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Biomedical subjects

C Z Wang

Publications and source records attributed to C Z Wang.

At least 37 records · Page 2Linked to original sources
PubMed2000

Synthesis of 3,3',5-trihydroxybiphenyl-2-carboxylic acid, a component of the bitterest natural product amarogentin and its coenzyme A and N-acetyl cysteamine thiol esters.

3,3',5-Trihydroxybiphenyl-2-carboxylic acid (6), an ester component of the bitter-tasting natural products amarogentin and amaroswerin, was synthesized in six steps in 13.6% overall yield. Its N-acetyl cysteamine thiol ester (9) and its coenzyme A thiol ester (8), a likely biosynthetic precursor of the amarums, were also prepared.

Coenzyme A↗
PubMed2000

Insulin secretion and differential gene expression in glucose-responsive and -unresponsive MIN6 sublines.

We have established two sublines derived from the insulin-secreting mouse pancreatic beta-cell line MIN6, designated m9 and m14. m9 Cells exhibit glucose-induced insulin secretion in a concentration-dependent manner, whereas m14 cells respond poorly to glucose. In m14 cells, glucose consumption and lactate production are enhanced, and ATP production is largely through nonoxidative pathways. Moreover, lactate dehydrogenase activity is increased, and hexokinase replaces glucokinase as a glucose-phosphorylating enzyme. The ATP-sensitive K(+) channel activity and voltage-dependent calcium channel activity in m14 cells are reduced, and the resting membrane potential is significantly higher than in m9 cells. Thus, in contrast to m9, a model for beta-cells with normal insulin response, m14 is a model for beta-cells with impaired glucose-induced insulin secretion. By mRNA differential display of these sublines, we found 10 genes to be expressed at markedly different levels. These newly established MIN6 cell sublines should be useful tools in the analysis of the genetic and molecular basis of impaired glucose-induced insulin secretion.

ATP-Binding Cassette Transporters↗
PubMed1999

Dose dependence and time course of smoke inhalation injury in a rabbit model.

The dose dependence and time course of smoke inhalation injury were determined in a rabbit model. Animals were insufflated with 18-90 breaths of cotton smoke or room air (control) at a rate of 18 breaths/min and tidal volume of 12 ml/kg. Smoke-exposed animals exhibited dose-related histologic effects with progressive deterioration of respiratory function during the postexposure period of observation (96 h). The smoke-exposed rabbits had reproducible injuries to both airway mucosa and lung parenchyma, manifested by disruption and sloughing of airway and alveolar epithelia, and exudation of protein-rich fluid and leukocytes into the airway and alveolar spaces. Significant effects were evident by 24 h postexposure. Smoke inhalation also affected the respiratory burst of alveolar macrophages. Generation of superoxide anions by alveolar macrophages at 48 h postexposure was increased significantly after smoke inhalation (54 breaths). The present rabbit model should be useful for studying the interactions between pulmonary epithelial cells and leukocytes after smoke inhalation and for determining the role that abnormal functioning of alveolar macrophages plays in the development of smoke inhalation injury.

Animals↗
PubMed1999

Subacute pituitary apoplexy-analysis of 17 cases.

We retrospectively study 17 cases (total cases 197), receiving surgery at Kaohsiung Medical College Hospital, which are proved to be subacute pituitary apoplexy via preoperative computerized tomograms, magnetic resonance imagings, operative findings and pathological proof. Fourteen patients had headache; 15 cases were with visual disturbance including visual defect, blindness. One case was found incidentally to have a cerebral vascular attack. None of these cases received bromocriptine. Preoperative computerized tomograms (CT) aided the initial diagnosis and magnetic resonance imaging (MRI) is preferred for radiological investigation in displaying the metabolic products of hemorrhage within the pituitary tumors. Operative findings revealed xanthochromic fluid with liquid-like tumor debris or chocolate-like content. All these patients received hormone supplement when pituitary apoplexy was highly suspected.

Acute Disease↗
PubMed1998

Evidence for pH sensitivity of tumor necrosis factor-alpha release by alveolar macrophages.

Alveolar macrophages (m phi) participate in inflammatory and immune responses in acidic microenvironments such as the interstitial fluids of tumors and abscesses. Two plasmalemmal H+ extruders interact to control the acid-base status of alveolar m phi, namely a V-type H+ pump (V-ATPase) and a Na+/H+ exchanger. The present study examined the effects of extracellular pH (pHo) and H+ transport inhibitors on tumor necrosis factor-alpha (TNF-alpha) release induced by endotoxin (lipopolysaccharide) in rabbit alveolar m phi. The amount and activity of TNF-alpha in m phi-conditioned media were determined by enzyme-linked immunosorbent assay and L929 fibroblast bioassay, respectively. TNF-alpha release was suppressed progressively at lower pHo values (< or = 7.0). Also, bafilomycin A1 (a specific inhibitor of V-ATPases) significantly reduced the amount and activity of TNF-alpha in m phi-conditioned media (pHo 7.4). However, bafilomycin caused a significant increase in the nonspecific cytotoxicity (i.e. bioactivity insensitive to TNF-alpha antibody) of m phi-conditioned media. The effects of bafilomycin specifically on TNF-alpha release followed a time course similar to that of acidic pHo, suggesting that both treatments acted on similar events in the lipopolysaccharide signal transduction pathway. Amiloride (an inhibitor of Na+ transporters including the Na+/H+ exchanger) also suppressed TNF-alpha release but displayed a time course of action different from the acidic pHo or bafilomycin.

Amiloride↗
PubMed1998

Cotton smoke inhalation primes alveolar macrophages for tumor necrosis factor-alpha production and suppresses macrophage antimicrobial activities.

The present study determined the effects of cotton smoke inhalation on the functioning of alveolar macrophages (mphi). Smoke inhalation led to dose-dependent impairment of respiratory gas exchange by 48 h postexposure and pulmonary edema by 96 h. Maximal effects were observed in animals ventilated with 54 breaths of cotton smoke (3-min exposure, 18 breaths/min). Macrophages were obtained at 48 h postexposure by bronchoalveolar lavage of rabbits subjected to 54 breaths of smoke or room air (control). Phagocytosis of opsonized bacteria and adherence to solid substratum were reduced in smoke-exposed mphi. Smoke inhalation primed mphi for release of tumor necrosis factor-alpha (TNF-alpha) induced by lipopolysaccharide (LPS). Smoke-exposed mphi were also primed for TNF-alpha release induced by phorbol myristate acetate, which suggests that the priming event occurred downstream of protein kinase C activation in the signal transduction pathway. Further, smoke exposure attenuated the inhibitory effects of phosphodiesterase inhibitors on LPS-induced TNF-alpha release. Thus, the priming event may be mediated through cAMP and/or protein kinase A. The data indicate that cotton smoke inhalation suppresses the antimicrobial activities of alveolar mphi and can lead to excessive mphi production of TNF-alpha. These mphi effects would be expected to contribute to the pathophysiological abnormalities associated with smoke inhalation injury.

Acute Disease↗
PubMed1996

Cloning and pharmacological characterization of a fourth P2X receptor subtype widely expressed in brain and peripheral tissues including various endocrine tissues.

We have isolated cDNA encoding a fourth member (P2X-4) of the ATP receptor P2X receptor family from a rat pancreatic islet cDNA library. Rat P2X-4 is a protein of 388 amino acids which shares 50%, 49%, and 47% identity with P2X-1, P2X-2, and P2X-3, respectively, and has two putative transmembrane segments. Rat P2X-4 mRNA is widely expressed in brain and peripheral tissues, including various endocrine tissues, and it is also expressed in various hormone-secreting cell lines. We have heterologously expressed the cloned P2X-4 in Xenopus laevis oocytes and have characterized its pharmacological properties. ATP, its analogs and ADP activate cation-selective ion channels. The order of agonist potency is ATP ADP 2-methyl- thioATP(2MeSATP) >> alpha beta-methelene-ATP (alpha betameATP). ATP-evoked currents are only partially blocked by suramin, reactive blue-2, or H2DIDS. The present study suggests that P2X-4, with pharmacological properties distinct from those of P2X-1+, P2X-2, and P2X-3, mediates extracellular ATP-induced biological effects in non-neuronal cells, including endocrine cells, as well as in neuronal cells.

Amino Acid Sequence↗
PubMed1996

Early effects of smoke inhalation on alveolar macrophage functions.

Alveolar macrophage (AM) dysfunctions have been implicated in the pathogenesis of smoke inhalation lung injury. We investigated the early (within 70 min) effects of smoke inhalation on AM. The cells were recovered by bronchoalveolar lavage from rabbits ventilated with cotton smoke for 5 min followed by O2/room air for 60 min (smoke-exposed) or with room air in place of smoke (control). Smoke injury caused arterial blood carboxyhaemoglobin levels to increase 11-fold and reduced arterial blood PO2 (measured approximately 1 h postinjury) by 25 per cent. Scanning electron micrographs revealed denudation of plasmalemmal pseudopods in smoke-exposed AM. Smoke exposure suppressed both AM adherence to plastic and phagocytosis of opsonized bacteria. Basal superoxide (O2-) production was elevated in smoke-exposed AM, compared with controls, whereas PMA-stimulated O2- production was unaffected. Smoke-exposed AM had reduced basal secretion of tumour necrosis factor-alpha (TNF-alpha), but displayed a greater TNF response to stimulation with LPS than did control cells. LPS-stimulated TNF-alpha releases from control and smoke-exposed AM were suppressed by phosphodiesterase inhibitors pentoxifylline and theophylline, and were enhanced by the lipoxygenase inhibitor, MK886. The early responses of AM to smoke inhalation lung injury are consistent with activation of O2- production and priming of TNF-alpha release, concurrent with a functional down regulation of phagocytosis.

Animals↗
PubMed1996

A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K+ channels.

We have cloned an isoform of the sulfonylurea receptor (SUR), designated SUR2. Coexpression of SUR2 and the inward rectifier K+ channel subunit Kir6.2 in COS1 cells reconstitutes the properties of K(ATP) channels described in cardiac and skeletal muscle. The SUR2/Kir6.2 channel is less sensitive than the SUR/Kir6.2 channel (the pancreatic beta cell KATP channel) to both ATP and the sulfonylurea glibenclamide and is activated by the cardiac K(ATP) channel openers, cromakalim and pinacidil, but not by diazoxide. In addition, SUR2 binds glibenclamide with lower affinity. The present study shows that the ATP sensitivity and pharmacological properties of K(ATP) channels are determined by a family of structurally related but functionally distinct sulfonylurea receptors.

ATP-Binding Cassette Transporters↗
PubMed1996

Cellular distribution of the P2X4 ATP receptor mRNA in the brain and non-neuronal organs of rats.

RNA blot analysis has shown that an ionotropic ATP receptor P2X4 is widely distributed, as compared with other P2X subtypes. Cellular distribution of the P2X4 ATP receptor mRNA was investigated by in situ hybridization technique in the brain and non-neuronal organs. In the brain, transcripts of the P2X4 were widely distributed in various regions, with the highest signals in the cerebellar Purkinje cells and granule cells. In other organs, intense and selective expression was detected in seminiferous tubules of the testis and intestinal crypts of the colon, suggesting an involvement of ATP in spermatogenesis and intestinal secretion. A low but significant level of the P2X4 mRNA was detected in the adenohypophysis and the cortex of the adrenal gland. The tissue- or cell-specific expression of the P2X4 mRNA is of importance to understand the functional roles of the purinergic transmission system.

Adrenal Glands↗
PubMed1995

Human gastric inhibitory polypeptide receptor: cloning of the gene (GIPR) and cDNA.

Gastric inhibitory polypeptide (GIP), which is released from the gastrointestinal tract, stimulates insulin secretion from pancreatic beta cells and plays a crucial role in the regulation of insulin secretion during the postprandial phase. We have isolated the human gene (GIPR) and cDNA encoding the GIP receptor by a combination of the conventional screening and polymerase chain reaction procedures. Human GIP receptor cDNA encodes a protein of 466 amino acids that is 81.5 and 81.2% identical to the previously cloned hamster and rat GIP receptor, respectively. Hydropathic analysis shows the presence of a signal peptide and seven potential transmembrane domains, a feature characteristic of the VIP/glucagon/secretin receptor family of G protein-coupled receptors. The human GIPR gene is about 13.8 kb long, consists of 14 exons, and carries 17 Alu repeats.

Amino Acid Sequence↗
PubMed1995

Experimental studies on early treatment of schistosomal infection with artemether.

An early treatment with artemether given in appropriate regimens was tested in mice, rabbits and dogs for prevention purposes. Artemether was administered intragastrically (ig) to the hosts on day 7 after infection with Schistosoma japonicum cercariae at a single dose, and the same dose of artemether was repeated every 1 or 2 weeks for 2-4 times. As a result, most of the female worms were killed before their oviposition with female worm reduction rates of 90-100%, resulting in protection of the host from damage induced by schistosome eggs. When rabbits were treated ig with artemether 10 mg kg-1 on day 7 after infection, followed by repeated dosing every week for 4 times, some parameters related to acute schistosomiasis, such as temperature, eosinophil count and eggs in the feces were negative, and low specific antigen and antibody levels in serum were seen. Further study showed that the appropriate regimens of Artemether were also effective in early treatment of reinfection with cercariae. When rabbits infected with 48-52 cercariae once every other day for 5 times were treated ig with artemether 15 mg kg-1, followed by repeated dosing every 1 or 2 week for 2- 3 times, the female worm reduction rates were 92.1-98.4%. Histopathological examination of the livers showed that the above-mentioned early treatment with Artemether exhibited a promising protective effect on dogs and rabbits. The major features included normal appearance of the liver resembling those of uninfected dogs and rabbits; few or no dispersed miliary egg tubercles appeared on the surface of the liver; the structure of the hepatic lobules was normal with normal arrangement of the liver bundles; few or no eggs appeared in the portal vein area and there was apparent diminution of total egg granuloma, comprising inflammatory, fibrous or scarred egg granuloma. On the basis of above-mentioned results, early treatment with Artemether could be recommended for field trial for controlling acute schistosomiasis, reducing infection rate and intensity of infection.

Animals↗
PubMed1994

Pulmonary inflammatory cell response to sustained endotoxin administration.

We have developed a model of human sepsis in sheep. Twenty-four hours after continuous infusion of Escherichia coli endotoxin (lipopolysaccharide) (10 ng.kg-1.min-1) was begun, pulmonary transvascular fluid flux was almost five times the baseline values, cardiac output was nearly doubled, and mean arterial pressure was reduced by approximately 20 mmHg. At this time, the animals were killed and their lungs were fixed by endotracheal installation of 2.5% glutaraldehyde at 25 cmH2O pressure. Morphometry was performed by point counting, and data were expressed as relative volume density. Pulmonary edema and congestion were observed in sheep receiving lipopolysaccharide, whereas sham controls appeared normal. There was an increase in interstitial volume density. There was a significant increase (P < 0.01) in volume density of the pulmonary intravasculature (180%), interstitial macrophages (270%), and mast cells (240%). The volume densities of intravascular and interstitial polymorphonuclear neutrophils also showed a small insignificant increase.

Animals↗
PubMed1994

Efficacy of cefazolin in promoting ovine tracheal epithelial repair.

Inhalation of toxic materials has been shown injurious to the upper airways. Because secondary infection can slow the repair process, we undertook this study to determine the efficacy of antibiotic therapy in promoting the healing process of acute tracheal wounds. In 18 anesthetized sheep, a portion of the cervical trachea was exposed to smoke from smoldering cotton cooled to 38 degrees C. Nine received the broad-spectrum antibiotic, cefazolin, while none received saline placebo. At 13 days after injury, nonciliated and ciliated cell counts were 75% and 33% respectively of noninjured trachea receiving placebo, while in those receiving cefazolin, nonciliated and ciliated cell counts increased to 93% and 114% of paired noninjured trachea, respectively. We suggest that cefazolin therapy allows cell proliferation and differentiation to proceed more rapidly than observed with placebo therapy and thus may be a helpful augmentor to the healing of an acute airway injury.

Animals↗
PubMed1993

Growth factors accelerate epithelial repair in sheep trachea.

Toxic gases and fumes have been shown to be injurious to the upper airways. Repair of this injury involves proliferation and migration of surviving nonciliated cells, followed by differentiation to a normal phenotype. Because recent results suggested that growth factors could improve the outcome of an airway injury, we undertook this study to determine the efficacy of these materials as an initial treatment to accelerate the healing process. In 24 anesthetized sheep, a portion of the trachea was exposed to smoke from smouldering cotton cooled to 37 degrees C. Twelve received aerosolized epidermal growth factor plus platelet derived growth factor, while twelve received placebo. At 10 days after injury, nonciliated and ciliated cells were totally absent in the injured trachea receiving the placebo. In animals receiving growth factors, nonciliated and ciliated cells, however, were present (56% and 31% of uninjured trachea, respectively). At 13 days after injury, nonciliated and ciliated cell counts in those receiving placebo were 67% and 33% of uninjured, respectively. In sheep receiving growth factors, tracheal nonciliated and ciliated cell counts had increased to 105% and 64% of uninjured trachea, respectively. We conclude that growth factors therapy after airway injury stimulates cell proliferation and differentiation, and this therapeutic intervention to accelerate the repair process in acute airway injury is an approach applicable to humans.

Animals↗
PubMed1993

Influence of detergent aerosol on lung microvascular permeability.

Noncardiogenic edema fluid often contains high levels of plasma proteins, which may inhibit the function of the lung surfactant complex and thus decrease interstitial hydrostatic pressures. We questioned whether, in the awake and standing animal, displacement of the alveolar surface lining would alter the permeability of the thin and sparsely supported pulmonary capillaries. Sheep prepared with lung lymph fistulae were given an aerosolized detergent (Det) to displace the lung surfactant complex. After the sheep were given Det, protein flux was significantly increased (P < 0.05). To validate the suggested permeability increase, pulmonary vein occluders were surgically implanted and experiments repeated with pulmonary arterial pressures elevated 10 mmHg above baseline. After 2 h of elevated pulmonary arterial pressure, lung lymph increased fivefold. At this time, lymph-to-plasma total protein concentration ratios for air and saline-plus-ethanol vehicle were significantly lower (P < 0.01) than baseline ratios (0.26 +/- 0.06 and 0.34 +/- 0.07, respectively). No significant difference could be shown in lymph-to-plasma ratios after the sheep were given Det. We conclude that disruption of the alveolar lining can cause a detectable increase in protein flux due, in part, to an increase in microvascular permeability.

Aerosols↗
PubMed1992

Cellular sequence of tracheal repair in sheep after smoke inhalation injury.

The cellular repair process of injured tracheal epithelium is described for sheep after exposure to toxic smoke containing high concentrations of acrolein. Fourteen fasted 3-4-year-old ewes had a portion of their cervical trachea exposed to cotton smoke for 20 min and then were sacrificed at various time intervals ranging from 1 to 22 days after exposure. Within 1 day of injury, columnar epithelium sloughed intact from the trachea with a concomitant reduction of nearly 35% in the basal cell population. At 2 days of recovery, the cellularity of the epithelium had increased and mitotic figures were observed in some tracheal epithelial and gland cells. By 8 days, undifferentiated hyperplastic cells increased to 30/100 microns, differentiated nonciliated columnar cells first appeared, and the basal cell population returned to a normal count of 13 cells/100 microns. Thirteen days after exposure, the undifferentiated hyperplastic cell population had declined to 7 cells/100 microns, nonciliated columnar cells were at control values, and some ciliated cells were identified. At 18 and 22 days, epithelium was normal in appearance and the count was 13 cells/100 microns. Data suggest that because the columnar epithelium sloughs intact with the cilia remaining active, toxic smoke may affect their attachment to the basal lamina. Furthermore, the regeneration process involves differentiation of hyperplastic cells in which they elongate down to the basal lamina, thus re-establishing the integrity of tall epithelium in the sheep trachea.

Animals↗