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Biomedical subjects

H Lee

Publications and source records attributed to H Lee.

At least 793 records · Page 44Linked to original sources

Hepatotoxicity of maternal ethanol consumption in rat offspring: an assessment with a study of the ontogenetic development of ethanol-oxidizing systems.

The effect of chronic maternal ethanol ingestion on the ontogenetic development of rat hepatic ethanol-oxidizing systems was investigated. Alcohol dehydrogenase (ADH) activity was first detected at day 19 of gestation. It then increased rapidly to reach adult levels by day 14 postnatally. The ontogenetic pattern, the specific activity and the affinity of the enzyme for its substrate or cofactor were not affected by chronic maternal ethanol consumption. Hepatic microsomal cytochrome P-450 content was first detected in trace amounts just prior to birth. It then increased rapidly in the first 10 days postnatally. Chronic maternal ethanol ingestion did not affect the developmental pattern but induced an increase in the total amount of P-450 detected throughout the postnatal period studied. Fat accumulation was found in fetal and postnatal livers and appeared to correlate with the emerging ability to oxidize ethanol by fetal ADH. The late appearance of the ADH and microsomal ethanol-oxidizing systems indicates that the fetal liver would be entirely dependent on maternal mechanisms to oxidize in-utero ethanol.

Alcohol Oxidoreductases↗

Bias and precision of cholesterol analysis by physician's office analyzers.

We studied the bias and precision of serum cholesterol analysis by physician's office analyzers. Total imprecision (CV range, %) for analysis of serum pools was: Abbott Vision 1.5%-1.9%; Ames Seralyzer 3.9%-4.5%; BMD Reflotron 2.3%-3.8%; Chrometrics Cholesterol Test System 2.3%-2.8%; Kodak DT-60 1.6%-2.2%. The Ames Seralyzer exhibited an excessive between-run component of variation. We collected, from 109 volunteers, samples of venous serum, heparin-treated whole blood, heparin-treated plasma, and fingerstick whole blood, and analyzed each type (where possible) with each system; serum was also analyzed in duplicate (by a proposed Reference Method) at the Centers for Disease Control. For assays with serum, the BMD Reflotron and Kodak DT-60 exhibited negative bias. All systems gave lower results for plasma and whole blood than for serum. All systems except the Kodak DT-60 were less precise for analysis of patients' sera than for analysis of serum pools; between-specimen variables may influence the results of these systems.

Cholesterol↗

Conformational activation of acylpapains and acylcathepsin B's: resonance Raman and kinetic evidence.

It is shown that, by extending the size of the substrate to meet papain's specificity requirement, conformational changes occur in bonds adjacent to the scissile linkage in the acyl enzyme. The resonance Raman (RR) spectra of the dithioacylpapains CH3OC(=O)-Phe-NHCH2C(=S)S-papain, CH3O(=O))-Gly-Phe-NHCH2C(=S)S-papain, and CH3OC(=O)-Gly-Gly-Phe-NHCH2C(=S)S-papain, formed from thiono ester substrates, are found to be very similar, indicating that each dithioacyl enzyme takes up an identical B-type conformation in the -NHCH2C(=S)SCH2-linkages. Moreover, the kcat and kcat/Km parameters for the reactions involving these intermediates are similar (in the ranges 0.51-0.67 s-1 and 44 100-68 200 M-1 s-1, respectively). For these reactions kcat = k3, the rate constant for deacylation. The strong structural similarities in the region undergoing catalytic transformation, taken with the similar k3's, show that placing glycine residues in papain's S3 and S4 subsites has little effect on the deacylation process. However, there are marked RR spectral and kinetic differences between the intermediates formed from these three substrates, all of which meet papain's requirement for Phe at the S2 subsite, and N-(beta-phenylpropionyl)glycine dithioacylpapain, C6H5(CH2)2C(=O)NHCH2C(=S)S-papain. The RR spectral differences indicate that changes occur in the torsional angles of the -NH-CH2-C(=S)-S-CH2- fragment upon going to the di-, tri-, and tetrapeptide-based substrates. The changes in these torsional angles are consistent with slight conformational activation since higher k3 values are found for the di-, tri-, and tetrapeptide-based substrates (0.51-0.67 s-1) compared to the k3 for C6H5(CH2)2C(=O)NHCH2C-(=S)S-papain of 0.165 s-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Acylation↗

Toxic and teratologic effects of verapamil on early chick embryos: evidence for the involvement of calcium in neural tube closure.

Toxic and teratologic effects of verapamil, a calcium antagonist, on chick embryos explanted at stage 8 (four-somite stage) and cultured for 6-8 hours were investigated. In general, embryos responded to verapamil in a dose-related manner. Concentrations lower than 2 micrograms/ml had no apparent effect on the development of embryos. A concentration of 15 micrograms/ml significantly increased the incidence of embryos (approximately 80% of viable embryos) with neural tube closure defects and less numerous somites. Higher concentrations (e.g., 30 micrograms/ml) were embryotoxic and over 90% of the embryos were either severely malformed or dead after 8 hours of incubation. Compared to controls, verapamil-treated neuroepithelial cells had smoother apical surfaces and less conspicuous microfilament bundles. The deleterious effects of verapamil (15 micrograms/ml) could be reversed by subculturing the affected embryos, within 3 hours of treatment, on nutrient medium alone or on nutrient medium containing 25 micrograms/ml chlorotetracycline (CTC), a calcium agonist, the latter being more effective provided that treatment did not exceed 4 hours. Exposure of the developing neuroepithelium to 15 micrograms/ml verapamil for 3-4 hours resulted in a significant reduction in free Ca2+ levels, as revealed by the pyroantimonate precipitation method, throughout neuroepithelial cells. Overall results suggest that verapamil causes neural tube closure defects by reducing intracellular free Ca2+ levels, thereby relaxing apical microfilament bundles of developing neuroepithelial cells.

Animals↗

omega-Iodophenyl fatty acids: a convenient method of radioiodination.

A solid-phase radioiodination technique for omega-iodophenyl fatty acids using ammonium sulfate is described. The radioiodinations are regioselective, high in yield (95%), short in reaction time (1 h) and capable of yielding high specific activity products although at lower yields. Purification is exceptionally simple: a single passage through an ion exchange column to remove unreacted I- is all that is required. Syntheses of several omega-iodophenyl fatty acids are also described.

Fatty Acids↗

Mutants of Pachysolen tannophilus with Improved Production of Ethanol from d-Xylose.

The conversion of d-xylose to ethanol by the yeast Pachysolen tannophilus is relatively inefficient in batch culture. The inefficiency has been attributed in part to concurrent utilization of ethanol in the presence of appreciable concentrations of d-xylose and to the formation of xylitol and other by-products. To increase the concentration of ethanol accumulated in batch cultures, UV-induced mutants of P. tannophilus were selected on the basis of diminished growth on ethanol. Eleven independent mutant loci that conferred the ethanol-defective phenotype were identified. Three led to a greater yield and volumetric rate of production of ethanol than the wild type. One also produced less xylitol and was characterized by a deficiency in activity for malate dehydrogenase.

Journal Article↗

Utilization of Xylan by Yeasts and Its Conversion to Ethanol by Pichia stipitis Strains.

Yeasts able to grow on d-xylose were screened for the ability to hydrolyze xylan. Xylanase activity was found to be rare; a total of only 19 of more than 250 strains yielded a positive test result. The activity was localized largely in the genus Cryptococcus and in Pichia stipitis and its anamorph Candida shehatae. The ability to hydrolyze xylan was generally uncoupled from that to hydrolyze cellulose; only three of the xylan-positive strains also yielded a positive test for cellulolytic activity. Of the 19 xylanolytic strains, 2, P. stipitis CBS 5773 and CBS 5775, converted xylan into ethanol, with about 60% of a theoretical yield computed on the basis of the amount of d-xylose present originally that could be released by acid hydrolysis.

Journal Article↗

Adaptive changes in rat liver plasma membranes after chronic alcohol administration and its subsequent withdrawal.

Rat hepatic plasma membranes isolated after chronic alcohol feeding displayed a different buoyant density range with a significantly increased peak density value when spun isopycnically in a 30-50% sucrose (w/w) gradient. This change persisted up to 48 h of withdrawal from alcohol. Analysis of membrane lipids revealed certain significant alterations in the phospholipids as well as the fatty acyl composition in individual phospholipids of the experimental plasma membranes. During withdrawal of alcohol for 48 h, all the alcohol-induced changes in the phospholipids returned to normal. Most initial changes in fatty acids reverted to the control composition during this time, but new changes in fatty acyl distribution were also observed. These were interpreted to represent readaptation to the withdrawal of the alcohol. It is not established how long this readaptation period lasts.

Alcoholism↗

Lack of cardiac effect from repeated doses of albuterol aerosol. A margin of safety.

To simulate the pattern of use by some patients at home, we studied the effect of frequently repeated inhalation of albuterol aerosol on cardiac rhythm. Fifteen stable outpatient asthmatic children, ages 9-14 years were treated with two puffs of albuterol aerosol (180 mcg) followed either by hourly placebo or hourly albuterol aerosol for 5 hours (10 puffs = 900 mcg) in a randomized, double-blind crossover study. Cardiac rhythm was Holter monitored and pulmonary function was tested hourly for 5 hours. Heart rate (HR) was analyzed at hourly intervals. Pretreatment heart rate of 95.4 bpm +/- 1.9 SEM declined by 0.4-3 (bpm) after single dose and declined by 2.2-5.6 (bpm) from 99.2 (bpm) +/- 2.3 SEM during multiple doses. No one developed arrhythmia, and side effects were infrequent on either day. Forced expiratory volume in 1 second (FEV1) increased similarly on both regimens. It remained stably elevated on the multiple doses, but it started to decline at 120 minutes after the single dose. Our study shows a substantial margin of safety in administration of albuterol aerosol to asthmatic children.

Adolescent↗

A clinical study of Gilles de la Tourette's syndrome in Korea.

Clinical data on 30 Korean patients of the authors with Gilles de la Tourette's syndrome are described, as well as data on seven other Korean cases from the literature. The overall characteristics and EEG findings were similar to those of Western patients, but there were fewer obsessive-compulsive behaviour problems, and family histories were less often positive.

Adolescent↗

Development of a kit-form analog of metaiodobenzylguanidine.

The synthesis and evaluation of two radiopharmaceutical analogs of metaiodobenzylguanidine (MIBG) are described. Unlike MIBG, these analogs are rapidly and conveniently radioiodinated at room temperature in clinically applicable kit form. Radioiodinated 4-amino-3-iodobenzylguanidine (AIBG) for injection is synthesized in 20 min using IODO-GEN as the radioiodide oxidant and an anion exchange filter for purification. AIBG shows an affinity for the heart and adrenal medullae of dog and monkey similar to that of MIBG. In addition, AIBG shows improved selectivity for the adrenergic nerves of the heart as demonstrated by chemical sympathectomy studies. Tomographic images of the dog heart and planar images of the dog adrenal medullae were obtained using [123I]AIBG and [131I]AIBG, respectively. Planar images of the monkey heart using [131I]AIBG were similar in quality to those reported previously with [131I]MIBG. In view of the facile radiosynthesis of AIBG, a clinical evaluation of this new agent is warranted.

3-Iodobenzylguanidine↗