Biomedical subjects

S H Chan

Publications and source records attributed to S H Chan.

At least 181 records · Page 10Linked to original sources

PubMed1992

Inhibition by locus coeruleus on the baroreceptor reflex response in the rat.

We evaluated the modulation of baroreceptor reflex (BRR) response by locus coeruleus (LC) in adult, male Sprague-Dawley rats anesthetized with urethane (1.5 g/kg, i.p.). Under an electrical stimulation condition that did not appreciably alter the basal systemic arterial pressure and heart rate, the LC significantly suppressed the BRR response. Microinjection of L-glutamate (1 nmol, 50 nl) into the LC essentially duplicated this depressant effect. Intracerebroventricular (i.c.v.) administration of the alpha 1-adrenoceptor antagonist, prazosin (6.5 nmol), appreciably blunted the inhibition by LC on the BRR response. Yohimbine (6.5 nmol), the alpha 2-adrenoceptor blocker, however, was ineffective. Direct microinjection of prazosin (50 pmol), but not yohimbine (50 pmol), into the terminal site of baroreceptor afferents at the nucleus tractus solitarii (NTS) also significantly blunted the suppressive effect of LC on the BRR response. These results suggest that the LC may produce an inhibition on the BRR response by a process that involves the alpha 1-adrenoceptors located in the NTS.

Adrenergic alpha-Antagonists↗

PubMed1992

Elicitation of penile erection following activation of the hippocampal formation in the rat.

We explore the possible involvement of the hippocampal formation in penile erection, using male, adult Sprague-Dawley rats that were anesthetized with pentobarbital sodium. The intracavernous pressure (ICP) was used as the experimental index for penile erection. Electrical activation of the hippocampal formation resulted in two patterns, viz, multiple and single episodes of elevation in ICP, along with visible penile erection and ejaculation. The former pattern exhibited an increase in ICP that was more sustained, with higher peak amplitude and longer latency. Furthermore, they originated respectively from the granule cells of the dentate gyrus and pyramidal cells of the CA1 and CA3 fields of the Ammon's horn. Chemical stimulation of the hippocampus with glutamate also elicited significant increase in ICP. These results thus provided direct evidence to establish that the hippocampal formation may be involved in central neural regulation of the erectile process.

Animals↗

PubMed1992

Participation of pertussis toxin-sensitive GTP-binding regulatory proteins in the suppression of baroreceptor reflex by neurotensin in the rat.

We evaluated the molecular mechanism that may underlie the suppressive effect of neurotensin (NT) on the baroreceptor reflex (BRR), using Sprague-Dawley rats that were anesthetized with sodium pentobarbital (50 mg/kg, i.p.). Intracerebroventricular (i.c.v.) application of NT (15 nmol) significantly inhibited the BRR response. Such an inhibition was appreciably antagonized by pretreating animals with i.c.v. injection of pertussis toxin (10 or 20 pmol), N-ethylmaleimide (1 or 2 nmol), forskolin (30 or 60 nmol) or phorbol 12-myristate 13-acetate (2 or 4 nmol), but not by cholera toxin (15 or 30 pmol). More specifically, pretreatments with bilateral microinjection into the nucleus tractus solitarius (NTS) of pertussis toxin (80 or 160 fmol), N-ethylmaleimide (80 pmol), forskolin (480 pmol) or phorbol 12-myristate 13-acetate (16 or 32 pmol) also blunted the NT-induced suppression of BRR, although cholera toxin (120 or 240 fmol), or 1,9-dideoxyforskolin (480 pmol) had no appreciable effect. These results suggest that a pertussis toxin-sensitive guanine nucleotide-binding regulatory protein(s), which is not likely to be Gs, possibly Gi or Gp, may be involved in the transmembrane signaling process that underlies the suppression of BRR response by NT at the NTS.

Animals↗

PubMed1992

Reversal by pertussis toxin and N-ethylmaleimide of the facilitation of baroreceptor reflex response by somatostatin in the rat.

We evaluated the transmembrane signaling mechanism that may underlie the facilitatory action of somatostatin (SOM) on baroreceptor reflex (BRR), using adult, male, Sprague-Dawley rats anesthetized with pentobarbital sodium (40 mg/kg, i.p.). Intracerebroventricular (i.c.v.) application of SOM (2 nmol) promoted a significant elevation in BRR response, induced by phenylephrine (5 micrograms/kg, i.v.). This potentiatory action of the tetradecapeptide was significantly reversed after pretreating animals with bilateral microinjection of pertussis toxin (25 ng) or N-ethylmaleimide (2 nmol) into the nucleus tractus solitarius (NTS), the terminal site for baroreceptor afferents. These results suggest that a pertussis toxin-sensitive GTP-binding regulatory protein, possibly Gi, may be involved in the modulation of the BRR by SOM at the NTS.

Afferent Pathways↗

PubMed1992

Mechanisms of IFN-gamma induction by natural killer cell stimulatory factor (NKSF/IL-12). Role of transcription and mRNA stability in the synergistic interaction between NKSF and IL-2.

We have investigated the molecular mechanisms regulating IFN-gamma production in human T lymphocytes stimulated by NK cell stimulatory factor (NKSF/IL-12). We show that NKSF synergizes with IL-2 and phorbol diesters inducing the accumulation of IFN-gamma mRNA in PHA-activated T cell blasts. NKSF regulates IFN-gamma mRNA expression in PHA blasts and the T leukemia cell line, TALL-103/2, at both the transcriptional and posttranscriptional levels. NKSF increases the transcriptional rate for IFN-gamma in both these cell types, as determined by nuclear run-on analysis. However, synergy between NKSF and IL-2 can be demonstrated only at the level of mRNA stability, and both cytokines are required to increase IFN-gamma mRNA half-life.

Blotting, Northern↗

PubMed1992

Recombinant DNA hepatitis B vaccine containing Pre-S components of the HBV coat protein--a preliminary study on immunogenicity.

A novel recombinant hepatitis B vaccine, trademarked Sci-B-Vac, was evaluated for safety, tolerability and immunogenicity in an open label trial performed in Singapore. The experimental vaccine, derived from Chinese hamster ovary (CHO) cells, consists of hepatitis B surface antigen (HBsAg) particles harbouring all three viral envelope polypeptides, the major S protein and the minor Pre-S2 and Pre-S1, in their glycosylated and non-glycosylated forms. The vaccine was administered intramuscularly at 0, 1 and 6 months. No unexpected adverse effects were observed. A high level anti-HBs response to Sci-B-Vac was indicative of its immunogenicity. Subsequent to the third injection, 100% and 92% of the 10 micrograms and 5 micrograms dose recipients, respectively, were seroprotected (anti-HBs titres greater than or equal to 10 mIU ml-1). Moreover, the geometric mean titres (GMT) of the anti-HBs response were very high: 2687 and 1473 mIU ml-1, respectively. An immunogenic advantage of Sci-B-Vac was also suggested by the rapid onset of antibody response: 96% of the 10 micrograms dose recipients were seroprotected with a GMT of 159 mIU ml-1, prior to the third injection.

Adolescent↗

PubMed1992

Intracavernous pressure as an experimental index in a rat model for the evaluation of penile erection.

This report communicates our attempt to design a small animal model for the evaluation of penile erection, based on the pharmacological responses of cavernous tissues in the rat that resemble those of human subjects. Male adult Sprague-Dawley rats anesthetized with pentobarbital sodium were used in conjunction with papaverine and prostaglandin E1, two vasoactive drugs most commonly used in clinical management of impotence. Intracavernous administration of papaverine (0.05, 0.1, 0.02, 0.4 or 0.8 mg.) induced a progressive increase in intracavernous pressure that peaked at 0.4 mg. This effect was associated with visible penile erection that became conspicuous when accompanied by additional bursts of transient intracavernous pressure fluctuations. The duration of papaverine-induced increase in intracavernous pressure was significantly shortened by clonidine (15 micrograms, intracavernous). Injection of prostaglandin E1 (1, 2 or 4 micrograms) into the corpus cavernosum also elicited an elevation in intracavernous pressure, but the responses exhibited acute tachyphylaxis. By manifesting a response to papaverine and prostaglandin E1 that is similar to that in human, we conclude that the intracavernous pressure in the rat may represent a suitable index for the evaluation of penile erection in small laboratory animals.

Alprostadil↗

PubMed1992

The thymic compartment responsible for positive selection of CD4+ T cells.

Our aim was to assess the generality of the observation that positive selection of CD4+ T cells is mediated by MHC class II molecules on epithelial cells of the thymic cortex. By appropriate matings of previously established transgenic and mutant mouse lines, we were able to produce animals that lacked MHC class II molecules; individuals expressing only the class II E complex, but in all the usual thymic compartments; animals that had E molecules in the thymic medulla but not in the cortex; and, reciprocally, individuals expressing the E complex in the thymic cortex but essentially not in the medulla. Those mice which displayed class II molecules in the cortex had normal numbers of CD4+CD8- T cells in the thymus and CD4+ T cells in the periphery, while 'bare' cortex mice were almost devoid of mature CD4 single positive cells. This finding serves to generalize observations from previous studies of similar design but limited to assaying positive selection of T cells which expressed a single transgenic E-restricted TCR or a subset of V beta 6+ TCRs.

Animals↗

PubMed1992

Antigen-specific tachycardia and hypotension in rodents.

Tachycardia and hypotension, two cardiovascular responses to anaphylaxis, were specifically induced by antigen in mice and rats, respectively. Intravenous injection of poly (Glu60Ala30Tyr10) (GAT) elicited tachycardia within 30-40 sec in GAT-primed B6 mice. Moreover, a minute amount of GAT (0.2 micrograms) was enough to sensitize the mice to subsequent GAT-induced tachycardia. Challenging doses ranging from 100 ng to 500 micrograms. could elicit tachycardia. The kinetics of tachycardia induction was different from that of antibody production or delayed-type hypersensitivity. Tachycardia was induced from day 6 after immunization, while delayed-type hypersensitivity developed as early as day 4, and anti-GAT antibodies were undetectable on day 6 and would not reach a maximum until day 8. Specific antigen-induced hypotension was also observed in rats. Furthermore, cardiovascular changes in both species could be passively transferred by heat-treated (56 degrees C, 30 min) sera from immunized animals. These benchmarks of antigen-induced cardiovascular changes in mice or rats could be used as models to study the immune control of cardiovascular changes in anaphylactic responses.

Amino Acid Sequence↗

PubMed1992

Identification and cloning of a novel heterogeneous nuclear ribonucleoprotein C-like protein that functions as a transcriptional activator of the hepatitis B virus enhancer II.

Liver specificity of hepatitis B virus (HBV) replication has been attributed to the action of its second enhancer (EII). We report here the characterization of EII and the subsequent isolation of a novel liver-specific DNA-binding protein which binds to and activates EII. The cDNA clone of the protein, designated E2BP, was isolated from a lambda gt11 expression library constructed from the hepatoma cell line HuH-6 which was screened with a binding site probe derived from EII. Sequence analysis of E2BP revealed 86.6% homology with a rat heterogeneous nuclear ribonucleoprotein C protein sequence, while conformational studies suggest a helix-loop-helix motif as a DNA-binding site. Cloned E2BP expressed in human fibroblasts by transient transfection displayed EII binding and activating characteristics similar to those of native E2BP in hepatocytes.

Amino Acid Sequence↗

PubMed1992

HLA in Singapore Chinese with rheumatoid arthritis.

The HLA-A, B, C, DR and DQ antigens were determined in 50 Singapore Chinese patients with rheumatoid arthritis (RA). There was a significant increase in the prevalence of HLA-Bw46, DRw53 and DQ3 in patients with RA. The linkage disequilibrium between Bw46 and DRw53 explains this association. This major histocompatibility complex association differs from the HLA-DR4 link in Caucasian populations and suggests that RA is an immunogenetically heterogeneous disease.

Adult↗

PubMed1992

Characterization of Mirabilis antiviral protein--a ribosome inactivating protein from Mirabilis jalapa L.

A protein was purified from root tubers of Mirabilis jalapa to homogeneity by ion-exchange chromatography on CM-Sepharose CL-6B and FPLC on Mono-S column. The purified protein was confirmed to be Mirabilis antiviral protein (MAP). However, in addition to its antiviral property, the MAP was demonstrated to possess abortifacient activity in pregnant mice, inhibitory effect on cell-free protein synthesis and antiproliferative effect on tumor cells. As judged from its biological and physiochemical properties, MAP is a type I ribosome-inactivating protein.

Abortifacient Agents↗

PubMed1992

[Mannitol reduces plasma hydrogen peroxide free radical in patients undergoing coronary artery bypass graft surgery].

During the procedure of coronary artery bypass graft surgery (CABG), the release of free oxygen radicals as a result of ischemia and reperfusion which plants the seeds of post-operative low cardiac output and arrhythmias has grave consequence on the reestablishment of cardiac function. A variety of chemical agents such as mannitol, allopurinol, catalase (Q-10) and superoxide dismutase (SOD) has proved to be considerably effective to improve the myocardial necrosis following ischemia and reperfusion. In this study we chose mannitol (0.2 gm/kg) as the free oxygen radicals scavenger and utilized mass spectrophotometric method to detect the variation of concentration of [H2O2], a by-product of free oxygen radical, in an attempt to evaluate the efficacy of mannitol in this regard in patients undergoing CABG. Patients were divided into experimental group (n = 19) and control group (n = 20). In the experimental group the concentration of [H2O2] changed from 61 +/- 24 microM/L pre-operatively to 77 +/- 18 microM/L post-operatively as against 75 +/- 31 microM/L and 99 +/- 31 microM/L respectively in the control group. In comparison, only the change in experimental group was statistically significant (p less than 0.05). We confirmed that mannitol functions considerably as a free oxygen radical scavenger since it reduces the production of [H2O2] in patients undergoing CABG.

Aged↗

PubMed1992

Comparison of the immune response of four different dosages of a yeast-recombinant hepatitis B vaccine in Singapore children: a four-year follow-up study.

The immunogenicity of four different dosages of yeast-derived hepatitis B vaccine (Merck, Sharp & Dohme: 0.6 micrograms, 1.25 micrograms, 2.5 micrograms and 5.0 micrograms), administered at 0, 1 and 6 months (0-1-6 schedule) intramuscularly, was evaluated in 122 seronegative healthy children 1-12 years of age. Three months after the first dose, 83.9-100% of the vaccinees seroconverted. Peak geometric mean titres (GMT) of between 1088 mlU/ml and 1699 mlU/ml were attained 3 months after completion of the vaccination schedule. After 24 months, anti-HBs (antibody to hepatitis B surface antigen) was detected in 93.1-100% of the vaccinees, but the GMT dropped to between 214.3 mlU/ml and 303.5 mlU/ml. After 48 months, 88.8-100% of the vaccinees continued to possess anti-HBs and 70.3-87% had titres above 10 mlU/ml. As expected, the GMT declined further to between 72.6 mlU/ml and 118.8 mlU/ml. There were no significant differences in seroconversion rates and GMT among the different dosage groups. All the vaccinees remained asymptomatic and free from hepatitis B virus infection. The study showed that reduced dosages of the vaccine (0.6 micrograms, 1.25 micrograms and 2.5 micrograms) were as immunogenic as the standard dose (5 micrograms); the 2.5-micrograms dose was recommended for the national childhood immunization programme in Singapore. No booster is necessary for at least four years after vaccination.

Antibody Formation↗

PubMed1991

Reduction in postsynaptic alpha 2-adrenoceptor activity by endogenous angiotensin III in the nucleus reticularis gigantocellularis of the rat.

We investigated in adult, male Sprague-Dawley rats anesthetized with pentobarbital sodium the synaptic location of the interaction between endogenous angiotensin III (AIII) and the alpha 2-adrenoceptors in the medulla oblongata that are involved in cardiovascular regulation. The circulatory suppressant efficacy of a centrally acting alpha 2-adrenoceptor agonist, guanabenz, was used as the experimental index. Direct bilateral microinjection of AIII (40 pmol) into the nucleus reticularis gigantocellularis (NRGC), a medullary site believed to be intimately related to the cardiovascular inhibitory actions of guanabenz, attenuated, whereas the selective AIII receptor antagonist, Ile7-AIII (20 nmol), potentiated, the circulatory suppressant effects of guanabenz (100 micrograms/kg, i.v.). These two respective actions were essentially unaffected by immunocytochemically verified depletion of noradrenergic nerve terminals in the NRGC, elicited by a selective noradrenergic neurotoxin, DSP4. These data suggest that endogenous AIII may exert a tonic inhibitory action on the alpha 2-adrenoceptors located postsynaptically on neurons in the NRGC that are involved in central cardiovascular regulation.

Adrenergic alpha-Antagonists↗

PubMed1991

Facilitation of baroreceptor reflex response by endogenous somatostatin in the rat.

We evaluated the potential participation of endogenous brain somatostatin-14 (SOM) in central cardiovascular regulation, using adult male Sprague-Dawley rats anesthetized with pentobarbital sodium (40 mg/kg, i.p.). Intracerebroventricular (i.c.v.) application of SOM (2 or 4 nmol) promoted a significant elevation in baroreceptor reflex (BRR) response, induced by phenylephrine (5 micrograms kg, i.v.). Blocking the endogenous SOM activity with its specific receptor antagonist, cyclo-[7-aminoheptanoyl-Phe-D-Trp-Lys-Thr(Bzl)] (2 or 4 nmol, i.c.v.) or antiserum against SOM (1:20, i.c.v.), on the other hand, appreciably attenuated the same response. These modulatory effects on the BRR response were essentially duplicated upon bilateral microinjections of SOM (320 pmol), SOM antagonist (320 pmol) or anti-SOM (1:20) into the caudal portion of the nucleus of tractus solitarius (NTS), the terminal site for baroreceptor afferents. These results suggest that neurons that contain SOM may participate in cardiovascular control by tonically facilitating the BRR, possibly by exerting an influence on the neurons at the NTS.

Animals↗

PubMed1991

Induction of interferon gamma production by natural killer cell stimulatory factor: characterization of the responder cells and synergy with other inducers.

We previously reported that natural killer cell stimulatory factor (NKSF), a heterodimeric lymphokine purified from the conditioned medium of human B lymphoblastoid cell lines, induces interferon gamma (IFN-gamma) production from resting peripheral blood lymphocytes (PBL) and synergizes with interleukin 2 in this activity. In this study, we show that human NKSF induces IFN-gamma production from both resting and activated human PBL and from freshly isolated murine splenocytes. Human T and NK cells produce IFN-gamma in response to NKSF, but resting PBL require the presence of nonadherent human histocompatibility leukocyte antigens DR+ (HLA-DR+) accessory cells to respond to NKSF. The mechanism(s) by which NKSF induces IFN-gamma production results in accumulation of IFN-gamma mRNA, is insensitive to cyclosporin A, and synergizes with those mediated by phytohemagglutinin, phorbol diesters, anti-CD3 antibodies, and allogeneic antigens, but not by Ca2+ ionophores. The ability of NKSF to directly induce IFN-gamma production and to synergize with other physiological IFN-gamma inducers, joined with the previously described ability to enhance lymphocyte cytotoxicity and proliferation, indicates that this lymphokine is a powerful immunopotentiating agent.

Animals↗

PubMed1991

Participation of noradrenergic neurotransmission in angiotensin III-induced dipsogenic behavior in the rat.

Conscious, adult, male Sprague-Dawley rats, instrumented with in-dwelling cannula for drug application into the lateral cerebral ventricle, were used to evaluate the participation of noradrenergic neurotransmission in angiotensin III (AIII)-induced dipsogenic behavior. Intracerebroventricular (i.c.v.) administration of AIII (20, 40 or 80 pmol) elicited a robust and dose-related drinking response. Chemical lesion produced by i.c.v. injection of the catecholaminergic neurotoxin, 6-hydroxydopamine (25 micrograms x 3), or the selective noradrenergic neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (250 micrograms), promoted significant antagonization of the dipsogenic behavior produced by AIII (40 or 80 pmol, i.c.v.). Under equimolar doses (3.25 or 6.50 nmol), the specific alpha 1-adrenoceptor blocker, prazosin, antagonized; the specific alpha 2-adrenoceptor antagonist, yohimbine, enhanced; and the nonselective alpha-adrenoceptor blocker, phentolamine, elicited minimal action, on AIII (40 pmol)-induced drinking response. These results suggest that central noradrenergic neurotransmission may participate actively in AIII-induced dipsogenesis, in a process that may involve both alpha 1- and alpha 2-adrenoceptors.

Adrenergic alpha-Antagonists↗