PubMed Health⌕ Search

Biomedical subjects

A Sen

Publications and source records attributed to A Sen.

At least 127 records · Page 7Linked to original sources
PubMed1993

Thermodynamics of the interaction of berberine with DNA.

The interaction of berberine [7,8,13,13a-tetrahydro-9-10-dimethoxy-2,3-(methylene dioxy)-berberinium] with calf thymus DNA has been studied by spectrophotometry in buffers of various salt concentrations and temperatures. Binding parameters obtained are best fit by the neighbour exclusion model. The salt and temperature dependence of the binding constants are used to estimate thermodynamic parameters involved in the complex formation of berberine with DNA. The binding process is exothermic over the entire range and the values of enthalpy and entropy change are strongly dependent on the salt concentration. The negative enthalpy and positive entropy changes compensate one another to produce a relatively small Gibbs' free energy change. Possible molecular contribution to the enthalpy and entropy changes is discussed.

Animals↗
PubMed1993

Expression of precursor and mature carnitine palmitoyltransferase II in Escherichia coli and in vitro: differential behaviour of rat and human isoforms.

cDNAs corresponding to the precursor and mature forms of rat carnitine palmitoyltransferase II (CPT II) were found to be readily expressed in Escherichia coli. In both cases, catalytically active immunoreactive protein was produced and became largely membrane-associated. The precursor form of the enzyme was not proteolytically processed. Removal of 126 bp from the 5' end of the cDNA coding region allowed expression of a truncated CPT II (lacking the N-terminal 17 residues of the mature protein), but this product was inactive. cDNAs encoding the precursor and mature forms of human CPT II resisted direct expression in E. coli. However, the impediment was overcome when the latter cDNA was ligated in-frame 3' to sequence encoding a glutathione S-transferase. This construct yielded abundant quantities of the corresponding fusion protein, a portion of which was soluble and catalytically active. In vitro transcription and translation of the various cDNAs established that the lower mobility on SDS/PAGE of rat CPT II compared with its human counterpart (despite their identical numbers of amino acids) is an intrinsic property of the primary sequences of the proteins themselves. Also, the human cDNA was found to contain an artifactual termination signal for T3 RNA polymerase that could be bypassed by the T7 polymerase. Thus rat CPT II can be expressed in active form in E. coli with characteristics similar to those of the enzyme in mitochondria, opening the way to future location of active sites within the molecule. An alternative expression system will be needed for similar studies on human CPT II.

Animals↗
PubMed1993

Comparison of serum, milk and urine as samples in an enzyme immunoassay for bovine leukaemia virus infection.

Serum, milk and urine specimens were taken from 15 bovine leukaemia virus (BLV)-positive and 20 BLV-negative cattle which had been determined previously to be infected or not by the use of a monoclonal enzyme-linked immunosorbent assay (ELISA). An ELISA was performed on the samples for the detection of IgG1 antibodies to the BLV surface glycoprotein, gp 51. The three types of samples had parallel optical density (OD) values apart from three urine samples which, although accepted as negative for anti-BLV antibodies, had numerically higher ODS than those of control BLV-negative animals. Therefore, detection of IgG1 antibodies against BLV in the urine of naturally infected animals could be an indication for the use of urine for diagnosis of BLV infection.

Animals↗
PubMed1993

The economics of life and death.

Mortality data can be used to analyze economic performance. Such information can illuminate critical aspects of the economic organization of society.

Adolescent↗
PubMed1992

Missing women.

Explore the source record for details and available documents.

Africa, Northern↗
PubMed1992

Cellular elimination of 2',2'-difluorodeoxycytidine 5'-triphosphate: a mechanism of self-potentiation.

2',2'-Difluorodeoxycytidine (dFdC, Gemcitabine) is a deoxycytidine analogue which, after phosphorylation to the 5'-di- and 5'-triphosphate (dFdCTP), induces inhibition of DNA synthesis and cell death. We examined the values for elimination kinetics of cellular dFdCTP and found they were dependent on cellular concentration after incubation of CCRF-CEM cells with dFdC and washing into drug-free medium. When the drug was washed out at low cellular dFdCTP levels (less than 50 microM), dFdCTP elimination was linear (t1/2 = 3.3 h), but it became biphasic at intracellular dFdCTP levels greater than 100 microM. Although the initial elimination rate was similar at all concentrations, at higher concentrations the terminal elimination rate increased with increasing cellular dFdCTP concentration, with a nearly complete inhibition of dFdCTP elimination at 300 microM. The deamination product 2',2'-difluorodeoxyuridine was the predominant extracellular catabolite at low cellular dFdCTP concentrations, whereas at high dFdCTP concentrations dFdC was the major excretion product. The dCMP deaminase inhibitor 3,4,5,6-tetrahydrodeoxyuridine transformed the monophasic dFdCTP degradation seen at low dFdCTP levels into a biphasic process, whereas the deoxycytidine deaminase inhibitor 3,4,5,6-tetrahydrouridine had no effect on dFdCTP elimination. An in situ assay indicated that dCMP deaminase activity was inhibited in whole cells, an action that was associated with a decreased dCTP:dTTP value. In addition, dFdCTP inhibited partially purified dCMP deaminase with a 50% inhibitory concentration of 0.46 mM. We conclude that dFdC-induced inhibition of dCMP deaminase resulted in a decrease of dFdCTP catabolism, contributing to the concentration-dependent elimination kinetics. This action constitutes a self-potentiation of dFdC activity.

Antimetabolites, Antineoplastic↗
PubMed1992

How much 'better' is good enough? The magnitude of treatment effect in clinical trials.

OBJECTIVES: Among the various factors required to calculate sample size for clinical trials, the magnitude of treatment effect anticipated is an important component. The objective of this report is to present some of the complexities involved in selection of treatment effect size in clinical trials. As a framework for discussion, an analysis of published reports related to surfactant therapy was carried out. DESIGN: Twenty-one consecutive exogenous surfactant trials for neonatal respiratory distress syndrome were analyzed. The "Methods" sections were reviewed for evaluating various components of sample size calculation, including the anticipated treatment effect size. RESULTS: Sixteen (76%) of the 21 reports provided a description of sample size calculations, and 12 of these gave some reasons for the choice of the anticipated treatment effect size. Expressed as percent change, the median treatment effect from intervention anticipated by the investigators was 50% (range, 15% to 90%), with a positively skewed distribution. The actual median percent reduction in adverse events from treatment (as compared with baseline) was 36% (range, 75% reduction to 5% excess). When the treatment effect was expressed as difference in adverse event rate, in the 14 (of 16) trials that could be analyzed, the median observed reduction in adverse events (death, bronchopulmonary dysplasia, or occurrence of respiratory distress syndrome) was 14.5% (range, 52% reduction to 2% excess). All trials except one concluded, however, that the intervention was effective, mostly based on additional subgroup calculations. CONCLUSIONS: Researchers often select sample sizes capable of detecting only large treatment effects, thus risking type II error, although sometimes a much smaller effect could be clinically important. While pragmatic considerations must be considered during the design of randomized clinical trials, researchers ought to present a rationale for anticipating a given magnitude of treatment effect in their sample size calculations. It may be possible to consider innovative trial designs that help determine the most appropriate treatment choice with the least possible sample size.

Confidence Intervals↗