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Biomedical subjects

S Kaur

Publications and source records attributed to S Kaur.

At least 127 records · Page 7Linked to original sources
PubMed1996

Motor actions of eliprodil in the normal and monoamine-depleted mouse: a role in the treatment of Parkinson's disease?

The non-competitive NMDA polyamine site antagonist, eliprodil, was examined for its effects on exploratory activity in non-habituated mice and for its antiakinetic potential in reserpine-treated mice. A low dose of eliprodil (5 mg/kg) weakly stimulated locomotion in naive animals, whilst higher doses depressed rearing (20-40 mg/kg) and grooming (40 mg/kg), consistent with a sedative action. At no dose did eliprodil cause ataxia. In 24 h reserpine-treated mice, eliprodil (10-40 mg/kg) reversed akinesia, but this effect was subject to considerable inter-animal variation and was not statistically significant. Eliprodil did not alter the motor recovery elicited by the dopamine D1 agonist SKF 38393, or the dopamine D2 agonist RU 24213, and suppressed the motor stimulation induced by L-DOPA. These results indicate that eliprodil displays a far lower propensity than many other NMDA receptor antagonists for disturbing posture and gait, but lacks the essential motor stimulant action required to make it a safe and effective antiparkinsonian agent, at least in the reserpine-treated mouse model of Parkinson's disease.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1996

Incidence and outcome of overt gastrointestinal bleeding in patients undergoing bone marrow transplantation.

The purpose of this study was to determine the prevalence, clinical patterns, and outcomes of gastrointestinal bleeding in consecutive patients treated at one bone marrow transplant center. We reviewed the clinical course of 579 consecutive bone marrow transplant recipients who underwent therapy from January 1986 through December 1993. These patients were evaluated for overt gastrointestinal bleeding, defined as hematemesis, melena, hematochezia, or a combination. Overt gastrointestinal bleeding was defined in 43 of 579 patients (7.4%), including 25 men and 18 women undergoing transplantation for hematologic disorders (N = 29) and solid tumors (N = 14). After high-dose cytotoxic chemotherapy, patients were given allogeneic (N = 10) or autologous (N = 33) hematopoietic progenitor cell support obtained from bone marrow, peripheral blood, or both. H2 blockers, sucralfate, or a combination were administered to all patients as prophylactic therapy. Bleeding manifestations included hematemesis(N = 24, melena (N = 8), hematochezia (N = 7), and combinations (N = 4). The median time from bone marrow infusion to the onset of overt gastrointestinal bleeding was 7.5 days (range: 0-45 days). Fourteen patients had evidence of orthostatic hypotension attributable to gastrointestinal bleeding. Esophagogastroduodenoscopy was performed in 26 patients; 18 had diffuse esophagitis and gastritis. Two patients with bleeding ulcers underwent successful electrocautery. Colonoscopy was performed in five patients and revealed a cecal ulcer in one subject, tumor recurrence in one patient, and colitis in another. No patients underwent surgical intervention. Only ine patient died as a result of gastrointestinal bleeding. Overt gastrointestinal bleeding is uncommon in patients undergoing bone marrow transplantation; most episodes are self-limited and do not contribute to overall mortality. Endoscopy is primarily diagnostic as most patients do not have lesions amenable to therapeutic procedures.

Adolescent↗
PubMed1996

Reduction of bleeding after heart operations through the prophylactic use of epsilon-aminocaproic acid.

UNLABELLED: Excessive postoperative bleeding after heart operations continues to be a source of morbidity. This prospective double-blind study evaluated epsilon-aminocaproic acid as an agent to reduce postoperative bleeding and investigated its mode of action. One hundred three patients were randomly assigned to receive either 30 gm epsilon-aminocaproic acid (51 patients) or an equivalent volume of placebo (52 patients). In a subset of these patients (14 epsilon-aminocaproic acid, 12 placebo), tests of platelet function and fibrinolysis were performed. RESULTS: By multivariate analysis, three factors were associated with decreased blood loss in the first 24 hours after operation: epsilon-aminocaproic acid versus placebo (647 ml versus 839 ml, p = 0.004), surgeon 1 versus all other surgeons (582 ml versus 978 ml, p = 0.002), and no intraaortic balloon versus intraaortic balloon pump use (664 ml versus 1410 ml, p = 0.02). No significant differences in platelet function could be demonstrated between the two groups. Inhibited fibrinolysis, as reflected by less depression of the euglobulin clot lysis and no rise in D-dimer levels, was significant in the epsilon-aminocaproic acid group compared with the placebo group. CONCLUSION: The intraoperative use of epsilon-aminocaproic acid reduces postoperative cardiac surgical bleeding.

Aminocaproic Acid↗
PubMed1996

Microbicidal mechanisms of liver macrophages in experimental visceral leishmaniasis.

To study the differential microbicidal potentials of liver macrophages, the oxygen-dependent and oxygen-independent pathways in Kupffer cells and immigrant macrophages of Leishmania donovani-infected BALB/c mice were investigated. Hydrogen peroxide assay was performed using horse radish peroxidase-dependent oxidation of phenol red to quantitate the reactive oxygen species produced. To examine the oxygen-independent pathway, the enzymes N-acetyl-beta-glucosaminidase (NAG) and beta-glucuronidase (beta G) were investigated after exposure of cells to lipopolysaccharide. Hydrogen peroxide release by Kupffer cells was significantly decreased only at 21 days postinfection, whereas hydrogen peroxide release by immigrant macrophages was significantly increased on all postinfection days with a maximum at 21 days postinfection. The pattern of release of NAG and beta G was similar in both cell populations with a peak at 21 days postinfection. The present study therefore suggests that Kupffer cells and immigrant macrophages adopt different pathways to cope with this infection.

Acetylglucosaminidase↗
PubMed1996

Disulfide bonds of herpes simplex virus type 2 glycoprotein gB.

Glycoprotein B (gB) is the most highly conserved envelope glycoprotein of herpesviruses. The gB protein is required for virus infectivity and cell penetration. Recombinant forms of gB being used for the development of subunit vaccines are able to induce virus-neutralizing antibodies and protective efficacy in animal models. To gain structural information about the protein, we have determined the location of the disulfide bonds of a 696-amino-acid residue truncated, recombinant form of herpes simplex virus type 2 glycoprotein gB (HSV gB2t) produced by expression in Chinese hamster ovary cells. The purified protein, which contains virtually the entire extracellular domain of herpes simplex virus type 2 gB, was digested with trypsin under nonreducing conditions, and peptides were isolated by reversed-phase high-performance liquid chromatography (HPLC). The peptides were characterized by using mass spectrometry and amino acid sequence analysis. The conditions of cleavage (4 M urea, pH 7) induced partial carbamylation of the N termini of the peptides, and each disulfide peptide was found with two or three different HPLC retention times (peptides with and without carbamylation of either one or both N termini). The 10 cysteines of the molecule were found to be involved in disulfide bridges. These bonds were located between Cys-89 (C1) and Cys-548 (C8), Cys-106 (C2) and Cys-504 (C7), Cys-180 (C3) and Cys-244 (C4), Cys-337 (C5) and Cys-385 (C6), and Cys-571 (C9) and Cys-608 (C10). These disulfide bonds are anticipated to be similar in the corresponding gBs from other herpesviruses because the 10 cysteines listed above are always conserved in the corresponding protein sequences.

Amino Acid Sequence↗
PubMed1996

Evidence for a phosphorylation site in cytomegalovirus glycoprotein gB.

As part of our vaccine program, we have purified a recombinant form of human cytomegalovirus glycoprotein B that is able to induce high titers of virus-neutralizing antibodies. The isolated protein was found to be phosphorylated at a serine residue in position -7 from the C terminus of the protein. The corresponding synthetic peptide, HLKDSDEEENV, was an efficient in vitro substrate of casein kinase II.

Amino Acid Sequence↗
PubMed1996

Amino-acid-dependent modulation of amino acid transport in Xenopus laevis oocytes.

We have measured rates of uptake of arginine, glutamine, glutamate, serine, phenylalanine and glycine in Xenopus laevis oocytes cultured for periods of up to 24h in saline in the presence or absence of a mixture of 20 amino acids at concentrations approximating those in Xenopus plasma. Amino acid supplementation increased the total intracellular amino acid concentration from 8.2 to 18.4 nmol per oocyte. Specific Na(+)-dependent amino acid transporters (systems B0,+, Xag-) exhibit 'adaptive regulation' (up-regulation during amino acid deprivation and down-regulation during amino acid supplementation). Na(+)-independent transporters of glutamate, glutamine and glycine (including system asc) display an opposite modulation in activity, which may help to combat amino-acid-induced oxidative stress by increasing the supply of glutathione precursors. Single amino acids at physiological plasma concentrations (0.47 mmol l-1 L-alanine, 0.08 mmol l-1 L-glutamate) mimicked at least some effects of the amino acid mixture. The mechanisms of transport modulation do not appear to include trans-amino acid or membrane potential effects and, in the case of Na(+)-independent transport, are independent of protein or mRNA synthesis. Furthermore, activation of protein kinase C by phorbol 12-myristate 13-acetate did not significantly affect endogenous glutamine and glutamate transport. The Xenopus oocyte appears to possess endogenous signalling mechanisms for selectively modulating the activity of amino acid transport proteins expressed in its surface membranes, a factor for consideration when using oocytes as an expression system for structure-function studies of cloned amino acid transporters.

Amino Acid Transport Systems↗
PubMed1996

Antigenic differences between axenic amastigotes & promastigotes of Leishmania donovani.

The axenic amastigotes of an Indian strain of L. donovani have been generated from the promastigote form at 37 degrees C in RPMI-1640 medium, pH 6.0 +/- 0.5, supplemented with 10 per cent heat inactivated foetal calf serum and these are being maintained through serial subculturing under the same conditions. The present study was carried out to differentiate axenic amastigote from the promastigote stage on the basis of their antigenic constitution and also to look for any immunoreactive antigen(s) specific to axenic amastigotes. SDS-PAGE analysis revealed a few stage specific and some conserved antigenic fractions in both the stages. On immunoblotting with immune sera raised against the membrane fractions of the axenic amastigotes, the 200 kDa antigenic fraction of axenic amastigote was found to be highly reactive. When the immune sera raised against the membranes of both stages were checked by immunofluorescence no cross reactivity was observed at higher dilutions. These findings showed that there are some antigenic diversities as well as similarities between the two stages of L. donovani cultured in vitro. Also, the 200 kD fraction of axenic amastigote appeared to be an immunodominant antigen specific to that stage.

Animals↗
PubMed1995

Antiparkinsonian action of dextromethorphan in the reserpine-treated mouse.

Dextromethorphan has been reported to be a weak antagonist of the ion channel associated with the NMDA receptor, and to have putative antiparkinsonian activity in man. This study looked at the effects of dextromethorphan in normal and monoamine-depleted mice, to determine whether it exhibited a behavioural profile with regard to motor activity that was consistent with NMDA receptor blockade. In normal mice, 5-80 mg/kg i.p. dextromethorphan caused modest muscle relaxation at the highest dose in all animals; hyperlocomotion and stereotypy were evident at 40 mg/kg i.p. in a fraction of mice (4/14). In 24 h reserpine-treated mice, locomotion was reinstated by the dopamine D1 receptor agonist 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine hydrochloride (SKF 38393, 30 mg/kg i.p.), the dopamine D2 receptor agonist N-n-propyl-N-phenylethyl-p-(3-hydroxyphenyl)ethylamine (RU 24213, 5 mg/kg s.c.) and L-3,4-dihydroxyphenylalanine (L-DOPA, 150 mg/kg i.p. in conjunction with benserazide 100 mg/kg i.p.). Dextromethorphan alone (10-40 mg/kg i.p.) caused non-significant arousal of monoamine-depleted mice, but potentiated synergistically movements elicited by SKF 38393 and L-DOPA, though not RU 24213. The possible use of dextromethorphan as an adjunct to L-DOPA in the treatment of Parkinson's disease in man, is discussed.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1995

Gsh-1: a novel murine homeobox gene expressed in the central nervous system.

We report the characterization of Gsh-1, a novel murine homeobox gene. Northern blot analysis revealed a transcript of approximately 2 kb in size present at embryonic days 10.5, 11.5, and 12.5 of development. The cDNA sequence encoded a proline rich motif, a polyalanine tract, and a homeodomain with strong homology to those encoded by the clustered Hox genes. The Gsh-1 expression pattern was determined for days E8.5 to E13.5 by whole mount and serial section in situ hybridizations. Gsh-1 transcription was restricted to the central nervous system. Expression is present in the neural tube and hindbrain as two continuous, bilaterally symmetrical stripes within neural epithelial tissue. In the mesencephalon, expression is seen as a band across the most anterior portion. There is also diencephalon expression in the anlagen of the thalamus and the hypothalamus as well as in the optic stalk, optic recess, and the ganglionic eminence. Moreover, through the use of fusion proteins containing the Gsh-1 homeodomain, we have determined the consensus DNA binding site of the Gsh-1 homeoprotein to be GCT/CA/CATTAG/A.

Amino Acid Sequence↗
PubMed1995

Primary liver cancer and survival in patients undergoing liver transplantation for hemochromatosis.

Cirrhotic patients with hereditary hemochromatosis (HHC) have an increased risk of primary liver cancer (PLC). The purpose of this study was to determine the prevalence of primary liver cancer in patients with HHC undergoing orthotopic liver transplantation (OLT). Five liver transplant centers were surveyed; clinical and pathological data on 37 patients with HHC undergoing OLT were retrospectively collected and analyzed. The diagnosis of HHC was established by a combination of serum transferrin-iron saturation, hepatic iron index (HII), and/or pattern of liver iron staining. The diagnosis of HHC had been unsuspected before OLT in 13 of 37 (35%). Primary liver cancer was found in the explants of 10 of 37 patients (27%) and was unsuspected in 7 of 10 (70%); 8 were hepatocellular carcinoma, and 2 were cholangiocarcinoma; foci of hepatocyte dysplasia were found in 6 additional patients. Mean (+/- SEM) hepatic iron content and HII in 20 patients without prior phlebotomy or bleeding were 17.2 mg/g dry weight (+/- 2.9) and 5.5 (+/- 0.8), respectively. The overall 1-year survival rate after OLT in the 37 HHC patients was 58% (v 55% for HHC patients with PLC). We draw the following conclusions: (1) the diagnosis of HHC is often unsuspected before OLT, and HHC should be evaluated pretransplantation by direct and indirect markers; (2) HHC patients undergoing OLT have a high prevalence of primary liver cancer, the majority being unsuspected; and (3) HHC patients have poorer than average survival after OLT, which cannot be explained solely by the presence of concomitant PLC.

Female↗
PubMed1995

Duodenal ulcer. Calcium status in isolated parietal cells.

Although the etiology of duodenal ulcer is not known, its treatment with drugs that reduce acid secretion is well accepted. The central role of calcium in stimulus-secretion coupling resulting in acid secretion by gastric parietal cells is documented. However, the status of intracellular calcium in gastric parietal cells in the basal state in patients with duodenal ulcer is not known. Multiple endoscopic gastric mucosal biopsies from the corpus of the stomach of 52 patients were processed and isolated parietal cells were studied. Intracellular calcium was estimated using fura-2-acetoxymethyl ester. Influx and efflux were determined by using radioactive calcium. Acridine orange retention was used to assess acid production. Only calcium influx at 20 min was significantly (P < 0.01) more in patients with duodenal ulcer as compared to the control group. There was no difference between the groups in calcium influx at 0 and 60 min; calcium efflux at 0, 20, and 60 min; intracellular free calcium and acid secretion. We conclude that in the unstimulated state calcium homeostasis in isolated parietal cells of patients with duodenal ulcer shows only a minimal difference as compared to controls.

Adult↗
PubMed1995

Role of reactive oxygen species in renal damage in experimental leprosy.

Renal involvement is known to occur in leprosy. In the present study the possible role of reactive oxygen species (ROS) in causation of renal damage in mice infected with Mycobacterium leprae has been investigated. At least six animals from each group (control and infected) were killed at 0 day, 3, 6 and 9 months postinfection. The results showed a significant increase in the chemiluminescence (CL) response of peritoneal macrophages which was maximum between 3 and 6 months. No significant increase was observed in CL response of blood neutrophils. A significant increase in lipid peroxidation was observed at 3 and 6 months as evident by an increase in malondialdehyde levels. The increased ROS production might be the cause of lipid peroxidation. The renal damage is alos evident by decrease in the activity of renal brush border membrane enzymes, namely, alkaline phosphatase, leucine aminopeptidase and r-glutamyl transpeptidase. Thus ROS might play a role during early stages of M. leprae infection but in the later stages other immunological mechanisms may overpower the effect of ROS.

Alkaline Phosphatase↗
PubMed1994

Gsh-4 encodes a LIM-type homeodomain, is expressed in the developing central nervous system and is required for early postnatal survival.

We present an initial characterization of the murine Gsh-4 gene which is shown to encode a LIM-type homeodomain. Genes in this category are known to control late developmental cell-type specification events in simpler organisms. Whole mount and serial section in situ hybridizations show transient Gsh-4 expression in ventrolateral regions of the developing neural tube and hindbrain. Mice homozygous for a targeted mutation in Gsh-4 suffer early postnatal death resulting from immature lungs which do not inflate. Prenatal administration of progesterone and glucocorticoid, to extend gestational term and accelerate maturation, resulted in lung inflation at birth. Nevertheless, the hormonally treated mutants generally failed to survive beyond an hour after birth, due to ineffective breathing efforts. It is concluded that Gsh-4 plays a critical role in the development of respiratory control mechanisms and in the normal growth and maturation of the lung.

Amino Acid Sequence↗
PubMed1994

Role of D1 receptor mechanisms in the potentiation of motor responses to L-dopa and apomorphine by MK 801 in the reserpine-treated mouse.

In 24 h reserpine-treated akinetic mice, locomotion was induced by the D1-selective agonist SKF 38393 (30 mg/kg IP), or by the mixed D1/D2 agonists L-dopa (150 mg/kg IP, plus benserazide 100 mg/kg IP) and apomorphine (0.5 mg/kg SC). The non-competitive NMDA receptor antagonist MK 801 (0.01-1.6 mg/kg IP) did not induce motor activity by itself, but potentiated the motor responses to L-dopa and apomorphine at roughly 10-fold lower doses than those which facilitated D1 responding. These data cast doubt on the notion that glutamate antagonists enhance the antiparkinsonian efficacy of mixed D1/D2 agonists solely through a D1 receptor mechanism.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1994

Further experience with pemphigus in children.

Seven children had pemphigus: six had pemphigus vulgaris and one pemphigus foliaceus. Four who had pemphigus vulgaris were administered dexamethasone pulses. Follow-up from six months to one year was uneventful; the disease was under control and there were no complications due to therapy. Our observations suggest that the clinical features, course, and principles of therapy for pemphigus in children are essentially the same as those in adults.

Adolescent↗