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Biomedical subjects

H Matsushita

Publications and source records attributed to H Matsushita.

At least 19 recordsLinked to original sources
PubMed2001

Fine chromosomal localization of the mouse Par2 gene that confers resistance against urethane-induction of pulmonary adenomas.

BALB/cByJ mice are 14 times more resistant to urethane-induction of pulmonary adenomas than the susceptible A/J strain. Our previous linkage analysis of (A/J x BALB/cByJ)F1 x A/J backcross mice provided statistical evidence that a major resistance locus of BALB/cByJ with a dominant effect, designated Par2 (Pulmonary adenoma resistance 2), exists within an approximately 25 cM section of distal chromosome 18. To facilitate molecular identification of the Par2 locus, the present study was conducted to finely localize its chromosomal position utilizing Par2-congenic mice. Male BALB/cByJ mice were mated with female C57BL/6J mice carrying recessive Par2 alleles and their male F1 progeny were backcrossed to female BALB/cByJ mice. A male backcross mouse heterozygous within the Par2 interval of 25 cM was randomly selected and again backcrossed to female BALB/cByJ mice. This backcross-selection cycle was simply repeated to produce semi-congenic mice with a general BALB/cByJ genetic background except for the Par2 interval, where the mice were heterozygous with paternal C57BL/6J alleles and maternal BALB/cByJ alleles. After the 6th or 7th backcross, nine male mice possessing a recombination within the paternal Par2 interval were retained and crossed to female A/J mice. Resultant progeny were treated with urethane and examined for lung tumor development in order to deduce the Par2 genotypes of the recombinants through linkage analysis. By comparing the deduced Par2 genotype of each recombinant with its recombinational breakpoint, the Par2 locus was confined to an approximately 0.5 cM region flanked by D18Mit103 and D18Mit188 loci. Our results indicate that fully congenic mice conventionally established by at least nine simple backcrosses or by the speed congenic method are not necessarily required for fine mapping of quantitative trait loci. In the case of the Par2 locus, we found that semi-congenic mice after as few as four simple backcrosses were useful for this purpose. The map information obtained in this study should enable subsequent positional cloning of the Par2 gene.

Adenomatosis, Pulmonary↗
PubMed2001

Diabetes mellitus enhances vascular matrix metalloproteinase activity: role of oxidative stress.

Diabetes mellitus (DM) is a primary risk factor for cardiovascular disease. Although recent studies have demonstrated an important role for extracellular matrix metalloproteinases (MMPs) in atherosclerosis, little is known about the effects of hyperglycemia on MMP regulation in vascular cells. Gelatin zymography and Western blot analysis revealed that the activity and expression of 92-kDa (MMP-9) gelatinase, but not of 72 kDa (MMP-2) gelatinase, were significantly increased in vascular tissue and plasma of two distinct rodent models of DM. Bovine aortic endothelial cells (BAECs) grown in culture did not express MMP-9 constitutively; however, chronic (2-week) incubation with high glucose medium induced MMP-9 promoter activity, mRNA and protein expression, and gelatinase activity in BAECs. On the other hand, high glucose culture did not change MMP-9 activity from vascular smooth muscle cells or macrophages. Electron paramagnetic resonance studies indicate that BAECs chronically grown in high glucose conditions produce 70% more ROS than do control cells. Enhanced MMP-9 activity was significantly reduced by treatment with the antioxidants polyethylene glycol-superoxide dismutase and N-acetyl-L-cysteine but not by inhibitors of protein kinase C. In conclusion, vascular MMP-9 activity is increased in DM, in part because of enhanced elaboration from vascular endothelial cells, and oxidative stress plays an important role. This novel mechanism of redox-sensitive MMP-9 expression by hyperglycemia may provide a rationale for antioxidant therapy to modulate diabetic vascular complications.

Animals↗
PubMed2001

Identification of co-mutagenic chlorinated harmans in final effluent from a sewage treatment plant.

Harman (1-methyl-9H-pyrido[3,4-b]indole) reacted readily with sodium hypochlorite in an aqueous medium to give the mono-chlorinated derivatives, which reportedly have greater co-mutagenic activity than harman in the presence of o-toluidine toward Salmonella typhimurium TA 98 with S9 mix. Mono-chlorinated harmans were detected by concentration using blue rayon (BR) and GC/MS analysis in the final effluent from a sewage treatment plant in Shizuoka, Japan. The amounts adsorbed for 24h were 1-45ng/gBR for mono-chlorinated harman and 110-730ng/gBR for harman.

Biotransformation↗
PubMed2001

Effects of a beta 3 adrenergic receptor agonist on bone and bone marrow adipocytes in the tibia and lumbar spine of the ovariectomized rat.

The object of this study was to investigate the effects of a b3 adrenergic receptor agonist (ARa) and estrogen on bone remodeling and bone marrow adipocyte differentiation. Ten-week-old female Sprague-Dawley rats underwent sham operation (Sham) or were ovariectomized (OVX) and were divided into four groups: Sham, Sham+ARa, OVX, and OVX+ARa groups. They were given orally the b3-ARa, BRL 35135, or vehicle daily for 4 weeks and their tibial and lumbar spinal bone and fat histomorphometric parameters were measured. In tibial proximal metaphysis, the adipocyte number per bone marrow unit volume (N.A/MV), and the percent adipocyte volume (AV/MV) values of the OVX and OVX+ARa groups were significantly higher than the Sham and Sham+ARa groups (P = 0.004, P = 0.008 in OVX, respectively), but ARa administration had no effect on bone remodeling or adipocyte differentiation. N.A/MV and AV/MV correlated negatively with the bone volume (BV/TV, r = -0.67, P = 0.001; r = -0.62, P = 0.004, respectively), and they correlated with the bone resorption parameters, i.e., the eroded surface (ES/BS), osteoclast surface (Oc.S/BS), and osteoclast number (N.Oc/BS) in tibial proximal metaphysis. In tibial distal metaphysis, the adipocyte volume per cell (AV/N.A) values of the OVX and OVX+ARa groups were significantly higher than those of the Sham and Sham+ ARa group (P = 0.003 in OVX). In the lumbar spine, the AV/N.A values of the Sham+ARa and OVX+ARa groups were significantly lower than the Sham and OVX groups values (P < 0.0001 in ARa administration), but OVX did not affect adipocyte differentiation. Beta3-ARa administration affects the bone marrow adipocyte differentiation, which is site-specific difference, although mainly negative in the context of bone.

Adipocytes↗
PubMed2001

Cyclic strain induces reactive oxygen species production via an endothelial NAD(P)H oxidase.

Vascular endothelial cells are constantly subjected to pressure-induced cyclic strain. Reactive oxygen species (ROS) have been implicated in atherosclerosis and vascular remodeling. Recent evidence indicates that a vascular NAD(P)H oxidase may be an important source of ROS in both physiologic and pathophysiologic situations. The aim of this study was to investigate cyclic strain-induced NAD(P)H oxidase activity in endothelial cells. ROS production was examined by electron paramagnetic resonance and lucigenin chemiluminescence. Cyclic strain-induced NAD(P)H oxidase activity was quantified by activity assay while the expression of p22phox was monitored by Northern blotting. Endothelial cells produce basal amounts of ROS that were enhanced by cyclic strain. Moreover subsequent stimulation with TNF-alpha resulted in significantly greater ROS production in cells previously exposed to cyclic strain as compared to static conditions. Cyclic strain resulted in a significant increase in message for the p22phox subunit as well as activity of the NAD(P)H oxidase. The induced oxidative stress was accompanied by increased mobilization of the transcription factor NFkappaB, an effect that was blocked by a pharmacological inhibitor of NAD(P)H. These results demonstrate a pivotal role for NAD(P)H oxidase in cyclic strain-induced endothelial ROS production and may provide insight into the modulation of vascular disease by biomechanical forces. J. Cell. Biochem. Suppl. 36: 99-106, 2001.

Blotting, Northern↗
PubMed2001

Identification and quantification of chlorinated bisphenol A in wastewater from wastepaper recycling plants.

Chlorinated derivatives of bisphenol A were detected in the final effluents of eight paper manufacturing plants in Shizuoka, Japan, where thermal paper and/or other printed paper is used as the raw material. Their amounts were determined by gas chromatography/mass spectrometry (GC/MS) after treatment with N, O-bis(trimethylsilyl)trifluoroacetamide, and ranged from traces to 2.0 microg/l. They are likely produced by chlorination of bisphenol A, which was released into the effluents from the pulping process of wastepaper, during or after bleaching with chlorine.

Benzhydryl Compounds↗
PubMed2001

A novel differentiation-inducing therapy for acute promyelocytic leukemia with a combination of arsenic trioxide and GM-CSF.

Arsenic trioxide (As2O3) effectively induces clinical remission via apoptosis in relapsed acute promyelocytic leukemia (APL). However, because this new anti-leukemic drug is also considered to be a poison, its possible adverse effects are a highly important issue related to its clinical use. We here investigated, both in vitro and in vivo, the effects of a combination of As2O3 and GM-CSF as a novel therapeutic approach for the treatment of APL. Treatment of both retinoic acid (RA)-sensitive and -resistant APL cell lines (NB4 and UF-1 cells, respectively), as well as primary APL cells with a combination of As2O3 and GM-CSF for 4 days resulted in inducing differentiation, but not apoptosis, to mature granulocytes. In addition, a combination of both agents induced degradation of the PML/RARalpha protein. GM-CSF was found to be associated with increased tyrosine phosphorylation of Jak2 kinase in both NB4 and UF-1 cells, and a specific inhibitor of Jak2, AG490, completely blocked the ability of GM-CSF to prevent apoptosis and induce differentiation of As2O3-treated UF-1 cells. In in vivo analysis, As2O3 induced differentiation of APL cells in a RA-resistant APL model of human GM-CSF-producing transgenic SCID mice that had a high level of human GM-CSF in their sera. In contrast, As2O3 alone diminished tumors in UF-1 cells transplanted into NOD/SCID mice via induction of apoptosis. In conclusion, a combination of As2O3 and GM-CSF appears to be a novel differentiation-inducing therapy in patients with APL, including relapsed or RA-resistant cases.

Animals↗
PubMed2001

Preferential recruitment of ataxin-3 independent of expanded polyglutamine: an immunohistochemical study on Marinesco bodies.

In an immunohistochemical study of Marinesco bodies--a neuronal intranuclear inclusion often seen in neurons of the substantia nigra of patients with hepatic encephalopathy--it was shown that one of the polyglutamine proteins, ataxin-3, is preferentially recruited into this inclusion, whereas other polyglutamine proteins (ataxin-2 and TATA box-binding protein) are not. This suggests that recruitment of each of the polyglutamine proteins may be differently regulated. Because this nuclear inclusion is thought to be formed in response to cellular stress, as occurs in hepatic encephalopathy, even in the absence of an expanded CAG/polyglutamine repeat, recruitment of ataxin-3 and ubiquitin into Marinesco bodies may represent a cellular response to noxious external stimuli unrelated to expanded CAG/polyglutamine.

Aged↗
PubMed2001

Serotonergic heterotypic sprouting in the unilaterally dopamine-depleted mouse neostriatum.

The effects of unilateral 6-hydroxydopamine (6-OHDA) treatment on striatal serotonin neurons in 12-day-old mice were studied using immunohistochemistry. The unilateral 6-OHDA lesions were evaluated with tyrosine hydroxylase (TH) immunohistochemistry. The majority of the TH-immunoreactive structures disappeared from the substantia nigra and neostriatum on the 6-OHDA lesioned side. However, the density of serotonin fibers was markedly increased throughout the 6-OHDA-depleted neostriatum 1 year later. These results suggest that serotonergic heterotypic sprouting may be permanent.

Age Factors↗
PubMed2001

Disseminated intravascular coagulation associated with intratumoral hemorrhage of ovarian cancer.

BACKGROUND: Ovarian carcinoma usually presents in an indolent manner. A patient with ovarian cancer rarely shows acute clinical features which require immediate medical intervention. CASE: We present a 36-year-old Japanese woman with an ovarian tumor, who suffered general fatigue and increased abdominal girth on admission. Her hemoglobin, platelet count and fibrinogen were decreased, and fibrin/fibrinogen degradation products were elevated, which determined the diagnosis of disseminated intravascular coagulation (DIC). Since computed tomography scan and magnetic resonance imaging revealed an intratumoral hemorrhage, an emergency laparotomy was performed. The patient was found to have ovarian cancer with a massive intratumoral hemorrhage, and DIC improved immediately after the operation. CONCLUSION: The clinician should be alert to the possibility that intratumoral bleeding of ovarian cancer might be associated with DIC.

Adult↗
PubMed2001

Contribution of Bcl-2, but not Bcl-xL and Bax, to antiapoptotic actions of hepatocyte growth factor in hypoxia-conditioned human endothelial cells.

Angiogenic growth factors play important roles in angiogenic responses, such as vasculogenesis and angiogenesis in response to hypoxia. A novel angiogenic growth factor, hepatocyte growth factor (HGF), has been reported to inhibit endothelial cell death. However, its molecular mechanisms are largely unknown. Thus, we studied (1) the effects of HGF on hypoxia-induced endothelial apoptosis and (2) the molecular mechanisms of the antiapoptotic actions of HGF in endothelial cells. Severe hypoxia increased the cell death rate in human aortic endothelial cells, whereas HGF significantly attenuated cell death. In addition, hypoxic treatment resulted in a significant increase in apoptotic cells, whereas HGF could attenuate apoptosis, accompanied by attenuation of the increase in caspase-3-like activity (P<0.01). Of importance, HGF significantly increased Bcl-2, an inhibitor of apoptosis, in a dose-dependent manner under normoxic and hypoxic conditions (P<0.01), whereas hypoxic conditions resulted in a significant decrease in Bcl-2. In contrast, HGF failed to affect Bcl-xL, which is also well known as an inhibitor of apoptosis under both normoxic and hypoxic conditions, whereas Bcl-xL was significantly decreased in endothelial cells exposed to hypoxia (P<0.01). No significant change in Bax, a promoter of apoptosis, was also observed in endothelial cells under hypoxia, whereas HGF did not affect BAX: Overall, this study demonstrated that HGF prevented endothelial cell death induced by hypoxia through its antiapoptotic action. The antiapoptotic mechanisms of HGF in hypoxia-induced endothelial cell death largely depend on Bcl-2, but not Bcl-xL and BAX:

Apoptosis↗
PubMed2001

Endothelial apoptosis induced by oxidative stress through activation of NF-kappaB: antiapoptotic effect of antioxidant agents on endothelial cells.

Injury of endothelial cells has been assumed to be an initial trigger of the development of atherosclerosis. In this study, we investigated the molecular mechanisms of endothelial cell death induced by hypoxia, which leads to oxidative stress. To study the relation between hypoxia-induced cell death and activation of nuclear factor-kappaB (NF-kappaB) in a hypoxic state, we evaluated the effect of 2 antioxidant drugs, probucol and pyrrolidine dithiocarbamate (PDTC), on human endothelial apoptosis. Although hypoxic treatment of human aortic endothelial cells resulted in a significant decrease in cell number and a significant increase in apoptotic cells compared with that of cells under normoxia (P<0.01), treatment with probucol (50 micromol/L) or PDTC (100 micromol/L) significantly attenuated the decrease in cell number (P<0.01) and was accompanied by inhibition of NF-kappaB activation. Furthermore, downregulation of bcl-2 caused by hypoxia was inhibited by these drugs. We further investigated the translocation of bax protein from the cytoplasm to the mitochondrial heavy fraction membrane, as translocation of bax protein is considered to be a determinant of apoptosis. Interestingly, we found that antioxidant treatment inhibited the translocation of bax protein caused by hypoxia. Moreover, upregulation of p53, a proapoptotic molecule, was observed in hypoxia, whereas treatment with probucol attenuated the expression of p53 accompanied by suppression of NF-kappaB activation. These data suggest functional links between p53 and endothelial apoptosis through the activation of NF-kappaB. Overall, the current study demonstrated that oxidative stress induced apoptosis in human aortic endothelial cells through the downregulation of bcl-2, translocation of bax, and upregulation of p53, probably through NF-kappaB activation. Oxidative stress may play an important role in endothelial apoptosis mediated by hypoxia, through the activation of NF-kappaB.

Anticholesteremic Agents↗
PubMed2001

Developmental changes in cerebrospinal fluid concentrations of monoamine-related substances in patients with dentatorubral-pallidoluysian atrophy.

Using a Coulochem electrode array system, we investigated the developmental changes of monoamine-related substances in patients with dentatorubral-pallidoluysian atrophy. The patterns observed in the developmental changes of tryptophan, tyrosine, homovanillic acid (HVA), 3-O-methyldopa, and 3-methoxy4-hydroxyphenyl glycol (MHPG) in patients with dentatorubral-pallidoluysian atrophy are quite different from those in control subjects. These abnormal developmental changes in monoamine-related substances may be implicated in age-related differences in clinical symptoms of dentatorubral-pallidoluysian atrophy.

Adolescent↗
PubMed2001

Hypoglycemia induced by secretion of high molecular weight insulin-like growth factor-II from a malignant solitary fibrous tumor of the pleura.

A 49-year-old woman with a malignant solitary fibrous tumor of the pleura presented with hypoglycemia. Most of the serum insulin-like growth factor II (IGF-II) existed as high molecular weight IGF-II. Furthermore, there were larger amounts of high molecular weight IGF-II found in the tumor cystic fluid than in the serum. After surgical resection of the tumor, high molecular weight IGF-II was not detected in the serum and the hypoglycemia resolved. Immunohistochemically, IGF-II was localized in the so-called Golgi area of the tumor cell. These findings suggest that hypoglycemia in this patient was caused by the high molecular weight IGF-II produced by the tumor.

Female↗
PubMed2001

Evidence of primary beta-cell destruction by T-cells and beta-cell differentiation from pancreatic ductal cells in diabetes associated with active autoimmune chronic pancreatitis.

OBJECTIVE: Diabetes associated with autoimmune chronic pancreatitis (ACP) is a subtype of diabetes that is responsive to corticosteroid treatment of progressive endocrine and exocrine dysfunction. However, little is known about pathological changes of islet and exocrine pancreas in ACP. RESEARCH DESIGN AND METHODS: We examined pancreatic specimens obtained on biopsy from four diabetic men with ACP (mean [range]: age 62 years [48-78], duration of ACP 3 months [1-5], duration of diabetes 1 month [0-3]) morphologically, immunohistochemically, and morphometrically. RESULTS: The pancreatic specimens in all cases exhibited inflammatory cell infiltration surrounding ductal cells and extensive fibrosis. Some islets were infiltrated with mononuclear cells with disrupted beta-cells. The subsets of T-cells infiltrated to the islets were mainly CD8(+). Islet beta-cell volume was decreased; the mean percentage area of beta-cells in the islets in four cases with ACP were 16% (range 13-20) (P = 0.0015 vs. type 2 diabetic patients, 48% [27-73], n = 8; P = 0.0002 vs. nondiabetic control subjects, 58% [39-77], n = 7). Preserved ductal cells were surrounded predominantly by CD8(+) or CD4(+) T-cells. Some cytokeratin 19-positive ductal cells contained insulin and glucagon, representing upregulated differentiation of islet cells from ductal cells. Insulin promoter factor-1 (IPF-1) was hyperexpressed in insulin-containing ductal cells. CONCLUSIONS: Diabetes associated with ACP is caused by T-cell-mediated mechanisms primarily involving islet beta-cells as well as pancreatic ductal cells. In ACP, ductal islet precursor cells were associated with IPF-1 hyperexpression, suggesting a critical role of IPF-1 on islet cell differentiation and eventual beta-cell restoration.

Acute Disease↗
PubMed2001

Systemic fusariosis after a preparative regimen including thiotepa, VP-16 and busulfan used for blood stem cell transplantation in Hodgkin's disease.

Fusarium infection is rare but important infection after bone marrow transplantation (BMT). A 27-year-old man developed systemic fusarial infection following severe skin damage probably caused by high-dose thiotepa administration. Systemic fusariosis rapidly progressed to a variety of organs despite antifungal treatment, and he finally died of this infection on day 75. Considering that this organism usually invades via damaged skin and that the penile lesion was the first manifestation of systemic fusariosis in this patient, careful examination of the skin might be helpful for early diagnosis of fusarial infection. His clinical course provided us with an important clue for diagnosis of fusarial infection.

Adult↗
PubMed2001

[A case of benign schwannoma arising in the brachial plexus with intrathoracic extension].

A case of benign schwannoma originating from the lowest trunk of the left brachial plexus with intrathoracic extension was reported. Intrathoracic growth of a schwannoma of the brachial plexus has been reported in only five cases in the literature. The patient was a 35-year-old man and had been pointed out an abnormal shadow at the left lung apex on the roentgenogram since 20-year-old. The tumor shadow was increased to seven cm from four in size on recent chest X-ray. We performed a video-assisted thoracoscopic surgery with the oblique skin incision at the left neck and removed the tumor completely and safely.

Adult↗