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Biomedical subjects

R Bhadra

Publications and source records attributed to R Bhadra.

At least 19 recordsLinked to original sources

Cascade PSI-BLAST web server: a remote homology search tool for relating protein domains.

Owing to high evolutionary divergence, it is not always possible to identify distantly related protein domains by sequence search techniques. Intermediate sequences possess sequence features of more than one protein and facilitate detection of remotely related proteins. We have demonstrated recently the employment of Cascade PSI-BLAST where we perform PSI-BLAST for many 'generations', initiating searches from new homologues as well. Such a rigorous propagation through generations of PSI-BLAST employs effectively the role of intermediates in detecting distant similarities between proteins. This approach has been tested on a large number of folds and its performance in detecting superfamily level relationships is approximately 35% better than simple PSI-BLAST searches. We present a web server for this search method that permits users to perform Cascade PSI-BLAST searches against the Pfam, SCOP and SwissProt databases. The URL for this server is http://crick.mbu.iisc.ernet.in/~CASCADE/CascadeBlast.html.

Internet↗

CNS activity of the methanol extract of Mallotus peltatus (Geist) Muell Arg. leaf: an ethnomedicine of Onge.

The aim of the present study was to investigate several neuropharmacological effects of the methanol extract and different fractions of Mallotus peltatus (Geist) Muell Arg. var acuminatus (Euphorbiaceae) leaves in Wistar albino rats and Swiss albino mice. General behavior, exploratory behavior, muscle relaxant activity and phenobarbitone sodium-induced sleeping time were studied. The results revealed that the crude extract at 200-300 mg kg(-1) p.o. and its fractions A and B at 50 mg kg(-1) caused a significant reduction in spontaneous activity (general behavioral profile), remarkable decrease in exploratory behavioral pattern (Y-maze and head dip tests), a reduction in muscle relaxant activity (rotarod, 30 degrees inclined screen and traction tests), and also significantly potentiated phenobarbitone sodium-induced sleeping time. The phytochemical study of crude leaf extract revealed the presence of tannin, triterpenoid, flavonoid, sterol, alkaloid and reducing sugar. Further fractionation and purification yielded two major fractions A (ursolic acid) and B (beta-sitosterol) with some fatty acids as the major compounds. The psychopharmacological activity of the crude leaf extracts appeared to be either due to fraction A (50 mg kg(-1)) or a combination of fractions A and B (50 mg kg(-1)) along with some fatty acids present in the n-butanol part of methanol extract of M. peltatus leaf (MEMPL).

Analgesics↗

Immunobiology of CD28 expression on human neutrophils. I. CD28 regulates neutrophil migration by modulating CXCR-1 expression.

CD28, described as a T cell costimulatory molecule so far, is expressed on human peripheral blood neutrophils, as shown by cell surface staining and immunoprecipitation with anti-CD28 monoclonal antibody, and by reverse transcription PCR. The phorbol 12-myristate 13-acetate-augmented expression of CD28 on these cells can be blocked by actinomycin D, an RNA transcription inhibitor, and staurosporin, a protein kinase inhibitor. Cross-linking of CD28 results in an early increase in IL-8 receptor A (IL-8RA or CXCR-1) expression and a concurrent increase in IL-8-induced chemotaxis. The expression of CXCR-1 is down-regulated by receptor internalization 3 h after CD28 cross-linking with concurrent decrease in IL-8-induced chemotactic migration. Thus, our results demonstrate for the first time that CD28 is expressed on human peripheral blood neutrophils and that CD28 may play an important role in the regulation of IL-8RA expression and migration of neutrophils in response to IL-8.

Adult↗

Studies on plant-mediated fate of the explosives RDX and HMX.

The fate of the explosives RDX and HMX on exposure to plants was investigated in 'natural' aquatic systems of Myriophyllum aquaticum for 16 days, and in axenic hairy root cultures of Catharanthus roseus for > or = 9 weeks. Exposure levels were: HMX, 5 mg/l; and RDX, approximately 8 mg/l. Exposure outcomes observed include: HMX, no transformation by aquatic plants, and minimal biological activity by axenic roots; and RDX, removal by both plant systems. In the case of RDX exposure to axenic roots, since 14C-RDX was included, removal was confirmed by the accumulation of 14C-label in the biomass. The intracellular 14C-label in these RDX studies was detected in two forms: intact RDX and bound unknown(s).

Azocines↗

Antimicrobial activity of Alstonia macrophylla: a folklore of bay islands.

The methanolic crude and methanol-aqueous extract of Alstonia macrophylla leaves and n-butanol part of the crude extract showed antimicrobial activity against various strains of Staphylococcus aureus, Staphylococcus saprophyticus, Streptococcus faecalis, Escherichia coli, Proteus mirabilis, Trichophyton rubrum, Trichophyton mentagrophytes var. mentagrophytes and Microsporum gypseum. The minimum inhibitory concentration (MIC) values ranges from 64 to 1000 microg/ml for bacteria and 32-128 mg/ml for dermatophytes. However, the strains of Pseudomonas aeruginosa, Klebsiella sp. and Vibrio cholerae showed resistance against in vitro treatment of the extracts up to 2000 microg/ml concentration, while the two yeast species were resistant even at 128 mg/ml concentration. The stem bark extract prepared similarly was found to be less active compared to the leaves. Phytochemical study indicates that the crude extract contains tannins, flavonoids, saponins, sterols, triterpene and reducing sugars. Further fractionation and purification of n-butanol part of the extract showed the presence of beta-sitosterol, ursolic acid, beta-sitosterol glucoside and a mixture of minor compounds only detected in TLC.

Anti-Bacterial Agents↗

Transient studies of light-adapted cultures of hairy roots of Catharanthus roseus: growth and indole alkaloid accumulation.

Cultures of C. roseus transgenic ("hairy") root clones LBE-6-1 and LBE-4-2 were adapted with periodic daily illumination to investigate the effect of light on growth and nutrient utilization, and the accumulation of the indole alkaloids. Light-adapted roots appeared green and had radially thickened morphology compared with dark-grown controls. Their growth rates were higher than dark-grown controls, with 45% lower doubling times: LBE-6-1, 3.6 days; LBE-4-2, 2.8 days. Relative to dark-grown controls, light-adapted growth increased the biomass (DW) of LBE-6-1 by 25%, but had no effect on the DW of LBE-4-2. The macronutrients NH4+, NO3-, Pi, and sugars, were depleted completely by light-adapted root cultures in that order. The specific and total levels of the indole alkaloid serpentine was enhanced and of tabersonine was lowered in both root clones, while the overall trends of growth and non-growth association of tabersonine and serpentine, respectively, remained unaltered by light adaptation. Ajmalicine accumulation was enhanced in LBE-6-1, but lowered in LBE-4-2; its accumulation was growth-associated in dark-grown LBE-6-1, but appeared non-growth associated in light-adapted cultures. The accumulation of tabersonine-related compounds, lochnericine, and hörhammericine exhibited growth-associated trends, and were either negatively affected or unaffected by light adaptation of LBE-6-1. Neither vindoline nor its precursor, deacetylvindoline, was detected.

Adaptation, Physiological↗

Quantification of metabolites in the indole alkaloid pathways of catharanthus roseus: implications for metabolic engineering

In this article, we present a review of the current state of metabolic engineering in Catharanthus roseus. A significant amount of research has contributed to characterization of several individual steps in the biosynthetic pathway of medicinally valuable alkaloids. However, knowledge of the regulation of these pathways is still sparse. Using hairy root cultures, we studied the responses of alkaloid metabolism to environmental stimulation such as light and elicitation. Through precursor feeding studies, the putative rate-limiting steps of the terpenoid pathway in hairy root cultures also have been examined. Relating this knowledge to specific events at the molecular level, and the cloning of corresponding genes are the next key steps in metabolic engineering of the C. roseus alkaloids. Copyright 1998 John Wiley & Sons, Inc.

Journal Article↗

Altered membrane permeability as the basis of bactericidal action of methdilazine.

The growth inhibition of Escherichia coli and Staphylococcus aureus was accompanied by significant release of K+ and UV-absorbing small molecules upon exposure to methdilazine, an extensively used phenothiazine antihistamine. A severe decrease in [U-14C] glucose uptake and a rapid efflux of hexose from sugar-preloaded bacteria were also observed but without visible cellular lysis. Considerable damage to membrane permeability by methdilazine was proposed to explain the rapid loss in cfu/mL of the bacteria.

Anti-Bacterial Agents↗

Hydroalcoholic human placental extract: skin pigmenting activity and gross chemical composition.

BACKGROUND: Vitiligo is a pigmentary disorder of the skin of unknown etiology. It is thought to be of autoimmune origin after demonstration of antibody-mediated destruction of melanocytes. Photochemotherapeutic PUVA therapy is widely used in vitiligo with about 33% success. Aqueous or hydroalcoholic extracts of human placenta of ill-defined composition have also been used therapeutically for vitiligo. A hydroalcoholic human placental extract has been developed by us with pigmenting activity based on experimental therapies. Its chemical analysis was the primary objective of this study. METHODS: For the guinea pig experiment, 20 drops of the extract or vehicle (60% alcohol) as control was topically applied around the nipples covering the areola zones of male immature white guinea pigs (wt. 175-250 g) daily for 60 days with 15 minutes infrared (IR) exposure used for vascular dilatation and enhancement of the absorption of the extract. Standard methods have been followed for all chemical analyses. RESULTS: The guinea pig experiment showed clear pigmentation and hypertrophy of the experimental nipples to varying degrees. Chemical analysis of the extract revealed the presence of small-molecular-weight proteins/peptides, lipids (including glycosphingolipids), carbohydrates, sialic acids, cholesterol, triglycerides, high density lipoproteins (HDL), and others, including amino acids, nucleotides, carotenes, vitamins, etc. CONCLUSION: Glycosphingolipids, known modulators of B and T cells, were reported capable of inducing adhesion, spreading, and motility of melanoma. It is present in the extract and, therefore, may lead to skin pigmentation through induction of melanocytes. Endothelin, a 21-amino acid peptide, detected in human placenta and possibly extractable by our process, has been reported to be indispensable for melanocyte growth.

Absorption↗

A new antileishmanial compound, phaseolinone.

Inclusion of phaseolinone, a newly described mycotoxin, at 20 micrograms per ml in a solid culture medium (blood agar overlay) and at 50 micrograms per ml in a liquid culture (medium 199) inhibited the growth of L. donovani promastigotes. About 90% of the motile promastigotes lost motility after exposure to 50 micrograms per ml of phaseolinone for 6-7 h and here 3-day-old culture was more sensitive than 7-day-old culture. In an in vitro assay, DNA dependent RNA polymerase activity of 3-day-old promastigotes was considerably inhibited in the presence of this toxin. Therefore, this key enzyme was suggested to be one of the sites of action of phaseolinone.

Animals↗

Immunomodulatory stimulation of an invertebrate circulatory lectin by its haptenic molecules of pathogenic origin.

2-keto-3-deoxy octonate and beta-glycerophosphate two important bacterial cell wall constituent molecules, haptenic in nature to an invertebrate (crab) circulatory lectin, carcinoscorpin, gave lectin induction after immunization of the crab, Carcinoscorpius rotunda-cauda. With the exception of erythrocyte, no other sialoglycoconjugate-containing substances (mucin, fetuin) sialodisaccharide O-[N-acetylneuraminyl-(2----6)2-acetamido-2-deoxy galactitol] and free sialic acid were effective in lectin induction. This induction of circulatory lectin failed to appear when, concanavalin A, epinephrine, cytochalasin B, methyl-alpha-D-mannoside and bovine serum albumin were used for immunization. But mechanical injury to crabs were extremely effective in such lectin induction by live crabs. LPS is lethal if used for immunization. The immunoregulatory induction of the circulatory lectin by pathogen-originated cell wall constituent molecules and mechanical injury may be considered as a humoral immune response.

Animals↗