Search PubMed⌕ Search

Biomedical subjects

S Roy

Publications and source records attributed to S Roy.

At least 307 records · Page 17Linked to original sources
PubMed1998

Molecular dynamics simulation of colchicinoids.

Colchicine, a tricyclic alkaloid, has a remarkable range of biological activities. It binds with tubulin and prevents the formation of microtubules. This compound consists of a six membered aromatic ring (A ring), a seven membered troponoid ring (C ring) and another seven membered aliphatic ring (B ring). Using molecular mechanics and molecular dynamics simulations as tools, conformational analysis of colchicine and its several important analogs were done. Molecular mechanics studies show that conformational space of these molecules have one low energy region. Taking the low energy minima as the starting conformation, molecular dynamics simulation for 100 pico seconds is done for each of the analogs and molecular dynamics simulation in solution is done for three representative compounds colchicine,isocolchicine and A-C compound. Internal coordinate trajectories show that the value of the dihedral angle C9-C7-C1-C14 (phi), (C7-C1 bond connects the A and C ring), is within 40 degrees to 50 degrees for all the compounds with fluctuations less than 15 degrees. These calculations indicate that there is an overall similarity in the dynamically averaged structure of all the drugs. The A ring and B ring of the compounds are more or less rigid. The C ring is somewhat flexible, the average conformation and motional properties show overall similarity. The potential energy curve and dynamics behaviour of colchicine and isocolchicine suggests that the difference in binding property of colchine and isocolchicine may originate from the positional difference of carbonyl oxygen and methoxy group of C ring, which is the only difference in the structures of the two compounds and this has no effect on the motional property and average conformations of these two compounds. From our study it is proposed that the movements occuring at various positions of the drug molecules are significantly correlated. It is suggested that such correlated motion may play an important role in the biological property of these compounds.

4-Chloro-7-nitrobenzofurazan↗
PubMed1998

Skeletal muscle and liver lipoyllysine content in response to exercise, training and dietary alpha-lipoic acid supplementation.

In human cells, alpha-lipoic acid (LA) is present in a bound lipoyllysine form in mitochondrial proteins that play a central role in oxidative metabolism. The possible effects of oral LA supplementation, a single bout of strenuous exercise and endurance exercise training on the lipoyllysine content in skeletal muscle and liver tissues of rat were examined. Incorporation of lipoyl moiety to tissue protein was not increased by enhanced abundance of LA in the diet. Endurance exercise training markedly increased lipoyllysine content in the liver at rest. A bout of exhaustive exercise also increased hepatic lipoyllysine content. A significant interaction of exhaustive exercise and training to increase tissue lipoyllysine content was evident. In vastus lateralis skeletal muscle, training did not influence tissue lipoyllysine content. A single bout of exhaustive exercise, however, clearly increased the level of lipoyllysine in the muscle. Comparison of tissue lipoyllysine data with that of free or loosely-bound LA results showed a clear lack of association between the two apparently related parameters. Tightly protein-bound lipoyllysine pool in tissues appeared to be independent of the loosely-bound or free LA status in the tissue.

Animals↗
PubMed1998

Spectroscopic study of Y210C lambda-repressor: implications for cooperative interaction.

A non-cooperative mutant of lambda-repressor, Y210C, has been purified and characterized. The mutant protein does not show any evidence of cooperative interaction as judged by difference near-UV circular dichroism spectra of DNA. The mutant protein also shows much weaker self-assembly as revealed by fluorescence anisotropy measurement. The far-UV circular dichroism spectrum of the protein shows a modest but significant reduction in the 220 nm range, suggesting a structural change. The Lehrer plot of acrylamide quenching of Y210C repressor at a predominantly dimeric concentration (0.5 microM) is almost identical with that of the wild-type protein at the same concentration. Transmission of operator-induced conformational change is also preserved in the mutant protein. Like that of the wild-type protein, cysteines of the mutant protein are unreactive to sulfhydryl reagents under native conditions. Most importantly, C210 is unreactive to sulfhydryl reagents under native conditions. This fact, coupled with the structural change observed in the far-UV CD spectra, suggests that C210 is located at the interior of the protein and exerts its effect indirectly on cooperative contact probably through destabilization of a reverse turn, of which it is an important part.

Bacteriophage lambda↗
PubMed1998

The safety of dipyridamole-thallium imaging in patients with critical aortic valve stenosis and angina.

Angina pectoris occurs in many patients with critical aortic valve stenosis, but in less than 50% of cases is it due to atherosclerotic coronary disease. Pre-operative coronary angiography is used to determine whether coronary revascularization is required in addition to aortic valve replacement. The aim of this study was to determine the safety and image quality of dipyridamole-thallium imaging (DPT) in excluding coronary artery disease requiring a coronary artery bypass graft in patients with aortic valve stenosis requiring aortic valve replacement. Dipyridamole-thallium imaging and coronary angiography were performed less than one month apart in patients with clinical and echo-Doppler evidence of aortic valve stenosis requiring aortic valve replacement. Coronary angiography and DPT were each interpreted by experienced observers blind to the other result. The safety of DPT was judged by symptoms, ECG changes, haemodynamic effects and the need for stress reversal. Image quality was determined from the myocardial-to-background thallium uptake ratio in a normal segment. Twelve patients with aortic valve stenosis (gradient 95 +/- 24 mmHg) were studied, all of whom had left ventricular hypertrophy. The dominant symptom was angina pectoris in eight patients, syncope in three and dyspnoea in one. None had previous myocardial infarction, but two were smokers, six were hyperlipidaemic and one was hypertensive. The patients tolerated DPT well and only one required stress reversal. The quality of the DPT images was good. The DPT image was entirely normal in eight (66%) patients, none of whom had coronary artery disease. Reversible defects were seen in four patients, all of whom had significant coronary artery disease. We conclude that DPT is safe in patients with aortic valve stenosis and angina pectoris. The image quality is good despite left ventricular hypertrophy. In patients with angina pectoris and aortic valve stenosis, coronary angiography can safely be restricted to those with abnormal myocardial perfusion results.

Aged↗
PubMed1998

Transcription regulation by repressosome and by RNA polymerase contact.

The original model of repression of transcription initiation is steric interference of RNA polymerase binding to a promoter by its repressor protein bound to a DNA site that overlaps the promoter. From the results described here, we propose two other mechanisms of repressor action, both of which involve formation of higher-order DNA-multiprotein complexes. These models also explain the problem of RNA polymerase gaining access to a promoter in the condensed nucleoid in response to an inducing signal to initiate transcription.

Amino Acid Sequence↗
PubMed1998

A PC-based Braille library system for the sightless.

This paper presents a novel multiclient braille reading system developed around a single low cost personal computer. The system primarily addresses the needs of the Braille libraries, where different texts are needed to be read by different users simultaneously. Moreover, the system can simultaneously cater to different texts written in different languages. This feature makes it specially suitable for use by multilingual nationalities. The major advantage of this system is its low cost, compared to the other systems available and is specially attractive for the developing or underdeveloped countries. The paper describes the system, first from the user point of view and then presents the hardware and software design details. The system performance has been evaluated by the sightless users and has shown encouraging results.

Blindness↗
PubMed1998

Circumvention of immunity to the adenovirus major coat protein hexon.

Immunity to adenoviruses is an important hurdle to be overcome for successful gene therapy. The presence of antibodies to the capsid proteins prevents efficacious adenovirus vector administration in vivo. We tested whether immunity to a particular serotype of adenovirus (Ad5) may be overcome with a vector that encodes the hexon sequences from a different adenovirus serotype (Ad12). We successfully constructed an adenovirus vector with a chimeric Ad5-Ad12 hexon which was not neutralized by plasma from C57BL/6 mice immunized with Ad5. The vector was also capable of transducing the livers of C57BL/6 mice previously immunized with Ad5.

Adenoviruses, Human↗
PubMed1998

14-3-3 facilitates Ras-dependent Raf-1 activation in vitro and in vivo.

14-3-3 proteins complex with many signaling molecules, including the Raf-1 kinase. However, the role of 14-3-3 in regulating Raf-1 activity is unclear. We show here that 14-3-3 is bound to Raf-1 in the cytosol but is totally displaced when Raf-1 is recruited to the plasma membrane by oncogenic mutant Ras, in vitro and in vivo. 14-3-3 is also displaced when Raf-1 is targeted to the plasma membrane. When serum-starved cells are stimulated with epidermal growth factor, some recruitment of 14-3-3 to the plasma membrane is evident, but 14-3-3 recruitment correlates with Raf-1 dissociation and inactivation, not with Raf-1 recruitment. In vivo, overexpression of 14-3-3 potentiates the specific activity of membrane-recruited Raf-1 without stably associating with the plasma membrane. In vitro, Raf-1 must be complexed with 14-3-3 for efficient recruitment and activation by oncogenic Ras. Recombinant 14-3-3 facilitates Raf-1 activation by membranes containing oncogenic Ras but reduces the amount of Raf-1 that associates with the membranes. These data demonstrate that the interaction of 14-3-3 with Raf-1 is permissive for recruitment and activation by Ras, that 14-3-3 is displaced upon membrane recruitment, and that 14-3-3 may recycle Raf-1 to the cytosol. A model that rationalizes many of the apparently discrepant observations on the role of 14-3-3 in Raf-1 activation is proposed.

14-3-3 Proteins↗
PubMed1998

Differential expression, abundance, and regulation of Na+-phosphate cotransporter genes in murine kidney.

Three classes of high-affinity Na+-Pi cotransporters are expressed in mammalian kidney. These include Npt1 (type I), Npt2 (type II), and the cellular receptors for gibbon ape leukemia virus (Glvr-1) and amphotropic murine retrovirus (Ram-1) (type III). We defined the tissue distribution as well as the relative renal abundance of Npt1, Npt2, Glvr-1, and Ram-1 mRNAs and examined the effects of low-Pi diet, the Hyp mutation, and growth hormone (GH) on their renal expression by ribonuclease protection assay. In normal mouse kidney, Npt1, Npt2, Glvr-1, and Ram-1 accounted for 15 +/- 1.0, 84 +/- 1.0, 0.5 +/- 0.2, and 0.5 +/- 0.3% of total Na+-Pi cotransporter mRNAs, respectively. Evidence was obtained for low-abundance Npt1 mRNA expression in liver and Npt2 mRNA expression in intestine, whereas Glvr-1 and Ram-1 mRNAs were also detected in bone, intestine, heart, and liver. Npt2 mRNA was localized to proximal tubules in the renal outer cortex, whereas Glvr-1 transcripts were detected throughout the kidney by in situ hybridization. The Hyp mutation elicited a significant reduction in renal Npt1 and Npt2 mRNAs (78 +/- 8 and 57 +/- 3% of normal, respectively), whereas neither low-Pi diet nor GH influenced the renal abundance of Npt1 and Npt2 transcripts. Renal Glvr-1 mRNA expression was significantly increased in Hyp mice and GH-treated mice (145 +/- 6 and 165 +/- 5% of control, respectively), whereas the renal abundance of Ram-1 transcript was unaffected by either the Hyp mutation, low-Pi diet, or GH treatment. In summary, we demonstrate that Npt2 is the predominant Na+-Pi cotransporter in mouse kidney, that Npt2 and Glvr-1 have distinct patterns of renal expression, and that the Hyp mutation modulates the renal expression of Npt1, Npt2, and Glvr-1 mRNAs. Our results suggest that increased renal Glvr-1 mRNA may contribute to GH stimulation of renal Na+-Pi cotransport.

Animals↗
PubMed1998

Twist and Notch negatively regulate adult muscle differentiation in Drosophila.

Twist is required in Drosophila embryogenesis for mesodermal specification and cell-fate choice. We have examined the role of Twist and Notch during adult indirect flight muscle development. Reduction in levels of Twist leads to abnormal myogenesis. Notch reduction causes a similar mutant phenotype and reduces Twist levels. Conversely, persistent expression, in myoblasts, of activated Notch causes continued twist expression and failure of differentiation as assayed by myosin expression. The gain-of-function phenotype of Notch is very similar to that seen upon persistent twist expression. These results point to a relationship between Notch function and twist regulation during indirect flight muscle development and show that decline in Twist levels is a requirement for the differentiation of these muscles, unlike the somatic muscles of the embryo.

Animals↗
PubMed1998

Hematuria.

Explore the source record for details and available documents.

Biopsy, Needle↗
PubMed1998

Women's health.

Explore the source record for details and available documents.

Female↗
PubMed1998

Coronary artery lesions in Takayasu's arteritis--clinical and angiographic study.

Two hundred and twenty five patients of Takayasu's arteritis were studied over 13 years. Male:Female ratio was 1:7. Mean age of the study population was 19 +/- 4 years. Of these 225 patients, 75 patients had symptoms and/or signs of cardiac involvement and these patients were subjected to coronary angiography. Significant coronary artery occlusion (i.e. more than 50% narrowing of luminal diameter) was present in 9 patients. Incidence of coronary artery lesions in Takayasu's arteritis is 12% in this study. The proximal segments of coronary arteries were involved while the distal segments were spared. Out of 34 patients with angina pectoris, only 3 patients had significant coronary arterial narrowing.

Adolescent↗
PubMed1998

Risk stratification by treadmill testing in acute myocardial infarction following thrombolytic therapy.

Survivors of acute myocardial infarction (AMI) should have risk stratification for assessment of their future risk of cardiovascular events. One of the important means of risk stratification is by treadmill test (TMT). Most of the algorithms for assessment were done in the prethrombolytic era. But in the post-thrombolytic era, risk stratification by TMT should be properly evaluated. Fifty males with confirmed AMI with age ranging from 38-62 years (mean 48 years) were tested with a symptom limited (Modified Bruce Protocol) TMT. The patients were followed up for a minimum of 6 months (range 6-10 months). Out of 50 patients, 38 reported for follow up. Among them 22 (Group A) had cardiac events and 16 (Group B) had no events. Among the patients (Group A), 6 had unstable angina, 7 had reinfarction, 2 had sudden death, 4 had coronary artery bypass grafting (CABG) and 3 had angioplasty. Comparison between the two groups, A and B in TMT parameters like ST segment depression > 2.5 mm (12 vs 9), no. of leads where ST depression occurred (66 vs 48) during exercise, mean work capacity (8.1 vs 7.9 mets), mean systolic blood pressure response were all statistically insignificant. Though TMT was believed to be a good prognostic indicator to assess further cardiac events after AMI, its efficacy in risk stratification after thrombolysis is yet to be determined. This study does not show its worth in post MI risk assessment.

Adult↗
PubMed1998

Expression of vascular endothelial growth factor in the human retina and in nonproliferative diabetic retinopathy.

Vascular endothelial growth factor (VEGF)/vascular permeability factor is a likely angiogenic mediator in proliferative diabetic retinopathy, and its role is under scrutiny in the pathogenesis of the capillary leakage characteristic of background diabetic retinopathy. To examine whether the diabetic milieu induces or increases retinal VEGF expression in humans, we examined retinas from nondiabetic eye donors and donors with 9 +/- 5 years of diabetes and documented microangiopathy. To identify possible confounding effects of the postmortem period, we also studied the postmortem stability of the VEGF transcript and the expression of the VEGF protein in rat retinas. In both human and rat retina we detected by Northern analysis a 4.2-kb VEGF mRNA species and by reverse transcriptase polymerase chain reaction the transcripts encoding VEGF165 (the most abundant), VEGF121, and VEGF189. By in situ hybridization and immunohistochemistry VEGF mRNA and protein co-localized at the ganglion cell, inner nuclear, and outer plexiform layers and in the walls of the blood vessels (where mRNA was scarce). The protein was additionally detected in photoreceptors. The abundance and distribution of VEGF mRNA and protein were not altered in the diabetic retinas, indicating that the diabetic environment is not sufficient to increase retinal VEGF expression. The demonstration that VEGF is constitutively expressed in the adult retina and is localized to discrete neural cells and their processes proposes a role for the cytokine in retinal homeostasis and/or function.

Aged↗
PubMed1998

Effects of viscoelastic ophthalmic solutions on cell cultures.

The development of mild but significant inflammation probably attributable to viscoelastic ophthalmic solutions in cataract surgery was recently brought to the notice of the authors, and hence a study of the effects of these solutions available in India, on cell cultures was undertaken. We studied the effects of 6 viscoelastic ophthalmic solutions (2 sodium hyaluronate designated as A and B, and 4 hydroxypropylmethylcellulose designated as C, D, E and F) on HeLa, Vero and BHK-21 cell lines in tissue culture microtitre plates using undiluted, 1:10 and 1:100 dilutions of the solutions, and in cover slip cultures using undiluted solutions. Phase contrast microscopic examination of the solutions was also done to determine the presence of floating particles. The products D and F produced cytotoxic changes in HeLa cell line and these products also showed the presence of floating particles under phase contrast microscopy. Other products did not have any adverse effects on the cell lines nor did they show floating particles. The viscoelastic ophthalmic pharmaceutical products designated D and F have cytotoxic effects on HeLa cell line which appears to be a useful cell line for testing these products for their toxicity. The presence of particulate materials in products D and F indicates that the methods used for purification of the solution are not effective.

Animals↗