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Biomedical subjects

S Chatterjee

Publications and source records attributed to S Chatterjee.

At least 325 records · Page 18Linked to original sources

Role of oxidized human plasma low density lipoproteins in atherosclerosis: effects on smooth muscle cell proliferation.

The effects of oxidized human plasma low density lipoproteins (Ox-LDL) on the proliferation of cultured aortic smooth muscle cells was studied, employing viable cell counting, [3H] thymidine incorporation into DNA, and the release of lactate dehydrogenase (LDH) into the medium. Oxidized LDL (prepared by incubation of LDL with copper sulfate) exerted a concentration-dependent stimulation (2 fold, compared to control) of aortic smooth muscle cell proliferation at low concentrations (0.1 micrograms-10 micrograms/ml medium). On the other hand, at high concentrations (25-200 micrograms/ml), Ox-LDL produced a pronounced decrease in viable cells, a decrease in the incorporation of [3H] thymidine into DNA, and an increase in the release of LDH in the medium. In this report, the previously postulated biological roles of oxidized-LDL in atherosclerosis are discussed in view of these findings.

Arteriosclerosis↗

Studies on endoplasmic reticulum--Golgi complex cycling pathway in herpes simplex virus-infected and brefeldin A-treated human fibroblast cells.

Brefeldin A (BFA), a fungal metabolite, significantly inhibited the release of herpes simplex virus type 1 (HSV-1) from infected human fibroblast cells. Electron micrographs of HSV-1-infected and BFA-treated human cells demonstrated the presence of enveloped particles trapped between outer and inner nuclear membranes. Analyses of viral glycoproteins B, C, and D (gB, gC, and gD) showed faster migrating, immature forms in BFA-treated cells when compared to the mature glycoproteins, as observed in the untreated control cells. The shift in mobilities of the glycoproteins in BFA-treated cells apparently was due to the disassembly of the Golgi complex when evaluated by an indirect immunofluorescence assay. The immature forms of gB, gC, and gD could not be detected on the surface of BFA-treated human fibroblast cells. Removal of BFA resulted in a reorganization of the Golgi complex and formation of fully glycosylated gB, gC, and gD. Moreover, the HSV-1 particles released from the treated cells after the removal of BFA completely restored the infectivity of the viral particles. Our results indicate that human fibroblast cells have an endoplasmic reticulum-Golgi cycling pathway.

Animals↗

Effect of (S)-1-[(3-hydroxy-2-phosphonyl methoxy) propyl] cytosine on the replication and morphogenesis of herpes simplex virus type 1.

Treatment of African green monkey kidney cells with 1 microgram/ml of (S)-1-[(3-hydroxy-2-phosphonyl methoxy) propyl] cytosine (HPMPC) inhibited the release of infectious herpes simplex virus type 1 (HSV-1) by more than 90%. Electron microscopic observations of HPMPC-treated monkey kidney cells demonstrated few intracellular or extracellular viral particles. The viral particles seen were without dense cores. In addition, HPMPC blocked cell fusion induced by HSV-1 in monkey kidney cells. Immunoblot analysis showed that HPMPC significantly blocked the expression of HSV-1-specific proteins. Furthermore, HPMPC inhibited the synthesis of viral DNA as determined by in situ hybridization. These results indicate that HPMPC inhibits the replication of HSV by blocking one of the events involved in DNA synthesis.

Animals↗

Quinalphos-induced suppression of spermatogenesis, plasma gonadotrophins, testicular testosterone production, and secretion in adult rats.

Quinalphos (O,O-diethyl-O-[quinoxalinyl-(2)-thionophosphate]) is a well-known organophosphorus insecticide used extensively in agriculture that adversely interferes with the activity of testicular steroidogenic enzymes in rats. To investigate its effects on spermatogenesis, the other function of testes, quantitative evaluation of different varieties of germ cells at stage VII of the seminiferous epithelium cycle, namely, type A spermatogonia (ASg), preleptotene spermatocytes (pLSc), midpachytene spermatcytes (mPSc), and step 7 spermatids (7Sd), along with the radioimmunoassay of plasma FSH, LH, testosterone, and testicular testosterone, were performed in Wistar rats following treatment with quinalphos (250 micrograms/kg, ip) for approximately one (13 days) and two cycles (26 days) of the seminiferous epithilium. Massive degeneration of all varieties of germ cells at stage VII, remarkable reduction in the sperm count, and significant reductions in plasma concentrations of FSH and testosterone, along with testicular testosterone, were observed after quinalphos treatment. Significant reduction in the plasma concentration of LH was observed only after treatment for two cycles. Administration of human chorionic gonadotrophin for 26 days in rats injected with quinalphos partially prevented the degeneration of germ cells and increased testosterone production. It is suggested that quinalphos may have a suppressive influence on gonadotrophin release but its direct detrimental action at the level of the testes may also be responsible for the observed changes in spermatogenesis and in testicular testosterone production in rats.

Animals↗

A multidisciplinary educational program to promote head and neck cancer screening.

An educational program to promote screening through primary health care for the squamous cell cancers of the buccal cavity, pharynx, and larynx as developed and implemented, and its impact on screening was documented. Providers of care for high-risk patients at seven inner-city health care sites in Boston were identified and targeted for training. Of the 327 providers who were targeted for training from December 1986 through June 1989, 261 (80%) attended educational sessions. Screening exams were documented on an average of 14.7 patients per targeted provider through December 1989. The educational program was associated with a large increase in documented screening for these cancers, compared with baseline rates. Several adaptations in the program were required, including a demonstration of efficient screening to address the concerns of these providers about time constraints. Variations in the quantity and quality of documented screening among health care sites were noted.

Boston↗

A comparison of octreotide delivered by continuous subcutaneous infusion with intermittent injection in the treatment of acromegaly.

This study was undertaken to evaluate GH, IGF1 and drug levels during incremental continuous subcutaneous infusion of octreotide and compare these parameters following long-term treatment of 300 micrograms 24 h-1 by intermittent injection in a group of acromegalic patients. Ten patients were treated by continuous subcutaneous infusion in increasing dose from 200 micrograms 24 h-1 to 1600 micrograms 24 h-1; this resulted in consistent 24-h growth hormone suppression (less than 5.0 mU l-1), and normalisation of IGF1; the optimum dose was 400 micrograms 24 h-1, the maximum dose was tolerated without any untoward effects. There was no deterioration in carbohydrate tolerance despite a marked decrease in fasting and stimulated insulin levels. After 1 year of maintenance treatment, 300 micrograms 24 h-1 by intermittent injection, patients were re-evaluated; GH levels were not so consistently suppressed over the 24-h period and carbohydrate tolerance had deteriorated. A sub-group of patients with sub-optimal GH suppression on this regimen were identified and reassessed after 6 weeks treatment with an increased dose, 600 micrograms 24 h-1 by intermittent injection; both mean GH suppression and carbohydrate tolerance improved. The dose of drug and method of administration is best adjusted for each patient to achieve optimum GH suppression, thereby minimise compensatory hyperinsuliaemia and hopefully reduce morbidity and mortality. Alterations in pituitary tumour size and acquisition of gallstones during treatment have been observed which substantiate the need to re-evaluate these parameters on routine follow-up of acromegalic patients on long-term octreotide.

Acromegaly↗

Effect of loading conditions on Doppler-derived transmitral flow indices in normal subjects and patients with coronary artery disease.

The influence of alterations in preload and afterload on left ventricular diastolic filling using echocardiography was examined in nine normal volunteers (NLS) and nine patients (PTS) with coronary artery disease. The sequential interventions used were handgrip to increase afterload, nitroglycerin to decrease preload, and nifedipine to decrease afterload. Transmitral flow was measured using pulsed-Doppler echocardiography. Measurements were made pre- and post interventions. With increase in afterload using handgrip, the A and E wave velocities and the A/E ratio increased in both groups: 0.62 +/- 0.14 versus 0.86 +/- 0.17 in NLS; 0.75 +/- 0.45 versus 0.84 +/- 0.50 in PTS (P less than 0.05). Following administration of nitroglycerin to reduce preload, the A wave velocities increased, the E wave velocity decreased in both groups, and the A/E ratio increased 0.57 +/- 0.11 versus 0.67 +/- 0.13 in NLS; 0.78 +/- 0.40 versus 0.91 +/- 0.44 in PTS (P less than 0.05). Following use of nifedipine, the A and E wave velocities decreased in both groups with an increase in the A/E ratio in the patient group 0.83 +/- 0.13 versus 0.89 +/- 0.11 (P = NS). Thus, both normal subjects and patients with coronary artery disease had similar changes in Doppler-derived indices of left ventricular filling following interventions that changed left ventricular preload and afterload.

Adult↗

Morphogenesis of human immunodeficiency virus type 1.

Human immunodeficiency virus (HIV) has been implicated as the etiologic agent of acquired immunodeficiency syndrome and is a member of the sub-family Lentivirinae within the family Retroviridae. HIV type 1 (HIV-1) contains three major genes, gag, pol and env, which code for (1) core proteins, (2) a protease, reverse transcriptase and integrase, and (3) envelope glycoproteins, respectively. The core proteins p17, p24 and p15 are derived from gag precursor, p55, by endoproteolytic cleavage. The two nucleic-acid-binding proteins p7 and p9 are synthesized from p15 by proteolytic cleavage. These two structural proteins are apparently needed for the ribonucleoprotein-core formation. The envelope glycoproteins gp120 and gp41 (gp120-gp41 complex) are also generated by cleavage env precursors, gp160. The assembly of HIV-1 particles, like other retroviruses, appears to involve the association of the env precursor gp160 with the gag proteins. There are several factors which influence the assembly and budding process of HIV-1. In this article, we describe important events in HIV-1 morphogenesis and factors which influence this aspect of the HIV-1 life cycle.

HIV-1↗

Aranorosinol A and aranorosinol B, two new metabolites from Pseudoarachniotus roseus: production, isolation, structure elucidation and biological properties.

Two new secondary metabolites, aranorosinol A (1) and aranorosinol B (2), were isolated from a strain of Pseudoarachniotus roseus. Their structures were elucidated on the basis of their spectral properties and chemical transformations and were found to be similar to aranorosin (3) isolated from the same strain.

Anti-Bacterial Agents↗

Mersacidin, a new antibiotic from Bacillus. Fermentation, isolation, purification and chemical characterization.

Mersacidin (1) is a new peptide antibiotic containing beta-methyllanthionine. It is classified as a member of the proposed lantibiotic group of antibiotics, and is produced by a species of Bacillus. Mersacidin has a molecular weight of 1,824 (C80H120N20O21S4). The antibiotic is active against Gram-positive organisms including methicillin-resistant Staphylococcus aureus, but has no activity against Gram-negative bacteria or fungi.

Anti-Bacterial Agents↗

Mersacidin, a new antibiotic from Bacillus. In vitro and in vivo antibacterial activity.

Mersacidin is a new peptide antibiotic of the proposed lantibiotic family. It is active in vitro and in vivo against Gram-positive bacteria including the methicillin-resistant Staphylococci. Its in vitro activity is less than those of vancomycin and erythromycin but it shows much higher activity in the in vivo system than can be expected from the in vitro testing results. A water soluble potassium salt has been prepared which has an activity profile similar to that of mersacidin, but has better in vivo activity against Streptococcus pyogenes than the parent compound.

Animals↗

Intraspecific sexual isolation in Drosophila.

Intraspecific sexual isolation was examined among wild strains of Drosophila malerkotliana, D. parabipectinata and D. pseudoananassae by multiple-choice method in Elens-Wattiaux mating chamber. In D. pseudoananassae, mating between two strains tested was random and isolation estimate was close to one. In one out of 6 crosses, involving geographic strains of D. malerkotliana, there was significant deviation from randomness and isolation estimate remained low which shows non-random (preferential or positive assortative) mating. In D. parabipectinata, the deviation from randomness was statistically significant due to higher number of homogamic matings in three crosses involving wild strains derived from geographically distant places and isolation estimate remained low in these crosses. The results provide evidence for incipient sexual isolation within D. malerkotliana and D. parabipectinata as a result of genetic divergence.

Animals↗

Congenital adrenal hyperplasia: experience at Calcutta.

Eight patients (7 females, 1 male) with congenital adrenal hyperplasia (CAH), were seen over a 24-month period beginning from March 1988. Seven patients had 21 hydroxylase (21-OH) deficiency while one had 11 beta hydroxylase deficiency. Of the 7 patients with 21-OH deficiency, 3 were of the salt losing (SL-CAH), and 4 were of the non-salt losing (NSL-CAH) type. The patients with NSL-CAH were diagnosed by their elevated 17-hydroxyprogesterone (17-OHP) levels. The 3 cases with SL-CAH were diagnosed on the basis of ambiguous external genitalia, typical electrolyte picture, normal female internal genitalia, sex chromatin and response to steroids. In one patient post-ACTH 17 OHP was alter measured. All 3 patients with SL-CAH were assigned the male sex. Sex reassignment was advised for two children; one accepted the advice and the child is doing well; one family did not accept sex reassignment and the child died. One patient died due to non-availability of fludrocortisone. Six patients are under follow-up. All are doing well except one patient with NSL-CAH who started treatment late. We conclude that a high index of suspicion, early diagnosis and meticulous patient education are the key features of successful management of CAH in India.

Adrenal Hyperplasia, Congenital↗

Lactosylceramide stimulates aortic smooth muscle cell proliferation.

We have investigated the effects of various sphingolipids on aortic smooth muscle cell proliferation employing viable cell counting, [3H] thymidine incorporation into DNA and the release of lactate dehydrogenase. Assays for UDP Gal: GlcCer Bl-4 galactosyltransferase (GalT-2) in control and treated cells were pursued simultaneously. Lactosylceramide stimulated cell proliferation in the order of 5 fold. Antibody against LacCer but not GbOse3Cer blocked the proliferative effects of LacCer in these cells. This phenomena was specific for aortic smooth muscle cells as LacCer decreased cell viability of aortic endothelial cells and had no effect on pulmonary endothelial cells. D-PDMP inhibited the activity of GalT-2 in smooth muscle cells and markedly prevented cell proliferation. In contrast, L-PDMP stimulated the activity of GalT-2 in smooth muscle cells and stimulated cell proliferation. Antibody against GalT-2 inhibited cell proliferation. Our findings suggest that the activation of GalT-2 leads to increased LacCer levels, which in turn, may be involved in aortic smooth muscle cell proliferation.

Animals↗

Etoposide (VP-16-213)-induced gene alterations: potential contribution to cell death.

We have shown previously a good correlation between etoposide-induced sister chromatid exchanges (SCE) and cytotoxicity. A semisynthetic derivative of podophyllotoxin, etoposide is also called Vepesid (Bristol; code designation VP-16-213, abbreviated VP-16). Since SCE represent DNA recombinational events, we hypothesized that VP-16-induced SCE might result in nonhomologous recombination in which segments of DNA were either deleted or added, leading to an alteration of gene sequences responsible for essential cell proteins. Alterations of such essential genes and consequent interference with formation of their products could consequently lead to cell death. To evaluate whether VP-16 treatment caused sufficient levels of DNA sequence alterations to interfere with gene product formation, we isolated hypoxanthine (guanine) phosphoribosyltransferase (HPRT)-deficient mutants from Chinese hamster V79 cells grown in the presence or absence of VP-16. DNA from 3 spontaneous mutants and 10 VP-16-induced mutants was analyzed by Southern blot hybridization to a full-length hamster HPRT cDNA probe. Most of the VP-16-induced mutants showed partial deletions and/or rearrangements of the HPRT gene. In contrast, spontaneous mutants showed negligible deletions or rearrangements. These results provide strong support for our hypothesis that deletion of genetic sequences may constitute an important component of the mechanism of VP-16-induced cell death.

Animals↗