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Biomedical subjects

Y Masuda

Publications and source records attributed to Y Masuda.

At least 667 records · Page 37Linked to original sources

Malignant mesotheliomas in Kure City, Japan: the relationship of asbestos exposure.

Eighteen patients with malignant mesothelioma were seen at Kure Mutual Aid Hospital over a 10-year period. According to occupational history, chest x-ray manifestations, and evidence of asbestos bodies in the tissue, 13 of these cases were definitely thought to be due to exposure to asbestos as a result of two or three of these items testing positive. Kure City is one of the major ship-building cities in Japan since the 1920s. Most of the 18 patients worked in ship building before and during World War II. Malignant mesothelioma appeared about 40 years after their first exposure to asbestos. In western countries, most malignant mesotheliomas are thought to be induced by exposure to asbestos fibers (1,2). Consequently, there has been a serious effort to deal with this problem recently, including lowering rate of exposure. In Japan, however, there have been few reports that asbestos fibers caused malignant mesothelioma (3). This report suggests that an increased incidence of malignant mesotheliomas in a specific area of Japan may also be due to exposure to asbestos fibers.

Adult↗

[Identification of polychlorinated phenyldibenzofurans (PCPDFs) in the casual rice oil associated with yusho].

The polychlorinated dibenzofuran (PCDF) fractions obtained from the causal rice oils associated with yusho were analyzed by capillary column gas chromatography with electron capture detection (ECD/GC) and capillary column gas chromatography-mass spectrometry (GC/MS) in negative chemical ionization (NCI) mode. The GC/MS analysis revealed that the PCDF fraction contained, in addition to PCDF congeners, penta-to octa-and probably nona-chlorinated phenyldibenzofuran (PCPDF) congeners in comparison with retention times and NCI mass spectra of PCPDF standards. The ECD/GC analysis showed the presence of at least 30 different PCPDF congeners in the rice oils.

Food Contamination↗

[Effects of 3-methylsulphonyl-4,5,3',4-tetrachlorobiphenyl and 7,8-benzoflavone on aryl hydrocarbon hydroxylase activity].

First, we examined the effects of 3-methylsulphonyl-4,5,3',4',-tetrachlorobiphenyl (3-MSF-TCB, 1.5 ppm) and 7,8-benzoflavone (ANF, 1.4 ppm) on aryl hydrocarbon hydroxylase (AHH) activity in cultured human lymphoblastoid cells and we have obtained the following results: (1) 3-MSF-TCB preferentially inhibited the enzyme activity induced by 2,3,4,7,8-pentachlorodibenzofuran (PenCDF) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and slightly stimulated the enzyme activity induced by 3-methylcholanthrene (MC). (2) ANF reduced well the AHH activities induced by all the three enzyme inducers and more strongly inhibited the PenCDF- or TCDD-induced enzyme activity (about 89%). (3) About 64 and 76% of basal (uninduced) AHH activity was lowered by 3-MSF-TCB and ANF, respectively. Second, we investigated the effect of 3-MSF-TCB (1.5-45 ppm) and ANF (1.4-42 ppm) on AHH activity of hepatic microsomes from the Ah nonresponsive (DDD) and responsive (C3H) strains of mice and we have got the following results: (1) 3-MSF-TCB and ANF enhanced or reduced the enzyme activity depending on both their concentrations and kinds of microsomes, namely, those prepared from untreated mice (control-microsomes) and mice treated with MC (MC-microsomes) or TCDD (TCDD-microsomes). (2) ANF showed higher potency for both the enhancement and the inhibition of the enzyme activity than 3-MSF-TCB. (3) The AHH activity of TCDD-microsomes seemed to be more greatly reduced with either 3-MSF-TCB or ANF than that of MC-microsomes. (4) The effects of 3-MSF-TCB and ANF on the enzyme activity of MC-microsomes of DDD mice and of control-microsomes of C3H mice.

Animals↗

[Concentration changes in PCB isomers in the blood in patients with PCB poisoning].

The blood of 3 yu-cheng patients sampled from 1980 to 1985 and of 14 yusho patients sampled from 1982 to 1988 were analyzed for 7 polychlorinated biphenyl (PCB) isomers by gas chromatography with a capillary column. The concentrations of PCBs in yu-cheng patients were up to 400 ppb and much higher than those of yusho patients. The high concentration of PCBs were decreased at biological half lives of about 50 months and 2,4,3',4'-tetra-CB and 2,4,5,3',4'-penta-CB were first decreased with time at half lives of about 12 months. Therefore, peculiar gas chromatographic pattern for yusho patients would be formed 3 years after the onset. The concentration and patterns of blood PCBs of yusho patient kept in similar levels during 1982 to 1988.

Adolescent↗

[Analysis of PCB- and PCT-methylsulfones in the blood in yusho patients].

Polychlorinated biphenyl (PCB)- and terphenyl (PCT)-methylsulfones were isolated from the blood of yusho patients sampled in 1987 and characterized by gas chromatography with mass spectrometry (GC/MS), electron capture detection (GC/ECD) and flame photometric detection (GC/FPD). GC/MS analysis for PCB-methylsulfones showed that all the blood tested (nine samples) contained the tri- and tetrachloro congeners. The concentrations of PCB-methylsulfones were estimated to be 15-120 ppb. PCT-methylsulfones detected in the same fraction, which were confirmed by GC/MS comparison with authentic samples as well as by GC/ECD and GC/FPD, consisted of tetra-, penta- and hexachloroterphenyl methylsulfone congeners. The levels of PCT-methylsulfones in six samples detected were preliminarily estimated to be 10-270 ppb, on the basis of a PCB-methylsulfone standard. Their origins and biological effects are unclear at present.

Food Contamination↗

Oxidation of diethyldithiocarbamate to disulfiram by liver microsomal cytochrome P-450-containing monooxygenase system.

We examined the involvement of cytochrome P-450 in the oxidation of diethyldithiocarbamate (DTC) to disulfiram (DS) by liver microsomes in the presence of NADPH. DS difference spectra of liver microsomes showed a peak and trough at about 385 and 418 nm, respectively, which disappeared after further addition of glutathione (GSH). DTC alone had little effect on the microsomal spectrum, however, the addition of NADPH gradually produced a spectral change having a trough at 416-417 nm, which waned upon further addition of GSH. Microsomal DS production was increased by phenobarbital pretreatment and decreased by carbon tetrachloride pretreatment, depending on the activity of the cytochrome P-450-monooxygenase system. With microsomes peroxidized by cumene hydroperoxide, the extent of NADPH-dependent DS production lowered in proportion to the decrease in cytochrome P-450. Inhibitors of cytochrome P-450 such as SKF-525A, metyrapone and n-octylamine dose-dependently inhibited the DS production. Sodium azide, an inhibitor of catalase, increased the DS production, whereas addition of exogenous catalase only slightly suppressed it. It is concluded that oxidation of DTC to DS by liver microsomes largely proceeds via the cytochrome P-450-containing monooxygenase system and partly by hydrogen peroxide generated during NADPH oxidation.

Animals↗

[An in vitro drug screening assay, scintillation assay, and its clinical application].

We have developed an in vitro drug screening test by scintillation assay with which we can assess the chemosensitivity of solid human tumors during the 5 days following tumor resection. We are able to evaluate 62% (271/439) of the human tumors' chemosensitivity results. Seventy-seven of these cases were examined for in vitro-in vivo correlations. In 14 of 33 in vitro sensitivity cases (42%) we found clinical responses. And, in 41 of 44 in vitro resistance cases (95%) we found progressive disease. These in vitro-in vivo correlations with the scintillation assay were similar to those in other reports with different types of chemosensitivity assay. The true-positive accuracy of these tests averaged 50%, while the true-negative accuracy averaged 90%. We think that tumor cell heterogeneity is one of the main reasons for low true positive accuracy in the drug screening assays. In some studies we implanted human tumors into nude mice. The resulting xenografts demonstrated that fresh human tumors are composed of heterogeneous subpopulations of cells with varying chemosensitivities and varying DNA indexes. This heterogeneic nature of human tumor cells means that a single biopsy specimen may not comprehensively define the chemosensitivity of a patient disease.

Drug Screening Assays, Antitumor↗

[Effects of dioxin congeners on aryl hydrocarbon hydroxylase activity].

In this study, we examined the effect of 1,3,6,8-tetrachlorodibenzo-p-dioxin (1,3,6,8-TCDD), octachlorodibenzo-p-dioxin (OCDD) and 2,4,6,8-tetrachlorodibenzofuran (2,4,6,8-TCDF) on aryl hydrocarbon hydroxylase (AHH) activity in cultured human lymphoblastoid cells. These compounds are considered to be no or less toxic isomers of polychlorinated dibenzo-p-dioxins (Dioxins) and polychlorinated dibenzofurans (Dibenzofurans). At a concentration of 90 ppb, 1,3,6,8-TCDD induced the enzyme activity about 2 times over the basal (untreated) AHH activity and 2,4,6,8-TCDF reduced the basal enzyme activity by about 40%. At a concentration of 5 ppb, OCDD enhanced the basal AHH activity by about 30%. In case of simultaneous treatment of 1,3,6,8-TCDD, OCDD or 2,4,6,8-TCDF with highly toxic 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD), at a concentration of 7.5 ppb of each compound, the AHH activities induced by 1,3,6,8-TCDD plus 2,3,7,8-TCDD and OCDD plus 2,3,7,8-TCDD were about 25% and 43%, respectively, higher than that induced by 2,3,7,8-TCDD alone. On the contrary, at the same concentration, the enzyme activity treated with 2,4,6,8-TCDF plus 2,3,7,8-TCDD were about 30% less than that treated with 2,3,7,8-TCDD alone. It has been reported that the AHH inducibility of Dioxins and Dibenzofurans correlates well with their toxic potency. Hence, taking the results of this study into account, we should clarify the biological and/or health consequences of the mixed contamination of no or less toxic and highly toxic congeners of Dioxins and Dibenzofurans by animal experiments and epidemiological studies.

Aryl Hydrocarbon Hydroxylases↗

[Systolic time intervals in mitral valve prolapse syndrome].

Systolic time intervals (STI) were measured in 135 patients with mitral valve prolapse syndrome (MVP). These patients were categorized as Group II (no or trivial mitral regurgitation) and Group III (moderate or severe regurgitation). The controls consisted of 120 normal subjects (Group I). The Group II patients tended to have increased ETc and shortened PEP. The Group III patients tended to have prolonged Q-I and decreased QIIc and ETc, reflecting mitral regurgitation. It was suggested that autonomic nervous system, especially sympathetic nerve, may play a role in changes of STI of the Group II patients.

Adolescent↗

Measurement of regional myocardial blood flow in hypertrophic cardiomyopathy: application of the first-pass flow model using [13N]ammonia and PET.

Positron emission tomography (PET) has become an important tool in the study of regional myocardial blood flow. The purpose of the present study was to measure regional myocardial blood flow using dynamic [13N]ammonia PET and the first-pass flow model. Thirteen patients with hypertrophic cardiomyopathy, and with a considerably thickened ventricular wall (25 mm or greater), were selected for the study in order to minimize errors due to spillover of radioactivity from blood to the myocardium and to the underestimation of myocardial activity caused by the partial volume effect. Arterial input function was determined by assigning a region of interest to the left atrial cavity on the PET images. Using left atrial and myocardial time-activity curves, regional myocardial blood flow was calculated using the first-pass flow model. Mean myocardial blood flow ranged from 47.8 to 76.5 ml/min per 100 g (63.0 +/- 9.4). Regional myocardial blood flow in the septum was significantly lower than in the anterior and lateral walls of the left ventricle (P less than .01). These results indicate the potential usefulness of dynamic PET in the measurement of regional myocardial blood flow in man.

Adult↗

Effect of a prostacyclin analog OP-2507 on acute ischemic cerebral edema in cats.

We evaluated the inhibitory activity of a novel prostacyclin analog, OP-2507 (15-cis-(4-n-propylcyclohexyl)-16,17,18,19,20-pentanor-9-deo xy-6,9 alpha- nitriloprostaglandin F1 methyl ester) on the brain edema induced by occlusion of the middle cerebral artery in cats. Middle cerebral artery occlusion for 4h caused a decrease of regional cerebral blood flow. The specific gravity of the cerebral cortex measured 4h after the middle cerebral artery occlusion as an index of cerebral edema showed a significant reduction. Intravenous infusion of OP-2507 at infusion rates of 10 and 50 ng/kg per min was started 30 min before the middle cerebral artery occlusion and was continued for 4.5 h. While OP-2507 did not affect the blood pressure, heart rate and regional cerebral blood flow before and after the middle cerebral artery occlusion, the reduction of the specific gravity of cerebral cortex was significantly prevented by OP-2507 treatment at both doses. Prostacyclin prevented the reduction of the specific gravity only at the higher dose of 50 ng/kg per min. The present results indicate the potential usefulness of OP-2507 in acute ischemic cerebral disorders.

Animals↗

Loss of 3-methylcholanthrene-inducible form of cytochrome P-450 in liver microsomes following administration of carbon disulfide in C57BL/6 Cr mice.

Early after administration of CS2 to untreated, phenobarbital (PB)-and 3-methylcholanthrene (3-MC)-pretreated C57BL/6 Cr mice: (1) the loss of cytochrome P-450 was enhanced by pretreatment with both inducers, but to a greater extent with 3-MC; (2) the decrease in 7-ethoxyresorufin (ER) O-deethylation activity was much greater than that of cytochrome P-450 in untreated and PB-pretreated mice, but both paralleled values in 3-MC-pretreated mice, in which ER O-deethylation activity was induced markedly, (3) the peak of the carbon monoxide-difference spectrum of microsomal reduced cytochrome P-450 (about 448 nm) in 3-MC-pretreated mice shifted toward 450 nm after administration of increasing doses of CS2; (4) similar tendencies were observed in vitro in items (1) to (3); (5) electrophoresis of microsomal proteins revealed a loss of each protein band induced by PB and 3-MC following CS2 administration; (6) in the reconstituted monooxygenase system using partially purified cytochrome P-450 and P-448 forms from PB- and 3-MC-treated rats, CS2 suppressed the drug-metabolizing activities exhibited by the P-448 form but had little or no effect on those by the P-450 form; and (7) in n-octylamine difference spectra of microsomes, loss of the 3-MC-induced high spin form of cytochrome P-450 was evident. These results indicate that the 3-MC-inducible form of cytochrome P-450 was more susceptible to CS2 than the PB-inducible form. The hepato-necrogenic action of CS2 was not enhanced by PB or 3-MC pretreatment in mice.

Animals↗

Growth control of A431 cells in protein-free medium: secretory products do not affect cell growth.

A431 cells grew at similar rates in protein-free Coon's modified Ham's F12 medium (PF-C-F12) with and without added bovine calf serum. The cells secreted a heparin-binding growth factor and a type-beta transforming growth factor, but their growth in PF-C-F12 was not affected by these factors, or by DNA synthesis factor from Rhodamine fibrosarcoma, basic fibroblast growth factor, insulin, human transferrin, bovine serum albumin, and their combinations. Growth of A431 cells in PF-C-F12 was not density dependent and was not affected by either addition of conditioned medium or replacement of conditioned medium by fresh medium. These results indicate that A431 cells have an intracellular mechanism for autonomous growth, and that their growth is not affected by factors that they secrete or by exogenous growth factors.

Cell Division↗

Stabilization of fibroblast growth factors by a non-cytotoxic zwitterionic detergent, 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate (CHAPS).

The potential usefulness of a zwitterionic detergent, 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate (CHPAS), in the stabilization of acidic and basic fibroblast growth factors (FGFs) was examined. Among several detergents, CHAPS was found to be not only non-cytotoxic but also most useful in handling the diluted preparations of FGFs. The advantages are as follows: 1) at lower concentrations than 0.01% CHAPS did not affect growth factor activity of calf serum (CS) and the growth rate of BALB/c 3T3 cells. The primary culture of rat prostate epithelium and colony formation of NRK-49F cells were hardly influenced by CHAPS lower than 0.003%; 2) the loss of FGFs that usually occurs due to their adherence to the surface of storage containers was effectively prevented by inclusion of 0.1% CHAPS; 3) the recovery of FGFs after storage or dialysis was significantly enhanced by inclusion of 0.1% CHAPS; 4) CHAPS at lower concentrations than 0.1% does not interfere with amino acid analysis, except that Thr may be misled only when the ratio of protein/CHAPS is low; 5) amino acid sequence analysis was hardly disturbed by CHAPS up to 0.5%. These results indicate that CHAPS is useful as a stabilizing agent for various kinds of polypeptides capable of showing biological activity at a low concentration.

Amino Acids↗

A compact and inexpensive device using an electronic calculator for measuring ambulatory activity in mice.

A device for measuring ambulatory activity in mice was developed. The device consisted of a plastic case, a bed plate, a step board (as a detector) and a calculator (as a recorder). A 2.2 cm width section was cut out from the middle of the case bottom in the direction of the minor axis and a step board, a width of 2 cm, was placed in the opening. A short bolt was screwed into one end of the step board and the head of the bolt was placed on the equal key of the calculator. The calculator counted the number of times the mouse stood on the step board. The validity of the device was demonstrated by measuring the effect of methamphetamine (1-4 mg/kg) on the ambulatory activity in mice.

Animals↗

Suppression of glomerular IgA deposition in ddY mice through periodic injections of lipopolysaccharides.

We investigated the role of lipopolysaccharides (LPS) in glomerular IgA deposition of ddY mice. The incidence of IgA deposition was lower in the LPS-injected mice at 10 and 13 months of age as compared with that of their age-matched controls (10 months, LPS 20% vs control 60%; 13 months, LPS 14% vs control 100%). Serum levels of IgA were lower in the LPS-injected mice than in the control mice. There were no appreciable differences in the percentage value of Thy-1+ cells, the ratio of Lyt-1+/Lyt-2+ cells, mitogenic responses, or IL-1 activities between the LPS-injected and the control mice. On the other hand, the IgA responses of spleen and Peyer's patch cells in the LPS-injected mice were lower than those observed in the control mice. These results suggest that the persistent use of LPS directly suppresses gut-associated lymphoreticular tissue (GALT), and that the lower IgA response in GALT induced by LPS causes suppression of glomerular IgA deposition in ddY mice.

Animals↗