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Biomedical subjects

K C Hwang

Publications and source records attributed to K C Hwang.

At least 19 recordsLinked to original sources
PubMed2003

Fullerene derivative attenuates ischemia-reperfusion-induced lung injury.

Reactive oxygen species are the major contributing factors to lung ischemia-reperfusion (IR) injury. In this study, we tested whether a water soluble antioxidant fullerene derivative [C(60)(ONO(2))(7 +/- 2)] attenuates IR lung injury. Young Wistar rats were divided into two groups: control and C(60)(ONO(2))(7 +/- 2). Under ventilation with 95% air-5% CO(2) gas mixture and a 2.5 cm H(2)O end-expiratory pressure, the isolated lungs were perfused with a physiological solution. The experimental protocol included three periods: baseline (10 min), ischemia (45 min) and reperfusion (60 min, ventilated with 95% O(2)-5% CO(2) gas mixture). Before and after ischemia, we measured pulmonary arterial pressure (Ppa), pulmonary venous pressure and lung weight (W). Then, pulmonary capillary pressure and filtration coefficient (K(fc)) were calculated. Ischemia caused increases in Ppa, W and K(fc) in the control group. For most cases, the above ischemia-induced increases were attenuated by the C(60)(ONO(2))(7 +/- 2) pretreatment. Our results suggest that the antioxidant C(60)(ONO(2))(7 +/- 2) attenuates IR-induced lung injury.

Animals↗
PubMed2001

Implication of the small GTPase Rac1 in the apoptosis induced by UV in Rat-2 fibroblasts.

Exposure of mammalian cells to ultraviolet (UV) light elicits a cellular response and also lead to apoptotic cell death. However, the role of Rac, a member of Rho family GTPases, in the UV-induced apoptosis has never been examined. In UV-irradiated Rat-2 fibroblasts, nuclear fragmentation began to be observed within 2 h and the total viability of Rat-2 cells were only about 15% at 6 h following by UV irradiation, whereas the total viability in Rat2-Rac(N17) cells stably expressing RacN17, a dominant negative Rac1 mutant, was almost close to 67%. Pretreatment with SB203580, a specific inhibitor of p38 kinase, likewise attenuated UV-induced cell death, but PD98059, a MEK inhibitor, did not. Thus, Rac1 and p38 kinase appear to be components in the apoptotic signaling pathway induced by UV irradiation in Rat-2 fibroblasts. In addition, our results show that p38 kinase stimulation by UV is dramatically inhibited by RacN17, suggesting that p38 kinase is situated downstream of Rac1 in the UV signaling to apoptosis.

Animals↗
PubMed2001

A novel recombinant basic fibroblast growth factor and its secretion.

Basic fibroblast growth factor (FGF-2) is a pleiotropic mitogen which plays an important role in cell growth, differentiation, migration, and survival in different cells and organ systems. Recently, several clinical applications for FGF-2 gene transfer are being evaluated in wound healing and collateral artery development to relieve myocardial and peripheral ischemia due to the ability of FGF-2 to regulate the growth and function of vascular cells. However, FGF-2 lacks a classical hydrophobic secretion signal peptide, the FGF-2 chimeras containing various signal sequences have been explored. In this study, a novel recombinant 4sFGF-2 was constructed by replacing nine residues from the amino-terminus of native FGF-2 (Met1 to Leu9) with eight amino acid residues of signal peptide of FGF-4 (Met1 to Ala8) to better increase the secretion level of FGF-2. When the recombinant FGF-2 gene, cloned into the expression vector with CMV promoter, was expressed in COS-7 cells, the recombinant 4sFGF-2 was highly secreted into the media. The secreted 4sFGF-2 showed the same biological activity as the native FGF-2 in the dose-response effects on DNA synthesis and cell growth of rat aortic smooth muscle cells (RASMCs) and NIH3T3 cells. The 4sFGF-2 also was able to activate MAPK as wild FGF-2 in RASMCs. These results indicate that a novel recombinant 4sFGF-2 may be useful as clinical applicability of angiogenic growth factor gene transfer.

3T3 Cells↗
PubMed2001

Photoreactivation of alloxanthine-inhibited xanthine oxidase.

Alloxanthine-inhibited xanthine oxidase (XOD) was found to be photoreactivated by irradiation of light of wavelengths in the range of 340-430 nm. The enzyme activity can be fully controlled to be on or off by many dark-light cycles. Electron spin resonance measurement shows the appearance of the molybdenum (V) ion and the reduced form of flavin adenine dinucleotide (FADH.) radical signals after irradiation of the alloxanthine-XOD complex. Electronic-absorption spectrum also shows the bleaching of Fe/S and flavin adenine dinucleotide chromophores at 375 and 450 nm as well as broad-band absorption of FADH. in the range of 500-700 nm. The quantum yield of photoreactivation of the enzyme activity is approximately 0.06. A photoinduced intraenzyme electron-transfer model is proposed to rationalize the photoreactivation process.

Allopurinol↗
PubMed2001

Risk factors of wheeze and allergy after lower respiratory tract infections during early childhood.

Lower respiratory tract infections (LRIs) during early childhood can lead to bronchial hyperreactivity or recurrent obstructive bronchitis. The role of LRIs in the pathogenesis of allergic diseases such as allergic rhinoconjunctivitis, atopic eczema, and bronchial asthma is less clear. The aim of this retrospective study was to determine the incidence of subsequent wheezing and atopy, and the known risk factors for allergic sensitization in 74 children hospitalized for acute LRIs of various etiologies from January 1994 through December 1994. Results showed that there are no differences in outcomes between patients with respiratory syncytial virus LRI, Chlamydia pneumoniae LRI, and LRIs caused by other agents. Although lower respiratory tract illnesses, especially those caused by respiratory syncytial virus during infancy, were associated with an increased risk of subsequent wheezing during early childhood, wheezing tended to disappear with increasing age in many children. This study also found recurrent episodes of wheezing during the first 5 years of life, and symptoms suggestive of allergic rhinoconjunctivitis were the only factors predictive of subsequent diagnosis of asthma for children who had LRIs during early childhood. In conclusion, this study suggests that prevention of recurrent wheezing LRIs and good control of allergic rhinoconjunctivitis is critical for preventing subsequent development of bronchial asthma.

Asthma↗
PubMed2000

Proline inhibits aggregation during protein refolding.

The in vitro refolding of hen egg-white lysozyme is studied in the presence of various osmolytes. Proline is found to prevent aggregation during protein refolding. However, other osmolytes used in this study fail to exhibit a similar property. Experimental evidence suggests that proline inhibits protein aggregation by binding to folding intermediate(s) and trapping the folding intermediate(s) into enzymatically inactive, "aggregation-insensitive" state(s). However, elimination of proline from the refolded protein mixture results in significant recovery of the bacteriolytic activity. At higher concentrations (>1.5 M), proline is shown to form loose, higher-order molecular aggregate(s). The supramolecular assembly of proline is found to possess an amphipathic character. Formation of higher-order aggregates is believed to be crucial for proline to function as a protein folding aid. In addition to its role in osmoregulation under water stress conditions, the results of this study hint at the possibility of proline behaving as a protein folding chaperone.

Animals↗
PubMed2000

Penicillamine induced lupus-like syndrome: a case report.

Several drugs have been suggested to cause lupus-like syndrome. However, penicillamine-induced lupus-like syndrome has only rarely been reported in patients with Wilson's disease. We describe a 6- year-old Taiwanese girl, with a diagnosis of Wilson's disease in November, 1997, who developed lupus-like syndrome 17 months after penicillamine treatment. After treatment with prednisolone and decrease in the dose of penicillamine, her symptoms subsided gradually. This is the first such case reported in a Taiwanese patient. Because the symptoms of drug-induced lupus (DIL) are nonspecific, subjective and variable, the diagnosis of DIL requires awareness of DIL-inducing potential of chronic medication.

Child↗
PubMed1999

C(60) and water-soluble fullerene derivatives as antioxidants against radical-initiated lipid peroxidation.

C(60), vitamin E, and three C(60) derivatives (polar 1 and water-soluble C(3)/D(3)C(60)s) were examined for their antioxidant effects on prevention of lipid peroxidation induced by superoxide and hydroxyl radicals. The protection effect on lipid peroxidation was found to be in the sequence: C(60) >/= vitamin E > 1 > none, for liposoluble antioxidants, and C(3)C(60) >> D(3)C(60) > none, for water-soluble ones. Fluorescence quenching of PyCH(2)COOH (Py = pyrene) by both C(3)- and D(3)C(60)s shows that the Stern-Volmer constant, K(SV), is about the same for both quenchers in aqueous solution. Upon addition of liposomes, the fluorescence quenching becomes more efficient: 5-fold higher in K(SV) for C(3)C(60) than for D(3)C(60). When Py(CH(2))(n)()COOH (n = 1, 3, 5, 9, or 15) was incorporated in lipid membranes, the K(SV)s all were small and nearly equal for D(3)C(60) but were quite large and different for C(3)C(60) with the sequence: n = 1 < 3 < 5 < 9 < 15. The better protection effect of C(3)C(60) on lipid peroxidation than that of D(3)C(60) is attributed to its stronger interaction with membranes. Overall, the antioxidation abilities of the compounds examined were rationalized in terms of the number of reactive sites, the location of antioxidant in lipid membranes, and the strength of interactions between antioxidants and membranes.

Antioxidants↗
PubMed1999

Effects of indoor environmental factors on risk for acute otitis media in a subtropical area.

The objective of this study was to examine the relationship between indoor environmental factors and acute otitis media in a subtropical area. A case-control study was performed using participants from a prevalence survey that included 219 school children with acute otitis media and 219 age- and gender-matched controls. The study was confined to 4164 primary school children aged 6-12 yr attending 8 primary schools in Kaohsiung rural municipalities who participated in a prevalence study of the health effects of an indoor environment. An acute otitis media case was defined as a child with acute symptoms (presenting with earache, fever, irritability, and/or discharge from the ear) diagnosed by a physician in the previous year. Controls selected from the same school did not have chronic or acute respiratory illness or an ear-related illness during the same period. Information regarding the home environment was obtained using a structured written questionnaire, completed by the parents of the children. Of the many indoor environmental factors included in this study, only living in a home with indications of dampness (mold, flooding, home dampness) showed an association with acute otitis media. It was concluded that dampness in the home is a new public health issue in subtropical areas.

Acute Disease↗
PubMed1998

Blockage of apoptotic signaling of transforming growth factor-beta in human hepatoma cells by carboxyfullerene.

Transforming growth factor-beta (TGF-beta) has been shown to induce apoptosis in normal hepatocytes and hepatoma cells both in vivo and in vitro. However, the mechanism by which TGF-beta induces apoptosis is not clear. The antiapoptotic activity of antioxidants including N-acetyl-L-cysteine (Ac-Cys), ascorbic acid and a novel free radical scavenger, carboxyfullerene (C60) on TGF-beta-treated human hepatoma Hep3B cells was examined. Only the water-soluble hexacarboxylic acid derivative of C60 was found to prevent TGF-beta-induced apoptosis. Antiapoptotic activity of C60 correlated its ability to eliminate TGF-beta-generated reactive oxygen species (ROSs). However, C60 did not interfere with TGF-beta-activated PAI-1 promoter activity in the Hep3B cells. These results indicate that the signaling pathway of TGF-beta-induced apoptosis may be related to the generation of ROSs and may be uncoupled from the TGF-beta-activated gene promoter activity. Furthermore, the regioisomer of C60 with a C3 symmetry was more potent in protecting cells from apoptosis than that with a D3 symmetry, and the C3 isomer had stronger interactions with lipid bilayers than the D3 isomer. The spectroscopic analysis revealed that the C3 isomer had stronger interactions with artificial lipid bilayers than the D3 isomer. Therefore, our study indicates that C60 may interact with membrane to eliminate TGF-beta-induced ROSs and to prevent apoptosis occur in human hepatoma cells.

Acetylcysteine↗
PubMed1998

Childhood asthma and the indoor environment in a subtropical area.

STUDY OBJECTIVES: The objective of this study is to examine the relationship between indoor environmental factors and childhood asthma in a subtropical area. DESIGN: A case-control study was performed using participants of a prevalence survey that included 165 schoolchildren with asthma and 165 age- and gender-matched control subjects. SETTING: The study was confined to 4,164 schoolchildren aged 6 to 12 years attending eight primary schools in Kaohsiung County rural municipalities who participated in a prevalence study concerning the health effects of the indoor environment. PARTICIPANTS: Cases (n=165) were defined as children with current asthma confirmed by a physician. Control subjects (n=165) were selected from the same school and class and matched for age and gender, and they did not have a previous diagnosis of asthma, history of physician-confirmed atopic diseases, persistent wheezing, cough, or phlegm, or reported chest illness, pneumonia, or bronchitis. MEASUREMENTS AND RESULTS: Information regarding the home environment was obtained using a structured written questionnaire, completed by the parents of the children. Of the many indoor environmental factors included in this study, only home dampness showed an association with asthma (odds ratio=2.65). CONCLUSIONS: We conclude that dampness in the home is a new public health issue in subtropical areas.

Air Pollution, Indoor↗
PubMed1996

Alpha 1-adrenergic receptor coupling with Gh in the failing human heart.

BACKGROUND: We recently demonstrated that Gh, which transfers the signal from the alpha 1-adrenergic receptor to the 69-kD phospholipase C, is the previously identified tissue-type transglutaminase (TGase II). The alpha 1-adrenergic receptor mediates actions of the sympathetic nervous system, including cardiac, arteriolar, and smooth muscle contractions. In human cardiac tissue, the expression of the alpha 1-adrenergic receptor is increased under pathophysiological conditions, but changes in the physiological response are small. Therefore, it has been suggested that the other components involved in the alpha 1-adrenergic receptor-mediated signaling pathway are probably altered. METHODS AND RESULTS: Immunological and biochemical studies with nonfailling and failing human heart tissues revealed that the GTP-binding and TGase activities of human heart TGase II (hhG alpha n) are downregulated in both ischemic and dilated cardiomyopathic human heart. In ischemic cardiomyopathy, the alpha 1-adrenergic receptor number increased twofold (27.0 fmol/mg) compared with the nonfailing (12.8 fmol/mg) and the dilated cardiomyopathic (15.6 fmol/mg) heart tissues, but the coupling of hhG alpha h with the alpha 1-adrenergic receptor did not increase. The intrinsic activity of hhG alpha h, was greatly decreased in membrane fractions, whereas the cytosolic TGase activity was not changed. In the dilated cardiomyopathic human heart, these intrinsic enzyme activities of hhG alpha h were also downregulated in the membrane fraction, whereas the amount of hhG alpha h protein was greatly increased (2.8-fold) compared with the nonfailing heart. CONCLUSIONS: The results of the present study clearly demonstrate that the alpha 1-adrenergic receptor in human heart couples with Gh (TGase II) and indicate that downregulation of hhG alpha h activity is associated with human cardiac failure but that the mechanism differs between ischemic and dilated cardiomyopathies.

Adolescent↗
PubMed1996

A 50 KDa protein modulates guanine nucleotide binding of transglutaminase II.

Regulation of cellular response is an important mechanism for controlling cellular functions. The transmembrane signaling of the hormone receptors is regulated by GTP-binding proteins (GTPases) and their associated proteins. Our previous studies demonstrated that the bifunctional GTP-binding protein, G alpha h (transglutaminase II), consistently copurified with an approximately 50 kDa protein (G Beta h) which is dissociated from G alpha h upon activation with GTP gamma S or AlF4-. Present immunological and biochemical studies on the regulation of the GTPase cycle of G alpha h, which involves the alpha 1-adrenoceptor and 50 KDa G beta h, reveal that the 50 kDa protein is indeed a G alpha h-associated protein and down regulates functions of G alpha h. Thus, polyclonal antibody against G Beta h coimmunoprecipitates GDP-bound G alpha h but not the GDP-AlF4--bound form. The GTP gamma S binding and GTPase activity of G alpha h are inhibited in a G beta h concentration dependent manner. Supporting this notion, G beta h accelerated GTP gamma S release from G alpha h and changes the affinity of G alpha h from GTP to GDP. Moreover, the ternary complex preparation exhibits TGase activity that is inhibited in the presence of the alpha 1-agonist and GTP. The GTP gamma S binding by the ternary complex, consisting of the alpha 1-agonist, the receptor, and Gh, is also inhibited by G beta h. The inhibition of GTP gamma S binding with the ternary complex requires a > or = 2.7-fold higher concentration of G beta h than the G alpha h alone, indicating that the receptor enhances the affinity of G alpha h for GTP. In addition, G beta h copurifies with an alpha 1-agonist, adrenoceptor, and G alpha h ternary complex, showing that the complex is a heterotetramer. Our data also suggest that G beta h does not directly interact with alpha 1-adrenoceptor. These findings clearly demonstrate that G alpha h associates with a novel protein which modulates the affinity of G alpha h for guanine nucleotides and that the GDP-bound Gh is the ground state for the counterpart activator, the alpha 1-adrenoceptor, in this signaling system.

Animals↗
PubMed1995

Interaction site of GTP binding Gh (transglutaminase II) with phospholipase C.

The GTP binding G alpha h (transglutaminase II) mediates the alpha 1B-adrenoreceptor signal to a 69-kDa phospholipase C (PLC). Thus, G alpha h possesses both GTPase and transglutaminase activities with a signal transfer role. The recognition sites of this unique GTP binding protein for either the receptor or the effector are completely unknown. A site on human heart G alpha h (hhG alpha h) has been identified that interacts with and stimulates PLC. Expressed mutants of hhG alpha h with deleted C-terminal regions lost the response to (-)-epinephrine and GTP and failed to coimmunoprecipitate PLC by the specific Gh7 alpha antibody. The interaction regions were further defined by studies with synthetic peptides of hhG alpha h and a chimera in which residues Val665-Lys672 of hhG alpha h were substituted with Ile707-Ser714 residues of human coagulation factor XIIIa. Thus, eight amino acid residues near the C terminus of hhG alpha h are critical for recognition and stimulation of PLC.

Amino Acid Sequence↗
PubMed1994

Synthesis of amphipathic porphyrins and their photoinduced electron transfer reactions at the lipid bilayer-water interface.

A one flask synthesis of cis-substituted amphipathic porphyrins is reported. These porphyrins were used to study electrostatic effects on photoinduced electron transfer across the lipid bilayer-water interface. A neutral porphyrin undergoes only dynamic interfacial electron transfer reactions irrespective of charge of the acceptor, although ionic strength effects indicate a negative charge on the porphyrin donor species. A dianionic porphyrin forms an interfacial static complex with a dicationic electron acceptor, methyl viologen, at low ionic strength. The electron transfer rate within the complex is slow, 10(5) approximately 10(6) s-1, which is attributed to a near orthogonal orientation between the donor and the acceptor pi orbitals.

Electrochemistry↗
PubMed1993

Photoinduced electron transport across a lipid bilayer mediated by C70.

Electron transport across a membrane is central to photosynthesis, to mitochondrial respiration and to the design of molecular systems for solar energy conversion. Relatively few synthetic molecules, however, have been shown to facilitate transport of electrons across a lipid bilayer. We report here that C70 can act as both a photosensitizer for electron transfer from a donor molecule and a mediator for electron transport across a lipid bilayer membrane. The steady-state photocurrent density obtained from the C70-bilayer system is about 40 times higher, at comparable light intensities, than that of the carotene-porphyrinquinone system, previously the most efficient artificial system. The C70-bilayer system has a quantum yield of about 0.04, while the stability (tens of minutes) and turnover number (electrons transported per C70 before decay) of 10(3) are one to three orders of magnitude greater than those of other systems. We anticipate that other higher fullerenes may also provide the basis for efficient transmembrane electron-transport systems.

Electron Transport↗
PubMed1990

Immunologic and virologic status of multitransfused thalassemic patients.

Viral markers of hepatitis B virus (HBV), cytomegalovirus (CMV) and human immunodeficiency virus (HIV), immunoglobulins and complements, T-cell subpopulation antibodies (OKT series) and mitogen responses have been investigated in 68 multitransfused thalassemic patients and in 46 age-matched children. Results showed (1) 56 patients (82.4%) had been exposed to HBV; 29 patients (42.6%) had been exposed to CMV and none were HIV infection. (2) Increased IgG, IgA, OKIal, and decreased C3, OKT3, OKT4, OKT4/OTK8 ratio showed in patients as compared to controls. (3) An apparent increase in lymphocyte proliferation was seen in patients' cultures with or without mitogen (PHA and ConA) stimulation. (4) No definite factors such as sex, age at first transfusion, number of transfusions or HBsAg carrier status correlated with the abnormal change of immunological tests. (5) Immunological investigation, done on 2 occasions six months apart, revealed no significant modifications except that 13 patients (19%) who were initially seronegative for CMV converted to seropositive. These investigations suggest that, although saline-washed RBC was used for the transfused patients, there was high prevalence of HBV and CMV infection. Further studies of lymphocyte function (i.e. lymphokines) are needed to understand the increased spontaneous proliferation in culture and PHA, ConA mitogen responses.

Adolescent↗