Biomedical subjects

S H Chan

Publications and source records attributed to S H Chan.

At least 145 records · Page 8Linked to original sources

PubMed1994

Polymorphism of T-cell receptor genes in nasopharyngeal carcinoma.

Germ-line TCR genes from 41 Singaporean Chinese patients with nasopharyngeal carcinoma and 54 Singapore Chinese normal subjects were investigated by restriction fragment length polymorphism (RFLP) analysis. Genomic DNA from BLCLs of patients and normal subjects was digested with the restriction endonucleases BamHI, EcoRI, HindIII, TaqI, transferred to nylon membrane by the Southern-blot technique and hybridized with radioactively labelled TCR cDNA probes. When the combination of BamHI/V beta II was used, NPC patients had a lower frequency of the 25/25-kb allelic pattern and a higher frequency of the 20-kb fragment compared to controls. With the combination of TaqI/V beta 8, the 4.3/3.2-kb fragment allelic frequency was lower in total NPC but particularly in patients with HLA B46. The result suggested that TCR restriction may be important in the pathogenesis of NPC.

B-Lymphocytes↗

PubMed1994

Differential neuronal responses to angiotensin III from the subfornical organ of normotensive and spontaneously hypertensive rats.

We previously reported that chronic central administration of angiotensin III (AIII) fails to produce sustained drinking behavior in spontaneously hypertensive rats (SHR), possibly because of the development of early desensitization of the angiotensin receptors. The present study extended these findings to the cellular level, using brain-slice preparation from Wistar-Kyoto rats (WKY) and SHR, in conjunction with single-neuron recording in the subfornical organ (SFO), a target site for angiotensin II-induced drinking. We found that a majority of the SFO neurons studied (13/18 in WKY, 20/28 in SHR) responded in a dose-related manner to AIII, given in the range of 10(-6)-10(-5) M. This excitation was receptor-specific, since it was reversed by Ile7-AIII (10(-4)-10(-3) M), the selective AIII antagonist. Bestatin (10(-5)-10(-4) M), an aminopeptidase B inhibitor, did not discernibly affect basal spike frequency when delivered alone. Nevertheless, given in combination with the heptapeptide, bestatin reduced the intensity and duration of SFO neuronal response in WKY to the higher dose (10(-5) M), and in SHR to both doses (10(-6) or 10(-5) M), of AIII. These data suggest that the SFO may also be a central site of action for AIII. Moreover, prolonging the action of AIII by protecting it from being metabolized with bestatin may produce desensitization of the angiotensin receptors on SFO neurons. This was particularly so in the SHR, which are thought to be defective in the degradation of the heptapeptide in the brain.

Aminopeptidases↗

PubMed1994

Substance P suppresses the activity of alpha 2-adrenoceptors of the nucleus reticularis gigantocellularis involved in cardiovascular regulation in the rat.

We evaluated possible interactions between substance P (SP) and the alpha 2-adrenoceptors in the nucleus reticularis gigantocellularis (NRGC) of the medulla oblongata involved in cardiovascular regulation. Adult, male Sprague-Dawley rats anesthetized with pentobarbital sodium (40 mg/kg, i.p., with 10 mg/kg/h i.v. supplements) were used. The circulatory suppressant efficacy of a centrally acting alpha 2-adrenoceptor agonist, guanabenz, was used as the experimental index. Bilateral microinjection of SP (300 or 600 pmol) into the NRGC, a medullary site that is critically involved in the cardiovascular depressive actions of guanabenz, significantly diminished the hypotensive and bradycardiac efficacy of the aminoguanidine compound (100 micrograms/kg, i.v.). This implied reduction in alpha 2-adrenoceptor activity in the NRGC by SP was antagonized by its selective receptor antagonist, [D-Pro2,D-Trp7,9]-SP (1200 pmol). Similarly, attenuation by SP of the cardiovascular suppressant effects of guanabenz was also reversed by immunocytochemically verified depletion of dopamine-beta-hydroxylase-immunoreactive nerve terminals in the NRGC, elicited by the selective noradrenergic neurotoxin, DSP4 (50 micrograms). These data suggest that SP may exert an inhibitory action on the alpha 2-adrenoceptors in the NRGC that are involved in central cardiovascular regulation, possibly via a presynaptic modulation on noradrenergic neurotransmission.

Adrenergic alpha-2 Receptor Antagonists↗

PubMed1994

Interaction between neuronal responses to nociception and hypertension in the nucleus reticularis gigantocellularis of the rat.

We evaluated the interactive effects of noxious stimuli and elevation in systemic arterial pressure on the responsiveness of spontaneously active neurons in the nucleus reticularis gigantocellularis (NRGC) of male, adult Sprague-Dawley rats anesthetized with pentobarbital sodium. In NRGC neurons that responded to both nociception (tail clamp) and transient hypertension elicited by phenylephrine (5 micrograms/kg, i.v.), the responsiveness to tail clamp was reduced upon simultaneous elevation in arterial pressure. This preferential response pattern did not appear to be affected by the level of anesthesia, since it was demonstrated in animals that were maintained by hourly bolus supplements or continuous infusion of pentobarbital sodium. These data offer a feasible cellular explanation for the documented correlation between elevated nociceptive threshold and hypertension. They also showed that NRGC may be a central integrator for the processing of nociceptive and cardiovascular information.

Anesthesia↗

PubMed1994

Involvement of G(o) alpha subtype of guanine nucleotide-binding regulatory protein at the locus coeruleus in fentanyl-induced muscular rigidity in the rat.

Previous work from our laboratory suggested that locus coeruleus (LC) and the coerulospinal noradrenergic pathway are intimately related to the elicitation of muscular rigidity by fentanyl. The present study attempted to identify the subtype of guanine nucleotide-binding regulatory protein that may participate in this process, using Sprague-Dawley rats anesthetized with ketamine and under mechanical ventilation. Immunofluorescent staining with a polyclonal antiserum directed against a 39-kDa protein that corresponds to the alpha subunit of G(o) revealed the presence of G(o) alpha immunoreactivity in neurons of the LC. Bilateral microinjection of the same G(o) alpha antiserum into the LC also significantly blunted the enhanced electromyographic activity recorded from the sacrococcygeus dorsalis lateralis muscle induced by intravenous administration of fentanyl (100 micrograms/kg). These results suggest that G(o) alpha protein at the LC may participate in the signal transduction process that underlies muscular rigidity induced by high-dose fentanyl.

Animals↗

PubMed1994

Power spectral analysis of electroencephalographic desynchronization induced by cocaine in rats: correlation with microdialysis evaluation of dopaminergic neurotransmission at the medial prefrontal cortex.

We evaluated the effect and action mechanisms of cocaine on electroencephalographic (EEG) activity in adult male Sprague-Dawley rats anesthetized with chloral hydrate (400 mg/kg, i.p., with 80 mg/kg/h supplements). On-line and real-time power spectral analysis of the EEG activity continuously quantified its root mean square (RMS) and mean power frequency (MPF) values, and the power of its spectral frequency components (low frequency: 0-4 Hz; high frequency: 4-20 Hz). Administration of cocaine (1.5 or 3.0 mg/kg, i.v.) dose-dependently induced EEG desynchronization, as manifested by a reduction in RMS and an elevation in MPF values, coupled with a differential decrease in both high and low frequency components. Samples collected by in vivo microdialysis at the medial prefrontal cortex (mPFC) and analyzed by HPLC showed that the elevation of cocaine and dopamine (DA) level in the dialysate reached its peak during the time interval when maximal activation of EEG occurred. This EEG activation was antagonized by microinfusion into the mPFC via reverse microdialysis of R(+)-SCH 23390, a selective antagonist for D-1 receptors; sulpiride, a selective antagonist for D-2 receptors; or haloperidol, a nonspecific dopamine antagonist. These results suggest that dopaminergic neurotransmission at the mPFC may be intimately related to the specific spectral pattern of alteration in EEG activity elicited by cocaine in the rat and that both D-1 and D-2 receptors may be involved in the process.

Animals↗

PubMed1994

In favor of the selective model of positive selection.

The mechanisms of thymocyte commitment towards the CD4+ and CD8+ lineage remain unresolved. Two models--one based on instruction, the other on selection--have previously been proposed. The instructional model has been popularly received based on results of earlier studies. However, our data from MHC class II, class I, and double-deficient mice suggest otherwise. There exists a significant population of CD4+ cells that is intermediate in maturity between CD4+ CD8+ and fully mature CD4+ CD8- thymocytes in class II-deficient animals; an analogous population of CD4-CD8+ cells exists in class I-negative mice. We suggest that a selective model in which two TCR-MHC molecule engagements are required: the first induces a random down-modulation of either CD4 or CD8 and some differentiation; the second, involving the participation of the appropriate coreceptor, permits end-stage differentiation.

Animals↗

PubMed1994

Power spectral analysis of electromyographic and systemic arterial pressure signals during fentanyl-induced muscular rigidity in the rat.

We have measured electromyographic (EMG) and systemic arterial pressure (SAP) signals during fentanyl-induced muscular rigidity in adult male Sprague-Dawley rats anaesthetized initially with ketamine 120 mg kg-1 i.p. during controlled ventilation. Fentanyl 100 micrograms kg-1 i.v. induced significant increase in EMG activity, recorded from the sacrococcygeus dorsi lateralis muscle. Power spectral analysis revealed that this was produced by an increase in the root mean square and a decrease in the mean power frequency values of the signals, signifying recruitment and synchronous activation of motor units. Together with transient hypotension and bradycardia, power spectral analysis of the SAP signals demonstrated a reduced but maintained power density of the frequency components that represent respiratory, baroreceptor and vasomotor activities. All these effects were only demonstrated unequivocally in rats maintained by i.v. infusion of ketamine until 10 min before the administration of fentanyl. We conclude that analysis of the temporal alterations in the spectral components of the EMG and SAP signals in rats during mechanical ventilation provides a sensitive method of measuring fentanyl-induced muscular rigidity and the accompanying alterations in haemodynamic variables.

Anesthesia, Intravenous↗

PubMed1994

HLA class 2 genes in Singaporean Chinese rheumatoid arthritis.

This study analysed HLA class 1 and 2 allele associations in Singaporean Chinese patients with RA. Seventy patients (ARA definite or classical) and 80 controls were typed for HLA class 1 alleles by serology and class 2 alleles by serology and the PCR/SSO method. RA patients had higher frequencies of DRB1*0405 (40 vs 12.5%; corrected probability value (PC) < 0.02, relative risk (RR) = 4.7, 95% confidence limit (CL) 2.1-10.6), DRB1*1001 (14.3 vs 1.3%; PC = 0.06, RR = 13.2, 95% CL 1.6-105.7), DQB1*0401 (38.6 vs 12.5%; P = 0.006, RR = 4.4, 95% CL 1.9-10.0) and DQB1*0501 (20 vs 5%; PC = 0.048, RR = 4.8, 95% CL 1.5-15.2). It is concluded that Chinese RA is associated primarily with HLA DRB1*0405 and DRB1*1001 which share common amino acid sequences in the third hypervariable region of the DR beta chains shown to be associated with RA in other ethnic groups. Patients without DRB1*0405 and *1001 had a higher frequency of DRB1*0901, which is in linkage disequilibrium with HLA B46 in the Chinese.

Adolescent↗

PubMed1994

Bleeding peptic ulcer--risk factors for rebleeding and sequential changes in endoscopic findings.

From September 1991 to December 1992, a prospective study was conducted to determine the risk factors and residual risk of rebleeding, and the evolutionary endoscopic changes in peptic ulcers that rebled. Emergency endoscopies were performed on 452 patients with haematemesis or a melaena, or both within 24 hours of admission. If the lesions were actively bleeding, then the patients were treated with injection sclerotherapy. A multivariate analysis of clinical, laboratory, and endoscopic variables of 204 patients with ulcer bleeding showed that hypovolaemic shock, a non-bleeding visible vessel, and an adherent clot on the ulcer base were independently significant in predicting rebleeding (p < 0.05). Considering these three factors according to the estimates of their regression coefficients showed that a non-bleeding visible vessel was the strongest predictor of rebleeding. The study of the residual risk of rebleeding after admission showed that most rebleeding episodes (94.1%), including all associated with hypovolaemic shock, surgical treatment, and death, occurred within 96 hours of admission. After this time, the residual risk of rebleeding was less than 1%. Study of the changes in endoscopic findings before and after rebleeding illustrated that all ulcers with a visible vessel or adherent clot showed at follow up endoscopy were derived from ulcers with initial major stigmata. It is concluded that hypovolaemic shock, a non-bleeding visible vessel, and an adherent clot on an ulcer base are of independent significance in predicting rebleeding. Observation for 96 hours is sufficient to detect most rebleeding episodes after an initial bleed from peptic ulcer.

Blood Vessels↗

PubMed1994

Molecular cloning and expression of Epstein-Barr virus antigens in the lambda gt11 expression vector: antibodies towards proteins from the BORF2 and BKRF4 reading frames in nasopharyngeal carcinoma patients.

An easy way to clone and screen for Epstein-Barr virus antigens significant in the diagnosis of nasopharyngeal carcinoma (NPC) has been developed. Two proteins cloned and expressed as fusion proteins in lambda gt11 have been identified to be expressed from 661 bp of the BORF2 and from 500 bp of the BNKRF4 reading frames. Western blotting studies on these proteins using serum from 16 NPC and 16 normal healthy individuals showed that 15 NPC patients have either IgG or IgA antibodies towards either protein whereas only 2 normal individuals were positive. Hence, IgG and IgA antibodies towards these antigens are of diagnostic value for NPC.

Antibodies, Viral↗

PubMed1994

Urinary cytodiagnosis: can it have a different prognostic implication than a diagnostic test?

In order to assess the clinical implications of the cytology of voided urine we analyzed 65 patients among 147 cases of transitional cell carcinoma (TCC) in relation to the cytohistologic correlation and prognostic significance. Urinary cytology detected 42.6% of bladder tumors, 59% of renal pelvic tumors, and 35.3% of ureteral carcinomas. None of the 3 cases of grade-1 upper urinary tract tumors was detected by preoperative urinary cytology. Tumors with positive cytology were associated with epidermal growth factor receptor expression (p = 0.0009) and a higher fraction of tumor proliferation as defined by Ki-67 immunohistochemistry (p = 0.0038). Anaplastic tumor cells in urine correlated fairly well with muscular invasion (p = 0.018) and the DNA aneuploidy of the tumor (p = 0.0038). Tumors with muscular invasion were more likely to be detected by cytologic examination (p = 0.013). In urinary bladder carcinoma (n = 107), patients with positive cytology had a higher incidence of tumor recurrence (p = 0.004), and had an unfavorable prognosis (p = 0.0001) with a median follow-up of 46 months. In Ta-T1 tumors (n = 87), urinary cytology had prognostic value in terms of risk of recurrence (p = 0.0001), and poor patient outcome (p = 0.0001). Our data suggest that urinary cytology can offer important biological information on TCC and may be used as a simple and effective short-term prognostic indicator.

Adult↗

PubMed1993

Participation of endogenous neuropeptide Y in the suppression of baroreceptor reflex response by locus coeruleus in the rat.

We evaluated the potential participation of endogenous brain neuropeptide Y (NPY) in the suppression of baroreceptor reflex (BRR) response by locus coeruleus (LC), using adult male Sprague-Dawley rats anesthetized with pentobarbital sodium (40 mg/kg, i.p.). Bilateral microinjection of an antiserum against NPY (1:20, 20 nl) into the caudal one-third level of the nucleus tractus solitarii (NTS), the terminal site for baroreceptor afferent fibers, significantly reversed the suppressive effect of electrical or chemical activation of the LC on the BRR response. Treatments with NPY (4.65 pmol, 20 nl), normal rabbit serum, aCSF and heat-inactivated NPY or NPY antiserum, on the other hand, were ineffective. The LC-promoted inhibition of the BRR response was also attenuated by the alpha 1-adrenoceptor antagonist prazosin (50 pmol, 20 nl), either microinjected alone or in combination with NPY antiserum into the bilateral NTS. Mathematical treatment of our data revealed that the depressive effect on the BRR response of NPY or NE released at the NTS following LC activation manifested different time-course and magnitude. The one by endogenous NPY maximized at 40 min and amounted to no more than 20% of, whereas that by NE peaked at 10 min and contributed no less than 30% to, the suppression. These results suggest that both endogenous NPY and NE may participate in the suppression of BRR response by the LC at the NTS.

Animals↗

PubMed1993

Power spectral analysis of the electroencephalographic and hemodynamic correlates of propofol anesthesia in the rat: intravenous infusion.

Based on the tail-flick response to noxious thermal stimuli, we determined in the present study that effective antinociception could be achieved in adult male Sprague-Dawley rats 15 min after intravenous infusion of propofol at 60 mg/kg/h. Simultaneous power spectral analysis of the electroencephalographic (EEG) and systemic arterial pressure signals further revealed a concomitant depression of the activity of all EEG frequency bands (delta, theta, alpha, beta), alongside hypotension, negative inotropic and chronotropic actions, and attenuated baroreceptor reflex and vasomotor activity. These effects were congruent with a plasma concentration of propofol in the arterial blood of 1.70 +/- 0.13 micrograms/ml, as determined by high-performance liquid chromatography.

Anesthesia↗

PubMed1993

Passive biophysical membrane properties of nucleus reticularis gigantocellularis neurons in brain slices from the rat.

This study employed intracellular recording coupled with the current clamp technique to characterize the passive biophysical membrane properties of neurons in the nucleus reticularis gigantocellularis (NRGC) of brain slices from adult, male Sprague-Dawley rats. We found that NRGC neurons possessed highly depolarized transmembrane potentials (-22.9 +/- 0.6 mV, n = 189). The 29 NRGC neurons that received further evaluation showed that they could be separated into two clusters, with significantly different membrane input resistances (3.51 +/- 0.89 vs 77.50 +/- 8.82 M omega) and membrane time constants (0.56 +/- 0.05 vs 1.27 +/- 0.12 ms). These membrane properties, which resembled qualitatively those we observed previously in cats in vivo, will form the basis for further evaluation of the ionic mechanisms that may underlie the actions of pharmacologic agents on the NRGC neurons.

Animals↗

PubMed1993

Participation of nucleus reticularis gigantocellularis in the antinociceptive effect of angiotensin III in the rat.

We evaluated the participation of nucleus reticularis gigantocellularis (NRGC), a medullary nucleus that plays an important role in the regulation of nociceptive processes, in the antinociceptive effect of angiotensin III (AIII), a biologically active peptide of the renin-angiotensin system. Adult, male Sprague-Dawley rats anesthetized with pentobarbital sodium (40 mg/kg, i.p., with 10 mg/kg/h i.v. infusion supplement) were used. Bilateral, site-specific microinjection of AIII (80 or 160 pmol) into the NRGC produced a dose-related increase in the latency of tail-flick response to noxious thermal stimuli (50 degrees C hot water). Such an antinociceptive action of AIII was blocked by concomitant administration of the AIII receptor antagonist, Ile7-angiotensin III (Ile7-AIII, 10 nmol). At the neuronal level, microiontophoretic application of AIII suppressed, Ile7-AIII reversibly, the responsiveness of nociception-related neurons in the NRGC to tail-clamping. These results demonstrated that central AIII may elicit antinociception via a process that may at least take place at the NRGC.

Analgesics↗

PubMed1993

Antagonization of fentanyl-induced muscular rigidity by denervation of the coerulospinal noradrenergic pathway in the rat.

The present study examined the effect of denervating the coerulospinal noradrenergic pathway on the muscular rigidity elicited by fentanyl in Sprague-Dawley rats anesthetized with ketamine. We demonstrated that the dopamine-beta-hydroxylase-positive nerve terminals arborizing on spinal motoneurons that innervate the sacrococcygeus dorsi lateralis (SCDL) muscle were significantly eliminated by DSP4 treatment. Unilateral microinjection of fentanyl (2.5 micrograms/50 nl) into the locus coeruleus of these animals also failed to evoke discernible increase in the electromyographic activity recorded from the SCDL muscle. These results lend further support for our previous finding that the coerulospinal noradrenergic neurotransmission is critically involved in fentanyl-induced muscular rigidity.

Animals↗

PubMed1993

Visualization of G(o)alpha subtype guanine nucleotide-binding regulatory protein in the medulla oblongata and pons of the rat.

This study reports on the visualization of G(o) protein in the medulla oblongata and pons of Sprague-Dawley rats, using a commercially available selective polyclonal antiserum against a 39-kDa protein corresponding to the alpha subunit of G(o). Specific immunofluorescent-staining was widely distributed in neuropils and neuronal cell bodies but displayed regional heterogeneity. The immunoreactive product exhibited a punctate appearance and was most pronounced in the cell membrane and cytoplasm of the perikarya and proximal dendrites whereas the nucleus remained unstained. Positive immunoreactivity of G(o)alpha was present in nucleus reticularis gigantocellularis, nucleus reticularis paramedialis, nucleus tractus solitarii, nucleus nervi hypoglossi, nucleus raphé pallidus, locus coeruleus, nucleus tractus mesencephali nervi trigemini and nucleus cuneatus. These results provided anatomic evidence to support the participation of G(o) protein in both sensory and motor functions that originate from the medulla oblongata and pons of the rat.

Animals↗