Search PubMed⌕ Search

Biomedical subjects

H Cheng

Publications and source records attributed to H Cheng.

At least 361 records · Page 20Linked to original sources
PubMed1993

Calcium sparks: elementary events underlying excitation-contraction coupling in heart muscle.

Spontaneous local increases in the concentration of intracellular calcium, called "calcium sparks," were detected in quiescent rat heart cells with a laser scanning confocal microscope and the fluorescent calcium indicator fluo-3. Estimates of calcium flux associated with the sparks suggest that calcium sparks result from spontaneous openings of single sarcoplasmic reticulum (SR) calcium-release channels, a finding supported by ryanodine-dependent changes of spark kinetics. At resting intracellular calcium concentrations, these SR calcium-release channels had a low rate of opening (approximately 0.0001 per second). An increase in the calcium content of the SR, however, was associated with a fourfold increase in opening rate and resulted in some sparks triggering propagating waves of increased intracellular calcium concentration. The calcium spark is the consequence of elementary events underlying excitation-contraction coupling and provides an explanation for both spontaneous and triggered changes in the intracellular calcium concentration in the mammalian heart.

Aniline Compounds↗
PubMed1993

Amino acid residues in Anabaena ferredoxin crucial to interaction with ferredoxin-NADP+ reductase: site-directed mutagenesis and laser flash photolysis.

Ferredoxin (Fd) functions in photosynthesis to transfer electrons from photosystem I to ferredoxin-NADP+ reductase (FNR). We have made several site-directed mutants of Anabaena 7120 Fd and have used laser flash photolysis to investigate the effects of these mutations on the kinetics of reduction of oxidized Fd by deazariboflavin semiquinone (dRfH.) and the reduction of oxidized Anabaena FNR by reduced Fd. None of the mutations influenced the second-order rate constant for dRfH. reduction by more than a factor of 2, suggesting that the ability of the [2Fe-2S] cluster to participate in electron transfer was not seriously affected. In contrast, a surface charge reversal mutation, E94K, resulted in a 20,000-fold decrease in the second-order rate constant for electron transfer from Fd to FNR, whereas a similar mutation at an adjacent site, E95K, produced little or no change in reaction rate constant compared to wild-type Fd. Such a dramatic difference between contiguous surface mutations suggests a very precise surface complementarity at the protein-protein interface. Mutations introduced at F65 (F65I and F65A) also decreased the rate constant for the Fd/FNR electron transfer reaction by more than 3 orders of magnitude. Spectroscopic and thermodynamic measurements with both the E94 and F65 mutants indicated that the kinetic differences cannot be ascribed to changes in gross conformation, redox potential, or FNR binding constant but rather reflect the protein-protein interactions that control electron transfer. Several mutations at other sites in the vicinity of E94 and F65 (R42, T48, D68, and D69) resulted in little or no perturbation of the Fd/FNR interaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1993

A method for calculating the mean absorption time of drugs undergoing reversible and first-pass metabolism.

A method has been derived for calculating the mean absorption time of an oral drug and its interconversion metabolite which is generated from the drug systemically and presystemically. The method evolves from the convolution integral and requires plasma AUC and AUMC values after separate intravenous administration of the drug and its interconversion metabolite and oral administration of the drug. It can also be used to calculate the mean input time of a drug undergoing reversible metabolism and administered by any other extravascular route. Results of a simulation study using both errorless and errant data indicate that, when the absorption rate constant of a drug or its interconversion metabolite is not much larger than the apparent elimination rate constant, the proposed method performs satisfactorily. However, when the absorption rate constant of a drug or its interconversion metabolite is much larger than the apparent elimination rate constant, the proposed method appears to be inaccurate.

Administration, Oral↗
PubMed1993

Pharmacokinetics and metabolic interconversion of intravenous 4-amino-5-chloro-2-[(methylsulfinyl)ethoxy]-N-[2-(diethylamino)ethyl] benzamide and its sulfide and sulfone metabolites in rats.

The pharmacokinetics of a new 5-hydroxytryptamine (5HT3) receptor antagonist, 4-amino-5-chloro-2-[(methylsulfinyl)ethoxy]-N-[2-(diethylamino)ethyl] benzamide (ML-1035, 1), and its sulfone and sulfide metabolites were examined in 12 rats. Each of these compounds (25.4 mumol/kg) was administered to rats intravenously. Their plasma concentrations were measured by high-performance liquid chromatography. These plasma data revealed that 1, a sulfoxide, underwent interconversion with its sulfide metabolite. However, no interconversion was observed between 1 and its sulfone metabolite. Examination of mean times and additional properties of the 1/sulfide metabolite system revealed that total exposure times of 1 and the sulfide metabolite were moderately and weakly, respectively, influenced by the metabolic interconversion process. However, the tissue distribution process strongly influenced the total exposure times of both compounds. The disposition of the sulfone metabolite of 1 was also strongly influenced by the tissue distribution process. In addition, < 3% of the intravenous dose of 1 or the sulfide was available to the general circulation as the sulfone metabolite.

Animals↗
PubMed1993

A multidimensional deconvolution method for evaluating the absorption of drugs undergoing reversible metabolism and presystemic metabolite formation.

A general multidimensional deconvolution method is developed primarily for application to the bioavailability assessment of drugs with reversible metabolism. The proposed approach involves fitting continuous functions to the experimental data and then applying a numerical deconvolution algorithm to the fitted curves. It is shown how the method may be used to determine the rates and extends of drug absorption and presystemic formation of interconversion metabolites. The proposed method is implemented as a FORTRAN subroutine called DCVSYS for the general multidimensional deconvolution problem involving any continuous functions and as a user-friendly PC-compatible program called NDCREV for evaluating the absorption of drugs undergoing reversible metabolism. The methods and computer programs are demonstrated by application to simulated drug and metabolite concentrations for a drug with reversible metabolism.

Absorption↗
PubMed1993

A simplified method for quantitation of iodine-123 iodobenzamide in human plasma: a technical note.

To establish a quantitative single-photon emission tomography (SPET) procedure for imaging CNS D2 dopamine receptors, measurement of unchanged iodine-123 iodobenzamide (123I-IBZM) (a selective D2 ligand) in human plasma was investigated. There are three possible radioactive components in human plasma: hydrophilic compounds (iodide ion, etc.), lipophilic metabolites, and unchanged IBZM. Based on the difference in lipophilicity of IBZM and its lipophilic metabolites (LM), a new quantitative method of analysis of 123I-IBZM using a simple solvent extraction was developed. The selective extraction was achieved with n-octane/phosphate buffer (0.1 M, pH 7.4). Extraction efficiency was 93.2% +/- 0.3% (n = 15) for IBZM from plasma, while 99.3% +/- 0.2% (n = 12) of LM remained in the aqueous plasma fraction. Twenty-one confirmation tests with plasma containing known ratios of IBZM/LM, ranging between 0.39 and 7.60, were performed. The experimental results were very close to the values of the true ratios over the wide range (accuracy approximately 99%, relative standard error 6.6%). The data from this simplified method are comparable to those obtained by the high-performance liquid chromatography method. This improved method provides an easy and accurate way to quantify unchanged IBZM in human plasma. With appropriate kinetic modeling and in conjunction with a dedicated SPET imaging device for measuring quantitative information, it may be possible to develop a practical method for measuring D2 receptor density in vivo.

Benzamides↗
PubMed1993

Estimation of the extent of the cutoff region from the spatial distribution of labelling and mitotic indices of intestinal crypts of a fixed length.

Current understanding of the pattern of proliferation within intestinal crypts involves the notion of a cutoff region introduced by Cairnie et al. (Exp. Cell. Res. 39, 539-553, 1965b). (Cells produced above the cutoff are non-cycling, whereas cells produced below the cutoff are cycling.) They contrasted the predicted distribution of proliferation in the extreme cases of a cutoff of width 0 (a sharp cutoff) with one eight cells wide (a slow cutoff) and concluded that the data were better explained by the latter. We have shown that crypt size variation artificially broadens the apparent distribution of proliferating cells in the crypt (Totafurno et al., Biophys. J. 54, 845-858, 1988). Here we show that the measurement and analysis of crypts of a specified height reduces this artifact. This work introduces the use of distance from the crypt base (in microns) to specify the location of cells within the crypt as an improvement over the cell position ordering traditionally used in the determination of the distribution of proliferating cells. We also show how to explicitly correct for several artifacts in the measurement of the labelling index. We conclude that cell proliferation within the crypt is more localized than previously realized; in fact, a cutoff as slow as eight cells wide is rejected.

Animals↗
PubMed1993

Mean residence time of oral drugs undergoing first-pass and linear reversible metabolism.

Equations for the mean residence times in the body (MRT) and AUMC/AUC of a drug and its metabolite have been derived for an oral drug undergoing first-pass and linear reversible metabolism. The mean residence times of the drug or interconversion metabolite in the body after oral drug are described by equations which include the mean absorption time (MAT), the mean residence times of the drug or metabolite in the body after intravenous administration of the drug, the fractions of the dose entering the systemic circulation as the parent drug and metabolite, and the systemically available fractions of the drug (Fpp) or metabolite (Fpm). Similarly, the AUMC/AUC of the drug and metabolite after oral drug can be related to the MAT, ratios of the fraction of the dose entering the systemic circulation to the systemically available fraction, the first-time fractional conversion of each compound, and AUMC/AUC ratios after separate intravenous administration of each compound. The Fpp and Fpm values, in turn, are related to the first-pass availabilities of both drug and metabolite and the first-time fractional conversion fractions. The application of these equations to a dual reversible two-compartment model is illustrated by computer simulations.

Animals↗
PubMed1993

Evaluation of sustained/controlled-release dosage forms of 3-hydroxy-3-methylglutaryl-coenzyme a (HMG-CoA) reductase inhibitors in dogs and humans.

Seven sustained/controlled-release dosage forms were designed for gastrointestinal delivery of lovastatin or simvastatin, two potent HMG-CoA reductase inhibitors for the treatment of hypercholesterolemia. The in vivo performance of these formulations was evaluated in dogs and healthy volunteers in terms of the cholesterol lowering efficacy and/or systemic concentrations of HMG-CoA reductase inhibitors. Results from the present and previous studies suggest that, through the controlled release of HMG-CoA reductase inhibitors, sustained lower plasma concentrations of HMG-CoA reductase inhibitors may result in an equal or better therapeutic efficacy.

Adult↗
PubMed1993

Dissociated eye movements in craniosynostosis: a hypothesis revived.

A characteristic pattern of dissociated eye movements was observed in a large proportion of our patients with a variety of craniosynostosis syndromes. These anomalies simulate overaction of the inferior oblique and underaction of the superior oblique muscles which, however, cannot fully explain the abnormalities. In a number of cases, excyclorotation of the muscle cone was observed, with the upper pole of the eye tilted away from the midline. It is postulated that such excyclorotation of the eyes will lead to dissociated eye movements which can be explained on physiological grounds according to Hering's law. This paper presents a review of our patients and evidence to support this hypothesis.

Adolescent↗
PubMed1993

Watertight sutures with fibrin glue: an experimental study.

A rat model was developed to test the watertightness of sutures and used to evaluate the value of fibrin glue (Tissucol, Immuno France, Tisseel, Immuno U.S., Inc.) in making conventional sutures watertight. Fibrin glue raised the mean hydrostatic pressure to which the skin suture resisted from 9.1 to 26.3 cm H2O, thus indicating that it enhances suture watertightness immediately after surgery. After 3 and 6 days, the pressure was increased, respectively, from 24.8 to 47.9 and from 56.5 to 73.3 cm H2O. For bladder sutures, the results are comparable.

Animals↗
PubMed1993

Characterization of two cis-acting DNA elements involved in the androgen regulation of the probasin gene.

The location and sequence of androgen responsive elements (AREs) in the 5'-flanking DNA of the androgen-regulated rat probasin (PB) gene were determined. The DNA- and steroid-binding domains of the rat androgen receptor [glutathione-S-transferase (GST)-AR1] and the DNA-binding domain and hinge region alone (GST-AR2) were expressed in Escherichia coli as isopropyl-B-D-thioglactopyranoside-induced fusion proteins with GST and purified using glutathione affinity chromatography. Band shift assays indicated that the AR1 peptide was at least five times more effective than AR2 in binding to PB 5'-flanking DNA (-426 to +28), although both gave qualitatively similar patterns and were displaced by anti-AR antibodies. DNase I footprinting experiments revealed two putative AREs: one between positions -236 and -223 (ARE-1) and the other between -140 and -117 (ARE-2). Hormonal regulation of PB was determined by cotransfecting reporter constructions containing the PB 5'-flanking region (-426 to +28) linked to the bacterial chloramphenicol acetyl transferase (CAT) gene with androgen, glucocorticoid, or progesterone receptor expression vectors into human prostatic carcinoma cells (PC-3). PB-CAT gene expression was more effectively induced by androgens than by glucocorticoids or progestins. Both 5'- and 3'-deletion mapping of the PB 5'-flanking DNA revealed that ARE-1 and ARE-2 were required for androgen regulation. A single base mutation in either ARE resulted in a more than 95% loss of androgen induction of CAT. In comparable transfection experiments, the PB hormone-responsive elements showed a greater induction by androgens than did mouse mammary tumor virus or tyrosine aminotransferase elements. Thus, the preferential androgen regulation of the PB gene involves the participation of two different cis-acting DNA elements that bind AR.

Amino Acid Sequence↗
PubMed1993

[Transformation of recombinant plasmid pRK 41 and amplification of full-length coding region of human brain myelin basic protein cDNA].

Transformation of the recombinant plasmid pRK41 containing 2.15 kd human brain myelin basic protein MBP)-coding sequence and 3' untranslated region (1.2 kb) into the E. coli JM109 was made by using Hanahan's method. Positive colonies were screened with digoxigenin oligo labelled rat brain MBP cDNA fragment (1.2 kb). To remove 3' untranslated region and obtain the full-length coding sequence of MBP cDNA, a pair of specific DNA primers was designed and synthesized. A 600 bp fragment was amplified from the recombinant plasmid, extracted from the positive colony by using polymerase chain reaction (PCR). The PCR fragment was isolated, and then digested with BamH I, Kpn I and BamH I + Kpn I. The results of restriction analysis indicate that the PCR amplified fragment is desirable and can be used directly to constract expression vectors.

Base Sequence↗
PubMed1993

[Epidemiologic studies on HCV and HBV infections among intravenous drug users in the area with high HIV infection].

To assess the prevalence of HBV and HCV infections among intravenous drug users (i.v. DUs) in Ruili county, Yunnan where there was a high HIV infection rate in i.v. DUs, the serological examination indicated that there was also a high anti-HCV antibody positive rate in this group. Among those with anti-HIV antibody, 73 (92%) were anti-HCV antibody positive. There was a close relationship between HIV infection and HCV infection. It may suggest that both are related to i.v. drug using. Although there is a high HBV infection background in Yunnan Province, the prevalence of HBV infection in i.v. DUs (68%) and that in the controls (52%) still show a significant difference.

Adolescent↗