Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Smokeless tobacco habits are associated with a high incidence of oropharyngeal cancer in India. Hence, the biological effects of occupational exposure to smokeless tobacco used for making bidis (the Indian version of cigarettes) were studied in 2 groups of bidi rollers designated BR-K and BR-S and in control subjects with no tobacco habits. Specific tobacco exposure and the electrophilic burden were determined by estimating urinary cotinine and thioethers respectively. Urine mutagenicity was tested with the Ames assay using Salmonella typhimurium strains TA98 and TA100. While cotinine was not detected in control samples, the mean cotinine levels (mmole/mole creatinine) in the BR-K and BR-S groups were 0.79 +/- 0.30 and 0.09 +/- 0.03 respectively. Urinary thioether excretion (mmole/mole creatinine) was significantly elevated in the BR-S group 4.59 +/- 0.52; p less than 0.001) but it was lower in the BR-K group (0.54 +/- 0.08; p less than 0.001) compared to the control (1.83 +/- 0.34). Furthermore, beta-glucuronidase-treated samples from both groups of bidi rollers exhibited increased mutagenicity to TA98 compared to the control group; in addition, BR-S samples exhibited direct mutagenicity to TA98. The results show that occupational tobacco exposure modulates the glutathione conjugation pathway and increases the mutagenic burden of bidi rollers.
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PMID:Biological monitoring of bidi rollers with respect to genotoxic hazards of occupational tobacco exposure. 192 57

Amino acid analysis of oxidized or reduced and carboxymethylated beta-glucuronidase have shown the presence of 24 cysteic acid or S-carboxymethylcysteine residues respectively per mole of the tetrameric enzyme. Titration of sulfhydryl groups gave eight cysteine residues, and by difference 16 half-cystine residues per mole. Six peptides containing radiolabelled cysteine residues were isolated from pepsin and chymotrypsin digest of reduced and S-carboxymethylated beta-glucuronidase by ion-exchange chromatography or gel filtration, followed by paper ionophoresis and paper chromatography. The peptides were analysed for amino acids and sequenced by the dansyl-Edman procedure. Peptides containing cysteic acid were selectively recovered from thermolysin digests of performic acid-oxidized glucuronidase. The amino acid sequences confirmed that there were only six different peptide sequences containing either cysteine or half-cystine residues in the tetrameric enzyme, supporting the presence of four identical subunits. These sequences wer: (A)-Val-Asx-Val-Ile-Cys-Val-Asx-Ser-Tyr- (B)-Gly-Asx-Leu-Cys-Ser-Gly- (C)-Phe-Val-Val-Ile-Asx-Glx-Cys-Pro-Gly-Val-Gly- (D)-Val-Val-Cys-Leu- (E)-Gln-Ser-Gly-Cys-Leu-Val-Lys-Gly-Tyr- (F)-Cys-Asp-Arg-Tyr-Gly-Ile-Val-Val-.
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PMID:Amino acid sequences containing cysteine or half-cystine residues in beta-glucuronidase. 721 58

A benztropine RIA based on polyclonal antisera raised in New Zealand white rabbits has been developed. The drug-protein conjugates employed had a variety of moles of benztropine hemisuccinate coupled per mole of protein (bovine serum albumin or bovine thyroglobulin). Six antisera were developed and the one with the highest titer was further evaluated for its cross reactivity to N-desmethylbenztropine (4%) and the antipsychotic agents fluphenazine, flupenthixol, chlorpromazine, and haloperidol (all < 1%). The selected antiserum demonstrated sufficient sensitivity to measure benztropine from 0.156 to 100 ng/mL plasma in a 200-microL plasma sample, with a mean CV of < 6%. The RIA was applied to the analysis of steady-state plasma samples obtained from patients undergoing treatment with benztropine and plasma samples obtained from human volunteers and dogs orally dosed with the drug. Both the human and dog plasma samples, when analyzed after hydrolysis with beta-glucuronidase/sulfatase, demonstrated increments in benztropine concentrations, suggesting the drug may be undergoing biotransformation to phase II metabolite(s). In addition, when benztropine was selectively extracted from the unhydrolyzed plasma samples, there was a significant decrease in drug level, which further suggested that the antiserum cross reacted with phase II metabolite(s). The shape of the plasma concentration versus time profile obtained from the dog studies suggested that the drug might also undergo enterohepatic recycling.
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PMID:Development of a sensitive and specific radioimmunoassay for benztropine. 825 87