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Biomedical subjects

G Reddy

Publications and source records attributed to G Reddy.

At least 55 records · Page 3Linked to original sources
PubMed1995

Dynamic changes in Rad51 distribution on chromatin during meiosis in male and female vertebrates.

Antibodies against human Rad51 protein were used to examine the distribution of Rad51 on meiotic chromatin in mouse spermatocytes and oocytes as well as chicken oocytes during sequential stages of meiosis. We observed the following dynamic changes in distribution of Rad51 during meiosis: (1) in early leptotene nuclei there are multiple, apparently randomly distributed, foci that by late leptonema become organized into tracks of foci. (2) These foci persist into zygonema, but most foci are now localized on Rad51-positive axes that correspond to lateral elements of the synaptonemal complex. As homologs synapse foci from homologous axes fuse. The distribution and involvement of Rad51 foci as contact points between homologs suggest that they may be components to early recombination nodules. (3) As pachynema progresses the number of foci drops dramatically; the temporal occurrence (mice) and physical and numerical distribution of foci on axes (chickens) suggest that they may be a component of late recombination nodules. (4) In early pachynema there are numerous Rad51 foci on the single axis of the X (mouse spermatocytes) or the Z (chicken oocytes) chromosomes that neither pair, nor recombine. (5) In late pachynema in mouse spermatocytes, but not oocytes, the Rad51 signal is preferentially enhanced at both ends of all the bivalents. As bivalents in spermatocytes, but not oocytes, begin to desynapse at diplonema they are often held together at these Rad51-positive termini. These observations parallel observations that recombination rates are exceptionally high near chromosome ends in male but not female eutherian mammals. (6) From diakinesis through metaphase I, Rad51 protein is detected as low-intensity fluorescent doublets that localize with CREST-specific antigens (kinetochores), suggesting that Rad51 participates, at least as a structural component of the materials involved, in sister kinetochore cohesiveness. Finally, the changes in Rad51 distribution during meiosis do not appear to be species specific, but intrinsic to the meiotic process.

Animals↗
PubMed1995

How specific is the first recognition step of homologous recombination?

The Escherichia coli RecA protein promotes homologous recognition in base triplets via non-Watson-Crick bonds that differ from those formed nonenzymically from DNA consisting of runs of purines or pyrimidines. Base substitutions reveal recognition to be permissive, consistent with a search for homology that achieves speed at the cost of precision.

Binding Sites↗
PubMed1995

Hematological effects of 1,3,5-trinitrobenzene (TNB) in rats in vivo and in vitro.

We studied the hematological effects of single and repeated exposure to 1,3,5-trinitrobenzene (TNB) in rats. Male F-344 rats were gavaged with TNB at 35.5 and 71 mg/kg in corn oil. Blood was collected 5 h and 24 h after a single oral dose or 24 h after daily oral doses for 4 or 10 d in four different set of experiments. A dose-dependent methemoglobinemia was present only in blood collected 5 h after a single dose. A highly significant dose-dependent anemia with reduced red cells, hemoglobin, and hemotocrit was present in rats receiving TNB for 4 or 10 d. A dose-dependent decrease in serum triglycerides was present in rats receiving TNB for 10 d. There was no hemolysis when rat erythrocytes were incubated with TNB (in vitro) for 9 h. Spectral changes of hemoglobin recorded during the incubation with TNB confirm methemoglobin formation and progressive denaturation of hemoglobin-forming hemichromes. The significance of methemoglobin and hemichrome formation is discussed, and a probable hypothesis for the hemolytic anemia is suggested.

Anemia, Hemolytic↗
PubMed1994

Joints made by RecA protein in the interior of linear duplex DNA: effects of single-stranded ends, length of homology, and dynamic state.

The importance of 3' single-stranded ends in homologous recombination led us to reevaluate reactions of single strands at homologous sites in the interior of linear duplex DNA. As the length of homology increased, the yield of joints increased up to about 2 kb of homology, at which the apparent yields were the same at either 3' or 5' single-stranded ends, or away from ends, although such joints were qualitatively different. In the presence of RecA protein and ATP, joints that formed between any of these single strands and interior sequences in duplex DNA were in a dynamic state in which they constantly recycled. Consequently, their apparent yields at steady state were sensitive to conditions of reaction, such as the concentrations of DNA, salt, and ATP vs ADP, observations which rationalize conflicting reports in the literature. The dynamic state of joints in the interior of duplex DNA strengthens the conclusion [see Burnett et al. (1994)] that RecA protein dissociates joints when it cannot displace the 5' end of a strand from the recipient duplex.

Adenosine Diphosphate↗
PubMed1994

Resolution of the three-stranded recombination intermediate made by RecA protein. An essential role of ATP hydrolysis.

Previous work has shown that triplex DNA is an intermediate in homologous pairing and strand exchange promoted by RecA protein. Heterology at the proximal end of duplex DNA blocks strand exchange, but triplex joints form nonetheless at the homologous distal end. Experiments on the formation and processing of distal joints revealed that the yield of distal joints depends critically on the concentration of RecA-coated single strands and the adequacy of the ATP-regeneration system, and reflects a steady state. Distal joints reversibly formed and dissociated, as shown by several methods, including a chase with unlabeled duplex DNA. Controls excluded a contribution of exonucleolytic nibbling to the formation of distal joints and the stability of the deproteinized product. RecA protein was bound preferentially by putative triplex sites both in isolated proximal and distal joints. These high affinity sites disappeared from proximal joints as strand exchange progressed, and disappeared from distal joints as the joints dissociated. Dissociation of distal joints under all conditions, however, was completely arrested by the addition of ATP gamma S. Distal triplex joints can be as long as six kilobases. The observed inhibition of the dissociation of such long non-productive triplex intermediates by ATP gamma S leads us to propose that an essential role of ATP hydrolysis in RecA recombinational exchanges may be to ensure that no potentially troublesome triplex DNA remains in the cell.

Adenosine Triphosphate↗
PubMed1994

The effect of ethnic differences on the pattern of HTLV-I-associated T-cell leukemia/lymphoma (HATL) in the United States.

Human T-cell lymphotropic virus Type I (HTLV-I) is the primary etiologic factor for adult T-cell leukemia/lymphoma (ATL). Although HTLV-I is endemic in Japan and the Caribbean islands, the reported clinical and epidemiologic features of ATL in these 2 parts of the world are quite different. ATL has been diagnosed at a younger age and is reported more frequently as the lymphomatous type rather than the acute type with leukemia in the Caribbean basin as compared with the presentation in Japan. In order to characterize ATL in the United States, a registry has been established at the National Cancer Institute for the purpose of recording all cases originally diagnosed in the United States. This registry was utilized to examine the effect of ethnic differences on age of onset and clinical features of ATL, using the same data base. Clinical and laboratory information was obtained from 177 patients suspected of having ATL, who were treated at the National Institutes of Health, or had biological samples sent for evaluation, or were reported in the literature. Histopathologic review and virologic studies were performed by standardized methods. Of 177 patients registered, 127 were considered as having ATL, according to an algorithm combining clinical, pathologic and laboratory features. Presenting features in the confirmed cases consisted primarily of lymphadenopathy (76.6%), hypercalcemia (72.5%), leukemia (82%), skin involvement (48.2%) and hepatomegaly (53.6%). Patients of Japanese ancestry were generally older (median age 63, range 51 to 73 years) than patients of African-American descent (median age 39, range 7 to 75 years) and presented more often with leukemia (90 vs. 69%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Active-site characterization of S1 nuclease. II. Involvement of histidine in catalysis.

Modification of the histidine residues of purified S1 nuclease resulted in loss of its single-stranded (ss)DNAase, RNAase and phosphomonoesterase activities. Kinetics of inactivation indicated the involvement of a single histidine residue in the catalytic activity of the enzyme. Furthermore, histidine modification was accompanied by the concomitant loss of all the activities of the enzyme, indicating the presence of a common catalytic site responsible for the hydrolysis of ssDNA, RNA and 3'-AMP. Substrate protection was not observed against Methylene Blue- and diethyl pyrocarbonate (DEP)-mediated inactivation. The histidine (DEP)-modified enzyme could effectively bind 5'-AMP, a competitive inhibitor of S1 nuclease, whereas the lysine (2,4,6-trinitrobenzenesulphonic acid)-modified enzyme showed a significant decrease in its ability to bind 5'-AMP. The inability of the substrates to protect the enzyme against DEP-mediated inactivation, coupled with the ability of the modified enzyme to bind 5'-AMP effectively, suggests the involvement of histidine in catalysis.

Aspergillus oryzae↗
PubMed1992

Active-site characterization of S1 nuclease. I. Affinity purification and influence of amino-group modification.

A simple procedure, involving heat-treatment, DEAE-Sephadex, AMP-Sepharose and Bio-Gel P-60 chromatography, was developed for the purification of S1 nuclease to homogeneity from commercially available Takadiastase powder. Chemical modification of the amino groups of purified S1 nuclease revealed that lysine is essential for single-stranded DNAase, RNAase and phosphomonoesterase activities associated with the enzyme. The kinetics of inactivation suggested the involvement of a single lysine residue in the active site of the enzyme. Additionally, lysine modification was accompanied by a concomitant loss of all the activities of the enzyme, indicating the presence of a common catalytic site responsible for the hydrolysis of single-stranded DNA, RNA and 3'-AMP. Substrate-protection and inhibitor-binding studies on enzyme modified with 2,4,6-trinitrobenzenesulphonic acid showed that lysine may be involved in the substrate binding.

Animals↗
PubMed1992

Differential cardiovascular effects of propranolol, atenolol, and pindolol measured by impedance cardiography.

We have evaluated Sramek's method of impedance cardiography as a non-invasive way of detecting the cardiovascular effects of drugs. We made cardiovascular measurements using the method during passive tilting and exercise 2 h after the oral administration of atenolol (50 and 100 mg), propranolol (40 and 80 mg), pindolol (5 and 10 mg), and placebo in seven separate studies involving eight healthy male volunteers. Equivalent doses of the pure antagonists atenolol (beta 1) and propranolol (beta 1, beta 2) produced similar reductions in heart rate, systolic blood pressure, and cardiac index, and increases in stroke volume and total peripheral resistance, particularly during exercise. In contrast the partial agonist pindolol produced increases in heart rate and cardiac index, and reductions in peripheral resistance at rest. During passive tilting and exercise pindolol reduced heart rate, but cardiac output and total peripheral resistance were unchanged except at the highest levels of exercise. The similar cardiovascular effects of atenolol and propranolol, but differing effects of pindolol, are consistent with reports using other methods of measurement. This suggests that impedance cardiography may have a place in the non-invasive assessment of the cardiovascular effects of drugs.

Adult↗
PubMed1991

Ferrate oxidation of murine leukemia virus reverse transcriptase: identification of the template-primer binding domain.

Treatment of murine leukemia virus reverse transcriptase (MuLV RT) with potassium ferrate, an oxidizing agent known to oxidize amino acids involved in phosphate binding domains of proteins, results in the irreversible inactivation of both the DNA polymerase and the RNase H activities. Significant protection from ferrate-mediated inactivation is observed in the presence of template-primer but not in the presence of substrate deoxynucleoside triphosphates. Furthermore, ferrate-treated enzyme loses template-primer binding activity as judged by UV-mediated cross-linking of radiolabeled DNA. Comparative tryptic peptide mapping by reverse-phase HPLC of native and ferrate-oxidized enzyme indicated the presence of two new peptides eluting at 38 and 57 min and a significant loss of a peptide eluting at 74 min. Purification, amino acid composition, and sequencing of these affected peptides revealed that they correspond to amino acid residues 285-295, 630-640, and 586-599, respectively, in the primary amino acid sequence of MuLV RT. These results indicate that the domains constituted by the above peptides are important for the template-primer binding function in MuLV RT. Peptide I is located in the polymerase domain whereas peptides II and III are located in the RNase H domain. Amino acid sequence analysis of peptides I and II suggested Lys-285 and Cys-635 as the probable sites of ferrate action.

Amino Acid Sequence↗
PubMed1990

A computerized approach to injury description.

The study of trauma has been handicapped from its inception by the absence of a single coherent method of cataloging injuries. The AIS and ICD-9 systems have failed to fill this void because they lack the precision necessary to describe surgically treated injuries. We conceived a simple system of injury description in which injuries are rapidly encoded using a microcomputer in sufficient detail to distinguish among millions of different injuries. This system is easily searched by a microcomputer and allows for the automatic assignment of AIS, ISS, and CPT codes. In this system a patient is described by a 'paragraph' consisting of any number of identically patterned 'sentences,' each describing one of the patient's injuries. Each 'sentence' is composed of a string of six 'words' from controlled vocabularies and has the following structure: "Body region, Organ, Anatomic region, Injury, Physiology, Treatment." Defining the vocabulary allowed for each 'word' in a 'sentence' is complex because the allowed vocabulary is dependent upon the preceding 'words' in a 'sentence,' but in practice a microcomputer simply provides short lists of acceptable choices at each step of injury description, and records the user's selections. Additionally, the microcomputer assigns AIS, ISS, and CPT codes appropriate to the injury description sentence. The ease of data entry, the fineness of detail captured, the automation of code assignment, and the accuracy of database searching for specific injuries, classes of injuries, or combinations of injuries, we believe will give this approach widespread application in academic trauma centers where an accurate and accessible trauma database is important.

Humans↗
PubMed1988

The diagnosis of polyarteritis nodosa. II. Empirical verification of a decision analysis model.

We evaluated our literature-based estimates of diagnostic test characteristics and aggressive and conservative strategies for the diagnosis of polyarteritis nodosa (PAN) by reviewing 1980 through 1985 data from the University of Chicago Medical Center, Michael Reese Hospital, and Northwestern University Medical School. Test specificity was calculated by reviewing pathology and radiology reports on all relevant procedures done at the University of Chicago Medical Center in 1984 and 1985. There were no reports of false-positive findings (including angiography); thus, test specificity was 100% for muscle, nerve, kidney, liver, and testicular biopsy, which was comparable with our literature-based estimate of 97%. Test sensitivity was based on the 18 confirmed cases of PAN from the 3 institutions and was similar to that in published reports, ranging from 0% for liver biopsy to 100% for visceral angiography. Review of each case for diagnostic test sequence showed an average of 2 diagnostic procedures to confirm the diagnosis (range 1-6). Eight of 18 patients were evaluated according to the conservative strategy we proposed from our literature-based decision analysis approach. No patient was evaluated with the aggressive strategy, although 1 patient had 6 invasive procedures. Of the remaining 10 patients, 9 represented cases that might have been confirmed had the conservative approach been used, and if it had been used, 6 patients would have had the diagnosis confirmed. Thus, the minimum sensitivity of our conservative strategy is 78%, although based on these data, it could be as high as 100%.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation Studies as Topic↗
PubMed1988

Subchronic toxicity study of 1,4-dithiane in the rat.

In a 90-day study, CD strain rats were dosed with 1,4-dithiane by daily gavage at 0, 105, 210, and 420 mg/kg/day (30 rats/sex/dose) in order to calculate a suggested drinking water criterion. No overt toxicity, treatment-related mortality, or ophthalmologic changes were found. Treatment-related decreases were found in female amylase, sorbitol dehydrogenase, and reticulocyte count, and in LDH 1 in both sexes, in LDH 3 in the males, and in LDH 5 in both sexes. Treatment-related increases were found in female liver and in male kidney and male thymus weight. A treatment-related decrease in female brain weight was also found. Significant changes in organ weight of dosed animals compared to control organ weight were observed at the 105 mg/kg/day dose in the spleen of both sexes, female brain, and the male kidneys. Three organs showed compound-related anatomic changes: nose, liver, and kidney. Anisotrophic crystals of undetermined chemical composition were deposited in the olfactory nasal mucosa of both sexes. These crystals were not composed of 1,4-dithiane because 1,4-dithiane is very soluble in ethanol and would not have been present after the slide preparation process. The crystals were present in similar amounts in both sexes of the high and intermediate dose groups. In the low dose group, however, the crystals were present in greater amounts in the females. Crystals were not observed in the control animals. The other treatment-related anatomic abnormalities were eosinophilic cytoplasmic granulation of the convoluted renal tubule cells in the high dose males and minimal hypertrophy of the centrilobular region of the liver in the high dose females. The animal no-observed-effect-level was 105 mg/kg/day. This study reports a novel form of toxicity (deposition of anisotrophic crystals in the olfactory mucosa) from 1,4-dithiane administered by gavage. The chemical composition of the crystals and the absorption, distribution, metabolism, and excretion of 1,4-dithiane are unknown at present.

Amylases↗
PubMed1986

Nizatidine: a new histamine receptor blocker in the treatment of active duodenal ulcers.

Forty-three patients with newly diagnosed duodenal ulcers were treated with a new histamine blocker, nizatidine, and with placebo. The incidence of complete endoscopic healing was 38, 74, and 82% in the nizatidine treated patients compared with 25, 37, and 50% in the placebo treated group after 2, 4, and 8 wk of treatment, respectively. Nizatidine was clearly more effective than placebo after 4 wk of treatment. The size of unhealed ulcers decreased more than 50% in 62, 50, and 50% in the nizatidine treated groups versus 27, 25, and 40% in the placebo treated groups after 2, 4, and 8 wk of treatment, respectively. The difference between the two was not statistically significant for any given period. There was a significant correlation between day pain relief and ulcer healing in both treatment groups. Nizatidine significantly improved day pain relief only after 8 wk of treatment (p less than 0.01). No patient developed any side effects as a result of nizatidine treatment, except that the serum creatinine level rose from 1.05 to 1.1 mg/100 ml but still remained within the normal accepted range. This study demonstrated that nizatidine at 150 mg po bid could be effectively used in the treatment of duodenal ulcer disease.

Clinical Trials as Topic↗