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Biomedical subjects

J Miyamoto

Publications and source records attributed to J Miyamoto.

At least 73 records · Page 4Linked to original sources
PubMed1987

Metabolism of 2- and 3-tert-butyl-4-hydroxyanisole (2- and 3-BHA) in the rat (I): Excretion of BHA in urine, feces and expired air and distribution of BHA in the main organs.

The mechanism of the carcinogenic or toxic action of BHA on rat forestomach was examined by studies on the excretion and tissue distribution of radioactivity in F344 male rats given tert-butyl- or methoxy-labelled 3-BHA orally. Within 2 days after a single oral dose of labelled BHA at 1 g/kg body wt, 87-96% of the 14C was excreted, mainly in the urine with smaller amounts in the feces and expired air. More 14C was found in the tissues of rats given the methoxy-labelled compounds. The distributions of 14C in the forestomach and the glandular stomach were similar. At 168 h after treatment, more 14C was found in the forestomach of rats given 2-BHA than in that of rats given 3-BHA. These results indicate that excretion of BHA is rapid, that 4-O-methyl demethylation may take place readily and that demethylated methyl group may become distributed non-specifically in tissues. The carcinogenic or toxic action of BHA on the forestomach does not seem to be due accumulation of BHA in the forestomach.

Air↗
PubMed1987

Metabolism of 2- and 3-tert-butyl-4-hydroxyanisole (2- and 3-BHA) in the rat. (II): Metabolism in forestomach and covalent binding to tissue macromolecules.

The mechanism of action of 2(3)-tert-butyl-4-hydroxyanisole (2-BHA or 3-BHA) on rat forestomach epithelium was studied by examining the metabolites of BHA in the stomach and the covalent binding of BHA to macromolecules in the forestomach epithelium. Male F344 rats 6 weeks old were given a single intragastric injection of 1 g/kg body wt of [tert-14C]-3-BHA (Bu-3-BHA) or [methyl-14C]-3-BHA (Me-3-BHA), and 6 h later BHA metabolites in the forestomach, glandular stomach and stomach contents were examined by thin-layer chromatography. No significant amounts of metabolites were detected in the forestomach or glandular stomach epithelium and almost all the radioactivity in these tissues was extracted with organic solvents. In in vitro experiments also, no significant amounts of metabolites were detected when the 9000 g supernatant of the forestomach or glandular stomach epithelium, or gastric juice was incubated with Bu-3-BHA in the absence or presence of NADPH. In binding studies, rats were given Bu-3-BHA, [tert-14C]-2-BHA (Bu-2-BHA), Me-3-BHA or [methyl-14C] butylated hydroxytoluene (Me-BHT) intragastrically at a dose of 1 g/kg body wt with or without pretreatment with unlabelled 1% 3-BHA or BHT in the diet for 6 days. Six hours after treatment with a labelled compound, the rats were sacrificed and the DNA, RNA and protein of their forestomach, glandular stomach, liver and kidney were isolated. Bu-3-BHA, Bu-2-BHA and Me-3-BHA did not bind covalently to forestomach DNA or RNA, and the amounts of radioactivity of these compounds bound to proteins in the 4 tissues were similar. These findings suggest that BHA acts on the forestomach epithelium directly without metabolic activation, and that its action is not related to its binding to DNA or RNA.

Animals↗
PubMed1987

Safety assessment in the research and development of new chemicals.

A variety of testings to be incorporated in the research and development program of new chemicals to assess their fates and effects onto man and his environment should be so designed as to duly furnish reliable preliminary information. A rapid in vivo assay for animal carcinogenicity and a model ecosystem for bioaccumulation in aquatic organisms are discussed as examples of these brief testings, while further research needs are mentioned to ultimately assess the impacts of chemicals to the whole environment.

Accident Prevention↗
PubMed1987

[One-year chronic dietary toxicity study of d.d-T80-prallethrin in rats].

d.d-T80-prallethrin, a pyrethroid insecticide for sanitary use, was administered to Crj : CD (Sprague Dawley) rats at concentrations of 120, 600 or 3,000 ppm in diet for one year to assess the chronic toxicity potential and the reversibility. The summarized results obtained are as follows: 1. Chronic toxicity study 3,000 ppm : Decreases in body weight gain, food consumption, and water intake were observed. Slight alopecia in the neck and/or back was noticed during the first and second weeks, but the animals were recovered thereafter. Slight anemic changes such as decreases in hemoglobin concentration, hematocrit value, MCV and MCH were observed in the females at 52 week. Blood biochemistry revealed increases in total cholesterol (in the males and females at 13, 26 and 52 weeks), phospholipid (in the males and females at 13, 26 and 52 weeks), albumin (in the males at 13 and 26 weeks, in the females at 52 week), total protein (in the males at 26 week, in the females at 52 week), A/G ratio (in the males at 13 week, in the females at 26 week), creatinine (in the males at 52 week), urea nitrogen (in the females at 52 week), GOT (in the males and females at 52 week) and GPT (in the males and females at 52 week), and decreases in triglyceride (in the females at 26 and 52 weeks) and alkaline phosphatase (in the males at 13 and 52 weeks). In urinalysis, an increase in bilirubin was observed in the males at 52 week. Gross-pathology revealed a lower incidence of accentuated lobular pattern of liver (in the males at 26 week) and a higher incidence of enlarged liver (in the males at 52 week). In organ weight, increases in liver (in the males and females at 26 and 52 weeks), kidney (in the males at 26 and 52 weeks) and thyroid weights (in the males at 26 and 52 weeks, in the females at 26 week), and decreases in spleen (in the females at 26 and 52 weeks) and adrenal weights (in the females at 52 week) were observed. Histopathological examination revealed a lower incidence of fatty metamorphosis in the liver of females at 52 week. 600 ppm: An increase in liver weight was observed in the males at 26 week. 120 ppm: No effect was observed. 2. Reversibility study Almost all the above chronic toxicities were reversible.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Effect of bepridil on membrane currents of rabbit sinoatrial node cells.

Effect of 1-[3-isobutoxy-2-(benzylphenyl) amino]propyl pyrrolidine hydrochloride (bepridil), a new antianginal agent, on membrane potentials and membrane currents of sinoatrial node cells of rabbits was examined using conventional microelectrode and double microelectrode voltage clamp methods. Bepridil at a concentration of 10 mumol/l caused an increase in spontaneous cycle length, and a decrease in maximum rate of rise of the action potential and action potential amplitude. The rate of diastolic depolarization (phase 4) was also decreased by the drug. In the voltage clamp experiment, bepridil reduced both the slow inward current (Isi) and the hyperpolarization activated current (Ih), and increased the recovery time constant of Isi, whereas the time-dependent potassium current (IK) was not altered significantly. The major effect, however, was the reduction of Isi. These electrophysiological findings suggest that bepridil has a depressant effect on the electrical activity of sinoatrial node mainly by mediating the depression of slow channel.

Action Potentials↗
PubMed1986

Differential metabolism of fenvalerate and granuloma formation. I. Identification of a cholesterol ester derived from a specific chiral isomer of fenvalerate.

On a single po administration of the four chiral isomers of fenvalerate ([RS]-alpha-cyano-3-phenoxybenzyl [RS]-2-(4-cholorophenyl)isovalerate) to rats and mice at 2.5 mg/kg, the [2R, alpha S]-isomer showed relatively higher residues in all analyzed tissues as compared with the other three isomers. Similarly, this isomer showed higher tissue concentrations than other isomers when mice were fed a diet containing 500 ppm of the [2S, alpha S]-, and [2R, alpha R]-isomers for 2 weeks. The [2R, alpha S]-isomer produced a lipophilic metabolite in all the examined tissues on the basis of thin-layer chromatography analysis, but not for the other isomers. The amounts of lipophilic metabolite differed among tissues, being higher in adrenal, liver, and mesenteric lymph nodes following feeding to mice at 500 ppm of the [2R, alpha S]-isomer for 2 weeks. However, the amount did not increase proportionally with time and apparently reached a plateau within a rather short time. This metabolite was identified as cholesteryl [2R]-2-(4-chlorophenyl)isovalerate ([2R]-CPIA-cholesterol ester) on the basis of spectroanalysis and chromatographic behavior after purification on silica gel, Florisil, thin-layer, and high-pressure liquid chromatography. The presence of the same metabolite also was indicated in rat tissues. The CPIA-cholesterol ester was rapidly formed and found in all the analyzed tissues of mice 1 hr after a single po administration of the [2R, alpha S]-isomer.

Animals↗
PubMed1986

Differential metabolism of fenvalerate and granuloma formation. II. Toxicological significance of a lipophilic conjugate from fenvalerate.

Male mice of the ddY strain were fed a diet containing the [2S, alpha S]-, [2S, alpha RS]-, [2R, alpha S]-, and [2R, alpha R]-isomers of fenvalerate. Microgranulomatous changes were observed only in mice treated with the [2R, alpha S]-isomer at 125 and 1000 ppm for 1, 2, or 3 months. In contrast, the changes did not occur in mice treated with the [2R, alpha R]-isomer under the same conditions. Feeding of the [2S, alpha S]- and [2S, alpha RS]-isomers for 1 year did not cause the microgranulomatous changes at 500 or 1000 ppm. To clarify the causative agent of granuloma formation, cholesterol ester of 2-(4-chlorophenyl)isovaleric acid (CPIA), a lipophilic conjugate from the [2R, alpha S]-isomer of fenvalerate, was injected iv into ddY mice. Microgranulomatous changes were observed in the liver of mice treated with the [2R]-, [2S]-, or [2RS]-CPIA-cholesterol ester 1 week after a single treatment of 1, 10, or 100 mg/kg, as well as in liver of mice treated with a single dose of 10 or 30 mg/kg of the [2R]-CPIA-cholesterol ester and kept up to 26 weeks afterward. Histochemistry and microscopic autoradiography of the liver of mice demonstrated the presence of tritium derived from 3H-labeled[2R]-2-(4-chlorophenyl)isovalerate and cholesterol. Histochemistry also was positive for cholesterol ester in livers of mice treated with the [2R, alpha S]-isomer of fenvalerate. These results lend support for the hypothesis that CPIA-cholesterol ester is the causative agent of microgranulomatous changes induced by fenvalerate.

Animals↗
PubMed1986

Stereoselective formation of a cholesterol ester conjugate from fenvalerate by mouse microsomal carboxyesterase(s).

In accordance with in vivo findings, of the four chiral isomers of fenvalerate (S-5602 Sumicidin, Pydrin, [RS]-alpha-cyano-3-phenoxybenzyl [RS]-2-(4-chlorophenyl)isovalerate), only the [2R, alpha S]-isomer (B-isomer) yielded cholesteryl [2R]-2-(4-chlorophenyl)isovalerate (CPIA-cholesterol ester) in the in vitro study using several tissue homogenates of mice, rats, dogs, and monkeys. There were species differences in the extent of CPIA-cholesterol-ester formation, with mouse tissues showing relatively higher activity than those of other animals. The kidney, brain, and spleen of mice showed relatively higher capacities to form this ester compared to other tissues, and the enzyme activity was mainly localized in microsomal fractions. The CPIA-cholesterol ester did not seem to be produced by three known biosynthetic pathways of endogenous cholesterol esters--acyl-CoA:cholesterol O-acyltransferase (ACAT), lecithin:cholesterol O-acyltransferase (LCAT), and cholesterol esterase. Carboxyesterase(s) of mouse kidney microsomes solubilized by digitonin hydrolyzed only the B alpha-isomer of fenvalerate, yielding CPIA, whereas they yielded the corresponding cholesterol ester in the presence of artificial liposomes containing cholesterol. Thus, it appears that the stereoselective formation of the CPIA-cholesterol ester results from the stereoselective formation of the CPIA-carboxyesterase complex only from the B alpha-isomer, which subsequently undergoes cleavage by cholesterol to yield the CPIA-cholesterol ester.

Animals↗
PubMed1986

Studies on the bradycardia induced by aprindine in rabbit sinoatrial node cells.

The effects of aprindine (1 X 10(-7) to 4 X 10(-6) M) were examined on membrane potential and current of rabbit sinoatrial node by means of conventional microelectrode and double microelectrode voltage clamp methods. Aprindine decreased, in a dose-dependent manner, the spontaneously firing frequency, the maximum rate of depolarization and the action potential amplitude, and prolonged the action potential duration at half-amplitude. The slope of the diastolic depolarization was also reduced by the drug. In the voltage clamp experiment, aprindine reduced the slow inward current (Isi), the time-dependent potassium current (Ik) and the hyperpolarization activated current (Ih). The recovery time constant of Isi was prolonged by aprindine, while the kinetics of Ik was not altered. It is indicated that aprindine does not have an effect on a specific conductance or a single current system, but that the drug exerts an inhibitory effect on the electrical activity of sinoatrial node.

Action Potentials↗
PubMed1986

Fenvalerate-induced granulomatous changes in rats and mice.

Wistar rats and ddY mice were fed diet containing 10 to 3000 ppm technical fenvalerate for the major portion of their life span. Microgranulomatous changes were observed in lymph nodes, liver and spleen of both rats and mice as well as in adrenals of rats. The no-effect level for microgranulomatous changes was 30 ppm for mice and 150 ppm for rats. Transmission electron microscopy of phagocytes in the granulomatous foci revealed needle- or rod-shaped crystalline bodies within the cytoplasm. To examine reversibility of the microgranulomatous changes, ddY mice were fed the diet containing technical fenvalerate at the levels of 1000 and 3000 ppm for 6 weeks, followed by rearing on the control diet for up to 12 months. The size and number of the microgranulomatous changes were reduced with time. The microgranulomatous changes were typical of foreign body granulomas; they did not have the appearance of granulomas formed in response to immunologic stimulus.

Adrenal Glands↗
PubMed1986

Study on bradycardia induced by diltiazem in the rabbit sinoatrial node.

Effects of 3-(acetyloxy)-5-[2-(dimethylamino)ethyl]-2, 3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one (diltiazem) on the membrane currents of rabbit sinoatrial node cells were examined using the double microelectrode voltage clamp technique. The transmembrane slow inward current (Isi) was reduced after 0.5 mumol/l diltiazem perfusion and Isi was nearly completely suppressed by 2.2 mumol/l diltiazem. As to the blockade of Isi, diltiazem revealed a dose-dependent fashion. Diltiazem also produced a slight decrease of both the steady-state current during depolarization and the tail current after repolarization in these concentration ranges, while the hyperpolarization activated current (Ih) was not affected significantly. Furthermore, higher concentration of diltiazem (10 mumol/l) decreased the steady-state outward current amplitude during depolarization, implying that diltiazem might reduce the potassium outward current (Ik). It is concluded that diltiazem suppressed Isi in a use-dependent manner, not surprisingly, but the drug exerted an additional effect of a decrease in Ik of sinoatrial node cells.

Action Potentials↗
PubMed1986

Electrophysiological effect of trapidil on rabbit sinoatrial node cells.

Effects of trapidil on the membrane potentials and currents of rabbit sinoatrial node cells were investigated by means of conventional microelectrode and double microelectrode voltage clamp methods. Trapidil (1 X 10(-4) M) increased the spontaneous firing frequency, the maximum rate of rise, action potential amplitude and the slope of the pacemaker depolarization. Action potential duration was shortened by the drug application. Voltage clamp experiments showed that trapidil increased both the slow inward current (isi) and the potassium outward current (iK). Trapidil fastened the recovery time constant of isi, while the drug did not change the time course of the outward current tail. The hyperpolarization-activated current (ih) was also increased by the drug. The results obtained indicate that at relatively high concentration trapidil produces a positive chronotropic effect on the sinoatrial node cells by mediating an increase in isi, iK and ih.

Animals↗
PubMed1985

Isolation of simian retroviruses closely related to human T-cell leukemia virus by establishment of lymphoid cell lines from various non-human primates.

Simian retroviruses closely related to human T-cell leukemia virus (HTLV) were isolated by establishing virus-producing lymphoid cell lines from 7 species of non-human primates. By co-cultivation with human umbilical cord-blood cells and/or in the presence of interleukin-2, lymphoid cell lines were successfully established from the chimpanzee. African green monkey, pig-tailed macaque, red-faced macaque, Formosan monkey, Japanese monkey and bonnet monkey that had antibodies against HTLV antigens. These cell lines reacted with human sera of ATL patients and monoclonal antibodies against p19 and p24 of HTLV antigens. Cellular DNAs contained the provirus sequences homologous to HTLV-I by Southern blot hybridization. Moreover, they produced extracellular type-C virus particles and RNA-dependent DNA polymerase. All of these lymphoid line cells had Tac antigen, interleukin-2 receptor, and those of chimpanzee and red-faced macaque had helper/induced T-cell markers, while those derived from African green monkey had suppressor/cytotoxic T-cell markers. Furthermore, simian HTLV-related viruses of pig-tailed macaque, red-faced macaque and Japanese monkey were transmitted to human lymphocytes on co-cultivation.

Animals↗
PubMed1984

Comparative metabolism of 3,5-di-tert-butyl-4-hydroxytoluene (BHT) in mice and rats.

In male and female DDY/Slc mice given single oral doses (20 or 500 mg/kg body weight) of 3,5-di-tert-butyl-4-hydroxytoluene (BHT) labelled with 14C at the p-methyl group, 14C was distributed mainly in the stomach, intestines, liver and kidney, and then excreted in the urine, faeces and expired air. During the 7 days after treatment, 41-65, 26-50 and 6-9% of the 14C dose was excreted in faeces, urine and expired air, respectively, and the total recovery was 96-98%. Levels of 14C in 21 male and 22 female tissues 7 days after treatment were less than 1 microgram BHT equivalents/g tissue (ppm) in mice given 20 mg/kg and less than 11 ppm in mice given 500 mg/kg. When [14C]BHT was given orally to male mice at 20 mg/kg/day for 10 days, 14C was rapidly excreted and did not exhibit any tendency to accumulate in any tissues. Thin-layer chromatography and high-performance liquid chromatography analyses showed that more than 43 metabolites were present in the urine and faeces of both species, and all of these were identified to determine metabolic pathways for BHT in mice and rats. Major metabolic reactions of [14C]BHT in mice were the oxidation of the p-methyl group attached to the benzene ring and of the tert-butyl groups. The products from the latter reaction were cyclized to some extent by reacting with the adjacent phenolic OH group to give hemiacetals or lactones. The carboxyl derivatives from the p-methyl oxidation were conjugated with glucuronic acid. When single oral doses of 20 or 500 mg [14C]BHT/kg were given to male Sprague-Dawley rats, metabolites similar to those in mice were found. However, the major biotransformation was oxidation of the p-methyl group, and oxidation of the tert-butyl groups was a minor reaction in rats.

Animals↗
PubMed1984

Prolactin and thyrotropin responses to thyrotropin-releasing hormone during the peripartal period.

To investigate the changes in pituitary responsiveness to hypothalamic releasing hormones during the periparturitional period, women undergoing labor and vaginal delivery were stimulated with thyrotropin-releasing hormone. The percentage of incremental changes in prolactin and thyroid-stimulating hormone were significantly lower in pregnant women at term than in nonpregnant control subjects. Evidence of augmented release of prolactin was disclosed after the onset of active labor. The percent increases in prolactin and thyroid-stimulating hormone were significantly higher at 24 hours post partum than at term. Administration of thyrotropin-releasing hormone to the gravid patient in active labor caused a brisk response in fetal thyroid-stimulating hormone, although the increase in fetal prolactin remained low. These findings suggest that the changes in serum triiodothyronine (T3) significantly influence the release of prolactin and thyroid-stimulating hormone in response to thyrotropin-releasing hormone during the periparturitional period.

Adult↗
PubMed1983

[Autopsy case of pancreatic carcinoma associated with B-cell derived lymphoma].

An autopsy case a 75-year-old man, with papillary adenocarcinoma of the pancreas associated with wide-spread metastasis from a malignant lymphoma is reported. We discuss the markedly lower incidence of pancreatic cancer in syncronal association with lymphoma. We applied an immunoperoxidase method (PAP) in the diffuse large-cell lymphoma to determine the immunological phenotype and found mu heavy chains and lambda light chains in the lymphoma cells. This suggests that the tumor cells were derived from B-lymphocytes.

Adenocarcinoma, Papillary↗