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Biomedical subjects

H T Cheung

Publications and source records attributed to H T Cheung.

At least 55 records · Page 3Linked to original sources
PubMed1984

A 1H n.m.r. study of the role of the glutamate moiety in the binding of methotrexate to Lactobacillus casei dihydrofolate reductase.

The binding of a series of amide derivatives of methotrexate to Lactobacillus casei dihydrofolate reductase has been studied by inhibition constant measurements and by 1H n.m.r. spectroscopy. Amide modification of the alpha-carboxylate of methotrexate was found to prevent interaction of the gamma-carboxylate with the imidazole of His 28. Estimates of the contributions to the binding energy from the alpha-carboxylate-Arg 57 and gamma-carboxylate-His 28 interactions have been made from a combination of inhibition and n.m.r. data.

Folic Acid Antagonists↗
PubMed1983

The metabolism and hormonal activity of some ring-C aromatic steroids.

The metabolism and steroid hormonal activity of the ring-C aromatic steroid 20 alpha,21-dihydroxy-17 beta-methyl-18-norpregna-4,8,11,13-tetraen-3-one (20 alpha,21-diol) was studied in rats and mice. The excretion of metabolites following intraperitoneal administration was monitored using tritium-labelled steroid. Of the total radioactivity, 15% was excreted in the urine after 2 days. Biliary excretion was rapid, with 80% of radioactivity collected over 12 h, while 67% was excreted in the faeces after 3 days. The metabolites isolated from bile and urine are conjugates, predominantly glucuronides, while only 5% of the dose was excreted as free unchanged steroid. The aglycones of the main metabolites from bile were identified as unchanged 20 alpha,21-diol and the two steroids 3 alpha,20 alpha,21-trihydroxy-17 beta-methyl-18-nor-5 alpha-pregna-8,11,13-triene and 3 beta, 20 alpha,21-trihydroxy-17 beta-methyl-18-nor-5 alpha-pregna-8,11,13-triene which resulted from reduction of the 4-ene-3-ketone system. Liver glycogen deposition, used as a measure of glucocorticoid activity, was induced in mice by 20 alpha,21-diol but not by its epimer the corresponding 20 beta,21-diol. Only the 20 alpha,21-diol was found to antagonise glycogen deposition when given simultaneously with cortisol. In adrenalectomised rats, the 20 alpha,21-diol produced a significant decrease in urinary Na+ excretion and increased K+ excretion. An equimolar dose of the 20 alpha,21-diol and deoxycorticosterone acetate gave a urinary excretion Na+/K+ ratio which reflected the combined mineralocorticoid effect of each steroid. The 20 beta, 21-diol produced no change in the urinary Na+/K+ ratio.

Animals↗
PubMed1983

Age-dependent changes in the cellularity and ultrastructure of the spleen of Fischer F344 rats.

The age-related changes in the cellularity (cells/gram of tissue) of the spleens and thymuses of Fischer F344 male rats were determined. A decline in the weight of the thymus with age was observed as previously reported by others. The decline was most drastic between 4 and 20 months of age. The spleen, however, increased in weight with age. The increase was almost linear between 4 and 30 months of age. Yet when the number of cells recovered from each organ as a function of age was determined, a decrease for both the thymus and the spleen was observed with increasing age. It was surprising to find that fewer cells were recovered from the spleens of old animals even though the weight of the spleen of the old animals was greater than the spleens from the younger animals. The ultrastructure of the splenic white pulp of rats ranging from 4 to 30 months of age was studied to determine the possible cause for the age-related decrease in cellularity of the spleen. The white pulp of the 4-month-old rats contained a large number of small lymphocytes, and the number of cells was found to decrease with increasing age. The 30-month-old animals had less than 20% the number of lymphocytes in the white pulp as the 4-month-old animals, and the white pulp exhibited an increased number of reticular cells and macrophages with enlarged cytoplasm. The decreased cellularity and increased structural disturbance might be significant in the age-related decline of spleen lymphocyte functions.

Aging↗
PubMed1983

Mechanism of the age-related decline in lymphocyte proliferation: role of IL-2 production and protein synthesis.

Although an age-related decline in mitogen-induced proliferation in spleen lymphocytes has been reported by numerous investigators, the molecular mechanism responsible is unknown. In this study, we compared the mitogen-induced proliferation, IL-2 production, and protein synthesis in spleen lymphocytes isolated from 4, 12, 20, and 30 month-old male Fischer F344 rats. IL-2 production by Con A-stimulated lymphocytes, as determined by the ability of the culture supernatants to support the growth of cultured T cells, declined over 72% between 4 and 30 months of age. This decline in IL-2 production paralleled a similar decrease in proliferation. Early protein synthesis by Con A-stimulated spleen lymphocytes was determined by measuring the incorporation of [3H]-valine into acid insoluble material, and this dropped 74% between 4 and 30 months of age. There was a strong correlation between the age-related decline in the three parameters tested. Based on these results, we propose that the age-related decline in protein synthesis may be the molecular basis for the similar decrease in IL-2 production and mitogenesis.

Aging↗
PubMed1982

Current concepts: I. The relationship between age-related changes in gene expression, protein turnover, and the responsiveness of an organism to stimuli.

A general decline in gene expression, translation and transcription, has been observed to occur with increasing age in a wide variety of organisms and tissues. Because the level of most enzymes and proteins remains relatively constant with increasing age, one would predict that the decline in gene expression would result in an age-related decline in protein turnover. Recent studies show that protein turnover in mouse liver and nematodes declines with increasing age. The decline in protein turnover could lead to an age-related decrease in the response of inducible enzymes to stimuli. This could explain the molecular basis for the decline in aging organisms to respond to a variety of environmental factors.

Aging↗
PubMed1982

Rat liver microsomal metabolites of 7-methylbenz[c]acridine.

The metabolism of the weak carcinogen 7-methylbenz[c]acridine (7MBAC) was examined in rat liver microsomes from 3-methylcholanthrene(MC)-induced animals by the use of mixed 14C- and 2H-labelled substrate. The three metabolites identified by spectroscopic and chromatographic examination were 7-OHMBAC and two dihydrodiols. The dihydrodiols were assigned structures consisted with attack on the 8,9- and 5,6- or K-region of the aromatic system.

Acridines↗
PubMed1980

Effects of nocodazole, a new synthetic microtubule inhibitor, on movement and spreading of mouse peritoneal macrophages.

Colchicine treatment enhances movement and suppresses spreading of mouse peritoneal macrophages. The effects of colchicine could result either from disruption or cytoplasmic microtubules or from other actions of colchicine on mammalian cell processes. Nocodazole is a new synthetic microtubule inhibitor that is structurally dissimilar to colchicine and is therefore unlikely to share with colchicine any common action besides of inhibition of microtubule assembly. Nocodazole was shown here to have activities similar to colchicine on macrophage migration and spreading. This supports the idea of a direct relationship between disruption of cytoplasmic microtubules and macrophage migration and spreading.

Animals↗
PubMed1979

Characteristics of a low-molecular-weight factor extracted from mouse tumors that affects in vitro properties of macrophages.

A dialysable low-molecular-weight factor capable of affecting in vitro properties of macrophages was extracted from four different mouse tumors. This factor not only modulates closely related properties of peritoneal macrophages such as spreading and migration but also inhibits lipopolysaccharde-induced tumoricidal activity of these cells. It can be extracted not only from tumor tissues but also from tumor cells grown in vitro. The appearance of this factor is unique to tumors and it is not present in detectable quantities in normal tissues. The factor from one of the tumors, Lewis lung carcinoma, was purified extensively and the partially purified factor retains all the above effects on macrophages. It is not sensitive to pronase or a mixture of bovine spleen phosphodiesterase II, E. coli alkaline phosphatase and pancreatic ribonuclease. The factor is lipid-like in character and it is soluble in both organic solvents and aqueous media. It has ionizable group(s) and is anionic at neutral pH but non-ionic under acidic conditions.

Alkaline Phosphatase↗
PubMed1979

Production of chemotactic activity in mixed leukocyte cultures: maximum effect caused by H-2I region disparity.

Primary mixed mouse leukocyte culture supernatants contain an activity chemotactic for mouse peritoneal exudate cells and it can be detected within 72 h after initiation of the culture. Disparity for H-21 region leads to maximum production of chemotactic activity whereas H-2K or H-2D region differences result in the production of significantly less activity. The rate of production of chemotactic activity follows closely the rate of incorporation of 3H-thymidine, and both attain the peak on day 4 after initiation of the culture. But whereas proliferation is sensitive to gamma-irradiation, chemotactic activity production is not. It is our hypothesis that proliferating cells are primarily responsible for the production of chemotactic activity. The possible relevance of chemotactic activity production to graft rejection is discussed.

Animals↗
PubMed1978

Effects of prostaglandins on the spreading, adhesion and migration of mouse peritoneal macrophages.

The effects of prostaglandins on the in vitro properties of mouse peritoneal macrophages namely spreading, adhesion and migration were investigated. PGE1 and PGE2 inhibit the spreading and adhesion of complete Freund's Adjuvant induced peritoneal macrophages significantly at concentrations of 1 ng per ml and above whereas they enhance the migration of these cells at concentrations of 100 ng per ml and above. PGA2 and PGB2 are less potent as they inhibit spreading and adhesion only at a concentration of 1 microgram per ml. At his concentration PGB2 enhances migration whereas PG2 has no effect. PGF 2alpha has no effect on the spreading, adhesion and migration of macrophages in the concentration range of 0.1 ng to 1,000 ng per ml.

Animals↗