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Biomedical subjects

S H Chan

Publications and source records attributed to S H Chan.

At least 235 records · Page 13Linked to original sources
PubMed1988

Effects of subunit V antibodies on the topology of the subunit and the activity of beef heart cytochrome-c oxidase.

Redox-sensitive epitopes on subunit V of beef heart cytochrome-c oxidase were demonstrated previously using polyclonal subunit-specific antibodies raised in rabbits. The antibodies only slightly inhibited electron transfer, and the accessibility of their epitopes depended on the presence of a membrane and on the redox state of the oxidase. The present paper describes additional preparations of antibodies raised against subunit V. These antibodies have an even higher subunit specificity, they are more than three times as inhibitory against electron transfer, and their binding does not require a membrane. Moreover, the redox-sensitive nature of their binding to detergent-dispersed oxidase is sensitive to the method of its isolation. We discuss inferences that can be drawn from a detailed quantitative comparison of the interactions of the two antibody preparations with the antigen in different environments. The techniques used in the comparison can be used to examine other perturbants of the oxidase as to their effects on specific segments of the enzyme.

Animals↗
PubMed1988

Antibodies as probes of cytochrome oxidase structure and function.

Antibodies have been raised in rabbits against whole beef heart cytochrome oxidase and against purified subunit V. Western blot analysis showed that antioxidase was largely composed of anti-II and anti-IV antibodies but some anti-I and antibodies against small subunits were elicited. Similar analysis of anti-V showed it to be relatively specific against subunit V. Three types of anti-V were identified by ELISA with intact enzyme: (i) weak binding and redox independent, (ii) stronger binding, redox-dependent (binding only to reduced or partially reduced enzyme), and membrane-independent, and (iii) moderate-binding, redox-dependent & membrane-dependent. Inhibition of enzyme activity by anti-oxidase was biphasic in time, indicating populations of rapidly- and slowly- reacting molecules. Variation of cytochrome c concentration showed partially competitive kinetics, but the antibody also affected 'internal' enzymatic events including the turnover rate with TMPD and the spin-state change in cytochrome a3 that follows reduction of cytochrome a. No spectral effects could however be seen. Antioxidase also inhibits proteoliposomal respiration with external cytochrome c but not that with internally-trapped cytochrome c. No functionally significant epitopes occur on the N (matrix) side of the membrane. The more strongly binding anti-V inhibits the isolated enzyme by at least 60%. The inhibition at high ionic strength induces a biphasic pattern with respect to cytochrome c concentration. Anti-V may thus slow the dissociation of cytochrome c from its complex with the enzyme. The redox-dependent, membrane-dependent anti-V (reported previously) gave only about 20% inhibition of the enzyme. The effective anti-V antibody had little if any influence on the activity of proteoliposomal oxidase in either orientation. Some sites on subunit V whose binding can give rise to inhibition are not accessible to anti-V when the enzyme is embedded in a functional membrane system.

Animals↗
PubMed1988

Immunology of renal transplantation in Singapore.

Renal transplantation is the best form of renal replacement therapy for patients suffering from endstage renal failure. While correcting the metabolic consequences of uremia, it is the only form of replacement therapy which permits full rehabilitation of the patient. However, the successful engraftment of a renal allograft is frequently limited by immunologically mediated graft loss which can be as high as 50% in the first year in cadaveric transplants. Since the beginning of the history of transplantation, various methods of modifying allograft rejection, both pretransplantation and posttransplantation have been studied. In this paper, we report the pretransplantation immunological factors that appear to modulate graft survival in renal transplantation in Singapore.

Blood Transfusion↗
PubMed1988

HLA and antibiotic allergic skin eruption.

Chinese patients with cutaneous eruption due to antibiotics were found to be positively associated with HLA-BW46 (RR = 2.5; 95% confidence limit 1.2-4.9) and negatively associated with HLA-B40 (RR = 0.46; 95% confidence limit 0.22-0.98). The association with HLA-BW46 was even higher in patients with ampicillin sensitivity (RR = 3.5; 95% confidence limit 1.4-9.0).

Anti-Bacterial Agents↗
PubMed1988

Subtype analysis of the hepatitis B surface antigen using monoclonal antibodies.

A series of monoclonal antibodies (mAb) were produced against the hepatitis B surface antigen (HBsAg) and their specificity tested against 2 separate panels of known HBsAg subtypes. Using an enzymeimmunoassay, mAbs that specifically bind to the 'a', 'd' and 'w' epitopes were identified. There were also a number of mAbs that expressed binding patterns that do not correspond to the standard serological classification--which is not unusual since the mAbs were of murine origin. These mAbs are at present being used to replace the conventional goat or guinea-pig derived HBsAg subtyping antisera which are available in limited quantities and often vary in titer.

Animals↗
PubMed1988

Monoclonal antibodies to blood group antigens.

To obtain haemagglutinating monoclonal antibodies as potential blood typing reagents 10 fusions were performed between mouse myeloma cells and spleen cells from mice immunised with either blood group substances or human red blood cells. Nineteen hybridomas with anti-A specificity and 10 with anti-B specificity were generated, Three were selected for further investigations. Some of these hybridoma clones produce and secrete both IgM and IgG.

ABO Blood-Group System↗
PubMed1987

Effects of bestatin on the central cardiovascular regulatory mechanisms in the rat.

We evaluated the effects of bestatin, the specific aminopeptidase-B and leucine aminopeptidase inhibitor, on the central cardiovascular regulatory mechanisms in Sprague-Dawley rats anesthetized with pentobarbital sodium (40 mg/kg, i.p.). Intracerebroventricular injection of bestatin (100 or 200 nmol/5 microliters) consistently elevated the basal systemic arterial pressure and heart rate. At the same time, this degradative enzyme blocker increased the sensitivity of the baroreceptor reflex responses as well as the efficacy of the modulatory actions of the medullary nucleus reticularis gigantocellularis on these reflexes. We speculate that enhancing the tonic activities of the endogenous neuropeptides in the brain by protecting them from their catabolic enzymes may affect the central cardiovascular regulatory machinery by modifying the operations of the baroreceptor feedback controls and their modulatory mechanisms.

Animals↗
PubMed1987

Interactions between guanabenz and clonidine in their antinociceptive effects in the rat.

Based on the hot-plate algesiometric assay in conscious Sprague-Dawley rats, we observed that both guanabenz and clonidine, at a subcutaneous dose of 5 and 1 mg/kg, respectively, exhibited significant antinociceptive potencies. Paradoxical actions on the hot-plate responses, however, were exerted by guanabenz at lower doses, varying from hyperalgesia (1 mg/kg) to no effect (2 mg/kg). A pretreatment of clonidine (1 mg/kg) substantially potentiated the antinociceptive efficacy of the two latter doses, but failed to further augment the pain-suppressive action of guanabenz at 5 mg/kg. These interactive effects of the two alpha-adrenoceptor agonists suggest that they may share a common mechanism(s) in their analgesic actions.

Analgesics↗
PubMed1987

A simple experimental index for the evaluation of inotropic responses.

The validity of the first derivative of systemic arterial pressure (SAdP/dt) as an indirect experimental index for the evaluation of inotropic responses was ascertained in rats anesthetized with pentobarbital sodium (40 mg/kg, i.p.), using the first derivative of left ventricular pressure (LVdP/dt) as the reference. We observed highly significant qualitative and quantitative (p less than 0.001) correlations between these two parameters, under five well-established experimental cardiovascular perturbations that are known to promote inotropic actions, viz, vagosympathetic trunk stimulation; intravenous administration of pentobarbital, epinephrine, or phenylephrine; and temporary common carotid artery occlusion. Preliminary experiments using isometric ventricular contraction as the reference also confirmed these observations. It is suggested that the SAdP/dt may qualify, at the systemic level, as an easily accessible experimental index for ventricular contractility.

Animals↗
PubMed1987

A cardioinhibitory area in the midbrain central tegmental field of cats.

A cardioinhibitory area in the central tegmental field of the midbrain (CIM) was studied in cats under chloralose-urethane anesthesia. Electrical and chemical (glutamate and DL-homocysteic acid) stimulations in this area produced marked bradycardia accompanied by mostly hypotension or minimal change in arterial pressure and by occasional hypertension particularly in the dorsal portion. CIM excitation potentiated the reflex bradycardia induced by IV phenylephrine, while bilateral electrolytic lesion of CIM neither changed the resting cardiovascular parameters nor the reflex bradycardia. The CIM bradycardia was not affected by supracollicular decerebration, but substantially reduced by unilateral vagotomy and completely eliminated by bilateral vagotomy. Destruction of the ambiguus nucleus (NA) and solitary and dorsal motor nuclei (NTS/DMV) abolished the bradycardia. Midline bisection at the midbrain-pontine level only slightly reduced the bradycardia while at the medullary level it was moderately attenuated. Electrolytic lesion of the cardioinhibitory area in gigantocellular reticular nucleus (GRN) abolished the bradycardia. These findings suggest that CIM is an independent mechanism which may send axons to GRN from which the axons may in turn synapse with the NTS/DMV complex and NA. Its final output may utilize both vagus nerves to modulate baroreceptor reflex in promoting bradycardia.

Animals↗
PubMed1986

Anatomic connections between nucleus reticularis rostroventrolateralis and some medullary cardiovascular sites in the rat.

Based on wheat germ agglutinin-conjugated horseradish peroxidase histochemistry in Sprague-Dawley rats, we identified a reciprocal and bilateral connection between the nucleus reticularis rostroventrolateralis (NRRVL) and the nucleus ambiguus. The rostral ventrolateral medulla also received bilateral inputs from the nucleus reticularis gigantocellularis (NRGC) and nucleus reticularis medullae oblongatae, a projection from the caudal ventrolateral medulla, and had a close relationship with the NRGC pars lateralis. Thus, apart from its well-established projection to the spinal sympathetic preganglionic neurons and innervation from the nucleus tractus solitarius, the NRRVL may also have rich connections with many medullary sites that participate in cardiovascular regulations.

Animals↗
PubMed1986

Anatomic and physiologic evaluation of a link between the nucleus reticularis gigantocellularis and nucleus ambiguous in the rat.

Localized microinjection of wheat germ agglutinin-conjugated horseradish peroxidase into the nucleus ambiguous (NA) of Sprague-Dawley rats retrogradely labeled neurons that were bilaterally located within the confine of the nucleus reticularis gigantocellularis (NRGC). These cells conformed with the Golgi description of cytoarchitectonic configurations and size distributions for neurons in this reticular nucleus. Furthermore, field potentials antidromically evoked at the NA by stimulating the vagus nerve were augmented by concurrent activations of bilateral NRGC sites that were themselves capable of eliciting hypotension and bradycardia. We conclude that the gigantocellular reticular nucleus may at least employ the cardiac vagal preganglionic neurons in the NA to exert its actions on the heart.

Animals↗
PubMed1986

Facilitation of lumbar monosynaptic reflexes by locus coeruleus in the rat.

The present study was initiated to delineate whether species difference exists between cats and rats in the descending influence of locus coeruleus (LC) on spinal motoneuronal activity. In male Sprague-Dawley rats anesthetized with chloral hydrate (400 mg/kg, i.p.), localized activation of LC promoted an exclusive facilitation of lumbar spinal extensor and flexor monosynaptic reflexes (MSRs). Such LC-evoked potentiations may vary in degree (37.5-147.4%), duration (70.6-72.9 ms) and latency (3.0-5.5 ms) among different animals. While minimally affecting the control MSRs, the alpha 1-adrenoceptor blocker prazosin (20 micrograms/kg, i.v.) significantly antagonized the enhancing effect of the LC on MSRs, suggesting the participation of noradrenergic neurotransmission in the process. Since these results are in general agreement with previous observations from our laboratory on the cat, we conclude that the LC exerts similar facilitatory actions on both extensor and flexor motoneuron activity of the hindlimb in at least two animal species, rat and cat.

Animals↗
PubMed1986

The roles of alpha 2-adrenoceptors in the nucleus reticularis gigantocellularis and vagal mechanism in the cardiovascular suppressive effects of guanabenz in the rat.

In pentobarbital-anesthetized rats, pretreatment with yohimbine (10 micrograms), which was microinjected into the bilateral nucleus reticularis gigantocellularis (NRGC), significantly antagonized the reduction in arterial pressure, and the force and rate of heart contraction normally promoted by systemic administration of guanabenz (10 micrograms/kg, i.v.). At the same time, the vasodepressive as well as negative inotropic and chronotropic effects of direct application of guanabenz (500 ng) into the NRGC were attenuated by bilateral cervical vagotomy or atropine sulfate (1 mg/kg, i.v.). We conclude that guanabenz may promote antihypertension by activating the alpha 2-adrenoceptors in the NRGC, which in turn elicits cardiovascular suppression by at least facilitating the vagal outflows to the heart.

Animals↗
PubMed1986

Evaluation of a low dose of hepatitis B vaccine given within a childhood immunisation programme in Singapore.

The feasibility of introducing low dose (5 micrograms) hepatitis B (HB) virus vaccination at birth and again 1 and 2 months later as part of an existing primary immunisation programme of childhood, was assessed in 662 healthy newborn Singapore children. The vaccine (B-Hepavac, Menck, Sharp and Dohme) was given to three neonatal groups: those born to HB surface antigen (sAg)-negative mothers, HBsAg-positive/HBeAg-positive mothers and HBsAg-positive/HBeAg-negative mothers. A dose of 5 micrograms was compared in a randomised study with the more usual 10 micrograms dose given at the same intervals. Neonates born to HBsAg-positive/HBeAg-positive mothers were also given hepatitis B immunoglobulin (HBIg) at birth. The 5 microgram dose of vaccine was as immunogenic as the 10 microgram dose in all three groups of children studied. At 1 year, anti-HBsAg seroconversion among infants of antigen-negative mothers was 95.8% for the 5 microgram dose and 91.9% for the 10 microgram dose. Suppression of anti-HBsAg formation was not seen even when maternal anti-HBsAg was present or HBIg given. Among infants born to HBsAg-positive/HBeAg-positive mothers, passive plus active immunisation was 100% protective at doses of 5 micrograms and 10 micrograms vaccine in the newborns who were HBsAg-negative at 24 h. Seroconversion after both the 5 and 10 microgram doses of vaccine was reduced, however, to 88% in each group of infants who were already HBsAg-positive at 24 h of age. Overall, passive plus active immunisation as well as HB vaccine alone (5 micrograms dose), given within the existing but expanded primary immunisation programme of childhood, was effective in preventing infection and the chronic carrier state in newborns exposed to risk of HB virus infection during infancy.

Carrier State↗
PubMed1986

Hepatitis B infection in prostitutes.

The prevalence of HBV markers in prostitutes is known to be higher than that of the normal population of similar age range in previous studies. This study showed a significant correlation between the duration of prostitution and the prevalence of HBV antibodies amongst the prostitutes. The prevalence of HBV antibodies doubled after the first year of prostitution. A two-year follow-up study of these prostitutes showed that 37% of HBsAg positive prostitutes lost the HBsAg. The seroconversion rate of HBsAg negative prostitutes was 10% during this two-year period. Early immunization against HBV infection should be considered in this high risk group in view of these findings.

Adult↗