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Biomedical subjects

A Parikh

Publications and source records attributed to A Parikh.

48 records · Page 3Linked to original sources
PubMed1993

Melanotic neuroectodermal tumour of infancy.

The melanotic neuroectodermal tumour of infancy is a rare, pigmented neoplasm that most frequently arises from the anterior maxillary alveolar ridge. It presents in the first few months of life, and usually follows a benign course. A classical case is presented and the clinical, radiological and pathological characteristics are discussed. The importance of early conservative surgical excision is emphasized with, in general, a good prognosis. This tumour, which many otolaryngologists may not be familiar with, should be included in the differential diagnosis of head and neck neoplasms in infants and young children.

Humans↗
PubMedDate not supplied

What makes P450s work? Searches for answers with known and new P450s.

Random mutagenesis has been developed as an approach for the study of human cytochrome P450 (P450) enzymes and their structure and function. Sensitive screening methods are critical for the success of this approach. We have developed one system that takes advantage of the ability of human P450 1A2 to activate heterocyclic amines to mutagenic products [A. Parikh, P. D. Josephy, and F. P. Guengerich, Biochemistry, 38, 5283-5289 (1999)]. Mutants with both attenuated and enhanced activity have been recovered and subjected to further kinetic analysis. For phenacetin O-deethylation, the E225I mutant had kcat 6x > wild type; D320A had kcat 1/10x < wild type (and Km 15 x > wild type). With all three P450s, the rate of first electron reduction was similar, and all had similar binding constants for phenacetin (approximately 15 microM). All three forms yielded intermolecular, noncompetitive kinetic deuterium isotope effects of 1.5-2 [DV and D(V/K)] for O-deethylation of [OCD2CH3]-phenacetin. All three forms of P450 1A2 also formed a minor product, the acetol (C-hydroxylation of the acetyl group). This reaction had a deuterium isotope effect of approximately 14 with all three forms of the enzyme, and C-H bond breaking is the rate-determining step. Another approach to P450 2A6 involves the recent observation that this P450 can accumulate indigo [E. M. J. Gillam, A. M. A. Aguinaldo, L. M. Notley, D. Kim, R. G. Mundkowski, A. A. Volkov, F. H. Arnold, P. Soucek, J. T. DeVoss, and F. P. Guengerich, Biochem. Biophys. Res. Commun 265, 469-472 (1999)]. Current results indicate that this process involves the conversion of endogenous indole to indoxyl by the P450. The reaction may be used in assays of random mutants and has some potential applications in industry.

Cytochrome P-450 CYP1A2↗
PubMedDate not supplied

Endothelial survival factors as targets for antineoplastic therapy.

Angiogenesis is essential for the growth and metastasis of solid tumors. The angiogenic process includes not only development of new blood vessels but also maintenance of the existing vasculature. Recent studies have demonstrated that several factors induce angiogenesis and also function as endothelial cell survival factors. Vascular endothelial growth factor, a potent angiogenic factor, is an endothelial cell survival factor whose tyrosine kinase receptors are limited to endothelial cells. Members of the angiopoietin family also bind to an endothelial cell-specific tyrosine kinase receptor. Angiopoietin-1 has been shown to stabilize endothelial cell networks, whereas angiopoietin-2 is antagonistic to angiopoietin-1 and destabilizes endothelial cell networks. Pericytes contribute to endothelial cell stabilization by cell-cell contact, secretion of survival factors, or both. In addition, integrins may function as endothelial cell survival factors by numerous mechanisms after binding to the extracellular matrix. The effects of many endothelial cell survival factors act in concert with vascular endothelial growth factor to enhance this essential step in angiogenesis. Targeting any of the aforementioned mechanisms for endothelial cell survival may provide novel therapeutic antineoplastic strategies.

Angiogenesis Inhibitors↗