Biomedical subjects

W C Chang

Publications and source records attributed to W C Chang.

At least 199 records · Page 11Linked to original sources

PubMed1993

Down-regulation of beta-adrenergic receptors on mononuclear leukocytes induced by dobutamine treatment in patients with congestive heart failure.

(+/-)-Dobutamine is a positive inotropic drug usually used to improve ventricular function in patients with congestive heart failure (CHF). However, it has been found that haemodynamic responses to dobutamine become blunted during continuous treatment. In this study we determined the time-dependent changes of beta-adrenergic receptors in CHF patients treated with dobutamine. Seven CHF patients received a continuous intravenous infusion of dobutamine (5 micrograms.kg-1 x min-1) for 96 h. Blood samples were obtained before and every 24 h after starting the therapy. The density of beta-adrenergic receptors on mononuclear leukocytes and the plasma concentrations of norepinephrine and epinephrine were determined. During dobutamine treatment the receptor density (fmol.mg-1, mean +/- SEM) gradually decreased from 42.8 +/- 4.4 (baseline) to 31.4 +/- 3.3 (P < 0.05), 25.2 +/- 4.0 (P < 0.01), 18.8 +/- 5.5 (P < 0.01) and 13.4 +/- 3.4 (P < 0.01) at 24, 48, 72 and 96 h, respectively. However, the plasma concentrations of norepinephrine and epinephrine were not significantly changed during the 96 h period of treatment. Thus, the beta-adrenergic receptors down-regulated as early as 24 h after the dobutamine treatment was begun in CHF patients. This receptor down-regulation was not associated with changes of plasma catecholamine concentrations, but was related rather to the development of drug tolerance to dobutamine.

Adult↗

PubMed1993

Effects of exercise training on the biosynthesis of prostacyclin and thromboxane in rats.

The effects of exercise training on eicosanoid levels were studied in male Wistar rats. One-month-old rats were trained on a drum exerciser at an intensity of around 70% of maximal oxygen consumption for 10 weeks (60 min day-1, 5 days week-1) after familiarization. Some animals of the same age did not exercise and served as a control. Two days after training, several blood vessels, including thoracic aortae, inferior vena cavae, external iliac arteries, external iliac veins, common carotid arteries and jugular veins, were excised and incubated for 10 min. Basal release of prostacyclin from these vessels was determined using [125I]radio-immunoassay (RIA) of 6-keto-PGF1 alpha. The levels of plasma prostacyclin and urinary metabolites of prostacyclin and thromboxane were also determined by RIA. Our results showed that trained animals had lower body weight and urine 11-dehydro-thromboxane B2 levels than the controls (P < 0.001 and P < 0.05, respectively). In contrast, urinary 2,3-dinor-6-keto-PGF1 alpha level was elevated after training (P < 0.05). Nonetheless, prostacyclin levels in plasma and from various dissected vessel segments, except thoracic aorta, did not change significantly after training. These findings suggest that exercise training may affect endogenous eicosanoid levels by increasing the basal release of prostacyclin and reducing the basal thromboxane level.

6-Ketoprostaglandin F1 alpha↗

PubMed1993

Human plasmin induces a receptor-mediated arachidonate release coupled with G proteins in endothelial cells.

Treatment of cultured bovine carotid artery endothelial cells with 10(-7) M plasmin increased arachidonate release coupled with the increase in prostacyclin production. The stimulatory effect of plasmin on arachidonate release could be divided into the early and late phases according to its calcium dependency and pertussis toxin sensitivity. The early phase of plasmin-induced arachidonate release was a calcium-dependent and pertussis toxin-sensitive response, which was observed within 20 min after plasmin treatment. The late phase was a calcium-independent and pertussis toxin-insensitive response, which was induced gradually from 20 to 60 min. Induction of the early phase of plasmin's effect required both the lysine binding and catalytic sites in plasmin molecule because it was inhibited either by the binding antagonist tranexamic acid or by the serine protease inhibitor aprotinin. Guanosine 5'-O-(2-thiotriphosphate) potentiated the effect of plasmin in permeabilized or nonpermeabilized cells, indicating that the early phase effect was mediated by a pertussis toxin-sensitive guanosine 5'-triphosphate (GTP)-binding protein. The late phase of plasmin's effect was due to the catalytic activity because it was inhibited by aprotinin but not by tranexamic acid. Microplasmin structurally having the catalytic sites induced a similar late phase effect. Plasmin did not elicit the metabolism of phosphatidyl polyphosphoinositides. These studies demonstrate that the activation of phospholipase A2, which results in arachidonate release, in the early phase of plasmin's effect is a receptor-mediation via GTP-binding protein that is not coupled through phospholipase C activation.

Animals↗

PubMed1993

The effect of intravenous infusion of prostaglandin E1 on cutaneous microcirculation in black foot disease.

In order to evaluate the effect of an intravenous infusion of prostaglandin E1 (PGE1), 80 micrograms/day for two weeks, on microcirculatory vasculature in seven patients (M:F = 3:4, age 60-78) with black foot disease (a peripheral vascular disease of undefined etiology), we applied laser Doppler velocimetry to measure the maximal cutaneous microcirculatory flow (LDF) at a proximal site near gangrenous ulcers of the foot. Maximal flow was induced by local warming to 42 degrees C with a modified laser Doppler heating probe. Three phasic measurements were recorded, i.e., during pretreatment, treatment and follow-up with the separation interval being two weeks. The net maximal LDF (LDF at 42 degrees C minus LDF at room temperature) increased from 8.8 +/- 4.0 to 11.9 +/- 4.0 volt, p < 0.05. Cutaneous vascular conductance (CVC) was calculated as LDF/mean BP. Mean BP showed no significant change before or after treatment. Net CVC was changed from 7.5 +/- 3.1 to 11.9 +/- 4.0 volt/100 mmHg, p < 0.05. The LDF dropped significantly during the two-week period between treatment and follow-up in five subjects (10.8 +/- 3.4 vs 4.6 +/- 1.8, p < 0.05), while the follow-up LDF was close to the control data (4.6 +/- 1.8 vs 6.3 +/- 2.2, p = NS). Hence, we conclude that PGE1 may beneficially enhance microcirculatory blood flow in black foot disease through direct vasodilatory effects.

Aged↗

PubMed1993

The induction and characterization of antiserum against human placenta 17-beta-hydroxysteroid dehydrogenase.

17-beta-Hydroxysteroid dehydrogenase was purified from human placenta. The purification process included the following steps: 50% saturated ammonium sulfate precipitation; heat treatment; affinity column chromatography; and preparative SDS gel electrophoretic elution. This enzyme was also characterized by HPLC gel filtration and two dimensional gel electrophoresis with isoelectrofocusing. The results indicate that the molecular weight of these enzymes in their native condition is around 68 kDa and 34 kDa in SDS PAGE. Therefore, the active form of the enzyme is an identical dimmer in nature. There are three charged isomers as demonstrated by isoelectrofocusing. The antiserum against the 17-beta-HSD was induced by injection of purified human placenta 17-beta-HSD in rabbits. The antiserum was collected and characterized by ELISA, immunohistochemistry, immunoblot and immunoprecipitation tests. The results showed that the antibody titer was over 1:12,800, and specificity against human placenta 17-beta-HSD was also observed.

17-Hydroxysteroid Dehydrogenases↗

PubMed1993

Carcinoid tumor of the thymus: report of two cases.

Carcinoid tumors of the thymus are rare. In 1972, Rosai and Higa first described these neoplasms as a distinct entity from thymomas. Clinically, they may be asymptomatic or present with symptoms of a growing mass and/or with ectopic endocrine secretion. Two cases of thymic carcinoid tumor without endocrine manifestations are presented. Microscopically, both tumors showed typical features of carcinoid, such as ribbons, festoons and rosette-like structures. Immunohistochemically, they were immunoreactive for neuron-specific enolase (NSE), chromogranin A and keratin. Electron microscopic examination was performed only in one case and numerous dense core neurosecretory granules were demonstrated. Thymic carcinoid tumors may pursue an aggressive but protracted clinical course. Along with radiotherapy and possibly adjunctive chemotherapy, complete surgical excision remains the best treatment today either for the primary tumor or for subsequent recurrences.

Adult↗

PubMed1992

Plasmin and the regulation of tissue-type plasminogen activator biosynthesis in human endothelial cells.

Plasmin inhibited the biosynthesis of tissue-type plasminogen activator (tPA) antigen by human umbilical vein endothelial cells (HUVEC) in a dose-dependent manner. The amount of tPA antigen found in the 24-h conditioned medium of cells treated with 100 nM plasmin for 1 h was 20-30% of that in the control group. However, in contrast to tPA, such treatment led to a 3-fold increase in plasminogen activator inhibitor (PAI) activity, whereas the amount of PAI type 1 antigen was unchanged. The effects of plasmin on HUVEC were binding- and catalytic activity-dependent and were specifically blocked by epsilon-aminocaproic acid. Microplasmin, which has no kringle domains, was less effective in reducing tPA antigen biosynthesis or enhancing PAI activity in HUVEC. Kringle domains of plasmin affected neither tPA antigen nor PAI activity of the cells. Other proteases including chymotrypsin, trypsin, and collagenase at comparable concentrations did not have a significant effect on the biosynthesis of tPA antigen or PAI activity of HUVEC. Thrombin stimulated the biosynthesis of tPA and PAI-1 antigens by HUVEC. Thrombin also stimulated an increase in the protein kinase activity in HUVEC, whereas plasmin inhibited the protein kinase activity of the cells. It is possible that plasmin regulates the biosynthesis of tPA in HUVEC through the signal transduction pathway involving protein kinase.

Aminocaproic Acid↗

PubMed1992

Insulin-like growth factor I stimulates transcription of the c-jun proto-oncogene in Balb/C 3T3 cells.

Treatment of quiescent Balb/c 3T3 cells with insulin-like growth factor I (IGF I) resulted in the stimulation of proto-oncogene c-jun transcription. Cells exposed to cycloheximide and IGF I together showed super-induction of c-jun transcripts. Nuclear run-off assay revealed that IGF I up-regulated c-jun only while cycloheximide was present. The stability of c-jun mRNA was markedly increased in the cells treated with IGF I. These results suggest that IGF I controls the expression of c-jun by increasing the transcriptional activity and stabilizing the existing transcripts.

3T3 Cells↗

PubMed1992

Epidermal growth factor enhances a microsomal 12-lipoxygenase activity in A431 cells.

12-Hydroxyeicosatetraenoic acid (12-HETE) is formed from arachidonic acid either by 12-lipoxygenase or by a cytochrome P450 monooxygenase. 12-Lipoxygenase is generally localized in the soluble cytosolic fraction, and the cytochrome P450 monooxygenase is a microsomal enzyme. In this study, 12-HETE biosynthesis and the regulation of 12-HETE biosynthesis by epidermal growth factor (EGF) in A431 cells were investigated. 12-HETE was biosynthesized from arachidonic acid by the microsomal fraction of A431 cells, but not by the cytosolic fraction. The formation of 12-HETE was inhibited by 5,8,11,14-eicosatetraynoic acid, nordihydroguaiaretic acid, and caffeic acid. Nordihydroguaiaretic acid at 10(-4) M and 5,8,11,14-eicosatetraynoic acid at 10(-5) M almost completely inhibited its formation. However, the formation of 12-HETE was not affected by the presence of an NADPH-generating system, carbon monoxide, or SKF 525A. The biosynthetic 12-HETE was analyzed by chiral stationary phase high performance liquid chromatography and was highly enriched in (12S)-HETE. We therefore concluded that the enzyme responsible for the formation of (12S)-HETE in the microsomes of A431 cells is a 12-lipoxygenase. The microsomal 12-lipoxygenase of A431 cells belongs to the "leukocyte-type" enzyme as determined by substrate specificity and enzyme kinetics studies. The microsomal 12-lipoxygenase oxygenated linoleic acid much faster than the cytosolic platelet 12-lipoxygenase and is a "self-catalyzed inactivation" enzyme. Treatment of cells with 50 ng/ml EGF significantly induced microsomal 12-lipoxygenase activity. The lag period for the expression of the stimulatory effect of EGF on 12-lipoxygenase activity was approximately 10 h. The stimulatory effect of EGF on 12-lipoxygenase activity was completely blocked by treatment with 35 microM cycloheximide, indicating a requirement for de novo protein biosynthesis. Furthermore, the presence of the endogenous inhibitor of 12-lipoxygenase (which masked (12S)-HETE biosynthesis in intact cells) was identified in the cytosolic fraction of A431 cells. The putative inhibitor was enzyme-selective. It inhibited the leukocyte-type 12-lipoxygenase, but not the "platelet-type" enzyme.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed1992

Human stomach aldehyde dehydrogenase cDNA and genomic cloning, primary structure, and expression in Escherichia coli.

An aldehyde dehydrogenase isozyme, ALDH3, which is strongly expressed in the stomach, may play a role in the oxidation of toxic aldehydes. Using reverse genetic approach, we cloned and characterized the cDNA and the gene for the ALDH3. The full length cDNA is 1624 base pairs (bp) in length and contains an open reading frame encoding 453 amino acid residues. The deduced amino acid sequence shows a high degree of resemblance to that of rat hepatocarcinoma ALDH. The human ALDH3 gene spans about 8 kb in length and consists of 10 exons. The putative TATA and CCAAT boxes are located in the consensus upstream distance from the transcription initiation site. Southern blot analysis of total genomic DNA argues against the proposed two-gene model for the ALDH3 isozymes (Yin, S.-J., Cheng, T.-C., Chang, C.-P., Chen, Y.-J., Chao, Y.-C., Tang, H.-S., Chang, T.-M., and Wu, C.-W. (1988) Biochem. Genet. 26, 343-360). Northern blot hybridization and analysis of PCR amplification products of cellular RNA demonstrated the existence of a high level of ALDH3 mRNA in human stomach and hepatoma cells, but a very low level in the normal liver. Expression of ALDH3 cDNA in Escherichia coli yielded a protein of 55 kDa, which exhibited kinetic properties similar to that found in ALDH3 isozyme purified from human stomach and liver, and was hybridizable with rabbit anti-human-hepatoma ALDH serum.

Aldehyde Dehydrogenase↗

PubMed1992

Effects of retinoids on endothelial cell proliferation, prostacyclin production and platelet aggregation.

In addition to their anti-inflammatory and anti-cancer activities, retinoids have been shown to affect angiogenesis, endothelial proliferation and the process of wound healing. While peripheral vascular occlusion has not been observed as an adverse effect clinically, the effects of retinoids on prostacyclin production in endothelial cells and platelet aggregation are not known. We examined the effects of tretinoin, isotretinoin and etretinate (3.3 x 10(-8) to 3.3 x 10(-5) M) on cytotoxicity by 51Cr-release assay, growth and prostacyclin in bovine carotid endothelial cell cultures, and the aggregation of human platelets induced by ADP. All retinoids showed either no or only small effects on cytotoxicity and human platelet aggregation. Prostacyclin production was not significantly affected except for tretinoin and isotretinoin at 3.3 x 10(-5) M. Endothelial proliferation was affected by all three retinoids in a dose-dependent fashion; for tretinoin and isotretinoin an inhibitory trend was noted as the concentration increased but the reverse was true for etretinate. Retinoids at 3.3 x 10(-5) M induced alterations of typical endothelial morphology; the cells became fibroblastoid. The results of prostacyclin production and platelet aggregation in the present study are consistent with the absence of peripheral vascular occlusion as a side effect clinically.

Animals↗

PubMed1992

Cytoprotective effect of reduced glutathione in hydrogen peroxide-induced endothelial cell injury.

The kinetic effects of hydrogen peroxide (H2O2) on cultured endothelial cells isolated from bovine carotid artery were studied. The cytoprotective effects of glutathione (GSH) on H2O2-induced cell injury were also investigated. H2O2-induced a dose- and time-dependent cell injury in cultured endothelial cells. H2O2-induced cell injury was blocked by simultaneous treatment by catalase, but not by superoxide dismutase. H2O2 also induced endogenous PGI2 biosynthesis, and the maximum PGI2 production was reached after 1 h treatment. Stimulation of PGI2 production was parallel with arachidonate release from H2O2-treated cells. However the prostaglandin biosynthesis enzyme activity in cells was inhibited by H2O2 treatment. When the cells were treated with GSH, the intracellular GSH reached a plateau after 3 h treatment. Both H2O2-induced cell injury and PGI2 production were significantly inhibited by the 3 h pretreatment with GSH. The cytoprotective effect of GSH was completely inhibited by buthionine sulfoximine which is a specific inhibitor of gamma-glutamylcysteine synthetase. The results indicate that the cytoprotective effect of GSH on H2O2-induced cell injury in cultured bovine carotid artery endothelial cells depends on the increase in intracellular GSH content.

Animals↗

PubMed1992

Inhibition of platelet activation and endothelial cell injury by polyphenolic compounds isolated from Lonicera japonica Thunb.

Effects of the polyphenolic compounds isolated from Lonicera japonica Thunb on platelet aggregation, platelet thromboxane biosynthesis and hydrogen peroxide-induced endothelial cell injury were studied. With regard to the inhibitory effect on human platelet aggregation, methyl caffeate, 3,4-di-O-caffeoylquinic acid and methyl 3,4-di-O-caffeoylquinate had a strong effect. They significantly inhibited the second wave of platelet aggregation induced by ADP. Concerning thromboxane biosynthesis triggered by calcium ionophore A23187 in platelets, methyl caffeate and methyl 3,4-di-O-caffeoylquinate had the most potent inhibitory effect. Methyl 3,4-di-O-caffeoylquinate directly inhibited the conversion of arachidonic acid to thromboxane by platelet microsomes, while methyl caffeate did not have any significant effect on thromboxane biosynthesis in platelet microsomes. In the prevention of hydrogen peroxide-induced endothelial cell injury in culture, protocatechuic acid, methyl caffeate, methyl chlorogenic acid and luteolin were significantly effective. The inhibitory effect on platelet activation and the cytoprotective effect on hydrogen peroxide-induced cell injury may explain the possible role of polyphenolic compounds isolated from Lonicera japonica Thunb in maintaining vascular homeostasis.

Animals↗

PubMed1992

The change of urinary 11-dehydro-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1 alpha in arteriogenic impotence.

Thromboxane A2 is a potent vasoconstrictor and a stimulus of platelet aggregation, which may contribute to hypercoagulability. The prostacyclin, prostaglandin I2, has exactly the opposite effect. Measurement of the major urinary metabolites, 11-dehydro-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1 alpha (prostaglandin F1 alpha) by radioimmunoassay can accurately reflect in vivo the biosynthesis of thromboxane A2 and prostaglandin I2, respectively. Group 1 consisted of 60 patients less than 50 years old. The mean urinary 11-dehydro-thromboxane B2 level of 3 patients with arteriogenic impotence was significantly greater than that of the 57 control volunteers: 2.66 +/- 0.65 versus 1.74 +/- 0.56 (plus or minus standard deviation) ng./mg. creatinine (p = 0.008). The prostaglandin F1 alpha levels for the patients and controls were 32.74 +/- 8.45 and 37.58 +/- 16.55 ng./mg. creatinine, respectively, which was not significantly different (p greater than 0.05). Group 2 consisted of 96 patients 50 years old or older. The 11-dehydro-thromboxane B2 concentration in the urine was 1.83 +/- 0.58, 2.54 +/- 1.12 and 1.91 +/- 0.73 ng./mg. creatinine in the 47 normal control volunteers, 20 patients with arteriogenic impotence and 29 with arteriogenic impotence plus intracavernous injection of 20 micrograms prostaglandin E1, respectively. The arteriogenic impotence group showed the significantly highest level among the 3 groups (p = 0.0025). Also, the urinary prostaglandin F1 alpha levels in these patients were 45.71 +/- 36.3, 57.71 +/- 35.53 and 59.30 +/- 45.08 ng./mg. creatinine, respectively, which was not significantly different (p greater than 0.05). For the 13 patients with arteriogenic impotence (group 3) we compared the urinary 11-dehydro-thromboxane B2 and prostaglandin F1 alpha levels before and after intracavernous injection of prostaglandin E1 by using a paired t test. The results showed that the change in 11-dehydro-thromboxane B2 levels was 2.78 +/- 1.09 versus 1.99 +/- 0.75 ng./mg. creatinine, which was significantly different (p = 0.005), whereas that for prostaglandin F1 alpha was 62.30 +/- 40.41 versus 58.86 +/- 44.26 ng./mg. creatinine, with no significant difference (p greater than 0.05). Our findings suggest that urinary 11-dehydro-thromboxane B2 may have an important role in the diagnosis and treatment of arteriogenic impotence.

6-Ketoprostaglandin F1 alpha↗

PubMed1992

Predicted secondary and tertiary structures of carp gamma-crystallins with high methionine content: role of methionine residues in the protein stability.

A systematic structural comparison of several carp gamma-crystallins with high methionine contents was made by the secondary-structure prediction together with computer model-building based on the established X-ray structure of calf gamma-II crystallin. The overall surface hydrophilicity profile and the distribution of helices, beta-sheets, and beta-turns along the polypeptide chains are very similar among these carp gamma-crystallins. In addition, their general polypeptide packing is close to the characteristic 2 domain/4 motif Greek key three-dimensional conformation depicted for the calf gamma-II crystallin. Interestingly, most hydrophobic methionine residues are located on the protein surface with only a few buried inside the protein surface or in the interface between two motifs of each domain. The exposed hydrophobic and polarizable methionine cluster on the protein surface may have a bearing on the crystallin stability and dense packing in the piscine species, and probably also provides a malleable nonpolar surface for the interaction with other crystallin components for the maintenance of a clear and transparent lens.

Amino Acid Sequence↗

PubMed1992

Effects of acute exercise on the biosynthesis of eicosanoids in rats.

We conducted this study to evaluate the effects of different intensities of acute exercise on the regulation of endogenous eicosanoid levels in male Wistar rats. The animals were divided into 4 groups; i.e.: control, mild exercise, moderate exercise and severe exercise. Immediately after exercise, animals were sacrificed. Plasma prostacyclin (PGI2) level and PGI2 release from two vessel segments (i.e., thoracic aorta and inferior vena cava) were determined by a specific 6-keto-PGF1 alpha (125I) radioimmunoassay. Urine thromboxane was determined by a specific 11-dehydro-TXB2 (125I) radioimmunoassay and normalized by urine creatinine. Although both plasma PGI2 and urine thromboxane tended to be elevated by severe exercise, only the increase in thromboxane was statistically significant (p < 0.05). In addition, PGI2 release from both vessels were not affected by different intensities of acute exercise. We also observed that aortic PGI2 release was greater than their corresponding veins in each group. We therefore conclude that only severe acute exercise, rather than mild or moderate exercise, may affect prostacyclin-thromboxane balance in rats.

Animals↗

PubMed1992

Pure rhabdomyosarcoma of the corpus uteri in a postpartum patient: report of a case and review of the literature.

Pure rhabdomyosarcomas originate in the female genital tract. They are uncommon and most often occur in infancy or childhood as sarcoma botryoides (embryonal rhabdomyosarcoma) which involve the vagina and cervix. Such tumors rarely occur in adults. A pure rhabdomyosarcoma of the uterus that arose in a postpartum patient is described. The pertinent literature is discussed.

Adult↗

PubMed1991

Gamma-crystallin genes in carp: cloning and characterization.

The carp gamma-crystallin gene family was found to be composed of at least three members: gamma m1, gamma m2 and gamma m3. The encoded products are very similar to other known gamma-crystallins but with their own peculiarities: (1) they all have a high methionine content: 12.4%, 14% and 8.4% in gamma m1, gamma m2 and gamma m3, respectively; and (2) the amino acid sequences are aberrant in the region before connecting peptides and its corresponding region in motif 4. Their protein structures might remain the same as those of other gamma-crystallins since they retain all the conserved amino acid residues essential for maintaining the loops in the protein structures.

Amino Acid Sequence↗