells to which lethal toxin had bound in the presence of calcium were protected when transferred to calcium-depleted culture medium, indicating a role for calcium at a postbinding stage. When ammonium chloride is present with lethal toxin, toxin accumulates in intracellular vesicles. Calcium-free medium protected these cells upon removal of the amine block, suggesting that calcium is also required at a step after internalization of lethal toxin. Calcium channel blockers inhibited 45Ca2+ uptake and protected cells against cytotoxicity. Calmodulin inhibitors also protected against the action of lethal toxin, suggesting involvement of calmodulin at a step during intoxication. We conclude that calcium is required at several steps in the intoxication of cells by anthrax lethal toxin.

Animals↗
PubMed1989

Effects on intestinal nutrient uptake and brush border membrane enzymes in response to atherogenic diet in rhesus monkeys.

Transport of nutrients and kinetic parameters (Vmax and Km) of brush border membrane (BBM) enzymes were studied in duodenum, jejunum, and ileum from atherogenic diet-fed monkeys. The Km remained unaltered while feeding of atherogenic diet resulted in higher Vmax of sucrase, maltase, and alkaline phosphatase and lower Vmax of gamma-glutamyltranspeptidase and leucine-aminopeptidase compared to controls. Na+-dependent D-glucose transport was higher in duodenum and jejunum and unaltered in ileum. In contrast to D-glucose transport, the transport of amino acids was decreased in all three intestinal segments from atherogenic diet-fed monkeys.

Alkaline Phosphatase↗
PubMed1988

Hepatic phosphatidylcholine synthesis in deficiency of lysine and threonine: effect of malathion.

Rats fed on a rice diet deficient in lysine and threonine showed increased activities of CDP-Choline pathway enzymes and incorporation of (methyl-3H)-choline into hepatic microsomal phosphatidylcholine, compared to rats fed on the same diet supplemented with lysine and threonine. However, the amount of microsomal phosphatidylcholine was significantly decreased in rats fed a deficient rice diet. These results suggest an enhanced phosphatidylcholine catabolism in rats fed on a rice diet deficient in lysine and threonine. Malathion administration reduced the amount of phosphatidylcholine in all the groups.

Animals↗
PubMed1988

Interleukin-1 alpha modulates collagen gene expression in cultured synovial cells.

The effects of porcine interleukin-1 (IL-1) alpha on collagen production were studied in cultured human rheumatoid synovial cells. Addition of 0.05-5 ng of IL-1/ml into the cultures resulted in a dose-dependent decreased rate of collagen released into the medium over 24 h. To determine whether this inhibition was due to secondary action of prostaglandin E2 (PGE2) secreted in response to IL-1, cultures were incubated in presence of various inhibitors of arachidonate metabolism. Depending on the cell strains, these inhibitors were able to suppress or diminish the effect of IL-1, suggesting that PGE2 is involved in the mechanism. Depression of collagen production caused by IL-1 mainly affected type I collagen and therefore led to a change in the type I/type III collagen ratio in the extracellular medium. Steady-state levels of mRNA for types I and III procollagens were estimated by dot-blot hybridization and compared with the amounts of respective collagens produced in the same cultures. IL-1 generally increased procollagen type I mRNA, but to a variable extent, as did indomethacin (Indo). Depending on the cell strain, the combination of indo and IL-1 could elevate the mRNA level of type I procollagen compared with Indo alone. These results did not correlate with the production rate of collagen in the medium, which was diminished by exposure to IL-1. The level of mRNA for collagen type III was not greatly changed by incubation with IL-1, and a better correlation was generally observed with the amount of type III collagen found in the medium. These data suggest that an additional control mechanism at translational or post-translational level must exist, counterbalancing the stimulatory effect of IL-1 on collagen mRNA transcription. It is likely that IL-1 could modulate the production of collagen in synovial cells by an interplay of different mechanisms, some of them limiting the effect of primary elevation of the steady-state mRNA level.

Bucladesine↗
PubMed1988

Fetal antigen retained by mature neurons and ependyma studied with a monoclonal antibody (6B9).

A mouse monoclonal antibody (MAb 6B9, isotype IgM) was raised against autopsy tissue samples from the central nervous system (CNS) of multiple sclerosis (MS) patients. By immunofluorescence microscopy, MAb 6B9 intensely stains most or all cells in fetal rats. However, MAb 6B9 differentially stains various cell types in adult rats. Neurons, ependymal cells, and adrenal chromaffin cells are stained intensely, whereas astrocytes and oligodendrocytes are not stained. The 6B9-reactive antigen (6B9 antigen) is sensitive to periodic acid, but insensitive to treatment with protease, RNase, or hyaluronidase. Results from immunofluorescence microscopy on semithin sections and cultured neuroblastoma cells indicate that 6B9 antigen is intracellular. This is supported by immunoelectron microscopy, where labeling for 6B9 antigen appears in the cytoplasm distinct from any identifiable organelle. Further studies on 6B9 antigen should reveal its chemical nature as well as the significance of developmental changes in its distribution.

Animals↗