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Biomedical subjects

W C Shyu

Publications and source records attributed to W C Shyu.

95 records · Page 6Linked to original sources

HLA class I antigen display on hepatocyte membrane in chronic hepatitis B virus infection: its role in the pathogenesis of chronic type B hepatitis.

It has been suggested that cytotoxic T cells are involved in the recognition and lysis of the infected hepatocytes in chronic hepatitis B virus infection, and that the target antigen is probably HBcAg which is displayed on the hepatocyte membrane during active viral replication. However, studies in other viral infection have demonstrated that cytotoxic T cells recognize viral antigen on the infected cells only in the context of HLA class I antigens. To test whether this mechanism is also operative in chronic hepatitis B virus infection, we studied the expression of HLA class I antigens in livers from 35 patients with chronic hepatitis B virus infection by indirect immunofluorescence using monoclonal antibody against HLA class I antigens. The blocking effect of monoclonal antibody against HLA class I antigens on the in vitro T cell cytotoxicity to autologous hepatocytes was also studied. The results revealed that HLA class I antigen was undetectable on the hepatocyte membrane in all of 10 HBeAg-positive carriers with minor hepatitic activity, whereas it was demonstrated in 15 (88%) of the 17 HbeAg-positive patients with chronic active liver disease and in 7 (87%) of the 8 anti-HBe-positive "normal" carriers. The in vitro T cell cytotoxicity to autologous hepatocytes in six HBeAg-positive patients with chronic active liver disease was significantly inhibited by preincubation of hepatocytes with monoclonal antibody (10 to 40 micrograms per ml) against HLA class I antigen, but not by monoclonal antibody against HLA class II antigens and non-HLA-associated surface molecules (Leu 11).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Single dose and multiple dose pharmacokinetics of 2'-fluoro-2',3'-dideoxyadenosine and 2'-fluoro-2',3'-dideoxyinosine, anti-HIV agents, in rats.

A single and multiple dose pharmacokinetic (PK) study was conducted in rats following oral administration of 2'-fluoro-2',3'-dideoxyadenosine (FddA) and 2'-fluoro-2',3'-dideoxyinosine (FddI) at three dose levels. Six rats/gender were assigned to one of the three FddA or FddI dose levels: 40, 250, and 1000 mg/kg/day. Three rats/gender were assigned to the PK study on day 1, while the remaining 3 rats/gender were assigned to the PK study on day 14. The rats received the appropriate doses of either FddA or FddI orally by gavage once a day for 14 days. Serial blood samples up to 24 h and cumulative urine samples (0-24 h) were collected on both days 1 and 14. Plasma and urine samples were analyzed for the concentrations of intact FddA and/or FddI using a validated assay. The data were subjected to non-compartmental PK analyses. Over the dose range of 40-1000 mg/kg. both FddA and FddI exhibited dose dependent pharmacokinetics in rats. Following FddA administration, there was a rapid and extensive in vivo conversion of FddA to FddI; FddI was the major circulating moiety as reflected by Cmax and AUC values (generally 2-3-fold greater than those of FddA at each dose level) as well as the amount excreted (%UR) in the urine. In contrast, following FddI administration, Cmax, AUC, and %UR values were 2-5-fold lower as compared to the FddI generated from FddA administration at each dose level, which also suggested that FddI was not absorbed as extensively as FddA. Based on the findings of this study, FddA is an excellent prodrug of FddI.

Animals↗

Cost analyses of home care and nursing home services in the southern Taiwan area.

This study compares the cost of long-term care provided at patient homes with that of long-term care provided in nursing homes in southern Taiwan. Caring for a patient with a high degree of dependence at home is more expensive than caring for a patient in a nursing home facility when family costs and provider costs are considered together. This phenomenon is not demonstrated for patients with medium degrees of dependence. To be cost-effective, home care services should target patients with medium physical disability, and nursing home care should focus on patients with high levels of dependence.

Activities of Daily Living↗

Factors determining the attitudes of family caregivers of dementia patients toward nursing home placement in Taiwan: comparisons between urban and semiurban areas.

This study sought to determine the factors that influence the attitudes of family caregivers of dementia patients toward nursing home placement. A telephone survey of primary caregivers was conducted in two metropolitan areas of Taiwan. Caregivers of dementia patients were recruited from the neurology and psychiatry outpatient departments of two medical centers in Taipei (a highly urbanized area, n=144) and two medical centers in Kaohsiung (an area of mixed farm and nonfarm sectors, n=134). Family caregivers were asked if they would place patients in a nursing home if their dementia progressed. The mental status of dementia patients was the most significant variable affecting caregivers attitudes toward nursing home placement. Family manpower available for caregiving at home was especially emphasized as a determining factor affecting the decision to use nursing home care by primary caregivers in highly urbanized areas.

Aged↗

Absorption, disposition, and metabolism of [14C]didanosine in the beagle dog.

The absorption, disposition, and metabolism of didanosine were investigated in three adult male beagle dogs that received a single iv and po solution dose of 200 mg (ca. 20 mg/kg) of [14C]didanosine. The dog model was "humanized" by predosing with pentagastrin (6 micrograms/kg). The po dose was in buffer, as administered in man. The iv and po sessions were separated by 1 week. Plasma, urine, and feces were collected and assayed for total radioactivity; plasma and urine samples were also analyzed for intact didanosine using validated HPLC/UV assays. Metabolic profiles of [14C]didanosine were obtained in plasma and urine. After iv dose, 87% and 0.5% of the administered radioactivity were recovered in urine and feces within 6 days, respectively; the corresponding recoveries were 84% and 2.1% after po dose. Oral absorption of didanosine was rapid and complete; but due to first pass metabolism, the absolute bioavailability of didanosine was 44%. Mean renal clearance of didanosine (110 ml/min) accounted for about 43% of the total body clearance. The mean steady state volume of distribution of didanosine was 9.6 liters. The mean terminal half-life of didanosine was 0.8 hr after iv or po administration. Five putative metabolites, M1 (allantoin), M2, M3 (uric acid), M4 (hypoxanthine), and M5 (xanthine) of didanosine were observed in plasma and/or urine. The sum of the five metabolites plus unchanged drug accounted for virtually all of the radioactivity in plasma and urine. Allantoin represented the major metabolite in both plasma and urine. The extent of metabolism and the proportion of dose excreted as unchanged didanosine were markedly route dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗