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Biomedical subjects

Y C Chang

Publications and source records attributed to Y C Chang.

At least 343 records · Page 19Linked to original sources

Serum ferritin level after resection of hepatocellular carcinoma. Correlation with alpha-fetoprotein level.

Total serum ferritin concentrations were serially estimated in 24 patients with primary hepatocellular carcinoma (HCC) for 4 to 8 weeks after resection of the tumor. The patients were divided into four groups according to the tumor size and the result of ferritin was compared with that of serum alpha-fetoprotein (AFP) levels. All patients had underlying parenchymal diseases of the liver (liver cirrhosis in 19 and chronic hepatitis in 5 cases). The serum ferritin levels did not reflect the therapeutic result of hepatic resection in most of the patients of all groups. Serum AFP levels, which were measured simultaneously with ferritin levels, were much superior to the ferritin estimation. The current study may indicate that ferritin cannot be used as a tumor marker in the follow-up of Japanese patients with HCC and associated liver disease. Acidic isoferritin, which is known to be produced in and secreted from HCC, should be measured for this purpose.

Adolescent↗

Function of pyridoxal 5'-phosphate in glycogen phosphorylase: 19F NMR and kinetic studies of phosphorylase reconstituted with 6-fluoropyridoxal and 6-fluoropyridoxal phosphate.

19F NMR spectroscopic properties of glycogen phosphorylase reconstituted with 6-fluoropyridoxal (6-FPAL) and 6-fluoropyridoxal phosphate (6-FPLP) were investigated. Analysis of the contribution of chemical shift anisotropy to the line width of the 6-FPLP-enzyme signal shows that the coenzyme molecule is tightly bound to the protein. The chemical shift of the fluorine nucleus in the free 6-FPLP protein is pH independent from pH 6 to pH 9.1. When the 6-FPLP-enzyme forms complexes with AMP, AMP plus glucose-1-P, and AMP plus inorganic phosphate, signals at -11.0, -13.1, and -10.4 ppm are observed, respectively. These different chemical shifts indicate that the protein in each complex has a distinct conformation. The exchange rate between the 6-FPLP-protein-AMP complex and the same complex with bound glucose-1-P is estimated to be 3300 +/- 700 s-1, and that between the 6-FPLP-protein-AMP complex and with bound inorganic phosphate is 500 +/- 100 s-1. The former exchange rate is 13 times faster than that of the same process for the 6-FPAL-enzyme. Analysis of the effects of temperature on the 19F line shape of the 6-FPLP enzyme in the presence of ligands shows that the exchange rates between different complexes drop significantly between 20 and 10 degrees C. Within this temperature range, Arrhenius plots of the enzymatic activities of the native and 6-FPLP-enzymes at varied temperatures also show a pronounced curvature.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗

An outbreak of N-hexane induced polyneuropathy among press proofing workers in Taipei.

The objective of this study was to determine the prevalence and the etiology of polyneuropathy observed among press proofing workers in Taipei. Neurological examinations of 59 workers, from 16 press proofing factories, were conducted. Fifty-four of those workers subsequently underwent studies of nerve conduction velocities. Samples of bulk solvent from the involved factories were analyzed for their contents using gas chromatography. Fifteen (25%) of the study group were found to have polyneuropathy. All 15 patients with polyneuropathy were from factories in which solvents containing n-hexane were regularly used, and there was a significant association between n-hexane concentration in the bulk samples and prevalence of polyneuropathy. The air concentration of n-hexane in one factory in which all six employees developed polyneuropathy was 190 ppm. Workers who were exposed to n-hexane at air levels of less than 100 ppm but who frequently worked overtime showed a significant slowing of motor nerve conduction velocities on median, ulnar, and peroneal nerves. Of 13 workers who regularly slept in the factory, 12 (92%) had polyneuropathy compared to three (7%) of 46 workers who did not sleep in the factory. The outbreak of polyneuropathy was attributed to a combination of the use of solvents with high contents of n-hexane, poor ventilation, and the practice of sleeping in the factories between shifts.

Adolescent↗

Second hepatic resection for recurrent hepatocellular carcinoma.

During the last 5 years, radical hepatic resection was performed in 91 patients with hepatocellular carcinoma (HCC). Thirty-one of them had tumour recurrence in the remaining liver during the follow-up period. Second hepatic resection was carried out on nine of them 4-38 months after the first hepatectomy. The ages of these patients ranged from 39 to 65 years with an average of 53.7. There were six men and three women. Eight patients had underlying cirrhosis of the liver and one chronic active hepatitis. Six patients are alive, four being free of HCC and two with disease, for 15-45 months after the first operation. Two patients died of systemic cancer dissemination. The remaining patient had tumour recurrence in the liver again and died of hepatic failure after the third laparotomy. The survival rate of these nine patients was significantly better than that of twenty-two patients who were treated by other palliative methods. The present result shows that a second hepatic resection is a possible and meaningful method of treatment for the patients with recurrent HCCs in the liver remnant.

Adult↗

Monoclonal antibodies to glutamic acid decarboxylase.

Five monoclonal antibodies that recognize chicken brain glutamic acid decarboxylase (GAD) have been selected and designated GAD-1 to -5. GAD-1 to -5 were selected on the basis of their ability to immunoprecipitate active GAD from crude brain extracts. GAD-1 recognizes an epitope that is conserved in many vertebrates; the epitope recognized by GAD-5 is restricted to the chicken. Radioimmunoassays with GAD-1 indicate that GAD is highly enriched in brain relative to other tissues. GAD was localized immunocytochemically with GAD-1 and GAD-2 in rat cerebellum, spinal cord, and retina. The staining pattern is in agreement with that obtained previously with polyclonal antisera to GAD. GAD from the chicken brain was purified by chromatography on an immunoaffinity column made of GAD-1. NaDodSO4/PAGE analysis of the immunoaffinity-purified GAD fractions shows a major band of 59 kDa and minor bands at 63 and 54 kDa.

Animals↗

Clinical experience with 118 hepatic resections for hepatocellular carcinoma.

During the recent 5 2/3 years, hepatic resection was performed on 118 patients with hepatocellular carcinoma. Ages ranged from 17 to 78 years with an average of 57 years. There were 101 males and 17 females. Underlying cirrhosis of the liver was found in 101 cases, and chronic hepatitis was found in 16 cases. Before surgery 62 patients had 71 associated conditions such as esophageal varices, diabetes mellitus, cholelithiasis, or peptic ulcer. Operations for the varices and cholelithiasis were performed simultaneously with hepatic resection in 15 and six patients, respectively. The operative mortality rate within 1 month was 7.6%, and the overall in-hospital death rate was 14.4%. In 94 patients with curative resection, the 2-year survival rate was 81.2% in patients without cirrhosis and 55.4% in patients with cirrhosis. The 4-year survival rate was 81.2% in the former and 34.8% in the latter group. The prognosis was significantly better in patients without cirrhosis than in those with cirrhosis. On the contrary, 21 of 24 patients with palliative resection died within 2 years despite extensive chemotherapy. The present results may indicate that the resectability rate of hepatocellular carcinoma is currently increasing, even in the presence of cirrhosis of the liver due to early detection of the tumor by current advances in diagnostic methods and also that major hepatic resection is possible in selected patients with cirrhosis.

Adolescent↗

Effect of halothane on the natural-abundance 13C NMR spectra of excised rat brain.

Halothane increases the intensity of the 30.5- and 129-ppm resonances in 13C nuclear magnetic resonance spectra of excised rat brain, of phospholipid vesicles prepared from chloroform-methanol extract of rat brain, and of brain excised from rats anesthetized with halothane. The 13C spin-lattice relaxation times of the 30.5- and 129-ppm resonances are increased in excised brain, or phospholipid vesicles, upon addition of halothane, and they are also increased in brain excised from rats anesthetized with halothane. Excised brain and its membrane-rich subcellular fractions interact with [14C]halothane reversibly. The interaction is virtually abolished when the phospholipids are extracted from the brain. The [14C]halothane content of the brain membranes is correlated with the halothane-induced increase in the integral of the 129-ppm resonance. From this correlation and from the phospholipid content of the membranes, a halothane concentration of 3.34 mM and a partition of 0.057 mol of halothane/mol of phospholipid may be calculated in the brain of anesthetized rats.

Animals↗

Studies of 6-fluoropyridoxal and 6-fluoropyridoxamine 5'-phosphates in cytosolic aspartate aminotransferase.

The chemical and spectroscopic properties of 6-fluoropyridoxal 5'-phosphate, of its Schiff base with valine, and of 6-fluoropyridoxamine 5'-phosphate have been investigated. The modified coenzymes have also been combined with the apo form of cytosolic aspartate aminotransferase, and the properties of the resulting enzymes and of their complexes with substrates and inhibitors have been recorded. Although the presence of the 6-fluoro substituent reduces the basicity of the ring nitrogen over 10 000-fold, the modified coenzymes bind predominately in their dipolar ionic ring forms as do the natural coenzymes. Enzyme containing the modified coenzymes binds substrates and dicarboxylate inhibitors normally and has about 42% of the catalytic activity of the native enzyme. The fluorine nucleus provides a convenient NMR probe that is sensitive to changes in the state of protonation of both the ring nitrogen and the imine or the -OH group of free enzyme and of complexes with substrates or inhibitors. The NMR measurements show that the ring nitrogen of bound 6-fluoropyridoxamine phosphate is protonated at pH 7 or below but becomes deprotonated at high pH around a pKa of 8.2. The bound 6-fluoropyridoxal phosphate, which exists as a Schiff base with a dipolar ionic ring at high pH, becomes protonated with a pKa of approximately 7.1, corresponding to the pKa of approximately 6.4 in the native enzyme. Below this pKa a single 19F resonance is seen, but there are two light absorption bands corresponding to ketoenamine and enolimine tautomers of the Schiff base. The tautomeric ratio is altered markedly upon binding of dicarboxylate inhibitors. From the chemical shift values, we conclude that during the rapid tautomerization a proton is synchronously moved from the ring nitrogen (in the ketoenamine) onto the aspartate-222 carboxylate (in the enolimine). The possible implications for catalysis are discussed.

Animals↗

Use of 6-fluoroderivatives of pyridoxal and pyridoxal phosphate in the study of the coenzyme function in glycogen phosphorylase.

6-Fluoropyridoxal phosphate (6-FPLP) has been synthesized. Its properties were studied, and it was used, along with 6-fluoropyridoxal (6-FPAL), to reconstitute apophosphorylase b. Kinetic studies of the resulting enzymes showed that phosphorylases reconstituted with 6-FPLP and 6-FPAL have characteristics similar to those of native and pyridoxal enzymes, respectively, except that the former two enzymes have lower Vmax values. 19F NMR and UV spectra of 6-FPLP phosphorylase showed that the coenzyme forms a neutral enolimine Schiff base. Because the UV and fluorescence spectra of 6-FPLP phosphorylase are comparable to those obtained with native phosphorylase, it further confirms the postulate that pyridoxal phosphate forms a neutral enolimine Schiff base in phosphorylase. The results suggest that the 3-OH group is protonated and the pyridine nitrogen unprotonated in both 6-FPLP phosphorylase and native enzyme. 19F NMR study of 6-FPLP- and 6-FPAL-reconstituted phosphorylases in the inactive and active states indicates that the protein structure near the coenzyme binding site undergoes certain changes when these enzymes are activated by the substrates and AMP. The comparison of the properties of 6-FPLP-reconstituted and native phosphorylases implies that the ring nitrogen of the coenzyme PLP in phosphorylase may interact with the protein during catalysis, and this interaction is important for efficient catalysis by phosphorylase.

Animals↗

The separation of phosphocreatine from creatine, and pH determination in frog muscle by natural abundance 13C-NMR.

Phosphocreatine can be separated from creatine in superfused frog muscle by natural abundance 13C-NMR, based on the difference in resonance frequency of their guanidino carbons. After taking into account the longitudinal relaxation times and nuclear Overhauser enhancement factors, the integrated peak areas of the guanidino carbons could be used for determination of the phosphocreatine-to-creatine ratio in the muscle. The pH dependence of the chemical shift of the C-2 carbon in the histidine ring of carnosine was used for estimation of the intracellular pH in the intact muscle.

Animals↗

Natural-abundance 13C NMR of brain.

In natural-abundance 13C NMR spectrum of excised rat brain 55 resonances were resolved. The chemical shifts of most of the resonances were well correlated with those of pure brain metabolites, determined under identical experimental conditions. These resonances were also found in the cytosol fraction and perchloric acid extract of the brain. Some brain resonances were not observed in the perchloric acid extract but only in the microsomes or cytosol.

Animals↗

Polychlorinated biphenyl poisoning: correlation of sensory and motor nerve conduction, neurologic symptoms, and blood levels of polychlorinated biphenyls, quaterphenyls, and dibenzofurans.

In 1979 in Taiwan, more than 2000 people were poisoned with rice cooking oil contaminated with polychlorinated biphenyls (PCB). One hundred ten patients were studied within one year of the exposure. The blood PCB levels were 39.3 +/- 16.6 ppb. The blood levels of the PCB derivatives, polychlorinated quaterphenyls (PCQ) and polychlorinated dibenzofurans (PCDF), were 8.6 +/- 4.8 and 0.076 +/- 0.038 ppb, respectively. Both the sensory and motor nerve conduction velocities (NCV) of the patients were significantly lower than the control. Abnormal slowing of sensory NCV was found in 43.6% and abnormal slowing of motor NCV was seen in 21.8%. Patients who had higher PCQ blood levels had significantly slower median nerve sensory NCV than those with lower PCQ levels. Patients with higher PCB blood levels had significantly slower peroneal nerve motor NCV than those with lower PCB levels.

Adolescent↗

Therapeutic blood levels of phenytoin in treatment of paroxysmal choreoathetosis.

Eight patients with paroxysmal choreoathetosis received phenytoin therapy, starting from 50 mg of oral phenytoin with a gradual increment of the dose. After successful control of the paroxysmal attacks, blood levels of phenytoin in these patients were measured by enzyme immunoassay. The mean phenytoin blood level was 5.2 +/- 3.2 micrograms/ml, with a range of 1.1-10.9 micrograms/ml. It is proposed that phenytoin can be maintained at a lower level in the treatment of paroxysmal choreoathetosis than in seizure control.

Adolescent↗

Characterization of the broad resonance in 31P NMR spectra of excised rat brain.

31P NMR spectra of excised rat brain showed a broad resonance between-12 and -13 ppm. Subcellular fractions of brain, rich in membranes, exhibited the broad resonance and it was also present in isolated myelin, the major membrane component of brain. However, it was absent in brain cytosol (161,100 X g supernatant). Raising the temperature of the brain above 50 degrees C caused a gradual downfield chemical shift of the broad resonance, to about -1 ppm at 90 degrees C. An even larger downfield shift was produced by halothane or deoxycholate with concomitant narrowing of the line width of this resonance. Vesicles prepared from the phospholipids of excised brain or isolated myelin showed the broad resonance, and halothane produced the same downfield shift and peak sharpening in brain phospholipid vesicles as that in the intact brain. The chemical shift anisotropy was estimated to be 45 ppm for both myelin and the brain, as characteristic for biological membranes. The T1 and T2 relaxation times of the perpendicular 31P chemical shift tensor component of the broad resonance were 0.66 sec and 1.6 msec, respectively, in the same range as those for other biological membranes. Halothane-treatment of the brain increased both the T1 and T2 times considerably, as expected from the disruption of the phospholipid bilayer in a membrane. These data indicate that the broad resonance in the 31P NMR spectrum of excised rat brain originates exclusively from the phosphate head group of membrane bound phospholipids. Similar broad resonances were found in autopsied human brain and porcine spinal cord and to a lesser extent in excised rat liver and kidney.

Animals↗