Masami Tanaka

Bio: Masami Tanaka is an academic researcher from Kyoto Prefectural University of Medicine. The author has contributed to research in topics: Multiple sclerosis & Neuromyelitis optica. The author has an hindex of 7, co-authored 11 publications receiving 304 citations.

Three susceptible loci associated with primary open-angle glaucoma identified by genome-wide association study in a Japanese population

Abstract: Primary open-angle glaucoma (POAG) is the major type of glaucoma. To discover genetic markers associated with POAG, we examined a total of 1,575 Japanese subjects in a genome-wide association study (stage 1) and a subsequent study (stage 2). Both studies were carried out at a single institution. In the stage 1 association study, we compared SNPs between 418 POAG patients and 300 control subjects. First, low-quality data were eliminated by a stringent filter, and 331,838 autosomal SNPs were selected for analysis. Poorly clustered SNPs were eliminated by a visual assessment, leaving 255 that showed a significant deviation (P < 0.001) in the allele frequency comparison. In the stage 2 analysis, we tested these 255 SNPs for association in DNA samples from a separate group of 409 POAG and 448 control subjects. High-quality genotype data were selected and used to calculate the combined P values of stages 1 and 2 by the Mantel-Haenszel test. These analyses yielded 6 SNPs with P < 0.0001. All 6 SNPs showed a significant association (P < 0.05) in stage 2, demonstrating a confirmed association with POAG. Although we could not link the SNPs to the annotated gene(s), it turned out that we have identified 3 genetic loci probably associated with POAG. These findings would provide the foundation for future studies to build on, such as for the metaanalysis, to reveal the molecular mechanism of the POAG pathogenesis.

Interferon-β1b Treatment in Neuromyelitis Optica

Abstract: Background: The effects of interferon-β1b (IFN-β1b) administration in multiple sclerosis (MS) patients have been confirmed, however, those in neuromyelitis opt

Anti-aquaporin 4 antibody in Japanese multiple sclerosis: the presence of optic–spinal multiple sclerosis without long spinal cord lesions and anti-aquaporin 4 antibody

Abstract: Background: Anti-aquaporin 4 (AQP4) antibodies were found in patients with neuromyelitis optica (NMO) and Japanese optic–spinal multiple sclerosis (OSMS). Objective: To review the clinical features and investigate anti-AQP4 antibodies of Japanese patients with multiple sclerosis (MS), with or without long spinal cord lesions (LCL). Methods: Anti-AQP4 antibodies were examined in the sera of 128 consecutive Japanese patients by the immunofluorescence method using AQP4 transfected cells. Results: The 45 LCL-MS patients included 28 with a long spinal cord lesion extending contiguously over three vertebral segments on sagittal T2 weighted images (long T2 lesion) and 17 with segmental cord atrophy extending more than three vertebral segments. We identified 25 patients with anti-AQP4 antibody with LCL and anti-AQP4 antibody. Anti-AQP4 antibody was found in 12/17 (70.6%) LCL-MS patients with segmental cord atrophy, and in 13/28 (46.4%) LCL-MS patients without segmental long cord atrophy (p = 0.135, Fisher’s exact test). Seropositive MS patients with LCL had more relapses than seronegative patients (p = 0.0004, Mann–Whitney U test). 9 patients with OSMS were negative for anti-AQP4 antibody who did not show LCL. Conclusion: These results suggest that an anti-AQP4 antibody is found not only in MS patients with long T2 lesions but also in patients with segmental cord atrophy extending more than three vertebral segments. It is a marker of LCL-MS showing frequent exacerbations. Japanese OSMS cases comprised those that were identical to NMO cases and those that were more closely related to classic MS.

Proteomic pattern analysis discriminates among multiple sclerosis-related disorders

Abstract: Objective: To use a new, unbiased biomarker discovery strategy to obtain and assess proteomic data from cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS)-related disorders. Methods: CSF protein profiles were analyzed from 107 patients with either MS-related disorders (including relapsing remitting MS [RRMS], primary progressive MS [PPMS], anti-aquaporin4 antibody seropositive–neuromyelitis optica spectrum disorder [SP-NMOSD], and seronegative-NMOSD with long cord lesions on spinal magnetic resonance imaging [SN-NMOSD]), amyotrophic lateral sclerosis (ALS), or other inflammatory neurological diseases (used as controls). CSF peptides/proteins were purified with magnetic beads, and directly measured by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The obtained spectra were analyzed with multivariate statistics and pattern matching algorithms. These analyses were replicated in an independent sample set of 84 patients composed of those with MS-related disorders or with other neurological diseases (the second cohort). Results: MS-related disorders differed considerably in terms of CSF protein profiles. SP-NMOSD and SN-NMOSD, both of which fit within the NMO spectrum, were distinguishable from RRMS with high cross-validation accuracy on a support vector machine classifier, especially in relapse phases. Some peaks derived from samples of relapsed SP-NMOSD can discriminate RRMS with high area under curve scores (>0.95) and this was reproduced on the second cohort. The similarity of proteomic patterns between selected neurological diseases were demonstrated by pattern matching analysis. To our surprise, the spectral differences between RRMS and PPMS were much larger than those of PPMS and ALS. Interpretation: Our findings suggest that CSF proteomic pattern analysis can increase the accuracy of disease diagnosis of MS-related disorders and will aid physicians in appropriate therapeutic decision-making. ANN NEUROL 2012;

Cytokine storm arising on the ocular surface in a patient with Stevens–Johnson syndrome

Abstract: Stevens–Johnson syndrome (SJS) and its more extreme variant, toxic epidermal necrolysis (TEN), are acute, adverse systemic reactions that can affect anyone who takes medications. SJS/TEN predominantly affects the skin and mucosal membranes and predisposes patients to life-threatening complications such as sepsis, respiratory dysfunction and multi-organ failure. Even when a patient does survive this disease, serious ocular discomfort and morbidity often persists life long.1 2 In May 2008, a 59-year-old female inpatient had a case of red eyes, and 2 days later she presented with a sudden onset of high fever and eruption and erosion in the mucocutaneous regions including the mouth, paronychia and bilateral conjunctivitis. Slit-lamp examination revealed a large epithelial defect of the conjunctiva with severe hyperaemia in both eyes (figure 1A,B). There was no viral or bacterial infection, and skin biopsy specimens of the erythematous macules revealed necrotic keratinocytes and liquefaction, compatible with the diagnosis of SJS. Steroid pulse therapy and intensive topical betamethasone (0.1%, 10 times daily) were …

Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients

Abstract: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%). Seropositive patients were found to be predominantly female (p 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome. This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients.

Aquaporin 4 and neuromyelitis optica.

Abstract: Summary Neuromyelitis optica is an inflammatory demyelinating disorder of the CNS. The discovery of circulating IgG1 antibodies against the astrocyte water channel protein aquaporin 4 (AQP4) and the evidence that AQP4-IgG is involved in the development of neuromyelitis optica revolutionised our understanding of the disease. However, important unanswered questions remain—for example, we do not know the cause of AQP4-IgG-negative disease, how astrocyte damage causes demyelination, the role of T cells, why peripheral AQP4-expressing organs are undamaged, and how circulating AQP4-IgG enters neuromyelitis optica lesions. New drug candidates have emerged, such as aquaporumab (non-pathogenic antibody blocker of AQP4-IgG binding), sivelestat (neutrophil elastase inhibitor), and eculizumab (complement inhibitor). Despite rapid progress, randomised clinical trials to test new drugs will be challenging because of the small number of individuals with the disorder.

EFNS guidelines on diagnosis and management of neuromyelitis optica

Abstract: Background and purpose: Neuromyelitis optica (NMO) or Devic's disease is a rare inflammatory and demyelinating autoimmune disorder of the central nervous system (CNS) characterized by recurrent attacks of optic neuritis (ON) and longitudinally extensive transverse myelitis (LETM), which is distinct from multiple sclerosis (MS). The guidelines are designed to provide guidance for best clinical practice based on the current state of clinical and scientific knowledge. Search strategy: Evidence for this guideline was collected by searches for original articles, case reports and meta-analyses in the MEDLINE and Cochrane databases. In addition, clinical practice guidelines of professional neurological and rheumatological organizations were studied. Results: Different diagnostic criteria for NMO diagnosis [Wingerchuk et al. Revised NMO criteria, 2006 and Miller et al. National Multiple Sclerosis Society (NMSS) task force criteria, 2008] and features potentially indicative of NMO facilitate the diagnosis. In addition, guidance for the work-up and diagnosis of spatially limited NMO spectrum disorders is provided by the task force. Due to lack of studies fulfilling requirement for the highest levels of evidence, the task force suggests concepts for treatment of acute exacerbations and attack prevention based on expert opinion. Conclusions: Studies on diagnosis and management of NMO fulfilling requirements for the highest levels of evidence (class I-III rating) are limited, and diagnostic and therapeutic concepts based on expert opinion and consensus of the task force members were assembled for this guideline.

Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma

Abstract: We conducted a genome-wide association study for primary open-angle glaucoma (POAG) in 1,263 affected individuals (cases) and 34,877 controls from Iceland. We identified a common sequence variant at 7q31 (rs4236601[ A], odds ratio (OR) = 1.36, P = 5.0 x 10(-10)). We then replicated the association in sample sets of 2,175 POAG cases and 2,064 controls from Sweden, the UK and Australia (combined OR = 1.18, P = 0.0015) and in 299 POAG cases and 580 unaffected controls from Hong Kong and Shantou, China (combined OR = 5.42, P = 0.0021). The risk variant identified here is located close to CAV1 and CAV2, both of which are expressed in the trabecular meshwork and retinal ganglion cells that are involved in the pathogenesis of POAG.

Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1

Abstract: We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 × 10-10) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 × 10-9). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010; rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 × 10-14, OR = 1.51, 95% CI 1.35-1.68; rs4977756 combined P = 1.35 × 10-14, OR = 1.39, 95% CI 1.28-1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma. © 2011 Nature America, Inc. All rights reserved.