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Biomedical subjects

U Sharma

Publications and source records attributed to U Sharma.

At least 19 recordsLinked to original sources
PubMed1998

Myelodysplastic syndrome and successful pregnancy.

A case of successful pregnancy in a 47-year-old Omani grand-multipara who had Myelodysplastic Syndrome (MDS) is described for the first time in Oman. A review of the literature suggests that in Japan the problem may be more common than elsewhere. The unusual features in the case reported here include, improvement in haematological parameters during the pregnancy contrary to expectation, and in addition, the religious and cultural factors that intruded into the clinical decision making process. Suggestions to combat the latter factors are made.

Female↗
PubMed1998

Human leucocytic antigens (HLA) in breast cancer.

HLA frequencies of fifty (50) female breast cancer patients were compared with 200 age matched female controls. A total of 20 HLA-A locus, 35 HLA-B locus and 8 HLA-C locus antigens were studied. The HLA-A2, A11, Aw19 and A30; HLA-B8, B14 and HLA Cw6 were found significantly higher than the controls. The HLA-A11, HLA-Aw19 and HLA-B8 were found protective whereas, HLA-A2, HLA-B14 and HLA-Cw6 were a risk for breast cancer. The prective antigens' probable involvement through immunogenic mechanism in breast cancer is emphasized in this article.

Adult↗
PubMed1997

Metabolic inactivation of cytochrome P4502B1 by phencyclidine: immunochemical and radiochemical analyses of the protective effects of glutathione.

Phencyclidine (PCP) inactivates the 7-ethoxy-4-trifluoromethylcoumarin O-deethylase activity of P4502B1 in a reconstituted system containing NADPH-cytochrome P450 (P450) reductase (reductase) and L-alpha-phosphatidylcholine, dilauroyl in a time-, concentration-, and NADPH-dependent manner. Catalytic activity of the enzyme could not be restored upon reconstitution with fresh reductase, indicating that the effect was on the P450 and not on the reductase. Although the kinetics suggested that PCP would be classified as a classical mechanism-based inactivator, protection against inactivation of P450 by PCP by the presence of an exogenous nucleophile, such as glutathione (GSH), indicated otherwise. There was no loss of spectrally detectable P450 associated with inactivation either in the presence or absence of GSH. When radiolabeled PCP was used to inactivate the enzyme and the reaction mixture analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, radioactivity was found to be associated with P450, reductase, and catalase that had been added to protect against oxidative damage. When GSH was included in the reaction mixtures, analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated a marked decrease in the binding to all three proteins. Correspondingly, analysis of the components of the inactivated sample by reversed-phase HPLC demonstrated that radioactivity was associated with P450, reductase, and catalase, and that there was a marked decrease in the labeling of all three proteins in the presence of GSH. The stoichiometry of binding of radiolabeled PCP to the proteins in the incubation mixture in the absence of GSH was 4:1. In the presence of GSH, no significant amount of radioactivity was incorporated into the proteins. An anti-PCP metabolite antibody was used to detect PCP metabolite adducts bound to the inactivated enzyme by Western blot analysis. The antibody recognized adducts bound to P450, reductase, and catalase. In the presence of GSH, there was a decrease in immunoreactivity, although binding of PCP to all three proteins was still detected. Because the added nucleophile protects against inactivation and protein labeling by PCP, these data suggest that the reactive intermediate may escape from the active site and attack other sites on the P450, as well as other proteins in the milieu.

Animals↗
PubMed1996

Human erythrocytes bearing electroinserted CD4 neutralize infection in vitro by primary isolates of human immunodeficiency virus type 1.

Human erythrocytes bearing electroinserted full-length CD4 (RBC-CD4) can bind and fuse with a laboratory strain of human immunodeficiency virus type 1 (HIV-1) or with T cells infected by HIV-1. Here we show that RBC-CD4 neutralize primary HIV-1 strains in an assay of cocultivation of peripheral blood mononuclear cells (PBMC) from HIV-1-infected persons with uninfected PBMC. RBC-CD4 inhibited viral p24 core antigen accumulation in these cocultures up to 10,000-fold compared with RBC alone. Viral p24 accumulation was inhibited equally well when measured in culture supernatants or in call extracts. The inhibition was dose-dependent and long-lived. Two types of recombinant CD4 tested in parallel were largely ineffective. The neutralization of primary HIV-1 by RBC-CD4 in vitro was demonstrated in PBMC cultures from 21 of a total of 23 patients tested at two independent sites. RBC-CD4 may offer a route to blocking HIV-1 infection in vivo.

Acquired Immunodeficiency Syndrome↗
PubMed1996

A proton nuclear magnetic resonance investigation of the conformation of daunomycin.

The 500 MHz proton NMR spectra of 4.95 mM daunomycin in D2O have been investigated in the temperature range 277-350 K. Down field shifts of approximately 0.15 to 0.20 ppm in 1H, 2H and 3H protons with increasing temperature indicate that daunomycin exists in aggregated form at 277 K which is stabilized by stacking of aromatic rings. The 7H, 10axH and 10eqH protons show a change in chemical shift of 0.12 to 0.16 ppm, while other ring A/sugar protons shift by 0.0 to 0.08 ppm due to self association. The drug exists in monomer state at about 350 K. The conformational features have been ascertained from NOESY spectra at 297 K. The 7H proton is found to be strongly coupled to 8axH (J = 5 Hz) as compared to 8eqH (J = 2 Hz), while the 4'H-5'H connectivity is not observed in the COSY spectra. Besides the NOESY cross peaks between the spin-spin coupled protons, several intramolecular NOEs are seen. The 8axH and 8eqH are equally distant from 5'H proton. The distances of 3'H and 4'H daunosamine sugar protons from the ring A protons--7H, 8eqH, 9COCH3--are in the range 2.9-3.1 A, giving moderate cross peaks in NOESY spectra. The observed results imply the existence of predominantly 9H8 half chair conformation of ring A in aqueous solution, which is marginally different from that obtained by X-ray crystal analysis.

Antibiotics, Antineoplastic↗
PubMed1996

Demarcation and transformation within homoeopathic knowledge. A strategy of professionalization.

Both the medically and non-medically qualified homoeopaths in Britain have engaged in a number of changes to the way that their knowledge is constructed and communicated. In this paper we describe these changes and link them to claims for legitimacy, status and authority in the health care market. The public presentation of homoeopathic knowledge claims are thus linked to a 'professional project'.

Chiropractic↗
PubMed1996

Peak expiratory flow rate of carpet weaving children.

OBJECTIVE: To assess the adverse influence of carpet weaving on lung functions and the nurtritional status of children employed in such factories. DESIGN: Comparison of the peak expiratory flow rate (PEFR) of the study group with controls of similar socio-economic status and correlate it with anthropometric values. SETTING: Field study. SUBJECTS: One hundred and ten boys, 6-15 years of age engaged in 23 carpet weaving factories of Jaipur city. OUTCOME MEASURES: Linear regression analysis using age, height and weight as independent variables and PEFR as the dependent variable. RESULTS: PEFR of carpet weaving children were significantly lower (p < 0.05) than controls for all except 6-7 years group. The height, weight and chest circumference of these children were also lower (p < 0.05). PEFR did not show significant difference when children were grouped according to their height. CONCLUSIONS: Children working in carpet weaving factories are shorter and lighter compared to normal school going children. As a consequence of the growth retardation, their PEFR values were also lower as compared to normal children.

Adolescent↗
PubMed1996

Inactivation of cytochrome P4502B1 by the monoamine oxidase inhibitors R-(-)-deprenyl and clorgyline.

The monoamine oxidase inhibitors R-(-)-deprenyl (deprenyl) and clorgyline inactivated the 7-ethoxy-4-trifluoromethylcoumarin O-deethylase activity of purified cytochrome P4502B1 (P4502B1) in a reconstituted system containing P4502B1, NADPH-cytochrome P450 oxidoreductase, and L-alpha-phosphatidylcholine dilauroyl as the lipid. The inactivation was time- and concentration-dependent. The inactivation required NADPH, demonstrated saturation kinetics, and no lag time for inactivation was observed. The inactivation was not affected by the presence of an excess exogenous nucleophile, such as glutathione. Deprenyl exhibited a KI (concentration of inactivator required for half-maximal inactivation) of 1.05 microM, and clorgyline had a KI of 1.5 microM. The maximum rate of inactivation of the enzyme at saturating levels of inactivator (kinactivation) was 0.23 min-1 for deprenyl and 0.28 min-1 for clorgyline. The partition ratio for deprenyl and clorgyline was between 2 and 3. Studies on the isozyme specificity of these compounds in microsomes from rats pretreated with specific inducers demonstrate that the inactivation was relatively specific for the major phenobarbital-inducible isozyme, P4502B1, because significant inactivation of P4501A1 and P4502E1 was not observed. When the purified P4502B1 in the reconstituted system was incubated with either inactivator in the presence of NADPH, there was approximately a 60-70% loss in spectrally detectable P450 over 5 min at a 1:21 ratio of P450 to inactivator. However, at this ratio of enzyme to inactivator, there was > 90% loss of the O-deethylase activity. This loss in enzyme activity was irreversible, and the protein did not regain activity after dialysis or extensive washing to remove excess inactivator.

Animals↗
PubMed1996

Formation of a metabolic intermediate complex of cytochrome P4502B1 by clorgyline.

The monoamine oxidase inhibitor clorgyline was found to inactivate purified reconstituted cytochrome P450 (P450) 2B1 in a time- and concentration-dependent manner (Sharma et al., Drug Metab. Dispos. 24, 669-675, 1996). In an attempt to explain the mechanism of inactivation, the possibility of the formation of a metabolic intermediate (MI) complex during the metabolism of clorgyline by P4502B1 was investigated. Incubation with clorgyline resulted in an absorbance peak with a maximum at 455 nm in the difference spectrum that is characteristic of an MI complex, and the magnitude of absorbance at 455 nm was dependent on both the concentration of clorgyline and NADPH. The MI complex was relatively stable and did not dissociate on standing or on removal of excess inactivator by a series of dilutions followed by microconcentration. When formed using limiting amounts of NADPH, the MI complex could be dissociated by the addition of 50 microM potassium ferricyanide. Clorgyline did not inactivate the 7-ethoxycoumarin O-deethylase activity of liver microsomes from beta-naphthoflavone-treated rats or the hydroxylation of p-nitrophenol by liver microsomes from pyridine-treated rats. However, low levels of MI complex formation were observed with these microsomes. Maximal MI complex formation was observed with liver microsomes from phenobarbital-treated rats. When the MI complex was dissociated by addition of an oxidant such as potassium ferricyanide (50 microM) in the absence of excess NADPH and excess inactivator, there was almost complete recovery of the catalytic activity of the enzyme and spectrally detectable P450. Thus, formation of the MI complex was responsible for the inactivation of P4502B1 and for the loss of spectrally detectable P450 during the incubation of the P450 with clorgyline in the presence of NADPH.

Animals↗
PubMed1995

Endoscopic variceal ligation in children.

Endoscopic variceal ligation, a mechanical mode of variceal obliteration, was used in the management of patients having extrahepatic portal vein obstruction. Fifteen patients (10 males, 5 females) had grade III varices. Their mean age was 8.13 years (range, 3 to 14 years). Obliteration was achieved in 14 patients (93.33%) after a mean number of 1.86 (range, 1 to 4) sessions. The mean number of bands required for variceal obliteration was 4.33 (range, 1 to 9). The number of bands required to obliterate each variceal column was 1.38. No patient required a blood transfusion, and there was only one recurrence of varices during the mean follow-up period of 9 months (range, 4 to 12 months). Postligation hemorrhage was encountered in one patient; there was no other complications. Endoscopic variceal ligation is an effective and safe method for early variceal obliteration in children.

Adolescent↗
PubMed1995

Cisapride.

Explore the source record for details and available documents.

Anti-Ulcer Agents↗
PubMed1994

Absence of recoverable infectious virus and unique immune responses in an asymptomatic HIV+ long-term survivor.

We have studied a woman with transfusion-acquired HIV who appears to have contained infectious virus to consistently undetectable levels over a 13-year period without antiviral treatment. She received the infected transfusion for intra- and postpartum blood loss immediately after delivery of her second child in 1981. She had no acute febrile syndrome and has never had HIV-associated clinical signs or symptoms in the 13 years since infection. She was first tested and found positive for HIV antibodies in 1985, and the infected blood donor was diagnosed with AIDS in 1986 and died of AIDS-related complications in 1989. Two other recipients of packed erythrocytes from this donor (in 1980 and 1982) also became infected and were subsequently diagnosed with AIDS. Between January 1986 and April 1994, in the setting of continuous and unambiguous Western blot HIV-specific antibodies and intermittently positive low-level HIV DNA signal after polymerase chain reaction (PCR) amplification, more than 30 separate cell cocultures performed in several independent laboratories failed to yield evidence of infectious virus, despite special efforts to induce and detect HIV replication. Immunologically, a strong in vitro proliferative response to HIV envelope proteins also distinguished this subject from other asymptomatic HIV+ individuals.

Adult↗