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C Lin

Publications and source records attributed to C Lin.

At least 325 records · Page 18Linked to original sources
PubMed1987

Characterization of D-2 dopamine receptors in a tumor of the rat anterior pituitary gland.

Dopamine receptors in the 7315a transplantable rat anterior pituitary tumor were characterized using radioligand binding assays with [3H]spiroperidol ([3H]SPD) and assays of adenylate cyclase activity. Scatchard analysis of the binding of [3H]SPD yielded linear plots and a Kd value of 73 pM. Studies of the inhibition of the binding of [3H]SPD were performed with a series of competing ligands, including the antagonists domperidone, (+)-butaclamol and sulpiride and the agonists dopamine, bromocriptine and N-propylnorapomorphine. Inhibition curves for the antagonists gave Hill coefficients of approximately 1, consistent with the presence of only a single class of binding sites with a high affinity for [3H]SPD. In contrast, the Hill coefficient for dopamine was significantly less than 1. When assays were carried out in the presence of 300 microM GTP, the inhibition curve for dopamine was shifted to the right and the Hill coefficient increased to approximately 1. An effect of GTP on the affinity of a receptor for agonists is consistent with the existence of at least two agonist affinity states. Inhibition of the binding of [3H]SPD by the partial agonist bromocriptine was not affected when assays were carried out in the presence of GTP. The uniform low affinity of the selective serotonin antagonist ketanserin for these sites indicated that the radioligand was not labeling serotonin-2 receptors in this tissue. A good correlation was observed between the Ki values for competing ligands measured in the tumor and in homogenates of rat striatal tissue. Dopamine was shown to inhibit forskolin-stimulated adenylate cyclase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclase Inhibitors↗
PubMed1986

[Comparison of in vitro assays for the cytotoxic effect of anticancer drugs].

The cytotoxic effects of three anticancer drugs, methotrexate (MTX), 5-fluorouracil (5-Fu) and oridonin (Rub A), were investigated using a human gastric adenocarcinoma cell line (MGc80-3) and a human esophageal cancer cell line (CaEs-17) by means of colony-forming assay, dye exclusion test, measurement of incorporation of 3H-thymidine into DNA and examination of mitotic index. MGc80-3 cells, exposed for 24 hr to increasing concentrations of MTX (0-1.6 micrograms/ml), 5-Fu (0-12 micrograms/ml) or Rub A (0-25 micrograms/ml), showed different types of dose-survival curves determined by colony-forming assay. It suggests that these drugs have different models of action. The killing effect of MTX and 5-Fu was obviously underestimated by dye exclusion; the cell numbers were reduced to about 30% and 60% of control, while the colony formation showed approximately 2.5 and 3.5-log kill. When CaEs-17 cells exposed for 6 hr to varying concentrations of Rub A (0-15 micrograms/ml), the reduction in cell number (15 micrograms/ml, T/C = 18.0%) was always less than that (15 micrograms/ml, T/C = 3.8%) in colony formation. Under the same condition, the mitotic index, however, increased with increasing dosage first, and then the T/C values, at higher concentrations (5-15 micrograms/ml), reached approximately 200%. Although the drug significantly inhibited the incorporation of 3H-thymidine, the pattern of the dose-response curve differed from the dose-survival curve. These findings in cytobiochemistry and morphology may contribute to explain the cytotoxicity of an anticancer drug, but failed in correlation with the data obtained by colony-forming assay which seems to be the most reliable method for determining drug-induced cell lethality.

Adenocarcinoma↗
PubMed1985

The excretion of rosaramicin in breast milk.

The excretion of rosaramicin, a macrolide antibiotic, was studied in the breast milk of ten lactating women. Breast milk and serum samples were collected for 48 hours after a single 250-mg oral dose of rosaramicin. Mean serum half-life, apparent volume of distribution, and oral clearance were 4.4 hours, 3.41 L/kg, and 6.34 mL/min/kg, respectively. Mean milk/serum ratio was 0.12 and the total amount of drug recovered over the first ten hours was 6.25 micrograms, approximately 0.0025% of the dose. A positive correlation between breast milk volume and breast milk clearance was found, suggesting that the amount of drug received by a nursing infant will depend on the volume of milk produced by the mother. Drug-induced toxicity from the parent drug is unlikely to occur in nursing infants since the amount of rosaramicin that a nursing infant could ingest is small.

Adult↗
PubMed1985

Relationship between production of epidermal growth factor receptors, gene amplification, and chromosome 7 translocation in variant A431 cells.

Synthesis of the epidermal growth factor (EGF) receptor has been analyzed in a series of variant A431 human epidermoid carcinoma cell clones reported to contain different amounts of EGF binding sites. The amount of EGF receptor protein, quantitated by immunoaffinity chromatography, and EGF receptor mRNA, quantitated by cDNA hybridization, were closely correlated to the extent of EGF receptor gene amplification. This correlation existed in variants selected for reduced EGF receptors and in revertants from those variants with increased EGF receptors. There was also a correlation between the frequency of translocation of chromosome 7, containing the EGF receptor gene, and EGF receptor protein. These results support gene amplification as the mechanism enhancing A431 cell EGF receptor protein and determining growth responses.

Carcinoma, Squamous Cell↗
PubMed1985

Pharmacokinetics of Sch 34343 in rats and dogs.

The pharmacokinetics of 14C-Sch 34343 were studied in rats and dogs following intravenous and intramuscular dosing. In both species, it was rapidly absorbed after intramuscular dosing. The serum AUC for total radioactivity and for intact drug after intramuscular dosing were similar to those obtained after intravenous dosing. Following both routes of drug administration, the elimination of half-life (T 1/2 beta) was 7 min in rats and 25-32 min in dogs. Following intravenous dosing of 14C-Sch 34343 to rats, radioactivity in tissues disappeared rapidly with time indicating no tissue accumulation. Highest concentrations of radioactivity were seen in the kidney. Liver, lung, skin and heart appeared to have concentrations of radioactivity similar to those of blood. Sch 34343 was excreted rapidly and primarily into the urine in both rats and dogs. After either route of dosing, urinary excretion of total radioactivity ranged from 84 to 93% and that of intact Sch 34343 from 41 to 51% of the dose, respectively. In addition, the effect of pretreatment with probenecid on the pharmacokinetics in rats and dogs and in anephric rats were also evaluated. Pretreatment with probenecid prolonged the elimination half-life in both rats and dogs. Anephric rats had a longer half-life than normal rats.

Animals↗
PubMed1984

High-pressure liquid chromatographic method for determination of Sch 28191 in biological fluids.

A high-pressure liquid chromatographic method has been developed for the measurement of N-D-ornithyl amphotericin B methyl ester (Sch 28191) in biological fluid. The method involves protein precipitation with methanol, followed by separation of the supernatant on a reverse-phase column and quantitation by absorbance at 405 nm. This technique resulted in a recovery of 97%. There was a good linear relationship between the peak height ratio and Sch 28191 concentrations ranging from 0.015 to 20 micrograms/ml. In addition, this method was specific for Sch 28191 since all of its analogs tested did not interfere with the assay. The method was reproducible with a lower limit of quantitation of 0.015 microgram/ml. Serum levels obtained from this method were in good agreement with those obtained from a microbiological assay only when drug concentrations were higher than 1.5 microgram/ml. The high-pressure liquid chromatographic method is useful in monitoring serum and urine drug levels in animals and should prove to be useful for pharmacokinetic studies of the drug with therapeutic doses in humans.

Amphotericin B↗
PubMed1984

Comparative pharmacokinetics of Sch 28191 and amphotericin B in mice, rats, dogs, and cynomolgus monkeys.

The pharmacokinetics of Sch 28191, the N-D-ornithyl methyl ester of amphotericin B, and amphotericin B were studied in mice, rats, dogs, and cynomolgus monkeys after an intravenous dose of 0.6 mg/kg was administered. The decline in the concentrations of Sch 28191 and amphotericin B in serum appeared to be biphasic in nature. The half-life at the distribution phase and the half-life at the elimination phase of Sch 28191 were similar to those of amphotericin B in all animals studied. The half-life at the distribution phase in serum was 0.9 to 1.5 h in all animals studied. The half-lives at the elimination phase in serum were 25 to 28 h in mice, 16 to 18 h in rats, 44 to 47 h in dogs, and 35 h in cynomolgus monkeys. The areas under the serum concentration-time curves of Sch 28191 were five- to eightfold larger than those of amphotericin B in rats, dogs, and cynomolgus monkeys but were only slightly larger than those of amphotericin B in mice. In dogs, the urinary excretion (over 9 days) of unchanged drug accounted for 23% of the Sch 28191 dose and 25% of the amphotericin B dose. The concentrations of Sch 28191 in serum were also studied after the intravenous administration of 0.3, 0.6, or 1.25 mg/kg to dogs. The serum concentration-time curves were parallel for these doses. There was a linear relationship between the areas under the concentration-time curves and the doses, indicating dose proportionality.

Amphotericin B↗
PubMed1983

Quantitative explanation for increased affinity shown by mixtures of monoclonal antibodies: importance of a circular complex.

Mixtures of some but not all monoclonal antibodies which bind to separate epitopes on human chorionic gonadotropin (hCG) show an increased affinity for the hormone. To find an explanation for the increase in affinity, we developed a mathematical model which predicts the quantities of intermediates formed when pairs of IgG1 mouse monoclonal antibodies having affinities of approximately 10(8) M-1 for hCG are mixed with the hormone. At low antibody concentrations (i.e. less than 1 nM or 0.15 micrograms/ml) analysis of possible antibody-hormone combinations, including linear and circular chains composed of less than 12 molecules of antibody and 12 molecules of hCG, suggests the increase in affinity is due to formation of a circular complex containing two molecules of antibody and two of hCG. Further, the model predicts that the circular complex will be the major species formed at antibody-antigen equivalence. This prediction is supported by experimental observations on the molecular weight of a new complex formed in the presence of hCG and the mixture of the monoclonal antibodies. In addition, based on experimental values of binding constants for individual antibodies to hCG, the model correctly quantifies the loss in complex observed in the presence of excess hCG antigen. At high antibody concentrations (i.e. greater than 10 nM or 1.5 micrograms/ml) the formation of linear chains of antibody hCG pairs becomes appreciable and contributes to the increase in apparent affinity of the mixture for hCG. These results suggest that the observed affinity of complex mixtures of antibody for antigens containing multiple epitopes calculated from Scatchard plots may not be related to the affinity or avidity of any of the antibody species for a given epitope.

Antibodies, Monoclonal↗