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Biomedical subjects

T Ito

Publications and source records attributed to T Ito.

At least 37 records · Page 2Linked to original sources
PubMed2006

[Aortic root enlargement in elderly patients].

From January 2003 to June 2005, 12 elderly patients with severe aortic stenosis underwent aortic root enlargement (ARE) by Nicks procedure. Their ages ranged from 74 to 87 with a mean of 79.3. Stented bioprosthesis were used in 11 cases. There was no death. Cardiothoracic ratio on chest X-ray decreased from 59.4 to 53.6% and New York Heart Association (NYHA) functional class improved from 3.4 to 1.3. Echocardiography also showed remarkable improvement, in peak pressure gradient (PG) from 98.3 to 20.7 mmHg, in left ventricular mass index (LVMI) 181 to 137 g/m2. LVM and LVMI regression rates were 25.3 and 22.3%, respectively. Comparative study of those with ARE alone and those with combined operation showed much hazardous effect in the latter, but no significant difference in echocardiographic findings postoperatively. ARE by Nicks procedure, if it could be performed without concomitant procedure, is a safe and effective option also in elderly patients with small aortic annulus.

Aged↗
PubMed2005

Ikaros is expressed in human extravillous trophoblasts and involved in their migration and invasion.

The transcriptional factor Ikaros was originally found to function as a key regulator of lymphocyte differentiation. In addition, we have reported that Ikaros regulates the human placental leucine aminopeptidase (P-LAP)/insulin-regulated aminopeptidase (IRAP) gene in choriocarcinoma trophoblastic cells, suggesting that Ikaros might be involved in placental development, while even its presence in human placenta remains undetermined. We therefore sought to clarify the location and roles of Ikaros in human placenta. Immunohistochemical analysis showed modest Ikaris expression in syncytium, and intense expression in extravillous trophoblasts (EVTs) in first trimester placenta. Western blot analysis showed that villous trophoblasts principally expressed Ikaros-2/3, while Ikaros-x (Ikx) was predominantly expressed in cultured EVTs. Furthermore, to investigate the functional role of Ikx in EVTs, the EVT cell line HTR-8/SVneo was infected with a retrovirus vector expressing the hemagglutinin (HA)-tagged dominant negative isoform Ikaros-6 (Ik6), which prevents the DNA-binding activity of Ikx. Antibody against HA showed successful transduction of Ik6 in HTR-8/SVneo cells on immunocytochemistry and Western blotting. Transduction of Ik6 significantly reduced the migratory and invasive abilities of HTR-8/SVneo cells. These results suggest that Ikx is involved in migration and invasion of EVTs in early placentation.

Adolescent↗
PubMed2005

Temperature-dependent Luttinger surfaces.

The Luttinger surface of an organic metal (TTF-TCNQ), possessing charge order and spin-charge separated band dispersions, is investigated using temperature-dependent angle-resolved photoemission spectroscopy. The Luttinger surface topology, obtained from momentum distribution curves, changes from quasi-2D (dimensional) to quasi-1D with temperature. The high temperature quasi-2D surface exhibits 4kF charge-density-wave (CDW) superstructure in the TCNQ derived holon band, in the absence of 2kF order. Decreasing temperature results in quasi-1D nested 2kF CDW order in the TCNQ spinon band and in the TTF surface. The results establish the link in momentum space between charge order and spin-charge separation in a Luttinger liquid.

Journal Article↗
PubMed2005

Muon spin relaxation studies of magnetic-field-induced effects in high-Tc superconductors.

Muon spin relaxation measurements in high transverse magnetic fields [FORMULA: SEE TEXT] revealed strong field-induced quasistatic magnetism in the underdoped and Eu-doped (La,Sr)2CuO4 and La1.875Ba0.125CuO4, existing well above Tc and TN. The susceptibility counterpart of Cu spin polarization, derived from the muon spin relaxation rate, exhibits a divergent behavior towards T approximately 25 K. No field-induced magnetism was detected in overdoped La1.81Sr0.19CuO4, optimally doped Bi2212, and Zn-doped YBa2Cu3O7.

Journal Article↗
PubMed2005

Energy structure of a finite Haldane chain in Y2BaNi0.96Mg0.04O5 studied by high field electron spin resonance.

This Letter presents the fine structure of energy levels for the edge states of a Haldane chain. In order to investigate the edge states, we have performed high field and multifrequency electron spin resonance (ESR) measurements of finite length S=1 antiferromagnetic chains in Y2BaNi0.96Mg0.04O5. Owing to the high spectral resolution by high fields and high frequencies, observed ESR signals can be separated into the contributions of the finite chains with various chain lengths. Our results clearly show that the edge spins actually interact with each other through the quantum spin chain and the interaction depends on the chain length N. This N dependence has been obtained experimentally for the first time, and shows that the correlation length xi in the real system is somewhat larger than that calculated by a simple Heisenberg model.

Journal Article↗
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

Neurovirulence of H7N7 influenza A virus: brain stem encephalitis accompanied with aspiration pneumonia in mice.

A mouse-adapted influenza A virus, A/equine/London/1416/73-MA (H7N7) caused viral pneumonia, ganglionitis and encephalitis after intranasal inoculation in mice. Virological and pathological data suggested that this virus spreads to the brain by both hematogenous and transneuronal routes, and produces encephalitic lesions similar to those seen in mice infected with H5 highly pathogenic avian influenza A viruses by intranasal infection. Some mice infected with this strain were affected by aspiration pneumonia, which may be caused by neurogenic dysfunction of the pharyngeal/laryngeal reflex due to brain stem encephalitis.

Animals↗
PubMed2005

A simple technique for circular-stapled Billroth I reconstruction in laparoscopic gastrectomy.

A simple surgical technique that facilitates circular-stapled Billroth I gastroduodenostomy in laparoscopic distal gastrectomy is described. After standard laparoscopic mobilization of the distal stomach, a small duodenotomy is made just distal to the pyloric ring. The anvil of a circular-stapling device, secured with a Vicryl suture, is introduced via the duodenotomy. The Vicryl suture is advanced anteriorly so that a center rod penetrates the anterior duodenal wall. The duodenum is staple-transected at this point, and the center rod is wrapped with the stapled duodenal stump by approximation of both edges using a suturing device. The circular-stapled gastroduodenostomy then is completed in a standard fashion. The authors have used this technique for three patients, and their early outcomes are promising.

Gastrectomy↗
PubMed2005

Autoantibodies against the amino terminal of alpha-enolase are a useful diagnostic marker of Hashimoto's encephalopathy.

We investigated autoantibodies and their epitope(s) in Hashimoto's encephalopathy associated with Hashimoto's thyroiditis. In a proteomic analysis, they proved to recognize alpha-enolase. We further searched the epitope region in alpha-enolase using different regions of recombinant proteins expressed in cultured human cells. The amino terminal region was recognized by autobodies from a much higher proportion of patients with Hashimoto's encephalopathy (83.3%; 5/6) than from patients with Hashimoto's thyroiditis (11.8%; 2/17), and not at all by sera from controls (25 healthy individuals and 25 controls with other neurological disorders) (0%; 0/50). Neither the carboxyl terminal nor the mid-region of alpha-enolase showed specificity for Hashimoto's encephalopathy. Autoantibodies against the amino terminal of alpha-enolase are a useful diagnostic marker for Hashimoto's encephalopathy.

Adult↗
PubMed2005

Striatal dopamine level increases in the urinary storage phase in cats: an in vivo microdialysis study.

Parkinson's disease is a common neurodegenerative disease that shows not only movement disorder, but also profound urinary dysfunction. Bladder hyperactivity is the major urodynamic abnormality. Therefore, the basal ganglia have been thought to modulate the micturition reflex. In six male adult cats under ketamine anesthesia, in which spontaneous isovolumetric micturition reflexes had been generated, we measured levels of striatal dopamine, in micturition and storage phases, using in vivo microdialysis. The striatal dopamine level significantly increased in the storage phase as compared with that in the micturition phase. It is suggested that striatal dopamine may inhibit the micturition reflex via the dopamine D1 receptor-GABAergic direct striatal output pathway, and that disruption of this pathway may be what leads to bladder hyperactivity in patients with Parkinson's disease.

Animals↗
PubMed2005

Increased expression of renin in chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy (CAN) is the main cause of renal transplant failure in the first decade posttransplant. The precise pathogenetic mechanism for CAN is not completely understood. A possible role of renin-angiotensin system for CAN has been suggested through clinical observations that angiotensin-converting enzyme inhibition and angiotensin II receptor blockers prevent CAN. METHODS: Distribution of renin-positive cells in allograft biopsy specimens was examined immunohistochemically in 23 renal transplant recipients diagnosed with CAN Biopsy specimens obtained from seven recipients with stable renal function were examined as controls. Histologic evaluation was performed based on the Banff 97 classification. RESULTS: Renin-positive cells were found in the juxtaglomerular apparatus (JGA) adjoining the afferent arterioles in both groups. When the number of renin-positive cells in JGA was defined as a renin index, it was significantly higher in the CAN than the control group (P = .007). There was no significant difference in age, interval between transplantation and biopsy, and blood pressure between groups. Only a significantly higher serum creatinine was found in the CAN group. CONCLUSIONS: The increased renin-positive cells in JGA suggest a significant role of the intrarenal renin-angiotensin system activation in the development of CAN.

Adult↗
PubMed2005

Synergistic effects on the inhibition of human CD8+ cytotoxic T lymphocytes-mediated killing against xenograft cells by coexpression of membrane-bound Human FasL and decoy Fas antigen.

The principal barrier to the use of pigs as donors to humans is hyperacute rejection mediated by the interaction of alpha-gal abundantly expressed on pig cells and the natural anti-Gal antibody, abundantly produced in humans. This antibody-mediated hyperacute rejection may be overcome by an alpha1, 3 galactosyltransferase gene-knockout pig. However, xenograft cells could be rejected by T cells, especially CD8+ cytotoxic T lymphocytes (CTL)-mediated response, because these elements show great cytotoxicity against xenografted cells. We previously demonstrated that the Fas/FasL pathway is a major contributor to CD8+ CTL function. Furthermore, we sought to prevent this cytotoxicity by overexpression of membrane-bound FasL carrying the deletion at the metalloproteinase cleavage site or by decoy Fas antigen that does not contain the death domain in its cytoplasmic region. To investigate the effects of coexpression of these molecules, we cotransfected both genes into swine endothelial cells (SEC). The double-overexpression effectively prevented CD8+ CTL-mediated killing. Although cotransfectants and single transfectants of either membrane-bound FasL or decoy Fas gene showed similar inhibition of cytotoxicity, the expression levels of decoy Fas in SEC cotransfectants were much lower than those of decoy Fas single transfectants. These data suggest that beneficial effects for prevention of CTL-mediated xenocytotoxicity may be produced by the double expression of these molecules. The overexpression of both molecules on xenografted cells may decrease the innate cellular response to xenografts creating a window of opportunity to facilitate xenograft survival.

Acute Disease↗
PubMed2005

IL-4-producing CD8(+) T cells may be an immunological hallmark of chronic GVHD.

Chronic graft-versus-host disease (cGVHD) occurs in approximately 60-80% of those who survive over 100 days after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the pathophysiology of cGVHD is poorly understood. To gain more insight into the immunological mechanism of cGVHD, we examine cytokine production of peripheral blood T cells from 19 patients in the chronic phase of allo-HSCT. The percentage of IFN-gamma-producing CD8(+) T cells among CD8(+) T cells was significantly higher in patients with or without cGVHD than in normal control subjects (P<0.001). On the other hand, the percentage of IL-4-producing CD8(+) T cells among CD8(+) T cells was significantly higher in patients with cGVHD (mean 3.3%; range 1.3-8.2%) than in patients without cGVHD (mean 1.2%; range 0.8-1.7%) and normal control subjects (mean 1.1%; range 0.1-1.6%) (both P<0.001). By contrast, the percentage of IL-4-producing CD4(+) T cells was not different among patients with and without cGVHD and normal controls. These findings suggest that IL-4-producing CD8(+) T cells may be an immunological marker of cGVHD.

Adolescent↗
PubMed2005

Exploring RNA interference as a therapeutic strategy for renal disease.

The short synthetic interfering RNA duplexes (siRNAs) can selectively suppress gene expression in somatic mammalian cells without nonselective toxic effects of double-stranded RNA (dsRNA). However, a selective in vivo delivery of siRNA transfer has not been reported in kidney. Here, we investigated whether injection of synthetic siRNAs via renal artery followed by electroporation could be effective and therapeutic in silencing specific gene in glomerulus. We investigated the effect of siRNA in rat cultured mesangial cells (MCs) and showed that siRNA sequence-specific suppression of transgene expression was over a 1000-fold more potent than that by antisense oligodeoxynucleotide (ASODN). Transfection of siRNA targeting luciferase into rat kidneys significantly inhibited expression of a cotransfected luciferase expression vector in vivo. The delivery of siRNA targeting enhanced green fluorescent protein (EGFP) in the transgenic 'green' rat reduced endogenous EGFP expression, mainly in glomerular MCs. Furthermore, RNAi targeting against TGF-beta1 significantly suppressed TGF-beta1 mRNA and protein expression, thereby ameliorated the progression of matrix expansion in experimental glomerulonephritis. In addition, vector-based RNAi also inhibited TGF-beta1 expression in vitro and in vivo. In conclusion, siRNA-directed TGF-beta1 silencing may be of therapeutic value in the prevention and treatment of fibrotic diseases.

Animals↗
PubMed2005

Significance of chemokine receptor expression in aggressive NK cell leukemia.

Natural killer (NK) cell-type lymphoproliferative diseases of granular lymphocytes can be subdivided into aggressive NK cell leukemia (ANKL) and chronic NK cell lymphocytosis (CNKL). One reason for the poor outcome in ANKL is leukemic infiltration into multiple organs. The mechanisms of cell trafficking associated with the chemokine system have been investigated in NK cells. To clarify the mechanism of systemic migration of leukemic NK cells, we enrolled nine ANKL and six CNKL cases, and analyzed the expression profiles and functions of chemokine receptors by flowcytometry and chemotaxis assay. CXCR1 was detected on NK cells in all groups, and CCR5 was positive in all ANKL cells. Proliferating NK cells were simultaneously positive for CXCR1 and CCR5 in all ANKL patients examined, and NK cells with this phenotype did not expand in CNKL patients or healthy donors. ANKL cells showed enhanced chemotaxis toward the ligands of these receptors. These results indicated that the chemokine system might play an important role in the pathophysiology of ANKL and that chemokine receptor profiling might be a novel tool for discriminating ANKL cells from benign NK cells.

Adult↗
PubMed2005

White blood cell count is associated with plasma total homocysteine in Japanese men.

White blood cell (WBC) count has been related to risk for coronary heart disease. The relationship may be due to the association between WBC count and cardiovascular risk factors. So far, it has been shown that WBC count is associated with body mass index, total cholesterol, triglyceride, glucose, blood pressure and some lifestyle factors. It is not known, however, whether WBC count is associated with other risk factors such as total homocysteine or gamma-glutamyl transferase. The association between WBC count, total homocysteine and gamma-glutamyl transferase was analyzed cross-sectionally in middle-aged Japanese men. In a univariate regression analysis WBC count was associated positively with total homocysteine (beta (standard regression coefficient) = 0.112; p<0.001) but not with gamma-glutamyl transferase (beta = 0.033; p = 0.309). In a multivariate analysis which included cigarette smoking, physical activity, ethanol consumption, vegetable intake and body mass index, the association between WBC count and total homocysteine remained significant (beta = 0.062; p = 0.026). The association may partially explain the reported association between elevated WBC count and cardiovascular disease.

Cardiovascular Diseases↗