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Biomedical subjects

H Y Chang

Publications and source records attributed to H Y Chang.

At least 163 records · Page 9Linked to original sources
PubMed1983

The rapid incorporation of radioactive fatty acid into triacylglycerols during the in vitro acylation of native lipids of neuronal nuclei.

Using neuronal nuclei (N1) and microsomes (P3) isolated from cerebral cortices of 15-day-old rabbits, the incorporation of [14C]oleate was followed in vitro, making use of fatty acid activation factors and endogenous membrane acyl acceptors. Of the lipids of N1, it was triacylglycerol which showed the highest rates of labelling and which represented 71-80% of the total incorporated radioactivity in this fraction. Specific rates of N1 triacylglycerol formation were 63-166 times those of P3 triacylglycerols (based upon membrane phospholipid content). In P3, phospholipids made up 85% of the total microsomal lipid labelling. The incorporation of oleate was dependent upon ATP and coenzyme A, and acyl-CoA synthetase activities were demonstrated in N1 and P3 (specific activity ratio, N1:P3 = 4.5). Using exogenous [14C]oleoyl-CoA, high rates of N1 triacylglycerol labelling were still seen relative to P3, but rates of diacylglycerol and phospholipid labelling were substantially elevated in both fractions in contrast to rates found using [14C]oleate. By increasing levels of endogenous diacylglycerol using preincubations with phospholipase C, a 3-fold increase was seen in specific rates of triacylglycerol formation in both fractions in subsequent assays with [14C]oleate. A 4.5-fold increase in N1 diacylglycerol concentrations was found when N1 was incubated for 10 min in the absence of fatty acid, ATP and coenzyme A. It is concluded that neuronal nuclei have a very active diacylglycerol acyltransferase as well as the ability to generate diacylglycerol substrates.

Acylation↗
PubMed1983

A comparison of the rates of incorporation of fatty acids during the rapid synthesis in vitro of endogenous triacylglycerols by neuronal nuclei.

The incorporation of radioactive palmitate, oleate, linoleate, and arachidonate into endogenous triacylglycerols was followed in vitro using neuronal nuclei (N1) isolated from cerebral cortices of 15-day-old rabbits. Specific rates of incorporation of fatty acids into N1 triacylglycerols were 33-42 times and more than 100 times the corresponding values for cerebral cortex homogenates and microsomal fractions (P3), respectively. Acyl-CoA synthetase specific activities in N1 were 2.2 to 3.2 times the specific rates for fatty acid incorporation into N1 triacylglycerols. Using single fatty acids, N1 acyl-CoA synthetase showed a preference for linoleate which was more highly marked in linoleate-palmitate and linoleate-arachidonate competitions. In fatty acid incorporation into N1 triacylglycerols a preference for linoleate in competition with palmitate was noted; however, there was also a relatively higher utilization of arachidonate shown competitively than was noted in acyl-CoA synthesis. The data suggested that N1 diacylglycerol acyl transferase shows a selectivity for arachidonoyl-CoA in comparison with CoA esters of palmitate or oleate. Molecular class analyses of radioactive triacylglycerol products indicated that native endogenous N1 diacylglycerols bearing arachidonate or fatty acids of equal or higher unsaturation were used preferentially in N1 triacylglycerol synthesis. This preference was significantly decreased when higher levels of endogenous diacylglycerols were produced in N1 following a phospholipase C preincubation.

Animals↗
PubMed1982

Selective desensitization of cardiac beta adrenoceptors by prolonged in vivo infusion of catecholamines in rats.

The effects of prolonged in vivo infusion of isoproterenol (400 micrograms/kg/hr) or norepinephrine (200 micrograms/kg/hr) from a minipump on the physiological reactivity and binding properties of cardiac beta and alpha-1 adrenoceptors were tested in rats. Infusion of either catecholamine significantly reduced the in vitro inotropic and chronotropic potency of isoproterenol in isolated left and right atria, respectively; desensitization was near maximal as early as after 2 hr of infusion. No significant change in the density of [3H]dihydroalprenolol-labeled beta receptors was evident at this time point in either atrial or ventricular tissue, although isoproterenol did decrease binding site density after 7 days of infusion. There was no change in the binding affinity or physiological blocking potency of dihydroalprenolol after isoproterenol infusion. The inotropic potency of phenylephrine in the presence of dihydroalprenolol was unaffected by infusion of either isoproterenol or norepinephrine and methoxamine failed to increase right atrial rate either in control or in isoproterenol-infused rats. There was also no change in the density and affinity of [3H]prazosin binding sites after isoproterenol infusion. These results indicate selective desensitization of cardiac beta receptors without changes in alpha-1 receptors by prolonged in vivo stimulation with catecholamines. This reaction pattern is different from the well documented effects of hypothyroidism, which include decreased sensitivity of cardiac beta and increased sensitivity of cardiac alpha-1 receptor-mediated responses in rats. Thus, the mechanisms responsible for altered receptor function in the two conditions appear to be different.

Animals↗
PubMed1981

A comparison of lysophosphatidylcholine acyltransferase activities in neuronal nuclei and microsomes isolated from immature rabbit cerebral cortex.

Using neuronal nuclei (N1) and microsomes (P3) isolated from cerebral cortices of 15-day-old rabbits, the activity of lysophosphatidylcholine acyltransferase (acyl CoA: 1-acyl-sn-glycerol-3-phosphorylcholine acyltransferase) was studied using palmitoyl-, oleoyl- and arachidonoyl-CoA and a pool of lysophosphatidylcholine labelled with [3H]palmitate, [3H]stearate or [3H]oleate. Generally, in the acylation of the three radioactive lysophosphatidylcholines with arachidonoyl-CoA, the N1-specific acylation activities were two to seven times those of P3. For oleoyl-coA smaller N1 : P3 specific activity ratios were found, differing significantly from unity for only the 1-palmitoyl and 1-stearoyl lysophosphatidylcholines. The N1 : P3 ratios for the two unsaturated acyl-CoA thioesters were usually found to increase as the lysophosphatidylcholine concentration was lowered from 100 to 25 microM. Thus, nuclear acylation rates, particularly with arachidonoyl-CoA, were less affected by lowering the acceptor concentration than were microsomal activities. At the high lysophosphatidylcholine concentration (100 microM), arachidonoyl-CoA was a superior substrate to oleoyl-CoA in the nuclear acylations of the 1-palmitoyl or 1-stearoyl acceptors. Such a preference was never seen for the microsomal fraction. Using oleoyl- and arachidonoyl-CoA, the nuclear enzymes also showed a greater preference for the 1-palmitoyl homologue over the 1-oleoyl homologue than did the microsomal enzymes. These results support the existence of neuronal nuclear lysophosphatidylcholine acyltransferases with different substrate preferences than shown by the microsomal fraction.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1980

The incorporation of radioactive fatty acids into the phospholipids of nerve-cell-body membranes in vivo.

1. Nerve cell bodies were isolated in bulk from cerebral cortices of 15 day-old rabbits after intrathecal injections of [(3)H]plamitate, [(3)H]oleate or [(3)H]arachidonate and [(14)C]glycerol. 2. Nuclear, microsomal and two mitochondrial fractions were isolated from homogenates of the radioactively labelled nerve cell bodies by using differential and discontinuous-gradient centrifugation. 3. After 7.5min in vivo, a high percentage (>80%) of the total (3)H-labelled fatty acid radioactivity was found in the membrane fractions of the nerve cell bodies, whereas after 60min in vivo 50% of the total [(14)C]glycerol radioactivity was found in the high-speed supernatant. 4. The specific radioactivities of phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol, and the radioactivity in neutral lipid and non-esterified fatty acid fractions were determined in the four subfractions, as were the distributions of several marker enzymes and nucleates. 5. With respect of (3)H-labelled fatty acid, the phospholipids of the nuclear fraction had the highest specific radioactivities of the four subfractions. However, for [(14)C]glycerol labelling, generally the (14)C specific radioactivities for individual phospholipids were comparable in the four subfractions. This latter observation suggests transport of phospholipids synthesized de novo between membranes of the nerve cell body. 6. Double-labelling experiments demonstrated that individual phospholipids and the combined neutral lipids of the nuclear fraction had higher labelling ratios of (3)H-labelled fatty acid/[(14)C]glycerol than did the corresponding lipids of the microsomal or mitochondrial fractions. 7. On the basis of the labelling results and the marker studies, it is proposed that it is indeed the nuclei of the nuclear fraction that have these lipids highly labelled with (3)H-labelled fatty acid, and the existence of nuclear acyl transferases that are responsible for this fatty acid incorporation is suggested.

Animals↗
PubMed1978

Fever and infection in leukemic patients: a study of 494 consecutive patients.

All of the febrile episodes occurring in 494 adults with acute leukemia were reviewed. There were an average of 2.39 febrile episodes per patient and the patients spent 28% of their days in the hospital with fever. Sixty-four percent of the febrile episodes were due to infection. The most common types of infection were disseminated infection and pneumonia, which together accounted for 69% of the total episodes of documented infection. The etiologic agent was identified in 73% of the documented infections and gram-negative bacilli were responsible for the great majority. The most common gram-negative bacilli causing infection were Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa. During the course of their leukemia, 31% of the patients had repeated episodes of infection caused by the same organism and 13% ahd repeated FUO's. Fever occurred most often when the patients had neutropenia (less than 500/mm3). The fatality rate from septicemia decreased from 84% in 1966 to 44% in 1972. The fatality rate for major infections caused by gram-positive cocci was 16%, for gram-negative bacilli was 37% and for fungi was 86%. Although infection remains a serious problem in leukemia patients, considerable progress has been made.

Acute Disease↗
PubMed1976

Causes of death in adults with acute leukemia.

The causes of death were investigated in 315 adults with acute leukemia during a 7-year period (1966-1972). Infection alone or in combination was the most common cause (75%), followed by hemorrhage (24%) and organ failure (9%). Most of the infections were either systemic or pulmonary. Seventy-five percent of the systemic infections and 72% of the pneumonias were caused by bacteria. Klebsiella pneumoniae, Escherichia coli and Pseudomonas aeruginosa were the most frequent organisms isolated. After 1968, there was a sharp decrease in the number of fatal infections caused by Pseudomonas aeruginosa and a marked increase in the incidence of fatal infections caused by Klebsiella spp. and E. coli. Infections caused by Gram-positive cocci occurred in only 3% of the cases. The incidence of systemic fungal infections was 13%; most common fungi causing infection were Candida spp. and Aspergillus spp. Eighty-five percent of 159 patients with a terminal neutrophil count of less than 100/mm3 died of infection, compared to 48% of 62 patients with a terminal neutrophil count of greater than 1000/mm3. Hemorrhage was mostly due to thrombocytopenia (61%) and disseminated intravascular coagulation (12%). This study indicates that infection continues to be the most common cause of death in patients with acute leukemia. Although advances in antibiotic therapy have changed the distribution of causative organisms, ultimate control of infection requires further improvements in supportive care measures which rectify impairments in the patients' host defense mechanisms.

Adolescent↗
PubMed1975

Feasibility of administering aminoglycoside antibiotics by continuous intravenous infusion.

Eleven patients each received gentamicin sulfate, tobramycin, and sisomicin by continuous intravenous infusion after an initial loading dose. Subsequent doses of antibiotic were adjusted in an attempt to maintain constant serum concentrations. There was considerable variation in the serum concentration from patient to patient and in the same patient from day to day with each drug. Although the dosages of gentamicin sulfate and tobramycin were similar, the serum concentrations of the latter drug were consistently lower. Despite the daily administration of doses of at least 300 mg of gentamicin and tobramycin per m(2) and 160 mg of sisomicin per m(2), nephrotoxicity occurred in only three patients. This is a low frequency of nephrotoxicity, considering the dosages of drug administered. Although therapeutic efficacy was not an objective of this study, 8 of 11 documented infections were cured. This approach to the administration of aminoglycoside antibiotics deserves therapeutic trials.

Adolescent↗
PubMedDate not supplied

Outbreak of Candida parapsilosis fungemia in neonatal intensive care units: clinical implications and genotyping analysis.

During a 5-month period, 17 infants hospitalized in neonatal intensive care units of a medical center and a branch hospital developed 18 episodes of Candida parapsilosis fungemia. The mean age at onset was 35 days. Prior to fungemia, all the infants had received hyperalimentation and antibiotics, and 15 infants had had central venous catheters. The presenting symptoms were variable but only vague in 40% of the episodes. Despite administration of antifungal agents, subsequent eradication of fungemia was achieved in only two-thirds of the episodes. None of the environmental samples was positive for C. parapsilosis, while 20% of hand-washing samples of staff working in both units yielded this microorganism. Four genotypes with two main types were identified from 14 outbreak strains and eight genotypes from 14 hand-washing strains, with one type predominant. The results suggest that C. parapsilosis fungemia increases the morbidity and mortality of neonates but does not cause acute lethal events. The outbreak was caused by two main genotypes, possibly via cross-infection by the hands of health care workers.

Candida↗
PubMedDate not supplied

Microbial models of soil metabolism: biotransformations of danofloxacin.

Danofloxacin is a new synthetic fluoroquinolone antibacterial agent under development for exclusive use in veterinary medicine. Such use could lead to deposition of low levels of danofloxacin residues in the environment in manure from treated livestock. This study was conducted to evaluate the potential for indigenous soil microorganisms to metabolize danofloxacin. Cultures of 72 soil microorganisms representing a diverse panel of bacteria, fungi and yeast were incubated with danofloxacin mesylate substrate and samples analyzed periodically by high performance liquid chromatography for loss of danofloxacin and formation of metabolites. Some samples were further analyzed by liquid chromatography-mass spectrometry and mass spectrometry to confirm metabolite identification. Twelve organisms, representing eight different genera, biotransformed danofloxacin to metabolites detectable by the chromatographic methods employed. Two Mycobacterium species, two Pseudomonas species, and isolates of Nocardia sp, Rhizopus arrhizus and Streptomyces griseus all formed N-desmethyldanofloxacin. The formation of the 7-amino danofloxacin derivative, 1-cyclopropyl-6-fluoro-7-amino-4-oxo-1,4-dihydroquinoline-3-carboxylic acid by cultures of Candida lipopytica, Pseudomonas fluorescens, two Mycobacterium species and three Penicillium species demonstrates the propensities of these cultures to completely degrade the piperazine ring. At least two additional and unidentified metabolite peaks were observed in chromatograms of Aspergillus nidulans and Penicillium sp cultures. Radiolabled [2-14C]danofloxacin added to cultures of the fungus Curvularia lunata was apparently mineralized, with approximately 31% of the radiolabel recovered as volatile metabolites after 24 h of incubation, indicating the susceptibility of the quinolone ring to microbial metabolic degradation.

Anti-Infective Agents↗
PubMedDate not supplied

Risk assessment of lung cancer and mesothelioma in people living near asbestos-related factories in Taiwan.

Estimates from environmental risk assessments are criticized by professionals who indicate that inaccuracies occur in exposure assessment, model selection, and determination of the population at risk. In the current study, we tackled the aforementioned issues and estimated the risks of lung cancer and mesothelioma caused by airborne asbestos among individuals who lived near asbestos factories in Taiwan. We conducted 8-h full-period samplings upwind and downwind from each factory, and we used transmission-electronic microscopy (10,000x) and phase-contrast microscopy to determine asbestos concentrations in and around each factory. We estimated the numbers of residents who lived in concentric circles of 200-m, 400-m, and 600-m diameters around each factory. A dose-response model for asbestos-induced lung cancer was adopted from a summary of seven epidemiological studies. The asbestos-mesothelioma models were patterned after the first-exposure-effect models developed by Peto and Finkelstein. The data obtained from phase-contrast microscopy significantly overestimated the risk, compared with transmission-electronic microscopy. The estimates we calculated from adopting the arithmetic mean were approximately 2-fold higher than those we calculated with the geometric mean. There were relatively low concentrations of asbestos in the study areas, thus causing an absence of a significant difference in risk estimates between different models for mesothelioma. Among the more than 20,000 residents who lived near 41 asbestos factories in Taiwan, we found that the numbers of expected excess deaths from lung cancer and mesothelioma were 5 and less than 1, respectively. We concluded that in future risk assessments for ambient asbestos exposure, investigators should adopt transmission-electronic microscopy and the geometric mean estimate. Moreover, Taiwan should enhance asbestos-control programs to assure the safety of residents who live near asbestos factories.

Adult↗
PubMedDate not supplied

Prediction of disease persistence after conization for microinvasive cervical carcinoma and cervical intraepithelial neoplasia grade 3.

We attempted to determine the significant variables and to predict the probability of disease persistence after conization for microinvasive cervical carcinoma and cervical intraepithelial neoplasia grade 3 (CIN3). We analyzed 133 patients from 2001 to 2002 who had a subsequent hysterectomy after conization. The histological findings of the cone specimens, together with the clinical parameters, were correlated with the presence of residual dysplasia in the hysterectomy specimen. The probability of having residual dysplasia was calculated based on the function of the significant variables obtained by logistic regression analysis. Of the 133 patients, 42 (31.6%) had residual disease in their hysterectomy specimens. Using multivariate analysis only for the postmenopausal state, positive endocervical curettage, positive margin, and microinvasive carcinoma were predictive of residual dysplasia. The probabilities of having residual dysplasia were about 0.99, 0.84, 0.4, 0.07, and 0.01 in patients with a presence of all four, any three, any two, any one, and no risk factors, respectively. The best cutoff probability determined by the receiver operating characteristic curve was 0.32, yielding a sensitivity of 81% and a specificity of 88%. Based on these results, patients with the presence of any two or more of the risk factors mentioned above should be considered as a high-risk group for having disease persistence after conization for the treatment of CIN3 and microinvasive carcinoma.

Adult↗
PubMedDate not supplied

Properties of phospholipase A2 isolated from rat serum.

Phospholipase A2 was extensively purified (1300- to 1400-fold) from rat serum using Sephadex G-100 chromatography. It eluted at a position corresponding to a molecular mass of about 15 kDa. This one purification step gave two bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The faster component had a molecular mass of 16 kDa and the slower band likely contained an aggregate of the faster component. Activity was associated with protein bands on nondenaturing gels. Enzyme activity was assessed using phosphatidylcholine or phosphatidylethanolamine labelled at sn position 2 with radioactive arachidonate. Phosphatidylethanolamine gave higher specific activities than phosphatidylcholine. The enzyme has an absolute requirement for Ca2+ and a pH optimum at 7.4. This pH optimum was more prominent for phosphatidylethanolamine. Activity was inhibited by oleate or arachidonate when phosphatidylcholine was used as substrate, but added free fatty acid did not significantly affect the hydrolysis of phosphatidylethanolamine. Addition of bovine serum albumin (fatty acid free) to assays increased the rate of release of arachidonate from phosphatidylcholine, but not from phosphatidylethanolamine. Phospholipase A2 is present in serum likely as a consequence of blood coagulation and may release fatty acids from cellular membranes following hemorrhage.

Animals↗