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Biomedical subjects

Y C Chang

Publications and source records attributed to Y C Chang.

At least 361 records · Page 20Linked to original sources
PubMed1983

Functions of the 5'-phosphoryl group of pyridoxal 5'-phosphate in phosphorylase: a study using pyridoxal-reconstituted enzyme as a model system.

Pyridoxal-reconstituted phosphorylase was used as a model system to study the possible functions of the 5'-phosphoryl group of pyridoxal 5'-phosphate (PLP) in rabbit muscle glycogen phosphorylase. Kinetic study was conducted by using competitive inhibitors of phosphite, an activator, and alpha-D-glucopyranose 1-phosphate (glucose-1-P) to study the relationship between the PLP phosphate and the binding of glucose-1-P to phosphorylase. Fluorine-19 nuclear magnetic resonance (19F NMR) spectroscopy of fluorophosphate bound to pyridoxal phosphorylase showed that its ionization state did not change during enzymatic catalysis. Evaluation of the apparent kinetic parameters for the activation of pyridoxal phosphorylase with different analogues having varied pKa2 values demonstrated a dependency of KM on pKa2. Molybdate, capable of binding as chelates in a trigonal-bipyramidal configuration, was tested for its inhibitory property with pyridoxal phosphorylase. On the basis of the results in this study, several conclusions may be drawn: (1) The bound phosphite in pyridoxal phosphorylase and, possibly, the 5'-phosphoryl group of PLP in native phosphorylase do not effect the glucose-1-P binding. (2) One likely function of the 5'-phosphoryl group of PLP in native phosphorylase is acting as an anchoring point to hold the PLP molecule and/or various amino acid side chains in a proper orientation for effective catalysis. (3) The force between the PLP phosphate and its binding site in phosphorylase is mainly electrostatic; a change of ionization state during catalysis is unlikely. (4) Properties of the central atoms of different anions are important for their effects as either activators or inhibitors of pyridoxal phosphorylase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Effect of oxyanions of the early transition metals on rabbit skeletal muscle phosphorylase.

The differential effects of the oxyanions of the early transition metals ions V(V), W(VI), and Mo(VI) on the catalytic activity and coenzyme binding of rabbit skeletal muscle phosphorylase are studied. The oligoanions of V(V), W(VI), and Mo(VI) are potent inhibitors of phosphorylase. Kinetic studies revealed that oligovanadates inhibit pyridoxal-reconstituted phosphorylase b by competing with both the substrate, glucose 1-phosphate, and the activator, phosphite, with K1 values of 4 microM and 6 microM, respectively. Oligovanadates in the millimolar concentration range inhibit phosphorylases a and b by competing with glucose 1-phosphate binding. The polymeric decavanadate and paratungstates caused time-dependent inactivation of phosphorylase. Spectral studies with tungstate and phosphorylase b revealed that the inactivation is due to deformation of the coenzyme site. Kinetic studies and the protective effects of substrate and effectors on inactivation and deformation by tungstate or vanadate suggest that deformation and inactivation is caused by a primary binding of the oligoanions at the glucose 1-phosphate site. Nuclear magnetic resonance (NMR) studies of vanadate-phosphorylase complexes and vanadate solutions under different conditions were carried out to ascertain the nature of vanadate ions interacting with functional groups in phosphorylase. The results suggest that decavanadate is the major protein-bound species. NMR studies also showed that guanidino groups react with decavanadate and suggest that arginine residues in phosphorylase are potential functional groups that can interact with decavanadate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Leukocyte-derived interferon (alpha) in human breast carcinoma. The American Cancer Society phase II trial.

A multi-institutional trials program was initiated to define the effects of interferons in disseminated human breast carcinoma. Interferon alpha, prepared from buffy coats, was administered intramuscularly at 3 x 10(6) U daily for an initial period of 28 days. Of 23 patients who entered the program, five had an objective partial response of 92 days mean duration at diverse sites of involvement. Patients who responded were significantly older (p = 0.05) than nonresponders. Dose escalation in eight patients did not result in any clear evidence of additional responses. Major toxicities were fatigue, anorexia with weight loss, and reversible leukopenia (less than 3.5 x 10(9) leukocytes/L in 16 patients). Natural killer cell and antibody-dependent cell-mediated cytotoxicity were significantly (p less than 0.05) enhanced 48 hours after interferon administration began but subsequently declined despite continued therapy. Serum beta 2-microglobulin concentration increased on day 15 (p less than 0.05) and remained significantly elevated on day 22 (p less than 0.005). Peak interferon titers (mean, 62 U) occurred 6 hours after interferon was started, varied widely between patients, and were higher and more persistent with dose escalation. Once an optimal dose is defined, prospectively randomized trials will define what role interferons may have in systemic therapy of breast carcinoma.

Adult↗
PubMed1982

A pilot study of mitomycin-C and tamoxifen (MT) versus dibromodulcitol, adriamycin, and tamoxifen (DAT).

The aim of this study was to compare the treatment efficacy of mitomycin-C plus tamoxifen (MT) to adriamycin, dibromodulcitol and tamoxifen (DAT) in previously treated patients with metastatic breast cancer. Thirty-two patients with measurable or evaluable disease were entered on the study. Twenty-three were prospectively randomized to receive DAT (Group 1) or MT (Group 2). Nine patients with prior exposure to adriamycin were directly assigned to receive MT (Group 3). Thirty-one patients were evaluable for response and toxicity. The hematological toxicities were comparable among the three treatment groups. DAT gave more nausea and vomiting than MT. One patient developed irreversible fatal congestive heart failure while receiving DAT. The response for Group 1 was 5/11, Group 2, 3/12, and Group 3, 3/8. The duration of response for patients in Group 1 was 455+, 315, 251, 239, 231 days, in Group 2 it was 328+, 144+, 119, and in Group 3 it was 35+, 84, and 112 days. The median time to treatment failure did not differ significantly between Group 1 (114 days), 2 (83 days) and 3 (61 days) (p = 0.24). The median survival time was similar among the three groups (p = 0.41). This pilot study suggests that MT and DAT are both effective treatment programs in patients with metastatic breast cancer who have failed prior chemotherapy regimens.

Antibiotics, Antineoplastic↗
PubMed1981

Phase I--II evaluation of combination cyclophosphamide, 5-fluorouracil, hexamethylmelamine, and prednisone in advanced breast cancer.

A four-drug combination of intermittent high-dose cyclophosphamide with 5-fluorouracil, hexamethylmelamine, and prednisone was given to 19 patients with advanced breast cancer. Objective response was documented in 7 of 18 evaluable patients. The median duration of response was 99 days. Response was observed in 6/7 patients without visceral disease and 1/11 patients with visceral disease. Toxicity was acceptable and no life-threatening toxicity was observed. Three patients have received the four-drug combination for more than 1 year without serious side effects. This regimen may serve as an alternative treatment for patients without visceral metastasis who have failed to respond to other combination chemotherapy regimens.

Adenocarcinoma↗
PubMed1979

Investigation of the human macrophage. I. Collection and in vitro cultivation.

By means of blister formation produced by cantharidin, a certain number of human macrophages could be readily obtained from the blister exudate. In the presence of 50% cell-free exudate, these cells were found to proliferate in vitro. The proliferating cells possessed the morphology and functional characteristics of macrophages.

Animals↗
PubMed1979

Investigation of the human macrophage. II. The in vitro cytotoxicity of macrophages.

Macrophage-mediated cytotoxicity in vitro was studied by a tritiated thymidine incorporation inhibition assay as well as by microscopic examination and optical transmitance determination. It was found that macrophages from patients with malignant diseases showed cytotoxic effects on two malignant human cell lines. The cytotoxic activity was more marked in patients who were clinically tumor-free. Some patients with benign diseases and normal subjects also exhibited cytotoxic macrophages. Macrophage-mediated cytotoxicity (MMC) was thus nonspecific in nature. Cell-free exudate from cancer patients did not influence MMC appreciably. The experimental methods and the possible significance of MMC are discussed.

Animals↗
PubMed1979

Antiemetic effect of intravenous diazepam in patients receiving cis-diamminedichloroplatinum II: a pilot study.

A pilot study suggesting the usefulness of intravenous diazepam as an antiemetic for adult patients receiving cis-diamminedichloroplatinum is presented. Observations included 24 patients and 34 courses of therapy. Patients received diazepam and prochlorperazine, and the incidence of vomiting and subjective evaluation of nausea were compared to previous courses of therapy with prochlorperazine alone. A positive response was observed in 87% of the patients. Use of other antiemetics is briefly reviewed.

Adolescent↗
PubMed1979

Colorimetric determination of hydralazine with 9-chloroacridine.

A spectrophotometric assay for hydralazine hydrochloride based on the interaction of the drug with 9-chloroacridine has been developed. The interaction shows an absorption maximum at 460 nm and is affected by temperature, heating time, and quantity of acridine reagent used. Color development is maximum when the drug is heated in the presence of a 30-fold molar excess of the acridine in a 50 +/- 1 degree C water bath for 1 hr. The method detects hydralazine hydrochloride in the 10(-5)--10(-6)M range with sensitivity to 0.2 micrograms/mL and 3--4% accuracy. Typical calibration data obtained from linear regression analysis of absorbance at various drug concentrations show r = 0.9997 (n = 6). Hydralazine can be determined in dosage forms that also contain varying quantities of reserpine and hydrochlorothiazide. The 9-chloroacridine method is as sensitive as other spectrophotometric procedures for hydralazine but also more accurate and precise, and involves fewer manipulative steps.

Acridines↗