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Biomedical subjects

Y Matsuura

Publications and source records attributed to Y Matsuura.

At least 19 recordsLinked to original sources

Use of hollow-core fibers to deliver nanosecond Nd:YAG laser pulses to form sparks in gases.

We report what is to our knowledge the first delivery of nanosecond laser pulses through flexible fibers to produce optical sparks in atmospheric-pressure gases. Our work employs a Nd:YAG laser beam (1.064 microm) delivered through a cyclic olefin polymer-coated silver hollow fiber. We studied the beam properties at the fiber exit as a function of the fiber launch geometry. We found that for a low-angle launch (approximately 0.01 rad half-angle), the exit beam has relatively high optical intensity (approximately 2 GW/cm2) and low light divergence (approximately 0.01 rad half-angle) and allows downstream spark formation. The effect of fiber bending on the exit beam and on the ability to make sparks is also investigated.

Journal Article↗

Dietary-fiber-degrading enzymes from a human intestinal Clostridium and their application to oligosaccharide production from nonstarchy polysaccharides using immobilized cells.

The secretion of nonstarchy polysaccharide-degrading enzymes from an anaerobic human intestinal bacterium, Clostridium butyricum- beijerinckii (isolated from human feces), was investigated. Growth of the bacterium was found when laminarin, konjac glucomannan, and pectic acid were added separately to the culture media as sole carbon source. The corresponding degrading enzymes for these dietary fibers, laminarinase (endo-1,3- beta-glucanase), endo-1,4-beta-mannanase, endo- and exo-pectate lyases, and pectin methylesterase, were then purified and characterized. These extracelluar enzymes, which were secreted by the bacterium in the human large intestine, were considered to contribute to digestion of the ingested dietary fibers to their oligosaccharides, following by short-chain fatty acid fermentation by the bacterium. We have developed cell immobilization techniques of the bacterium on cellulose-foam carriers that are effective for continuous production of the oligosaccharides from the dietary fibers in a fed-batch reactor system. From 9 g of pectic acid, a total of 3.96 g of 4,5-unsaturated digalacturonic acid was produced over 40 h in four 500-ml batchcultures. In the same manner, the corresponding oligosaccharides were obtained from konjac glucomannan and laminarin with average conversion rates of around 30-40%.

Adsorption↗

Characterization of pseudotype VSV possessing HCV envelope proteins.

The genome of hepatitis C virus (HCV) encodes two envelope glycoproteins (E1 and E2), which are thought to be responsible for receptor binding and membrane fusion resulting in virus penetration. To investigate cell surface determinants important for HCV infection, we used a recombinant vesicular stomatitis virus (VSV) in which the glycoprotein gene was replaced with a reporter gene encoding green fluorescent protein (GFP) and produced HCV-VSV pseudotypes possessing chimeric HCV E1 or E2 glycoproteins, either individually or together. The infectivity of the pseudotypes was determined by quantifying the number of cells expressing the GFP reporter gene. Pseudotypes that contained both of the chimeric E1 and E2 proteins exhibited 10--20 times higher infectivity on HepG2 cells than the viruses possessing either of the glycoproteins individually. These results indicated that both E1 and E2 envelope proteins are required for maximal infection by HCV. The infectivity of the pseudotype virus was not neutralized by anti-VSV polyclonal antibodies. Bovine lactoferrin specifically inhibited the infection of the pseudotype virus. Treatment of HepG2 cells with Pronase, heparinase, and heparitinase but not with phospholipase C and sodium periodate reduced the infectivity. Therefore, cell surface proteins and some glycosaminoglycans play an important role in binding or entry of HCV into susceptible cells. The pseudotype VSV possessing the chimeric HCV glycoproteins might offer an efficient tool for future research on cellular receptors for HCV and for the development of prophylactics and therapeutics for hepatitis C.

Animals↗

Anticoagulant properties of a sulfated galactan preparation from a marine green alga, Codium cylindricum.

An anticoagulant was isolated from a marine green alga, Codium cylindricum. The anticoagulant was composed mainly of galactose with a small amount of glucose, and was highly sulfated (13.1% as SO3Na). The anticoagulant properties of the purified anticoagulant were compared with that of heparin by assays of activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) using normal human plasma. The anticoagulant showed similar activities with heparin, however, weaker than heparin. On the other hand, the anticoagulant did not affect PT even at the concentration at which APTT and TT were strongly prolonged. The anticoagulant did not potentiate antithrombin III (AT III) and heparin cofactor II (HC II), thus the anticoagulant mechanism would be different from that of other anticoagulants isolated so far from the genus Codium.

Anticoagulants↗

Molecular mechanism of translocation through nuclear pore complexes during nuclear protein import.

The trafficking of macromolecules between cytoplasm and nucleus through nuclear pore complexes is mediated by specific carrier molecules such as members of the importin-beta family. Nuclear pore proteins (nucleoporins) frequently contain sequence repeats based on FG cores and carriers appear to move their cargo through the pores by hopping between successive FG cores. A major question is why some macromolecules are transported while others are not. This selectivity may be generated by the ability to bind FG repeats, a local concentration of carrier-cargo complexes near the entrance to the pore channel, and steric hindrance produced by high concentrations of nucleoporins in the channel.

Active Transport, Cell Nucleus↗

The effects of norepinephrine and prostaglandin E1 on pharmacokinetics of lidocaine in isolated perfused rat liver.

We hypothesized that depression of liver function by norepinephrine can be improved by prostaglandin E1. Isolated perfused rat liver was selected as an experimental model, since the flow rate can be regulated in it. Twenty-one rats were randomly allocated to three groups: control, norepinephrine, and norepinephrine and prostaglandin E1 groups. The liver was perfused in a recirculating system at a constant flow rate of 20 ml/min. After administration of two milligrams of lidocaine in each group, lidocaine and monoethylglycinexylidide concentrations in the recirculating system were measured. Lidocaine pharmacokinetics were analyzed using the SAAM II program, including metabolic rate from lidocaine to monoethylglycinexylidide using time-concentration curves. Norepinephrine significantly increased perfusion pressure and the area under the time-concentration curve for lidocaine. Norepinephrine decreased the clearance and the elimination rate constant of lidocaine compared with those in the control group. Although administration of prostaglandin E1 after infusion of norepinephrine did not significantly change perfusion pressure, it significantly (p < 0.05) improved metabolic rate, clearance and the elimination rate constant of lidocaine in the isolated rat liver model.

Alprostadil↗

Ubiquitin-mediated degradation of hepatitis C virus core protein is regulated by processing at its carboxyl terminus.

Hepatitis C virus core protein, in addition to being a component of the viral capsid, has a number of regulatory functions. Here we showed two bodies of evidence indicating that a fraction of the core protein species is a substrate of the ubiquitin (Ub)-proteasome pathway of targeted proteolysis. First, the core protein processing the C-terminal hydrophobic region is metabolically unstable, and incubation with a proteasome inhibitor led to a significant accumulation of the protein. Second, an in vivo ubiquitylation assay indicates conjugation of multi-Ub chain to the unstable core protein. In contrast, a stable form of core protein, p21, is also able to be ubiquitylated, but it links to a single or only a few Ub moiety. Therefore, processing event(s) at the C-terminal hydrophobic domain of HCV core protein may affect the ubiquitylation pathway, particularly the efficiency of the multi-Ub chain assembly, resulting in stable, matured core proteins.

Binding Sites↗

Characterization of cell-surface determinants important for baculovirus infection.

Baculovirus gp64 envelope glycoprotein is a major component of the envelope of the budded virus and is involved in virus entry into the host cells by endocytosis. To investigate the cell-surface molecules important for infection of baculovirus into mammalian cells, we constructed a recombinant baculovirus, Ac64-CAluc, which has gp64 and luciferase genes under the polyhedrin and the CAG promoter, respectively. For controls, we constructed recombinant viruses possessing vesicular stomatitis virus (VSV) G protein, mouse hepatitis virus (MHV) S protein, or green fluorescent protein (GFP) gene under the polyhedrin promoter and the luciferase gene under the CAG promoter (AcVSVG-CAluc, AcMHVS-CAluc, and AcGFP-CAluc). Treatment of HepG2 cells with phospholipase C markedly reduced the reporter gene expression by Ac64-CAluc or AcVSVG-CAluc in a dose-dependent manner, whereas AcMHVS-CAluc was shown to be resistant to the treatment. Inhibition with purified lipids and susceptibility to the mutant CHO hamster cell lines deficient in phospholipids synthesis suggest that the interaction of gp64 and phospholipids on the cell surface might play an important role in baculovirus infection into mammalian cells.

Animals↗

Biological characteristics of neuroblastoma with partial deletion in the short arm of chromosome 1.

BACKGROUND: Neuroblastoma shows remarkable heterogeneity, resulting in favorable and unfavorable outcomes. It is well known that almost all cases with MYCN amplification have a poor prognosis. We have previously reported that unfavorable tumors show high telomerase activity, whereas favorable tumors show low or nil activity. We also found that the unfavorable neuroblastoma often have a loss of heterozygosity (LOH) at the MYCL locus. PROCEDURE: To clarify the biological and clinical profiles of tumors with genetic abnormalities of the short arm of chromosome 1, we performed deletion mapping on 1p on 92 neuroblastoma tissues and corresponding noncancerous samples obtained from 92 cases for 24 micro- or minisatellite loci. RESULTS: LOH was detected in at least one locus of 1p in 43 (47%) cases. All samples were classified into four groups according to the deleted pattern: interstitial deletion (group I, n = 20), short terminal deletion (group ST, n = 6), large terminal deletion (group LT, n = 17), and without detectable deletion (group N, n = 49). All group I cases, whose SRO (shortest region of overlap) was at 1p36.1-2, survived disease free, and none of them showed MYCN amplification or high telomerase activity except for one case. On the other hand, in group LT cases, who showed a large terminal deletion from D1S162 (1p32-pter), including the SRO of group 1, only 5 out of 17 have survived disease free, and 13 showed MYCN amplification or high telomerase activity. The six group ST cases showed small terminal deletion from 1p36.3 with modest prognosis, similar to the group N. CONCLUSIONS: Thus, we propose three loci, 1p36.1-2, 1p32-34, and 1p36.3, as the candidate loci of neuroblastoma suppressor genes on chromosome 1p responsible for groups I, LT, and ST, respectively. Among them, the 1p32-34 locus may be associated with aggressiveness of tumor progression, possibly due to MYCN amplification and/or telomerase reactivation, while the remaining two loci may not.

Adult↗

Kupffer cell function in ischemic and nonischemic livers after hepatic partial ischemia/reperfusion.

Hepatic partial ischemic/reperfusion (I/R) injury, in which ischemic and nonischemic areas of the liver are likely to respond to each other after reperfusion, often occurs following hepatobiliary surgical procedures. Kupffer cells (KCs) are considered to play a major role in hepatic I/R injury. To study the activation of KCs in ischemic and nonischemic liver tissues following hepatic I/R, we investigated the superoxide generation and proinflammatory cytokine production of KCs in both liver parts in a rat model of partial hepatic I/R injury. KC superoxide generation in the ischemic and nonischemic lobes was upregulated 6 and 24 h after reperfusion, respectively, and then accelerated. The production of interleukin-1beta (IL-1beta) by KCs in the ischemic lobes increased during the early and late phases, 6 h and 48-72 h after reperfusion, respectively. A late increase in IL-1beta production was also observed in the nonischemic lobes. Production of tumor necrosis factor-alpha (TNF-alpha) increased 6-24h after reperfusion in both lobes. Upregulation of IL-1beta mRNA in the ischemic lobes preceded the upregulation of TNF-alpha mRNA in both lobes. The hepatic partial I/R process results in activation of KCs in ischemic and nonischemic areas of the liver. The KCs are activated during the early phase after reperfusion in the ischemic areas, followed by activation in both the ischemic and nonischemic areas. This could be a cause of liver dysfunction after partial hepatic I/R during surgery.

Animals↗

Clinical implication of orbital ultrasound monitoring during selective cerebral perfusion.

BACKGROUND: We evaluated clinical relevance of orbital ultrasound (OUS) monitoring to neurological events in aortic surgery associated with selective cerebral perfusion (SCP). METHODS: In 24 consecutive cases, blood flow was monitored at central retinal artery (CRA) and retrobulbar vessels. The threshold perfusion pressure for detecting CRA flow in the color Doppler mode (BPt) was determined in individual eyes. RESULTS: The BPt ranged from 25 to 71 mm Hg. Events (infarction, anisocoria, delirium) occurred in 8 cases. Infarction occurred in all 3 cases when retrobulbar flow was severely impaired for 40 minutes or longer, while none of the remaining 21 cases had infarction (p = 0.0005). Among the latter cases, perfusion pressure was below BPt for longer than 100 minutes in all 5 cases with events, and in 5 of 16 cases without events (p = 0.0124). No significant difference was found in age, duration of cardiopulmonary bypass, SCP, and circulatory arrest, and duration of blood pressure below 50 mm Hg. CONCLUSIONS: Sustained hypoperfusion detected with OUS monitoring is related to an occurrence of neurological events.

Aged↗

Clinical analysis of results of a simple left atrial procedure for chronic atrial fibrillation.

BACKGROUND: We have performed a simple left atrial procedure for eliminating chronic atrial fibrillation (AF) associated with mitral valve disease. This article analyzes the midterm results of this procedure. METHODS: Thirty-two patients were enrolled in this study concomitant with mitral valve operations. Patients were divided into two groups (AF- and AF+). We examined the efficacy of this operation and atrial function for more than 12 months of follow-up. RESULTS: In a total of 98.5 patient years of follow-up, AF was absent 3 years after operation in 74%. Of preoperative and intraoperative variables, only long duration o

Aged↗

Cardiac papillary fibroelastoma on the pulmonary valve: a rare cardiac tumor. okaken@mcai.med.hiroshima-u.ac.jp.

We report the case of a patient with a rare papillary fibroelastoma on the pulmonary valve visualized before surgical intervention. The tumor was an encapsulated, rounded mass. The gelatinous membrane on the surface tore easily, and multiple fronds appeared. This case emphasizes that when there is an encapsulated mass attached to a valve, the initial excision of valve tissue should be as minimal as possible. To avoid unnecessary injury to the valve, it is simple and practical to confirm that the tumor has the appearance of a sea anemone, thus identifying it as a papillary fibroblastoma, a benign tumor.

Aged↗

Endovascular stent-grafting via the aortic arch for distal aortic arch aneurysm: an alternative to endovascular stent-grafting.

OBJECTIVE: We have experienced transaortic stent-grafting for treating distal arch aneurysm or type B dissection. This paper is to mainly report the surgical aspect of these procedures. METHODS: Fifteen patients underwent this surgery, including 12 men and three women ranging from 47 to 83 years. Twelve had aneurysms and three aortic dissection. Concomitant surgery was necessary in seven patients (coronary artery bypass grafting in five, tricuspid annuloplasty in one, and replacement of ascending aorta and/or total arch replacement in three cases). A stent graft (Gianturco Z-stent and Intervascular prosthesis) was loaded in a 30-F sheath catheter. Under circulatory arrest, selective cerebral perfusion was established, and the sheath catheter was inserted through aortotomy into descending aorta and the stent graft was deployed at an appropriate level. The proximal end of graft was sutured to the aorta just distal to the left subclavian artery with inclusion method at the posterior wall. Concomitant surgery was done during cooling or rewarming period. TEE was utilized to visualize every endovascular manipulation to avoid unintended intimal injury or misplacement of graft and to assess the surgical results in the operative theater. RESULTS: Aneurysm was successfully excluded except in one patient who had a proximal endoleak and distal endoleak due to underestimation of aortic diameter. There was one operative mortality caused by cerebral infarction, possibly due to debris from femoral arterial cannulation. In the remaining patients, there was no enlargement of residual aneurysm. The excluded aneurysmal sac gradually regressed and disappeared within 2 years in five patients and the thrombosed false lumen completely shrunk within 1 year in two patients. One patient had paraplegia, possibly because the graft was intentionally advanced deeply to cover the thick and fragile atheromatous layer in order to avoid destruction of the atheroma by an expanded graft. CONCLUSIONS: Endovascular stent graft via the aortic arch is an acceptable treatment for distal arch aneurysms close to or involving left subclavian artery or type B dissections, especially for those cases requiring other cardiac procedures. It can lead to regression and disappearance of aneurysm or dissection in the mid-term follow-up.

Aged↗

ik3-1/Cables is a substrate for cyclin-dependent kinase 3 (cdk 3).

p70ik3-1 (a 70-kDa protein) contains a cyclin box, and binds to p35cdk3 in vivo and in vitro [Matsuoka, M., Matsuura, Y., Semba, K. & Nishimoto, I. (2000) Biochem. Biophys. Res. Commun. 273, 442-447]. In spite of its structural similarity to cyclins, p70ik3-1 does not activate cyclin-dependent kinase 3 (cdk3)-mediated phosphorylation of pRb, histone H1, or the C-terminal domain of RNA polymerase II. Here, we report that Ser274 of p70ik3-1 is phosphorylated by cdk2 or cdk3 bound to cyclin A and to cyclin E in vitro. We also found that in COS7 cells in which cyclin E and cdk3 were ectopically overexpressed, the phosphorylation level of Ser274 in coexpressed p70ik3-1 is upregulated. We therefore conclude that p70ik3-1 is a substrate for cdk3-mediated phosphorylation.

Animals↗

Identification of immunodominant hepatitis C virus (HCV)-specific cytotoxic T-cell epitopes by stimulation with endogenously synthesized HCV antigens.

Hepatitis C virus (HCV)-specific CD8(+) cytotoxic T lymphocytes (CTL) are believed to play an important role in the pathogenesis of liver cell injury and viral clearance in HCV infection. Because HCV does not efficiently infect human cells in vitro and primary infected hepatocytes cannot be used as stimulator/target cells for CTL analysis, development of efficient systems to activate and expand CTL in vitro, reproducing antigen presentation to CTL occurring during natural infection, is mandatory to study CTL activity and to define the hierarchy of immunodominance of CTL epitopes. To achieve this goal, 5 different defective adenoviruses carrying structural and nonstructural HCV genes (core, core-E1-E2, E2, NS3-NS4A, NS3-NS5A) were used to induce the endogenous synthesis of HCV proteins in human adherent mononuclear cells in vitro and to allow their entry into the HLA class I cytosolic pathway of antigen processing. The cytolytic activity of peripheral blood lympho-mononuclear cells (PBMC) from HLA-A2(+) HCV-infected patients stimulated with recombinant adenovirus-infected cells was tested against target cells either pulsed with a panel of synthetic peptides containing the HLA-A2 binding motif or infected with recombinant vaccinia viruses carrying HCV genes. Our study defines a reproducible system to stimulate and expand HCV-specific CTL in vitro that mimics the conditions of antigen encounter in vivo. By this approach, we have identified several HLA-A2-restricted epitopes that should correspond to immunodominant HCV sequences recognized by CTL during natural infection. Therefore, these amino acid sequences represent ideal candidates for the design of therapeutic vaccines for chronic HCV infection.

Adenoviridae↗

Demonstration of the pH sensitive binding of multivalent carbohydrate ligands to immobilized Shiga-like toxin 1 B subunits.

The cytotoxic effects of Shiga-like toxins from enterohemorrhagic Escherichia coli O157:H7 depend on the recognition of carbohydrate determinants by B subunits. As a specific carbohydrate ligand, globotriaosylceramide has been characterized. We developed an alternative binding assay using multivalent carbohydrate ligands. We prepared globotriose-conjugated poly-lysine, and measured their binding to immobilized recombinant B subunits by an ELISA format. The signals representing ligand binding were dependent on the amount of immobilized B subunits as well as on the concentration of the ligands. The ligand binding activity was lost in an acidic environment, in which changes in the local conformation of the B subunits have been reported. Furthermore, pH dependent dissociation of the ligands from the B subunits was observed. We also demonstrate that antiserum from mice immunized with the B subunits specifically interferes with ligand binding. This suggests further potential for an assay to screen for blocking antibodies that could inhibit toxin internalization into host cells.

Animals↗

Glassy cell carcinoma of the uterine cervix: combination chemotherapy with paclitaxel and carboplatin in recurrent tumor.

Combination chemotherapy with paclitaxel and carboplatin every 4 weeks for 3 cycles was administered for recurrent glassy cell carcinoma of the uterine cervix in a 67-year-old Japanese female. The response rate was 56% under computed tomography (partial response). However, the effect was transient even with follow-up radiotherapy, and further cases need to be accumulated to determine a successful treatment modality.

Aged↗