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Biomedical subjects

U Sharma

Publications and source records attributed to U Sharma.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Cisapride.

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Anti-Ulcer Agents↗

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↗

Health status of carpet weaving children.

A cross-sectional study was undertaken to determine the health status of children engaged in carpet weaving factories of Jaipur City. Two hundred and ninety school going boys of similar socio-economic status served as controls. A higher prevalence of signs of nutritional deficiencies was observed in carpet weaving children. Analysis of the presenting complaints and the illness suffered in the past six months also revealed a significantly higher morbidity in these children. A statistically significant difference was also observed in anthropometric measurements of the two groups.

Adolescent↗

Human immunodeficiency virus type 1 enhances intracellular growth of Mycobacterium avium in human macrophages.

Disseminated Mycobacterium avium infections are common in patients with AIDS and result in a reduced life expectancy. Human monocytes/macrophages are important target cells for both human immunodeficiency virus (HIV) and M. avium. We have studied the interaction in vitro of M. avium and HIV type 1 (HIV-1) in human macrophages. Human monocytes isolated from the peripheral blood of healthy individuals were infected with HIV-1, M. avium, or both. The intracellular growth of M. avium and the replication of HIV-1 were monitored for up to 5 weeks. Intracellular mycobacterial growth was seen in all M. avium infected cell cultures and was paralleled by increased production of interleukin 1 alpha and beta. Preinfection of the macrophages with HIV-1 reduced the interleukin 1 production and accelerated the intracellular growth of M. avium. These findings may explain in part the impaired control of mycobacterial infections seen with patients with AIDS.

Cells, Cultured↗

Electrophysiological and histopathological changes in peripheral nerves of postnatally undernourished and rehabilitated young rhesus monkeys.

Nerve condition velocity of ulnar and tibial nerves and qualitative histology of ulnar nerve were studied in young rhesus monkeys. Motor nerve condition velocity of both the nerves and amplitude of sensory response of ulnar nerve were significantly decreased in even moderate protein calorie malnourished (PCM) group of monkeys. Increased paranodal gap, segmental demyelination, thin myelinated fibres and prominent Schmidt Lanterman Clefts were also observed in PCM group. There was complete recovery in motor nerve conduction velocity in the nerves of both limbs while partial in amplitude of sensory response in proximal segment of ulnar nerve on nutritional rehabilitation of 10-12 weeks.

Animals↗