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Kazuo Fujihara

Publications and source records attributed to Kazuo Fujihara.

11 recordsLinked to original sources
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

Interferon-alpha significantly reduces cerebrospinal fluid CD4 cell subsets in HAM/TSP.

We, for the first time, analyzed T cell and natural killer (NK) cell subsets in the cerebrospinal fluid (CSF) in nine patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) treated with interferon-alpha (IFN-alpha). The CD4/CD8 ratio in CSF was significantly lower after the therapy, which is mainly attributable to the significant reduction in CD4+ cells, especially CD25+CD4 and CD45RO+CD4 cell subsets. Meanwhile, NK, natural T and NKT cell subsets in the CSF remained unchanged. There was no CSF lymphocyte subset significantly associated with the clinical efficacy of IFN-alpha in this small-scale study, and more patients should be analyzed to ascertain the link.

Aged↗
PubMed2003

Inflammatory demyelinating disease mimicking malignant glioma.

UNLABELLED: The differential diagnosis between inflammatory demyelinating disease and malignant glioma is difficult based only on neuroimaging methods. METHODS: Four patients with inflammatory demyelinating disease who presented with clinical and neuroimaging findings strongly suggestive of malignant glioma were examined. RESULTS: MRI showed a mass lesion with prolonged T1 and T2 values and gadolinium enhancement in all cases. Proton MR spectroscopy and (201)Tl SPECT showed findings supportive of the diagnosis of malignant glioma in all cases. However, surgical biopsy revealed inflammatory demyelinating disease. After the diagnosis, 2 patients were treated by steroid administration and 2 were just observed. The gadolinium enhancement of all lesions decreased and finally disappeared. CONCLUSION: Such cases illustrate the importance of considering a demyelinating lesion in the differential diagnosis of a mass lesion. The difficulties encountered in establishing the correct diagnosis of inflammatory disease are related to the variations in the radiologic appearance, which require exclusion of gliomas or other brain tumors by surgical biopsy before the therapeutic strategy can be selected.

Adult↗
PubMed2003

[Clinical subtypes of multiple sclerosis and the immuno-pathogeneses].

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). MS is classified into clinical subtypes, such as relapsing-remitting MS, primary and secondary progressive MS, benign MS and malignant MS. In Japan, the classification based on the lesion distribution is also commonly used. There are two subtypes in this classification, conventional MS, in which demyelinating plaques are disseminated within CNS, and optic spinal MS, or relapsing neuromyelitis optica, characterized by the selective involvement of the optic nerves and spinal cord. Clinical manifestations and MRI findings of the clinical subtypes and their immuno-pathology are reviewed with emphasis on the unique features of Japanese MS.

Central Nervous System↗
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↗
PubMed2003

[Chemokines and chemokine receptors in multiple sclerosis].

Findings of chemokines and chemokine receptors in multiple sclerosis(MS) are reviewed. MS is a T-helper type 1 (Th1) dominant condition, and Th1-associated chemokine receptors(CCR5 and CXCR3) on CD4- and CD8-positive T cells and their ligands are upregulated in the CNS of the patients with active disease. Meanwhile, Th2-associated chemokine receptors(CCR3 and CCR4) on CD4- and CD8-positive T cells are suppressed during relapse. Their expressions are useful immunological measures of disease activity, clinical subtypes and therapy. CCR7 and the ligands are expressed in the CNS of MS and may be important for the recruitment of immune cells committed to immunological memory and antigen presentation.

Animals↗
PubMed2002

Expression of OX40 in muscles of polymyositis and granulomatous myopathy.

OX40 is selectively expressed on activated autoreactive memory T cells and these OX40+ lymphocytes may play a crucial role in autoimmune diseases. To determine whether OX40+ lymphocytes are involved in the pathomechanism of human inflammatory muscle diseases, we immunohistochemically examined the distribution of OX40+ cells in muscles from patients with polymyositis and granulomatous myopathy, and compared with that of cells bearing other activation markers, such as IL-2 receptor (IL-2R) and HLA-DR. In polymyositis, OX40+ mononuclear cells were found predominantly in the perivascular sites and to a lesser degree in the endomysium. Scanty IL-2R+ mononuclear cells were located only in the endomysium and HLA-DR was expressed on half of the mononuclear cells distributed diffusely in the perivascular sites and in the endomysium. Mononuclear cell infiltration in the perivascular sites was greater in the muscles in which OX40+ cells were present in the perivascular sites than in those without OX40+ cells in the perivascular sites (p<0.05). In granulomatous myopathy, OX40+ cells were detected in the centers of the granulomas. In contrast, IL-2R+ cells were present at the periphery of the granulomas and HLA-DR was detected on mononuclear cells throughout the granulomas. OX40+ mononuclear cells with specific distributions in muscles may be involved in the pathomechanism of polymyositis and granulomatous myopathy, and can be a candidate molecule of selective immunotherapy in these diseases.

Adult↗
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↗