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Biomedical subjects

A Matsui

Publications and source records attributed to A Matsui.

At least 73 records · Page 4Linked to original sources
PubMed2000

[Chemo/endocrine therapy for breast cancer patients].

Standard adjuvant chemo/endocrine therapy for breast cancer patient is based upon St. Gallen's consensus 1998. Recent development in the field of adjuvant chemo/endocrine therapy is an usage of LH-RH analogue with tamoxifen for premenopausal hormone receptor positive women, and also an emerging role of taxans. Orally given 5-FU derivatives may work in adjuvant settings. The third generation aromatase inhibitors have established their role in second line hormone therapy for the advanced or recurrent breast cancer patients. High dose chemotherapy should not be used in outside clinical trials.

Anastrozole↗
PubMed2000

Glycoprotein 130 and c-kit signals synergistically induce thrombopoietin production by hematopoietic cells.

We have reported that simultaneous activation of glycoprotein (gp) 130 and c-kit signals by interleukin (IL)-6, soluble IL-6 receptor (sIL-6R), and stem cell factor (SCF) promotes proliferation of human hematopoietic progenitor cells and their differentiation into erythroid, myelocytic, and megakaryocytic cells. We recently found that erythropoietin produced by erythroid progenitors stimulates erythropoiesis via gp130 and c-kit signals. Here we examined thrombopoietin (TPO) production by hematopoietic cells cultured with IL-6, sIL-6R, and SCF. Reverse transcription-polymerase chain reaction analysis indicated that hematopoietic cells generated from cord blood CD34+ cells with the 3 factors expressed a minor splice variant of TPO messenger RNA, P1 delta E2, which can be translated to TPO protein more efficiently than regularly spliced isoforms. The reduction in c-mpl, receptors for TPO, by antisense oligodeoxynucleotides suppressed the generation of erythroid, myelocytic, and pluripotent progenitors in suspension culture, plus colony formation of megakaryocytic progenitors in addition to these progenitors in clonal culture of cord blood CD34+ cells with IL-6, sIL-6R, and SCF. The addition of anti-human TPO antibody to the clonal culture also suppressed colony formation. These findings indicate that TPO production by hematopoietic cells stimulated by IL-6, sIL-6R, and SCF is involved in promoting their own growth.

Antigens, CD↗
PubMed1999

Structure based development of novel specific inhibitors for cathepsin L and cathepsin S in vitro and in vivo.

Specific inhibitors for cathepsin L and cathepsin S have been developed with the help of computer-graphic modeling based on the stereo-structure. The common fragment, N-(L-trans-carbamoyloxyrane-2-carbonyl)-phenylalanine-dimethyla mide, is required for specific inhibition of cathepsin L. Seven novel inhibitors of the cathepsin L inhibitor Katunuma (CLIK) specifically inhibited cathepsin L at a concentration of 10(-7) M in vitro, while almost no inhibition of cathepsins B, C, S and K was observed. Four of the CLIKs are stable, and showed highly selective inhibition for hepatic cathepsin L in vivo. One of the CLIK inhibitors contains an aldehyde group, and specifically inhibits cathepsin S at 10(-7) M in vitro.

Animals↗
PubMed1999

Inhibition of hepatic stellate cell contraction during activation in vitro by vascular endothelial growth factor in association with upregulation of FLT tyrosine kinase receptor family, FLT-1.

Activated hepatic stellate cells produce vascular endothelial growth factor (VEGF). VEGF has been shown to act on mesenchymal cells as well. If hepatic stellate cells can express FLT tyrosine receptor family, flt-1 and KDR/flk-1, their function might be regulated by VEGF in an autocrine manner. This hypothesis was tested using hepatic stellate cells isolated from normal rats. Northern blot analysis and immunocytochemical study revealed that hepatic stellate cells cultured for 3 days on plastic dishes expressed both flt-1 and KDR/flk-1. When the culture was prolonged to 10 days, the flt-1 mRNA expression was increased, whereas both KDR/flk-1 mRNA and protein expressions diminished. DNA and collagen syntheses were minimal in the cells cultured for 3 days, but marked in those cultured for 10 days. Addition of recombinant human VEGF to the culture medium did not change both syntheses but attenuated an increase of smooth muscle alpha-actin expression in the cells during culture on plastic dishes and also contraction of collagen gels on which the cells were cultured. We conclude that VEGF may inhibit contraction of hepatic stellate cells appearing during activation by culture, probably through attenuation of smooth muscle alpha-actin expression via upregulated VEGF receptor, flt-1.

Animals↗
PubMed1999

Expression of osteopontin in Kupffer cells and hepatic macrophages and Stellate cells in rat liver after carbon tetrachloride intoxication: a possible factor for macrophage migration into hepatic necrotic areas.

Activated Kupffer cells and macrophages accumulate in necrotic areas in the liver. Osteopontin, an extracellular matrix with RGD sequence, has been shown to act as a chemokine that can induce monocyte migration. The possibility that osteopontin can play a role in infiltration of both cells into hepatic necrotic areas was investigated in rats. Northern blot analysis revealed that osteopontin mRNA expression was minimal in Kupffer cells and hepatocytes immediately after isolation from normal rats, but slight in hepatic stellate cells assumed nearly quiescent in function after 3 days of culture on plastic dishes. When rat received carbon tetrachloride, liver necrosis developed between 1 and 3 days following the intoxication. In these rats, osteopontin mRNA expression assessed by quantitative competitive RT-PCR was increased in the liver later than 1 day with its peak at 2 days following the intoxication. Kupffer cells and hepatic macrophages and hepatic stellate cells isolated from such liver showed marked expression of osteopontin mRNA on Northern blotting. Immunohistochemical examination disclosed that osteopontin was stained in macrophages including Kupffer cells and stellate cells in the necrotic areas. On electron microscopy, osteopontin stains were present in the Golgi apparatus in these cells. Recombinant human osteopontin promoted migration of Kupffer cells isolated from normal rats and cultured in a Transwell cell culture chamber in a dose-related manner. We conclude that activated Kupffer cells and hepatic macrophages and stellate cells express osteopontin. These cells might contribute to the infiltration of Kupffer cells and macrophages into hepatic necrotic areas by expressing osteopontin.

Animals↗
PubMed1999

Expressions of vascular endothelial growth factor in nonparenchymal as well as parenchymal cells in rat liver after necrosis.

Vascular endothelial growth factor (VEGF) can induce proliferation of sinusoidal endothelial cells. Its mRNA expression was increased in proliferating rat hepatocytes in primary culture. To clarify a role of VEGF in liver after necrosis, expressions of VEGF and its receptors were measured in the liver or liver cells isolated from rats after carbon tetrachloride intoxication. Hepatic VEGF mRNA expression increased later than 24 h after the intoxication and became prominent at 168 h when liver necrosis disappeared, while hepatic mRNA expressions of its receptors increased between 24 and 72 h. VEGF mRNA expression was increased in Kupffer cells, hepatic macrophages and stellate cells isolated from rats between 24 and 72 h after the intoxication and in hepatocytes at 168 h compared to those cells from normal rats. Immunohistochemical VEGF stains were comparable to such results. Vascular endothelial cells existed abundantly in the necrotic areas, and sinusoidal endothelial cells appeared following disappearance of the necrotic areas. VEGF mRNA expression in hepatocytes isolated from 70% resected liver was increased at 12 h after the operation and became marked between 72 and 168 h. Similar increase of hepatic VEGF expression was immunohistochemically seen. In conclusion, VEGF derives from nonparenchymal as well as parenchymal cells in rat liver after necrosis. The former might contribute to vascular endothelial cell proliferation and the latter to sinusoidal endothelial cell regeneration.

Animals↗
PubMed1999

Persistence and clinical outcome of hepatitis G virus infection in pediatric bone marrow transplant recipients and children treated for hematological malignancy.

The natural course and the clinical significance of hepatitis G virus (HGV) infection were investigated in 106 pediatric patients who received chemotherapy for hematological malignancy or underwent bone marrow transplantation (BMT) using HGV-RNA and antibodies to the HGV-E2 protein (anti-E2). HGV markers were detected in 21 patients (19.8%; HGV-RNA in 19 and anti-E2 in 2). Longitudinal analysis of these HGV-infected patients showed that 1 had anti-E2 before the initial blood transfusion, 14 had persistent viremia, and 6 became clear of circulating HGV-RNA after completion of therapy, although 5 of the 6 HGV-cleared patients never developed anti-E2. Reactivation of HGV infection during chemotherapy was observed in two anti-E2-positive, HGV-RNA-negative patients; the reappearance of the same HGV strain was confirmed by phylogenetic analysis. Among BMT survivors without other known causes of liver dysfunction, HGV-RNA-positive patients had a higher peak serum alanine amino transferase (ALT) value than negative patients. Contrary to previous reports, immunosuppressed patients can apparently recover from HGV infection without detectable anti-E2 and some patients who supposedly recovered from HGV infection can nonetheless suffer exacerbation when subsequently immunosuppressed.

Adolescent↗
PubMed1999

Deranged blood coagulation equilibrium as a factor of massive liver necrosis following endotoxin administration in partially hepatectomized rats.

Activated Kupffer cells provoke massive liver necrosis after endotoxin stimulation through microcirculatory disturbance caused by sinusoidal fibrin deposition in rats undergoing 70% hepatectomy. In these rats, serum activities of purine nucleoside phosphorylase (PNP) and alanine transaminase (ALT) were increased at 1 and 5 hours, respectively, following endotoxin administration. When 70% resected liver was perfused with Dulbecco's modified Eagle medium (DMEM) containing heat-inactivated fetal calf serum, the increase in both enzyme activities was not affected by addition of endotoxin during perfusion, suggesting that activated Kupffer cells injured neither sinusoidal endothelial cells nor hepatocytes. The activity of tissue factor, an initiator of blood coagulation cascade, was much higher in Kupffer cells isolated from partially hepatectomized rats than in those from normal rats. In contrast, mRNA expressions of tissue factor pathway inhibitor (TFPI) as well as thrombomodulin were almost undetectable in normal and partially resected livers. When recombinant human TFPI was injected intravenously in 70% hepatectomized rats, TFPI was markedly stained on the surfaces of sinusoidal endothelial cells and microvilli of hepatocytes on immunohistochemistry. In these rats, endotoxin-induced liver injury was significantly attenuated compared with rats given no TFPI. Similar attenuation was also found in rats receiving recombinant human thrombomodulin. These results suggest that fibrin deposition developing in 70% hepatectomized rats after endotoxin administration may be caused by deranged blood coagulation in the hepatic sinusoids through increasing tissue factor activity in Kupffer cells and minimal TFPI and thrombomodulin in endothelial cells. The destruction of sinusoidal endothelial cells as well as hepatocytes may occur as a result of microcirculatory disturbance caused by such sinusoidal fibrin deposition.

Alanine Transaminase↗
PubMed1999

Detection of histamine-induced capillary protein leakage and hypovolaemia by determination of indocyanine green and glucose dilution method in dogs.

OBJECTIVE: The plasma volume of histamine-induced protein capillary leakage may be overestimated when this is determined using the indocyanine green (ICG) dilution method (Vd-ICG), since this dye binds to plasma proteins. The initial distribution volume of glucose (IDVG) has been shown to indicate the central extracellular fluid volume including plasma. Accordingly, the overestimation would be detected by a higher Vd-ICG/IDVG ratio. Our study was intended to examine whether the simultaneous measurement of these two variables can evaluate histamine-induced protein leakage and associated hypovolaemia. DESIGN: Prospective animal study. SETTING: Institutional animal research laboratory. SUBJECTS: Twenty-four anaesthetized and ventilated mongrel dogs. INTERVENTIONS: Anaesthetized animals were mechanically ventilated and received infusions of normal saline (n = 8), histamine 50 microg/kg per h (n = 8), or histamine 100 microg/kg per h. The Vd-ICG and IDVG were calculated using a one-compartment model by simultaneous administration of ICG 0.5 mg/kg, and glucose 100 mg/kg followed by serial arterial blood sampling. MEASUREMENTS AND RESULTS: In both histamine groups, a significant elevation of haematocrit and a decrease of plasma albumin concentration were found (p<0.05). Although the IDVG decreased following histamine administration (p<0.05), the Vd-ICG remained unchanged. The Vd-ICG/IDVG ratio increased in a dose-dependent manner after histamine administration (p<0.05), but remained unchanged following normal saline administration. CONCLUSION: The results suggest that the Vd-ICG/IDVG ratio and the IDVG are useful in evaluating the magnitude of the leakage and hypovolaemia.

Animals↗
PubMed1999

Plasma lipoprotein (a) levels in children with minimal lesion nephrotic syndrome.

We studied the plasma lipoprotein (a)[Lp(a)] levels in 31 children with minimal lesion nephrotic syndrome (MLNS) in both stages of acute NS and remission. The mean Lp(a) levels in acute NS were significantly higher than those of the controls. The Lp(a) levels in remission were significantly lower than the Lp(a) levels in acute NS. In addition, the Lp(a) levels in remission were not significantly different from those of the controls. However, there were 5 patients whose Lp(a) levels remained higher than 30 mg/dl (the generally accepted limit for cardiovascular risk) after remission. Two of these 5 patients had Lp(a) levels greater than 40 mg/dl. In these patients apoprotein (a) [apo(a)] phenotypes were of lower molecular weight than those of the other 23 patients whose apo(a) phenotypes were examined. Additional episodes of relapse may put the patient with sustained elevated Lp(a) levels at significant risk for the development of cardiovascular disease in the long term.

Adolescent↗
PubMed1999

No association between atopic asthma and a coding variant of Fc epsilon R1 beta in a Japanese population.

Susceptibility to atopic diseases is known to involve genetic factors. The Gly237 allele of a polymorphism (Glu237Gly) of the Fc epsilon R1 beta gene is reportedly associated with atopic asthma in Japanese. To confirm this association, we conducted transmission disequilibrium tests in 76 families identified through atopic asthmatics. A case-control study was also carried out in atopic asthmatic subjects and non-atopic controls. The Gly237 allele was not preferentially transmitted to atopic asthma-affected offspring. Neither the Gly237 allele nor the Gly237/Gly237 + Glu237/Gly237 genotypes were significantly more prevalent in the atopic asthmatics than in the controls. This study failed to confirm a substantial role of the Gly237Glu polymorphism of the Fc epsilon R1 beta gene in the genetic predisposition for atopic asthma in this Japanese population.

Amino Acid Substitution↗
PubMed1999

Study of the functional share of lysosomal cathepsins by the development of specific inhibitors.

To analyze the functional share of individual cathepsins, we developed powerful and specific inhibitors for individual cathepsins using computer graphics of substrate binding pockets based on X-ray crystallography. These new inhibitors were named CLIK group. Epoxy succinate peptide derivatives, CLIK-066, 088, 112, 121, 148, 181, 185 and 187, are typical specific inhibitors for cathepsin L. Aldehyde derivatives CLIK-060 and CLIK-164 showed specific inhibition against cathepsin S and cathepsin K, respectively. We found that pyridoxal phosphate (PLP), a coenzyme form of vitamin B6, inhibits all cathepsins and also new artificially synthesized pyridoxal derivatives, CLIK-071 and -072, in which the phosphate esters of PLP were replaced by propionic acid, exhibited strong inhibition for cathepsins. Furthermore, CLIK-071 was easy to incorporate into cells and showed powerful inhibition for intracellular cathepsins. Using these selective inhibitors, the allotment of individual cathepsin functions in cells has been studied as follows. Cathepsin L and/or K participate in bone resorption based on bone type-1 collagen degradation and the L-type protease inhibitors suppressed the bone resorption. Cathepsins B and S participate in antigen presentations based on antigen processing and invariant chain degradation, respectively. Also cathepsin L participates in cell apoptosis mediated by caspase III activation.

Animals↗
PubMed1999

Visualization of regional myocardial depolarization by tangential component mapping on magnetocardiogram in children.

BACKGROUND: Tangential components to the body surface on magnetocardiography theoretically reflect regional myocardial current sources just below the gradiometer. The usefulness of tangential component mapping on magnetocardiography in determination of regional myocardial abnormalities has not been investigated in children. METHODS: Twenty-six children with ventricular hypertrophy, including a child with a left ventricular diverticulum (aged 7 to 15), and age matched 22 healthy children (aged 7 to 15) were studied. Tangential components on magnetocardiography were measured using a newly-developed super-conducting quantum interference device system housed in a magnetically shielded room. Isomagnetic maps and current vector maps were constructed from the data obtained. RESULTS: The peak magnetic fields and current dipoles were demonstrated to be located at the interventricular septum initially, and then were shifted to the anterior and inferior walls of the left ventricle and to the right ventricular outflow tract, successively. In patients with right ventricular hypertrophy whose systolic right ventricular pressure was over 60 mmHg, the peak magnetic fields were located in the right half with rightward directed current vectors throughout ventricular depolarization. In patients with left ventricular hypertrophy, the maximal magnetic fields during depolarization were shifted to the hypertrophic site, showing significantly stronger forces than those in healthy children (35.5+/-11.7 pT vs 26.5+/-11.9 pT, p < 0.01). In a patient with left ventricular diverticulum, two discrete depolarizing current dipoles were visualized. The mean time required in measuring MCGs among all subjects was 10 minutes. CONCLUSION: The time course as well as the location of the regional electrical activities of the myocardium in children can be visualized, in a short time, as a two-dimensional projection to the frontal plane by tangential component mapping on magnetocardiography.

Adolescent↗
PubMed1999

Lack of association of atopy/asthma and the interleukin-4 receptor alpha gene in Japanese.

BACKGROUND: Susceptibility to the development of atopic diseases is known to involve genetic factors. Several investigators have reported the interleukin-4 (IL-4) receptor alpha gene to be involved in the development of atopy. Recent study has shown that the R allele of a polymorphism in the IL-4 receptor alpha chain gene (Q576R) to be associated with atopy. OBJECTIVE: The objective of this study was to evaluate the possible role of the IL-4 receptor alpha gene in modulating allergic response and asthma in the Japanese population. METHODS: We conducted linkage analysis using microsatellite markers flanking the IL-4 alpha receptor gene in 82 families ascertained through asthmatic children. The IL-4 receptor Q576R polymorphism was also genotyped by PCR-restriction fragment length polymorphism analysis. RESULTS: We did not find evidence for linkage of the asthma and atopy phenotypes with the markers D16S298 and D16S403 (P = 0.10 and P = 0.56, respectively, for the atopy phenotype and P = 0.17 and P = 0.60, respectively, for the asthma phenotype). The IL-4 receptor R576 allele was not preferentially transmitted to atopy- or asthma-affected children (chi2 = 1.67, P = 0.24 for atopy and chi2 = 0.91, P = 0.40 for asthma). In addition, the prevalence of the R576 allele among parents with and without atopy was similar, 20 of 81 (24.7%) parents with atopy and 22 of 77 (28.6%) parents without atopy. CONCLUSION: Our findings indicate that the IL-4 receptor alpha gene does not exert a substantial influence on the inheritance of atopy or asthma in this Japanese population.

Adolescent↗
PubMed1999

Genetic relationship and distribution of the Japanese wild boar (Sus scrofa leucomystax) and Ryukyu wild boar (Sus scrofa riukiuanus) analysed by mitochondrial DNA.

Mitochondrial genetic variations were used to investigate the relationships between two Japanese wild boars, Japanese wild boar (Sus scrofa leucomystax) and Ryukyu wild boar (S.s. riukiuanus). Nucleotide sequences of the control (27 haplotypes) and cytochrome b (cyt-b) regions (19 haplotypes) were determined from 59 Japanese wild boars, 13 Ryukyu wild boars and 22 other boars and pigs. From phylogenetic analyses, the mtDNA of Ryukyu wild boar has a distinct lineage from that of Japanese wild boar, which was classified into the Asian pig lineage. This result suggests that the Ryukyu wild boar has a separate origin from the Japanese wild boar.

Animals↗