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Biomedical subjects

J T Lau

Publications and source records attributed to J T Lau.

At least 73 records · Page 4Linked to original sources

Suxamethonium myalgia: an ethnic comparison with and without pancuronium pretreatment.

The incidence of myalgia after suxamethonium was determined in 200 fit military male dental patients of European, Chinese and Nepalese descent. Half received pancuronium 1 mg and the other half received saline pretreatment on a randomised double-blind basis. The percentage incidence of postsuxamethonium myalgia after saline or pancuronium was found to be: Europeans 26%, 13%; Chinese 13%, 7%; Nepalese 20%, 14%. Although pancuronium reduced the incidence of myalgia by about 50% overall, these values were not significantly different from each other. The recovery of spontaneous ventilation following suxamethonium was quicker in the Europeans than in the Asians (p < 0.05). Pancuronium pretreatment also delayed the recovery of spontaneous ventilation and recovery from neuromuscular block (p < 0.05) but this was independent of ethnicity. The Europeans recovered from anaesthesia more quickly than the Asians. It was concluded that ethnicity affected recovery from suxamethonium and from anaesthesia but was not of clinical relevance to the incidence of myalgia in male Asians and Europeans.

Adolescent↗

An ethnic comparison of the sympathetic response to tracheal intubation.

The sympathetic response to orotracheal intubation was examined in five Europeans, 15 Chinese, and seven Nepalese male patients. Plasma adrenaline and noradrenaline concentrations were assayed using high performance liquid chromatography with colorimetric detection. There was a significant rise in noradrenaline concentrations following intubation in the Chinese and the concentrations decreased over 5 min. Similar increases were seen in the Europeans and Nepalese. The mean plasma catecholamine concentrations were comparable, which suggests that there are no ethnic differences in the groups studied. A wide interindividual variation of catecholamine concentrations was found.

Adolescent↗

n-butyrate reduces the expression of beta-galactoside alpha 2,6-sialyltransferase in Hep G2 cells.

n-Butyrate, a short chain fatty acid that is produced by colonic bacterial fermentation, is detectable in portal blood and induces differentiation in various human neoplastic cell lines. Earlier reports indicated approximately 20-fold induction in vitro by n-butyrate of the sialyltransferase that catalyzes terminal glycosylation of GM3 ganglioside in HeLa and colon cancer cells. We previously isolated a 1.3-kilobase cDNA for a human beta-galactoside alpha 2,6-sialyltransferase, for which N-linked glycoproteins are the acceptors. We report here that treatment of Hep G2 cells with 5 mM n-butyrate for 24 h reduced beta-galactoside alpha 2,6-sialyltransferase mRNA levels by approximately 90%. Reductions in mRNA level were followed by approximately 75 and approximately 90% reductions, respectively, in specific beta-galactoside alpha 2,6-sialyltransferase enzyme activity after treatment for 24 and 36 h with 5 mM n-butyrate. However, in contrast with earlier reports of enhanced ganglioside synthesis in response to n-butyrate treatment, incubation of Hep G2 cells with n-butyrate did not alter the ganglioside pattern as assessed by thin layer chromatography of lipids extracted from treated cells. Nuclear run-on reactions indicated that the rate of transcription of beta-galactoside, alpha 2,6-sialyltransferase was not altered by treatment with 5 mM n-butyrate for 24 h, but the effects of this treatment on cytoplasmic levels of beta-galactoside alpha 2,6-sialyltransferase mRNA were largely negated by co-treatment with actinomycin D or cycloheximide. Therefore, our results show that n-butyrate reduces expression of mature beta-galactoside alpha 2,6-sialyltransferase mRNA by post-transcriptional mechanisms.

Antigens, CD↗

Analysis of kidney mRNAs expressed from the rat beta-galactoside alpha 2,6-sialyltransferase gene.

beta-Galactoside alpha 2,6-sialyltransferase (SiaT-1), like other glycosyltransferases, is differentially expressed in rat tissues. Two distinct size classes of SiaT-1 mRNAs expressed in rat kidney are comprised of at least three SiaT-1 transcripts. One mRNA, RKE, represents the larger transcript class (4.7 kb) and predicts a polypeptide identical to the hepatic SiaT-1. In transfected Chinese hamster ovary (CHO) cells, RKE polypeptides exhibit hemi-perinuclear staining with a SiaT-1 antibody (Ab-267) that is consistent with Golgi localization. RKE transfectants display cell-surface alpha 2,6-sialic acid linkages as determined by lectin affinity staining. Two other mRNAs, RKA and RKB, are members of a smaller size class (3.6 kb) that comprise predominant SiaT-1 transcripts in rat kidney. Both RKA and RKB encode polypeptides that are missing the amino-terminal 232 residues, but retain 171 amino acids of RKE carboxy-terminal sequence information. A short, leucine-rich peptide present in the divergent amino-terminus of RKA has sequence similarity to the secretory signal domain of several eukaryotic secretory and cell-surface proteins. In transfected CHO cells, both RKA and RKB polypeptides display an immunostaining pattern that is distinct from that of the Golgi-associated SiaT-1 protein (RKE). Furthermore, RKA or RKB transfectants do not display alpha 2,6-sialic acid linkages on cell-surface glycoconjugates. Consistent with the expression of divergent SiaT-1 mRNAs in rat kidney, protein blot analysis of rat tissue homogenates with Ab-267 reveals that in addition to protein that co-migrates with hepatic SiaT-1, rat kidney expresses a unique size class of SiaT-1 proteins.

Amino Acid Sequence↗

Inter-ethnic differences in postoperative pethidine requirements.

A preliminary study of 24 hours' postoperative analgesia using a patient-controlled analgesia technique was undertaken in eight European and fourteen Asian adult patients. All patients had upper abdominal surgery and received weight-related doses of pethidine postoperatively via a Cardiff Palliator. Both groups had a similar degree of analgesia as assessed by visual analogue score but the Asian patients were more sedated in the postoperative period. The Asian patients made 24% fewer demands for analgesia and had a smaller mean (SD) pethidine consumption, 7.62 (2.04) mg.kg-1, compared with the European patients, 9.97 (2.14) mg.kg-1, (P less than 0.05) during the first 24 hours. Further research is necessary to determine whether the smaller requirement for analgesia in Asian patients is a result of pharmacokinetic or pharmacodynamic differences.

Adult↗

Assessment of glucose tolerance test criteria for diagnosis of diabetes in Chinese subjects.

OBJECTIVE: To examine and compare WHO diagnostic criteria for diabetes mellitus. RESEARCH DESIGN AND METHOD: The relationship between FPG and 2-h glucose are examined in 680 OGTTs with a quadratic regression model and ROC analysis. Simultaneous measurements of HbA1 and fructosamine are also compared with multiple linear regression. RESULTS: Two hundred eighteen subjects (32%) had 2-h glucose greater than or equal to 11.1 mM, of which only 86 had FPG greater than or equal to 7.8 mM. Only 2 subjects had FPG greater than 7.8 mM and 2-h glucose less than 7.8 mM. Of subjects with 2-h glucose less than 7.8 mM (n = 332), only 9 had FPG greater than 6.0 mM. From the quadratic model, the predicted FPG corresponding to 2-h glucose = 11.1 mM was 5.7 mM, whereas the predicted 2-h glucose corresponding to FPG = 7.8 mM was 15.2 mM. ROC analysis showed that, with 2-h glucose greater than or equal to 11.1 mM as indicating diabetes, an FPG of 5.6 mM gave an intersect for sensitivity and specificity of 87%. HbA1 and fructosamine correlated more closely with 2-h glucose and area under the OGTT curve than with FPG. CONCLUSIONS: Given that a 2-h glucose cutoff of 11.1 mM can be justified from other studies, our results suggest that the FPG cutoff of 7.8 mM when used for screening purposes should be reduced. At a suggested value of 7.0 mM, specificity remains 98.5%, whereas sensitivity increases to 57%.

China↗

Psychiatric morbidity in a Chinese primary school in Hong Kong.

The psychiatric morbidity among 718 Chinese primary school children from a lower middle social class area in Hong Kong was studied, using a two-stage design. The screening procedures included two parts, a multi-component scale and a battery of probing questions. The screening procedures achieved an overall sensitivity of 75% and a specificity of 97%. The findings on prevalence were: (i) a total prevalence of all definite psychiatric cases of 16.3%; (ii) prevalence according to diagnostic categories: emotional disorder, 8.8%; conduct disorder, 2.0%; mixed disturbance of emotion and conduct, 3.0%; hyperkinetic syndrome, 1.0%; hyperkinetic conduct disorder, 1.0%; and Gilles de la Tourette's syndrome, 0.4%; (iii) boys 2.7 times more affected than girls; (iv) emotional disorder much more common than conduct disorder, even in boys; and (v) the prevalence of borderline cases was 19.5%. The mean duration of morbidity for all definite cases was 41.7 months. About half of all definite cases were seriously impaired in one or more areas of functioning and the other half moderately impaired. These results were compared with findings obtained from studies done in other countries.

Affective Symptoms↗

Effects of alpha-interferon and prednisone on serum-soluble interleukin-2 receptor (sIL-2R) in chronic hepatitis B infection.

The level of serum-soluble interleukin-2 receptor (sIL-2R) was measured in 32 patients to investigate the effect of prednisone and alpha-interferon therapy on chronic hepatitis B virus infection. All the patients were seropositive for hepatitis B surface antigen and hepatitis B e antigen, with histological evidence of chronic persistent or chronic active hepatitis. Twenty-six patients received oral prednisone, followed by subcutaneous recombinant alpha-interferon, and six patients received multivitamin tablets and served as controls. After 4 wk of prednisone in reducing dosage, serum sIL-2R fell significantly from 673.6 +/- 52.9 U/ml to 584.8 +/- 39.4 U/ml (mean +/- SE, p less than 0.05). It rose to 733.4 +/- 45.7 U/ml (p less than 0.05) on the 4th wk of interferon, but returned to pretreatment level at completion of interferon. There was a significant correlation between serum sIL-2R and alanine aminotransferase levels (r = 0.36, p less than 0.001). The level of serum sIL-2R before treatment and its response to prednisone and interferon were not useful in predicting seroconversion of hepatitis B e antigen and anti-hepatitis B e.

Adolescent↗

Transcriptional regulation of the liver beta-galactoside alpha 2,6-sialyltransferase by glucocorticoids.

Hepatic expression of the beta-galactoside alpha 2,6-sialyltransferase is at least in part specified by circulatory glucocorticoids. In this report we use the glucocorticoid agonist, RU362, and the antagonist, RU486, to demonstrate the participation of the glucocorticoid receptor pathway in beta-galactoside alpha 2,6-sialyltransferase regulation. The existing pool of sialyltransferase mRNA is turned over with an approximate half-life of 13 h, and presence of dexamethasone does not alter this rate of degradation. By means of nuclear run-off assays and measurement of nuclear unprocessed transcripts we demonstrate that dexamethasone induction of beta-galactoside alpha 2,6-sialyltransferase mRNA in rat Reuber H35 cells is mediated by a transcriptional enhancement mechanism. The same initiation site is utilized for sialyltransferase transcription in both basal- and hormone-stimulated synthesis. Sialyltransferase sequences residing upstream of this transcriptional initiation point are used to control chloramphenicol acetyltransferase expression in fusion constructs following transient transfection into H35 cells to demonstrate the presence of a functional promoter. Although no element with similarity to the known GRE consensus sequence resides within this promoter region, chloramphenicol acetyltransferase expression under the control of the sialyltransferase promoter is subject to a low (1.6-fold) but reproducible induction in response to dexamethasone. Implications of this observation to glucocorticoid regulation are discussed.

Animals↗

Rat beta-galactoside alpha 2,6-sialyltransferase genomic organization: alternate promoters direct the synthesis of liver and kidney transcripts.

The rat beta-galactoside alpha 2,6-sialytransferase gene is differentially utilized by liver and kidney in the generation of mRNAs that predict substantially divergent polypeptides. In order to determine the biosynthetic relationship between these sialyltransferase mRNA isoforms, genomic sequences were isolated and analysed. Five exons that span at least 40 kb of DNA carry the coding information for the liver beta-galactoside alpha 2,6-sialyltransferase protein. An additional exon contains only sequences for the 5'-untranslated leader of the liver mRNA. In contrast, the predominant kidney mRNAs from this gene share only three coding exons that specify the carboxyl terminal 42% of the liver sialyltransferase protein sequence. In addition, these kidney mRNAs contain information from two other exons that comprise the 5' divergent region of these transcripts. Primer extension and S1 nuclease protection analysis demonstrate that the hepatic and kidney specific mRNAs are transcriptionally initiated at different sites within the sialyltransferase gene. While the hepatic sialyltransferase mRNAs are transcribed from the first exon, the kidney transcripts are initiated from a site within the third intron. Genomic regions upstream of both transcriptional initiation sites can regulate expression of the bacterial chloramphenicol acetyltransferase gene in transiently transfected L cells. Together, the data implicate multiple promoters as a principle mechanism in the generation of kidney and liver gene product diversity in sialyltransferase expression.

Animals↗

Isolation and characterization of a partial cDNA for a human sialyltransferase.

A probe generated from the coding sequence of the rat hepatic beta-galactoside alpha 2,6-sialyltransferase was used to screen a human cDNA library constructed of human submaxillary gland mRNA lambda gt-11. We report the isolation and characterization of a human cDNA, HSM-ST1, that is putatively the human homolog of the beta-galactoside alpha 2,6-sialyltransferase. The largest human clone contains a 1.3 kb cDNA insert and is predicted to encompass 75% of the coding sequence as well as a small portion of the 3' untranslated region. Comparative analysis of this insert with the rat hepatic alpha 2,6-sialyltransferase sequence indicates 79% nucleotide similarity between the two sequences in the predicted coding region. On the amino acid level, the degree of conservation is 86%. Substantial sequence similarity is observed in the 3'-untranslated region between the rat and human sequences as well. S1 nuclease analysis was performed to demonstrate the expression of HSM-ST1 transcripts in the human hepatoma cell line, HepG2, and in the human colonic adenocarcinoma cell lines, LS174T.

Amino Acid Sequence↗

Tissue-specific expression of beta-galactoside alpha-2,6-sialyltransferase. Transcript heterogeneity predicts a divergent polypeptide.

The beta-galactoside alpha-2,6-sialyltransferase represents a member of a family of sialyltransferases which catalyze the terminal addition of sialic acid to maturing carbohydrate chains. We surveyed rat tissues using cDNA probes complementary to coding and noncoding domains of the rat liver alpha-2,6-sialyltransferase. In addition to the expected differences in the level of sialyltransferase mRNA among the tissues, there were dramatic qualitative differences as well. Hepatic sialyltransferase probes hybridize to mRNAs of varying size on Northern blots. A tissue-dependent pattern of expression of these transcripts is documented. Evidence is presented that the multiple transcripts are generated from a common gene sequence. At least one instance of alternate splicing in the generation of the kidney sialyltransferase transcripts is predicted by S1 nuclease analysis. We report the isolation of a rat kidney cDNA clone, RKA, that substantiates this tissue-specific alternate splicing event. The RKA insert, although less than full-length, apparently encodes a polypeptide divergent from the reported hepatic alpha-2,6-sialyltransferase (1). RNA blot analysis indicates that the RKA-type transcripts represent a significant proportion of sialyltransferase RNA in rat kidney. Another class of kidney cDNA clones, RKE, is colinear with the hepatic sialyltransferase sequence. RNA blots probed for the divergent and common regions suggest that complex processing pathways are operative in the tissue-specific expression of sialyltransferase mRNA.

Amino Acid Sequence↗

Regulation of beta-galactoside alpha 2,6-sialyltransferase gene expression by dexamethasone.

The hepatic acute phase response is accompanied by increased levels of Gal beta 1-4GlcNAc alpha 2,6-sialyltransferase activity in liver and in circulation. Previous studies suggested that cytokines and glucocorticoids mediate the induction of this sialyltransferase activity. In this study the regulation of sialyltransferase expression by dexamethasone in H35 rat hepatoma cells is assessed by Northern hybridization and enzyme activity assays. Exposure of H35 cells to 1 microM dexamethasone for 24 h causes a 3-4-fold enrichment of sialyltransferase mRNA and a corresponding increase in enzymatic activity. The induction of sialyltransferase mRNA begins within 3 h of dexamethasone treatment and reaches a plateau within 24 h. Sialyltransferase mRNA induction is dose dependent; the minimum concentration of dexamethasone necessary for induction is 10(-8) M, and induction was maximal at 10(-6) M. Induction is sensitive to actinomycin D, suggesting that regulation may be exerted by altering the rate of mRNA synthesis. Puromycin and cycloheximide are ineffective in blocking induction, suggesting that de novo protein synthesis is not required for induction. Finally, dexamethasone alone is sufficient for maximum induction of sialyltransferase mRNA. In contrast, maximal induction of alpha 1-acid glycoprotein, a well studied hepatic acute phase reactant, requires both dexamethasone and cytokines, implying that different pathways exist for the induction of participants in the acute phase response.

Animals↗

Sequences that confer beta-tubulin autoregulation through modulated mRNA stability reside within exon 1 of a beta-tubulin mRNA.

Synthesis of alpha- and beta-tubulin is controlled in animal cells by a novel autoregulatory mechanism: the concentration of unpolymerized subunits specifies the level of tubulin mRNAs. Using transient DNA transfection, we have localized the sequences that identify a beta-tubulin RNA as a substrate for autoregulation. Insertion of as few as 106 nucleotides (57 bases of 5' untranslated region and 49 coding nucleotides) from a beta-tubulin gene into a thymidine kinase gene is sufficient to make expression of the resultant chimeric RNA regulated as if it were an authentic beta-tubulin mRNA. Furthermore, all 5' untranslated region sequences can be deleted without disrupting regulation. We conclude that this novel autoregulatory pathway is specified by cytoplasmic events that modulate mRNA stability through sequences lying within the first 16 translated codons of a beta-tubulin mRNA.

Animals↗

Diagnosis of peptic ulcer in children: the past and present.

The problem of diagnosis of peptic ulcer in children was analysed in a series of 50 consecutive cases. Atypical symptomatology occurred frequently and resulted in errors in diagnosis in six instances: perforated ulcer was misdiagnosed as appendicitis in five and bleeding ulcer was misdiagnosed as Meckel's diverticulitis in one. Barium meal was the investigation employed in earlier years but had proven unsatisfactory, being incorrect in four out of 22 examinations. Fiberoptic endoscopy was introduced in recent years and having achieved correct diagnosis in 20 patients with no errors, has established itself as the choice of investigation.

Adolescent↗

Hirschsprung's disease and mongolism.

Two mongoloid patients with Hirschsprung's disease are presented. Mongoloid children who have severe constipation should be investigated for Hirschsprung's disease.

Adult↗