Biomedical subjects

M Oshima

Publications and source records attributed to M Oshima.

At least 19 recordsLinked to original sources

PubMed2006

Chromosomal instability by beta-catenin/TCF transcription in APC or beta-catenin mutant cells.

Adenomatous polyposis coli (APC/Apc) gene encodes a key tumor suppressor whose mutations activate beta-catenin/T-cell factor (TCF)-mediated transcription (canonical Wnt signaling). Here, we show that Wnt signaling can cause chromosomal instability (CIN). As an indicator of CIN, we scored anaphase bridge index (ABI) in mouse polyps and ES cells where Wnt signaling was activated by Apc or beta-catenin mutations. We found three to nine times higher ABI than in wild-type controls. Furthermore, karyotype analysis confirmed that the Wnt signal-activated ES cells produced new chromosomal aberrations at higher rates; hence CIN. Consistently, expression of dominant-negative TCFs in these cells reduced their ABI. We also found that Wnt signal activation increased phosphorylation of Cdc2 (Cdk1) that inhibited its activity, and suppressed apoptosis upon exposure of the cells to nocodazole or colcemid. The data suggest that Wnt signaling stimulates the cells to escape from mitotic arrest and apoptosis, resulting in CIN. In human gastric cancer tissues with nuclear beta-catenin, ABI was significantly higher than in those without. These results collectively indicate that beta-catenin/TCF-mediated transcription itself increases CIN through dysregulation of G2/M progression.

Adenoma↗

PubMed2006

Photoemission from buried interfaces in SrTiO3/LaTiO3 superlattices.

We have measured photoemission spectra of SrTiO3/LaTiO3 superlattices with a topmost SrTiO3 layer of variable thickness. A finite coherent spectral weight with a clear Fermi cutoff was observed at chemically abrupt SrTiO3/LaTiO3 interfaces, indicating that an "electronic reconstruction" occurs at the interface between the Mott insulator LaTiO3 and the band insulator SrTiO3. For SrTiO3/LaTiO3 interfaces annealed at high temperatures (approximately 1000 degrees C), which leads to Sr/La atomic interdiffusion and hence to the formation of La(1-x)Sr(x)TiO3-like material, the intensity of the incoherent part was found to be dramatically reduced whereas the coherent part with a sharp Fermi cutoff was enhanced due to the spread of charge. These important experimental features are well reproduced by layer dynamical-mean-field-theory calculation.

Journal Article↗

PubMed2006

Analysis of cadmium in food by multiple prompt gamma-ray spectroscopy.

The Cd concentration in food is a public concern related to the human health. In order to remove Cd-polluted food, the development and validation of a rapid and sensitive method of Cd analysis is required. By applying the multiple gamma-ray detection method to prompt gamma-ray analysis (PGA), the influence from nuclei which emit only one prompt gamma-ray at a time at every neutron capture reaction can be reduced, therefore the quantification limit of Cd is improved significantly. The limit of Cd contained in rice in the case of MPGA was evaluated, and under our proposed experimental conditions, it may be possible to quantify Cd content in rice to within 0.2 ppm in 10 min.

Cadmium↗

PubMed2006

Accelerated onsets of gastric hamartomas and hepatic adenomas/carcinomas in Lkb1+/-p53-/- compound mutant mice.

Germline mutations in the LKB1 gene are responsible for Peutz-Jeghers syndrome (PJS), which is characterized by gastrointestinal hamartomas and increasing risk of cancer. Mice with Lkb1(+/-) mutation develop gastric hamartomas after >20 weeks of age, and hepatocellular adenomas and carcinomas >30 weeks. It has been reported that, in PJS patients, carcinomas progressed from hamartomas contain p53 mutations, and that LKB1 regulates p53-dependent apoptosis. To investigate the roles of LKB1 and p53 mutations in tumorigenesis, we constructed compound mutant mice of Lkb1 and p53 genes. In the Lkb1(+/-)p53(-/-) mice, formation of gastric hamartomas and hepatic tumors was accelerated. However, histopathology of hamartomas was similar between Lkb1(+/-)p53(-/-) and Lkb1(+/-) mice, and Lkb1 genotype remained heterozygous, suggesting that the p53 mutation affected hamartoma initiation. Contrary to the heterozygous hamartomas in the stomach and duodenum, the hepatic adenomas in Lkb1(+/-)p53(-/-) mice showed loss of Lkb1 heterozygosity (LOH), suggesting that lack of p53 stimulated Lkb1 LOH and tumor initiation in the liver. Taken together, these results indicate that lack of p53 causes earlier onsets of gastric hamartomas and hepatic tumors in Lkb1(+/-)p53(-/-) mice.

AMP-Activated Protein Kinases↗

PubMed2006

Mutant murine leukemia virus Gag proteins lacking proline at the N-terminus of the capsid domain block infectivity in virions containing wild-type Gag.

We have investigated the properties of murine leukemia virus Gag mutants in which the p12-CA cleavage site is altered. In one mutant, the cleavage is blocked; in the other, the conserved proline at the N-terminus of CA has been replaced with glycine. No infectivity was detected in either mutant. Mutant particles cannot synthesize full-length DNA upon infecting permissive cells. Particles composed of a mixture of wild-type and mutant proteins have severely impaired infectivity. These mixed particles are defective in their ability to synthesize DNA upon infection, but this defect is less severe than the loss of infectivity. Thus, proteins lacking the correct N-terminus of CA inhibit DNA synthesis and also interfere with formation or integration of a full-length, normal provirus. The results imply that CA proteins function as part of a large, highly organized structure in reverse transcription and apparently at a later step as well.

Animals↗

PubMed2006

Detection of a 5' end subgenome of hepatitis C virus terminating at nucleotide 384 in patients' plasma and liver tissues.

Quadri and Negro [Dig Liver Dis 2001; 33: 480] reported greater distribution of 5' end genomic RNA of hepatitis C virus (HCV) over its 3' end in the liver of patients with recurrent hepatitis C after liver transplantation. We not only confirmed their results by quantifying the 5' end subgenomes in various specimens by using dilution and real-time polymerase chain reaction methods, but also discovered that such subgenomes terminated at nucleotide (nt) 384 of the viral genome or in its immediate upstream. The subgenomes in the plasma uniformly, with a few exceptions, ended at this position, while those in the liver more heterogeneously at various points upstream of nt 384. Subgenome populations ending some points in the downstream of nt 384 were not detected. The amount of the 5' end subgenome, while fluctuating during the clinical course of the patients, exceeded that of the longer sized HCV genomes which included the intact genome, and, when the relative ratio of the 5' end subgenome increased, the amount of longer sized HCV RNA tended to decrease, suggesting a suppressive effect of the 5' end subgenome on viral replication.

Alanine Transaminase↗

PubMed2004

Nature of the well screened state in hard X-ray Mn 2p core-level photoemission measurements of La1-xSrxMnO3 films.

Using hard x-ray (HX; hnu=5.95 keV) synchrotron photoemission spectroscopy (PES), we study the intrinsic electronic structure of La(1-x)Sr(x)MnO(3) (LSMO) thin films. Comparison of Mn 2p core-levels with soft x-ray (SX; hnu approximately 1000 eV) PES shows a clear additional well-screened feature only in HX PES. Takeoff-angle dependent data indicate its bulk (> or =20 A) character. The doping and temperature dependence track the ferromagnetism and metallicity of the LSMO series. Cluster model calculations including charge transfer from doping-induced states show good agreement, confirming this picture of bulk properties reflected in Mn 2p core-levels using HX PES.

Journal Article↗

PubMed2004

Development of spontaneous tumours and intestinal lesions in Fhit gene knockout mice.

The fragile histidine triad (FHIT) gene is frequently inactivated in various types of tumours. However, the system-wide pathology caused by FHIT inactivation has not been examined in detail. Here we demonstrate that Fhit gene knockout mice develop tumours in the lymphoid tissue, liver, uterus, testis, forestomach and small intestine, together with structural abnormalities in the small intestinal mucosa. These results suggest that Fhit plays important roles in systemic tumour suppression and in the integrity of mucosal structure of the intestines.

Acid Anhydride Hydrolases↗

PubMed2004

Simultaneous expression of COX-2 and mPGES-1 in mouse gastrointestinal hamartomas.

Cyclo-oxygenase (COX)-2 is induced in various types of cancer tissues. Here, we demonstrate stromal expression of both COX-2 and microsomal prostaglandin E(2) synthase (mPGES)-1 in gastrointestinal hamartomas developed in Lkb1(+/-), Smad4(+/-) and Cdx2(+/-)mice. These results suggest that PGE(2) produced by COX-2 and mPGES-1 plays an important role in hamartoma development regardless of the mutated genes causing hamartomas.

AMP-Activated Protein Kinases↗

PubMed2004

Psychosocial predictors of successful delivery after unexplained recurrent spontaneous abortions: a cohort study.

OBJECTIVE: To examine psychosocial predictors of successful pregnancy after recurrent spontaneous abortions (RSA). METHOD: We administered two waves of semi-structured interview and self-report questionnaire battery to a consecutive series of 46 couples who had had two RSAs (baseline before third pregnancy, and immediately after third pregnancy was ascertained), and followed them through their third pregnancy. RESULTS: Of the 46 couples, four miscarried for karyotypal abnormalities and six without any known cause. When the latter six were compared with the remaining 36 women, they reported less social support satisfaction, a more stable attribution for the causes of past abortions, and more depressed mood in the preceding year. Taken altogether, this psychosocial model was able to predict 93% of the pregnancy outcomes correctly. CONCLUSION: Psychosocial variables (depression, attribution and social support) are robust predictors of the prospective pregnancy and suggest possible points of intervention in couples with RSA.

Abortion, Spontaneous↗

PubMed2004

A case of tuberculous tenosynovitis in a patient with systemic lupus erythematosus.

A 52-year-old woman with systemic lupus erythematosus (SLE) was infected with tuberculosis (TB) on her forearm and hand, after 16 years of steroid therapy. Debridements and anti-TB therapy were performed successfully. Recently, the risk of significant morbidity from TB has been on the rise; this appears to be a complication of steroid therapy used to treat AIDS and some collagen vascular diseases. It is thought that steroid therapy causes an increased risk of TB. In this paper, we report our experience of this SLE patient who developed tuberculous tenosynovitis. We suggest that TB infection must be considered in the differential diagnosis whenever a patient presents with a chronic wrist or hand inflammation that is non-responsive to steroid treatment. Once TB infection is suspected, both histopathological and bacteriological examinations should be performed. Emergent treatment includes surgical debridement and the institution of early anti-TB therapy immediately after completing histopathological examination.

Female↗

PubMed2003

Ta 5d band symmetry of 1T-TaS1.2Se0.8 in the commensurate charge-density-wave phase.

We present a detailed angle-resolved photoemission study on the layered transition-metal dichalcogenide 1T-TaS1.2Se0.8 in the commensurate charge-density-wave (CDW) phase. A drastic reduction in the spectral weight along the high symmetry line GammaM, particularly around the point M, is observed when s-polarized light was used. This implies that the initial state must be symmetric with respect to a mirror plane perpendicular to the line GammaK, which is consistent with conventional band calculations in the absence of the CDW. We conclude that there is only a limited amount of modification of the electronic structure of 1T-TaS1.2Se0.8 in the commensurate CDW phase due to the CDW-related potential.

Journal Article↗

PubMed2002

Isotopic ratio of 129I/127I in seaweed measured by neutron activation analysis with gamma-gamma coincidence.

129I is a long-lived (1.6 x 10(7) y) radionuclide that is produced in nature as the result of spontaneous fission of heavy elements and reaction of xenon with cosmic rays. Recently, however, artificial sources from nuclear power plants and nuclear test explosions have become a significant component of environmental radioactive iodine. Coincidence gamma-ray detection using Ge detectors makes it possible to simultaneously resolve the numerous gamma-rays produced by neutron activation. In this study, the coincidence gamma-ray detection technique was combined with neutron activation analysis to determine the radioactive iodine composition of seaweed. The ratio of 129I/127I in this common Japanese food item collected from the Ibaraki prefecture has been derived without the need for radiochemical purification. The isotopic ratio of 129I/127I in Kajime algae is 3.5(5) x 10(-10).

Gamma Rays↗

PubMed2002

CDX2 expression in the stomach with intestinal metaplasia and intestinal-type cancer: Prognostic implications.

CDX2, a transcriptional factor expressed in the intestine, is implicated in the development and maintenance of the intestinal mucosa. Recent studies have demonstrated that CDX2 is expressed in the intestinal metaplasia of the stomach and intestinal-type gastric cancer, while it is not expressed in the normal gastric mucosa. To investigate the role of CDX2 in gastric cancer, we determined CDX2 expression and cell proliferation rate in various types of gastric cancer tissues by immunostaining. Surgically dissected gastric cancer tissues were collected from 40 patients. Consistent with previous reports, CDX2 was expressed in most gastric mucosa samples with intestinal metaplasia (89%, 16/18), although it was not found in the adjacent normal mucosa. CDX2 expression was also detected in 64% (18/28) of intestinal-type gastric cancer cases, whereas it was not observed in the diffuse-type gastric cancer (0/12). Moreover, the CDX2-positive gastric cancer samples showed significantly lower index for Ki-67 immunostaining, indicating reduced cell proliferation rates than in the CDX2-negative samples. Importantly, multivariate analysis for the overall survival rate revealed that the CDX2-positive gastric cancer patients survived significantly longer than the CDX2-negative patients. Even among the intestinal-type gastric cancer cases, the CDX2-positive group showed a lower Ki-67 index and longer postoperative survival than the CDX2-negative group. These results collectively indicate that CDX2 expression in gastric cancer tissues can be a novel prognostic marker for patient survival.

Aged↗

PubMed2001

Separation and determination of n-alkylamines and histamine by capillary zone electrophoresis using salicylaldehyde-5-sulfonate as a derivatizing reagent.

Sodium salicylaldehyde-5-sulfonate (SAS) was investigated as a derivatizing reagent for the separation and determination of primary amines by capillary zone electrophoresis (CZE). The amines were derivatized with SAS to the corresponding Schiff bases before their determination. Optimal conditions for the formation reactions of the Schiff bases and the CZE analysis were investigated in details. The Schiff bases were formed almost completely within 9 min in 40%(v/v) ethanol solution at 40 degrrees C. A migrating solution containing 40%(v/v) ethanol and 20 mM phosphate buffer (pH 7.8) was found to be preferable for the stability of the Schiff bases. Eight kinds of n-alkylamines were derivatized with SAS under the optimal conditions and the derivatives were successfully separated by a CZE analysis. The proposed method allows simultaneous, sensitive and sufficiently precise determination of the n-alkylamines with the alkyl chain length from 3 to 12 of methylene groups. The derivatization process with SAS was successfully applied to the detection of histamine at a very low level. The detection limit was 2.5-10(-6) M, and it was improved in the order of 8 times compared with the CZE analysis without derivatization.

Aldehydes↗

PubMed2001

Complex formation analysis of water-soluble calixarenes by capillary zone electrophoresis.

The equilibria of complex formation reactions between various kinds of cations and anionic calixarenes in an aqueous solution were analyzed by capillary zone electrophoresis on the basis of the change in electrophoretic mobility of the calixarenes. The apparent electrophoretic mobility of the calixarenes decreased with increasing concentrations of alkali metal ions and quaternary ammonium ions. Equilibrium constants were determined by a non-liner least-squares analysis using the changes in apparent electrophoretic mobility. The complex formation constants obtained with alkali metal ions were in the order of 10(2.3) - 10(3.0), and those with quaternary ammonium ions were 10(2.9) - 10(4.2), providing less selectivity among them. The selectivity of the calixarene toward alkali metal and quaternary ammonium ions in aqueous solution involves flexible structure, and compensative interactions of electrostatic and hydrophobic interactions. From the results obtained in this work, the electrophoretic method has proved to be useful for analyzing the reactivity of anionic calixarene in aqueous solution.

Alkalies↗

PubMed2001

Comparative study of glycosyltransferase activities in Caco-2 cells before and after enterocytic differentiation using lectin-affinity high-performance liquid chromatography.

Human colonic adenocarcinoma Caco-2 cells differentiate into enterocytes by induction with sodium butyrate after confluence. Our previous studies have shown that there are high levels of H type 1 blood group antigen and core 2 structure present in O-glycans of the glycoproteins from these differentiated cells and these O-glycans appear to be indispensable for the process of differentiation of the cells (J. Amano and M. Oshima, 1999, J. Biol. Chem. 274, 21209-21216). Here, we have determined the glycosyltransferase activities using lectin-affinity HPLC because the method enabled easy separation and identification of mixtures of isomeric oligosaccharide structures due to the high resolution and reproducibility. The activities of beta 3-galactosyltransferase, alpha 2-fucosyltransferase, which are responsible for H type 1 antigen biosynthesis, and core 2 beta 6-N-acetylglucosaminyltransferase in differentiated Caco-2 cells were higher than those in undifferentiated cells. These results demonstrate that an increase in specific glycosyltransferase activities brought on a change of the O-glycan structures during differentiation.

Animals↗

PubMed2001

Chemoprevention of intestinal polyposis in the Apcdelta716 mouse by rofecoxib, a specific cyclooxygenase-2 inhibitor.

Mutations in the human adenomatous polyposis (APC) gene are causative for familial adenomatous polyposis (FAP), a rare condition in which numerous colonic polyps arise during puberty and, if left untreated, lead to colon cancer. The APC gene is a tumor suppressor that has been termed the "gatekeeper gene" for colon cancer. In addition to the 100% mutation rate in FAP patients, the APC gene is mutated in >80% of sporadic colon and intestinal cancers. The Apc gene in mice has been mutated either by chemical carcinogenesis, resulting in the Min mouse Apcdelta850, or by heterologous recombination, resulting in the Apcdelta716 or Apedelta1368 mice (M. Oshima et al., Proc. Natl. Acad. Sci. USA, 92: 4482-4486, 1995). Although homozygote Apc-/- mice are embryonically lethal, the heterozygotes are viable but develop numerous intestinal polyps with loss of Apc heterozygosity within the polyps (M. Oshima et al., Proc. Natl. Acad. Sci. USA, 92: 4482-4486, 1995). The proinflammatory, prooncogenic protein cyclooxygenase (COX)-2 has been shown to be markedly induced in the Apcdelta716 polyps at an early stage of polyp development (M. Oshima et al., Cell, 87: 803-809, 1996). We demonstrate here that treatment with the specific COX-2 inhibitor rofecoxib results in a dose-dependent reduction in the number and size of intestinal and colonic polyps in the Apcdelta716 mouse. The plasma concentration of rofecoxib that resulted in a 55% inhibition of polyp number and an 80% inhibition of polyps > 1 mm in size is comparable with the human clinical steady-state concentration of 25 mg rofecoxib (Vioxx) taken once daily (A. Porras et al., Clin. Pharm. Ther., 67: 137, 2000). Polyps from both untreated and rofecoxib- or sulindac-treated Apcdelta716 mice expressed COX-1 and -2, whereas normal epithelium from all mice expressed COX-1 but minimal amounts of COX-2. Polyps from either rofecoxib- or sulindac-treated mice had lower rates of DNA replication, expressed less proangiogenic vascular endothelial-derived growth factor and more membrane-bound beta-catenin, but showed unchanged nuclear localization of this transcription factor. This study showing the inhibition of polyposis in the Apcdelta716 mouse suggests that the specific COX-2 inhibitor rofecoxib (Vioxx) has potential as a chemopreventive agent in human intestinal and colon cancer.

Animals↗