Novel mutation in EIF2B gene in a case of adult-onset leukoencephalopathy with vanishing white matter.
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Adult↗
Biomedical subjects
Masaru Matsui
Publications and source records attributed to Masaru Matsui.
Severe disease, unaltered leukocyte migration, and reduced IFN-gamma production in CXCR3-/- mice with experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) is a CD4(+) Th1 T cell-mediated disease of the CNS, used to study certain aspects of multiple sclerosis. CXCR3, the receptor for CXCL10, CXCL9, and CXCL11, is preferentially expressed on activated Th1 T cells and has been proposed to govern the migration of lymphocytes into the inflamed CNS during multiple sclerosis and EAE. Unexpectedly, CXCL10-deficient mice were susceptible to EAE, leaving uncertain what the role of CXCR3 and its ligands might play in this disease model. In this study, we report that CXCR3(-/-) mice exhibit exaggerated severity of EAE compared with wild-type (CXCR3(+/+)) littermate mice. Surprisingly, there were neither quantitative nor qualitative differences in CNS-infiltrating leukocytes between CXCR3(+/+) and CXCR3(-/-) mice with EAE. Despite these equivalent inflammatory infiltrates, CNS tissues from CXCR3(-/-) mice with EAE showed worsened blood-brain barrier disruption and more von Willebrand factor-immunoreactive vessels within inflamed spinal cords, as compared with CXCR3(+/+) mice. Spinal cords of CXCR3(-/-) mice with EAE demonstrated decreased levels of IFN-gamma, associated with reduced inducible NO synthase immunoreactivity, and lymph node T cells from CXCR3(-/-) mice primed with MOG(35-55) secreted less IFN-gamma in Ag-driven recall responses than cells from CXCR3(+/+) animals. CXCR3(-/-) lymph node T cells also showed enhanced Ag-driven proliferation, which was reduced by addition of IFN-gamma. Taken with prior findings, our data show that CXCL10 is the most relevant ligand for CXCR3 in EAE. CXCR3 does not govern leukocyte trafficking in EAE but modulates T cell IFN-gamma production and downstream events that affect disease severity.
Animals↗
Hyperostosis frontalis interna associated with hypogonadism in an elderly man.
Hyperostosis frontalis interna (HFI), symmetric thickening of the inner table of the frontal bone, is relatively common in women but very rare in men. We report the case of an elderly male patient with HFI. This patient was accompanied by primary hypogonadism, which may be related to the underlying pathogenesis of HFI.
Aged↗
"Burst and slow complexes" in nonconvulsive epileptic status.
Generalized 1Hz, burst-and-slow-wave complexes were observed in a comatosed patient with acute disseminated encephalomyelitis (ADEM) when she showed extremely intractable, generalized convulsions and fragmented myoclonus in the whole body. Two types of short-latency SEPs were obtained separately during the burst and slow phase of the EEG (SEP-burst and SEP-slow, respectively), which showed a two fold greater amplitude of N20 in the former than in the latter. This suggests enhanced responsiveness to the peripheral stimuli during the burst phase as compared with the slow phase. CSF and serum were positive for autoantibodies to NMDA receptors. The "burst and slow complexes" reported here are considered to be an atypical EEG pattern of a generalized epileptic phenomenon.
Adult↗
Anti-inflammatory effect of linear polarized infrared irradiation on interleukin-1beta-induced chemokine production in MH7A rheumatoid synovial cells.
We examined the anti-inflammatory effect of infrared linear polarized light irradiation on the MH7A rheumatoid fibroblast-like synoviocytes (FLS) stimulated with the proinflammatory cytokine interleukin (IL)-1beta. Expression of messenger ribonucleic acids (mRNAs) encoding IL-8, RANTES (regulated upon activation, normal T cell expressed and secreted), growth-related gene alpha (GROalpha), and macrophage inflammatory protein-1alpha (MIP1alpha) was measured using real-time reverse transcription polymerase chain reaction, and the secreted proteins were measured in the conditioned media using enzyme-linked immunosorbent assays. We found that irradiation with linear polarized infrared light suppressed IL-1beta-induced expression of IL-8 mRNA and, correspondingly, the synthesis and release of IL-8 protein in MH7A cells. This anti-inflammatory effect was equivalent to that obtained with the glucocorticoid dexamethasone. Likewise, irradiation suppressed the IL-1beta-induced expression of RANTES and GROalpha mRNA. These results suggest that the irradiation of the areas around the articular surfaces of joints affected by rheumatoid arthritis (RA) using linear polarized light may represent a useful new approach to treatment.
Anti-Inflammatory Agents↗
[Falls in peripheral neuropathy].
Falling accidents are predisposing factors in worsening the quality of life. Causes of falls included gait and balance problems, visual disorder, cognitive impairment and drugs. However, falls in neuropathic patients are not often investigated. We studied the actual condition and causes of falls associated with neuropathy. One hundred and ninety-three patients (122 males and 71 females, ages 57 +/- 15 years) with neuropathy were selected for evaluation. In all patients, more than half a year had passed since the onset of symptoms and the present condition was considered comparatively stable. We divided the patients into 2 groups: falling or non-falling. Patients experiencing accident accompanied by external injury once or more in the past year, or patients who answered "often fell" (1 time or more per month) on flat ground or in their residence comprised the fall group. The severity of disease was evaluated by modified Rankin Scale (0 to 5). The relationship between falls and neuropathic symptoms (proximal muscle weakness, distal muscle weakness, aching or numbness, and the position and vibration sensory loss) was statistically examined. The distribution of patients in the fall group according to modified Rankin Scale of neuropathy was scale 5: 0/0 (0%), scale 4: 5/36 (14%), scale 3: 24/72 (33%), scale 2: 7/56 (13%), and scale 1: 1/19 (5%). There were six fractures among all patients. Regarding the etiology, the fall group showed a high level of axonal neuropathies (44%). On analysis according to condition and symptoms in the patients with a score of 2, 3, or 4 who demonstrated a high rate of falls, there was a strong correlation between deep sensory loss and fall (p < 0.05). However, as independent factors, there were no correlations between falling and proximal muscle weakness, distal muscle weakness or aching numbness, respectively. We thought it necessary to add ataxic gait resulting from deep sensory loss to one of the fall risks.
Accidental Falls↗
Low CSF hypocretin-1/orexin-A associated with hypersomnia secondary to hypothalamic lesion in a case of multiple sclerosis.
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Adult↗
Xenopus XsalF: anterior neuroectodermal specification by attenuating cellular responsiveness to Wnt signaling.
Here we show that XsalF, a frog homolog of the Drosophila homeotic selector spalt, plays an essential role for the forebrain/midbrain determination in Xenopus. XsalF overexpression expands the domain of forebrain/midbrain genes and suppresses midbrain/hindbrain boundary (MHB) markers and anterior hindbrain genes. Loss-of-function studies show that XsalF is essential for the expression of the forebrain/midbrain genes and for the repression of the caudal genes. Interestingly, XsalF functions by antagonizing canonical Wnt signaling, which promotes caudalization of neural tissues. XsalF is required for anterior-specific expressions of GSK3beta and Tcf3, genes encoding antagonistic effectors of Wnt signaling. Loss-of-function phenotypes of GSK3beta and Tcf3 mimic those of XsalF while injections of GSK3beta and Tcf3 rescue loss-of-function phenotypes of XsalF. These findings suggest that the forebrain/midbrain-specific gene XsalF negatively controls cellular responsiveness to posteriorizing Wnt signals by regulating region-specific GSK3beta and Tcf3 expression.
Animals↗
Treatment of experimental autoimmune encephalomyelitis with the chemokine receptor antagonist Met-RANTES.
Specific chemokines and chemokine receptors have been implicated in inflammatory demyelinating diseases of the central nervous system (CNS), including multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). Amino-terminal modifications of chemokines can alter receptor interactions, converting agonists to specific antagonists. To examine the function in EAE of murine types 1 and 5 CC chemokine receptors (CCR1 and CCR5), we used Met-RANTES, a peptide that blocks both receptors; controls received heat-inactivated peptide. There was no effect of active treatment on acute-monophasic EAE, regardless whether compound was given at onset or in a pre-treatment regimen. Administered at disease onset, Met-RANTES modestly but significantly ameliorated fixed neurological disability at the endpoint of chronic-relapsing EAE. Met-RANTES treatment did not reduce CNS cellular infiltrates or up-regulation of CCR1 and CCR5 in affected CNS tissues. Analysis of a subset of mice suggested a trend towards reduced axonal pathology in those receiving active treatment. These data indicate that chemokine receptor blockade with Met-RANTES does not affect leukocyte trafficking in chronic-relapsing EAE. Further analysis of the effects of chemokine receptor blockade may need to focus on leukocyte activation within the affected CNS as well as trafficking events.
Animals↗