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S K Sharma

Publications and source records attributed to S K Sharma.

At least 415 records · Page 23Linked to original sources
PubMed1990

Development of a sensitive activity assay for high-volume evaluation of human renin inhibitory peptides in rat serum: results with U-71,038.

A sensitive activity assay for high volume evaluation of human renin inhibitory peptides (RIPs) in rat sera (range 2-80 ng/ml) was developed based on the low affinity of RIPs to rat renin and their high affinity to human renin. The utility of this activity assay was tested by measuring concentrations of a human RIP, U-71,038 (BOC-Pro-Phe-N-MeHis-Leu psi [CHOHCH2]Val-Ile-Amp), in rat sera, determined by the activity assay, by a sensitive radioimmunoassay (RIA), and by tracking tritiated drug. Rats were given radiolabeled drug as an intravenous bolus, and blood samples were collected at various times after dosing. The serum level of U-71,038 equivalents was determined by the three techniques. Whole blood was also counted for total radioactivity to evaluate the potential for U-71,038 incorporation into red blood cells. Results from the three serum assays indicate good agreement between the calculated U-71,038 equivalents for the 30 min and 1 hr collection times. The 2 and 4 hr collection times show excellent agreement for the activity assay and RIA; [3H]-U-71,038 determinations gave substantially higher values. Serum levels for U-71,038 determined 30 min after dosing averaged less than 300 ng equivalents/ml suggesting that less than 1% of the administered dose was in the systemic circulation at that time. Thus, U-71,038 was rapidly cleared. At the 4 hr collection time, the level of U-71,038 equivalents, as determined by activity assay and RIA, was ten times the in vitro IC50 for the renin inhibitory activity of U-71,038.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Inactivation and clearance of an anti-CEA carboxypeptidase G2 conjugate in blood after localisation in a xenograft model.

Studies with a conjugate of carboxypeptidase G2 (CPG2) and the F(ab')2 fragment of monoclonal anti-CEA antibody, A5B7, have shown specific localisation in a human colon tumour xenograft, LS174T, growing in nude mice. The conjugate reaches a peak concentration in the tumour within 24 h but enzyme activity in blood remains above a critical value for therapeutic purposes for several days. Here we describe a new monoclonal antibody, SB43, raised against CPG2 which is capable of reducing enzyme activity in blood. In vitro studies demonstrated specific binding of SB43 to CPG2 causing inactivation. Moreover, in the nude mouse model SB43 was also capable of inactivating the enzyme in the circulation within minutes of administration. Radiolabelled native SB43 persisted in blood for several days and appreciable non-specific uptake into the xenograft was also observed. Uptake of SB43 by the tumour, with possible inactivation of CPG2 at this site, could be limited by first coupling the antibody to galactose. This ensured recognition and excretion of SB43 and SB43-enzyme complexes via the liver and their rapid removal from the circulation. Galactosylation had no effect on the ability of SB43 to inactivate the enzyme.

Animals↗
PubMed1990

Defined neurofilament, tau, and beta-amyloid precursor protein epitopes distinguish Alzheimer from non-Alzheimer senile plaques.

Eight antisera and one monoclonal antibody to synthetic peptides that corresponded to domains extending over the entire length of the beta-amyloid precursor protein (beta-APP), and an antiserum to the full-length 695-amino acid form of the beta-APP, were raised to probe the composition of the core and corona of senile plaques (SPs). We localized distinct beta-APP domains, including the beta-amyloid protein or A4 region, within the SPs of 13 end-stage Alzheimer disease (AD) and 13 age-matched control samples of hippocampus and entorhinal cortex. The composition of SPs also was probed with antibodies to defined epitopes in tau (tau) as well as the large and mid-size neurofilament (NF) proteins. The most important observations were that beta-APP domains outside the A4 region were largely restricted to SP coronas in the AD samples, together with tau and NF determinants, whereas the same epitopes were absent from A4-positive blood vessels and exceptionally rare in non-AD SPs. Indeed, samples from a subset of the non-AD cases contained a considerable number of A4-positive SPs totally devoid of any of the other beta-APP, tau, and NF epitopes. These observations suggest that the deposition of the A4 protein in AD SPs results from the local processing of beta-APPs in association with tau and NF protein fragments. It is unclear whether this association is fortuitous or linked by common mechanisms. However, differences between the complement of beta-APP, tau, and NF protein epitopes in AD versus non-AD brains implicate a defect involving one or more steps in the posttranslational modification, degradation, or elimination of these proteins in AD brains, and this may account for the massive numbers of SPs that characterize AD.

Alzheimer Disease↗
PubMed1990

Ureterovaginal fistula: summary of 18 years' experience.

Ureterovaginal fistula is an uncommon complication of pelvic operations. We report 31 such cases seen over an 18-year period, all of which followed surgery for benign gynaecological conditions. Most patients had no urinary symptoms until the sudden onset of incontinence 1 to 4 weeks post-operatively. Diagnosis was established by a combination of intravenous urography, cystography, cystoscopy, retrograde ureteropyelography and dye studies. Twenty-nine patients underwent ureteroneocystostomy, 10 with a Boari flap and 19 by a direct method; fistulas healed in 2 patients following conservative treatment. Renal salvage was achieved in all cases.

Adult↗
PubMed1990

MR imaging of uterine carcinoma: correlation with clinical and pathologic findings.

Thirteen patients with clinical stages I and II endometrial carcinoma were examined with magnetic resonance (MR) imaging before surgery. Depth of invasion and stage of disease were assessed, and the results were compared with those from MR images of the surgical specimens and pathologic findings. Staging with MR imaging was accurate in 11 of 13 patients (85%). Our results agree with previous reports that MR imaging is an accurate, noninvasive method of assessing depth of myometrial invasion and cervical involvement. We anticipate that MR imaging will have an increasing role in treatment of patients with endometrial carcinoma.

Aged↗
PubMed1990

Isolated testicular metastases from renal cell carcinoma.

Testicular metastasis from renal cell carcinoma is very rare. Herein we report a case of left-side renal cell carcinoma initially diagnosed to be clinically stage II, which developed left-side testicular metastases 2 months following radical nephrectomy. High inguinal orchiectomy was carried out. The patient was asymptomatic 2 months later. Although renal vein involvement in renal cell carcinoma is common and its extension into inferior vena cava well documented, tumour invasion of spermatic veins is rare.

Aged↗
PubMed1990

Effect of verapamil inhalation on bronchial asthma.

The effect of inhaled verapamil 20 mg on pulmonary functions and arterial blood gases in 15 patients with extrinsic bronchial asthma was studied in single-blind fashion. A significant decrease (p less than 0.05) in airway resistance and a significant increase (p less than 0.01) in specific conductance was observed after verapamil inhalation. A small increase (p less than 0.1) was observed in forced vital capacity and peak expiratory flow rate after verapamil inhalation; however, this was not statistically significant. None of the parameters of pulmonary function tests showed a significant change after normal saline inhalation. A significant fall in PaO2 (p less than 0.05) and PaCO2 (p less than 0.05) was noted after normal saline inhalation. PaCO2 showed a significant fall (p less than 0.01) after verapamil inhalation. Alveolar arterial oxygen gradient P(A-a)O2 widened significantly (p less than 0.001) after normal saline inhalation. A larger dose (20 mg) of verapamil inhalation produces a significant bronchodilator effect on large airways, but does not produce a significant change in arterial oxygen tension from the baseline value in patients with bronchial asthma.

Administration, Inhalation↗
PubMed1990

Effect of 4% lidocaine inhalation in bronchial asthma.

The effect of 4% lidocaine inhalation was studied in a single-blind fashion in 18 patients with chronic stable asthma. Inhalation of normal saline solution was used as placebo. None of the parameters except flow rate at 50% of vital capacity (V50) showed any statistically significant change from baseline values. V50 at 15 min was significantly lower (p less than 0.05) after 4% lidocaine inhalation. Considering more than 10% change from the baseline value as significant, 8 of 15 patients showed decrease in airway resistance (Raw) and 7 of the 15 patients showed an increase in specific airway conductance (SGaw) after 15 min of inhalation. However, V50 (8/18 patients), flow rate at 25% vital capacity [V25 (6/15 patients], and forced expiratory flow rate at 25-75% of the vital capacity (FEF25-75) (5/15 patients) showed a decrease after 15 min of 4% lidocaine inhalation. No change in pulmonary function was noted after 30 min of lidocaine inhalation. It is concluded from this study that lidocaine produces a small bronchodilatory effect on the large airways and a bronchoconstrictor effect on the small airways after 15 min of inhalation, but this effect is not statistically significant. It can be safely used as topical agent for bronchoscopy in patients with bronchial asthma.

Administration, Inhalation↗
PubMed1990

Effect of angiotensinogen concentration on renin activity following nephrectomy and adrenalectomy: implications in the activation of plasma prorenin.

We have studied the effects of bilateral nephrectomy and adrenalectomy on angiotensinogen concentration, plasma renin activity, and total plasma renin activity obtained after trypsin activation in rats and compared with controls. Our results show that the plasma angiotensinogen concentration of nephrectomized (NX) rats is 5-fold higher than that of adrenalectomized (AX) rats. On the other hand, plasma angiotensinogen concentration of AX rats was about 2.5-fold lower than that of control rats. While NX rat plasma possess no renin activity, its mixing (1:1, v/v) with AX plasma results in 2-fold increase in renin activity over that observed for AX plasma alone. These results suggest that the apparent increase in renin activity upon mixing these two plasmas is at least partly due to an overall increase in angiotensinogen concentration in the mixture. To show that it is not due to activation of NX plasma prorenin by a convertase from AX plasma, prorenin-free NX rat plasma was prepared by using an anti-renin immunoaffinity column. When this prorenin-free NX plasma was mixed (1:1, v/v) with AX, again a 2-fold increase in renin activity was observed which is attributed to the overall increase in plasma angiotensinogen in the mixture. It is concluded that rat plasma prorenin is probably not activated within the circulation by a prorenin convertase from the rat kidney.

Adrenal Glands↗
PubMed1990

Ultrasonic measurements of portal vasculature in diagnosis of portal hypertension. A controversial subject reviewed.

In a prospective ultrasound study, the various factors possibly influencing the portal vasculature were evaluated in normal subjects; the correlation of portal diameters with physical factors such as age, sex, and body texture was poor, whereas the caliber variation was significant with respiration, posture, and meal. Considering the fasting state, supine decubitus, and deep inspiration as suitable and standard variables, the diameters were compared in 100 healthy subjects and 50 patients with portal hypertension. The upper normal limits of portal, splenic, and superior mesenteric vein diameters were reported as 16, 12, and 11 mm, respectively, and the dimensions above these values provided an overall sensitivity of 72%, an accuracy of 91%, and a specificity of 100% in diagnosing the patients with suspected portal hypertension.

Adolescent↗
PubMed1990

Kainic acid induced epileptogenesis in developing normal & undernourished rats--a computerised EEG analysis.

Experimental epilepsy was induced in developing normal, undernourished and subsequently rehabilitated rats by locally injecting graded doses of Kainic acid (KA) in the right frontal cortex. Frequency and power spectral analysis of EEG was carried out to assess the progressive changes in EEG during KA-epileptogenesis. Undernourished animals were highly susceptible to seizure discharge. They exhibited generalized tonic-clonic discharge and had episodes of clinical seizures even after temporary neuronal recovery. Increase in power of delta, theta and decrease in alpha power was observed in the compressed spectral array (CSA) of undernourished animals. Delayed neuronal recovery with reduced background EEG and marked electrosilence in response to intra-rectal sodium valproate was observed in undernourished animals. Rehabilitated animals exhibited partial recovery which was related to the body weight gain. Spike frequency, spike amplitude and neuronal recovery time were not significantly differet between normal and undernourished animals at lower doses of KA (7.5-60 ng) whereas at higher doses (120-500 ng) marked differences were observed in these parameters. In KA treated undernourished rats 3H-glycine incorporation was significantly higher than normal in the hippocampus and spinal cord and lower in the cerebellum.

Age Factors↗
PubMed1990

Seizure susceptibility & intra rectal sodium valproate induced recovery in developing undernourished rats.

The seizure threshold and therapeutic potential of intrarectal sodium valproate were studied in young developing normal and undernourished rats, using the penicillin model. Undernourished rats were highly susceptible to seizure discharge. They exhibited generalised electrocortical inhibition and repeated episodes of epileptic discharges even after temporary neuronal recovery. Delayed spontaneous and drug induced neuronal recovery, low spike frequency and amplitude (P less than 0.001) reduced background EEG and marked electrocortical silence in response to intrarectal (25 mg/kg) sodium valproate treatment, was observed in the undernourished animals. Rehabilitated animals exhibited partial neuronal recovery which was related to the improvement in body weight. Analysis of spike frequency, spike amplitude and neuronal recovery time showed that both normal and undernourished animals behaved in a similar fashion at lower doses of penicillin (2.5 to 15 IU). Significant differences in the electrophysiological parameters were observed between the two groups at higher doses of penicillin (20 to 30 IU).

Administration, Rectal↗
PubMed1990

Substrate specificity and inhibitor structure-activity relationships of recombinant human renin: implications in the in vivo evaluation of renin inhibitors.

Homogeneous, active recombinant human renin obtained from Chinese hamster ovary (CHO) cells was characterized in vitro by (i) determination of its relative rates of hydrolysis of plasma angiotensinogens (ANGs) from human, monkey, baboon, rat, pig, rabbit, hamster, and dog and (ii) analysis of several synthetic ANG-based, inhibitors ranging in IC50 from 10(-10) to 10(-6) M. Comparison of the recombinant human renin with human kidney renin showed that these enzymes were indistinguishable from each other in terms of their plasma ANG specificities and inhibition by synthetic renin inhibitors. Porcine kidney renin was also characterized and shown to display plasma ANG hydrolysis profiles and inhibitor potencies that were markedly different from those of human renins. Finally, the results using the above plasma ANGs extend previous studies showing that the substrate specificity of human renin may be influenced by the amino acid residues at P2 (i.e., Ile, Val, or Tyr) and P3 (i.e., His or Tyr) sites. The relevance of these data to in vivo evaluation of renin inhibitors in animal models is discussed.

Amino Acid Sequence↗
PubMed1990

Evaluation of hepatoprotective activity of picroliv (from Picrorhiza kurroa) in Mastomys natalensis infected with Plasmodium berghei.

Administration of picroliv, a standardized fraction of alcoholic extent of Picrorhiza kurroa (3-12 mg/kg/day for two weeks) simultaneously with P. berghei infection showed significant protection against hepatic damage in Mastomys natalensis. The increased levels of serum glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), alkaline phosphatase, lipoprotein-X (LP-X) and bilirubin in the infected animals were marked reduced by different doses of picroliv. In the liver, picroliv decreased the levels of lipid peroxides and hydroperoxides and facilitated the recovery of superoxide dismutase and glycogen. Picroliv had no effect on the degree of parasitaemia.

Animals↗