Biomedical subjects

H M Chang

Publications and source records attributed to H M Chang.

At least 91 records · Page 5Linked to original sources

PubMed1992

Prediction of relapse or survival after resection in human hepatomas by DNA flow cytometry.

To investigate the change of DNA content and the effect of synthetic phase (S-phase) fraction on hepatocytes and hepatomas, DNA content and S-phase fraction were measured by flow cytometry in human livers and hepatoma tissues. The ploidy status of nontumor parts of resected hepatoma, fetal liver, and focal nodular hyperplasia were diploid, similar to that of the normal liver. Three patterns of DNA ploidy in human hepatoma cells were newly classified, namely, pattern I, diploid tumors; pattern II, aneuploid tumors with single G0/G1 peak; and pattern III, aneuploid tumors with more than one G0/G1 peaks. Among the 130 resectable hepatomas measured for DNA ploidy status, 84 (64.6%) were pattern I, 20 (15.4%) pattern II, and 26 (20%) pattern III. Multivariate analyses for those 130 patients who underwent hepatic resection showed that, in addition to tumor size, DNA ploidy was another prognostic factor in predicting overall survival and disease-free survival. Patients with small tumors (less than 5 cm) had a significantly higher overall survival rate than those with large tumor (greater than 5 cm). Patients with pattern III hepatomas had a significantly lower overall survival rate and a higher recurrent rate than did those with pattern I or pattern II tumors. The S-phase fraction was a significant predictor of overall survival rate in patients with pattern II, but not with pattern I, tumors. We conclude that DNA flow-cytometric measurements of ploidy and S-phase fraction are potential important prognostic predictors in patients with resectable hepatomas.

Adult↗

PubMed1992

Differential expression of glycosylphosphatidylinositol-anchored proteins in a murine T cell hybridoma mutant producing limiting amounts of the glycolipid core. Implications for paroxysmal nocturnal hemoglobinuria.

A T cell hybridoma mutant, which expressed a markedly reduced level of glycosylphosphatidylinositol (GPI)-anchored proteins on the cell surface, was characterized. The surface expression level of Thy-1 was approximately 17% of the wild-type level, whereas the surface expression of Ly-6A was approximately 2.4% of the wild-type level. We show here that these cells synthesized limiting amounts of the GPI core and that the underlying defect in these cells was an inability to synthesize dolichyl phosphate mannose (Dol-P-Man) at the normal level. The defect in Ly-6A expression could be partially corrected by tunicamycin, which blocked the biosynthesis of N-linked oligosaccharide precursors and shunted Dol-P-Man to the GPI pathway. Full restoration of Thy-1 and Ly-6A expression, however, required the stable transfection of a yeast Dol-P-Man synthase gene into the mutants. These results revealed that when the GPI core is limiting, there is a differential transfer of the available GPI core to proteins that contain GPI-anchor attachment sequences. Our findings also have implications for the elucidation of the defects in paroxysmal nocturnal hemoglobinuria.

Animals↗

PubMed1992

[Proliferation of lymphocytes T and B by prehispanolone LC-5504 of Leonurus hereterophyllus Sweet].

Leonurus hereterophyllus Sweet is a traditional Chinese herbal medicine used to treat menstrual disturbances in woman. A new labdane diterpene, prehispanolone LC-5504, namely 9 alpha, 13R,15,16-diepoxy-labdane-14-en-7-one, had been isolated. The authors studied the synergism of labdane diterpene, prehispanolone LC-5504 and Con A and LPS on T cells and B cells proliferation of BALB/c female mice in vitro. They showed that: (1) proliferation of T cells was demonstrated by administration of LC-5504 of various concentrations together with Con A. This proliferation was 5-8 times stronger than that observed when Con A was used alone. Such effect on T cells was not observed when LC-5504 was used alone. (2) Proliferation of B cells was not observed whether LC-5504 was used alone or together with LPS.

Animals↗

PubMed1991

Functional analysis of T-cell mutants defective in the biosynthesis of glycosylphosphatidylinositol anchor. Relative importance of glycosylphosphatidylinositol anchor versus N-linked glycosylation in T-cell activation.

The glycosylphosphatidylinositol (GPI) anchor, potentially capable of generating a number of second messengers, such as diacylglycerol, phosphatidic acid, and inositol phosphate glycan, has been postulated to be involved in signal transduction in various cell types, including T-cells. We have identified a panel of T-cell hybridoma mutants that are defective at various steps of GPI anchor biosynthesis. Since they were derived from a functional T-T hybridoma, we were able to determine the precise role of the GPI anchor in T-cell activation. Two mutants were chosen for this analysis. The first mutant is defective at the first step of GPI anchor biosynthesis, i.e. in the transfer of N-acetylglucosamine to a phosphatidylinositol acceptor. Thus, it cannot form any GPI precursors or GPI-like compounds. Interestingly, this mutant can be activated by antigen, superantigen, and concanavalin A in a manner comparable to the wild-type hybridoma. These data strongly suggest that the GPI anchor, its precursor, or its potential cleavage product, inositol phosphate glycan, is not required for the early phase of T-cell activation. The second mutant is able to synthesize the first two GPI precursors, but is not able to add mannose residues to them due to a deficiency in dolichol-phosphate-mannose (Dol-P-Man) biosynthesis. Unexpectedly, all of the Dol-P-Man mutants are defective in activation by antigen, suprantigen, and concanavalin A despite normal T-cell receptor expression. Here, we show that the activation defect was due to a pleiotropic glycosylation abnormality because Dol-P-Man is required for both GPI anchor and N-linked oligosaccharide biosynthesis. When the yeast Dol-P-Man synthase gene was stably transfected into the mutants, full expression of surface GPI-anchored proteins was restored. However, N-linked glycosylation was either partially or completely corrected in different transfectants. Reconstitution of activation defects correlates well with the status of N-linked glycosylation, but not with the expression of GPI-anchored proteins. These results thus reveal an unexpected role of N-linked glycosylation in T-cell activation.

Antigens, CD↗

PubMed1991

Identification of defects in glycosylphosphatidylinositol anchor biosynthesis in the Thy-1 expression mutants.

A number of eukaryotic proteins are anchored to the membrane by glycosylphosphatidylinositol (GPI), of which the core structure is conserved from protozoan to mammalian cells. Here, we used a panel of thymoma mutants, which synthesize Thy-1 but cannot express it on the cell surface, to study the GPI biosynthetic pathway in mammalian cells. These mutants have been assigned into six complementation classes (A, B, C, E, F, H) by the technique of somatic cell hybridization. Using a combination of metabolic labeling and chemical/enzymatic tests, the biosynthetic defects were mapped to four different steps. Class A, C, and H mutants cannot transfer N-acetylglucosamine (GlcNAc) to a phosphatidylinositol acceptor, suggesting that the first step of GPI synthesis is regulated by at least three genes. The Class E mutant does not synthesize dolichol-phosphate-mannose, the donor for the first mannose residue transferred to the GPI core, and thus cannot form any mannose-containing GPI precursors. Class B and F mutants are defective in the addition of the third mannose residue or ethanolamine phosphate, respectively, to the elongating GPI core. Our findings have implications for the biosynthesis and attachment of the mammalian GPI anchor.

Autoradiography↗

PubMed1991

Miltirone, a central benzodiazepine receptor partial agonist from a Chinese medicinal herb Salvia miltiorrhiza.

Ten diterpene quinones, which inhibited the binding of [3H]flunitrazepam to central benzodiazepine receptors with IC50s ranging from 0.3 to 36.2 microM, were isolated from the ethereal extract of the roots of Salvia miltiorrhiza. Among these natural products, miltirone has the highest potency (IC50 = 0.3 microM). It was orally active in an animal model used to predict clinical tranquilizing effects. Unlike diazepam, miltirone behaved as a partial agonist in the central benzodiazepine receptor binding and behavioural tests. Moreover, it produced no acute muscle relaxant effect and did not induce drug dependence and withdrawal reactions after chronic administration in mice.

Abietanes↗

PubMed1991

Structure-activity relationship of miltirone, an active central benzodiazepine receptor ligand isolated from Salvia miltiorrhiza Bunge (Danshen).

Twenty one o-quinonoid-type compounds and one coumarin-type compound related to miltirone (1) have been synthesized with the aim to identify the key structural elements involved in miltirone's interaction with the central benzodiazepine receptor. On the basis of their inhibition of [3H]flunitrazepam binding to bovine cerebral cortex membranes, it is apparent that ring A of miltirone is essential for affinity. Although increasing the size of ring A from six-membered to seven- and eight-membered is well-tolerated, the introduction of polar hydroxyl groups greatly reduces binding affinity. The presence of 1,1-dimethyl groups on ring A is, however, not essential. On the other hand, the isopropyl group on ring C appears to be critical for binding as its removal decreases affinity by more than 30-fold. It can, however, be replaced with a methyl group with minimal reduction in affinity. Finally, linking ring A and B with a -CH2CH2- bridge results in analogue 89, which is 6 times more potent than miltirone at the central benzodiazepine receptor (IC50 = 0.05 microM).

Animals↗

PubMed1991

[Prevention and treatment of isoproterenol induced ventricular fibrillation in rats by aqueous extract of Salvia miltiorrhiza].

Acute fatal ventricular fibrillation (VF) in male Sprague-Dawley rats was induced by subcutaneous injection of isoproterenol (1 mg or 5 mg/kg body weight) to two groups of rats of different body weights (525 +/- 21 g or 387 +/- 11 g) respectively. VF occurred in all control rats resulting in 96% death with only 4% spontaneously reverted and survived. Pretreatment of animals, with or without pentobarbital anaesthesia, with an aqueous extract of Salvia miltiorrhiza (SM-H, i.p., 5 g herb/kg body weight) significantly reduced J-point displacement and VF induced by isoproterenol. Survival rate was significantly raised compared with the control (P less than 0.05). Immediate intravenous injection of SM-H (5 g herb/kg body weight) to poisoned rats which developed VF caused 71% of them to recover temporarily their sinus rhythm and significantly prolonged their survival time (P less than 0.05).

Animals↗

PubMed1990

Correction of a defect in mammalian GPI anchor biosynthesis by a transfected yeast gene.

Glycosylphosphatidylinositol (GPI) serves as a membrane anchor for a large number of eukaryotic proteins. A genetic approach was used to investigate the biosynthesis of GPI anchor precursors in mammalian cells. T cell hybridoma mutants that cannot synthesize dolichol-phosphate-mannose (Dol-P-Man) also do not express on their surface GPI-anchored proteins such as Thy-1 and Ly-6A. These mutants cannot form mannose-containing GPI precursors. Transfection with the yeast Dol-P-Man synthase gene rescues the synthesis of both Dol-P-Man and mannose-containing GPI precursors, as well as the surface expression of Thy-1 and Ly-6A, suggesting that Dol-P-Man is the donor of at least one mannose residue in the GPI core.

Animals↗

PubMed1990

[Protective action of Salvia miltiorrhiza aqueous extract on chemically induced acute myocardial ischemia in rats].

Aqueous extract of Salvia miltiorrhiza (SM-H) can protect the acute myocardial ischemia and arrhythmia of Sprague-Dawley rats induced by isoproterenol (ISO) or BaCl2 with the following results: (1) intraperitoneal injection (i.p.) of SM-H for 3 to 5 days or intravenously (i.v.) just once significantly reduced the death rate of the animals, (2) i.v. SM-H pretreatment significantly increased the lethal dose of BaCl2 infusion, (3) i.p. SM-H significantly decreased premature ventricular contraction, ventricular fibrillation, bradycardia and mortality rate induced by bolus i.v. of BaCl2, and (4) i.p. SM-H also significantly reduced ECG J-point displacement of rats induced by ISO.

Animals↗

PubMed1989

Sufentanil, morphine, met-enkephalin, and kappa-agonist (U-50,488H) inhibit substance P release from primary sensory neurons: a model for presynaptic spinal opioid actions.

An in vitro model system for analysis of presynaptic inhibitory actions of spinal opioids has been applied. Embryonic sensory neurons derived from chick dorsal root ganglia were grown in primary cell culture, and the release of substance P was evoked by electrical field stimulation during exposure to drugs with well-demonstrated affinity for opioid receptors. This allowed a pharmacologic characterization of the inhibitory actions of specific opioid agonists on the release of substance P as measured by radioimmunoassay (RIA). Sufentanil (0.5 microM), a high affinity mu receptor agonist, U-50,488H (25 microM), a selective kappa receptor agonist, and morphine (10 microM), an agonist with high affinity for mu and delta receptors, inhibited the evoked release of substance P by approximately 60%, 40%, and 50%, respectively. For sufentanil the response was demonstrated to be dose-dependent. As is the case for its analgesic action in vivo, morphine was approximately 50-fold less potent than sufentanil on a molar basis in this assay. The actions of sufentanil, U-50-488H and morphine were mimicked by the endogenous opioid peptide met-enkephalin, and its stable synthetic analog D-ala2-met5-enkephalinamide (DAME). Naloxone (25 microM), an opioid receptor antagonist, blocked the inhibitory action of sufentanil (0.5 microM), morphine (5 microM), and DAME (5 microM), but not U-50,488H (10 microM). The action of U-50,488H was partially blocked by the antagonist naltrexone (25 microM). Stereo-selectivity of agonist action was confirmed by the failure of dextrorphan (50 microM), an inactive opioid isomer, to inhibit the release of substance P.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1989

Multitest skin testing values of cell-mediated immunity among healthy individuals in Taiwan.

The multitest CMI system, a disposable device that simultaneously applies seven standardized preloaded antigens and diluent control, is a major advance for measurement of delayed type hypersensitivity (DTH) in assessment of cell-mediated immunity (CMI). The system was tested in 84 healthy volunteers, 42 in each sex, aged 4-62 years, to determine normal values for incidence and size of DTH responses to each of seven antigens. Incidence of positive responses to individual antigens varied from 84.5% to 11%, more than half of volunteers were reactive to Tuberculin, Candida and Diphtheria, and a third to Tetanus, Streptococcus and Tricophyton. 95.3% of volunteers to one or more antigens, and about two thirds to three or more. To better assess CMI, a two-part score based on 48-hour readings was employed. The mean number of positive antigens ranged between 2.2 and 3.3, the mean sum of their millimeter induration ranged between 10.8 and 18.2, the average sum of diameters were 16.7 mm in males and 15.2 mm in females. There was no statistic significance to sex and age during scoring, although there was somewhat higher in males, young and mature age groups. In our series, Tuberculin reaction is the highest one in this seven antigens, about 4.76% of volunteers are anergy. A statistical zone (95% confidence limits) of reduced DTH scores (hypoergy) was identified, it reveals sum of diameters less than 9mm in males and 7mm in females, number of positive antigens are less than 2 in each sex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1988