Biomedical subjects

Hikoaki Fukaura

Publications and source records attributed to Hikoaki Fukaura.

5 recordsLinked to original sources

PubMed2005

CSF pleocytosis and expansion of spinal lesions in Japanese multiple sclerosis with special reference to the new diagnostic criteria.

New diagnostic criteria for multiple sclerosis (MS) were recently proposed from the international panel on the diagnosis of MS, and they include exclusion criteria, such as lesions extending over more than two vertebral segments on spinal MRI and CSF pleocytosis of more than 50/mm3. We reviewed the clinical features of 158 patients who satisfied the diagnostic criteria for MS except for having the above atypical paraclinical findings. All patients exhibited two or more clinical attacks and objective clinical evidence of multiple lesions without any evidence of other disorders. Thirty-three (20.9%) patients had one or both atypical paraclinical findings. Twenty-one out of the 33 patients were classified as having optico-spinal MS (OSMS), and the other 12 as non-OSMS patients with atypical large expanding or destructive cerebral, cerebellar or brainstem lesions on MRI as well as one or both atypical paraclinical findings. Based on this heterogeneity in clinical findings in MS, there is an urgent need to develop a common general concept of the "MS" syndromes, and the ethnic-related heterogeneity should be considered in the revised criteria for the diagnosis of MS.

Adolescent↗

PubMed2004

Attack-related severity: a key factor in understanding the spectrum of idiopathic inflammatory demyelinating disorders.

Understanding the spectrum of idiopathic inflammatory demyelinating disorders (IIDD) is a fundamental issue for the diagnosis and treatment of these disorders as well as for the approach to their pathogenesis. The spectrum of IIDD is usually classified according to clinical course and lesion distribution. We compared the demographic features, clinical characteristics, laboratory findings, and genetic backgrounds between 193 Japanese patients with and without clinically or radiographically fulminant attacks who all satisfied the diagnostic criteria for multiple sclerosis (MS). "Fulminant attacks" in the current study represent attack-related clinically or radiologically severe relapses but do not necessarily mean severe disability. Patients with fulminant attacks were clinically and immunogenetically distinct from those free of such attacks, and the previously described characteristics of the opticospinal form of MS (OSMS) or neuromyelitis optica (NMO) were mostly shared by patients with fulminant attacks. HLA profiles were similar among patients with fulminant attacks irrespective of the lesion distributions. The GG homozygous and G alleles of the CTLA4 gene A/G coding SNP at position 49 in exon 1 were significantly more common in patients with fulminant attacks than in those without. Attack-related severity may be an important factor if validated by prospective studies defining criteria and establishing relationships to disease course and treatment regimens.

Adolescent↗

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

[Susceptibility genes for multiple sclerosis].

Multiple lines of evidence support the role of genetic factors for susceptibility to multiple sclerosis (MS), although unknown environmental factors must play an important role in developing MS. In this paper, we review the reports studied for the possible associations between Japanese MS and candidate genes by using case-control method. As for HLA alleles, HLA-DRB1*1501 and -DPB1*0501 allele have been confirmed to be associated with conventional MS and opticospinal MS, respectively. Some polymorphisms of vitamin D receptor gene, estrogen receptor gene, CTLA-4 gene, and osteopontin gene were reported to be associated with conventional MS. Appropriate case ascertainment and collection as well as proper statistical method are needed to isolate the susceptibility genes for MS.

Alleles↗

PubMed2003

[IL-18 in multiple sclerosis].

IL-18, previously named interferon-gamma inducing factor, is produced by monocytes/macropharges, dendritic cells, B cells and other APC cells as well as by astrocytes, microglia. IL-18 is a unique cytokine that stimulates both Th1 and Th2 responses depending on its cytokine milieu. Caspase-1 regulates the cellular export of IL-18. Anti IL-18 antibodies prevent EAE. IL-18 directs autoreactive T cells and promotes autodestruction in CNS via induction of IFN-gamma by NK cells in EAE. IL-18 is expressed in MS plaque. Common IL-18 promoter polymorphisms influence the expression on IL-18. IL-18 is linked to raised IFN-gamma in MS and is induced by activated CD4(+) T cells via CD40-CD40 ligand interaction. IL-18 in MS is suppressed by treatments such as GA and IFN-beta.

Adjuvants, Immunologic↗