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Dive into the research topics where Makoto Hirotani is active.

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Featured researches published by Makoto Hirotani.


Clinical Neurology and Neurosurgery | 2005

Brain 3D-SSP SPECT analysis in dementia with Lewy bodies, Parkinson's disease with and without dementia, and Alzheimer's disease

Yasunori Mito; Kazuto Yoshida; Ichiro Yabe; Kenichi Makino; Makoto Hirotani; Kunio Tashiro; Seiji Kikuchi; Hidenao Sasaki

OBJECTIVES Cerebral blood flow was compared among patients with dementia with Lewy bodies (DLB), Parkinsons disease with dementia (PDD), Parkinsons disease without dementia (PD), and Alzheimers disease (AD) using three-dimensional stereotactic surface projection (3D-SSP) analysis. PURPOSE We attempt to clarify the difference of reduction pattern on SPECT among patients having DLB, PDD, PD, AD. PATIENTS AND METHODS Six patients with DLB, 7 patients with PDD who were matched with the DLB patients for age, unified Parkinsons disease rating scale-III (UPDRS-III) score, and degree of cognitive function disorders, 21 patients with PD who were matched with the DLB patients for age, UPDRS-III score, 12 patients with AD who were matched with the DLB patients for age and degree of cognitive function disorders, and 12 control subjects. All patients were examined by N-isopropyl-p[123I] iodoamphetamine single photon emission computed tomography (123I-IMP SPECT), and obtained images were analyzed with 3D-SSP using an image-analysis software, iSSP ver. 3.5. RESULTS Although DLB and PDD showed similar cerebral perfusion reduction pattern at the lateral parietal association and lateral temporal association and precuneus on SPECT by the pixel-by-pixel comparison, greater perfusion reduction was observed in DLB than in PDD. Cerebral perfusion was decreased at the occipital lobe of the DLB patients compared with the AD patients. CONCLUSIONS The regional pattern of blood flow reduction in the brain was found to be different among DLB, PD, and AD. Greater blood flow reduction was observed in DLB, although DLB and PDD showed similar reduction pattern. These regional differences were considered to suggest different and disease-specific combinations of underlying pathological and neurochemical processes.


Journal of the Neurological Sciences | 2012

Increased prevalence, incidence, and female predominance of multiple sclerosis in northern Japan

Hideki Houzen; Masaaki Niino; Makoto Hirotani; Toshiyuki Fukazawa; Seiji Kikuchi; Keiko Tanaka; Hidenao Sasaki

OBJECTIVE To carry out the third epidemiologic surveillance of multiple sclerosis (MS) in Tokachi province, on the northernmost island of Japan, and to compare the results of the present survey on the prevalence, incidence, and characteristics of MS and neuromyelitis optica (NMO) with those of previous surveys performed in 2001 and 2006. METHODS A data processing sheet was sent to all MS-related institutions in Tokachi province, and all sheets were collected in March 2011. The criteria of Poser were used for diagnosing MS and the criteria proposed by Wingerchuk for diagnosing NMO. We then compared the results of the present survey with those of previous surveys performed in 2001 and 2006 in the same community. RESULTS Fifty-seven patients diagnosed with MS according to the criteria of Poser were identified. The prevalence was 16.2/100,000 in 2011, which was higher than in the previous studies. The female/male ratio of MS was 2.63, 2.75, and 3.38 in 2001, 2006, and 2011, respectively. Three patients fulfilled the criteria for diagnosis of NMO in 2011; the prevalence of NMO was 0.9/100,000. CONCLUSIONS The results of this study suggest that the prevalence and the female predominance of MS have been increasing, due to an increase in the incidence after 1990, and that the prevalence of NMO is relatively low in northern Japan.


Journal of Neuroimmunology | 2010

Decreased IL-10 production mediated by Toll-like receptor 9 in B cells in multiple sclerosis

Makoto Hirotani; Masaaki Niino; Toshiyuki Fukazawa; Seiji Kikuchi; Ichiro Yabe; Shinsuke Hamada; Yasutaka Tajima; Hidenao Sasaki

The complexity of the roles of Toll-like receptors (TLRs) is attributable to their ability to promote or suppress autoimmune diseases. Recent studies have demonstrated that B cells regulate autoimmune diseases, including multiple sclerosis (MS), by producing interleukin (IL)-10. By using CpG DNA as a TLR9 agonist, we investigated the immunoregulatory functions of B cell via TLR9 in MS. Our results indicate that TLR9-mediated IL-10 production by B cells was significantly decreased in MS, and this decrease is likely due to decreased TLR9 expression in memory B cells, suggesting a role of TLR9 in immunoregulation in MS.


Neuroscience Letters | 2009

Memory and naïve B-cell subsets in patients with multiple sclerosis.

Masaaki Niino; Makoto Hirotani; Yusei Miyazaki; Hidenao Sasaki

Memory and naïve B cells are considered to play distinct roles in immune regulation. However, the roles of memory and naïve B-cell subsets in multiple sclerosis (MS) have not yet been elucidated. In this study, we examined whether memory and naïve B-cell subsets differ between patients with MS and healthy subjects and whether interferon beta (IFNbeta)-1b can affect these subsets in patients with MS. We also studied these subsets in relapsing and remitting stages of MS. Subjects included 31 patients with relapsing-remitting MS in the remitting stage, of which 15 were treated with IFNbeta-1b and 16 were not treated, and 22 healthy control subjects. For 11 of the 16 untreated patients, blood samples were also obtained in the relapsing stage. Expression of CD5, CD80, CD86, CCR5, CXCR3, CD11a, and CD49d in memory and naïve B cells in blood samples was examined by flow cytometry. The percentages of CD86(+) cells and CCR5(+) cells in the naïve B-cell subset were significantly higher in untreated patients than in control subjects or IFNbeta-treated patients. In patients with MS, the percentages of CD86(+) cells and CCR5(+) cells in the naïve B-cell subset and the percentage of CD5(+) cells in the memory B-cell subset were significantly greater in the remitting stage than in the relapsing stage. These results indicate that memory and naïve B-cell subsets, especially CD86(+) naïve B cells, CCR5(+) naïve B cells, and CD5(+) memory B cells, might be useful in the study of the pathogenesis of and therapy for MS.


Central nervous system agents in medicinal chemistry | 2009

Estrogens as Potential Therapeutic Agents in Multiple Sclerosis

Masaaki Niino; Makoto Hirotani; Toshiyuki Fukazawa; Seiji Kikuchi; Hidenao Sasaki

The disease activity of multiple sclerosis (MS) is known to be ameliorated during pregnancy, and pregnancy is also found to be protective in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Estrogen levels increase during pregnancy and basic researches have shown that estrogens have immunomodulatory effects on immune cells. The importance of estrogen in pathogenic autoimmune diseases has also been demonstrated in EAE by altering hormone levels. Mice treated with estrogen experienced significantly decreased EAE severity and delayed onset of disease as a result of neuroprotective and anti-inflammatory effects. Brain atrophy has been detected at the early stages of MS by using MRI; thus, as a neuroprotective agent, estrogen might be effective against brain atrophy. Estrogens effects are primarily mediated by the nuclear estrogen receptor (ER), and recent studies have shown the presence of nuclear ERs on the cells involved in the immune response. There have been some reports on genetic polymorphisms of ERs in MS. In this review paper, we discuss increasing evidence that points to a link between estrogen and MS. We also analyze the therapeutic potential of estrogens in MS and review current genetic studies on ER.


Journal of Neurology, Neurosurgery, and Psychiatry | 2015

A nationwide survey of combined central and peripheral demyelination in Japan

Hidenori Ogata; Dai Matsuse; Ryo Yamasaki; Nobutoshi Kawamura; Takuya Matsushita; Tomomi Yonekawa; Makoto Hirotani; Hiroyuki Murai; Jun-ichi Kira

Objectives To clarify the clinical features of combined central and peripheral demyelination (CCPD) via a nationwide survey. Methods The following characteristics were used to define CCPD: T2 high-signal intensity lesions in the brain, optic nerves or spinal cord on MRI, or abnormalities on visual-evoked potentials; conduction delay, conduction block, temporal dispersion or F-wave abnormalities suggesting demyelinating neuropathy based on nerve conduction studies; exclusion of secondary demyelination. We conducted a nationwide survey in 2012, sending questionnaires to 1332 adult and paediatric neurology institutions in Japan. Results We collated 40 CCPD cases, including 29 women. Age at onset was 31.7±14.1 years (mean±SD). Sensory disturbance (94.9%), motor weakness (92.5%) and gait disturbance (79.5%) were common. Although cerebrospinal fluid protein levels were increased in 82.5%, oligoclonal IgG bands and elevated IgG indices were detected in 7.4% and 18.5% of cases, respectively. Fifteen of 21 patients (71.4%) had abnormal visual-evoked potentials. Antineurofascin 155 antibodies were positive in 5/11 (45.5%). Corticosteroids, intravenous immunoglobulins and plasmapheresis resulted in an 83.3%, 66.7% and 87.5% improvement, respectively, whereas interferon-β was effective in only 10% of cases. CCPD cases with simultaneous onset of central nervous system (CNS) and peripheral nervous system (PNS) involvement exhibited greater disability, but less recurrence and more frequent extensive cerebral and spinal cord MRI lesions compared to those with temporarily separated onset, whereas optic nerve involvement was more common in the latter. Conclusions CCPD shows different characteristics from classical demyelinating diseases, and distinctive features exist between cases with simultaneous and temporarily separated onset of CNS and PNS involvement.


Clinical Immunology | 2012

Decreased interferon-α production in response to CpG DNA dysregulates cytokine responses in patients with multiple sclerosis.

Makoto Hirotani; Masaaki Niino; Toshiyuki Fukazawa; Hiroaki Yaguchi; Masakazu Nakamura; Seiji Kikuchi; Hidenao Sasaki

Type I interferons (IFNs), represented by IFN-α and β, activate immune effector cells belonging to the innate and adaptive immune systems. Plasmacytoid dendritic cells (pDCs) produce IFN-α in response to CpG DNA. We aimed to examine the impact of pDC-produced IFN-α on the adaptive immune system in Multiple Sclerosis (MS). Our results demonstrated that CpG DNA-induced IFN-α production was significantly decreased in PBMCs from MS patients. Decreased levels of IL-12 p70, IFN-γ, and IL-17 and increased level of IL-10 were found in CpG DNA-treated PBMCs of healthy subjects unlike in those from MS patients. In samples pre-treated with IFN-α and IFN-β, decreased levels of IL-12 p70, IFN-γ, and IL-17 and increased level of IL-10 were detected in PBMCs from MS patients. These results suggest that CpG DNA-induced decreased IFN-α production causes pro-inflammatory cytokine secretion, and either IFN-α or IFN-β induces anti-inflammatory cytokine secretion in the adaptive immune system in MS.


Neuroscience Letters | 2015

Level of plasma neuregulin-1 SMDF is reduced in patients with idiopathic Parkinson’s disease

Yuka Hama; Ichiro Yabe; Koichi Wakabayashi; Takahiro Kano; Makoto Hirotani; Yuriko Iwakura; Jun Utsumi; Hidenao Sasaki

Parkinsons disease (PD) is characterised by the progressive loss of dopaminergic neurons, neurons that are regulated by the development, protection and function of neuregulin-1 (NRG1)-ErbB4 signals, in the substantia nigra (SN). NRG1 is a neurotrophic differentiation factor and one of its isoforms is a sensory and motor neuron-derived factor (SMDF), mostly expressed in neurons. To examine the relationship between NRG1 SMDF and PD, we tested whether NRG1 SMDF can be detected and measured in plasma and whether their level in plasma correlates with the clinical severity of PD. We detected NRG1 SMDF to be immunoreactive in plasma. Using an ELISA method specific for NRG1 SMDF, we found that NRG1 SMDF levels were significantly reduced in sporadic PD as compared to controls. However, levels of plasma NRG1 SMDF showed no correlation with the clinical severity of PD. Additionally, we found that there was a correlation of NRG1 SMDF levels in CSF with that in plasma where levels in plasma were significantly higher, at approximately ten times that in CSF. Finally, we also examined the expression of NRG1 SMDF in the post-mortem brain using immunohistochemistry and showed that Lewy bodies in the SN of patients with PD were immunoreactive for NRG1 SMDF. In summary, we found that the reduction of plasma NRG1 SMDF is specifically associated with PD, but has no correlation with the clinical severity of PD. These findings of NRG1 SMDF may provide important complementary information for diagnosing the onset of PD.


Cerebellum & Ataxias | 2017

Validity and reliability of a pilot scale for assessment of multiple system atrophy symptoms

Masaaki Matsushima; Ichiro Yabe; Ikuko Takahashi; Makoto Hirotani; Takahiro Kano; Kazuhiro Horiuchi; Hideki Houzen; Hidenao Sasaki

BackgroundMultiple system atrophy (MSA) is a rare progressive neurodegenerative disorder for which brief yet sensitive scale is required in order for use in clinical trials and general screening. We previously compared several scales for the assessment of MSA symptoms and devised an eight-item pilot scale with large standardized response mean [handwriting, finger taps, transfers, standing with feet together, turning trunk, turning 360°, gait, body sway]. The aim of the present study is to investigate the validity and reliability of a simple pilot scale for assessment of multiple system atrophy symptoms.MethodsThirty-two patients with MSA (15 male/17 female; 20 cerebellar subtype [MSA-C]/12 parkinsonian subtype [MSA-P]) were prospectively registered between January 1, 2014 and February 28, 2015. Patients were evaluated by two independent raters using the Unified MSA Rating Scale (UMSARS), Scale for Assessment and Rating of Ataxia (SARA), and the pilot scale. Correlations between UMSARS, SARA, pilot scale scores, intraclass correlation coefficients (ICCs), and Cronbach’s alpha coefficients were calculated.ResultsPilot scale scores significantly correlated with scores for UMSARS Parts I, II, and IV as well as with SARA scores. Intra-rater and inter-rater ICCs and Cronbach’s alpha coefficients remained high (> 0.94) for all measures.ConclusionThe results of the present study indicate the validity and reliability of the eight-item pilot scale, particularly for the assessment of symptoms in patients with early state multiple system atrophy.


Muscle & Nerve | 2013

Novel GNE compound heterozygous mutations in a GNE myopathy patient.

Huaying Cai; Ichiro Yabe; Shinichi Shirai; Hiroaki Nishimura; Makoto Hirotani; Takahiro Kano; Hideki Houzen; Kazuto Yoshida; Hidenao Sasaki

Introduction: Molecular studies have revealed that some patients with myopathies with rimmed vacuoles have pathogenic mutations in the UDP‐N‐acetylglucosamine‐2‐epimerase/N‐acetylmannosamine kinase (GNE) and Z‐band alternatively spliced PDZ motif‐containing protein (ZASP) genes. Methods: We investigated a patient with distal myopathy with rimmed vacuoles by muscle biopsy and sequenced 6 candidate genes. Results: The patient carried GNE compound heterozygous missense mutations (p.V421A and p.N635K) and a ZASP variant (p.D673N). This patient also presented with distal weakness sparing the quadriceps muscles and had atypical results for Z‐band‐associated protein immunostaining. This finding indicates that the GNE mutations are pathogenic, and the diagnosis is compatible with GNE myopathy. Conclusions: By combining pathological studies and candidate gene screening, we identified a patient with GNE myopathy due to novel GNE compound heterozygous mutations. Muscle Nerve 48: 594–598, 2013

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