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Masahito Tanaka

Publications and source records attributed to Masahito Tanaka.

12 recordsLinked to original sources
PubMed2006

The selective Rho-kinase inhibitor Fasudil is protective and therapeutic in experimental autoimmune encephalomyelitis.

We studied the role of fasudil, a selective Rho-kinase inhibitor, in experimental autoimmune encephalomyelitis (EAE). Both parenteral and oral administration of fasudil prevented the development of EAE induced by proteolipid protein (PLP) p139-151 in SJL/J mice. Specific proliferation of lymphocytes to PLP was significantly reduced, together with a downregulation of interleukin (IL)-17 and a marked decrease of the IFN-gamma/IL-4 ratio. Immunohistochemical examination also disclosed a marked decrease of inflammatory cell infiltration, and attenuated demyelination and acute axonal transaction. These results may provide a rationale of selective blockade of Rho-kinase by oral use of fasudil as a new therapy for multiple sclerosis.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2006

CSF cytokine and chemokine profiles in acute disseminated encephalomyelitis.

We simultaneously measured 16 cytokines/chemokines in cerebrospinal fluid (CSF) from 14 patients with acute disseminated encephalomyelitis (ADEM) and 20 controls using a fluorescent bead-based immunoassay. A variety of cytokines, such as IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-gamma, TNF-alpha, G-CSF and MIP-1beta, were significantly elevated in ADEM. In particular, G-CSF showed a marked 38-fold increase compared to the control mean. Significant positive correlations with inflammatory parameters in CSF, such as cell counts and protein levels, were found for IFN-gamma, IL-6 and IL-8. In contrast, IL-17 produced by activated CD4(+) memory T cells was not increased. The results suggested that various cytokines related to activation of macrophages/microglias and Th(1) and Th(2) cells are upregulated in CSF in ADEM.

Chemokines↗
PubMed2006

Development of vacuum-ultraviolet circular dichroism measurement system using a polarizing undulator.

We have developed an improved circular dichroism (CD) and linear dichroism (LD) simultaneous measurement system for the vacuum ultraviolet (VUV) region by polarization modulation techniques using a four-period Onuki-type crossed undulator as a polarized light source. The system has been constructed at the VUV beamline BL-5 in the electron storage ring TERAS, at AIST. Our improvements, in particular the adoption of an optical chopper as the detection method of incident light, have resulted in a flat baseline and a consequent simplification of the Mueller matrix calculation for our optical system. Based on the Mueller matrix calculation, we have successfully measured real VUV-CD and LD spectra of leucine films for wavelengths down to 160 nm with absolute optical constants. The obtained spectra show good consistency with spectra measured by conventional methods.

Journal Article↗
PubMed2006

Intrathecal upregulation of granulocyte colony stimulating factor and its neuroprotective actions on motor neurons in amyotrophic lateral sclerosis.

To investigate cytokine/chemokine changes in amyotrophic lateral sclerosis (ALS), we simultaneously measured 16 cytokine/chemokines (interleukin [IL]-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 [p70], IL-13, IL-17, interferon-gamma, tumor necrosis factor-alpha, granulocyte colony stimulating factor [G-CSF], macrophage chemoattractant protein-1 [MCP-1], and macrophage inflammatory protein-1beta) in cerebrospinal fluid (CSF) and sera from 37 patients with sporadic ALS and 33 controls using a multiplexed fluorescent bead-based immunoassay. We also conducted immunohistochemical analyses from 8 autopsied ALS cases and 6 nonneurologic disease controls as well as cell culture analyses of relevant cytokines and their receptors. We found that concentrations of G-CSF and MCP-1 were significantly increased in ALS CSF compared with controls. In spinal cords, G-CSF was expressed in reactive astrocytes in ALS cases but not controls, whereas G-CSF receptor expression was significantly decreased in motor neurons of spinal cords from ALS cases. Biologically, G-CSF had a protective effect on the NSC34 cell line under conditions of both oxidative and nutritional stress. We suggested that G-CSF has potentially neuroprotective effects on motor neurons in ALS and that downregulation of its receptor might contribute to ALS pathogenesis. On the other hand, MCP-1 correlated with disease severity, which may aggravate motor neuron damage.

Aged↗
PubMed2006

Internal carotid artery obstruction derived from persistent arterial wall dissection associated with old trivial trauma.

A 59-year-old man presented with acute onset of visual loss in his right eye. He was treated under a diagnosis of retinal artery thrombosis. Ultrasonography revealed obstruction of the ipsilateral internal carotid artery (ICA). He had no risk factor for stroke and he denied any history of trauma. Follow-up ultrasonography obtained 6 months later showed spontaneous ICA recanalization. Cerebral angiography demonstrated an arterial wall flap suggesting ICA dissection at the craniocervical junction. He then remembered suffering hemicranial headache and Horner's sign of several days' duration after jumping off a stepladder 1 year earlier. The present case is quite unusual in that persistent carotid arterial wall dissection was thought to proceed to ICA obstruction and manifested as retinal ischemia after a long asymptomatic period.

Blindness↗
PubMed2006

[Kanji-predominant alexia with agraphia in opticospinal multiple sclerosis].

Alexia with agraphia is very rare symptom in multiple sclerosis. We present a patient of opticospinal multiple sclerosis with kanji-predominant alexia with agraphia. A 55-year-old, right-handed man was admitted to our hospital because of difficulty in reading and writing in August 2001. The patient had been diagnosed as having relapsing-remitting opticospinal multiple sclerosis eight years prior to admission. Language examination showed alexia with agraphia predominantly affecting kanji and also mild naming difficulties, but a good comprehension and a normal repetition. T2-weighted MRI demonstrated hyperintensity area in the left temporo-parietal lobe, involving the white matter beneath the postero-inferior temporal lobe and inferior parietal lobule. On brain SPECT, low blood perfusion was observed in the left temporo-parietal regions. Although agraphia for kana and alexia for both kana and kanji improved after steroid therapy, agraphia for kanji did not improve. After the treatment, high intensity area of inferior parietal lobule was disappeared on MRI, and the hypoperfusion of inferior parietal lobule on brain SPECT was also improved, but the lesion of left postero-inferior temporal lobe did not show any remarkable changes. We considered that the kanji-predominant alexia with agraphia was due to the lesions of left inferior parietal lobule and postero-inferior temporal lobe, and agraphia for kanji was due to the lesion of left postero-inferior temporal lobe.

Agraphia↗
PubMed2005

Upregulation of vascular growth factors in multiple sclerosis: correlation with MRI findings.

Vascular permeability changes precede the development of demyelinating lesions in multiple sclerosis (MS), and vessel wall thickening and capillary proliferation are frequently seen in autopsied MS lesions. Although vascular growth factors are critical for inducing such vascular changes, their involvement in MS has not been extensively studied. Thus, we examined the involvement of various vascular growth factors in MS according to their clinical phase and subtype. We measured serum levels of vascular endothelial growth factor (VEGF), acidic and basic fibroblast growth factors (FGF) and platelet-derived growth factors (PDGFs)-AA, -AB and -BB in 50 patients with MS (27 opticospinal MS and 23 conventional MS patients) and 33 healthy controls using sandwich enzyme immunoassays. Correlations between growth factor changes and brain and spinal cord MRI findings were then analyzed. Serum VEGF concentrations were significantly higher in MS patients in relapse than in controls (p = 0.0495) and in MS patients in remission (p = 0.0003), irrespective of clinical subtype. Basic FGF was significantly increased in conventional MS patients, but not opticospinal MS patients compared with controls (p = 0.0291), irrespective of clinical phase. VEGF at relapse showed a significant positive correlation with the length of spinal cord lesions on MRI (r = 0.506, p = 0.0319). The results suggest that an increase in serum VEGF concentration might be involved in MS relapse and the formation of longitudinally extensive spinal cord lesions.

Adult↗
PubMed2005

Intrathecal activation of the IL-17/IL-8 axis in opticospinal multiple sclerosis.

There are two distinct subtypes of multiple sclerosis in Asians, opticospinal (OS-multiple sclerosis) and conventional (C-multiple sclerosis). In OS-multiple sclerosis, selective and severe involvement of the optic nerves and spinal cord is characteristic, though its mechanisms are unknown. The present study aimed to find out possible differences in the cytokine/chemokine profiles in CSF between OS-multiple sclerosis and C-multiple sclerosis and to delineate the relationships between these profiles and neuroimaging and pathological features. Sixteen cytokines/chemokines, namely interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1beta (MIP-1beta), were measured simultaneously in CSF supernatants from 40 patients with relapsing-remitting multiple sclerosis (20 OS-multiple sclerosis and 20 C-multiple sclerosis) at relapse and 19 control patients with spinocerebellar degeneration (SCD), together with intracellular production of IFN-gamma and IL-4 in CSF CD4+ T cells. In CSF supernatants relative to controls, IL-17, MIP-1beta, IL-1beta and IL-13 were only significantly increased in OS-multiple sclerosis patients, while TNF-alpha was only significantly increased in C-multiple sclerosis patients, using a cut-off level of 1 pg/ml. IL-8 was significantly elevated in both OS-multiple sclerosis and C-multiple sclerosis patients. MCP-1 was significantly decreased in both OS-multiple sclerosis and C-multiple sclerosis patients, while IL-7 was only significantly decreased in C-multiple sclerosis patients. IL-17, IL-8 and IL-5 were significantly higher in OS-multiple sclerosis patients than in C-multiple sclerosis patients. The increases in IL-17 and IL-8 in OS-multiple sclerosis were still significant even after exclusion of the patients undergoing various immunomodulatory therapies. Assays of intracellular cytokine production revealed that both the IFN-gamma+IL-4- T-cell percentage and intracellular IFN-gamma/IL-4 ratio in CSF cells were significantly greater in C-multiple sclerosis patients than in controls. Contrarily, OS-multiple sclerosis patients showed not only a significantly greater percentage of IFN-gamma+IL-4- T cells than controls but also a significantly higher percentage of IFN-gamma-IL-4+ T cells than C-multiple sclerosis patients. Among the cytokines elevated in multiple sclerosis, only IL-8 showed a significant positive correlation with the Expanded Disability Status Scale of Kurtzke score. Both the length of the spinal cord lesions on MRI and the CSF/serum albumin ratio had a significant positive correlation with IL-8 and IL-17 in multiple sclerosis, in which the spinal cord lesions were significantly longer in OS-multiple sclerosis than in C-multiple sclerosis. Three of six spinal cord specimens from autopsied OS-multiple sclerosis cases demonstrated numerous myeloperoxidase-positive neutrophils infiltrating necrotic lesions. These findings strongly suggest that in OS-multiple sclerosis, in addition to the Th1 cell upregulation seen in C-multiple sclerosis, intrathecal activation of the IL-17/IL-8 axis inducing heavy neutrophil infiltration contributes to extensive spinal cord lesion formation.

Adult↗
PubMed2005

Comparison of the clinical courses of the opticospinal and conventional forms of multiple sclerosis in Japan.

We evaluated the clinical courses of 216 patients with multiple sclerosis (MS) diagnosed according to the recommended diagnostic criteria of McDonald et al (10). Sixty-five patients clinically displaying selective involvement of the optic nerves and spinal cord were classified as opticospinal MS (OS-MS), while the other 151 showing disseminated involvement of the central nervous system were classified as conventional MS (C-MS). The disease duration did not differ significantly between the two subtypes (11.2 years vs. 11.5 years). In addition to a higher age of onset, female preponderance and higher Kurtzke's expanded disability status scale (EDSS) scores, the OS-MS patients showed a markedly lower frequency of secondary progressive MS than the C-MS patients (4.6% vs. 29.1%, p=0.0001). The EDSS scores of the C-MS patients were significantly correlated with the disease duration, while those of the OS-MS patients were not. Among the C-MS patients, the frequency of secondary progressive MS was significantly more common in patients with a disease duration of more than 10 years than in those with a shorter duration. These results suggest that the irreversible disability in OS-MS is determined by relapses, rather than by chronic progression, whereas C-MS has a similar clinical course to MS in Westerners.

Adult↗
PubMed2005

[A patient with focal dystonia induced by golf and presenting a decrease in activity of cerebral motor cortex on task].

We here report a 45-year-old man with left arm focal dystonia induced by golf. He was a swimming instructor. From 35 years of age, he swung a golf club for 4 hours everyday. At 37 years of age, he noted difficulties in moving left arm when swinging, and developed involuntary movement of left arm toward his back thereafter. His involuntary movement was exacerbated even in several years after stopping both golf and swimming. Neurologically, simultaneous contraction was observed in left triceps and biceps muscles and his left arm dropped when raising arm to front. A 'sensory trick' was also observed. Thus, he was diagnosed as having a rare focal dystonia, and its clinical characteristics and course were basically different from those of 'yips', a focal dystonia that is characterized by anxiety and distal dominant dystonia presenting only on golf. Magnetic resonance imaging (MRI), FDG-positron emission CT (FDG-PET), C11-Raclopride PET and 99mTc-single photon emission CT (SPECT) revealed no abnormality in cerebral cortex and basal ganglias. However, motor evoked potentials (MEPs) were not evoked bilaterally when magnetic stimulation was applied on primary motor cortex. On functional MRI (fMRI), 40 seconds raising left arm task-induced activation in the right primary motor, supplementary motor, and premotor areas was apparently decreased, while left motor areas, the normal side, were reasonably activated. Motor-associated areas are generally overactivated by task in focal dystonia patients whereas excitability in primary motor area is decreased in idiopathic generalized dystonia. Therefore, dystonia of the present case appears to be similar to focal dystonia clinically but may partly have a mechanism similar to idiopathic generalized dystonia as shown in the fMRI studies.

Arm↗
PubMedDate not supplied

Circular dichroism of amino acid films in UV-VUV region.

Circular dichroism (CD) spectra of sublimated films of alanine and alanine dipeptide were measured in UV-VUV region. When a film has some linear anisotropy, the apparent CD signal is known to be strongly distributed by linear anisotropy. In order to obtain the true CD spectra, we examined this disturbance for L-alanine films. We measured linear dichroism spectra and CD spectra as a function of the sample rotation angle, turning the sample over. On the basis of these measurements, we concluded that the linear anisotropy contribution to CD was sufficiently small for carefully prepared films. In addition, we revealed that it is essential for accurate measurement to prepare thin film of which thickness is smaller than 100 nm for the case of alanine films. CD of amino acid films was compared with that of aqueous solution. Sign of CD signal of solid films was observed to be the same for aspartic acid, but it was reversed from that of aqueous solution for alanine and alanine dipeptide.

Alanine↗