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Biomedical subjects

M Qian

Publications and source records attributed to M Qian.

106 records · Page 6Linked to original sources
PubMed1993

Intramolecular electron transfer in ferredoxin II from Desulfovibrio desulfuricans Norway.

In order to elucidate the role of the two (4Fe-4S) clusters in ferredoxins and to determine whether an electron-transfer mechanism may occur between the clusters, the in vitro reduction of cytochrome c3 and cytochrome c553 by Desulfovibrio desulfuricans Norway ferredoxin II was studied using spectrophotometric techniques. Ferredoxin II, covalently cross-linked with either cytochrome c3 or c553, is an obligate intermediate in cytochrome reduction by pyruvate dehydrogenase. Both titration of the complex formation under 1H-NMR spectroscopy and cross-linking experiments between ferredoxin II and either cytochrome c3 or cytochrome c553 gave a stoichiometric ratio of 1:1. Modelling the protein yielded differences between the charge distributions around the two (Fe-S) clusters. The fact that Cluster 2 is blocked in the electron-transfer domain facing the cytochrome interacting heme, indicates Cluster 1 receives electron from pyruvate dehydrogenase. Consecutively, cytochrome reduction occurs owing to an intramolecular electron exchange between the two clusters of the ferredoxin. The properties of two (Fe-S) cluster ferredoxins are compared to those of monocluster ferredoxins and discussed in evolutionary terms.

Amino Acid Sequence↗
PubMed1993

Structure and molecular model refinement of pig pancreatic alpha-amylase at 2.1 A resolution.

The previously reported structural model of porcine pancreatic alpha-amylase has been corrected and improved by a genuinely independent structure solution. The electron density map was established by multiple isomorphous replacement (m.i.r.; using 5 derivatives) and subsequent solvent-flattening at 2.8 A resolution. The sequence was built into the well-defined regions of the m.i.r. map; this partial model was refined using a simulated annealing refinement method with phase restraints. Phase combination of m.i.r. phases and phases of the partial model allowed the completion of the model. The final refinement was based on 29,838 independent reflections in the 8 to 2.1 A resolution range. A final R-factor of 15.6% was obtained with a model obeying standard geometry within 0.014 A in bond lengths and 2.8 degrees in bond angles. The final model consists of all 496 amino acid residues, 1 calcium ion, 1 chloride ion and 353 water molecules. The model is described in detail; the calcium and chloride binding sites are characterized.

Animals↗
PubMed1993

Pharmacokinetic evaluation of drug interactions with anti-human immunodeficiency virus drugs. VI. Effect of the calcium channel blocker nimodipine on zidovudine kinetics in monkeys.

Coadministration of zidovudine (AZT) and nimodipine, a calcium-channel blocker, is a potential therapeutic regimen in acquired immunodeficiency syndrome patients based on the report that nimodipine can prevent human immunodeficiency virus-induced neurotoxicity in vitro. An evaluation of the pharmacokinetics of AZT and its glucuronide metabolite 3'-azido-3'-deoxy-5'-O-beta-D-glucopyranurosylthymidine (GAZT) in the presence and absence of nimodipine in monkeys was undertaken. After 20 mg/kg of AZT given i.v. in the presence and absence of nimodipine, nimodipine caused a significant reduction (41%) in the volume of distribution of AZT at steady state and a 22% decrease in total clearance. The disposition of GAZT was also influenced by nimodipine, causing a large increase in its area under the plasma concentration-time curve. Renal excretion data for AZT and GAZT, although inconclusive, suggested nimodipine caused a decrease in the renal clearance of AZT with a minimal change in the renal clearance of GAZT. The combined effects of nimodipine on the clearance of AZT and volume of distribution at steady state produced no change in its elimination half-life.

Animals↗
PubMed1992

High-performance liquid chromatographic determination of the calcium channel blocker nimodipine in monkey plasma.

A new high-performance liquid chromatographic (HPLC) assay was developed for the determination of nimodipine in monkey plasma. An ethyl acetate extraction procedure was employed with a reversed-phase HPLC separation for the analysis. Absolute recovery of nimodipine from plasma was over 95% with a lower limit of quantitation of 10 ng/ml. This method was applied to a preliminary pharmacokinetic study in which 0.25 mg/kg nimodipine was administered intravenously to three monkeys. Protein binding and stability of nimodipine in monkey plasma were also examined. The pharmacokinetic parameters of nimodipine in monkeys were similar to those obtained in humans and indicate that monkeys are an appropriate animal model for further pharmacokinetic investigations.

Animals↗
PubMed1992

Pharmacokinetic evaluation of drug interactions with anti-HIV drugs, II: Effect of 2',3'-dideoxyinosine (ddI) on zidovudine kinetics in monkeys.

The pharmacokinetic basis of a drug interaction between zidovudine (AZT) and 2',3'-dideoxyinosine (ddI) was investigated in normal monkeys. Five animals received 20 mg/kg of AZT intragastrically in the absence and presence of ddI. ddI was administered intravenously to produce steady-state ddI plasma concentrations for 30 min. Plasma and urine samples were analyzed for AZT, its major glucuronide metabolite, GAZT, and ddI by high-performance liquid chromatography (HPLC). Resultant AZT and GAZT concentration data were analyzed by noncompartmental methods. Statistical analysis indicated no differences in AZT's apparent total clearance, apparent volume of distribution at steady-state, and elimination half-life due to ddI, however, the mean apparent total clearance decreased from 2.92 to 1.67 L/h/kg, and the mean apparent volume of distribution at steady-state decreased from 5.79 to 3.43 L/kg in the presence of ddI. Incomplete urine collections in most animals prevented conclusions from being made about ddI's effect on renal elimination parameters. Nonetheless, the urinary GAZT/AZT ratio, a parameter not influenced by incomplete urine collection, was significantly reduced in the presence of ddI. Although additional studies will be useful to characterize the full importance of the interaction, there is evidence to suggest that both renal and metabolic elimination of AZT and renal elimination of GAZT may be inhibited by ddI.

Animals↗
PubMed1989

Normal and leukemic lymphocyte membrane fluidity and response to stimulation with ConA and PHA.

In our experiment, lymphocyte membrane was labeled by DPH fluorescence probe. The rate of rotation of the probe can be measured from the value of fluorescence polarization (PDPH). With this method useful information could be provided about membrane fluidity of lymphocytes. It was found that the F value (unit of lipid fluidity of membrane) of leukemic lymphocytes was obviously higher than that of normal ones. Furthermore, the F value of cultured leukemic Ts lymphocytes was the highest. In contrast with normal spleen T-lymphocytes or mixed lymphocytes, the response of malignant lymphocytes to the stimulation with ConA or PHA was reflected in the decrease of PDPH value or the increase of F value. Unexpectedly, the F value of T-lymphocytes from "615" mouse not injected with tumour cells was also higher than that of the mixed. The possibility of using the membrane fluidity as a diagnostic criterion was also discussed.

Animals↗
PubMed1981

Markov chain as a model of Hill's theory on circulation.

Establishing a model for various kinds of vivid metabolic systems of living organisms is an subject, uneasy but of great significance. Hill has constructed a theoretical framework for discussions of metabolic systems, such as active transport, muscle contraction, etc. The basic method of his framework is diagram calculation for the cycle flux on the metabolic cycles of those systems [2, 7] He has successively found that the result from diagram calculations agrees with the data of the numbers of completing different cycles given by random test (Monte Carlo test), but has not yet proved that the former is just the circulation rate in the sense of trajectory. In this paper, the model of a Markov chain is used to define the circulation rate in the sense of trajectories and, by deriving the remaining Markov chains, we calculate the expression of circulation rate which coincides with Hill's result obtained from diagrams. And hence we verify that Hill's cycle flux is equivalent to the circulation rate defined by trajectory. Besides, this paper establishes a connection between Hill's free energy of small systems and the potential of a Markov chain which is suggested by Hou Zhenting.

Markov Chains↗
PubMedDate not supplied

Pharmacokinetic evaluation of drug interactions with anti-human immunodeficiency virus drugs. V. Effect of soluble CD4 on 2',3'-dideoxycytidine kinetics in monkeys.

This study was conducted to determine if soluble CD4 (ST4) altered the pharmacokinetics of 2',3'-dideoxycytidine (ddC) in nonhuman primates. Each of six monkeys received 5 mg/kg of ddC iv in the absence and presence of two different iv regimens of ST4. The ST4 regimens produced steady-state plasma concentrations of 10.3 micrograms/ml (N = 3) and 22.2 micrograms/ml (N = 3) for 30 min following ddC administration. Pharmacokinetic parameters for ddC and ST4 were calculated based on plasma and urine concentrations of ddC and plasma concentrations of ST4. Following combined ddC and ST4 administration, in both the low- and high-dose ST4 groups, plasma concentration-time profile of ddC were similar for each monkey, and no statistical differences were observed in the pharmacokinetic parameters compared with those obtained when ddC was given alone. Complete urinary excretion data for ddC was obtained in 3 of the 6 animals studied. At the low ST4 dose, one animal had a reduced renal clearance of ddC, whereas at the high ST4 dose two animals recorded an increased renal clearance of ddC. ST4 plasma concentrations were comparable to in vitro concentrations of antiviral activity, with pharmacokinetic parameters similar to those reported previously. The kinetic information provides a basis for rational dosage design for combination chemotherapeutic regimens of ddC and ST4 in human immunodeficiency virus infection.

Animals↗