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M Ichimura

Publications and source records attributed to M Ichimura.

At least 19 recordsLinked to original sources
PubMed2006

Observation and control of transverse energy-transport barrier due to the formation of an energetic-electron layer with sheared ExB flow.

Off-axis electron-cyclotron heating in an axisymmetric barrier mirror produces a cylindrical layer with energetic electrons, which flow through the central cell and into the end region. The layer, producing a localized bumped ambipolar potential Phi(C), forms a strong shear of radial electric fields E(r) and peaked vorticity with the direction reversal of E(r)xB sheared flow near the Phi(C) peak. Intermittent vortexlike turbulent structures near the layer are suppressed in the central cell by this actively produced transverse energy-transport barrier; this results in T(e) and T(i) rises surrounded by the layer.

Journal Article↗
PubMed2006

IL-18 gene polymorphism confers susceptibility to the development of anti-GAD65 antibody in Graves' disease.

AIMS: This study aimed to investigate whether interleukin-18 (IL-18) gene polymorphisms are associated with the development of antibody against the 65-kDa isoform of recombinant human glutamic acid decarboxylase (GAD65Ab) in patients with Graves' disease. METHODS: A total of 398 unrelated Japanese patients with Graves' disease, with and without GAD65Ab, were recruited. Three single nucleotide polymorphisms in the IL-18 gene were examined and the polymorphic allele and the genotype and haplotype frequencies calculated. RESULTS: The frequency of the GG genotype at position -4675 of the IL-18 gene was significantly lower in Graves' disease patients with GAD65Ab than those without (4% vs. 24%, P = 0.0126). The -4675C allele frequency was significantly greater in patients with GAD65Ab than those without (69% vs. 53%, P = 0.0168). The homozygous -4675G/-607A/-137G haplotype was less common in Graves' disease patients with GAD65Ab than those without (4% vs. 23%, P = 0.0144). CONCLUSIONS: These findings in a Japanese population indicate that Graves' disease patients carrying the GG genotype at position -4657 of the promoter of the IL-18 gene or a gene in linkage disequilibrium with the -4675G/-607A/-137G haplotype have a low risk for the development of GAD65Ab in Graves' disease.

Adolescent↗
PubMed2005

Observation of the effects of radially sheared electric fields on the suppression of turbulent vortex structures and the associated transverse loss in GAMMA 10.

Vortexlike turbulent structures in hot-ion mode plasmas with several keV are observed in the case with a radially produced weak shear of electric fields E(r). However, a strong E(r) shear formation due to a high ion-confining potential phi(c) production clears up these vortices together with plasma-confinement improvement and disappearance of both drift-wave and turbulencelike Fourier spectral signals. These findings are based on three-time progress in phi(c) in comparison to phi(c) attained 1992-2002. The significant advance of phi(c) is well extended in line with proposed potential-formation physics scalings.

Journal Article↗
PubMed2003

Progress in pursuit of therapeutic A2A antagonists: the adenosine A2A receptor selective antagonist KW6002: research and development toward a novel nondopaminergic therapy for Parkinson's disease.

Research and development of the adenosine A2A receptor selective antagonist KW6002 have focused on developing a novel nondopaminergic therapy for Parkinson's disease (PD). Salient pharmacologic features of KW6002 were investigated in several animal models of PD. In rodent and primate models, KW6002 provides symptomatic relief from parkinsonian motor deficits without provoking dyskinesia or exacerbating existing dyskinesias. The major target neurons of the A2A receptor antagonist were identified as GABAergic striatopallidal medium spiny neurons. A possible mechanism of A2A receptor antagonist action in PD has been proposed based on the involvement of striatal and pallidal presynaptic A2A receptors in the "dual" modulation of GABAergic synaptic transmission. Experiments with dopamine D2 receptor knockout mice showed that A2A receptors can function and anti-PD activities of A2A antagonists can occur independent of the dopaminergic system. Clinical studies of KW6002 in patients with advanced PD with L-dopa-related motor complications yielded promising results with regard to motor symptom relief without motor side effects. The development of KW6002 represents the first time that a concept gleaned from A2A biologic research has been applied successfully to "proof of concept" clinical studies. The selective A2A antagonist should provide a novel nondopaminergic approach to PD therapy.

Adenosine A2 Receptor Antagonists↗
PubMed2002

Chronic inflammatory demyelinating polyneuropathy presenting with features of GBS.

The authors report five patients with inflammatory demyelinating polyneuropathy with a Guillain-Barré syndrome (GBS)-like onset and initial clinical features, but with persistent symptoms similar to chronic inflammatory demyelinating polyneuropathy (CIDP). Patients in the chronic phase improved with corticosteroid or IV immunoglobulin therapy. Patients with apparent GBS who show persistent symptoms may benefit from corticosteroids or other treatment that is beneficial in the management of CIDP.

Adolescent↗
PubMed2001

KF31327, a new potent and selective inhibitor of cyclic nucleotide phosphodiesterase 5.

The effects of KF31327 (3-ethyl-8-[2-(4-hydroxymethylpiperidino)benzylamino]-2,3-dihydro-1H-imidazo[4,5-g]quinazoline-2-thione dihydrochloride) on phosphodiesterase 5 (cyclic GMP-specific phosphodiesterase) activity and platelet aggregation were investigated and compared with those of sildenafil, a well-known phosphodiesterase 5 inhibitor. KF31327 inhibited phosphodiesterase 5 from canine trachea (K(i)=0.16 nM) more potently than sildenafil (K(i)=7.2 nM). The kinetic analysis revealed that KF31327 was a non-competitive inhibitor. In the presence of nitroglycerin (nitric oxide generator), both compounds inhibited the collagen-induced aggregation of rabbit platelets at less than 0.1 microM, augmenting intracellular cyclic GMP level without affecting cyclic AMP. In contrast, in the absence of nitroglycerin, a higher concentration (10 microM) of KF31327 was required to inhibit platelet aggregation and increased both cyclic nucleotide levels. However, 10 microM sildenafil did not affect aggregation despite elevation of cyclic GMP comparable to that in the presence of nitroglycerin. These results indicate that in the presence of nitroglycerin, the inhibition of platelet aggregation by KF31327 is due to the elevation of cyclic GMP, whereas the mechanism underlying the inhibition without nitroglycerin might be related to a rise in intracellular cyclic AMP.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2001

Generalized scaling laws of the formation and effects of plasma-confining potentials for tandem-mirror operations in GAMMA 10.

The main operations from 1979 to 2000 in the GAMMA 10 tandem-mirror, characterized in terms of the high-potential mode having kV-order plasma-confining potentials and the hot-ion mode yielding fusion neutrons with 10-20 keV bulk-ion temperatures, are summarized and generalized as a result of scalings of the formation and the effects of the potentials. The wide validity of potential-formation physics from Cohen's theory and the validity of the generalized Pastukhov's theory for the effects of thermal-barrier potentials on electron confinement are verified and consolidated through electron-energy balance.

Journal Article↗
PubMed2001

Adenosine A(2A) receptor enhances GABA(A)-mediated IPSCs in the rat globus pallidus.

1. The actions of adenosine A(2A) receptor agonists were examined on GABAergic synaptic transmission in the globus pallidus (GP) in rat brain slices using whole-cell patch-clamp recording. GP neurones were characterized into two major groups, type I and type II, according to the degree of time-dependent hyperpolarization-activated inward rectification and the size of input resistance. 2. The A(2A) receptor agonist 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamido- adenosine (CGS21680; 0.3-3 microM) enhanced IPSCs evoked by stimulation within the GP. The actions of CGS21680 were blocked by the A(2A) antagonists (E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine (KF17837) and 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM241385). 3. The CGS21680-induced increase in IPSCs was associated with a reduction in paired-pulse facilitation. CGS21680 (0.3 microM) increased the frequency of miniature IPSCs (mIPSCs) without affecting mIPSC amplitude. These observations demonstrated that the enhancement of IPSCs in the GP was attributable to presynaptic, but not postsynaptic, A(2A) receptors. 4. The results suggest that A(2A) receptors in the GP serve to inhibit GP neuronal activity, thereby disinhibiting subthalamic nucleus neurone activity. Thus, the A(2A) receptor-mediated presynaptic regulation in the GP, together with the A(2A) receptor-mediated intrastriatal presynaptic control of GABAergic neurotransmission described previously, may play a crucial role in controlling the neuronal functions of basal ganglia. This A(2A) receptor-mediated presynaptic dual control in the striatopallidal pathway could also afford the mode of action of A(2A) antagonists for ameliorating the symptoms of Parkinson's disease in an animal model.

Animals↗
PubMed2001

Age of onset influences clinical features of chronic inflammatory demyelinating polyneuropathy.

Chronic inflammatory demyelinating polyneuropathy (CIDP), which can occur through life from childhood to old age, presents a wide variety of clinical phenotypes. We investigated the relationship between age of onset and phenotype in 124 CIDP patients. Clinical symptoms, pathologic findings and electrophysiologic features were assessed according to age at onset: juvenile, younger than 20-years-old; adult, 20 to 64; and elderly, older than 64 (total n=124). Half of the juvenile group showed subacute progression initially, while most patients in the elderly group showed chronic insidious progression (chi(2)=23.2, P<0.0001). Motor dominant neuropathy was prominent in juveniles, while sensorimotor neuropathy was frequent in the elderly group (chi(2)=27.0, P<0.0001). A relapsing and remitting course predominated in the juvenile group (chi(2)=8.50, P=0.0143). Demyelinating and axonal degenerating features in sural nerve biopsy and in nerve conduction studies were common to three age groups. The subperineurial edema was more prominent in the juvenile and adult groups (P=0.006). Functional recovery was common in all three age groups, but was least apparent in the elderly group (P=0.00062). Demyelinating features in studies of nerve conduction and biopsy specimens was common to all three age groups, and was a useful diagnostic feature. Clinical features of CIDP differ by age of onset, which is a factor to consider in diagnosis, therapy, and prognosis.

Adult↗
PubMed2001

Synthesis and characterization of alkanethiolate-coordinated iron porphyrins and their dioxygen adducts as models for the active center of cytochrome p450: direct evidence for hydrogen bonding to bound dioxygen.

Two kinds of novel cytochrome P450 models, which have alkanethiolate axial ligands and hydroxyl groups inside molecular cavities, were designed and synthesized as functional O(2) binding systems. A superstructured porphyrin, designated as "twin-coronet" porphyrin, was used as the common framework of the model complexes. This porphyrin bears four binaphthalene bridges on the both sides and forms two pockets surrounded by the bulky aromatic rings. Thiobenzyloxy and thioglycolate moieties, which contain an alkanethiolate group exhibiting various electron-donating abilities and degrees of bulkiness, were covalently linked to twin-coronet porphyrin to yield thiolate-coordinated hemes, TCP-TB and TCP-TG (twin-coronet porphyrin with thiobenzyloxy and thioglycolate groups), respectively. Both ferric complexes exhibited high stability during usual experimental manipulation under air and were characterized by MS, UV/vis, ESR spectroscopies, and CV. The ESR spectra exhibited low-spin signals (TCP-TB: g = 2.334, 2.210, 1.959; TCP-TG: g = 2.313, 2.209, 1.966). The cyclic voltammogram of TCP-TB in CH(3)CN gave a quasi-reversible wave which corresponds to the Fe(III)/Fe(II) redox couple: E(p)()(/2) = -1.35 V (vs Fc/Fc(+)). On the other hand, TCP-TG showed a fine reversible wave: E(1/2) (Fe(III)/Fe(II)) = -1.12 V. The stable dioxygen adducts were formed in the reaction of the ferric complexes with KO(2) under an oxygen atmosphere and characterized by UV/vis and resonance Raman (RR) spectroscopies. In the RR spectra, the nu(O--O) bands of the dioxygen adducts were observed at 1138 cm(-1) (TCP-TB) and 1137 cm(-1) (TCP-TG). The hypothesis that hydrogen bonding between the bound oxygen and the hydroxyl groups of the binaphthyl moieties could increase their stability was verified by RR spectroscopy. When all hydroxyl groups were deuterated, only the frequencies of the nu(O--O) bands were upshifted by 2 cm(-1) without any perturbation in the porphyrin skeleton. This work shows the first direct evidence for a hydrogen bond to dioxygen in an oxy form of a thiolate-coordinated heme model system. These results are discussed in context of the process of dioxygen binding and activation in cytochrome P450.

Cytochrome P-450 Enzyme System↗
PubMed2001

Study on free radicals and pancreatic fibrosis--pancreatic fibrosis induced by repeated injections of superoxide dismutase inhibitor.

The exact mechanisms of the development of pancreatic fibrosis are still unknown. To clarify the relationship between pancreatic fibrosis and free radicals, the effect of the administration of a superoxide dismutase (SOD) inhibitor, diethyldithiocarbamate (DDC), on pancreatic fibrosis in rats was studied. A single intraperitoneal injection of 500 mg/kg of DDC significantly reduced SOD activity and significantly increased lipid peroxidation products in the pancreas, showing no histologic changes of inflammation or necrosis. Repeated administration of 500 mg/kg DDC, twice a week, caused inter- and intralobular fibrosis with atrophy of acinar cells in the pancreas for at least 2 weeks without fibrosis of the liver and kidney. Administration of allopurinol showed preventive effects against DDC-induced pancreatic fibrosis. In conclusion, repeated administration of DDC, which caused pancreatic fibrosis, is a new experimental model of pancreatic fibrosis from the viewpoint of oxidative stress.

Allopurinol↗
PubMed2001

Postgastrectomy polyneuropathy with thiamine deficiency.

OBJECTIVE: Polyneuropathy has been reported after gastrectomy performed to treat various lesions. Although thiamine deficiency is a possible cause of this neuropathy, the pathogenesis still remains to be clarified. Seventeen patients with peripheral neuropathy with thiamine deficiency after gastrectomy are described. METHODS: Seventeen patients with polyneuropathy after gastrectomy accompanied by thiamine deficiency were selected. Patients were restricted to those with total or subtotal gastric resection to treat ulcer or neoplasm. Patients who had undergone operations to treat morbid obesity were excluded. RESULTS: Intervals between the operation and onset of neuropathy varied from 2 months to 39 years. Most patients did not seem malnourished. Serum concentrations of B vitamins other than thiamine were nearly normal. Symmetric motor-sensory polyneuropathy, predominantly involving the lower limbs, had progressed over intervals varying from 3 days to 8 years. Relative degrees of motor and sensory impairment also varied extensively. Some cases that progressed rapidly mimicked Guillain-Barré syndrome. Electrophysiological and pathological findings were those of axonal neuropathy. Substantial functional recovery from polyneuropathy was seen in most patients by 3 to 6 months after initiating thiamine supplementation. Motor recovery was better than sensory recovery. CONCLUSIONS: Various symptoms were seen in patients with postgastrectomy neuropathy. Thiamine deficiency should be considered in the differential diagnosis of motor-sensory polyneuropathy after gastrectomy.

Activities of Daily Living↗
PubMed2001

Spinal cord magnetic resonance imaging demonstrates sensory neuronal involvement and clinical severity in neuronopathy associated with Sjögren's syndrome.

OBJECTIVES: To determine spinal cord MRI findings in neuronopathy associated with Sjögren's syndrome and their correlation with severity of sensory impairment. METHODS: Clinical and electrophysiological features, pathological findings in the sural nerve, and hyperintensity on T2* weighted MRI in the spinal dorsal columns were evaluated in 14 patients with neuronopathy associated with Sjögren's syndrome. RESULTS: Of 14 patients, 12 showed high intensity by T2* weighted MRI in the posterior columns of the cervical cord. High intensity areas were seen in both the fasciculus cuneatus and gracilis in nine patients, who showed severe and widespread sensory deficits in the limbs and trunk; these patients also had a high frequency of autonomic symptoms. Somatosensory evoked potentials often could not be elicited. Hyperintensity restricted to the fasciculus gracilis was seen in three patients, who showed sensory deficits restricted to lower limbs without trunk involvement, or with only partial limb involvement; no autonomic symptoms were noted. The two patients who did not show high intensity areas in the dorsal columns showed restricted sensory involvement in the limbs. All patients showed axonal loss predominantly affecting large fibres, without axonal sprouting. CONCLUSIONS: High intensity areas on T2* weighted MRI in the spinal dorsal columns reflect the degree of sensory neuronal involvement in neuronopathy associated with Sjögren's syndrome; this finding could also be a helpful marker for estimating severity of this neuronopathy.

Aged↗
PubMed2000

Isoforms of JSAP1 scaffold protein generated through alternative splicing.

We have identified four isoforms of c-Jun NH(2)-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1), a scaffold protein that participates in JNK mitogen-activated protein kinase cascades, termed JSAP1a, JSAP1b, JSAP1c, and JSAP1d. The previously identified JSAP1 was renamed JSAP1a to avoid confusion. Analyses of the exon-intron structure of the jsap1 gene indicated that the isoforms are generated through alternative splicing involving exons 5 and 6. The mRNA expression levels of the JSAP1 isoforms differed among the mouse tissues examined. We also investigated the region of JSAP1 responsible for its interaction with JNK, and found that the JNK-binding domain is located between aa residues 201 and 217 in JSAP1a, which is encoded by part of exon 6. As all the JSAP1 isoforms contain this binding domain, we examined the binding affinity of the JSAP1 isoforms for JNK1, JNK2, and JNK3. JSAP1c and JSAP1d, which contain a 31-aa sequence not present in JSAP1a or JSAP1b, had a lower binding affinity for the JNKs, especially JNK3. These results suggest that JSAP1c and JSAP1d may attenuate the scaffolding activity of JSAP1a and/or JSAP1b in JNK cascades, especially the JNK3 cascades.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Clinicopathological features of Churg-Strauss syndrome-associated neuropathy.

We assessed the clinicopathological features of 28 patients with peripheral neuropathy associated with Churg-Strauss syndrome. Initial symptoms attributable to neuropathy were acute painful dysaesthesiae and oedema in the dysaesthetic portion of the distal limbs. Sensory and motor involvement mostly showed a pattern of mononeuritis multiplex in the initial phase, progressing into asymmetrical polyneuropathy, restricted to the limbs. Parallel loss of myelinated and unmyelinated fibres due to axonal degeneration was evident as decreased or absent amplitudes of sensory nerve action potentials and compound muscle action potentials, indicating acute massive axonal loss. Epineurial necrotizing vasculitis was seen in 54% of cases; infiltrates consisted mainly of CD8-positive suppressor/cytotoxic and CD4-positive helper T lymphocytes. Eosinophils were present in infiltrates, but in smaller numbers than lymphocytes. CD20-positive B lymphocytes were seen only occasionally. Deposits of IgG, C3d, IgE and major basic protein were scarce. The mean follow-up period was 4.2 years, with a range of 8 months to 10 years. Fatal outcome was seen only in a single patient, indicating a good survival rate. The patients who responded well to the initial corticosteroid therapy within 4 weeks regained self-controlled functional status in longterm follow-up (modified Rankin score was < or = 2), while those not responding well to the initial corticosteroid therapy led a dependent existence (P < 0.01). In addition the patients with poor functional outcomes had significantly more systemic organ damage caused by vasculitis (P < 0.05). Necrotizing vasculitis mediated by cytotoxic T cells, leading to ischaemic changes, appears to be a major cause of Churg-Strauss syndrome-associated neuropathy. The initial clinical course and the extent of systemic vasculitic lesions may influence the long-term functional prognosis.

Adult↗
PubMed1999

Axonal and perikaryal involvement in chronic inflammatory demyelinating polyneuropathy.

OBJECTIVES: To assess the extent of loss of myelinated nerve fibres and spinal motor neuron loss in chronic inflammatory demyelinating polyneuropathy (CIDP), a clinicopathological study was conducted on biopsied sural nerves and necropsied spinal cords from patients with CIDP. METHODS: The myelinated fibre pathology of 71 biopsied sural nerves and motor neuron pathology of nine necropsied spinal cords at L4 levels in patients with CIDP were quantitatively and immunohistochemically assessed. RESULTS: Myelinated nerve fibre density was significantly diminished to 65.4% of the control values (p <0.0001), correlating inversely with the extent of segmental demyelination and remyelination (r = -0.43, p < 0.0005) and duration of illness (r = -0.31, p < 0.01). Numbers of large spinal motor neurons in CIDP were variably but significantly diminished (range from 46.0 to 97.6% of the age matched control value (p < 0.005)), and reactive astrogliosis was evident in the ventral horn in CIDP. The frequency of ventral horn neurons exhibiting central chromatolysis and the accumulation of phosphorylated high molecular weight neurofilament protein was significantly higher in CIDP than in controls (p<0.01 and p<0.05). CONCLUSIONS: The loss of nerve axons and spinal motor neurons is common in CIDP, and extensive in some cases. These neuronal and axonal losses may influence the functional prognosis in CIDP.

Adolescent↗
PubMed1999

Purification and characterization of alkaline phosphatase from Bacillus stearothermophilus.

Soluble alkaline phosphatase from the thermophilic bacterium Bacillus stearothermophilus was purified by a combination of chromatographic methods, and its properties were examined. The purified enzyme had specific activity of 4.43 micromol p-nitrophenol/min per mg of protein and seemed to be a single band on SDS/PAGE with a molecular mass of 32 kDa. Its apparent Km for p-nitrophenyl phosphate was 1.114 mM. The enzyme exhibited an optimal pH of approx. 9.0 and exhibited its highest activity at 60-70 degrees C. It also showed a bivalent cation requirement for activity, with maximal enhancement in the presence of Mg2+. In addition, significant thermal stability was observed in comparison with counterparts from mesophiles. Its partial N-terminal sequence was T1FSIVAFDPATGELGIAVQ19 as estimated by automated Edman degradation method. A search on the SwissProt database did not reveal any similar protein sequences from other sources.

Alkaline Phosphatase↗