PubMed Health⌕ Search

Biomedical subjects

D Sharma

Publications and source records attributed to D Sharma.

At least 19 recordsLinked to original sources
PubMed2001

Decreased glutamate receptor 2 expression and enhanced epileptogenesis in immature rat hippocampus after perinatal hypoxia-induced seizures.

Hypoxic encephalopathy is the most common cause of neonatal seizures and can lead to chronic epilepsy. In rats at postnatal days 10-12 (P10-12), global hypoxia induces spontaneous seizures and chronically decreases seizure threshold, thus mimicking clinical aspects of neonatal hypoxia. We have shown previously that the acute and chronic epileptogenic effects of hypoxia are age-dependent and require AMPA receptor activation. In this study, we aimed to determine whether hypoxia-induced seizures and epileptogenesis are associated with maturational and seizure-induced changes in AMPA receptor composition and function. Northern and Western blots indicated that glutamate receptor 2 (GluR2) mRNA and protein expression were significantly lower in neocortex and hippocampus at P10-12 compared with adult. After hypoxia-induced seizures at P10, GluR2 mRNA was significantly decreased within 48 hr, and GluR2 protein was significantly decreased within 96 hr. AMPA-induced Co(2+) uptake by neurons in hippocampal slices indicated higher expression of Ca(2+)-permeable AMPA receptors in immature pyramidal neurons compared with adult. In slices obtained 96 hr after hypoxia-induced seizures, AMPA-induced Co(2+) uptake was significantly increased compared with age-matched controls, and field recordings revealed increased tetanus-induced afterdischarges that could be kindled in the absence of NMDA receptor activation. In situ end labeling showed no acute or delayed cell death after hypoxia-induced seizures. Our results indicate that susceptibility to hypoxia-induced seizures occurs during a developmental stage in which the expression of Ca(2+)-permeable AMPA receptors is relatively high. Furthermore, perinatal hypoxia-induced seizures induce increased expression of Ca(2+)-permeable AMPA receptors and an increased capacity for AMPA receptor-mediated epileptogenesis without inducing cell death.

Aging↗
PubMed2001

Insights into Wnt binding and signalling from the structures of two Frizzled cysteine-rich domains.

Members of the Frizzled family of seven-pass transmembrane proteins serve as receptors for Wnt signalling proteins. Wnt proteins have important roles in the differentiation and patterning of diverse tissues during animal development, and inappropriate activation of Wnt signalling pathways is a key feature of many cancers. An extracellular cysteine-rich domain (CRD) at the amino terminus of Frizzled proteins binds Wnt proteins, as do homologous domains in soluble proteins-termed secreted Frizzled-related proteins-that function as antagonists of Wnt signalling. Recently, an LDL-receptor-related protein has been shown to function as a co-receptor for Wnt proteins and to bind to a Frizzled CRD in a Wnt-dependent manner. To investigate the molecular nature of the Wnt signalling complex, we determined the crystal structures of the CRDs from mouse Frizzled 8 and secreted Frizzled-related protein 3. Here we show a previously unknown protein fold, and the design and interpretation of CRD mutations that identify a Wnt-binding site. CRDs exhibit a conserved dimer interface that may be a feature of Wnt signalling. This work provides a framework for studies of homologous CRDs in proteins including muscle-specific kinase and Smoothened, a component of the Hedgehog signalling pathway.

Alanine↗
PubMed2001

Acetyl-L-carnitine enhances Na(+), K(+)-ATPase glutathione-S-transferase and multiple unit activity and reduces lipid peroxidation and lipofuscin concentration in aged rat brain regions.

This study investigated the effects of chronically administered acetyl-L-carnitine (ALC) on sodium potassium adenosine triphosphatase (Na(+), K(+)-ATPase), glutathione-S-transferase (GST), glutathione peroxidase (GPx), multiple unit activity (MUA) and lipid peroxidation (LP) and lipofuscin (LF) concentration in brain regions: cerebral cortex, hippocampus, striatum and thalamus, of 24-month-old rats. The activity of Na(+), K(+)-ATPase and GST was enhanced; that of GPx was unaffected. The MUA was increased while the levels of LP and LF were decreased. These novel data provide new additional evidence concerning the antiaging attributes of ALC.

Acetylcarnitine↗
PubMed2001

Expansion mutation frequency and CGG/GCC repeat polymorphism in FMR1 and FMR2 genes in an Indian population.

Based on molecular screening, we estimated the frequencies of fragile X syndrome and FRAXE syndrome in an institutionalized population (n = 130) in New Delhi, India. Eligibility criteria for inclusion of subjects in the study were mild/moderate mental retardation, with/without family history, and the fragile X clinical phenotype. Screening by Southern hybridization revealed an overall frequency of 0.077 of the syndrome in the sample population. The disorder was observed with a high frequency (0.1) among males as compared to females (0.027). No expansions of FMR2 allele were observed in the same study sample. CGG/GCC allelic polymorphism of FMR1 and FMR2 were established from a total of 392 X chromosomes, using the radioactive polymerase chain reaction-polyacrylamide gel electrophoresis method. Distinct repeat sizes, repeat ranges, and repeat modes characterised the FMR1 and FMR2 alleles. In the X chromosomes of both MR individuals and unaffected controls, unimodal values of 29 and 15 repeats in FMR1 and FMR2 genes, respectively, were observed. Allele frequency distribution was symmetrical at the FMR1 locus whereas a significant positive skew was observed for the FMR2 alleles. The observed heterozygosity of the FMR1 gene was 0.772 compared to 0.839 of FMR2. Correlation of CGG/GCC repeats of FMR1 and FMR2 did not show any association of repeat sizes at these two loci (correlation coefficient, rho = 0.09). CGG/GCC repeat variation at FMR1 and FMR2 loci observed in this study sample are different from that reported for the other Caucasian and Asian populations.

Adolescent↗
PubMed2001

Imaging of frontal sinus disease: concepts, interpretation, and technology.

Imaging of the frontal sinus is an integral part of patient evaluation. High-resolution computed tomography (CT) imaging is the preferred modality for evaluation of sinus inflammatory disease. Magnetic resonance (MR) imaging plays an important role in differentiating tumors from inflammatory diseases and serves as a problem-solving tool.

Carcinoma, Squamous Cell↗
PubMed2001

Selective attentional bias to alcohol related stimuli in problem drinkers and non-problem drinkers.

AIMS: The issues explored in this study were whether a patient group of problem drinkers selectively attend to alcohol-related stimuli and the time course of any interference from alcohol-related stimuli in comparison with two control groups of non-problem drinkers. DESIGN: A 3 x 2 x 2 x 5 factorial design was used. Drinking group (low, high and problem) and word order (alcohol-neutral, neutral-alcohol) were between-participant factors, and word type (alcohol, neutral) and presentation block (1-5) were within participant factors. PARTICIPANTS: Three groups were used, 20 participants from a local community alcohol Service (CAS) and 40 participants (student volunteers) in two control groups. The two control groups were differentiated as scoring high or low on the Alcohol Use Disorders Identification Test (AUDIT). MEASUREMENTS: A modified computerized Stroop colour naming test was used to measure response latencies. Anxiety was measured using the State-Trait Anxiety Inventory. FINDINGS: The CAS group showed significantly longer reaction times to respond to the colour of alcohol-related words than to neutral category words. Although the interference was smaller for the high AUDIT group it was significant. No significant interference was found in the low AUDIT group. There was no statistical evidence that the interference habituated in the three groups. CONCLUSIONS: The present study showed it is possible to use a modified Stroop task as a measure of implicit processing of alcohol stimuli. Despite the fact that all participants were asked to ignore the words, they were unable to do so. Alcohol-related words produced more interference than neutral category words in a group of problem drinkers and a control group of high alcohol drinkers.

Adult↗
PubMed2001

A modified technique of devascularization for surgical management of portal hypertension in children.

In developing countries surgery is indicated in patients with portal hypertension for a variety of reasons. This study prospectively evaluates a modified technique of devascularization for secondary prophylaxis of variceal bleeding in patients with portal hypertension of different aetiologies. Transabdominal extensive oesophagogastric devascularization combined with transmural ligation of oesophageal and gastric varices was performed in 16 paediatric patients (nine with extrahepatic portal venous obstruction, and seven with non-cirrhotic portal fibrosis) in an elective setting. The Sugiura devascularization procedure was modified to minimize the operating time and to avoid the problems associated with oesophageal transection and anastomosis. The operative mortality rate as well as the oesophageal leak rate was zero. One patient developed an oesophageal stricture. During a 12-month follow-up, patients were seen with residual varices (2), recurrent varices (3) and rebleeding (1). Porto-systemic encephalopathy was seen in one patient only. This technique is a simple, straightforward, safe and effective modification of the Sugiura procedure in controlling bleeding, providing good quality of life with minimal porto-systemic encephalopathy.

Child↗
PubMed2001

Amoeboma of ascending colon with multiple amoebic liver abscesses.

A case of amoeboma of the ascending colon with multiple amoebic liver abscess is being presented; which was mistakenly diagnosed as carcinoma of ascending colon with multiple secondaries in liver. Awareness of this previously unreported association is important because it adds to our knowledge of the spectrum of intestinal amoebiasis.

Animals↗
PubMed2001

A comparative of the effect of tamoxifen on serum lipid and lipoprotein profile in premenopausal & postmenopausal women with breast carcinoma & associated risk of vascular complication.

To examine the effect of tamoxifen on serum lipid and lipoprotein profile of premenopausal and postmenopausal patients of breast carcinoma (with and without vascular disease) we performed a short term evaluation of serum lipid and lipoprotein profile of 38 pre and 42 post menopausal subjects of breast carcinoma (with and without vascular disease) at baseline and during 3 and 6 months of tamoxifen therapy. The lipid & Lp profile of premenopausal patients of Breast carcinoma without vascular disease showed no significant variation after 3 and 6 months of tamoxifen treatment than the corresponding baseline values, but in premenopausal subjects of breast cancer with vascular disease and post menopausal subjects of breast carcinoma (both with and without vascular disease), Serum TC, Apo-B and Lp (a) were significantly decreased and serum HDL and Apo A-I were elevated significantly, However serum TG remain unaltered in premenopausal patients of breast carcinoma with vascular disease but found to be elevated significantly in postmenopausal subjects of breast cancer, both, with and without vascular disease, after 3 and 6 months of tamoxifen treatment, than the corresponding baseline values. Also, the comparison of the results of the present study for pre and postmenopausal patients of breast cancer revealed that the administration of tamoxifen, as adjuvant therapy for breast cancer, is beneficial for postmenopausal patients of breast carcinoma with vascular disease as the drug minimises the risk of vascular disease by bringing significant improvement in serum lipid and Lp profiles of the patients but does not have any significant beneficial effect on familial hyperlipidemic patients of breast cancer.

Antineoplastic Agents, Hormonal↗
PubMed2001

The role of time pressure on the emotional stroop task.

Although a wide range of methodologies have been employed in examining the emotional Stroop effect, little systematic investigation of these experimental manipulations has taken place. Two experiments were designed to investigate the role of time pressure in the emotional Stroop effect. It is shown that time pressure has an important role to play in determining not only the magnitude of the effect but also in whether it is possible to observe any effect at all.

Color↗
PubMed2000

Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial--the Losartan Heart Failure Survival Study ELITE II.

BACKGROUND: The ELITE study showed an association between the angiotensin II antagonist losartan and an unexpected survival benefit in elderly heart-failure patients, compared with captopril, an angiotensin-converting-enzyme (ACE) inhibitor. We did the ELITE II Losartan Heart Failure Survival Study to confirm whether losartan is superior to captopril in improving survival and is better tolerated. METHODS: We undertook a double-blind, randomised, controlled trial of 3,152 patients aged 60 years or older with New York Heart Association class II-IV heart failure and ejection fraction of 40% or less. Patients, stratified for beta-blocker use, were randomly assigned losartan (n=1,578) titrated to 50 mg once daily or captopril (n=1,574) titrated to 50 mg three times daily. The primary and secondary endpoints were all-cause mortality, and sudden death or resuscitated arrest. We assessed safety and tolerability. Analysis was by intention to treat. FINDINGS: Median follow-up was 555 days. There were no significant differences in all-cause mortality (11.7 vs 10.4% average annual mortality rate) or sudden death or resuscitated arrests (9.0 vs 7.3%) between the two treatment groups (hazard ratios 1.13 [95.7% CI 0.95-1.35], p=0.16 and 1.25 [95% CI 0.98-1.60], p=0.08). Significantly fewer patients in the losartan group (excluding those who died) discontinued study treatment because of adverse effects (9.7 vs 14.7%, p<0.001), including cough (0.3 vs 2.7%).

Aged↗
PubMed2000

Meta-analysis of observed mortality data from all-controlled, double-blind, multiple-dose studies of losartan in heart failure. Losartan Heart Failure Mortality Meta-analysis Study Group.

Clinical studies of heart failure utilizing losartan, an angiotensin-II receptor antagonist, found that this drug is well tolerated and demonstrates hemodynamic, neurohormonal, and symptomatic improvement. To assess all-cause mortality in heart failure patients treated with losartan, a meta-analysis including 1,896 patients was performed on 6 controlled, double-blind, multiple-dose studies, regardless of sample size or duration of follow-up. A combination of logarithmic (log) odds ratios with a continuity correction was utilized for the meta-analysis. Treatment groups were comparable with regard to demographic characteristics, heart failure characteristics, and concomitant cardiovascular therapies. Concomitant use of open-label angiotensin-converting enzyme (ACE) inhibitors was not allowed in any study. The mean left ventricular ejection fraction obtained in individual studies ranged from 23% to 31%. Seven hundred forty patients were randomized to control therapy and 1,154 patients were randomized to losartan therapy. There were 36 deaths (3.12%) in the losartan groups compared with 47 in the control groups (6.35%) during the double-blind periods. The odds of dying in the losartan groups were 0.51 times (0.31 to 0.81) that of dying in the control groups (p = 0.004). In this analysis, treatment with losartan provided a beneficial effect upon survival. However, because the number of deaths in these studies is relatively small and the follow-up relatively short, a large confirmatory study is needed to assess the mortality benefit of losartan compared with an ACE inhibitor.

Adult↗
PubMed2000

Trypanosoma cruzi: roles for perforin-dependent and perforin-independent immune mechanisms in acute resistance.

CD8+ T cells have been shown to be required for acute resistance to infection with the protozoan parasite, Trypanosoma cruzi, the causative agent of Chagas' disease. However, to date, the mechanism by which CD8+ T cells mediate protection in vivo has not been determined. While CD8+ T cells can exhibit cytolytic function, they also secrete cytokines such as IFN-gamma, which is known to mediate protection against T. cruzi infections. To determine whether cytolysis is an important effector function in vivo, we have compared outcomes of T. cruzi infection in normal and perforin-deficient mice. Our results indicate that while perforin-dependent cytolytic mechanisms clearly make a major contribution to acute resistance to T. cruzi infection, this contribution may be strain and challenge dose-dependent, since perforin-deficient mice challenged with lower doses of a less virulent strain survived and were subsequently resistant to challenge with virulent organisms. In vivo depletion studies demonstrated that survival of perforin-deficient mice challenged with low doses of T. cruzi requires both CD4+ and CD8+ T cells and is dependent on IFN-gamma secretion. These studies document the participation of both perforin-dependent cytotoxic and perforin-independent, IFN-gamma-dependent immune mechanisms in acute resistance to T. cruzi infection.

Animals↗
PubMed2000

Congenital diaphragmatic hernia "occulta".

Congenital diaphragmatic hernia usually presents with cyanotic attacks, dyspnoea and dextrocardia, a typical triad which is almost considered pathognomonic. The case records of 10 patients (out of a total of 20) of congenital diaphragmatic hernia presenting beyond the neonatal period were reviewed retrospectively. Age and symptoms at presentation and signs elicited were paid special attention. All the patients underwent operative repair of hernia under general anaesthesia. Given below is an explanation for such a high incidence of late presentation in our series. This nomenclature (Congenital Diaphragmatic Hernia "Occulta") will help clinicians in remembering this entity if and when such patients present to the clinicians.

Child↗
PubMed2000

13C NMR chemical shifts can predict disulfide bond formation.

The presence of disulfide bonds can be detected unambiguously only by X-ray crystallography, and otherwise must be inferred by chemical methods. In this study we demonstrate that 13C NMR chemical shifts are diagnostic of disulfide bond formation, and can discriminate between cysteine in the reduced (free) and oxidized (disulfide bonded) state. A database of cysteine 13C C(alpha) and C(beta) chemical shifts was constructed from the BMRB and Sheffield databases, and published journals. Statistical analysis indicated that the C(beta) shift is extremely sensitive to the redox state, and can predict the disulfide-bonded state. Further, chemical shifts in both states occupy distinct clusters as a function of secondary structure in the C(alpha)/C(beta) chemical shift map. On the basis of these results, we provide simple ground rules for predicting the redox state of cysteines; these rules could be used effectively in NMR structure determination, predicting new folds, and in protein folding studies.

Adaptor Proteins, Signal Transducing↗