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Biomedical subjects

M Inoue

Publications and source records attributed to M Inoue.

At least 55 records · Page 3Linked to original sources
PubMed2005

Suppression of PI3K/mTOR pathway rescues LLC cells from cell death induced by hypoxia.

Cancer cells in solid tumors are challenged by various microenvironmental stresses, including hypoxia, and cancer cells in hypoxic regions are resistant to current cancer therapies. To investigate the mechanism of resistance to hypoxia in cancer cells, we examined mouse Lewis lung carcinoma (LLC) cells, which died due to necrosis at high density under hypoxic but not under normoxic conditions. Levels of mammalian target of rapamycin (mTOR), a central regulator of cellular energy, are reported to be suppressed in hypoxia. We found that phosphorylation of two molecules downstream to it, ribosomal p70 S6 kinase (S6K) and ribosomal protein S6, was markedly suppressed by hypoxia. Overexpression of the active form of S6K increased the sensitivity of LLC cells to hypoxia. On the other hand, inhibition of PI3K or mTOR dramatically reduced hypoxia-induced cell death under hypoxic conditions. Under hypoxic conditions, blockade of the PI3K or mTOR pathway increased levels of intracellular ATP and delayed decreases in pH and glucose level in culture medium, without affecting the cell cycle.

Adenosine Triphosphate↗
PubMed2005

Confinement of a large number of antiprotons and production of an ultraslow antiproton beam.

We have used a radio frequency quadrupole decelerator to decelerate antiprotons emerging from the CERN Antiproton Decelerator from MeV- to keV-scale energy, and collected five decelerated pulses in a multiring trap. Some 5 x 10(6) antiprotons were stacked in this way. Cooling of the trapped antiprotons by a simultaneously trapped electron plasma was studied nondestructively via shifts in plasma mode frequencies. We have also demonstrated the first step in extracting a 10-500 eV antiproton beam from the trap.

Journal Article↗
PubMed2005

Impact of alcohol drinking on total cancer risk: data from a large-scale population-based cohort study in Japan.

We conducted a cohort study of alcohol consumption and total cancer incidence and mortality in 73,281 subjects (35,007 men and 38,274 women) aged 40-59 years old at baseline over a 10-year follow-up period. During 1990-2001, a total of 3403 cases of newly diagnosed cancer and 1208 cancer deaths were identified. In men, the lowest risk of developing cancer was observed among occasional drinkers, and a linear positive association with increased ethanol intake was noted (hazard ratio 1.18 for 1-149 g per week, 1.17 for 150-299 g per week, 1.43 for 300-449 g per week, 1.61 for > or = 450 g per week, P for trend < 0.001). The positive relation was similar for cancer incidence and mortality, but was more striking among current smokers and alcohol-related cancers. Relatively few women were regular drinkers. Our results suggest that increased ethanol intake linearly elevates the risk of cancer, and that nearly 13% of cancers among males in this study were due to heavy drinking (> or = 300 g per week of ethanol), to which smoking substantially contributed. The simultaneous reduction of smoking is therefore important for reducing the effect of alcohol on cancer risk.

Adult↗
PubMed2005

A patient with untreated tongue carcinoma surviving for 15 years.

A rare case of untreated tongue carcinoma survived for 15 years is presented. A 43-year-old Japanese woman was referred to our department with a 1.8 cm x 1.0 cm white and red non-indurated lesion of the left border of the tongue. The histological examination showed a diagnosis of well-differentiated squamous cell carcinoma. We informed the patient and her family that she had a Stage I tongue carcinoma and needed to receive treatment immediately. However, they refused treatment. Fifteen years later, the patient presented again, complaining of a 55 mm x 40 mm painful gradual-growth swelling of the same site as before, and the clinical stage was T3N2aM0 (Stage IV). The patient agreed to receive radical surgery following preoperative chemoradiotherapy this time. Currently the patient has been free of recurrence for 4 years. Clinical and immunohistochemical features of this rare case are presented and discussed.

Adult↗
PubMed2005

Protein expression of Mdm2 and p53 in hyperplastic and neoplastic lesions of the canine circumanal gland.

Hyperplastic and neoplastic lesions of the circumanal gland in dogs were examined immunohistochemically for nuclear expression of Mdm2 and p53 proteins. Mdm2 nuclear labelling was detected in 64.3% of hyperplastic lesions and 70.7% of adenomas, the immunolabelling being stronger in the latter. Mdm2 reactivity in reserve-like cells in adenomas showed wide variation, the immunoreactive cells ranging from 4 to 80%. No reactivity was shown in 81.9% of adenocarcinomas. In contrast to Mdm2 reactivity, each of 14 hyperplastic lesions and 11 adenocarcinomas, and 60 of 65 adenomas (92.3%) failed to show nuclear p53 reactivity. These results suggest that increased expression of Mdm2 is an early event in circumanal gland tumorigenesis, and may be present in the absence of nuclear p53 protein accumulation.

Adenocarcinoma↗
PubMed2005

Seasonal variation of 228Ra/226Ra ratio in seaweed: implications for water circulation patterns in coastal areas of the Noto Peninsula, Japan.

To examine water circulation patterns of coastal water, 72 seaweed (Sargasso) samples and 27 coastal water samples were collected from coastal areas of the Noto Peninsula, Japan, during the period from December 1998 to June 2002. The (228)Ra and (226)Ra activities of those samples were measured by low-background gamma-ray spectrometry. There was a wide range of activities of (228)Ra (0.5-2Bq/kg-fresh) and (226)Ra (0.5-1.2Bq/kg-fresh) in the Sargasso samples. The (228)Ra/(226)Ra activity ratio of Sargasso samples exhibited seasonal variation with minimum values in June ((228)Ra/(226)Ra= approximately 1) and maximum values in December (1.5-2.5), which was mainly governed by changes in (228)Ra activity. It is also notable that the seasonal variation of the (228)Ra/(226)Ra ratio of Sargasso is in approximate agreement with that of the ambient coastal water. Sargasso samples appear to have retained the (228)Ra/(226)Ra ratio of the ambient coastal waters, and the temporal variations in that ratio provide insight into seasonal changes in water circulation in the Noto Peninsula coastal area.

Environmental Monitoring↗
PubMed2005

Localization and properties of respiratory neurons in the rostral pons of the newborn rat.

The distribution and discharge pattern of respiratory neurons in the 'pneumotaxic center' of the rostral pons in the rat has remained unknown. We performed optical recordings and whole-cell patch clamp recordings to clarify respiratory neuron activity in the rostral pons of a brainstem-spinal cord preparation from a newborn rat. Inspiratory nerve activity was recorded in the 4th cervical nerve and used as a trigger signal for optical recordings. Respiratory neuron activity was detected in the limited region of the rostral-lateral pons. The main active region was presumed to be primarily the Kölliker-Fuse nucleus. The location of respiratory neurons was further confirmed by Lucifer Yellow staining after conducting whole-cell recordings. From a membrane potential analysis of the respiratory neurons in the rostral pons, the respiratory neurons were divided into four types: inspiratory neuron (71.9%), pre-inspiratory neuron (5.3%), post-inspiratory neuron (19.3%), and expiratory neuron (3.5%). A noticeable difference between pontine and medullary respiratory neurons was that post-inspiratory neurons were more frequently encountered in the pons. Application of a mu-opioid agonist, [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin, transformed the burst pattern of post-inspiratory neurons into that of pre-inspiratory neurons. The electrical stimulation of the sensory root of the trigeminal nerve induced three types of responses in 85% of pontine respiratory neurons: inhibitory postsynaptic potentials (42.7%), excitatory postsynaptic potentials (37.7%) and no response (15.1%). Our findings provide the first evidence in the rat for the presence of respiratory neurons in the rostral pons, with localization in the lateral region approximately overlapping with the Kölliker-Fuse nucleus.

Animals↗
PubMed2005

Effect of FTY720 in rat small bowel transplantation: expression of mucosal addressin cell adhesion molecule-1.

AIM: Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) mediates the homing of lymphocytes to gut-associated tissues (GALT). We performed a semiquantitative analysis of MAdCAM-1 expression during small bowel graft rejection in rat treated with FTY720. METHODS: Orthotopic small bowel transplantations (SBT) were performed from BN rats to LEW rats. Isografted animals served as controls. Three groups of SBT animals were studied on days 3, 5, 7 after operations (Isograft, untreated allograft, allograft with FTY720). FTY720 was orally administered by gavage (1 mg/kg/d) to allograft models on 7 consecutive days. Cryostat sections were prepared from grafts, including Peyer's patches (PPs). Indirect immunoperoxidase staining was performed using mAbs against MAdCAM-1. The degree of vascular endothelial staining on high endothelial venules (HEV) in the PPs was graded from 1 (low levels) to 5 (high levels), and in the vessels of the lamina propia from 1 (faint), to 2 (low at the base of villi), 3 (low to the middle of villi), 4 (high to the middle of villi), to 5 (high to villi tip). RESULTS: The graft survival was prolonged in the FTY720-treated group. MAdCAM-1 expression on HEVs in PPs was down-regulated during rejection. In contrast its expression on endothelial cells of vessels in the lamina propria was up-regulated during rejection. In the FTY720-treated groups, MAdCAM-1 expression on HEVs in PPs was up-regulated and its expression on endothelial cells of vessels in the lamina propria was down-regulated compared with untreated allograft group. CONCLUSIONS: Alteration in MAdCAM-1 expression may be associated with the development of SB graft rejection. The vessels at the base of villi, which are associated with lymphocyte recruitment, may become sites of intestine immune reactivity during the early phase of small bowel allograft rejection. FTY720 was found to prevent the down-regulation of MAdCAM-1 expression on HEVs in PPs and the up-regulation of its expression on endothelial cells of vessels in the lamina propria while also prolonging small bowel allograft survival.

Animals↗
PubMed2005

Unrelated donor bone marrow transplantation for 100 pediatric patients: a single institute's experience.

In all, 100 unrelated donor bone marrow transplantations (UD-BMT) were performed in our institute between October 1993 and January 2003. Of 93 evaluable patients, 73 patients had hematological malignancy, 13 had nonmalignancy and seven had lymphoproliferative disease. The estimated 9-year event-free survival (EFS) rate was 57.1+/-5.5% in all patients. In the following analyses of the patients with hematological malignancy, the standard group had significantly better EFS than the high-risk group (61.5+/-7.0 vs 35.6+/-9.7%, P=0.02), and the EFS rate of the tacrolimus (FK-506)+methotrexate (MTX)+/-methylprednisolone prophylactic group for graft-versus-host disease was superior to that of the FK-506 without MTX group (75.7+/-8.0 vs 55.8+/-7.6%, P=0.02). When we compared the EFS rates of the FK506+MTX+/-methylprednisolone (mPSL) group and the HLA-matched related donor BMT group in our institute, these were almost similar (75.7+/-8.1 vs 68.4+/-9.3%). Therefore, UD-BMT using FK-506+MTX+/-mPSL is a safe and useful method for children with hematological malignancy who require allogeneic BMT.

Adolescent↗
PubMed2005

Isolation of gene sets affected specifically by polyglutamine expression: implication of the TOR signaling pathway in neurodegeneration.

Transcriptional dysregulation as a result of sequestration of essential transcription factors into protein aggregates formed by polyglutamine (polyQ) expansions can lead to late-onset progressive neurodegeneration. DNA microarray analysis of Drosophila expressing polyQ in the compound eye over time revealed large numbers of transcriptional changes at the earliest stages of the disease including repression of the transient receptor potential calcium channels in a polyQ-induced cell death specific manner. While significant differences in expression profiles were found between the Drosophila compound eye and polyQ-sensitive neural cells, a number of possible key overlapping regulators were extracted. Among these, PDK1 was shown to act as a mediator for polyQ-toxicity, suggesting the involvement of the TOR pathway in polyQ-induced neurodegeneration.

3-Phosphoinositide-Dependent Protein Kinases↗
PubMed2005

Efficient and stable Sendai virus-mediated gene transfer into primate embryonic stem cells with pluripotency preserved.

Efficient gene transfer and regulated transgene expression in primate embryonic stem (ES) cells are highly desirable for future applications of the cells. In the present study, we have examined using the nonintegrating Sendai virus (SeV) vector to introduce the green fluorescent protein (GFP) gene into non-human primate cynomolgus ES cells. The GFP gene was vigorously and stably expressed in the cynomolgus ES cells for a year. The cells were able to form fluorescent teratomas when transplanted into immunodeficient mice. They were also able to differentiate into fluorescent embryoid bodies, neurons, and mature blood cells. In addition, the GFP expression levels were reduced dose-dependently by the addition of an anti-RNA virus drug, ribavirin, to the culture. Thus, SeV vector will be a useful tool for efficient gene transfer into primate ES cells and the method of using antiviral drugs should allow further investigation for regulated SeV-mediated gene expression.

Animals↗
PubMed2005

Phenotypic differences between electrocardiographic and echocardiographic determination of hypertrophic cardiomyopathy in genetically affected subjects.

OBJECTIVES: In the molecular era, two types of phenotypic differences are recognized between electrocardiography (ECG) and echocardiography in hypertrophic cardiomyopathy (HCM); ECG abnormalities in carriers without left ventricular hypertrophy (LVH), and normal ECG patterns in carriers with LVH. The goal of this study was to evaluate the diagnostic value of ECG for detecting carriers without LVH, and also to assess normal ECG patterns in carriers with LVH from the genetic standpoint of HCM. SETTING: A matched case-control study in a university hospital and general hospitals in Japan. PATIENTS AND DESIGN: ECG and echocardiographic findings were analysed in 173 genotyped subjects (107 genetically affected, 66 unaffected) from families with disease-causing mutations in four genes. RESULTS: ECG abnormalities were found in 18 (54.5%) of 33 nonhypertrophic carriers, but only nine (13.6%) of 66 noncarriers (P < 0.001). For detecting nonhypertrophic carriers, ST-T abnormalities showed the highest accuracy amongst the three major ECG criteria. In contrast, normal ECG patterns were found in eight (10.8%) of 74 carriers with LVH. The sensitivity of ECG for detecting carriers with LVH in families with the cardiac myosin-binding protein C, cardiac troponin T and cardiac troponin I gene mutations was 83%, 88% and 94% respectively. CONCLUSION: These findings suggest that ECG may have favourable diagnostic value even for detecting nonhypertrophic carriers. Furthermore, diagnostic value of ECG may differ according to the genes involved. Our data may contribute to interpretation of phenotypic differences between ECG and echocardiography from the viewpoint of molecular genetics of HCM.

Adult↗
PubMed2005

Interferon reduces somatic mutation of mitochondrial DNA in liver tissues from chronic viral hepatitis patients.

SUMMARY: We recently reported that the genetic instability resulting in the high rate of mitochondrial DNA (mtDNA) mutation in noncancerous liver tissue is consistent with the multicentric hepatocarcinogenesis detected clinically. Interferon (IFN) has been reported to reduce hepatocarcinogenesis in individuals with hepatitis virus infection. Liver biopsy specimens were obtained from 26 patients with chronic hepatitis C virus (HCV) infection before and after IFN therapy (total dose: 252 million units). The mean (+/-SD) age of the study population was 45 +/- 9 years and 13 (50%) were male [mode of acquisition: blood transfusion (27%), unknown (73%); viral load: 5.2 +/- 1.1 k copies/mL; duration of infection: 17 +/- 9 years (65%), unknown (35%); genotype: I (4%), II (80%), III (8%), IV (8%); alcohol intake: positive (31%), negative (69%)]. DNA samples were extracted from the specimens and subjected to direct sequencing. The mtDNA mutation frequency in the D-loop was increased in liver specimens from individuals with HCV infection compared with 21 controls (2.5 vs 0.6, P < 0.001). IFN therapy decreased the mtDNA mutation (mean difference = 0.7, P < 0.001) and the decreased number of mtDNA mutations was positively correlated with suppression of the total histological activity index score (mean difference = 1.3, P < 0.01). These results clearly indicate that the mutational rate of mtDNA is strongly associated with IFN therapy. Thus, analysis of mtDNA could provide a new criterion for the therapeutic evaluation of the effect of IFN, and may be useful for the prediction of risk of carcinogenesis.

Adult↗
PubMed2005

Ultrastructural study of the extra-articular Leeds-Keio ligament prosthesis.

BACKGROUND: There have been several histological studies of the Leeds-Keio ligament in anterior cruciate ligament reconstruction, but there have been few of the Leeds-Keio ligament in the extra-articular portion. AIMS/METHODS: To report the histological and ultrastructural findings of two cases of medial patellofemoral ligament reconstruction using the Leeds-Keio ligament, removed 6.1 years and 8.7 years after implantation. RESULTS: In both cases, the tissue over the Leeds-Keio ligament was a ligament-like tissue. Electron microscopy showed that the diameter of the collagen fibrils in the tissue over the Leeds-Keio ligament was unimodal in the case investigated 6.1 years after implantation but bimodal in the case investigated after 8.7 years. CONCLUSIONS: The tissue over the Leeds-Keio ligament may continue to grow with prolonged periods of mechanical stress.

Adolescent↗
PubMed2005

Contralateral pharyngeal paralysis caused by medial medullary infarction.

A patient with unilateral upper medial medullary infarction presented with contralateral paralysis of the pharyngeal constrictor muscle in association with lemniscal sensory loss, pyramidal insufficiency, and central facial palsy on the same side. Individual differences in supranuclear control of the pharyngeal muscles may explain this rare occurrence. The combination of these signs is described as a syndrome of upper medial medullary lesion.

Brain Stem Infarctions↗