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Biomedical subjects

Y Muraki

Publications and source records attributed to Y Muraki.

At least 19 recordsLinked to original sources

Discovery of a cool planet of 5.5 Earth masses through gravitational microlensing.

In the favoured core-accretion model of formation of planetary systems, solid planetesimals accumulate to build up planetary cores, which then accrete nebular gas if they are sufficiently massive. Around M-dwarf stars (the most common stars in our Galaxy), this model favours the formation of Earth-mass (M(o)) to Neptune-mass planets with orbital radii of 1 to 10 astronomical units (au), which is consistent with the small number of gas giant planets known to orbit M-dwarf host stars. More than 170 extrasolar planets have been discovered with a wide range of masses and orbital periods, but planets of Neptune's mass or less have not hitherto been detected at separations of more than 0.15 au from normal stars. Here we report the discovery of a 5.5(+5.5)(-2.7) M(o) planetary companion at a separation of 2.6+1.5-0.6 au from a 0.22+0.21-0.11 M(o) M-dwarf star, where M(o) refers to a solar mass. (We propose to name it OGLE-2005-BLG-390Lb, indicating a planetary mass companion to the lens star of the microlensing event.) The mass is lower than that of GJ876d (ref. 5), although the error bars overlap. Our detection suggests that such cool, sub-Neptune-mass planets may be more common than gas giant planets, as predicted by the core accretion theory.

Journal Article↗

Successful nonsurgical management of perforation complicating endoscopic submucosal dissection of gastrointestinal epithelial neoplasms.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is a novel technique used for the treatment of gastrointestinal neoplasia. One of its major limitations, however, is the complication of perforation. PATIENTS AND METHODS: We included in our study all the cases of perforation that occurred during ESD procedures for gastrointestinal epithelial neoplasia between February 2000 and February 2005. Clinical outcomes after perforation were investigated. RESULTS: Perforation was experienced at 27 lesions in 27 patients (four in the esophagus, fourteen in the stomach, seven in the colon, and two in the rectum). Fibrosis under the lesions was confirmed histologically in seven patients (26 %). Immediate closure using endoclips was performed in all patients except for three asymptomatic patients in whom a stomach perforation was first noticed when free air was noticed on a radiograph the morning after the ESD procedure. Air accumulation was detected radiographically in 21 patients (78 %). The mean duration of antibiotic treatment was 6.7 days and the patients were fasted for a mean period of 5.3 days. The mean maximum body temperature was 37.3 degrees C, the mean white blood cell count was 9733/mm3, and the mean C-reactive protein level was 5.0 mg/dl. All the patients were discharged well from the ward after a mean time of 12.1 days after ESD, and no recurrence caused by tumor spread from the perforation occurred in any patient after a median follow-up period of 36 months (range 9 - 52 months). CONCLUSION: Successful nonsurgical management after ESD complicated by perforation is a highly feasible option if intensive conservative treatments are used following immediate endoscopic closure of the perforation.

Aged↗

A learning curve for endoscopic submucosal dissection of gastric epithelial neoplasms.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) has become a widely accepted method for treating gastrointestinal neoplasms. The objective of our study was to assess the learning curve for ESD of gastric epithelial neoplasms. PATIENTS AND METHODS: Clinicopathological data were retrospectively collected from 383 ESD procedures for gastric epithelial neoplasms that were performed over a 5-year period. Thirteen endoscopists were involved as operators during this period. In study 1, the performance of the two principal operators was assessed every 25 patients. In study 2, the performance of all 13 operators was assessed according to their experience. RESULTS: In study 1, the caseloads of the two principal operators were 188 and 118 ESD procedures. There were no significant differences found between successive groups of 25 patients with regard to en-bloc resection rate and bleeding and perforation complication rates. The size of the lesions and the resected specimen diameter increased significantly as the number of treated cases increased, whereas the average procedure time decreased significantly. In study 2, the operators' caseloads ranged from 1 to 188 cases, with 11/13 operators having experience of fewer than 30 cases. There was no significant difference in treatment efficacy and complication rates between the operators throughout the study period. The lesions were mainly located in the lower part of the stomach in the procedures performed by the 11 less experienced endoscopists. The procedure times shortened as experience in the method increased. CONCLUSIONS: Constant rates of both treatment efficacy and complications were achieved over a 5-year period of experience with ESD. A decrease in procedure time was found to be a marker of proficiency in this technique.

Clinical Competence↗

Ex-vivo study of high-magnification chromoendoscopy in the gastrointestinal tract to determine the optimal staining conditions for endocytoscopy.

BACKGROUND AND STUDY AIMS: Endocytoscopy allows the observation of living cells in the gastrointestinal tract. Consistently clear views are essential for clinical application of the technique, but these are not always obtained. The aim of this study was to determine an appropriate staining regimen for endocytoscopy. MATERIALS AND METHODS: This was an ex-vivo animal study in which we stained freshly resected porcine esophagus, stomach, and colon with different concentrations of three dyes (1%, 0.5%, and 0.25% crystal violet; 5%, 2.5%, and 1% methylene blue; and 1%, 0.5%, and 0.25% toluidine blue) and assessed them after different exposure times (10 seconds, 30 seconds, 60 seconds, and 90 seconds). The images obtained were evaluated according to the staining status of the cytoplasm and the nucleus, and the contrast between the cytoplasm and the nuclei, and the optimal staining conditions for each organ were determined. Additionally, freshly resected human esophagus, stomach, and colon tissues were tested under the dye/exposure conditions that were found to be the most appropriate in the animal study. RESULTS: After intensive mucus removal, high-quality images were obtained using methylene blue and toluidine blue. The optimum conditions for endocytoscopic observation were obtained after staining with 1% methylene blue in the esophagus and with 0.25% toluidine blue in the stomach and the colon, after 60 seconds of exposure to the dye. This was confirmed in the human specimens. CONCLUSIONS: This study provides important information on appropriate staining conditions for endocytoscopy. Further ex-vivo and in-vivo studies are necessary before this technique comes into standard use, however.

Animals↗

Association of mannose binding lectin (MBL) gene polymorphism and serum MBL concentration with characteristics and progression of systemic lupus erythematosus.

OBJECTIVE: To determine whether occurrence, characteristics, and progression of systemic lupus erythematosus (SLE) are associated with polymorphism of the mannose binding lectin (MBL) gene and with serum MBL concentration. METHODS: Codon 54 MBL gene polymorphism of 147 patients with SLE and 160 healthy controls was determined by polymerase chain reaction-restriction fragment length polymorphism. Serum concentration of MBL was measured by enzyme immunoassay. Fluctuations of serum MBL were analysed with respect to disease characteristics and activity. RESULTS: Frequency of homozygosity for codon 54 minority allele was 6% (9/147) in patients with SLE, and significantly higher than in controls (p = 0.0294, Fisher's exact test). MBL polymorphism in patients with SLE was not significantly associated with disease characteristics or immunological phenotypes. Patients homozygous for the B allele tended to have a higher risk of infection during treatment. Levels of C3 and CH(50) were slightly, but significantly, associated with serum MBL concentration in patients with SLE homozygous for the majority allele. During the course of SLE, serum MBL concentration increased in 6/14 patients, and decreased in 7 after initiation of immunosuppressive treatment. CONCLUSIONS: MBL gene polymorphism influences susceptibility to SLE, but has no direct effect on disease characteristics. Serum MBL levels fluctuate during the course of SLE in individual patients. MBL genotyping may be useful in assessing the risk of infection during treatment of SLE.

Adolescent↗

Search for low-mass exoplanets by gravitational microlensing at high magnification.

Observations of the gravitational microlensing event MOA 2003-BLG-32/OGLE 2003-BLG-219 are presented, for which the peak magnification was over 500, the highest yet reported. Continuous observations around the peak enabled a sensitive search for planets orbiting the lens star. No planets were detected. Planets 1.3 times heavier than Earth were excluded from more than 50% of the projected annular region from approximately 2.3 to 3.6 astronomical units surrounding the lens star, Uranus-mass planets were excluded from 0.9 to 8.7 astronomical units, and planets 1.3 times heavier than Saturn were excluded from 0.2 to 60 astronomical units. These are the largest regions of sensitivity yet achieved in searches for extrasolar planets orbiting any star.

Journal Article↗

Characterization of antigenically and genetically similar influenza C viruses isolated in Japan during the 1999-2000 season.

Between October 1999 and May 2000, a total of 28 strains of influenza C virus were isolated in four Japanese prefectures: Yamagata, Miyagi, Saitama and Hiroshima. Antigenic analysis showed that the 28 isolates were divided into three distinct antigenic groups, and viruses belonging to different antigenic groups were co-circulating in each of the four prefectures. Phylogenetic analysis of the seven protein genes demonstrated that the viruses having a similar genome composition spread in various areas of Japan during the same period. Furthermore, phylogenetic analysis showed that most of the influenza C viruses isolated in various areas of the world between the 1970s and 1980s were closely related to the contemporary Japanese viruses in all gene segments. These observations suggest that the influenza C viruses cause epidemics in some communities during the same season and that antigenically and genetically similar influenza C viruses spread throughout Japan and may be circulating worldwide.

Adolescent↗

Detection of ion channel activity in Xenopus laevis oocytes expressing Influenza C virus CM2 protein.

To demonstrate the ion channel activity of Influenza C virus CM2, we expressed this protein in oocytes of Xenopus laevis and measured whole cell currents by a two-electrode voltage-clamp method. It was found that the inward currents were induced upon hyperpolarizing the oocyte membranes. The amplitude of the currents increased slowly with time during the hyperpolarizing pulse, and the current-voltage relationship was nonlinear, having a slope that increased with the level of hyperpolarization. These results suggest strongly that CM2 forms a voltage-activated ion channel. The current amplitude was increased to a small extent by lowering the external pH. We also found that the anti-influenza A virus drug amantadine hydrochloride failed to attenuate the inward currents of CM2-expressing oocytes induced by hyperpolarization. The reversal voltage of tail currents was affected by the reduction of [Cl-], but neither by the change of [Na+] nor by that of [K+]. Furthermore, the amplitude of the inward currents was decreased by an anion channel blocker. The data presented here suggest that CM2 protein forms a voltage-activated ion channel permeable to chloride ion.

Animals↗

Biochemical properties of the P42 protein encoded by RNA segment 6 of influenza C virus.

P42, encoded by a colinear transcript of Influenza C virus RNA segment 6 (M gene), is an integral membrane protein which is cleaved by signal peptidase to generate M1' and CM2 composed of N-terminal 259 amino acids and C-terminal 115 amino acids, respectively. Herein, the biochemical features of P42 were investigated. N-glycosylated form of P42, designated P44, forms disulphide-linked dimers and tetramers. P44 is transported to the Golgi apparatus, but not to the trans-Golgi, since P44 is completely sensitive to endoglycosidase H. P44 and P42 are unstable irrespective of N-glycosylation or oligomerization. 26S proteasome inhibitor, lactacystin prevented the degradation of P42 as well as M1', but not that of P44 efficiently, suggesting that P44 is degraded by another protease besides the 26S proteasome.

Animals↗

Frequent reassortment among influenza C viruses.

In a 9-year survey from December 1990 to December 1999 in Sendai City, Japan, we succeeded in isolating a total of 45 strains of influenza C virus. These 45 strains were isolated in clusters within 4 months in a year, especially from winter to early summer. Previous studies of the hemagglutinin-esterase genes of various influenza C virus isolates revealed the existence of five distinct virus lineages (Aichi/1/81-, Yamagata/26/81-, Mississippi/80-, Sao Paulo/82-, and Kanagawa/1/76-related lineage) in Japan between 1970 and the early 1990s (Y. Matsuzaki, K. Mizuta, H. Kimura, K. Sugawara, E. Tsuchiya, H. Suzuki, S. Hongo, and K. Nakamura, J. Gen. Virol. 81:1447-1452, 2000). Antigenic and genetic analyses of the 45 strains showed that they could be divided into these five virus lineages and a few antigenic groups were cocirculating in Sendai City. In 1990 and 1991 the dominant antigenic group was the Aichi/1/81 virus group, and in 1992 it was Yamagata/26/81 virus group. The Mississippi/80 virus group was isolated from 1993 to 1996, and the Yamagata/26/81 virus group reemerged in 1996 and continued to circulate until 1999. This finding led us to a speculation that the replacement of the dominant antigenic groups had occurred by immune selection within the human population in the restricted area. Phylogenetic analysis of seven RNA segments showed that 44 viruses among the 45 strains isolated in our surveillance work were reassortant viruses that have various genome compositions distinguishable from those of the reference strains of the each lineage. This observation suggests that the reassortment between two different influenza C virus strains occurs frequently in nature and the genome composition of influenza C viruses may influence their ability to spread in humans.

Antigens, Viral↗

The acceleration of cosmic-ray protons in the supernova remnant RX J1713.7-3946.

Protons with energies up to approximately 10(15) eV are the main component of cosmic rays, but evidence for the specific locations where they could have been accelerated to these energies has been lacking. Electrons are known to be accelerated to cosmic-ray energies in supernova remnants, and the shock waves associated with such remnants, when they hit the surrounding interstellar medium, could also provide the energy to accelerate protons. The signature of such a process would be the decay of pions (pi(0)), which are generated when the protons collide with atoms and molecules in an interstellar cloud: pion decay results in gamma-rays with a particular spectral-energy distribution. Here we report the observation of cascade showers of optical photons resulting from gamma-rays at energies of approximately 10(12) eV hitting Earth's upper atmosphere, in the direction of the supernova remnant RX J1713.7-3946. The spectrum is a good match to that predicted by pion decay, and cannot be explained by other mechanisms.

Journal Article↗

Antigenic and genetic characterization of influenza C viruses which caused two outbreaks in Yamagata City, Japan, in 1996 and 1998.

During the 3 years from January 1996 to December 1998, a total of 33 strains of influenza C virus were isolated from 10,726 throat swab specimens collected from children with acute respiratory illness who visited two pediatric clinics in Yamagata City, Japan. These 33 strains were isolated in clusters during two different periods, 20 strains in May to August 1996 and the remaining 13 in March to June 1998. Antigenic analysis with monoclonal antibodies to the hemagglutinin-esterase (HE) glycoprotein and phylogenetic analysis of seven RNA segments showed that the 33 influenza C viruses isolated were antigenically and genetically similar and that they were reassortant viruses which had obtained PB2, PB1, HE, M, and NS genes from a C/pig/Beijing/115/81-like virus and P3 and NP genes from a C/Mississippi/80-like virus. These observations suggest strongly that during the survey period of 3 years, two outbreaks of influenza C occurred in Yamagata City, both of which were caused by a reassortant virus having the genome composition described above.

Adolescent↗

Role of individual oligosaccharide chains in antigenic properties, intracellular transport, and biological activities of influenza C virus hemagglutinin-esterase protein.

The hemagglutinin-esterase (HE) glycoprotein of influenza C virus is composed of three domains: a stem domain active in membrane fusion (F), an acetylesterase domain (E), and a receptor-binding domain (R). The protein contains eight N-linked glycosylation sites, four (positions 26, 395, 552, and 603) in the F domain, three (positions 61, 131, and 144) in the E domain, and one (position 189) in the R domain. Here, we investigated the role of the individual oligosaccharide chains in antigenic properties, intracellular transport, and biological activities of the HE protein by eliminating each of the glycosylation sites by site-specific mutagenesis. Comparison of electrophoretic mobility between the wild-type and the mutant proteins showed that while seven of the glycosylation sites are used, one (position 131) is not. Analysis of reactivity of the mutants with anti-HE monoclonal antibodies demonstrated that glycosylation at position 144 is essential for the formation of conformation-dependent epitopes. It was also evident that glycosylation at the two sites in the F domain (positions 26 and 603), in addition to that in the E domain (position 144), is required for the HE molecule to be transported from the endoplasmic reticulum and that mutant HEs lacking one of these three sites failed to undergo the trimer assembly. Removal of an oligosaccharide chain at position 144 or 189 resulted in a decrease in the esterase activity. By contrast, two mutants lacking an oligosaccharide chain at position 26 or 603, which were defective not only in cell surface expression but in trimerization, possessed full-enzyme activity, suggesting that the HE monomers present within the cell have acetylesterase activity. Fusion activity of cells expressing each of mutant HEs was found to be comparable with the ability of the protein to be transported to the cell surface, suggesting that there is no specific oligosaccharide chain that plays a critical role in promoting membrane fusion.

Acetylesterase↗

Antigenic and genetic analyses of influenza B viruses isolated in Lusaka, Zambia in 1999.

Previous studies of the hemagglutinin (HA) genes of various influenza B virus isolates demonstrated the existence of two antigenically distinct virus lineages represented by B/Victoria/2/87 and B/Yamagata/16/88, respectively. Here, we investigated the antigenic and genetic characteristics of influenza B viruses isolated from children living in Lusaka, Zambia between January and May 1999. Antigenic analysis with chicken antiviral sera showed that all the Zambian isolates had the HA protein belonging to B/Yamagata/16/88-related lineage. Furthermore, phylogenetic analyses of the eight RNA segments performed by using the total or partial nucleotide sequences of the two representative Zambian strains (B/Lusaka/270/99 and B/Lusaka/432/99) as well as the previously reported sequences suggested that the Zambian viruses are closely related to the recently circulating reassortants represented by B/Shiga/T30/98 and B/Yamanashi/166/98 which acquired the genes coding for three polymerase proteins (PB2, PB1, and PA), HA, nucleoprotein, and matrix protein from a B/Yamagata/16/88-like parent and the gene encoding nonstructural proteins (NS1 and NS2) from a B/Guandong/8/93-like parent.

Animals↗

Development of the fiber neutron monitor for the energy range 15-100 MeV on the International Space Station (ISS).

In order to investigate the space environment, a new neutron monitor has been prepared. The sensor consists of scintillation fibers (FIB) and will be on board the exposed facility of the Japanese Experimental module (Kibo) of the International Space Station (ISS). The sensor is one of the instruments which measures the particle and plasma environment around the ISS. The sensor will be used by the cosmonauts who work on the ISS, to help them avoid a strong particle radiation which may arrive soon. We believe that such an alert is necessary for the cosmonauts to prevent unnecessary radiation from the sun. Furthermore, the sensor will be very useful in understanding the particle acceleration mechanism at the solar surface. The design of the Engineering Model (EM) was finished and its properties were investigated. This report discusses these results.

Equipment Design↗

Inhibitory effect of statins on fetal bovine serum-induced proliferation of rat cultured mesangial cells and correlation between their inhibitory effect and transport characteristics.

Mesangial cells play an important role in physiologic functions, including the regulation of glomerular filtration, and as a pathogenic factor for proliferative glomerulonephritis. We compared the potencies of the inhibitory effects of simvastatin acid, lovastatin acid, and pravastatin on fetal bovine serum (FBS)-induced proliferation of rat cultured mesangial cells, and examined the correlation between their inhibitory effects and intracellular concentrations. We also investigated the transport of the statins in the cells, and whether or not their intracellular concentrations were determined by their transport characteristics. It appeared that the growth inhibitory effects on FBS-induced proliferation of mesangial cells of simvastatin acid and lovastatin acid were approximately the same, but that of pravastatin was extremely weak compared with the others. The growth inhibitory effects of these agents were suggested to depend, at least in part, on the amount incorporated intracellularly. Simvastatin acid, lovastatin acid, and pravastatin appeared to be taken up by mesangial cells via a common carrier, the uptake capacity being determined by their lipophilicity. Therefore, it was thought that the growth inhibitory effects of the statins partially depended on their carrier-mediated uptake by mesangial cells.

Animals↗

Fas expression and Fas monoclonal antibody-induced apoptosis in a human squamous cell carcinoma cell line, SCC-25.

Fas antigen is a cell surface protein that mediates apoptosis via signal transduction from the plasma membrane. Using reverse transcriptase-polymerase chain reaction (RT-PCR), messenger RNA for Fas antigen was detected in the human oral squamous cell carcinoma cell line, SCC-25. In serum-free medium, a monoclonal anti-Fas antibody (CH-11) induced Fas antigen expression in SCC-25 cells, as determined by immunocytochemistry and Western blotting, using an anti-Fas polyclonal antibody (Fas D) as primary antibody. Fas antigen was localized to the cytoplasm and the cell membrane. The molecular weight of the protein recognized by Western blot analysis was 35,000, consistent with the value reported for the Fas antigen. The CH-11 antibody did not induce Fas antigen expression in serum-containing medium. To determine whether CH-11 could induce apoptosis in oral squamous cell carcinoma, we examined its effects on the survival of cultured SCC-25 cells. Anti-Fas monoclonal antibody in serum-free medium induced cytotoxicity in SCC-25 cells in a time-dependent manner up to 8 h, as determined by phase-contrast microscopy and WST-1 assay. Marked nuclear condensation and fragmentation of chromatin were observed in the CH-11-treated cells using Hoechst 33342 staining. This anti-Fas monoclonal antibody also induced DNA ladder formation in SCC-25 cells in a time-dependent manner. The present results indicate that the anti-Fas monoclonal antibody (CH-11) may mediate apoptosis by binding to the Fas antigen expressed in SCC-25 cells.

Antibodies, Monoclonal↗

Fas antigen expression and outcome of oral squamous cell carcinoma.

Paraffin sections of biopsy specimens obtained from 46 patients with oral squamous cell carcinomas were stained with both anti-peptide antibody against human Fas antigen and monoclonal mouse antibody against human proliferating cell nuclear antigen (PCNA). The patients received chemotherapy with a combination of carboplatin and peplomycin sulfate or mitomycin C and peplomycin sulfate before surgery. The relation between the expression of Fas antigen and the clinical features of each case was examined. The correlation between PCNA and Fas antigen expression was also studied. The mean PCNA labeling index of the 22 Fas-negative cases was 46.9%, which was significantly higher than that of the 24 Fas-positive cases (39.5%). Strong correlations were found between the expression of Fas antigen and the response to chemotherapy, tumor recurrence, and survival. The Fas-negative group had only a minor response to chemotherapy and a poor outcome, whereas the Fas-positive group had a better response to chemotherapy and a good outcome. Although lymph node metastasis was significantly related to survival, there was no correlation between Fas antigen expression and lymph node metastasis. The Kaplan-Meier survival curve of patients positive for Fas antigen was significantly better than that of patients negative for Fas antigen. Our results suggest that Fas antigen expression is an independent predictor of outcome whose usefulness should be evaluated in prospective studies.

Actuarial Analysis↗