Search PubMed⌕ Search

Biomedical subjects

Y Takeuchi

Publications and source records attributed to Y Takeuchi.

At least 343 records · Page 19Linked to original sources
PubMed1998

[Pharmaceutical and pharmacological development of antitumor prostaglandins].

Antitumor Prostaglandins such as delta 12PGJ2 and delta 7PGA1 possess a cross-conjugated dienone unit and exhibit unique antitumor effect. Lipid microshere (w/o type emulsion) was selected as pharmaceutical formulation because of physicochemical properties of prostaglandin. 13,14-Dihydro-15-deoxy-delta 7-PGA1 methyl ester (TEI-9826) were selected as a candidate for clinical trial. In a rat and mouse serum in vitro, TEI-9826 rapidly metabolized to 13,14-dihydro-15-deoxy-delta 7-PGA1 (TOK-4528), but TOK-4528 is stable as well as delta 12PGJ2. Lipid microshere containing TEI-9826 at the content of 5 mg/ml exhibited administration route and schedule dependent antitumor effect in vivo using Colon 26 bearing mouse model, which suggested that duration of serum concentration was important for antitumor effect. One of the antitumor mechanism of antitumor PG might be an induction of the cyclin-dependent kinase inhibitor p21. PPAR gamma also might be important. New type homogenizer, high pressure jet flow type homogenizer was developed in the study of antitumor prostaglandin.

Animals↗
PubMed1998

[Arterial redistribution of extrahepatic collaterals to the liver under temporary balloon occlusion of the proper hepatic artery].

Three patients with liver metastases receiving transarterial chemotherapy underwent embolization of extrahepatic collaterals to the liver under temporary balloon occlusion of the proper hepatic artery. Enhancement in the liver and tumors was observed at CT arteriography through the right inferior phrenic artery and was accentuated under balloon occlusion in all patients. A Cyanoacrylate-Lipiodol mixture was infused through the right inferior phrenic artery to occlude arterial communications with intrahepatic arteries. Better contrast agent distribution was obtained in all patients after embolization. It is suggested that this procedure can be effective for arterial redistribution against extrahepatic collaterals to the liver.

Antineoplastic Agents↗
PubMed1998

[Clinical evaluation of hepatic bruit audible in patients with alcoholic hepatitis].

It is well accepted that many patients with alcoholic hepatitis have an audible bruit over the liver (hepatic bruit) in western countries. However, this sign has not been discussed in Japan. The aim of this study was to assess the significance of the hepatic bruit in Japanese patients with alcoholic hepatitis. Hepatic bruit was specifically searched for on auscultation by two physician in consecutive patients (6 alcoholic hepatitis, 58 other alcoholic liver disease, 128 nonalcoholic liver disease including 16 hepatocellular carcinoma). Hepatic bruit was detected in 5 of 6 (83%) patients with alcoholic hepatitis, and in 1 of 16 (6%) patients with hepatocellular carcinoma. In any of other liver diseases, hepatic bruit was not detected. We conclude that hepatic bruit may be an important diagnostic finding in Japanese patient with alcoholic hepatitis as it is in western countries.

Adult↗
PubMed1998

[A case of non-photosensitive, self-induced epileptic seizures with pacygyria].

We report an 11-year-old boy with a non-photosensitive epileptic self-induced seizures, pacygyria and familial ataxia. His grandmother and aunts had dysarthria, and his mother had developed progressive ataxia and myoclonus since 40 years old. His older sister had ataxia, mental retardation and epilepsy. As for the boy, motor developmental delay with muscle hypertonicity of left extremities was recognized at the age of 5 months. Mental retardation and ataxia was recognized at the age of 3 years and slight mental regression is recognized at the age of 11 years. No special findings were detected in an examination of his blood and cerebrospinal fluid, including amino acids, lysosomal enzymes activity and genetic analysis for dentatorubralpallidoluysian atrophy. Brain magnetic resonance imaging revealed pachygyria of the right cerebral cortecies. At the age of two, he began to induce seizures with impairment of consciousness in himself by waving his right hand over his face which was directed toward a source of bright light. At the age of seven, he developed spontaneous seizures with impairment of consciousness. An EEG showed frequent spikes in the occipital areas, on the right and left sides occurring either independently or synchronously. Intermittent photic stimulation and pattern stimulation did not induce a paroxysmal discharge in EEG. Ictal EEG suggested that the origin of the seizures was the occipital lobe. Treatment with valporate and zonisamide was effective in reducing the seizures. The findings of our case imply the pathogenesis of self-induced seizures and the relationship between PME and neuronal migration disorders.

Ataxia↗
PubMed1998

[Types and dimensions of mineral fibers in the atmosphere and from lungs of residents in the urban area].

OBJECTIVE: The objective of this study was to estimate the types and origin of the mineral fibers in the lungs of residents in the urban area. METHODS: Mineral fibers in the atmosphere from 21 urban areas were analyzed by direct transfer-analytical transmission electron microscopy (ATEM). Lung tissues of 36 urban residents without occupational asbestos exposure were also analyzed by ATEM after low temperature ashing. Measurement of dimensions of all types of mineral fibers, identification of asbestos, and classification of nonasbestos fibers according to the combination of main elements were carried out. RESULTS: 1. Chrysotile, amosite, actinolite, tremolite and 11 types of nonasbestos fibers were found in both the lung tissues and the atmospheric samples. The fibers, mainly composed of Al and Si, contributed 16.3% and 62.3% of the atmospheric samples and lung tissues respectively. On the other hand, the proportion of the fibers mainly composed of S and Ca were 43.7% and 0.0% in the atmosphere and lung tissues respectively. Those fibers mainly composed of P and Fe were 0.4% and 18.4% in the atmosphere and lung tissues respectively. 2. Fifteen types of nonasbestos fibers were found exclusively in the atmosphere. The average proportions for ten of these were less than 0.5% each. 3. Crocidolite was found exclusively in the lung tissues. 4. No significant difference in the geometric mean of length and diameter of asbestos was found between the atmospheric samples and lung tissues. Some types of nonasbestos fibers had significantly larger length and diameter in the atmospheres than in the lung tissues (p < 0.01). CONCLUSION: The results suggest that mineral fibers found in lung tissues could be classified into three groups on the basis of their behavior. 1) Some fibers, such as amphibole asbestos and fibers composed of Al and Si, are inhaled from the atmosphere and remain in the lung tissues for a long time. 2) Some fibers, such as those composed of S and Ca, are inhaled from the atmosphere and eliminated from the lung tissues within a relatively short time. 3) Some fibers found more in the lung tissues than in the atmospheres, such as those composed of P and Fe, are suspected to be generated in the lungs.

Air Pollutants↗
PubMed1997

Estimation of the numerical densities of neurons and synapses in cerebral cortex.

In this paper we discuss a stereological technique, 'the unfolding method', for a quantitative study of the nervous system [1,31]. Stereology implies a geometric analysis of structures and textures, and is a method to derive directly metric properties of structures from two-dimensional sections on the basis of geometrico-statistical reasoning [36,37]. Recent advances in the stereological method allow quantitative analysis [8,19,27,32]. Images on sections provide only two-dimensional information, but the stereological method can offer three-dimensional and quantitative information [19]. The need for quantitative analysis is more important and useful in the central nervous system (CNS) than in other organs. Two functional units, neurons and synapses, are of particular interest in evaluating CNS function. Numerical densities of neurons and synapses in rat visual cortex were estimated using the unfolding method at light and electron microscopic levels, respectively. Once the numerical densities of neurons and synapses were obtained, synapse-to-neuron ratios could be calculated. The ratios are interpreted as a means to obtain an index of interneuronal connectivity [9]. The unfolding method may become a powerful strategy in neuroscience research when numerical estimates are performed in restricted areas such as cortical layers II-IV, because this method is less time-consuming than other stereological methods [6,21,22].

Animals↗
PubMed1997

Inhibition of plating of human T cell leukemia virus type I and syncytium-inducing types of human immunodeficiency virus type 1 by polycations.

We examined the effects of polycations, namely, diethylaminoethyl-dextran (DEAE-dextran) and hexadimethrine bromide (Polybrene), on infection with the retroviruses human T cell leukemia virus types I and II (HTLV-I and HTLV-II) and human immunodeficiency virus type 1 (HIV-1). The plating of vesicular stomatitis virus (VSV) pseudotype bearing envelope antigens of HTLV-I [VSV(HTLV-I)] was inhibited about 2- and 10-fold by treatment with DEAE-dextran and Polybrene, respectively. The formation of HTLV-I viral DNA detected 1 day after infection was also inhibited by these polycations. In contrast, polycations enhanced the plating of the VSV (HTLV-II) pseudotype two- to threefold. The polycations did not affect the plating efficiency of HTLV-I or HTLV-II when added after virus adsorption. Infection of human T cell lines, peripheral blood lymphocytes (PBLs), or brain-derived cells with syncytium-inducing (SI) types of HIV-1 strains (GUN1 and IIIB) was inhibited 3- to 20-fold by polycations. However, infection of PBLs or monocyte-derived macrophages with the macrophage-tropic Ba-L or SF162 strain was enhanced 1.5- to twofold by polycations. On the other hand, syncytium formation in coculture induced by HTLV-I, HTLV-II, or HIV-1 was enhanced two- to threefold unanimously by DEAE-dextran or Polybrene. Although polycations have been used to potentiate human retrovirus adsorption, they inhibited infection of cell-free HTLV-I or SI-type HIV-1 strains.

Animals↗
PubMed1997

Differentiation and transforming growth factor-beta receptor down-regulation by collagen-alpha2beta1 integrin interaction is mediated by focal adhesion kinase and its downstream signals in murine osteoblastic cells.

Interaction of type I collagen (COL(I)) with alpha2beta1 integrin causes differentiation and transforming growth factor (TGF)-beta receptor down-regulation in osteoblastic cells (Takeuchi, Y., Nakayama, K., and Matsumoto, T. (1996) J. Biol. Chem. 271, 3938-3644). The TGF-beta receptor down-regulation enables cells to escape from the inhibition of differentiation by TGF-beta. To clarify how the cell-matrix interaction regulates these phenotypic changes, signaling pathways were examined in murine MC3T3-E1 cells. Attachment of cells to COL(I) stimulated tyrosine phosphorylation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK), a mitogen-activated protein kinase (MAPK), and enhanced MAPK activity. Inhibition of tyrosine kinase by herbimycin A, destruction of focal adhesion by cytochalasin D, or overexpression of antisense FAK mRNA prevented the activation of ERK/MAPK and the increase in alkaline phosphatase (ALP) activity. Transient expression of a MAPK-specific phosphatase, CL100, also suppressed the elevation of ALP activity. In addition, introduction of a constitutively active MAPK kinase enhanced ALP activity in the absence of collagen production. TGF-beta receptor down-regulation was abrogated by treatments that inactivate FAK, whereas the expression of CL100 had no effect. These results demonstrate that COL(I)-alpha2beta1 integrin interaction facilitates differentiation and down-regulates TGF-beta receptors via the activation of FAK and its diverse downstream signals. These signaling pathways may play an important role in the sequential differentiation of osteoblasts during bone formation.

3T3 Cells↗
PubMed1997

Overproduction of Mpd2p suppresses the lethality of protein disulfide isomerase depletion in a CXXC sequence dependent manner.

The third multicopy suppressor gene of the PDI1 deletion from Saccharomyces cerevisiae, MPD2, was isolated and characterized. The MPD2 gene encodes a protein with a putative signal sequence, ER retention signal, and a disulfide isomerase active site like sequence. The amino acid sequence around the active site like sequence is similar to the thioredoxin-like domains of PDI and PDI related proteins, although the similarity is comparatively low. A delta-pdi1 strain over-producing Mpd2p showed slow growth and was sensitive to 1 mM dithiothreitol. Mpd2p can be detected in wild type cells and is a glycoprotein. Although the MPD2 gene was not essential for growth, overexpression of the gene partially restored the maturation defect of carboxypeptidase Y caused by the PDI1 deletion. Mutagenesis analysis revealed that Mpd2p can compensate for the loss of PDI with its CXXC sequence.

Amino Acid Sequence↗
PubMed1997

Angiogenic and HIV-inhibitory functions of KSHV-encoded chemokines.

Unique among known human herpesviruses, Kaposi's sarcoma-associated herpesvirus (KSHV or HHV-8) encodes chemokine-like proteins (vMIP-I and vMIP-II). vMIP-II was shown to block infection of human immunodeficiency virus-type 1 (HIV-1) on a CD4-positive cell line expressing CCR3 and to a lesser extent on one expressing CCR5, whereas both vMIP-I and vMIP-II partially inhibited HIV infection of peripheral blood mononuclear cells. Like eotaxin, vMIP-II activated and chemoattracted human eosinophils by way of CCR3. vMIP-I and vMIP-II, but not cellular MIP-1alpha or RANTES, were highly angiogenic in the chorioallantoic assay, suggesting a possible pathogenic role in Kaposi's sarcoma.

Animals↗
PubMed1997

Effect of sodium tauroursodeoxycholate (UR-906) on liver dysfunction in bile duct-ligated rats.

We investigated the effect of sodium tauroursodeoxycholate (UR-906) on cholestasis in common bile duct-ligated rats in comparison with the effect of dehydrocholic acid. UR-906 (30-180 mumol/kg) and dehydrocholic acid (180 mumol/kg) were intravenously given once daily for consecutive 20 days in rats and the common bile duct was ligated for the last 10 days. On the next day after the last test drug administration, serum biochemical and plasma hemostatic variables were determined. UR-906 significantly ameliorated the elevation of serum cholesterol, phospholipid, bilirubin and bile acid concentrations in bile duct-ligated rats. UR-906 significantly suppressed the prolongation of plasma prothrombin time and activated partial thromboplastin time. Furthermore, UR-906 significantly suppressed the decreases in plasma coagulation factor II and X activities. However, dehydrocholic acid did not cause significant changes in any of the variables examined in this model. These results suggest that UR-906 has a beneficial effect against cholestasis induced by bile duct ligation in rats and that this drug may be useful in the treatment of clinical cholestatic disorders.

Animals↗
PubMed1997

The biochemical studies on phalloidin-induced cholestasis in rats.

We investigated sequential changes in bile flow, serum and biliary biochemical parameters in phalloidin-induced cholestasis in rats. Intrahepatic cholestasis was induced by administration with phalloidin (500 microg/kg) for 7 days, and then the animals were allowed to survive for 1, 2, 4, 7, 14 and 28 days after the last treatment. In phalloidin-treated rats, bile flow significantly decreased up to 4 days of recovery, compared with the control animals. In contrast, serum ALP activity, LAP activity, cholesterol concentration and phospholipid concentration exhibited a marked elevation throughout the recovery periods. For biliary parameters, bilirubin excretion rate was unchanged but, cholesterol excretion rate showed a marked decrease throughout the recovery periods. These results demonstrate that some parameters, particularly important indexes of cholestasis (serum ALP, cholesterol, bile flow and so on), continued significant changes at least 4 days after the last administration of phalloidin. These results demonstrate that successive treatment with phalloidin can cause damage in most of serum and biliary parameters at a chronic stage of cholestasis. Thus, our findings may provide useful information for diagnosis of drug-induced cholestasis and help to further elucidate the biochemical mechanisms of drug-induced cholestasis in humans.

Animals↗
PubMed1997

A cohort mortality study of construction workers.

This report presents a mortality study among the 17,344 members of the Construction Workers' Health Insurance Society of Mie Prefecture in Japan. The study period was between 1973 and 1993. During this period, 480 members died. Age-specific mortality rates of Mie Prefecture were used as comparison standards. Significantly elevated standardized mortality ratio (SMR) and proportionate mortality ratio (PMR) were observed for "accidents and adverse effects." In addition, the PMRs of all cancers and "cancers of trachea, bronchus and lung" were also significantly elevated. The job classifications were reorganized into three groups, according to the frequency of asbestos exposure the workers experienced on the construction sites. The asbestos exposure was based on job classifications among 7,411 workers who had completed a self-administered survey questionnaire. In the frequent-exposure group, the PMR was significantly elevated for all cancers. In the medium-exposure group, the SMRs were significantly elevated for all cancers and "cancer of trachea, bronchus and lung." The PMR was significantly elevated for "cancer of trachea, bronchus and lung." In the less-exposure, group, the PMR was significantly elevated for "accidents and adverse effects." This study provided support for the hypothesis that working in the construction industry might be associated with high risks for asbestos-associated cancers and accidental deaths.

Accidents, Occupational↗
PubMed1997

Failure to down-regulate Bcl-2 protein in thymic germinal center B cells in myasthenia gravis.

The most unusual characteristic of myasthenia gravis (MG) is that the thymus has germinal centers (GC). Cultured thymic lymphocytes from MG patients spontaneously produce anti-acetylcholine receptor antibodies, indicating that autoreactive B cells have escaped negative selection. To investigate the underlying mechanism, we examined the expression of the apoptosis-related protein Bcl-2 in GC B cells (defined as CD19+ CD38+ cells) in the thymus in 14 MG patients using three-color flow cytometry. GC in MG patients did not show the normal down-regulation of Bcl-2 (the frequency of Bcl-2+ GC B cells in the MG thymus and in control tonsils 54.3 +/- 16.2% versus 20.6 +/- 8.0%; mean +/- SD. p < 0.0001). In contrast, Bcl-2 in GC in the mediastinal lymph nodes from four patients was down-regulated to a relatively normal level. Using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method to detect DNA fragmentation in situ, the frequency of TUNEL+ cells in GC in the MG thymus was lower than in control tonsils. These results suggest that autoreactive B cells which normally undergo apoptosis in GC may survive because of Bcl-2 up-regulation in this unusual location.

Adolescent↗