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Biomedical subjects

S H Chan

Publications and source records attributed to S H Chan.

At least 289 records · Page 16Linked to original sources

The effect of specific antibodies on oxygen uptake and H+ pumping by cytochrome c oxidase vesicles.

Antibodies to solubilized cytochrome c oxidase and to subunit III were incubated with liposomal oxidase. In oxygen uptake experiments, the inhibiting effects on RCI of anti-oxidase (primarily anti- subunits II and IV) and anti-III were by different mechanisms: the former, by inhibiting the uncoupled rate; the later, by stimulating the coupled rate. In experiments with H+ translocation, anti-oxidase was without effect, while anti-III was a potent inhibitor of proton pumping. These results are conclusive evidence for redox-linked proton extrusion from the vesicles by the oxidase (and its subunit III).

Antibodies↗

Correlated effects of clonidine on single-neuron activities in the gigantocellular reticular nucleus, arterial pressure and heart rate in the cat.

In chloralose-urethane anesthetized cats, intravenous administration of clonidine (10 micrograms/kg) promoted an increase in single-neuron discharges in the gigantocellular reticular nucleus that exhibited a degree and time-course parallel to the hypotension and bradycardia produced by the imidazoline compound. This observation was taken to be a positive indication that clonidine may pharmacologically activate (or disinhibit) neurons in this reticular nucleus, which in turn elicits vasodepression and cardioinhibition.

Animals↗

Epstein-Barr virus specific T-cell response in nasopharyngeal carcinoma patients.

There is a substantial body of evidence suggesting an association between Epstein-Barr virus (EBV) and undifferentiated nasopharyngeal carcinoma (NPC). The present study has compared a group of NPC patients (newly diagnosed and long-term survivors) and controls for EBV-specific T-cell immunity using the regression of transformation assay. Newly diagnosed patients (17 tested) when compared with either long-term survivors (20 tested) or controls (30 tested) showed a significant impairment in virus-specific T-cell immunity (p = 0.036, p = 0.043 respectively). Furthermore, donors with IgA antibody to EBV showed a significant depression in virus-specific T-cell immunity compared with donors without IgA antibody (19 IgA-positive, 48 IgA-negative; p = 0.0025). These results may be important in explaining the postulated role of EBV in the aetiology of NPC.

Antibodies, Neoplasm↗

HLA and nasopharyngeal carcinoma in Chinese--a further study.

This paper reports the results of 8 years of HLA typing of newly diagnosed nasopharyngeal carcinoma (NPC) patients among Chinese in Singapore, and compares the HLA profile of NPC cases with that of the normal Chinese population. Earlier results had indicated an association with A2 and BW46, but the heterogeneity of the earlier case series, which contained a proportion of long-term survivors, obscured other aspects of the relationship. In this paper, the risk associated with A2 (relative risk = 1.5) and BW46 (relative risk = 1.9) is confirmed, showing a much higher relative risk in the presence of both antigens, and a risk is also demonstrated for B17 (relative risk = 2.1). Relative risks of less than unity are observed for AII (relative risk = 0.5) and B13 (relative risk = 0.5). Data from family studies indicate the importance of the haplotype A2.BW46 in determining risk for NPC.

Adult↗

Qualitative analysis of intracellular characteristics of spontaneous neurons in the nucleus reticularis gigantocellularis of the cat.

The intracellular characteristics of spontaneous neurons in the nucleus reticularis gigantocellularis (NRGC) of cats were evaluated. Apart from an irregular pattern of spontaneous discharge, we demonstrated that out of 895 successfully impaled NRGC neurons, 744 had a relatively low transmembrane potential of -12 to -40 mV. Many reticular neurons manifested spontaneous pre-potentials and post-spike depolarizations, from which action potentials were observed to arise. It is discussed that the spontaneous nature of NRGC neuronal discharge may be the result of continuous presynaptic bombardments because of the special anatomic and physiologic features of the reticular formation. Alternatively, the NRGC neurons may possess pacemaker-like membrane properties.

Animals↗

Redox-dependent accessibility of subunit V of cytochrome oxidase. A novel use of ELISA as a probe of intact membranes.

Beef heart cytochrome c oxidase subunit V was isolated by a new one-step procedure. The product was homogeneous to 99% and immunogenically competent. The resulting antibodies inhibited the whole enzyme. A variation of ELISA (enzyme-linked immunosorbent assay) is described which, using a homogeneous antigen, probes the surface of intact membranes to a high degree of specificity. We showed that the subunit is accessible on the surface of inside-out mitochondrial inner membrane particles only when the particles were reduced with ascorbate and N,N,N',N'-tetramethyl-p-phenylene-diamine but is inaccessible on the surface of right-side-out particles regardless of the presence of reductants. These findings have implications with respect to the topography of the enzyme per se and in relation to its neighbors, and with respect to the degree of coupling between electron transport and proton pumping by the enzyme.

Animals↗

Adenine nucleotide transport in hepatoma mitochondria. Characterization of factors influencing the kinetics of ADP and ATP uptake.

Initial velocity measurements of [3H]ADP and [3H]ATP uptake have been made with mitochondria isolated from Morris hepatomas of differing growth rates, and factors known to influence the rates of nucleotide exchange have been examined in an effort to determine whether the elevated rates of aerobic glycolysis in these tumors can be attributed to altered carrier activity. These studies included the determination of the apparent kinetic constants for nucleotide uptake as a function of the mitochondrial energy state and the dependence of transport rates on temperature. Also included in these studies were measurements of the mitochondrial levels of endogenous inhibitors, divalent cations and internal adenine nucleotides. Results obtained showed that with mitochondria isolated from the various tumor lines, the apparent kinetic constants for nucleotide uptake are different from those of control rat or regenerating liver mitochondria; the apparent Vmax values for both ADP and ADP uptake are significantly lower. Furthermore, under conditions of a high-energy state, the Km and Vmax values for ATP uptake are greater than the Km and Vmax value for ADP uptake but that under uncoupled conditions, the opposite is observed. Comparison of the levels of mitochondrial Ca2+, Mg2+, long-chain acyl-CoA ester and adenine nucleotide from the various mitochondria showed that important differences exist between liver and hepatoma mitochondria in the levels of Ca2+, long-chain acyl-CoA ester and AMP. Mitochondrial Ca2+ levels are elevated 3-5--fold in all tumor lines, and for Morris 7777 hepatoma (a rapidly growing tumor) by a remarkable 70-fold; whereas the levels of acyl-CoA ester and AMP are significantly lower in the more rapidly growing tumors. Arrhenius plots for nucleotide uptake in mitochondria from liver and hepatoma are characterized as being biphasic, having similar activation energies above and below the break point temperature (28-38 and 6-16 kcal/mol, respectively). However, the transition temperature for mitochondria from the various hepatomas is uniformly 4-5 degrees C lower than mitochondria from control liver. The latter difference may reflect a variation in membrane composition, most probably lipid components. It is concluded that the presence of elevated levels of Ca2+ and lower levels of AMP in hepatoma mitochondria and difference of membrane compositions may play an important role in limiting adenine nucleotide transport activity in vivo and that the impaired carrier activity may contribute to higher rates of aerobic glycolysis observed in these tumors.

Acyl Coenzyme A↗

HLA system in Chinese children with insulin-dependent diabetes mellitus.

HLA in 12 unrelated Chinese paediatric patients with insulin dependent diabetes mellitus (IDDM) were found to have an increased frequency of BW22, B17 and AW33. BW22 was observed in 5/12 (41.7%) of IDDM patients compared to 40/330 normal unrelated Chinese controls (p less than 0.005, rr = 5.2). AW33 and B17 were observed in 6/12 (50.0%) and 7/12 (58.3%) of IDDM patients respectively, compared to 36/330 and 46/330 in the normal controls respectively (AW33: corrected p less than 0.0026, RR = 8.2, B17: corrected p less than 0.0026, rr = 8.6). HLA B8, B15 and B18 did not demonstrate any significant association with IDDM in this series of patients. The results of this study further emphasize the well recognized race specificity in HLA antigen distribution in normal population as well as disease states.

Child↗

HLA and skin disease in the Chinese.

The HLA associations in skin diseases among the Chinese were reviewed. Tuberculoid leprosy was associated with B17 (RR = 4.1). This HLA association was reinforced in the finding of excess HLA haplotype sharing among affected siblings in multiple case families. In psoriasis the associations were with A1, AW30 and B13. The relative risk associated with AW30, B13 was 16.1. In SLE, mild patients were associated with B13 (RR = 3.7) and severe patients with B17.

Asian People↗

Adenine nucleotide transport in hepatoma mitochondria and its correlation with hepatoma growth rates and tumor size.

Initial rates of [3H]adenosine diphosphate and [3H]adenosine triphosphate uptake were measured in mitochondria isolated from normal rat liver, regenerating liver, mouse hepatoma BW7756, and four Morris hepatomas (7777, 7800, 7794A, and 16) of varying degrees of malignancy. Results obtained demonstrate that (a) the apparent Km and Vmax values for adenosine diphosphate and adenosine triphosphate uptake are significantly lower in hepatoma compared to normal or regenerating liver mitochondria, (b) the Vmax values for adenosine diphosphate uptake correlate with tumor growth rate, and (c) the Km values for adenosine triphosphate in both hepatoma and normal mitochondria are lowered in the presence of added uncoupling agents; however, the extent of decrease is much less in fast-growing tumors than in slow-growing tumors and normal tissues. Studies examining the causes of reduced transport rates in hepatoma mitochondria showed that they are independent of the mitochondrial energy state and associated with substantially lower levels of the total and exchangeable adenine nucleotides. Additional studies revealed that transport rates are also dependent on the size of the tumor from which the mitochondria are isolated. Mitochondria isolated from small tumors (less than 2 g) had higher transport rates as well as higher levels of exchangeable and total adenine nucleotides than those isolated from larger tumors (4 to 6 g). Endogenous inhibitor levels also varied as a function of tumor size; free fatty acid levels increased, whereas acyl coenzyme A levels declined in mitochondria isolated from larger tumors. These results seem to indicate that, during the progression of tumor growth, mitochondria are experiencing cellular environmental changes that will affect overall tumor cell metabolism.

Adenosine Diphosphate↗