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P Srinivas

Publications and source records attributed to P Srinivas.

28 records · Page 2Linked to original sources
PubMed1998

Hypercalcaemia in patients with newly diagnosed tuberculosis in Malaysia.

SETTING: University Hospital, Kuala Lumpur, Malaysia. OBJECTIVE: To determine the incidence of hypercalcaemia in Malaysian patients with newly diagnosed tuberculosis (TB) before the commencement of antituberculosis treatment. DESIGN: A prospective study of consecutive patients with newly diagnosed bacteriologically and/or histologically proven tuberculosis in our institution from September 1994 to March 1996. RESULTS: Of a total of 120 patients (67 males, 53 females), 68 had pulmonary TB, nine had pulmonary and pleural TB, 18 had pleural TB without chest radiograph evidence of lung involvement, 16 had various other forms of extra-pulmonary TB and nine had disseminated TB. The mean age of the patients was 44.3 (+/-18.0) years. The mean albumin-adjusted serum calcium concentration was 2.53 (+/-0.22) mmol/l. Hypercalcaemia was present in 27.5% of the patients, but only 12% of these patients showed symptoms of hypercalcaemia. The type of TB and, in the case of pulmonary TB, the radiographic extent of lung involvement, had no effect on the serum calcium level. CONCLUSION: Hypercalcaemia is not uncommon among Malaysian patients with newly diagnosed TB, but it is rarely symptomatic.

Adolescent↗
PubMed1997

Site-specific nicking in vitro at ori T by the DNA relaxase of Tn5252.

Tn5252 is a promiscuous streptococcal element capable of madiating horizontal spread of multiple antibiotic resistance. To begin understanding the functional role of a transfer-related region in Tn5252, its nucleotide sequence was determined. Sequence of this 3. 3-kb DNA segment revealed the presence of six open reading frames. The predicted amino acid sequence of one of the open reading frames, ORF9, showed similarity to a predicted protein product of the lactococcal conjugative plasmid, pC1528. The deduced primary protein sequence of another, ORF4, showed strong structural similarity to conserved regions of various prokaryotic DNA relaxases that initiate conjugal transfer by strand- and site-specific cleavage at the transfer origin. A hybrid protein containing the ORF4 protein fused to the carboxyl terminal end of maltose binding protein was purified from Escherichia coli and found to specifically nick plasmids carrying a 2-kb DNA segment derived from the transposon. The nicking reaction is protein concentration-dependent. These results imply that the conjugative transposition of Tn5252 may involve rolling circle replication and transfer of a unique DNA strand.

Amino Acid Sequence↗
PubMed1989

Fast atom bombardment and tandem mass spectrometry for structure determination of cysteine, N-acetylcysteine, and glutathione adducts of xenobiotics.

Fast atom bombardment mass spectrometry (FAB/MS) and FAB combined with tandem mass spectrometry (MS/MS) were examined for their applicability to the structure determination of xenobiotics conjugated with the members of the glutathione family (glutathione, cysteine, and N-acetylcysteine). Comparisons between FAB/MS and thermospray MS data are made. FAB/MS is generally successful at generating molecular ion species under both positive and negative ion conditions. Upon collisional activation the adducts undergo characteristic cleavages around the sulfur providing structural information about the conjugate. The analysis of the N-acetylcysteine conjugate isolated from rat urine is presented as an example of the application of FAB/MS/MS to biological problems.

Acetylcysteine↗
PubMedDate not supplied

Metabolism of citral, an alpha,beta-unsaturated aldehyde, in male F344 rats.

Citral is a naturally occurring aliphatic aldehyde of the terpene series and is an isomeric mixture of geranial and neral. It is the main component (approximately 80%) of lemongrass oil, which is found in all citrus fruits and used extensively in the food, cosmetic, and detergent industries. In this study, urinary metabolites of citral in male F344 rats were characterized and identified by comparison with synthetic standards of known stereochemistry. Stereospecific oxidation of citral at the C-8 methyl was investigated, as was the hydrolytic sensitivity of biliary and urinary metabolites. For metabolite identification, urine was collected over dry ice for 24 hr after a single po 500 mg/kg dose of [14C]citral. Elimination in urine was rapid, with approximately 50% of the dose excreted within 24 hr. The urine was fractionated by reverse-phase HPLC, monitoring both radioactivity and UV. Synthetic standards were prepared; a comparison of their spectra with the isolated metabolites was used for identification. Citral was rapidly metabolized and excreted as metabolites, including several acids and a biliary glucuronide. Seven urinary metabolites were isolated and identified: 3-hydroxy-3,7-dimethyl-6-octenedioic acid; 3,8-dihydroxy-3,7-dimethyl-6-octenoic acid; 3,9-dihydroxy-3,7-dimethyl-6-octenoic acid; E- and Z-3,7-dimethyl-2,6-octadienedioic acid; 3,7-dimethyl-6-octenedioic acid; and E-3,7-dimethyl-2,6-octadienoic acid. Although citral is an alpha,beta-unsaturated aldehyde and has the potential of being reactive, the urinary metabolites of citral appear to arise from metabolic pathways other than nucleophilic addition to the double bond.

Acyclic Monoterpenes↗
PubMedDate not supplied

Metabolism of 1-chloro-2-methylpropene. Evidence for reactive chloroaldehyde intermediates.

Recent metabolism and disposition studies of 1-chloro-2-methylpropene (dimethylvinyl chloride) revealed cysteine and N-acetylcysteine conjugates of 3-chloro-2-methylpropenoic acid as the major metabolites. In the present studies we have investigated various steps in the metabolic pathway to determine which step was responsible for the observed trans (E)-stereochemistry of these metabolites. In vitro incubation studies of dimethylvinyl chloride with rat liver microsomes indicated cytochrome P-450-catalyzed aliphatic hydroxylation to be only stereoselective. Both (E)- and (Z)-3-chloro-2-methylpropenols formed in an identical ratio of 2:1 in incubations with microsomes from untreated male and female rats and phenobarbital-treated male rats. No alcohol formation was observed in incubations using microsomes from beta-naphthoflavone-treated male rats. Investigation of the subsequent conjugation reactions of sulfur nucleophiles with haloenoic carbonyl compounds showed that both (E)- and (Z)-3-chloro-2-methylpropenals reacted rapidly with N-acetylcysteine, the E-adduct being the sole product in either case. In contrast, the Michael reaction of the corresponding acids with N-acetylcysteine was very sluggish. Also, whereas the E-acid yielded exclusively the corresponding E-adduct, the Z-isomer afforded both Z- and E-conjugates in the ratio of 3:4. Glutathione S-transferases had poor activity towards conjugation of glutathione with these acids. Formation of only an E-glutathione conjugate could be observed from either the E- or Z-acid in these enzymatic reactions. Direct Michael reaction of glutathione with (E)-3-bromo-2-methylpropenoic acid, used in chemical synthesis of the conjugates, yielded both the E- and Z-adducts in the ratio of 95:5.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗