Search PubMed⌕ Search

Biomedical subjects

H Murakami

Publications and source records attributed to H Murakami.

At least 19 recordsLinked to original sources
PubMed2007

Coulomb explosion of K-shell ionized krypton clusters studied by multiple-ion coincidence momentum imaging.

The Coulomb explosion of K-shell ionized krypton clusters with an average size N of 160 has been studied by electron-multiple-ion-coincidence measurements in which the time-of-flight (TOF) of ions was measured by using a position sensitive detector. The authors have sorted the TOF spectra by the number of coincidence ion signals, Ncoin, and found that singly charged fragment ions such as Kr+, Kr2+, and Kr3+ are dominant for Ncoin>or=2, and that multiply charged ions are detected mainly for Ncoin=1. The Ncoin dependence of the peak widths in the TOF spectra reveals that the average momentum of the Kr+ ions increases with Ncoin, while those of Kr2+ and Kr3+ decrease. These results have been more directly confirmed by the momentum imaging measurements. The authors propose that the heavier ions are produced in the central part of clusters where the Coulomb interactions from the surrounding ions are more effectively canceled out due to the higher symmetry.

Journal Article↗
PubMed2007

Expression of CD55 and CD59 on peripheral blood cells in patients with lymphoproliferative disease of granular lymphocytes.

Lymphoproliferative disease of granular lymphocytes (LDGL) is a disorder characterized by the clonal expansion of granular lymphocytes. It has recently been shown that the clonal expansion of granular lymphocytes occurs in patients with paroxysmal nocturnal hemoglobinuria (PNH) in a subclinical fashion. To test the possibility that LDGL patients share a PNH phenotype, we obtained peripheral blood cells from 20 patients with LDGL and examined the expression of the glycosylphosphatidyl inositol (GPI)-anchored proteins, CD55 and CD59. Compared with normal controls, however, a defective expression of CD55/59 was not observed on either granulocytes or erythrocytes from LDGL patients. An unexpected finding was the significantly lower CD55/59 expression on granular lymphocytes from patients with CD16(+)CD56(-) phenotype LDGL than from patients with CD16(+)CD56(+) phenotype LDGL, or natural killer (NK) and NK/T lymphocytes from healthy individuals. The positive correlation between the expression of CD56 and CD55/59 might have some relevance to the functional properties of the CD56(+) subset of large granular lymphocytes.

CD55 Antigens↗
PubMed2006

The Src tyrosine kinase Hck is required for Tel-Abl- but not for Tel-Jak2-induced cell transformation.

Tel-Abl and Tel-Jak2 are fusion proteins associated with human haematologic neoplasms. They possess constitutive tyrosine kinase activity and activate common downstream signalling pathways like Stat-5, PI3-K/Akt, Ras/MapK and NF-kappaB. In this study, we showed the specific requirement of Src family members for the Tel-Abl-mediated cell growth, activation of Stat5, PI3-K/Akt and Ras/MapK while dispensable for Tel-Jak2. Hck was found strongly phosphorylated in Tel-Abl-expressing Ba/F3 cells and sensitive to imatinib mesylate treatment, providing evidence that Hck is a target of Tel-Abl tyrosine kinase activity. Overexpression of a kinase dead form of Hck inhibits the proliferation of Ba/F3 cells expressing Tel-Abl as the phosphorylation of Akt and Erk1/2. These results argue for an important role of Hck in Tel-Abl oncogenic signalling.

Benzamides↗
PubMed2006

Independent risk factors for chronic cyclosporine induced nephropathy in children with nephrotic syndrome.

BACKGROUND: Cyclosporine A (CsA) has been widely used in children with steroid dependent and steroid resistant nephrotic syndrome (NS) because of its efficacy in relieving these patients from systemic side effects of steroids. However, its long term use is controversial, since chronic CsA induced nephropathy (CsAN) may develop in a considerable number of patients. AIMS AND METHODS: In order to clarify the risk factors for the development of CsAN, the clinical characteristics of children with steroid dependent or steroid resistant NS taking CsA (target blood trough levels 50-150 ng/ml) for more than six months, managed at a single centre, were retrospectively analysed. RESULTS: Thirteen of 30 children (24 boys and 6 girls) taking CsA (mean duration 43 months, range 6-144) had CsAN defined as the presence of CsA associated arteriopathy with or without striped tubulointerstitial lesions. The multivariate analysis revealed that CsA treatment for more than 36 months and an age younger than 5 years at the start of CsA treatment were independent risk factors for the development of CsAN. The univariate analysis also showed that patients with CsAN had more frequent relapses during CsA treatment than those without CsAN. CONCLUSION: An alternative treatment should be seriously considered after a 36 month administration of CsA in order to prevent CsAN. Data also suggest that CsA treatment in children younger than 5 years should be avoided if possible.

Adolescent↗
PubMed2006

Radiation myelopathy after radioactive iodine therapy for spine metastasis.

A case of radiation myelopathy after radioactive iodine therapy is reported. This is the first report to describe radiation myelopathy after I-131 therapy. A 62-year-old female with spinal metastasis of T10 received I-131 therapy. She presented with radiation myelopathy 34 months after the irradiation. We need to recognize the possibility of this serious complication even in the case of I-131 therapy. There is a risk of radiation myelopathy even after I-131 therapy, especially in cases with spinal cord compression such as this.

Female↗
PubMed2006

An immunohistological study of the integration at the bone-tendon interface after reconstruction of the anterior cruciate ligament in rabbits.

We studied bone-tendon healing using immunohistochemical methods in a rabbit model. Reconstruction of the anterior cruciate ligament was undertaken using semitendinosus tendon in 20 rabbits. Immunohistochemical evaluations were performed at one, two, four and eight weeks after the operation. The expression of CD31, RAM-11, VEGF, b-FGF, S-100 protein and collagen I, II and III in the bone-tendon interface was very similar to that in the endochondral ossification. Some of the type-III collagen in the outer layer of the graft, which was deposited at a very early phase after the operation, was believed to have matured into Sharpey-like fibres. However, remodelling of the tendon grafted into the bone tunnel was significantly delayed when compared with this ossification process. To promote healing, we believe that it is necessary to accelerate remodelling of the tendon, simultaneously with the augmentation of the ossification.

Animals↗
PubMed2005

Corneodesmosin (CDSN) gene association with psoriasis vulgaris in Caucasian but not in Japanese populations.

PSORS1 on chromosome 6p21.3, which contains the MHC, is a major susceptibility locus for psoriasis vulgaris. This region is characterized by strong linkage disequilibrium and contains the corneodesmosin (CSDN) gene, an attractive candidate for psoriasis susceptibility based on its putative biological function in keratinocyte adhesion, and HLA-Cw6, an established marker for psoriasis susceptibility. We compared two genetically independent populations in order to define the major psoriasis susceptibility gene, a British Caucasian population comprising parent-offspring trios analysed by the transmission disequilibrium test (TDT) and a Japanese case-control population. All individuals were investigated for CDSN polymorphism (+619, +1236, +1240 and +1243) and HLA-C association. Our data confirms strong association with HLA-Cw6 and CDSN allele 5 (+619T, +1240G, +1243C) in the Caucasian cohort (TDT, P = 5.4 x 10(-6)) and in addition defines this region further by identifying a high-risk CDSN haplotype (allele 5 and +1236T, P = 8.5 x 10(-8)). In contrast no association was observed in the Japanese cohort for any HLA-C or CDSN alleles. This data supports a role for the CDSN gene in Caucasian populations with psoriasis. However the lack of association with HLA-Cw6 and CDSN alleles in Japanese psoriasis patients may be because Japanese patients exhibit a form of psoriasis similar to late onset or Type II psoriasis vulgaris in contrast to early onset or Type I disease characterizing our Caucasian population.

Adolescent↗
PubMed2005

Invasive phenotype and apoptosis induction of Plesiomonas shigelloides P-1 strain to Caco-2 cells.

AIMS: The mechanism of the host cell invasion of Plesiomonas shigelloides and its capability to induce apoptosis were investigated. METHODS AND RESULTS: We performed a time course experiment on the bacterial adherence and invasion of the P. shigelloides P-1 strain into Caco-2 cells using an invasion assay and flow cytometry. The adherence of P. shigelloides to the Caco-2 cells was almost completed within 10 min after the infection. Thereafter, P. shigelloides starts internalization within the Caco-2 cells, which was completed within 60 min after the infection. Based on the invasion assay using nocodazole, cytochalasin D, and genistein, it became clear that the mechanism of the internalization depended on the signal transduction followed by the rearrangement of the cytoskeletal protein. Based on the DNA laddering and TUNEL methods, the cytotoxicity of the Caco-2 cells by the invasion of P. shigelloides occurred through the induction of apoptosis. CONCLUSIONS: This work demonstrated that the mechanism of invasion of P. shigelloides into Caco-2 cells and the invasion of P. shigelloides induces apoptotic cell death. SIGNIFICANCE AND IMPACT OF THE STUDY: This work revealed the virulence factor, which may be important for understanding of the pathogenesis of P. shigelloides.

Apoptosis↗
PubMed2005

Comparison between partial agonist (ME3412) and antagonist (alosetron) of 5-hydroxytryptamine 3 receptor on gastrointestinal function.

Therapeutic use of 5-hydroxytryptamine 3 (5-HT(3)) receptor antagonists for diarrhoea-predominant irritable bowel syndrome may be accompanied by constipation. We hypothesized that ME3412, 5-chloro-2-(1,4-diazacycloheptan-1-yl)-7-methylbenzoxazole, a novel partial agonist of the 5-HT(3) receptor, would minimize constipation without reducing antidiarrhoeal activity. Receptor binding studies showed that ME3412 is highly selective for the human 5-HT(3) receptor (K(i) = 1.51 nmol L(-1)). A 5-HT(3) receptor agonist, 2-methyl-5-HT, caused contractile response in the isolated guinea-pig ileum and accelerated secretion in the guinea-pig colonic mucosal preparation. ME3412 and 5-HT(3) receptor antagonist, alosetron, antagonized the 2-methyl-5-HT-induced responses with similar potency in insurmountable and surmountable manner, respectively. ME3412 caused weak agonism in isolated ileum strips and also in the colonic mucosa with intrinsic activity of 0.09 and 0.59, respectively. In conscious dogs, alosetron (3 microg kg(-1) i.v.) suppressed the migrating motor complex (MMC), whereas a relatively high dose (300 microg kg(-1)) of ME3412 was required for inhibition of MMC. ME3412 and alosetron suppressed 5-HT induced-diarrhoea in mice. In contrast, ME3412 did not significantly affect colonic propulsion compared with alosetron. These results imply that the partial agonist may relieve diarrhoea with low risk of inducing constipation.

Animals↗
PubMed2005

Association between neuroleptic drug-induced extrapyramidal symptoms and dopamine D2-receptor polymorphisms in Japanese schizophrenic patients.

The aim of the present study is to examine the relationship between dopamine D2-receptor gene (DRD2) polymorphisms (Taq1A, Taq1B, -141C Ins/Del) and the risk of extrapyramidal adverse effects (EPS), assessed according to the Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS), or the maintenance dose of antipsychotics in schizophrenic patients. The DIEPSS score was significantly higher in patients bearing the -141C Del allele than in those without it. Taq1A and Taq1B restriction fragment length polymorphisms (RFLPs) did not significantly affect the DIEPSS score. On the other hand, maintenance doses of neuroleptics and antiparkinsonian drugs were significantly higher in patients with the B1 allele of Taq1B RFLP than in those without it, while the Taq1A RFLP and -141C Ins/Del polymorphisms were not significantly related to the maintenance doses. In conclusion, the risk of EPS may be increased in patients with the -141C Del allele of the DRD2 gene. In these patients, antipsychotics should be administered with caution.

Adult↗
PubMed2004

Expression of protein gene product 9.5 (PGP9.5)/ubiquitin-C-terminal hydrolase 1 (UCHL-1) in human myeloma cells.

The neuron cytoplasmic protein gene product 9.5 (PGP9.5)/ubiquitin-C-terminal hydrolase 1 (UCHL-1) protein is a thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal of ubiquitin, and is involved in the processing of ubiquitin precursors and ubiquinated proteins. Although this molecule is known as a specific tissue marker for the neuroendocrine system, many reports have indicated that PGP9.5 is a marker for certain tumour types, such as cancer of the lung, colon, and pancreas. The expression of PGP9.5 in myeloma cells was examined. PGP9.5 seemed to be expressed specifically in myeloma cells as compared with other haematological malignant cells. In addition, in myeloma cells subjected to growth-factor starvation, the upregulation of PGP9.5 was observed in association with that of p27(Kip1), a cyclin-dependent-kinase inhibitor, although the upregulation caused by irradiation was milder. In contrast, the hypoxic culture of myeloma cells induced down-regulation of PGP9.5. These results suggested that PGP9.5 may be a good marker for myeloma among haematological malignancies. In addition, it may indicate certain cellular features of myeloma cells, such as sensitivity to proteasome inhibitors.

Biomarkers, Tumor↗
PubMed2004

A novel and effective approach of developing aggressive experimental autoimmune gastritis in neonatal thymectomized BALB/c mouse by polyinosinic:polycytidylic acid.

Neonatal thymectomy induces autoimmune gastritis (AIG) in 40-70% of BALB/c mice. We presumed that induction of autoimmunity by polyinosinic:polycytidylic acid (poly I:C) might allow development of a more aggressive model of AIG. A group of BALB/c mice were thymectomized on day 3 after birth. Neonatal thymectomized mice were either injected with poly I:C or phosphate-buffered saline (PBS). Non thymectomized neonatal BALB/c mice were injected with only poly I:C. All neonatal thymectomized mice injected with poly I:C developed 3 cardinal features of AIG: (1) moderate to severe degree gastritis (2) presence of autoantibody to H(+)/K(+) ATPase and (3) loss of parietal cells. However, only 70% of the PBS-treated neonatal thymectomized BALB/c mice developed some, but not, all features of AIG. A mild degree of AIG was seen in 12 of 31 nonthymectomized BALB/c mice administered with only poly I:C. Administration of poly I:C in neonatal thymectomized BALB/c mice in the first and second week appeared to be the most effective for induction of aggressive AIG. The levels of interleukin (IL)-6, IL-12p70, interferon-gamma and tumour necrosis factor-alpha were significantly higher in poly I:C-injected thymectomized mice compared to PBS-injected neonatal thymectomized mice (P < 0.05). The frequencies of CD4(+)CD25(+) regulatory T cells in the spleen were significantly decreased in neonatal thymectomized mice administered with poly I:C compared to PBS-treated neonatal thymectomized mice (P < 0.01). Taken together, these results suggest that induction of inflammatory cytokines and reduction of regulatory T cells by poly I:C might contribute to the development of an aggressive model of AIG in neonatal thymectomized BALB/c mice.

Animals↗
PubMed2004

Isolation and functional analysis of circulating dendritic cells from hepatitis C virus (HCV) RNA-positive and HCV RNA-negative patients with chronic hepatitis C: role of antiviral therapy.

Hepatitis C virus (HCV) RNA has been localized in antigen-presenting dendritic cells (DCs) from patients with chronic hepatitis C (CHC). DCs from patients with CHC also exhibit impaired functional capacities. However, HCV RNA in DCs and functional impairment of DCs in CHC might be independent or interrelated events. Moreover, the impact of antiviral therapy on the functions of DCs in CHC is not well documented. In order to address these issues, we took advantage of antiviral therapy in these patients. Ten patients with CHC, expressing HCV RNA in circulating DCs, became negative for HCV RNA in circulating DCs after therapy with interferon-alpha and ribavirin for 4 weeks. The functions of DCs from HCV RNA+ patients (isolated before antiviral therapy) and HCV RNA- patients (isolated 4 weeks after antiviral therapy) were compared in allogenic mixed leucocyte reactions. In comparison to circulating DCs from normal control subjects, DCs from HCV RNA+ patients had a significantly decreased capacity to stimulate allogenic T lymphocytes (P < 0.01) and produce interleukin-12 (P < 0.05). However, the allostimulatory capacity of circulating DCs from HCV RNA- patients was several-fold higher compared to that of HCV RNA+ DCs from the same patient. DC from HCV RNA- patients also produced significantly higher levels of interleukin-12 compared to HCV RNA+ DCs from the same patient (P < 0.01). Taken together, this study is the first to provide experimental evidence regarding the impact of HCV RNA and antiviral therapy on the function of DCs in patients with CHC.

Adult↗
PubMed2004

Decreased interferon-alpha production and impaired T helper 1 polarization by dendritic cells from patients with chronic hepatitis C.

Patients with chronic hepatitis C (CHC) are unable to prime and maintain vigorous T cell responses that are initiated during the acute phase of hepatitis C virus (HCV) infection. As dendritic cells (DCs) induce and regulate both innate and adaptive immune responses, the aim of this study was to analyse two critical functions of DCs: firstly, production of interferon (IFN)-alpha and, secondly, polarization of T helper 1 lymphocytes. The frequencies of plasmacytoid DC (PDC) and myeloid DC (MDC) were estimated in 63 patients with CHC and 34 normal controls using four-colour flow cytometry. Circulating DCs were isolated from peripheral blood of CHC patients (n = 10) and normal controls (n = 10). These DCs were cultured with herpes simplex virus-1 to evaluate their capacity to produce IFN-alpha. The capacity of DCs to induce polarization of autologous naive CD4(+) T lymphocytes to IFN-gamma-producing effector T lymphocytes was also assessed. The frequencies of PDCs producing intracellular IFN-alpha (P < 0.01) and the levels of IFN-alpha in culture supernatant of PDCs (P < 0.01) were significantly lower in patients with CHC compared to those of normal controls. The numbers of MDC were significantly lower in patients with CHC (8.2 (6.0)/ micro l, median (interquartile range), n = 63) compared to normal control (11.7 (7.8)/ micro l, n = 34) (P < 0.01). Moreover, DCs from patients with CHC induced significantly lower numbers of IFN-gamma-producing effector T lymphocytes compared to that of controls (P < 0.01). This study indicates that the low IFN-alpha-producing capacity and impaired T helper 1 polarization ability of DCs from patients with CHC might be responsible for the typical low anti-HCV immune responses in these patients.

Adult↗
PubMed2004

Akt activation and localisation correlate with tumour invasion and oncogene expression in thyroid cancer.

INTRODUCTION: Akt activation is involved in the pathogenesis of inherited thyroid cancer in Cowden's syndrome and in sporadic thyroid cancers. In cell culture, Akt regulates thyroid cell growth and survival; but recent data suggest that Akt also regulates cell motility in non-thyroid cell lines. We therefore sought to evaluate the role of Akt in thyroid cancer progression. METHODS: We evaluated 46 thyroid cancer, 20 thyroid follicular adenoma, and adjacent normal tissues samples by immunohistochemistry for activated Akt (pAkt), Akt 1, 2, and 3, and p27 expression. Immunoblots were performed in 14 samples. RESULTS: Akt activation was identified in 10/10 follicular cancers, 26/26 papillary cancers, and 2/10 follicular variant of papillary cancers, but in only 4/66 normal tissue samples and 2/10 typical benign follicular adenomas. Immunoactive pAkt was greatest in regions of capsular invasion; and was localised to the nucleus in follicular cancers and the cytoplasm in papillary cancers, except for invasive regions of papillary cancers where it localised to both compartments. Immunoactive Akt 1, but not Akt 2 or Akt 3, correlated with pAkt localisation, and nuclear pAkt was associated with cytoplasmic expression of p27. In vitro studies using human thyroid cancer cells demonstrated that nuclear translocation of Akt 1 and pAkt were associated with cytoplasmic p27 and cell invasion and migration. Cell migration and the localisation of Akt 1, pAkt, and p27 were inhibited by PI3 kinase, but not MEK inhibition. DISCUSSION: These data suggest an important role for nuclear activation of Akt 1 in thyroid cancer progression.

Adenoma↗
PubMed2003

Durable remission induced by rituximab-containing chemotherapy in a patient with primary refractory Burkitt's lymphoma.

We describe a 65-year-old man diagnosed with Burkitt's lymphoma arising from the intestine. The tumor cells had a mature B-cell immunophenotype and rearrangement of the c-myc gene. The patient was treated with intensive multiagent chemotherapy. After four courses of chemotherapy, an ileus developed due to a residual abdominal disease. We administered rituximab in combination with the same chemotherapy regimen. A dramatic clinical improvement was observed and abnormal uptake by 18F-fluorodeoxyglucose positron emission tomography disappeared. The patient experienced complete remission for 1 year. This encouraging result indicates that rituximab might be an important treatment choice in management of Burkitt's lymphoma.

Aged↗
PubMed2003

Development of efficient strategies for the production of genetically modified pigs.

Although pronuclear DNA micro-injection has long been the most reliable method to produce transgenic pigs, the efficiency of production of transgenic offspring is generally plagued by 1% of the DNA-injected embryos. Therefore, a problem with this method is the need for large numbers of pronuclear stage embryos. One great advancement would be the use of in vitro-matured (IVM) oocytes for the purpose of transgenic pig production. High developmental competence of IVM oocytes was proven by transfer of parthenogenetic IVM oocytes. A combined method of sperm vectors with the IVM of oocytes would make the production of transgenic pigs remarkably feasible. Rate of blastocyst formation following intracytoplasmic sperm injection (ICSI) by frozen sperm was over 20%, and transgene was expressed in approximately 50% of blastocysts generated. Somatic cell nuclear transfer would enable more efficient and sophisticated genetic modification of the pig. Simultaneous comparison between two nuclear transfer methods by electro-fusion and intracytoplasmic injection revealed clear differences in the pattern of nuclear remodeling and development of the reconstructed embryos. To specify the donor cell type that allows efficient genetic modification and easy reprogramming or to establish such cell lines is a critical issue in pig cloning. We tested pre-adipocytes from the subcutaneous adipose tissue of adult pigs for nuclear transfer. Cell cycle synchronization by differentiation induction is unique to the pre-adipocytes. Frequency of apoptosis was low in the cells synchronized by differentiation induction compared with other synchronization methods, including serum starvation, confluency, and chemical treatment. It would be of great worth if cryopreserved clone embryos were available. We have demonstrated that cryopreservation of in vitro-produced porcine embryos as well as clone blastocysts is possible by our unique method.

Animals↗