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Y Ito

Publications and source records attributed to Y Ito.

At least 73 records · Page 4Linked to original sources
PubMed2004

Time course of gene expression after the injection of adenoviral vectors containing CTLA4IG gene.

INTRODUCTION: In vivo gene transfection using a recombinant adenoviral vector leads to diminished gene expression in a time-dependent manner that disappears within 4 weeks. CTLA4Ig blocks CD28-mediated costimulatory signal, and inhibits immune responses. We investigated the duration of transgene expression after administration of adenoviral vector containing CTLA4Ig gene (AdCTLA4Ig). METHODS: We injected 1 x 10(9) plaque forming units (pfu) of AdCTLA4Ig into rats (n = 7) via the tail vein. Thereafter, the blood samples were collected for assay of serum CTLA4Ig levels using enzyme-linked immunosorbent assay. RESULTS: The CTLA4Ig level reached the maximum (range, 65-86 microg/mL; average, 75 microg/mL) on days 3 to 5 after injection. Detectable levels of CTLA4Ig were observed up to 49 days. When we injected AdCTLA4Ig in combination with FTY720 administration, the maximum levels were higher and the detectable levels persisted longer. CONCLUSIONS: Because directly injected adenoviral transgene expression had been reported to disappear between 21 to 30 days, we conclude that AdCTLA4Ig inhibits the immune response and prolongs the transgene (CTLA4Ig gene) expression. Some additional immunosuppressants, like FTY720, may be useful to enhance AdCTLA4Ig effects.

Abatacept↗
PubMed2004

Smooth muscle hamartoma of the abomasum in a calf.

This report describes a case of smooth muscle hamartoma of the abomasum in a 6-month-old steer humanely killed because of severe pneumonia. At necropsy, marked thickening of the abomasal wall in the area of the pylorus was found. On cut section, the thickness of the submucosal layer, extending from the submucosa to the muscularis propria, was seen to be increased to 3 cm. The upper (i.e., nearest to the gut lumen) half of the sectioned thickening was composed mainly of adipose-like tissue and the lower half mainly of muscle-like tissue. Histologically, the submucosal layer was composed of fibroadipose tissue, within which were embedded, to varying degrees, numerous well-defined, haphazardly oriented, thin to thick bundles of smooth muscle fibres. This appears to be the first report of smooth muscle hamartoma of the stomach or abomasum in animals, including man.

Abomasum↗
PubMed2004

Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model.

The prognosis of patients with malignant glioma is extremely poor, despite the extensive surgical treatment that they receive and recent improvements in adjuvant radio- and chemotherapy. In the present study, we propose the use of gene-modified mesenchymal stem cells (MSCs) as a new tool for gene therapy of malignant brain neoplasms. Primary MSCs isolated from Fischer 344 rats possessed excellent migratory ability and exerted inhibitory effects on the proliferation of 9L glioma cell in vitro. We also confirmed the migratory capacity of MSCs in vivo and showed that when they were inoculated into the contralateral hemisphere, they migrated towards 9L glioma cells through the corpus callosum. MSCs implanted directly into the tumor localized mainly at the border between the 9L tumor cells and normal brain parenchyma, and also infiltrated into the tumor bed. Intratumoral injection of MSCs caused significant inhibition of 9L tumor growth and increased the survival of 9L glioma-bearing rats. Gene-modification of MSCs by infection with an adenoviral vector encoding human interleukin-2 (IL-2) clearly augmented the antitumor effect and further prolonged the survival of tumor-bearing rats. Thus, gene therapy employing MSCs as a targeting vehicle would be promising as a new therapeutic approach for refractory brain tumor.

Adenoviridae↗
PubMed2004

A prospective study of body size and colon cancer mortality in Japan: The JACC Study.

OBJECTIVE: To determine whether body size measurements are risk factors for colon cancer death among the Japanese. DESIGN AND SUBJECTS: A nationwide prospective study, the Japan Collaborative Cohort (JACC) Study from 1988 to 1999. The present analysis included 43 171 men and 58 775 women aged 40-79 y who respond to a questionnaire on current weight and height, weight around 20 y of age, and other lifestyle factors. Body mass index (BMI) at baseline and 20 y of age (B-BMI and 20-BMI, respectively) were calculated. RESULTS: We identified 127 deaths from colon cancer during the follow-up of 424 698 person-years among men and 122 deaths during the follow-up of 591 787 person-years among women. After adjustments for the lifestyle factors known to modify the risk of colon cancer, weight at baseline showed a significant positive association in women, while no such association was seen in men. There was also a significant trend of increasing risk with the increase in B-BMI among women. Women with B-BMI >/=28 kg/m(2) had a relative risk (RR) of 3.41 (95% confidence interval (CI): 1.44-8.06) compared with those with BMI of 20-<22 kg/m(2). 20-BMI also presented the same trend of increasing risk as B-BMI. Women with 20-BMI of <22 and B-BMI of >26 kg/m(2), that is, excessive BMI gain, had a high RR of 3.41 (95% CI 1.29-9.02) compared with those with 20-BMI of <22 and B-BMI of <22 kg/m(2). There were no corresponding trends of colon cancer risk for B-BMI, 20-BMI, or BMI change among men. CONCLUSIONS: These study data suggest that obesity and excessive weight gain are associated with the risk of colon cancer death in Japanese women but no such relationship was found in Japanese men.

Adult↗
PubMed2004

Molecular characterization of a 10-kDa buckwheat molecule reactive to allergic patients' IgE.

BACKGROUND: Using the sera from buckwheat (BW)-allergic patients, several putative causative molecules were reported. However, few molecules were determined on the molecular structure. We demonstrated in 2000 that the major allergen with 24 kDa (BW24KD) is a legumin-like storage protein. OBJECTIVE: The aim of this study was to isolate and characterize further a major allergen with 10 kDa by molecular cloning. METHODS AND RESULTS: Buckwheat allergens were identified by immunoblotting analysis using sera from 14 allergic and two nonallergic individuals. We identified a protein with 10 kDa (BW10KD) that reacted with immunoglobulin E (IgE) more strongly than with IgG and IgA in 57% of the allergic patients but not with IgE in nonallergic individuals. Analyses were performed by N-terminal amino acid sequencing and molecular cloning. Physiological significance was assessed by an immunoblotting experiment showing that the reactivity of an allergic patient's serum IgE to BW10KD was competitively inhibited by natural BW extracts. CONCLUSION: Molecular cloning experiments indicated that BW10KD as a BW allergen was a member of the 2S-albumin multigene family.

Adolescent↗
PubMed2004

Development of a fast neutron spectrometer composed of silicon-SSD and position-sensitive proportional counters.

A new fast neutron spectrometer has been developed. The spectrometer is composed of a silicon surface barrier detector and three position-sensitive proportional counters with methane gas working as counting gas and a radiator. A collimated incident neutron interacts with a hydrogen atom in the methane gas to generate a recoil proton. The position information on the path of the recoil proton obtained from the three position-sensitive proportional counters gives the recoil angle. In the meanwhile, the energy of the recoil protons is measured with the three proportional counters and the silicon surface barrier detector. The characteristics of the spectrometer were evaluated with a monoenergetic neutron beam. The best energy resolution was 1.8% for 5.0 MeV neutrons.

Computer Simulation↗
PubMed2004

Development of a tiny neutron probe with an optical fibre for BNCT.

We have developed a tiny neutron probe detector as a monitor of a thermal neutron flux for boron neutron capture therapy. The detector consists of an optical fibre and a small neutron probe. We have used a film-like ZnS(Ag) scintillator and a 6LiF neutron converter for the neutron probe. In order to improve the gamma-neutron discrimination ability, vacuum evaporation of 6LiF onto the ZnS(Ag) film has been done. In order to improve the neutron detection efficiency, we made use of a wavelength-shifting fibre as the probe material. The characteristics of the above two types of fibre probe detector have been evaluated experimentally.

Body Burden↗
PubMed2004

Characterization of gamma rays existing in the NMIJ standard neutron field.

Our laboratory provides national standards on fast neutron fluence. Neutron fields are always accompanied by gamma rays produced in neutron sources and surroundings. We have characterised these gamma rays in the 5.0 MeV standard neutron field. Gamma ray measurement was performed using an NE213 liquid scintillator. Pulse shape discrimination was incorporated to separate the events induced by gamma rays from those by neutrons. The measured gamma ray spectra were unfolded with the HEPRO program package to obtain the spectral fluences using the response matrix prepared with the EGS4 code. Corrections were made for the gamma rays produced by neutrons in the detector assembly using the MCNP4C code. The effective dose equivalents were estimated to be of the order of 25 microSv at the neutron fluence of 10(7) neutrons cm(-2).

Algorithms↗
PubMed2004

Tie-1 tyrosine kinase expression in human thyroid neoplasms.

AIMS: To investigate tie-1 expression in human thyroid neoplasms. Recent studies have demonstrated that receptor-type tyrosine kinases (RTKs) contribute to carcinoma progression. Tie-1 is one of the RTKs and plays a role in angiogenesis, although its pathophysiological significance in human carcinoma is still to be elucidated. METHODS AND RESULTS: Immunohistochemical expression of tie-1 was studied in various thyroid neoplasms. Tie-1 immunoreactivity was only occasionally observed in normal follicular cells. In papillary carcinoma, tie-1 was classified as positive in carcinoma cells in 55.7% of the cases and was more frequently expressed in those of smaller size with an absence of a poorly differentiated lesion. In contrast, tie-1 was positive in only 8.3% of anaplastic carcinoma and no cases of follicular carcinoma or adenoma were positive. CONCLUSIONS: These results suggest that tie-1 has a role in thyroid tumorigenesis, especially in the early phase of papillary carcinoma, but it is not important in the progression of anaplastic carcinoma or follicular tumour.

Carcinoma↗
PubMed2004

Pathological study on the relationship between C4d, CD59 and C5b-9 in acute renal allograft rejection.

In order to evaluate the activation or inhibition of the later phases of classical complement cascade in renal allograft presenting with acute rejection, particularly with C4d deposition on the peritubular capillary (PTC), we observed the expression of CD59 and C5b-9 on the PTC. Subjective cases were divided into two groups, an acute rejection group, of 4 males and 6 females, and a normal donor group, of 5 males and 5 females. Renal biopsies were performed at the onset of acute rejection and at the transplant operation, before reperfusion. C4d deposition on PTC was found in three of 10 cases (30%) with biopsy proven acute rejection, whereas CD59 on PTC was positively expressed in all of the rejection cases. Although C5b-9 was not observed on PTC in the acute rejection group, it was intensively deposited on the tubular basement membrane (TBM) in five cases, including the three with positive C4d on PTC. In the normal donor group, CD59 on PTC was intensively observed, whereas C5b-9 was weakly expressed on TBM. CD59, a complement regulatory factor, works as an inhibitory factor against the formation of C5b-9, a membrane attack complex. From our data, we noted the dissociation between the depositions of C4d and C5b-9 on PTC. The substantially expressed CD59 on PTC may affect this dissociation between C4d and C5b-9 on PTC. The intensive deposition of C5b-9 on TBM in acute rejection cases may suggest an independent immunological injury attacking tubular cells.

Acute Disease↗
PubMed2004

Identification of an epitope from the epithelial cell adhesion molecule eliciting HLA-A*2402-restricted cytotoxic T-lymphocyte responses.

Because the epithelial cell adhesion molecule (Ep-CAM) is expressed in almost all carcinomas and human leucocyte antigen (HLA)-A*2402 is the most common allele in many ethnic groups, including Japanese, the identification of peptide sequences, which elicit HLA-A*2402-restricted Ep-CAM-specific cytotoxic T-lymphocyte (CTL) responses, would facilitate specific immunotherapy for various histological types of carcinomas. An epitope was identified through the following steps: (i) computer-based epitope prediction from the amino acid sequence of Ep-CAM, (ii) major histocompatibility complex (MHC) stabilization assay to determine the affinity of the predicted peptide with HLA-A*2402 molecules, (iii) stimulation of CD8+ T cells with peptide-pulsed dendritic cells and (iv) testing the CTL specificity by means of enzyme-linked immunospot (ELISPOT) assays, CTL assays and MHC/peptide-tetramer staining. Peripheral CD8+ T cells of four of five healthy donors after three rounds of stimulation with the peptide Ep-CAM173-181 (RYQLDPKFI) secreted interferon-gamma in ELISPOT assays when exposed to the peptide. A CTL clone specific to the peptide efficiently lysed Ep-CAM-expressing cancer cell lines in an HLA-A*2402-restricted fashion. Endogenous processing and presentation of the peptide in a lung cancer cell line were confirmed by means of cold target inhibition assays. The CTL clone was also lytic to normal bronchial epithelial cells but to a lesser extent at low effector: target ratios. All these data suggest that the peptide-specific CTL responses may play some roles both in anti-cancer and autoimmune reactions. The peptide should prove useful to study anti-Ep-CAM CTL responses among population possessing HLA-A*2402.

Biomarkers, Tumor↗
PubMed2004

Parathyroid invasion, nodal recurrence, and lung metastasis by papillary carcinoma of the thyroid.

AIMS: Parathyroid invasion by papillary thyroid carcinoma (PTC) is found in a small proportion of surgical specimens, but the clinicopathological relevance of this phenomenon is not well understood. This study investigated the possible prognostic relevance of parathyroid invasion in PTC. METHOD: Parathyroid involvement was seen in 14 patients with PTC, and the clinicopathological characteristics and follow up data of these patients were analysed and compared with 164 patients without parathyroid involvement, in whom histological parathyroid examination had been undertaken, and 177 other patients without parathyroid examination (341 patients without parathyroid involvement in total). RESULTS: Parathyroid invasion was found in older patients and there were more male patients in this group than in those without parathyroid invasion. These patients had more extrathyroid extension and were frequently in an advanced stage of disease. Lung metastasis was seen in two of the 14 patients, which was significantly more than that seen in control cases. Moreover, male patients with parathyroid invasion and those who were older than 55 years had reduced disease free survival compared with those without parathyroid invasion. CONCLUSION: Parathyroid invasion seen in thyroid carcinoma may be an important histological feature indicating a greater chance of nodal recurrence and lung metastasis.

Age Factors↗
PubMed2004

Papillary carcinoma of the thyroid in Japan: subclassification of common type and identification of low risk group.

AIMS: Papillary thyroid carcinoma (PTC) is classified into two subgroups-common type and other histological variants. Correlations between further subgrouping of the common type and patient prognosis are not well documented. AIMS: To introduce two novel histological parameters to characterise PTC-loss of cellular polarity and loss of cellular cohesiveness. To investigate a new subgroup of common type PTC with possible prognostic value. METHODS: In total, 213 patients with PTCs larger than 1 cm were studied. Histological characteristics of these PTCs, including tumour growth pattern, encapsulation, extrathyroidal invasion, loss of cellular polarity, and loss of cellular cohesiveness were examined and correlated with disease free survival (DFS). RESULTS: Multivariate analysis revealed that invasive growth of unencapsulated PTC, in addition to sex (male) and tumour size (>4 cm) were significant and independent parameters for poor DFS, whereas loss of cellular polarity and cohesiveness, old age (>60 years), extrathyroid invasion, and completeness of surgery were significant only in univariate analysis. PTCs that showed expansive growth and retained cellular polarity had a favourable course, with no recurrence and no cancer related deaths. In contrast, PTCs exhibiting loss of cellular polarity and/or invasive growth with no tumour capsule had a higher risk of recurrence. CONCLUSION: Cytological features alone cannot predict patient outcome in PTC. This study indicates for the first time that loss of cellular polarity and the tumour growth pattern are useful parameters for identifying the so called low risk group in common type PTC and in predicting patient outcome in terms of tumour recurrence and cancer related death.

Age Factors↗
PubMed2004

Influence of serum from rats with fulminant hepatic failure on hepatocytes in a bioartificial liver system.

Fulminant hepatic failure (FHF) is a life-threatening condition marked by many excessively increased unmetabolized toxins and growth factors. Recently developed bioartificial liver (BAL) systems containing hepatocytes can be used to treat patients with FHF However, the behavior of these hepatocytes on exposure to FHF serum in vitro remains unclear. In the present study, we used FHF rat models and the sera from these rats (i.e., FHF serum) contained elevated inflammatory cytokines (TNF-alpha, IL-1beta, and IL-6), HGF, and TGF-beta1. In addition, 1x10(8) hepatocytes were harvested from the livers of inbred rats and incubated with microcarrier beads. Four hours later, the hepatocyte-coated beads were inoculated into a hollow-fiber module (=BAL system). FHF serum or normal control serum circulated for 6 hours through the BAL system. Expressions of mRNA for albumin, GST A1, CYP 1A2, OTC and c-fos were investigated by RT-PCR, and PCNA staining was performed before and after perfusion. The expressions of albumin, GST A1, and CYP 1A2 mRNAs were markedly decreased, whereas those of OTC and c-fos were modestly decreased. PCNA positive cells were low and showed no difference between FHF and normal serum-exposed hepatocytes. In conclusion, the exposure of hepatocytes to hypercytokinemia, including inflammatory cytokines and positive and negative growth factors, caused a loss in liver specific functions. This environment also failed to facilitate hepatocyte regeneration.

Animals↗
PubMed2004

[Surgical treatment of left ventricular-right atrial communication complicated with aortic and mitral valves regurgitation: report of a case].

A 50-year-old man with a heart murmur from early childhood and a one year history of general fatigue was admitted. Cardiac examination showed a left ventricular-right atrial (LV-RA) communication, and aortic and mitral valve regurgitation (III/IV). At surgery, the LV-RA communication was located in the atrioventricular membranous portion 3 mm above the septal leaflet of the tricuspid valve. The etiology of the LV-RA communication was congenital and valvular diseases were acquired changes caused by sclerosis due to infected endocarditis or hypertension. The diameter of the LV-RA communication defect was 6 mm, and the fibrous tissue around the defect was closed directly. Next, double-valve replacement was performed safely. However, the day after surgery, the patient developed complete atrioventricular block and implantation of a DDD pacemaker was required. He was discharged without other complication. We recommend the careful closure of the LV-RA communication defect, if the defect is small and rich in fibrous tissue.

Aortic Valve Insufficiency↗
PubMed2004

Reconstruction of the anterior cruciate ligament. Single- versus double-bundle multistranded hamstring tendons.

A total of 108 patients with unilateral instability of the knee, associated with rupture of the anterior cruciate ligament, was prospectively randomised for arthroscopic single- or double-bundle reconstruction of the ligament using hamstring tendons. The same post-operative rehabilitation protocol was used for all. The patients were followed up for a mean of 32 months (24 to 36). We measured the anterior laxity and joint position sense at different angles of flexion of the knee to determine whether both bundles in the double-bundle reconstruction contributed to the stability of the joint and proprioception. No significant difference was found between the two groups with regard to anterior laxity measured by the KT-2000 arthrometer with the knee at 20 degrees or 70 degrees flexion nor with regard to proprioception. A notchplasty was required less often in the double- compared with the single-bundle reconstruction. We did not find any advantage in a double-bundle as opposed to a single-bundle reconstruction in terms of stability or proprioception.

Adolescent↗