Hepatitis B and C viruses in the development of hepatocellular carcinoma.
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Biomedical subjects
Publications and source records attributed to M W Yu.
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Serum samples of 9691 male adults had been collected and frozen for a prospective study of hepatocellular carcinoma in Taiwan. After an average follow-up period of 4.6 years, testosterone levels in the stored serum were measured by radioimmunoassay using commercial kits for 35 cases of newly developed hepatocellular carcinoma, 63 hepatitis B surface antigen-negative and 77 hepatitis B surface antigen-positive matched controls. Elevated testosterone levels were found to be associated with an increased risk of hepatocellular carcinoma. The association remained significant after the adjustment for effects of other hepatocellular carcinoma risk factors, including hepatitis B surface antigen carrier status, positivity of serum antibody to hepatitis C virus, cigarette smoking, alcohol drinking, past liver disease history, and dietary habits. The multivariate-adjusted relative risk of hepatocellular carcinoma for men with testosterone levels in the upper tertile was 4.1 (95% confidence interval = 1.3-13.2) compared with those having levels in the middle or lower tertiles (P = 0.016). The results consistent with those observed in animal experiments support the hypothesis that testosterone plays a role in the etiology of human hepatocellular carcinoma.
In order to examine perinatal mortality and prevalence of major congenital malformations in twins, deliveries in four teaching hospitals in Taipei City were studied. Among a total of 73,264 deliveries from October 1985 to June 1989, there were 844 pairs of twins. The zygosity of the twin pairs was determined by sex, placentation and 12 red blood cell antigens. There were 482 MZ and 252 DZ twin pairs identified, but the zygosity of a further 110 twin pairs was indeterminable due to lack of information on plancentation and/or blood types. A total of 4,573 singletons delivered in one study hospital from July 1986 to June 1987 were also studied as controls. The perinatal mortality rate was 7.5% for MZ twins, 1.4% for DZ twins, and 0.7% for singletons. The concordance rate of perinatal death was significantly higher in MZ (60%) than in DZ (0%) twins. The prevalence of major congenital malformations was 2.7% for MZ twins, 1.0% for DZ twins, and 0.6% for singletons. The concordance rate of major congenital malformations was 18% for MZ twins, but no DZ pair was concordant in any major congenital malformation. The concordance rate of facial clefts was 29% for MZ twins. There were 2 sets of conjoined twins giving a prevalence rate of 2.7 per 100,000 deliveries. These findings showing the prevalence of perinatal mortality and major congenital malformation to be highest in MZ twins, intermediate in DZ twins and lowest in singletons, suggest the importance of intrauterine environments in the determination of perinatal mortality and congenital malformations.
Delivery records of public hospitals and local health centers were analyzed to investigate the secular trend of multiple births from 1955 to 1990 in Taiwan. Twinning rates decreased gradually from the late 1950s to 1973, slightly increased and remained stable from 1974 to 1980, and then increased strikingly from 1981 to 1990. During the study period, MZ rates were consistently higher than DZ rates except in 1986 when a higher DZ rate was observed. The highest MZ rate of 7.7 per 1,000 deliveries was observed in 1985, while the highest DZ rate of 4.6 per 1,000 deliveries was observed in 1986. The triplet incidence rate also declined from the early 1960s to 1973 and then increased markedly from 1974 to 1990. A case-control study including 482 MZ and 252 DZ twin pairs and 1,496 singletons was carried out in four teaching hospitals in Taipei City between October 1985 and June 1989 to examine factors related to twinning. The zygosity of twin pairs was determined by sex, placentation and red blood cell antigens. Multiple logistic regression analysis showed that the higher the maternal age, the lower the MZ and DZ rates, while the higher the parity, the higher the rates. There was no association of paternal age or of maternal educational level with twinning rates.
This nonconcurrent cohort study was carried out to evaluate the association of neonatal jaundice with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and its interactions with other risk factors. The G-6-PD enzyme activity of 12,379 neonates was screened by a semi-quantitative fluorometric assay and double-checked by a quantitative method to identify a G-6-PD deficient cohort of 333 neonates. Matched with these on birth date, sex and delivery hospital were a G-6-PD normal cohort of 653 neonates. Neonatal jaundice was defined by a peak serum bilirubin (PSB) level of > or = 15 mg/dl. A significant association between G-6-PD deficiency and neonatal jaundice was observed in male but not female neonates. There was an inverse dose-response relation between G-6-PD activity and neonatal jaundice among male neonates. Both hypoxia/asphyxia and maternal hepatitis B surface antigen (HBsAg) carrier status were associated with an increased risk of neonatal jaundice among G-6-PD deficient but not G-6-PD normal male neonates. Based on multiple regression analyses, an additively synergistic effect on PSB level and severe jaundice (PSB > or = 20 mg/dl) was observed for G-6-PD deficiency and maternal HBsAg carrier status.
The output of progesterone, androstenedione, and estradiol-17 beta from the five largest preovulatory follicles (F1 to F5 in descending order) of 30 57-wk-old Single Comb White Leghorn hens killed 3 to 3.5 h prior to the next midsequence ovulation was measured by radioimmunoassay of incubation media. Follicles were incubated for 3 h at 39 C with different levels of bovine luteinizing hormone (bLH) (0, .125, .25, .5, 1.0, and 2.0 micrograms per follicle) in Medium 199 and HEPES (N-2-hydroxyethyl piperazine-N'-2-ethane sulfonic acid) (pH = 7.2). The amount of incubation media used was calculated in proportion to follicular size. In the absence of exogenous bLH, the average amount of progesterone produced in vitro by the F1 preovulatory follicle was 113 ng per follicle. In contrast, the average amount of progesterone produced by the F2 to F5 follicles combined was 3.75 ng. The output of androstenedione was highest (P less than .05) in F2, when compared with any of the other follicles in the hierarchy, including F1. The low secretion (less than 2.5 ng per follicle) of estradiol-17 beta from F1 to F5 follicles supports a previous conclusion that large follicles are probably not the major source of estradiol-17 beta in laying hens. The five largest follicles removed from hens killed shortly (less than 4 h) after an in vivo surge of LH were refractory to exogenous bLH stimulation. The amount of progesterone, androstenedione, and estradiol-17 beta obtained by the incubation of intact large follicles is consistent with published results obtained by the incubation of isolated follicular cells. Incubation of intact follicles provides a relatively simple, yet reliable, procedure for the measurement of steroidogenesis of avian large follicles.
Day-old male Hubbard broilers (960) were assigned to one of four treatments (two pens of 120 birds per treatment) to evaluate the effects of high (150 lx) versus low (5 lx) light intensity and constant 23 h light (L):1 h dark (D) versus increasing (6L:18D increasing 4 h/wk to 23L:1D) photoperiod in a 2 x 2 factorial arrangement of treatments. Birds were raised to 8 wk on a typical commercial four-diet program. Low-intensity birds were heavier than high-intensity birds from 2 to 8 wk (3.25% heavier at 8 wk). Birds raised under constant photoperiod were heavier than birds raised under increasing photoperiod from 2 to 5 wk and at 7 wk of age (1.71% heavier at 7 wk). High-intensity bird carcasses had lower percentage body fat, weight of fat, and higher percentage body protein at 8 wk compared with low-intensity bird carcasses (7.77, 10.76, and 1.77%, respectively). High-intensity birds had smaller abdominal fat pads (weight and percentage of body weight) at 8 wk compared with low-intensity birds (15.46 and 12.17%, respectively). Photoperiod did not affect body composition. Birds treated with increasing photoperiod had larger testes (weight and percentage of body weight) at 8 wk compared with birds under the constant photoperiod (29.36 and 30.51%, respectively). Birds treated under increasing photoperiod had higher plasma androgen concentrations at 7 wk compared with birds under constant photoperiod (testosterone, .270 versus .188 ng/mL; androstenedione, .632 versus .494 ng/mL).(ABSTRACT TRUNCATED AT 250 WORDS)
The influence of feed allowance on growth and carcass characteristics was investigated with female Indian River broiler breeders. Four feeding programs were imposed: FF, provided ad libitum access to feed throughout; FR, provided ad libitum access to feed from 0 to 18 wk of age and restricted thereafter; RF, provided ad libitum access to feed from 0 to 4 wk, restricted from 4 to 18 wk, and consumed feed ad libitum thereafter; RR, provided ad libitum access to feed from 0 to 4 wk of age and restricted thereafter. All birds received a starter diet (2,739 kcal ME/kg, 19.1% CP) from 0 to 3 wk of age, a grower diet (2,729 kcal ME/kg, 15.5% CP) from 3 to 22 wk of age, and a layer diet (2,889 kcal ME/kg, 14.6% CP) from 22 to 62 wk of age. Restricted feeding (limited amount, fed daily) was based on commercial BW guidelines. Feed restriction (37.2% of ad libitum intake) during rearing (4 to 18 wk) slowed growth. At 18 wk of age, restricted birds (RF, RR) had an average BW of 1.9 kg and a shank length of 9.2 cm compared with ad libitum-fed birds (FF, FR), which had an average BW of 4.2 kg and a shank length of 10.8 cm. Despite the large difference in BW, percentage carcass protein did not differ significantly between the two rearing treatments; however, percentage carcass fat was almost four times greater in ad libitum-fed than in feed-restricted birds. The growth deficit remained significant to 62 wk of age in RF birds compared with FF birds. During the prebreeding period (18 to 23 wk), feed intake of RF birds was 209% that of RR birds and 133% that of FF birds. At sexual maturity, the BW of RF birds was 3.6 kg, compared with 4.6, 4.5, and 2.6 kg for FF, FR, and RR birds, respectively. Stepwise regression indicated that BW was the most important (R2 = .363, P = .0001) among 11 variables in determining the number of large (greater than 10 mm) follicles in the ovaries of breeders at sexual maturity.
The influence of feed allowance during rearing (4 to 18 wk) and breeding (18 to 62 wk) on ovarian morphology and egg production was examined. During rearing, beginning at 4 wk of age, 400 Indian River pullets that had been full-fed from 1 day of age either continued to be full-fed (F, n = 200) or were feed restricted (R, n = 200), following commercial practice. At 18 wk of age, 100 birds (within +15% of the mean BW) in each of F and R rearing groups were further assigned to be full-fed (n = 50) or feed restricted (n = 50) during breeding. Thus, based on feed allowance during rearing and breeding, four treatment groups were formed (FF, FR, RF, and RR). Feed restriction during rearing significantly delayed oviduct development and age at sexual maturity (age at first egg). Compared with feed restriction during both rearing and breeding (RR), ad libitum feeding beginning at 18 wk of age (RF) significantly increased the weight of the ovary and the number of large follicles at sexual maturity but did not significantly affect the age at sexual maturity. Feed restriction during rearing, breeding, or both significantly reduced the incidence of erratic ovipositions, defective eggs, and multiple ovulations. The incidence of erratic ovipositions was positively correlated (r = .692, P less than or equal to .001) with the laying of soft-shelled and shell-less eggs and negatively correlated (r = -.508, P less than or equal to .001) with the production of settable eggs to 62 wk of age. Compared with ad libitum feeding, controlled feeding during breeding significantly improved both settable and total egg production. Among the four feeding regimens, Treatment RR resulted in the highest fertility and hatchability.
The influence of feed allowance during rearing (4 to 18 wk) and breeding (18 to 62 wk) on in vitro follicular steroidogenesis was examined. Four feeding programs were imposed: FF, consumed feed ad libitum throughout; FR, provided ad libitum access from 0 to 18 wk of age and restricted thereafter; RF, provided ad libitum access to feed from 0 to 4 wk, restricted from 4 to 18 wk, and consumed feed ad libitum thereafter; RR, consumed feed ad libitum from 0 to 4 wk of age and restricted thereafter. All birds received a starter diet (2,739 kcal ME/kg, 19.1% CP) from 0 to 3 wk of age, a grower diet (2,729 kcal ME/kg, 15.5% CP) from 3 to 22 wk of age, and a layer diet (2,889 kcal ME/kg, 14.6% CP) from 22 to 62 wk of age. Restricted feeding was based on commercial guidelines. At 33 wk of age, 10 to 12 (FF = 10, FR = 12, RF = 10, and RR = 11) birds from each feeding regimen were killed by cervical dislocation and the follicles removed for in vitro steroidogenesis. Feed allowance during breeding (18 to 62 wk) had a significant effect on in vitro follicular steroidogenesis at 33 wk of age. In broiler breeders fed ad libitum, some of the F2 (second largest) follicles had an endocrine profile characteristic of the F1 (largest) preovulatory follicles, secreting very little androstenedione and large amounts of progesterone. In feed-restricted birds, only the F1 follicles, which were destined to ovulate next, secreted any significant amount of progesterone into the culture media. Compared with restricted feeding, ad libitum feeding significantly increased the production of androstenedione in small white follicles (less than 1 mm).(ABSTRACT TRUNCATED AT 250 WORDS)
In order to assess the association between antibodies to hepatitis C virus (anti-HCV) and hepatocellular carcinoma (HCC), as well as the interaction of anti-HCV with other HCC risk factors in Taiwan, a total of 127 pairs of newly diagnosed HCC patients and healthy community controls were studied. Case-control pairs were individually matched for age (+/- 3 years), sex, residence, and ethnicity. Serum samples from study subjects were examined for anti-HCV by enzyme immunoassays as well as hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) by radioimmunoassays using commercial kits. The habits of cigarette smoking, alcohol drinking, and peanut consumption were obtained through standardized interviews according to a structured questionnaire. Both the anti-HCV as well as the carrier status of HBsAg and HBeAg were significantly associated with HCC showing a multivariate-adjusted odds ratio of 24.8 for carriers of HBsAg alone, 33.5 for carriers of both HBsAg and HBeAg, and 23.7 for those who were positive for anti-HCV. The population-attributable risk percentage was estimated as 3% for anti-HCV alone, 69% for HBsAg carrier status alone, and 6% for both anti-HCV and HBsAg in Taiwan. There were also synergistic effects on HCC development for anti-HCV with HBsAg carrier status, cigarette smoking, and habitual alcohol drinking.
Patients with uraemia have abnormal platelet function that may be partially corrected by haemodialysis, cryoprecipitate or 1-desamino-8-D-arginine vasopressin (DDAVP). We studied the platelet von Willebrand factor receptor, glycoprotein Ib (GPIb), and plasma von Willebrand factor (vWF) in uraemic patients undergoing chronic haemodialysis. Using the slope of agglutination of formalin-fixed platelets as an index of response to ristocetin (with a constant amount of normal plasma as a source of vWF), we found the response of platelets from uraemic patients, both before (2.7 +/- 1.5, n = 40) and after dialysis (1.2 +/- 1.2, n = 40) to be significantly less than that for normal controls (14.1 +/- 10.2, n = 20; P less than 0.001). In addition, the agglutination response of platelets obtained after dialysis was less than that of platelets obtained before dialysis (P less than 0.001). Immunoblotting demonstrated decreased or absent staining of glycocalicin, a subunit of GPIb, in platelet lysates from 25 patients. All platelet samples with reduced glycocalicin also had decreased responses to ristocetin. Tritium-labelled platelets from seven patients showed decreased labelling of a protein with an electrophoretic mobility equivalent to that of GPIb (140,000 daltons). In addition, platelets with the lowest levels of surface GPIb, as demonstrated by flow cytometry, also had decreased ristocetin agglutination and decreased staining on immunoblot. Levels of von Willebrand factor antigen and ristocetin cofactor in plasma from 10 patients were generally within the normal range, although postdialysis levels tended to be higher than pre-dialysis levels. The pre- and post-dialysis plasma vWF multimeric patterns were normal.
We constructed a recombinant plasmid that can express the entire pre-S2 sequence of hepatitis B surface antigen (HBsAg) as a fusion protein in E. coli. The hybrid protein, which comprises the bacterial TrpLE protein and the pre-S2 sequence, was the prominent protein that was found in cell extracts. As determined by immune blot analysis, this protein reacted with human HBV convalescent sera, as well as with sera from animals immunized with either purified HBsAg or isolated polypeptides containing pre-S2. It bound specifically to 125I-polymerized human albumin cross-linked with glutaraldehyde but not to 125I-monomeric human albumin. A novel adjuvant formulation was used in place of Freund's adjuvant to immunize guinea pigs with the recombinant product. The antisera obtained from serial bleedings were found to react with HBsAg of both d and y subtypes. These antisera were also shown to react solely with HBsAg polypeptides which contain of HBsAg to solid-phase polymerized the binding of HBsAg to solid-phase polymerized human albumin.
In order to examine the chronologic changes in genetic variance and heritability of anthropometric characteristics of Chinese infants in Taiwan, a total of 521 pairs of same-sexed twin neonates given birth in four major general teaching hospitals in Taipei City were studied. Based on the placental pattern and 12 red blood cell antigens, 428 MZ and 93 DZ twin pairs were identified and followed up to the age of one year. There was no significant genetic variance for all anthropometric characteristics adjusted for sex and gestational week before the age of six months. After adjusting for sex and gestational week, a significant genetic variance was observed at the age of six months, with heritability values of 0.51 (weight), 0.63 (head circumference), 0.77 (chest circumference), and 0.53 (arm circumference), as well as at one year, although with considerably lower heritability values. This implies that growth is dynamically determined by both genetic and environmental factors during infancy.
In order to examine the genetic variance and heritability of temperament among Chinese infants in Taiwan, a total of 62 pairs of same-sexed twin infants given birth in four major general teaching hospitals in Taipei City were studied. Based on placentation and 12 red blood cell antigens, 44 MZ and 18 DZ pairs were identified. Temperament was assessed at the age of six months by the Chinese edition of Carey's Temperament scale. Significant genetic variance was observed for activity level, approach or withdrawal, intensity of reaction, quality of mood, and threshold of responsiveness, with a heritability of 0.64, 0.56, 0.74, 0.39, and 0.45, respectively. There was no significant intrapair difference in temperamental characteristics between monochorionic and dichorionic MZ twins.
In order to examine the chronological changes in genetic variance and heritability of arterial systolic and diastolic blood pressure (SBP and DBP of Chinese infants in Taiwan, a total of 339 same-sexed twin neonates born in four major general teaching hospitals in Taipei City were studied. Based on placentation and 12 red blood cell antigens, 274 monozygotic (MZ) and 65 dizygotic (DZ) twin pairs were identified and followed up to the age of one year. Both SBP and DBP were measured by Doppler blood pressure monitor. Within-pair mean squares of SBP and DBP were consistently smaller in MZ than DZ twins at ages one month and over. The findings remained unchanged after the adjustment for the effects of age, sex, gestational age, placentation and physical state during blood pressure measurement. Falconer's heritability indices for adjusted SBP and DBP at ages two months and over ranged from 0.29 to 0.55 and from 0.27 to 0.45, respectively. The study indicates an important genetic influence on blood pressure during infancy.
In order to examine the genetic variance and heritability of serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides, a total of 349 pairs of same-sexed twin neonates born in four major general teaching hospitals in Taipei City were studied. Based on the placental pattern and 12 red blood cell antigens, 271 monozygotic (MZ) and 78 dizygotic (DZ) twin pairs were identified. There was a significant genetic variance for total cholesterol, HDL-C, LDL-C, and triglycerides both unadjusted and adjusted for sex, gestational age and placentation. The unadjusted heritability of total cholesterol, HDL-C, LDL-C, and triglycerides was 0.59, 0.30, 0.25 and 0.75, respectively; while the corresponding adjusted heritability was 0.74, 0.38, 0.31, and 0.49, respectively. Intrapair variance of serum lipids was not significantly different between monochorionic and dichorionic MZ twins.