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Biomedical subjects

A Bhargava

Publications and source records attributed to A Bhargava.

At least 37 records · Page 2Linked to original sources
PubMed2001

The serum- and glucocorticoid-induced kinase is a physiological mediator of aldosterone action.

Aldosterone plays a major role in regulating sodium and potassium flux in epithelial tissues such as kidney and colon. Recent evidence suggests that serum- and glucocorticoid-regulated kinase (SGK) is induced by aldosterone and acts as a key mediator of aldosterone action in epithelial tissues. Induction of SGK messenger RNA (mRNA) has previously been shown within 30 min of addition of supraphysiological doses of aldosterone to Xenopus A6 cells and within 4 h in rat kidney in vivo. In this study we determined the time course of SGK induction, at doses of aldosterone in the physiological range, in rat kidney and colon, using Northern and Western blot analyses and in situ hybridization and determined concurrent changes in urinary sodium and potassium excretion by Kagawa bioassay. On Northern blot analysis, SGK mRNA levels were significantly elevated in both kidney and colon 60 min after the injection of aldosterone. SGK protein in late distal colon was significantly elevated 2 and 4 h after aldosterone treatment. In situ hybridization showed SGK mRNA to be induced in renal collecting ducts and distal tubular elements in both cortex and medulla by doses of aldosterone of 0.1 microg/100 g BW or more within 30 min of steroid treatment. Significant changes in urinary composition were similarly seen with an aldosterone dose of 0.1 microg/100 g BW from 90 min after aldosterone injection. The early onset of SGK induction in kidney and colon and the correlation with urinary changes in terms of both time course and dose response suggest that SGK plays an important role in mediating the effects of aldosterone on sodium homeostasis in vivo.

Aldosterone↗
PubMed2001

Software framework for a surgical guidance system using magnetic markers.

Use of active, optical tracking Surgical Guidance systems provides line of sight problems to the surgeon. We plan to use a new magnetic system, 'Aurora' from Northern Digital Inc. (Canada) and Mednetix AG (Switzerland), in intra-operative fluoroscopy to develop an integrated system for surgical guidance. Here we outline the modules developed for use with this system, including a novel registration method.

Algorithms↗
PubMed2000

Discovery of a new class of p38 kinase inhibitors.

The MAP kinase p38 has been implicated in cytokine signaling, and its inhibitors are potentially useful for the treatment of arthritis and osteoporosis. Novel small-molecule inhibitors of p38 kinase were derived from a combinatorial chemistry effort and exhibit activity in the nanomolar range. Very steep structure-activity relationships are observed within this class.

Antirheumatic Agents↗
PubMed2000

1-Phenyl-5-pyrazolyl ureas: potent and selective p38 kinase inhibitors.

Inhibitors of the MAP kinase p38 are potentially useful for the treatment of arthritis and osteoporosis. Several 2,3-dichlorophenyl ureas were identified as small-molecule inhibitors of p38 by a combinatorial chemistry effort. Optimization for cellular potency led to the discovery of a new class of potent and selective p38 kinase inhibitors, exemplified by the 1-phenyl-5-pyrazolyl urea 7 (IC50 = 13 nM).

Antirheumatic Agents↗
PubMed2000

Plasma membrane calcium pump isoform 1 gene expression is repressed by corticosterone and stress in rat hippocampus.

Glucocorticoids (GCs) are critical to learning and memory, in large part because of their actions in the hippocampus. Chronic high levels of GCs have profound effects on hippocampal structure and function and can even result in irreversible neurodegeneration. Hippocampal GC actions are mediated by intracellular receptors that modulate the transcription of specific target genes. In a screen for genes repressed by GCs in rat hippocampus, we identified plasma membrane calcium pump isoform 1 (PMCA1), a plasma membrane calcium ATPase. In Northern blots, PMCA1 was repressed approximately 33% after a high, but not a low dose of the GC, corticosterone (B), suggesting glucocorticoid (but not mineralocorticoid) receptor-mediated repression. Furthermore, in situ hybridization demonstrated that B significantly downregulated PMCA1 mRNA in all brain regions examined. Repression of PMCA1 was also observed in cultured hippocampal neurons, but only when the cells were in the differentiated state. Stress also repressed PMCA1 expression in hippocampus of adrenal-intact animals, and a clear inverse correlation between B level and PMCA1 mRNA could be discerned. However, other non-B-dependent factors appeared to be involved in the response of PMCA1 to stress because, unlike exogenous B, cold stress did not repress PMCA1 in brain regions other than hippocampus. Moreover, in the presence of constant B (B-replaced, adrenalectomized animals), cold stress led to increased hippocampal PMCA1 expression. These observations suggest that repression of PMCA1 represents one molecular mechanism by which corticosteroids regulate Ca(2+) homeostasis and hence influence neuronal activity. Moreover, other stress-related neurohumoral factors appear to counter the repressive effects of B. Defects in the balance between GC-mediated and non-GC-mediated effects on PMCA1 expression may have adverse effects on neuronal function and ultimately result in irreversible neuronal damage.

Adrenalectomy↗
PubMed2000

Modeling the effects of maternal nutritional status and socioeconomic variables on the anthropometric and psychological indicators of Kenyan infants from age 0-6 months.

This paper presents a comprehensive empirical analysis of the factors affecting growth and psychological development of over 100 infants from birth to age 6 months in the Embu region of Kenya. The analysis was divided into four parts. First, infants' birth weight, and length and head circumference as measured few days after birth, were modeled using multiple regression models. Maternal prepregnancy body mass index (BMI), gestation period, and parity were associated with infants' anthropometric measurements (P < 0.05). Second, the scores on seven clusters of the Brazelton Neonatal Behavioral Assessment Scale were explained by health and socioeconomic indicators. While the models had poor predictive power, the scores were comparable to those reported in the literature for Puerto Rican and African American infants. The third part of the analysis modeled infant growth between 1-6 months by analyzing longitudinal data on length, head circumference, and weight. Dynamic models were postulated for the effects of nutritional, socioeconomic, and environmental factors and morbidity on anthropometric variables. The results showed that infants' calcium intakes were positively associated with length (P < 0.05). Maternal BMI and hemoglobin concentration were positively associated with infant weight (P < 0. 05); infant morbidity was negatively associated with weight (P < 0. 05). Lastly, the infants' scores at 6 months on the Bayley Motor Scale and on eight items from the Bayley Infant Behavior Record were explained using anthropometric, socioeconomic, and psychological variables. The infants' arm circumference and intake of protein were significant predictors of scores on the Bayley Motor Scale. In addition, time spent by the mother talking to the infant was positively associated with the scores on the Bayley Infant Behavior Record. The empirical results have implications for identifying vulnerable children in developing countries.

Adult↗
PubMed2000

Günther Tulip filter: preliminary clinical experience with retrieval.

PURPOSE: The Günther Tulip filter is a permanent filter that has a hook to permit retrieval. The authors report their preliminary clinical evaluation of the filter with regard to feasibility and safety of retrieval. MATERIALS AND METHODS: Nine men and six women who ranged in age from 17 to 79 years (mean, 51 years) underwent treatment with use of the Günther Tulip filter. Patients judged to require caval interruption for < 14 days were selected to receive the filter and retrieval was planned for all patients. Indications for filter placement were: recent pulmonary embolism (PE) or proximal deep vein thrombosis (DVT) with a contraindication to anticoagulation (11 patients), massive PE treated with thrombolytic therapy (one patient), PE with heparin-induced thrombocytopenia (one patient), and prophylaxis after major trauma (two patients). Patients were followed for inferior vena cava (IVC) thrombosis, bleeding, and recurrent DVT or PE. RESULTS: In all nine patients in whom it was attempted, the filter was successfully snared and retrieved via a jugular approach. The mean implantation period was 8.6 days (range, 5-13 days). Retrieval required 2.2-13 minutes (mean 5.3 minutes) of fluoroscopy. No caval injuries occurred as a result of retrieval. All retrieved filters had strands of organized thrombus on the filter struts. The patients were followed for 52-285 days (mean, 115 days) after retrieval. One patient developed a recurrent DVT 230 days after retrieval. No other patients developed a recurrent DVT and no patients developed IVC thrombosis, bleeding, or PE. Six filters were not retrieved: five because of an ongoing contraindication to anticoagulation and one because the patient died of causes unrelated to the filter. CONCLUSION: This preliminary study confirms the feasibility and safety of retrieval of the Günther Tulip filter up to 13 days after implantation.

Adolescent↗
PubMed2000

Role of SGK in mineralocorticoid-regulated sodium transport.

Mineralocorticoids stimulate electrogenic Na+ transport in tight epithelia by altering the transcription of specific genes. Although the earliest mineralocorticoid effect is to increase the activity of the epithelial sodium channel (ENaC), ENaC mRNA and protein levels do not change. Instead, physiologic observations suggest that a mineralocorticoid target gene(s) encodes an ENaC regulator(s). To begin to identify and characterize mineralocorticoid-regulated target genes, we used suppression-subtractive hybridization to generate a cDNA library from A6 cells, a stable cell line of Xenopus laevis of distal nephron origin. A serine-threonine kinase, SGK, was identified from this screen. Sequence comparison revealed that frog, rat, and human SGK are 92% identical and 96% similar at the amino acid level. SGK mRNA was confirmed by Northern blot to be strongly and rapidly corticosteroid stimulated in A6 cells. In situ hybridization revealed that SGK was strongly stimulated by aldosterone in rat collecting duct but not proximal tubule cells. Low levels of SGK were present in rat glomeruli, but SGK was unregulated in this structure. Finally, SGK stimulated ENaC activity approximately sevenfold when coexpressed in Xenopus laevis oocytes. These data suggest that SGK is an important mediator of aldosterone effects on Na+ transport in tight epithelia. In view of the existence of SGK homologues in invertebrates, it is interesting to speculate that SGK is an ancient kinase that was adapted to the control of epithelial Na+ transport by early vertebrates as they made the transition from a marine to a freshwater environment.

Amino Acid Sequence↗
PubMed1999

Epithelial sodium channel regulated by aldosterone-induced protein sgk.

Sodium homeostasis in terrestrial and freshwater vertebrates is controlled by the corticosteroid hormones, principally aldosterone, which stimulate electrogenic Na+ absorption in tight epithelia. Although aldosterone is known to increase apical membrane Na+ permeability in target cells through changes in gene transcription, the mechanistic basis of this effect remains poorly understood. The predominant early effect of aldosterone is to increase the activity of the epithelial sodium channel (ENaC), although ENaC mRNA and protein levels do not change initially. Rather, the open probability and/or number of channels in the apical membrane are greatly increased by unknown modulators. To identify hormone-stimulated gene products that modulate ENaC activity, a subtracted cDNA library was generated from A6 cells, a stable cell line of renal distal nephron origin, and the effect of candidates on ENaC activity was tested in a coexpression assay. We report here the identification of sgk (serum and glucocorticoid-regulated kinase), a member of the serine-threonine kinase family, as an aldosterone-induced regulator of ENaC activity. sgk mRNA and protein were strongly and rapidly hormone stimulated both in A6 cells and in rat kidney. Furthermore, sgk stimulated ENaC activity approximately 7-fold when they were coexpressed in Xenopus laevis oocytes. These data suggest that sgk plays a central role in aldosterone regulation of Na+ absorption and thus in the control of extracellular fluid volume, blood pressure, and sodium homeostasis.

Aldosterone↗
PubMed1998

Can pulmonary venous hypertension be graded by the chest radiograph?

AIM: The chest radiograph is widely used for the diagnosis and follow-up of patients with pulmonary venous hypertension (PVH) caused by rheumatic heart disease. Observer accuracy and interobserver agreement on the radiographic diagnosis of PVH is rarely assessed. We have studied this accuracy and agreement in 120 consecutive patients. METHODS AND RESULTS: Patients were selected on the basis of mean pulmonary capillary wedge pressures (PCWP) obtained in the basal state. A chest radiograph was obtained within the 24 h before catheterization and was assessed by two observers blinded to the diagnosis and PCWP. PVH was graded as absent (PCWP < 12 mmHg); mild (PCWP 12-19 mmHg; redistribution of blood flow and hilar haze); moderate (PCWP 20-25 mmHg; septal oedema, pleural effusion) and severe (PCWP > 25 mmHg; alveolar oedema). Observer and interobserver agreement was quantified by using the Kappa (kappa) statistic. The radiological assessment coincided with the measured PCWP in 52% of the patients according to observer 1 and 43% of the patients according to observer 2 (kappa 0.36 and 0.24), indicating poor agreement with haemodynamic values. Interobserver agreement was poor (kappa 0.3-0.35). Observer accuracy and interobserver agreement increased when the radiographic criteria were used to distinguish patients with normal PCWP from those with abnormal pressures when 85% and 78% of radiographs were correctly classified (kappa 0.6 and 0.5) by observers 1 and 2, respectively. Overall agreement was significant (kappa 0.6). In differentiating patients with a PCWP > 20 mmHg from those with a PCWP < 20 mmHg, 78% and 75% of radiographs were correctly classified, giving kappa values of 0.6 and 0.5. Overall observer agreement was significant (kappa 0.6). CONCLUSION: The chest radiograph is useful in detecting the presence of PVH and in distinguishing significant elevations in PCWP (> 20 mmHg) from mildly elevated PCWP. There is poor correlation between haemodynamic and radiographic findings when more precise grading of the severity of PVH is attempted.

Adolescent↗
PubMed1998

Ocular allergic disease.

Ocular allergy is a common condition that usually affects the conjunctiva of the eye and is therefore often referred to as allergic conjunctivitis. The severity of the disease can range from mild itching and redness, as seen in seasonal allergic conjunctivitis, to the more serious vision threatening forms of ocular allergy which affect the cornea, such as atopic keratoconjunctivitis. The pathogenesis of allergic conjunctivitis involves a complex mechanism which centers around IgE-mediated mast cell degranulation and release of multiple preformed and newly formed inflammatory mediators. The diagnosis of allergic conjunctivitis is usually a clinical one which can be made based on a thorough history and careful examination. Treatment of ocular allergy should begin with conservative measures including allergen avoidance, environmental control, ocular irrigation and cold compresses. Pharmacotherapy of allergic conjunctivitis consists of several classes of drugs. Antihistamines are widely used to treat mild conditions such as seasonal and perennial conjunctivitis and potent new agents such as levocabastine and emedastine are now available. Mast cell stabilizers such as sodium cromoglycate are both safe and effective and are commonly used in ocular allergy. More effective mast cell stabilizers such as nedocromil, lodoxamide and olopatadine are now being used. Nonsteroidal antiinflammatory drugs have demonstrated only limited efficacy and, as such, are not widely used. Topical steroids are very effective in treating signs and symptoms but are reserved for only refractory cases due to their serious side effects. Loteprednol and rimexelone are newer corticosteroids which reportedly have less of an effect on intraocular pressure. Cyclosporine has recently been shown to be highly effective in cases of vernal keratoconjunctivitis and atopic keratoconjunctivitis while producing no adverse effects.

Journal Article↗
PubMed1998

Posterior medial meniscus-femoral insertion into the anterior cruciate ligament. A case report.

Medial meniscal anomalies are rare. The anterior horn insertion into the anterior cruciate ligament is the most common. In the course of an arthroscopy for torn lateral meniscus, an anomalous band in continuity with the posterior horn of the medial meniscus was observed to insert into the anterior cruciate ligament. Although the tibial portion of the anterior cruciate was redundant, the anomalous band provided tension to the anterior cruciate ligament and a negative pivot shift. A previously unreported posterior medial meniscal femoral insertion is described.

Adolescent↗
PubMed1996

Vectors for a 'double-tagging' assay for protein-protein interactions: localization of the CDK2-binding domain of human p21.

We report the construction of three new vectors which can be used for the 'double-tagging' assay previously reported [Germino et al., Proc. Natl. Acad. Sci. USA 90 (1993) 933-937]. The vectors include two plasmids (pTrc.BCCP and pTrc.EZZ::BCCP) which encode different 'tags' for the capture of a target protein of interest on a filter coated with either avidin or IgG, respectively. The first plasmid (pTrc.BCCP) encodes the C terminus of the biotin carboxylase carrier protein (BCCP) under the control of the Ptac promoter, while the second produces fusions to an IgG-binding domain (EZZ). The gene encoding a protein of interest can be inserted into these plasmids and thereby direct the production of a fusion protein which is biotinylated in vivo and can bind to avidin, or a fusion protein which can bind to IgG. The third is a positive-selection, phase lambda expression vector (lambdaFJG2) which permits the construction of lacZ::cDNA fusion proteins which retain beta-galactosidase activity. The insertion of an active ecoRVR gene between the cloning sites (EcoRI and HindII or NotI) permits the positive selection of inserts. The C-terminal two-thirds of the mouse retinoblastoma-encoding gene (containing the E1A-binding pocket) was cloned into pTrc.BCCP and pTrc.EZZ::BCCP, while the 13S E1a gene was cloned into lambdaFJG2. We show that the interaction between these two proteins can be detected using the 'double-tagging' filter assay, and that this assay has high sensitivity and specificity for detecting this interaction. Finally, we have used these vectors to localize the CDK2-binding domain of the cyclin-dependent kinase inhibitor, p21. These results closely correspond to those obtained using the yeast two-hybrid assay, as well as in vitro binding assays.

Adenovirus E1A Proteins↗
PubMed1996

Profile and characteristics of animals bites in India.

Animal bites and so also the incidence of rabies in India are on rise. There are regional differences in the animal responsible for the bite. Different practices including use of traditional remedies are prevalent for wound treatment. In India this report analyses the profile and characteristics of animal bites in 869 patients from various regions. Apart from dog and cat, other animals such as cow, monkey, horse, pigs, camel were responsible for bite and could be possible vectors in transmission of rabies. Traditional remedies such as application of chilly paste is still practiced in state of Rajasthan.

Adolescent↗