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Biomedical subjects

S Mandal

Publications and source records attributed to S Mandal.

At least 55 records · Page 3Linked to original sources
PubMed1995

Effect of thyroxine on experimental bronchospasm in guinea pigs.

Effect of Thyroxine was studied in histamine induced bronchospasm in guinea pigs. Chronic treatment with the drug significantly protected against experimental bronchospasm. Thyroxine also potentiated salbutamol evoked bronchodilation in this experimental model. Up-regulation of beta-2 adrenoceptors in bronchial smooth muscle may be the probable mechanism of action of thyroxine.

Albuterol↗
PubMed1993

Hyperaggregation of platelets detected by whole blood platelet aggregometry in newly diagnosed noninsulin-dependent diabetes mellitus.

Twenty-five newly diagnosed cases of noninsulin-dependent diabetes mellitus were studied at the time of diagnosis and again after metabolic control of diabetes was achieved (approximately 3 months later) for platelet aggregation abnormalities in whole blood by the impedance method. Adenosine diphosphate in 10 and 20 mumol/L final concentrations and arachidonic acid in 25 and 50 mmol/L final concentrations were used as agonists. Patients had a significant hyperaggregation of platelets (P < 0.01) at the time of diagnosis compared with age-matched healthy control subjects. After metabolic control of blood glucose was achieved using oral hypoglycemic agents (n = 20) and diet regulation alone (n = 5), there was a significant decrease in platelet aggregation (P < 0.01). There was a positive relationship between blood glucose levels and whole blood platelet aggregation with adenosine diphosphate (P < 0.02 and < 0.05, with 10 mumol/L and 20 mumol/L, respectively), but there was no relationship between aggregation and glycosylated hemoglobin levels. Thus, platelet hyperaggregation was present even at the time of diagnosis in patients with diabetes mellitus in the absence of any vascular complications, and there was significant improvement in platelet hyperaggregation after metabolic control of blood glucose levels was achieved.

Adult↗
PubMed1993

Ocimum sanctum Linn--a study on gastric ulceration and gastric secretion in rats.

The antiulcerogenic property of Ocimum sanctum Linn (Tulsi) was studied in pyloric ligated and pyloric ligated & aspirin treated rats. The extract of OSL reduced the ulcer index, free & total acidity on acute and chronic administration. Seven days pretreatment with the drug increased the mucous secretion also. It may be concluded that OSL extract has antiulcerogenic property against experimental ulcers, and it is due to its ability to reduce acid secretion and increase mucous secretion.

Animals↗
PubMed1992

Metabolism of silicon as a probable pathogenicity factor for Mycobacterium & Nocardia spp.

The role of silicon (Si) in metabolism and growth of 22 strains of mycobacteria and 3 strains of nocardiae, which were mostly pathogenic, was studied on Kirchner's medium solidified with sodium metasilicate (KSM) and the C-free solidified metasilicate minimal medium (SMM) consisting of mineral salts only. On KSM, initial growth of mycobacteria appeared to be better, compared with that on Lowenstein-Jensen medium (LJM), although subsequent growth on the former was slower. On SMM lacking C, growth of mycobacteria and nocardiae could be achieved, only after repeated passages. These findings indicate that the mycobacteria and nocardiae are able to utilise Si at least to a limited extent, possibly as an alternative to C, with greater chances of survival.

Culture Media↗
PubMed1991

Bacterial expression and secretion of various single-chain Fv genes encoding proteins specific for a Salmonella serotype B O-antigen.

Active single-chain Fv molecules encoded by synthetic genes have been expressed and secreted to the periplasm of Escherichia coli using the ompA secretory signal. Four different constructs were developed to investigate the effects of peptide linker design and VL-VH orientation on expression, secretion, and binding to a Salmonella O-polysaccharide antigen. Peptide linker sequences derived from the elbow regions of the Fab molecule were used alone or in combination with the flexible (GGGGS)2 sequence. VL and VH domain order in the single chain molecules had a profound effect on the level of secretion but hardly influenced total expression levels, which were approximately 50 mg/liter, chiefly in the form of inclusion bodies. With VL in the NH2-terminal position, the amount of secreted product obtained was 2.4 mg/liter, but when VH occupied this position the yield was less than 5% of this value. Enzyme immunoassays of the four products showed domain order and linker sequence affected antigen binding by less than an order of magnitude. Attempts to express active Fv from dicistronic DNA were unsuccessful, but active Fv was obtained from single-chain Fv by enzymic cleavage at a site in the elbow linker peptide. The thermodynamic binding parameters of intact and cleaved single-chain Fvs determined by titration microcalorimetry were similar to those of bacterially produced Fab and mouse IgG.

Amino Acid Sequence↗
PubMed1990

Inhibition of N-nitrosobenzylmethylamine-induced esophageal tumorigenesis in rats by ellagic acid.

In this report, we describe the ability of ellagic acid (EA), a phenolic compound present in a number of fruits and nuts, to inhibit N-nitrosobenzylmethylamine (NBMA) tumorigenesis in the rat esophagus. When administered in a semi-purified diet at concentrations of 0.4 and 4 g/kg, EA produced a significant (21-55%) decrease in the average number of NBMA-induced esophageal tumors after 20 and 27 weeks of the bioassay. EA exhibited inhibitory effects toward preneoplastic lesions as well as neoplastic lesions. Tumors were not observed in vehicle-control rats or in rats that received EA alone.

Animals↗
PubMed1990

Synthesis and expression in Escherichia coli of DNA encoding the murine lambda 1 chain of a monoclonal antibody specific for Salmonella serotype B O-antigen.

A 658 bp DNA sequence corresponding to the murine lambda 1 chain of a monoclonal antibody, Se155-4, specific for the Salmonella serotype B O-antigen, was designed using Escherichia coli preferred codons and chemically synthesized by ligation of synthetic fragments into a linearized plasmid followed by transformation into E. coli. A synthetic signal peptide (ompA) was fused to express the L chain as a free polypeptide into the periplasm of E. coli cells. After isolation and purification, heterologous recombination of the E. coli L chain with mouse H chain gave an active antigen-binding protein. The activity was 15-20% when compared to protein created by an equivalent association of isolated natural mouse L and H chains as measured by a direct EIA assay. In inhibition experiments with the polysaccharide antigen, the two proteins showed identical titration curves and 50% inhibition points, indicating comparable KA values.

Amino Acid Sequence↗
PubMed1990

Lactose- and heparin-inhibitable agglutinin from human fetal brain.

An agglutinin activity which was sensitive to lactose and heparin was estimated during prenatal brain development. The agglutinin showed higher specific activities in cerebral cortex and midbrain. There was an increase in lectin specific activity in all the brain regions with development. In addition to brain, other fetal organs also showed the presence of developmentally regulated agglutinin. Cerebral cortical agglutinin was purified by Sepharose CL-6B gel filtration and asialofetuin- and heparin-Sepharose affinity chromatography. Purified agglutinin was strongly inhibited by lactose, asialofetuin, and heparin. It showed no requirement for divalent cations and was maximally active at pH 8.0. Electrophoretic characterization showed the aggregate nature of the agglutinin, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis gave subunit molecular weights of 58,000, 45,000, and 24,000.

Agglutinins↗
PubMed1989

Metabolic activation of 6-nitrochrysene in explants of human bronchus and in isolated rat hepatocytes.

It has previously been shown that 6-nitrochrysene can be activated to electrophilic species capable of reacting with DNA through metabolic pathways that form N-hydroxy-6-aminochrysene or trans-1,2-dihydroxy-1,2-dihydro-6-aminochrysene as critical intermediates. Since the lung is a known target tissue for the carcinogenic action of polycyclic nitroaromatic hydrocarbons, we investigated the metabolism and DNA binding of [3H]6-nitrochrysene in 11 specimens of human bronchus. Analysis of medium from [3H]6-nitrochrysene-treated explants indicated the presence of trans-9,10-dihydroxy-9,10-dihydro-6-nitrochrysene (0.04-330 pmol/mg epithelial DNA), trans-1,2-dihydroxy-1,2-dihydro-6-nitrochrysene (12-1700 pmol/mg epithelial DNA), 6-aminochrysene (1.6-2200 pmol/mg epithelial DNA), and trans-1,2-dihydroxy-1,2-dihydro-6-aminochyrsene (3.6-610 pmol/mg epithelial DNA). Both the levels and the relative proportions of these metabolites varied widely in explants from different individuals. The amount of DNA recovered and the level of DNA modification were sufficient for adduct analysis in eight of the 11 cases for which metabolite data were obtained. Five additional bronchial specimens for which metabolite data were not obtained were also analyzed for carcinogen-DNA adducts. The levels of binding varied from 0.06 to 30.5 pmol [3H]6-nitrochrysene bound/mg DNA (two adducts per 10(8) nucleotides-10 adducts per 10(6) nucleotides). HPLC analyses of enzymatic hydrolysates of the explant DNA indicated that 11 of 13 cases contained adducts with retention times identical to those of adducts derived from trans-1,2-dihydroxy-1,2-dihydro-6-aminochrysene or N-hydroxy-6-aminochrysene. The adduct derived from trans-1,2-dihydroxy-1,2-dihydro-6-aminochrysene was the major adduct detected in eight of 13 cases. The reasons for the variation in metabolism and adduct formation observed in [3H]6-nitrochrysene-treated explants of bronchus from different donors are not known but may reflect differences in the activities of enzymes responsible for the metabolism of this compound. The influence of induction of drug metabolizing enzymes on the activation pathway of 6-nitrochrysene in an intact cell system was tested using rat hepatocytes. 6-Nitrochrysene was incubated with freshly isolated hepatocytes from rats that were either untreated or pretreated with phenobarbital, 3-methylcholanthrene or Aroclor 1254. Although the levels of adducts were similar in all cases, the pattern of DNA adducts formed in these hepatocytes was dependent on the nature of the pretreatment of the rats. As previously reported, hepatocytes from untreated rats contained adducts derived from N-hydroxy-6-aminochrysene.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced DNA adduct formation and tumorigenicity in the lung of F344 rats by dietary phenethyl isothiocyanate.

F344 rats fed diets containing phenethyl isothiocyanate (PEITC, 3 mumol/g diet), a cruciferous vegetable component, before and during treatment with the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), developed about 50% fewer lung tumors than NNK-treated rats fed control diets. NNK-induced liver and nasal cavity tumors in rats were, however, not affected by this dietary treatment. The effects of PEITC diets on the formation of DNA adducts by NNK were also investigated in these target tissues. DNA methylation and pyridyloxobutylation by NNK were both decreased by 50% in lung of rats fed PEITC diets compared to that of rats fed control diets, but the levels of DNA methylation were not affected in liver and nasal mucosa. These results correlated with those from the carcinogenicity bioassay, suggesting that DNA alkylations could be used as indicators for screening inhibitors of NNK tumorigenesis. A slight increase in the number of tumors of the exocrine pancreas was observed in PEITC-fed rats with or without NNK treatments. However, these incidences were not statistically significant when compared to the control groups. The potential toxicity of PEITC at concentrations ranging from 0.75 mumol to 6 mumol/g diet was evaluated in a 13-week study. The only toxicity caused by this treatment was minimal fatty metamorphosis in the liver. Considering the widespread human exposure to NNK through tobacco use, it is of practical importance to demonstrate inhibition of lung tumors induced by this carcinogen. These results provide a basis for studies designed to discover agents of better efficacy for the prevention of NNK-induced tumorigenesis.

Alkylation↗
PubMed1988

Cathepsin D and 2',3'-cyclic nucleotide 3'-phosphohydrolase in developing human foetal brain.

Three peaks of proteinases were observed with hemoglobin, bovine serum albumin and casein as substrates at the pH of 3.5, 6.5 and 8.5, in prenatal human cerebral cortex. Cathepsin D (EC 3.4.23.5) was the most prominent, with hemoglobin as the preferred substrate. The enzyme was partially purified by Concanavalin A - Sepharose affinity chromatography and the nature of the active site was assessed with proteinase inhibitors. Inhibitor studies showed that similar to pepstatin A, benzethonium chloride was also strongly inhibitory to the enzyme. The distribution of cathepsin D, a neuronal marker, and 2',3'-cyclic nucleotide 3'-phosphohydrolase (EC 3.1.4.37), a oligodendroglial marker in foetal brain regions with increasing gestation revealed that neurogenesis and gliogenesis occur concomitantly from earlier periods of gestation. Glial marker acquisition was particularly high in medulla and in spinal cord between 20 and 25 weeks of gestation.

Brain↗
PubMed1988

Inhibition of N-nitrosobenzylmethylamine metabolism and DNA binding in cultured rat esophagus by ellagic acid.

The effect of ellagic acid (EA), a naturally occurring plant phenol, on the metabolism, DNA binding and DNA adduct formation of N-nitrosobenzylmethylamine (NBMA) in cultured explants of rat esophagus was investigated. Explants were incubated in medium containing EA at non-toxic concentrations of 10, 50 and 100 microM for 16 h, followed by the addition of 1 microM [3H]NBMA and EA for 12 h. Explant DNA was isolated by phenol extraction and hydroxylapatite chromatography, and benzaldehyde formation was determined by HPLC analysis of the culture medium. EA produced a significant inhibition in the total covalent binding of NBMA metabolites to DNA and in the production of benzaldehyde in the medium. After acid hydrolysis of the isolated DNA, the NBMA--DNA adducts were separated by HPLC. EA caused a dose-dependent decrease in the formation of N7-methylguanine and O6-methylguanine adducts. These results suggest that EA inhibits both the metabolism of NBMA and the binding of NBMA metabolites to DNA in cultured rat esophagus.

Animals↗
PubMed1987

Inhibition of aflatoxin B1 mutagenesis in Salmonella typhimurium and DNA damage in cultured rat and human tracheobronchial tissues by ellagic acid.

Ellagic acid (EA), a plant phenol found in various fruits and nuts, was examined for its ability to inhibit aflatoxin B1 (AFB1) mutagenesis in strain TA 100 of Salmonella typhimurium. In the presence of rat liver S-9 microsomal preparation, EA (1.5 microgram/plate) inhibited the number of mutations induced by AFB1 (0.5 microgram/plate) by 50%. EA at a dose of 1000 micrograms/plate inhibited the mutation frequency by greater than 90%. EA was also tested for its ability to inhibit the DNA binding and adduct formation of AFB1 in cultured explants of rat trachea and human tracheobronchus. Explants were incubated in medium containing EA at concentrations of 10, 50 and 100 microM for 16 h followed by the addition of 1 microM [3H]AFB1 and EA for 24 h. DNA was isolated by phenol extraction and hydroxylapatite chromatography. EA caused a dose-dependent inhibition in the covalent binding of AFB1 to the DNA of both the rat trachea (9-57% inhibition) and human tracheobronchus (24-79% inhibition). After acid hydrolysis of the isolated DNA, the AFB1-DNA adducts were separated by h.p.l.c. In tissues from both species, the major AFB1- DNA adducts were AFB1-N7-Gua [8,9-dihydro-8-(N7-guanyl)-9-hydroxyAFB1] and AFB1-N7-FaPyr (major) [8,9-dihydro-8- (2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl formamido)-9-hydroxyAFB1], and the formation of these adducts was reduced by 28-76% in the presence of EA. These data indicate that EA has the potential to act as a naturally occurring inhibitor of AFB1-related respiratory damage in rats and in humans.

Aflatoxin B1↗