To which extent Ureaplasma urealyticum (mycoplasma) genital infection is responsible for male infertility.
Explore the source record for details and available documents.
Genital Diseases, Male↗
Biomedical subjects
S K Roy
Publications and source records attributed to S K Roy.
Human liver oxidative metabolism of O6-benzylguanine.
The oxidation of O6-benzylguanine, an inactivator of O6-alkylguanine-DNA alkyltransferase, was examined using human liver cytosol, microsomes, and several P450 isoforms. Incubation of O6-benzylguanine with human liver cytosol resulted in the formation of O6-benzyl-8-oxoguanine, which was inhibited by menadione, a potent inhibitor of aldehyde oxidase. Inhibition by allopurinol, a xanthine oxidase inhibitor, was less dramatic. Oxidation of O6-benzylguanine also occurred with pooled human liver microsomes and was inhibited by both furafylline and troleandomycin, selective inhibitors of CYP1A2 and CYP3A4, respectively. Human P450s CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2E1, and CYP3A4 expressed in Hep G2 hepatoma cells using vaccinia virus vectors were incubated with 10 or 200 microM O6-benzylguanine. At 10 microM, O6-benzylguanine was oxidized primarily by CYP1A2 and to a lesser extent by CYP3A4. However, an appreciable increase in CYP3A4 contribution was noted at 200 microM. CYP1A2 exhibited a more than 200-fold higher relative catalytic activity (Vmax/Km) compared with CYP3A4. Therefore, at therapeutically relevant concentrations of O6-benzylguanine, CYP1A2 could be primarily involved in its oxidation since it shows a much lower Km value (1.3 microM) than CYP3A4 (52.2 microM) and cytosol (81.5 microM). However, one would expect interindividual variation in the extent of oxidation of O6-benzylguanine depending on the levels of aldehyde oxidase, CYP1A2, and CYP3A4.
Carcinoma, Hepatocellular↗
Bile, bacteria, and gallbladder carcinogenesis.
Explore the source record for details and available documents.
Bile↗
An XYY male with acute lymphoblastic leukemia.
Explore the source record for details and available documents.
Child↗
Peroxidative xenobiotic oxidation by partially purified peroxidase and lipoxygenase from human fetal tissues at 10 weeks of gestation.
1. Present study reports the ability of partially purified peroxidase and lipoxygenase from human fetal tissues at 10 weeks of gestation to oxidize selected xenobiotics in vitro. 2. Peroxidase was found to oxidize four different chemicals in the presence of H2O2. Sodium azide and potassium cyanide inhibited peroxidase activity towards guaiacol in a concentration-dependent manner. 3. The dioxygenase and co-oxidase activities of lipoxygenase towards linoleic acid and four model xenobiotics, respectively, were observed. Both the catalytic activities of lipoxygenase were significantly inhibited by < 1.0 microM nordihydroguaiaretic acid. 4. These findings suggest that peroxidase and lipoxygenase may be important pathways for peroxidative xenobiotic oxidation in human fetal tissues.
Female↗
Urine of tobacco/areca nut chewers causes genomic damage in Chinese hamster ovary cells.
The chromosome-damaging effects of urine concentrates (UCs) from tobacco plus areca nut (T/AN) chewers (a highly popular habit and a major risk factor for oral cancer in India) were evaluated on Chinese hamster ovary (CHO) cells employing two cytogenetic end-points, namely chromosome aberration (CA) and sister chromatid exchange (SCE) frequencies. Urine creatinine levels were comparable between controls and T/AN chewers. CA and SCE frequencies in CHO cells were found to be elevated significantly (P < 0.001) following treatment with UCs prepared from T/AN chewers (UC-T/AN chewers) as well as with UCs of non-chewer controls (UC-control subjects). Moreover, elevation of these two parameters by UC-T/AN chewers was significantly higher in comparison to that of UC-controls. The results of the present study indicated that besides the oral cavity, which is a target organ for T/AN chewers, mutagens/carcinogens in tobacco and areca nut might be playing a causative role in cancer of the urinary bladder as well.
Animals↗
Molecular epidemiology of toxigenic Vibrio cholerae in Bangladesh studied by numerical analysis of rRNA gene restriction patterns.
Cholera is endemic in Bangladesh, and a regular seasonal pattern of cholera epidemics occurs. We examined the clonal relationships among 103 clinical and environmental Vibrio cholerae isolates belonging to O1, O139, or non-O1 non-O139 serogroups isolated during epidemic and interepidemic periods in Bangladesh and compared them with those of 51 V. cholerae isolates from four countries in Asia and Africa. These studies were done by a computer-assisted numerical analysis of the restriction endonuclease cleavage patterns of rRNA genes (ribotypes). Unweighed pair-group cluster analysis of BglI- and HindIII-generated band patterns revealed 16 clusters. Ribotypes were defined as clusters of strains possessing > 98% similarity. The results showed that 154 isolates could be differentiated into 15 different ribotypes, and strains belonging to 3 of these ribotypes (ribotypes I, V, and VIIIA and VIIIB) were isolated more frequently during the epidemic periods than during interepidemic periods in Bangladesh. Classical vibrios belonged to six different ribotypes (ribotypes I to VI), with a mean similarity coefficient of 0.84, and the El Tor vibrios belonged to five different ribotypes (ribotypes VIIIA and IX to XII), with a mean similarity coefficient of 0.82. A single clone of El Tor vibrios (ribotype XII) was resident in Tanzania, whereas Nigeria, Syria, and India shared toxigenic El Tor strains with Bangladesh. Cholera toxin (CT)-positive O139 vibrios isolated from Bangladesh and India belonged to a single ribotype (ribotype VIIIB) and were > 98% similar to one of the ribotypes of El Tor vibrios (ribotype VIIIA), but a CT-negative O139 vibrio from Argentina (ribotype XIII) was < 75% similar to the same cluster of El Tor vibrios, thus suggesting more than one possible origin for O139 vibrios. Strains belonging to the same ribotypes (ribotypes VIII to X) were isolated from both patients and surface water in Bangladesh, indicating possible transmission through surface water. A clone of a CT-positive environmental isolate of non-O1 V. cholerae (ribotype VII) was found to be closely related (76.3% similarity) to a clone of classical vibrios (ribotype I) and was only between 27.2 and 56.1% similar to clusters of El Tor, O139, and two other non-O1 nontoxigenic clones.
Bacterial Typing Techniques↗
Transforming growth factor-beta receptor type II expression in the hamster ovary: cellular site(s), biochemical properties, and hormonal regulation.
The hormonal regulation of transforming growth factor-beta (TGF beta) receptor type II (T beta RII) protein expression in the hamster ovary was evaluated by [125I]TGF beta 1 cross-linking, immunolocalization, and immunoprecipitation of T beta RII using receptor-specific antibodies. Granulosa cells of preantral and antral follicles, and interstitial and luteal cells showed strong signal on day 1 at 0900 h; interstitial and luteal staining was maximum. Immunoreactivity in the interstitium fell by day 2 and reappeared on day 4. A sharp reduction of immunostaining occurred after the gonadotropin surge. In hypophysectomized hamsters, FSH induced T beta RII in both granulosa and interstitial cells, but LH was effective only on interstitial cells. Whereas 17 beta-estradiol (17 beta E2) efficiently induced interstitial T beta RII, progesterone severely attenuated E2 induction of receptor protein. Apart from a membrane-associated form of T beta RII, a novel cytosolic form of T beta RII was detected. The cytosolic T beta RII is a glycoprotein with N'-linked oligosaccharides, like its membrane counterpart, possessing serine-threonine kinase activity that is TGF beta sensitive. The membrane-associated T beta RII disappeared on day 2 of the cycle, but reappeared by day 4 in the morning. A good correlation was found with the cytosolic form. Hypophysectomy diminished, whereas FSH, LH, and 17 beta E2 increased both forms of T beta RII; however, LH induction of the cytosolic form was greater than that by FSH. Progesterone prevented T beta RII protein integration to the membrane, but testosterone and dihydrotestosterone were also effective in T beta RII induction in the membrane. A high E2/progesterone ratio was an important determinant in T beta RII induction in the cell membrane. These results provide the first direct evidence for the presence of a functional T beta RII in the ovary. The receptor is a serine/threonine kinase and exists as distinct cytosolic and membrane forms that show a unique relationship during the estrous cycle. The induction of ovarian T beta RII is critically and temporally influenced by gonadotropins and ovarian steroid hormones.
Animals↗
Pharmacokinetics of O6-benzylguanine in rats and its metabolism by rat liver microsomes.
O6-Benzylguanine is an effective inhibitor of the DNA repair protein, O6-alkylguanine-DNA alkyltransferase, and enhances the effectiveness of 1,3-bis(2-chloroethyl)-1-nitrosourea in cells in culture and animal tumor models. To prepare O6-benzylguanine for clinical trials and to determine the availability and disposition of O6-benzyl-7,8-dihydro-8-oxoguanine (O6-benzyl-8-oxoguanine), its major metabolite, pharmacokinetic parameters of these compounds were investigated in male Sprague-Dawley rats. Noncompartmental pharmacokinetic parameters were determined following intravenous administration of O6-benzylguanine or O6-benzyl-8-oxoguanine in rats. Half-life, clearance, and volume of distribution were respectively, 1.6 hr, 160 ml/hr/kg, and 405 ml/kg for O6-benzylguanine, and 1.2 hr, 312 ml/hr/kg, and 507 ml/kg for O6-benzyl-8-oxoguanine. At least 37% of O6-benzylguanine was converted to O6-benzyl-8-oxoguanine after administration of O6-benzylguanine. Renal excretion accounted for 8 and 62% of the administered O6-benzylguanine and O6-benzyl-8-oxoguanine, respectively. Administration of phenobarbital to rats before O6-benzylguanine resulted in a 17- to 19-fold increase in the amount of oxidized product in the urine. Kinetic constants, KM and Vmax were estimated as 19.6 microM and 0.02 nmol/min/mg protein and 13.4 microM and 0.96 nmol/min/mg protein, for uninduced and induced rat liver microsomes, respectively. The use of inhibitors of cytosolic enzymes, xanthine oxidase, and aldehyde oxidase indicated that aldehyde oxidase is primarily involved in the cytosolic oxidation of O6-benzylguanine.
Animals↗
Superoxide generation by lipoxygenase in the presence of NADH and NADPH.
The ability of soybean lipoxygenase to mediate NAD(P)H oxidation and concomitant superoxide generation in the presence of linoleic acid was examined. At optimum pH of 8.3, lipoxygenase oxidized both NADH and NADPH in the presence of 700 microM linoleic acid. The oxidation of NAD(P)H was biphasic. The initial rates of NADH and NADPH oxidation were 130 and 140 nmoles/min/nmole of enzyme respectively and the corresponding final rates were 344 and 350 nmoles/min/nmole of enzyme. The apparent Km values calculated for NADH and NADPH oxidation were 13 microM and 117 microM respectively. NAD(P)H oxidation was accompanied by the reduction of either ferricytochrome c or nitroblue tetrazolium (NBT) which can be abolished (approx. 85%) by superoxide dismutase (SOD) suggesting the generation of superoxide anion radicals. Under optimal conditions, the rates of superoxide generation, measured as the SOD-inhibitable reduction of ferricytochrome c, were 325 and 235 nmoles/min/nmole of enzyme for NADH and NADPH respectively. Under identical experimental conditions, the SOD-inhibitable NBT reduction rates were 308 and 210 nmoles/min/nmole of enzyme for NADH and NADPH respectively. Both NADH and NADPH could be regenerated after oxidation using the appropriate dehydrogenases. These results strongly suggest that lipoxygenase not only generates lipid hydroperoxides but can also generate superoxide via oxidation of pyridine nucleotides and may, therefore, significantly contribute to oxidative stress in cells.
Alcohol Dehydrogenase↗
Synthesis of oligodeoxynucleoside methylphosphonates utilizing the tert-butylphenoxyacetyl group for exocyclic amine protection.
Oligodeoxynucleoside methylphosphonates were synthesized using methylphosphonamidite monomers incorporating the base labile tert-butylphenoxyacetyl (t-BPA) protecting group on the exocyclic amines of dA, dC, and dG. Synthesis of the oligodeoxynucleoside methylphosphonates required only a small change in oxidation solution from standard DNA synthesis. The increased lability of the t-BPA group over the standard benzoyl and isobutyryl protection permitted the use of milder basic deprotection conditions. Deprotection of the nucleoside bases and release from support was best accomplished by a short treatment with ammonia saturated methanol. This procedure resulted in minimal backgone degradation with no base modifications. Analysis of the resultant oligodeoxynucleoside methylphosphonates by reverse phase HPLC and MALDI-TOF mass spectroscopy are described.
Acylation↗
Photoidentification of mannosyltransferases of dolichol cycle in the mammary gland. Purification and characterization of GDP-Man:Man beta 1-->4GlcNAc beta 1-->4GlcNAc-P-P-dolichol mannosyltransferase.
Glc3Man9GlcNAc2-P-P-Dol serves as the major precursor for the biosynthesis of asparagine-linked glycoproteins in eukaryotes. The first 5 of the 9 mannosyl residues during the assembly of the oligosaccharide moiety within the dolichol cycle in the endoplasmic reticulum are incorporated directly by the action of GDP-Man-requiring mannosyltransferases while the remaining last 4 mannosyl residues are transferred by Man-P-Dol-requiring enzymes. In an earlier study (Shailubhai, K., Illeperuma, C., Tayal, M., and Vijay, I. K. (1990) J. Biol. Chem. 265, 14105-14108), we identified the enzyme UDP-Glc:Dol-P glucosyltransferase by photolabeling rat mammary microsomes with 5-N3-[beta-32P]UDP-Glc. Applying a similar strategy, GDP-hexanolamine-125I-azidosalicylic acid, an analog of GDP-Man, was found to photolabel two polypeptides of 37 and 69 kDa among the microsomal proteins of the rat mammary gland. A differential ammonium sulfate saturation (60-80%) of the detergent-solubilized microsomal proteins enriched the 69-kDa polypeptide. Photolabeling of this polypeptide was specifically inhibited by guanine-containing nucleotides and nucleotide-sugars and was associated with a GDP-Man-requiring mannosyltransferase. The mannosyltransferase was purified nearly 16,000-fold and shown to contain the 69-kDa polypeptide. The purified enzyme catalyzes the transfer of [14C]Man from GDP-[14C]Man to Man beta 1-->4GlcNAc beta 1-->4GlcNAc-P-P-Dol in alpha 1,3-linkage to give [14C]Man alpha 1-->3Man beta 1-->4GlcNAc beta 1-->4GlcNAc-P-P-Dol as the product. Antibodies raised against the 69-kDa polypeptide removed the enzymatic activity from the detergent extract of the rat mammary microsomes and reacted specifically with a polypeptide band of the same size on immunoblots. The purified enzyme showed a pH optima of 7.4-7.8, Km approximately 4 microM for GDP-Man, approximately 2-fold activation by phosphatidylcholine, and a strong inhibition by sulfhydryl-selective reagents, N-ethylmaleimide and p-chloromercuribenzoate. The availability of the highly purified enzyme and a monospecific antibody should allow its molecular cloning for investigating the regulation of the machinery for protein N-glycosylation upon hormonally modulated growth and differentiation of the mammary gland during its ontogeny.
Animals↗
Management of acute diarrhoea in diabetic patients using oral rehydration solutions containing glucose, rice, or glycine.
OBJECTIVE: To assess the risk of hyperglycaemia with two standard oral rehydration solutions that contain carbohydrate compared with a carbohydrate free solution during rehydration of diabetic patients with acute diarrhoea. DESIGN: Prospective randomised allocation to one of three oral rehydration solutions (World Health Organisation (glucose), rice, or glycine) groups after admission to hospital with acute diarrhoea. SETTING: Dhaka hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh. SUBJECTS: 45 diabetic patients aged between 15 and 60 who had had diarrhoea for fewer than three days on admission. MAIN OUTCOME MEASURES: Fluctuation of blood glucose concentrations measured three times a day, daily stool output, and time taken for recovery from diarrhoea. RESULTS: There were no significant differences in blood glucose concentrations, stool output, and duration of recovery from diarrhoea among the three groups. CONCLUSIONS: Oral rehydration solutions containing glucose, rice powder, or glycine can be safely administered to diabetic patients with acute diarrhoea and some dehydration.
Acute Disease↗
Regulation of ovarian follicular development: a review of microscopic studies.
Follicular development in the mammalian ovary is a complex process regulated by an orchestrated action of the pituitary gonadotropins, e.g., follicle stimulating hormone (FSH) and luteinizing hormone (LH), and local ovarian factors, such as peptide growth factors and steroids. The mechanism of endocrine/paracrine/autocrine regulation of folliculogenesis (i.e., cell proliferation and functions) has been addressed largely by biochemical means. However, the availability of immunological and molecular tools now enables us to undertake critical microscopic studies revealing the ovarian cell-type specific synthesis and/or accumulation of many of these local peptide modulators, their roles in the proliferation and differentiation of follicular cells, and their regulation by gonadotropins and local factors. The objective of this review is to provide a comprehensive yet complete picture of the endocrine/autocrine regulation of mammalian folliculogenesis as revealed by microscopic studies. Efforts have been made to include adequate research information relevant to update our understanding of the process of follicular development; however, to maintain the brevity, many equally important studies could not be included. This review confirms that FSH and LH are still the primary stimuli for follicular development. However, it is clear that the actions of these hormones at the cell level involve a host of peptide factors which are produced locally by different follicular cell types and which are powerful modulators of gonadotropin actions. The temporal and spatial expression of the genes of these modulators, the synthesis of active factors, their interactions, and the dynamics of their receptors on the follicular cell surface may be the ultimate determinants of cellular events which are crucial to coordinated growth and differentiation of follicular cells leading to folliculogenesis and ovulation.
Animals↗
Dioxygenase and co-oxidase activities of rat hepatic cytosolic lipoxygenase.
The role of rat liver cytosolic lipoxygenase in the metabolism of benzidine was studied using linoleic acid as a cosubstrate. Under optimum assay conditions, cytosolic dioxygenase activity in the presence of 3.5 mM linoleic acid at pH 7.2 was 74.07 +/- 1.43 nmoles/min/mg protein. Benzidine was oxidized at the rate of 3.18 +/- 0.13 nmoles/min/mg cytosolic protein to benzidine diimine at pH 7.2 in the presence of 3.65 mM linoleic acid. Both dioxygenase and co-oxidase reactions were inhibited by nordihydroguaiaretic acid in a concentration-dependent manner. Partially purified preparations of rat liver lipoxygenase, free of hemoglobin, exhibited a dioxygenase activity of 223.1 +/- 65.9 nmoles/min/mg protein and co-oxidase activity of 6.1 +/- 0.5 nmoles/min/mg protein toward benzidine. These results suggest that hepatic lipoxygenase may play an important role in the metabolism of this hepatocarcinogen.
Animals↗
Lipid peroxidation product in bile from patients with carcinoma of the gallbladder: a preliminary study.
Samples of gall bladder bile from patients with and without carcinoma of the gallbladder were examined for lipid peroxidation (free radical oxidation) products. 4-hydroxynonenal (HNE) was found in higher concentration in the bile of patients with carcinoma of the gall bladder. There was also a highly significant difference in the concentration of HNE among carcinoma of the gall bladder, cholelithiasis and control group of patients with miscellaneous abdominal disorders. This is the first study of lipid peroxidation in carcinoma of the gall bladder.
Aldehydes↗
Glutathione S-transferase mediated detoxification and bioactivation of xenobiotics during early human pregnancy.
Glutathione S-transferase (GST) with activity towards CDNB as a substrate from human intrauterine conceptual tissues (HICT) at 6-10 weeks of gestation was purified approximately 200-fold by GSH coupled Sepharose 4B affinity chromatography. The preparations of affinity purified HICT-GST were used in all the experiments. There was no significant difference in specific activity of GST towards CDNB among 6-, 8- and 10-week-old HICT. GST specific activity decreased with an increase in the gestational age using p-nitrobenzyl chloride and 3,4-dichloro-1-nitrobenzene as the second substrate. Similarly, the lower the gestational age, the higher was the degree of GST mediated ethylene dibromide (EDB) conjugation with GSH. Covalent binding of [14C]EDB to DNA and protein was greater in the presence of HICT-GST at 6 weeks gestation than that at 10 weeks gestation. These results suggest that HICT possess a significant amount of GST capable of detoxification or activation of xenobiotics during the critical organogenesis period.
DNA-Binding Proteins↗
Persistent diarrhoea: efficacy of a rice-based diet and role of nutritional status in recovery and nutrient absorption.
A diet based on rice powder, soya-bean oil, glucose, egg-white and salts was given to twenty-six patients of different nutritional status aged 4-18 months with persistent diarrhoea and twenty-five age-matched controls without diarrhoea. Clinical response was monitored during 1 week of dietary treatment and absorption of macronutrients was estimated during a 72 h balance study. Twenty-one patients (81%) recovered from diarrhoea within 7 d. There were significant relationships between nutritional indices, recovery, and absorption of total energy, fat and N. The absorption of fat, protein and carbohydrate in the better nourished controls without diarrhoea was significantly higher than in patients with persistent diarrhoea with better nutrition or malnutrition. The duration of diarrhoea was significantly longer in lighter patients (weight-for-age < 65% NCHS (1976) standard), in wasted patients (weight/height < 80% of NCHS) and those with mid upper arm circumference (MUAC) less than 110 mm. There were negative relationships between the period of recovery and the coefficient of absorption of fat (P < 0.001), total energy intake (P < 0.01) and MUAC (P < 0.05). Weight-for-age and MUAC showed most effective discriminative power for absorption of nutrients. However, the coefficients of absorption for carbohydrate were not different for any pair of nutritional groups. Absorption of all nutrients was also correlated negatively with severity of persistent diarrhoea on admission. The results of the present study indicate that a rice-based diet is highly effective in the management of persistent diarrhoea and less malnutrition aggravates nutrient malabsorption, increases duration and severity of diarrhoea and less severely malnourished patients do not absorb nutrients as well as healthy controls. Malnutrition and the initial severity of diarrhoea are significant determinants of clinical prognosis and nutrient absorption in persistent diarrhoea.
Body Weight↗