Yuichi Hayashi

Gifu University, Gihu, Gifu, Japan

Are you Yuichi Hayashi?

Claim your profile

Publications (44)85.59 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Antiendothelial cell antibodies (AECAs) have been detected in patients who have autoimmune and inflammatory diseases. Previous studies showed that AECAs against human umbilical vein endothelial cells were detected in healthy subjects. In the present study, we evaluated AECAs against human brain microvascular endothelial cells (HBMEC) in serum. We detected 250 antigen spots that reacted with AECAs in serum samples from 30 healthy subjects by 2-dimensional immunoblot using primary cultured HBMEC as the antigen source. There were 10 spots that corresponded to common target antigen spots and reacted with AECAs in serum samples from > 25% of the 30 healthy subjects. We identified 7 proteins that corresponded to 8 of the 10 spots by mass spectrometry: 78-kDa glucose-regulated protein, dihydropyrimidinase-related protein 2, heterogeneous nuclear ribonucleoprotein L, vimentin, perilipin 3, alpha-enolase, and annexin A2. The results suggest that these 7 HBMEC proteins are major target antigens of natural AECAs.
    Current neurovascular research. 01/2015;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the clinical, genetic, and neuroradiologic presentations of idiopathic basal ganglia calcification (IBGC) in a nationwide study in Japan. We documented clinical and neuroimaging data of a total of 69 subjects including 23 subjects from 10 families and 46 subjects in sporadic cases of IBGC in Japan. Mutational analysis of SLC20A2 was performed. Six new mutations in SLC20A2 were found in patients with IBGC: 4 missense mutations, 1 nonsense mutation, and 1 frameshift mutation. Four of them were familial cases and 2 were sporadic cases in our survey. The frequency of families with mutations in SLC20A2 in Japan was 50%, which was as high as in a previous report on other regions. The clinical features varied widely among the patients with SLC20A2 mutations. However, 2 distinct families have the same mutation of S637R in SLC20A2 and they have similar characteristics in the clinical course, symptoms, neurologic findings, and neuroimaging. In our study, all the patients with SLC20A2 mutations showed calcification. In familial cases, there were symptomatic and asymptomatic patients in the same family. SLC20A2 mutations are a major cause of familial IBGC in Japan. The members in the families with the same mutation had similar patterns of calcification in the brain and the affected members showed similar clinical manifestations.
    Neurology 01/2014; · 8.30 Impact Factor
  • Nihon Naika Gakkai Zasshi 12/2013; 102(12):3223-6.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Amyotrophic lateral sclerosis (ALS), which is the most serious form of degenerative motor neuron disease in adults, is characterized by upper and lower motor neuron degeneration, skeletal muscle atrophy, paralysis, and death. Some patients with respiratory-dependent ALS die of sudden cardiac arrest or anoxic encephalopathy following circulatory collapse, which may be associated with sympathetic hyperactivity. Cardiac [(123)I] MIBG scintigraphy is a diagnostic method of cardiac sympathetic function. However, few reports have addressed cardiac sympathetic function in ALS patients using this technique. We investigated cardiac sympathetic function in 63 ALS patients and 10 healthy volunteers using cardiac [(123)I] metaiodobenzylguanidine (MIBG) scintigraphy [heart/mediastinum ratio (H/M ratio) in the early phase and washout ratio (WR)] at the time of diagnosis. The WR of cardiac [(123)I] MIBG scintigraphy, which indicates cardiac sympathetic activity, was significantly increased in ALS patients compared with controls. ALS patients with an increased WR exhibited a significantly higher progression rate compared with those with normal WR. Moreover, the survival of ALS patients with increased WR was significantly decreased compared with those with normal WR. These results suggested that some patients with ALS have sympathetic hyperactivity at the time of diagnosis. ALS patients may suffer from chronic cardiac sympathetic hyperactivity, which is associated with sudden cardiac death and stress induced cardiomyopathy. Increased WR in cardiac [(123)I] MIBG scintigraphy may be a predictive factor in ALS patients.
    Journal of Neurology 06/2013; · 3.84 Impact Factor
  • Yuichi Hayashi, Takashi Inuzuka
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Paraneoplastic neurological syndrome (PNS) is a rare disorder caused by the remote effects of cancer is considered as caused by humoral or cell-mediated immunity. Several autoantibodies related to PNS have been discovered since the 1980s. These antibodies were classified into 2 categories based on the PNS diagnostic criteria recommended by PNS Euronetwork in 2004: well-characterized onconeural antibodies and partially characterized onconeural antibodies. Recently, techniques for the detection of these antibodies have been developed. Additional autoantibodies have been shown for neural surface antigens related to autoimmune-mediated encephalitis in patients with and without cancer. Because the PNS neurological symptoms often precede tumor diagnosis, the antibodies are useful diagnostic markers for PNS and occult tumors. Anti-tumor therapies are essential for PNS, and successful immunotherapies depend on the location of antigens, whether intracellular or on the surface of membranes. Generally, the latter cases are responsive to therapy. Only a limited numbers of cases with intracellular antigens have been improved by early and aggressive immunotherapies. Neurologists should be alert for PNS and check the presence of autoantibodies at the start of therapies when encountering rapidly progressive neurological symptoms of unknown origin. Here, we describe the relationship between onconeural antibodies, clinical features, tumor types, and response to immunotherapies.
    Brain and nerve = Shinkei kenkyū no shinpo 04/2013; 65(4):385-93.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We studied longitudinal changes of the levels of anti-amyloid beta (anti-Abeta) antibody, amyloid beta (Abeta) protein, and interleukin 8 (IL-8) in cerebrospinal fluid (CSF) of a patient with cerebral amyloid angiopathy-related inflammation (CAA-ri) in whom steroid treatment resulted in clinical improvement. The diagnosis of CAA-ri was established with brain biopsy. Levels of anti-Abeta 42 antibody, Abeta 40, Abeta 42 and IL-8 in CSF were measured in the CAA-ri patient at 23 time points in the 8-month clinical course. These CSF samples were divided into 2 groups: those obtained before (n = 12) and those after (n = 11) oral corticosteroid therapy was started. We compared these levels between CSF samples obtained before and after therapy. The mean levels of anti-Abeta 42 antibody and IL-8 were significantly higher in CSF samples of the CAA-ri patient before oral corticosteroid therapy than those after therapy. A positive correlation was noted between levels of anti-Abeta 42 antibodies and IL-8 in CSF of this patient. There were no significant differences of mean levels of Abeta 40 and Abeta 42 between CSF samples obtained before and after oral corticosteroid therapy. It was possible that the autoinflammatory process with anti-Abeta 42 antibodies and IL-8 may have been involved in the pathogenesis of CAA-ri, and that corticosteroid therapy directly affected levels of anti-Abeta 42 antibody and IL-8. In summary, CAA-ri encephalopathy is a relapsing or progressive disorder and may be treatable by adequate immunosuppressive therapy. The anti-Abeta 42 antibody in CSF is a useful biological marker for therapeutic monitoring of CAA-ri.
    Journal of Neuroinflammation 03/2013; 10(1):39. · 4.90 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Gastrointestinal symptoms are frequent complaints in patients with myotonic dystrophy type 1 (MyD1) and may be associated with reduced gastrointestinal motility caused by smooth muscle dysfunction. Although previous studies have found delayed gastric emptying (GE) in MyD1 patients, the relationship between GE and symptoms has been unclear. We investigated GE in 23 MyD1 patients and 20 healthy volunteers using the (13)C-acetate breath test. The MyD1 patients were divided into two groups: those with gastrointestinal symptoms (n = 9) and those without gastrointestinal symptoms (n = 14). The GE function was estimated using the (13)C-acetate breath test as half-emptying time (HET) and peak time of the (13)C-%-dose-excess curve (T (max)). GE (HET and T (max)) was more significantly delayed in patients with MyD1 than in the controls. The GE in MyD1 patients with gastrointestinal symptoms was significantly delayed compared to those without gastrointestinal symptoms. The GE in MyD1 patients with gastrointestinal symptoms was more significantly delayed than in the controls. The GE was significantly delayed in MyD1 patients with gastrointestinal symptoms for >5 years as compared to those with the disease for <5 years, while GE of MyD1 patients without gastrointestinal symptoms did not correlate with the duration of the disease. The GE in MyD1 patients did not correlate with the muscular disability rating scale. These findings suggest that impairment of GE evolves over time and that the progression of delayed GE and skeletal muscle impairment are independent. Smooth muscle impairment may be affected at an earlier stage in MyD1.
    Journal of Neurology 01/2013; · 3.84 Impact Factor
  • Yuichi Hayashi, Tetsuya Suwa, Takashi Inuzuka
    Internal Medicine 01/2013; 52(1):161-2. · 0.97 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We report an 84-year-old woman with left lower limb muscle weakness and numbness who also had weakness in her right lower limb, which showed spontaneous partial improvement. Neurological examination revealed lower extremity weakness and sensory disturbance in all modalities, predominantly distally on the left side. Laboratory studies yielded normal results, except for a slightly high erythrocyte sedimentation rate. Nerve conduction studies showed axonal neuropathy in the right tibial nerve, and loss of action potentials in other lower limb nerves. Histological study of the left sural nerve revealed mainly loss of axons and differences in the density of fascicules in the axons. In addition, inflammatory cells infiltrated around small blood vessels. Therefore, we diagnosed nonsystemic vasculitic neuropathy. Magnetic resonance imaging revealed that she also had spondylosis deformans and radiculopathy, which was more difficult to differentiate. Neural biopsy was important for diagnosis.
    Nippon Ronen Igakkai Zasshi Japanese Journal of Geriatrics 01/2013; 50(3):400-3.
  • [Show abstract] [Hide abstract]
    ABSTRACT: AIM: To investigate the frequency of calcification in the basal ganglia and the dentate nuclei in the cerebellum, and compare the difference in age and area, we examined the brain computed tomography (CT) images of all patients in two representative university hospitals in Japan. METHODS: We examined the brain CT images of 2526 patients in Gifu University Hospital (UH) and 2573 patients in Niigata UH. These patients were examined in these hospitals from October 2009 to September 2010. RESULTS: Punctate calcification of the basal ganglia was observed in 435 of 2526 patients (17.2%) in Gifu UH and 530 of 2573 patients (20.6%) in Niigata UH. The frequency of calcification increased with age. Patchy calcification of the basal ganglia was observed in 32 (1.3%) and 50 patients (1.9%) in Gifu UH and Niigata UH, respectively. Among patients aged over 65 years, 24 (2.1%) and 34 (3.1%) patients showed patchy calcification in Gifu UH and Niigata UH, respectively. Calcification of the cerebellar dentate nuclei was detected in just seven and four patients in Gifu UH and Niigata UH, respectively. CONCLUSION: Compared with previous reports, the frequency of calcification of the basal ganglia in this study markedly increased. This might be because of the increased number of older adults and the increased sensitivity of CT. Geriatr Gerontol Int 2012; ●●: ●●-●●.
    Geriatrics and Gerontology International 12/2012; · 1.58 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The remarkable calcification of the basal ganglia and cerebellum has been traditionally called Fahr's disease, but this nomenclature is criticized for including heterogeneous diseases. To determine the pattern of some biological metals in the hair of patients with Fahr's disease, we investigated the levels of 24 bioelements in the hair of 28 patients (17 males and 11 females) with Fahr's disease and compared them with those of three age-, sex-, and living region-matched controls (84 controls in total). Interestingly, we found decreases in the levels of several bioelements [calcium (Ca), copper (Cu), iron (Fe), mercury (Hg), iodine (I), nickel (Ni), phosphate (P), lead (Pb), and selenium (Se)] in the hair of patients. This is in contrast to our previous finding of increases of Cu, Fe, zinc (Zn), and magnesium (Mg) in the cerebrospinal fluid (CSF) of patients. The decreased level of Cu in the hair was the most prominent and pathognomonic, while the increased level of Cu in the CSF had been found to be the most significant in patients. More significant correlations between two bioelements in the hair were recognized in patients than controls. Although Fahr's disease has been considered to be a heterogenous entity, the significant tendencies of several bioelements in the hair of patients in this study suggest metabolic disorders of bioelements, especially biometals, on the background. Some transporters, especially P transporter such as PiT2, of bioelements will be involved in the different distribution of bioelements in the body of patients.
    Biological trace element research 10/2012; · 1.92 Impact Factor
  • Neurology 10/2012; 79(15):1625. · 8.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The pathogenesis of cerebral small vessel disease (CSVD) in the elderly is poorly understood. Endothelial cell activation and dysfunction may play a causal role in the pathogenesis of CSVD. It was reported that anti-endothelial cell antibodies (AECAs) are associated with endothelial cell dysfunction and inflammation. We hypothesized that AECAs may be associated with the pathogenesis of CSVD. We examined AECAs in sera from 12 elderly subjects with CSVD, 12 elderly subjects without CSVD, and 18 healthy volunteers by 2-dimensional immunoblotting using primary cultured human brain microvascular endothelial cells as the antigen source. We identified 4 AECAs that were detected in sera from more than one-half of the elderly subjects with CSVD. Subsequently, we analyzed the target antigens of these 4 antibodies by liquid chromatography-tandem mass spectrometry. The target antigens of these 4 antibodies were tropomyosin alpha-4 chain (TPM4), vimentin, alpha-enolase, and annexin A2. Among these 4 antibodies, the anti-TPM4 antibody was significantly more frequently detected in sera from the elderly subjects with CSVD than the other subjects. We determined the anti-TPM4 antibody level in sera from 21 elderly subjects with CSVD and 25 subjects without CSVD by enzyme-linked immunosorbent assay. The anti-TPM4 antibody level was significantly higher in the subjects with than without CSVD. Therefore, an autoimmune, inflammatory process with high levels of anti-TPM4 antibody may contribute to the development of CSVD in the elderly.
    Current neurovascular research 09/2012; · 3.23 Impact Factor
  • Nihon Naika Gakkai Zasshi 01/2012; 101(1):157-60.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent studies suggest that microvascular abnormalities are involved in pathology and progression of Alzheimer's disease. The purpose of this study was to examine the presence of antibodies against cerebral microvascular endothelial cells specific for Alzheimer's disease, and to evaluate the association of these antibodies with cognitive impairment. The study included patients with Alzheimer's disease (age ≥60 years; 24 patients), control subjects without neurological diseases (age ≥60 years; 19 subjects), patients with multiple sclerosis (all ages; 17 patients), and healthy control subjects (age <40 years; 18 subjects). Serum was analyzed with 2-dimensional electrophoresis and Western blot, with cultured human brain microvascular endothelial cells as the antigen source. The anti-Tom40 antibody was identified significantly more frequently in patients with Alzheimer's disease than control subjects or patients with multiple sclerosis. In patients with Alzheimer's disease, the mean scores for the Mini-Mental State Examination were significantly lower for patients who were positive for anti-Tom40 antibody than those who were negative for anti-Tom40 antibody. In summary, the anti-Tom40 antibody is significantly associated with cognitive impairment in patients with Alzheimer's disease.
    Journal of Alzheimer's disease: JAD 01/2012; 29(2):373-7. · 3.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Autonomic failure is one of the criteria according to the second consensus statement for the diagnosis of multiple system atrophy (MSA). Gastrointestinal symptoms are frequent complaints in patients with MSA and may be associated with reduced gastrointestinal motility due to autonomic nervous system dysfunction. However, there are few reports on gastric emptying in patients with MSA. We investigated gastric emptying in 25 patients with MSA, 20 patients with sporadic adult-onset ataxia of unknown etiology (SAOA), and 20 healthy volunteers using the (13)C-acetate breath test. Gastric emptying function is estimated by this test as the half-emptying time (HET) and peak time of the (13)C-%-dose-excess curve (T (max)), with expirations collected for 4 h after a test meal and determination of (13)CO(2) content using an infrared (IR) spectrophotometer. The HET and T (max) of gastric emptying were significantly delayed in patients with MSA as compared to those in SAOA and controls (p < 0.01). The HET and T (max) were not significantly different between SAOA and controls. No correlation existed between the HET or T (max) and the duration or severity of the disease in MSA patients. These results suggested that gastric emptying was significantly delayed in patients with MSA, and the delay already appeared in the early stage of the disease. Delayed gastric emptying is one of the autonomic failures and may be a clinical marker of MSA.
    Journal of Neurology 01/2012; 259(7):1448-52. · 3.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The population in Japan is aging at a faster rate than in other countries in the world. It is speculated that the number of patients with late-onset amyotrophic lateral sclerosis (ALS) will increase even more in the future. However, few studies have been undertaken on the characteristics of patients with late-onset ALS in Japan. This study sought to investigate the clinical features of patients with late-onset ALS compared with those with early-onset ALS using the progression rate (ΔFS). Forty-five patients with sporadic ALS were divided into 2 groups: 23 patients with early-onset of ALS (<65 years; early onset) and 22 patients with late-onset ALS (≥65 years; late onset). Every patient was followed up from the time of initial diagnosis to the primary endpoint (death or time culminating in death without tracheostomy or ventilation assistance including noninvasive positive pressure ventilation) or for at least 48 months after initial diagnosis. ΔFS in the patient group with late onset was significantly higher than that of the group with early onset (p=0.010). Survival of patients with late onset was significantly decreased compared to that of patients with early onset (p=0.031). Our finding suggested that patients with late-onset ALS showed more rapid disease progression than those with early-onset ALS using ΔFS.
    Internal Medicine 01/2012; 51(6):579-84. · 0.97 Impact Factor
  • Takashi Inuzuka, Yuichi Hayashi, Akio Kimura
    [Show abstract] [Hide abstract]
    ABSTRACT: Paraneoplastic neurological syndrome (PNS) is a rare disorder caused by the remote effects of cancer and is considered as immune-responses to the molecules on cancer which cross-react with self-antigens in the nervous system. Since the 1980s, several specific anti onconeural antibodies have been reported, which are useful diagnostic markers of PNS and occult cancer. Only a few onconeural antibodies have been identified as primary effectors of neurological damage. Recently sophisticated methods for the detection of new or low titer antibodies have been developed. Several new auto-antibodies against receptors or ion channels on the surface of neuronal membrane, such as NMDA receptors, AMPA receptors, GABA(B) receptors and VGKC complexes, have been reported in the patients with encephalopathy including limbic encephalitis. These diseases can be associated with tumor, but they are more often non-paraneoplastic. These antibodies are generally good biomarkers for effective immunomodulatory treatment for immune-mediated encephalitis with not only consciousness disturbance but also dementia, seizures and psychiatric symptoms which sometimes mimic schizophrenia. Further studies are required to clarify the exact mechanisms underlying neuronal damage in immune-mediated neurological diseases including PNS, which may lead to the development of more rational therapies and greater understanding of immunology in the nervous system.
    Rinshō shinkeigaku = Clinical neurology. 11/2011; 51(11):834-7.
  • [Show abstract] [Hide abstract]
    ABSTRACT: We measured the levels of some biological metals: copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), and zinc (Zn) in the cerebrospinal fluid (CSF) in patients with neurodegenerative diseases (52 patients with amyotrophic lateral sclerosis (ALS)), 21 patients with Alzheimer's disease (AD), and 20 patients with Parkinson's disease (PD) by inductively coupled plasma mass spectrometry (ICP-MS). The diagnoses were additionally supported by neuroimaging techniques for AD and PD. In ALS, the levels of Mg (p<0.01 significant difference), Fe, Cu (p<0.05), and Zn (p<0.10) in CSF were higher than those in controls. Some patients showed very high levels of Cu and Zn before the critical deterioration of the disease. In AD, the levels of Cu and Zn in CSF were significantly higher in patients with late-onset AD (p<0.01). In PD, we found significantly increased levels of especially Cu and Zn in particular (p<0.01) and Mn (p<0.05) in CSF. A multiple comparison test suggested that the increased level of Mg in ALS and that of Mn in PD were the pathognomonic features. These findings suggest that Cu and Zn in particular play important roles in the onset and/or progression of ALS, AD, and PD. Therefore, Cu-chelating agents and modulators of Cu and Zn such as metallothionein (MT) can be new candidates for the treatment of ALS, AD, and PD.
    Journal of the neurological sciences 02/2011; 303(1-2):95-9. · 2.32 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A 40-year-old man presented with weakness of neck extensor muscles. Cervical magnetic resonance imaging showed high-intensity areas in muscles of the left lateral cervical region on T2-weighted images. Fluorodeoxyglucose-positron emission tomography scan demonstrated striking fluorodeoxyglucose uptake by multiple skeletal muscles of the neck, chest, and abdominal region. Muscle biopsy demonstrated peripheral T-cell lymphoma, unspecified. The diagnosis was primary skeletal muscle peripheral T-cell lymphoma. Primary skeletal muscle non-Hodgkin's lymphoma of T-cell immunophenotype is extremely rare and fluorodeoxyglucose-positron emission tomography demonstrated striking fluorodeoxyglucose uptake in multiple skeletal muscles and served as a quite useful modality for the diagnosis of this patient.
    Internal Medicine 01/2011; 50(18):2021-4. · 0.97 Impact Factor