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Biomedical subjects

M L Chang

Publications and source records attributed to M L Chang.

At least 19 recordsLinked to original sources
PubMed2005

Signal transduction pathways of nitric oxide release in primary microglial culture challenged with gram-positive bacterial constituent, lipoteichoic acid.

Between one-third and one-half of all cases of sepsis are known to be caused by gram-positive microorganisms through the cell wall component, e.g. lipoteichoic acid (LTA). Gram-positive bacteria are also known to induce encephalomyelitis and meningeal inflammation, and enhance the production of nitric oxide (NO) via expression of inducible nitric oxide synthase (iNOS) in murine tissue macrophages. It remains to be explored if LTA could activate microglia considered to be resident brain macrophages. We report here that LTA derived from gram-positive bacteria (Staphylococcus aureus) significantly induces NO release and iNOS expression in primary microglia. LTA-induced NO accumulation was detected at 2 h in microglial culture and was significantly attenuated by pretreatment with anti-CD14, complement receptor type 3 (CR3) or scavenger receptor (SR) antibodies. LTA activated mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinase, p38 MAPK or c-Jun N-terminal kinase in cultured microglia. LTA-elicited microglial NO production was also drastically suppressed by SB203580 (p38 MAPK inhibitor) or pyrrolidine dithiocarbamate (an inhibitor of nuclear factor kappaB), indicating that p38 MAPK and nuclear factor kappaB were involved in microglial NO release after LTA challenge. These results suggest that gram-positive bacterial product such as LTA can activate microglia to release NO via the signal transduction pathway involving multiple LTA receptors (e.g. CD14, CR3 or SR), p38 MAPK and nuclear factor kappaB. The in vivo study further confirmed that administered intracerebrally LTA induced considerable noticeable iNOS, phospho-IkappaB and phospho-p38 MAPK expression in microglia/macrophages.

Animals↗
PubMed2003

Recent developments on the role of mitochondria in poly(ADP-ribose) polymerase inhibition.

Numerous pathophysiological disorders involve some element of oxidative stress and bioenergetic deficit. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors have been used recently as a promising new therapeutic strategy aimed at halting the bioenergetic decline associated with oxidative brain insults and other conditions. PARP-1 uses NAD+ as a substrate and is activated during stressful circumstances, mainly in the nucleus. PARP-1 inhibitors are well known for blocking the excessive consumption of NAD+, thereby preserving energy metabolism. But what is the role of mitochondria in this process? Recent investigations have begun to focus on whether mitochondrial function can also be preserved by PARP-1 inhibitors. This review will present some of the latest mechanistic evidence documenting the potential involvement of PARP-1 inhibitors in protecting mitochondrial function and preventing necrosis, apoptosis and mitochondrial calcium cycling.

Animals↗
PubMed2001

Association between genetic polymorphism of tumor necrosis factor-alpha and risk of oral submucous fibrosis, a pre-cancerous condition of oral cancer.

Many cytokines have been thought to play important roles in the pathogenesis of oral submucous fibrosis (OSF), an areca nut chewing-specific pre-cancerous condition characterized by the deposition of collagen in oral submucosa. Tumor necrosis factor-alpha (TNF-alpha), situated in the class III region of human leukocyte antigen (HLA), is a mediator with multiple functions, including the regulation of inflammatory reaction and transcriptions of collagen and collagenase. In total, 809 male subjects were recruited for assessment of the association of OSF with a bi-allelic promoter-region (-308) polymorphism on the TNFA gene. The high production allele, TNF2, was significantly lower among OSF subjects (n = 166) than in areca-chewing controls (n = 284). This association was independent of oral cancer status. The multivariate-adjusted odds ratio for the TNFA 11 genotype was 2.6 (95% confidence interval = 1.4-4.9; p = 0.004). The finding may imply a multifunctional etiological factor of TNF-alpha in OSF pathogenesis.

Adult↗
PubMed2001

Parkinson's disease--redox mechanisms.

Parkinson's disease occurs in 1% of people over the age of 65 when about 60% of the dopaminergic neurons in the substantia nigra of the midbrain are lost. Dopaminergic neurons appear to die by a process of apoptosis that is induced by oxidative stress. Oxygen radicals abstract hydrogen from DNA forming DNA radicals that lead to DNA fragmentation, activation of DNA protective mechanisms, NAD depletion and apoptosis. Oxygen radicals can be formed in dopaminergic neurons by redox cycling of MPP+, the active metabolite of MPTP. This redox cycling mechanism involves the reduction of MPP+ by a number of enzymes, especially flavin containing enzymes, some of which are found in mitochondria. Tyrosine hydroxylase is present in all dopaminergic neurons and is responsible for the synthesis of dopamine. However, tyrosine hydroxylase can form oxygen radicals in a redox mechanism involving its cofactor, tetrahydrobiopterin. Dopamine may be oxidized by monoamine oxidase to form oxygen radicals and 3,4-dihydroxyphenylacetaldehyde. This aldehyde may be oxidized by aldehyde dehydrogenase with the formation of oxygen radicals and 3,4-dihydroxyphenylacetic acid. The redox mechanisms of oxygen radical formation by MPTP, tyrosine hydroxylase, monoamine oxidase and aldehyde dehydrogenase will be discussed. Possible clinical applications of these mechanisms will be briefly presented.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2001

Brain oxidative stress--analytical chemistry and thermodynamics of glutathione and NADPH.

Oxidative stress occurs in the brain due to stroke, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, trauma, aging and other conditions. Analysis of the effects of oxidative stress can involve quantitation of brain GSH, GSSG, NADPH and NADP. Reliable and rapid assays have been developed for these compounds and will be presented in detail. The assays have been used to analyze the effects of brain oxidative stress. Thermodynamic calculations can be performed to find the observed electrochemical potentials of the GSSG/GSH and the NADP/NADPH couples during oxidative stress. The biochemical consequences of these thermodynamic changes in the cell will be discussed as well as the defense mechanisms available to the cell to recover from oxidative stress.

Animals↗
PubMed2001

Cyclical mechanical stretching increases the expression of vascular endothelial growth factor in rat vascular smooth muscle cells.

BACKGROUND AND PURPOSE: Mechanical forces have profound effects on vascular smooth muscle cells (VSMCs). The mechanism by which mechanical stimuli regulate vascular endothelial growth factor (VEGF) expression and regulation has yet to be elucidated. We investigated the effect of cyclical mechanical stretching on regulation of the VEGF gene in VSMCs. MATERIALS AND METHODS: Cultured rat VSMCs grown on a flexible membrane base were stretched by applying a vacuum at 60 cycles/minute. VEGF concentration in the cultured media was determined by enzyme-linked immunoassay. VEGF gene expression was determined by Western blot and Northern blot. The location of VEGF in the VSMC was studied immunohistochemically. Chimeric constructs of the VEGF promoter were deleted and the promoter activity was determined by luciferase activity. RESULTS: VEGF concentration increased by 21 to 32% as early as 10 minutes after stretching and remained at this level for up to 12 hours. The concentration of VEGF reached a maximum of 2.8-fold over that in control cells by 2 hours after stretching and declined slightly thereafter. The amount of VEGF mRNA in stretched cells increased as early as 1 hour after stretching, reached a maximum of 3.2-fold over the amount in control cells by 2 hours, and remained at this level for up to 6 hours after stretching. Immunohistochemical study confirmed increased VEGF expression in VSMCs after stretching. Stretched cells transfected with a Sac-Nhe fragment showed only 46% of the luciferase activity of unstretched control cells. However, stretched cells transfected with chimeric plasmids containing a Spe-Nhe fragment showed 2.8-fold luciferase activity over that in control cells. CONCLUSIONS: Cyclical mechanical stretching upregulates expression of the VEGF gene in VSMCs at the transcription level. The VEGF 5'-flanking region contains a negative stretch-response element located in the 0.4-kb Sac-Pst fragment and a positive stretch-response element located in the 0.6-kb Spe-Sac fragment.

Animals↗
PubMed2000

"Paper-clip" type triple helix formation by 5'-d-(TC)3Ta(CT)3Cb(AG)3 (a and b = 0-4) as a function of loop size with and without the pseudoisocytosine base in the Hoogsteen strand.

The formation of a DNA "paper-clip" type triple helix (triplex) with a common sequence 5'-d-(TC)(3)T(a)()(CT)(3)C(b)()(AG)(3) (a and b = 0-4) was studied by UV thermal melting experiments and CD spectra. These DNA oligomers form triplexes and duplexes under slightly acidic and neutral conditions, respectively. The stability of the formed triplexes (at pH 4.5) or duplexes (at pH 7.0 or 8.0) does not vary significantly with the size of the loops (a and b = 1-4). At pH 6.0, the triplex stability is, however, a function of a and b. It is also interesting to note that the oligomer 5'-d-(TC)(3)(CT)(3)(AG)(3) (a and b = 0) forms a stable triplex at pH 4.5 with a slightly lower T(m) value, due to dissociation of a base triad at one end and a distorted base triad at the other, observed by (1)H NMR. Thus, we have here a model system, 5'-d-(TC)(3)T(a)(CT)(3)C(b)(AG)(3), that could form a triplex effectively with (a and b = 1-4) and without (a and b = 0) loops under acidic conditions. In addition, the triplex formation of oligomers with replacement of one, two, or three 2'-deoxycytidine in the Hoogsteen strand by either 2'-deoxypseudoisocytidine (D) or 2'-O-methylpseudoisocytidine (M) was also studied in the sequence 5'-d-(TX)(3)T(2)(CT)(3)C(2)(AG)(3) (where X is C, D, or M). Both CD spectra and UV melting results showed that only D3 [(TX)(3) = (TD)(3)] and M3 [(TX)(3) = (TM)(3)] were able to form the paper-clip structure under both neutral and acidic conditions. This is because the N(3)H of a pseudoisocytosine base can serve as a proton donor without protonation. We hereby proved that the 2'-deoxypseudoisocytidine, similar to 2'-O-methylpseudoisocytidine, could replace 2'-deoxycytidine in the Hoogsteen strand to provide triplex formation at neutral pH.

Adenine↗
PubMed2000

Expression of cyclin-dependent kinase 6 (cdk6) and frequent loss of CD44 in nasal-nasopharyngeal NK/T-cell lymphomas: comparison with CD56-negative peripheral T-cell lymphomas.

Lymphomas involving the nasal and nasopharyngeal region mainly include CD56-positive natural killer (NK)/T-cell lymphomas, CD56-negative peripheral T-cell lymphomas (PTL), and B-cell lymphomas. Among these, the CD56-positive lymphoma, presumably of an NK/T-cell nature, is frequently seen in Asian, Mexican, and South American patients. NK cells are proposed to be closer developmentally to T cells than to other lymphoid cells, because bipotential common progenitor cells of NK/T-cell lineage have been isolated. In this study, we collected 47 cases of nasal lymphoma and investigated the phenotypic difference between NK/T-cell lymphoma and PTL by examining the pattern of the developmentally differentially expressed molecules cdk6 (cyclin-dependent kinase 6), CD44, CD117, and by examining the rearrangement of the T-cell receptor gene (TcR-GR). cdk6, an essential regulator of the cell cycle in G1 progression, was over-expressed in a subset of cortical thymocytes, but absent in mature thymocytes. In contrast, CD44, a glycosylated adhesion molecule, was absent in cortical thymocytes, but present in mature thymocytes and peripheral activated T cells. We found both over-expression of nuclear cdk6 (n-cdk6) and frequent absence of CD44 in nasal CD56-positive NK/T-cell lymphomas, in contrast to most nasal CD56-negative PTL, which were CD44-immunoreactive with weak or no expression of n-cdk6. Almost all tested cases of NK/T-cell lymphoma displayed a germ-line configuration of TcR, without evidence of gene rearrangement. Thus, there seems to be a useful distinction between the classical NK/T type of nasal lymphoma (CD56+/n-cdk6+/CD44-/TcR-GR-) and PTL (CD56-/n-cdk6-/CD44+/TcR-GR+) involving the nasal region. The presence of Epstein-Barr virus does not seem to be a good marker for distinguishing between NK/T lymphoma and PTL involving the nasal region.

Adult↗
PubMed2000

Complete nucleotide sequence and genome organization of hibiscus chlorotic ringspot virus, a new member of the genus Carmovirus: evidence for the presence and expression of two novel open reading frames.

The complete nucleotide sequence of hibiscus chlorotic ringspot virus (HCRSV) was determined. The genomic RNA (gRNA) is 3,911 nucleotides long and has the potential to encode seven viral proteins in the order of 28 (p28), 23 (p23), 81 (p81), 8 (p8), 9 (p9), 38 (p38), and 25 (p25) kDa. Excluding two unique open reading frames (ORFs) encoding p23 and p25, the ORFs encode proteins with high amino acid similarity to those of carmoviruses. In addition to gRNA, two 3'-coterminated subgenomic RNA (sgRNA) species were identified. Full-length cDNA clones derived from gRNA and sgRNA were constructed under the control of a T7 promoter. Both capped and uncapped transcripts derived from the full-length genomic cDNA clone were infectious. In vitro translation and mutagenesis assays confirmed that all the predicted ORFs except the ORF encoding p8 are translatable, and the two novel ORFs (those encoding p23 and p25) may be functionally indispensable for the viral infection cycle. Based on virion morphology and genome organization, we propose that HCRSV be classified as a new member of the genus Carmovirus in family Tombusviridae.

3' Untranslated Regions↗
PubMed2000

Effects of norepinephrine on apoptosis in rat neonatal cardiomyocytes.

BACKGROUND AND PURPOSE: Norepinephrine (NE) is elevated in heart failure and can induce apoptosis in adult cardiac myocytes. However, it is not known whether NE can induce apoptosis in neonatal cardiac myocytes. This study examined the ability of NE to stimulate apoptosis in rat neonatal cardiac myocytes in vitro. METHODS: Neonatal rat cardiac myocytes were exposed to NE alone, NE + propranolol, or NE + prazosin for 24 hours. Apoptosis was assayed by DNA laddering with agarose gel electrophoresis and immunofluorescent terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Reverse transcription polymerase chain reaction was used to evaluate the expression of Mcl-1. Creatine kinase activity in the cultured medium was used as a measure of the toxicity of NE on myocytes. RESULTS: NE increased DNA laddering on agarose gel electrophoresis and increased the number of apoptotic cells in a dose-dependent manner. No increase in apoptosis was found in response to NE doses between 1 and 50 mumol/L. NE at concentrations of 100 to 400 mumol/L increased apoptosis from 10% to 31% of cells. The ability of NE to stimulate apoptosis in rat neonatal cardiac myocytes was completely blocked by propranolol, but not prazosin. NE treatment at high concentrations sharply reduced the level of Mcl-1 mRNA, coincident with the increase in the number of apoptotic cells. Creatine kinase activity in the cultured medium was similar among the controls and NE-treated myocytes. CONCLUSIONS: Our results showed that NE at high concentrations stimulated apoptosis in rat neonatal cardiac myocytes in vitro. Apoptosis induced by NE was associated with down-regulation of Mcl-1. However, NE at the same concentration was not toxic to rat neonatal cardiac myocytes.

Animals↗
PubMed2000

Symptomless cyst formation at the location of a biloma resolved with a single aspiration: case report.

A biloma is an encapsulated bile collection outside the biliary tree. The underlying causes include iatrogenic, traumatic, and spontaneous injury of the biliary tree. Its diagnosis is based upon clinical history, imaging studies, and needle aspiration with chemical analysis of the fluid. Biloma usually presents as a simple or septated cyst or a cyst with internal contents. The symptomatic biloma if left untreated may result in significant morbidity and even mortality. In past reports, the mainstay of management relied on bile flow diversion and/or bile drainage to achieve elimination of bile as well as complete resolution of the cyst. We report on a 58-year-old woman with a 9.0 x 5.4 cm cyst between the right liver and the upper role of the kidney after wedge resection for a hepatoma in the right lobe. She suffered from abdominal pain and fever. A single percutaneous needle aspiration with chemical analysis confirmed the diagnosis of biloma and relieved her symptoms. The biloma vanished immediately. However, a recurrent symptomless cyst was detected at the same site 6 months later. Its content was proven to be clear transudate, and it was left untreated. If a biloma has no communication with the biliary tree, and the proximal biliary tree has neither stricture nor stones, percutaneous aspiration alone may achieve resolution.

Bile↗
PubMed1999

Plant alkaloid tetrandrine downregulates protein kinase C-dependent signaling pathway in T cells.

Tetrandrine, a purified traditional Chinese medicinal herb that acts as an immunosuppressant and a Ca2+ channel blocker, has been clinically used to treat patients with arthritis, silicosis and hypertension. Since T cells play a critical role as autoreactive and pathogenic population in autoimmune diseases, in this study, we examined the immunosuppressive effect of tetrandrine on human peripheral blood T cells. We showed that tetrandrine inhibited phorbol 12-myristate 13-acetate (PMA) + ionomycin-induced T cell proliferation, interleukin-2 secretion and the expression of the T cell activation antigen, CD71. Further investigation of the molecular mechanism demonstrated that tetrandrine inhibited the expression of the protein kinase C-dependent interleukin-2 receptor alpha chain and CD69 but not the expression of the Ca2+-dependent CD40 ligand and CD69. Interestingly, when tetrandrine and cyclosporin A were added together, significant synergism in the suppression of T cell activation was observed. Moreover, of the several tetrandrine analogues studied, hernandezine was the most potent inhibitor of protein kinase C signaling events. These results also suggest that the protein kinase C-inhibitory capacity of tetrandrine and its analogues may not be associated with their function as Ca2+ channel blockers. Lastly, we showed that, within therapeutic concentrations, tetrandrine and its analogues could induce cellular apoptosis, which is defective in autoimmune diseases. In conclusion, our findings provide novel information about the molecular mechanism of the immunosuppressive effect of tetrandrine and its analogues in human peripheral blood T cells.

Alkaloids↗
PubMed1999

Hormonal profiles and immunological studies of male lupus in Taiwan.

The aims of this study were to describe hormonal profiles, cytokine production and Fc-gamma receptor (Fcgamma-R) distribution in male lupus patients in Taiwan, and to look for any differences between our patients and normal individuals. Sixteen newly diagnosed and untreated male lupus patients were studied. Hormonal profiles were determined by radioimmunoassay. Interleukin-1 (IL-1) and IL-1 receptor antagonist (IL-1ra) production from both monocytes and neutrophils was determined by ELISA and murine thymocyte proliferation assay. The FcgammaR distribution on both monocytes and neutrophils was detected by flow cytometer. There were no significant differences in FSH, LH, testosterone, oestradiol, and beta-HCG blood levels in male lupus patients compared with normal individuals; however, the prolactin level in lupus patients was significantly higher than in normal individuals. Furthermore, there was no difference in IL-1 and IL-1ra production from both monocytes and neutrophils among male and female lupus patients, and normal individuals. Male lupus patients have a significantly lower FcgammaRII distribution on both monocytes and neutrophils when compared with female lupus patients and normal individuals. It was concluded that the high prolactin level and low FcgammaR distribution may play a role in the pathogenesis and prognosis of male lupus.

Adult↗
PubMed1999

Effects of anti-rheumatic herbal medicines on cellular adhesion molecules.

OBJECTIVE: To test the hypothesis whether herbal medicines ameliorate inflammatory diseases via the modulation of cellular adhesion molecules (CAMs). METHODS: Human neutrophils, synovial fibroblasts, and endothelial cells were incubated with different concentrations of Tripterygium Wilfordii Hook-f (TWH-f) or Tetrandrine in the presence or absence of interleukin 1 (IL1). The amount of soluble E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cellular adhesion molecule-1 (VCAM-1) secreted by cells were determined by ELISA. The cell surface expression of these three CAMs was detected by flow cytometry. RESULTS: TWH-f at high concentration (50 ng/ml) has a significant (p<0.05) inhibitory effect on both the secretion and the expression of the cellular adhesion molecules. However, Tetrandrine did not demonstrate the same effects. CONCLUSIONS: The cellular adhesion molecules of the endothelium and leucocytes may constitute excellent targets for the development of new anti-inflammation medicines. These results indicate that TWH could be a potential therapeutic agent in the treatment of inflammatory diseases.

Alkaloids↗
PubMed1999

Mechanism of immunosuppression of the antirheumatic herb TWHf in human T cells.

OBJECTIVE: To investigate the immunosuppressive mechanism of Tripterygium wilfordii Hook-F (TWHf) in human T cells. TWHf, a traditional Chinese medicinal herb for rheumatoid arthritis, has been shown to inhibit the function of immune effector cells such as neutrophils, macrophages, and B lymphocytes. METHODS: T cell survival was evaluated with trypan blue exclusion assay, morphologic changes with Wright's stain, the induction of endonuclease activity with DNA fragmentation assay, and the subdiploid DNA content with flow cytometry. T cell activation was measured with interleukin 2 (IL-2) ELISA and the expression of several surface molecules with flow cytometry. RESULTS: At high dosages, TWHf caused inhibition of T cell proliferation and this mechanism was mediated through the induction of apoptosis. TWHf, in noncytotoxic dosages, was as potent as cyclosporin A and more potent than prednisolone and cyclophosphamide in inhibiting IL-2 production from activated T cells. TWHf also inhibited both phorbol 12-myristate 13-acetate induced IL-2Ralpha expression and ionomycin induced CD40 ligand expression. TWHf did not reverse downregulated expression of CD3 and CD4 by phorbol ester stimulation. CONCLUSION: This is the first evidence that the immunosuppressive mechanism of TWHf in T cells was mediated through both downregulation of T cell receptor signaling pathway and induction of cellular apoptosis, which is defective in autoimmune diseases.

Antirheumatic Agents↗
PubMed1998

The clinical features and prognosis of male lupus in Taiwan.

Our objective was to describe the clinical manifestations, laboratory data, and prognosis in male Chinese lupus patients in Taiwan. Seventy-two male lupus patients, diagnosed and followed in Tri-Service General Hospital between 1983 and 1996, were studied and their clinical data analyzed, retrospectively. The mean age at diagnosis was 34+/-16 y (mean+/-s.d., range: 13-82 y). The peak incidence of age at diagnosis was between 13 and 40 years. The three most frequent clinical manifestations were renal disease, 75%; malar rash, 61%; and arthritis, 53%. The three most frequent abnormal laboratory findings were anti-nuclear antibodies (ANA), 97%; hypocomplementemia, 76%; and anti-ds DNA, 57%. The 1-, 5-, and 10-year survival rates were 85%, 76%, and 75%, respectively. In summary, a higher frequency of renal disease, malar rash and photosensitivity, but a lower frequency of arthritis and lymphadenopathy were demonstrated in our 72 ethnic Chinese male Taiwanese lupus patients compared to previous reports of Caucasians. The prognosis seems to be similar to that of both Chinese and Caucasian males but seems to be poor when compared to either Chinese or Caucasian female lupus patients.

Adolescent↗
PubMed1998

cDNA cloning and expression analysis of the human UDPglucose dehydrogenase.

A cDNA clone encoding the human UDPglucose dehydrogenase was isolated from a liver cDNA library. The cDNA is 2,355 bp in length with an open reading frame which is capable of encoding a protein of 494 residues. The predicted primary sequence of the gene product is in good agreement with that of the bovine enzyme determined previously found by means of protein sequencing. Two major transcripts of the UDPglucose dehydrogenase gene with sizes of 2.8 and 2.35 kb, respectively, were observed by Northern analysis. The gene was found to be expressed in a variety of tissues with the highest level in liver, consistent with the physiological function of the enzyme in excretion of endo- and xenobiotics compounds.

Amino Acid Sequence↗