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Biomedical subjects

B Chandrasekaran

Publications and source records attributed to B Chandrasekaran.

At least 19 recordsLinked to original sources
PubMed1995

Synchronization of cells in the S phase of the cell cycle by 3'-azido-3'-deoxythymidine: implications for cell cytotoxicity.

The mechanism of synergy between 3'-azido-3'-deoxythymidine (AZT) and anticancer agents was investigated with emphasis on cell-cycle events. Exposure of exponentially growing WiDr human colon carcinoma cells to AZT resulted in synchronization of cells in the S phase of the cell cycle. Following treatment with AZT at 50 or 200 microM, 62% +/- 3% or 82% +/- 4% of the cells were in the S phase as compared with 36% +/- 2% in the control. Bromodeoxyuridine uptake studies revealed that the synchronized cells actively synthesized DNA. At concentrations of up to 200 microM, AZT produced a cytostatic rather than cytotoxic effect as indicated by viability and cell growth measurements. At 200 microM, AZT-induced synchronization was significant (P = < 0.001) after 12 h of drug exposure, reached a maximum at 24 h, and reversed to baseline levels by 72 h even in the continued presence of the drug. This indicates that AZT-induced cytostasis is a transient and reversible effect. The cell-cycle events seen with AZT in WiDr cells were also observed in eight of nine human tumor cell lines tested. Isobologram analysis of WiDr cells preexposed to AZT for 24 h and then exposed to either AZT-5-fluorouracil or AZT-methotrexate for a further 72 h revealed synergy between AZT and the anticancer agents, indicating that AZT-induced synchronization may have therapeutic benefits.

Antineoplastic Agents↗
PubMed1994

Composite fish culture for mosquito control in rice fields in southern India.

Composite culture of edible fishes (common carp, Cryprinus carpio; silver carp, Hypopthalmithys molitrix, grass carp, Ctenopharyngodon idella; catla, Catla catla; rohu, Labeo rohita; and mrigal, Cirrhinus mrigala) in rice fields in the Cauvery delta of Tamil Nadu, southern India, resulted in 81.0% reduction in the immature mosquito population of anophelines and 83.5% of culicines. Analysis of fish feces for mosquito larval head capsules showed that common carp and silver carp are effective larvivores. The selective feeding of common carp on culicines and silver carp on anophelines is correlated to their trophic niches. Net profit in the fish-cum-rice fields was 2.5 times greater than fields in which rice alone was cultured. Hence, rice-cum-fish culture can be recommended to the farming community in this area.

Animals↗
PubMed1992

Deoxypyrimidine-induced inhibition of the cytokinetic effects of 1-beta-D-arabinofuranosyluracil.

Ara-U-induced S-phase accumulation and the interaction between high concentrations of ara-U (HiCAU) and ara-C were investigated in L1210 leukemia cells in vitro. Treatment of exponentially growing L1210 murine leukemia cells with ara-U (200-1000 microM) for 48 h caused a dose-dependent accumulation of cells in the S-phase. The extent of this ara-U-induced S-phase accumulation correlated with ara-U incorporation into DNA and with increases of up to 172% and 464% in the specific activities of deoxycytidine kinase and thymidine kinase, respectively, over control values. Metabolism of 1 microM ara-C following the exposure of cells to ara-U (1 mM) resulted in 4.5 pmol araC DNA/mg protein vs 2.1 pmol/mg protein in control cells. Although 48-h exposure of cells to 200 and 400 microM ara-U is not cytotoxic, it enhances the cytotoxicity of ara-C (10-100 microM) 4- to 10-fold. Ara-U-induced S-phase accumulation is inhibited by deoxypyrimidine nucleosides but not by pyrimidine or deoxypurine nucleosides. Some of the ara-U and ara-C concentrations used in this study are achievable in clinical practice, and ara-U/ara-C interactions may explain in part the unique therapeutic utility of high-dose ara-C.

Animals↗
PubMed1989

Modulation of the metabolism and pharmacokinetics of 1-beta-D-arabinofuranosylcytosine by 1-beta-D-arabinofuranosyluracil in leukemic mice.

The interaction between high concentrations of 1-beta-D-arabinofuranosyluracil (HiCAU) and 1-beta-D-arabinofuranosylcytosine (ara-C) was investigated in vivo with emphasis on cell kinetics, pharmacokinetics, and drug metabolism. Mice bearing L5178Y leukemia were given a 48-h s.c. infusion of high-dose ara-U (HiDAU) to achieve a plasma level of 0.5 to 1 mM. A total dose of 7.35 g/kg/day for 2 days was nontoxic; the mean survival of control (saline treated) leukemic mice was 12.2 +/- 1.8 days and 11.7 +/- 2.0 days for the HiDAU-treated leukemic mice. Using flow cytometry, cell cycle progression of L5178Y ascites cells was monitored during HiDAU infusion. At 48 h, the proliferative index (PI) percentage of the leukemic cells is significantly different (P less than 0.001) in HiDAU-treated leukemic mice (mean = 50.8) versus control (mean = 45.6). A higher PI percentage is associated with accumulation of cells in S phase. This effect was highly variable in the ara-U-treated mice, and the ara-U "perturbed" group was defined as those mice whose cells had an increase in the PI to greater than or equal to 50%. The higher PI percentage in HiDAU-treated mice correlated with HiCAU in ascites fluid, leukemic cells, and kidney of perturbed mice. HiCAU in the "ara-U-perturbed" group altered the plasma pharmacokinetics of high-dose ara-C (HiDAC, 1 g/kg), increased the cellular metabolism of ara-C to 1-beta-D-arabinofuranosylcytidine triphosphate (ara-CTP) (3-fold), and increased ara-C-DNA synthesis (3-fold). In mice bearing the L5178Y leukemia, a 48-h infusion of ara-U followed by a 24-h s.c. infusion of 40 mg/kg resulted in a 260% increase in life span and seven 90-day survivors among 16 treated mice. In contrast, ara-U or ara-C alone had a negligible therapeutic effect. ara-U-induced alterations in the systemic pharmacokinetics of ara-C are the result of inhibition of cytidine deaminase activity by HiCAU in liver and kidneys. This results in a decrease in ara-C catabolism and prolongs the plasma half-life of ara-C. The dual alteration of the pharmacokinetics of ara-C and cytokinetics of the leukemia cells by HiCAU results in enhanced survival of leukemic mice. These results may help explain the clinical utility of HiDAC treatment programs for patients with acute leukemia.

Animals↗
PubMed1985

Biochemical mechanisms for the scheduled synergism of (alpha S, 5S)-2 amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid and 5-fluorouracil in P388 leukemia.

A study was made of the in vivo effects of equitoxic doses of AT-125 and 5-FU combination, being administered either simultaneously (% ILS 152) or with a 6-h pretreatment with AT-125 (% ILS 184). To examine the biochemical basis for the scheduled synergism, measurements were made of the concentration of PRPP, the specific activities of CPS II, cytidine, thymidine, uridine, deoxyuridine kinases, and fluorinated nucleotide formation in P388 tumors and the small intestine. Two hours after in vivo simultaneous treatment of mice bearing tumors the concentration of PRPP increased 9- and 6-fold above baseline in the tumor and the small intestine, respectively. In the AT-125 pretreatment arm the concentration of PRPP increased 18- and 7-fold above baseline in the tumor and the small intestine, respectively. CPS II activity was reduced to 28%-18% of control in the tumors in the simultaneous and pretreatment groups, respectively, whereas it remained unchanged in the small intestine. Specific activities of cytidine kinase (5.5 +/- 1), thymidine kinase (4.0 +/- 1.6), uridine kinase (35.6 +/- 6.5), and deoxyuridine kinase (2.4 +/- 1.1) nmol/mg protein/h remained unchanged with treatment. In concert with the increased intratumor concentration of PRPP, fluorinated nucleotide formation was proportionally increased in the treatment arms. These results indicate the importance of drug scheduling of the above two agents in treating P388 leukemia.

Animals↗
PubMed1984

Expert systems as aids for interpretive reporting.

Interpretive reporting is an established part of the function of many clinical laboratories. Of the three types of information included in these reports, expert system technology is being demonstrated as useful in producing interpretive comments. The ability of expert systems to explain their reasoning and to be easily updated make them superior to prior attempts to computerize this type of interpretation using traditional computer languages. In the future, the broader application of these systems in realistic clinical environments should be expected given recent commercial success in embedding such programs in laboratory instruments.

Information Systems↗
PubMed1980

Conceptual representation of patient data bases.

Design of a computer-based assistant for patient data bases is discussed. A conceptual model for such an assistant, which can represent signs, symptoms, lab data, and radiological and morphological findings is described. The query language, interpretive reports, summary findings, and related issues in providing intelligent consultation are discussed. The role of such assistants in the context of a decision-making environment--human or automated--is emphasized.

Cholestasis↗