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Ichiro Nakashima

Publications and source records attributed to Ichiro Nakashima.

18 recordsLinked to original sources
PubMed2007

Alteration of cystatin C in the cerebrospinal fluid of multiple sclerosis.

The protein profiles in the cerebrospinal fluid of 10 patients with multiple sclerosis (MS), 10 patients with neuromyelitis optica (NMO), 8 inflammatory disease control patients, and 4 noninflammatory disease control patients were screened by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Peaks of 12.5 kDa were significantly lower in multiple sclerosis, NMO, and inflammatory disease control patients than in noninflammatory disease control patients, and 13.4 kDa peaks were higher in NMO than in inflammatory disease control patients. Further analyses demonstrated that both peaks were cystatin C. Enzyme-linked immunosorbent assay showed that the cystatin C levels tended to be lower in multiple sclerosis and NMO. Alterations of cystatin C may relate to the pathogeneses of demyelinating diseases.

Cystatin C↗
PubMed2006

Establishment of a new sensitive assay for anti-human aquaporin-4 antibody in neuromyelitis optica.

Neuromyelitis optica (NMO) is a devastating neurologic disease characterized by severe optic neuritis and transverse myelitis. Recently, its disease-specific serum autoantibody, NMO-IgG, was discovered with indirect immunofluorescence. However, the substrates of the immunofluorescence assay were not human but mouse brain tissues, which could influence the sensitivity and specificity of the antibody. The target antigen of NMO-IgG was recently identified as aquaporin-4 (AQP4) water channel protein, which is mainly expressed in brain and spinal cord. In the present study, we have established human cell lines that stably express human AQP4 and used these cells to detect and titrate anti-AQP4 antibody present in the sera of patients with NMO by immunofluorescence assay. The results were compared with those of the original NMO-IgG assay. We tested the sera from 10 patients with NMO, 10 with MS and five with other neurological disorders. Among the patients with NMO, six were NMO-IgG-positive. However, using the new anti-AQP4 antibody assay, we showed that eight patients with NMO including the six NMO-IgG-positives were positive for anti-AQP4 antibody. The staining pattern of AQP4-expressing cells treated with each serum of these eight NMO patients corresponded to that with a commercially available anti-AQP4 antibody. The antibody titer (maximum serum dilution for positive staining) ranged from 64x to 16,384x. The serum dilution titers were reproducible in blinded studies. In contrast, the patients with MS or other neurological disorders showed negative for anti-AQP4 antibody. Thus, the newly developed anti-AQP4 antibody assay appears to have a higher sensitivity for NMO than the original NMO-IgG assay and is expected to be useful for the diagnosis of NMO.

Adult↗
PubMed2005

Chemokine profile in the cerebrospinal fluid and serum of Vogt-Koyanagi-Harada disease.

We analyzed the concentrations of four chemokines in the cerebrospinal fluid (CSF) and sera in Vogt-Koyanagi-Harada disease (VKH), an autoimmune uveomeningitis syndrome against melanocyte-associated proteins, with ELISA. CSF-CXCL10/IP-10 and CSF-CCL17/TARC were significantly elevated in VKH than in controls. In the majority of VKH cases and controls, CSF-CXCL10 was higher than serum-CXCL10, and CSF-CCL17 was lower than serum-CCL17. CCL11/Eotaxin was not different between groups. CSF-CCL2/MCP-1 was significantly lower in VKH than in control. The changes in VKH were essentially similar to those in multiple sclerosis, a known Th1-dominant condition.

Adolescent↗
PubMed2004

CSF-chemokines in HTLV-I-associated myelopathy: CXCL10 up-regulation and therapeutic effect of interferon-alpha.

We measured four chemokines in the cerebrospinal fluid (CSF) in human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) with ELISA. CXCL10/IP-10, a T cell type 1 (Th1)-associated chemokine, was significantly elevated in HAM/TSP compared with controls, and the values were even significantly higher in HAM/TSP than in multiple sclerosis (MS) in which CXCL10/IP-10 up-regulation was previously reported. Among Th2-associated chemokines, CCL17/TARC and CCL11/Eotaxin in HAM/TSP were not different from those in controls. As shown in MS, CCL2/MCP-1 was significantly lower in HAM/TSP than in control. Following interferon (IFN)-alpha therapy in HAM/TSP, CCL2/MCP-1 became significantly higher than that before therapy, which may reflect a Th2 induction, while CXCL10/IP-10 remained elevated.

Adult↗
PubMed2004

Oligoclonal IgG bands in Japanese patients with multiple sclerosis. A comparative study between isoelectric focusing with IgG immunofixation and high-resolution agarose gel electrophoresis.

A low prevalence of oligoclonal IgG bands (OB) has been reported as a unique feature of Japanese multiple sclerosis (MS) as compared with Western MS. We compared the frequency of OB between isoelectric focusing (IEF) and agarose gel electrophoresis (AGE) in 59 Japanese patients with clinically definite MS [39 with conventional form of MS (CMS) and 20 with optic-spinal form of MS (OSMS)]. The frequency of IEF-OB in total MS was 54%, whereas that of AGE-OB was only 17%. When OSMS was excluded, the frequency increased to 77% by IEF, whereas it remained 23% by AGE. Our study strongly suggests that IEF is highly effective for detecting OB in Japanese MS patients.

Adult↗
PubMed2004

CSF chemokine levels in relapsing neuromyelitis optica and multiple sclerosis.

The pathogenesis of relapsing neuromyelitis optica (RNMO) remains unknown. We, for the first time, studied the levels of four chemokines in the cerebrospinal fluid in RNMO with ELISA and compared the data with those in multiple sclerosis (MS) and control. CXCL10/IP-10 and CCL17/TARC were significantly elevated in both RNMO and MS. Conversely, CCL2/MCP-1 was significantly lower in MS, but not in RNMO, than in control. CCL11/Eotaxin was not different between groups. None of the four chemokines studied was significantly different between RNMO and MS.

Age of Onset↗
PubMed2004

Ibudilast, a nonselective phosphodiesterase inhibitor, regulates Th1/Th2 balance and NKT cell subset in multiple sclerosis.

We investigated the immunoregulatory effects of ibudilast, a nonselective phosphodiesterase inhibitor, at a clinically applicable dose (60 mg/day p.o. for four weeks) in multiple sclerosis (MS) patients. Sensitive real-time PCR for quantifying cytokine mRNA in the blood CD4+ cells revealed that the ibudilast monotherapy significantly reduced tumour necrosis factor-alpha and interferon (IFN)-gamma mRNA and the IFN-gamma/interleukin-4 mRNA ratio, suggesting a shift in the cytokine profile from Th1 toward Th2 dominancy. In a flow cytometric analysis, natural killer T cells, which have been reported to relate to Th2 responses in MS and its animal model (experimental autoimmune encephalomyelitis), increased significantly after the therapy. None of the significant immunological changes were seen in healthy subjects or untreated MS patients. Ibudilast may be a promising therapy for MS and its clinical effects warrant further study.

Adult↗
PubMed2003

Complementarity-determining region 3 spectratyping analysis of the TCR repertoire in multiple sclerosis.

Multiple sclerosis (MS) is considered to be an autoimmune disease mediated by T cells reactive with Ags in the CNS. Therefore, it has been postulated that neuroantigen-reactive T cells bearing particular types of TCRs are expanded clonally during the course of the disease. However, there is a controversy with regard to the TCR usage by T cells associated with the development of MS. By the use of complementarity-determining region 3 spectratyping analysis that is shown to be a useful tool for identification of pathogenic TCR in autoimmune disease models, we tried to demonstrate that spectratype was T cells bearing particular types of TCR are activated in MS patients. Consequently, it was found that Vbeta5.2 were often oligoclonally expanded in peripheral blood of MS patients, but not of healthy subjects. Sequence analysis of the complementarity-determining region 3 region of spectratype-derived TCR clones revealed that the predominant TCR clone was different from patient to patient, but that similar results were obtained in a patient examined at different time points. More importantly, examination of cerebrospinal fluid T cells and longitudinal studies of PBLs from selected patients revealed that Vbeta5.2 expansion was detectable in the majority of patients examined. These findings suggest that Vbeta5.2 spectratype expansion is associated with the development of MS and that TCR-based immunotherapy can be applicable to MS patients if the TCR activation pattern of each patient is determined at different stages of the disease.

Adolescent↗
PubMed2003

[Magnetic resonance imaging for the diagnosis of multiple sclerosis].

Magnetic resonance imaging(MRI) is very useful as a method form confirming the lesion distribution of multiple sclerosis(MS). Although MS should be diagnosed primarily on clinical grounds, MRI aids the diagnosis by providing paraclinical evidence for the dissemination in both time and space. Recently, a new guideline for MS diagnosis was proposed by International Panel. This guideline set out to integrate MRI into the overall diagnostic scheme because of its unique sensitivity to pathological changes. In Japanese, however, the so-called optic-spinal form of MS, which is characterized by the selective involvement of the optic nerves and the spinal cord, is relatively common. Moreover, most of Japanese MS patients without oligoclonal bands show atypical brain lesions which do not fulfill the MRI criteria for brain abnormality.

Asian People↗
PubMed2002

Pure optic-spinal form of multiple sclerosis in Japan.

We evaluated the clinical and laboratory features of the optic-spinal form of multiple sclerosis (OSMS) with no brain lesions on repeated MRI--termed pure OSMS. By reviewing the medical records of 118 Japanese clinically definite multiple sclerosis patients seen between 1988-1999, we found 10 patients (8.5%), nine of whom were women, with only relapsing optic neuritis (ON) and myelitis (MY) clinically and consistently normal brain MRI during follow-ups of >or=5 years. Three patients suffered severe ON and MY, but the other seven had mild disease (six were graded 1 in the Disability Status Scale). Despite frequent relapses, mild pure OSMS was characterized by younger onset and mild spinal symptoms as in 'benign' classical multiple sclerosis (CMS). MRI often revealed multiple cervico-thoracic cord lesions of variable lengths. Oligoclonal IgG bands (OB) were negative in all cases. HLA-DPB1*0501, whose association with OSMS has been reported, was positive only in six patients (including three patients with severe pure OSMS). Four patients with DRB1*1501-DQB1*0602, to which CMS is closely linked, had mild disease. Though pure OSMS was heterogeneous with regard to clinical severity and human leukocyte antigen (HLA) class II alleles, this form of multiple sclerosis was characterized by a definite female preponderance and negative OB that distinguished it from CMS.

Adult↗
PubMed2002

[Pathogenesis of optic-spinal MS].

We reviewed the clinical and immunological features of optic-spinal multiple sclerosis (OSMS), or relapsing neuromyelitis optica. OSMS has collected much attention as to whether it is a distinct entity from conventional MS (CMS). However, OSMS plus minor cerebral and brainstem/cerebellar involvement and the later conversion into CMS had been a diagnostic dilemma. To overcome such problems and delineate the features of OSMS, we analyzed 'Pure OSMS' with which patients had only relapsing optic neuritis and myelitis clinically and consistently normal brain MRI during 5 years or longer follow-ups. As a result, we found that this type of MS was characterized by a definite female preponderance and negative oligoclonal IgG bands (OB), although 'Pure OSMS' was heterogeneous with regards to the clinical severity and HLA class II alleles. Previously reported immunological data in OSMS include negative OB and no elevation of IL-10 or matrix metalloproteinase-9 in the cerebrospinal fluid (CSF) during relapses. In addition, we recently demonstrated that the CCR5+ Th1 cell subset in CSF during relapses, which significantly increased in CMS, remained low in OSMS. These unique clinical and immunological findings probably relate to fundamental differences in the pathogeneses of OSMS and CMS and deserve further characterization.

Female↗
PubMedDate not supplied

A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis.

BACKGROUND: Neuromyelitis optica is an inflammatory demyelinating disease with generally poor prognosis that selectively targets optic nerves and spinal cord. It is commonly misdiagnosed as multiple sclerosis. Neither disease has a distinguishing biomarker, but optimum treatments differ. The relation of neuromyelitis optica to optic-spinal multiple sclerosis in Asia is uncertain. We assessed the capacity of a putative marker for neuromyelitis optica (NMO-IgG) to distinguish neuromyelitis optica and related disorders from multiple sclerosis. METHODS: Indirect immunofluorescence with a composite substrate of mouse tissues identified a distinctive NMO-IgG staining pattern, which we characterised further by dual immunostaining. We tested masked serum samples from 102 North American patients with neuromyelitis optica or with syndromes that suggest high risk of the disorder, and 12 Japanese patients with optic-spinal multiple sclerosis. Control patients had multiple sclerosis, other myelopathies, optic neuropathies, and miscellaneous disorders. We also established clinical diagnoses for 14 patients incidentally shown to have NMO-IgG among 85000 tested for suspected paraneoplastic autoimmunity. FINDINGS: NMO-IgG outlines CNS microvessels, pia, subpia, and Virchow-Robin space. It partly colocalises with laminin. Sensitivity and specificity were 73% (95% CI 60-86) and 91% (79-100) for neuromyelitis optica and 58% (30-86) and 100% (66-100) for optic-spinal multiple sclerosis. NMO-IgG was detected in half of patients with high-risk syndromes. Of 14 seropositive cases identified incidentally, 12 had neuromyelitis optica or a high-risk syndrome for the disease. INTERPRETATION: NMO-IgG is a specific marker autoantibody of neuromyelitis optica and binds at or near the blood-brain barrier. It distinguishes neuromyelitis optica from multiple sclerosis. Asian optic-spinal multiple sclerosis seems to be the same as neuromyelitis optica.

Adult↗