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Biomedical subjects

S Chawla

Publications and source records attributed to S Chawla.

At least 19 recordsLinked to original sources
PubMed1999

Control of recruitment and transcription-activating function of CBP determines gene regulation by NMDA receptors and L-type calcium channels.

Recruitment of the coactivator CBP by signal-regulated transcription factors and stimulation of CBP activity are key regulatory events in the induction of gene transcription following Ca2+ flux through ligand- and/or voltage-gated ion channels in hippocampal neurons. The mode of Ca2+ entry (L-type Ca2+ channels versus NMDA receptors) differentially controls the CBP recruitment step to CREB, providing a molecular basis for the observed Ca2+ channel type-dependent differences in gene expression. In contrast, activation of CBP is triggered irrespective of the route of Ca2+ entry, as is activation of c-Jun, that recruits CBP independently of phosphorylation at major regulatory c-Jun phosphorylation sites, serines 63 and 73. This control of CBP recruitment and activation is likely relevant to other CBP-interacting transcription factors and represents a general mechanism through which Ca2+ signals associated with electrical activity may regulate the expression of many genes.

CREB-Binding Protein↗
PubMed1999

Gastrointestinal imaging: a systems analysis comparing digital and conventional techniques.

OBJECTIVE: The purpose of this study was to compare digital and conventional methods of gastrointestinal imaging based on the cost of image storage and estimated overall costs, radiation exposure to the patient, and duration of the examination. MATERIALS AND METHODS: Our study sample consisted of 128 patients who underwent conventional gastrointestinal studies (64 double-contrast upper gastrointestinal examinations and 64 double-contrast barium enemas) and 139 patients who underwent digital gastrointestinal studies (66 double-contrast upper gastrointestinal examinations and 73 double-contrast barium enemas). The number of images and films for each study was recorded, and the mean cost of image storage and the estimated overall costs for digital versus conventional studies were calculated. Both the duration of fluoroscopy and the time from start to completion of the study were obtained from our radiology information system. From these data, we calculated mean radiation exposure to the patient and the duration of the examination. Finally, referring physicians completed a questionnaire about their level of satisfaction with paper prints generated from digital gastrointestinal studies. RESULTS: When digital studies were compared with conventional studies, the mean cost of image storage decreased by 45% and the estimated overall 10-year costs decreased by 8%. The mean number of spot images increased by 8% for upper gastrointestinal examinations and by 25% for barium enema examinations, whereas the mean duration of fluoroscopy decreased by 4% and by 10%, respectively. As a result, radiation exposure to patients increased by only 2%, a difference that did not approach statistical significance. Finally, the mean duration of examinations decreased by 24% for upper gastrointestinal examinations and by 33% for barium enemas. Approximately 85% of the physicians who completed the questionnaires indicated that they reviewed the paper prints generated from digital studies and that they would like to continue receiving them. CONCLUSION: Digital gastrointestinal imaging systems are associated with higher initial costs than conventional systems, but the long-term costs of these digital imaging systems are slightly less because of the lower cost of image storage, and radiation exposure to patients is comparable. The shorter duration of digital examinations is a potential benefit of this technology, allowing improved patient throughput. Finally, referring physicians have a high level of satisfaction with paper prints generated from digital imaging.

Attitude of Health Personnel↗
PubMed1998

CBP: a signal-regulated transcriptional coactivator controlled by nuclear calcium and CaM kinase IV.

Recruitment of the coactivator, CREB binding protein (CBP), by signal-regulated transcription factors, such as CREB [adenosine 3', 5'-monophosphate (cAMP) response element binding protein], is critical for stimulation of gene expression. The mouse pituitary cell line AtT20 was used to show that the CBP recruitment step (CREB phosphorylation on serine-133) can be uncoupled from CREB/CBP-activated transcription. CBP was found to contain a signal-regulated transcriptional activation domain that is controlled by nuclear calcium and calcium/calmodulin-dependent (CaM) protein kinase IV and by cAMP. Cytoplasmic calcium signals that stimulate the Ras mitogen-activated protein kinase signaling cascade or expression of the activated form of Ras provided the CBP recruitment signal but did not increase CBP activity and failed to activate CREB- and CBP-mediated transcription. These results identify CBP as a signal-regulated transcriptional coactivator and define a regulatory role for nuclear calcium and cAMP in CBP-dependent gene expression.

Animals↗
PubMed1998

Comparison of single-dose oral granisetron versus intravenous ondansetron in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy: a multicenter, double-blind, randomized parallel study.

PURPOSE: The antiemetic effectiveness and safety of single-dose oral granisetron were compared with intravenous (I.V.) ondansetron in chemotherapy-naive patients who received moderately emetogenic chemotherapy. PATIENTS AND METHODS: In this double-blind, parallel-group study, patients naive to emetogenic chemotherapy (N = 1,085) who were scheduled to receive cyclophosphamide- (500 to 1,200 mg/m2) or carboplatin (> or = 300 mg/m2) based chemotherapy, were randomized to receive either oral granisetron (n = 542) or I.V. ondansetron (n = 543). Efficacy assessments included the proportion of patients in each treatment group with total control over the 24 and 48 hours following chemotherapy initiation, as well as incidence and severity of nausea and emesis and use of antiemetic rescue medication. Prophylactic corticosteroids were allowed. Safety assessment was based on patients' reports of adverse experiences. RESULTS: Approximately 80% of patients received prophylactic corticosteroids. Single-dose oral granisetron (2 mg) and I.V. ondansetron (32 mg) resulted in equivalent levels of total emetic control during the first 48 hours after chemotherapy. The proportion of nausea- and emesis-free patients at 24 and 48 hours were also approximately equivalent. The most commonly reported adverse experiences were headache, asthenia, and constipation. More patients who received ondonsetron than granisetron reported dizziness (9.6% v 5.4%, respectively; P = .011) and abnormal vision (4.2% v 0.6%, respectively; P < .001). CONCLUSION: A single oral dose of granisetron (2 mg) resulted in equivalent levels of antiemetic protection as I.V. ondansetron (32 mg). Both agents were well tolerated, although more dizziness and abnormal vision were reported with ondansetron. Because the two antiemetic regimens exhibited equivalent efficacies, additional factors such as convenience and cost of therapy should be considered.

Administration, Oral↗
PubMed1998

Stromal sarcoma of the breast: a case report.

Malignant mesenchymal tumours of the breast are rare neoplasms. Their incidence varies from 1%-3% of all malignant breast tumours (1). Stromal sarcoma of the breast is an extremely uncommon tumour (2). We present a rare case of advanced stromal sarcoma of the breast successfully managed with radical surgery and radiotherapy.

Adult↗
PubMed1997

Calcium controls gene expression via three distinct pathways that can function independently of the Ras/mitogen-activated protein kinases (ERKs) signaling cascade.

Calcium ions are the principal second messenger in the control of gene expression by electrical activation of neurons. However, the full complexity of calcium-signaling pathways leading to transcriptional activation and the cellular machinery involved are not known. Using the c-fos gene as a model system, we show here that the activity of its complex promoter is controlled by three independently operating signaling mechanisms and that their functional significance is cell type-dependent. The serum response element (SRE), which is composed of a ternary complex factor (TCF) and a serum response factor (SRF) binding site, integrates two calcium-signaling pathways. In PC12 cells, calcium-regulated transcription mediated by the SRE requires the TCF site and is not inhibited by expression of the dominant-negative Ras mutant, RasN17, nor by the MAP kinase kinase 1 inhibitor PD 98059. In contrast, TCF-dependent transcriptional regulation by nerve growth factor or epidermal growth factor is mediated by a Ras/MAP kinases (ERKs) pathway targeting the TCF Elk-1. In AtT20 cells and hippocampal neurons, calcium signals can stimulate transcription via a TCF-independent mechanism that requires the SRF binding site. The cyclic AMP response element (CRE), which cooperates with the TCF site in growth factor-regulated transcription, is a target of a third calcium-regulated pathway that is little affected by the expression of RasN17 or by PD 98059. Thus, calcium can stimulate gene expression via a TCF-, SRF-, and CRE-linked pathway that can operate independently of the Ras/MAP kinases (ERKs) signaling cascade in a cell type-dependent manner.

Animals↗
PubMed1997

Gene regulation by nuclear and cytoplasmic calcium signals.

Calcium entry into neuronal cells through N-methyl-D-aspartate (NMDA)-type glutamate receptors or L-type voltage-gated calcium channels is a key event in the control of gene expression following electrical activation. Calcium acts both in the cytoplasm and the nucleus to activate signalling pathways that stimulate gene expression through different DNA regulatory elements. Differential control of transcription by spatially distinct calcium signals provides a mechanism by which a single second messenger can generate diverse transcriptional responses. This may allow for stimulation-specific modulation of gene expression critical for adaptive changes in the nervous system.

Calcium↗
PubMed1997

Distinct functions of nuclear and cytoplasmic calcium in the control of gene expression.

Calcium entry into neuronal cells through voltage or ligand-gated ion channels triggers neuronal activity-dependent gene expression critical for adaptive changes in the nervous system. Cytoplasmic calcium transients are often accompanied by an increase in the concentration of nuclear calcium, but the functional significance of such spatially distinct calcium signals is unknown. Here we show that gene expression is differentially controlled by nuclear and cytoplasmic calcium signals which enable a single second messenger to generate diverse transcriptional responses. We used nuclear microinjection of a non-diffusible calcium chelator to block increases in nuclear, but not cytoplasmic, calcium concentrations following activation of L-type voltage-gated calcium channels. We showed that increases in nuclear calcium concentration control calcium-activated gene expression mediated by the cyclic-AMP-response element (CRE), and demonstrated that the CRE-binding protein CREB can function as a nuclear calcium-responsive transcription factor. A second signalling pathway, activating transcription through the serum-response element (SRE), is triggered by a rise in cytoplasmic calcium and does not require an increase in nuclear calcium.

Animals↗
PubMed1997

Integration of generalized vulnerability to drug and alcohol addiction.

The vulnerability to develop addiction to alcohol has been well established in familial and genetic studies. Similar familial and genetic studies have supported a vulnerability to drug addiction. The co-occurrence of alcohol and drug addiction in the same individuals is highly prevalent in clinical populations. Common putative neurochemical mechanisms underlie addiction to both alcohol and drugs, namely, in the mesolimbic pathway and the locus ceruleus in the brain. Treatment strategies are directed at both alcohol and multiple drug addictions in patient populations. The formulation of a generalized vulnerability that extends to both alcohol and drug addiction is not only possible but necessary to explain the substantial numbers of individuals who develop both alcohol and drug addictions. Future research that is pertinent and relevant may depend on the understanding of a generalized vulnerability to develop alcohol and drug addiction and its application in diagnostic strategies and treatment models.

Alcoholism↗
PubMed1995

Synthesis of 3-arsonopyruvate and its interaction with phosphoenolpyruvate mutase.

3-Arsonopyruvate was prepared in four steps from glycine. The arsenic-carbon bond was formed by a Meyer reaction between alkaline arsenite and 2-bromo-3-hydroxy-2-(hydroxymethyl)propionic acid; the 3-arsono-2-hydroxy-2-(hydroxymethyl) propionic acid formed was oxidized with periodate to give 3-arsonopyruvate. This proves to be an alternative substrate for phosphoenolpyruvate mutase, giving pyruvate, which was assayed using lactate dehydrogenase. The K(m) is 20 microM, similar to that observed for the natural substrate phosphonopyruvate (17 microM), whereas the kcat. of 0.01 s-1 was much lower than that for phosphonopyruvate (58 s-1). Arsonopyruvate competitively inhibited the action of the mutase on phosphonopyruvate.

Arsenicals↗
PubMed1995

A study on the nutritional status of adolescent girls.

One hundred and twenty school girls in the age group of 13-15 years from four Government schools of Ludhiana city were selected for the study. On the basis of their family income they were divided into three experimental groups i.e. income group I (IgI), income group II (IgII) and income group III (IgIII). The results showed that the intake was low for all the foods. However, the consumption of fruits, milk and milk-products, sugar and jaggery, fats and oils by the subjects of IgII and IgIII was significantly higher (p < 0.05) than IgI. The mean daily intake of energy, protein, iron, calcium, vitamin A & vitamin C was inadequate while the intake of fibre was adequate by the subjects as compared to ICMR recommendations. There was no significant difference in energy, protein and iron intakes among the subjects of three groups. However, the fibre intake by the subjects of IgI was significantly higher (p < 0.05) than the subjects of IgIII, whereas the intake of calcium, vitamin A and ascorbic acid by the subjects of IgII & IgIII was significantly higher (p < 0.05) than those of IgI. The average body weights and heights of the subjects were normal. The haemoglobin (Hb) level of the subjects ranged from 8.5-12.5 g/dl with a mean value of 10.73 + 0.07 and reported that only 23 percent of the subjects had acceptable level.

Adolescent↗
PubMed1995

Enolase and the arsonomethyl analogue of 2-phosphoglycerate.

(RS)-3-Arsono-2-(hydroxymethyl)propionic acid was synthesized by the action of alkaline arsenite on 3-bromo-2-(bromomethyl)propionic acid. It is a substrate for yeast enolase (EC 4.2.1.11) with a Km of 6.5 mM (for 2-phospho-D-glycerate Km = 0.08 mM). The catalytic constant of the enzyme with the arsonomethyl analogue is 230 times lower than with 2-phosphoglycerate.

Arsenicals↗
PubMed1994

The Nd:YAG laser in caries removal.

This paper shows how a laser can be used in the various stages of caries removal prior to the placement of a glass-ionomer restoration. In the future the laser may prove to be a valuable tool in enabling the dentist to perform surgical procedures with maximum comfort to the patient.

Anesthesia, Dental↗
PubMed1993

Predictors of perioperative morbidity and mortality in repeat valve replacement: a seven-year experience.

Forty-nine consecutive repeat cardiac valve replacements in 46 patients were reviewed to define in-hospital morbidity, mortality, and determinants of risk. The overall operative mortality rate was 10.2%; it was 9% for the first reoperation and 25% for the second (four patients). The mortality rate was 12% at the mitral position (25 patients), 11% at the aortic position (18 patients), and 0% for repeat double valve replacement (four patients). Univariate and multivariate stepwise logistic regression models show that age over 70 years and the use of an intraaortic balloon pump preoperatively predict operative mortality, and age over 70, preoperative care in the coronary care unit, endocarditis, and the presence of an intraaortic balloon pump are determinants of perioperative morbidity in patients undergoing repeat valve replacement. Based on these data, close follow-up of patients with initial valve replacement is encouraged so that reoperation to correct prosthetic malfunction or periprosthetic leak can be done before hemodynamic collapse occurs. Furthermore, since age was the most significant factor affecting mortality (P < .01) and since most of the deaths (80%) in this study occurred in patients with torn bioprosthetic leaflets, the use of bioprostheses for initial valve replacement in patients under 70 years of age is discouraged.

Adult↗
PubMed1992

Minor emergency clinic: key to the future of successful hospitals.

This project set out to determine whether there is a relationship between the minor emergency facility an individual uses and their choice of a hospital for in-patient care. In studying this relationship, the factors that are important to persons choosing a clinic or hospital facility, as well as the influence of a physician, were also identified. A structured, undisguised telephone survey was used for interviewing a randomly selected sample population of 189 San Angelo residents. Analysis of the survey data indicated that dependency does exist between minor emergency clinic use and the hospital chosen for in-patient care. The results of this study also suggested that hospitals' marketing strategy should shift the emphasis of their advertising from the hospital itself to their physician association and clinics. In addition, a number of other interesting observations concerning the relative importance of various medical factors to the participants was also explored.

Ambulatory Care Facilities↗
PubMed1991

Cardio-vascular effects of vecuronium & pancuronium in patients undergoing elective closed mitral valvotomy.

Vecuronium, a monoquaternary analogue of pancuronium, the neuromuscular blocker, was compared with pancuronium in 50 patients undergoing elective closed mitral valvotomy. The patients were randomly divided into two groups of 25 each, and the muscle relaxants were administered in a dose of 0.1 mg/kg body weight. Both the agents produced identical intubating conditions at 3 min. Vecuronium showed a significantly shorter onset of action, as compared to pancuronium. The latter significantly increased the heart rate throughout the period of study whereas vecuronium significantly decreased the heart rate, 25 min after administration. There was significant increase in the mean arterial pressure (MAP) at tracheal intubation in both the groups, which persisted throughout the period of study in pancuronium group. There was a significant fall in MAP at 30 min after relaxant in vecuronium group. The incidence of arrythmias was similar and significant in both the groups. Vecuronium, thus showed a quicker onset of action with minimal haemodynamic effects, as compared to pancuronium in patients undergoing closed mitral valvotomy.

Adolescent↗
PubMed1991

ERCP in the evaluation of choledochal cyst due to anomalous pancreatobiliary junction.

With the application of endoscopic retrograde cholangio pancreatography (ERCP), the association of anomalous pancreatobiliary junction and choledochal cyst is being increasingly recognized. We describe here the ERCP findings in three patients who had this anomaly in association with fusiform (Type I) choledochal cyst. Two of our patients also had evidence of pancreatitis. The importance of ERCP in the preoperative assessment of such patients is highlighted.

Adolescent↗