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Biomedical subjects

A Cheng

Publications and source records attributed to A Cheng.

At least 145 records · Page 8Linked to original sources

Adenosine 5'-diphosphate as an allosteric effector of phosphorylase kinase from rabbit skeletal muscle.

Equilibrium binding and activity studies indicate that adenosine 5'-diphosphate binds to phosphorylase kinase with high affinity at a site, or sites, distinct from the catalytic site. Equilibrium dialysis at pH 6.8 and 8.2, with and without Mg2+, and with phosphorylated and nonphosphorylated enzyme preparations revealed approximately 8 ADP binding sites per alpha 4 beta 4 gamma 4 delta 4 hexadecamer, with Kd values ranging from 0.26 to 17 microM. Decreasing the pH from 8.2 to 6.8 or removing the Mg2+ enhanced the affinity for ADP. At pH 6.8, ADP stimulated the phosphorylase conversion and autophosphorylation activities of the nonactivated enzyme. Analogs of ADP with modifications at the 2'-, 3'-, and 5'-positions allowed determination of structural requirements for the stimulation of activity. ADP seems to alter the conformation of the beta subunit because addition of the nucleotide inhibits its dephosphorylation by phosphoprotein phosphatase and its chemical cross-linking by 1,5-difluoro-2,4-dinitrobenzene. The binding affinities and effects of ADP suggest that it may function physiologically as an allosteric effector of phosphorylase kinase.

Adenosine Diphosphate↗

Utilization of conical equilibrium dialysis cells to shorten equilibration time.

Equilibrium dialysis is commonly used to characterize the binding properties of macromolecules; however, it is not always preferred because of the lengthy time required to reach equilibrium. Consequently, other methods have been developed. This paper compares the disadvantages of various methods for obtaining binding data and shows that utilization of a conically shaped chamber can accelerate the process of equilibrium dialysis. For cylindrical and conical cells of different dimensions a linear relationship was found for the time of equilibration versus the ratio of volume to surface area. Minimizing the volume to surface area ratio by using a conical chamber shortens the time of equilibration by more than half and facilitates sampling of the chambers' contents.

Dialysis↗

Hepatic injury induced by anesthetic agents in rats.

Recent studies on rats pretreated with phenobarbital indicate that anesthetic agents may produce hepatic injury even when metabolism of the anesthetic is almost negligible. This implies that anesthesia per se may cause hepatic injury. To evaluate this possibility, we determined the amount of hepatic injury produced by halothane, enflurane, isoflurane, thiopental, and fentanyl in rats pretreated with phenobarbital. Anesthetics were administered in doses ranging from 0.04-1.1 MAC (or their equivalent for thiopental or fentanyl) and were given with 10% oxygen for 2 h. Liver specimens taken 24 h later were examined microscopically for hepatic injury. At concentrations of 5-40% of MAC, all anesthetics produced more hepatic injury than did control conditions (i.e., exposure to only 10% oxygen for 2 h). There were no systematic differences among agents, nor did starvation before anesthetic exposure produce a difference among agents. Therefore, mechanisms other than anesthetic metabolism are needed to explain hepatic injury produced by anesthetic agents.

Anesthetics↗

Effect of oxygen concentration, hyperthermia, and choice of vendor on anesthetic-induced hepatic injury in rats.

Although hypoxic rats exposed to anesthetics may develop hepatic injury, divergent results have been obtained. These discrepancies might be due to different levels of hypoxia, hypothermia, or choice of vendor. Male Sprague-Dawley rats purchased from Zivic-Miller were pretreated with phenobarbital for 4 days. After 24 h without phenobarbital, they were exposed to 2 h of hypoxia and halothane, enflurane, isoflurane, thiopental, or fentanyl. Rectal temperature was kept between 36.5 degrees C and 38.5 degrees C. All agents given in 10% oxygen produced more hepatic injury than did control conditions (exposure to 10% oxygen alone) (P less than 0.01). Only halothane given in 12% and 14% oxygen produced hepatic injury. No agent given in 20% or 100% oxygen demonstrated hepatotoxicity. In a separate study, rectal temperatures were kept between 32 degrees C and 34 degrees C during 2 h of exposure to 0.3 MAC halothane, enflurane, or isoflurane in 10% oxygen. Hypothermia prevented hepatotoxicity by enflurane and isoflurane, but not by halothane. Finally, although livers of rats obtained from Zivic-Miller were injured, specific pathogen-free rats from Charles River were not injured or were less injured by enflurane, thiopental, or fentanyl. Apparently, minor changes in experimental conditions can substantially affect results; hepatic hypoxia per se, anesthetic metabolism (especially that of halothane), and perhaps anesthesia itself may produce hepatic injury.

Anesthetics↗

Synthetic and preliminary hemodynamic and whole animal toxicity studies on (R,S)-, (R)-, and (S)-2-methyl-3-(2,4,5-trihydroxyphenyl)alanine.

The synthesis, resolution, and absolute configuration assignment of 2-methyl-3-(2,4,5-trihydroxphenyl)alanine (6-OH-alpha-Me-Dopa) are reported. Hemodynamic studies in the rat have shown that this structural analogue and potential metabolite of the clinically useful drug (S)-alpha-Me-Dopa possesses weak hypotensive activity which resides in the R enantiomer. LD50 studies in mice have established that 6-OH-alpha-Me-Dopa is over four times more toxic than alpha-Me-Dopa. Chronic exposure to 6-OH-alpha-Me-Dopa leads to renal and hepatic lesions. The case of oxidation of this hydroquinone to the electrophilic quinone species may contribute to its enhanced toxicity compared to alpha-Me-Dopa.

Animals↗

Vitamin A supplements in hemodialysis patients.

A total of 14 hemodialysis patients were followed for an average of 8.4 months after stopping oral vitamin A supplements (5,000 U daily). No change occurred in the mean vitamin A plasma levels. 11 of the 14 patients were followed for an average of 16.3 months, and no change was noted in the mean vitamin A level. Vitamin A intake does not seem to effect the plasma vitamin A level in hemodialysis patients. This is consistent with the possibility that the vitamin A levels in hemodialysis patients are increased because of an increase in retinol binding protein.

Adult↗

Immune response to a purified cytoplasmic protein of Neisseria gonorrhoeae.

This paper describes studies based on the hypothesis that the immunogenicity of the gonococcus is impaired by a component toxic to immunocytes. Cytoplasm of colony type 1 gonococci was found to contain a protein fraction beta+t not present in colony type 4 gonococci. From the results of further analysis it is tentatively deduced that beta+t consists of a toxic component Tbeta-t and an immunogen.

Amino Acids↗

Preliminary observations on the protective action of a cytoplasmic immunogen of Neisseria gonorrhoeae.

A non-toxic protein, termed beta(-t), consisting of lysine, aspartic acid, threonine, serine, glutamic acid, glycine, and alanine (1.2:1.3:1.3:3:2.2:7:1) was isolated, by the polyacrylamide gel electrophoresis, from an isoelectric toxic proteinaceous fraction beta(+1) of the type 1 cytoplasm of N. gonorrhoeae. The beta(-t) antigen elicited delayed hypersensitivity and vigorous primary and secondary humoral responses in rabbits, and it conferred immune protection against intraocular gonococcal infections.

Amino Acids↗

A biotin-avidin based screening test for methamphetamine in urine.

A biotin-avidin based screening test for methamphetamine in urine samples has been developed. The assay method utilizes the immunoprecipitin reaction between an antibody to methamphetamine and a conjugate prepared by complexing avidin with a biotinyl amphetamine derivative. The rates of the immunoprecipitin reaction is monitored on the Beckman ARRAY 360 nephelometer. Methamphetamine inhibits the precipitin reaction, and the extent of inhibition allows the quantitation of methamphetamine in the urine samples. Using a cut-off value of 0.7 microgram ml-1, the assay correctly predicted 83 of 84 samples (98.8%) confirmed to be positive by GC-MS (> 500 ng ml-1). Of 59 GC-MS confirmed negative samples, 46 samples were found to be negative by this method as compared to 34 samples determined with the EMIT assay. Within-run and between-run relative standard deviations near the cut-off value were less than 4%. Cross-reactivity with amphetamine was < 7%.

Antibodies↗

Rearrangements of the cellular p53 gene in erythroleukaemic cells transformed by Friend virus.

There is now good evidence that the cellular protein, p53, is involved in the transformation process, although its precise role is unknown. It was reported recently that expression of the p53 gene can immortalize cells and that the p53 gene can replace the myc oncogene in a myc-ras immortalization/transformation assay. We have investigated whether p53 is involved in the progression towards the neoplastic state in vivo and report here that erythroleukaemic cell lines transformed by different isolates of Friend leukaemia virus show altered expression of the cellular p53 gene. High levels of p53 protein are found in certain lines, but the protein is undetectable in others. This heterogeneity in p53 gene expression is associated with heterogeneity in tumorigenicity. We demonstrate that genomic rearrangements are responsible for p53 gene inactivation in these cell lines and that they occur in vivo during the natural progression of Friend virus-induced erythroleukaemia.

Animals↗

Imaging characteristics of a small germanium camera.

A high purity germanium gamma-camera has been developed and is currently being evaluated. This camera incorporates unique performance parameters such as a 2 mm full-width spatial response function with rejection of multiple-scatter in the detector, a 2.2% FWHM energy resolution for 99 mTc, a 180 nsec paralyzable dead-time, and a 2 mu sec non-paralyzable dead-time. Imaging studies demonstrate the superior capabilities of this instrument.

Animals↗

ABCs of cardiovascular disease risk management.

The past 20 years have witnessed a marked decline in morbidity and mortality from cardiovascular disease. This decline has been due in large part to advances in coronary risk factor modification and a better understanding of the atherosclerotic process. Compelling scientific and clinical trial evidence proves that comprehensive risk factor modification extends patient survival and reduces cardiovascular and cerebrovascular events. This article reviews the ABCs of optimal medical and lifestyle management in patients with documented atherosclerotic vascular disease as well as in those adults who are at increased risk for the development of cardiovascular disease, based on contemporary clinical trial evidence.

Adrenergic beta-Antagonists↗

The atypical fluorescent body of the interphase nuclei of buccal mucosal cells and its relationship to the Y chromosome.

Buccal mucosal cells from 30 males and 20 females were examined for fluorescent bodies in the interphase nuclei. Chromosomal analysis using peripheral blood, stained with quinacrine mustard (QM), was carried out on the 30 males. The calculated lengths of the Y chromosome were found to be related to the percentage of the total fluorescent bodies, both normal (F-body) and atypical (Fa-body), and also to the proportion of Fa-bodies present in the interphase nuclei. The long Y individuals had a higher percentage of fluorescent bodies and a higher proportion of Fa-bodies while the short Y individuals had a lower percentage of fluorescent bodies and a lower proportion of Fa-bodies.

Cell Nucleus↗