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Biomedical subjects

R Sharma

Publications and source records attributed to R Sharma.

At least 181 records · Page 10Linked to original sources
PubMed2000

CopA: An Escherichia coli Cu(I)-translocating P-type ATPase.

The copA gene product, a putative copper-translocating P-type ATPase, has been shown to be involved in copper resistance in Escherichia coli. The copA gene was disrupted by insertion of a kanamycin gene through homologous recombination. The mutant strain was more sensitive to copper salts but not to salts of other metals, suggesting a role in copper homeostasis. The copper-sensitive phenotype could be rescued by complementation by a plasmid carrying copA from E. coli or copB from Enterococcus hirae. Expression of copA was induced by salts of copper or silver but not zinc or cobalt. Everted membrane vesicles from cells expressing copA exhibited ATP-coupled accumulation of copper, presumably as Cu(I). The results indicate that CopA is a Cu(I)-translocating efflux pump that is similar to the copper pumps related to Menkes and Wilson diseases and provides a useful prokaryotic model for these human diseases.

Adenosine Triphosphatases↗
PubMed2000

The role of inflammatory mediators in chronic heart failure: cytokines, nitric oxide, and endothelin-1.

There is now considerable evidence to suggest that neurohormonal and immune mechanisms may play a central role in the pathogenesis of chronic heart failure (CHF), which is likely to have important implications for the management of this condition. It has been proposed that CHF is a state of immune activation with inflammatory cytokines contributing to both the central and the peripheral manifestations of this syndrome. The immune system is the body's natural defence mechanism against infection and other stresses, which has several different components that interact with each other in a complex manner. The main components which are thought to be relevant to the pathogenesis of CHF are: cytokines, adhesion molecules, autoantibodies, nitric oxide, and endothelin-1, and this review will concentrate on these factors. This article will also discuss the potential role of anti-cytokine therapies in the treatment of CHF.

Autoantibodies↗
PubMed2000

Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder: a postmortem brain study.

BACKGROUND: Reelin (RELN) is a glycoprotein secreted preferentially by cortical gamma-aminobutyric acid-ergic (GABAergic) interneurons (layers I and II) that binds to integrin receptors located on dendritic spines of pyramidal neurons or on GABAergic interneurons of layers III through V expressing the disabled-1 gene product (DAB1), a cytosolic adaptor protein that mediates RELN action. To replicate earlier findings that RELN and glutamic acid decarboxylase (GAD)(67), but not DAB1 expression, are down-regulated in schizophrenic brains, and to verify whether other psychiatric disorders express similar deficits, we analyzed, blind, an entirely new cohort of 60 postmortem brains, including equal numbers of patients matched for schizophrenia, unipolar depression, and bipolar disorder with nonpsychiatric subjects. METHODS: Reelin, GAD(65), GAD(67), DAB1, and neuron-specific-enolase messenger RNAs (mRNAs) and respective proteins were measured with quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) or Western blot analyses. Reelin-positive neurons were identified by immunohistochemistry using a monoclonal antibody. RESULTS: Prefrontal cortex and cerebellar expression of RELN mRNA, GAD(67) protein and mRNA, and prefrontal cortex RELN-positive cells was significantly decreased by 30% to 50% in patients with schizophrenia or bipolar disorder with psychosis, but not in those with unipolar depression without psychosis when compared with nonpsychiatric subjects. Group differences were absent for DAB1,GAD(65) and neuron-specific-enolase expression implying that RELN and GAD(67) down-regulations were unrelated to neuronal damage. Reelin and GAD(67) were also unrelated to postmortem intervals, dose, duration, or presence of antipsychotic medication. CONCLUSIONS: The selective down-regulation of RELN and GAD(67) in prefrontal cortex of patients with schizophrenia and bipolar disorder who have psychosis is consistent with the hypothesis that these parameters are vulnerability factors in psychosis; this plus the loss of the correlation between these 2 parameters that exists in nonpsychotic subjects support the hypothesis that these changes may be liability factors underlying psychosis.

Activating Transcription Factor 1↗
PubMed2000

Surgical therapy for the univentricular heart.

The natural history of the univentricular physiology is determined primarily by the presence (severity) or absence of obstruction to pulmonary blood flow and secondarily by the single ventricular cardiomyopathy that develops in response to chronic volume overload. Important obstruction to pulmonary blood flow will affect survival because of severe hypoxia and may necessitate surgical treatment (systemic to pulmonary artery shunt or cavopulmonary shunt depending on the age of the patient and a host of other factors). In the absence of significant obstruction to pulmonary blood flow, the symptomatology is one of congestive heart failure with later development of irreversible pulmonary vascular disease. In this situation, a pulmonary artery band is indicated to limit pulmonary blood flow and reduce pulmonary artery pressures to acceptable levels. Even in the presence of significant limitation of pulmonary blood flow, the single ventricle is a volume-loaded ventricle as it receives both pulmonary and systemic venous return. Chronic volume overload and persistent hypoxia is detrimental to ventricular function and gradually lead to the development of atrioventricular valve incompetence. Complete separation of oxygenated and deoxygenated blood may be obtained by ventricular septation in suitable cases (beyond the scope of this presentation) or by systemic venous diversion to the pulmonary (the Fontan circulation) arteries thus achieving complete oxygenation simultaneous with abolition of any recirculation.

Fontan Procedure↗
PubMed2000

Diet influences the colonisation of Campylobacter jejuni and distribution of mucin carbohydrates in the chick intestinal tract.

The objectives of this study were to evaluate the effect of diet on the colonisation by Campylobacter jejuni of the chick caeca, and to determine whether the viscosity of the intestinal contents and mucin carbohydrates were altered by the diet. The diets investigated were maize based, wheat-based or wheat-based supplemented with xylanase. The xylanase-supplemented diet reduced the viscosity and lowered the numbers of Camp. jejuni. Feeding the enzyme-supplemented diet increased the amount of neutral and sulphated mucins in the goblet cells of the small and large intestines and caecum. An abundance of sulphated and carboxylated mucins was seen in the surface goblet cells of the large intestine with the maize- and wheat-based diets. Both the diet supplemented with xylanase and the maize diets increased crypt-surface glycosylation of the sialic acid residues. The analysed data from the combined sites showed significant differences in the amount of neutral and acidic mucins when comparing the wheat and the wheat plus xylanase diets. However, no changes were shown in the staining intensity of sulphated mucins between the three diets. Significant differences in the glycosylation of sialic acid and in the N-acetylglucosamine residues were shown between dietary groups. These results provide evidence that the wheat diet supplemented with xylanase leads to greater changes in the mucin composition and carbohydrate expression of goblet cell glycoconjugates, which are associated with a reduction in intestinal viscosity and decreased numbers of Camp. jejuni.

Animals↗
PubMed2000

Tuberculosis of the skull. A case report and review of the literature.

A case of tuberculosis of frontal, ethmoid, and sphenoid bones with intracranial extension is presented. The patient had presented with a history of painless left frontal swelling for the previous 7 months. A diagnosis of tubercular etiology was established with the histopathology of the biopsy specimen. The patient was kept on antitubercular treatment for 18 months. She responded well, with a marked resolution of symptoms and radiologic findings. At the end of treatment, there was no clinical or radiological evidence of disease. At 6-month and 1-year follow-ups, there was no evidence of recurrence or reactivation of the disease.

Adolescent↗
PubMed2000

Univentricular repair: is routine fenestration justified?

BACKGROUND: A decade after the introduction of baffle fenestration, the outcome of Fontan-type repair for hearts with a functional single ventricle finally looks promising. Our study was designed to assess the impact of fenestration on the outcome of univentricular repairs. METHODS: From January 1988 to December 1997, 348 patients (104 with tricuspid atresia and 244 with other morphological diagnoses) underwent univentricular repair at our institute. Since 1994, routine fenestration of the atrial baffle was performed in all patients (n = 126). RESULTS: The overall Fontan failure rate was 14% (50 of 348) and included 45 early deaths and five Fontan take downs. Absence of fenestration was the only and highly significant predictor of Fontan failure (risk ratio [RR] 3.3, 95% confidence interval [CI] 1.49 to 7.31, p = 0.002). Significant pleural effusion was seen in 27% of patients. Absence of fenestration of the atrial baffle (RR 3.97, 95% CI 2.17 to 7.26, p < 0.001) and aortic cross-clamp time more than 60 minutes (RR 2.15, 95% CI 1.3 to 3.5, p = 0.002) were found to be significant risk factors. The follow-up ranged from 6 to 120 months (mean 46.0 +/- 18.0 months). There were 12 late deaths and 5 patients were lost to follow-up. Actuarial survival (Kaplan Meier) at 90 months was 81% +/- 4%. Two hundred and fifty-eight patients (90%) were in New York Heart Association class I at their last follow-up visit. Oxygen saturation in the fenestrated group ranged from 85% to 94% (mean 89%). Thirty patients (26%) had spontaneous closure of the fenestration over a mean period of 34 months, and there has been no incidence of late systemic thromboembolism. In no instance has there been a need to close the fenestration. CONCLUSIONS: Elective fenestration of the intraatrial baffle is associated with decreased Fontan failure rate and decreased occurrence of significant postoperative pleural effusions. Routine elective fenestration of the atrial baffle may, therefore, be justified in all univentricular repairs.

Actuarial Analysis↗
PubMed2000

Neurological evaluation and intelligence testing in the child with operated congenital heart disease.

BACKGROUND: The immediate and intermediate-term neurodevelopmental outcome in infants undergoing open heart procedures using deep hypothermic cardiopulmonary bypass was assessed prospectively. METHODS: One hundred consecutive infants (age 2 to 174 days) were operated on using either deep hypothermic bypass only (group A, n = 28), or with associated circulatory arrest (group B, n = 72). Early neurological outcome was recorded. Survivors underwent mental development evaluation after 31 to 55 months. Fifty other children of similar demographic profile but without heart disease were also tested as controls. RESULTS: In group A, there were two neurological deaths. In group B, 5 patients had clinical seizures, 1 had monoparesis and 1 had hyperkinetic syndrome with decreased attention span. Mean mental performance quotient was 90.0+/-8.2 in group A, and 89.1+/-6.8 in group B, (group A vs. B, p = 0.60). Mean mental performance quotient in the control group was 101.4+/-8.4, which was significantly higher than the patient population (p << 0.001). No correlation was found between duration of circulatory arrest and postoperative mental performance quotient. CONCLUSIONS: There was significant retardation of mental development in infants operated with deep hypothermic cardiopulmonary bypass. However, use of total circulatory arrest and its duration did not affect clinical outcome up to preschool age.

Brain Damage, Chronic↗
PubMed2000

Right ventricular outflow tract after non-conduit repair of tetralogy of Fallot with coronary anomaly.

BACKGROUND: A total of 25 patients with tetralogy of Fallot and an important coronary artery crossing the right ventricular outflow tract underwent complete repair without use of an extracardiac conduit between January 1990 and December 1994. Repair was exclusively done by the transatrial or transatrial-transpulmonary approach. Age of these patients ranged from 1 to 12 years (mean 3.6 years). Three of the patients had already received a systemic to pulmonary artery shunt. METHODS: All patients reporting for follow-up (n = 18) were subjected to transthoracic echocardiography and, if required, cardiac catheterization and angiography. Right ventricle to pulmonary artery gradients were noted preoperatively, at discharge following repair and at follow-up study. RESULTS: Mean follow-up was 40.6 months (24 to 62 months). Mean early postoperative gradient was 23.5+/-13.4 mm Hg and 4 patients had significant (> 30 mm Hg) gradients. Mean late postoperative gradient was 20.6+/-12.4 mmHg and 2 patients had gradients greater than 30 mmHg. All the patients were in New York Heart Association functional class I at the time of last follow-up. CONCLUSIONS: Acceptable gradients across the right ventricular outflow tract are achievable following repair of tetralogy of Fallot in the presence of anomalous coronary artery across the right ventricular outflow tract using the transatrial or transatrial-transpulmonary approach. Most gradients were found not to vary significantly on subsequent follow-up.

Child↗
PubMed2000

Surgical myocardial revascularization without cardiopulmonary bypass.

BACKGROUND: Though coronary artery bypass grafting (CABG) without cardiopulmonary bypass is being performed with increasing frequency, in the absence of adequate angiographic follow-up, safety, reproducibility, and efficacy of the procedure remain doubtful. In this prospective study, we report the results obtained by 100% angiographic follow-up of 96 consecutive patients. METHODS: A total of 96 patients (age range 33 to 76 years) underwent CABG without cardiopulmonary bypass. Single vessel disease was present in 46 (47.9%) patients, double vessel disease in 31 (32.3%), and triple vessel disease in 19 (19.8%) patients. All patients were operated through a standard midsternotomy and an optimal combination of pharmacological and mechanical methods were used to restrict cardiac movements during anastomosis. All patients underwent coronary angiography before discharge from the hospital. RESULTS: A total of 160 grafts were placed (range 1 to 4 grafts per patient, average 1.7+/-0.3 grafts per patient). A single graft was placed in 46 patients, double grafts in 38, triple grafts in 10, and quadruple grafts in 2 patients. Various grafts included pedicled left internal mammary artery (LIMA) (n = 95), free LIMA (n = 1), right internal mammary artery (n = 14), radial artery (n = 24), right gastroepiploic artery (n = 5), and saphenous vein grafts (n = 21). Operative mortality was 1.0% (1 of 96). Two patients required reoperation for excessive bleeding. Mean hospital stay was 5.7+/-1.2 days. Overall angiographic patency was 95.0% with LIMA patency of 97.9% (93 of 95). One patient with block in midsegment of LIMA was reoperated using cardiopulmonary bypass. Follow-up ranged from 4 to 17 months (mean 8.2+/-3.1 months). Two patients (one with narrowed LIMA to left anterior descending artery anastomosis, and one with patent anastomosis) had residual angina. CONCLUSIONS: Coronary artery bypass grafting without cardiopulmonary bypass is a reproducible, effective, and safe option in selected group of patients. A conscientious approach in patient selection and route of operation is required.

Adult↗
PubMed2000

The relationship of the erythrocyte sedimentation rate to inflammatory cytokines and survival in patients with chronic heart failure treated with angiotensin-converting enzyme inhibitors.

OBJECTIVES: The object of the study was to assess the relationship between erythrocyte sedimentation rate (ESR) and inflammatory cytokine production in chronic heart failure (CHF). Our findings lead us to re-evaluate the prognostic value of the ESR in assessing patients with CHF. BACKGROUND: The search for simple prognostic markers in CHF that can be assessed anywhere at low cost is important. Increases in ESR are related to the acute phase response in states of inflammation and infection. METHODS: Initially, we studied ESR in relation to plasma levels of inflammatory cytokines in 58 CHF patients. The findings prompted us to analyze the mortality predictive power of ESR compared with established risk factors in these patients and (retrospectively) in a second group of 101 clinically stable CHF patients who had ESR measured. RESULTS: In all 159 CHF patients (age 62+/-2 years, New York Heart Association [NYHA] class 2.7+/-0.1), ESR ranged from 1 to 96 mm/h (median 14 mm/h). The ESR was correlated with tumor necrosis factor (TNF)-alpha (r = 0.31, p<0.05), soluble TNF receptor-1 (r = 0.48, p<0.0005), soluble TNF receptor-2 (r = 0.39, p<0.005) and interleukin 6 (r = 0.45, p<0.005) levels. High ESR levels indicated a poor prognosis (p<0.0001), and this was independent of age, NYHA class, ejection fraction and peak oxygen consumption (p < 0.005). Patients with ESR above median (> or =15 mm/h) compared with patients with ESR <15 mm/h had an impaired survival (hazard ratio 2.62, 95% confidence interval 1.58-4.36, p<0.0001). CONCLUSIONS: Our study demonstrates that in CHF a high ESR is an unfavorable prognostic sign, independent of patients' symptomatology and ventricular function. These results are in diametrical contrast to previous results. This may reflect a change in the underlying pathophysiology due to today's treatment with angiotensin-converting enzyme inhibitors.

Adult↗
PubMed2000

Systematic approach to dipole localization of interictal EEG spikes in children with extratemporal lobe epilepsies.

OBJECTIVES: To assess the reliability of dipole localization based on residual variances (RV), using equivalent current dipole analysis of interictal EEG spikes in children with extratemporal lobe epilepsy. METHODS: Four pediatric patients with extratemporal lobe epilepsy were studied. Digital EEG was recorded from 19 scalp electrodes. Computer programs for spike detection and clustering analysis were used to select spikes. Dipoles were calculated 5 times for each spike using different initial guesses by the moving dipole model. Standard deviation (SD) of the dipole positions was calculated at each time point in the 5 trials. RESULTS: We analyzed the dipoles at 1097 time points from 4 patients. Among 106 time points with RV < 2%, the SD was < 1 mm in 78 (74%), while in those with SD > 1 mm the dipole positions varied between 2.8 and 52.6 mm. Of dipoles with RV < 1%, 26 of 27 (96%) had an SD < 1 mm; the one dipole with SD > 1 mm varied within 2.5 mm. The dipole localizations with RV < 2% corresponded to the epileptogenic zones identified on intracranial invasive video EEG and intraoperative ECoG. CONCLUSIONS: The systematic approach of equivalent current dipole analysis using spike detection, clustering analysis, and an RV < 2% as a standard is useful for identifying extratemporal epileptic regions.

Adolescent↗
PubMed2000

Mechanism of glycine transport in mouse mammary tissue.

The mechanism of glycine transport in lactating mouse mammary gland was investigated. Three Na+-dependent systems of glycine transport, distinguished on the basis of their ionic requirement and sensitivity to 2-(methylamino)isobutyric acid (MeAIB), were A (Na+-dependent, MeAIB-sensitive); (Na++Cl-)-dependent, MeAIB-insensitive; and Na+-dependent, Cl--independent, MeAIB-insensitive. These systems were further distinguished on the basis of inhibition analysis and sensitivity to pH of the extracellular medium and preloading mammary tissue with amino acids. The uptake of glycine via the A system (Km 0.53 mM) was inhibited by preloading mammary tissue with alanine, while glycine uptake mediated by the (Na++Cl-)-dependent, MeAIB-insensitive system (Km 0.47 mM) was downregulated by preloading mammary tissue with all amino acids (alanine, sarcosine and histidine) tested. Treatment of mammary tissue with N-ethylmaleimide inhibited the uptake of glycine via both these systems. Decreasing the pH of the extracellular medium inhibited the uptake of glycine via the A system but not the (Na++Cl-)-dependent, MeAIB-insensitive system. On the basis of ionic requirement, system A appears to comprise two components, one dependent on Na+ plus Cl- and the other on Na+ alone. Insulin upregulated the A system-mediated uptake of glycine in pregnant mouse mammary tissue cultured in vitro, while the (Na++Cl-)-dependent, MeAIB-insensitive system remained unaffected.

Amino Acids↗
PubMed2000

Heterogeneity of cationic amino acid transport systems in mouse mammary gland and their regulation by lactogenic hormones.

The mechanism of cationic amino acid transport in lactating mouse mammary gland was investigated. Two Na(+)-independent systems of arginine transport were discriminated on the basis of their sensitivity to leucine. The leucine-sensitive uptake of arginine (Km 0.4 mM) was through a broad specificity system that interacted with both cationic and neutral amino acids, and was inhibited by preloading mammary tissue with neutral amino acids. The leucine-insensitive uptake was identified as the y+ system (Km 0.76 mM). Preloading mammary tissue with cationic amino acids increased the uptake of arginine by the y+ system. Decreasing the pH of the external medium to 6.0 suppressed the y+ system-mediated uptake by approximately 25%, whereas the broad specificity system remained unaffected. Lactogenic hormones upregulated the y+ system-mediated uptake of arginine in pregnant mouse mammary tissue cultured in vitro, although the broad specificity system remained unaffected. The y+ system-mediated uptake increased 2-fold with insulin alone and 4-fold with the combination of insulin, cortisol and prolactin.

Amino Acids↗
PubMed2000

Polyampholyte gelatin adsorption to colloidal latex: pH and electrolyte effects on acrylic and polystyrene latices.

Polyampholytic gelatin adsorption onto two model, aqueous colloidal dispersions of like size and surface charge density, but varying hydrophobicity are reported. Adsorption isotherms and hydrodynamic layer thickness of the adsorbed gelatin layer are reported for variations of solution pH (above the gelatin IEP) and electrolyte concentration. A van't Hoff analysis of the temperature dependence of the dilute-limiting adsorption equilibrium constants provides evidence for adsorption driven by electrostatic polarization to like-charged surfaces, as well as additional hydrophobic interactions with polystyrene colloidal surfaces. It is demonstrated how these measurements can be used to predict the perikinetic stability of gelatin-coated colloidal latices and, hence, are useful for the rational formulation of dispersions containing polyampholytes.

Acrylates↗
PubMed2000

Purification and characterization of intestinal adenosine deaminase from mice.

Adenosine deaminase (ADA) was isolated from small intestine of mice and purified to utmost homogeneity. SDS-PAGE of purified ADA gave a molecular weight of 41 kDa. Western blot analyses gave a single reactive band at 41 kDa and the other band was an associated ADA binding protein. The purified enzyme was more stable in the alkaline pH. The optimum pH and the pI values were about 7.0 and 4.96, respectively. Km values of the small intestinal ADA for adenosine and 2'-deoxyadenosine were 23 and 16 microM, respectively. Purine riboside was a competitive inhibitor with Ki of 5 microM, whereas 2'-3'-o-isopropylidene adenosine acted as an uncompetitive inhibitor (Ki 66 microM). Activity of ADA was inhibited by the presence of theophylline (-40%), caffeine (-30%), and L-cysteine (-50%). Significantly, Hg2+ (100 microM) inhibited 98% of the initial ADA activity. In addition, various purine analogs such as inosine, purine, alpha-adenosine and adenine showed variable inhibitions on the activity of ADA. Relative ADA activity towards 3'-deoxyadenosine and 6-chloropurine riboside was lower by 30% and 40%, respectively. However, the activity towards 2'-o-methyl adenosine was higher (30%) compared to the activity obtained using adenosine.

Adenosine Deaminase↗
PubMed2000

Expression of four genes of bacteriophage MB78 from contiguous open reading frames: the genomic organization as deduced by sequence analysis.

Four proteins of bacteriophage MB78 having apparent molecular weights as 35, 14, 21 and 16 kDa are expressed from 3.9 kb SalI-HindIII fragment located almost in the middle of the phage genome. Analysis of the sequence supported by some experimental evidences suggest that these four proteins are expressed from polycistronic message without any intercistronic gap. Stop and start codons of consecutive ORFs overlap and rare initiation codons are used. Computer analysis of the sequence suggests the presence of two more open reading frames within the ORFs of 35 and 16 kDa proteins but in the opposite orientation, i.e. in the complementary strand.

Amino Acid Sequence↗