Biomedical subjects

H Yoshimura

Publications and source records attributed to H Yoshimura.

At least 91 records · Page 5Linked to original sources

PubMed1993

[Effects of cyclophosphamide on spontaneous testicular and pancreatic lesions in WBN/Kob rats].

This study was undertaken to investigate the effects of cyclophosphamide (CP) on spontaneous pancreatitis and testicular atrophy of WBN/Kob rats. CP was given daily in drinking water to groups of 20 male 6-week-old WBN/Kob rats at doses of 0 (control), 1.25 or 2.5 mg/kg for 20 weeks. The final body weight in the 2.5 mg/kg CP group was significantly lower than that in the control group. There were no significant differences in blood glucose levels and weights of the pancreas and testis between groups. On histopathological examinations, pancreatitis and testicular atrophy were noted in each group. However, the incidence of pancreatitis characterized by inflammatory cell infiltration and fibrosis in the 2.5 mg/kg CP group was significantly decreased as compared to the control group. In contrast, testicular atrophy was more severe in the 2.5 mg/kg CP group than in the control group. Thus the results demonstrated that CP has inhibitory effects on the development of pancreatitis and enhancing effects on the development of testicular atrophy in WBN/Kob rats.

Administration, Oral↗

PubMed1993

The antimicrobial activity in vitro of cefpirome and 6 other beta-lactam antibacterial agents against clinical isolates.

The in vitro activity of cefpirome (CPR) was compared with that of cefazolin (CEZ), cefotiam (CTM), flomoxef (FMOX), cefotaxime (CTX), ceftazidime (CAZ) and imipenem/cilastatin (IPM/CS) against 384 clinical isolates, for tested by the both microdilution method. The activity of CPR against Staphylococcus aureus (MIC50, 1 microgram/ml) and Enterococcus faecalis (MIC50, 8 micrograms/ml) was better than CTX and CAZ, but slightly less than IPM/CS. CPR and other antibacterial agents were not effect against methicillin resistant S. aureus and Enterococcus faecium. The activity of CPR against Enterobacteriaceae was as good as that of CTX, CAZ, and IPM/CS, and more effective than CEZ, CTM and FMOX. The MIC50 of CPR for Acinetobacter calcoaceticus (2 micrograms/ml) and the MIC50 of CPR for Pseudomonas aeruginosa (8 micrograms/ml) were as good as that of CAZ. Conclusionly, CPR was a new broad spectrum cephalosporin as compared with used cephalosporins.

Anti-Bacterial Agents↗

PubMed1993

Purification and characterization of a novel 46.5-kilodalton esterase from mouse hepatic microsomes.

A novel membrane-bound esterase was purified from mouse hepatic microsomes. The purified protein (ES46.5K) showed a single protein-staining band on sodium dodecyl sulfate-polyacrylamide gel with a minimum molecular weight of 46.5 Kdalton. ES46.5K possessed esterase activity toward 11-acetoxy-delta 8-tetrahydrocannabinol (11-OAc-delta 8-THC) (27.1 mumol/min/mg protein) and p-nitrophenylacetate (119 mumol/min/mg protein), and these activities were 38 and 47 times, respectively, as high as those of microsomes. The N-terminal amino acid sequence of the protein was as follows: G-K-T-I-S-L-L-I-S-V-V-L-V-A-Y-Y-L-Y-I. This sequence has no homology to those of the known carboxylesterases, indicating that this enzyme is a novel type of esterase bound to the microsomal membrane.

Amino Acid Sequence↗

PubMed1993

[Inducing ability of co-planar PCBs toward bilirubin UDP-glucuronyltransferase of liver microsomes: the remarkable difference between guinea pigs and rats].

The induction of liver microsomal UDP-glucuronyltransferase (UGT) activity toward bilirubin by pretreatment with 3, 4, 3', 4'-tetrachlorobiphenyl (TCB), 3, 4, 5, 3', 4'-pentachlorobiphenyl (PenCB) and 3-methylcholanthrene (MC) was studied in guinea pigs and rats. In addition, microsomal benzo(a)pyrene 3-hydroxylase and cytosolic DT-diaphorase activities were also measured for the comparison. All of the PenCB, TCB and MC significantly induced the bilirubin UGT activity of guinea pig liver microsomes. The highest induction (6-fold over the control) was seen in the PenCB-treated animal, and MC (3.2-fold) and TCB (2.4-fold) were less effective. On the other hand, the induction of benzo(a)pyrene 3-hydroxylase and DT-diaphorase activities of guinea pigs was not so remarkable as that of bilirubin UGT activity. In the guinea pig, the inducibility of bilirubin UGT activity seemed to be correlated with the toxicity induced with PenCB, TCB and MC. In contrast to the guinea pig, UGT activity toward bilirubin in the rat was significantly decreased by the treatment with the inducers described above. These results suggest that bilirubin UGT activity in the guinea pig can be an index for the toxicity of polychlorinated biphenyls as like as benzo(a)pyrene 3-hydroxylase and DT-diaphorase activities in the rat.

Animals↗

PubMed1993

[Metabolism in vivo of 2, 4, 6, 2', 4', 6'-hexachlorobiphenyl in dog and partial characterization of cytochrome P-450 isozyme responsible for biotransformation of the congener].

We reported previously that the dog is a unique species which can metabolize 2, 4, 5, 2', 4', 5'-hexachlorobiphenyl (HCB) by unusual mechanism via 2,3-arene oxide intermediate formation. 2, 4, 5, 2', 4', 5'-HCB is known as one of the PCB congeners showing the highest concentration in the blood of Yusho patients at present. Therefore, further investigation on the mechanism of biotransformation of PCB in the dog is very useful to obtain informations about metabolic fates of persistent congeners in the bodies of Yusho patients. In the present study, we examined in vivo metabolic pathways of 2, 4, 6, 2', 4', 6'-HCB in a dog, and also a role of cytochrome P-450 isozymes in its metabolism. In these experiments, three major metabolites were found in feces of the dog. These were identified to be 3-hydroxy-2, 4, 6, 2', 4', 6'-HCB (M-1), 4-hydroxy-2, 6, 2', 4', 6'-pentachlorobiphenyl (M-2) and 3, 4-dihydroxy-2, 6, 2', 4', 6'-PenCB (M-3), which were previously identified as the major metabolites in vitro. 4-Hydroxy-2, 3, 6, 2', 4', 6'-HCB has also been isolated as a metabolite in vitro, but not detected in this in vivo study. In conclusion, the present in vivo study supported the previous in vitro results that the dog metabolizes this congener at least two mechanisms including direct hydroxylation and arene oxide formation. It was also indicated that cytochrome P-450 isozymes responsible for metabolism of this congener may be in part different from those catalyzing the 2, 4, 5, 2', 4', 5'-HCB metabolism.

Animals↗

PubMed1993

[A new trial of plachitin particles for intraarterial chemoembolization therapy in rabbit].

Plachitin, which is reconstituted by the combination of CDDP and chitin, has been reported to have a slow releasing property of CDDP and an antitumor effect. The antitumor effect and pharmacokinetics of Plachitin for intraarterial chemoembolization therapy were studied in rabbits using VX2 tumor inoculated in the hind limb. One gram of Plachitin contained 300 mg CDDP, and the form of Plachitin was modified into particles (about 50 microns in diameter). Plachitin was injected into the femoral artery. The study was carried out in four groups. The tumor growth ratio was significantly lower in the Plachitin group than in the CDDP, chitin, and control groups (p < 0.05). Tumor regression was noticed only in the Plachitin group. The tumor platinum (Pt.) level was higher than the serum Pt. level for 5 days after Plachitin injection. From the above results it can be concluded that Plachitin particles released CDDP slowly around the tumor and the tumor growth was suppressed by the additive effect of CDDP and embolization. Plachitin was considered a useful agent for chemoembolization therapy for the cancer patients.

Animals↗

PubMed1993

[A case of T-cell lymphoma showing multiple nodular shadows and an elevated titer of human T-lymphotropic virus type I (HTLV-I) antibody].

A 42-year-old man, born in Chiba prefecture, was admitted to our hospital because of multiple nodular shadows on chest X-ray film and an elevated titer of human T-lymphotropic virus type I (HTLV-I) antibody. The pulmonary lesion was diagnosed as T-cell lymphoma by open lung biopsy. There has been only one previous report of T-cell lymphoma showing multiple nodular shadows on chest X-ray. The elevated titer of HTLV-I antibody strongly suggested that the present case was one of adult T-cell lymphoma.

Adult↗

PubMed1992

[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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗