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Biomedical subjects

K Shanker

Publications and source records attributed to K Shanker.

At least 19 recordsLinked to original sources

Large-scale meta-analysis of cancer microarray data identifies common transcriptional profiles of neoplastic transformation and progression.

Many studies have used DNA microarrays to identify the gene expression signatures of human cancer, yet the critical features of these often unmanageably large signatures remain elusive. To address this, we developed a statistical method, comparative metaprofiling, which identifies and assesses the intersection of multiple gene expression signatures from a diverse collection of microarray data sets. We collected and analyzed 40 published cancer microarray data sets, comprising 38 million gene expression measurements from >3,700 cancer samples. From this, we characterized a common transcriptional profile that is universally activated in most cancer types relative to the normal tissues from which they arose, likely reflecting essential transcriptional features of neoplastic transformation. In addition, we characterized a transcriptional profile that is commonly activated in various types of undifferentiated cancer, suggesting common molecular mechanisms by which cancer cells progress and avoid differentiation. Finally, we validated these transcriptional profiles on independent data sets.

Cell Transformation, Neoplastic↗

BioBuilder as a database development and functional annotation platform for proteins.

BACKGROUND: The explosion in biological information creates the need for databases that are easy to develop, easy to maintain and can be easily manipulated by annotators who are most likely to be biologists. However, deployment of scalable and extensible databases is not an easy task and generally requires substantial expertise in database development. RESULTS: BioBuilder is a Zope-based software tool that was developed to facilitate intuitive creation of protein databases. Protein data can be entered and annotated through web forms along with the flexibility to add customized annotation features to protein entries. A built-in review system permits a global team of scientists to coordinate their annotation efforts. We have already used BioBuilder to develop Human Protein Reference Database http://www.hprd.org, a comprehensive annotated repository of the human proteome. The data can be exported in the extensible markup language (XML) format, which is rapidly becoming as the standard format for data exchange. CONCLUSIONS: As the proteomic data for several organisms begins to accumulate, BioBuilder will prove to be an invaluable platform for functional annotation and development of customizable protein centric databases. BioBuilder is open source and is available under the terms of LGPL.

Computational Biology↗

Human protein reference database as a discovery resource for proteomics.

The rapid pace at which genomic and proteomic data is being generated necessitates the development of tools and resources for managing data that allow integration of information from disparate sources. The Human Protein Reference Database (http://www.hprd.org) is a web-based resource based on open source technologies for protein information about several aspects of human proteins including protein-protein interactions, post-translational modifications, enzyme-substrate relationships and disease associations. This information was derived manually by a critical reading of the published literature by expert biologists and through bioinformatics analyses of the protein sequence. This database will assist in biomedical discoveries by serving as a resource of genomic and proteomic information and providing an integrated view of sequence, structure, function and protein networks in health and disease.

Computational Biology↗

The HUPO PSI's molecular interaction format--a community standard for the representation of protein interaction data.

A major goal of proteomics is the complete description of the protein interaction network underlying cell physiology. A large number of small scale and, more recently, large-scale experiments have contributed to expanding our understanding of the nature of the interaction network. However, the necessary data integration across experiments is currently hampered by the fragmentation of publicly available protein interaction data, which exists in different formats in databases, on authors' websites or sometimes only in print publications. Here, we propose a community standard data model for the representation and exchange of protein interaction data. This data model has been jointly developed by members of the Proteomics Standards Initiative (PSI), a work group of the Human Proteome Organization (HUPO), and is supported by major protein interaction data providers, in particular the Biomolecular Interaction Network Database (BIND), Cellzome (Heidelberg, Germany), the Database of Interacting Proteins (DIP), Dana Farber Cancer Institute (Boston, MA, USA), the Human Protein Reference Database (HPRD), Hybrigenics (Paris, France), the European Bioinformatics Institute's (EMBL-EBI, Hinxton, UK) IntAct, the Molecular Interactions (MINT, Rome, Italy) database, the Protein-Protein Interaction Database (PPID, Edinburgh, UK) and the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING, EMBL, Heidelberg, Germany).

Database Management Systems↗

Phylogeography of olive ridley turtles (Lepidochelys olivacea) on the east coast of India: implications for conservation theory.

Orissa, on the east coast of India, is one of the three mass nesting sites in the world for olive ridley turtles (Lepidochelys olivacea). This population is currently under threat as a result of fishery-related mortality; more than 100 000 olive ridleys have been counted dead in the last 10 years in Orissa. In general, the globally distributed olive ridley turtle has received significantly less conservation attention than its congener, the Kemp's ridley turtle (L. kempi), because the latter is recognized as a distinct species consisting of a single endangered population. Our study of mitochondrial DNA haplotypes suggests that the ridley population on the east coast of India is panmictic, but distinct from all other populations including Sri Lanka. About 96% of the Indian population consisted of a distinct 'K' clade with haplotypes not found in any other population. Nested clade analysis and conventional analysis both supported range expansions and/or long-distance colonization from the Indian Ocean clades to other oceanic basins, which suggested that these are the ancestral source for contemporary global populations of olive ridley turtles. These data support the distinctiveness of the Indian Ocean ridleys, suggesting that conservation prioritization should be based on appropriate data and not solely on species designations.

Animals↗

Development of human protein reference database as an initial platform for approaching systems biology in humans.

Human Protein Reference Database (HPRD) is an object database that integrates a wealth of information relevant to the function of human proteins in health and disease. Data pertaining to thousands of protein-protein interactions, posttranslational modifications, enzyme/substrate relationships, disease associations, tissue expression, and subcellular localization were extracted from the literature for a nonredundant set of 2750 human proteins. Almost all the information was obtained manually by biologists who read and interpreted >300,000 published articles during the annotation process. This database, which has an intuitive query interface allowing easy access to all the features of proteins, was built by using open source technologies and will be freely available at http://www.hprd.org to the academic community. This unified bioinformatics platform will be useful in cataloging and mining the large number of proteomic interactions and alterations that will be discovered in the postgenomic era.

BRCA1 Protein↗

An evaluation of toxicity of Taxus baccata Linn. (Talispatra) in experimental animals.

A toxicological study was performed in albino mice and rat with methanolic extract and isolated alkaloid of Taxus baccata Linn. (family: Taxaceae). LD(50) study showed the higher toxic activity in stem (TXA-1,2,3) as compared with leaf (TXB-1,2,3) extract. As the extract were further fractionated into crude alkaloids and purified by chromatography the toxicity of these fractions were found to be in increasing order as follows: methanolic extract (1) < crude alkaloidal fraction (2) < purified alkaloidal fraction (3). The effects of leaf and stem extract of T. baccata were studied on certain biochemical and haematological parameters of mice and rat after 10, 20 and 30 days of exposure. Among the parameters examined, the exposed animal exhibited significant decrease in total leukocyte count (TLC), lymphocytes and cholesterol level (mg/dl), whereas increase was observed in serum transminases (SGOT, SGPT) and alkaline phosphatase (AP) of TXA-1 and TXB-1 treated groups indicating toxic conditions associated due to liver involvement.

Animals↗

Uptake and translocation of selenium by maize (Zea mays) from its environmentaly important forms.

Pot culture studies were conducted to examine the effect of selenite (SeO3(2-)) and selenate (SeO4(2-)) on the uptake and translocation of root absorbed selenium in maize Zea mays plants grown in sand and soil culture. Increasing selenium supplementation (0.5-6.00 microg/ml), increased the selenium retention in roots, but there was little transfer of selenium from shoot to grains. The study indicates that selenite species (less mobile) also accumulates in maize plants when supplied in solution form. Selenium does not cause any adverse effect on the maize plants (dry matter yield vs concentration, no significant correlation, p>0.05).

Biological Availability↗

Small mammal trapping in tropical montane forests of the upper Nilgiris, southern India: an evaluation of capture-recapture models in estimating abundance.

Capture-mark-recapture was used to study small mammal populations in tropical montane forests in southern India. Eleven plots in six montane forest patches were sampled from February-October, 1994. Six species were captured, including four rodents and two shrews. PROGRAM CAPTURE was used to derive estimates of density of the most abundant species in the study area, Rattus rattus Linnaeus. The coefficient of variation of the density estimate was used as an index of precision. The coefficient of variation decreased exponentially with increasing capture probability and with an increase in trapping duration. The coefficient of variation and the capture probability were not correlated with estimates of density. The density estimate increased with trapping duration, as did trap mortality. The latter may have been due to the trend of increased mortality with recaptures of the same individual, which in turn may have been due to weight loss over consecutive captures. Estimates of density derived using four estimators were different for 2, 3, 4 and 5 days of trapping. The coefficient of variation was highest for the generalized removal estimate and lowest for Darroch's estimate. The models and estimators could not be applied to more than one species, and for this species, only in select habitats in a few seasons. Therefore, models of density estimation developed for temperate areas may not be suitable for tropical habitats due to low densities of small mammals in these habitats.

Animals↗

Levels of glutathione reductase and glutathione peroxidase of human platelets in unstable angina and myocardial infarction.

Levels of glutathione peroxidase and glutathione reductase were measured in the platelets of 30 patients, 10 of them affected by unstable angina, 10 of them reperfused after myocardial infarction and 10 matched healthy controls. The specific activities of both the enzymes were lowered in both group of patients. Glutathione reductase activity resulted markedly lowered.

Angina, Unstable↗

Anti-inflammatory benzopyran-2-ones and their active oxygen species (aos) scavenging activity.

Benzopyrano derivatives were synthesized and evaluated for their anti-inflammatory, ulcerogenic activities and toxicity studies. The in-vitro studies comprised of anti-proteolytic activity, lipid peroxidation inhibitory and reducing activities against alpha, alpha-diphenyl-beta-picrylhydrazyl (DPPH). Two potent compounds were studied further for their inhibition of lipid peroxidation and effect on Superoxide dismutase (SOD) activity in-vivo. These compounds were found promising in all the parameters studied, thereby signifying inter-relationship between their anti-inflammatory activity and anti-oxidant properties.

Animals↗

Early experience with real-time CT-fluoroscopy for an intracranial lesion.

We have developed a real-time CT-fluoroscopy (CTF) system of which the initial trial was reported in 1993. This paper deals with the early clinical experience with this system. A third-generation scanner equipped with a slip-ring (Toshiba) was used. Images were reconstructed and displayed at a rate of 6/s with a 0.83-second delay time using a newly designed array processor. CTF was carried out in 12 cases (10 brain hemorrhages, 2 tumors). Good-quality fluoroscopic images were obtained in all cases. Real-time monitoring with CTF of needle placement and advancement was useful for accurate puncture needle biopsy and evacuation of the lesions. No serious complication was experienced in this series.

Biopsy, Needle↗

Indolyl nicotinic hydrazides and their neurological studies.

2-Substituted-indole-3-carboxaldehyde I was cyclised with nicotinic acid hydrazide II with few drops of glacial acetic acid which resulted in 2-substituted-2-methyl-3 (2-substituted-3-indole-3-yl-methylene imino) indolyl aldehyde III. Catalytic reduction of III by Pd/C and hydrazine hydrate (99%) in N,N'-dimethyl formamide (DMF) yielded compound IV. III further underwent reaction with thioglycolic acid and anhydrous ZnCl2 to give VI. Compound VIII were synthesised from IV by the reaction of substituted arylaldehyde in the presence of anhydrous sodium acetate and VII with 2-chloropropionic acid in the presence of Et3N respectively. III underwent cyclisation with chloroacetyl chloride and Et3N in DMF to yield compound V. Diazotisation of III with various substituted arylamines afforded IX. The compounds were evaluated for their C.N.S., anti-parkinsonian and MAO inhibitory activities.

Animals↗

Novel appearance of placental nuclear monoamine oxidase: biochemical and histochemical evidence for hyperserotonomic state in preeclampsia-eclampsia.

OBJECTIVE: The aim of this study was to explore the relevance of placental monoamine oxidase at the subcellular level in the etiology of the hyperserotonomic state in preeclampsia-eclampsia. STUDY DESIGN: The study was conducted on placentas from 20 normal pregnant women and 25 women with varied severity of preeclampsia-eclampsia. Placental serotonin and subcellular monoamine oxidase activity were determined. Histochemical localization of monoamine oxidase was done in placental sections and cell isolates. RESULTS: Placental serotonin increases with severity (rsystolic 0.84, rdiastolic 0.83) and monoamine oxidase decreases (rsystolic 0.86, rdiastolic 0.79). Placental monoamine oxidase showed marked changes in preeclampsia-eclampsia. Histochemical localization of monoamine oxidase showed diffused low activity evenly throughout the cytoplasm and nucleus of the syncytiotrophoblastic cells in preeclampsia-eclampsia; in contrast, normal placenta showed high activity in the cytoplasm without any activity in the nucleus of syncytiotrophoblastic cells. Detection of monoamine oxidase activity in nuclei of the placenta in preeclampsia-eclampsia is a novel finding. Monoamine oxidase activity at the subcellular level further strengthens this observation. A severity-dependent decrease was present in the nuclei of placentas with preeclampsia-eclampsia. The use of specific substrates and inhibitors revealed the presence of monoamine oxidase in mitochondria and nucleus. CONCLUSION: The study delineates an impaired catabolism of placental serotonin in preeclampsia-eclampsia. The novel appearance of monoamine oxidase in nuclei in proximity to its normal site and low activity resulting in a hyperserotonomic state may lead to preeclampsia-eclampsia.

Adult↗