Biomedical subjects

G B Singh

Publications and source records attributed to G B Singh.

At least 19 recordsLinked to original sources

PubMed1995

CLONEPLACER: a software tool for simulating contig formation for ordered shotgun sequencing.

This communication describes a software tool that enables one to simulate large-scale regional mapping using an ordered shotgun sequencing approach. The analysis routines that are provided yield an estimate of the depth of coverage of the physical map, the largest contig formed, and the number of gaps remaining at any given juncture in the project. A detailed listing describing the span of each contig within the physical map is also presented. This provides an a priori means of estimating the resources that will be required to undertake any megabase mapping or sequencing project. CLONEPLACER provides the much needed guide to deriving the optimal strategy.

Chromosome Mapping↗

PubMed1995

DNAView: a quality assessment tool for the visualization of large sequenced regions.

This communication describes DNAView, a graphical tool for the visualization and printing of large nucleic acid sequences. DNAView uses color coding to compactly display genomic segments of up to 100 kb on a single printed page. The specific color schemes integrated into DNAView can highlight 'local aggregate' properties of large segments of DNA. We have also incorporated a confidence expression for the assigned sequence. This is represented by base color intensity that is proportional to the number of times that base was sequenced. Areas of interest, such as exons, introns, repetitive elements and splice sites, can be emphasized using overlays. The colored image can be saved in a standard TIFF image file format that may be imported and annotated by other application software.

Base Sequence↗

PubMed1995

Testicular toxicity of Di(2-ethylhexyl)phthalate in developing rats.

To understand the factors involved in the enhanced testicular toxicity of di(2-ethylhexyl)phthalate (DEHP) in developing animals, po doses of 50, 100, 250 or 500 mg DEHP/kg were administered to 25-d-old albino rats for 30 consecutive days. Activities of testicular and hepatic cytochrome P-450 enzymes were determined. A dose-dependent increase in the activities of lactate dehydrogenase and gamma-glutamyl transpeptidase and a decrease in sorbitol dehydrogenase was observed in the testes. The activity of beta-glucuronidase increased at dosages of 250 and 500 mg/kg, while acid phosphatase decreased. Testes had marked destructive changes in the advanced germ cell layers at dosages of 250 and 500 mg/kg, which supports biochemical studies indicating that DEHP interacts with the maturation process of the testes. The dose-dependent decrease in hepatic cytochrome P-450 levels and the activities of ethylmorphine N-demethylase and aniline hydroxylase suggest that impaired metabolism of DEHP could lead to higher amounts of the diester or its metabolites reaching the testes; this may result in enhanced vulnerability of the testes to DEHP in developing animals.

Aging↗

PubMed1994

Attenuation of benzanthrone toxicity by ascorbic acid in guinea pigs.

Oral administration of benzanthrone (BA) (50 mg/kg body wt/day) to guinea pigs for 30 days resulted in depletion of ascorbic acid (ASA) in the liver, adrenals, and blood serum and in growth retardation (36%) and an increase (18%) in relative liver weight when compared to controls. BA treatment showed a tendency toward normocytic anemia with a decrease in hemoglobin content, reduction in RBC counts, and lowered packed cell volume. Guinea pigs treated with BA showed histopathological changes in liver including fibrosis, bile duct proliferation, and focus necrosis. Testes showed marked damage of seminiferous tubules with vacuolar degeneration and irregular and distorted interstitial spaces. BA showed evidence of patchy glomerular congestion, tubular lesions, and damaged epithelial cells in kidney, while urinary bladders had mild congestion in lamina propria and submucosa. Hepatic GOT, GPT, and LDH were found to be significantly decreased (17.5-33.5%), whereas activities of these enzymes showed a significant elevation in serum of BA-exposed guinea pigs. BA treatment also led to significant decrease of testicular hyaluronidase (29.8%) and LDH (19.8%) and significant depletion of lactic acid content (14.7%). Prior daily oral supplementation with ASA (50 mg/kg body wt) to BA-administered guinea pigs resulted in marked improvement of histopathological and biochemical changes observed in liver, testis, kidney, and urinary bladder of BA-exposed animals. These results suggest that extra supplementation of ASA could attenuate the toxic manifestations of BA.

Animals↗

PubMed1994

ISWAC: proposed system for the integrated assembly of chromosomes.

The generation of a physical map as an integral part of sequence project management is a problem that present computer systems do not address. Primarily, the analysis performed is based solely on the information available from a single knowledge level. Management systems that are currently available do not adequately model the multi-layer top down strategy that is most often utilized to manage large scale sequencing projects. Single layered approaches reflect an algorithmic inadequacy since interacting data sets are required to provide a good solution. The analysis tool that is currently under development termed ISWAC, the Integrated System for Wholistic Assembly of Chromosomes, overcomes these limitations by integrating information available from five layers of knowledge. These knowledge layers utilize information from the linkage map, physical map, restriction map, clone strategy map and the DNA sequence itself. The approach we are implementing, reviews current project status and continually refines the experimental strategy necessary to efficiently complete the sequencing task. To facilitate project completion the system is designed to interactively recommend strategies based on partial information. The utility of this tool is enhanced by implementing knowledge representation techniques that allow reasoning with approximate concepts characteristic of these data-sets. In addition, the raw physical data is maintained within an integrated map database to ease data verification. This paper presents the first discussion of the design specifications for a computer system to assimilate the various forms of data that are being generated as part of the human genome project. It was specifically written to stimulate discussion regarding data standardization, translation, analysis and most important, an understandable user-interphase for the molecular biologist. We would hope that interested readers would respond by assisting in the definition of a set of universal data standards and adopting them in their laboratories.

Algorithms↗

PubMed1994

Anti-inflammatory properties of 3-methylpyrazolin-5-(4 H)-one-4-[3'-methoxy-4' (2'',3'',4'',6''-tetra-O-acetyl-beta-D-glycopyranosyl]benzylidene (compound IIIA).

Oral treatment of compound IIIA exhibited dose related inhibitory action in acute tests of carrageenan, histamine and dextran-induced oedema in rats. Marked inhibitory action of the compound was found when it was administered intraperitoneally in animals. It displayed prominent anti-arthritic activity in chronic tests of adjuvant and formaldehyde-induced arthritis in rats. It prevented the arthritis associated rise in total leucocyte count and erythrocyte sedimentation rate. It also lowered the levels of exudate volume and migration of leucocytes in carrageenan induced pleurisy in rats. It did not exhibit any analgesic, antipyretic or ulcerogenic effect. No mortality was recorded up to 2 g/kg in mice on oral or intraperitoneal treatment over a period of 72 hr.

Animals↗

PubMed1993

Modulation by ascorbic acid of the cutaneous and hepatic biochemical effects induced by topically applied benzanthrone in mice.

Modulation of biochemical markers by ascorbic acid was investigated in mice to which benzanthrone (BA) was applied topically (150 nmol/mouse) twice a week for 34 wk. After BA exposure without ascorbic acid, in the skin there were significant decreases in the activities of aryl hydrocarbon hydroxylase (AHH; 38% decrease relative to controls) and ethoxyresorufin-O-deethylase (EROD; 39%), and enhancement of the activities of quinone reductase (41% increase), tyrosinase (82%) and histidine decarboxylase (HDC; 190%). BA exposure also caused significant inhibition of hepatic AHH, EROD and glutathione-S-transferase activities, with concomitant increases in the activities of histidase (52%) and HDC (58%). Ascorbic acid given orally (5 mg/mouse) or topically (1 mg/mouse) twice weekly for 34 wk to BA-treated mice resulted in substantial protection against the effects of BA on these enzyme markers in both the skin and the liver. These results suggest that ascorbic acid could be useful in preventing the biochemical and toxicological manifestations caused by BA in laboratory animals.

Administration, Topical↗

PubMed1992

Comparative study of the biodisposition of benzanthrone in different rodent species.

The bio-elimination and organ retention of [14C]benzanthrone, an anthraquinone dye intermediate, were determined in rats, mice and guinea pigs. Urinary excretion of benzanthrone during 96 hr was higher in guinea pigs (28%) compared with rats and mice (19%). However, faecal elimination during 96 hr was higher in rats (39%) and mice (42%) than in guinea pigs (25%). Urinary elimination of benzanthrone in rats and mice was highest between 12 and 24 hr, while guinea pigs showed a peak value between 24 and 48 hr. The maximum amount of radiolabelled benzanthrone was eliminated through faeces at 24-48 hr in all the three animal species. The retention of [14C]benzanthrone in the liver was comparable in rats (11.2%) and mice (11.9%), while in guinea pigs it was substantially higher (21.9%). The testes of rats and mice were devoid of radioactivity, whereas those of guinea pigs showed a marginal retention (1.25%) of 14C. The present study suggests that guinea pigs are more prone to benzanthrone toxicity than are rats and mice since the bio-elimination of this compound is slower and its organ retention is higher in this species.

Animals↗

PubMed1992

Effect of extraneous supplementation of ascorbic acid on the bio-disposition of benzanthrone in guinea pigs.

The bio-elimination and organ retention of orally administered [14C]benzanthrone, an anthraquinone dye intermediate, were determined in control and ascorbic acid-supplemented guinea pigs. Urinary excretion of benzanthrone in control and ascorbic acid-treated animals during 96 hr was 27.9 and 30.5%, respectively, with peak elimination at 48 hr. Faecal elimination in control and supplemented animals during 96 hr was 24.5 and 38.8%, respectively, with a peak at 48 hr. The organ retention of radiolabelled benzanthrone at the end of 96 hr was of the order of 39% in control animals (gastro-intestinal tract 16%; liver 22%; testis 1.2%); ascorbic acid supplementation reduced benzanthrone retention to 19.5% (gastro-intestinal tract 12.7%; liver 6.8%). Overall, pretreatment of guinea pigs with ascorbic acid caused a 32% enhancement in the clearance of radiolabelled benzanthrone through the urine and faeces, while organ retention was reduced by about 50%. A prophylactic dose of ascorbic acid may prevent benzanthrone-induced toxic symptoms in exposed workers.

Animals↗

PubMed1992

Anti-inflammatory activity of oleanolic acid in rats and mice.

Oleanolic acid displayed anti-inflammatory activity in carrageenan and dextran-induced oedema in rats. It elicited marked anti-arthritic action in adjuvant-induced polyarthritis in rats and mice and in formaldehyde-induced arthritis in rats. Oleanolic acid checked the inflammation-induced increased serum transaminase levels. It reduced exudate volume and inhibited leucocyte infiltration in carrageenan-induced pleurisy in rats. It is devoid of any analgesic, antipyretic or ulcerogenic action. Oleanolic acid did not affect the parturition time in pregnant rats or castor oil-induced diarrhoea in rats. Oral LD50 was found to be greater than 2 g kg-1 in mice and rats.

Adrenalectomy↗

PubMed1992

The influence of low protein diet on the testicular toxicity of di(2-ethylhexyl)phthalate.

Oral administration of di(2-ethylhexyl)phthalate (DEHP) at 1000 mg/kg body weight to adult male albino rats maintained on low protein (LP) diet for 15 d resulted in a greater decrease in absolute and relative weights of the testis and in epididymal sperm count than in those rats maintained on a normal protein (NP) diet. A marked increase in the activity of testicular beta-glucuronidase and gamma-glutamyl transpeptidase (GGT) in the LP-fed animals suggested that LP diet enhanced the vulnerability of Sertoli cells towards DEHP. A greater decrease in the activity of testicular acid phosphatase, lactate dehydrogenase isoenzyme-X (LDH-X) and sorbitol dehydrogenase (SDH) in the LP-fed animals occurred in comparison to NP-fed animals. Degeneration of mature germinal cells in the LP-fed animals on exposure to DEHP suggested that LP diets enhance the susceptibility of the testis towards DEHP.

Administration, Oral↗

PubMed1992

P-aminodiphenylamine induced biochemical changes in sex organs of male albino rats.

Intraperitoneal administration of p-aminodiphenylamine (p-ADPA), an aromatic amine of wide industrial applications, / 42.5 mg/kg body weight for 180 days significantly decreased the activities of testicular lactate dehydrogenase and hyaluronidase and lactic acid content indicating arrest of spermatogenesis. Patchy necrosis of the testis was confirmed histopathologically. No change in testicular cholesterol, fructose content of coagulating glands and dorso-lateral prostate and activities of alkaline phosphatase in seminal vesicle and acid phosphatase in ventral prostate support normal androgenic status.

Animals↗

PubMed1991

Bio-elimination and organ retention profile of benzanthrone in scorbutic and non-scorbutic guinea pigs.

The retention and bio-elimination of benzanthrone (BA) in scorbutic and non-scorbutic guinea pigs was investigated to understand the protective role of ascorbic acid. Oral intubation of 14C-BA to scorbutic and non-scorbutic guinea pigs showed a total recovery of around 91% radioactivity through urine, faeces and tissues. Recovery of radiolabelled BA through urine (28%) and faeces (22%) up to 96 hrs averaged 50%, whereas residual radioactivity in liver and testis experienced a recovery of 29% in scorbutic animals. In non-scorbutic animals there was an increased recovery of radioactivity through urine (37%) and faeces (31%) with a decrease in retention (10%) in liver and testis. These results suggest that ascorbic acid facilitates the mobilization and bio-elimination of BA and thereby can decrease the toxicity of the compound.

Animals↗

PubMed1991

Interaction of benzanthrone with cytochrome P450: altered patterns of hepatic xenobiotic metabolism in rats.

Benzanthrone, an anthraquinone dye intermediate, is commonly used for the synthesis of a number of polycyclic vat and disperse dyes. Our prior studies have shown that benzanthrone can be metabolized by rat hepatic microsomal cytochrome P450 (P450) (Biochem. Int., 18, 1989, 1237). In this study, the interaction of benzanthrone with rat hepatic microsomal P-450 and its effect on xenobiotic metabolism have been investigated. Parenteral administration of benzanthrone (40 mg/kg body weight) for 3, 7, or 21 days caused no change in the relative body weight or organ weight of rats. The levels of P450 were found to be reduced (33%-50%) in all the benzanthrone-exposed animals at all the time periods. In vitro addition of benzanthrone caused a spectral change with oxidized P450 and concentration-dependent reduction in the carbon monoxide spectrum of dithionite-reduced P450. The addition of benzanthrone to hepatic microsomes prepared from phenobarbital-treated rats resulted in spectral changes characterized by an absorbance maximum at 397 nm indicative of type I binding. In vitro addition of benzanthrone showed a concentration-dependent inhibition of hepatic aminopyrine N-demethylase (APD) and ethoxyresorufin-O-deethylase (ERD) activities with respective I50 values of 9.5 x 10(-4) and 8.0 x 10(-5) M. However, the inhibition of aryl hydrocarbon hydroxylase (AHH) even at the highest concentration of benzanthrone (10(-2) M), was of the order of only 29%. In vivo administration of benzanthrone also led to the inhibition of APD, AHH, and ERD activities at all treatment times although the magnitude of inhibition was of a lower order.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Inhibition of leukotriene B4 formation in rat peritoneal neutrophils by an ethanolic extract of the gum resin exudate of Boswellia serrata.

Suspensions of rat peritoneal polymorphonuclear leukocytes (PMNL) elicited with glycogen were stimulated by calcium and ionophore to produce leukotrienes and 5-HETE from endogenous arachidonic acid (AA). We investigated the effect of ethanolic extracts of the gum resin exudate of Boswellia serrata. A concentration-dependent inhibition of LTB4 and 5-HETE production by different charges of exudate extracts were found. All products of the 5-lipoxygenase (5-LOx) from endogenous arachidonic acid (AA) in PMNL were reduced to the same extent by the extracts tested. The ethanolic extract of the gum resin also decreased 5-LOx mediated metabolisation of exogenously added AA to LTB4 and 5-HETE. Since steroidal-type anti-inflammatory drugs do not exert an immediate effect in the test system used, we conclude that the activity of the 5-LOx itself represents the side of inhibition by the gum resin extract. Therefore, an inhibition of 5-LOx catalysed mediator synthesis might be involved in the previously reported anti-inflammatory activity in vivo.

Animals↗

PubMed1991

Metabolic disposition of 14C-metanil yellow in guinea pigs.

The absorption, metabolism and excretion of 14C-metanil yellow was studied in guinea pigs. Following administration of a single po dose of 5 mg dye (7.6 mu Ci)/kg body weight, 83.4% was excreted through urine and feces within 96 h with the majority accounted for in feces. Liver, kidney and spleen did not have marked accumulation of counts, whereas testes and gastrointestinal tract retained 1.9 and 9.7% of the radioactivity, respectively. Analysis of urine and feces detected 2 azo-reduction metabolites of metanil yellow which were characterized by TLC and IR, NMR and mass spectroscopic studies as metanilic acid and p-aminodiphenylamine.

Animals↗

PubMed1990

Hypotensive action of a Coscinium fenestratum stem extract.

A 50% ethanol extract of Coscinium fenestratum stem material (AECF) has been found to possess hypotensive action in anaesthetised dogs, rats and guinea pigs in a dose-related pattern. The fall in blood pressure was not modified by alpha and beta adrenergic blockers, cholinergic and histaminergic antagonists or by ganglion blocking agents. The effect was more pronounced in spinal-transected animals. AECF non-specifically inhibited the pressor responses to epinephrine, norepinephrine, DMPP and depressor responses to acetylcholine and histamine. AECF failed to exhibit any hypotension when administered via cannula into the lateral cerebral ventricle. Given orally to mice, AECF did not exhibit grossly observable central nervous effects up to doses of 800 mg/kg. The oral LD50 was estimated to be 1200 mg/kg in mice.

Animals↗

PubMed1990

Testicular toxicity of di-n-butyl phthalate in adult rats: effect on marker enzymes of spermatogenesis.

Di-n-butyl phthalate (DBP) was administered to adult male rats by gavage at the doses of 250, 500 and 1000 mg/kg body weight/day for 15 days. A significant decrease in epididymal spermatozoa counts was observed at 500 and 1000 mg/kg doses of DBP. The activity of sorbitol dehydrogenase was found to be significantly decreased while that of lactate dehydrogenase, gamma-glutamyl transpeptidase, beta-glucuronidase, and glucose-6-phosphate dehydrogenase, significantly increased in the animals exposed to 500 and 1000 mg/kg of DBP. Decrease in the activity of acid phosphatase was also observed at all dose levels. Histopathological studies revealed marked degeneration of seminiferous tubules, further confirming testicular toxicity of DBP. The results suggest that testicular atrophy caused by DBP is associated with an alteration in the activities of enzymes related with specific events of spermatogenesis.

Animals↗