Search PubMed⌕ Search

Biomedical subjects

T Chen

Publications and source records attributed to T Chen.

At least 433 records · Page 24Linked to original sources
PubMed1976

Hepatic toxicity in the rhesus monkey treated with chenodeoxycholic acid for 6 months: biochemical and ultrastructural studies.

The long term administration of chenodeoxycholic acid in man has to be regarded with caution because chenodeoxycholic acid has caused liver damage in various species of animals, including primates. To study the effect of three doses of chenodeoxycholic acid (10, 40, and 100 mg per kg per day) on hepatic function and morphology, biliary bile acid composition and the reversibility of changes were investigated in 22 rhesus monkeys. After 6 months of treatment with 40 and 100 mg per kg per day, bile duct proliferation, portal tract inflammation and fibrosis, bile canalicular bleb formation, and hypertrophy of the smooth endoplasmic reticulum were associated with elevated serum levels of oxaloacetic transaminase, glutamic pyruvic transaminase, and leucine aminopeptidase. In the bile, the proportion of chenodeoxycholic acid and its bacterial metabolite, lithocholic acid, rose to approximately 85 and 10% of the total bile acids. After chenodeoxycholic acid was withdrawn for 3 months, the hepatic morphological lesions persisted in some animals although biliary bile acid composition returned to normal. No hepatic abnormalities were seen in the animals treated with 10 mg per kg per day. The findings suggest that long term treatment of rhesus monkeys with high doses of chenodeoxycholic acid results in severe hepatic histological lesions that can persist after discontinuation of the bile acid.

Alanine Transaminase↗
PubMed1975

Energy-dependent calcium sequestration activity in rat liver microsomes.

MgATP-dependent calcium sequestering activity of rat liver microsomes has been characterized. This activity is linear over a 90-min period and specifically requires MgATP. Substitution of CTP, UTP, GTP, or ADP will not support calcium uptake. Oxalate, which serves as a trapping agent in calcium uptake of skeletal muscle microsomes, is required to maintain net accumulation of calcium. The reaction is temperature-dependent and has an apparent Vmax of 11.2 nmol/mg of protein/min. The apparent Km for calcium is 23.2 muM calculated from total calcium concentration, and approximately 4.6 muM based on free calcium concentration, and apparent Km for ATP is 1.8 mM. Calcium uptake activity normally measured in presence of 100 mM KCl is only slightly depressed if 100 mM NaCl is substituted and is considerably depressed when 200 mM sucrose replaces KCl. An appropriate hydrolysis of ATP is associated with the calcium uptake. Separation of smooth and rough endoplasmic reticulum on sucrose gradients indicates a considerably lower specific activity per mg of protein in the fraction enriched with rough endoplasmic reticulum. Azide, at a level which completely inhibits liver mitochondrial calcium sequestration, has no effect on the liver microsomal system. Oligomycin, which inhibits ATP-dependent calcium uptake of liver mitochondria, has a considerably lesser effect on calcium uptake of liver microsomes. p-Chloromercuribenzoate and mersalyl inhibit the liver microsomal calcium pump at levels as low as 10- minus 7 M. Calcium uptake activity is considerably reduced in adult female rats. Weanling rats, both male and female, have calcium uptake activities like that of the adult males. Because of the higher activity in the male rat, the fatty acid composition of the liver microsomal phospholipids was analyzed. The male rat had a higher percentage of linoleic and palmitic acids in the microsomal phospholipids. Endoplasmic reticulum and plasma membrane are postulated to play a role in regulation of the levels of free cytoplasmic calcium in the mammalian liver.

Adenosine Triphosphate↗
PubMed1975

Toxicity of chenodeoxycholic acid in the rhesus monkey.

Chenodeoxycholic acid is an important drug for the treatment of cholesterol cholelithiasis in man. Although no toxicity has been demostrated in man, liver lesions develop in rhesus monkeys treated with chenodeoxycholic acid. To elucidate the mechanism of toxicity, chenodeoxycholic acid. To elucidate the mechanism of toxicity, chenodeoxycholic acid was fed daily to three groups of 6 animals each at the following dose: 10, 40, and 100 mg per kg; 2 separate animals were not treated and served as controls. After 1 month, the animals were killed. During the treatment period, most blood tests (e.g., blood count, blood urea nitrogen, albumin, SGOT, lactate dehydrogenase) remained within normal limits, but there was a significant dose-related increase in serum leucine aminopeptidase levels. The percentage of lithochlic acid, the 7-dehydroxylated bacterial metabolite of chenodeoxycholic acid, rose from 1% in the control animal to almost 14% in the 100 mg per kg-treated group. Liver biopsies obtained before treatment and at necropsy showed no significant changes. Thus, exposure of the liver to increased amounts of lithocholic acid during chenodeoxycholic acid treatment might result in elevation of serum leucine aminopeptidase activity.

Animals↗
PubMed1972

Somatic cell genetic assignment of peptidase C and the Rh linkage group to chromosome A-1 in man.

The segregation of the human peptidase-C phenotype in five different series of human-mouse hybrid clones was examined. The chromosome constitution of these hybrids was determined by quinacrine mustard fluorescence, Giemsa banding, and constitutive heterochromatin staining. That the clones could be classified without exception either as human peptidase C positive/ A-1 positive (14 clones), or as peptidase C negative/ A-1 negative (12 clones) indicates that peptidase C can be assigned to the human A-i chromosome. Data from an extensive series of human-mouse clones used provide support for the syntenic association between peptidase C and phosphoglucomutase-1 and by inference a linkage of both to Rh factor group.

Animals↗
PubMed1970

Mapping of a human genetic regulator element by somatic cell genetic analysis.

The ES-2 esterase is a kidney-associated esterase and is expressed in a cloned mouse renal adenocarcinoma cell line. Somatic cell hybridization of the mouse renal adenocarcinoma with either mouse or human fibroblasts leads to the marked reduction of ES-2 esterase titer. The extinction of ES-2 esterase activity in mousexhuman hybrids is reversible. Extinction correlates with the presence of the human C(10) chromosome in the somatic cell hybrids; whereas reexpression of the ES-2 esterase is observed in hybrids which have lost C(10). Thus, the proposed regulator element involved is probably structurally linked to C(10); however, linkage to a member of the D or G groups cannot be completely excluded.

Adenocarcinoma↗
PubMed1970

Controlled production of proliferating somatic cell hybrids.

The techniques described permit the controlled production of large numbers of proliferating somatic cell hybrids in a relatively short period of time. Sendai virus is used to promote cell hybridization. beta-propriolactone is employed as the inactivating agent of Sendai virus since it produces complete loss of viral infectivity while preserving viral fusion capacity. Cells are fused in monolayer, instead of in suspension, since fixing cells in two dimensions permits one to control cell contacts during the fusion event through the expedient of varying multiplicities of the parental cells and the total cell density. Under the conditions described, a several hundred fold increase in the number of hybrid clones obtained is seen as compared to the controls.

Adenocarcinoma↗