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Biomedical subjects

A R Reddy

Publications and source records attributed to A R Reddy.

At least 19 recordsLinked to original sources
PubMed1995

Formulation of the reference Indian adult: anatomic and physiologic data.

Data on heights and weights of Indian males and females of various ages are presented. The weights of specific organs obtained from post-mortem records of accident cases of Indian adults and children are also presented to provide some inputs towards formulation of an Indian Reference Man for radiation protection purposes. An intercomparison of the present data with the data available from other sources including those for ICRP Reference Man, Woman, and Child has been made. The daily intakes of air, water, and dietary constituents of an average Indian adult are also given.

Adolescent↗
PubMed1994

Proline-protein interactions: protection of structural and functional integrity of M4 lactate dehydrogenase.

A well defined labile isozyme, rabbit muscle M4-lactate dehydrogenase was denatured under freeze-thaw, heat and GuHCl treatment in the presence and absence of proline, and the corresponding structural changes of the enzyme were monitored through fluorescence and CD spectral studies. The data reveal that proline confers protection to the structural integrity of the enzyme, thereby protecting its activity. This was attributed to its property of forming hydrophilic colloids in aqueous media with a hydrophobic backbone interacting with protein. Unlike other osmolytes, proline is proposed to act on the enzyme stability not only by inducing preferential hydration of proteins but also through the interactions of its multimeric hydrophobic backbone with the solvent-accessible hydrophobic regions of the enzyme.

Animals↗
PubMed1994

Regulatory differences in developmental expression of alcohol dehydrogenase are related to interspecies differences in ethanol tolerance of Drosophila.

Biochemical properties and expression patterns of alcohol dehydrogenase were compared among members of the virilis phylad of Drosophila. Quantitative differences in stage- and tissue-specific expression of ADH of D. virilis, D. novamexicana, D. texana and D. americana were observed. These differences seem to correlate with the temporal differences in ethanol tolerance among these species. Quantitative differences in ADH protein levels account for most, if not all, of the activity differences between species. Analysis of the interspecific hybrids revealed that these differences arise by a mechanism affecting monomer synthesis. A comparison with earlier studies, where independently evolved regulatory differences were related to adaptations, revealed contrasting underlying mechanisms.

Adaptation, Physiological↗
PubMed1992

Organ weights in autopsy cases from an urban apex hospital.

The available limited anatomical and physiological data have been compiled for Indian adult as a part of ongoing efforts in the country to formulate an Indian Reference Man for radiation protection purposes. The parameters included weight, height, body surface area, weight of various organs (brain, heart, kidney, lung, liver etc.), total body water, extra-cellular water, blood volume, specific gravity, total lung capacity, vital capacity etc. The data have been drawn from post-mortem studies (566 males and 185 females) and other data from published work on 433 healthy male and 137 female volunteers. Data gaps have been filled by the method of pooling wherever necessary. This paper presents the intercomparison of the present data with the data available from other sources. The data from various Indian sources indicate a similar trend. However, a significant difference (P less than 0.01) was observed in organ weights and total body weights, in comparison to the Bhabha Atomic Research Centre (BARC) values. The present data are not comprehensive enough to suggest definitive norms of the Indian Reference Man.

Adult↗
PubMed1991

Inhibition of cellular thymidylate synthesis by cytotoxic propenal derivatives of pyrimidine bases and deoxynucleosides.

A series of cytotoxic propenal (3-oxoprop-1-enyl) derivatives of pyrimidine bases and deoxynucleosides was evaluated for their ability to block thymidylate synthesis in intact and permeabilized murine leukemia L1210 cells. Several were potent inhibitors of this process, likely contributing to their cytotoxicity. The IC50 values of thymidine-3-propenal, the prototype of this series, in intact and permeabilized L1210, L-M and L-M(TK-) cells were 21, 7.5, and 75 microM and 1.5, 1.7, and 3.5 microM, respectively. The related base analogue, thymine-1-propenal, is a product of bleomycin-induced DNA strand-scission; the results of the present study bear on the mode of action of this antibiotic.

Acrolein↗
PubMed1991

Species-specific differences in tissue-specific expression of alcohol dehydrogenase are under the control of complex cis-acting loci: evidence from Drosophila hybrids.

Differences in the expression of alcohol dehydrogenase in the hindgut and testis of adult Drosophila virilis, D. texana, D. novamexicana and D. borealis flies were observed. These heritable differences do not arise due to chromosomal rearrangements, since the polytene chromosome banding patterns did not reveal any such gross chromosomal rearrangements near the Adh locus in any of the tested species. Analysis of the interspecific hybrids revealed that these differences are controlled by complex cis-acting genetic loci. Further, the cis-acting locus controlling the expression of ADH in testis was found to be separable by crossing-over.

Alcohol Dehydrogenase↗
PubMed1988

Nucleosides. 150. Synthesis and some biological properties of 5-monofluoromethyl, 5-difluoromethyl, and 5-trifluoromethyl derivatives of 2'-deoxyuridine and 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyluracil.

A new synthesis of 5-(monofluoromethyl)- and 5-(difluoromethyl)-2'-deoxy-2'-fluoro-beta-D-arabinofuranosyluracil (F-FMAU and F2-FMAU) is reported. 3',5'-Di-O-(tert-butyldiphenyl)silylated thymidine or FMAU was photochemically brominated with NBS to the corresponding alpha-monobromide, which was hydrolyzed to the 5-hydroxymethyl derivative. Further oxidation of the latter with MnO2 afforded the 5-formyluracil nucleoside. Treatment of these nucleosides with DAST in CH2Cl2 gave the protected alpha-fluorinated nucleosides. Desiylation with TBAF afforded the desired free nucleosides. Also, 5-(trifluoromethyl)-2'-deoxy-2'-fluoro-beta-D-arabinofuranosyluracil (F3-FMAU) was synthesized by copper-catalyzed trifluoromethylation of 5-iodo-2'-fluoro-ara-U (FIAU). These new nucleosides were studied in comparison with the corresponding 2'-deoxy-erythro-pentofuranosyl derivatives, for their inhibitory activity against cellular thymidylate synthase (TS) and [3H]TdR incorporation into DNA, cytotoxicity against HL-60 cells, and antiviral activity against herpes simplex types 1 and 2 (HSV-1 and -2). F2-TDR and F3-TDR strongly inhibited TS and were also quite cytotoxic and antiherpetic, whereas FTDR was only active in the antiviral assay. In the 2'-fluoroarabino series, fluorine substitution at the alpha-methyl function did not alter significantly the antiherpetic activity. Although FMAU and F-FMAU did not inhibit TS to any significant extent, F2-FMAU and F3-FMAU were weakly inhibitory. The latter nucleosides did not inhibit [3H]TDR incorporation into DNA, while all the other alpha-fluorinated thymine nucleosides inhibited the incorporation of radioactivity of [3H]TDR into DNA to various extents. F2-FMAU and F3-FMAU were about 2 orders of magnitude less cytotoxic against HL-60 cells than were F2-TDR and F3-TDR. The results strongly suggest that in both the 2'-deoxy-2'-fluoroarabino and the 2'-deoxy-erythro-pentofurano series the cytotoxic action of the alpha,alpha-difluoro and alpha,alpha,alpha-trifluoro derivatives may involve the inhibition of TS. The synthesis of [2-14C]F2-FMAU, as an experimental imaging agent, is also described. Unfortunately, the highly selective uptake of the labeled compound within infected brain regions previously noted with [2-14C]FMAU was not detected with the derivative [2-14C]F2-FMAU.

Animals↗
PubMed1985

Inhibition of DNA polymerase alpha from leukemic and normal human cells by partially thiolated human deoxyribonucleic acids.

In continuing search for exploitable biochemical differences between cancer and normal cells at the level of DNA replication, leukemic and "normal" hematopoietic cells from four different, established human cell lines were grown in culture flasks, and both the DNA and the DNA polymerase alpha were isolated in each case from the harvested (5-10 g wet weight) cell pellets. The four selected cell lines included a "normal" lymphoblastoid B-cell line (RPMI-1788), a pre-B cell (NALM-6) and a T-cell (MOLT-4) acute lymphoblastic leukemias, and a promyelocytic leukemia (HL-60). The DNA polymerase alpha enzyme of the two B-cell lines (both the leukemic and the "normal") showed the usual sensitivity toward inhibition by aphidicolin, while those from the two other leukemic cell lines were remarkably resistant to the antibiotic. Partially thiolated polycytidylic acid (MPC) strongly inhibited only the DNA polymerase alpha of the "normal" cell line, whereas the corresponding enzymes of all three leukemic cell lines were relatively insensitive to MPC. In contrast, the partially thiolated DNAs derived from the leukemic cell lines more strongly inhibited the DNA polymerase alphas of the leukemic cell lines than that of the "normal" cell line. These results indicate the existence of some structural differences between the DNA polymerase alpha enzymes (as well as between the DNAs) of human cells of different lineage and, particularly, of leukemic vs. "normal" character; such differences could be exploited in the design of selective antitemplates for chemotherapy.

Animals↗
PubMed1984

Comparison of tryptic peptide profiles of alcohol dehydrogenase from Drosophila melanogaster at different ages: a rapid procedure using high performance liquid chromatography.

Age-related changes in the primary structure of alcohol dehydrogenase (ADH) from three different strains (Adh-F, Adh-D and Adh-S) of Drosophila melanogaster have been investigated by tryptic peptide analysis. The procedure involves isolation of 14C-labelled ADH, immunoprecipitation and HPLC separation of tryptic peptides. This method is rapid, reproducible and sensitive. By using this procedure it is demonstrated that there are no significant differences between the ADH tryptic peptide profiles of young (10-day-old) and old (50-day-old) flies. The usefulness of this procedure for screening mutant and variant enzymes is discussed.

Aging↗
PubMed1980

Adh-negative mutants: detection of an altered tryptic peptide in a mutant enzyme of Drosophila.

Adhnll is an ethyl methanesulfonate induced mutant that lacks detectable alcohol dehydrogenase activity. A number of indirect lines of evidence have indicated that the mutation responsible for this loss in enzyme activity is localized in the Adh structural gene. We present more direct evidence for this hypothesis here. Utilizing a newly developed procedure for comparing tryptic peptides of Drosophila alcohol dehydrogenase obtained from different strains, we show that the alcohol dehydrogenase-like protein isolated from Adhnll exhibits an altered peptide profile when compared to that of wild type. The implications of this finding as well as the utility of the method for attacking other genetic and developmental problems are discussed.

Alcohol Oxidoreductases↗
PubMed1979

Effect of methyl thiouracil on radioiodine thyroidal retention in rats.

Some goitrogens like methyl thiouracil (MTU) because of their thynamide grouping act as antithyroid drugs inhibiting the organification of iodide, but do not alter the iodide transport. Their administration to an intact animal, therefore, might alter the thyroidal iodine kinetics. Here an attempt has been made to study the effect of MTU on thyroidal iodine kinetics in rats as well as to find out whether any difference in kinetics could be detected between different radioiodines, viz., 131I, 125I, and 123I. Cumulated thyroidal activity which is a time integral of the activity has been taken as the parameter to represent the sum effect of thyroidal iodine kinetics over a specific time period of interest. From the in vivo thyroidal activity measurements, carried out over extended periods of time, the cumulated activity was calculated for both MTU treated and normal rats that received 131I, 125I, or 123I at different times before the MTU start. Within a day of the start of the MTU there is a rapid loss of thyroidal iodine. The severity of the loss depended upon the time that elapsed between the start of the MTU schedule and the particular radioiodine administered. The absence of isotopic effect on the uptake as well as on the rate of uptake for the three different radioiodine isotopes studied has been brought out.

Administration, Oral↗
PubMed1978

Microscopic dose distributions due to iodine isotopes in thyroid.

Microscopic electron dose distributions inside and outside the colloid spheres of thyroid tissue of radii 15-150 micron containing 1.5 muCi/g 123I, 125I, 131I, and 132I uniformly distributed have been calculated by the application of Berger's scaled absorbed dose functions approximately standard polynomial regression techniques. For 131I, 123I and 132I whose electron or effective beta energy ranges are at least few times more than the sphere sizes considered the contributions of energy emitted from neighbouring follicles have been included into the dose calculations. Additionally, the frequency mean and energy mean of microscopic event-size distributions in small spherical 125I sources have been computed in rad per one 125I disintegration.

Electrons↗