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Biomedical subjects

S Sharma

Publications and source records attributed to S Sharma.

At least 901 records · Page 50Linked to original sources
PubMed1994

Delay of experimentally induced preterm labour in rats with calcium channel blockers and salbutamol.

The effect of some calcium channel blockers on spontaneous activity of uterine strips obtained from 16 day pregnant rats was observed and compared with salbutamol. Nifedipine (2.9, 14 nM), verapamil (2, 10 nM) and diltiazem (11,22nM) both at low and high doses significantly abolished spontaneous contractions which was gradual and persistent. However, salbutamol (4.2, 21 nM) abolished spontaneous activity immediately but the response was shortlived. The effect of these agents was also investigated on experimentally induced preterm labour in rats (ovariectomized on day 16 of pregnancy). In the control group only 21% of foetuses were retained at the end of 48 hr. Nifedipine, verapamil, diltiazem and salbutamol administered ip 8 hourly protected 91%, 90%, 78% and 61% of foetuses from delivery at 48 hr respectively. The rank order of efficacy was nifedipine > verapamil > diltiazem > salbutamol.

Albuterol↗
PubMed1994

Symptom management in esophageal cancer.

Most patients with esophageal cancer present late with regional or distant metastases and have a poor prognosis. They have many debilitating physical and psychosocial problems. Proper symptom management improves quality of life. The continuity of health care in advanced disease can be best provided by hospice home care programs. Appropriate comfort measures will alleviate terminal restlessness in a dying patient and permit them to die with dignity.

Anorexia↗
PubMed1994

Activity of alpha-anilinobenzyl cyanides and 2-methoxycarbonylamino-1-phenylimidazoles, a new class of antifilarial agents.

The activity of alpha-anilinobenzyl cyanides (2a-f), 5-aryl-4,5-dihydro-2-methoxycarbonylamino-1-phenylimidazoles (5a-d) and 2-methoxycarbonylamino-1-phenyl-1,3-diazaspiro[4:5]dec-2-ene (5f) have been tested for their micro- and macrofilaricidal activity against Litomosoides carinii and Acanthocheilonema viteae in rodents. In this test alpha-anilinobenzyl cyanides (2a-b), 5-(4-methoxyphenyl)-4,5-dihydro-2-methoxy-carbonylamino-1-phenylim idazole (5b) and 2-methoxycarbonylamino-1-phenyl-1,3-diazaspiro[4:5]dec-2-ene (5f) were found to possess marked filaricidal activity at doses ranging from 3-100 mg/kg given parenterally or orally for 5 days.

Animals↗
PubMed1993

Usefulness and tolerability of hirulog, a direct thrombin-inhibitor, in unstable angina pectoris.

In an open-label pilot study of 20 patients with unstable angina (Braunwald class I-IIIB), hirulog was administered as a continuous intravenous infusion for 5 days in a dose of 0.2 mg/kg/hour to produce an activated partial thromboplastin time of approximately 200% of control. The primary end points of the study were: death, development of a transmural myocardial infarction, and intractable angina needing interventions such as an intraaortic balloon pump insertion, angioplasty and surgery. The secondary end points were the presence of an intracoronary thrombus detected on angiography and hemorrhagic complications during therapy. There was no death or transmural infarction in this study cohort; however, 1 patient developed intractable angina. Intracoronary thrombus was documented in 2 patients. Infusion of hirulog resulted in a steady prolongation of the activated partial thromboplastin time without any hemorrhagic or other adverse effect. Hirulog appears to be an effective antithrombotic agent that is tolerated well and may have advantages over heparin in the management of patients with unstable angina.

Aged↗
PubMed1993

Deamidation of HPr, a phosphocarrier protein of the phosphoenolpyruvate:sugar phosphotransferase system, involves asparagine 38 (HPr-1) and asparagine 12 (HPr-2) in isoaspartyl acid formation.

Histidine-containing protein, HPr, of the phosphoenolpyruvate:sugar phosphotransferase system in Escherichia coli, when incubated at elevated temperatures forms many species of protein. The two major species are HPr-1 and HPr-2, which have been shown to lack one or two amides, respectively (Anderson, B., Weigel, N., Kundig, W., and Roseman, S. (1971) J. Biol. Chem. 246, 7023-7033). The formation of HPr-1 and HPr-2 is shown to be pH-dependent and does not occur readily below pH 6. Investigation of the identities and properties of the two residues that deamidate involved creation of site-directed mutants at the 6 glutamine and 2 asparagine residues of HPr; description of their deamidation species by isoelectric focusing; determination of their relative antibody binding properties; assay of their phosphoacceptor and phosphodonor activities; characterization of tryptic and V8-protease peptides; obtaining two-dimensional nuclear magnetic resonance spectra of HPr, HPr-1, and several mutants. It was determined that the sequential deamidation of Asn-38 and Asn-12 yields HPr-1 and HPr-2. Both residues exist as Asn-Gly pairs, and both deamidations probably form isoaspartyl acid. HPr from Bacillus subtilis and Staphylococcus carnosus which also have Asn-Gly at residues 38 and 39 form HPr-1 species presumably by deamidation. HPr from Streptococcus faecalis which does not have Asn-38 does not form a HPr-1 species. The E. coli mutant HPrs, N12D and Q51E, residues that may be involved in the active site, had impaired phosphohydrolysis properties and decreased phosphoenolpyruvate:sugar phosphotransferase system activity.

Amino Acid Sequence↗
PubMed1993

Comparative analysis of NFAT (nuclear factor of activated T cells) complex in human T and B lymphocytes.

Nuclear factor of activated T cells (NFAT) is a transcriptional activator that binds to sequences in the interleukin-2 (IL-2) promoter and is thought to be largely responsible for the T cell-specific inducibility of IL-2 expression. Electrophoretic mobility shift assays (EMSA) showed that specific NFAT binding activity could also be induced in human B cells. The B cell NFAT complex, however, was not functional, since it failed to activate transcription from an NFAT-driven chloramphenicol acetyltransferase (CAT) construct. Competition with an AP-1 motif or with anti-Jun and anti-Fos antibodies abolished binding to the NFAT motif in both T and B cells, indicating that Jun and Fos are critical for NFAT complex formation in both cell types. Purified recombinant Jun and Fos proteins failed to bind directly to the NFAT motif. However, when combined with unstimulated B or T cell extracts, full-length, but not truncated, Jun/Fos heterodimers were able to form an NFAT complex, indicating the presence of a constitutively expressed nuclear factor(s) in B and T cells necessary for the formation of the NFAT complex in both cell types. An NFAT oligonucleotide carrying mutations in the 5' purine-rich part of the NFAT sequence failed to form a complex and to compete with the wild type motif for NFAT complex formation in both T and B cells. We therefore propose a model whereby a core NFAT complex consisting of Jun, Fos, and a constitutive nuclear factor is formed in both T and B cells, but an additional factor and/or post-translational modification of a factor, missing in B cells, might be required for transactivation by NFAT.

B-Lymphocytes↗
PubMed1993

Evaluation of mutagenesis for epitope mapping. Structure of an antibody-protein antigen complex.

The location and description of epitopes on proteins describe the basis of immunological specificity. The 2.8-A structure of the phosphocarrier protein, HPr from Escherichia coli, complexed to the Fab fragment of the monoclonal antibody, Jel42, has been determined. This allows the first comparison of epitope predictions from extensive site-directed mutagenesis experiments, coupled with biological activity studies (Sharma, S., Georges, F., Klevit, R. E., Delbaere, L. T. J., Lee, J. S., and Waygood, E. B. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 4877-4881), with those from x-ray analysis. There are 14 amino acid residues of E. coli HPr that interact with the Jel42 antigen-binding site. Nine of these were correctly assigned by the mutagenesis studies. Of the 5 remaining residues, Met-1 could not be altered; two others appear to have critical roles in determining protein conformation; the other 2 residues have a minimal effect on antibody binding since they are located on the periphery of the epitope with one face of their side chains in van der Waals contact with the antibody and the other face in contact with solvent. Four residues were incorrectly assigned to the epitope. These residues were located adjacent to epitope residues that were likely perturbed by these mutations. This study demonstrates that mutations which caused greater than 10-fold changes in antibody binding affinity were correctly assigned to the epitope by the mutagenesis experiments. Guidelines are also presented in order to minimize incorrect assignments.

Amino Acid Sequence↗
PubMed1993

Percutaneous mitral valvotomy using Inoue and double balloon technique: comparison of clinical and hemodynamic short term results in 350 cases.

The results of percutaneous mitral valvotomy (PMV) by double balloon (N = 230, Group I) and Inoue single balloon (N = 120, Group II) technique were compared. The groups were similar with respect to baseline characteristics. Following PMV there were marked symptomatic and haemodynamic benefits in both the groups. There was significant increase in mitral valve area (MVA) estimated by Gorlin's equation (Group I: from 0.83 +/- 0.18 cm2 to 2.10 +/- 0.45 cm2, p < 0.001; Group II: from 0.83 +/- 0.17 cm2 to 2.16 +/- 0.39 cm2, p < 0.001) and by echoplanimetry (Group I: from 0.84 +/- 0.18 cm2 to 1.91 +/- 0.35 cm2, p < 0.001; Group II: from 0.88 +/- 0.17 cm2 to 1.96 +/- 0.30 cm2, p < 0.001). However, the percentage increase in MVA in the two groups by echoplanimetry (Group I: 136 +/- 59; Group II: 130 +/- 51; p = NS) and by Gorlin's equation (Group I: 164 +/- 69; Group II: 168 +/- 61; p = NS) were not statistically significant. Results were considered optimal when increase in MVA was > or = 1.5 cm2, percentage increase was > or = 50, and mitral regurgitation was < 2/4. Out of 216 patients in Group I where PMV could be performed, optimal results were achieved in 184 (85.2%) by Gorlin's equation and 178 (82.4%) by echoplanimetry. In Group II, out of 116 patients, optimal results were achieved in 107 (92.2%) by Gorlin's equation and 103 (89%) by echoplanimetry. Incidence of mitral regurgitation although higher in Group II (24.1% vs. 18.9%) was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Catheter atherectomy of intimal fibroplasia of the common iliac artery.

An 18-year-old woman presented with renovascular hypertension and left lower extremity claudication. Aorto-iliac angiography showed stenotic lesions in the left renal artery and the left common iliac artery. For uncontrolled hypertension, nephrectomy was performed and histopathology of the renal artery showed intimal fibroplasia, an uncommon type of fibromuscular dysplasia. The left common iliac artery lesions were treated with directional atherectomy, which produced excellent immediate angiographic and symptomatic improvement.

Adolescent↗