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Biomedical subjects

L C Chang

Publications and source records attributed to L C Chang.

At least 37 records · Page 2Linked to original sources
PubMed1999

Complete nucleotide sequence of pig (Sus scrofa) mitochondrial genome and dating evolutionary divergence within Artiodactyla.

The complete nucleotide sequence of the pig (Sus scrofa) mitochondrial genome, containing 16613bp, is presented in this report. The genome is not a specific length because of the presence of the variable numbers of tandem repeats, 5'-CGTGCGTACA in the displacement loop (D-loop). Genes responsible for 12S and 16S rRNAs, 22 tRNAs, and 13 protein-coding regions are found. The genome carries very few intergenic nucleotides with several instances of overlap between protein-coding or tRNA genes, except in the D-loop region. For evaluating the possible evolutionary relationships between Artiodactyla and Cetacea, the nucleotide substitutions and amino acid sequences of 13 protein-coding genes were aligned by pairwise comparisons of the pig, cow, and fin whale. By comparing these sequences, we suggest that there is a closer relationship between the pig and cow than that between either of these species and fin whale. In addition, the accumulation of transversions and gaps in pig 12S and 16S rRNA genes was compared with that in other eutherian species, including cow, fin whale, human, horse, and harbor seal. The results also reveal a close phylogenetic relationship between pig and cow, as compared to fin whale and others. Thus, according to the sequence differences of mitochondrial rRNA genes in eutherian species, the evolutionary separation of pig and cow occurred about 53-60 million years ago.

Amino Acids↗
PubMed1999

Examination of the signal transduction pathways leading to activation of extracellular signal-regulated kinase by formyl-methionyl-leucyl-phenylalanine in rat neutrophils.

The signaling pathways leading to extracellular signal-regulated kinase (ERK) activation in formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated rat neutrophils were examined. fMLP-stimulated ERK activation based on immunoblot analysis with antibodies against the phosphorylation form of ERK was attenuated by the pretreatment of cells with pertussis toxin but not with a dual cyclo-oxygenase/lipoxygenase inhibitor BW755C. Exposure of cells to the tyrosine kinase inhibitor genistein, phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY294002, or protein kinase C (PKC) inhibitors Gö6976, Gö6983, and GF109203X inhibited fMLP-stimulated ERK phosphorylation in a concentration-dependent manner. In addition, both the phospholipase C (PLC) inhibitor U73122 and the Ca2+ chelator BAPTA attenuated ERK activation. These results indicate that G(i/o) protein, tyrosine kinase, P13K, PKC, and PLC/Ca2+, but not arachidonate metabolites, act upstream of fMLP-stimulated ERK activation.

Animals↗
PubMed1999

A novel function of emodin: enhancement of the nucleotide excision repair of UV- and cisplatin-induced DNA damage in human cells.

Nucleotide excision repair (NER) is the main pathway by which mammalian cells remove carcinogenic DNA lesions caused by UV light and many other common mutagens. To explore the effect of emodin on NER, its influence on the repair of UV- and cisplatin-induced DNA damage in human fibroblast cells (WI38) was evaluated. Emodin increased unscheduled DNA synthesis (UDS) of UV-treated cells and reduced cisplatin-induced DNA adducts in WI38 in a concentration-dependent manner, indicating that emodin might promote NER capability in cells. The resultant NER complex is a cooperative assembly of XPF, ERCC1, XPA, RPA, and XPG subunits. The gene regulations of the subunits after emodin treatment were determined by reverse transcription-polymerase chain reaction (RT-PCR) using specific primers. Among the subunits, the expression of ERCC1 in WI38 cells was up-regulated significantly after emodin treatment. All other expressions remained essentially unchanged. In addition, calcium influx in WI38 was increased in proportion to the concentration of emodin. Since UV-induced NER is Ca2+ dependent, elevation of calcium influx may be another mechanism by which emodin facilitates DNA repair. In conclusion, emodin can increase the repair of UV- and cisplatin-induced DNA damage in human cells, and elevated ERCC1 gene expression and Ca2+-mediated DNA repair processes may be involved in the repair mechanism of emodin.

Antineoplastic Agents↗
PubMed1999

2-Hydroxymethyl-1-naphthol diacetate (TAC) suppresses the superoxide anion generation in rat neutrophils.

We have investigated the inhibitory effect of 2-hydroxymethyl-1-naphthol diacetate (TAC) on the respiratory burst of rat neutrophils and the underlying mechanism of action was also assessed in this study. TAC caused concentration-related inhibition of the formylmethionyl-leucyl-phenylalanine (fMLP) plus dihydrocytochalasin B (CB)- and phorbol 12-myristate 13-acetate (PMA)-induced superoxide anion (O2*-) generation (IC50 10.2+/-2.3 and 14.1+/-2.4 microM, respectively) and O2 consumption (IC50 9.6+/-2.9 and 13.3+/-2.7 microM, respectively) of neutrophils. TAC did not scavenge the generated O2*- during dihydroxyfumaric acid autoxidation. TAC inhibited both the transient elevation of [Ca2+]i in the presence or absence of [Ca2+]o (IC50 75.9+/-8.9 and 84.7+/-7.9 microM, respectively) and the generation of inositol trisphosphate (IP3) (IC50 72.0+/-9.7 microM) in response to fMLP. Cytosolic phospholipase C (PLC) activity was also reduced by TAC at a same range of concentrations. The PMA-induced PKC-beta associated to membrane was attenuated by TAC (about 80% inhibition at 30 microM). Upon exposure to fMLP, the cellular cyclic AMP level was decreased in neutrophils pretreated with TAC. TAC attenuated fMLP-induced phosphorylation of mitogen-activated protein kinase (MAPK) p42/44 (IC50 17.4+/-1.7 microM), but not p38. The cellular formation of phosphatidic acid (PA) and, in the presence of ethanol, phosphatidylethanol (PEt) induced by fMLP was inhibited by TAC in a concentration-dependent manner (IC50 25.4+/-2.4 and 25.9+/-1.4 microM, respectively). TAC had no effect on the O2*- generation of PMA-stimulated and arachidonic acid (AA)-stimulated NADPH oxidase preparations. However, TAC caused concentration-related decrease of the membrane associated p47phoX in PMA-stimulated neutrophils (about 80% inhibition at 30 microM). We conclude that inhibition by TAC of the neutrophil respiratory burst is probably attributable to the blockade of the p42/44 MAPK and phospholipase D (PLD) pathways, the membrane translocation of PKC, and to the failure in assembly of a functional NADPH oxidase complex. Blockade of the PLC pathway by TAC probably plays a minor role.

Animals↗
PubMed1999

Flavonoid constituents of Chorizanthe diffusa with potential cancer chemopreventive activity.

An ethyl acetate-soluble extract of Chorizanthe diffusa was found to exhibit significant antioxidant activity, as judged by scavenging stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals and inhibition of 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced free radical formation with cultured HL-60 cells. Bioassay-directed fractionation of this extract using the DPPH antioxidant assay as a monitor led to the isolation of five structurally related flavonoids (1-5), including the novel compound 5,8,3',4',5'-pentahydroxy-3, 7-dimethoxyflavone (1). Isolates 1-5 demonstrated varying degrees of antioxidant or antimutagenic activity. Two of the compounds, 5,7,3', 4'-tetrahydroxy-3-methoxyflavone (2) and quercetin (4), were subsequently found to inhibit carcinogen-induced preneoplastic lesions in a mouse mammary organ culture model. Inhibitory activity of this type is known to correlate with cancer chemopreventive effects in full-term models of tumorigenesis.

Animals↗
PubMed1999

Inhibition by magnolol of formylmethionyl-leucyl-phenyl alanine-induced respiratory burst in rat neutrophils.

The influence of the plant product magnolol on neutrophil superoxide anion (O2-*) generation has been investigated in the rat. Intraperitoneal injection of magnolol (30mg kg(-1)) significantly inhibited the formylmethionyl-leucyl-phenylalanine (fMLP)-induced respiratory burst in rat whole blood ex-vivo. Magnolol also inhibited the 02-* generation with an IC50 (concentration resulting in 50% inhibition) of 15.4+/-1.6 microM and O2 consumption in rat neutrophils in-vitro. Magnolol weakly inhibited the O2-* generation in the xanthine-xanthine oxidase system, decreased cellular cyclic AMP level and had no effect on cyclic GMP levels. It weakly inhibited neutrophil cytosolic protein kinase C activity but did not alter porcine heart protein kinase A activity. Magnolol attenuated fMLP-induced protein tyrosine phosphorylation with an IC50 of 24.0+/-1.9 microM and the phosphorylation of mitogen-activated protein kinase p42/44 with an IC50 of 28.5+/-4.5 microM. However, magnolol alone activated neutrophil phospholipase D activity as determined by the formation of phosphatidic acid and phosphatidyl-ethanol in the presence of ethanol. In the presence of NADPH, the arachidonate-activated NADPH oxidase activity in a cell-free system was weakly suppressed by magnolol. These results suggest that the inhibition of respiratory burst in fMLP-activated neutrophils by magnolol is probably attributable mainly to the attenuation of protein tyrosine phosphorylation and p42/44 mitogen-activated protein kinase activation, and partly to the suppression of protein kinase C and NADPH oxidase activities.

Animals↗
PubMed1999

Proinflammatory cytokines and fibrinolytic enzymes in tuberculous and malignant pleural effusions.

OBJECTIVES: To measure tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in pleural effusions caused by tuberculosis (TB) and malignancy and their relationship with plasminogen activator inhibitor type I (PAI-1) and tissue type plasminogen activator (tPA), and to compare the differences between tuberculous and malignant pleural effusions. In addition, the relationship between the effusion levels of these parameters and the development of residual pleural thickening was evaluated in the patients with tuberculous pleurisy. DESIGN: Prospective study. MATERIALS AND METHODS: TNF-alpha, IL-1beta, PAI-1, and tPA were measured simultaneously in blood and pleural fluid using an enzyme-linked immunosorbent assay in 33 patients with tuberculous and in 30 patients with malignant pleural effusions. Residual pleural thickening was measured and defined as a pleural thickness of >/= 10 mm found on chest radiographs at the completion of anti-TB chemotherapy in tuberculous pleurisy patients. RESULTS: In both groups, the levels of proinflammatory cytokines and fibrinolytic enzymes were significantly higher in pleural fluid than in blood. The levels of TNF-alpha and PAI-1 were significantly higher in tuberculous than in malignant effusions. In contrast, malignant pleural fluid had significantly higher values of tPA than did tuberculous pleural fluid. In tuberculous effusions, the values of PAI-1 and the PAI-1/tPA ratio correlated positively and the levels of tPA correlated negatively with those of TNF-alpha and IL-1beta. In malignant pleural fluid, positive correlations were found between the values of proinflammatory cytokines (TNF-alpha and IL-1beta) and PAI-1. Residual pleural thickening was found in 9 of 33 patients (27. 3%) with tuberculous pleurisy. The pleural fluid values of TNF-alpha, IL-1beta, and PAI-1 were significantly higher and the concentrations of tPA were significantly lower in tuberculous pleurisy patients with residual pleural thickening. CONCLUSIONS: Compared to malignant pleural effusion, fibrinolytic activity in pleural fluid was reduced in tuberculous effusion. Pleural inflammation caused by TB may enhance the release of proinflammatory cytokines, particularly TNF-alpha, which subsequently may increase PAI-1 and decrease tPA in pleural fluid. The imbalance of PAI-1 and tPA in pleural space may lead to fibrin deposition and pleural thickening.

Antitubercular Agents↗
PubMed1998

Plasminogen activation by streptokinase via a unique mechanism.

The mechanism of human plasminogen (HPlg) activation by streptokinase (SK)-type activator was investigated with recombinant truncated SK peptides. An enzyme-substrate intermediate of HPlg.SK. HPlg ternary complex was demonstrated by a sandwich-binding experiment. Formation of the ternary complex was saturable, HPlg-specific, and inhibited by 6-aminocaproic acid. Three interaction sites between SK and HPlg were demonstrated. SK-(220-414) bound to HPlg with two binding sites: one to the micro-HPlg region, the catalytic domain of HPlg, and one to the kringle 1-5 region, with Kd values of 1.50 x 10(-7) and 2.44 x 10(-6) M, respectively. SK-(16-251) bound to a single site on the kringle 1-5 region of HPlg with a Kd of 4.09 x 10(-7) M. SK-(220-414) and SK-(16-251) competed for binding on the same or nearby location on the human kringle 1-5 domain. Combination of SK-(220-414) and SK-(16-251), but not either peptide alone, could effectively activate HPlg. In addition, SK-(16-251) dose-dependently enhanced the activation of HPlg by SK-(16-414), while the HPlg activation by SK-(16-414) was inhibited by SK-(220-414). We conclude that the HPlg that binds to the COOH-terminal domains of SK functions as an enzyme to catalyze the conversion of substrate HPlg that binds to the NH2-terminal domain of SK to human plasmin.

Aminocaproic Acid↗
PubMed1998

The rhamnose moiety of solamargine plays a crucial role in triggering cell death by apoptosis.

Solamargine, solasodine and khasianine steroidal alkaloids are utilized to determine the role of carbohydrate moiety in the mechanism of apoptosis. The C3 side chain of solamargine, khasianine and solasodine contains 4'Rha-Glc-Rha2', 4'Rha-Glc and H, respectively. Solamargine possessed potent cytotoxicity to human hepatoma cells, while the cytotoxicity of khasianine was greatly diminished. Nevertheless, only solamargine could induced "sub-G1" of apoptotic feature in flowcytometry. Thus, the 2'Rha moiety of solamargine may play a crucial role in triggering cell death by apoptosis. In addition, the molecular modeling of solamargine indicated that the 2'Rha moiety was adjacent to the rigid steroid structure, and drastically changed the dihedral angle of the glycosidic bond. The regulations of TNFR I and II expression by different carbohydrate moieties were also distinct. It implied that the carbohydrate moieties of steroidal alkaloids might alter the binding specificity to steroid receptors and consequently regulate the gene expression in different manners.

Antigens, CD↗
PubMed1998

Activity-guided isolation of steroidal alkaloid antiestrogen-binding site inhibitors from Pachysandra procumbens.

Four novel steroidal alkaloids, (+)-(20S)-20-(dimethylamino)-3-(3'alpha-isopropyl)-lactam-5alpha-+ ++preg n-2-en-4-one (1), (+)-(20S)-20-(dimethylamino)-16alpha-hydroxy-3-(3'alpha-isopropyl) -la ctam-5alpha-pregn-2-en-4-one (2), (+)-(20S)-3-(benzoylamino)-20-(dimethylamino)-5alpha-pregn-2-en-++ +4beta -yl acetate (3), and (+)-(20S)-2alpha-hydroxy-20-(dimethylamino)-3beta-phthalimido-5 alpha- pregnan-4beta-yl acetate (4), as well as five known compounds, (-)-pachyaximine A (5), (+)-spiropachysine (6), (+)-axillaridine A (7), (+)-epipachysamine D (8), and (+)-pachysamine B (9), were isolated from Pachysandra procumbens, using a bioassay-guided fractionation based on inhibition of 3H-tamoxifen binding at the antiestrogen binding site (AEBS). Compounds 1-7 and 9 demonstrated significant activity as AEBS-inhibitory agents, and compounds 3, 5 and 9 were found to potentiate significantly the antiestrogenic effect mediated by tamoxifen in cultured Ishikawa cells. The structure elucidation of compounds 1-4 was carried out by spectral data interpretation.

Alkaloids↗
PubMed1998

Preparation of a novel streptokinase mutant with improved stability.

The novel mutant streptokinase, SK-K59E, can activate human plasminogen as efficiently as the purified commercially available streptokinase. Several peptide bonds including Lys59-Ser60 in native streptokinase were hydrolyzed in reaction with plasmin and peptides of small molecular masses were generated. The plasminogen activator activity of native streptokinase in reaction with human plasmin declined to 25% of the original activity in a 120-min incubation. On the other hand, the NH2-terminal peptide of SK-K59E remained intact in reaction with plasmin and the activator activity of streptokinase decreased to 75% of the original activity in 120 min. The major degraded peptide fragments of native streptokinase in reaction with plasmin had molecular masses of 36 and 30 kDa. However, two major peptide fragments of 42 and 34 kDa were observed in the reaction of SK-K59E with human plasmin. The 42 kDa peptide fragment, which contained NH2-terminal of streptokinase, could activate human plasminogen as efficiently as the native streptokinase. SK-K59E can induce greater degree of caseinolysis and fibrinolysis than the native streptokinase. In conclusion, the results demonstrate that the prevention of cleavage at Lys59 of streptokinase prolongs the half-life of streptokinase in complex with plasmin and that the NH2-terminal of streptokinase (Ile1-Lys59) plays an important role in maintaining its stability.

Enzyme Stability↗
PubMed1998

Space changes after premature loss of the mandibular primary first molar: a longitudinal study.

The purpose of this study was to evaluate the space changes after premature loss of the primary mandibular first molar. Twenty-one children (12 boys and 9 girls), with premature loss of the primary mandibular first molar, were selected from the children's dental clinic for this study. The age ranged from 5.1 to 7.2 years with an average of 6 years and 11 months. Mandibular study casts were made from alginate impression for each initial examination and a follow-up examination eight months later. Four measurements including D+E (first and second primary molars) space, arch width, arch length and arch perimeter were tested for comparisons between the initial examination and the follow-up examination eight months later. The D+E space of intact primary molars served as a control. The results showed that the D+E space on the extraction side after the follow-up examination eight months later was significantly shorter than the control side (p = 0.025) and less than the initial D+E space (p < 0.001). However, there were no significant differences on arch width, arch length, and arch perimeter between the initial examination and the follow-up examination eight months later (p > 0.05). It is concluded that the space change after the eruption of the first permanent molar in the mandible is mostly distal movement of the primary cuspid during the early stage of premature loss of the primary first molar.

Child↗
PubMed1998

Multiple lymphomatous polyposis of the gut: case report.

Multiple lymphomatous polyposis (MLP) is an uncommon type of primary non-Hodgkin's gastrointestinal B-cell lymphoma characterized by the presence of multiple lymphomatous polyps along the gut. We present a patient with MLP in which the involvement was unusually widespread. The diagnosis was confirmed by the typical polyposis lesion, histology, phenotyping and clinical presentations. A 68-year-old man had a large mass at the ileocecal valve as well as multiple polyps along the whole digestive tract. At the time of diagnosis, lymphoma had involved bone marrow, peripheral blood, spleen, prostate and peripheral lymph nodes. The patient received 8 courses of chemotherapy with no remission. He died of pneumonia 11 months after diagnosis. Clinically, the diagnosis may be confused with epithelial polyps; and histologically, the diagnosis must be distinguished from benign lymphoid proliferations as well as other types of lymphoma. The prognosis for patients with MLP is relatively poor (the median survival is usually less than 3 years).

Aged↗
PubMed1998

High-grade mucoepidermoid carcinoma of the breast: case report.

Mucoepidermoid carcinoma of the breast is very rare. Only 14 cases have been reported in the English language literature. All of these patients were women with ages ranging from 46 to 72 years. Five of the cases involved high-grade mucoepidermoid carcinomas and 9 were low-grade. All of the patients with low-grade mucoepidermoid carcinoma were disease-free in the follow-up period. Four patients with high-grade mucoepidermoid carcinoma died from the disease 7 to 30 months after surgery and all 4 were found to have distant metastasis. The case of mucoepidermoid carcinoma of the breast discussed here was histopathologically high-grade. The patient has remained disease-free 4 years after modified radical mastectomy and adjuvant chemotherapy. Diagnose of mucoepidermoid carcinoma of the breast is more difficult than mucoepidermoid carcinoma in the salivary gland due to possible confusion with metaplastic carcinoma or squamous cell carcinoma. Special histological stains are definitely needed for differential diagnosis.

Breast Neoplasms↗
PubMed1997

Ganglion cyst and synovial cyst of the temporomandibular joint. Two case reports.

Ganglion cysts and synovial cysts are lesions rarely associated with the temporomandibular joint. Ganglion cysts arise from myxoid degeneration of the connective tissue of the joint capsule, are filled with viscoid fluid or gelatinous material, and have a fibrous lining. Synovial cysts also contain gelatinous fluid and are lined with cuboidal to somewhat flattened cells consistent with a synovial origin. One case of a ganglion cyst and one case of a synovial cyst of the temporomandibular joint are presented, and their differential diagnosis and management are discussed.

Adult↗
PubMed1997

Activity-guided isolation of constituents of Tephrosia purpurea with the potential to induce the phase II enzyme, quinone reductase.

An isoflavone, 7,4'-dihydroxy-3',5'-dimethoxyisoflavone (1), and a chalcone, (+)-tephropurpurin (2), both novel compounds, as well as six constituents of known structure, (+)-purpurin (3), pongamol (4), lanceolatin B (5), (-)-maackiain (6), (-)-3-hydroxy-4-methoxy-8,9-methylene-dioxypterocarpan (7), and (-)-medicarpin (8), were obtained as active compounds from Tephrosia purpurea, using a bioassay based on the induction of quinone reductase (QR) activity with cultured Hepa 1c1c7 mouse hepatoma cells. Additionally, three inactive compounds of known structure, 3'-methoxydaidzein, desmoxyphyllin B, and 3,9-dihydroxy-8-methoxycoumestan, were isolated and identified. The structure elucidation of compounds 1 and 2 was carried out by spectral data interpretation.

Animals↗
PubMed1997

Alteration of endogenous antioxidant enzymes in naturally occurring hypertrophic cardiomyopathy.

We have recently developed a porcine model with naturally occurring hypertrophic cardiomyopathy (HCM). Similar to humans, occluded intramural coronary artery and damaged mitochondria are frequently observed in these animals in which the disease is thought to be associated with the local ischemia of myocardium. In view of antioxidant functions involved in the ischemic injury, we measured the expression of endogenous antioxidant enzymes in the tissues with and without HCM. The results showed a significant increase of Cu,Zn-superoxide dismutase (SOD), but not Mn-SOD, and decrease of catalase (CAT) activities in the various areas of HCM hearts. It was demonstrated that SOD/CAT ratios in the HCM hearts were significantly higher than those in normals and were found to be dramatically correlated with the severity of cardiac hypertrophy. The altered SOD/CAT ratio was also consistent with increase in lipid damage. We hypothesize that the elevated SOD combined with an inadequate amount of H2O2 scavenging enzyme may lead HCM heart at oxidative stress risk. However, the pathogenic role of imbalanced antioxidant enzyme needs to be further explored.

Animals↗