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Biomedical subjects

C Tong

Publications and source records attributed to C Tong.

90 records · Page 5Linked to original sources

Presence of anti-gamma-FA-reactive antigens in spontaneous and carcinogen-induced malignancies of experimental animals.

Immunochemical analysis of various tumors, representing 12 different tissue sites of origin, revealed a gamma-fetal antigen(gamma-FA)-like component in 17 of 23 malignant neoplasms of the mouse. This antigen was identified in extracts of spontaneous and carcinogen-induced murine tumors as well as in extracts of hepatic tumors initiated in the rat with diethylnitrosamine. The occurrence of gamma-FA in 75% of the malignant tumors examined and its presence in the sera of rodents bearing transplanted and primary cancers suggests an associative relationship of potential diagnostic value. This possibility is supported by the observation that immunoprecipitable gamma-FA appeared in the sera of hepatocarcinogen-treated rats several weeks prior to the detection of alpha-fetoprotein.

Animals↗

Differences between rat liver epithelial and fibroblast cells in metabolism of purines.

Epithelial and fibroblast cells from adult rat liver were found to differ markedly in their metabolism of the purine hypoxanthine. Both cell types took up hypoxanthine and possessed hypoxanthine-guanine phosphoribosyl transferase for phosphoribosylating the purine. However, in the transferase assay, lysates from epithelial cells converted hypoxanthine predominantly to inosine monophosphate, with small amounts of the nucleoside inosine as product, whereas fibroblast cell lysates converted hypoxanthine predominantly to inosine. The inosine appeared not to be produced by direct ribosylation of the base, since fibroblast cell lysates had less purine nucleoside phosphorylase activity than epithelial cell lysates. Rather, the inosine produced by fibroblast lysates appeared to be derived from inosine monophosphate through catabolism of the mononucleotide by 5' nucleotidase. An inhibitor of 5' nucleotidase, thymidine triphosphate, reduced the amount of inosine formed.

Adenosine Monophosphate↗

Definition of conditions for the detection of genotoxic chemicals in the adult rat-liver epithelial cell/hypoxanthine-guanine phosphoribosyl transferase (ARL/HGRPT) mutagenesis assay.

Conditions for the detection of genotoxic chemicals in the adult rat-liver epithelial cell/hypoxanthine-guanine phosphoribosyl transferase (ARL/HGPRT) mutagenesis assay have been defined. These included (1) a 3-day exposure to activation-dependent carcinogens; (2) a minimum of 14 days for induced mutant expression; (3) seeding density of 1 x 10(4) cells per cm2 for selection of mutants; (4) use of 6-thioguanine and (5) acceptance of genotoxicity of test chemicals if induced mutant incidence is significantly above that of the parallel run control and beyond the 98% confidence limits of the mean of the population spontaneous mutant incidence. With this protocol, the ARL/HGPRT mutagenesis assay has the capacity to activate representative members of the mycotoxin, aminoazo dye, aromatic amine and nitrosamine-types of carcinogens. This assay, offering additional metabolic parameters through intrinsic metabolic capability and providing a reliable end-point of clear biologic significance serves as a useful supplement to the Salmonella/microsome bacterial mutagenesis assay in a battery for the detection of genotoxic chemicals.

Animals↗

Cell cycle-specific mutagenesis at the hypoxanthine phosphoribosyltransferase locus in adult rat liver epithelial cells.

The cell cycle specificity of chemical mutagenesis was studied by use of two cell synchronization techniques, one a nontoxic technique involving serum deprivation and the other a double thymidine block, to obtain rat liver epithelial cells in different phases of the cell cycle to be exposed to chemical mutagens. For both methyl methanesulfonate and N-methyl-N'-nitro-N-nitrosoguanidine, there was a cell cycle specificity of chemical mutagenesis, with the most sensitive phase being the period of DNA synthesis.

Cell Cycle↗

5'-Nucleotidase activities in cultured rat liver epithelial and fibroblast cells.

Cell cultures of adult rat liver produced two distinct morphologic cell types: epithelial cells polygonal in shape and growing in nests of closely apposed cells, and fibroblast cells stellate in shape with little cell-cell contact at low density growth, but aligning in parallel arrays at high density. These two morphologic variants displayed dramatic differences in histochemically demonstrable 5'-nucleotidase activities. Fibroblast cells exhibited great activity throughout the cytoplasm with no concentration of activity in the cell membrane. The lesser activity in epithelial cells was concentrated on the cell membrane. The importance of this finding to the interpretation of data derived from experiments with whole liver homogenates is discussed.

Animals↗

Serum dopamine-beta-hydroxylase activity in schizophrenia.

On the basis of a report that serum DBH activity was significantly decreased in schizophrenics, we reexamined this relationship. Serum DBH activity was studied in 90 normal controls and 78 schizophrenics. No significant differences were found for the groups as a whole. The incidence of serum DBH activity below the median for normal controls was significantly less in chronic paranoid schizophrenics than in normal controls.

Antipsychotic Agents↗

Tissue distribution and biochemical properties of an interspecific tumour-associated gamma foetal antigen.

A late-gestation neonatal antigen (gamma foetal antigen; gamma-FA) immunologically and biochemically unrelated to murine alpha-foetoprotein, was identified in several spontaneous and carcinogen-induced sarcomas and hepatic carcinomas of the mouse and rat. An approximate mol. wt of 35,000 for gamma-FA from both foetus and tumour was obtained by molecular-sieve chromatography and sucrose-gradient centrifugation. Radial immunodiffusion analyses of organ extracts indicated that gamma-FA could be found in several neonatal tissues, the highest concentration occurring in the spleen. In the 2-month-old mouse, only splenic tissue contained gamma-FA and at much lower levels than in the organ of the newborn mouse.

Animals↗

Characterization of analog resistance and purine metabolism of adult rat-liver epithelial cell 8-azaguanine-resistant mutants.

Adult rat-liver epithelial cultures were sensitive to the lethal effects of 8-azaguanine (AG), but lines contained variants resistant to AG. The frequency of retrievable AG-resistant colonies varied with both the concentration of AG used and the seeding density of the population under selection. Cells resistant to AG were also cross-resistant to 6-thioguanine and unable to grow in medium containing hypoxanthine, aminopterin and thymidine. Resistance was stable. AG resistance was due to a deficiency of hypoxanthine-guanine phosphoribosyl transferase (HGPRTase) activity which was not caused by an inhibitor. In the assay for HGPRTase, a substantial amount of product appeared as inosine (In) in addition to inosine monophosphate (IMP). Purine nucleoside phosphorylase will generate In from hypoxanthine and, indeed, the cells did possess this activity. However, several findings indicated that the In was derived from IMP by catabolism by 5'-nucleotidase (NTase): (1) IMP decreased as In increased and (2) the inhibitors of NTase, adenosine monophosphate and thymidine triphosphate, reduced the generation of In by over 90% without inhibiting purine nucleoside phosphorylase. The cells possessed substantial NTase activity, 35% of which was located in the cytosol along with 69% of HGPRTase. Several lines of evidence suggested that the NTase activity limited the amount of 8-azaguanylic acid presented to the cells by catabolising the nucleotide and, thereby, reducing the toxicity of available AG.

Animals↗

Enhancement of mutagenesis during cell replication of cultured liver epithelial cells.

The susceptibility to mutagenesis of proliferating and non-proliferating mammalian cells was studied in cultured rat liver epithelial cells. Cells brought to growth quiescence by a non-toxic means were stimulated to proliferate and both types of cultures were exposed to methyl methanesulfonate (MMS). Cultures enriched in proliferating cells were more susceptible to both the toxic and mutagenic action of the mutagen than were quiescent cultures with a low level of proliferation.

Cell Cycle↗

Inhibition of growth of mouse ehrlich ascites by normal tissue extracts.

A dialyzable component from the aqueous extracts of mouse skeletal muscle and liver inhibited in vitro growth of a mouse Ehrlich ascites. A similar component was not detected in extracts of spleen, kidney, lung, skin, serum or small intestine. The muscle component appeared to be different from that of the liver in its resistance to heat and its stability in the culture medium. Both components however were stable on storage at 4, 23 and 37 degrees C for 72 h. Intraperitoneal injection of the muscle and liver component into mice previously innoculated with Ehrlich ascites significantly decreased tumor incidence in these animals as compared with the control.

Animals↗

Mitral valve replacement: mechanical versus bioprosthetic valves--a clinical review.

A review of the literature was conducted in an attempt to justify the exclusive use of either mechanical or tissue prostheses in the mitral position. In addition, the University of Toronto experience with mitral valve replacement was reviewed, including a five year follow-up from the Toronto General Hospital. Both studies concluded that there was no significant advantage for the use of either type of valve based upon freedom from thromboembolism, freedom from anticoagulant-related hemorrhage and freedom from all valve-related mortality/morbidity. Tissue valves were shown to be significantly poorer substitutes in terms of freedom from primary valve failure (P less than 0.05) and freedom from reoperation due to valve-related complications (P less than 0.07). The clinical results from the Toronto General Hospital correlated with those reported in the literature and suggested the preferential use of mechanical valves during mitral valve replacement based primarily on their durability and a consequent lesser need for reoperation.

Bioprosthesis↗