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Biomedical subjects

S H Chan

Publications and source records attributed to S H Chan.

At least 217 records · Page 12Linked to original sources

Differential effects of prazosin and yohimbine on fentanyl-induced muscular rigidity in rats.

Whereas muscular rigidity is a well-known phenomenon that is related to anesthesia induced by large doses of narcotic drugs, the precise underlying mechanism(s) remain to be fully elucidated. This study investigated the possible role of noradrenergic neurotransmission and the participation of alpha-adrenoceptors in this phenomenon. Male Sprague-Dawley rats, under ketamine-induced anesthesia (120 mg/kg, i.p.) and with proper control of respiration, body temperature and end-tidal CO2 were used. Intravenous administration of fentanyl (100 micrograms/kg) consistently caused a significant increase in the electromyographic (EMG) activity, recorded from both gastrocnemius and abdominal rectus muscles. This implied muscular rigidity was markedly antagonized by pretreatment with the specific alpha 1-adrenoceptor blocker, prazosin (50 or 250 micrograms/kg, i.v.). This antagonism occurred in spite of a high level of fentanyl in the plasma, as determined by radioimmunoassay. The specific alpha 2-adrenoceptor blocker, yohimbine (1.15 or 2.3 mg/kg, i.v.), on the other hand, not only failed to prevent fentanyl-induced activation of the EMG, but actually potentiated the response. It is concluded that noradrenergic neurotransmission, possibly originating from the locus coeruleus, may participate in the elicitation of muscular rigidity by fentanyl. Furthermore, this process may involve an excitatory action through alpha 1-, and an inhibitory action through alpha 2-adrenoceptors, in the spinal cord.

Animals↗

Fentanyl-induced muscle rigidity in unanesthetized and ketamine- or thiopental-anesthetized rats.

This study was undertaken to search for an alternative experimental model in the evaluation of fentanyl-induced muscle rigidity. Unanesthetized, spontaneously ventilating Sprague-Dawley rats, and rats anesthetized with either ketamine or thiopental whose ventilation was mechanically controlled, were studied. Intravenous administration of fentanyl (25, 50, or 100 micrograms/kg) caused an increase in electromyographic (EMG) activity in both unanesthetized and ketamine-anesthetized, but not in thiopental-anesthetized, animals. Muscle rigidity was more prominently manifested in the gastrocnemius muscle, when compared with the rectus abdominis muscle. Hypoxemia was exhibited during the course of rigidity by both spontaneously ventilating and ketamine-anesthetized rats, but not by thiopental-anesthetized animals. In addition, unanesthetized, spontaneously ventilating rats developed hypercarbia and respiratory acidosis. The authors suggest that, in addition to using unanesthetized animals, EMG activity in the gastrocnemius muscle of rats anesthetized with ketamine in whom ventilation is controlled may provide an alternative approach in the evaluation of fentanyl-induced muscle rigidity.

Anesthesia↗

Biotyping of Campylobacter pylori.

Ninety-one biochemical tests were done on each of 50 strains of Campylobacter pylori isolated from the gastric mucosa of patients with gastritis and peptic ulcers in Singapore. The API ZYM system distinguished three biotypes of C. pylori. The organism was found to be biochemically different from C. jejuni and C. coli. We propose a biochemical identification kit that would be of use in identifying and differentiating biotypes of C. pylori, and would distinguish them from C. jejuni and C. coli.

Bacterial Typing Techniques↗

HLA Bw46 and DR9 associations in Graves' disease of Chinese patients are age- and sex-related.

The HLA-A, -B antigens in 159 Chinese patients with Graves' disease were compared with those of 330 controls. The HLA-DR antigens of the patients were also studied in 100 normals. Analysis of the increased prevalence of Bw46, according to the sex and age of onset of disease of the patients, showed that the strong association of Bw46 resided with male patients (n = 58), Pc = 0.0000052, RR = 4.2. Although the frequency of Bw46 was also increased in female patients (n = 101), it was statistically not significant. For the DR9 antigens, the strong association with male patients was also observed, viz. Pc = 0.019, RR = 3.2. Males also had higher risks of Graves' disease if they had homozygous Bw46 at presentation. Further analysis by age of onset of disease revealed the segregation of significant association with Bw46 for the males at 1-19 yr, Pc = 0.0011, RR = 17.5 HLA associations (Bw46 and DR9) with Graves' disease in Chinese are observed primarily in males, especially those whose known ages of onset of the disease are between 1-19 yr (Bw46).

Adult↗

HLA and allopurinol drug eruption.

Strong HLA associations were found in Southern Chinese patients with skin eruptions due to allopurinol. The positive associations were with AW33 (Pc = 1.7 x 10(-5); relative risk [RR] = 15.0, 95% confidence limit 5.2-42.9) with B17/BW58 (Pc = 2.9 x 10(-9); RR = 46.3, 95% confidence limit 10.3-209.2). The negative association was with A2 (Pc = 8.3 x 10(-5), RR = 0). The findings suggested a genetic predisposition to cutaneous drug reactions.

Allopurinol↗

Relative predispositional effects (RPEs) of marker alleles with disease: HLA-DR alleles and Graves disease.

A method is described to reveal the relative predispositional effects (RPEs) (predisposing, protective, or neutral) of the HLA alleles or of any other marker system that is associated with a disease. When the disease is associated with two or more alleles of a locus, the RPE method identifies the associations sequentially according to their strength; thus the problem that a strong association with one allele can create misleading deviations in the frequencies of other alleles is alleviated. Using this method, we have examined the relative effects of HLA-DR alleles in susceptibility to Graves disease in the Caucasian population. The well-established positive association with DR3 was confirmed as the strongest effect. In addition, a negative association was found between DR5 and Graves disease. The reduced frequency of DR5 among patients is statistically significant and is not a result of the increase in DR3. Finally, when patients were divided according to the presence or absence of eye disease, the latter showed a significant increase in the frequency of DR4. With family data, linkage to HLA of Graves disease was established in both Caucasian and Chinese families by the sib-pair method.

Alleles↗

The hepatitis B immunization programme in Singapore.

A voluntary immunization programme to prevent perinatal transmission of hepatitis B virus (HBV) infection in Singapore was implemented on 1 October 1985 as an integral component of the national childhood immunization programme. Up to April 1988, a total of 68,845 mothers who attended government maternal and child health clinics were screened for the disease. Of these, 2432 (3.5%) were positive for hepatitis B surface antigen (HBsAg) and 904 (1.3%) for hepatitis B e antigen (HBeAg). Virtually all the babies born to carrier mothers completed the full immunization schedule; and in addition, those of HBeAg-positive mothers were given a dose of hepatitis B immunoglobulin at birth. The hepatitis B immunization programme was extended on 1 September 1987 to cover all newborns. About 90% of the 15,943 babies delivered in government institutions from September 1987 to April 1988 were immunized at birth, with the subsequent doses being administered at maternal and child health clinics at 4-6 weeks and 5 months later. More than 85% of the children given the full course of plasma-derived and yeast-derived hepatitis B vaccine from birth continued to have protective antibody to HBV two years after immunization. The programme is being closely monitored to assess the duration of immunity and the need for booster doses, while seronegative adults are also being encouraged to be vaccinated.

Adolescent↗

Screening for NPC.

This paper discusses the criteria of cancer screening in general and of nasopharyngeal carcinoma in particular. It also discusses the screening results in China and the strategy for screening of this cancer in Singapore.

Antibodies, Viral↗

Two monoclonal antibody lines directed against subunit IV of cytochrome oxidase: a study of opposite effects.

Two monoclonal lines of antibodies were isolated with specificities against the amino half of Subunit IV of beef heart cytochrome oxidase. The lines had nonoverlapping epitopes. Both bound to the matrix face of membranous oxidase, neither bound to the cytoplasmic face. One line (QA4/C4) stimulated electron transfer in soluble or membranous oxidase, while the other (QA4) inhibited that activity by both oxidase preparations. These effects on electron transfer activity were not altered by the inclusion or omission of detergent. ATP depressed the binding of either antibody to either soluble or membranous oxidase. In the absence of ATP, QA4/C4 stimulated electron transfer only in the high affinity phase of cytochrome c oxidation (with decreased KM and increased Vmax), causing slight inhibition in the low affinity phase (with decreased KM). In the presence of ATP, QA4/C4 abolished the high affinity phase, but did not alter the ATP influence on the low affinity phase. In the absence of ATP, antibodies of line QA4 abolished the low affinity phase, leaving a high affinity phase similar to that induced by ATP. In the presence of ATP, QA4 abolished the high affinity phase, leaving a low affinity phase similar to that seen with ATP alone. This behavior is consistent with the dissection of two catalytic sites for cytochrome c and more than one ATP affector site.

Adenosine Triphosphate↗

Reduction in baroreceptor reflex response by angiotension III and its modification by Ile7-angiotensin III and bestatin in the rat.

We evaluated the participation of endogenous brain angiotensin III (AIII) in central cardiovascular regulation, using the intracerebroventricular injection technique in Sprague-Dawley rats anesthetized with pentobarbital sodium (50 mg/kg, i.p.). AIII (100 pmol) promoted an elevation in systemic arterial pressure and a reduction in the baroreceptor reflex (BRR) response. Its specific antagonist, Ile7-AIII (100 nmol), and the aminopeptidase inhibitor, bestatin (200 nmol), on the other hand, augmented the response of the same reflex. The suppressive action of AIII (100 pmol) on the BRR was attenuated, and the enhancing effect of Ile7-AIII (100 nmol) was potentiated, however, when these two peptides were administered simultaneously with bestatin (200 nmol). All these events were significantly different from their controls during the first 10-15 min following injection, parallel to the time course of a discernible action of AIII on systemic arterial pressure. We discussed that the endogenous AIII in the central nervous system may participate in cardiovascular control by tonically inhibiting the BRR, in concert with other brain neuropeptides.

Angiotensin II↗

Comparative histopathology of resected bronchial cancers of women in Hong Kong and Japan.

Pathological findings relating to lung cancers removed surgically from women at the Kowloon Hospital (KH), Hong Kong, and the Cancer Institute Hospital (CIH), Japan (77 and 54 cases respectively), were examined in order to clarify possible differences between Hong Kong Chinese and Tokyo Japanese women. Adenocarcinoma was the most frequent subtype encountered in both hospitals, but the rate was higher in CIH (90.9% in CIH and 68.8% in KH); that of large-cell carcinoma was second in KH where the rate was higher (14.3% in KH and 0%, in CIH). A remarkable difference was observed in the location of adenocarcinomas; the percentages of central and peripheral types were 60.4% and 24.5% respectively in KH, but 4% and 96% respectively in CIH. The proportion of the central type (45.5%) was higher than that of the peripheral type (27.3%) in large-cell carcinomas of KH. The number of adenocarcinomas having a bronchiolo-alveolar pattern (which is observed more frequently in peripheral-type adenocarcinomas) was higher in CIH (50%) than in KH (17%). Tall columnar cells were observed more often in KH (43.1% in KH and 20.8% in CIH), and hobnail and cuboidal cells more often in CIH (31.4 and 80.4% respectively in KH, and 54.2 and 95.8% respectively in CIH). The difference may be explained by the frequent presence of tall columnar cells in the glands of central carcinomas, and hobnail and cuboidal cells in peripheral adenocarcinomas. The frequent occurrence of the central type of adenocarcinoma and large-cell carcinoma appears characteristic of the lung carcinomas removed from women in Hong Kong. This suggests the existence of exogenous causative agents for lung cancer in Hong Kong females.

Adenocarcinoma↗

Concomitant hypotensive and antinociceptive effects of guanabenz in conscious rats: involvement of nucleus reticularis gigantocellularis.

Subcutaneous administration of guanabenz (1, 2, 5, or 8 mg/kg) in conscious Sprague-Dawley rats exerted concomitant suppressive actions on systolic pressure (tail-cuff sphygmomanometric measurement) and pain responses (hot-plate algesio-metric assay) that varied both in degree (antinociception much greater than hypotension) and response pattern. Furthermore, both depressive effects were appreciably attenuated by bilateral lesions of the nucleus reticularis gigantocellularis in the medulla oblongata. It is speculated that separate subpopulations of neurons within this reticular nucleus may be involved in the expression of hypotension and antinociception by this amino-guanidine derivative.

Analgesia↗

Characterization of alpha-adrenoceptors in the nucleus reticularis gigantocellularis involved in the cardiovascular depressant effects of guanabenz in the rat.

The participation of alpha-adrenoceptors in the nucleus reticularis gigantocellularis in the hypotensive, negative inotropic and chronotropic effects induced by guanabenz, was examined in rats anesthetized with pentobarbital sodium (40 mg/kg, i.p.). Pretreatment with alpha-adrenoceptor antagonists yohimbine (10 micrograms), phentolamine (2.5 micrograms) and phenoxybenzamine (20 micrograms), which were injected bilaterally into the nucleus reticularis gigantocellularis, significantly antagonized the cardiovascular suppressant effects normally produced by systemic administration of guanabenz (10 micrograms/kg, i.v.). Pretreatment with prazosin (0.25 microgram) did not affect the vasodepressive, but significantly attenuated the bradycardic actions of guanabenz. The general trend of "antagonization potency" shown by the alpha-adrenergic blockers, against the cardiovascular effects of guanabenz, was in the order: yohimbine greater than phentolamine greater than phenoxybenzamine greater than prazosin. It is concluded that while the alpha 2-adrenoceptors in the nucleus reticularis gigantocellularis are more critically involved in the antihypertensive actions of guanabenz, the possibility exists that alpha 1-adrenoceptors may also participate, in part.

Adrenergic alpha-Antagonists↗

Correlated effects of guanabenz on single-neuron activity in the nucleus reticularis gigantocellularis, systemic arterial pressure and heart rate in the rat.

The simultaneous effects of guanabenz on the activity of single-neurons in the nucleus reticularis gigantocellularis of the medulla oblongata, systemic arterial pressure and heart rate were assessed in Sprague-Dawley rats, anesthetized with pentobarbital sodium (40 mg/kg, i.p.). Of the 35 arterial pressure-related neurons (neurons that temporally altered their spike rhythm subsequent to fluctuations in arterial pressure) which were evaluated in this reticular nucleus, 32 changed their discharge frequencies that exhibited a degree and time-course parallel to the hypotension promoted by the amino-guanidine compound (5, 10 or 20 micrograms/kg, i.v.). More importantly, these alterations neuronal activity preceded the occurrence of the induced vasodepression, signifying a causative relationship between the two events. Four of the 5 non-arterial pressure-related neurons in the gigantocellular reticular nucleus, on the other hand, manifested no basic modification in their spike frequencies in relation to the hypotension induced by guanabenz. These observations provided further support for the idea that the nucleus reticularis gigantocellularis participates actively in the cardiovascular suppressive actions of the aminoguanidine compound.

Action Potentials↗

Effect of recombinant gamma interferon on hepatocellular carcinoma cell lines.

The effects of recombinant gamma interferon (rIFN-gamma) were tested on 4 different hepatocellular carcinoma (HCC) cell lines PLC/PRF/5, HepG2, Hep3B and SK-Hep1. Exposure of these HCC cells to 100/ml of rIFN-gamma induced high levels of major histocompatibility complex (MHC) class I expression on their membrane, but not class II antigens. The enhancement of class I antigen synthesis occurs without a corresponding increase in synthesis of HBsAg by HBV genome positive PLC/PRF/5 and Hep3B cells. A 5 log dose of rIFN-gamma also did not trigger the integrated HBV genome into active replication as indicated by a lack of HBcAg and HBeAg synthesis. These results point to a possible role for the use of rIFN-gamma to enhance tumour cell recognition by the host immune system via the increased MHC class I expression.

Carcinoma, Hepatocellular↗