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Biomedical subjects

A C Chan

Publications and source records attributed to A C Chan.

At least 235 records · Page 13Linked to original sources
PubMed1983

Modulation of platelet thromboxane and malonaldehyde by dietary vitamin E and linoleate.

Thromboxane (TXB2) and malonaldehyde (MDA) production by thrombin-stimulated washed platelet were evaluated in rats fed 6 combinations of dietary vitamin E (0, 100, 1000 ppm) and linoleate (6.5 and 17.0 en%) for 23 weeks. The molar ratio of MDA:TXB2 was consistently near 3 in all groups studied. In animals receiving the lower linoleate diets, TXB2 and MDA synthesis were inversely related to the dietary vitamin E concentrations and the levels of MDA and TXB2 were positively correlated (r = 0.99) with decreasing vitamin E in the diet. High dietary linoleate (17.0 en%), independent of vitamin E status, reduces TXB2 and MDA synthesis. The importance of dietary antioxidant on platelet prostanoid synthesis is discussed.

Animals↗
PubMed1983

Effect of dietary vitamin E on sulfolipid synthesis in rat submandibular salivary gland.

The effect of feeding diets containing various levels of vitamin E for 6 months on the in vitro synthesis of sulfolipids in rat submandibular salivary glands (SMG) was elucidated. The incorporation of [35S]sulfate into sulfolipid of SMG from rats on deficient or "normal" vitamin E diets was quite similar, however, the uptake was significantly increased in glands from rats on diets high in vitamin E. Whereas, in many instances, antioxidants can mimic the effect of vitamin E, in the present study, the antioxidant N,N'-diphenyl-p-phenylene diamine (DPPD) was actually found significantly to depress sulfolipid-labeling below that noted in SMG from all other diets. The results suggest that in the synthesis of SMG sulfolipid the action of vitamin E may be more than that of a simple antioxidant.

Animals↗
PubMed1983

Differential effects of megavitamin E on prostacyclin and thromboxane synthesis in streptozotocin-induced diabetic rats.

Diabetic subjects tend to develop microvascular complications believed to be due to platelet hyperaggregability. This increased platelet sensitivity is though to be the result of an imbalance of PGI2 and TXA2 production in diabetes. This study sought to determine whether megavitamin E supplementation could restore PGI2/TXA2 balance in streptozotocin-diabetic rats. Endogenous release of PGI2 by isolated aorta, determined via radioimmunoassay of its stable metabolite, 6-keto-PGF1 alpha, was significantly greater (P less than 0.05) in rats receiving 100x the normal vitamin E requirement than in untreated diabetic rats. PGI2 synthesis was negatively correlated with plasma glucose levels (r = -0.87, P less than 0.05) in non-fasted rats at sacrifice. Vitamin E supplementation, at both the 10x and the 100x level, significantly depressed (P less than 0.05) thrombin-stimulated synthesis of TXA2 in washed platelet. PGI2 and TXA2 production were expressed as a ratio. Megavitamin E therapy appears to increase this ratio over that seen in the diabetic animal. The data suggest that vitamin E, at high levels, exerts an ameliorating influence of the PGI2/TXA2 imbalance of diabetes.

Animals↗
PubMed1983

Identification and partial characterization of the secreted form of the fourth component of human complement: evidence that it is different from major plasma form.

Immunoprecipitation of human C4 from plasma followed by NaDodSO4/polyacrylamide gel electrophoresis under reducing conditions revealed the expected alpha, beta, and gamma chains as well as a smaller quantity of a molecule containing an alpha chain (p98) approximately equal to 5,000 daltons heavier than the normal alpha chain. Further studies on p98 indicated that it covalently incorporated methyl-amine, was present at a concentration of approximately equal to 8% of the principal plasma form of the C4 alpha chain, and was found in highly purified C4 preparations. Hep G2, a human hepatoma-derived cell line, was found to secrete a C4 molecule in which the alpha chain had a molecular weight identical to that of the p98 protein found in plasma. The secreted C4 molecule possessed hemolytic activity. The 5,000-dalton difference in the alpha chain was localized to the COOH terminus and was attributed to an additional polypeptide. We propose that p98 is the alpha chain of the secreted form of C4, which is processed extracellularly by proteolytic cleavage to the principal C4 molecule found in plasma.

Complement C4↗
PubMed1983

Differential effects of dietary vitamin E and antioxidants on eicosanoid synthesis in young rabbits.

This study was designed to evaluate the effects of dietary vitamin E and synthetic antioxidants on prostacyclin (PGI2) synthesis in isolated aorta segments and perfused hearts as well as thromboxane (TxA2) synthesis in thrombin-stimulated washed platelets. Weanling male New Zealand rabbits were fed a vitamin E-deficient basal diet or the basal diet supplemented with either all-rac-alpha-tocopherol acetate or propyl gallate or DPPD (N,N'-diphenyl-p-phenylenediamine). After 30 days on the diet, plasma tocopherol level, pyruvate kinase and liver microsomal NADPH oxidase were determined. DPPD but not propyl gallate prevented the development of myopathy. None of the synthetic antioxidants could substitute for vitamin E in decreasing enzymatic lipid peroxidation. PGI2 release by the aorta was lowered in vitamin E deficiency and was highest with DPPD supplementation. In the Langendorff perfused heart, however, PGI2 release was highest in the vitamin E-deficient group, possibly due to cardiomyopathy. TxA2 synthesis by washed platelets challenged with thrombin was independent of the antioxidant status of the animal. The data showed that dietary antioxidants selectively affect eicosanoid synthesis in different tissues.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Identification and structural characterization of two incompletely processed forms of the fourth component of human complement.

Immunoprecipitates of human C4 from EDTA-plasma were incubated with [14C]methylamine and analyzed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and fluorography. In addition to finding label in the alpha-chains of the secreted (C4s) and predominant plasma (C4p) forms of C4, two additional molecules with apparent molecular weights of approximately 168,000 (p168) and approximately 125,000 (p125) covalently incorporated methylamine, indicating the presence of an internal thioester bond. These two molecules were present at a concentration of approximately 5% of total plasma C4 and were not immunoprecipitated by antisera to C3 or alpha 2-macroglobulin. A human hepatoma-derived cell line (HepG2), in addition to synthesizing C4s and small quantities of the polypeptide precursor of C4 (pro-C4), was found to secrete p168 and p125 at concentrations of 14 +/- 4.8 and 21 +/- 9.2% (mean +/- SD), respectively, of total secreted C4. These molecules were not found intracellularly. Both molecules were present on reduced, but not nonreduced, SDS-polyacrylamide gels. Chido (C4B) and Rodgers' (C4A) alloantisera precipitated the C4A and C4B variants of pro-C4, p168, p125, and C4s. Both tryptic and Staphylococcus aureus V8 protease peptide analyses showed homology between p168 and the beta- and alpha-chains and between p125 and the alpha- and gamma-chains. Partial NH2-terminal sequencing revealed that the beta-chain was NH2-terminal in p168 and that the alpha-chain was NH2-terminal in p125. Taken together, these data indicate that p168 and p125 represent uncleaved beta-alpha- and alpha-gamma-fragments of pro-C4, respectively. Thus, in most individuals, plasma C4 consists of five structurally distinct molecules, the single polypeptide precursor (pro-C4), the three-subunit secreted (C4s) and predominant plasma (C4p) forms of C4, and two incompletely processed two-subunit molecules with uncleaved beta-alpha- (p168) or uncleaved alpha-gamma (p125)-subunits. In addition, all five molecules are observed for both C4A (Rodgers) and C4B (Chido) structural genes.

Amino Acid Sequence↗
PubMed1982

Biphasic modulation of platelet phospholipase A2 activity and platelet aggregation by mepacrine (quinacrine).

The modulation of rat platelet phospholipase A2 (phosphatide 2-acylhydrolase, EC 3.1.1.4) and rat platelet aggregation by mepacrine was investigated. The 2-acyl specificity of phospholipase A2 activity was confirmed by using 1-[14C]palmitoyl-2-[3H]arachidonylphosphatidylcholine as substrate. Under optimal pH, phospholipase A2 activity was not affected by aspirin but was inhibited by indomethacin. Contrary to previous reports, a biphasic modulatory role of mepacrine on phospholipase A2 activity and platelet aggregation was demonstrated. The data suggest that platelet aggregation is mediated via phospholipase A2.

Animals↗
PubMed1981

Decreased prostacyclin synthesis in vitamin E-deficient rabbit aorta.

Rabbit aorta predominantly synthesizes prostacyclin (PGI2), a potent inhibitor of platelet aggregation and a strong vasodilator. We report here the effect of vitamin E depletion and repletion on endogenous release of PGI2 by rabbit aorta. Serum pyruvate kinase was monitored for myopathy. The endogenous release of PGI2 by the aorta, detected as its stable metabolite 6-keto-PGF1 alpha, was inhibited by indomethacin and was inversely related to the size of aorta sections. Deficient aorta synthesized significantly less PGI2 than those from control animals. Repletion of deficient animals for 48 h completely restored the PGI2 release to a level comparable to the control values. The data showed that PGI2 synthesis by aorta can be influenced by dietary vitamin E.

6-Ketoprostaglandin F1 alpha↗
PubMed1980

The effects of vitamin E depletion and repletion on prostaglandin synthesis in semitendinosus muscle of young rabbits.

The effects of dietary vitamin E-depletion and repletion on the cyclooxygenase activity was studied in the semitendinosus muscle of rabbits. The prostaglandin (PG) cyclooxygenase system in rabbit semitendinosus muscle was characterized and found to depend on reduced glutathione and 1-epinephrine as cofactors. Skeletal muscle cyclooxygenase generates PGE2 and PGF2 alpha at a ratio approximately equal to one. Weanling New Zealand white rabbits were fed a vitamin E-deficient diet for 4 to 5 weeks. Controls received 50 mg dl-alpha-tocopherol acetate twice weekly. Vitamin E deficiency caused a significant reduction in cyclooxygenase activity but did not change the PGE2/PGF2 alpha ratio. Oral supplementation of tocopherol acetate promptly returned the cyclooxygenase activity back to the control values within 48 hours. The decreased cyclooxygenase activity explains in part the increased level of arachidonic acid in skeletal muscle phospholipid previously reported in this laboratory. The possible involvement of decreased prostaglandin endoperoxides with platelet aggregation in vitamin E deficiency is discussed.

Animals↗
PubMed1980

The effects of vitamin E depletion and repletion on prostaglandin dehydrogenase activity in tissues of young rabbits.

The key enzyme controlling prostaglandin (PG) catabolism, 15-hydroxyprostaglandin dehydrogenase (PGDH), was characterized in rabbit tissues. The apparent Michaelis constant (Km) using PGE2 as substrate was found to be 5.3, 4.0, 4.0 and 7.1 microM for semitendinosus and soleus muscles, heart and kidney, respectively. The effect of dietary vitamin E depletion and repletion on the PGDH activity in these tissues was studied. Vitamin E deficiency caused an elevation of PGDH activity in rabbit skeletal muscles but not in the heart and kidney. Oral supplementation of tocopherol acetate to the deficient animals did not affect the skeletal muscle PGDH activity. A long period of refeeding (30 days) was required to suppress the elevated PGDH level to the control values. The data indicates a higher turnover of the PGs in the vitamin E-deficient rabbit skeletal muscles. The significance of such a change in connection to prostaglandin metabolism is discussed.

Animals↗
PubMed1979

Elevated levels of a calcium-activated muscle protease in rapidly atrophying muscles from vitamin E-deficient rabbits.

A Ca2+-activated proteolytic enzyme that partially degrades myofibrils was isolated from hind limb muscles of normal rabbits and rabbits undergoing rapid muscle atrophy as a result of vitamin E deficiency. Extractable Ca2+-activated protease activity was 3.6 times higher in muscle tissue from vitamin E-deficient rabbits than from muscle tissue of control rabbits. Ultrastructural studies of muscle from vitamin E-deficient rabbits showed that the Z disk was the first myofibrillar structure to show degradative changes in atrophying muscle. Myofibrils prepared from muscles from vitamin E-deficient rabbits showed partial or complete loss of Z-disk density. Sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that the amount of troponin-T (37 000 daltons) and alpha-actinin (96 000 daltons) was reduced in myofibrils from atrophying muscle as compared to myofibrils prepared from control muscle. In vitro treatment of purified myofibrils with purified Ca2+-activated proteolytic enzyme produced alterations in myofibrillar ultrastructure that were identical to the initial alterations occurring in myofibrils from atrophying muscle (i.e. weakening and subsequent removal of Z disks). Additonally the electrophoretic banding pattern of Ca2+-activated proteolytic enzyme-treated myofibrils is very similar to that of myofibrils prepared from muscles atrophying as a result of nutritional vitamin E deficiency. The possible role of Ca2+-activated proteolytic enzyme in disassembly and degradation of the myofibril is discussed.

Animals↗
PubMed1978

Rehabilitating effect of vitamin E therapy on the ultrastructural changes in skeletal muscles of vitamin E-deficient rabbits.

Ultrastructural repair of the morphological damages produced in nutritional muscular dystrophy was studied by refeeding dystrophic rabbits with vitamin E. Weanling (1.2 kg body weight) rabbits were fed a vitamin E-deficient diet for 24 days. Half of this group was then sacrificed and the remainder was given an initial oral dose of 50 mg of DL-alpha-tocopherol acetate and a vitamin E supplemented diet for 28 days. Control animals were fed a vitamin E supplemented diet with 50 mg of DL-alpha-tocopherol acetate per kilogram of diet. Abnormalities of dystrophic muscles included streaming Z-disk, degenerated mitochondria, fragmented sacroplasmic reticulum and development and aggregation of myelin figures. The effect of vitamin E therapy resulted in significant repair of the dystrophic muscle. Small localized sections of rehabilitated muscle revealed abnormal mitochondria and residual myelin figures.

Animals↗
PubMed1977

Loss of DNA repair capacity during successive subcultures of primary rat fibroblasts.

Cultures of fibroblasts from newborn rats and successive subcultures of these cells were treated with 4-nitroquinoline-1-oxide to induce DNA repair. DNA from the cultures was examined by velocity sedimentation in alkaline sucrose gradients immediately after drug treatment and after a post-treatment incubation period of 3 h. Early passage cells were able to repair the damage that appeared as single strand breaks, however, by the seventh subculture this activity was not apparent. Measurements of repair synthesis showed a partial loss of this capacity with successive subculture. The results fit a model in which 4NQO causes two kinds of DNA modification, one of which is alkali labile and appears as a single-strand break. Both modifications are subject to excision repair, but each is recognized initially by a specific endonuclease. In the late passage cells, the endonuclease specific for the alkali labile modification is absent.

4-Nitroquinoline-1-oxide↗
PubMed1976

Modified Vi tests in the screening of typhoid carriers.

Two tests for the estimation of Vi antibody in sera were studied and their validity in the screening of typhoid carriers was assessed. One was a modified Vi haemagglutination test in which Vi-coated glutaraldehyde-fixed erythrocytes were used as the antigen and Vi antibody resistant to treatment with 2-mercaptoethanol was titrated. The other was a fluorescent Vi antibody test in which acetone-fixed bacterial Vi cells were used as the antigen and the total Vi antibody was titrated. In both tests, the antigens used were stable so that standardization of the tests would not be difficult. The modified Vi haemagglutination test was found equally sensitive but more specific in giving less false positives than the conventional Vi haemagglutination test. The fluorescent Vi antibody test was however found superior to both tests not only in giving less false positives but also in detecting more typhoid carriers.

Agglutination Tests↗
PubMed1976

Reduced DNA repair during differentiation of a myogenic cell line.

Repair synthesis induced by 4-nitroquinoline-1-oxide (4NQO) in L6 myoblasts before and after cellular fusion was measured by [3H] thymidine incorporation into unreplicated DNA. The level of repair synthesis was reuced after the cells had fused into myotubes. The terminal addition of radioactive nucleotides into DNA strands occurred only to a minor extent, and the dilution of [3H] thymidine by intracellular nucleotide pools was shown not to be responsible for the observed difference in repair synthesis, Both the initial rate and the overall incorporation of [3H] thymidine were found to be 50% lower in the myotubes. 4NQO treatment of myoblasts and myotubes induced modifications in the DNA which were observed as single-strand breaks during alkaline sucrose sedimentation. After the myoblasts were allowed a post-treatment incubation, most of the single-strand breaks were not longer apparent. In contrast, a post-treatment incubation of myotubes did not change the extent of single-strand breakage seen. Both myoblasts and myotubes were equally effective in repairing single-strand breaks induced by X radiation. It would appear that when myoblasts fuse, a repair enzyme activity is lost, probably an endonuclease that recognizes one of the 4 NQO modifications of DNA. The result observed is a partial loss of repair synthetic ability and a complete loss of ability to remove the modification that appears as a single-strand break in alkali.

4-Nitroquinoline-1-oxide↗