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A R Reddy

Publications and source records attributed to A R Reddy.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1987

Impairment of Photorespiratory Carbon Flow into Rubber by the Inhibition of the Glycolate Pathway in Guayule (Parthenium argentatum Gray).

Cut shoots of guayule (Parthenium argentatum Gray) were treated with four inhibitors of the glycolate pathway (alpha-hydroxypyridinemethanesulfonic acid; isonicotinic acid hydrazide, glycine hydroxamate, and amino-oxyacetate, AOA) in order to evaluate the role of photorespiratory intermediates in providing precursors for the biosynthesis of rubber. Photorespiratory CO(2) evolution in guayule leaves was severely inhibited by AOA. Application of each of the four inhibitors has resulted in a significantly decreased incorporation of (14)C into rubber fractions suggesting that the glycolate pathway is involved in the biosynthesis of rubber in guayule. However, the application of each of the glycolate pathway inhibitors showed no significant effect on photosynthetic CO(2) fixation in the leaves. The inhibitors individually also reduced the incorporation of labeled glycolate, glyoxylate, and glycine into rubber, while the incorporation of serine and pyruvate was not affected. The effective inhibition of incorporation of glycolate pathway intermediates in the presence of AOA was due to an inhibition of glycine decarboxylase and serine hydroxymethyltransferase. It is concluded that serine is a putative photorespiratory intermediate in the biosynthesis of rubber via pyruvate and acetyl coenzyme A.

Journal Article↗
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↗
PubMed1976

Physical and radiobiological bases of the use of 125I in the management of thyrotoxicosis.

Increasing interest is recently shown in the use of 125I as an alternative isotope to 131I for the management of thyrotoxicosis based on the postulate that there is a relative sparing of the reproductive integrity of the thyroid follicular cell and a consequent possibility of smaller incidence of hypothyroidism after therapy. A review of the dosimetric, radiobiological anc clinical aspects of the use of 125I are presented here. For the same activity though 125I gives smaller mean gland dose than 131I, the dose computations at microscopic level have revealed that there is a preferential irradiation of the apical membrane compared to the nucleus of the follicular cell. The ratio of the dose to the apical membrane and that to the nucleus increases with the decrease of the percentage colloid mass of the gland. Radiobiological significance of this non-uniform dose distribution across a follicular cell, with 125I , is brought out using rat thyroid as the biological system. For the same mean gland dose the follicular cell survival is larger with 125I than with 131I. 24 H radioiodine uptake is reduced in case of 131I treatment whereas it is not affected with 125I. Pilot clinical trials using 125I for the management of thyrotoxicosis are underway in some centres. Preliminary results from centres using doses 3--4 times that of the conventional 131I dose are not very different from those with conventional 131I therapy. Centres that used doses same as or less than the conventional 131I doses, reported smaller incidence of hypothyroidism.

Animals↗
PubMed1976

A modified geometric factor approach to internal gamma ray dosimetry.

In internal gamma-ray dosimetry, the conventional geometric factor approach, where the "effective absorption coefficient" is taken as 0 or 0-028 cm-1, irrespective of source energy, leads to significant errors especially in the low energy region. An ettempt has been made in this paper to modify the approach to increase the accuracy of calculation and to extend its usefulness to low energies while retaining its inherent simplicity. The modification consists in replacing the effective absorption coefficient by the attenuation coefficients appropriate to the source energies and taking into account the effects due to multiple scattering by using point source build-up factor. The method has been applied for the particular case of dosimetry of a sphere. Comparison of the results obtained by this method with those got from Monte Carlo computations indicates excellent agreement at higher energies and a departure of around 15 per cent only at lower energies (as against a variation of 400 per cent when conventional geometric factor approach is used).

Absorption↗