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Biomedical subjects

C S Yang

Publications and source records attributed to C S Yang.

At least 343 records · Page 19Linked to original sources
PubMed1989

Modulation of cytochrome P450 isozymes in human liver, by ethanol and drug intake.

Cytochromes P450 (P450) are a family of isozymes which play an important role in xenobiotic metabolism. The concentration of three P450 isozymes, namely P450-IIE1(A1c),-IIIA(NF) and -IIC8-10(MP) has been measured in human liver biopsies of patients with different alcohol and drug intake status. All these three P450s were expressed in all subjects. Ethanol intake increased P450-IIE1(A1c) content with no effect on the content of the two other P450s. Drug intake (barbiturates) increased both P450-IIIA(NF) and -IIC8-10(MP) content without any effect on P450-IIE1(A1c). This paper brought, at protein level, further evidence of the importance of environmental conditions on P450 isozyme pattern, and therefore, on drug metabolizing capacity of human liver.

Adult↗
PubMed1989

A human-human hybridoma which produces antibodies to polioviruses.

A human-human hybridoma which produced antibodies to Sabin strain poliovirus types 3 and 2 was established. This hybridoma was constructed by fusing a HAT-sensitive variant of a human lymphoblastoid subline R4-4-6 with peripheral blood lymphocytes of a donor who had been previously immunized with poliovirus Sabin vaccines and had shown high titer of neutralizing antibodies against these viruses. This hybridoma had been cultured for more than one year and the neutralizing activities of the culture supernatants against poliovirus type 3 could still be detected. Cross neutralization with poliovirus type 2 was also observed. Karyotypic analyses of this hybrid showed that the chromosome numbers were distributed mainly between 80 and 100. Dot immunobinding assays also confirmed the reactivities of this hybridoma supernatants with poliovirus type 3 and, slightly, with type 2.

Antibodies, Monoclonal↗
PubMed1989

[Doppler flow velocity wave forms of the maternal uterine artery and fetal umbilical artery in normal pregnancy and pregnancy induced hypertension].

A simple non-invasive continuous-wave Doppler ultrasound system was used to record the flow velocity wave forms of the maternal uterine artery and the fetal umbilical artery in 113 normal pregnancies and 39 cases of PIH or essential hypertension complicating pregnancy. The systolic/diastolic (S/D) ratio of flow velocities was measured as an index of peripheral resistance. In normal pregnancy the umbilical artery velocity wave S/D ratio declined from 3.9 to 2.1 during the 20th to 40th week while the uterine artery S/D ratio remained constant between 1.8 to 1.9. After the 30th week, either an umbilical artery S/D ratio greater than or equal to 3, or uterine artery S/D ratio greater than 2.6 was defined as abnormal. In 32 PIH cases there were 9 with abnormal umbilical artery S/D ratio and 4 with abnormal uterine artery S/D ratio and the umbilical arterial change seemed to precede the uterine arterial. The rate of abnormal velocity wave forms in PIH was significantly higher than that in normal pregnancy. If both uterine and umbilical artery wave forms were abnormal the fetal outcome was usually poor. The results showed that the method is good for predicting the fetal outcome and once again supported the hypothesis that spasm of arterioles and venules in the placenta leading to high peripheral resistance especially in the fetal side may play an important role in the pathogenesis of PIH.

Adult↗
PubMed1989

Infection of human T-cell leukemia virus type I and development of human T-cell leukemia lymphoma in patients with hematologic neoplasms: a possible linkage to blood transfusion.

Among 354 adult patients with either hematological malignancy or aplastic anemia, eight were positive for anti-HTLV-I antibodies; six of eight had received multiple transfusions. There was an approximately 3.5-fold increase (P less than .001) of HTLV-I seropositivity in the patients with hematologic disease (8 of 354, 2.23%) compared to the healthy adults older than 20 years (34 of 5252, .65%). Two hematological patients, one with Hodgkin's disease and one with acute promyelocytic leukemia, were found to be positive for HTLV-I, and developed and died of adult T-cell leukemia/lymphoma (ATL) subsequently. Both were long-term survivors of the primary disease and had received multiple transfusions. The latent period from blood transfusion to onset of ATL was 6 months and 11 years, respectively. Immunocompromised patients, who were seropositive for HTLV-I, may be at increased risk for ATL compared to healthy carriers of HTLV-I, and the latent period may be shorter.

Antibodies, Viral↗
PubMed1989

Nutritional status in Linxian, China: effects of season and supplementation.

The ability of a supplement to counteract seasonal alterations in nutritional status for certain vitamins was studied in Linxian, an area in northern China with high rates of esophageal cancer. 150 subjects took one daily pill from April to August (16 weeks), whereas 50 subjects did not take any supplement. Deficiencies of ascorbic acid, riboflavin, folic acid, retinol and tocopherol were prevalent at the outset of the study. The changes in diet occurring between the end of the winter (April) and the start of the autumn vegetable harvest (August) were reflected in greatly improved ascorbic acid status and slightly improved riboflavin status. Plasma retinol, tocopherol, alpha-carotene and beta-carotene were little affected by season, whereas erythrocyte folate levels declined. The ascorbic acid, riboflavin, folate, retinol and tocopherol status of the supplemented subjects was significantly improved. After 16 weeks of supplementation, erythrocyte folate levels of subjects with esophageal dysplasia were improved but remained significantly lower than those of normal supplemented subjects, targeting folic acid as a nutrient of particular interest in this precancerous condition.

Anthropometry↗
PubMed1988

Human ethanol-inducible P450IIE1: complete gene sequence, promoter characterization, chromosome mapping, and cDNA-directed expression.

The human P450IIE1 gene, coding for an ethanol-inducible nitrosamine-metabolizing P-450, was isolated from a lambda EMBL3 genomic library and completely sequenced. The human gene spanned 11,413 base pairs and contained nine exons and a typical TATA box. Upstream and downstream DNAs of 2788 and 559 base pairs were also sequenced and compared to the rat gene. Significant areas of sequence similarity were observed within 140 base pairs upstream of the transcription start site in the rat and human genes. Human DNA 539 base pairs upstream of the transcription start site was inserted into the expression vector pSVOAL delta 5', and luciferase activity was detected when the constructs were introduced into a rat hepatoma cell line. The activity was over 100-fold lower than that of pRSVL, a Rous sarcoma virus LTR-driven luciferase gene. By use of panels of rodent-human cell hybrids, the gene was mapped to chromosome 10 (CYP2E locus). A full-length cDNA, constructed with the first exon of the genomic clone and a partial cDNA clone, was expressed in COS cells and found to code for N-nitrosodimethylamine demethylase activity.

Animals↗
PubMed1988

Effect of diallyl sulfide on rat liver microsomal nitrosamine metabolism and other monooxygenase activities.

It has been reported that p.o. administration of diallyl sulfide (DAS), a naturally occurring component of garlic (Allium sativum), inhibits 1,2-dimethylhydrazine-induced colon and liver cancer in rodents. A possible mechanism for this protective effect is inhibition of hepatic activation of the procarcinogen. The effect of DAS on P450IIE1, an isozyme of cytochrome P-450 which is active in the oxidative metabolism of dimethylhydrazine, was conveniently assayed in the present study by determination of N-dimethylnitrosamine demethylase (NDMAd) activity at 1 mM N-dimethylnitrosamine in Sprague-Dawley rat liver microsomal incubations. DAS was found to be a competitive inhibitor of NDMAd, in contrast to the irreversible inactivation of NDMAd produced by carbon tetrachloride incubated under similar conditions. The inhibition by DAS of the demethylation of several substrates was selective. The thioether was most potent against N-dimethylnitrosamine, less effective against N-nitrosomethylbenzylamine, and essentially ineffective against benzphetamine and ethylmorphine. Microsomes prepared at 3 h after DAS administration (200 mg/kg in corn oil intragastrically) showed moderate inhibition (less than 30% inhibition compared to control microsomes) of several demethylase activities; however, microsomes prepared 18 h posttreatment showed a marked decrease (about 80% inhibition compared to controls) in NDMAd activity, minor effects on other demethylase activities, and a 6-fold increase in pentoxyresorufin dealkylation. These trends at 18 h agreed with immunoblot analyses which showed suppression in the level of P450IIE1 and an elevation in P450IIB1. The selective inhibition of P450IIE1 activity and suppression of its level in microsomes may contribute to the reported chemoprotective effects of DAS.

Allyl Compounds↗
PubMed1988

Seroepidemiology of human T-cell lymphotropic virus type I infection in Taiwan.

The epidemiological characteristics of human T-cell lymphotropic virus type I infection in Taiwan have been explored by an island-wide community-based survey, which was carried out among residents in 19 townships and metropolitan precincts randomly selected through stratified sampling. Serum specimens of 7278 healthy subjects were screened by enzyme-linked immunosorbent assay and confirmed by Western blot method. A total of 103 subjects showed positive or weak reactions by enzyme-linked immunosorbent assay, but only 35 of them were confirmed to be positive by Western blot analysis. The anti-human T-cell lymphotropic virus type I antibody positive rate was 4.81/1000. The seropositive rate increased with age in both males and females, and females had a greater seropositive rate than males for all the age groups. Aborigines and Hakka Taiwanese had higher seropositive rates than Fukien Taiwanese and Mainland Chinese. Those people with lower educational levels were found to be associated with higher anti-human T-cell lymphotropic virus type I seropositive rates.

Adult↗
PubMed1988

Mechanism of induction of cytochrome P-450ac (P-450j) in chemically induced and spontaneously diabetic rats.

Previous studies demonstrated that a microsomal high-affinity N-nitrosodimethylamine demethylase activity and cytochrome P-450ac (an acetone/ethanol-inducible form) were induced by streptozotocin-induced diabetes in rats. In the present work, the induction was studied in detail in two chemically induced (by streptozotocin and alloxan) diabetic rat models and one spontaneously (BB/Wor) diabetic rat model. All the diabetic conditions caused increases in three parameters: (a) microsomal N-nitrosodimethylamine demethylase activity which is known to be a good indicator of the level of P-450ac; (b) the levels of P-450ac as determined by immunoblot analysis; and (c) the levels of mRNA of P-450ac as determined by hybridization assays with a cDNA probe for this enzyme. These increases were abolished by treatment of the diabetic rats with insulin. The results suggest that the pathophysiological condition of diabetes is responsible for the induction of P-450ac and elevation of mRNA is involved in all of the three diabetic models investigated.

Animals↗
PubMed1988

Metabolism of N-nitrosodialkylamines by human liver microsomes.

The metabolism of N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine, N-nitrosobenzylmethylamine, and N-nitrosobutylmethylamine was investigated in incubations with human liver microsomes. All of the 16 microsomal samples studied were able to oxidize NDMA to both formaldehyde and nitrite at NDMA concentrations as low as 0.2 mM; the rates of product formation of the samples ranged from 0.18 to 2.99 nmol formaldehyde/min/mg microsomal protein (median, 0.53 nmol). At a concentration of 0.2 mM NDMA, the rates of denitrosation (nitrite formation) were 5 to 10% (median, 6.3%) those of demethylation (formaldehyde formation); the ratio of denitrosation to demethylation increased with increases in NDMA concentration, in a similar manner to rat liver microsomes. Immunoblot analysis with antibodies prepared against rat P-450ac (an acetone-inducible form of cytochrome P-450) indicated that the P-450ac [P-450j (isoniazid-inducible form)] orthologue in human liver microsomes had a slightly higher molecular weight than rat P-450ac and the amounts of P-450ac orthologue in human liver microsomes were highly correlated with NDMA demethylase activities (r = 0.971; P less than 0.001). Analysis of four selected microsomal samples showed that human liver microsomes exhibited at least three apparent Km and corresponding Vmax values for NDMA demethylase. This result, suggesting the metabolism of NDMA by different P-450 enzymes, is similar to that obtained with rat liver microsomes, even though most of the human samples had lower activities than did the rat liver microsomes. The high affinity Km values of the four human samples ranged from 27 to 48 microM (median, 35 microM), which were similar to or slightly lower than those observed in rat liver microsomes, indicating that human liver microsomes are as efficient as rat liver microsomes in the metabolism of NDMA. The human liver microsomes also catalyzed the dealkylation and denitrosation of other nitrosamines examined. The rates of product formation and the ratios of denitrosation to dealkylation varied with the structures and concentrations of the substrates as well as with the microsomal samples tested. The results indicate that human liver microsomes are capable of metabolizing N-nitrosodialkylamines via the pathways that have been established with rat liver microsomes.

Cytochrome P-450 Enzyme System↗
PubMed1988

Disruption of sustentacular (Sertoli) cell tight junctions and regression of spermatogenesis in vitamin-A-deficient rats.

The relationship between the intactness of sustentacular (Sertoli) cell tight junctions and the status of spermatogenesis was examined in rats fed a vitamin-A-deficient diet after weaning (VAD rats). Both serum and testicular retinol concentrations of the VAD rats declined to a nadir by 80 days of age. At this time, it was observed that Sertoli cell tight junctions of the VAD animals were intact and complete spermatogenesis was maintained. Leakage in Sertoli cell tight junctions, as demonstrated by the presence of lanthanum in the adluminal compartment of the seminiferous epithelium, was first observed in 90-day-old VAD rats. Severe regression of spermatogenic cells was noted in 100-day or older VAD animals. These results suggest that severe germ cell loss observed during chronic vitamin A deficiency may result from abnormal intratubular environment due to the disruption of the blood-testis barrier.

Animals↗
PubMed1988

[Natural killer cell activity in nasopharyngeal carcinoma before and after radiotherapy].

From 1984 through 1986, a total of 20 patients with biopsy confirmed nasopharyngeal carcinoma (NPC) were randomly selected for studies on natural killer cell (NK) activity before and at the end of radiotherapy. Lymphocyte separation was done by centrifuge of heparinized peripheral blood with Ficoll-Hypaque and monocytes were removed by Petri dish adhesion. K562 cells were used as target cells of NK activity. The lymphocyte-target reaction of 4 hours was done and the ratio was 50:1, 25:1, and 12.5:1. The results of 50:1 was taken as the NK activity. The mean value of NK activity in NPC patients after radiotherapy was 43.0 +/- 21.1%, this is not significantly different from 41.2 +/- 23.6% before radiotherapy. On the other hand, before radiotherapy, the patients with too high NK activity (greater than 40%) or too low NK activity (less than 20%) had a mild tendency toward median value (20%-40%) after radiotherapy.

Female↗