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Biomedical subjects

T Higuchi

Publications and source records attributed to T Higuchi.

At least 685 records · Page 38Linked to original sources
PubMed1978

Clinical analysis of tamoxifen, an anti-neoplastic agent, in plasma.

Tamoxifen, a phenylstilbene derivative, is currently being used to treat metastatic breast cancer. We describe an analytical method for monitoring the parent drug and its 4-hydroxylated derivative in whole blood and plasma. After extraction from biological media, the analytes are converted to highly fluorescent products by ultraviolet irradiation, and then separated by liquid-chromatography on a muBondapak CN column, with spectrofluorometric detection of components. Detection limits for tamoxifen and its 4-hydroxy derivative are 1 and 2 microgram/liter of biological fluid, respectively. Conditions have been optimized so that the reaction proceeds fast enough for convenient sample handling without jeopardizing fluorescence yield due to the photocatalyzed degradation of the fluorescent product. Evidence suggests that the fluorophore being monitored is a phenanthrene derivative.

Breast Neoplasms↗
PubMed1978

Microsomal enzymes in patients with gastric carcinoma as determined by plasma half-life of antipyrine.

Metabolism of antipyrine was studied in 12 patients with gastric carcinoma and 5 control subjects with peptic ulcer matched for sex, body weight, height, and smoking history. The mean antipyrine half-life was significantly longer (21.5 +/- 1.5 hr) in 3 patients with disseminated gastric carcinoma compared to control subjects (9.3 +/- 1.5 hr) (P less than 0.001). There was no significant difference in the mean antipyrine half-life between 9 patients with localized gastric carcinoma and control subjects. Similarily, the mean metabolic clearance rate of antipyrine was significantly lower (22.8 +/- 5.0 ml/hr/kg) in patients with disseminated gastric carcinoma compared to control subjects (52.6 +/- 13.4 ml/hr/kg) (P less than 0.02). Thus, the presence of gastric carcinoma in humans might alter antipyrine elimination. Significant negative correlation was observed between antipyrine half-life and albumin concentration (r = -0.786, P less than 0.01). These observations indicate that the decrease in antipyrine half-life is not primarily due to the presence of tumor but rather to the nutritional status of an individual.

Antipyrine↗
PubMed1977

High-performance liquid chromatographic analysis of dianhydrogalactitol in plasma by derivatization with sodium diethyldithiocarbamate.

A high-performance liquid chromatographic method is described for measuring submicrogram quantities of dianhydrogalactitol, a promising anti-neoplastic agent, in plasma. The drug is derivatized directly in plasma with sodium diethyldithiocarbamate to form a bis(dithiocarbamoyl) ester which absorbs UV light at 254 nm (am 17,000). The derivatized product is then extracted quantitatively into chloroform and separated by normal phase chromatography (muBondpak CN column). Dianhydrogalactitol concentration below 50 ng/ml of plasma can be detected in the eluent.

Chemical Phenomena↗
PubMed1977

Acetylacroninium salts as soluble prodrugs of the antineoplastic agent acronine.

The low aqueous solubility of acronine (approximately 2 mg/liter) has been overcome by identification of quaternary prodrug salts exhibiting apparent molar solubilities two to five orders of magnitude greater than acronine. The synthesis and kinetics of hydrolysis of the various prodrug acetylacroninium salts were studied, and the half-life for hydrolysis under conditions approximating the in vivo situation was estimated to be about 5 min. Such rapid reversion, together with the greatly increased solubility, appears to qualify the prodrug for intravenous use.

Acronine↗
PubMed1977

Improved delivery through biological membranes. 4. Prodrugs of L-dopa.

Various classes of transient derivatives of L-Dopa have been synthesized, systematically protecting one or more of the main sites of metabolism in the molecule: the carboxy function, the amino, and/or the catechol system. The derivatives studied include carboxy esters, phenol esters, amides, peptides, and various combinations of these functions. A number of these derivatives effectively prevent the metabolism of L-Dopa prior to and/or during the absorption process, resulting in a significantly better bioavailability of the drug. In vivo studies using dogs showed up to 2.5-fold increase in L-Dopa blood levels. The metabolism as well as toxicity aspects of the prodrugs is also discussed.

Administration, Oral↗
PubMed1977

A preliminary Pharmacokinetic study of dianhydrogalactitol (NSC-132313) disposition in the dog.

The pharmacokinetics of dianhydrogalactitol (DAG), NSC-132313, were studied in the beagle dog at doses of 3 mg - kg-1 and 6 mg - kg-1. DAG concentrations in plasma were determined by a gas chromatographic method capable of specifically detecting the parent drug and differentiating between it and products of its degradation or metabolism. Plasma disappearance time curves were generated and shown to follow simple two-compartment model behavior after iv administration of DAG. Distribution and elimination of DAG appeared to be dose-independent in the limited dose range studied. After iv administration, the drug was rapidly distributed throughout extracellular fluids (volume of the central compartment = 462 ml - kg-1) and subsequently was rapidly cleared (total body clearance = 23.4 ml - min-1 - kg-1) and eliminated (t1/2, b = 26.2 min) from the animal. Experiments (in vitro) with the use of radiolabeled DAG indicated that the drug binds reversibly and irreversibly to red blood cells.

Animals↗
PubMed1977

Antibody titer and clinical course of pemphigus.

The relationship between the titer of pemphigus antibody and the clinical course of the disease was investigated in 15 patients with various types of pemphigus. Although antibody titers generally ran parallel to fluctuations of the clinical course, the elevation of antibody titer appeared to follow the re-appearance or exacerbation of the lesions on 10 occasions in 6 patients, while it appeared to precede the latter only on 2 occasions in 2 patients. In addition, the disappearance of the antibody was considerably delayed after disappearance of skin lesions in 2 cases. These findings suggest that the pemphigus antibody is the result of skin damage, rather than the cause of pemphigus itself.

Adult↗
PubMed1977

Comparative study of 6-mercaptopurine metabolism in human leukemic leukocytes and L1210 cells.

Leukocytes from patients with leukemia and L1210 cells from mice were examined for the rate of formation and cellular concentration of phosphoribosylpyrophosphate, the rate of thioinosinic acid formation, and a number of selected enzymes involved in purine nucleotide synthesis. The amount of thioinosinic acid formed in L1210 cells was much higher than that in human leukemic leukocytes. In cell extracts, the synthesis of thioinosinic acid was similar in both cell types, and the amount of purine phosphoribosyltransferase was not rate limiting in either case. Much higher concentrations and rates of formation of phosphoribosylpyrophosphate were found in L1210 cells than in human leukemic leukocytes. The difference in response to 6-mercaptopurine between L1210 cells and human leukemic leukocytes might be attributed to their difference in supply of phosphoribosylpyrophosphate. Phosphoribosylpyrophosphate-amidotransferase was found to be high in L1210 cells, but was not detected in human leukemic leukocytes.

Animals↗
PubMed1977

Characterization of tumour virus proteins. I. Radioimmunoassay of the P27 protein of avian viruses.

The major structural protein of avian oncornaviruses, a core component of about 27000 daltons, has been measured by radioimmunoassay. The purified protein was labelled with 125Iodine by chloramine-T method. The immune serum titer was defined as the highest serum dilution able to precipitate 50% of the labelled antigen present in the system. Standard competition curve was constructed in order to determine the equivalents of protein, in a system with limiting antibody concentration. In the experimental conditions used, 0.14 ng of AMV-P27 inhibited 50% of 125I-AMV-P27 (1.0 ng) precipitation. The 125I-AMV-P27 vs anti-AMV-P27 system was used to study the competition of normal cells, purified virus suspension, productive cells and supernatant fluids. Most of the chicken embryo fibroblasts showed expression of this viral component. The phenomena of cell transformation, the increase in total protein, and the expression of P27 were studied in rapid transformation of CEF by RSV-SRA.

Alpharetrovirus↗
PubMed1977

Characterization of tumour virus proteins. II. Expression of the protein P30 in transformed productive and non-productive Ki/NRK cells.

The structural protein of murine tumour virus P30 has been measured by radioimmunoassay. The titer of each serum was determined by using as antigen the purified Rauscher viral protein labeled with 125iodine. Standard competition curve was constructed in order to determine the equivalent of protein to inhibit the precipitation reaction under limited antibody concentration. Competition by purifed Kirsten virus suspension, normal rat kidney cells, transformed-productive and transformed non-productive cells were measured in homologous and heterologous system. Type, group and interspecies determinants were characterized using the proper antigen-antibody system. Once the proteins have interspecie determinants, it is possible that we might be able to use some mammalian virus protein as tool to determine the presence of viral protein in human processes.

Animals↗
PubMed1977

Effects of phenobarbital and endotoxin on the lethality and metabolism of 6-mercaptopurine in male BALB/c mice.

In male BALB/c mice, a combination of individually non-lethal doses of 6-mercaptopurine and endotoxin was significantly lethal. In contrast, mice treated with phenobarbital were resistant to this lethal effect. The high levels of thioinosinic acid in mice that were treated with endotoxin contrasted significantly with the levels in phenobarbital-treated mice. On the other hand, the concentration of hypoxanthine was increased by the administration of phenobarbital and decreased by the administration of endotoxin. The sleeping time and levels of pentobarbital hydroxylase found in endotoxin-treated mice were consistent with the lethality and levels of thioinosinic acid. After mice were treated with endotoxin, their sleeping time was prolonged, which agrees with the course of the stimulatory effects of 6-mercaptopurine anabolism. However, there were no significant differences in hypoxanthine-guanine phosphoribosyltransferase. Furthermore, contrary to expectation, there were significant increases in xanthine oxidase after treatment with endotoxin. Thus, the metabolism of 6-mercaptopurine might be modified by hepatic microsomal enzyme activity.

Animals↗