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Biomedical subjects

Y Kishimoto

Publications and source records attributed to Y Kishimoto.

At least 19 recordsLinked to original sources

Search for the invisible decay of neutrons with KamLAND.

The Kamioka Liquid scintillator Anti-Neutrino Detector is used in a search for single neutron or two-neutron intranuclear disappearance that would produce holes in the -shell energy level of (12)C nuclei. Such holes could be created as a result of nucleon decay into invisible modes (inv), e.g., n--> 3v or nn--> 2v. The deexcitation of the corresponding daughter nucleus results in a sequence of space and time-correlated events observable in the liquid scintillator detector. We report on new limits for one- and two-neutron disappearance: tau(n--> inv) > 5.8 x 10(29) years and tau (nn--> inv) > 1.4 x 10(30) years at 90% C.L. These results represent an improvement of factors of approximately 3 and >10(4) and over previous experiments.

Journal Article↗

Phase separation in A-site-ordered perovskite manganite LaBaMn2O6 probed by 139La and 55Mn NMR.

139La- and 55Mn-NMR spectra demonstrate that the ground state of the A-site-ordered perovskite manganite LaBaMn2O6 is a spatial mixture of the ferromagnetic and antiferromagnetic regions, which are assigned to the metallic and the insulating charge ordered state, respectively. This exotic coexisting state appears below 200 K via a first-order-like formation of the antiferromagnetic charge ordered state inside the ferromagnetic metal one. The Mn spin-spin relaxation rate indicates that the ferromagnetic region coexisting with the antiferromagnetic one in LaBaMn2O6 is identical to the bulk ferromagnetic metal phase of the disordered form La0.5Ba0.5MnO3 in spite of the absence of A-site disorder. This suggests a mesoscopic rather than nanoscopic nature of the ferromagnetic region in LaBaMn2O6.

Journal Article↗

Experimental investigation of geologically produced antineutrinos with KamLAND.

The detection of electron antineutrinos produced by natural radioactivity in the Earth could yield important geophysical information. The Kamioka liquid scintillator antineutrino detector (KamLAND) has the sensitivity to detect electron antineutrinos produced by the decay of 238U and 232Th within the Earth. Earth composition models suggest that the radiogenic power from these isotope decays is 16 TW, approximately half of the total measured heat dissipation rate from the Earth. Here we present results from a search for geoneutrinos with KamLAND. Assuming a Th/U mass concentration ratio of 3.9, the 90 per cent confidence interval for the total number of geoneutrinos detected is 4.5 to 54.2. This result is consistent with the central value of 19 predicted by geophysical models. Although our present data have limited statistical power, they nevertheless provide by direct means an upper limit (60 TW) for the radiogenic power of U and Th in the Earth, a quantity that is currently poorly constrained.

Journal Article↗

Measurement of neutrino oscillation with KamLAND: evidence of spectral distortion.

We present results of a study of neutrino oscillation based on a 766 ton/year exposure of KamLAND to reactor antineutrinos. We observe 258 nu (e) candidate events with energies above 3.4 MeV compared to 365.2+/-23.7 events expected in the absence of neutrino oscillation. Accounting for 17.8+/-7.3 expected background events, the statistical significance for reactor nu (e) disappearance is 99.998%. The observed energy spectrum disagrees with the expected spectral shape in the absence of neutrino oscillation at 99.6% significance and prefers the distortion expected from nu (e) oscillation effects. A two-neutrino oscillation analysis of the KamLAND data gives Deltam(2)=7.9(+0.6)(-0.5)x10(-5) eV(2). A global analysis of data from KamLAND and solar-neutrino experiments yields Deltam(2)=7.9(+0.6)(-0.5)x10(-5) eV(2) and tan((2)theta=0.40(+0.10)(-0.07), the most precise determination to date.

Journal Article↗

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↗

Gene expression relevant to osteoclastogenesis in the synovium and bone marrow of mature rats with collagen-induced arthritis.

OBJECTIVES: To investigate gene expression relevant to osteoclastogenesis in the synovium and bone marrow during the development of collagen-induced arthritis (CIA) in mature rats. METHODS: Total messenger RNAs (mRNAs) were obtained from CIA synovium and bone marrow after immunization. First, reverse transcriptase-polymerase chain reactions (RT-PCR) were carried out to detect the mRNA encoding receptor activator of NF-kappaB (RANK), RANK ligand (RANKL), osteoprotegerin (OPG), tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6 and the osteoclast markers tartrate-resistant acid phosphatase (TRAP) and cathepsin K. Secondly, the genes detected clearly by RT-PCR were quantified using real-time PCR. RESULTS: In the synovium, expression of all genes was confirmed by specific single bands in RT-PCR. In real-time PCR, the expression levels of TNF-alpha, IL-1beta, IL-6, RANKL, TRAP and cathepsin K mRNA increased, whereas the expression levels of RANK and OPG were unchanged and decreased respectively. RANKL expression was highly correlated with the two osteoclast markers. In the bone marrow, RT-PCR did not clearly detect the expression of IL-6, RANKL or OPG mRNA. Quantitative real-time PCR showed that TNF-alpha, RANK and TRAP mRNA expression did not change significantly with time, and that IL-1beta and cathepsin K changed slightly compared with those in the synovium. CONCLUSIONS: In the early stages of arthritis, synovial RANKL is closely involved in osteoclastogenesis, and various changes in synovial cytokines, including down-regulation of OPG, probably accelerate osteoclast formation. In contrast, cytokine mRNA in the bone marrow showed little fluctuation. We suggest that synovial cytokines affect osteoclastogenesis not only in the synovium but in the bone marrow.

Animals↗

High sensitivity search for nu;e's from the sun and other sources at KamLAND.

Data corresponding to a KamLAND detector exposure of 0.28 kton yr has been used to search for nu;(e)'s in the energy range 8.3<E(nu;(e))<14.8 MeV. No candidates were found for an expected background of 1.1+/-0.4 events. This result can be used to obtain a limit on nu;(e) fluxes of any origin. Assuming that all nu;(e) flux has its origin in the Sun and has the characteristic 8B solar nu(e) energy spectrum, we obtain an upper limit of 3.7 x 10(2) cm(-2) s(-1) (90% C.L.) on the nu;(e) flux. We interpret this limit, corresponding to 2.8 x 10(-4) of the standard solar model 8B nu(e) flux, in the framework of spin-flavor precession and neutrino decay models.

Journal Article↗

Fhit expression in human gastric adenomas and intramucosal carcinomas: correlation with Mlh1 expression and gastric phenotype.

The fragile histidine triad (FHIT) gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumour suppressor gene involved in a variety of tumours, including gastric carcinomas. Recently, it has been reported that the FHIT gene may be a target of damage in some of mismatch-deficient tumours. To clarify further the role of the Fhit protein in gastric carcinogenesis, we investigated whether Fhit expression in early gastric neoplasia is associated with mismatch repair protein expression and cellular phenotype. Fhit, Mlh1 and phenotypic expression were evaluated immunohistochemically in 87 early gastric neoplasias, comprising 32 adenomas and 55 intramucosal carcinomas, resected by endoscopic mucosal resection therapy. Significant loss or reduction of Fhit expression was noted in four (12.5%) of the 32 adenomas and 21 (38.2%) of the 55 intramucosal carcinomas. The rate of abnormal Fhit expression was significantly higher in intramucosal carcinomas than in adenomas (P=0.021). Moreover, reduced Fhit expression was found to be significantly associated with loss of Mlh1 expression in early gastric neoplasia (P=0.0011). Furthermore, we also detected a significant association between reduced Fhit expression and gastric phenotype (P=0.0018). These results suggested that reduced Fhit expression occurs in the early stage of gastric carcinogenesis and could be correlated with a lack of Mlh1 expression and gastric phenotype.

Acid Anhydride Hydrolases↗

Blood dendritic cells are decreased in acute graft-versus-host disease.

The recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) often develop acute graft-versus-host disease (aGVHD), which is closely related to morbidity and mortality. However, the essential part of the immune responses elicited in aGVHD remains largely unknown. We attempt to determine if peripheral blood dendritic cells (PBDCs) are altered in aGVHD, and find that the number of PBDCs (both myeloid and lymphoid DCs) is significantly decreased. Immunohistochemical staining of the biopsied skin from patients with aGVHD demonstrates that a number of fascin(+) cells with dendritic projections infiltrate the dermis of the skin. Based on these findings, we hypothesize that the PBDCs are recruited to the affected tissues and may thus play important roles in immune responses elicited in aGVHD.

Acute Disease↗

Intra-arterial steroid-injection therapy for steroid-refractory acute graft-versus-host disease with the evaluation of angiography.

We treated three patients with steroid-refractory acute graft-versus-host disease (aGVHD) with intra-arterial steroid-injection therapy (IAST). Two patients with gut aGVHD received IAST into both superior and inferior mesenteric arteries, while one patient with liver aGVHD received IAST into the proper hepatic artery. The volume of stools and the bilirubin level improved soon after IAST. Angiography of the superior and inferior mesenteric arteries was performed in the two patients with steroid-refractory gut aGVHD, and identical abnormal findings were obtained. IAST might be an earlier option for steroid-refractory aGVHD.

Acute Disease↗

Preferential expression of the vasoactive intestinal peptide (VIP) receptor VPAC1 in human cord blood-derived CD34+CD38- cells: possible role of VIP as a growth-promoting factor for hematopoietic stem/progenitor cells.

Primitive hematopoietic progenitor cells such as severe combined immunodeficiency- repopulating cells and long-term culture-initiating cells are enriched in CD34+CD38- cells derived from various stem cell sources. In this study, to elucidate the features of such primitive cells at the molecular level, we tried to isolate genes that were preferentially expressed in umbilical cord blood (CB)-derived CD34+CD38- cells by subtractive hybridization. The gene for VPAC1 receptor, a receptor for the neuropeptide vasoactive intestinal peptide (VIP), was thereby isolated and it was shown that this gene was expressed in both CD34+CD38- and CD34+CD38+ CB cells and that the expression levels were higher in CD34+CD38- CB cells. Next, we assessed the effects of VIP on the proliferation of CD34+ CB cells using in vitro culture systems. In serum-free single-cell suspension culture, VIP enhanced clonal growth of CD34+ CB cells in synergy with FLT3 ligand (FL), stem cell factor (SCF), and thrombopoietin (TPO). In serum-free clonogenic assays, VIP promoted myeloid (colony-forming unit-granulocyte/macrophage (CFU-GM)) and mixed (CFU-Mix) colony formations. Furthermore, in Dexter-type long-term cultures, VIP increased colony-forming cells at week 5 of culture. These results suggest that VIP functions as a growth-promoting factor of CB-derived hematopoetic progenitor cells.

ADP-ribosyl Cyclase↗

Absence of mutations in the Wilms' tumor gene wt1 in de novo non-small cell lung cancers.

We recently demonstrated that the WT1 gene was overexpressed in the majority of de novo lung cancers regardless of cancer subtypes. Here, we examined WT1 genomic DNA in 38 cases of de novo non-small cell lung cancers (NSCLC) for mutations using direct sequencing. The sequencing analysis showed no mutations of WT1 genomic DNA in any of 38 de novo non-small cell lung cancers examined. These results indicated that the non-mutated, wild-type WT1 gene played an important role in de novo NSCLC.

Adult↗

First results from KamLAND: evidence for reactor antineutrino disappearance.

KamLAND has measured the flux of nu;(e)'s from distant nuclear reactors. We find fewer nu;(e) events than expected from standard assumptions about nu;(e) propagation at the 99.95% C.L. In a 162 ton.yr exposure the ratio of the observed inverse beta-decay events to the expected number without nu;(e) disappearance is 0.611+/-0.085(stat)+/-0.041(syst) for nu;(e) energies >3.4 MeV. In the context of two-flavor neutrino oscillations with CPT invariance, all solutions to the solar neutrino problem except for the "large mixing angle" region are excluded.

Journal Article↗

A new ultimate anus-preserving operation for extremely low rectal cancer and for anal canal cancer.

To avoid permanent colostomy, we perform a new ultimate anus preserving operation for extremely low rectal cancer or for anal canal cancer. According to our pathologic study, two different removal methods of anal canal were theoretically considered. One is internal sphincter resection (ISR method), and the other is both deep-superficial external sphincter and internal sphincter resection (ESR method). Six patients received ISR and ten patients ESR. No severe intraoperative complications occurred and the postoperative course was uneventful. All patients receiving ISR had excellent anal function without soiling. Some patients receiving ESR sometimes complained of night soiling but satisfied the anus preservation. The median follow-up was 15 months, (range, 3-28 months). We had recurrences in two female patients receiving ISR. One had para-aortic and lateral lymph node recurrences without anastomotic recurrence. She underwent lateral and para-aortic lymphadenectomy, but died of lung metastasis, regardless of intensive chemotherapy. Another had pelvic recurrence with abdominal dissemination. She underwent abdominoperineal resection and is alive with pelvic re-recurrence. ISR and ESR are excellent procedures for anus preservation, but ISR needs a strict indication.

Anus Neoplasms↗

Sensitive detection of human telomerase reverse transcriptase mRNA in the serum of patients with hepatocellular carcinoma.

BACKGROUND/AIM: Telomerase reverse transcriptase protein (hTERT) mRNA has been reported to be detectable by reverse transcription polymerase chain reaction (RT-PCR) in the serum of patients with breast cancer. We measured serum hTERT mRNA in patients with hepatocellular carcinoma (HCC), and examined its clinical usefulness. METHODS: We performed RT-PCR to detect the expression of hTERT mRNA in 78 patients with HCC, 10 with liver cirrhosis (LC), 12 with chronic hepatitis (CH), and 34 healthy individuals without any liver diseases and cancers, and statistically analyzed the association with clinical parameters which include age, sex, etiology, Child classification, underlying liver disease, biochemical data, alpha-fetoprotein (alpha-AFP) number and size of tumor, and histological differentiation of HCC regarding HCC patients. RESULTS: 70 of 78 (89.7%) patients with HCC, 7 of 10 (70.0%) with LC, and 5 of 12 (41.7%) with CH were positive for hTERT expression, whereas all healthy individuals were negative for it. A multivariate analysis showed that positivity of hTERT mRNA was independently associated with AFP, tumor size, and differentiation degree. CONCLUSIONS: These results suggest that this assay is sensitive enough to detect hTERT mRNA in serum, and that it would be applicable for early detection and diagnosis of HCC or other cancers by a quantitative method.

Aged↗

Effects of long-term administration of sulindac on APC mRNA and apoptosis in colons of rats treated with azoxymethane.

PURPOSE: Non-steroidal anti-inflammatory drugs, including sulindac, have been shown to exhibit anti-colon cancer activity; however, the detailed mechanisms concerning continuous long-term administration are still unclear. Therefore, we examined the anti-colon carcinogenesis effects of sulindac after prolonged administration. METHODS: Administration of AOM, a colon-specific carcinogen, induced colonic preneoplastic lesions, which can progress to carcinomas about 40-50 weeks after AOM administration. We studied the effects of sulindac on the incidence of preneoplastic lesions, proliferative activity of colonic cells (AgNORs), tumor suppressor adenomatous polyposis coli (APC) gene expression, and apoptosis using AOM-treated rat colon mucosa at 4 weeks and 40 weeks (early and late stage of colon carcinogenesis, respectively). RESULTS: Sulindac suppressed the development of preneoplastic lesions induced by AOM at 4 weeks and 40 weeks by about 50% ( P<0.01); the proliferative activity of colonic cells increased by AOM was suppressed almost completely. Furthermore, APC expression was significantly increased by sulindac at both the early and late stages ( P<0.01). However, apoptosis was clearly increased at the early stage ( P<0.01), but not at the late stage. CONCLUSIONS: APC overexpression induced by sulindac can suppress colon carcinogenesis at both the early and late stages, but apoptosis might work as one of anti-cancer mechanisms at the early stage of colon carcinogenesis.

Adenomatous Polyposis Coli Protein↗

Short wavelength temperature gradient driven modes in tokamak plasmas.

New unstable temperature gradient driven modes in an inhomogeneous tokamak plasma are identified. These modes represent temperature gradient (ion and electron) driven modes destabilized in the short wavelength regions with k( perpendicular )rho(i,e)>>1, respectively. The instability occurs due to a specific plasma response that significantly deviates from Boltzmann distribution in the regions k( perpendicular )rho(i,e)>>1.

Journal Article↗

Interaction between small-scale zonal flows and large-scale turbulence: a theory for ion transport intermittency in Tokamak plasmas.

Interaction between small-scale zonal flows and large-scale turbulence is investigated. The key mechanism is identified as radially nonlocal mode coupling. Fluctuating energy can be nonlocally transferred from the unstable longer to the stable or damped shorter wavelength region, so that the turbulence spectrum is seriously deformed and deviates from the nonlinear power law structure. Three-dimensional gyrofluid ion-temperature gradient (ITG) turbulence simulations show that an ion transport bursting behavior is consistently linked to the spectral deformity with the causal role of ITG-generated zonal flows in tokamak plasmas.

Journal Article↗