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Biomedical subjects

A Bhattacharya

Publications and source records attributed to A Bhattacharya.

At least 55 records · Page 3Linked to original sources

Nonsense-mediated mRNA decay in Saccharomyces cerevisiae.

Cell survival depends on the precise and correct production of polypeptides. Eukaryotic cells have evolved conserved proofreading mechanisms to get rid of incomplete and potentially deleterious proteins. The nonsense-mediated mRNA decay (NMD) pathway is an example of a surveillance mechanism that monitors premature translation termination and promotes degradation of aberrant transcripts that code for nonfunctional or even harmful proteins. In this review we will describe our current knowledge of the NMD pathway, analyzing primarily the results obtained from the yeast Saccharomyces cerevisiae, but establishing functional comparisons with those obtained in higher eukaryotes. Based on these observations, we present two related working models to explain how this surveillance pathway recognizes and selectively degrades aberrant mRNAs.

Codon, Nonsense↗

An automated annotation tool for genomic DNA sequences using GeneScan and BLAST.

Genomic sequence data are often available well before the annotated sequence is published. We present a method for analysis of genomic DNA to identify coding sequences using the GeneScan algorithm and characterize these resultant sequences by BLAST. The routines are used to develop a system for automated annotation of genome DNA sequences.

Algorithms↗

Characterization of a retrotransposon-like element from Entamoeba histolytica.

The protozoan parasite Entamoeba histolytica is the causative agent of amoebiasis. The genome organization of this organism is not well understood. We had earlier reported the presence of a multicopy sequence, HMc, in E. histolytica. Subsequent analysis showed that HMc is a member of a retrotransposon family that we have named the E. histolytica retrotransposon-like element (EhRLE). Four other members of this family have been characterized. The EhRLE family is distributed across all chromosomes of the parasite. There are 140 copies, which show minor sequence variation with respect to one another (2--4% from the consensus sequence). From a sequence analysis of five members of the EhRLE family, the complete EhRLE unit is estimated to be 4086 bp in length. It has a 27-mer inverted repeat at its ends. A pairwise comparison with sequences in the database showed a highly significant match of a part of EhRLE with reverse transcriptases (RT), especially those encoded by non-long terminal repeat retrotransposons. There are stop codons in all the five EhRLEs, but a continuous open reading frame of 464 amino acids could be reconstructed by comparing the sequences of several EhRLEs. The reconstructed sequence showed a much better identity with RT as compared with any of the original EhRLE sequences. The non-pathogenic species, Entamoeba dispar, also contains this element, with 85% sequence identity with EhRLE. The data suggest that EhRLE may be a retrotransposon, but many of its members are probably nonfunctional due to the accumulation of mutations.

Amino Acid Sequence↗

Successful transdiaphragmatic cardiac resuscitation through midline abdominal incision in patient with flail chest.

This case report describes a transdiaphragmatic approach through an already present vertical midline abdominal incision for performing internal cardiac compressions in a 30-year-old male road accident victim. The patient had a flail chest with haemopneumothorax and haemoperitoneum. Exploratory laparotomy followed by splenectomy was performed under general anaesthesia but the patient developed a witnessed cardiac arrest in postoperative period. Successful resuscitation using internal cardiac compression by a transdiaphragmatic approach through the midline abdominal incision that was not extended proximally is described.

Accidents, Traffic↗

Anti-oxidant effect of Withania somnifera glycowithanolides in chronic footshock stress-induced perturbations of oxidative free radical scavenging enzymes and lipid peroxidation in rat frontal cortex and striatum.

The antioxidant activity of Withania somnifera (WS) glycowithanolides was assessed in chronic footshock stress induced changes in rat brain frontal cortex and striatum. The stress procedure, given once daily for 21 days, induced an increase in superoxide dismutase (SOD) and lipid peroxidation (LPO) activity, with concomitant decrease in catalase (CAT) and glutathione peroxidase (GPX) activities in both the brain regions. WS glycowithanolides (WSG), administered orally 1 h prior to the stress procedure for 21 days, in the doses of 10, 20 and 50 mg/kg, induced a dose-related reversal of the stress effects. Thus, WSG tended to normalise the augmented SOD and LPO activities and enhanced the activities of CAT and GPX. The results indicate that, at least part of chronic stress-induced pathology may be due to oxidative stress, which is mitigated by WSG, lending support to the clinical use of the plant as an antistress adaptogen.

Administration, Oral↗

Comparison of caloric intake and weight outcomes of an ad lib feeding regimen for preterm infants in two nurseries.

BACKGROUND: Effects on caloric intake and weight gain of an ad libitum (ad lib) feeding regimen for preterm infants may be specific to a special care nursery. OBJECTIVE: To explore across two nurseries the similarity of effect on caloric intake and weight gain of an ad lib feeding regimen compared with a prescribed regimen and the similarity of effect of caloric intake on weight gain. METHODS: All infants participating in the multi-site randomized clinical trial (RCT) of the ad lib feeding regimen were <35 weeks gestational age at birth and had birth weight appropriate for gestational age. Data on caloric intake and weight gain were collected at two nurseries (A, n=22; B, n=78) with the same feeding regimen protocols. Two strategies were used to explore similarity of regimen effect on caloric intake and weight gain. Repeated measures analysis of variance (ANOVA) was used to examine the effect on caloric intake and weight gain of time, feeding regimen, and time-by-regimen interaction for each nursery. RESULTS: In both nurseries, regimen effects were reasonably consistent for caloric intake and weight gain. Caloric intake was lower across nurseries for infants fed ad lib. After accounting for caloric intake, the ad lib regimen did not affect weight gain. The time-by-regimen interaction effect on caloric intake was significant in both nurseries. Caloric intake for infants fed ad lib increased significantly over 5 days. CONCLUSIONS: Despite differences between nurseries in infant characteristics and in protocol implementation, the feeding regimen effect was consistent for caloric intake and weight gain. Further support was found for the development of infant self-regulatory capacity.

Analysis of Variance↗

Biocatalytic potential of Fusarium globulosum lipase in selective acetylation/deacetylation reactions and in ester synthesis.

AIMS: The present study was carried out to assess the potential of Fusarium globulosum lipase (FGL) for chemoselective and regioselective biotransformations for the synthesis of industrially important organic compounds. METHODS AND RESULTS: Different acetylation/deacetylation reactions and ester synthesis reactions were carried out in organic media. Fusarium globulosum lipase showed exclusive selectivity for the acetylation of the alcoholic hydroxyl group over the phenolic hydroxyl group of the hydroxymethylated phenols and aryl alkyl ketones. This also led to the enantiomeric resolution of the aryl alkyl ketone. In contrast, the lipase showed reversed selectivity in deacetylation where it preferred the phenolic acetoxy group over the alcoholic acetoxy moiety of the peracetates of hydroxymethylated compounds. The enzyme also exhibited strict regioselection for deacetylation at the para position of the peracetate of an aryl alkyl ketone. In addition, the lipase also synthesized a variety of industrially important fatty acid esters of sugars, sugar alcohols, alcohols and ascorbic acid with high preference for middle-chain fatty acids. CONCLUSION: Fusarium globulosum lipase shows versatile catalytic potential in terms of chemo-, enantio- and regioselectivity and fatty acid specificity in carrying out a variety of industrially important biotransformations. SIGNIFICANCE AND IMPACT OF THE STUDY: The biocatalytic potential of FGL can thus be utilized for the synthesis and modification of different types of polyphenolic compounds and esters. These compounds find widespread uses as surfactants, bioactive analogues, antioxidants and flavour components in the food, detergent, pharmaceutical and cosmetic industries.

Acetylation↗

Radioisotope scintigraphy in the diagnosis of hepatic hydrothorax.

BACKGROUND: Pleural effusion in cirrhotic patients (hepatic hydrothorax) may result from migration of ascitic fluid across defects in the diaphragm. Biochemical analysis of ascitic and pleural fluid provides only indirect information about the nature and origin of the effusion. The present study was performed in order to demonstrate the presence/absence of peritoneo-pleural communication by radioisotope imaging. METHODS: Ten patients with cirrhotic ascites and pleural effusion were studied with 99mTc sulfur colloid scintigraphy to look for movement of the radiotracer from the peritoneal to the pleural cavity. Serum-ascitic albumin gradient (SAAG) and serum-pleural fluid albumin gradient (SPAG) values were determined in eight patients to examine the nature of the ascitic and pleural fluids. RESULTS: Transdiaphragmatic movement of ascitic fluid into the pleural space was demonstrated (generally within 2 h of intraperitoneal injection of the radiotracer) in eight of 10 patients; six on the right side, one on the left and one bilaterally. Two patients in whom pleural fluid was transudative on SPAG values were negative for peritoneo-pleural communications. CONCLUSIONS: Radionuclide scintigraphy is a simple, safe and relatively non-invasive method to confirm passage of ascitic fluid across the diaphragm.

Adult↗

Regulation of the uPA gene in various grades of human glioma cells.

Urokinase-type plasminogen (uPA) activator regulates a variety of processes, including morphogenesis, cell differentiation, migration, and invasion. In previous studies, we demonstrated that uPA levels are significantly higher in anaplastic astrocytoma and glioblastoma than in low-grade glioma and normal brain tissue. In the present study, our goal was to determine whether the increase in uPA production in higher-grade gliomas is caused by an increase in mRNA stability or increased transcription of the gene in three human glioma cell lines of various grades (H4, SW1783, UWR3). The half-life of uPA mRNA was about 14 h in UWR3 and 8 h in SW1783 cells. In transient transfection studies of the wild-type -2109-bp human uPA promoter in the different grades of cell lines, the uPA promoter activity was increased two-fold in SW1783, anaplastic astrocytoma cells and six-fold in UWR3 glioblastoma cells, as compared with the uPA promoter activity in low-grade H4 cells. Using human uPA promoter chloramphenicol acetyl transferase (CAT) constructs with mutations of the AP-1 element at -1967 or the PEA-3 cis element at -1973, the activity of the uPA promoter was decreased 4-fold to 10-fold in all three human glioma cell lines. In transient transfection assays, the uPA promoter was stimulated 2.2-fold in UWR3 and SW1783 cells and 3.7-fold in H4 cells in response to phorbol-12-myristat-13-acetate. We further studied the activation and inhibition of uPA promoter by co-expression of a transactivation domain lacking c-jun: a dominant negative ERK1 and ERK2 mutant and a dominant negative c-raf in glioblastoma cell line showed repressed uPA promoter activity compared with the effect of the empty expression vector. We conclude from our findings that increased transcription is the more likely mechanism underlying the increase in uPA production in high-grade gliomas.

Gene Deletion↗

Regulation of the urokinase-type plasminogen activator receptor gene in different grades of human glioma cell lines.

We reported previously that the production of urokinase-type plasminogen activator receptor (uPAR) protein is greater in high-grade glioblastomas than in low-grade gliomas. Transcriptional activation of the uPAR gene or increased stability of the uPAR mRNA that encodes this protein could cause the increased production of this protein in cell lines of different grades of gliomas. We found similar half-life of uPAR mRNA of 10-12 h in glioblastoma multiforme (UWR3) and anaplastic astrocytoma (SW1783) cells. However, the human uPAR promoter was up-regulated 6-8-fold in SW1783 cells and 11-13-fold in UWR3 cells as compared with its activity in low-grade gliomas, a finding that correlates well with previous findings of increases in uPAR mRNA and protein levels in higher-grade gliomas. uPAR mRNA level was increased 11-fold over a 24-h period in low-grade glioma cell lines after treatment with phorbol myristate acetate. The region spanning -144 to -123 bp of the human uPAR promoter that contains the Sp-1 site and a PEA-3 element and an AP-1 site at -184 plays major roles in uPAR promoter activity in glioblastoma cells. Specific antibodies used in an electrophoretic mobility shift assay identified fra-1, fra-2, Jun D, and c-Jun proteins in the nuclear protein complex that bind a 51-mer containing the AP-1 consensus sequence at -184 and its flanking sequences in the uPAR promoter. We further studied the inhibition of uPAR promoter by coexpression of a transactivation domain lacking C-Jun; a dominant-negative ERK1 and ERK2 mutant and a dominant-negative C-raf in glioblastoma cell lines showed the repressed uPAR promoter activity compared with the effect of the empty expression vector. We conclude from our findings that increased transcription is the more likely mechanism underlying the increase in uPAR production in high-grade gliomas.

Chloramphenicol O-Acetyltransferase↗

Effect of LY287045, a thrombin/trypsin inhibitor, on thrombin and trypsin-induced aortic contraction and relaxation.

The active site tripeptide arginal inhibitor of thrombin, LY287045, was used to study thrombin-induced aortic relaxation and contraction, two responses that differ both pharmacologically and physiologically. Although thrombin (10(-7) M) and trypsin (10(-6) M) were tachyphylactic upon repeated administration, trypsin contracted the aorta following thrombin-induced contraction. LY287045 (10(-7) M) attenuated thrombin-induced vasorelaxation, but not vasoconstriction with -log K(B) of 8.4. LY287045 (10(-7) M) also attenuated vasorelaxation, but not vasoconstriction to trypsin, another serine-protease with a thrombin-like catalytic triad, with similar potency (-log K(B) = 8.6) to that for thrombin. Consistent with these vascular effects, LY287045 inhibited the protease activity of both thrombin and trypsin. To explore further the selective inhibitory effect of LY287045 on protease-induced relaxation, we examined the effect of LY287045 on the nitric oxide and prostacyclin pathways and found that LY287045 did not alter vascular responses mediated by nitric oxide or prostacyclin. Likewise, LY287045 did not exert a direct inhibitory effect on the relaxant protease-activated receptor (PAR) since relaxation to the PAR-2-activating peptide was not blocked. The selective effect of LY287045 to inhibit only protease-induced endothelial-dependent relaxation demonstrated that protease inhibition will not affect all protease responses equally. Furthermore, increases in trypsin and thrombin have been associated with inflammation and angiogenesis. To the extent that these findings suggest that LY287045 exhibit dual protease inhibition of endothelial responses, LY287045 may have specific utility in hypotensive inflammatory diseases and in cancer metastases where both trypsin and thrombin have been implicated as causative agents.

Animals↗

Prominence of symptoms and level of stigma among depressed patients in Calcutta.

A pilot study of 29 patients for research on clinical depression employed the framework of cultural epidemiology to examine illness-related experience, meaning, behaviour with a Bengali version of the explanatory Model Interview Catalogue (EMIC). This report examined patterns of distress and stigma with reference to the most troubling patient-specified symptom. All subjects were psychiatric outpatients in the Institute of Psychiatry, Calcutta, and met Diagnostic and Statistical Manual (DSM)-IV criteria for a major depressive episode. Only 5 patients (17.2%) identified sadness as the most troubling problem, and 48.3% specified pains and other somatic symptoms instead. An internally consistent stigma scale with Cronbach's alpha of .67, comprised 13 items, was used to assess stigma. In addition to the scale score for each subject, the contribution of each item was reported and compared. A suggestive, though not significantly lower value of the stigma score for patients reporting somatic symptoms as most troubling, compared with sadness, was consistent with findings from prior studies showing a positive relationship between the magnitude of depression and stigma. These findings are discussed with reference to their impact on recognition and help seeking among patients, and recognition and management of depression by general practitioner. Culturally distinctive presentations and social contexts of depression and other mental illnesses should be addressed in professional training and public health communications.

Adult↗

Oscillatory exchange coupling and positive magnetoresistance in epitaxial oxide heterostructures

Oscillation in the exchange coupling between ferromagnetic La(2/3)Ba(1/3)MnO3 layers with paramagnetic LaNiO3 spacer layer thickness has been observed in epitaxial heterostructures of the two oxides. This behavior is explained within the RKKY model employing an ab initio calculated band structure of LaNiO3, taking into account strong electron scattering in the spacer. Antiferromagnetically coupled superlattices exhibit a positive current-in-plane magnetoresistance.

Journal Article↗

The genome of Entamoeba histolytica.

Estimation of genome size of Entamoeba histolytica by different methods has failed to give comparable values due to the inherent complexities of the organism, such as the uncertain level of ploidy, presence of multinucleated cells and a poorly demarcated cell division cycle. The genome of E. histolytica has a low G+C content (22.4%), and is composed of both linear chromosomes and a number of circular plasmid-like molecules. The rRNA genes are located exclusively on some of the circular DNAs. Karyotype analysis by pulsed field gel electrophoresis suggests the presence of 14 conserved linkage groups and an extensive size variation between homologous chromosomes from different isolates. Several repeat families have been identified, some of which have been shown to be present in all the electrophoretically separated chromosomes. The typical nucleosomal structure has not been demonstrated, though most of the histone genes have been identified. Most Entamoeba genes lack introns, have short 3' and 5' untranslated regions, and are tightly packed. Promoter analysis revealed the presence of three conserved motifs and several upstream regulatory elements. Unlike typical eukaryotes, the transcription of protein coding genes is alpha-amanitin resistant. Expressed Sequence Tag analysis has identified a group of highly abundant polyadenylated RNAs which are unlikely to be translated. The Expressed Sequence Tag approach has also helped identify several important genes which encode proteins that may be involved in different biochemical pathways, signal transduction mechanisms and organellar functions.

Animals↗

Antioxidant activity of Bacopa monniera in rat frontal cortex, striatum and hippocampus.

The effect of a standardized extract of Bacopa monniera Linn. was assessed on rat brain frontal cortical, striatal and hippocampal superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities, following administration for 7, 14 or 21 days. The effects induced by this extract (bacoside A content 82% +/- 0.5%), administered in doses of 5 and 10 mg/kg, orally, were compared with the effects induced by (-) deprenyl (2 mg/kg, p. o.) administered for the same time periods. Bacopa monniera (BM) induced a dose-related increase in SOD, CAT and GPX activities, in all the brain regions investigated, after 14 and 21 days of drug administration. On the contrary, deprenyl induced an increase in SOD, CAT and GPX activities in the frontal cortex and striatum, but not in the hippocampus, after treatment for 14 or 21 days. The results suggest that BM, like deprenyl, exhibits a significant antioxidant effect after subchronic administration which, unlike the latter, extends to the hippocampus as well. The results suggest that the increase in oxidative free radical scavenging activity by BM may explain, at least in part, the cognition- facilitating action of BM, recorded in Ayurvedic texts, and demonstrated experimentally and clinically.

Animals↗

Effect of Withania somnifera glycowithanolides on iron-induced hepatotoxicity in rats.

Glycowithanolides, consisting of equimolar concentrations of sitoindosides VII-X and withaferin A, isolated from the roots of Withania somnifera Dunal, have been reported to have an antioxidant effect in the rat brain frontal cortex and striatum. In the present study, the effect of 10 days of oral administration of these active principles, in graded doses (10, 20 and 50 mg/kg), was noted on iron overload (FeSo(4), 30 mg/kg, i.p.) induced hepatotoxicity in rats. Apart from hepatic lipid peroxidation (LPO), the serum enzymes, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase, were assessed as indices of hepatotoxicity. Silymarin (20 mg/kg, p.o.) was used for comparison. Iron overload induced marked increase in hepatic LPO and serum levels of the enzymes, which was attenuated by WSG in a dose-related manner, and by silymarin. The results indicate that the reported use of WS in Ayurveda for hepatoprotection against heavy metals and other environmental toxins, may be due the antioxidant action of WSG.

Administration, Oral↗