Search PubMedSearch

Biomedical subjects

H Yoshimura

Publications and source records attributed to H Yoshimura.

At least 37 records · Page 2Linked to original sources

[Effect of a coplanar PCB on lipid metabolism: the remarkable difference between rats and guinea pigs].

We studied the effect of 3, 4, 5, 3', 4'-pentachlorobiphenyl (PenCB) on lipid metabolism by determining the level of triacylglycerol and total cholesterol in rats and guinea pigs. Male Wistar rats and male Hartley guinea pigs received PenCB in corn oil one at a dose of 25 mg/kg i.p. and 0.5 mg/kg i.p., respectively. Pair-fed control group of both species were treated with the vehicle and given the amount of chow matched with that taken by the PenCB-treated animals. Free-fed control group was treated with vehicle and was given the chow ad libitum. The plasma was collected on the day 5 after the treatment and the liver was removed. The plasma triacylglycerol level in guinea pigs treated with PenCB was significantly higher than those in free- and pair-fed controls, whereas no significant difference was observed in PenCB-treated rats from both control groups. The plasma cholesterol level was also higher in PenCB-treated guinea pigs than in the two control groups, though the level in rats was significantly lower than the corresponding control values. The hepatic triacylglycerol and cholesterol levels were increased significantly in both species by the PenCB treatment. Although lipid metabolism was disordered in both animals by treatment with PenCB, the responsiveness was remarkably different between guinea pigs and rats. These differences could be associated with species difference in susceptibility toward toxic chlorinated aromatic hydrocarbons.

Animals

[Extended operation for lung cancer: concomitant resection of the heart or the great vessels with the lung].

We have analysed our experience in 43 patients with lung cancer invading the heart or great vessels who underwent surgical resection of the invaded portion of the mediastinal organs as well as the primary tumor, and have reviewed the literature on the subject of the extended operation for lung cancer invading the heart or great vessels. Among our experience of those 43 patients, a single mediastinal organ was resected in 32 patients (the left atrium in 20, the main pulmonary artery in 7, superior vena cava in 3 and the adventitia of the aorta in 2), and more than two mediastinal organ were resected in 11 patients (the main pulmonary artery and the other in 8, and the left atrium and esophagus or trachea in 3). There were 34 squamous cell carcinomas, 4 adenocarcinomas, 3 large cell carcinomas and 3 other cell types. Pathology disclosed 6 patients had pT 3 tumor (Group 1, 24 patients had pT 4 tumor that had invaded to a single mediastinal organ (Group 2) and 11 patients had pT 4 tumor that had invaded to more than two mediastinal organs (Group 3). The 5 year survival rate in patients of Group 1, 2 and 3 were 80%, 32.2% and 0%, respectively. There were statistical differences among the survivals of those three groups. We conclude that extended resection for lung cancer invading the heart or great vessels is justified if the invasion is limited to a single mediastinal organ. Several problems on such extended resection were discussed.

Aorta, Thoracic

Development of Purkinje cell bodies and processes with basic fibroblast growth factor-like immunoreactivity in the rat cerebellum.

The development of basic fibroblast growth factor-like immunoreactivity was investigated in the nuclei, cell bodies and processes of Purkinje cells with attention to basic fibroblast growth factor-containing neuronal input to the deep cerebellar nuclei. Immunoblot analysis with the use of the antisera against basic fibroblast growth factor revealed that crude homogenate of the developing rat cerebellum exhibits a main band with the same molecular weight (18,000 mol. wt) as basic fibroblast growth factor in all the postnasal stages examined. Cerebellar cells were not labeled with the antisera during embryonic life. Under light microscopy, basic fibroblast growth factor-like immunoreactivity was detected initially in cortical cells located close to deep cerebellar fissures of the newborn rat but not in superficial cortical regions. It was difficult to determine whether or not they are Purkinje cells at the fusiform stage. On postnatal day 7, immunoreactive Purkinje cells were identified throughout the cerebellar cortex, and they expressed basic fibroblast growth factor-like immunoreactivity mainly in the apical cytoplasm and proximal dendrites. From postnatal day 14 to postnatal day 28, basic fibroblast growth factor-like immunoreactivity was noted not only throughout the cytoplasm of Purkinje cells but also in the nuclei of the immunopositive cells. Our statistical analysis showed that Purkinje cells with nuclear immunoreaction peaked on postnatal day 21. At these stages, nerve fibers immunoreactive for basic fibroblast growth factor were numerous in the cerebellar medulla and deep cerebellar nuclei. After postnatal day 42, Purkinje cells with intense immunoreactivity in the nuclei showed a marked decrease in number, and immunoreactive structures were distributed in the cerebellum in a fashion similar to that in adult rats. Electron microscopy demonstrated that immunoreactivity was located mainly in the apical cytoplasm of Purkinje cells on postnatal day 7 and throughout the cytoplasm and in the nuclear euchromatin from postnatal day 14 to postnatal day 28, as was expected from light-microscopic observations. Immunoreactivity, even though distributed diffusely in the cytoplasm, was absent from the lumen of endoplasmic reticulum and mitochondria. A small population of Purkinje cell axon terminals forming synapses with the soma and dendrites of deep cerebellar nucleus neurons began to express basic fibroblast growth factor on postnatal day 21. This is much later than the starting age for synaptogenesis between Purkinje cells and deep cerebellar nucleus neurons. The age-dependent changes in the localization of basic fibroblast growth factor within Purkinje cell nucleus, soma and processes suggest a complex transport system of this factor within Purkinje cells during postnatal development.

Aging

[Change in serum G-CSF levels in patients with Graves' disease by treatment with methimazole].

We evaluated the determination of serum G-CSF in the diagnosis of granulocytopenia due to methimazole (MMI) in 54 patients with Graves' disease, while they were being treated with MMI, by way of measuring WBC counts and serum levels of G-CSF, thyroid hormones, IgE, and interleukin-2. Serum TSH was measured by immunoradiometric assay, serum G-CSF was done by enzyme immunoassay, thyroid hormones and IgE were done by radioimmunoassay, and serum Interleukin-2 was done by enzyme-linked immunosorbent assay. The population whose G-CSF levels were higher than the minimum detectable level (30pg/ml) was 6 (30%) in normal subjects, 4 (22%) in patients with untreated Graves' disease, 2 (12%) in patients with treated euthyroid Graves' disease, 3 (23%) in patients with Graves' disease who had gone through agranulocytosis, and 2 (33%) in patients with Graves' disease complicated with granulocytopenia. There was no significant change in WBC counts for 4 weeks, but there was a significant difference between WBC counts before treatment and those at 8 weeks after treatment. We observed no significant change of serum G-CSF levels in patients with Graves' disease under treatment. However, there were significantly high levels of serum G-CSF and significantly low counts of WBC in patients with Graves' disease complicated with granulocytopenia induced by MMI, compared with those in normal subjects, patients with untreated Graves' disease, patients with treated euthyroid Graves' disease, and patients with euthyroid Graves' disease who had gone through agranulocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Mouse hepatic microsomal oxidation of aliphatic aldehydes (C8 to C11) to carboxylic acids.

Addition of saturated and alpha, beta-unsaturated aliphatic aldehydes (C8 to C11) significantly increased NADPH oxidation with mouse hepatic microsomes, and the aldehydes themselves were oxidized to the corresponding carboxylic acids. When these aldehyde substrates were incubated similarly under oxygen-18 gas and the carboxylic acids formed were analyzed by GC-MS after methylation, it was indicated that oxygen-18 was significantly incorporated into the carboxylic acids formed from alpha, beta-unsaturated aldehydes, but not significantly into the carboxylic acids formed from saturated aldehydes. These results indicate that enzyme and/or mechanism responsible for the oxidation of these two types of aldehydes is different from each other.

Alcohols

High-performance liquid chromatographic determination of pamaquine, primaquine and carboxy primaquine in calf plasma using electrochemical detection.

A high-performance liquid chromatographic method with electrochemical detection is described for quantification of pamaquine, primaquine and carboxy primaquine in calf plasma. After the proteins had been precipitated with acetonitrile, the drugs were separated on a 5-microns C18-modified polymer gel column with an isocratic mobile phase. The detection limit was 0.01 microgram/ml in plasma for all three compounds. The applicability of the method in pharmacokinetic studies was demonstrated by determining the plasma concentrations of the three substances in calves administered a single dose of pamaquine or primaquine.

Aminoquinolines

Immunochemical characterization of a cytochrome P450 isozyme and a protein purified from liver microsomes of male guinea pigs and their roles in the oxidative metabolism of delta 9-tetrahydrocannabinol by guinea pig liver microsomes.

A protein (designated as protein-B) was purified from liver microsomes of adult male guinea pigs by an affinity chromatography with omega-aminooctyl Sepharose 4B, followed by HPLC using DEAE-5PW and hydroxyapatite columns which had been used to purify a cytochrome P450 (P450) isozyme (P450-A) from the same subcellular fraction (Narimatsu et al., Biochem Biophys Res Commun 172: 607-613, 1990). Protein-B had a molecular mass of 49 kDa in SDS-PAGE, but did not show absorbance at 417 nm for heme. Further, it did not show any oxidative activities towards aniline (AN), d-benzphetamine (d-BP), p-nitroanisole (p-NA) or delta 9-tetrahydrocannabinol (delta 9-THC) in a reconstituted system including dilauroylphosphatidylcholine, NADPH-P450 reductase, and cytochrome b5. However, antiserum against protein-B raised in rabbits suppressed liver microsomal oxidative activities towards d-BP and p-NA dose-dependently. The antibody decreased delta 9-THC oxidative activity most effectively, but did not decrease AN hydroxylation activity. Antiserum against P450-A suppressed all the activities towards these four substrates, especially towards delta 9-THC, in liver microsomes of male guinea pigs. Moreover, reconstitution with hemin made it possible for protein-B to produce some oxidative activity toward delta 9-THC. These results suggest that protein-B is also a cytochrome P450 isozyme which has lost a heme moiety during purification steps. Both P450-A and protein-B could have a role as cytochrome P450 isozymes in the oxidative metabolism of drugs, especially that of delta 9-THC by the liver microsomes of adult male guinea pigs.

Amino Acid Sequence

Preservation of endothelium-dependent vasodilation in the spastic segment of the human epicardial coronary artery by substance P.

The objective of this study was to determine if endothelium-dependent vasodilation is preserved in the spastic segment of the epicardial coronary artery. Segmental responses of the coronary artery to substance P were examined by the use of a quantitative angiographic technique in 21 patients with variant angina. Coronary diameter at the basal state did not differ between the spastic and the nonspastic segments (2.3 +/- 0.2 mm, 2.3 +/- 0.4 mm, p greater than 0.05). Changes in coronary diameter in response to substance P did not differ between segments with ergonovine-induced spasm and nonspastic segments. Maximal dilation averaged 27.1 +/- 9.5% in the spastic segment and 24.4 +/- 9.6% in the nonspastic segment (expressed as a percent increase over the value before drug administration). It appears that both the potential of the endothelium to release endothelium-dependent relaxing factor and the dilating response of the smooth muscle to endothelium-dependent relaxing factor are preserved, even in the spastic segment.

Angina Pectoris, Variant

Tissue-specific expression, induction, and inhibition through metabolic intermediate-complex formation of guinea pig cytochrome P450 belonging to the CYP2B subfamily.

The tissue-specific expression and induction of P450GP-1, a constitutive form of cytochrome P450 of the guinea pig classified into the CYP2B subfamily, were studied. Prior to these studies, a P450 form (P450GP-1 PB) was purified from phenobarbital-treated guinea pigs and the properties were compared with those of the P450GP-1. This form was judged to be the same as P450GP-1 existing in untreated animals by comparisons of their N-terminal amino acid sequences, peptide maps, and affinities toward anti-P450GP-1 antibody. Immunostaining of P450GP-1 revealed that the lung and small intestine as well as the liver of untreated guinea pigs contain P450GP-1, while none or only small amounts of this P450 form were observed in the kidney, heart, spleen, urinary bladder, and testis. The amount of liver P450GP-1 protein expressed in untreated guinea pigs was estimated to be 19.4% of the total cytochrome P450 and this form was increased 1.7-fold by phenobarbital treatment. Similarly, intestinal P450GP-1 was increased by phenobarbital treatment. However, lung P450GP-1 was not increased by the treatment. It was also observed that the liver P450GP-1 is induced with SKF-525A to the same extent as with phenobarbital. On the other hand, dexamethsone, p,p'-dichlorodiphenyltrichloroethane, and isosafrole showed no or only a weak ability to increase the liver P450GP-1 content. The drug-metabolizing activities in the liver microsomes of SKF-525A-pretreated guinea pigs were lower than those in phenobarbital-treated animals, although the P450GP-1 protein was induced equally by these treatments. The low activities of SKF-525A-treated animals in the drug metabolisms were attributed to the formation of the metabolic-intermediate complex between P450GP-1 and SKF-525A metabolite. These results permitted us to conclude that the tissue specificity in the expression of guinea pig P450 belonging to the CYP2B subfamily and the inducibility with chemicals are similar to those of rat CYP2B1, although the constitutive expression of guinea pig liver P450GP-1 is much higher than that of CYP2B1.

Amino Acid Sequence

Amplification of plasmid (L factor) DNA and increased production of a plasmid gene product (gamma-interferon) in mouse L cells.

It has previously been reported that composite DNAs derived from L factor, a polyoma-related mammalian plasmid, can be established in several mouse cell lines after transfection. Here, we report that the copy number of a plasmid composite DNA consisting of L factor, pBR DNA, dihydrofolate reductase (dhfr) gene, and gamma-interferon (gamma-IFN) gene was increased more than 10-fold after two successive adaptations of the plasmid-bearing mouse L cells to increasing concentrations of methotrexate (MTX), an inhibitor of dhfr. The structure of the amplified L factor plasmid remained intact during prolonged cell culture, but the copy number remained to be amplified only when the selective pressure (presence of MTX in the medium) has been exerted during the culture. Cells bearing the amplified plasmid produced a higher level of gamma-IFN compared with the original clone, which was likely to be derived from the plasmid gamma-IFN gene amplified along with L factor and the dhfr gene.

Animals

Basic fibroblast growth factor-like immunoreactivity in Purkinje cells of the rat cerebellum.

An antiserum against basic fibroblast growth factor was characterized by immunoblot experiments and used to investigate immunohistochemically the projection fields and fine structures of basic fibroblast growth factor-containing cerebellar Purkinje cells. The antiserum demonstrated clearly purified basic fibroblast growth factor and basic fibroblast growth factor-like molecules of the same molecular weight in homogenates of the adult rat cerebellum. Light and electron microscopic immunohistochemistry revealed that a large number of Purkinje cells, if not all, send immunoreactive dendrites to the molecular layer and basic fibroblast growth factor-containing axons to the deep cerebellar and lateral vestibular nuclei, where basic fibroblast growth factor nerve terminals form synapses with the soma and dendrites of neurons labeled weakly with basic fibroblast growth factor. Nerve cells with basic fibroblast growth factor had immunoreaction deposits mainly in free ribosomes, those attached to the endoplasmic reticulum and in the nuclear euchromatin. These findings suggest that basic fibroblast growth factor is present in cerebellar Purkinje cells and undergoes two modes of transport, one to axon terminals and the other to nuclear euchromatin, known as the RNA transcription zone.

Animals

In vivo measurement of spatial dose distribution with thermoluminescent sheet around high dose-rate intracavitary source: application to rectal cancer.

For intracavitary high dose-rate radiation therapy, a thermoluminescent [TL] sheet for in vivo measurement of spatial dose distribution around source has been recently developed. The TL sheet was found to have a linear response with a very wide dynamic range from at least 0.002 cGy to 5000 cGy for 60Co gamma-rays. This TL sheet (40 cm x 50 cm x 200 microns), which is composed of Teflon mixed with BaSO4:Eu doped powder, is very flexible and can be cut to the desired size. In addition, this sheet is easy to handle because of its insensitivity to room light. The spatial dose distribution is displayed in a color mode by using a newly developed TL sheet readout system. For a clinical application, the TL sheet was wrapped on an applicator for intracavitary radiation therapy of a rectal cancer and was inserted into the rectum. The location of the TL sheet could be confirmed with diagnostic X ray film. After irradiation with high dose-rate 60Co source, the in vivo relative dose distribution on the surface of the rectum was determined. This TL sheet provided a convenient means of measuring the relative dose distributions around 60Co sources of various patterns in intracavitary radiation therapy.

Brachytherapy

Evaluation of imaging properties of a laser film digitizer.

In this paper we provide a quantitative assessment of the basic imaging properties of a laser film digitizer. The characteristic curve of the digitizer was determined in terms of the relationship between input optical density and output pixel value. Spatial resolution of the laser digitizer was characterized using the presampling modulation transfer function (MTF), which was measured using a curve fitting technique with an angulated slit. For the noise analysis, we compared the Wiener spectra of uniformly exposed film samples before and after digitization. The effects of different sampling distances and scanning directions were investigated. Our results show that the characteristic curve of the laser digitizer was linear. The presampling MTFs of the digitizer were similar at different sampling distances and were substantially greater in the vertical scanning direction than in the horizontal direction. The noise of the digitized film sample was mainly affected by the presampling MTF and structure noise of the digitizer.

Evaluation Studies as Topic

Promoting effects of cigarette smoke on the respiratory tract carcinogenesis of Syrian golden hamsters treated with diethylnitrosamine.

The potential short-term promoting effects of cigarette smoke on the development of tumors in the respiratory system were investigated in male Syrian golden hamsters. Three groups (1, 2 and 3) of 30 animals each received a single s.c. injection of 100 mg/kg body wt of diethylnitrosamine (DEN) at the commencement of experiment 1. They were then exposed to non-filter cigarette (NC) smoke, filter-tip cigarette (FC) smoke and sham smoke respectively, in a Hamburg II type smoking machine from week 1 to week 12. In addition, groups 4, 5 and 6 (10 animals each) were exposed to the NC smoke, FC smoke or sham smoke respectively, for the same time period without prior DEN treatment. In the DEN-treated groups, epithelial hyperplasias and/or papillomas were induced, the incidences and numbers/animal of these lesions in groups 1 and 2 being significantly increased as compared to group 3 values. In experiment 2, two groups of 25 hamsters each were exposed to cigarette smoke or sham smoke for up to 12 weeks, five animals in each group being killed for immunohistochemical analysis using BrdU antibodies and measurement of lipid peroxides in the lung and serum at weeks 1, 2, 4, 8 and 12. Small aggregations of macrophages (smoke cells) in the lung alveoli was observed in the smoke-exposed group, but no significant increase in the numbers of BrdU positive cells in any compartment of the respiratory system was apparent. Animals of this group showed a tendency for increased lung malondialdehyde levels at weeks 2 and 12, but not weeks 4 and 8.

Animals

Effects of caffeine, nicotine, ethanol and sodium selenite on pancreatic carcinogenesis in hamsters after initiation with N-nitrosobis(2-oxopropyl)amine.

The modulating effects of caffeine, nicotine, ethanol and sodium selenite on development of N-nitrosobis(2-oxopropyl)-amine (BOP)-initiated pancreatic tumors were investigated. Female Syrian golden hamsters were given s.c. injections of BOP (10 mg/kg body weight) or saline alone once a week for 3 weeks and then administered 2000 p.p.m. caffeine, 25 p.p.m. nicotine, 20% ethanol or 4 p.p.m. sodium selenite in their drinking water for the next 37 weeks. Control animals were given tap water alone after BOP initiation. Only the BOP-treated groups developed pancreatic adenocarcinomas and dysplasias. The multiplicity of pancreatic carcinomas was significantly higher (P less than 0.05) in animals receiving caffeine than in the controls. In addition, caffeine treatment slightly increased the incidence of carcinomas. Nicotine and ethanol also showed tendencies to enhance pancreatic carcinogenesis, although there were statistically no significant differences regarding lesion development. In contrast, sodium selenite administration was associated with a tendency for a decrease in the number of carcinomas and dysplasias. Thus, among these chemicals of obvious significance to human life-style, caffeine enhanced the development of pancreatic tumors when administered during the post-initiation phase in this hamster model.

Animals