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Biomedical subjects

S K Sharma

Publications and source records attributed to S K Sharma.

At least 325 records · Page 18Linked to original sources
PubMed1994

Antibody-directed enzyme prodrug therapy (ADEPT). A three-phase study in ovarian tumor xenografts.

Antibody-directed enzyme prodrug therapy (ADEPT) has been studied in a human ovarian carcinoma xenograft grown subcutaneously in nude mice. Radioimmunoassay of supernatants obtained from tumor homogenates showed these to contain carcinoembryonic antigen (CEA). Biodistribution studies with 125I-labeled monoclonal anti-CEA antibody, A5B7, and its F(ab')2 fragment showed localization in these xenografts. The AB57-F(ab')2 fragment conjugated to a bacterial enzyme, carboxypeptidase G2 (CPG2), and, radiolabeled with 125iodine, also localized in the xenografts. The radiolabeled conjugate cleared from blood faster than the antibody alone. The percentage of injected dose per gram in tumor at 24 h postinjection was about fivefold lower than antibody alone. Tumor-to-blood ratio at 72 h after injection of the radiolabeled conjugate was 7 and the tumor-to-normal tissue ratios at this time point ranged from 20 (liver) to 75 (colon). A three-phase ADEPT antitumor study was carried out in which A5B7-F(ab')2-CPG2 was allowed to localize and was followed by accelerated inactivation/clearance of blood CPG2 by a galactosylated anti-CPG2 antibody (SB43gal). A benzoic acid mustard-derived prodrug was injected 24 h after the conjugate, which led to growth delay in this tumor compared to the control untreated group. Further antitumor studies in this model are in progress.

Animals↗
PubMed1994

Picrotoxin and pentylene tetrazole induced seizure activity in pyridoxine-deficient rats.

Computerized electroencephalography and thalamic ventro-posterior lateral (VPL) unit activities were recorded from pyridoxine-deficient and pair-fed pyridoxine-supplemented adult male rats. Pyridoxine-deficient animals exhibited slow electroencephalograms (EEG) represented by the dominance of delta activity and reduced seizure thresholds to local (VPL) application of either picrotoxin or pentylene tetrazole. Frequency and amplitude of thalamic VPL unit activity were significantly reduced in pyridoxine-deficient rats as compared to pyridoxine-supplemented controls. Pyridoxine-deficient rats exhibited irregular unit activity with frequent bursts and electrosilent periods in response to local (VPL) picrotoxin or pentylene tetrazole microinjections. They also exhibited severe seizure discharge activity of prolonged duration at any given dose of either picrotoxin or pentylene tetrazole. This was represented by significantly increased burst frequency, burst duration and reduced seizure latencies. Unit activity was transformed into burst discharge activity with intermittent electrosilent zones during picrotoxin or pentylene tetrazole epileptogenesis. Cerebral gamma aminobutyric acid (GABA) level was reduced and glutamate concentration increased in pyridoxine-deficient rats when compared with pyridoxine-supplemented controls. Local (VPL) microinjection of GABA or pyridoxine induced neuronal recovery in both convulsant-treated normal and pyridoxine-deficient rats. Neuronal recovery was however delayed in pyridoxine-deficient rats. Neuronal recovery was associated with a significant increase in EEG background frequency and reduction in delta frequencies in the EEG records of both normal and pyridoxine-deficient rats. Reduced seizure threshold and delayed neuronal recovery are related to the significantly reduced brain regional GABA and elevated glutamate levels in pyridoxine-deficient rats.

Animals↗
PubMed1994

Anesthetic management of a parturient with mixed mitral valve disease and uncontrolled atrial fibrillation.

This case report describes the anesthetic management of a 32-year-old parturient with combined severe mitral regurgitation and moderate mitral stenosis, complicated by fast atrial fibrillation. The advantageous effects of epidural analgesia during labor and vaginal delivery and the importance of invasive monitoring are discussed. We also report the rare complication of right bundle branch block related to the use of a pulmonary artery catheter.

Journal Article↗
PubMed1994

Antibody directed enzyme prodrug therapy (ADEPT). A review of some theoretical, experimental and clinical aspects.

The concept of generating cytotoxic agents from non-toxic prodrugs at tumour sites by antibody vectored enzyme introduces a wide range of opportunities. Various prodrug-enzyme combinations have been described and encouraging results reported in xenograft models. Whilst the mouse model is a valuable tool in this approach translation to the human patient may expose more complex issues. The objective of restricting drug action to tumour sites and thus allowing greatly increased cytotoxic action requires more precise restriction of enzyme activity to tumour sites than has been achieved with an antibody vector and natural clearance alone. Assisted clearance mechanisms have been found effective. Alternatively, or additionally, the difference between prodrug and active drug creates the opportunity to degrade active drug selectively in blood and thus protect normal tissues. In order to give more than one cycle of treatment it will be necessary for the antibody-enzyme conjugate to be nonimmunogenic or for the concurrent administration of immunosuppressive agents. A pilot scale clinical trial with a prototype prodrug indicated the feasibility of antibody directed enzyme prodrug therapy (ADEPT).

Animals↗
PubMed1994

Allergic bronchopulmonary aspergillosis: a comparative evaluation of computed tomography with plain chest radiography.

Computed tomography (CT) was done in 15 consecutive patients with allergic bronchopulmonary aspergillosis (ABPA). When compared with chest X-ray, CT was found to be superior in the diagnosis of bronchiectasis in patients with ABPA. Of the 90 lobes studied, CT detected bronchiectasis in 57 lobes and plain chest X-ray in 44 lobes. In addition to central bronchiectasis, peripheral bronchiectasis was diagnosed with CT in 18 of the 57 lobes. Follow-up CT was done in two patients after treatment for detection of progression or regression of bronchiectatic lesions. One patient showed radiological as well as clinical improvement, while the other patient presented with a recurrence of symptoms 4 months after stopping treatment. Computed tomography showed radiological progression of bronchiectasis and the patient was successfully treated with corticosteroids (thus preventing further bronchial damage). It is concluded from this study that CT is superior to plain chest X-ray in the diagnosis of bronchiectasis in patients with ABPA. Being non-invasive, it is also helpful in monitoring the course of bronchiectasis in these patients.

Adult↗
PubMed1994

Urological complications of advanced lymphoma.

Vicarious manifestations of 12 cases of urinary tract lymphomas (non-Hodgkin's and Hodgkin's) are presented to illustrate various urogenital problems in this group. Since the majority with urogenital involvement had an advanced disease, only palliative treatment was given in most of the cases. With the exception of testicular and primary renal lymphoma, ablative surgery is not indicated. Urological intervention was required to salvage renal function and at times to obtain tissue for histopathological diagnosis. Chemotherapy and/or radiotherapy was given as a preferred treatment according to individual needs following the judicious biopsy. A brief review of the literature is included.

Adult↗
PubMed1994

Gunshot wounds of the male external genitalia.

The explosive increase of violence in our society has imposed hazards of gunshot injuries on the civilian population. The genitourinary system is no longer exempted from such assaults. Although male external genitalia are amongst less commonly involved organs, in a span of 14 months, 4 such cases were managed at our institute. Our experience of such injuries is being highlighted so as to draw attention to their increasing incidence and association with injuries of other organs. Three patients had haemorrhagic shock at initial presentation. They were managed by resuscitation, debridement and repair of wounds Urethral injuries were dealt initially by diversion and subsequently urethroplasty was performed. In a follow-up of 6-12 months, all the patients were reported to be having normal erections and none of them have developed urethral stricture.

Adolescent↗
PubMed1994

Adjunctive thrombolytic therapy during angioplasty for ischemic rest angina. Results of the TAUSA Trial. TAUSA Investigators. Thrombolysis and Angioplasty in Unstable Angina trial.

BACKGROUND: Acute closure is increased after angioplasty in unstable angina, and adjunctive intracoronary thrombolytic therapy has been used successfully to increase angiographic success. The role of prophylactic thrombolytic therapy during angioplasty in unstable angina is unknown. METHODS AND RESULTS: Four hundred sixty-nine patients with ischemic rest pain with or without a recent (< 1 month) infarction were randomized in double-blind fashion to intracoronary urokinase or placebo. Randomization was carried out in two sequential phases. In phase I, 257 patients were randomized to 250,000 U of urokinase or placebo given in divided doses at the time of angioplasty. In phase II, 212 patients were randomized to 500,000 U of urokinase or placebo in divided doses. All patients were pretreated with aspirin, and activated clotting times were followed to maintain them at > 300 seconds during angioplasty. Angiographic end points of thrombus after angioplasty were insignificantly decreased by urokinase (30 [13.8%] versus 41 [18.0%] with placebo; P = NS). Acute closure, on the other hand, was increased with urokinase (23 [10.2%] versus 10 [4.3%] with placebo; P < .02). The difference in acute closure between urokinase and placebo was more striking at the higher dose of urokinase (P < .04) than in phase I at the lower urokinase dose (P = NS). Adverse in-hospital clinical end points (ischemia, infarction, or emergency coronary artery bypass surgery) were also increased with urokinase versus placebo (30 [12.9%] versus 15 [6.3%], respectively; P < .02). Angiographic and clinical end points were worse with urokinase in unstable angina without recent infarction than with angioplasty after a recent infarction. CONCLUSIONS: Adjunctive urokinase given prophylactically during angioplasty for ischemic rest angina as administered in this trial is associated with adverse angiographic and clinical events. These detrimental effects may be related to hemorrhagic dissection, lack of intimal sealing, or procoagulant or platelet-activating effects of urokinase.

Angina, Unstable↗
PubMed1994

Effect of parenteral magnesium sulfate on pulmonary functions in bronchial asthma.

Eighteen patients with bronchial asthma were studied in a single-blind fashion. Each patient received an infusion of magnesium sulfate (MgSO4.7H2O 50% W/V) in a dose equivalent to 10 mmol of elemental magnesium. The airways resistance showed a significant decrease (p < 0.01) while SGaw increased significantly (p < 0.001) with MgSO4 infusion. FEV1 (p < 0.01), FEF25-75% (p < 0.05), and V50 (p < 0.05) also showed statistically significant increase (p < 0.001) with MgSO4 infusion. Significant changes in Raw (p < 0.01) and SGaw (p < 0.01) persisted at 10 and 20 min following MgSO4 infusion. No significant side effects were observed with MgSO4 infusion. It is concluded that modest improvement in airways resistance and specific conductance and only small improvement in maximal expiratory flow rates is consistent with a predominant effect of MgSO4 on large airways in patients with bronchial asthma.

Adolescent↗
PubMed1994

Engineering of the human-immunodeficiency-virus-type-1 (HIV-1) reverse transcriptase gene to prevent dimerization of the expressed chimaeric protein: purification and characterization of a monomeric HIV-1 reverse transcriptase.

We report here a human-immunodeficiency-virus-type-1 (HIV-1) recombinant reverse transcriptase (RT) engineered to contain a 26-amino-acid linker insertion from the tether domain of feline leukaemia virus (FLV) RT. The chimaeric protein was expressed in Escherichia coli and migrated on SDS/PAGE as a 68 kDa band. A monomeric form of the chimaeric HIV-1 RT has been prepared by the coordinated applications of immobilized-metal-affinity chromatography and gel filtration on Superose 12 columns. The monomeric nature of this chimaeric HIV-I RT was further characterized by cross-linking studies using disuccinimidyl suberate. The RNA-dependent DNA polymerase activity of the monomeric chimaeric HIV-1 RT was 35% that of the heterodimeric (p66/p51) HIV-1 RT. These results support our recent studies on the monomeric polymerase domain (p51 RT) which exhibited an RNA-dependent DNA polymerase activity equal to 33% of that of the p66/p51 heterodimeric HIV-1 RT (Evans, Kezdy, Tarpley and Sharma [1993] Biotechnol. Appl. Biochem. 17, 91-102). The inability of the monomeric chimaeric HIV-1 RT to display polymerase activity like that of the heterodimeric HIV-1 RT is attributed to a decrease in the processive rate of DNA synthesis (75%) and DNA binding (65%). However, the monomeric chimaeric HIV-1 RT (p68) exhibited RNAase H activity like that of the heterodimeric form (p66/p51) of HIV-1 RT. These results suggest that the linker insertion from FLV RT does not interfere with the RNAase H activity associated with the monomeric HIV-1 RT.

Amino Acid Sequence↗
PubMed1994

Noninvasive estimation of pulmonary artery wedge pressure by dual-M-mode-echocardiography.

Pulmonary artery wedge pressure (PAWP) measurement is invasive, associated with complications, contraindications and its high cost limits its use in clinical practice. We evaluated the use of dual-M-mode-echocardiography as a possible noninvasive alternative method in 20 patients for estimating the PAWP. The interval from the Q-wave of the electrocardiogram (ECG) to the mitral valve closure on the mitral valve M-mode-echocardiogram (Q-MVC), the interval between the aortic valve closure and mitral valve E point (AVC-E) on aortic and mitral valve M-mode-ECG respectively and the ratio of these intervals (Q-MVC/AVC-E) was correlated to the mean PAWP measured at catheterization. The mean PAWP correlated excellently with Q-MVC/AVC-E ratio [r = 0.89, p < 0.0001, y = 14.51 (Q-MVC/AVC-E) + 6.71]. The estimation of PAWP by a dual-M-mode-ECG offers a useful estimate of mean PAWP noninvasively.

Adolescent↗
PubMed1994

Energy expenditure and ventilatory responses during Siddhasana--a yogic seated posture.

Reports of energy expenditure and ventilatory responses to yogic seated posture of Siddhasana are lacking in literature. Various cardio-ventilatory responses were studied in states of the horizontal supine, chair-sitting and Siddhasana. It was observed that sitting in Siddhasana posture was characterised by greater minute ventilation, larger tidal volume, higher oxygen consumption, greater CO2 elimination, higher heart frequency greater oxygen pulse and lesser as compared with other two postures. These observations suggest that Siddhasana is a mild type of exercise and may have its application in conditions of low cardio-respiratory reserves especially in individuals in whom heavy exercises are contra-indicated.

Adult↗
PubMed1993

Purification and reconstitution of the delta opioid receptor.

The delta opioid receptor has been purified, in an active form, by succinylmorphine affinity chromatography. The receptor was purified partially from bovine frontal cortex and to apparent homogeneity from neuroblastoma x glioma hybrid NG108-15 cells as observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by silver staining. Antiserum to the purified bovine receptor inhibited ligand binding to membranes and immunoprecipitated a 58 kDa protein from NG108-15 cells. Reconstitution of the receptor with lipids enhanced binding by 9-fold. The 58 kDa band protein after electroelution and reconstitution with lipids also showed specific binding, indicating that the receptor could be renatured even after SDS-PAGE in an appropriate lipid environment.

Animals↗