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Biomedical subjects

Masafumi Ito

Publications and source records attributed to Masafumi Ito.

At least 19 recordsLinked to original sources
PubMed2006

Targeted disruption of Gb3/CD77 synthase gene resulted in the complete deletion of globo-series glycosphingolipids and loss of sensitivity to verotoxins.

To examine whether globotriaosylceramide (Gb3/CD77) is a receptor for verotoxins (VTs) in vivo, sensitivity of Gb3/CD77 synthase null mutant mice to VT-2 and VT-1 was analyzed. Although wild-type mice died after administration of 0.02 microg of VT-2 or 1.0 microg of VT-1, the mutant mice showed no reaction to doses as much as 100 times that administered to wild types. Expression analysis of Gb3/CD77 in mouse tissues with antibody revealed that low, but definite, levels of Gb3/CD77 were expressed in the microvascular endothelial cells of the brain cortex and pia mater and in renal tubular capillaries. Corresponding to the Gb3/CD77 expression, tissue damage with edema, congestion, and cytopathic changes was observed, indicating that Gb3/CD77 (and its derivatives) exclusively function as a receptor for VTs in vivo. The lethal kinetics were similar regardless of lipopolysaccharide elimination in VT preparation, suggesting that basal Gb3/CD77 levels are sufficient for lethal effects of VTs.

Animals↗
PubMed2006

Establishment of a myeloid leukemia cell line, TRL-01, with MLL-ENL fusion gene.

We established a leukemia cell line derived from therapy-related acute myeloid leukemia with the t(11;19) by xenotransplantation into the NOD/SCID mouse with IL-2Rgamma(c)-/- (NOG mouse). The cell line, TRL-01, could be serially transplanted from mouse to mouse and also grown in an adherence-dependent manner on a murine bone marrow stroma cell line, HESS-5. TRL-01 had the same immunophenotype as the original leukemia cells: positive for CD13, CD33, CD11a, CD18, CD29, CD49d, CD49e, CD54, CD62L, and CD117, and negative for CD3, CD4, CD8, CD19, CD34, CD41a, CD41b, CD135, and myeloperoxidase. Translocation (11;19)(q23;p13) in both the original sample and TRL-01 generated MLL-ENL chimeric transcripts joining exon 6 and exon 4, respectively, which has a novel isoform. In cultures of TRL-01, addition of GM-CSF, SCF, and G-CSF and adhesion to fibronectin-coated plates promoted transient proliferation and survival, although they did not support long-term culture. Subcutaneous injection caused a tumor to form only when HESS-5 was coinjected at the same site. These results suggest that TRL-01 is a useful cell line for studying not only the leukemia-related biology of MLL-ENL but also the intercellular association between leukemia and stroma.

Adult↗
PubMed2006

High titer of ADAMTS13 inhibitor associated with thrombotic microangiopathy of the gut and skeletal muscle after allogeneic hematopoietic stem cell transplantation.

Transplantation-associated thrombotic microangiopathy (TMA) is one of the main complications after hematopoietic stem cell transplantation (HSCT). At the time of onset of gut TMA, a patient developed a high titer of an inhibitor of the non-immunoglobulin G type to ADAMTS13, which physiologically hydrolyzes von Willebrand factor to control spontaneous intravascular thrombus formation. The patient developed symptoms of myositis, a disorder that has occasionally been reported to manifest after HSCT and to resemble some idiopathic autoimmune diseases. However, a muscle biopsy specimen presented pathologic findings of TMA, including microvascular platelet thrombus formation, without inflammatory lymphocyte infiltration. ADAMTS13 activities returned to normal after steroid treatment, and the improvement of TMA symptoms followed. This patient appears to represent a rare case of post-HSCT TMA associated with the development of an ADAMTS13 inhibitor.

ADAM Proteins↗
PubMed2006

Classic polyarteritis nodosa presenting rare clinical manifestations in a patient with hemophilia A.

A 35-year-old patient with hemophilia A presented with rapidly progressive polyarteritis nodosa (PAN). He had been infected with hepatitis B virus (HBV) by repeated transfusion and was positive for hepatitis B surface antigen but negative for hepatitis B surface antibody. The patient presented symptoms of acute epididymitis followed by emergency admission because of acute appendicitis. On day 7 of admission, he complained of severe back pain, and computerized tomography (CT) showed massive perirenal hematoma. On day 49, mild monoplegia in the left arm suddenly developed, and CT and magnetic resonance imaging revealed multiple cerebral infarctions. Factor VIII replacement therapy was attenuated; however, cerebral infarction was progressive and extended throughout the cerebral hemispheres. He was diagnosed with classic polyarteritis nodosa (cPAN), and pulse methylprednisolone was continued. The patient died of supratentorial herniation, and autopsy revealed that vasculitis associated with intimal thickening was present in the liver, pancreas, intestine, kidneys, and larger-sized cerebral arteries. The development of cPAN appeared to have originated from chronic HBV infection, and this is the first report of cPAN in hemophilia patients. Concomitant hemorrhagic and thrombotic manifestations of cPAN are hardly treatable in patients with coagulation disorders, and the current case may represent a rare transfusion-related complication in hemophilia patients.

Adult↗
PubMed2006

[A case of aseptic meningitis caused by relapsing polychondritis].

We report a patient of relapsing polychondritis (RP) with antecedent aseptic meningitis. A 65-year-old man has developed headache and fever. Neurological examination showed meningeal signs, and cerebrospinal fluid (CSF) examination revealed meningeal inflammation which contained 450 polymorphonuclear cells/microl, 302 mononuclear cells/microl, and 0 red cells/microl, with 79 mg protein/dl. Serologic testing for autoimmune disease as well as the culture and cytology of CSF were negative. He admitted our hospital as having aseptic meningitis and experienced antibiotic therapy. However, his pyrexia continued and he developed repeating visual and hearing impairment reacting to steroid. Three months later, he became behaviorally deaf, and bilateral auricular chondritis occurred with nonerosive seronegative inflammatory polyarthritis. The result of condral biopsy was consistent with the diagnosis of RP showing cartilage surrounded by an intense inflammatory cell response with a decreased number of chondrocytes. A clinical diagnosis was made and prednisolone 60 mg/day was begun with the result of resolution of the auricular chondritis, and slight improvement of his deafness. Aseptic meningitis is a rare complication of RP. Only one report detailed RP patient who had preceding meningitis. RP is a potentially lethal disease resulting from suffocation by airway collapse, the complications of a cardiac large vessel, and so on. For improvement of a life prognosis, an early diagnosis and treatment are indispensable. Although RP is a rare discovery, it is necessary that RP should be taken into consideration and be differentiated as a cause of relapsing aseptic meningitis.

Aged↗
PubMed2006

[Successful salvage therapy with cladribine and rituximab for a patient with a relapsed Asian variant of intravascular large B-cell lymphoma].

The Asian variant of intravascular large B-cell lymphoma (AIVL) is a rare aggressive lymphoma characterized by various clinical symptoms, hemophagocytic syndrome and predominant growth within vessels. We present a 73-year-old man with relapsed AIVL who had been treated with six courses of CHOP regimen. A half year later, he presented with high fever, sweat, dementia and hepatosplenomegaly without lymphadenopathy. A bone marrow biopsy showed prominent hemophagocytosis and immunological staining disclosed an augmented intrasinusal pattern of atypical large lymphocytes characteristic of the CD20+ and CD5+ phenotypes. As salvage therapy, CND-R (rituximab, cladribine, mitoxantrone, dexamethasone) was performed, and the clinical symptoms immediately and dramatically improved. Subsequently, CND-R therapy was repeated every 4 weeks. No serious adverse events were observed with the exception of grade 4 neutropenia and grade 3 thrombocytopenia. After completion of the fifth course, a bone marrow biopsy pathologically confirmed complete remission, leading to termination of this therapy. The patient has remained in remission for more than 15 months. CND-R therapy, which is effective for indolent lymphoma, may be one of the candidates in salvage therapy for relapsed AIVL.

Aged↗
PubMed2005

In-line type micropulse lidar with an annular beam: experiment.

An in-line type compact micropulse lidar (MPL) with an annular beam was developed for low-altitude cloud measurement. An optical circulator and a couple of axicon prisms for an annular beam were installed on the lidar optics. The advantage of using the in-line MPL is its ability to obtain a near-range measurement with a narrow field of view of 0.1 mrad and to obtain a depolarization measurement of the orthogonally polarized echoes caused by ice crystals of a low-altitude cloud. The total insertion loss of the lidar optics was 3 dB. Detectors such as avalance photodiode detectors can be operated in an analog mode near the breakdown voltage because of the high isolation of the optical circulator. The ideal lidar echo variation from the nearest distance was verified by measuring the mountain echoes at various distances. The depolarization measurement of a low-altitude ice cloud was also demonstrated.

Journal Article↗
PubMed2005

In-line type micropulse lidar with an annular beam: theoretical approach.

An in-line type micropulse lidar (MPL) with an annular beam was designed and the transmitting and receiving characteristics were analyzed. Because the in-line MPL utilizes a common telescope for a transmitter and a receiver and the annular beam always overlaps with the receiver's field of view (FOV), it can measure near-range lidar echoes with a narrow FOV. The transmitting annular beam changes its shape to a nearly nondiffractive beam through propagation. It improves the spatial resolution of the lidar observation. The receiving characteristics showed the ideal lidar echo variation, which was inversely proportional to the square of the distance the beam propagated, even if it was in the near range.

Journal Article↗
PubMed2005

Dietary fish oil attenuates cardiac hypertrophy in lipotoxic cardiomyopathy due to systemic carnitine deficiency.

OBJECTIVE: 1,2-Diacylglycerol (DAG), a lipid second messenger that activates protein kinase C (PKC), is increased with a distinct fatty acid composition in the heart of the juvenile visceral steatosis (JVS) mouse, which develops pathological cardiac hypertrophy with lipid accumulation induced by the perturbation of fatty acid beta-oxidation due to systemic carnitine deficiency. Fish oil (FO) may exert its beneficial effects on the cardiomyopathy in JVS mice by modifying the molecular species composition of myocardial DAG. To test this hypothesis, we investigated the effects of dietary FO on the hypertrophied hearts in JVS mice. METHODS: Both control and JVS mice were fed a FO diet (containing 10% FO) or a standard diet from 4 weeks of age. RESULTS: At 8 weeks of age, the ventricular-to-body weight ratio in JVS mice was 2.7-fold higher than that in controls (9.9 +/- 0.1 vs. 3.7 +/- 0.1 mg/g, P < 0.01) and was reduced by dietary FO (7.7 +/- 0.1 mg/g, P < 0.01 vs. JVS mice). In JVS mice, myocardial DAG levels were elevated by 2.3-fold with a distinct fatty acid composition with increases in C18:1n-7,9 and C18:2n-6 fatty acids compared with controls; dietary FO had no effects on the total DAG levels but significantly altered the fatty acid composition of DAG with reduction of both fatty acid species. Immunoblot analysis showed that dietary FO prevented the membrane translocation of cardiac PKCs alpha, beta2, and epsilon in JVS mice. Dietary FO did not affect the plasma and myocardial total carnitine levels in JVS mice. Furthermore, dietary FO significantly improved the progressive left ventricular dysfunction and survival rate in JVS mice. CONCLUSIONS: Dietary FO may attenuate cardiac hypertrophy with improvements in cardiac function and survival in JVS mice via modification of the molecular species composition of myocardial DAG and the consequent inhibition of PKC redistribution. These results suggest the implication of the molecular species composition of DAG in the pathogenesis of lipotoxic cardiomyopathy due to perturbations of fatty acid beta-oxidation.

Animals↗
PubMed2005

Mitochondrial genome polymorphisms associated with type-2 diabetes or obesity.

Although a strong correlation between type-2 diabetes and obesity has been found, no comparative analysis between diabetes and obesity has been performed with respect to mitochondrial DNA (mtDNA) polymorphisms. To test the hypothesis that certain mitochondrial single nucleotide polymorphisms (mtSNPs) might be associated with obesity or type-2 diabetes, we determined the entire sequences of the mitochondrial genomes from 96 patients with type-2 diabetes and those from 96 young obese adults by direct sequencing and compared the frequencies of mtSNPs between these two groups. A mtSNP, 8684C > T (T53I) in the mitochondrial ATP synthase subunit 6 gene (ATP6), was detected in 5 of the 96 patients with type-2 diabetes, whereas this substitution was not detected in any of the 96 young obese adults. Two mtSNPs, 3497C > T (A64V) in NADH dehydrogenase subunit 1 gene (ND1) and 1119T > C (472U > C) in the 12S rRNA gene, were detected in 5 of the 96 young obese adults, whereas these substitutions were not detected in any of the 96 diabetic patients. The 8684C > T transition associated with type-2 diabetes represents haplogroup M8a, and the 3497C > T and 1119T > C transitions predisposing to obesity represent haplogroup B4c. These results suggest that distinct mtSNPs contribute to susceptibility to type-2 diabetes or obesity, pointing out the necessity of large-scale case control studies.

Adult↗
PubMed2005

Endoscopic resection of Peutz-Jeghers polyps throughout the small intestine at double-balloon enteroscopy without laparotomy.

BACKGROUND: Small-bowel enteroscopy with the double-balloon method was developed to improve access to the small intestine. This study evaluated the usefulness of this method for the resection of small-intestinal Peutz-Jeghers polyps. METHODS: Two patients with Peutz-Jeghers syndrome underwent nonsurgical double-balloon enteroscopic resection of polyps throughout the small intestine. OBSERVATIONS: Multiple polyps in the jejunum were successfully resected via the oral route, as were the polyps in the ileum via the anal route. All 18 polyps (10-60 mm in size) were resected without subsequent bleeding or perforation. Histopathologically, 3 large polyps (>30 mm diameter) were hamartomas with adenomatous components. CONCLUSIONS: Double-balloon enteroscopy was safe and useful for the diagnosis and the treatment of Peutz-Jeghers polyps throughout the small intestine. Double-balloon enteroscopic polypectomy might preclude complications of Peutz-Jeghers syndrome, including intussusception, bleeding, and tumorogenesis, thereby obviating the need for multiple laparotomies.

Adult↗
PubMed2005

Engraftment of NOD/SCID/gammac(null) mice with multilineage neoplastic cells from patients with juvenile myelomonocytic leukaemia.

Several lines of evidence indicate the clonal nature of juvenile myelomonocytic leukaemia (JMML), involving myeloid, erythroid, megakaryocyte and B-lymphoid lineages. However, it is unclear whether the T-lymphocyte lineage is involved. We demonstrated that cells from six patients with JMML repopulated in non-obese diabetic/severe combined immunodeficient/gammac(null) mice and differentiated into granulocytes, monocytes, erythrocytes, B lymphocytes, T lymphocytes and natural killer cells. The percentage of human CD45 antigen-positive cells ranged from 41% to 73% in the murine bone marrow 12 weeks after transplantation. To examine the involvement of lymphocyte subpopulations, we purified human CD3(+), CD19(+) and CD56(+) cells from murine bone marrow cells transplanted from a patient with monosomy 7. Fluorescence in situ hybridization (FISH) showed the clonal marker in 96-100% of purified CD3(+), CD19(+) and CD56(+) subpopulations. These findings support the concept that JMML originates in transplantable multilineage haematopoietic stem cells. This novel murine xenotransplant model should be useful for investigating the nature of stem cells and testing new therapies for patients with JMML.

Animals↗
PubMed2005

New views on antidiarrheal effect of wood creosote: is wood creosote really a gastrointestinal antiseptic?

Wood creosote, the principal ingredient in Seirogan, has a long history as a known gastrointestinal microbicidal agent. When administered orally, the intraluminal concentration of wood creosote is not sufficiently high to achieve this microbicidal effect. Through further animal tests, we have shown that antimotility and antisecretory actions are the principal antidiarrheal effects of wood creosote. Wood creosote inhibits intestinal secretion induced by enterotoxins by blocking the Cl(-) channel on the intestinal epithelium. Wood creosote also decreases intestinal motility accelerated by mechanical, chemical, or electrical stimulus by the inhibition of the Ca(2+) influx into the smooth muscle cells. In this overview, the antimotility and antisecretory effects of wood creosote are compared with those of loperamide. Wood creosote was observed to inhibit stimulated colonic motility, but not normal jejunal motility. Loperamide inhibits normal jejunal motility, but not stimulated colonic motility. Both wood creosote and loperamide inhibit intestinal secretion accelerated by acetylcholine. Wood creosote was found to have greater antisecretory effects in the colon than loperamide. Based upon these findings, we conclude that the antidiarrheal effects of wood creosote are due to both antisecretory activity in the intestine and antimotility in the colon, but not due to the microbicidal activity as previously thought. Wood creosote was found to have no effects on normal intestinal activity. These conclusions are supported by the results of a recent clinical study comparing wood creosote and loperamide, which concluded that wood creosote was more efficacious in relieving abdominal pain and comparable to loperamide in relieving diarrhea.

Animals↗
PubMed2005

[Clinical features and treatment of Fisher syndrome].

To clarify the clinical features of patients with Fisher syndrome, we reviewed detailed clinical profiles and laboratory findings in 267 cases. The men:women ratio was about 3:2, median age at onset 42 years, and the two peaks were 30-39 and 50-59. Sixty two percent of the patients had an antecedent illness with upper respiratory infectious symptoms. As initial symptoms, 63% had diplopia, 33% ataxic gait, and 17% dysesthesia of the upper and/or lower limbs. Besides ophthalmoplegia, ataxia, and areflexia, blepharoptosis (42%), internal ophthalmoplegia (35%), facial palsy (25%), and bulbar palsy (16%) were present. Limb weakness was significant in 25% and sensory impairment in 52%. CSF albuminocytological dissociation was present in 80% after the second week. Most patients were given intravenous immunoglobulin (59%). None died, and almost all had a monophasic remitting course and a generally good outcome.

Adult↗
PubMed2004

HIV-1 nef suppression by virally encoded microRNA.

BACKGROUND: MicroRNAs (miRNAs) are 21 to approximately 25-nucleotides (nt) long and interact with mRNAs to trigger either translational repression or RNA cleavage through RNA interference (RNAi), depending on the degree of complementarity with the target mRNAs. Our recent study has shown that HIV-1 nef dsRNA from AIDS patients who are long-term non-progressors (LTNPs) inhibited the transcription of HIV-1. RESULTS: Here, we show the possibility that nef-derived miRNAs are produced in HIV-1 persistently infected cells. Furthermore, nef short hairpin RNA (shRNA) that corresponded to a predicted nef miRNA (approximately 25 nt, miR-N367) can block HIV-1 Nef expression in vitro and the suppression by shRNA/miR-N367 would be related with low viremia in an LTNP (15-2-2). In the 15-2-2 model mice, the weight loss, which may be rendered by nef was also inhibited by shRNA/miR-N367 corresponding to suppression of nef expression in vivo. CONCLUSIONS: These data suggest that nef/U3 miRNAs produced in HIV-1-infected cells may suppress both Nef function and HIV-1 virulence through the RNAi pathway.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Nuclear factor of activated T cells (NFAT) is involved in the depolarization-induced activation of growth hormone-releasing hormone gene transcription in vitro.

GHRH plays a pivotal role in the regulation of both synthesis and secretion of GH in the anterior pituitary. In this study, we examined the molecular mechanism of depolarization-induced GHRH gene transcription using the hypothalamus cell line, Gsh+/+, revealing the involvement of the transcription factor called nuclear factor of activated T cells (NFAT). GHRH, NFAT1, NFAT4, and related genes were endogenously expressed in Gsh+/+ cells and the rat arcuate nucleus, where NFAT1 and GHRH were colocalized. Cellular excitation with high potassium potently stimulated endogenous GHRH gene 5'-promoter activity as well as the NFAT-mediated gene transcription, the former being further enhanced by coexpression of NFAT. On the other hand, cyclosporin A (a calcineurin-NFAT inhibitor) or EGTA (a calcium chelator) significantly blocked the depolarization-induced GHRH gene transcription. EMSA and site-directed mutagenesis experiments showed the direct binding of NFAT at five sites of the GHRH promoter, among which the relative importance of three distal sites (-417/-403, -402/-387, -317/-301) was suggested. Finally, elimination of all five sites completely abolished the NFAT-induced GHRH gene up-regulation. Altogether, our results suggest that the transcription factor NFAT is involved in the depolarization-induced transcriptional activation of GHRH gene in the neuronal cells.

Animals↗
PubMed2004

Sinoatrial node dysfunction and early unexpected death of mice with a defect of klotho gene expression.

BACKGROUND: Homozygous mutant mice with a defect of klotho gene expression (kl/kl) show multiple age-related disorders and premature death from unknown causes. METHODS AND RESULTS: The kl/kl mice subjected to 20-hour restraint stress showed a high rate (20/30) of sudden death, which was associated with sinoatrial node dysfunction (conduction block or arrest). Heart rate and plasma norepinephrine of kl/kl mice, unlike those of wild-type (WT) mice, failed to increase during the stress. Intrinsic heart rate after pharmacological blockade of autonomic nerves in kl/kl mice was significantly lower than that in WT mice (380+/-33 versus 470+/-44 bpm; n=7). The sinus node recovery time after an overdrive pacing (600 bpm, 30 seconds) in kl/kl mice was significantly longer than in WT mice (392+/-37 versus 233+/-24 ms; n=6). In isolated sinoatrial node preparations, the positive chronotropic effect of isoproterenol was significantly less, whereas the negative chronotropic effect of acetylcholine was significantly greater in kl/kl than in WT mice. There was no degenerative structural change in the sinoatrial node of kl/kl mice. The precise localization of klotho was analyzed in newly prepared klotho-null mice with a reporter gene system (kl(-geo)). Homozygous kl(-geo) mice showed characteristic age-associated phenotypes that were almost identical to those of kl/kl mice. In the kl(-geo) mice, klotho expression was recognized exclusively in the sinoatrial node region in the heart in addition to parathyroid, kidney, and choroid plexus. CONCLUSIONS: In the heart, klotho is expressed solely at the sinoatrial node. klotho gene expression is essential for the sinoatrial node to function as a dependable pacemaker under conditions of stress.

Aging, Premature↗