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H Ito

Publications and source records attributed to H Ito.

At least 199 records · Page 11Linked to original sources
PubMed2001

G2-chromosome aberrations induced by high-LET radiations.

We report measurement of initial G2-chromatid breaks in normal human fibroblasts exposed to various types of high-LET particles. Exponentially growing AG 1522 cells were exposed to gamma rays or heavy ions. Chromosomes were prematurely condensed by calyculin A. Chromatid-type breaks and isochromatid-type breaks were scored separately. The dose response curves for the induction of total chromatid breaks (chromatid-type + isochromatid-type) and chromatid-type breaks were linear for each type of radiation. However, dose response curves for the induction of isochromatid-type breaks were linear for high-LET radiations and linear-quadratic for gamma rays. Relative biological effectiveness (RBE), calculated from total breaks, showed a LET dependent tendency with a peak at 55 keV/micrometer silicon (2.7) or 80 keV/micrometer carbon (2.7) and then decreased with LET (1.5 at 440 keV/micrometer). RBE for chromatid-type break peaked at 55 keV/micrometer (2.4) then decreased rapidly with LET. The RBE of 440 keV/micrometer iron particles was 0.7. The RBE calculated from induction of isochromatid-type breaks was much higher for high-LET radiations. It is concluded that the increased production of isochromatid-type breaks, induced by the densely ionizing track structure, is a signature of high-LET radiation exposure.

Cell Line↗
PubMed2001

Therapeutic effects of FTY720, a new immunosuppressive agent, in a murine model of acute viral myocarditis.

OBJECTIVES: This study examines the efficacy of FTY720 (FTY), a new immunosuppressor, in the treatment of acute viral myocarditis in a murine model. BACKGROUND: Immunosuppressive agents have no proven therapeutic efficacy in experimental or clinical myocarditis. METHODS: Encephalomyocarditis virus was inoculated i.p. in DBA/2 mice on day 0. Postinoculation treatment consisted of FTY 10 mg/kg/day p.o. (FTY group), or cyclosporine A (CsA) 40 mg/kg/day p.o. (CsA group) or distilled water p.o. only (control group). Survival until day 14, as well as cardiac histopathology, virus concentrations, cytokines (interleukin [IL]-2, IL-12, interferon [IFN]-gamma and tumor necrosis factor [TNF]-alpha) and nitric oxide (NO) on day 5 were examined. RESULTS: In the control and CsA groups, all mice died within 10 and 7 days, respectively. However, in the FTY group, 27% of the animals survived up to day 14. Compared with the control group, 1) histological scores were significantly lower in the FTY group but unchanged in the CsA group; 2) virus concentration was significantly higher in the CsA group but not in the FTY group; 3) expressions of IL-2, IL-12 and IFN-gamma in the heart were suppressed in both the FTY and CsA groups, though suppression was weaker in the FTY group; 4) TNF-alpha and NO were significantly increased in the CsA group but not in the FTY group. CONCLUSIONS: FTY720 had a significant therapeutic effect in acute experimental myocarditis without inducing excessive virus replication. This report is the first to describe a beneficial effect by an immunosuppressive agent in the treatment of acute viral myocarditis.

Acute Disease↗
PubMed2001

Predictive factors for development of the no-reflow phenomenon in patients with reperfused anterior wall acute myocardial infarction.

OBJECTIVES: We sought to elucidate the clinical factors related to the development of no-reflow phenomenon after successful coronary reperfusion in patients with an acute myocardial infarction (AMI). BACKGROUND: Myocardial contrast echocardiography revealed that the no-reflow phenomenon is observed in some patients with a reperfused AMI, and those patients usually have poor functional and clinical outcomes. It is still unknown what clinical factors are related to the development of the no-reflow phenomenon. METHODS: Myocardial contrast echocardiography was performed 15 min after successful coronary reperfusion therapy in 199 patients with an anterior wall AMI who underwent successful coronary reperfusion with primary coronary angioplasty within 24 h after the onset of AMI. Multiple logistic regression analysis was used to identify independent predictors of the no-reflow phenomenon. RESULTS: Seventy-nine patients showed the no-reflow phenomenon. Univariate analysis indicated that pre-infarction angina within 48 h before symptom onset, Killip class, Thrombolysis in Myocardial Infarction flow grade 0 on the initial coronary angiogram, the number of abnormal Q-waves and the wall motion score (WMS) on the echocardiogram obtained at hospital admission are related to the no-reflow phenomenon. Multivariate logistic regression analysis revealed that all of these factors, except for Killip class, are independent predictive factors of the no-reflow phenomenon. CONCLUSIONS: Development of the no-reflow phenomenon is related to the severity of myocardial damage (number of Q-waves), the size of the risk area (WMS) and the occlusion status of infarct-related artery. In addition, ischemic preconditioning (pre-infarction angina) seems to be the factor that attenuates the no-reflow phenomenon.

Adult↗
PubMed2001

Mechanism of prostaglandin D(2)-stimulated heat shock protein 27 induction in osteoblasts.

We previously showed that prostaglandin D(2) (PGD(2)) stimulates activation of protein kinase C (PKC). We investigated whether PGD(2) stimulates the induction of heat shock protein (HSP) 27 and HSP70 in osteoblast-like MC3T3-E1 cells and the mechanism underlying the induction. PGD(2) increased the levels of HSP27 while having little effect on HSP70 levels. PGD(2) stimulated the accumulation of HSP27 dose dependently in the range between 10 nM and 10 microM. PGD(2) induced an increase in the levels of mRNA for HSP27. The PGD(2)-stimulated accumulation of HSP27 was reduced by staurosporine or calphostin C, inhibitors of PKC. PGD(2) induced the phosphorylation of p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase. The HSP27 accumulation induced by PGD(2) was significantly suppressed by PD98059, an inhibitor of the upstream kinase of p44/p42 MAP kinase, or SB203580, an inhibitor of p38 MAP kinase. Calphostin C suppressed the PGD(2)-induced phosphorylation of p44/p42 MAP kinase and p38 MAP kinase. PD98059 or SB203580 suppressed the PGD(2)-increased levels of mRNA for HSP27. These results strongly suggest that PGD(2) stimulates HSP27 induction through p44/p42 MAP kinase activation and p38 MAP kinase activation in osteoblasts and that PKC acts at a point upstream from both the MAP kinases.

Animals↗
PubMed2001

Megastigmane glycosides and an acylated triterpenoid from Eriobotrya japonica.

Two new megastigmane glycosides, eriojaposides A (1) and B (2), and a new acylated triterpenoid (3) were isolated along with nine known compounds from a leaf extract of Eriobotrya japonica. The structures of 1--3 were characterized as (6R,9R)-3-oxo-alpha-ionyl-9-O-beta-xylopyranosyl-(1' '-->6')-beta-glucopyranoside, (6R,9R)-3-oxo-alpha-ionyl-9-O-alpha-rhamnopyranosyl-(1' '-->6')-beta-glucopyranoside, and 3 alpha-trans-feruloyloxy-2 alpha-hydroxyurs-12-en-28-oic acid, respectively, on the basis of spectral and chemical evidence.

Asia↗
PubMed2001

Prognostic significance of changes in prostate-specific antigen in patients with metastasis prostate cancer after endocrine treatment.

Patients with metastatic prostate cancer respond to androgen withdrawal therapy, but progression to androgen independence is frequently observed. To clarify the predictor of response to endocrine therapy, the role of PSA changes and the prognosis of the patients were evaluated in 115 Japanese cases of prostate cancer with distant metastases treated with androgen withdrawal therapy. When patients were divided according to the pretreatment PSA value (high, > or = 500, median; 500 > PSA > or = 100, low; 100 >), patients whose initial PSA levels were high had a worse cause-specific survival. PSA value at 3 or 6 months following endocrine treatment, PSA nadir, and percent decrease of PSA were associated with prolonged survival. Clinical relapse was observed in 68 patients. Patients with distant recurrence had shorter time to PSA elevation than those with local recurrence. In metastatic prostate cancer patients treated with androgen withdrawal, serial measurement of PSA could distinguish nonfavorable responders early in the course of treatment and assist in monitoring for disease progression.

Aged↗
PubMed2001

Survival of memory T cells specific for Japanese cypress pollen allergen is maintained by cross-stimulation of putative pectate lyases from other plants.

In view of recent studies on the mechanisms of the survival of peripheral memory T cells, we tested the biologic role of pectate lyase, a pectin-degrading enzyme, as the cross-reactive antigen required for the recurring survival signals for human T cells specific for Cha o 1, a pollen allergen molecule of the Japanese cypress. We determined a 16-mer epitope peptide for the T-cell clone, and prepared synthetic oligopeptides of homologous regions in putative pectate lyase of other plants. Of these homologous peptides, ZePel (Zinnia elegans), ban 17 (banana), and Amb a 1.1 (short ragweed) induced strong proliferative responses of the Cha o 1-specific T-cell clone in vitro. In addition, suboptimal doses of peptide homologs derived from banana and short ragweed enhanced the survival potency of this T-cell clone without detectable proliferative responses to the peptides. When there was no antigen stimulation, the T-cell clone decreased in viable cell number and lost antigen-specific proliferation activity on day 6 during in vitro incubation. On the other hand, T-cell clones incubated with these survival-inducing peptides maintained proliferative activity to Cha o 1 even on day 9. Serum derived from the donor patient did not contain detectable levels of IgE specific to banana or short ragweed by CAP-RAST. These results show that human T cells specific for pollen allergen seem to use cross-reactive pectate lyase peptides to deliver survival signals even in the absence of pollen allergen, and memory T cells maintained in such a manner might be functioning at the onset of allergic pollinosis, although pollen allergens are seasonal.

Allergens↗
PubMed2001

Telepathology for the biopsy specimens from human allografted kidney: effectiveness and pitfalls.

This study was conducted to examine the validity and accuracy of telepathology for biopsy specimens from allografted kidney. The still video images of paraffin sections were transmitted via a two-way telephone by use of a digitized telephone network, ISDN. The quality of the transmitted images was sufficient for the diagnosis, especially at higher magnification. A total of 37 needle biopsy specimens from the 31 allografted kidneys were presented for consultation and diagnosed by an expert pathologist at Tottori University, until July 2000. The average number of transmitted images was 7.1 (range 3-12). Of the 37 specimens, diagnoses by telepathology agreed well with those made through direct microscopy in the 30 specimens. Insufficient or improper diagnosis was made in four specimens, in which proper and pathognomonic still images were not transmitted. Three cases were not diagnosed by telepathology because of the difficulty in making differential diagnosis. From these results, we concluded that telepathology is useful for transplantation pathology, in spite of limitations in some cases.

Biopsy, Needle↗
PubMed2001

Inclusion body myositis associated with hepatitis C virus infection.

The case of a 77-year-old woman with hepatitis C virus infection with a 5-year history of muscle weakness and mild disturbance of gait is reported. Steroid therapy did not improve her symptoms. She developed HCV-related liver cirrhosis and hepatocellular carcinoma, and muscle biopsy revealed inclusion body myositis. Immunohistochemistry showed that the nonstructural region of HCV and 8-hydroxy-2'-deoxyguanosine, a marker of DNA damage by reactive oxygen species, were present in striated muscle cells of this patient.

Aged↗
PubMed2001

Mechanisms involved in the establishment of tolerance through costimulatory blockade and BMT: lack of requirement for CD40L-mediated signaling for tolerance or deletion of donor-reactive CD4+ cells.

We have previously shown that high levels of multiline-age mixed hematopoietic chimerism and systemic T-cell tolerance can be achieved in mice without myeloablation through the use of anti-CD40L and costimulatory blockade alone (plus CTLA4Ig) or with recipient CD8 depletion and allogeneic bone marrow transplantation. Chimeric mice permanently accept donor skin grafts (> 100 days), and rapidly reject third-party grafts. The mechanisms by which costimulatory blockade facilitates the engraftment of allogeneic hematopoietic cells have not been defined. To further understand the in vivo mechanisms by which the administration of anti-CD40L mAb facilitates the engraftment of donor bone marrow and rapidly tolerizes CD4+ T cells, we analyzed the establishment of chimerism and tolerance in CD40L -/- mice. We demonstrate here that anti-CD40L mAb treatment is required only to prevent CD40L/CD40 interactions, and that no signal to the T cell through CD40L is necessary for the induction of CD4+ tolerance. Peripheral deletion of donor-reactive CD4+ T cells occurs rapidly in CD40L -/- mice receiving bone marrow transplantation (BMT), indicating that this deletion in the presence of anti-CD40L is not due to targeting of activated CD4+ cells by the antibody. Complete CD4+ cell tolerance is observed by both skin graft acceptance and in vitro assays before deletion is complete, indicating that additional mechanisms play a role in inducing CD4+ T-cell tolerance as the result of BMT in the presence of CD40/CD40L blockade.

Animals↗
PubMed2001

The role of epigenetic modifications in retinoic acid receptor beta2 gene expression in human prostate cancers.

The retinoic acid receptor (RAR) beta gene is a putative tumor suppressor gene on chromosome 3p24, where a high incidence of loss of heterozygosity is detected in many types of tumors. Retinoic acid suppresses cancer cell growth through binding to RARs, especially RARbeta, indicating a critical role in mediating anticancer effects. Selective loss or down-regulation of RARbeta mRNA and protein has been reported in prostate cancers (PCas), although the mechanisms remain unclear. We investigated the role of epigenetic modification in RARbeta2 gene silencing. Aberrant methylation was detected in 11 of 14 (79%) primary PCas, 9 of 10 (90%) hormone-refractory PCas, and 2 of 4 (50%) PCa cell lines, but not in any normal prostate samples. Chromatin immunoprecipitation assay showed that all RARbeta2-negative cells (LNCaP, PC3, and DU145) were hypoacetylated at both histones H3 and H4. After exposure to 5-aza-2prime;-deoxycytidine treatment, Trichostatin A and all-trans retinoic acid induced partial demethylation, increased accumulation of acetylated histones, and markedly restored the expression of RARbeta2 in RARbeta2-negative cells. These data suggest that the RARbeta2 gene may be one of the frequently silenced genes by epigenetic modifications in PCa.

Base Sequence↗
PubMed2001

Estimation of anti-platelet drugs on human platelet aggregation with a novel whole blood aggregometer by a screen filtration pressure method.

1. The effects of anti-platelet drugs on human whole blood aggregation were evaluated using a novel whole blood aggregometer by a screen filtration pressure (SFP) method. 2. The SFP whole blood aggregometer was found to successfully detect whole blood aggregation induced by ADP, collagen and TRAP by measuring the SFP of blood samples. The platelet aggregation threshold index (PATI), the concentration of agonist required with an inducing pressure rate of 50%, varied time-dependently after collection of blood. High values for ADP and collagen were noted immediately after blood collection, suggesting low aggregation activity of platelets, and gradually increase thereafter. 3. Cilostazol (phosphodiesterase 3 inhibitor), dipyridamole, aspirin and tirofiban all inhibited whole blood aggregation in vitro. Inhibitory effects of cilostazol and dipyridamole, but not tirofiban, were markedly enhanced 6 or 7 fold by long pre-incubation (60 min), compared with short pre-incubation (2 min). Such enhancement was only observed with ADP- and not collagen-induced whole blood aggregation. A similar phenomenon was also observed for aggregation with platelet rich plasma (PRP). Cilostazol inhibition of ADP-induced platelet aggregation was more potent with PRP than whole blood (PATI(200)=3.80+/-0.95 microM for whole blood; 2.04+/-0.61 microM for PRP). Inhibitory effects of dipyridamole were attenuated in PRP without erythrocytes. 4. These results demonstrate that the SFP aggregometer can sensitively detect anti-platelet aggregatory effects of various kinds of drugs. So that it is a useful tool for evaluation of anti-platelet drugs.

Adenosine Diphosphate↗
PubMed2001

Relation between body composition and age in healthy Japanese subjects.

OBJECTIVE: To describe the relation between body composition and age measured by dual-energy X-ray absorptiometry (DXA) in healthy Japanese adults. DESIGN: Cross-sectional study. SUBJECTS AND MEASUREMENTS: The subjects were 2411 healthy Japanese adults (males 625, females 1786, age 20--79 y) who attended the Fukuoka Health Promotion Center, Fukuoka, Japan for health check-up. Body composition was determined by DXA (QDR-2000, Hologic) for the whole body and three anatomical regions of arms, legs and trunk. RESULTS: The mean values of body mass index (BMI) and percentage fat mass (%FM) were 23.2+/-3.1 (s.d.) kg/m(2) and 21.8+/-6.8% for males and 22.1+/-3.3 kg/m(2) and 32.0+/-7.5% for females, respectively. For males, curvilinear relations with the peaks in their forties or fifties were seen for the variables associated adiposity, ie BMI, waist and hip circumference, waist-hip ratio, total or regional fat mass (FM), %FM and ratio of trunk FM to leg FM. For females, most of these variables increased linearly in older subjects. Lean mass (LM), bone mineral content (BMC) and bone mineral density (BMD) of the whole body and appendicular LM were relatively constant until the forties and then decreased in both sexes. The rates of decrease in the total or appendicular LM were larger for males than for females, whereas those in BMC or BMD were larger for females than for males. CONCLUSIONS: This study presents the first detailed data on body composition in Japanese, which may be useful when comparing with populations of different racial and ethnic backgrounds and studying ill subjects.

Absorptiometry, Photon↗
PubMed2001

Histological changes in the hypofunctional pituitary gland following conventional radiotherapy for adenoma.

AIMS: Although delayed hypopituitarism is a common complication of conventional radiotherapy of sellar tumours, histological changes that may account for it have been rarely reported. To elucidate the changes, hypofunctional pituitary glands following irradiation were studied. METHODS AND RESULTS: Two pituitary glands obtained at autopsy from patients who had been irradiated for adenoma and exhibited hypopituitarism were examined. In both cases diffuse fibrosis was observed in the adenohypophysis, whereas the neurohypophysis remained unchanged. Immunohistochemistry showed that stellate-shaped S100 protein-positive cells were increased in number and distributed among the endocrine cells. Some irradiated endocrine cells showed dense granular immunoreactivity for mitochondrial protein, cytochrome oxidase and manganese-superoxide dismutase. In addition to faint reactivity with anti-cytokeratin 8, 18 antibody, many cells were densely positive with anti-cytokeratin 1, 5, 10, 14 antibody. CONCLUSIONS: These results indicate that radiation- induced fibrosis is associated with an increased number of folliculo-stellate cells and the presence of metabolic dysfunctional mitochondria resembling mitochondria in oncocytes. Squamous metaplasia in the irradiated endocrine cells was also noted. Various intracellular changes may participate in delayed pituitary hypofunction following radiotherapy.

Adenoma↗
PubMed2001

Contribution of conformational stability of hen lysozyme to induction of type 2 T-helper immune responses.

It is important to identify characteristics that confer on proteins the potential to induce allergenic sensitization and allergenic disease. Protein allergens carry T-cell epitopes that are capable of inducing a type 2 T helper (Th2) cell response. There is limited information regarding factors that govern the allergenicity of proteins. We previously reported that a decrease in the conformational stability of hen-egg lysozyme (HEL) enhanced its capacity to activate HEL-specific T cells owing to the increased susceptibility to intracellular antigen processing. To determine whether the conformational stability of HEL makes for a critical contribution to allergenic sensitization in vivo, we immunized BALB/c mice with HEL derivatives of different conformational stability, but which retained a similar three-dimensional structure. The magnitude of in vivo T-cell responses, evaluated by ex vivo proliferative responses of lymph node T cells from mice primed with various HEL derivatives, was inversely correlated with conformational stability, as was interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) production by splenic T cells in response to HEL. Immunization of the least stable derivative led to a potent IL-4 response and to immunoglobulin E (IgE) antibody production. We propose that the intrinsic allergenicity of proteins can be determined by the degree of conformational stability.

Animals↗
PubMed2001

Specific localization of the basigin protein in human testes from normal adults, normal juveniles, and patients with azoospermia.

Basigin is a transmembrane protein belonging to the immunoglobulin superfamily. Specific localization of the protein in normal human testes, from those of a 2-year-old boy to those of a 50-year-old man, and in testes with Sertoli cell only syndrome and germ cell arrest, is reported. Basigin localization was determined using an immunohistochemical technique with an antibody against human basigin. In the normal adult testes, basigin was detected at the periphery of both spermatocytes older than zygotene and round spermatids. In the juvenile testes, it was expressed in accordance with the appearance of pachytene spermatocytes. In this study, pachytene spermatocytes were detected in an 11-year-old boy. Basigin was not expressed in immature testes with germ cells younger than pachytene spermatocytes, namely in testes from boys aged 2-9 years. In testes from adult patients with Sertoli cell only syndrome, basigin was expressed at the periphery of Sertoli cells, but localization was confined to the adluminal compartment of the seminiferous tubule. In testes with germ cell arrest, the protein was expressed on germ cells from pachytene spermatocytes to step 2 spermatids, where present. The results show that in the normal human testes basigin is expressed with the onset of spermatocyte differentiation. Because human basigin is expressed in adult testes with Sertoli cell only syndrome, the protein seems to be synthesized in Sertoli cells and expression continues after these cells dedifferentiate in the seminiferous epithelium.

Adolescent↗