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Biomedical subjects

S Chatterjee

Publications and source records attributed to S Chatterjee.

At least 37 records · Page 2Linked to original sources

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

The herpes simplex virus 1 segment inversion site is specifically cleaved by a virus-induced nuclear endonuclease.

Nuclear extracts from several tissue culture cell lines (human, primate, and murine) contain an endonuclease that specifically cleaves sequences at the herpes simplex virus 1 (HSV-1) segment inversion site. Mapping studies identified the preferential site of cleavage as a set of tandemly repeated dodecamers, the DR2 repeats. Endonuclease levels vary according to the proliferative state of the cell; little or no activity is detectable in extracts from quiescent cells, whereas high levels are expressed in dividing cells. Also, infection of density-arrested BSC-1 cells with HSV-1 induces a substantial increase (at least 35-fold) in endonucleolytic activity, which is first detectable at about 1 hr after infection at 32 degrees C. The elevated levels of enzyme activity then persist throughout the viral life cycle. In addition to the HSV-1 DR2 repeats, certain other G+C-rich sequences with an asymmetric distribution of purines and pyrimidines on the DNA strands and with appropriate sequences and lengths are substrates for the nuclease. These data indicate that target site recognition by the enzyme is conformation specific rather than sequence specific.

Animals

Suppressive effect of quinalphos on the activity of accessory sex glands and plasma concentrations of gonadotrophins and testosterone in rats.

Biochemical estimation of prostatic acid phosphatase and fructose content in accessory sex glands, along with radioimmunoassay of plasma gonadotrophins (FSH and LH) and testosterone were performed in Wistar rats following treatment with quinalphos, an organophosphorus insecticide, for 13 and 26 days. Prostatic acid phosphatase activity and fructose content of the accessory sex glands, and plasma levels of testosterone and FSH were significantly lower in all rats treated with quinalphos. However, the degree of inhibition was more extensive in the 26 day-treatment group who, in addition also exhibited a significant reduction in relative weights of the testes and accessory sex organs, and plasma levels of LH. All these adverse effects of quinalphos were prevented when exogenous HCG was administered in concomitant with the insecticide for 26 days. These results suggest that quinalphos may exert a suppressive effect on the functional activity of accessory sex glands by decreasing testicular testosterone production following inhibition of pituitary gonadotrophins release.

Animals

Apical expression of herpes simplex virus type 2 glycoproteins in human neuroblastoma cells.

The expression of herpes simplex virus type 2 (HSV-2) glycoproteins on the surface of human neuroblastoma cells has been investigated using Millipore Millicell culture plate inserts. Utilizing a modified radioimmunoassay, we learned that glycoproteins B, C, D, E, and I were expressed predominantly on the apical membrane domain of the infected neuroblastoma cells. The unidirectional transport of HSV-2 glycoproteins was substantiated by the analysis of extracellular glycoproteins released from neuroblastoma cells. The results suggest that the evaluated HSV-2 glycoproteins were transported primarily to the apical plasma membrane domain of human neuroblastoma cells.

Cell Membrane

Evaluation of a test based on baculovirus-expressed glycoprotein G for detection of herpes simplex virus type-specific antibodies.

An immunoblot assay for discrimination of antibodies to herpes simplex virus (HSV) types 1 and 2 was devised using extracts of recombinant-baculovirus-infected insect cells expressing HSV-1 or -2 glycoprotein G (gG1 or gG2). The assay was evaluated by comparing its results with those obtained by using an immunodot assay based on gG immunopurified from HSV-1- and HSV-2-infected cells. Each of 110 human serum specimens was tested blindly and independently three times. At a serum dilution of 1:20, the maximum specificities were 96% and 100% and the maximum sensitivities were 100% and 92% for gG1 and gG2, respectively. Reproducibility was 99% among readers and 95% among individually tested samples of each specimen. Results obtained in two laboratories from a different set of 15 serum specimens were in complete agreement, indicating the assay is accurate and reproducible. The ease of antigen production should allow the test to become widely available.

Animals

Carbohydrate tolerance and serum lipids in acromegaly before and during treatment with high dose octreotide.

Carbohydrate tolerance and serum lipids were studied in 14 patients with acromegaly before and in response to treatment with high dose somatostatin analogue (octreotide) over a 14-week period. Patients were assessed with respect to growth hormone (GH) profile, IGF1, HbA1, fasting lipids, and the GH, glucose, and insulin response to a standard 75 g oral glucose tolerance test (OGTT) before and during therapy. Prior to treatment mean fasting serum insulin levels were 11.7 +/- 2.8 (+/- SE) mU I-1 with a mean insulin response to OGTT of 49.8 +/- 10.8 mU I-1. Twelve of the 14 patients responded to octreotide with a reduction in mean 24-h serum GH (32.9 +/- 9.3 to 4.3 +/- 0.9 mU I-1), suppression of GH at 60 min during OGTT (3.0 +/- 0.8 mU I-1) and normalization of serum IGF1 (71 +/- 7 to 27 +/- 3 (normal 9-48 nmol I-1)). In this group the fasting insulin levels fell to 2.2 +/- 0.7 mU I-1 (p less than 0.01), and mean insulin response during OGTT was reduced (46.6 +/- 15.0 to 12.3 +/- 2.3 mU I-1) (p less than 0.01). Despite the reduction in insulin secretion there was no significant deterioration in fasting blood glucose (4.8 +/- 0.2 vs 4.6 +/- 0.4 mmol I-1), HbA1 (7.2 +/- 0.3 vs 6.8 +/- 0.3%) or mean blood glucose response to OGTT (7.9 +/- 0.7 vs 8.2 +/- 0.5 mmol I-1). Fasting triglycerides were reduced with treatment from 1.5 +/- 0.2 to 1.1 +/- 0.1 mmol I-1 (p = 0.04) in the responsive group, but serum cholesterol levels were not significantly altered (5.3 +/- 0.3 vs 5.2 +/- 0.3 mmol I-1).

Acromegaly

Intracellular maturation and sorting of two herpes simplex virus type 1 glycoproteins. Immunogold staining of ultrathin cryosections.

Simultaneous immunocytochemical triple staining of ultrathin cryosections of herpes simplex virus type 1-infected cells was carried out using monoclonal antibodies specific for glycoprotein C, glycoprotein D and alpha + beta tubulin. The viral glycoproteins were identified in the cytoplasm, in the Golgi sacs, on the plasma membrane and on the surface of intra- and extracellular virus particles, but not on the nuclear membrane. The glycoproteins identified in the cytoplasm outside the Golgi region were not always confined to the membranes of vesicles, but were often located in close proximity to the tubulin-labelled structures. The glycoproteins C and D were usually codistributed in the cytoplasm, and both accumulated in the Golgi sacs in the same membrane domains. As the glycoproteins occur in close proximity to the microtubular structures, we speculate that these might be directly involved in the intracellular transport of viral glycoproteins.

Freezing

Inhibition of human immunodeficiency virus type 1-induced cell fusion by recombinant human interferons.

Pretreatment of HeLa T4 cells with recombinant alpha, beta, or gamma interferon (IFN) was found to significantly inhibit syncytium formation induced by the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein. All three IFNs were found to be potent inhibitors of fusion in a system in which Spodoptera frugiperda cells, infected with a baculovirus recombinant expressing the HIV-1 envelope protein, were cocultivated with HeLa T4 cells. In addition, these IFNs were also found to block HeLa T4 cell fusion induced by the HIV-1 envelope proteins expressed from a vaccinia virus recombinant. Furthermore, the IFNs inhibited cell fusion between HIV-1 envelope glycoprotein-expressing cells and either immortalized or fresh CD4+ lymphocytes pretreated with the IFNs. These results suggest that further testing of human IFNs for therapy of HIV-1 infection will be of interest.

Animals