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Biomedical subjects

K C Chang

Publications and source records attributed to K C Chang.

At least 19 recordsLinked to original sources

Standard anti-tuberculosis treatment and hepatotoxicity: do dosing schedules matter?

A nested case-control study was conducted in order to examine whether dosing schedules of standard pyrazinamide-containing anti-tuberculosis (TB) treatment (standard treatment) might affect hepatotoxicity. The present authors retrospectively identified all patients with hepatitis using biochemical criteria from a cohort of 3,007 clinic patients who commenced anti-TB treatment from January 1 to June 30, 2001. Each case with hepatitis between 1-9 weeks post-TB treatment was compared using conditional logistic regression analysis with two controls selected randomly from patients without hepatitis in the same period and matched by sex, age and standard treatment. Impacts of sex and age were examined by logistic regression analysis of cases and patients without hepatitis. Hepatitis occurred in 167 patients, of whom 96 qualified as cases. A conditional logistic risk model identified hepatitis B surface antigen carriage as the only risk factor (odds ratio (95% confidence interval (CI)) 1.8 (1.1-3.1)). Logistic regression analysis showed that sex was nonsignificant but ageing increased the odds of hepatitis. The risk of hepatitis increased from 2.6% (1.9-3.5%) to 4.1% (3.2-5.3%) as age exceeded 49 yrs. Dosing schedules in the first 9 weeks have little impact on hepatotoxicity. If patients at risk of both hepatitis and relapse receive standard treatment, daily dosing is preferable.

Adult↗

Inherited myopathy of great Danes.

A hereditary, non-inflammatory myopathy occurring in young great Danes with distinctive histological features in muscle biopsy specimens is reviewed. Onset of clinical signs is usually before one year of age and both sexes are affected. Clinical signs are characterised by exercise intolerance, muscle wasting, and an exercise-induced tremor. Although most affected dogs have a severe form of the disease, occasional dogs may have a less pronounced form and survive into adulthood with an acceptable quality of life. Litters containing affected puppies are born to clinically unaffected parents, and an autosomal recessive pattern of inheritance is likely. All recorded cases have had fawn or brindle coat coloration. Elevated serum creatinine kinase concentrations and spontaneous electrical activity in skeletal muscles are frequently found. While originally reported (Targett and others 1994) as a central core myopathy in this breed, the histochemical characteristics of the distinct cytoarchitectural structures differ from those of the well-characterised central core myopathy in human beings. In fact, these structures differ from any known myopathy in human beings and likely represents a unique non-inflammatory myopathy affecting dogs. Until this myopathy is characterised further, the name inherited myopathy in great Danes is suggested.

Animals↗

Phorbol ester up-regulates aldose reductase expression in A549 cells: a potential role for aldose reductase in cell cycle modulation.

Over-expression of aldose reductase (AR) has been observed in many cancer cells. To clarify the role of AR in tumor cells, we investigated the pathways mediating expression of the AR gene induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent tumor promoter. In A549 human lung adenocarcinoma cells, TPA elicited a dose- and time-dependent increase in AR mRNA level with an elevated enzyme activity. The TPA-induced increase in mRNA level and promoter activity of the AR gene was significantly attenuated in the presence of an inhibitor of protein kinase C, tyrosine kinase, or nuclear factor kappaB (NF-kappaB). TPA augmented the NF-kappaB-dependent gene transcription, indicating the involvement of NF-kappaB in this regulation. Accumulation of TPA-treated cells in S phase was almost completely abolished in the presence of ethyl 1-benzyl-3-hydroxy-2(5H)-oxopyrrole-4-carboxylate, an AR inhibitor. Taken together, TPA augmented the promoter activity of the AR gene via the activation of protein kinase and NF-kappaB. The inhibition of AR may assist in the chemotherapy of malignant tumors by suppressing the rapid growth of cancer cells.

Aldehyde Reductase↗

Tuberculin response in BCG vaccinated schoolchildren and the estimation of annual risk of infection in Hong Kong.

BACKGROUND: In Hong Kong there has been nearly universal neonatal BCG vaccination coverage since 1980. METHOD: 21 113 schoolchildren aged 6-9 years were skin tested with one unit of tuberculin (PPD RT-23) using the intradermal technique during a routine BCG revaccination programme. Information on sex, date of birth, date of tuberculin testing, and tuberculin reaction size at 72 hours was retrieved. The annual risk of tuberculous infection (ARTI) was estimated by three different approaches. RESULTS: Significantly higher tuberculin positive rates were found in girls and with increasing age at all commonly used cut-off points (5, 10, and 15 mm). Using a cut-off point of > or =10 mm and the formula 1- (1 - tuberculin positive rate)(1/age), the ARTI was estimated to be 1.93% (95% CI 1.84 to 2.03) for girls and 1.41% (95% CI 1.33 to 1.50) for boys. Using the differences in the tuberculin positive rate between the 6-7 year and 8-9 year age groups, the ARTI became 1.90% (95% CI 1.09 to 2.70) and 1.84% (95% CI 1.15 to 2.54) for girls and boys, respectively. When the prevalence of infection was estimated by locating a secondary peak of the tuberculin reaction distribution curve at 15 mm and assuming a symmetrical distribution of reaction sizes among those infected around this peak, the corresponding ARTI was much lower at 0.52% (95% CI 0.46 to 0.59) and 0.43% (95% CI 0.37 to 0.49) for girls and boys, similar to that estimated indirectly from the prevalence of disease. CONCLUSION: The ARTI as estimated by conventional methods was unexpectedly high among BCG vaccinated children and did not agree with that anticipated from the annual incidence of active disease. Further studies are needed to address the discrepancies, including the possible interaction between BCG and other environmental stimuli.

Age Factors↗

Structural characteristics of purified beta-conglycinin from soybeans stored under four conditions.

Four storage conditions including adverse conditions [84% relative humidity (RH), 30 degrees C], mild conditions (57% RH, 20 degrees C), cold conditions (4 degrees C), and uncontrolled ambient conditions were used for storing soybeans. The storage time was 9 months for the adverse conditions and 18 months for the other three conditions. Beta-conglycinin was purified and characterized with respect to its molecular properties. After storage under the adverse conditions, beta-conglycinin showed no significant changes in total sugar content, surface hydrophobicity, free SH and SS bonds, and amino acid composition within 6 months; however, it showed a significant decrease in surface hydrophobicity and a significant increase in total free SH and total SH including SS content after 6 months. Analysis of the secondary structure showed a significant increase in alpha-helix content, but a significant decrease in beta-sheet content after 3 months. For the other three conditions, no significant changes occurred to the structures of beta-conglycinin when compared to the control. The molecular mass of beta-conglycinin remained in the range of 199-212 kDa for all conditions during the entire storage periods.

Amino Acids↗

Socio-economic factors and tuberculosis: a district-based ecological analysis in Hong Kong.

BACKGROUND: Relatively little is known about the impact of socio-economic factors on tuberculosis in a metropolitan city with high disease incidence. METHOD: District-specific tuberculosis notification rates for 1995--1997 and 2000--2002 were indirectly sex- and age-adjusted and compared with the socio-economic characteristics in the 1996 by-census and 2001 census. RESULTS: The differences between the 18 districts persisted after 3-year averaging and indirect standardisation. Only the percentage of population born locally, the percentage of the population widowed or divorced and the percentage of households residing in rooms or bedsits were consistently associated with the standardised notification ratios (SNR) for both periods, the first being negatively so (all P < 0.05). In a combined analysis with a general linear model for both periods, birth in China, residence <7 years, speaking other Asian languages, being married and in a single household were also significantly associated with the SNR (all P < 0.05). Using a backward conditional approach, only local birth, being married, and residing in rooms or bedsits were independent predictors of SNR (all P < 0.05). There was no significant association between SNR and socio-economic indices on education, occupation, unemployment and income. CONCLUSION: Socio-economic factors other than simple poverty are affecting the district-specific tuberculosis rates in Hong Kong.

Female↗

Risk factors for defaulting from anti-tuberculosis treatment under directly observed treatment in Hong Kong.

OBJECTIVE: To identify risk factors for defaulting from anti-tuberculosis treatment. SETTING: Directly observed treatment in Hong Kong Government chest clinics. DESIGN: Defaulters were recruited from a cohort of tuberculosis patients registered from 1 January to 31 March 1999. Three controls per case, matched for age and sex, were selected randomly from the cohort. Patient factors, initial tuberculosis characteristics and treatment-related variables were collected by review of medical records. RESULTS: On matching 102 defaulters and 306 controls, a logistic risk model of default that considered patient factors, initial disease characteristics and treatment-related factors identified seven risk factors: current smoking (OR 3.00, 95% CI 1.41-6.39), past TB with default (OR 6.23, 95% CI 1.95-19.91), poor initial adherence (OR 117.21, 95% CI 13.52-1015.92), fair initial adherence (OR 11.02, 95% CI 2.15-56.43), unknown initial adherence (OR 6.59, 95% CI 3.47-12.49), treatment side effects (OR 13.30, 95% CI 3.23-54.79), and subsequent hospitalisation (OR 0.27, 95% CI 0.11-0.67). Its predictive power was 85%. Another model that considered only factors on registration for treatment gave a lower predictive power of 70%. CONCLUSIONS: Treatment default could be predicted fairly accurately by considering patient and treatment-related factors.

Antitubercular Agents↗

Development of a rapid titration method for predicting optimal coagulant concentration for filled tofu.

A rapid titration method was developed for predicting the optimal coagulant concentration for making filled tofu. Cooked soymilk (350 mL, 20 degrees C) in a 400 mL beaker was stirred by a magnetic stirrer to form a swirl. The quick-acting coagulant solution (20.0 Brix) was added into the soymilk at 1.0 mL/min. The swirl depth decreased when the soymilk viscosity increased as a result of increasing the concentration of coagulant in the soymilk. At a suitable stirrer speed, the swirl finally disappeared but the soymilk still maintained rotation, and then the swirl reappeared after around 1 min. The critical point of coagulant concentration (CPCC) was calculated on the basis of the volume of coagulant consumed to get the swirl to disappear. The influences of several factors on the CPCC were investigated, including coagulant addition rate, soymilk temperature, soymilk concentration, soymilk volume, stir bar length, and container size. For validation, 33 soybean samples were used to determine their CPCCs and make filled tofus. The results indicated that CPCC was a characteristic parameter of soymilk and could be used as an effective indicator for predicting optimal coagulant concentration.

Food Handling↗

Identification of microsatellites in expressed muscle genes: assessment of a desmin (CT) dinucleotide repeat as a marker for meat quality.

We investigated the presence of dinucleotide repeats (microsatellites) in a porcine skeletal muscle cDNA library. In total, microsatellites were found in nearly 4% of all muscle cDNA clones, of which CT- and TG-repeats were the most prevalent. We found a near full-length desmin cDNA clone with a CT-repeat sited downstream from its stop codon. From 44 commercially reared pigs, six allelic length polymorphisms were identified at this microsatellite locus (128, 131, 134, 135, 136, and 138 bp), whose desmin genotypes were associated with pH change after slaughter (P=0.031) and colour variation of meat (P<0.001 for hue, P<0.005 for lightness, and P=0.014 for b colour). Two of the genotypes (131/131 bp and 131/135 bp) were consistent with paler meat. This finding indicates the usefulness of the cDNA library approach to generate markers for marker-assisted selection and suggests that the desmin microsatellite could be a possible selection marker.

Animals↗

Cluster characterisation and temporal expression of porcine sarcomeric myosin heavy chain genes.

Members of the myosin heavy chain (MyHC) gene family are subjected to temporal regulation of gene switching during development. One strategy to the identification of cis-acting regulatory elements that are involved in temporal or fibre-type specific regulation is to undertake a comparative analysis of the MyHC gene family between the pig, an important target species, and other mammals, like human whose entire genome has been recently sequenced. Towards this end, we report here on the isolation, and characterisation of the porcine cardiac (MyHC slow/beta and alpha) and skeletal MyHC (embryonic, 2a, 2x, 2b and perinatal) gene clusters, and their structural comparisons with mouse and human clusters. The genome organisation of both clusters in the pig, human and mouse is conserved as having the same gene order, similar intergenic distances, and in the same head-to-tail orientation. For a period of pre-natal muscle growth, relative expression of MyHC isoforms, as determined by TaqMan real-time RT-PCR, correlated with the gene order in the skeletal MyHC cluster (embryonic > 2a > 2x > 2b) suggesting the possible presence of DNA elements on the same side as the MyHC embryonic gene that direct temporal regulation.

Alternative Splicing↗

Smoking and tuberculosis in Hong Kong.

OBJECTIVE: To study the relationship between smoking and tuberculosis in Hong Kong. METHOD: Indirect sex and age adjustment was used to compare the prevalence of ever smokers between a sample of 851 patients from the 1996 tuberculosis notification registry and the general population. The clinical characteristics of smokers and non-smokers were compared by stratified univariate analysis and multiple logistic regression. RESULTS: Tuberculosis patients were more likely to have smoked than population controls. The respective odds ratios for ever smoking between tuberculosis patients and population controls were 2.44 and 2.08 for males and females aged 16-64 (Mantel-Haenszel weighted OR = 2.40, P < 0.001), and 2.09 and 2.83 for males and females aged > or = 65 (Mantel-Haenszel weighted odds ratio = 2.19, P < 0.001). Male sex, age > or = 65, working at onset of illness, regular alcohol use, drug abuse and absence of contact history were associated with ever smokers (all P < 0.05). Ever smokers were more likely to have cough (OR 1.69), dyspnoea (OR 1.84), upper zone involvement (OR 1.67), cavity (OR 1.76), miliary lung involvement (OR 2.77), positive sputum culture (OR 1.43), but less isolated extrathoracic involvement (OR 0.31), even after controlling for the confounding background variables (all P < 0.05). CONCLUSION: There was a consistent association between smoking and tuberculosis. More aggressive lung involvement was also found among ever smokers.

Adolescent↗

Extracranial head and neck schwannomas: a review of 8 years experience.

Schwannomas of the head and neck are uncommon tumors that arise from cranial, peripheral or autonomic nerves. In this study we review a series of 52 cases of schwannoma originating in the head and neck region over an 8-year period. All the tumors were benign, with the exception of one malignant schwannoma. The age range of the patients studied was 13-76 years and there was a predilection for males. Twenty-five schwannomas occurred in the scalp, face and external ear canal, 9 in the oral or nasal cavity and 18 in the neck. Seven cases of neck schwannoma originating from the major nerve system were found in the parapharyngeal space, all of which were located in the post-styloid compartment. Cervical plexus schwannomas originated either in the peripheral nerves or in an unidentified area of the nervous system; seven tumors were found in the posterior triangle of the neck and two in the anterior triangle. Two of the tumors originating in the brachial plexus were located in the posterior neck and one in the anterior neck. Tumors originating in the vagus nerve or sympathetic chain were all located in the anterior triangle of the neck.

Adolescent↗

Respiratory insufficiency in a Chinese adult with mitochondrial myopathy.

Mitochondrial myopathy is an important but uncommon cause of respiratory insufficiency in adults. We report the first case of respiratory insufficiency associated with adult-onset mitochondrial myopathy seen in a Chinese adult in Hong Kong. The patient presented with peripheral oedema and shortness of breath over 2 to 3 days. There was a history of gradual progressive limb weakness over approximately 2 years, hypertrophic cardiomyopathy, intermittent diarrhoea, and weight loss. The diagnosis was made by skeletal muscle biopsy and molecular study, which revealed the A3243G point mutation.

Adult↗

Spontaneous nanoscale corrugation of ion-eroded SiO2: the role of ion-irradiation-enhanced viscous flow.

Grazing incidence x-ray scattering was used to determine the temperature and ion-energy dependence of nanoscale corrugations that form on an amorphous SiO2 surface eroded by Ar+ ions. The corrugation wavelength lambda* shows a nearly linear dependence on ion energy. Between room temperature and approximately 200 degrees C, lambda* depends weakly on temperature and above approximately 200 degrees C it shows an Arrhenius-like increase. Ion-assisted viscous relaxation in a thin surface layer is shown to be the dominant smoothing process during erosion; the rate of viscous smoothing scales as (lambda*)(-4).

Journal Article↗

Antithrombotic effects of YS-49 and YS-51--1-naphthylmethyl analogs of higenamine.

The antiplatelet and antithrombotic effects of YS-49 and YS-51--l-naphthylmethyl analogs of higenamine, which is a benzyl-tetrahydroisoquinoline alkaloid isolated from Aconitum japonicum (Ranunculaceae)--were investigated. YS-49 and YS-51 showed inhibitory activities to both human and rat platelet aggregation induced by ADP, collagen and epinephrine. They were more inhibitory to epinephrine-induced aggregation (IC(50); 3.4 and 1.7 microM of YS-49, and 6.0 and 6.3 microM of YS-51 to human and rat platelets, respectively) than ADP- or collagen-induced aggregation. The antithrombotic effects of YS-49 and YS-51 were also observed in both mouse acute thrombosis model and rat arterio-venous shunt (AV shunt) model. The oral administration of YS-49 and YS-51 (50 or 100 mg/kg) increased the recovery rates from the acute thrombotic challenge in mice and lowered the weight of thrombus formed inside the AV shunt tube in rats.

Alkaloids↗

Identification of genes associated with natural competence in Helicobacter pylori by transposon shuttle random mutagenesis.

To identify genes involved in DNA transformation, we generated 1500 insertion mutants of a Helicobacter pylori strain by transposon shuttle mutagenesis. All mutant strains were screened for their frequency of natural transformation. A total of 20 mutant strains were found to exhibit a significantly decreased transformation frequency. DNA sequencing revealed seven genetic loci, including the reported comB locus, HP0017 (a putative virB4 homologue) and five loci without database match (HP0015, HP1089, HP1326, HP1424, and HP1473) from the 20 mutants. Reknockout of HP1326 revealed no impairment in natural transformation, while the other 5 mutants showed the same defective in natural transformation. Mutation of HP0017 severely impaired natural transformation both chromosome and plasmid DNA. Slot blot analysis revealed that some noncompetent strains had decreased virB4 RNA expression levels compared with competent strains. Nineteen ORFs had decreased expression levels in virB4 knockout mutant by microarray. Therefore, our data indicate that HP0017 is a virB4 homologue and is essential in the natural competence of H. pylori. HP0015, HP1089, HP1424, and HP1473 genes could be also involved in natural transformation.

Blotting, Southern↗

GTPase stimulation in shrimp Ras(Q(61)K) with geranylgeranyl pyrophosphate but not mammalian GAP.

BALB/3T3 cells were transformed by transfection with DNA encoding the mutated ras(Q(61)K) from shrimp Penaeus japonicus (Huang et al., 2000). The GTPase-activating protein (GAP) in the cytosol fraction was significantly expressed and degraded, compared to untransformed cells on the western blot. To understand this in more detail, the interaction of the bacterially expressed shrimp Ras (S-Ras) with GAP was investigated using GAP purified from mouse brains. SDS-polyacrylamide gel electrophoresis revealed the monomers of the purified GAP to have a relative mass of 65,000. Since the purified GAP was bound to the Ras conjugated affinity sepharose column with high affinity and its GTP hydolysis activity upon binding with tubulin was suppressed, the purified enzyme was concluded to be neurofibromin-like. The purified GAP enhanced the intrinsic GTPase activity of the S-Ras, to convert it into the inactive GDP-bound form, in agreement with findings for GTP-bound K(B)-Ras in vitro. To compare the effects between isoprenoids and GAP on the GTP-hydrolysis of Ras, we applied the GTP-locked shrimp mutant S-Ras(Q(61)K) and GTP-locked rat mutant K(B)-ras(Q(61)K). Radioassay studies showed that geranylgeranyl pyrophosphate at microg level catalyzed the GTP hydrolysis of S-Ras(Q(61)K) and K(B)-ras(Q(61)K) competently, but not farnesyl pyrophosphate or the purified GAP. The present study provides the view that the geranylgeranyl pyrophosphate at carboxyl terminal CAAX assists GTP hydrolysis to Ras proteins probably in a manner similar to the substrate assisted catalysis in GTPase mechanism.

Animals↗