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S H Chan

Publications and source records attributed to S H Chan.

At least 91 records · Page 5Linked to original sources
PubMed1997

Enhancement of spontaneous baroreflex by antisense c-fos oligonucleotide treatment in the NTS of the rat.

We evaluated the hypothesis that basal Fos protein at the nucleus tractus solitarii (NTS), the primary terminal site for baroreceptor afferents, exerts a tonic inhibitory modulation on the spontaneous baroreceptor reflex (BRR) control machinery, which is responsible for beat-to-beat regulation of resting systemic arterial pressure (SAP). In adult male Sprague-Dawley rats anesthetized and maintained with pentobarbital sodium, microinjection bilaterally into the caudal NTS of a 15-mer antisense oligonucleotide that targets against the initiation codon of c-fos mRNA (5'-129 to 143-3') significantly enhanced the spontaneous BRR response, as determined by transfer function analysis of SAP and heart rate signals. The same treatment also diminished baseline Fos-like immunoreactivity in the absence of acute cardiovascular perturbation. Control treatments with artificial cerebrospinal fluid, sense cDNA, or antisense oligonucleotides that either target against a different site of the c-fos mRNA (5'-135 to 149-3') or with three mismatched nucleotides in the antisense sequence, were ineffective. These observations support the notion that, under minimal cardiovascular perturbation, basal expression of Fos protein in the NTS may represent an early step in the cascade of intracellular events that leads to long-term inhibitory modulation of beat-to-beat baroreflex control of blood pressure.

Afferent Pathways↗
PubMed1997

Effect of thyroid hormone on urinary excretion of epidermal growth factor.

Thyroid hormones were demonstrated to upregulate the synthesis of epidermal growth factor (EGF) mRNA and proEGF in the kidneys in vivo. This prospective study was performed to examine the extent of the hypothyroid state in modulating EGF excretion in the urine (U-EGF; n = 23). Patients with thyroid cancer were serially followed up from the euthyroid status, which was retained by thyroxine supplement after thyroidectomy, to the hypothyroidism in preparing for 131I whole body scanning. Paired thyroid function panel, including triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), and U-EGF levels were measured on a weekly basis. Logarithmically transformed values of U-EGF were inversely correlated with TSH serum levels (p = 0.0000), but positively associated with T4 levels (p = 0.0005). No apparent correlation was observed with the T3 serum content, age and gender of the patients (p > 0.1, respectively). If the interval of measurement was taken into consideration, serum TSH was the most significant factor in association with U-EGF (p = 0.0003). Our data indicate that excretion of EGF in human urine depends substantially upon thyroid hormone support.

Adult↗
PubMed1997

Relationship between mesial temporal seizure focus and elevated serum prolactin in temporal lobe epilepsy.

We evaluated the relationship between mesial temporal seizure focus and serum prolactin (PRL) in patients before and after they underwent anterior temporal lobectomy (ATL) for medically intractable temporal lobe epilepsy (TLE). These patients had a confirmed unilateral epileptogenic focus in mesial temporal structures, a postictal rise in serum PRL 15 to 20 minutes after onset of complex partial seizures, and were refractory for more than 2 years to antiepileptic drugs. Presurgical interictal serum PRL levels were significantly elevated (16.47 +/- 0.85 ng/mL, n = 62) and declined after ATL to normal values (patients, 9.63 +/- 0.55 ng/mL, n = 54; normal subjects, 8.99 +/- 0.57 ng/mL, n = 52). Serial evaluations indicated that normalization was seen 3 months after surgery (9.42 +/- 1.22 ng/mL, n = 9). The postsurgical reduction in serum PRL was similar in men and women, in patients with epileptogenic focus on either side of mesial temporal structures, and was unaffected by antiepileptic medication. We conclude that PRL is elevated following seizures and that a seizure focus in mesial temporal structures may exert a sustained excitatory influence on PRL release in patients with medically intractable TLE.

Adolescent↗
PubMed1997

Association of HLA-DRB1*0405 with extraarticular manifestations and erosions in Singaporean Chinese with rheumatoid arthritis.

OBJECTIVE: To determine the association of disease related HLA-DRB1 locus with disease severity and extraarticular features in Singaporean Chinese patients with rheumatoid arthritis (RA). METHODS: 70 patients with RA and 80 controls were typed for HLA class II alleles by the polymerase chain reaction-sequence specific oligonucleotide probe method. RESULTS: 56 patients (80%) had erosive disease; 51 were seropositive (73%), and 16 had extraarticular features (23%). Patients with HLA-DRB1*0405 had significantly higher prevalence of extraarticular features (43 vs 10%; p = 0.001) and erosions (93 vs 71%; p = 0.022) compared to those without the allele. There was also a greater frequency of seropositivity and joint surgery, and a higher number of second line agents used by patients with HLA-DRB1*0405 in comparison to those without, although the difference was not statistically significant. CONCLUSION: HLA-DRB1*0405 is associated with the presence of extraarticular features and erosions in Singaporean Chinese patients with RA.

Adolescent↗
PubMed1996

Participation of Fos protein at the nucleus tractus solitarius in inhibitory modulation of baroreceptor reflex response in the rat.

We investigated the physiologic role of Fos protein at the nucleus tractus solitarius (NTS) in the modulation of baroreceptor reflex (BRR) in adult, male Sprague-Dawley rats that were anesthetized and maintained with pentobarbital sodium (40 mg/kg, i.p., with 10 mg/kg/h i.v. infusion supplements). Repeated and scheduled activation of the baroreceptors by transient hypertension induced by i.v. administration of phenylephrine (2.5, 5.0 or 10.0 micrograms/kg) resulted in a significant increase in Fos-like immunoreactivity (Fos-LI), primarily in the caudal part of the NTS. This increase in Fos-LI in the barosensitive NTS neurons was appreciably reduced by bilateral microinjection into the caudal NTS of an antisense oligonucleotide (20 pmol, 20 nl) designed to target a region of the c-fos mRNA that flanks the initiation codon (5'-129 to 143-3'). The same treatment also discernibly enhanced the BRR response, but elicited no appreciable effect on systemic arterial pressure or heart rate. On the other hand, bilateral application to the NTS of the corresponding sense oligonucleotide (20 pmol, 20 nl) or an antisense cDNA (20 pmol, 20 nl) that targeted a different site of the c-.fos mRNA (5'-135 to 149-3') was ineffective. These results suggest that expression of the inducible c-fos gene in the NTS may represent an early step in the cascade of intracellular events that leads to long-term inhibitory modulation of baroreflex control of blood pressure.

Animals↗
PubMed1996

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

We evaluated the potential participation of endogenous brain galanin (GAL) 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., with 15 mg/kg/h i.v. infusion supplements). Our physiologic and pharmacologic results demonstrated that bilateral microinjection of GAL antiserum (1:20, 20 nl) into the nucleus tractus solitarii (NTS), the terminal site for baroreceptor afferent fibers, significantly attenuated the suppressive effect of LC on the BRR response. Pretreatment with the same amount of normal rabbit serum (1:20) or heat-inactivated GAL antiserum (1:20), on the other hand, was ineffective. Microinjection of GAL (100 pmol) into the bilateral NTS also appreciably depressed the BRR response. Histochemically, retrogradely labeled neurons were distributed in the LC following microinjection of fast blue into the NTS. Immunofluorescent staining further revealed that some of these fast blue labeled LC neurons also showed positive immunoreactivity to GAL. These results suggest that a direct galaninergic projection to the NTS may participate in the suppression of BRR response by the LC.

Amidines↗
PubMed1996

Concurrent elicitation of electroencephalographic desynchronization and penile erection by cocaine in the rat.

It is well-known from animal and human studies that, as a central nervous stimulant, cocaine induces electroencephalographic (EEG) desynchronization. Cocaine also purportedly increases sexual behavior as an aphrodisiac. Whether the effects of cocaine on EEG activity and penile erection are mechanistically linked, however, remains to be fully elucidated. We evaluated whether this link exists, based on simultaneous recording of EEG signals from the somatosensory cortex and intracavernous pressure (ICP, as experimental index for penile erection) in adult, male Sprague-Dawley rats. Under intraperitoneal chloral hydrate anesthesia (400 mg/kg, i.p.), both intravenous (i.v.) and intracavernous (i.c.) administration of cocaine (1.5 or 3.0 mg/kg, and 75 or 150 micrograms) dose-dependently induced discernible EEG desynchronization, as represented by a decrease in root mean square and an increase in mean power frequency values, and an increase in ICP. However, the same administration of cocaine in animals under pentobarbital sodium anesthesia (50 mg/kg, i.p.) failed to significantly affect EEG activity, despite an appreciable dose-dependent elevation in ICP. On the other hand, intracerebroventricular administration of cocaine (7.5, 15, or 30 micrograms) induced significant EEG activation without affecting ICP. I.c. application of papaverine (400 micrograms) elicited a discernible increase in ICP, but failed to evoke EEG desynchronization. These results suggest that the concurrent EEG desynchronization and penile erection elicited by cocaine may take place without a mutually causative relationship.

Animals↗
PubMed1996

Growth kinetics of colorectal adenoma-carcinoma sequence: an immunohistochemical study of proliferating cell nuclear antigen expression.

Tumorigenesis is a multistep process that begins with the abrogation of normal controls of cell proliferation. The authors examined the in vitro growth kinetics and compartment shift through the adenoma-carcinoma sequence of the human colon by determining the labelling indexes of proliferating cell nuclear antigen (PCNA) in normal mucosae (n = 10), adenomas (n = 88), and carcinomas (n = 20). Carcinoma cells had a significantly higher PCNA index than adenomas or control specimens (P = .0001). There also was a difference in the PCNA index between the histological subtypes of adenomas (P = .03), whereas no significant difference was observed for dysplastic grade, tumor size, or location (P > .1). Tubular and tubulovillous adenomas, adenomas with mild dysplasia, small (< 10 mm) adenomas, and proximally located adenomas revealed shift of cell proliferation toward the middle portion of the colonic glands. The PCNA in the villous, moderate or severe dysplastic, larger or distally located adenomas appeared to be diffuse (P = .04, 0.02, 0.07, and 0.06, respectively). In addition, the transitional mucosa neighboring carcinoma showed an elevation of the mean PCNA index together with an upward shift of cell proliferation compared with the controls (P = .03). These results suggest a stepwise increment of proliferating activity with compartment shift of the proliferating zone through the adenoma-carcinoma sequence. The information essentially supports contemporary understanding of the carcinogenic processes in the human colon.

Adenoma↗
PubMed1996

Implications of urinary basic fibroblast growth factor excretion in patients with urothelial carcinoma.

1. Angiogenesis occurs in response to wounding, and is of vital importance for tumour growth and metastasis. Basic fibroblast growth factor, a well-known angiogenic factor, has been suggested to be a urine marker for urothelial carcinoma. However, the relevance of its detection has not been evaluated in a large number of patients. 2. Immunoassay of basic fibroblast growth factor was performed on urine samples from different aetiologies of urothelial disorder. Expression of basic fibroblast growth factor in the corresponding tumour was correlated with the urine level. 3. The excretion of basic fibroblast growth factor (ng/g creatinine) was significantly elevated in both inflammatory and neoplastic urological diseases compared with normal individuals (P < 0.05), while it was normalized in tumour-free subjects (P < 0.01). Receiver operating characteristic plotting revealed a sensitivity of 40% for tumour diagnosis at the cut-off point of 3.29 ng/g creatinine. The sensitivity of the test in predicting tumour recurrence was only 14%. The basic fibroblast growth factor level in urine showed a positive association with increasing age of cancer patients (P = 0.02) and with tumour grading (P = 0.05). However, no important relationship was observed regarding tumour stage, size, number, shape or degree of local inflammatory reaction (P > 0.01). Pairwise analysis of the basic fibroblast growth factor level in urine and its expression in corresponding tumours did not reveal a conspicuous correlation (r = -0.097, P = 0.43). 4. Our results suggested that estimation of urinary basic fibroblast growth factor cannot be satisfactory as a tumour marker. The measurement may represent one of the tissue responses to injury or the host-tumour interactions. A longitudinal study is required to elucidate the role of basic fibroblast growth factor in order to select the appropriate treatment strategy for urothelial carcinoma.

Adult↗
PubMed1996

Spectral analysis of arterial pressure variability during induction of propofol anesthesia.

We studied the effect of continuous infusion of propofol on spectral components in systemic arterial pressure (SAP) signals in 35 consenting patients undergoing abdominal surgery. Anesthesia was induced with intravenous bolus administration of propofol (2.0 mg/kg), followed by infusion at either 5 mg.kg-1.h-1 (Group 1, n = 18) or 10 mg.kg-1.h-1 (Group 2, n = 17). Tracheal intubation was facilitated by administration of vecuronium (0.1 mg/kg). The SAP signal was subjected to off-line spectral analysis to obtain changes in power of the very low frequency (VLF; 0.00-0.08 Hz), low frequency (LF; 0.08-0.15 Hz), high frequency (0.15-0.25 Hz); and very high frequency (VHF; 0.80-1.60 Hz) components. Venous blood for the measurement of plasma concentration of propofol was collected at 5 min before bolus injection of propofol; at 5, 10, and 15 min after infusion of propofol; and immediately after endotracheal intubation. Infusion of propofol significantly decreased the total power of SAP spectrum in both groups, especially the VLF, LF, and VHF components at all intervals except postintubation. Immediately after tracheal intubation, patients in Group 1 showed a significant increase in mean arterial pressure when compared with those in Group 2 (118 +/- 5 mm Hg vs 102 +/- 5 mm Hg, P < 0.05). Similar change was also seen in the VLF component (7.4 +/- 0.7 mm Hg2 vs 4.4 +/- 0.5 mm Hg2, P < 0.05). After tracheal intubation, patients in Group 1 showed 15.7-, 3.3-, and 4.4-fold increase in the VLF, LF, and VHF components, respectively. There were 14.1-, 2.8-, and 2.8-fold increases in the respective components of the SAP signal in Group 2. At all intervals, the spectral components of SAP, however, did not correlate well with the plasma concentration of propofol in either group. These results suggest that spectral analysis of SAP signals may provide an alternative for assessing autonomic activities, such as the sympathetic response, to tracheal intubation during propofol anesthesia.

Abdomen↗
PubMed1996

Nitric oxide as a mediator of cocaine-induced penile erection in the rat.

1. The effect of local application of cocaine to the corpus cavernosum on intracavernous pressure (ICP), an experimental index for penile erection, was examined in Sprague-Dawley rats anaesthetized with chloral hydrate. The potential involvement of dopamine, noradrenaline or nitric oxide as the chemical mediator in this process, and the pharmacological action of cocaine as a local anaesthetic in the induced increase in ICP, were also investigated. 2. Intracavernous (i.c.) administration of cocaine (40, 80 or 160 micrograms) to the corpus cavernosum resulted in a dose-related increase in both amplitude and duration of ICP. 3. The elevation of ICP induced by cocaine (160 micrograms, i.c.) was not significantly influenced by prior injection into the corpus cavernosum of either the D1 or D2 dopamine receptor antagonist, R-(+)-SCH 22390 (250 pmol) or (-)-sulpiride (250 pmol). 4. Similarly, penile erection promoted by cocaine (160 micrograms, i.c.) was not appreciably affected by i.c. pretreatment with the alpha 1-, alpha 2-, or beta-adrenoceptor antagonist, prazosin (50 pmol), yohimbine (50 pmol) or propranolol (5 nmol). 5. Whereas lignocaine (4 mumol, i.c.) depressed penile erection induced by papaverine (400 micrograms, i.c.), local application of cocaine (160 micrograms) into the corpus cavernosum still elicited significant elevation in ICP in the presence of lignocaine or papaverine. 6. The increase in ICP induced by cocaine (160 micrograms, i.c.) was attenuated dose-dependently by prior cavernosal administration of the NO synthase inhibitor, N omega-nitro-L -arginine methyl ester (L-NAME, 0.5, 1 or 5 pmol) or NG-monomethyl-L-arginine (L-NMMA, 2.5, 5 or 10 pmol). The blunting effect of L-NAME or L-NMMA was reversed by co-administration of the NO precursor, L-arginine (1 nmol, i.c.). 7. Pretreatment by local application into the corpus cavernosum of methylene blue (2.5 mumol), an inhibitor of cytosolic guanylyl cyclase, antagonized cocaine-induced penile erection. 8. Direct i.c. administration of a NO donor, nitroglycerin (10 or 20 nmol), mimicked the local action of cocaine by promoting a significant increase in ICP. 9. It is concluded that cocaine may induce penile erection by increasing ICP via a local action on the corpus cavernosum. This process did not appear to involve either dopamine or noradrenaline as the chemical mediator, nor the pharmacological action of cocaine as a local anaesthetic. On the other hand, it is likely that initiation and maintenance of penile erection elicited by cavernosal application of cocaine engaged an active participation of NO and subsequent activation of guanylyl cyclase in the corpus cavernosum.

Anesthetics, Local↗
PubMed1996

Auto- and cross-spectral analysis of cardiovascular fluctuations during pentobarbital anesthesia in the rat.

We applied auto- and cross-spectral analysis of systemic arterial pressure (SAP) and heart rate (HR) signals to quantify the effects of pentobarbital sodium on short-term cardiovascular fluctuations in adult, male Sprague-Dawley rats. Intravenous administration of pentobarbital, delivered as a bolus injection (5, 10, or 20 mg/kg) or continuous infusion (10, 20, or 40 mg.kg-1.h-1), elicited only mild hypotension and tachycardia. This was accompanied by a dose-related depression of the very low (0-0.25 Hz) and low (0.25-0.8 Hz)-frequency components of both SAP and HR signals and high (0.8-2.4 Hz)-frequency component of HR signals. Cross-spectral analysis of SAP and HR signals during intravenous infusion of pentobarbital revealed a maintained coherence in the high-frequency range, together with a gradual and dose-related decrease in magnitude of transfer function and baro-receptor reflex sensitivity. Stable plasma concentration and all hemodynamic parameters were observed during 120 min of infusion at 20 mg.kg-1.h-1. Under this dosing condition, autonomic blockade by phentolamine, propranolol, or atropine still evoked discernible but differential reductions in the SAP and HR spectral components. Our data suggest that continuous intravenous administration of pentobarbital at 20 mg.kg-1.h-1 offers maintained anesthesia while preserving the capacity of cardiovascular regulation.

Anesthesia↗
PubMed1996

Participation of galanin in baroreflex inhibition of heart rate by hypothalamic PVN in rat.

We investigated the role of galanin (Gal) in the suppression of baroreceptor reflex (BRR) response by the paraventricular nucleus of the hypothalamus (PVN) in adult male Sprague-Dawley rats that were anesthetized with pentobarbital sodium. Electrical stimulation (10-s train of 1-ms rectangular pulses at 20-40 microA and 10-20 Hz) of, and microinjection of L-glutamate (1 nmol) into, the PVN significantly inhibited BRR response to transient hypertension induced by phenylephrine (5 micrograms/kg iv). Such a PVN-induced BRR suppression was appreciably antagonized by local administration of Gal antiserum (1:20), but not heat-inactivated Gal antiserum (1:20), to the nucleus tractus solitarius (NTS) bilaterally. Microinjection of Gal (100 pmol) into the NTS bilaterally also resulted in a Gal antiserum-reversible inhibition of the BRR response. Immunohistochemical results demonstrated that the distribution of Gal-containing neurons in the parvocellular subnucleus of the PVN overlapped substantially with the hypothalamic loci on which electrical or chemical activation elicited suppression of the BRR response that was significantly blunted by microinjection of Gal antiserum into the NTS. These results suggest that the PVN may participate in central cardiovascular regulation by suppressing the BRR response via galaninergic neurotransmission at the NTS.

Animals↗
PubMed1996

Transfer function analysis of ventilatory influence on systemic arterial pressure in the rat.

We evaluated the hypothesis that fluctuations in systemic arterial pressure (SAP) are under the influence of the respiratory pumping mechanism subjected to a modulatory action by the autonomic nervous system that is exerted primarily on the heart. Computer-generated broad-band mechanical ventilation (0-3 Hz) was applied to Sprague-Dawley rats that were anesthetized with ketamine and paralyzed with pancuronium. We observed excellent coherence between lung volume and SAP signals at ventilatory rates between 0.5 and 2.5 Hz; this coherence was unaffected by phentolamine, propranolol, atropine, bilateral vagotomy, or ventilatory stroke volume at 2-4 ml. Whereas bilateral vagotomy exerted no discernible effect, propranolol elicited a significant frequency-dependent (0.5-1.5 Hz) reduction in the magnitude of lung volume-SAP and lung volume-pulse pressure transfer functions. There was also a shift toward 0 degree for the phase of the lung volume-SAP transfer function over the same frequency range. We conclude that the high-frequency component (0.8-2.4 Hz) of the SAP spectrum may be generated by the respiratory pumping mechanism. However, the lower-frequency end of this mechanical influence is subjected to additional amplification by the autonomic nervous system, in which the beta-adrenergic system played a major role via its influence on the heart.

Adrenergic beta-Antagonists↗
PubMed1996

Clinical presentation and prognostic factors in sodium monofluoroacetate intoxication.

BACKGROUND: The diagnosis of sodium monofluoroacetate intoxication in humans is usually based on a history of ingestion and clinical findings. Although several previous reports have described the clinical course and outcome of patients who ingested this drug, prognostic indicators of short-term survival are not available. METHODS: A retrospective study of 38 consecutive cases of sodium monofluoroacetate poisoning at the National Cheng Kung. University Hospital, 1988-1993, to analyze the clinical findings and to predict mortality. RESULTS: Seven of 38 patients (18%) died. The most common symptom was nausea or vomiting (74%). The most frequent ECG finding was nonspecific ST-T and T wave abnormalities (72%). Hypocalcemia (42%) and hypokalemia (65%) were the common electrolyte abnormalities. The clinical and laboratory characteristics were compared for the survival and mortality groups. Significant differences in hypotension, respiratory rate, pulse rate, creatinine, potassium, elevated alanine aminotransferase, pH, PCO2, APACHE II score, and subjective respiratory distress were noted. Discriminant analysis identified hypotension, increased serum creatinine, and decreased pH as the most important predictors of mortality, with sensitivity of 86% and specificity of 96%. CONCLUSIONS: Hypotension and the early onset of metabolic acidosis and increased serum creatinine are associated with poor short-term survival. These prognostic variables can be useful in the care of patients with suspected sodium monofluoroacetate intoxication. It is suggested that all such patients should be observed intensively for at least 48 h.

Adult↗
PubMed1996

A new pre-S containing recombinant hepatitis B vaccine and its effect on non-responders: a preliminary observation.

Nine healthy subjects who had no detectable antibody response when initially vaccinated with hepatitis B vaccine (plasma derived and/or yeast derived) were revaccinated with three 20 micrograms doses of a new recombinant hepatitis B (HB) vaccine (SCI-B-VAC) derived from Chinese hamster ovary (CHO) cells and consisting of both the major S protein and the minor pre-S (S1 and S2) proteins of the viral coat. Seroconversion was successful in 78% of these non-responders after the second dose and just before the third vaccination. The geometric mean titres of the antiHBs were 587 iu/l one month after the course of vaccination. This study, though preliminary, indicated that pre-S containing CHO vaccine is effective in inducing antibody response in S-vaccine non-responders and also suggested that the added pre-S region in HBV vaccine helps antiHBs production. Frequency of HLA B46 and B15 were higher in non-responders compared to normal subjects (P = 0.04) supporting the possibility that genetic factors may modulate the immune response to HB vaccination.

Adult↗