Biomedical subjects

Vimal Kapoor

Publications and source records attributed to Vimal Kapoor.

5 recordsLinked to original sources

PubMed2006

Preliminary evidence for a link between schizophrenia and NMDA-glycine site receptor ligand metabolic enzymes, d-amino acid oxidase (DAAO) and kynurenine aminotransferase-1 (KAT-1).

Preliminary investigations, studying gene expression and biochemical activities of enzymes d-amino acid oxidase (DAAO) and kynurenine aminotransferase-1 (KAT-1), revealed elevated cerebellar KAT-1 and DAAO activities in post-mortem brain samples from schizophrenic versus normal individuals. In addition, we have identified a transcript of DAAO, which was expressed in significantly higher quantities in the diseased cerebellum but not detected in the parietal cortex where DAAO activity is absent.

Alternative Splicing↗

PubMed2006

Djinn Lite: a tool for customised gene transcript modelling, annotation-data enrichment and exploration.

BACKGROUND: There is an ever increasing rate of data made available on genetic variation, transcriptomes and proteomes. Similarly, a growing variety of bioinformatic programs are becoming available from many diverse sources, designed to identify a myriad of sequence patterns considered to have potential biological importance within inter-genic regions, genes, transcripts, and proteins. However, biologists require easy to use, uncomplicated tools to integrate this information, visualise and print gene annotations. Integrating this information usually requires considerable informatics skills, and comprehensive knowledge of the data format to make full use of this information. Tools are needed to explore gene model variants by allowing users the ability to create alternative transcript models using novel combinations of exons not necessarily represented in current database deposits of mRNA/cDNA sequences. RESULTS: Djinn Lite is designed to be an intuitive program for storing and visually exploring of custom annotations relating to a eukaryotic gene sequence and its modelled gene products. In particular, it is helpful in developing hypothesis regarding alternate splicing of transcripts by allowing the construction of model transcripts and inspection of their resulting translations. It facilitates the ability to view a gene and its gene products in one synchronised graphical view, allowing one to drill down into sequence related data. Colour highlighting of selected sequences and added annotations further supports exploration, visualisation of sequence regions and motifs known or predicted to be biologically significant. CONCLUSION: Gene annotating remains an ongoing and challenging task that will continue as gene structures, gene transcription repertoires, disease loci, protein products and their interactions become more precisely defined. Djinn Lite offers an accessible interface to help accumulate, enrich, and individualize sequence annotations relating to a gene, its transcripts and translations. The mechanism of transcript definition and creation, and subsequent navigation and exploration of features, are very intuitive and demand only a short learning curve. Ultimately, Djinn Lite can form the basis for providing valuable clues to plan new experiments, providing storage of sequences and annotations for dedication to customised projects. The application is appropriate for Windows 98-ME-2000-XP-2003 operating systems.

Alternative Splicing↗

PubMed2003

Inhibition of indoleamine 2,3-dioxygenase activity in IFN-gamma stimulated astroglioma cells decreases intracellular NAD levels.

Astroglia provide essential metabolic and neurotropic support to cells within the CNS and participate in the cellular immune response with microglia/macrophages following activation by the pro-inflammatory cytokine IFN-gamma. Activation of glial cells results in local oxidative stress and induction of a number of proteins including the enzyme indoleamine 2,3-dioxygenase (IDO). As a rate-limiting enzyme, IDO regulates tryptophan catabolism via the kynurenine pathway producing a series of metabolic precursors (some of which are neurotoxic) before complete oxidation to the essential pyridine nucleotide NAD. Inhibition of this pathway may therefore prove therapeutic in neuroinflammatory disease by reducing production of cell toxins. However, kynurenine metabolism may also be cytoprotective through de novo synthesis of cellular NAD levels. We investigated the hypothesis that IDO activity is directly involved in maintenance of intracellular [NAD] in activated astroglial cells through control of de novo synthesis. Exposure to IFN-gamma increased IDO activity from 7+/-1 nmol to 129+/-11 nmol kynurenine/hr/mg protein. Inhibition of IDO activity with either 6-chloro-D-tryptophan (competitive inhibition), or 3-ethoxy beta-carboline (non-competitive inhibition) resulted in a dose-dependent decrease in IDO activity that correlated directly with decreasing [NAD] (R(2)=0.92 and 0.81, respectively). These results support the hypothesis that one important consequence of increasing IDO activity in astroglial cells during inflammation is to maintain NAD levels through de novo synthesis from tryptophan. Inhibition of kynurenine pathway metabolism under these conditions may significantly decrease cell viability and CNS functions unless alternate precursors for NAD synthesis are available.

Astrocytes↗

PubMed2003

Extraction and chromatography-mass spectrometric analysis of the active principles from selected Chinese herbs and other medicinal plants.

Medicinal herbs have a long history of use in the practice of traditional Chinese medicine and a substantial body of evidence has, over recent decades, demonstrated a range of important pharmacological properties. Western biomedical researchers are examining not only the efficacy of the traditional herbal products but, through the use of a range of bioassays and analytical techniques, are developing improved methods to isolate and characterize active components. This review briefly describes the different extraction methodologies used in the preparation of herbal extracts and reviews the utility of chromatography-mass spectrometry for the analysis of their active components. In particular, applications of gas or liquid chromatography with mass spectrometry for the isolation and characterization of active components of ginseng are critically assessed. The analysis of toxic substances from herb extracts with mass spectrometric techniques is also discussed along with the potential for mass spectrometric methods to investigate the proteomics of herbal extracts.

Chromatography↗

PubMed2002

A missense mutation in kynurenine aminotransferase-1 in spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) are the most extensively used animal model for genetic hypertension, increased stroke damage, and insulin resistance syndromes; however, the identification of target genes has proved difficult. SHR show elevated sympathetic nerve activity, and stimulation of the central blood pressure control centers with glutamate or nicotine results in exaggerated blood pressure responses, effects that appear to be genetically determined. Kynurenic acid, a competitive glutamate antagonist and a non-competitive nicotinic antagonist, can be synthesized in the brain by the enzyme kynurenine aminotransferase-1 (KAT-1). We have previously shown that KAT-1 activity is significantly reduced in SHR compared with normotensive Wistar Kyoto rats (WKY). Here we show that KAT-1 contains a missense mutation, E61G, in all the strains of SHR examined but not in any of the WKY or outbred strains. Previous studies on F2 rats from a cross of stroke-prone SHR and WKY have shown a suggestive level of linkage between elevated blood pressure and the KAT-1 locus on chromosome 3. In addition, the mutant enzyme expressed in Escherichia coli displays altered kinetics. This mutation may explain the enhanced sensitivity to glutamate and nicotine seen in SHR that may be related to an underlying mechanism of hypertension and increased sensitivity to stroke.

Alleles↗