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Biomedical subjects

H Y Chang

Publications and source records attributed to H Y Chang.

At least 55 records · Page 3Linked to original sources

Acute and chronic phase platelet aggregability studies in Chinese patients after implantation of a permanent transvenous pacemaker.

It has been suggested that the incidence of thromboembolic events always increases in patients after insertion of a transvenous pacemaker. Blood samples from twenty consecutive patients (fifteen males and five females) before and after pacemaker implantation was retained for platelet aggregability studies which were analyzed separately with ADP, collagen, epinephrine and arachidonic acid. The maximal amplitude of platelet aggregatory curve was detected by an aggregometer. The samples collected the day before pacemaker implantation (day 0) were used as self-control. Day 1 and day 3 after pacemaker implantation were defined as the acute phase, while day 30 was defined as the chronic phase. The maximal amplitude of platelet aggregatory curve was observed to be lowest on day 1 and then return to normal on day 3 and day 30. The results of platelet aggregability, however, showed no significant difference (P>0.05) between self-control and post-implantation samples. In conclusion, there was no significant change in platelet aggregability for either acute or chronic phases after pacemaker implantation. Antiplatelet medications may not be necessary for the prevention of thromboembolic events after the implantation of a pacemaker.

Aged↗

Dissecting Fas signaling with an altered-specificity death-domain mutant: requirement of FADD binding for apoptosis but not Jun N-terminal kinase activation.

Fas is a cell surface death receptor that regulates peripheral tolerance and lymphoid homeostasis. In many pathologic conditions, ectopic Fas activation mediates tissue destruction. Several proteins that can bind to the cytoplasmic death domain of Fas have been implicated in Fas signal transduction. Here we show that FADD, which couples Fas to pro-caspase-8, and, Daxx, which couples Fas to the Jun N-terminal kinase pathway, bind independently to the Fas death domain. We have isolated a death domain mutant, termed FasDelta, that selectively binds Daxx but not FADD. In tranfected tissue culture cells, FasDelta activated Jun N-terminal kinase normally but was impaired in cell death induction. These results suggest that FADD and Daxx activate two independent pathways downstream of Fas and confirm the essential role of FADD binding in apoptosis induction.

Adaptor Proteins, Signal Transducing↗

Natural mass infection by heterophyid metacercariae in aquacultured Japanese eel in Taiwan.

A natural mass infection of heterophyid metacercariae in aquacultured Japanese eel Anguilla japonica in Taiwan was observed. Of the 28,000 adult eels in 2 ponds, about 25,000 (90%) showed swollen, cloudy and white eyes. Although morbidity was about 90%, there was no mortality among the affected eels. Histopathological sections showed edema and hemorrhage of the eye. Numerous metacercariae were observed in the muscle tissues around the eyeball, the subcutaneous tissue and even in the cartilage. Of the 6 eels digested with artificial gastric juice, all were found to contain metacercariae in their muscle tissues. The average number of metacercariae recovered from the 6 eels was 1219, with a range of 50 to 3762. These metacercariae, when fed orally to immunodeficient (scid) mice, developed into adult worms which were identified as Procerovum cheni Hsu 1950. The naturally infected eels were transferred to a new pond without snails and their eye lesions were not apparent anymore after 2 wk. In a follow-up investigation, 19 of 20 apparently healthy eels in a nearby aquaculture farm were found to harbour metacercariae in their muscles. However, the number of the metacercariae ranged from 1 to 14, with an average of 4.21. This is the first report of heterophyid metacercariae causing mass morbidity in aquacultured eels.

Anguilla↗

Lysophosphatidic acid, alkylglycerophosphate and alkylacetylglycerophosphate increase the neuronal nuclear acetylation of 1-acyl lysophosphatidyl choline by inhibition of lysophospholipase.

Neuronal nuclei were isolated from rabbit cerebral cortex, and lipid acetylation reactions were studied because of the high nuclear concentration of acetyltransferases that generate platelet activating factor (PAF) and its acyl analogue AcylPAF. The neuronal nuclear acetylation of 1-palmitoyl lysophosphatidylcholine (lyso PC) was found to be increased more than twofold when low concentrations of lyso PC were incubated in acetylation assays in the presence of 1-palmitoyl lysophosphatidic acid (lyso PA) or 1-hexadecyl glycerophosphate (AGP). This effect was not found for a variety of other acidic and neutral 1-acyl lysoglycerophospholipids. At 4 microM concentrations, AGP was the more effective in increasing rates of lyso PC acetylation, while lyso PA was more effective at 25-35 microM. 1-Stearoyl, 1-alkenyl and 1-decanoyl analogues of lyso PA were all less effective than 1-palmitoyl lyso PA. Phosphatidic acid was considerably less effective than lyso PA, while the acetylated analogue of AGP, AAcGP (alkylacetylglycerophosphate), increased rates of lyso PC acetylation to maxima similar to those seen with lyso PA or AGP. In addition, AAcGP promoted these maxima at considerably lower concentrations (2-4 microM). A mechanism for these effects was suggested when nuclear envelopes (NE), isolated in the presence of PMSF, showed these maximal acetylation rates at low lyso PC concentrations, and these rates were not elevated by the presence of lyso PA. PMSF is a protease inhibitor but can also inhibit lysophospholipase activity. We found a nuclear lysophospholipase that degraded lyso PC at rates more than 13 times those of nuclear lyso PC acetylation. PMSF did inhibit this nuclear lysophospholipase, as did lyso PA, AGP and AAcGP. Kinetic analyses of the effects of lyso PA, AGP and AAcGP on lyso PC lysophospholipase indicated that these three lipids acted as competitive inhibitors for the lyso PC substrate. It is possible that low rates of lyso PC acetylation seen in neuronal nuclei at low lyso PC concentrations, are caused by lyso PC loss mediated by a very strong nuclear lysophospholipase. The effects of lyso PA, AGP and AAcGP in boosting rates of lyso PC acetylation likely come from the inhibition of nuclear lysophospholipase and a preservation of lyso PC concentrations. Competing neuronal nuclear reactions for low endogenous levels of lyso PC may regulate the formation of AcylPAF, and rising lyso PA, AGP or AAcGP concentrations can increase rates of nuclear AcylPAF synthesis.

Acetylation↗

Stepwise chromosome evolution in Drosophila albomicans.

A 'stepwise chromosome evolution model' is proposed to elaborate the two stages of the sex chromosome evolution of Drosophila albomicans. To explain the occurrence of both a 3-X and a 3-Y in this species it is proposed that these chromosomes evolved sequentially. The selection forces acting in the two stages are different. The genic composition in the first fused sex chromosome of D. albomicans was supposed to be selectively superior to the primitive unfused chromosomes, thus the fused chromosome could overcome the meiotic structural incompatibility and be maintained in the population during the first stage. When the second fusion occurred, the newly fused sex chromosome was preferentially selected, as it could provide a meiotic pairing partner for the first fusion. The fused sex chromosomes were eventually fixed in the population. Based on this model, we tried to determine which fused chromosome, 3-X or 3-Y, established first. The karyotyping result of four experimental hybrid populations showed that the fused 3-X, as opposed to 3-Y, chromosome has higher fitness values. However, without the coexistence of 3-X, 3-Y is excluded rapidly. Therefore, 3-X is likely to be the first fused chromosome in the stepwise chromosome evolution model. The formation and fixation of the fused 3-Y chromosome occurred subsequently.

Animals↗

Optimal design for a study of butadiene toxicokinetics in humans.

The derivation of the optimal design for an upcoming toxicokinetic study of butadiene in humans is presented. The specific goal of the planned study is to obtain a precise estimate of butadiene metabolic clearance for each study subject, together with a good characterization of its population variance. We used a two-compartment toxicokinetic model, imbedded in a hierarchical population model of variability, in conjunction with a preliminary set of butadiene kinetic data in humans, as a basis for design optimization. Optimization was performed using Monte Carlo simulations. Candidate designs differed in the number and timing of exhaled air samples to be collected. Simulations indicated that only 10 air samples should be necessary to obtain a coefficient of variation of 15% for the estimated clearance rate, if the timing of those samples is properly chosen. Optimal sampling times were found to closely bracket the end of exposure. This efficient design will allow the recruitment of more subjects in the study, in particular to match prescribed levels of accuracy in the estimate of the population variance of the butadiene metabolic rate constant. The techniques presented here have general applicability to the design of human and animal toxicology studies.

Administration, Inhalation↗

Effects of N(omega)-nitro-L-arginine (L-NOARG) on blood flow and vasomotion in rat diaphragm microcirculation during hemorrhagic hypotension.

The role of N(omega)-nitro-L-arginine (L-NOARG), a nitric oxide (NO) synthase inhibitor, in the control of blood flow and vasomotion in rat diaphragm microcirculation during hemorrhagic hypotension was investigated by means of laser Doppler flowmetry (LDF). Fifty-six Sprague-Dawley rats were divided into seven groups. Ten minutes after one-stage hemorrhage to 40-60% of initial blood pressure, the rats received 15 min topical superfusion of saline (group 1, time control), 0.1 mM L-NOARG (group 2), 10 mM L-arginine (group 3), or vehicle (0.1% DMSO and 0.9 mN NaOH, group 4). For groups 5 and 6, L-NOARG or its vehicle was superfused for 15 min without hemorrhage. In group 7, the vasodilator responses to the endothelium-dependent vasorelaxant acetylcholine (ACH) and the endothelium-independent vasorelaxant sodium nitroprusside (SNP) were assessed at rest and after 25 min of hemorrhagic hypotension. The results showed no significant differences in blood flow, fundamental frequency, or relative amplitude of the rat diaphragm microcirculation before or after administration of the test agents among the first four groups during hemorrhagic hypotension or in groups 5 and 6 during sham operation without hypoperfusion. Hemorrhagic hypotension significantly decreased the vasodilator response to ACH (p = 0.003), but not to SNP. We conclude that NO did not play an important role in the regulation of blood flow or vasomotion in rat diaphragm microcirculation during acute hemorrhagic hypotension.

Animals↗

Characterization of mdcR, a regulatory gene of the malonate catabolic system in Klebsiella pneumoniae.

The Klebsiella pneumoniae mdcR gene, which encodes a LysR-type regulator, was overexpressed in Escherichia coli. Purified MdcR was found to bind specifically to the control region of either the malonate decarboxylase (mdc) genes or mdcR. We have also demonstrated that MdcR is an activator of the expression of the mdc genes, whereas it represses the transcription of the putative control region of mdcR, PmdcR, indicating a negative autoregulatory control.

Amino Acid Sequence↗

Recognition of handwritten similar Chinese characters by self-growing probabilistic decision-based neural network.

Recognition of similar (confusion) characters is a difficult problem in optical character recognition (OCR). In this paper, we introduce a neural network solution that is capable of modeling minor differences among similar characters, and is robust to various personal handwriting styles. The Self-growing Probabilistic Decision-based Neural Network (SPDNN) is a probabilistic type neural network, which adopts a hierarchical network structure with nonlinear basis functions and a competitive credit-assignment scheme. Based on the SPDNN model, we have constructed a three-stage recognition system. First, a coarse classifier determines a character to be input to one of the pre-defined subclasses partitioned from a large character set, such as Chinese mixed with alphanumerics. Then a character recognizer determines the input image which best matches the reference character in the subclass. Lastly, the third module is a similar character recognizer, which can further enhance the recognition accuracy among similar or confusing characters. The prototype system has demonstrated a successful application of SPDNN to similar handwritten Chinese recognition for the public database CCL/HCCR1 (5401 characters x200 samples). Regarding performance, experiments on the CCL/HCCR1 database produced 90.12% recognition accuracy with no rejection, and 94.11% accuracy with 6.7% rejection, respectively. This recognition accuracy represents about 4% improvement on the previously announced performance. As to processing speed, processing before recognition (including image preprocessing, segmentation, and feature extraction) requires about one second for an A4 size character image, and recognition consumes approximately 0.27 second per character on a Pentium-100 based personal computer, without use of any hardware accelerator or co-processor.

China↗

Time course of pharmacological modulation of peak eosinophilic airway inflammation after mite challenge in guinea pigs: a therapeutic approach.

BACKGROUND: It is well known that eosinophilic airway inflammation develops after allergen challenge in sensitized humans and animals. However, the detailed time course of suppression of early eosinophilic airway inflammation by pharmacological agents given just after challenge has not been discussed. Therefore, we aimed to evaluate the time course relationship of the suppression of peak eosinophilia by anti-cytokines and pharmacological agents given several hours after the aerosol challenge by a therapeutic approach. METHODS: We used crude mite extract as an allergen to create a sensitization and inhalation challenge, and performed bronchoalveolar lavages (BAL) after the inhalation challenge to observe the degree of eosinophilic airway inflammation in guinea pigs. Various anti-cytokines (anti-IL-3 and anti-IL-5) and pharmacological agents (dexamethasone, theophylline, and roxithromycin) were given within several hours after the acute aeorosol challenge to evaluate the suppressive effect on peak eosinophilia in BAL fluid, which occurred 24 h after the challenge. RESULTS: Our results show that anti-IL-5 and dexamethasone, given within 4 and 8 h after the inhalation challenge, respectively, inhibit the acute allergen-induced peak eosinophilia in BAL fluid. However, anti-IL-3, theophylline, and roxithromycin had no effect on peak eosinophilic airway inflammation after challenge. CONCLUSION: These observations suggest that several hours are needed to complete the process of cytokine-induced recruitment of eosinophils from the blood to the airways after acute allergen challenge. This may be the optimal time to administer anti-cytokines and dexamethasone to attenuate the subsequent eosinophilic airway inflammation after acute allergen-induced asthmatic attacks.

Aerosols↗

Predicting factors for outcome of tube thoracostomy in complicated parapneumonic effusion for empyema.

STUDY OBJECTIVES: To determine the predicting factors for outcome of tube thoracostomy in patients with complicated parapneumonic effusion (CPE) or empyema. DESIGN AND SETTINGS: Retrospective chart review over a 55-month period at a tertiary referred medical center. PATIENTS AND MEASUREMENTS: The medical charts of patients with empyema or CPE were reviewed. Data including age, gender, clinical symptoms, important underlying diseases, leukocyte count, duration of preadmission symptoms, interval from first procedure to second procedure, the time from first procedure to discharge (recovery time), the amount of effusion drained, administration of intrapleural streptokinase, chest tube size and position, loculation of pleural effusion, and characteristics and culture results of pleural effusion were recorded and compared between groups of patients with successful and failed outcome of tube thoracostomy drainage. RESULTS: One hundred twenty-one patients were selected for study. One hundred of these patients had received tube thoracostomy drainage with 53 successful outcomes and 47 failed outcomes of chest tube drainage. Nineteen patients received decortication directly, and the other two received antibiotics alone. Univariate analysis showed that pleural effusion leukocyte count, effusion amount, and loculation of pleural effusion were significantly related to the outcome of chest tube drainage. Multiple logistic regression analysis demonstrated that loculation and pleural effusion leukocyte count < or = 6,400/uL were the only independent predicting factors related to failure of tube thoracostomy drainage. CONCLUSIONS: Loculation and pleural effusion leukocyte count < or = 6,400/microL were independent predicting factors of poor outcome of tube thoracostomy drainage. These results suggest that if the initial attempt at chest tube drainage fails, early surgical intervention should be considered in good surgical candidates with loculated empyema or pleural effusion with leukocyte count < or = 6,400/microL.

Aged↗

Applications of an acute assessment methodology used for combustion facilities.

Two approaches for evaluating potential health impact from short-term (1 hour) inhalation exposure to air emissions from combustion facilities are presented. This information was included as part of the health risk assessment (HRA) conducted for each proposed facility in conjunction with regulatory requirements for obtaining an operating permit. Since the facilities being evaluated have either not yet been constructed or are not yet operational, air concentrations (particulate and vapor) must first be estimated using data from similar and operational facilities. A chemical's modeled air concentration was then compared to its acute toxicity value (ATV) selected from established Occupational Exposure Limits (OEL) or acute toxicity databases, if available. Analogous to the current USEPA approach for estimating noncancer health effects, acute hazard quotients (AHQs) were summed and compared to a level of one. When the summation of the AHQs exceeded unity, the chemicals were separated by target organ and health effects based on acute exposures. The author recognizes that the use of OELs has its limitations. However, due to the lack of acute toxicity data and the advantage of the completeness of the databases for OELs, this approach may be the best way to evaluate for acute health concerns for the more than 70 compounds that may be emitted from these facilities.

Air Pollutants, Occupational↗

Characterization of a putative Pseudomonas UDPglucose pyrophosphorylase.

A UDP-glucose pyrophosphorylase encoding gene was identified through functional complementation screening by using an Escherichia coli galU mutant. Sequence analysis of the gene indicated that it is most likely derived from a Pseud monas sp. The gene is located immediately upstream and transcribed in the same direction of the gor (glutathione reductase) gene and is capable of encoding a protein 30,943 daltons in size. The gene product synthesized in Escherichia coli was purified and its biochemical properties characterized. The recombinant UDP-glucose pyrophosphorylase exhibited a molecular weight of 130 kDa, suggesting a tetrameric organization of the gene product. Two mutant forms of the enzyme were identified. The activity of the mutant enzyme with a tyrosine to histidine (Y26 1H) substitution was found to be greatly reduced. On the other hand, the tyrosine to cysteine (Y84C) substitution resulted in an enzyme that functions normally at 37 degrees C but rather poorly at temperatures lower than 30 degrees C.

Amino Acid Sequence↗

Varicella pneumonia complicated by acute respiratory distress syndrome in an adult.

Primary varicella infection is uncommon in adults, but carries a higher rate of morbidity and mortality than in children. Pneumonia is the most common complication of primary varicella infection in adults. However, varicella pneumonia complicated with acute respiratory distress syndrome (ARDS) is very rare. We report a case of ARDS secondary to varicella pneumonia in a 26-year-old man with primary varicella. The patient was otherwise healthy and had no evidence of human immunodeficiency virus infection. The initial chest radiograph showed bilateral reticulonodular infiltrates, which quickly evolved to diffuse alveolar consolidations. Arterial blood gas analysis revealed a ratio of arterial partial pressure to fraction of inspired oxygen of 87. Abnormal liver function and thrombocytopenia were also noted. Treatment consisted of mechanical ventilatory support and intravenous administration of acyclovir. His pulmonary condition gradually improved and he was successfully weaned from the ventilator 1 week later. He was discharged on the 15th hospital day with a favorable outcome. His pulmonary function improved progressively, with normal spirometry and lung volumes, but persistent mild impairment of diffusing capacity, 6 months after discharge.

Adult↗

Identification of a novel family of human Rab-like small GTP-binding proteins.

The presence of a novel family of Rab-like proteins (Rlp) in the human genome is reported. The gene encoding the Rlp-2 was isolated from a human lymphocyte genomic library. The Rlp-2 gene is intronless and was mapped to chromosome Xq21.3 using fluorescence in situ hybridization. Several cDNA clones encoding the Rlp-1 were identified in a human hippocampus lambda library. Northern analysis revealed a 2.1-kb transcript of Rlp-1 expressed predominantly in brain, heart and skeletal muscle. The transcript was also observed in all examined regions of the human brain at a similar level. An additional gene, termed Rlp-3, which is highly related to Rlp-1 and Rlp-2, was found in the GenBank Data Base. The predicted molecular mass for Rlp is approximately 31 kDa and is consistent with that of Rlp-1 synthesized in Escherichia coli.

Amino Acid Sequence↗

Effects of mutations in the starch-binding domain of Bacillus macerans cyclodextrin glycosyltransferase.

Cyclodextrin glycosyltransferase (CGTase) is an industrially important enzyme that produces cyclodextrins (CD) from starch by intramolecular transglycosylation. CGTase consists of five globular domains labeled A through E. To better understand the role of domain E in CGTase catalysis, we have constructed several mutants of Bacillus macerans CGTase. Removing the entire E domain resulted in an inactive enzyme. Adding six amino acids between domains D and E caused a decrease in activity and thermostability. Replacing domain E with the similar starch-binding domain from Aspergillus awamori glucoamylase I caused a drastic decrease in activity, indicating the necessity of correct alignment of bound substrate. Substituting tyrosine residue 634 (Tyr634) with phenylalanine had very little effect on activity or thermostability. Substituting Tyr634 with glycine resulted in a 25% increase of specific cyclization and starch-hydrolyzing activities compared with that of the wild-type enzyme. The latter mutant was less thermostable. The results of this study indicate that domain E is important for the stability and integrity of B. macerans CGTase.

Bacillus↗

Activation of apoptosis signal-regulating kinase 1 (ASK1) by the adapter protein Daxx.

The Fas death receptor can activate the Jun NH2-terminal kinase (JNK) pathway through the receptor-associated protein Daxx. Daxx was found to activate the JNK kinase kinase ASK1, and overexpression of a kinase-deficient ASK1 mutant inhibited Fas- and Daxx-induced apoptosis and JNK activation. Fas activation induced Daxx to interact with ASK1, which consequently relieved an inhibitory intramolecular interaction between the amino- and carboxyl-termini of ASK1, activating its kinase activity. The Daxx-ASK1 connection completes a signaling pathway from a cell surface death receptor to kinase cascades that modulate nuclear transcription factors.

Adaptor Proteins, Signal Transducing↗

Essential role of CED-4 oligomerization in CED-3 activation and apoptosis.

Control of the activation of apoptosis is important both in development and in protection against cancer. In the classic genetic model Caenorhabditis elegans, the pro-apoptotic protein CED-4 activates the CED-3 caspase and is inhibited by the Bcl-2-like protein CED-9. Both processes are mediated by protein-protein interaction. Facilitating the proximity of CED-3 zymogen molecules was found to induce caspase activation and cell death. CED-4 protein oligomerized in cells and in vitro. This oligomerization induced CED-3 proximity and competed with CED-4:CED-9 interaction. Mutations that abolished CED-4 oligomerization inactivated its ability to activate CED-3. Thus, the mechanism of control is that CED-3 in CED-3:CED-4 complexes is activated by CED-4 oligomerization, which is inhibited by binding of CED-9 to CED-4.

Apoptosis↗