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Biomedical subjects

R P Sharma

Publications and source records attributed to R P Sharma.

At least 73 records · Page 4Linked to original sources
PubMed1997

CSF neurotensin concentrations and antipsychotic treatment in schizophrenia and schizoaffective disorder.

OBJECTIVE: The relationship between CSF neurotensin concentrations and measures of psychopathology in patients with schizophrenia or schizoaffective disorder was examined before and after treatment with antipsychotic drugs. METHOD: CSF neurotensin concentrations were measured in 42 drug-free patients with schizophrenia or schizoaffective disorder. For 18 of these patients, CSF neurotensin was measure again after 4 weeks of antipsychotic treatment. RESULTS: Significantly higher levels of pretreatment psychopathology were observed in the patients with the lowest CSF neurotensin concentrations. Furthermore, improvements in overall psychopathology and, particularly, negative symptoms were correlated with increases in CSF neurotensin concentrations during treatment. CONCLUSIONS: These findings provide further evidence for a role of neurotensin the pathophysiology of psychosis and in the mechanism of action of antipsychotic drugs.

Adult↗
PubMed1996

An investigation of the mechanism of inhibition of the Ca(2+)-ATPase by phospholamban.

The Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum has been reconstituted with peptides corresponding to the hydrophobic domain of phospholamban (PLB) with or without the three Cys residues replaced by Ala, and with PLB with the three Cys residues replaced by Ala [PLBcys-(1-52)]. Reconstitution with the hydrophobic domain of PLB[PLB(25-52)] was found to decrease the apparent affinity of the ATPase for Ca2+ with no effect on the maximal rate of ATP hydrolysis observed at saturating concentrations of Ca2+. Reconstitution with PLBCys-(1-52) decreased both the apparent affinity for Ca2+ and the maximal activity; the effect on maximal activity followed from a decrease in the rate of the Ca2+ transport step (E1PCa2-->E2P) as observed with the hydrophilic domain PLB(1-25). The concentration dependences of the effects of the hydrophobic domain and of the whole PLB molecule were very similar, suggesting that the hydrophilic domain made little contribution to the affinity of the ATPase for PLB. The effect of PLB on the ATPase was dependent on the molar ratio of phospholipid to ATPase, suggesting partition of the PLB between its binding site on the ATPase and the bulk lipid phase in the membrane. Neither PLB nor its hydrophobic domain affected the rates of phosphorylation or dephosphorylation of the ATPase. Despite their effects on the apparent affinity of the ATPase for Ca2+, neither PLB nor its hydrophobic domain had any effect on the true affinity of the ATPase for Ca2+, as measured from changes in the tryptophan fluorescence of the ATPase. The effects of PLB on the activity of the ATPase are the sum of the effects of its hydrophilic and hydrophobic domains.

Animals↗
PubMed1996

The effect of N-terminal acetylation on Ca(2+)-ATPase inhibition by phospholamban.

The peptide Ac-MEKVQYLTRSAIRRASTIEMPQQAR (Ac-PLB(1-25)) representing residues 1-25 of phospholamban (PLB) inhibited the maximal activity of the Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum by about 53%, with a Kd value of 5 microM; the equivalent non-acetylated peptide PLB(1-25) had no effect. However, it was found that the non-acetylated peptide increased the effective Kd value for inhibition by Ac-PLB(1-25) consistent with competitive binding to the ATPase, with a Kd value of 8 microM for PLB(1-25). The non-acetylated peptide must therefore be able to bind to the ATPase, but in a conformation that does not lead to inhibition of the ATPase. The identity of the N-terminal residue is important in determining the strength of binding; replacement of the Met residue by Ile led to fourfold weaker binding, again with only binding of the acetylated peptide leading to inhibition of ATPase activity.

Acetylation↗
PubMed1996

Age of illness onset and schizophrenic symptomatology during an inpatient washout period.

The authors examine the relationship between the age of illness onset and the ability to tolerate a medication-free period in a sample of acutely ill schizophrenic patients. Patients were admitted to an inpatient research unit for the treatment of acute and recurrent psychiatric symptoms. Prior medications were discontinued upon admission to the unit for purposes of clinical research and behavioral assessment uncontaminated by medication side effects. The age of illness onset was significantly and positively correlated with the duration of hospital washout. Furthermore, age of illness onset was significantly correlated with the BPRS total score and the BPRS hostility/suspiciousness factor measured at the end of washout. Our results suggest that early onset schizophrenics deteriorate more rapidly in an acute episode than do their later age of onset counterparts.

Acute Disease↗
PubMed1996

Molecular mapping and tagging of genes in crop plants.

In India, molecular mapping and tagging of agronomically important genes using RFLP and RAPD markers have been carried out in three different crops: rice, mustard and chickpea. In rice, tagging of genes for resistance to gall midge and blast has been accomplished. Molecular mapping of cooking quality traits in rice is in progress. For fingerprinting rice cultivars, suitable probe enzyme combinations have been identified. In mustard, a partial RFLP linkage map has been constructed and one of the yellow seed-coat colour loci has been mapped. Significant associations of RFLP markers with quantitative traits have also been established. Potential use of RAPD markers to identify heterotic groups among mustard accessions has been demonstrated. In chickpea, the occurrence of considerable interspecific DNA polymorphism as revealed by RAPD analysis has facilitated construction of a partial linkage map.

Agriculture↗
PubMed1996

Metabolic responses during initial days of altitude acclimatization in the eastern Himalayas.

The study was carried out on 16 men (aged 20-30 years) to evaluate daily metabolic responses during the early phase of altitude acclimatization at moderate altitudes between 3100 and 4200 m in the Eastern Himalayas. Resting (R) and submaximal exercise (E) oxygen consumption (IVO2) at 100 W at sea level (SL) were 3.25 (SEM 0.15) and 20.31 (SEM 0.77) ml/kg per min respectively. On day 1 at 3110 m both R and E IVO2 decreased (P < 0.001) and subsequently remained constant. At 3445 m these values tended to increase over the 3110 m values but were lower than the SL values. At 4177 m the decline in IVO2 was significantly greater (P < 0.01) than at the preceding altitudes. Pulmonary ventilation (IVE) increased consistently (P < 0.001) with increase in altitude. The arterial oxygen saturation (SaO2) at different altitudes was lower (P < 0.001) than SL values. The cardiac frequency (fC) at R and E was higher (P < 0.001) at altitude; the values at 3110 and 3445 m were significantly lower (P < 0.001) than at 4177 m. Blood pressure (BP) increased (P < 0.001) on the first day at each altitude. The systolic BP tended to decline towards SL values but the diastolic BP remained high (P < 0.001) throughout. The resting blood lactic acid concentration, [la-]bl, showed a decline (P < 0.001) only at 4177 m. The [la-]bl at E was similar at 3110 and 3445 m but was higher (P < 0.01) at 4177 m. These observations suggest that acclimatization to a mid-altitude of 3445 m can be safely avoided where rapid ascent to higher altitude is required.

Acclimatization↗
PubMed1996

Temporal expression of retinoic acid receptors in hamster fetus during organogenesis and alteration by retinoic acid treatment.

Retinoic acid receptors alpha, beta and gamma (RAR alpha, beta, gamma) mRNAs from whole 8- to 15-day-old hamster fetuses were characterized and quantitated by Northern blots and solution hybridization using riboprobes from cloned hamster RAR cDNAs, derived from 12-day fetal hamster library. Two RAR alpha transcripts of approximately 3.1 and approximately 3.5 kb, one transcript of RAR beta approximately 2.8 kb and one transcript of RAR gamma approximately 3.1 kb were observed. The relative abundance levels of these transcripts were RAR gamma > beta > alpha. RAR beta and gamma levels peaked at day 11, increasing approximately 4-fold (beta) and approximately 2.5-fold (gamma) above their initial values at day 8. RAR alpha did not change appreciably and peaked on day 14 at 1.7 x of its lowest level at day 9. Regulation patterns of the three RARs diverged between days 8 and 9 and 13 and 14 postcoitum (p.c.) and coordinately increased between days 9 and 13 and decreased between days 14 and 15 p.c. In 12-day-old conceptuses exposed to all-trans-retinoic acid, RAR alpha did not increase significantly, but RAR beta increased 12-fold at 4 hr and RAR gamma 2-fold at 1 hr after the maternal treatments.

Animals↗
PubMed1996

The effect of aflatoxin B1 on cytokine mRNA and corresponding protein levels in peritoneal macrophages and splenic lymphocytes.

Male CD-1 mice were used to test the in vivo effects of aflatoxin B1 (AFB1) on the genetic expression of major cytokines produced by macrophages (interleukin (IL)- 1 alpha, IL-6 and tumour necrosis factor alpha (TNF)) and splenic lymphocytes (IL-2, interferon gamma (IFN gamma), and IL-3), activated in vitro with lipopolysaccharide (LPS) and concanavalin A (Con A), respectively. Animals were treated with 0, 0.03, 0.145 or 0.7 mg AFB1/kg body weight orally every other day for 2 weeks. No significant effects of the toxin on the weights of liver, kidney, spleen, or thymus, or in red blood cell counts were noted, but white blood cell counts were significantly elevated at the low (0.03 mg/kg) dose. Cytokine mRNA levels were measured by Northern blots or cDNA amplification and the secreted protein levels were measured by immunoassay. AFB1 had a marked effect on macrophage-produced cytokines. The mRNA levels increased significantly at the low (IL-1 alpha) or medium dose (IL-6 and TNF), their corresponding protein levels were generally suppressed. The levels of IL-1 alpha secreted protein were significantly suppressed at all dosages, and those of IL-6 and TNF at the high dose. The low dose of AFB1 slightly decreased both mRNA and protein levels of lymphocytic IL-2, IFN gamma, and IL-3, only IL-2 mRNA decreasing significantly (P < or = 0.05). It appears that AFB1 treatment preferentially affects macrophage functions, and in particular, it decouples the close correlation usually observed between transcriptional and translational controls of IL-1 alpha, IL-6 and TNF production by these cells.

Aflatoxin B1↗
PubMed1996

Taxanes from in vitro cultures of the Himalayan yew Taxus wallichiana.

Culture conditions have been standardized for initiation of callus cultures of Himalayan yew (Taxus wallichiana) using young stem and needle explants from mature trees. Cultures were established on a modified Murashige and Skoog's medium supplemented with various levels of auxins (2.4-D, NAA) and cytokinin (kinetin). A medium containing 0.25 mg/l kinetin and 5.0 mg/l 2.4-D was optimal for stem callus growth whereas the presence of 0.25 mg/l kinetin along with 3.0 mg/l NAA in the medium supported optimal needle callus growth. Growth of stem callus was faster than needle callus growth. Supplementation of ascorbic acid (30 mg/l) amongst various anti-phenolic agents tested significantly reduced browning of initiated callus. Two taxanes (2-deacetoxytaxinine 1 and 2'-deacetoxyaustrospicatine) known to occur in stem bark, have also been isolated from undifferentiated tissue of T. wallichiana in equal or higher yields, for the first time.

Antineoplastic Agents, Phytogenic↗
PubMed1996

Prediction of haloperidol steady-state levels in plasma after a single test dose.

Because of large interindividual variabilities in the pharmacokinetics of haloperidol (HPDL), empirically adjusting the dose to achieve steady-state levels in plasma (Css) is a time-consuming process. We report a method to individualize dose to achieve a desired Css from an observed drug level 24 hours after a single 15-mg test dose of HPDL. Drug-free schizophrenic and schizo-affective patients were blindly and randomly assigned to achieve a low (< 5 ng/ml), medium (10-18 ng/ml), or high (> 25 ng/ml) Css range of HPDL. On day 1 of the study, each patient received an oral "test" dose of HPDL (15 mg), and blood was drawn 24 hours later to determine drug levels in plasma (C24h). The first 34 patients (group I) were then maintained empirically on 2, 5 to 8, or 10 to 15 mg twice daily of oral HPDL concentrate for 5 days to achieve a low, medium, or high Css range, respectively. For the next 58 patients (group II), the dose of HPDL to achieve the assigned Css range was computed by using C24h in a prediction formula. Application of the C24h correctly predicted the maintenance dose required to achieve the Css in 73.2% of the cases. Further, there was a highly significant correlation (R2 = 0.877, p < 0.0001) between the predicted dose and the actual dose required to achieve the targeted Css range. On the basis of these results, we have formulated a nomogram to help predict the maintenance dose required to achieve low, medium, or high HPDL targeted ranges at various C24h values.

Adult↗
PubMed1996

Combined transrectal sonographic and fluoroscopic guidance for deep pelvic abscess drainage.

We attempted to determine the feasibility, safety, and success of transrectal catheter drainage of deep pelvic abscesses using a combination of transrectal sonography and fluoroscopic guidance. In this retrospective review of five cases, transrectal catheters were placed within abscess cavities over a 20 month period. Clinical improvement was prompt, catheters were removed within 7 days, and no complications were detected. No patient required further intervention (follow-up 2 to 20 months). Transrectal sonographically guided catheter drainage proved to be safe and effective in our series. This method is a promising alternative to the posterior (sciatic notch) approach when the anterior transabdominal approach is contraindicated.

Abdominal Abscess↗
PubMed1996

Isolation and subcloning of chitinase clone from chickpea genomic library.

Chickpea genomic library constructed earlier in phage lambda (EMBL-3) was screened for the presence of chitinase clone using tobacco chitinase cDNA as a probe. Positive clones obtained by primary screening of plaques (2 x 10(6)) were ascertained by secondary and tertiary screening. Presence of chitinase insert in the positive clones obtained, was further confirmed by restricting phage DNA with Sal I and then doing southern with tobacco chitinase. The insert band was eluted out and subcloned in puc 19 plasmid.

Chitinases↗
PubMed1995

The hydrophilic domain of phospholamban inhibits the Ca(2+)-ATPase--the importance of the method of assay.

The peptide MEKVQYLTRSAIRRASTIEMPQQAR-Cys representing residues 1-25 of phospholamban (PLN) decreases by 40% the maximal state rate of ATP hydrolysis by the Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum (SR), measured at saturating concentrations of Ca2+. The pattern of Ca2+ uptake by SR vesicles in the presence of oxalate is complex, with an initial fast phase being followed by a lag phase and a second, slower phase of Ca2+ accumulation. PLN(1-25) reduces the rate of the slower phase of Ca2+ accumulation by 30%. However, if the level of accumulation of Ca2+ is measured after 2 min., the effect of PLN(1-25) is much less marked. It is concluded that PLN(1-25) inhibits the ATPase, but that the effects of this inhibition are not apparent under some assay conditions.

Amino Acid Sequence↗
PubMed1995

Constrained peptide analogues of transforming growth factor-alpha residues cysteine 21-32 are mitogenically active. Use of proline mimetics to enhance biological potency.

Two proline mimetics, the enantiomers of 2-aza-bicyclo[2,2,1]heptane-3-carboxylic acid, have been incorporated in place of Pro30 into synthetic peptides based on the B-loop beta-sheet sequence of human transforming growth factor-alpha (TGF-alpha) (residues Cys21-Cys32). The peptides were further modified by inclusion of an N-terminal phenylalanine and constrained by formation of an intramolecular disulfide bond. While no mitogenic response was observed in the parental NR6 cell line, the peptides stimulated DNA synthesis in NR6/HER cells (NR6 fibroblasts transfected with the human epidermal growth factor receptor). Induction of DNA synthesis was dose dependent, with EC50 values in the range 130-330 microM; in the presence of low doses of TGF-alpha, the mitogenic effect of the peptides was additive, up to the plateau response achieved by maximal doses of TGF-alpha alone. These effects are consistent with the peptides acting via the same mechanism as TGF-alpha. Analysis of the structure of the peptides by NMR indicated that the presence of the mimetics significantly increased the propensity of the peptidyl-proline bond to adopt the cis conformation. These data confirm the role of the beta-sheet in receptor activation, and emphasize the importance of presentation of peptides in an appropriate conformation for recognition.

Amino Acid Sequence↗
PubMed1995

Modulation of the receptor binding affinity of amphiregulin by modification of its carboxyl terminal tail.

Amphiregulin (AR), a heparin-binding, epidermal growth factor (EGF) receptor ligand has homology with EGF but exhibits a lower affinity for the EGF receptor than EGF. As the mature form of AR is truncated at the C terminus and lacks a conserved leucine residue known to be essential for high affinity binding of EGF to the EGF receptor, wild-type AR (AR1-84), a C-terminally extended AR construct incorporating six residues from the predicted coding sequence of AR (AR1-90) and a similarly extended construct with a Met86 to Leu substitution (AR1-90(leu86)) were expressed as recombinant proteins in yeast, purified by heparin affinity and C18 reverse phase chromatography and their relative biological activities determined. The growth factors were tested in mitogenesis and EGF receptor autophosphorylation assays and their relative order of potencies was found to be leu86 > met86 > wt. The AR1-90(leu86) construct was found to be 50- to 100-fold more active than wild type AR1-84 consistent with previously reported studies of the role of the equivalent C-terminal leucine in EGF or TGF alpha. Significantly, the C-terminally extended form of AR, AR1-90, which utilized six residues from the predicted coding sequence, was 10-times more active than wild type AR1-84. This difference in activity of the C-terminally extended form of AR may be of biological significance since differential proteolytic processing of the AR precursor in vivo could result in production of multiple forms of the growth factor with differing affinities for the EGF receptor and hence differing biological potencies.

Amphiregulin↗
PubMed1995

Localization of retinoic acid receptors in anterior-human embryo.

Retinoic acid receptors (RARs) are nuclear transcription factors that are activated by all-trans-retinoic acid or 9-cis-retinoic acid and are found in all tissues but predominantly in developing fetus, dividing tumor cells, and adult skin. Three forms of these receptors, alpha, beta, and gamma, have been described. In this paper we report the presence of RAR alpha and beta determined by hybridization with anti-sense messenger RNA, and histochemical localization of the three forms of RARs using monospecific polyclonal antibodies in various tissues of early human embryos. In a 54-day-old embryo, RAR alpha was expressed primarily in the liver and the brain, with somewhat lesser expression in the intestine. RAR beta was the highest in the brain, followed by a restricted expression in the intestine and the liver. Other organs, i.e., adrenal, kidney, and testis, did not show measurable amounts of RAR beta. The immunohistochemical localization in anterior sections of a 43-day-old embryo indicated that RAR alpha was present in the neuroepithelial cells and in cells lining the primitive pharyngeal sac, dorsal aorta, and pericardium. RAR beta was somewhat less prevalent in same tissues, whereas the expression of RAR gamma was the lowest of the three RARs in any tissues examined. Results indicated that RAR alpha and beta appear at early stages of human embryonic development and their expression is restricted to certain types of tissues.

Blotting, Northern↗
PubMed1995

Cerebrospinal fluid levels of phenylacetic acid in mental illness: behavioral associations and response to neuroleptic treatment.

Cerebrospinal fluid levels of phenylacetic acid (CSF PAA) were obtained from normal controls and from drug-free psychiatric inpatients (schizophrenia, major depression, mania, and schizoaffective disorder). Post-treatment CSF PAA levels were obtained from 16 patients after 4 weeks of neuroleptic treatment. Phenylacetic acid levels were higher in women and were significantly correlated with age. There were no differences in CSF PAA levels between the various diagnostic groups and no difference between the paranoid and the nonparanoid subtypes of schizophrenia. CSF PAA was significantly correlated with several measures of psychopathology, especially the Brief Psychiatric Rating Scale hostility/suspiciousness factor. Neuroleptic treatment did not result in significant PAA changes. These findings are discussed in light of the amphetamine-like role ascribed to phenylethylamine, the precursor of PAA.

Adult↗