Biomedical subjects
Publications and source records attributed to H Y Chang.
We report a case of a 44-year-old female thyroid cancer patient with a pituitary tumour. 131I whole body scanning showed a change of chest uptake from a unilateral crescent uptake to a bilateral full breast uptake pattern. Hyperprolactinaemia and a pituitary tumour were diagnosed as a result of observing the 131I breast uptake.
Caucasians and Asians are among those with the highest risk for involutional osteoporosis. To obtain accurate data about the prevalence of osteoporosis or osteopenia in different age groups, a large epidemiological study is necessary. Quantitative ultrasound (QUS) of bone is a promising technique in assessing bone microarchitecture in addition to bone mass. This study had two aims. The first was to establish bone mineral density (BMD) using QUS in subjects with no obvious disease undergoing routine health examination. The second was to determine risk factors for osteoporosis in Taiwan in order that better prevention and treatment measures may be provided for these patients. A prospective study of the risk factors for fracture was conducted in the health examination division of Chang Gung Medical Center in Linkou, Taiwan, from January 1996 to December 1997. Broadband ultrasound attenuation of the right heel was measured with an achilles bone densitometer (Lunar, Nauheim, Germany). A total of 16,862 subjects were examined, including 9,314 women (mean age 51.5+/-11.7 years) and 7,548 men (mean age 51.1+/-12.1 years). The incidence of osteoporosis in all subjects increased from 1.13% in the 21--30-year-old age group to 54.55% in those over 80 years of age. 12.02% of the subjects had osteoporosis and 34.45% had osteopenia. From multivariate analysis, bone density evaluated by QUS showed a relationship with age, gender, body mass index, waist/hip ratio, smoking and frequency of exercise. In conclusion, BMD evaluated by QUS is not found to be higher in Taiwan than elsewhere. The role of QUS in predicting fractures in Taiwan requires further investigation.
A 34-year-old male laboratory worker suffered from asthenospermia and fertility problems. He was suspected of having been exposed to solvents used at work due to a malfunction of the ventilation system in his laboratory from August 1996 to April 1997. A laboratory walk-through and air and bulk sample collection were performed to determine the possible exposure levels of chemical hazards in his job. The scenario was reconstructed to simulate the worker's previous exposure during the ventilation shutdown period. It was found that the worker was possibly exposed to chloroform at levels of 10 or 50 times higher than the permissible exposure limit or the threshold limit value of 2 hr/day, 5.5 days/week, and 4.25 weeks/month for 8 months. Because chloroform is known to be spermatotoxic, the possibility of chloroform causing the worker's asthenospermia cannot be ruled out. Further study on spermatotoxicity of chloroform is warranted.
The aim of this study was to assess the effect of the long-term different diabetic therapies on the plasma leptin level in type 2 diabetic subjects. We measured plasma leptin, body fat and fasting plasma insulin in 96 type 2 diabetic male subjects. They had received the same treatment regimen for more than one year (3.5 +/- 2.3 years, mean +/- SD) and were weight-stable over the previous three months. The distribution was as follows: diet control group: 32, oral hypoglycemic agent (OHA) group: 32, and insulin group: 32. The results showed that the plasma leptin level of the different therapy groups was all positively correlated with body fat. The fasting insulin levels were significantly higher (p < 0.0001) in the insulin group than those in the other two groups. The fasting insulin of the OHA group was also greater than that of the diet group but was not statistically significant. The leptin concentrations were significantly higher in the insulin group (p < 0.001) and OHA group (p = 0.0082) than that in the diet group. The leptin concentrations of insulin group were also significantly higher (p = 0.0021) than that of the OHA group. Stepwise multiple regression analysis revealed that the significant differences in the leptin level of whole group was mainly affected by fasting insulin (p < 0.0001), followed by fat percentage (p = 0.001), fat distribution (p = 0.009) and fasting sugar (p = 0.02), whereas there was no association of leptin with age, height, glycosylated hemoglobin A1c, lipid, or blood pressure. We concluded that long-term different diabetic therapies may affect the plasma leptin level, which is mediated mainly by insulin changes. This insulin effect is independent of body fat and may be superior to the fat effect on plasma leptin in the type 2 diabetic patients.
The control of spasticity is often a significant problem in the management of patients with spasticity. The aim of this study was to evaluate the effect of a single session of prolonged muscle stretch (PMS) on the spastic muscle. Seventeen patients with spastic hemiplegia were selected to receive treatment. Subjects underwent PMS of the triceps surae (TS) by standing with the feet dorsiflexed on a tilt-table for 30 minutes. Our test battery consisted of four measurements including the modified Ashworth scale of the TS, the passive range of motion (ROM) of ankle dorsiflexion, the H/M ratio of the TS, and the F/M ratio of the tibialis anterior (TA). The results indicated that the passive ROM of ankle dorsiflexion increased significantly (p < 0.05) compared to that before PMS treatment. Additionally, PMS reduced motor neuron excitability of the TS and significantly increased that of the TA (p < 0.05). These results suggest that 30 minutes of PMS is effective in reducing motor neuron excitability of the TS in spastic hemiplegia, thus providing a safe and economical method for treating stroke patients.
OBJECTIVE: To evaluate the prevalence of hyperuricemia in Taiwan. METHODS: A multi-stage stratified sampling scheme was used in Nutrition and Health Survey, which was conducted in Taiwan between 1993 and 96. Complete biochemical and questionnaire data for 2754 males and 2953 females aged 4 years and older were included in the analysis. The colorimetric enzymatic method was used to measure plasma uric acid in fasting blood samples. Information on self-reported, physician-diagnosed gout was also obtained. RESULTS: The uric acid values of males were found to reach a peak between the ages of 13 and 18 and decrease slightly after 18. The uric acid values of females were stable before the age of 18, decreasing slightly between 19 and 44 years, and increasing in the mid to older age groups (> or = 45 years). Twenty-six percent of adult males (> or = 19 years) and 22% of older males (> or = 45 years) either had hyperuricemia (serum uric acid > 458.0 microM or 7.7 mg/dl) or were taking medication for it. Seventeen percent of adult females and 23% of older females either had hyperuricemia (serum uric acid > 392.57 microM or 6.6 mg/dl) or were taking medication for it. Both adult males and females in mountainous areas, who were primarily aboriginal, had the highest prevalence of hyperuricemia (> 50%) among the 7 survey areas. Mean body mass index (BMI), alcohol consumption, and prevalence of gout were among the highest in mountainous people compared to all included in the study. Multivariate analysis showed that mountainous area, age and BMI are important factors associated with hyperuricemia in males, whereas mountainous area, Class II townships, and BMI are the factors associated with hyperuricemia in females. CONCLUSIONS: We found a high prevalence of hyperuricemia in Han Chinese in Taiwan despite a lack both of obesity and high alcohol consumption. Mountainous people (mainly aborigines) in Taiwan have an even higher prevalence of hyperuricemia, which cannot be completely explained by obesity and alcohol consumption. Genetic components and other environmental factors may have contributed to this pattern of hyperuricemia.
BACKGROUND AND PURPOSE: In outcome analyses of clinical trials and mortality follow-up studies, the underlying cause of death (UCOD) is commonly assigned either by official coders or by a panel of physicians. We evaluated the validity of UCOD assigned by official coders by comparison with the assignments of a panel of physicians who reviewed the available medical records of the deceased. METHODS: The comparisons focused on deaths occurring from October 1995 through June 1998 in a series of residents in a veterans home. Because of limited resources, only the first 104 deaths that occurred during the study period were included. Agreement rate, sensitivity, specificity, and kappa statistics were calculated to assess the consistency of coder versus physician panel assignment of UCOD by selected main causes of death. For 32 of the 104 deaths, the panel concluded that the information obtained from medical records was insufficient to determine the UCOD, and the following analyses were confined to the other 72 deaths. RESULTS: For the 72 deaths considered by the panel to have sufficient information to determine UCOD, all four physicians agreed on a single UCOD in 50 (69%) cases, while three or four agreed in 66 (92%) cases. A consensus was reached in cases with disagreement. The two procedures completely agreed in 40 (56%) of the deaths. For general category UCOD, the kappa value was high for cancer (0.83) and cardiovascular disease (CVD, 0.73) but only moderate for pulmonary disease (PD, 0.60). When the UCOD assigned by the panel was used as the gold standard, official coders showed relatively low sensitivity for correct determination of UCOD in cases of CVD (0.76) compared with cancer (0.86) and PD (0.80). CONCLUSIONS: Given the high inter-physician consistency and the relatively low sensitivity of official coders in assigning CVD as the UCOD, we conclude that the use of clinical review panels would provide more accurate UCOD assignments for use in outcome analyses in mortality follow-up studies and clinical trials in Taiwan.
Rhodopsin is essential for photoreceptor morphogenesis; photoreceptors lacking rhodopsin degenerate in humans, mice, and Drosophila. Here we report that transgenic expression of a dominant-active Drosophila Rho guanosine triphosphatase, Drac1, rescued photoreceptor morphogenesis in rhodopsin-null mutants; expression of dominant-negative Drac1 resulted in a phenotype similar to that seen in rhodopsin-null mutants. Drac1 was localized in a specialization of the photoreceptor cortical actin cytoskeleton, which was lost in rhodopsin-null mutants. Thus, rhodopsin appears to organize the actin cytoskeleton through Drac1, contributing a structural support essential for photoreceptor morphogenesis.
CoA-independent transacylase activities generating alkylacylglycerophosphocholine (AAGPC) from alkylglycerophosphocholine (1-alkyl GPC) were considerably enriched in neuronal nuclei isolated from rabbit cerebral cortex. Specific nuclear transacylation activities were 13 times the corresponding microsomal values. Several lysophospholipids, notably 1-acyl glycerophosphocholine (1-acyl GPC), 1-alkenyl GPC and 1-alkenyl GPE (1-alkenyl glycerophosphoethanolamine) inhibited the transacylation of 1-alkyl GPC. The inhibitory effects of 1-acyl GPC were seen in the presence of MAFP (methyl arachidonoylfluorophosphonate) or free oleate, compounds that inhibit neuronal nuclear lysophospholipase. When neuronal nuclei were preincubated with 1-alkyl GPC, the radioactive AAGPC product served as donor in transacylation reactions, to generate 1-alkyl GPC. In these nuclear reactions, 1-palmitoyl GPE and 1-palmitoyl GPC appeared to be poor acceptor substrates, when compared with corresponding 1-alkyl and 1-alkenyl analogues. The presence of free oleate or MAFP in the reactions containing 1-acyl GPC boosted the release of 1-alkyl GPC from AAGPC. These observations are of particular relevance to brain ischemia in which lysophospholipid, free fatty acid, and platelet-activating factor (PAF) levels rise dramatically. PAF can be made by the nuclear acetylation of 1-alkyl GPC, which is formed by nuclear transacylation mechanisms. Yet transacylase also removes 1-alkyl GPC, and thus this enzyme activity can regulate 1-alkyl GPC availability. Our observations indicate that lysophospholipids promote the formation of 1-alkyl GPC from nuclear AAGPC via transacylation, while free fatty acid likely prolongs the lifetime of 1-acyl lysophospholipids substrates by lysophospholipase inhibition. Similarly, once 1-alkyl GPC is formed, other lysophospholipids effectively compete with this 1-alkyl analogue and reduce its conversion back to AAGPC by transacylation. Free oleate, in this case, sustains 1-acyl lysophospholipid inhibitors of 1-alkyl GPC transacylation. Thus the cycle of transacylation may favour 1-alkyl GPC formation during ischemia, increasing levels of 1-alkyl GPC for nuclear acetylation reactions and PAF formation. The nuclear generation of PAF is of considerable importance as PAF can play regulatory roles in transcription events associated with inflammation.
Inducible nitric oxide synthase (iNOS) is a molecule of great interest, given the numerous biological activities of nitric oxide and the documented expression of iNOS in several CNS pathologies. There also appears to be species-dependent regulation of iNOS expression as well as CNS-specific regulation. In this study, we have examined cultures of cytokine-activated primary human astrocytes as a model system with which to study the mechanisms of iNOS regulation in human CNS. As one of the major functions of astrocytes is spatial buffering of K+ ion, we examined the effect of high extracellular KCI on astrocyte iNOS expression. The results demonstrate that KCI at 25-75 mM potently inhibits astrocyte nitrite production stimulated by interleukin-1 (IL-1)/interferon-gamma (IFNgamma). In addition, several potassium channel inhibitors such as CsCl, tetraethylammonium, and 4-aminopyridine as well as nigericin inhibited astrocyte iNOS expression induced by IL-1/IFNgamma. These results demonstrate a novel role for astrocyte potassium channel activity in modulation of astrocyte function. They further suggest neural-specific mechanisms for glial iNOS regulation.
BACKGROUND: In Taiwan, distributions of body composition are usually generated for children, adolescent, and middle-aged groups. This study describes three anthropometric measures (i.e., height, weight, and body mass index [BMI]) of elderly persons in Taiwan. METHODS: The data was derived from a prospective cross-sectional, population-based geriatric survey funded by the National Department of Health in Taiwan in 1991. A total of 2,600 subjects were successfully evaluated. A descriptive analysis was performed to generate distributions of height, weight, and BMI of elderly persons. Based on these descriptive data, the prevalence of overweight and obesity was estimated, and a cross-national comparison on the prevalence of obesity was made. RESULTS: Age-group-specific means and standard deviations for height, weight, and BMI of Taiwanese elderly persons were presented. By gender, the elderly men were taller and heavier than the elderly women: however, the women had a higher mean value of BMI (kg/m2). The prevalence of overweight was 27.3% in men and 34.9% in women; the prevalence of obesity was 3.2% in men and 6.4% in women. The prevalence of obesity for the elderly men and women in Taiwan was lower than in Kuwait, Sweden, the United States, and the Native Americans, but higher than in Japan. CONCLUSIONS: The comparison indicates cross-cultural differences existing in the prevalence of obesity, which may be due to aging, nutritional status, or environmental factors. For future research, the relationship of anthropometric data to socioeconomic status and behavioral factors will be examined.
Klebsiella pneumoniae is a common cause of septicemia and urinary tract infections. The PCR-supported genomic subtractive hybridization was employed to identify genes specifically present in a virulent strain of K. pneumoniae. Analysis of 25 subtracted DNA clones has revealed 19 distinct nucleotide sequences. Two of the sequences were found to be the genes encoding the transposase of Tn3926 and a capsule polysaccharide exporting enzyme. Three sequences displayed moderate homology with bvgAS, which encodes a two-component signal transduction system in Bordetella pertussis. The rest of the sequences did not exhibit homology with any known genes. The distribution of these novel sequences varied greatly in K. pneumoniae clinical isolates, reflecting the heterogeneous nature of the K. pneumoniae population.
Klebsiella pneumoniae has emerged as the leading liver abscess pathogen in Taiwan, with the percentage rising from 30% in the 1980s to over 80% in the 1990s. Most of the patients with K. pneumoniae liver abscess are diabetic and without biliary tract disease. Some patients develop serious extrahepatic complications such as endophthalmitis, meningitis, lung abscess, and necrotizing fasciitis. Pulsed-field gel electrophoresis (PFGE) was used for cluster analysis of 96 isolates from patients with liver abscess and 60 isolates from patients with other diseases. A total of 136 PFGE types were identified. Among the 96 liver abscess-associated isolates, 60 (62.5%) were classified in major cluster A. Cluster A included 41 PFGE types (types 1 to 41) which had a genetic similarity of at least 72.4% +/- 9.4%. The PFGE patterns of cluster A strains are so similar that they could have originated from the same ancestor. This study demonstrates that cluster A plays an important role in the high incidence of K. pneumoniae liver abscess in Taiwan.
Caspases are a large family of evolutionarily conserved proteases found from Caenorhabditis elegans to humans. Although the first caspase was identified as a processing enzyme for interleukin-1beta, genetic and biochemical data have converged to reveal that many caspases are key mediators of apoptosis, the intrinsic cell suicide program essential for development and tissue homeostasis. Each caspase is a cysteine aspartase; it employs a nucleophilic cysteine in its active site to cleave aspartic acid peptide bonds within proteins. Caspases are synthesized as inactive precursors termed procaspases; proteolytic processing of procaspase generates the tetrameric active caspase enzyme, composed of two repeating heterotypic subunits. Based on kinetic data, substrate specificity, and procaspase structure, caspases have been conceptually divided into initiators and effectors. Initiator caspases activate effector caspases in response to specific cell death signals, and effector caspases cleave various cellular proteins to trigger apoptosis. Adapter protein-mediated oligomerization of procaspases is now recognized as a universal mechanism of initiator caspase activation and underlies the control of both cell surface death receptor and mitochondrial cytochrome c-Apaf-1 apoptosis pathways. Caspase substrates have bene identified that induce each of the classic features of apoptosis, including membrane blebbing, cell body shrinkage, and DNA fragmentation. Mice deficient for caspase genes have highlighted tissue- and signal-specific pathways for apoptosis and demonstrated an independent function for caspase-1 and -11 in cytokine processing. Dysregulation of caspases features prominently in many human diseases, including cancer, autoimmunity, and neurodegenerative disorders, and increasing evidence shows that altering caspase activity can confer therapeutic benefits.
The mechanism of adenosine-induced vasodilation in rat diaphragm microcirculation was investigated using laser Doppler flowmetry. Adenosine (10(-5), 3.2 x 10(-5), and 10(-4) M), the nonselective adenosine agonist 5'-N-ethylcarboxamido-adenosine (NECA) (10(-8)-10(-7) M), the specific A(2A) agonist 2-p-(2-carboxyethyl)phenyl-amino-5'-N-ethyl carboxamidoadenosine (CGS-21680) (10(-8)-10(-7) M), and the adenosine agonist with higher A(1)-receptor affinity, R-N(6)-phenylisopropyladenosine (R-PIA) (10(-7), 3.2 x 10(-7), and 10(-6) M) elicited a similar degree of incremental increase of microcirculatory flow in a dose-dependent manner. The ATP-dependent potassium (K(ATP)) channel blocker glibenclamide (3.2 x 10(-6) M) significantly attenuated the vasodilation effects of these agonists. Adenosine-induced vasodilation could be significantly attenuated by the nonselective adenosine antagonist 8-(p-sulfophenyl)-theophylline (3 x 10(-5) M) or the selective A(2A) antagonist 4-(2-[7-amino-2-(2-furyl)[1,2, 4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl) phenol (ZM-241385, 10(-6) M), but not by the selective A(1) antagonist 8-cyclopentyl-1, 3-dipropylxanthine (5 x 10(-8) M). Adenylate cyclase inhibitor N-(cis-2-phenyl-cyclopentyl) azacyclotridecan-2-imine-hydrochloride (MDL-12330A, 10(-5)M) effectively suppressed the vasodilator response of adenosine and forskolin. These results suggest that adenosine-induced vasodilation in rat diaphragm microcirculation is mediated through the stimulation of A(2A) receptors, which are coupled to adenylate cyclase activation and opening of the K(ATP) channel.
Our new oropharyngeal intubation wedge made from a plastic 3-ml syringe has been used successfully for the expansion of the oropharyngeal cavity and visualization of vocal cords for endotracheal intubation in the rat. All the animals we used tolerated the intubation and ventilation procedures in a series of experiments. After the proper setting of the respirator, vital signs were maintained within normal range. The postmortem examination and measurements in the upper airway confirmed that the endotracheal tube was properly sited and also demonstrated the precise size of the device that should be used. The main advantages of this method include low cost, simplicity, and reliability. Furthermore, because no expensive, elaborate, difficult-to-operate, or hard-to-get special equipment is needed, this technique can be used in every laboratory.
BACKGROUND: Iron deficiency constitutes the major cause of erythropoietin hyporesponse in uremic patients receiving erythropoietin therapy; therefore, iron supplementation is necessary for these patients. Recent data suggested that intravenous iron supply is a preferable route for iron supplementation. However, it remains unclear whether a single large dose or multiple small doses are a better way of administering an intravenous iron supply. METHODS: To determine the effect of different dosing schedules of intravenous iron therapy on the hematocrit level, we randomly assigned 18 patients to 3 groups. The first group of patients (n = 6) received a single dose of 800 mg intravenous fesin (ferric saccharate). The second group of patients (n = 6) received 400 mg intravenous fesin once weekly for 2 successive weeks. The third group of patients (n = 6) received 120 mg of intravenous fesin for 7 successive hemodialysis sessions. EPO was given at a fixed dose for all individuals in the study period. RESULTS: The results showed that all 3 groups of patients had a progressive increase in hematocrit (Hct) level following intravenous iron therapy. Serum ferritin levels increased rapidly following iron therapy and then declined gradually in all 3 groups. But no statistical significance could be found among the 3 groups because of the small patient number. Also, no differences were observed in Hct or serum ferritin levels among these 3 groups of patients at all stages. CONCLUSION: In this study, we found that a large single dose as well as small multiple doses of parenteral iron therapy had similar effects in correcting the iron deficiency in hemodialysis patients treated with erythropoietin. To save manpower and costs, we recommend the large single dosing schedule.
Neuronal nuclei were isolated from immature rabbit cerebral cortex and nuclear lysophospholipase activities studied using two different 1-acyl lysophospholipids: lysophosphatidylcholine (lysoPC) and lysophosphatidic acid (lysoPA). Our interest in these two lysolipids arose from the observation that lysoPA could promote the acetylation of lysoPC by substantially inhibiting a very active nuclear lysoPC lysophospholipase activity, in a competitive manner (R.R. Baker, H. -y. Chang, Mol. Cell. Biochem. (1999) in press). As there was also evidence for nuclear lysoPA deacylation, it was of interest to see whether one activity could possibly utilize both lysolipid substrates. We now have evidence for two separate lysophospholipase activities in neuronal nuclei. The lysoPC lysophospholipase activity was the more active, more highly enriched in the neuronal nuclei, and showed optimal activity at pH 8.4-9, while the lysoPA lysophospholipase activity was maintained over a much broader pH range. The lysoPC activity was substantially inhibited by free fatty acid, and showed considerable stimulation by serum albumin, while the activity utilizing lysoPA was much less affected by these agents. When lysoPC was added to incubations containing radioactive lysoPA, there was no significant inhibition found in rates of release of radioactive fatty acid, indicating that the lysoPA lysophospholipase activity did not utilize the lysoPC substrate. In incubations with lysoPC, MgATP and CoA brought about a sizable formation of phosphatidylcholine whose radioactivity was equally distributed between the sn-1 and sn-2 positions suggesting labelling both directly from the lysoPC substrate and from fatty acid produced by the lysophospholipase activity. By comparison, with the radioactive lysoPA substrate, MgATP and CoA promoted relatively lower levels of phosphatidic acid formation whose principal labelling came directly from the radioactive lysoPA. Largely because of the high activity of the nuclear lysoPC lysophospholipase, there is considerable potential in the neuronal nucleus to limit the use of lysoPC in other reactions, such as the formation of acylPAF (1-acyl analogue of platelet activating factor). It is of interest that conditions associated with brain ischaemia such as increased free fatty acid levels, falling pH and declines in MgATP may allow a preservation of neuronal nuclear lysoPC levels for acetylation. The existence of a separate lysophospholipase activity for lysoPA allows an independent control of lysoPA which can serve as an important regulator of the nuclear lysoPC lysophospholipase.