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Biomedical subjects

Y C Chang

Publications and source records attributed to Y C Chang.

At least 253 records · Page 14Linked to original sources

Incidence and factors associated with intrahepatic recurrence following resection of hepatocellular carcinoma.

BACKGROUND: The long-term survival rate after liver resection of hepatocellular carcinoma (HCC) is far from satisfactory, mainly because of high intrahepatic recurrence (IHR) rates. This study was aimed to clarify clinicopathologic factors relevant to IHR after resection of HCC. METHODS: The 10-year cumulative intrahepatic recurrence rates were analyzed in terms of seven clinical and eight pathological factors in 201 patients with curative hepatic resection. RESULTS: IHR was found in 121 patients during the follow-up period. The overall IHR rates were 22% at 1 year, 43% at 2 years, 62% at 3 years, 72% at 4 years, 75% at 5 years, and 75% at 10 years. Age, sex, and serum alpha-fetoprotein level, hepatitis B virus markers, and extent of liver resection were not significantly related to the IHR rate. Postoperative chemotherapy mainly with anthracycline tended to suppress IHR (P = 0.0889), but preoperative chemoembolization did not affect IHR. The presence of cirrhosis, satellite nodules, and venous invasion and the absence of capsule formation were associated with higher recurrence rates throughout the observation. Positive surgical margin (< or = 5 mm) was also associated with a higher IHR rate. Although not significant, well-differentiated HCCs showed a higher recurrence rate in comparison with poorly differentiated tumors. Size and number of tumor did not influence the IHR rate. CONCLUSIONS: Accurate patient selection and adequate hepatic reserve are important considerations in the management of HCC by resection.

Aged↗

Tryptophan fluorescence quenching in rabbit skeletal myosin rod.

The solvent accessibility of the four tryptophans of rabbit skeletal muscle myosin rod was investigated using steady-state and time-resolved fluorescence quenching by iodide, acrylamide, and cesium. The quenching by iodide and acrylamide was biphasic; the discrete, long lifetime component was quenched with bimolecular collision constants (kq) of 1 x 10(9) M-1 s-1 and 1.6 x 10(9) M-1 s-1, respectively, while the Gaussian distributed, short lifetime component was quenched with a kq value of 0.3 x 10(9) M-1 s-1 and 0.04 x 10(9) M-1 s-1, respectively. Comparison with kq values for N-acetyl-tryptophanamide indicated that the fractional solvent accessibility was about 25% for the long and less than 10% for the short lifetime component. Cesium quenching was monophasic and provided evidence of an excess of positive charge around these tryptophans. Our findings cast doubt on the general application of the simple coiled-coil model to describe coiled-coil interactions in this protein in solution.

Acrylamide↗

Identification of Aspergillus brlA response elements (BREs) by genetic selection in yeast.

The brlA gene of Aspergillus nidulans plays a central role in controlling conidiophore development. To test the hypothesis that brlA encodes a transcriptional regulator and to identify sites of interaction for the BrlA polypeptide, we expressed brlA in Saccharomyces cerevisiae (yeast) strains containing Aspergillus DNA sequences inserted upstream of a minimal yeast promoter fused to the Escherichia coli lacZ gene. Initially, a DNA fragment from the promoter region of the developmentally regulated rodA gene was tested and shown to mediate brlA-dependent transcriptional activation. Two additional DNA fragments were selected from an Aspergillus genomic library by their ability to respond to brlA in yeast. These fragments contained multiple copies of a sequence motif present in the rodA fragment, which we propose to be sites for BrlA interaction and designate brlA response elements (BREs). DNA fragments containing BREs upstream of a minimal Aspergillus promoter were capable of conferring developmental regulation in Aspergillus. Deletion of BREs from the upstream region of rodA greatly decreased its developmental induction. Multiple copies of a synthetic oligonucleotide with the consensus sequence identified among the BREs mediated brlA-dependent transcriptional activation in yeast. The results show that a primary activity of brlA is transcriptional activation and tentatively identify sites of interaction for the BrlA polypeptide.

Aspergillus nidulans↗

Liver resection for hepatocellular carcinoma. Results of 229 consecutive patients during 11 years.

OBJECTIVE: This study analyzed the results in 229 patients with primary hepatocellular carcinoma (HCC) who were treated by radical hepatic resection in the past 11 years. SUMMARY BACKGROUND DATA: Due to marked advances in diagnostic and therapeutic methods, the therapeutic strategy for HCC has changed significantly. However, there are still many problems to be solved when hepatic resection is to be performed for HCC associated with chronic liver disease. A satisfactory result may be possible only when all of accurate operative indication, skillful surgical technique, and sophisticated postoperative management are met. METHODS: There were 188 men and 41 women. Age ranged from 32 to 79 years averaging 60.8. Underlying cirrhosis of the liver was found in 177 patients, and chronic hepatitis was found in 47 instances. Before surgery, 114 patients had 157 associated conditions; diabetes mellitus in 66, esophageal varices in 42, cholelithiasis in 22, peptic ulcer in 12, and miscellaneous in 15 cases. In addition to various types of hepatic resection, 69 patients underwent concomitant operations such as cholecystectomy, the Warren shunt, splenectomy, partial gastrectomy, and so forth. RESULTS: The 30-day (operative) mortality rate was 7.0%, and there were eight additional late deaths (3.5%). Child's class, bromosulphalein (BSP) test, and the estimated blood loss during surgery were good predictors for operative death. The cumulative 5- and 10-year survival rates for all patients were 26.4% and 19.4%, respectively. At present, 110 patients are alive; 2 more than 10 years and 21 more than 5 years. Younger age, absence of cirrhosis, smaller tumor, and postoperative chemotherapy were associated with increased survival. CONCLUSIONS: The results of hepatic resection in 229 patients with HCC were analyzed. Child's class, BSP test, and blood loss during surgery were good predictors for operative death. The 5- and 10-year survival rates were 26.4% and 19.4%, respectively. Age, liver cirrhosis, tumor size, and postoperative chemotherapy were prognostic factors. Multidisciplinary approach with liver resection, postoperative chemotherapy, and liver transplantation will be a realistic direction for the surgical treatment of HCC in future.

Blood Loss, Surgical↗

Familial aggregation of periodontal indices.

Analysis of three measures of periodontal health (plaque index, gingival index, and attachment loss) was carried out on 178 individuals in 75 families examined as part of a family study of periodontal health. Original participants in this study were volunteers recruited from the University of Maryland Dental Clinic, and were selected independently of any specific dental disease or condition. Relatives were invited to participate in the family study so that the extent of familial aggregation of indices of periodontal health could be assessed. By means of an analysis of variance model for persons nested within families, evidence for familial aggregation of plaque index was found both before and after adjustment for covariates such as age, gender, race, and reported oral hygiene habits. While a substantial fraction of variance in gingival index and attachment loss was also due to differences among families, neither attained statistical significance in these data. Examination of familial correlations (e.g., parent-offspring, sib-sib, spouse correlations) confirmed that plaque index showed greater familial resemblance compared with other measures of periodontal health. Both mean gingival index and mean attachment loss showed a stronger correlation between mothers and offspring compared with fathers and offspring. This suggests that further analysis of models for separating genetic and environmental effects may be appropriate for plaque index, but complete analysis of other periodontal indices will require more flexible statistical models for separation of genetic and cultural inheritance while considering gender-specific expression and transmission, as well as incorporation of information from covariates.

Adolescent↗

beta-N-methylamino-L-alanine (L-BMAA) decreases brain glutamate receptor number and induces behavioral changes in rats.

Rats receiving intracerebroventricular administration of 10 nanomoles of L-BMAA (beta-N-methylamino-L-alanine) were found to grow more slowly and contain less brain L-(3H) glutamate binding sites than rats receiving injection of phosphate-buffered saline (PBS). It was also noticed that rats receiving L-BMAA injection inevitably developed a characteristic behavioral pattern, including loss of mobility and keeping their heads in a tilted position with occasional side to side movement. This unique behavioral pattern was not observed in rats receiving injection of PBS. Rats receiving injection of beta-N-oxalylamino-L-alanine, another toxic plant amino acid, showed a decrease in brain L-(3H) glutamate binding sites, however, without the characteristic behavioral change as induced by L-BMAA. It was further found that rats receiving injection of L-BMAA plus 2-amino-5-phosphonovalerate were similar to those injected with PBS with respect to their L-(3H) glutamate binding activity and behavioral pattern. Results obtained here show that L-BMAA at nanomole level is able to elicit neurotoxic effects on rats and that these toxic effects are mediated by N-methyl-D-asparate-subtype L-glutamate receptors. The results also show that a decrease in glutamate receptor number results from L-BMAA treatment, suggesting an involvement of altered glutamate receptor level in the manifestation of L-BMAA neurotoxicity.

2-Amino-5-phosphonovalerate↗

Liver resection in the aged (seventy years or older) with hepatocellular carcinoma.

BACKGROUND: Thirty-two patients who were 70 years of age or older underwent hepatic resection in the treatment of hepatocellular carcinoma. There were 25 men and 7 women. Age ranged from 70 to 84 years, averaging 74 +/- 3 years (mean +/- SD). Underlying liver diseases were associated in all patients but one, cirrhosis of the liver in 22, and chronic hepatitis in nine. METHODS AND RESULTS: The operative mortality rate within 1 month was 12.5%, and the overall in-hospital death rate was 18.8%. The 5-year survival rate was 17.6% for all patients and 24.3% when six hospital deaths were excluded. The Child's grade was a good predictor for early and late morbidity and death, the 5-year survival rate of patients with Child's class A disease being 30%. Retrospective comparisons were conducted between the current patients and patients younger than 50 years old who had been operated on during the same period: resectability rate, 61.5% versus 57.8%; hospital mortality rate, 18.8% versus 11.6%; and 5-year survival rate, 24.3% versus 48.6%, respectively. CONCLUSIONS: These results seem to indicate that the treatment policy of hepatocellular carcinoma in the aged should be identical to that in young people.

Age Factors↗

Efficient precipitation and accurate quantitation of detergent-solubilized membrane proteins.

The protein assay method of I. Polacheck and E. Cabib (Anal. Biochem. 117, 311-314, 1981) has been modified to provide a general method for quantitating protein samples in the presence of detergents. Dilute detergent-solubilized membrane proteins, by using ribonucleic acid as a carrier, have been efficiently precipitated here by trichloroacetic acid (TCA) in the presence of sodium dodecyl sulfate (SDS). Washing the pellets once with TCA solution has removed most of the reagents present in the original sample. The washed sample could then be quantitated by the Lowry method (O. J. Lowry, N. J. Rosebrough, A. L. Farr, and R. J. Randall, J. Biol. Chem. 193, 265-275, 1951). This procedure could be used to assay protein solutions of a concentration as low as 5 micrograms/ml in the presence of the following reagents: Triton X-100, Triton X-114, Tween 20, N-octylglucoside, deoxycholate, cholate, Thesit, octanoyl-N-methylglucamide, isotridecylpoly (ethyleneglycoether)n, Nonidet P-40, glucose, methyl-D-glucopyranoside, methyl-D-mannopyranoside, N-acetyl-glucosamine, Mn2+, Ca2+, Mg2+, and many buffer reagents. Proteins solubilized from porcine brain myelin sheath and synaptic plasma membranes were quantitated by amino acid analysis and by the TCA/SDS precipitation method described here. The resultant protein concentrations were almost identical. The results have suggested this TCA/SDS precipitation method to be useful for quantitating dilute protein samples containing high concentrations of detergents and other reagents commonly employed in studying membrane proteins.

Animals↗

Fetal hemoglobin levels in sickle cell disease and normal individuals are partially controlled by an X-linked gene located at Xp22.2.

Fetal hemoglobin (Hb F) production in sickle cell (SS) disease and in normal individuals varies over a 20-fold range and is under genetic control. Previous studies suggested that variant Hb F levels might be controlled by genetic loci separate from the beta-globin complex on chromosome 11. Using microscopic radial immunodiffusion and flow cytometric immunofluorescent assays to determine the percentage of F reticulocytes and F cells in SS and nonanemic individuals, we observed that F-cell levels were significantly higher in nonanemic females than males (mean +/- SD, 3.8% +/- 3.2% v 2.7% +/- 2.3%). F-cell production as determined by F reticulocyte levels in SS females was also higher than in SS males (17% +/- 10% v 13% +/- 8%). We tested the hypothesis that F-cell production in both normal and anemic SS individuals was controlled by an X-linked locus with two alleles, high (H) and low (L). Using an algorithm to determine the 99.8% confidence interval of a normal distribution in nonanemic individuals, we estimated that males and females with at least one H allele had greater than 3.3% F cells. Comparisons of male-male or female-female SS sib pairs with discordant F reticulocyte levels distinguished two phenotypes in SS males (L, less than 12%; H, greater than 12%) and three phenotypes in SS females (LL, less than 12%; HL, 12% to 24%, HH greater than 24%). Linkage analysis using polymorphic restriction sites along the X chromosome in eight SS and one AA family localized the F-cell production (FCP) locus to Xp22.2, with a maximum lod score (logarithm of odds of linkage v independent assortment) of 4.6 at a recombination fraction of 0.04.

Adult↗

Xenotransplantation of alpha-fetoprotein-producing gastric cancers into nude mice. Characteristics and responses to chemotherapy.

Three human alpha-fetoprotein (AFP)-producing gastric cancers (AFPGC) were xenotransplanted into the lateral abdominal wall of nude mice. Two tumors were established and passed over ten generations. These tumors retained their ability to secrete AFP and their characteristic hepatoid features microscopically. Serum levels of AFP in the mice were elevated as the tumors grew. Through serial transplantation, the degree of differentiation was not altered. Neither local invasion nor distant metastasis were encountered during the observation periods. Both strains had an aneuploid pattern of DNA by flow cytometric examinations. The responses of these tumors to five chemotherapeutic agents were investigated using various doses. The high AFP-titer strain (AFPGC-2) showed a marked regression or suppression of tumor growth after administration of both mitomycin C (MMC) and cisplatin (CDDP). The low-titer strain (AFPGC-1) had substantial sensitivity only to MMC. The growth of both tumors was not suppressed by 5-fluorouracil, doxorubicin, or epirubicin. These findings suggest that the characteristics of AFPGC are preserved in the xenograft model of nude mice. In addition, MMC and CDDP may be active to some extent against this rare, but highly malignant cancer.

Animals↗

Comparison between diploid and aneuploid hepatocellular carcinomas: a flow cytometric study.

Nuclear DNA content of hepatocellular carcinoma (HCC) was estimated by flow cytometry after hepatic resection in 91 patients during the past 5 years. There were 53 diploid and 38 aneuploid tumours. Clinicopathological features were compared retrospectively between the patients with diploid and those with aneuploid HCC. DNA ploidy did not show any correlation with age, sex, alcohol abuse, hepatitis B virus, serum alpha-fetoprotein level or underlying liver disease. Histopathologically, the incidence of HCC less than 2 cm in diameter tended to be higher in the diploid group but no difference was seen for large tumours (greater than 5 cm). The grade of tumour differentiation also tended to be higher in this group of small HCC. The ploidy pattern did not influence the rate of capsule or daughter nodule formation, or venous invasion. There were no significant differences in survival rate or in the incidence and time of intrahepatic tumour recurrence between the two groups. This study may indicate that nuclear DNA ploidy is not a particularly predictive factor for the surgical treatment of HCC.

Aneuploidy↗

Chlorophyll a/b-binding protein genes are differentially expressed during soybean development.

The levels of chlorophyll a/b-binding protein (Cab) gene polysomal poly(A)+ mRNA were quantitated throughout the development of Glycine max L. Cab mRNAs were abundant in young expanding leaves, representing 6.1% of the leaf mRNA population. Lower Cab mRNA levels were present in embryos, stems, and cotyledons of developing seedlings; the lowest levels were found in roots where they accounted for 0.04% of the polysomal poly(A)+ mRNA of this organ. To determine the contribution of different members of the Cab gene family to the Cab mRNA populations, a quantitative S1 nuclease reconstruction assay was developed. Cab3, Cab4, and Cab5 mRNAs were detected in all stages examined during soybean development but their levels underwent differential changes. Cab3 encodes the most abundant Cab mRNA in young leaves, developing embryos, and in Stage VII cotyledons from the developing soybean seedling. The levels of Cab mRNAs were compared to the levels of ribulose-1,5-bisphosphate carboxylase small subunit gene mRNA and differences in their patterns of accumulation were noted. Collectively these data indicate that during soybean embryogenesis developmental control mechanisms supersede light-regulatory signals.

Cloning, Molecular↗

Characterization of L-glutamate and kainate binding sites in the brain of a freshwater fish, Telapilia monsanbica.

[3H]Kainate and L-[3H]glutamate binding sites in a rich source of kainate binding sites, fish brain, have been thoroughly analysed here for the purpose of studying the correlation between kainate binding sites and L-glutamate receptors in vertebrate CNS. The brain of a freshwater fish, Telapilia monsanbica, was found to contain three types of kainate binding sites: Type 1 sites (Kd = 1050 +/- 380 microM, Bmax = 4 +/- 4 pmol/mg), Type 2 sites (Kd = 133 +/- 20 nM, Bmax = 190 +/- 20 pmol/mg), and Type 3 sites (Kd = 23 +/- 15 nM, Bmax = 28 +/- 19 pmol/mg). The dissociation constants of L-glutamate to Type 1, 2 and 3 sites were, respectively, 0.28 +/- 0.04, 5.5 +/- 0.2 and 137 +/- 28 microM. Pharmacological characterization of these binding sites showed that Type 1 and 2 sites, respectively, corresponded to N-methyl-D-aspartate-subtype L-glutamate receptors and non-N-methyl-D-aspartate L-glutamate receptors. Autoradiographic studies showed that Type 1 and 2 sites were distributed widely in fish brain, indicating the involvement of L-glutamate receptors in various brain functions. Type 3 sites, on the other hand, were relatively insensitive to most endogenous amino acids and were only found in the molecular layer of cerebellum and torus longitudinalis. Type 3 sites possibly representing a distinctive class of receptor has been suggested by the results.

Animals↗

DNA ploidy pattern in synchronous and metachronous hepatocellular carcinomas.

DNA ploidy of hepatocellular carcinoma (HCC) was studied in 28 patients using a flow cytometric method. Fourteen patients had two HCCs synchronously, and the remaining 14 had tumor recurrence in the remnant liver 3-41 months after curative resection of primary HCCs. DNA ploidy pattern and histopathologic parameters were compared between the synchronous and metachronous HCCs. Among those with synchronous HCCs, both tumors were diploid in 7 cases and aneuploid in 2 instances. Five patients had HCCs of different DNA ploidy pattern. On the other hand, 5 of 14 patients with metachronous HCCs had a consistent DNA ploidy between primary and recurrent tumors. In 4 cases, the first tumor was diploid whereas the recurrent HCC was aneuploid or tetraploid. In the remaining 5 cases, the primary HCC was aneuploid, but the recurrent tumor was diploid. Assuming that the difference in DNA ploidy pattern indicates a different clonal origin, the current results indicate that at least 36% of synchronous HCCs and 64% of recurrent HCCs develop in a multicentric fashion.

Adult↗

Comparison between the clinicopathologic features of AFP-positive and AFP-negative gastric cancers.

We compared 27 cases of alpha-fetoprotein (AFP)-positive gastric cancer with 478 cases of AFP-negative gastric cancer in our department. The incidences of AFP-positive gastric cancer were 5.4% (27/505), 7.2% (23/218), and 2.1% (4/187) for overall, advanced, and early cases of gastric cancer, respectively. Sex, age distribution, pathologic type, and serum carcinoembryonic antigen levels were similar between these two groups. Borrmann III type cancer, lymph node metastasis, lymphatic and venous microinvasion of the gastric wall, and incidence of synchronous and metachronous liver metastasis occurred more often in the AFP-positive group. It was suspected that the character of early venous invasion contributed to the high incidence of liver metastasis. Liver metastasis occurred in 72% of AFP-positive patients, all of whom died within 2 yr. Long-term survival of the AFP-positive group was worse than that of the negative group. The 1-, 3-, 5-, and 7-yr survival rates of both groups were 38.7%, 11.6%, 11.6%, 11.6%, and 71.3%, 57.8%, 52.8%, 49.6%, respectively (p less than 0.001).

Female↗

Long-term results after modified distal splenorenal shunt with expanded PTFE interposition.

Forty consecutive patients with esophagogastric varices underwent a modified distal splenorenal shunt with expanded polytetrafluoroethylene (PTFE) interposition and were followed up for 12 to 66 months (mean 44.7). The operations were urgent in 9, elective in 14, and prophylactic in 17 patients. There were 24 males and 16 females. Age ranged from 32 to 76 years with an average of 53.8. The causes of portal hypertension were liver cirrhosis in 32, chronic hepatitis in 4, idiopathic portal hypertension in 3, and primary biliary cirrhosis in 1. Twenty-six patients were in Child's class A, 6 in class B, and 8 in class C. The operative death rate within 1 month was 2.5% and the overall in-hospital mortality rate was 5%. The shunt patency rate was 97.2% at early and 100% at late examinations. Only one patient (2.5%) had upper gastrointestinal bleeding. Hepatic encephalopathy was seen in 8 (20.5%) of 39 surviving patients. Six patients died of liver failure and another six died from various causes during the follow-up period. Twenty-six patients (65%) are alive at present. The 1-, 3-, and 5-year cumulative survival rates were 87.4%, 73.3% and 48.8%, respectively. The current modified shunt can be carried out more safely and easily and yield a similar result to that with the original Warren shunt. In order to avoid hepatic encephalopathy and liver failure, however, it is not wise to persist in this procedure.

Adult↗

Progesterone receptor in hepatocellular carcinoma. Correlation with androgen and estrogen receptors.

Progesterone receptors (PgR), estrogen receptors (ER), and androgen receptors (AR) were assayed consecutively for hepatocellular carcinoma (HCC) that was surgically removed from 19 men and three women. The methods of receptor assay were the enzyme immunoassay (EIA) for PgR and the dextran-coated charcoal (DCC) technique for ER and AR. The patients ranged in age from 32 to 77 years (average, 60.3 years). No patients had received any specific anti-cancer therapy before tissue collection. All patients but one had underlying liver disease: cirrhosis in 13 and chronic hepatitis in eight. The positive rate of each receptor was 18% for PgR, 48% for ER, and 82% for AR. The titer was highest for AR, intermediate for ER, and lowest for PgR. The titers of PgR in four PgR-positive patients ranged from only 1.1 to 3.0 fmol/mg of protein. There was no relationship between PgR, ER, and AR in terms of positivity and titer. Also, other clinical and histopathologic data did not influence the positivity or concentration of these three sex hormone receptors. It can be concluded that no or little PgR exists in the cytosol of untreated HCC.

Adult↗