Biomedical subjects
S H Chan
Publications and source records attributed to S H Chan.
HLA and sexually transmitted diseases in prostitutes.
The HLA profile of 148 unrelated, Chinese prostitutes (56 with repeated gonococcal infection, 31 with syphilis, 31 with gonorrhoea and syphilis, and 30 with no evidence of infection) was compared with that of 238 unrelated, healthy, Chinese control subjects. The joint occurrence of AW19 B17 was observed in 25.8% of prostitutes with double infections compared with 6.7% of control subjects, while that of A11 B15, on the other hand, was associated with a resistance to syphilis and gonorrhoea. The latter profile was observed in 46.7% of prostitutes in business for more than two years who were resistant to disease, in 30% of prostitutes with an overall disease resistance, in 13.4% of control subjects, and in only 3.2% of prostitutes with combined syphilis and gonorrhoea. Because of the statistical uncertainty when multiple variables are being analysed these studies should be repeated in other groups of prostitutes of the same and different ethnic origins.
HLA antigens in three normal southern Chinese dialect groups--Cantonese, Hokkiens and Teochew.
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HLA and Chinese HBsAg carriers.
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Hepatitis B antigen in a dialysis unit: five years experience.
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A computer analysis of factors influencing the cerebello-thalamo-cortical signals.
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HLA and thyrotoxic periodic paralysis.
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Immunological studies on cytochrome c oxidase: arrangements of protein subunits in the solubilized and membrane-bound enzyme.
Seven protein subunits of cytochrome c oxidase from bovine heart were isolated by gel filtration in the presence of sodium dodecyl sulphate (subunits I, II and III) and guanidine hydrochloride (subunits V, VI and VII), and ion-exchange chromatography in 6 M urea (subunit IV) after the enzyme had been dissociated in 6 M guanidine hydrochloride. When analysed by highly cross-linked sodium dodecyl sulphate/polyacrylamide gel electrophoresis in the presence of urea, the apparent molecular weights were = I, 36700; II, 24300; III, 20400; IV, 17300; V, 12300; VI, 8700: and VII, 5100. Monospecific rabbit antisera were obtained against subunits I, IV, V, VI and VII and a mixture of subunits II and III. These subunit-specific antisera with the exception of anti-I serum all cross-reacted with the detergent-solubilized native oxidase. Enzymatic studies on purified oxidase indicated that immunoglobulins against subunits II + III, IV, V, VI and VII respectively caused 25, 65, 20, 30 and 25% inhibition while anti-I immunoglobulin did not inhibit the activity. The subunit-specific antisera were used to examine the arrangements of the subunits in the membrane. Enzymatic studies using bovine heart mitochondria and rat liver mitochondrial digitonin particles showed that anti-(II + III) serum, anti-V serum and anti-VII serum all inhibited the oxidase activity while the other antisera did not. On the other hand, results of using 125I-labelled immunoglobulins showed that anti-IV, anti-V and anti-VII sera were bound to the surface of inverted vesicles (matrix side) while all other antisera were not. These results indicate that cytochrome oxidase subunits II and III are situated on the outer surface, and subunit IV is exclusively on the matrix surface while subunits V and VII are exposed on both surfaces of the mitochondrial membrane. Subunits I and VI are buried within the membrane, not exposed on either side.
Structure and orientation of cytochrome c oxidase in crystalline membranes. Studies by electron microscopy and by labeling with subunit-specific antibodies.
The structure and the orientation of cytochrome c oxidase molecules in crystalline cytochrome c oxidase membranes (Vanderkooi, G., Senior, A.E., Capaldi, R.A., and Hayashi, H. (1972) Biochim. Biophys. Acta 274, 38-48) were studied by image analysis of electron micrographs and by reacting the crystalline preparations with immune gamma-globulins against individual cytochrome c oxidase subunits. Binding of gamma-globulins to the membranes was detected by the following two methods: (a) electrophoretic identification of gamma-globulin polypeptides in the washed membranes; (b) electron microscopic examination of the negatively stained membranes. The membranes bound immune gamma-globulins against subunit IV (which faces the matrix side in intact mitochondria) but failed to bind immune gamma-globulins against subunits II + III (which face the outer side of the inner membrane in intact mitochondria). In contrast, solubilized cytochrome c oxidase bound either of the two immune gamma-globulins. All cytochrome c oxidase molecules in the crystalline membranes are thus asymmetrically arranged so that subunit IV faces outward and subunits II + III face toward the interior. This orientation is opposite to that found with intact mitochondria. The data also suggest that the crystalline membranes form closed vesicles which are impermeable to externally added gamma-globulins.
Biosynthesis of mitochondrial membrane proteins: co-ordination with special reference to cytochrome c oxidase.
This paper reviews mechanisms by which the rate of synthesis of subunits of mitochondrial inner membrane protein complexes and the assembly of these subunits are co-ordinated. Current models are evaluated and critically discussed in the light of some recent evidences. The focus is on the incorporation of cytoplasmically-synthesized cytochrome c oxidase subunits in the development of a newer model, which introduces some twists into a combination of several current ideas. A mechanism which governs both organized assembly and the co-ordination of rates of polypeptide synthesis is illustrated and the principles of the model are applied to the elucidation of some odd features of certain mutants. The possibilities that mitochondrial ATPase and cytochrome c reductase may also be synthesized and assembled according to this model are discussed.
Mitochondrial ATPase activities of hepatoma BW7756 and ascites tumor cells. Influence of MG2+ ions, free fatty acids, and uncouplers.
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The participation of medullary reticular formation in clonidine-induced hypotension in rats.
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HLA and thyrotoxicosis (Graves' disease) in Chinese.
HLA locus A and B typing was performed on 86 Chinese thyrotoxicosis (Graves' Disease) patients and 238 normal Chinese subjects. The frequency of HLA-Bw46 (Sin 2) was found to be significantly higher among the patients than controls (x2 = 26.15, corrected P less than .003, relative risk = 3.74). The risk associated with Bw46 was reflected in the Bw46 heterozygotes. The relative risks of the joint occurrence of Bw46/B40 and Bw46/B13 were 8.74 and 5.88 respectively.
Uncoupling activity of endogenous free fatty acids in rat liver mitochondria.
Changes in the respiratory control index (RCI) and ADP:O ratio were found to be related to alterations in the free fatty acids levels of rat liver mitochondria aging in 0.25 M sucrose- Tris buffer at 0 degrees C. Free fatty acid levels increased with time after isolation of mitochondria while a concomitant decrease in the RCI and ADP:O ratio occurred. The changes in free fatty acid levels corresponded with the reported increasing levels of phospholipase A activity in aged mitochondrial preparations. Washing these mitochondria with sucrose buffer containing 1% defatted bovine serum albumin (BSA) counteracted the aging effect on the RCI (E.G., 2.5 to 3.5) and reduced the free fatty acid levels (e.g., 50 to 16 nmol/mg protein). This reversible phenomenon could be repeated several times during the in vitro aging at 0 degrees C. Use of 125I-iodinated BSA showed that approximately 5 microgram BSA/mg mitochondria was adsorbed by the mitochondrial membranes during washing. These results indicate a direct correlation between the level of endogenous fatty acids and the uncoupling of mitochondrial oxidative phosphorylation. The mechanism of counteracting the aging effect by BSA involves the removal of some of the free fatty acids.
General immunological status of nasopharyngeal carcinoma patients in Singapore.
Newly diagnosed NPC patients were found to have impaired general T-cell functions, as determined in vivo by the Mantoux test and in vitro by the PHA response assay. Treated remission patients were as hyporesponsiveness as newly diagnosed patients. PHA hyporesponsiveness was associated with the HLA profile of A2-B Sin 2 and with high antibody titres to EBV-related antigens, in particular to the early antigen. Impaired responses in the Mantoux or PHA tests were associated with poor survival. The impaired response could be partially or totally restored by in vitro treatment of the hyporesponsive lymphocytes with levamisole.
Familial primary hepatocellular carcinoma.
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Nasopharyngeal carcinoma and histocompatibility antigens.
New data are presented concerning the relationship between NPC and HLA antigens among Chinese. When attention is confined to newly diagnosed cases, it can be shown that, apart from the increased risk associated with the joint occurrence of A2 and B-Sin 2, there is also an increased risk associated with BW17 and a decrease in risk associated with A11. Among long-term survivors, however, BW17 is appreciably decreased, whereas A2 in the absence of B-Sin 2 or BW17 is increased. Among Malays, a non-Chinese group, there is an excess among NPC patients of a locus A blank, a blank which is probably associated with the AW19 complex.
Genetic components in susceptibility to nasopharyngeal carcinoma.
A series of blood samples from more than 200 histologically confirmed Chinese patients with NPC in Singapore were typed for 25 genetically controlled red-cell enzyme and five serum protein systems. A comparable number of patients suspected of having NPC but histologically negative and a series of healthy unrelated Chinese were typed for the same systems. The gene frequencies of NPC patients and controls differed by 4% or more in four of the 11 systems that showed variation; a further system, G6PD deficiency, also showed a significant difference between the two series but was excluded because of possible unreliability of the results from patients. Smaller differences existed in several other systems, including chromosome 6 markers closely linked to HLA. An analysis of differences within dialect groups showed a consistent effect for PGD, but for red-cell acid phosphatase there was a reversal of the difference between patients and controls among the Cantonese. These results need a larger series to confirm their validity. A breakdown of patients into those 30 years of age or older and those under 30 slightly enhanced the differences in gene frequencies. A multivariate analysis, using genetic distance statistics, showed a significant difference between NPC patients and controls, which is evident also when they are compared in the separate dialect groups. The histologically negative patients occupied an intermediate position. The study indicates that etiological factors resulting in clinically and histologically confirmed NPC operate on a genetically distinct subpopulation of Chinese in Singapore.