Search PubMed⌕ Search

Biomedical subjects

M C Chang

Publications and source records attributed to M C Chang.

At least 37 records · Page 2Linked to original sources
PubMed2001

Pharmacological characterization and antithrombotic effect of agkistin, a platelet glycoprotein Ib antagonist.

1. Agkistin, purified from the snake venom of Formosan Agkistrodon acutus, belongs to the family of C-type lectin GPIb binding proteins. It is a heterodimeric molecule, consisting of alpha- (16.5 kDa) and beta- (15.5 kDa) subunits with a molecular mass of 32,512 Daltons examined by SDS - PAGE and mass spectrometry. 2. In vitro, agkistin concentration-dependently inhibited ristocetin-induced human platelet agglutination and aggregation in the presence of vWF. It also inhibited TXA2 formation and prolonged the latent period in triggering aggregation by a low concentration of thrombin (0.03 u x ml(-1)). 3. 125I-agkistin specifically bound to unactivated human platelets in a saturable manner with a KD value of 223+/-10.6 nM. This binding reaction was rapid and reversible. Monoclonal antibodies, AP1 and 6D1 raised against platelet GPIb, almost completely blocked 125I-agkistin binding to platelets. However, monoclonal antibody 7E3 raised against GPIIb/IIIa complex, trigramin, a GPIIb/IIIa antagonist, ADP and EDTA did not affect 125I-agkistin binding reaction. 4. Agkistin (250 microg x kg(-1)) significantly prolonged the bleeding time and induced transient thrombocytopenia of mice when given intravenously. Furthermore, it markedly inhibited platelet plug formation in irradiated mesenteric venules of fluorescein-treated mice in vivo. 5. In conclusion, agkistin inhibits ristocetin induced platelet aggregation mainly through its specific binding to platelet GPIb, thereby blocking the interaction between GPIb and vWF. In addition, agkistin exhibits antithrombotic activity in vivo.

Amino Acid Sequence↗
PubMed2001

Acinar cell carcinoma with hypervascularity.

Acinar cell carcinoma is an uncommon malignancy with a reported incidence of 1% among exocrine tumors of the pancreas. The case of a 60-year-old Taiwanese man who presented with obstructive jaundice, abdominal pain, and body weight loss is described here. A mixed clinical picture of islet cell tumor and ductal carcinoma of the pancreas was shown to be a hypervascular tumor at the pancreatic head region with an irregular stricture at the common channel of the common bile and pancreatic ducts. The patient had normal levels of plasma carcinoembryonic antigen, carbohydrate antigen 19-9, alpha-fetoprotein, but an increase in plasma levels of insulin and C-peptide. Immunohistochemical stains and electron microscopic examination of the tumor was consistent with acinar cell carcinoma.

Carcinoma, Acinar Cell↗
PubMed2001

Chronic valproate treatment decreases the in vivo turnover of arachidonic acid in brain phospholipids: a possible common effect of mood stabilizers.

Both (Li(+)) and valproic acid (VPA) are effective in treating bipolar disorder, but the pathway by which either works, and whether it is common to both drugs, is not agreed upon. We recently reported, using an in vivo fatty acid model, that Li(+) reduces the turnover rate of the second messenger arachidonic acid (AA) by 80% in brain phospholipids of the awake rat, without changing turnover rates of docosahexaenoic or palmitic acid. Reduced AA turnover was accompanied by down-regulation of gene expression and protein levels of an AA-specific cytosolic phospholipase A(2) (cPLA(2)). To see if VPA had the same effect on AA turnover, we used our in vivo fatty acid model in rats chronically administered VPA (200 mg/kg, i.p. for 30 days). Like Li(+), VPA treatment significantly decreased AA turnover within brain phospholipids (by 28-33%), although it had no effect on cPLA(2) protein levels. Thus, both mood stabilizers, Li(+) and VPA have a common action in reducing AA turnover in brain phospholipids, albeit by different mechanisms.

Acyl Coenzyme A↗
PubMed2001

Chronic nutritional deprivation of n-3 alpha-linolenic acid does not affect n-6 arachidonic acid recycling within brain phospholipids of awake rats.

Using an in vivo fatty acid model and operational equations, we reported that esterified and unesterified concentrations of docosahexaenoic acid (DHA, 22 : 6 n-3) were markedly reduced in brains of third-generation (F3) rats nutritionally deprived of alpha-linolenic acid (18 : 3 n-3), and that DHA turnover within phospholipids was reduced as well. The concentration of docosapentaenoic acid (DPA, 22 : 5 n-6), an arachidonic acid (AA, 20 : 4 n-6) elongation/desaturation product, was barely detectable in control rats but was elevated in the deprived rats. In the present study, we used the same in vivo model, involving the intravenous infusion of radiolabeled AA to demonstrate that concentrations of unesterified and esterified AA, and turnover of AA within phospholipids, were not altered in brains of awake F3-generation n-3-deficient rats, compared with control concentrations. Brain DPA-CoA could be measured in the deprived but not control rats, and AA-CoA was elevated in the deprived animals. These results indicated that AA and DHA are recycled within brain phospholipids independently of each other, suggesting that recycling is regulated independently by AA- and DHA-selective enzymes, respectively. Competition among n-3 and n-6 fatty acids within brain probably does not occur at the level of recycling, but at levels of elongation and desaturation (hence greater production of DPA during n-3 deprivation), or conversion to bioactive eicosanoids and other metabolites.

Acyl Coenzyme A↗
PubMed2001

Left atrial and ventricular ball thrombi complicating rheumatic heart disease with combined mitral and aortic stenosis.

A 42-year-old woman with chronic mitral stenosis was admitted for progressive dyspnea, palpitation, and weakness of lower extremities. Echocardiography revealed rheumatic, thickened, and stenotic mitral and aortic valves, and two free-floating ball thrombi were detected in the left atrium and ventricle, respectively. She died suddenly the next day, probably due to mitral or aortic outflow obstruction by the ball thrombi. We believe that the occurrence of free-floating ball thrombi in both the left atrium and left ventricle concomitantly has never been reported.

Aged↗
PubMed2001

Areca nut extract and arecoline induced the cell cycle arrest but not apoptosis of cultured oral KB epithelial cells: association of glutathione, reactive oxygen species and mitochondrial membrane potential.

There are 600 million betel quid (BQ) chewers in the world. BQ chewing is a major etiologic factor of oral cancer. Areca nut (AN) and arecoline may inhibit the growth of oral mucosal fibroblasts (OMF) and keratinocytes. In this study, AN extract (100-800 microg/ml) and arecoline (20-120 microM) inhibited the growth of oral KB cells by 36-90 and 15-75%, respectively. Exposure to arecoline (> 0.2 mM) for 24 h induced G(2)/M cell cycle arrest of OMF and KB cells. Areca nut extract (> 400 microg/ml) also induced G(2)/M arrest of KB cells, being preceded by S-phase arrest at 7-h of exposure. No evident sub-G(0)/G(1) peak was noted. Marked retraction and intracellular vacuoles formation of OMF and KB cells were observed. Glutathione (GSH) level, mitochondrial membrane potential (Deltabetam) and H(2)O(2) production of KB cells were measured by flow cytometry. GSH level [indicated by 5-chloromethyl-fluorescein (CMF) fluorescence] was depleted by 24-h exposure of KB cells to arecoline (0.4-1.2 mM) and AN extract (800-1200 microg/ml), with increasing the percentage of cells in low CMF fluorescence. By contrast, arecoline (0.1-1.2 mM) and AN extract (800-1200 microg/ml) induced decreasing and increasing H(2)O(2) production (by 2',7'-dichloro- fluorescein fluorescence), respectively. Hyperpolarization of Deltabetam (increasing of rhodamine uptake) was noted by 24-h exposure of KB cells to arecoline (0.4-1.2 mM) and AN extract (800-1200 microg/ml). AN extract (100- 1200 microg/ml) and arecoline (0.1-1.2 mM) induced little DNA fragmentation on KB cells within 24 h. These results indicate that AN ingredients are crucial in the pathogenesis of oral submucous fibrosis (OSF) and oral cancer by differentially inducing the dysregulation of cell cycle control, Deltabetam, GSH level and intracellular H(2)O(2) production, these events being not coupled with cellular apoptosis.

Apoptosis↗
PubMed2001

Estimation of intra-abdominal pressure by bladder pressure measurement: validity and methodology.

BACKGROUND: Increased intra-abdominal pressure (IAP) is an adverse complication seen in critically ill, injured, and postoperative patients. IAP is estimated via the measurement of bladder pressure. Few studies have been performed to establish the actual relationship between IAP and bladder pressure. The purpose of this study was to confirm the association between intravesicular pressure and IAP and to determine the bladder volume that best approximates IAP. METHODS: Thirty-seven patients undergoing laparoscopy had intravesicular pressures measured with bladder volumes of 0, 50, 100, 150, and 200 mL at directly measured intra-abdominal pressures of 0, 5, 10, 15, 20, and 25 mm Hg. Correlation coefficients and differences were then determined. RESULTS: Across the IAP range of 0 to 25 mm Hg using all of the tested bladder volumes, the difference between IAP and intravesicular pressures (bias) was -3.8 +/- 0.29 mm Hg (95% confidence interval) and measurements were well correlated (R2 = 0.68). Assessing all IAPs tested, a bladder volume of 0 mL demonstrated the lowest bias (-0.79 +/- 0.73 mm Hg). When considering only elevated IAPs (25 mm Hg), a bladder volume of 50 mL revealed the lowest bias (-1.5 +/- 1.36 mm Hg). A bladder volume of 50 mL in patients with elevated IAP resulted in an intravesicular pressure 1 to 3 mm Hg higher than IAP (95% confidence interval). CONCLUSION: Intravesicular pressure closely approximates IAP. Instillation of 50 mL of liquid into the bladder improves the accuracy of the intravesicular pressure in measuring elevated IAPs.

Abdomen↗
PubMed2001

Determining optimal cardiac preload during resuscitation using measurements of ventricular compliance.

BACKGROUND: While the right ventricular end-diastolic volume index (RVEDVI) has been shown to be a better indicator of preload than cardiac filling pressures, optimal values during resuscitation from trauma are unknown. This study examines right ventricular stiffness as a guide to optimal values of RVEDVI. METHODS: Prospective study of 19 critically injured patients monitored with a volumetric pulmonary artery catheter during resuscitation. Per resuscitation protocol, the target RVEDVI was > or = 120 mL/m2. Sequential fluid boluses of 500 to 1000 mL were administered to obtain at least four values of RVEDVI and right ventricular end-diastolic pressure (estimated by central venous pressure [CVP]). For each patient, nonlinear regression was used to construct the ventricular compliance curve based on the equation, CVP = aek(RVEDVI), where k is the coefficient of chamber stiffness. RESULTS: Overall, the derived compliance curves had excellent fit with the theoretical equation (mean R2, 0.95 +/- 0.04). Mean k was 0.043 +/- 0.012 (range, 0.029-0.067). For each patient, mean RVEDVI during resuscitation was significantly correlated with k (R2 = 0.75, p < 10-5) indicating that chamber stiffness, measured during initial fluid administration, may be used to determine RVEDVI during the ensuing resuscitation. CONCLUSION: In critically injured patients, bedside assessment of right ventricular compliance is possible and may help determine optimal values of RVEDVI during resuscitation.

Adult↗
PubMed2001

Admission base deficit in pediatric trauma: a study using the National Trauma Data Bank.

BACKGROUND: The base deficit, an important indicator of physiologic derangement after severe injury in adults, has not been specifically examined in the pediatric trauma population. The purpose of this study was to assess the ability of the admission base deficit to predict injury severity and outcome in the pediatric trauma population. METHODS: The study group included all patients in the National Trauma Data Bank over a 2-year period aged 0 to 12 years with a base deficit (0 to -30 mEq/L) recorded from the emergency department. Age, presence of a severe closed head injury, and base deficit were analyzed with respect to mortality and other indicators of injury severity. RESULTS: A total of 515 patients constituted the study group. Base deficit less than -4 mEq/L (p < 0.001) and the presence of a closed head injury (odds ratio, 3.8; p < 0.05) were predictors of mortality. For the group, an admission base deficit of -8 mEq/L corresponded to a probability of mortality of 25%. Significant correlations were found between base deficit and emergency department systolic blood pressure, Injury Severity Score, and Revised Trauma Score. There was no relationship between age and mortality. CONCLUSION: In injured children, the admission base deficit reflects injury severity and predicts mortality. The probability of mortality increases precipitously in children with a base deficit less than -8 mEq/L, and should alert the clinician to the presence of potentially lethal injuries or uncompensated shock.

Child↗
PubMed2001

Endotoxin-adapted septic shock leukocytes selectively alter production of sIL-1RA and IL-1beta.

During septic shock, circulating levels of anti-inflammatory mediators are increased relative to those of pro-inflammatory. The reduced capacity of septic shock blood leukocytes in expressing pro-inflammatory genes in response to bacterial lipopolysaccharide endotoxin (LPS) may contribute to reductions in these mediators, but the reasons for persistent increases in circulating anti-inflammatory mediators are unknown. We determined whether septic shock leukocytes that have adapted to LPS induction of the IL-1beta gene could continue to express sIL-1RA in response to LPS. Septic shock whole-blood leukocytes and neutrophils (PMNs) selectively maintained production of sIL-1RA after treatment with LPS while limiting that of IL-1beta. Repressed transcription of IL-1beta and rapid decay of IL-1beta mRNA in septic shock neutrophils correlated with reductions in levels of IL-1beta after stimulation with LPS. Transcription of sIL-1RA mRNA was also suppressed, but the ability of LPS to stimulate events that lead to efficient translation of a stable sIL-1RA mRNA appeared responsible for maintaining sIL-1RA production. We conclude that LPS adaptation of septic shock leukocytes selectively influences signaling pathways that regulate transcription, mRNA processing, and translation, leading to changes in the balance of production of pro- and anti-inflammatory mediators.

Adaptation, Physiological↗
PubMed2001

Identification and characterization of the three chitin-binding domains within the multidomain chitinase Chi92 from Aeromonas hydrophila JP101.

The gene (chi92) encoding the extracellular chitinase of Aeromonas hydrophila JP101 has been cloned and expressed in Escherichia coli. The mature form of Chi92 is an 842-amino-acid (89.830-kDa) modular enzyme comprised of a family 18 catalytic domain, an unknown-function region (the A region), and three chitin-binding domains (ChBDs; Chi92-N, ChBD(CI), and ChBD(CII)). The C-terminally repeated ChBDs, ChBD(CI) and ChBD(CII), were grouped into family V of cellulose-binding domains on the basis of sequence homology. Chitin binding and enzyme activity studies with C-terminally truncated Chi92 derivatives lacking ChBDs demonstrated that the ChBDs are responsible for its adhesion to unprocessed and colloidal chitins. Further adsorption experiments with glutathione S-transferase (GST) fusion proteins (GST-CI and GST-CICII) demonstrated that a single ChBD (ChBD(CI)) could promote efficient chitin and cellulose binding. In contrast to the two C-terminal ChBDs, the Chi92-N domain is similar to ChiN of Serratia marcescens ChiA, which has been proposed to participate in chitin binding. A truncated derivative of Chi92 that contained only a catalytic domain and Chi92-N still exhibited insoluble-chitin-binding and hydrolytic activities. Thus, it appears that Chi92 contains Chi92-N as the third ChBD in addition to two ChBDs (ChBD(CI) and ChBD(CII)).

Aeromonas hydrophila↗
PubMed2001

Regulation of Kv1.3 channels in activated human T lymphocytes by Ca(2+)-dependent pathways.

Activated T lymphoblasts respond more effectively to mitogenic stimuli than resting T cells, partly through differences in Ca(2+) signaling, which in turn depend on K(+) channel activity. Both Kv1.3 and Ca(2+)-activated K(+) (SK4) channels are up-regulated in T lymphoblasts. Since Ca(2+)- and calmodulin (CaM)-dependent signal-ing are key pathways in T-cell activation, we investigated their involvement in regulating the Kv1.3 current. Kv1.3 in lymphoblasts was significantly inhibited by elevating internal Ca(2+) to the micromolar level. It was also reduced in a Ca(2+)-dependent manner by inhibiting CaM with W-7 or calmidazolium. Part of the CaM-dependence is likely through CaM kinase since the current was also inhibited by the antagonist, KN-62, but not by the inactive analogue, KN-04. Kinase inhibition, unlike CaM inhibition, was only effective at physiological temperatures, a difference that implies involvement of more than one mechanism. We demonstrated a biochemical association of Kv1.3 protein in lymphoblasts with the multifunctional type II CaM kinase, but not with calmodulin. Thus, Kv1.3 forms a multi-protein complex with CaM kinase II (which binds to Ca(2+)/CaM) and previously identified proteins (e.g., PSD-95, src tyrosine kinase) that position the channel to respond to signaling pathways that are crucial for T-cell activation and proliferation.

Calcium↗
PubMed2001

Immunohistochemical evaluation of cadherin and catenin expression in early gastric carcinomas: correlation with clinicopathologic characteristics and Helicobacter pylori infection.

Dysfunction of E-cadherin and catenin has been linked to invasiveness and differentiation of tumors. This study aimed to characterize the expression of cadherins and catenins in early gastric carcinoma and their relationship to clinicopathologic characteristics and Helicobacter pylori infection. E-cadherin and alpha-, beta- and gamma-catenins were strongly expressed in normal epithelium but abnormal immunoreactivity of at least one of these four proteins was noted in 48 (90.6%) of 53 early gastric carcinomas. Only 5 cases with intestinal-type tumors had intact expression of E-cadherin and alpha-, beta-, and gamma-catenins. Abnormal immunoreactivity in the tumor tissue was observed in 18 patients (34.0%) for E-cadherin, in 35 (66.0%) for alpha-catenin, in 20 (37.7%) for beta-catenin, and in 37 (69.8%) for gamma-catenin. In diffuse-type tumors, abnormal expression of E-cadherin (60.9 vs. 13.3%, p < 0.0005), alpha-catenin (82.6 vs. 53.3%, p < 0.05) and gamma-catenin (91.3 vs. 53.3%, p < 0.005) was more frequent than in the intestinal type. Ten tumors with lymph node metastasis showed a relatively higher frequency of abnormal expression of E-cadherin (70 vs. 25.6%, p < 0.05) but a lower frequency of abnormal expression of beta-catenin (10 vs. 44.1%, p = 0.07) than those without metastasis. No significant association was found between cadherin/catenin expression and the depth of invasion or the H. pylori status. It was concluded that abnormal expression of E-cadherin and the catenin-mediated cell-cell adhesion system occurs frequently in early gastric carcinogenesis and may play an important role in the genesis of histologic differentiation and in the mode of metastasis of early gastric carcinomas.

Armadillo Domain Proteins↗
PubMed2001

Thrombin-stimulated growth, clustering, and collagen lattice contraction of human gingival fibroblasts is associated with its protease activity.

BACKGROUND: Thrombin is a serine protease produced following gingival tissue injury or inflammation. It regulates the functional behavior of injury-neighboring cells via the activation of specific protease-activated receptors (PAR). Thrombin's role in gingival tissue healing and inflammatory response processes is not yet well understood. METHODS: We investigated the effects of thrombin on gingival fibroblast (GF) growth [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay], collagen lattice contraction, and associated morphological changes. RESULTS: Thrombin (>1 U/ml), but not thrombin receptor (PAR-1) agonist peptide (SFLLRN, single letter amino acid code, abbreviated as TRAP, 1 to 50 microg/ml), stimulated the growth and clustering of cultured human GF in vitro. Growth-stimulatory effects of thrombin were inhibited by D-Phe-Pro-ArgCH2Cl (PPACK), a serine protease inhibitor. By contrast, trypsin (>10 microg/ml), a PAR-2 activator, suppressed the growth of GF. Thrombin (>0.2 U/ml) and TRAP (10 to 25 microg/ml), but not trypsin, prostaglandin E2 (0.01 to 0.5 microg/ml), or bovine serum albumin (BSA) (1 to 80 microg/ml), induced the GF-populated collagen lattice contraction within 30 to 60 minutes of exposure. The thrombin-induced collagen lattice contraction was inhibited by PPACK (20 microg/ml) and an actin filament polymerization inhibitor, cytochalasin B (1 microg/ml). The collagen lattice contraction induced by TRAP was also inhibited by cytochalasin B, but not by PPACK. Using a reverse-transcriptase polymerase chain reaction (RT-PCR), the expression of PAR-1, and to a lesser extent PAR-3, was observed for human GF, although little PAR-2 and PAR-4 expression was noted. CONCLUSIONS: These results indicate that thrombin is important in periodontal wound healing and inflammatory processes by promoting the growth and contraction of GF. The stimulatory effects of thrombin are associated with its protease activation of thrombin receptors.

Amino Acid Chloromethyl Ketones↗
PubMed2001

Selective dopamine receptor stimulation differentially affects [3H]arachidonic acid incorporation, a surrogate marker for phospholipase A2-mediated neurotransmitter signal transduction, in a rodent model of Parkinson's disease.

Our laboratory has developed a technique whereby radiolabeled long-chain fatty acids are injected intravenously in awake rats to pulse-label brain lipids, mainly phospholipids, to measure regional brain lipid metabolism by autoradiography. The brain incorporation of [(3)H]arachidonic acid ([(3)H]AA), a polyunsaturated fatty acid, may reflect regional changes in neurotransmitter signal transduction using phospholipase A(2). Using this radiotracer, we examined the brain dopamine system in rats with a chronic unilateral 6-hydroxydopamine lesion of the substantia nigra pars compacta, a model of Parkinson's disease. Four weeks after lesioning, rats received either vehicle; SKF38393 or quinpirole (LY-171,555) (D(1)- and D(2)-dopamine-like agonists, respectively); or (+)-butaclamol (D(1)/D(2) antagonist) followed by either vehicle, SKF38393, or quinpirole. They then were infused with [(3)H]AA and their brains processed for autoradiography. SKF38393 increased [(3)H]AA incorporation into the lesioned side compared with the intact side in the caudate putamen, somatosensory and motor cortices and subthalamic nucleus, but decreased incorporation in the ipsilateral ventrolateral thalamus. Quinpirole increased ipsilateral [(3)H]AA incorporation in the caudate putamen and somatosensory and motor cortices, and decreased it in the ventrolateral thalamus. (+)-Butaclamol blocked this effect. The data suggest up-regulation in basal ganglia and cortical dopamine circuits mediated by phospholipase A(2) ipsilateral to the substantia nigra lesion.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2001

Delivery and turnover of plasma-derived essential PUFAs in mammalian brain.

Polyunsaturated fatty acids (PUFAs) are critical to nervous system function and structure, but their rates of incorporation from plasma into brain have not been evaluated. In the adult rat, calculations based on our model show that at least 3;-5% of esterified brain arachidonic acid (AA) and 2;-8% of esterified brain docosahexaenoic acid (DHA) are replaced daily by unesterified PUFAs in plasma. These rates, when related to unlabeled brain PUFA composition, give half-lives of 1-2 weeks for plasma-brain exchange of AA and DHA. In the human brain, the arachidonate replacement rate is 0.3% per day. Although unesterified plasma PUFA concentrations are low, their rates of incorporation into brain are sufficient to compensate for metabolic and efflux losses, so that PUFA transport from plasma into brain as a component of a lipoprotein is unnecessary. Dietary supplementation, by altering plasma unesterified PUFA concentrations, can regulate brain PUFA content and may help to treat brain diseases involving PUFA imbalance.

Animals↗
PubMed2001

Mediastinal impalement with survival: a case report.

Mediastinal impalement injuries are rare and often fatal. Very few instances of survival after mediastinal impalement have been reported. We present the unusual case of an 18-year-old man who was involved in a motor vehicle crash in which a wooden fencepost intruded through the windshield and impaled him through the superior mediastinum. The patient remained hemodynamically stable and had no other significant injuries except a left pneumothorax. Arteriogram revealed a bovine aortic arch with the wooden piece passing over the aortic arch between the two brachiocephalic arteries at the precise point that a normal left common carotid artery would have been located. No other injuries were seen on arteriogram, venogram, or esophagram. The foreign body was extracted via thoracotomy along with resection of the apex of the left lung and ligation of the thoracic duct. The patient was discharged on hospital day eight and was doing quite well at one-year follow-up with no residual effects of his accident.

Accidents, Traffic↗