Biomedical subjects

Jun Nomura

Publications and source records attributed to Jun Nomura.

17 recordsLinked to original sources

PubMed2006

[Acute monoblastic leukemia with tetrasomy 8].

Tetrasomy 8 is a rare chromosomal abnormality in acute leukemia, and it has recently been considered as a poor prognostic factor. A 20-year-old woman was admitted because of purpura on the upper and lower limbs in February 2002. On admission, her leukocyte count was 6.5 x 10(9)/l with 66% of blasts, the hemoglobin level was 11.2 g/dl, and the platelet count was 101 x 10(9)/l. The bone marrow aspirate contained 85.6% of peroxidase-negative, alpha-naphthyl-butyrate esterase-positive, and CD4+ CD56+ blast cells. Karyotypic analysis of the bone marrow cells showed 48, XY, + 8, + 8[17]/47, XY, +8[3]. The patient was diagnosed as having AML (M5a), and treatment with daunorubicin (70 mg x 5 days) and cytosine arabinoside (150 mg x 7 days) resulted in a complete remission. She relapsed four months later, however, with an extramedullary tumor in T12. Remission could not be achieved, and the patient underwent allogeneic peripheral blood stem cell transplantation from her HLA-identical mother. Her clinical course was almost uneventful except for a phlegmon in the right leg, but on day 49 a relapse occurred, and she died of acute renal failure on day 73. This case strongly illustrates the characteristic of tetrasomy 8 as a poor prognostic factor in acute leukemia.

Adult↗

PubMed2005

Positive regulation of Fas gene expression by MSSP and abrogation of Fas-mediated apoptosis induction in MSSP-deficient mice.

MSSP has been identified as a transcription factor that regulates the c-myc gene. MSSP was later found to positively or negatively regulate a variety of genes, including alpha-smooth actin, MHC class I, MHC class 2 and the thyrotropin receptor. The knockout mice for the Mssp gene developed by us revealed that these mice became partially embryonic lethal due to a low concentration of progesterone at E2.5. In this study, we further analyzed Mssp-knockout mice and found that the expression of the Fas gene was repressed, resulting in abrogation of Fas-mediated induction of apoptosis both in Mssp-knockout mice and primary thymocytes. MSSP was then found to stimulate promoter activity of the Fas gene by binding to a region spanning -1035 to -635 in chromatin immunoprecipitation assays. Binding of MSSP in the MSSP-binding sequence, TCTAAT, located in this region was confirmed by mobility shift assays, and deletion of this sequence from the Fas promoter was found to result in loss of MSSP-dependent stimulating activity. The results suggest that MSSP is an important mediator for Fas-induced apoptosis in vivo and in vitro.

Animals↗

PubMed2005

Nocturnal onset and development of Bell's palsy.

OBJECTIVE/HYPOTHESIS: To examine the mechanism and pathophysiology of idiopathic peripheral facial palsy (Bell's palsy), the mode of onset of facial palsy was investigated. STUDY DESIGN: Retrospective case review. METHODS: We identified the point at which patients with facial palsy first noticed their illness using our medical charts for 648 patients and information from 3,580 facial palsy cases who visited an Internet site; we found that the time of a patient's first awareness of his or her illness was mentioned in 258 (204 Bell's palsy) and 53 cases, respectively. These cases were divided into three periods: morning, afternoon, and night. RESULTS: The ratio of morning:afternoon:night in the two groups was 141:30:33 and 50:0:3, respectively. These findings indicate that the majority of patients first noticed their palsy in the morning. CONCLUSION: Because several hours are required for facial palsy to develop before becoming apparent, this suggests that the onset and development of facial palsy occurred during sleep, when circulatory dynamics are reduced. In humans, ischemia is more likely to occur and produce facial palsy than virus reactivation.

Adolescent↗

PubMed2005

Enhanced expression of transferrin receptor confers UV-resistance in human and monkey cells.

One of the most intriguing biological subjects is cell-surface molecules that regulate the susceptibility of human cells to cell-killing effects after irradiation with far-ultraviolet light (UV, principally 254 nm wavelength). Human RSa cells have unusual sensitivity to UV-induced cell-killing. We searched for molecules on the cell-surface of RSa cells that were present in different amounts as compared to a variant of these cells, UV(r)-1 cells, which have increased resistance to UV cell-killing. Among the 21 molecules examined, the amount of transferrin receptor (TfR) protein was found to be 2-fold higher in UV(r)-1 cells compared with in RSa cells. The amounts of this protein were also higher in the UV-resistant hematopoietic cell lines, CEM6 and Daudi, as compared to the UV-sensitive cell lines, Molt4 and 697. Culturing of UV(r)-1 cells in a medium containing anti-transferrin antibodies resulted in sensitization of the cells to UV cell-killing as demonstrated by colony formation assay. Similar results were observed by treatment of the cells with TfR siRNA. In contrast, overexpression of TfR protein led to a resistance to UV cell-killing in RSa cells and monkey COS7 cells as demonstrated by both colony formation and apoptosis assay. In TfR-overexpressing cells, reduction of p53 and Bax protein was observed after UV-irradiation. Thus, TfR expression appears to be involved in the regulation of UV-resistance, possibly via modulation of the amount of p53 and Bax protein.

Animals↗

PubMed2005

Mitochondria-independent induction of Fas-mediated apoptosis by MSSP.

Fas-mediated apoptosis has been proposed to play an important role in homeostasis. Fas triggers apoptosis after stimulation by its ligand FasL or the Fas ligand agonist anti-Fas antibody through a mitochondria-dependent or -independent pathway, and MSSP has been identified as a transcription factor that regulates the c-myc gene and was later found to positively or negatively regulate a variety of genes, including alpha-smooth actin, MHC class I, MHC class 2 and the thyrotropin receptor. We further found that expression of the Fas gene was repressed, resulting in abrogation of the Fas-mediated induction of apoptosis both in Mssp-knockout mice and primary thymocytes. MSSP was then found to stimulate promoter activity of the Fas gene by binding to a specific region. In this study, to identify the MSSP-dependent Fas-induced apoptosis pathway, primary fibroblasts from MSSP (+/+) and MSSP (-/-) cells were treated with the combination of interleukin 1-beta and interferon-gamma and expression of the Fas gene was examined. The results showed that the Fas gene was expressed at the same levels in the two cell types. Furthermore, when these cells were treated with the anti-Fas antibody, it was found that cytochrome C was not released in the cytosol and that activations of caspase 8 and caspase 3 occurred in primary fibroblasts from MSSP (+/+) cells but not from MSSP (-/-) cells. These results indicate that Fas-mediated apoptosis induced by MSSP occurs independently of mitochondria.

Animals↗

PubMed2004

Bacterial DNA induced iNOS expression through MyD88-p38 MAP kinase in mouse primary cultured glial cells.

To study the role of bacterial DNA in the immune function of the brain, we examined the effect of CpG-DNA on the inducible nitric oxide synthase (iNOS) expression in mouse primary cultured glial cells. The expression of Toll-like receptor 9 (TLR9), the receptor of bacterial DNA, was detected by RT-PCR. We observed an increase in iNOS mRNA 6 h after CpG-DNA application. The expression of iNOS protein peaked at 12 h and declined thereafter. CpG-DNA increased p38 mitogen-activated protein kinase (MAPK) activation in primary cultured glial cells. SB203580, a specific inhibitor of p38 MAP kinase, inhibited the CpG-DNA-induced iNOS expression. Moreover, CpG-DNA failed to activate p38 MAP kinase and iNOS induction in the primary cultured glial cells prepared from myeloid differentiation factor 88 (MyD88) deficient mice. Therefore, it is suggested that functional receptor for bacterial DNA exists in primary cultured glial cells and CpG-DNA induces iNOS expression via the MyD88-p38 MAP kinase-dependent mechanisms. Thus, the present results point to the important role of bacterial DNA by acting on glial cells to operate brain immune function.

Adaptor Proteins, Signal Transducing↗

PubMed2004

[Non-myeloablative stem cell transplantation from an HLA identical sibling donor in a case of treatment-related acute myelogenous leukemia].

A 50-year-old man was admitted to our hospital because of thrombocytopenia during a follow up study of diffuse large B-cell lymphoma in second complete remission. He was diagnosed as having therapy-related acute myelgenous leukemia (t-AML) on the basis of the bone marrow findings and his chemotherapeutic agent history including alkylating agents. Complete remission was achieved by induction chemotherapy. Although allogeneic stem cell transplantation was thought to be needed, the patient was thought to be ineligible for any myeloablative conditioning regimen because of his age and the history of long term chemoradiotherapy. A non-myeloblative regimen was thus selected. After preconditioning with fludarabine, cyclophosphamide and cytarabine, the patient underwent peripheral blood stem cell transplantation from an HLA identical sibling donor. Complete donor chimeras were obtained on day 28 after transplantation. Regimen related toxicities over grade 2 were not observed. Although he suffered from mild chronic graft-versus-host disease(GVHD), he is in good condition without any signs of relapse during a follow-up period of 33 months. It is suggested that non-myeloablative transplantation is feasible and benefical for patients with t-AML who are often ineligible for myeloablative transplants because of their histories of long term chemoradiotherapies.

HLA Antigens↗

PubMed2004

Cyclic stretch induced MAPK phosphorylation stronger than static stretch.

The environment for living organism in space has microgravity and/or hypergravity and/or any kind of mechanical stresses. Cellular response may differ from the variety of mechanical stress. Mitogen-activated protein kinases (MAPKs) pathway is related to various cellular events. In the present study it was investigated the serial measurement of MAPK phosphorylation using western-blotting analysis following with three types of cyclic stretch, static, 0.1 Hz and 0.25 Hz. The result was that induction of MAPK phosphorylation had peaks within 2 to 4 hours and attenuated, while induction of p38 phosphorylation in 0.1 Hz stretch had a peak at 6 hours later and the strongest. Thus, there might be differential cellular response depends upon the frequency of cyclic stretch .

Blotting, Western↗

PubMed2003

A beta-induced TNF-alpha expression and acetylcholine action in mouse glial cells.

The brains in patients with Alzheimer's disease show chronic inflammatory responses characterized by activated glial cells and increased expression of cytokines. It is of interest to determine whether acetylcholine (ACh) affects Abeta-induced cytokine expression in the glial cells. Since it has been shown that alpha7 subunits of nicotinic ACh receptors are expressed in glial cells and that Abeta(1-42) binds to alpha7, we examined the effects of cholinergic agonists, carbachol, nicotine and oxotremorine-M, on Abeta-induced TNF-alpha expression in mouse glial cells. We did not observe any regulatory effects of ACh on Abeta-induced TNF-alpha transcription in the glial cells. We discuss the pathophysiological roles of ACh in glial cells in the brains of patients with Alzheimer's disease.

Acetylcholine↗

PubMed2003

The presence and functions of muscarinic receptors in human T cells: the involvement in IL-2 and IL-2 receptor system.

The existence and functions of muscarinic acetylcholine (mACh) receptors in human T lymphocytes were investigated. RT-PCR analysis demonstrated the presence of M(1) and M(2) subtypes of mACh receptors in human T lymphocytes. Pretreatment with oxotremorine-M (Oxo-M) caused the increase in phytohemagglutinin-induced IL-2 production. Since 4-DAMP suppressed Oxo-M-caused enhancement in IL-2 production, M(1) receptors seem to be involved in the enhancement of the production. Oxo-M stimulated IL-2 receptor mRNA expression and DNA synthesis. Our results suggest that muscarinic receptors, perhaps M(1) receptors are involved in the enhancement of TCR-induced IL-2 production and IL-2 receptor expression in human T lymphocytes. Thus muscarinic receptors positively modulate cell growth in human T lymphocytes by the autocrine mechanism through enhancing expression of both IL-2 and the receptors.

Acetylcholine↗

PubMed2003

Increased levels of UV-induced protease activity in human UVAP-1 cells exposed to gravity-changing stress: involvement of E-64-sensitive proteases in suppression of UV mutagenicity.

Under the 1G condition, the increase in antipain-sensitive protease activity promptly after UV (mainly 254 nm wavelength) irradiation in cultured human cells is detected and found to be one of the intriguing events involved in suppression of cell mutability. It was found that two cell lines, RSa and its variant UVAP-1 cells are applicable; the former is hypermutable and not susceptible to protease activation, while the latter is hypomutable and susceptible. In the present study it was investigated whether the increase in protease activity by UV irradiation is also observed in hypomutable human UVAP-1 cells exposed to gravity-changing stress and whether the increase is involved in suppression of UV mutagenicity. Exposure of human UVAP-1 cells to gravity-changing stress such as free-fall and parabolic flight prior to UV irradiation resulted in a pronounced increase in protease activity, but not to hypergravity conditions (2 and 10G) prior to UV irradiation. To characterize the proteases, components of lysates from the cells exposed to free-fall prior to UV irradiation were fractionated by high performance liquid chromatography, indicating two separate fractions with highly increased levels of E-64-sensitive protease activity. In the cells treated with E-64 during their exposure to free-fall, K-ras codon 12 base substitution mutation was detected after UV irradiation, although the mutation was not detected after UV irradiation alone. Thus, the increase in E-64-sensitive protease activity may be involved in the suppression of UV mutagenicity in UVAP-1 cells exposed to free-fall.

Antipain↗

PubMed2003

Age-related alterations in the expression of glial cell line-derived neurotrophic factor in the senescence-accelerated mouse brain.

Senescence-accelerated mouse prone 8 (SAMP8) and prone 10 (SAMP10) are useful murine model of accelerated aging. SAMP8 shows marked impairment of learning and memory, whereas SAMP10 shows brain atrophy and aging-associated depressive behavior. This study examined the expression of glial cell line-derived neurotrophic factor (GDNF) in SAMP8 and SAMP10 brains, relative to that in SAM resistant 1 (SAMR1) controls, which age normally. Hippocampal GDNF mRNA expression decreased in an age-dependent manner (10- vs 2-month-old animals) in the SAMR1, but not in the SAMP8 or SAMP10 strains. Furthermore, GDNF mRNA expression in 2-month-old SAMP8 and SAMP10 strains was less than in SAMR1 specimens of the same age. The number of surviving neurons in the CA1 region decreased with age in SAMP8 and SAMP10, and also decreased relative to the number of neurons in 10-month-old SAMR1 controls. Immunohistochemistry revealed that cells that were positive for GDNF-like activity in 10-month-old SAMP8 and SAMP10 were diffusely distributed, in part, around the pyramidal cell layer in the hippocampus. These findings suggest that low GDNF expression in young SAMP8 and SAMP10 may be involved in hippocampal dysfunctions, such as age-related learning impairment and neuronal death.

Aging↗

PubMed2003

[Abscopal effect of small intestinal NK/T-cell lymphoma].

The abscopal effect is characterized by the spontaneous regression of unirradiated tumors resulting from the effect of irradiation on remote tissue. We report a case of NK/T-cell lymphoma of the small intestine that achieved complete remission as a result of an abscopal effect. A 74-year-old Japanese woman was referred to our hospital because of ileus and suspected perforation of the gastrointestinal tract. An emergency operation was performed and a perforated ulcerative tumor in the small intestine and enlarged mesenteric lymph nodes were found. Histopathological examination of the resected small bowel showed infiltration of large lymphoid cells with irregular nuclei and they were positive for CD3, CD56, TIA-1 and granzyme B. Physical examination did not reveal any lymphadenopathy in the neck, axillary or inguinal regions, skin involvement or nasal infiltration. The CT scans revealed multiple tumors in her upper abdomen and an obstructing conglomerate of small intestinal tumors. The patient did not show any response to CHOP therapy and radiotherapy was delivered to the lower abdominal field for the treatment of the ileus at a total dose of 44 Gy. Two months after radiotherapy, abdominal CT scans showed the disappearance of not only the tumors in the irradiation field but also the upper abdominal tumors that had not been irradiated. The patient has remained in complete remission for 15 months.

Aged↗

PubMed2003

Effect of resistance training on changes in lymphocyte subpopulation during head-down-tilt bed rest.

Head-down-tilt (HDT) bed rest imitates microgravity-like conditions for a supine human body on the ground. On the other hand, resistance training is used to eliminate unfavorable physical changes in astronauts under a microgravity environment during spaceflight. Twelve healthy males voluntarily participated in a 20-day -6 degrees HDT bed rest study. The ratio of CD3-positive peripheral blood lymphocytes were analyzed by immunofluorescence staining. Volunteers who undertook resistance-training during HDT bed rest were designated as the resistance training group (RTG), and those who did not as non-resistance-training group (N-RTG). We could not observe significant differences in the ratio of CD3-positive peripheral blood lymphocytes between RTG and N-RTG. Thus, resistance training during HDT bed rest might not have a significant effect on changes in the ratios of CD3-positive PBL.

Adult↗

PubMed2002

Effects of 3-D clino-rotation on gene expression in human fibroblast cells.

Continuous variation in the direction of the gravity vector leads to various cellular responses including modulation of gene expression. Complementary DNA (cDNA) array analyses are available to observe the variation of gene expression under different conditions. In this study, expression levels of 588 representative genes were compared using the Atlas human cDNA expression array in human fibroblast cells with and without 3-dimensional (3-D) clinostat. Five upregulated and 8 downregulated genes were detected. Among these genes, upregulation of XRCC1, and downregulation of ERB-B2 and p21(Cip1/Waf1) were confirmed by RT-PCR. These results suggested that the gene expression levels of XRCC1, ERB-B2 and p21(Cip1/Waf1) were modulated by vector-averaged microgravity induced by 3-D clinostat in human fibroblast cells. Our findings may be a basis for the biological study of 3-D culture systems.

Cell Culture Techniques↗

PubMed2002

Establishment and characterization of GSA-1, a human cell line highly susceptible to apoptosis after free-fall.

The induction of apoptosis by microgravity and/or gravity-changing stress is considered to be one of the important causes of cell death, although the molecular mechanisms of the apoptotic event remain unclarified. In this study, we established a cell line, GSA-1, from ethyl methanesulfonate-treated human RSa cells. GSA-1 cells were highly susceptible to apoptosis after a free-fall; 24.4% of these cells underwent apoptosis after free-fall, compared with only 6% of the RSa cells. The apoptosis of GSA-1 cells was augmented by ultraviolet (UV, principally 254-nm wavelength) irradiation before free-fall to a greater extents than those in RSa cells. The molecular mechanisms of apoptosis included p53 and Bax proteins; the expression of nuclear p53 and cytoplasmic Bax in GSA-1 cells increased at 4 h after free-fall irrespective of irradiation. In addition, the rate of removal of cyclobutane pyrimidine dimer (CPD) in UV-irradiated GSA-1 cells was higher in cells exposed to free-fall than in those under the 1-G condition. Our results suggested that in GSA-1 cells, free-fall accelerates apoptosis, and that this process is associated with the accumulation of p53 and Bax, as well as CPD removal. Thus, GSA-1 cells should be useful for investigating the mechanism of cellular response, including the induction of apoptosis under gravity-changing stress.

Apoptosis↗

PubMed2002

CD56 positive intestinal T-cell lymphoma: treatment with high dose chemotherapy and autologous peripheral blood stem cell transplantation.

A 63-year-old man presented with a perforation of the small intestine. A diagnosis of intestinal T-cell lymphoma (ITCL) was made from CD (cluster differentiation) 3 positivity and a rearrangement of T-cell receptor genes. The tumor also expressed CD56, which suggests it belongs to a rare subtype derived from activated cytotoxic intraepithelial T lymphocytes. Although the prognosis of ITCL has been considered to be very poor irrespective of CD56 positivity, complete remission was achieved in this case by high dose chemotherapy followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) even after relapse. Auto-PBSCT in the earlier stage of the disease might improve the prognosis.

Antineoplastic Combined Chemotherapy Protocols↗