PubMed Health⌕ Search

Biomedical subjects

Masahiro Kimura

Publications and source records attributed to Masahiro Kimura.

At least 19 recordsLinked to original sources

Novel transparent nano- to micro-heterogeneous substrates for in-situ cell migration study.

Transparent substrates having heterogeneities ranging from nanometer to micrometer lateral length scale were fabricated to study cell migration. The surfaces were generated using thin films of block copolymers and homopolymer blends on ultra smooth transparent polyethylene terephthalate films. Results show that the lateral size scale of the surface heterogeneities affects fibroblast (NIH-3T3) adhesion, spreading and motility. More specifically, fibroblasts migrate faster on micron-sized than on nanometer-sized heterogeneities. Cell movements and morphology on the micron patterned surfaces resemble cells cultured in a 3D environment. These surfaces, therefore, can potentially be utilized as models to study cell behavior in physiologically relevant conditions which can add to our fundamental understanding of cell-substrate interactions and facilitate development of surfaces for medical devices.

3T3 Cells↗

A novel gene, RSRC2, inhibits cell proliferation and affects survival in esophageal cancer patients.

In Japan and China, esophageal cancer is common and more than 90% of esophageal cancers are squamous cell carcinoma. Esophageal squamous cell carcinoma (ESCC) shows a poor prognosis, but the mechanism of ESCC and target genes for treatment remains unclear. We searched for genes related to ESCC, and identified a novel gene, FLJ11021, which was designated arginine/serine-rich coiled-coil 2 (RSRC2). We sought to determine the role of RSRC2 in the proliferation of esophageal cell lines and to examine the relationship between RSRC2 and clinicopathologic factors and ESCC prognosis. Expression of RSRC2 was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR) in 70 primary ESCCs and paired noncancerous esophageal mucosa. To determine the role of RSRC2 in ESCC cell proliferation, we used vector-based transfection and small interfering RNA methods. Our results show that RSRC2mRNA levels in all ESCC cell lines (TE1-15, excluding TE7) were lower than those in a human esophageal squamous epithelial cell line (Het-1A). Cell proliferation of an ESCC cell line was inhibited by overexpression of RSRC2, while reduced expression was accompanied by tumor progression. RSRC2 expression levels were significantly correlated with depth of invasion, lymph node metastasis, lymphatic invasion and vascular invasion. Moreover, ESCC patients with low RSRC2mRNA expression had significantly shorter post-operative survival time than those with high expression. In vitro study revealed that RSRC2 might play a role in cell proliferation. Our study demonstrated that RSRC2 expression may be a novel tumor suppressor of esophageal cancer cell growth and a prognostic factor in ESCC.

Aged↗

RNASEN regulates cell proliferation and affects survival in esophageal cancer patients.

PURPOSE: MicroRNAs (miRNA) are small noncoding RNAs thought to be involved in physiologic and developmental processes by negatively regulating the expression of target genes. Little is known about the role of miRNAs in normal and cancer cells. It is possible that deregulation of miRNA may contribute to the oncogenesis of some cancers. We studied the expression level of the miRNA processing enzyme (DICER1, DGCR8, and RNASEN) in esophageal squamous cell carcinoma (ESCC). EXPERIMENTAL DESIGN: The expression levels of DICER1, DGCR8, and RNASEN mRNA in 73 ESCC tissues were compared with that in corresponding normal esophageal epithelium by Taqman real-time reverse-transcription PCR. We also examined RNASEN protein expression in 27 cell lines. The role of RNASEN in cell proliferation in ESCC cells was assessed by small interfering RNA. Paraffin sections of ESCC patients were immunohistochemically investigated. RESULTS: We found that RNASEN expression levels were enhanced in a fraction of esophageal cancers. Multivariate Cox regression analysis showed that the prognostic effect of RNASEN (P = 0.0036) seems to be independent of disease stage (P = 0.0060). Knockdown of RNASEN in esophageal cancer cell lines resulted in a 46% to 85% reduction in cell number. In an immunohistochemical study, the intensity of RNASEN expression was often increased in the tumor compared with that in normal epithelium. CONCLUSIONS: The relationship between the RNASEN expression and the prognosis of the ESCC patients warrants a further study on the role of miRNA and tumor progression.

Adult↗

Expression and prognostic roles of PABPC1 in esophageal cancer: correlation with tumor progression and postoperative survival.

The prognosis of patients with esophageal cancer remains poor. TNM classification is not sufficient to predict their prognosis, and novel predictive markers of the prognosis of esophageal cancer patients are therefore needed. Poly A binding protein, cytoplasmic 1 (PABPC1) plays a role in post-transcriptional control of mRNA and may be involved in tumorigenesis. PABPC1 expression has not been studied in esophageal cancer. Expression of PABPC1 was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR) using LightCycler in 41 primary esophageal squamous cell carcinomas (ESCCs) and their paired normal esophageal mucosa. We examined the correlation between PABPC1 expression and the clinicopathological factors and prognosis of ESCC patients. Reduced expression of PABPC1 was accompanied by locally invasive tumors (t-factor, p=0.0145) and more advanced tumors (pathologic stage, p=0.0264). Moreover, ESCC patients with low PABPC1 mRNA expression had a significantly shorter postoperative survival time than those with high expression (median survival, 3.1 vs. 6.5 months, p=0.002). In esophageal cancer, reduced expression of PABPC1 was correlated with local tumor progression and poor prognosis after surgery.

Aged↗

Expression of ACP6 is an independent prognostic factor for poor survival in patients with esophageal squamous cell carcinoma.

ACP6 (acid phosphatase 6, lysophosphatidic) is a lysophosphatidic acid (LPA)-specific phosphatase that hydrolyzes LPA to monoacylglycerol and is involved in lipid metabolism in the mitochondria. Its role in oncogenesis and cancer progression has not been studied. In this study, we examined the expression of ACP6 mRNA and evaluated its clinical significance in esophageal squamous cell carcinoma (ESCC). Expression of ACP6 mRNA was quantified by real-time reverse transcription polymerase chain reaction using the LightCycler in 70 esophageal ESCC specimens and their paired normal esophageal mucosa. The data were analyzed with reference to clinicopathological factors. ACP6 mRNA expression in esophageal cancer tissue was significantly lower than that in corresponding normal esophageal mucosa (P=0.0301). Among the esophageal cancer tissues, ACP6 mRNA expression significantly correlated with local tumor invasion (T factor, P=0.0461) and lymph node metastasis (P=0.0128). Furthermore, low ACP6 mRNA expression was associated with a significantly shorter survival time compared with high expression (log-rank test, P=0.0358). In multivariate analysis, ACP6 mRNA expression emerged as a significant independent factor (P=0.0148). Impaired ACP6 expression may lead to more aggressive invasion of ESCC, and ACP6 mRNA expression level could be an independent prognostic factor for patients with ESCC.

Aged↗

Assignment of the gene for porcine insulin-like growth factor binding protein 1 to chromosome 18 and detection of polymorphisms in intron 2 by PCR-RFLP.

We have obtained a partial cDNA and three BAC clones for the porcine insulin-like growth factor binding protein 1 gene (IGFBP-1). Results of fluorescence in situ and radiation hybrid (RH) mapping assigned this gene to porcine chromosome (SSC) 18q24-qter. We found two types of polymerase chain reaction-restriction-fragment-length polymorphisms (PCR-RFLP) in intron 2 by using FokI and AluI.

Animals↗

Fibroblast adhesion to micro- and nano-heterogeneous topography using diblock copolymers and homopolymers.

Polymeric substrates of different surface chemistry and length scales were found to have profound influence on cell adhesion. The adhesion of fibroblasts on surfaces of oxidized polystyrene (PS), on surfaces modified with random copolymers of PS and poly(methyl methacrylate) [P(S-r-MMA)] with topographic features, and chemically patterned surfaces that varied in lateral length scales from nanometers to microns were studied. Surfaces with heterogeneous topographies were generated from thin film mixtures of a block copolymer, PS-b-MMA, with homopolymers of PS and PMMA. The two homopolymers macroscopically phase separated and, with the addition of diblock copolymer, the size scales of the phases decreased to nanometer dimensions. Cell spreading area analysis showed that a thin film of oxidized PS surface promoted adhesion whereas a thin film of P(S-r-MMA) surface did not. Fibroblast adhesion was examined on surfaces in which the lateral length scale varied from 60 nm to 6 microm. It was found that, as the lateral length scale between the oxidized PS surfaces decreased, cell spreading area and degree of actin stress fiber formation increased. In addition, scanning electron microscopy was used to evaluate the location of filopodia and lamellipodia. It was found that most of the filopodia and lamellipodia interacted with the oxidized PS surfaces. This can be attributed to both chemical and topographic surface interactions that prevent cells from interacting with the P(S-r-MMA) at the base of the topographic features.

Actins↗

Surface free energies of silica fillers and their relation to the adsorption of poly(ethylene terephthalate).

The surface free energy of modified silica as well as of PET oligomers was evaluated through measurements of specific retention volumes of several probe molecules by use of the adsorption and adhesion principles in inverse gas chromatography. The nondispersive component of surface free energy of most silica fillers was larger than the dispersive component and the acidic component was much larger than the basic one, which indicated that the surfaces of most silica fillers were rather acidic. These methods were also applied to PET oligomer and it was found that the surface free energy of PET oligomer, regardless of preparation method, consisted of an almost dispersive component, suggesting that the surface of PET was neutral. The amount of PET oligomer adsorbed for the heat-treated silica fillers in acidic solvent increased linearly with increased acidic component of the surface free energy, which indicates that the acidic component of the surface free energy may be responsible for the adsorption. However, the adsorption amount on modified silica is much smaller than that for the heat-treated silica fillers because of steric hindrance caused by the attached organic chain, suggesting that the adsorption cannot be determined only by the surface free energy.

Adsorption↗

Fabrication of a gradient heterogeneous surface using homopolymers and diblock copolymers.

The strength of the interfacial interactions and the length scale over which these interactions occur are key factors in understanding the thin film behavior of polymer blends and diblock copolymers, adhesion, wettability, and recognition processes of cells and random heteropolymers on surfaces. Here, gradient heterogeneous surface topographies were prepared using thin films of mixtures of homopolymers and diblock copolymers to vary the lateral size scale of heterogeneities from the microscopic to nanoscopic. Dewetting, phase separation, and cell adhesion were used to demonstrate the utility of these surfaces having gradient heterogeneous topographies. By tuning the lateral size scale of the heterogeneities, surface patterns can be engineered to meet a specific function. Gradient surfaces offer a straightforward method to optimize various length scales of heterogeneity.

Journal Article↗

Modeling of growing networks with directional attachment and communities.

In this paper, we propose a new network growth model and its learning algorithm to more precisely model such a real-world growing network as the Web. Unlike the conventional models, we have incorporated directional attachment and community structure for this purpose. We show that the proposed model exhibits a degree distribution with a power-law tail, which is an important characteristic of many large-scale real-world networks including the Web. Using real Web data, we experimentally show that predictive ability can be improved by incorporating directional attachment and community structure. Also, using synthetic data, we experimentally show that predictive ability can definitely be improved by incorporating community structure.

Algorithms↗

[Differential diagnosis of hepatitis: development of new laboratory tests for autoimmune hepatitis and progress in pathophysiology].

Liver dysfunction has been found in 8.1% of postpartum women in the general population. This dysfunction was speculated to be developed by postpartum aggravation of subclinical autoimmune hepatitis. Therefore, we developed two methods for detection of autoantibodies to liver-specific antigens: an ELISA for anti-liver-specific arginase antibodies, and a highly sensitive radioligand assay for anti-CYP2D6 antibodies. Basic examinations of dilution curve, inhibition study and reproducibility were satisfactory for clinical application in both assays. Anti-arginase antibodies and anti-CYP2D6 antibodies were found in 28.6% and 42.6% of patients with autoimmune hepatitis, respectively. There was no correlation between the two autoantibodies and thus, combined use of these antibodies detects 55.3% of autoimmune hepatitis. Autoimmune hepatitis exists frequently when we include mild cases.

Arginase↗

Excision repair cross complementing 3 expression is involved in patient prognosis and tumor progression in esophageal cancer.

The prognosis of patients with esophageal cancer remains poor. TNM classification is not sufficient to predict the prognosis. Therefore, novel predictive markers of the prognosis of esophageal cancer patients are awaited. The abnormality of the nucleotide excision repair (NER) is often involved in human cancers. Excision repair cross complementing 3 (ERCC3) contributes to NER. In esophageal cancer, ERCC3 expression has not been studied. Expression of ERCC3 was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR) using LightCycler in 43 primary esophageal squamous cell carcinomas (ESCCs) and their paired normal esophageal mucosa. We examined the correlation between the ERCC3 expression and the clinicopathological factors and prognosis of ESCC patients. ERCC3 expression level was significantly correlated with the pathologic stage, tumor size and local invasiveness (t-factor) in esophageal cancer tissues. Reduced expression of ERCC3 was accompanied with tumor progression (p=0.0049) and higher pathologic stage (p=0.020). Moreover, ESCC patients with low ERCC3 mRNA expression had significantly shorter post-operative survival time than those with high expression (p=0.0003). In esophageal cancer, reduced expression of ERCC3 was correlated with local tumor progression and poor prognosis after operation.

Aged↗

Effect of substituents on the thermal decomposition of diazirines: experimental and computational studies.

The thermal decomposition of phenylchlorodiazirine (1), phenyl-n-butyldiazirine (2), and 2-adamantane-2,3'-[3H]diazirine (3) has been studied in solution in the presence of C(60). The C(60) probe technique indicates that in the decomposition diazirine 1 yielded exclusively phenylchlorocarbene, diazirine 2 yielded mainly a diazo intermediate, and diazirine 3 yielded a mixture of carbene and diazo compound. In the case of diazirine 2, 13% of (E)-1-phenyl-1-pentene resulted from the direct thermal rearrangement of diazirine without the participation of a carbene. As well, the thermal decomposition of these diazirines has been studied theoretically with ab initio and density functional methods. The experimental results are broadly in agreement with the theoretical predictions. The calculations further indicate that the rebound reaction between carbene and molecular nitrogen leading to the formation of a diazo intermediate is an important reaction in the gas-phase decomposition of diazirine.

Journal Article↗

Adenosine A(1) receptor-mediated presynaptic inhibition at the calyx of Held of immature rats.

At the calyx of Held synapse in brainstem slices of 5- to 7-day-old (P5-7) rats, adenosine, or the type 1 adenosine (A1) receptor agonist N6-cyclopentyladenosine (CPA), inhibited excitatory postsynaptic currents (EPSCs) without affecting the amplitude of miniature EPSCs. The A1 receptor antagonist 8-cyclopentyltheophylline (CPT) had no effect on the amplitude of EPSCs evoked at a low frequency, but significantly reduced the magnitude of synaptic depression caused by repetitive stimulation at 10 Hz, suggesting that endogenous adenosine is involved in the regulation of transmitter release. Adenosine inhibited presynaptic Ca(2+) currents (IpCa) recorded directly from calyceal terminals, but had no effect on presynaptic K+ currents. When EPSCs were evoked by IpCa during simultaneous pre- and postsynaptic recordings, the magnitude of the adenosine-induced inhibition of IpCa fully explained that of EPSCs, suggesting that the presynaptic Ca(2+) channel is the main target of A1 receptors. Whereas the N-type Ca(2+) channel blocker omega-conotoxin attenuated EPSCs, it had no effect on the magnitude of adenosine-induced inhibition of EPSCs. During postnatal development, in parallel with a decrease in the A1 receptor immunoreactivity at the calyceal terminal, the inhibitory effect of adenosine became weaker. We conclude that presynaptic A1 receptors at the immature calyx of Held synapse play a regulatory role in transmitter release during high frequency transmission, by inhibiting multiple types of presynaptic Ca(2+) channels.

Adenosine↗

Non-existence of positive glitches in spectra using the YB(66) double-crystal monochromator of BL15XU at Spring-8.

YB(66) is suitable for dispersing synchrotron radiation in the 1-2 keV energy range with a 2d lattice spacing of 1.17 nm. When used with an undulator there are no positive glitches at 1385.6 and 1438 eV in spectra dispersed by a YB(66) 400 double-crystal monochromator as observed using bending-magnet or wiggler beamlines. The transmission function of a YB(66) double-crystal monochromator has been measured by means of a Si PIN photodetector, and X-ray absorption near-edge structure (XANES) of Mg, Al and Si were measured at high resolution. From all of these experiments it has been clarified that a YB(66) double-crystal monochromator is well suited for soft X-ray beamlines on third-generation light sources.

Journal Article↗

Successful unrelated cord blood transplantation in an infant with Wiskott-Aldrich syndrome following recurrent cytomegalovirus disease.

We describe successful unrelated cord blood transplantation in a 14-month-old boy with Wiskott-Aldrich syndrome. He had been suffering from recurrent cytomegalovirus (CMV) pneumonia. Ganciclovir was given pretransplantation and posttransplantation, and CMV antigenemia was monitored as a marker of reactivation. The conditioning regimen was cyclophosphamide, busulfan, and antithymocyte globulin. The patient received an HLA 1-locus-mismatched cord blood unit, and the total number of infused nucleated cells was 9.0 x 10(7)/kg. Neutrophil engraftment was achieved on day +20, and a platelet count greater than 50 x 10(9)/L was achieved on day +51. A normal lymphoproliferative response to phytohemagglutinin mitogen was detectable 7 months posttransplantation. Long-term use of ganciclovir prevented CMV reactivation and did not compromise engraftment.

Antiviral Agents↗