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Biomedical subjects

T H Chang

Publications and source records attributed to T H Chang.

At least 55 records · Page 3Linked to original sources

Effects of a pyranocoumarin compound isolated from a Chinese medicinal plant on ischemic myocardial dysfunction in anesthetized dogs.

A pyranocoumarin compound, 3'-angeloyloxy-4'-acetoxy-3',4'-dihydroseselin (Pd-Ia), isolated from Bai-Hua Qian-Hu, a Chinese medicine, is known to possess a Ca2+ channel antagonist action. We examined the effect of Pd-Ia on cardiohemodynamics and regional myocardial dysfunction after transient ischemia in anesthetized open-chest dogs. I.v. injections of Pd-Ia (0.1-3.0 mg/kg, n = 7) significantly and dose dependently increased coronary blood flow and decreased mean aortic pressure, maximal rate of rise in left ventricular pressure, rate pressure product and systemic vascular resistance, together with a slight increase in heart rate. Diltiazem (0.03-1.00 mg/kg, n = 6) showed effects on the cardiohemodynamics similar to those of Pd-Ia, except for a marked decrease in heart rate. The effects of Pd-Ia on mean aortic pressure and rate pressure product were approximately 10 times less potent than those of diltiazem. In the second experiment, the effect of a 30-min infusion of Pd-Ia (0.15 mg/kg/min) or vehicle on regional myocardial dysfunction was examined in 16 anesthetized dogs subjected to a 15-min occlusion of the left anterior descending coronary artery followed by a 3-h reperfusion. Infusion of Pd-Ia was started 15 min before coronary occlusion. The vehicle caused a decrease in percent segment shortening throughout the reperfusion period (n = 8). However, Pd-Ia at the dose that produced no significant changes in cardiohemodynamics resulted in a marked improvement in percent segment shortening of the ischemic and reperfused myocardium (n = 8, P < 0.05 vs. control group).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Immune response to a hepatitis C virus nonstructural protein in chronic hepatitis C virus infection.

The immune responses to a hepatitis C virus nonstructural protein (T3Ag) overlapping with the C100-3 antigen were examined in three groups of patients with chronic non-A, non-B hepatitis. Group I included 20 cases positive for both anti-C100-3 and the second-generation anti-HCV test (anti-HCV-II): Group II, five cases with anti-C100-3(-)/anti-HCV-II(+); and Group III, seven cases negative for both tests. HCV RNA was detectable in 20 (100%), 4 (80%) and 0 (0%) patients in each group, respectively. Proliferative responses of peripheral blood mononuclear cells to T3Ag were present in 16 (80%), 3 (60%) and 0 (0%) cases in each group, respectively (p < 0.05). Removal of CD8+ T cells from peripheral blood mononuclear cells resulted in a conversion of unresponsiveness to significant proliferation to T3Ag in the remaining cases in groups I and II, but not in group III. This change paralleled the antigen-induced production of interferon-gamma and interleukin-2, but not interleukin-4. The removal also enhanced the T3Ag-stimulated anti-C100-3 antibody production from cultured peripheral blood mononuclear cells in group II patients. These results indicate that the T3Ag-specific type 1 T helper cells play an important role in regulating anti-C100-3 antibody secretion in hepatitis C patients.

Adult↗

Presence of hepatitis B surface antigen (HBsAg)-specific cytotoxic T cells in asymptomatic HBsAg carriers.

To investigate whether there is any evidence of an immune stimulation against hepatitis B virus surface antigen (HBsAg) in asymptomatic HBsAg carriers, proliferative and cytotoxic responses to HBsAg were measured in their peripheral blood lymphocytes. Although the majority of asymptomatic carriers had no proliferative response to HBsAg, 3 (25%) of 12 carriers showed significant T cell proliferation against HBsAg. In addition, using HBsAg-expressing autologous lymphoblastoid cell line (LCL) as target cells, HBsAg-specific cytotoxic activity was found in 2 of 3 asymptomatic HBsAg carriers who had a proliferative response against HBsAg. Furthermore, 6 cytotoxic T lymphocyte (CTL) clones were isolated from 1 asymptomatic carrier. The epitope recognized by 2 CTL clones was mapped to the major HBsAg residues 158-172. These CTL clones were able to produce interferon-gamma, tumor necrosis factor-alpha, or granulocyte-macrophage colony-stimulating factor. These findings demonstrate the presence of HBsAg-specific, major histocompatibility complex class I-restricted CTL in asymptomatic HBsAg carriers.

Adult↗

Effects of 3'-angeloyloxy-4'-acetoxy-3',4'-dihydroseselin on cardiohemodynamics in anesthetized dogs.

Cardiohemodynamic effects of 3'-angeloyloxy-4'-acetoxy-3',4'-dihydroseselin (Pd-Ia) isolated from the Chinese medicinal plant Peucedanum praeruptorum Dunn were compared with those of diltiazem (Dil) in anesthetized open-chest dogs. Pd-Ia 3 mg.kg-1 increased coronary blood flow from 25 +/- 11 to 58 +/- 16 ml.min-1 (n = 7, P < 0.01) and decreased mean aortic pressure (MAP) from 13 +/- 2 to 8 +/- 1 kPa (P < 0.01), rate pressure product (RPP) from 1.9 +/- 0.5 to 1.3 +/- 0.3 MPa.bpm (P < 0.05), +dp/dtmax from 246 +/- 56 to 160 +/- 36 kPa.s-1 (P < 0.01) and systemic vascular resistance from 19 +/- 4 to 12 +/- 7 Pa.ml-1.min-1 (P < 0.05), together with an increase in HR. Dil showed effects similar to those of Pd-Ia except for a marked decrease in HR. The effects of Pd-Ia on MAP and RPP were approximately one-tenth as potent as those of Dil. The results demonstrated that Pd-Ia was a Ca2+ channel blocker.

Animals↗

Effect of dl-praeruptorin A on calcium current in ventricular cells of guinea pig.

With patch clamp technic (whole cell recording), the effect of dl-praeruptorin A (Pra), an ingredient of Peucedanum praeruptorum Dunn on calcium current (ICa) in the single ventricular cells of guinea pig was studied. Results showed that under Cs/Cs condition, when the holding potential was -40 mV and in the presence of Pra (1, 10, 100 mumol.L-1), ICa was decreased dose-dependently from 2.02 +/- 0.24, 2.00 +/- 0.12, 2.12 +/- 0.33 nA (control) to 1.60 +/- 0.24, 1.32 +/- 0.08, 1.16 +/- 0.43 nA, respectively, and their inhibitory rates were 21%, 33.5%, 45%, respectively. The current-voltage relation curve showed that the reversal potential of ICa was +60 mV; the potential producing peak value of ICa was about 0 mV. The results indicated that Pra had a Ca2+ channel blocking effect.

Animals↗

Effects of 3'-angeloyloxy-4'-acetoxy-3',4'-dihydroseselin on myocardial dysfunction after a brief ischemia in anesthetized dogs.

The effect of a 30-min infusion of 3'-angeloyloxy-4'-acetoxy-3', 4'-dihydroseselin (Pd-Ia), a coumarin isolated from Peucedanum praeruptorum Dunn 0.15 mg.kg-1.min-1 on regional myocardial dysfunction was examined in 16 anesthetized open-chest dogs subjected to a 15-min occlusion of the left anterior descending coronary artery followed by a 3-h reperfusion. Segment lengths of left ventricular wall were measured with an ultrasonic micrometer. The control caused a decrease in the % of segment shortening (SS%) throughout the reperfusion period (n = 8), while Pd-Ia ameliorated segment function immediately after reperfusion and restored the SS% to 41 +/- 51% of the baseline value (n = 8, P < 0.05 vs control) 5 min after reperfusion without any significant changes in cardiohemodynamics. The improvement of myocardial function induced by Pd-Ia was maintained at least 3 h after reperfusion. These findings revealed that Pd-Ia had a cardioprotective action in stunned myocardium.

Animals↗

Four yeast spliceosomal proteins (PRP5, PRP9, PRP11, and PRP21) interact to promote U2 snRNP binding to pre-mRNA.

We have analyzed the functions of several pre-mRNA processing (PRP) proteins in yeast spliceosome formation. Here, we show that PRP5 (a DEAD box helicase-like protein), PRP9, and PRP11 are each required for the U2 snRNP to bind to the pre-spliceosome during spliceosome assembly in vitro. Genetic analyses of their functions suggest that they and another protein, PRP21, act concertedly and/or interact physically with each other and with the stem-loop IIa of U2 snRNA to bind U2 snRNP to the pre-mRNA. Biochemical complementation experiments also indicate that the PRP9 and PRP11 proteins interact. The PRP9 and PRP11 proteins may be functioning similarly in yeast and mammalian cells. The requirement for ATP and the helicase-like PRP5 protein suggests that these factors might promote a conformational change (involving either the U1 or U2 snRNP) that is required for the association of U2 snRNP with the pre-mRNA.

Adenosine Triphosphate↗

Whole-cell patch clamp measurements and berberine inhibition of hyperpolarization-activated inward current in rabbit sinoatrial node cells.

Single rabbit sinoatrial node (SAN) cells were isolated by means of an enzymatic dispersion procedure and used for the whole-cell patch clamp experiment. At a holding potential of -40 mV, a time- and voltage-dependent inward current, I(f), was activated at different hyperpolarization potentials from -60 mV to -110 mV. The current-voltage relation curve showed that I(f) was activated at potential more negative than -40 mV. Five min after treatment by CsCl 2 mmol.L-1-containing Tyrode solution, I(f) was almost completely blocked. At a hyperpolarization potential of -110 mV, I(f) was reduced from 1.7 +/- 0.2 nA of the control to 1.2 +/- 0.4 nA after superfusing with Tyrode solution containing berberine (Ber) 1 mumol.L-1 for 5 min. And it was difficult to wash out this action. Ber also had inhibitory effects on other currents to a certain extent. The results indicate that I(f) is a Cs(+)-sensitive current and that the negative chronotropic effect of Ber may be due to the inhibition of I(f) that functions as an important pacemaking modulator for the spontaneous depolarization of SAN tissue.

Action Potentials↗

Heterogeneous blood pressure response to furosemide and captopril in primary aldosteronism.

The hypertension associated with primary aldosteronism (PA) is often regarded as volume dependent/salt-sensitive. However, not all patients sustain an increase in blood pressure upon sodium loading. In order to examine the sodium sensitivity in PA, 21 patients with aldosteronoma were tested for acute hypotensive response to intravenous furosemide and oral captopril. Ten patients having a decrease in mean blood pressure (MBP) exceeding 5% at the second hour after a 20 mg furosemide injection were defined as diuretic-responders (DR), while the remainder were defined as diuretic-non-responders (DN). The DR group had a higher baseline MBP (135 +/- 6 [mean +/- SE] vs 121 +/- 4 mmHg, p < 0.05) and serum sodium concentration (145.7 +/- 1.4 vs 143.0 +/- 0.7 mmol/L, p < 0.05) than the DN group. The extent of natriuresis induced by furosemide was not different between the two subgroups. Following 100 mg of captopril administered orally, the DR group had a smaller change in MBP (%) than the DN group (3.08 +/- 5.14 vs -7.78 +/- 3.37, p < 0.05). According to the different BP responses to furosemide and captopril, we conclude that PA patients may be further divided into DR and DN. The DR group had a good response to diuretics whereas the DN group responded better to converting enzyme inhibitors. This classification of PA in terms of blood pressure response to furosemide may have therapeutic implications.

Adult↗

Production and characterization of monoclonal antibodies against alpha and beta spectrin subunits.

Twenty monoclonal antibodies against human erythrocyte spectrin were generated using purified native spectrin as the immunogen. Thirteen out of 20 monoclonal antibodies reacted to the alpha subunit, and the remaining seven monoclonal antibodies reacted to the beta subunit in Western blot analysis. One anti-beta subunit and two anti-alpha subunit monoclonal antibodies cross-reacted with the cell lysate of the non-erythroid T. lymphoma, J. Jhan, cell line. Identification of 20 monoclonal antibodies to the respective tryptic domains was also achieved. The specificity of these antibodies to respective tryptic domains of spectrin confirms the alignments and uniqueness of each of the previously identified five domains in the alpha subunit and four domains in the beta subunit, and establishes the identity of proteolytic daughter peptide fragments.

Animals↗

Valve ring abscess associated with infective endocarditis: echocardiographic features and clinical observations.

The presence of a valve ring abscess in patients with infective endocarditis adds appreciably to the expected rates of morbidity and mortality. From January 1989 to October 1991, a total of 43 consecutive patients with infective endocarditis seen at National Taiwan University Hospital were enrolled in this study. There were 30 men and 13 women, ranging in age from 14 to 75 years (mean +/- SD 38.5 +/- 15.0 years). The presence of infective endocarditis was documented by surgery in 26 patients and was based on a clinical diagnosis in the remaining 17 patients. A valve ring abscess was detected in five patients, either by transthoracic or transesophageal echocardiography, and all were confirmed at surgery. Aortic valve endocarditis was more frequently found in patients with valve ring abscesses (100% vs 31.6%, p < 0.01), and the infecting organism was most often Staphylococcus aureus (60.0% vs 15.8%, p < 0.05). The proportion of urgent operations was also higher in the group with abscesses (80.0% vs 23.7%, p < 0.05). The hospital mortality was 40.0% in patients with abscesses and 5.3% in patients without abscesses, but the difference did not reach significance (p = 0.056). Transthoracic echocardiography identified valve ring abscesses in the first three patients, but transesophageal echocardiography was more useful in detecting abscesses located in the posterior aspect of the aortic root in the other two patients, in which the lesion was overlooked or only suspected by the transthoracic approach.(ABSTRACT TRUNCATED AT 250 WORDS)

Abscess↗

Mapping the putative RNA helicase genes by sequence overlapping.

An 'electronic' gene mapping procedure based on computer-aided search for overlapping gene sequences was used to identify adjacent genes and localize several putative RNA helicase genes to different chromosomes. PRP28 and AMD1 genes map to the right arm of chromosome IV next to sup2, which encodes a tyrosine tRNA. PRP16, previously mapped to chromosome XI, is tightly linked to MRP-L20. PRP22 is adjacent to PRE1, whose chromosomal location is currently unknown. The utility of this approach in yeast gene mapping is evaluated.

Chromosome Mapping↗

Characterization and nucleotide sequences of the variable regions of a monoclonal antibody against alpha-fetoprotein.

alpha-Fetoprotein (AFP) is a well-known tumor marker of hepatocellular carcinoma (HCC). Monoclonal antibodies against AFP possessing specific binding ability to HCC are potential candidates for immunoscintigraphy and immunotherapy. A new monoclonal antibody against AFP (0325-6-9) was isolated. Its specificity and targeting tumor ability were characterized by enzyme-linked immunosorbent assay (ELISA), cell immunostain and complement killing. These results suggest that 0325-6-9 is specific to hepatoma cells. The nucleotide sequences of variable regions of 0325-6-9 were determined by M13 dideoxynucleotide sequencing method. With the information of nucleotide sequence, this antibody then could be modified by recombinant technology for its usage in in vivo diagnosis and immunotherapy.

Amino Acid Sequence↗

Acute exacerbations of chronic type B hepatitis are accompanied by increased T cell responses to hepatitis B core and e antigens. Implications for hepatitis B e antigen seroconversion.

T cell proliferative responses to hepatitis B virus-encoded envelope antigen (S + preS2 + preS1), recombinant core antigen (HBcAg), and natural hepatitis B e antigen (HBeAg) were examined in 22 HBeAg-positive patients with chronic type B hepatitis and 17 healthy hepatitis B surface antigen (HBsAg) carriers. The results showed that HBeAg-positive patients had (a) higher levels of T cell responses to HBcAg/HBeAg than those of healthy HBsAg carriers (P less than 0.001 and P less than 0.01, respectively); (b) a further increase in these T cell responses during acute exacerbations (P less than 0.05 and P less than 0.05, respectively); (c) subsidence in the T cell responses to HBcAg/HBeAg after recovery from acute exacerbations and HBeAg seroconversion, whereas the responses would persist at high levels if the patients did not enter a clinical remission; and (d) low levels of T cell responses to S + preS2 + preS1 either before or after HBeAg seroconversion. The appearance of increasing T cell responses to HBcAg/HBeAg usually occurred in the early phase of acute exacerbations. These findings imply that HBcAg/HBeAg-specific T cells play an important role in the exacerbations of chronic hepatitis B and in HBeAg seroconversion. HBcAg/HBeAg-specific precursor T cell frequencies were serially studied in selected cases by limiting dilution assay. Elevation (two- to fourfold) of HBcAg/HBeAg-specific precursor T cell frequencies contributed to the increase of HBcAg/HBeAg-specific T cell proliferation during acute exacerbations.

Adult↗

Purification of radioiodinated human insulin by high performance liquid chromatography for a sensitive radioimmunoassay.

The optimal sensitivity of a radioimmunoassay depends on the purity of the radiolabeled antigen. The conventional purification methods are not complete and are time consuming. The combination of a Sep-pak C18 cartridge and high performance liquid chromatography (HPLC) for the purification of 125I-labeled insulin in our study revealed that the Sep-pak cartridge can serve as the preliminary step to remove unreacted radioactive iodide, the reactants, and labeled but presumably damaged materials unadsorbed to the cartridge. The fractions eluted from the Sep-pak containing high radioactivity and high immunoreactivity to the antibody were chosen for further purification by HPLC to eliminate undesirable radiolabeled substances with a lesser immunoreactivity. The purified radiolabeled insulin was used to develop a sensitive radioimmunoassay with detecting limits of 0.03 microU/mL per tube.

Chromatography, High Pressure Liquid↗

Colorectal ornithine decarboxylase activity in human mucosa and tumors: elevation of enzymatic activity in distal mucosa.

To examine the value of ornithine decarboxylase (ODC) assay as a biological marker of potential malignancy in large bowel, we harvested 43 colorectal carcinoma, 7 adenoma, 6 polyps, and 77 normal-appearing mucosa at surgery from patients with colorectal carcinoma. In addition, 13 normal rectal mucosa were obtained at biopsy from patients with benign diseases or diseases unrelated to colorectal carcinoma as normal control. ODC activity was significantly higher in polyps and adenocarcinomas than in normal-appearing mucosa from patients with colorectal carcinoma. ODC activity in normal-appearing mucosa varied throughout the large intestine, with significantly higher activities in the distal segment of the large bowel. The higher ODC activity detected in the sigmoid colon and rectum correlates with the larger incidence of tumor development in this region of the large bowel. This observation needs to be taken into consideration when ODC activities of the colorectal mucosa are measured as biological markers of potential malignancies.

Adenoma↗