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Biomedical subjects

R Chowdhury

Publications and source records attributed to R Chowdhury.

At least 19 recordsLinked to original sources

12alpha-hydroxystigmast-4-en-3-one: a new bioactive steroid from Toona ciliata (Meliaceae).

In a bioassay guided phytochemical investigation of Toona ciliata (Fam. Meliaceae), a new hydroxy steroidal ketone, 12alpha-hydroxystigmast-4-en-3-one (1) was isolated from the petroleum ether extract of the plant together with two known steroids and three C-methyl coumarins. The structure of 1 was established by means of spectroscopic analyses. Compound 1 was found cytotoxic in a brine shrimp lethality bioassay with LC50 of 9.9 microg/ml and it also showed significant antitumor activity with Ti50 value of 14.1 microg/ml in a potato disc bioassay.

Animals↗

Triterpene constituents from the leaves of Melicope indica.

Phytochemical investigation of a petroleum ether extract of Melicope indica afforded two unusual pentacyclic triterpenes viz. neohop-13(18)-en-3alpha-ol (1) and fern-8(9)-en-3beta-ol (2) and the ubiquitous steroids, stigmasterol and sitosterol. The structures of 1 and 2 were independently elucidated on the basis of 2D NMR data and confirmed by comparison with those of related compounds. While compound 1 is a new natural product, this is the first report of occurrence of fern-8(9)-en-3beta-ol (2) from the genus Melicope.

Magnetic Resonance Spectroscopy↗

Alkaloids of Zanthoxylum budrunga.

Pseudophrynamine, lunacridine and the new compound 2-(2',4',6'-trimethyl-heptenyl)-4-quinozolone were isolated from the leaves of Zanthoxylum budrunga.

Alkaloids↗

Antibacterial activity and cytotoxicity of extractives from Uvaria hamiltonii stem bark.

The extracts as well as piperolactum C, goniopedaline, 6beta-hydroxystigmasta-4,22-dien-3-one and a mixture of cis- and trans-4-hydroxymelleins obtained from Uvaria hamiltonii stem bark exhibited mild to moderate in vitro antibacterial activity. The results obtained were compared with a standard antibiotic, kanamycin. In a brine shrimp lethality bioassay the pet-ether, dichloromethane, methanol extracts and a major alkaloid, piperolactum C were found to exhibit mild to moderate cytotoxicity.

Animals↗

Linkage disequilibrium mapping provides further evidence of a gene for reading disability on chromosome 6p21.3-22.

Linkage disequilibrium (LD) mapping was used to follow up reports of linkage between reading disability (RD) and an 18 cM region of chromosome 6p21.3-22. Using a two-stage approach, we tested for association between RD and 22 microsatellite markers in two independent samples of 101 (Stage 1) and 77 (Stage 2) parent/proband trios in which RD was rigorously defined. The most significant replicated associations were observed between combinations of markers D6S109/422/1665 (Stage 1, P=0.002 (adjusted for multiple testing); Stage 2, P=0.0001) and D6S506/1029/1660 (Stage 1, P=0.02 (adjusted), Stage 2, P=0.0001). The only two-marker association observed in both samples was with D6S422/1665 (P=0.01, 0.04). No single marker showed replicated association but D6S506 produced values of P=0.01 and 0.08 which were significant when combined (P=0.02). We observed weaker and less consistent evidence of association in a region of confirmed linkage to RD in previous studies. The most consistently significant haplotypic association D6S109/422/1665, showed association with single-word reading, spelling, phonological awareness, phonological decoding, orthographic accuracy and random automised naming, but not with vocabulary or Attention Deficit Hyperactivity Disorder. Our findings strongly support the presence of a gene contributing to RD in a region of chromosome 6 between markers D6S109 and D6S1260, but do not rule out the presence of a gene between D6S1556 and MOG.

Adolescent↗

Novel derivatives of 3-(dipropylamino)chroman. Interactions with 5-HT1A and D2A receptors.

Novel 8-aryl and 8-aroyl substituted derivatives of 3-(dipropylamino)chroman are described. The compounds have been prepared by a palladium catalyzed reaction of iodoarenes and a stannylated derivative of [eta6-3-(dipropylamino)chroman]Cr(CO)3. Several of the compounds have high affinity for 5-HT1A receptors whereas the affinity for D2A receptors is lower, the 8-arylated derivatives being slightly more potent than the 8-aroylated analogues.

Animals↗

The effect of leptin on Lep expression is tissue-specific and nutritionally regulated.

Leptin, the product of the Obese (Lep) gene, orchestrates behavioral and metabolic responses to nutrient intake. Here, we demonstrate tissue-specific autoregulation of Lep. Moderate increases in circulating leptin considerably decreased Lep expression in adipose tissue and induced lep expression in skeletal muscle, a tissue that normally does not express this gene. Changes in nutrient availability resulted in rapid alterations in Lep autoregulation. These findings demonstrate negative feedback regulation of Lep in fat, and indicate that leptin secretion can function as a vehicle of 'cross-talk' between adipose tissue and skeletal muscle, leading to tissue-specific modulation of the 'leptin signal'.

Adipose Tissue↗

Role of DnaK in in vitro and in vivo expression of virulence factors of Vibrio cholerae.

The dnaK gene of Vibrio cholerae was cloned, sequenced, and used to construct a dnaK insertion mutant which was then used to examine the role of DnaK in expression of the major virulence factors of this important human pathogen. The central regulator of several virulence genes of V. cholerae is ToxR, a transmembrane DNA binding protein. The V. cholerae dnaK mutant grown in standard laboratory medium exhibited phenotypes characteristic of cells deficient in ToxR activity. Using Northern blot analysis and toxR transcriptional fusions, we demonstrated a reduction in expression of the toxR gene in the dnaK mutant strain together with a concomitant increase in expression of a htpG-like heat shock gene that is located immediately upstream and is divergently transcribed from toxR. This may be due to increased heat shock induction in the dnaK mutant. In vivo, however, although expression from heat shock promoters in the dnaK mutant was similar to that observed in vitro, expression of both toxR and htpG was comparable to that by the parental strain. In both strains, in vivo expression of toxR was significantly higher than that observed in vitro, but no reciprocal decrease in htpG expression was observed. These results suggest that the modulation of toxR expression in vivo may be different from that observed in vitro.

Animals↗

Prolyl hydroxylase and tissue inhibitor of metalloproteinase in pure pancreatic juice in patients with chronic pancreatitis.

Prolyl hydroxylase is a key enzyme in collagen synthesis, and tissue inhibitor of metalloproteinase (TIMP) is known to suppress collagenolytic enzymes. To see whether the levels of these two enzymes in serum and human pure pancreatic juice (PPJ) are good indicators of pancreatic fibrosis in chronic pancreatitis (CP), we examined 15 controls, 14 alcoholics without evident pancreatic diseases (7 current drinkers and 7 former drinkers), and 19 patients with CP. Levels of the two enzymes were determined by a sandwich enzyme immunoassay method. TIMP-1 levels in PPJ were significantly higher in patients with CP than in controls and alcoholics, with overlap in only a few exceptional patients. A significant inverse correlation between TIMP-1 and bicarbonate output in PPJ was observed. Prolyl hydroxylase levels in PPJ, in contrast, were significantly higher in current drinkers than in patients with CP, controls, and former drinkers, with overlap in only a few exceptional patients with relapsing CP. Identical results were obtained even when the enzyme levels were expressed as nanograms per milligram of protein. Serum levels of prolyl hydroxylase and TIMP-1 showed no significant differences among controls, current alcoholics, former alcoholics, and patients with CP. These results indicate that the raised level of TIMP-1 in PPJ, unlike that of prolyl hydroxylase, is a good indicator of pancreatic fibrosis in CP.

Adult↗

Risk of job-related injury among construction laborers with a diagnosis of substance abuse.

This study attempts to determine whether a diagnosis of substance abuse among construction laborers is associated with an increased risk of work-related injuries. Records for construction laborers in Washington State who were covered by health insurance through the local union were matched against workers' compensation records in the Washington State Department of Labor and Industries. Using the health insurance records, we identified those who had a diagnosis of substance abuse during the two-year period 1990-1991. Using the workers' compensation records, we were then able to compare injury rates for those with substance abuse diagnoses with the rates for those without such diagnoses. The total cohort consisted of 7,895 laborers. Among the 422 who had a substance abuse diagnosis, the rate of time-loss injuries per 100 full-time equivalent workers was 15.1, compared with 10.9 among the remainder of the cohort. Most of the difference appeared in the 25-34-year age group, in which the rate of injury per 100 full-time equivalent workers was 23.6 for substance abusers, compared with a rate of 12.2 for non-substance abusers, for a statistically significant relative risk of 1.93. The study suggests that younger workers might be an appropriate target for interventions aimed at reducing the level of substance abuse as a way of preventing injuries on the job. Studies by others have indicated some degree of success in this direction through the use of employee assistance programs in which the worker is referred to specific programs or providers for treatment. The state legislature in Washington has recently passed legislation providing incentives for the use of employee assistance programs. More effort is needed, however, to evaluate the effectiveness of such programs.

Accident Proneness↗

The rpoH gene encoding sigma 32 homolog of Vibrio cholerae.

The Vibrio cholerae rpoH gene coding for the heat-shock sigma factor, sigma 32, has been cloned and shown to functionally complement Escherichia coli rpoH mutants. The nt sequence of the gene has been determined and the deduced aa sequence is more than 80% homologous to the E. coli rpoH gene product. Downstream of the V. cholerae rpoH gene, an unidentified dehydrogenase gene (udhA) is present on the opposite strand facing rpoH. The predicted secondary structure of the 5'-proximal region of V. cholerae rpoH mRNA is apparently different from the conserved secondary structures of the rpoH mRNA reported for several bacterial species. The 'RpoH box', a stretch of 9 aa (QRKLFFNLR) unique to sigma 32 factors, and the 'downstream box' sequence complementary to a part of the 16S rRNA, have been detected.

Amino Acid Sequence↗

Bile affects production of virulence factors and motility of Vibrio cholerae.

The effect of bile on the expression of cholera toxin (CT) and the major subunit of the toxin-coregulated pilus (TcpA) and on motility was examined in the Vibrio cholerae O1 classical-biotype strains 0395 and 569B. Although the motility of the cells increased significantly in the presence of bile, transcription of the ctxAB genes, encoding CT, and of the tcpA gene was drastically reduced. In toxR mutant strains, motility is higher than in the wild-type strain and was further increased, by about 150%, in the presence of bile. Bile represses CT production in strain 569B-55, a toxR mutant of strain 569B, which normally produces more than 80% of the amount of CT synthesized in the wild-type cells. These results suggest that bile may target some factor other than ToxR that is involved in the regulation of CT production and motility. Bile has no effect on the relative amounts of the two outer membrane porins, OmpU and OmpT, which are under ToxR control.

Animals↗

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Acquired Immunodeficiency Syndrome↗

Investigations into the mechanism of action of a novel nitric oxide generator on cellular respiration.

Nitric oxide may regulate cellular respiration by competition with oxygen at mitochondrial cytochrome oxidase. Using an astrocyte-derived cell line, we have compared the mechanism of action of the nitric oxide-generating compound Roussin's black salt with that of sodium nitroprusside on cellular oxygen consumption. Intense light exposure induced the release of large quantities of nitric oxide from both of the donor compounds. However, in room light only Roussin's black salt generated low levels of the radical. Simultaneous measurement of oxygen consumption and of nitric oxide production demonstrated that sodium nitroprusside only had inhibitory actions when exposed to intense light (nitric oxide release), whereas Roussin's black salt had inhibitory actions in room light. Extracellular haemoglobin did not prevent the inhibition of respiration rate induced by Roussin's black salt even though stimulation of nitric oxide release on light exposure was markedly reduced. Preincubation of cells with Roussin's black salt and subsequent measurement of levels of light-liberated nitric oxide demonstrated that the compound was rapidly internalised. The uptake of sodium nitroprusside was minimal. These data suggest that, in contrast to sodium nitroprusside, the cellular internalisation of Roussin's black salt allows site-directed nitric oxide release and very effective inhibition of cellular respiration.

Animals↗

Heat shock response and heat shock protein antigens of Vibrio cholerae.

Sixteen heat shock proteins (Hsps) have been identified in the hypertoxinogenic strain 569B of Vibrio cholerae which are synthesized in response to small and large elevations of temperature. The induction of the Hsps is necessary for the cells to survive the deleterious effects of heat. There is no difference in the pattern of induction of the Hsps in V. cholerae strains varying in levels of toxinogenicity. One of the major low-molecular-mass Hsps, a 16-kDa protein, is preferentially degraded following shift down of temperature. This protein is induced at a much lower level at high temperatures in cells maintained in the laboratory for a prolonged period. The only Hsp located in the outer membrane of V. cholerae cells is a 23-kDa protein. Western immunoblot analysis with human immune sera collected from convalescent cholera patients revealed that this protein is markedly immunogenic. The human immune serum also reacted with the 69- and 16-kDa major Hsps and the 88-, 66-, and 46-kDa Hsps but not with the 61-kDa major Hsp identified as the groEL gene product. All major Hsps reacted with rabbit anti-V. cholerae sera. Ethanol stress leads to the induction of four of the major Hsps and three additional proteins.

Adaptation, Biological↗

Prevalence of dental caries in handicapped children of Calcutta.

A total of 1042, 3-14-year-old children with different types of handicapping conditions when recorded for dental caries using WHO 1987 caries recording index revealed that dental caries experience was higher in handicapped children than normal children. The prevalence of dental caries was highest in mentally retarded children followed by cerebral palsied, blind, epileptic, physically handicapped, children with Down's syndrome and deaf and dumb. Higher deft+DMFT was recorded in mandibular teeth compared to maxillary teeth.

Adolescent↗