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Biomedical subjects

S Chatterjee

Publications and source records attributed to S Chatterjee.

At least 91 records · Page 5Linked to original sources

Chronic effect of smoking on the electrocardiogram.

The electrocardiograms (ECG) of 232 male non-smokers and 224 male smokers, aged 20-60 years, devoid of cardiovascular diseases, were studied. Among these subjects 5.2% of non-smokers and 6.7% of smokers had pathological ECGs. Non-pathological ECGs of 220 non-smokers and 209 smokers were analyzed for R, S and T-wave amplitudes, P and QRS axes and P-R, QRS and Q-Tc intervals. The 2 groups did not differ significantly from each other for R and T-wave amplitudes in any of the age groups except for 40-60 years, in which R-amplitude obtained from standard limb leads was significantly lower in smokers. S-amplitude recorded from standard limb leads was significantly lower in smokers of all ages combined. The reverse phenomenon was noted for S-amplitude obtained from precordial leads. R, S and T-amplitudes decreased with the advancement of age at a relatively higher rate in smokers. These waves had significant negative correlation with pack years of smoking habit. QRS and P axes differed significantly between smokers and non-smokers. The rate of shifting of these axes to the left with increasing age was relatively higher in non-smokers. Lung function did not show any relation to electrocardiogram in normal healthy subjects. These results indicate that aging affects electrocardiographic wave patterns and that this aging effect is modified by long term smoking.

Adult

Camptothecin hypersensitivity in poly(adenosine diphosphate-ribose) polymerase-deficient cell lines.

Mutant cell lines, derived from the Chinese hamster V79 cell line, deficient in poly(adenosine diphosphate-ribose) polymerase activity, and previously shown to be resistant to topoisomerase II inhibitors, were found to be hypersensitive to camptothecin, a topoisomerase I inhibitor. In all the cell lines, camptothecin induced dose-dependent protein-associated DNA single-strand breaks and sister chromatid exchanges. The increased sensitivity to camptothecin-induced cytotoxicity was not associated with an increase in DNA single strand breaks or sister chromatid exchanges. These results suggest the absence of any direct causal relation between (1) camptothecin induced sister chromatid exchanges and cytotoxicity or (2) camptothecin induced DNA strand breaks and cytotoxicity. The hypersensitivity of these mutant cell lines to camptothecin suggests that poly(adenosine diphosphate-ribose) polymerase is involved with topoisomerase I in modulating camptothecin induced cytotoxicity.

Animals

Immunomodulatory role of thyroid hormones: effect on humoral immune response to Salmonella typhi O antigen.

Effect of long term administration of thyroid hormones and the removal of thyroid on humoral antibody response to S. typhi O antigen was studied in male albino rats of HM strain. Humoral antibody response to S. typhi O antigen was enhanced in animals pretreated with T3 or T4 at a dose of 10 micrograms daily for 15 days. Administration of thyroid hormones simultaneously along with antigen, resulted in suppression of antibody response. In thyroidectomized animals, the antibody titer to S. typhi O antigen was decreased; this decrease in antibody titer was restored to normal level following hormone supplementation. Thyroidectomy significantly depressed TLC as well. Total leucocyte count and absolute lymphocyte count were increased following hormone treatment. Present findings, thus show the lymphoproliferative response of thyroid hormones and their effect on antibody response suggesting the immunomodulatory role of thyroid hormones.

Animals

Effect of thyroid hormones on delayed type hypersensitivity reaction.

The effect of long term administration of thyroid hormones and its deprivation on delayed type hypersensitivity (DTH) reaction to 2-4 dinitrochlorobenzene (DNCB) was studied. Animals were either pre-treated with thyroid hormones (T3 or T4) for 15 days and then subjected to DNCB skin test or the animals received thyroid hormones and simultaneously subjected to DNCB skin test. In both the cases DTH reaction was found to be increased significantly. When DNCB skin test was performed in the thyroidectomized animals, DNCB skin reaction was significantly decreased and the reaction was restored to normal following supplementation of thyroid hormones to the thyroidectomized animals. TLC and ALC were increased significantly following hormone treatment and thyroidectomized animals. TLC hand, induced significant depression in the count which was restored by hormone administration to the thyroidectomized animals.

Animals

Regulation of glycosphingolipid glycosyltransferase by low density lipoprotein receptors in cultured human proximal tubular cells.

We have shown previously that low density lipoproteins (LDL) suppressed the synthesis of lactosylceramide in normal human proximal tubular cells, but stimulated such synthesis in proximal tubular cells from LDL receptor negative subjects (Chatterjee, S., Clarke, K., and Kwiterovich, P.O., Jr. (1986) J. Biol. Chem. 261, 13474-13479). To understand the mechanism(s) of this effect of LDL, we have studied here the effects of LDL on the activity of UDP-GalCer:beta-galactosyltransferase (GalT-2). Maximum suppression (70-80%) of the activity of GalT-2 in normal proximal tubular cells at 37 degrees C occurred at a LDL concentration of 25 micrograms/ml medium. Such suppression was not observed either when the cells were incubated with LDL at 4 degrees C, or when the cells were preincubated with leupeptin, followed by incubation with LDL at 37 degrees C. High density lipoproteins and fetuin did not suppress the activity of GalT-2 in normal proximal tubular cells. In contrast LDL modified by reductive methylation (M-LDL, 100 micrograms/ml) stimulated the activity of GalT-2, approximately 3-fold. The effects of LDL and M-LDL were not related to their glycosphingolipid content. Much less suppression and stimulation of the activity of GalT-2 in proximal tubular cells by LDL and M-LDL, respectively, was found in normal human skin fibroblasts, Chinese hamster ovary cells, and bovine smooth muscle cells, suggesting that the LDL-mediated effect may be tissue-specific. In cells grown to very high density, the activity of the LDL receptor is decreased, and there was less suppression of GalT-2 activity by LDL. In normal proximal tubular cells, LDL stimulated the activity of UDP-Gal:LacCer, alpha-galactosyltransferase activity, UDP-Gal:LcOse3Cer, beta-galactosyltransferase, and CMP-NeuAc:LacCer,alpha-sialyltransferase activity but did not alter the activity of sulfotransferase. In conclusion, LDL that entered the normal proximal tubular cells via the LDL receptor-mediated pathway decreased GalT-2 activity, an effect that was dependent upon the binding, internalization, and degradation of receptor-bound LDL. In contrast LDL that entered normal or LDL receptor-negative proximal tubular cells via an LDL receptor-independent pathway failed to suppress GalT-2 activity, and led to a stimulation of LacCer synthesis.

Cell Count

Morphological and biochemical effects of gentamicin and cyclosporin-A on urinary cell phospholipids and phospholipases in man.

The morphology, lipid composition, and activity of sphingomyelinase (E.C. 3.1.4.12) and phospholipases A (E.C. 3.1.1.32) and C (E.C. 3.1.4.3) were studied in the urinary cells from four normal subjects, four patients receiving gentamicin (G), and four patients receiving cyclosporin-A (CsA). We report that abnormal urinary excretion of proximal tubular cells occurred in patients receiving G and CsA. Membrane-enclosed sudanophilic material and numerous vacuoles were found in the cytoplasm of the proximal tubular cells from both patients receiving G and those receiving CsA. Patients receiving G shed higher levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and sphingomyelin (SM) in the order of 78%, 38%, and 30% relative to normal. In contrast, the excretions of phosphatidylinositol (PI) and PC were 50% and 30% lower, respectively, in patients receiving CsA as compared to control. Sphingomyelin levels, however, were moderately elevated in these patients' urinary renal tubular cells. The activity of acid sphingomyelinase was one half the normal level in the cells of patients receiving G and CsA. The most striking result was a tenfold decrease in the activity of neutral sphingomyelinase in patients receiving G. In contrast, the activity of neutral sphingomyelinase in patients receiving CsA was similar to control. Phospholipase A activity was decreased and increased 35% and 15%, respectively, in urinary proximal tubular cells from patients receiving G and CsA. We conclude that deficient neutral sphingomyelinase activity precedes phospholipid (PL) overloading and gross pathological changes in patients receiving gentamicin but not in patients receiving cyclosporin-A.

Adult

Lithium: evidence for reduction in circulating testosterone levels in mice following chronic administration.

Lithium, the widely-used antipsychotic drug, is known to exert adverse effects on a number of endocrine organs. In the present investigations, the effects of chronic lithium administration on circulating levels of testosterone and plasma and pituitary levels of luteinizing hormone (LH) were evaluated in order to examine whether or not the pituitary-gonadal axis is a probable target of lithium action. Adult male C57BL/6 mice, maintained on a fixed photoperiodism (LD 14:10), were administered lithium orally, by being fed on a specially prepared chow containing 0.4% lithium chloride for 15 or 30 days, while their matched controls were maintained on standard laboratory chow. At the termination of the respective experimental schedules, the animals were decapitated, their blood collected, and plasma was separated and stored frozen. Pituitaries were quickly removed, weighed, homogenized, centrifuged and their supernatants were stored frozen. Testosterone in plasma and LH in pituitary and plasma were quantitated by standard RIA methods. Plasma Li concentration was determined by using flame photometric methods. A significant suppression in testosterone levels was noted after both 15 (p less than .01) and 30 (p less than .05) days of lithium treatment, but both pituitary and plasma LH levels remained unchanged at both the periods. It is, therefore, suggested that lithium exerts its effect directly at the level of the Leydig cells rather than through the pituitary-gonadal axis. Since the noted lithium-induced reduction of testosterone was manifested when the plasma lithium levels were within (or around) the therapeutic range, these results may have important clinical implications.

Animals

Parallelism between male mating propensity and chromosome arrangement frequency in natural populations of Drosophila ananassae.

Mating ability of different karyotypes due to sub-terminal (alpha or In(2L)A) inversion in 2L from two natural populations of Drosophila ananassae was investigated. The results show that the average number of females inseminated by a single male in 12-hour period varies for different karyotypes in males. The analysis of variance indicates that the differences are highly significant for males in both the populations studied. However, the averages for different karyotypes in females show no variation and thus homo- and heterokaryotypic females are equally receptive. The males heterozygous for inversion show greater mating propensity as compared with homokaryotypic males which provides evidence for heterosis associated with AL inversion in D. ananassae with respect to male mating activity. Furthermore, the comparison of male mating propensity with chromosome arrangement frequency in both the natural populations suggests that there is a correlation between mating propensity and chromosome arrangement frequency in natural populations of D. ananassae.

Animals

Protection against herpetic ocular disease by immunotherapy with monoclonal antibodies to herpes simplex virus glycoproteins.

In this paper we describe the ability of monoclonal antibodies to prevent herpetic stromal or interstitial keratitis following corneal infection in an outbred mouse model. Monoclonal antibodies recognizing antigenic determinants on glycoproteins B, C, D, and E of herpes simplex virus type 1 were injected intraperitoneally into CF-1 outbred mice 24 or 48 h following inoculation of the cornea with the RE strain of herpes simplex virus type 1. Passive, postexposure immunization with monoclonal antibodies had little effect on the severity of the initial corneal infection or the frequency of latent viral infections in the trigeminal ganglia, except for virus-neutralizing antibodies specific for glycoproteins B and D. A significant correlation was found between the severity of epithelial keratitis and the frequency of latent ganglionic infections. However, immunization with monoclonal antibodies protected the mice against encephalitis and prevented the development of necrotizing stromal keratitis that leads to permanent corneal scarring and blindness. This form of herpetic ocular disease does not respond to antiviral chemotherapy. Since nonneutralizing monoclonal antibodies were just as effective in prevention of encephalitis and stromal keratitis as ones that neutralized the virus in vitro, and antibodies were not administered until 24 or 48 h after corneal inoculation, we suggest that inactivation of infectious virus is not the only protective mechanism in this model.

Animals

Effect of aldrin on spermatogenesis, plasma gonadotrophins and testosterone, and testicular testosterone in the rat.

Quantitative evaluation of the different varieties of germ cells at stage VII of the seminiferous epithelium cycle, namely type-A spermatogonia (ASg), preleptotene spermatocytes (pLSc), mid-pachytene spermatocytes (mPSc) and step 7 spermatids (7Sd), along with radioimmunoassay of plasma gonadotrophins (FSH and LH), testosterone and testicular testosterone were performed in Wistar rats following treatment with aldrin (polycyclic chlorinated hydrocarbon insecticide) for approximately one (13 days) or two cycles (26 days) of the seminiferous epithelium. Extensive degeneration of all varieties of germ cells at stage VII, reduction in the sperm count and significant reductions in plasma concentrations of LH and testosterone were observed following aldrin treatment. The reduction in plasma concentrations of FSH was statistically significant only after treatment for two cycles. The inhibitory effect of aldrin on plasma gonadotrophins, testosterone levels, testicular testosterone content and numbers of 7Sd and ASg was maximum after treatment for two cycles. Administration of human chorionic gonadotrophin along with aldrin treatment for two cycles partially prevented the degeneration of germ cells and enhanced testosterone production. The results indicate that aldrin may have a direct inhibitory influence on gonadotrophin release, but the possibility of a direct action of the insecticide at the level of the testes is also discussed.

Aldrin

Spirometric standards for non-smokers and smokers of India (eastern region).

Three hundred thirty-four healthy male non-smokers and 300 healthy male smokers of the age range 20-60 years were investigated for their spirometric lung functions by the method and technique recommended by American Thoracic Society. It was found that FVC, FEV1, FEV1%, FEF 200-1,200, FEF 25-75%, FEF 75-85%, MVV, and PEFR were significantly lower in smokers. When the subjects were blocked into several half decades these differences persisted. These functions deteriorated with age both in smokers and non-smokers, but in the former group the functions were reduced to a greater extent. Significant negative correlation was obtained between lung functions and smoking histories. Separate multiple regression equations were developed separately for non-smokers and smokers. The sensitivity of the tests was determined. The FEF 25-75% and FEV1 were found to be most sensitive in detecting early airway obstruction. When comparison of lung function was made among American, European, Jordanian, Negro, and Pakistani subjects, it was found that the former three groups are superior to the remaining. Negroes and Pakistanis are comparable to Indians in respect to their lung function. These differences in these functions between the nations of developed countries and the underdeveloped or developing countries might be attributable to the differences in their life-style, physical activity status, nutritional status, environmental condition, and race and ethnicity. The spirometric functions of Indians in the Eastern region of India are comparable to North-West Indians and superior to Southern Indians.

Adult

Effects of thiazide on erythrocyte sodium and potassium concentrations and Na+K+ATPase in hypertensive patients.

The mechanism of thiazide induced sodium and potassium transport across the cell membranes of humans has not been extensively studied. To assess the effects of thiazide diuretics on erythrocyte sodium transport and potassium distribution we measured intracellular sodium and potassium, sodium-potassium ATPase activity (with and without ouabain) and total body potassium in normokalemic and mildly hypokalemic hypertensive patients. We also measured serum and urine sodium, potassium, calcium and magnesium, plasma renin activity and serum aldosterone levels. The study patients, on long-term thiazide, had measurements obtained during, one month after cessation and one month after resumption of thiazide. In this study of normokalemic and mildly hypokalemic hypertensives there were no significant measurement changes, in contrast to previous studies of severely hypokalemic hypertensives. These results suggested that thiazide did not routinely affect erythrocyte active membrane transport and potassium distribution in the absence of severe hypokalemia.

Aldosterone

Cell cycle dependent variation of calmodulin in Tetrahymena.

The level of calmodulin (CaM), a ubiquitous calcium-binding protein of eukaryotic cells was determined at different phases of the cell cycle in a synchronized Tetrahymena population. It was found that the concentration of CaM at G1 was approximately half of the concentration of S and this 2 x G1 level of CaM was maintained through the G2 and M stages of the cell cycle. To ascertain the role of CaM in the initiation of DNA synthesis, the cells were treated with trifluoperazine (TFP), a CaM antagonist, and EGTA (Ca2+-chelator) at the G1/S boundary. It was found that DNA synthesis was inhibited in these drug-treated cells. The uptake of the nucleotide precursor was not affected in TFP and EGTA treated cells, thus excluding the possibility of alteration in the membrane transport properties. Treatment with TFP failed to inhibit the synchronous mitotic division in Tetrahymena. The existence of a variable content of CaM through the cell cycle of Tetrahymena was demonstrated, suggesting the possible involvement of this Ca2+-binding protein in the nuclear DNA replication process.

Animals

Effects of gentamicin on sphingomyelinase activity in cultured human renal proximal tubular cells.

We have previously shown that cultured human proximal tubular cells (PT) incubated with gentamicin contain numerous "myeloid bodies." This morphological change was accompanied by the storage of phosphatidylcholine and sphingomyelin. In order to delineate the biochemical mechanisms responsible for the accumulation of sphingomyelin in cells incubated with gentamicin, we pursued detailed studies on the activity of sphingomyelinase. Characterization studies on sphingomyelinase revealed that this enzyme has a bimodal pH optima in PT cells. Optimum activity was observed at pH 5.6 (designated as acid sphingomyelinase, A-SMase) and at pH 7.4 (designated as neutral sphingomyelinase, N-SMase). The activity of both the enzymes increased proportionately in control cells as a function of days of incubation. The activity of A-SMase was 16% lower in cells incubated with gentamicin as compared to control. The most striking observation was a gradual decline in the activity of N-SMase in cells incubated with gentamicin. Thus, following 21 days of incubation of cells with 0.3 mM gentamicin, the N-SMase was 2.7-fold lower than control cells. Mg2+ stimulated and Triton X-100 inhibited the activity of N-SMase. Whereas Mg2+ had no effects, Triton X-100 stimulated the activity of the A-SMase in PT cells. Moreover, A-SMase was relatively more heat-resistant than the N-SMase. The Km values for sphingomyelin using A-SMase in control cells and cells incubated with gentamicin were 0.07 X and 0.016 X 10(-7) M, respectively, whereas the Km values for sphingomyelin using N-SMase in control cells and cells incubated with gentamicin were 1.8 X and 1.5 X 10(-7) M, respectively. These findings suggest that gentamicin exerts a competitive inhibition of the A-SMase in PT cells. In contrast, gentamicin exerts a noncompetitive inhibition of the N-SMase in PT cells. Subcellular fractionation studies revealed that A-SMase was exclusively localized in the "lysosome-rich" fraction, whereas most, if not all, the N-SMase was localized in the microsomal fraction and "plasma-membrane"-rich fraction in cultured PT cells. Cells incubated with gentamicin for 21 days contained 25% lower activity of A-SMase associated with the lysosomal fraction as compared to control. In contrast, N-SMase activity in the microsomal and plasma membrane fraction was one-half as compared to control. We conclude that gentamicin-mediated decrease in sphingomyelinase activity may be responsible for the storage of sphingomyelin in cultured human PT cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Cells, Cultured