Osamu Yahara

Asahikawa Medical University, Asakhigava, Hokkaidō, Japan

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Publications (35)100.61 Total impact

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    ABSTRACT: A 70-year-old man with multiple ischemic strokes was diagnosed with cardiac embolism and treated with dabigatran. Three months later, he suddenly developed vertigo and vomiting. Magnetic resonance imaging, showed recurrent lesions and blood tests revealed hypercoagulability, hypoproteinemia, and elevated cytokeratin 19 fragments that serve as a tumor marker of lung cancer. Chest computed tomography showed there were small nodules in bilateral lungs and swollen mediastinal lymph nodes. A conclusive diagnosis was impossible because the patient declined invasive procedures. We suspected primary lung cancer and diagnosed concomitant arterial thrombosis. We initially administered low-molecular-weight heparin, which we later changed to vitamin K antagonist. Although stroke did not recur thereafter, liver metastasis resulted in death 6 months later. The effectiveness of novel oral anticoagulants for preventing the Trousseau syndrome remains unclear. Further study is needed to prevent venous and arterial thromboses arising from the Trousseau syndrome.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 07/2014; 23(6). DOI:10.1016/j.jstrokecerebrovasdis.2013.12.019 · 1.67 Impact Factor
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    ABSTRACT: A 59-year-old man presented with refractory anemia, choreoathetosis in the left upper extremity, an unsteady gait and cognitive dysfunction. The laboratory findings showed a marked decrease in ceruloplasmin. Magnetic resonance images revealed iron deposition in the brain and visceral organs. Iron accumulation was also observed in hepatocytes. Genetic analyses of the ceruloplasmin gene revealed a novel homozygous mutation of c.2185 delC in exon 12. The oral chelator deferasirox was effective in treating the left-side choreoathetosis and unsteady gait. Providing early treatment using deferasirox may be useful for preventing the progression of symptomatic neurological dysfunction.
    Internal Medicine 07/2013; 52(13):1527-30. DOI:10.2169/internalmedicine.52.0102 · 0.90 Impact Factor
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    ABSTRACT: Both the appearance of cytoplasmic inclusions containing phosphorylated TAR DNA-binding protein (TDP-43) and inefficient RNA editing at the GluR2 Q/R site are molecular abnormalities observed specifically in motor neurons of patients with sporadic amyotrophic lateral sclerosis (ALS). The purpose of this study is to determine whether a link exists between these two specific molecular changes in ALS spinal motor neurons. We immunohistochemically examined the expression of adenosine deaminase acting on RNA 2 (ADAR2), the enzyme that specifically catalyzes GluR2 Q/R site-editing, and the expression of phosphorylated and non-phosphorylated TDP-43 in the spinal motor neurons of patients with sporadic ALS. We found that all motor neurons were ADAR2-positive in the control cases, whereas more than half of them were ADAR2-negative in the ALS cases. All ADAR2-negative neurons had cytoplasmic inclusions that were immunoreactive to phosphorylated TDP-43, but lacked non-phosphorylated TDP-43 in the nucleus. Our results suggest a molecular link between reduced ADAR2 activity and TDP-43 pathology.
    Acta Neuropathologica 04/2010; 120(1):75-84. DOI:10.1007/s00401-010-0678-x · 10.76 Impact Factor
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    ABSTRACT: Myotonic dystrophy type 2 (DM2) is caused by expansion of a tetranucleotide CCTG repeat in intron 1 of the ZNF9 gene on chromosome 3q21. All studied DM2 mutations have been reported in Caucasians and share an identical haplotype, suggesting a common founder. We identified a Japanese patient with DM2 and showed that the affected haplotype is distinct from the previously identified DM2 haplotype shared among Caucasians. These data strongly suggest that DM2 expansion mutations originate from separate founders in Europe and Japan and are more widely distributed than previously recognized.
    Neurogenetics 03/2008; 9(1):61-3. DOI:10.1007/s10048-007-0110-4 · 2.88 Impact Factor
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    ABSTRACT: To determine the effective dose of cabergoline in Japanese patients with restless legs syndrome (RLS). Six cases of idiopathic RLS and three of RLS with Parkinson disease (PD) participated in an open clinical preliminary trial. All cases were diagnosed based on the clinical criteria of the International RLS Study Group. Three RLS cases (1.3%) were detected out of 229 consecutive cases with PD. RLS severity was evaluated with International RLS Study Group (IRLSSG) Rating Scale Version 2.2 before and one year after the treatment with cabergoline. For 6 idiopathic RLS patients, the IRLSSG questionnaire scores improved from 25.5+/-3.7 to 10.7+/-8.9 (p=0.028, Wilcoxon test) with 1 mg of daily cabergoline at the endpoint. For 3 RLS cases with PD, the score was 21.7+/-3.7 before the treatment, and RLS symptoms completely disappeared with 1 mg of cabergoline. One of RLS cases with PD required additional cabergoline later because of parkinsonism. No adverse event with cabergoline was reported in this study. One mg of daily cabergoline is effective in some Japanese patients of RLS.
    Internal Medicine 02/2006; 45(7):453-5. DOI:10.2169/internalmedicine.45.1555 · 0.90 Impact Factor
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    ABSTRACT: Treatment with a free radical scavenger could be a new option for ischemic brain attack, however, little is known about the alteration of oxidative stress markers induced by edaravone, a novel free radical scavenger, in human ischemic brain attack. We investigated the effects of edaravone on the oxidative stress markers in patients with ischemic brain attack. Twenty-one patients with ischemic brain attack and 19 controls were enrolled in this study. Blood samples were obtained just before and soon after the first administration of edaravone (30 mg) or ozagrel (40 mg). Intracellular reactive oxygen species of neutrophils were measured using 6-carboxy-2', 7'-dichlorodihydrofluorescin diacetate and a fluorescence-activated cell sorter. Superoxide from neutrophils, induced by phorbol myristate acetate (PMA), was determined by luminol-amplified chemiluminescence assay. Treatment with 30 mg of edaravone significantly decreased the intracellular reactive oxygen species (ROS) of neutrophils (Wilcoxon test, p=0.0001) and PMA-induced superoxide produced by neutrophils (Wilcoxon test, p=0.001). Ozagrel did not alter the intracellular ROS or superoxide production of neutrophils. Reduction of intracellular ROS and suppression of superoxide production in neutrophils provide a potential explanation for the clinical efficacy of edaravone in patients with ischemic brain attack.
    Internal Medicine 02/2006; 45(1):1-4. DOI:10.2169/internalmedicine.45.1491 · 0.90 Impact Factor
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    Journal of the Neurological Sciences 01/2004; 217(1). DOI:10.1016/j.jns.2003.09.009 · 2.47 Impact Factor
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    ABSTRACT: Twenty-two years after the first survey, a follow-up study was performed on the prevalence of multiple sclerosis (MS) in Asahikawa, a city in northern Japan. The crude prevalence of MS rose from 2.5/100,000 (in 1975) to 10.2/100,000 (in 2002). The clinical diagnosis was established using the Poser diagnostic criteria, and the degree of physical disability was determined using the Expanded Disability Status Scale (EDSS). The distribution of patients according to the clinical form of MS was 65% with relapsing-remitting MS, 19% with secondary chronic progressive MS and 16% with the primary chronic progressive forms of MS. Symptoms at onset in the present study less often affected optic nerves (3%) than previously reported in Japan and was more like that seen in western MS series. Although prevalence of MS increase four-fold in Japan over the last two decades, it remains uncertain whether this apparent increase is real or reflects better ascertainment.
    Journal of the Neurological Sciences 11/2003; 214(1-2):7-9. DOI:10.1016/S0022-510X(03)00165-5 · 2.47 Impact Factor
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    ABSTRACT: A 36-year-old man was referred to our hospital with complaints of high fever and headache. A diagnosis of miliary tuberculosis with tuberculous meningitis was made. He was treated with isoniazid (400 mg/day), rifampicin (300 mg/day), ethambutol (750 mg/day), pyrazinamide (1.0 g/day) and prednisolone (60 mg/day). However, he lost consciousness because of hydrocephalus on the second day of hospitalization. Emergency cerebrospinal fluid drainage improved his neurological symptoms. After two months, he again complained of headache with nausea and double vision. Numerous tuberculomas were found not only in the cerebrum but also in the liver, the spleen and the retina. Recurrent hydrocephalus was treated with a V-P shunt, and combination therapy with four antituberculous agents was maintained for 18 months. He was discharged in a healthy condition, although a mild left facial palsy remained. In addition, we examined the inflammatory cytokine levels in both the CSF and the serum over the period of the patient's hospitalization. We concluded that the cytokine levels in the CSF may be associated with the progress and the prognosis of tuberculous meningitis.
    05/2003; 41(4):294-9.
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    ABSTRACT: We reported a 62-year-old woman had sensorimotor neuropathy with small cell lung carcinoma (SCLC) and anti-GM1 antibody. She was admitted with several months history of progressive numbness, walking disturbance and anorexia. Neurologic examination revealed severe numbness and deep sensory disturbance of extremities and body, and mild weakness of distal extremities. Deep tendon reflexes were absent. Her limbs were ataxic. Nerve conduction studies showed no sensory evoked responses. CSF protein was elevated. Sural nerve biopsy revealed severe loss of myelinated fibers and perivascular mononuclear cells surrounding the perineurial vessel. Vasculitic neuropathy was diagnosed, and prednisolone was started, with no benefit. In the clinical course, she developed cough attacks and was found the lymphnode swelling in the mediastinum and supraclavicular fossa, which was diagnosed SCLC. Although anti-Hu antibody were not detected, anti-GM1 antibody was positive. She was treated with intravenous immunoglobulin, with transient improvement. The rare case of the paraneoplastic peripheral neuropathy with SCLC and anti-GM1 antibody was reported.
    Rinsho shinkeigaku = Clinical neurology 10/2002; 42(9):878-80.
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    ABSTRACT: Cortical silent period (SP) of the limb muscles is thought to reflect the cortical excitability. However, the lingual SP has not been examined precisely even in normal subjects. We investigated SP in the tongue induced by transcranial magnetic stimulation (TMS) in 18 controls. Surface electrodes were placed on the lingual dorsum using a bipolar technique. A round coil (13.5 cm in outer diameter) connected with Magstim 200 stimulator was placed on the motor cortex of the tongue, and the intensity of the stimulation was increased stepwise to maximum. SP was detected in all subjects especially at the contralateral side to the stimulated side, without contamination of peripheral SP. The duration of SP depended on the stimulus intensity, while the degrees of muscle contraction did not influence SP. SP of the tongue showed similar characteristics to that of limb muscles. This suggests that SP of lingual muscles can be clinically useful for the evaluation of corticobulbar excitability.
    Journal of the Neurological Sciences 01/2002; 193(1):37-41. DOI:10.1016/S0022-510X(01)00647-5 · 2.47 Impact Factor
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    ABSTRACT: We describe a case of a 21-year-old man with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) who presented with hypoxic ventilatory depression. He had chronic hypoventilation, which was not explained by weakness of respiratory muscles. His hypercapnic ventilatory response was not impaired. In contrast, hypoxic ventilatory depression was observed in the isocapnic progressive hypoxic response test. After exposure to hypoxic conditions, his respiratory frequency decreased and tidal volume was unchanged. The hypoxic ventilatory depression was partially blocked by pretreatment with aminophylline. In conclusion, we need to be careful with patients with MELAS who are hypoxaemic because a vicious circle of hypoxia and hypoventilation can occur.
    Respirology 12/2001; 6(2):163 - 166. DOI:10.1046/j.1440-1843.2001.00318.x · 3.35 Impact Factor
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    ABSTRACT: We describe a case of a 21-year-old man with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) who presented with hypoxic ventilatory depression. He had chronic hypoventilation, which was not explained by weakness of respiratory muscles. His hypercapnic ventilatory response was not impaired. In contrast, hypoxic ventilatory depression was observed in the isocapnic progressive hypoxic response test. After exposure to hypoxic conditions, his respiratory frequency decreased and tidal volume was unchanged. The hypoxic ventilatory depression was partially blocked by pretreatment with aminophylline. In conclusion, we need to be careful with patients with MELAS who are hypoxaemic because a vicious circle of hypoxia and hypoventilation can occur.
    Respirology 07/2001; 6(2):163-6. · 3.35 Impact Factor
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    ABSTRACT: A 24-year-old woman presented with progressive muscle atrophy and weakness of the right upper extremity. Subsequently her weakness rapidly extended to the left upper extremity, neck and lower extremities. Neurological examination disclosed involvement of the lower motor neuron system. She died 7 months after the onset. There was neuronal loss and reactive gliosis in the anterior horns of the spinal cord and much less frequently in the motor cortex. Basophilic cytoplasmic inclusions were observed in the thalamus and brain stem as well as the upper and lower motor neurons. Ultrastructurally, the inclusions lacked a limiting membrane and consisted of a meshwork of filamentous structures associated with granules. The inclusions failed to react with antibodies against phosphorylated neurofilament or cystatin C. Most of the inclusions show no reaction with anti-ubiquitin antibody, however, a few inclusions show granular reaction product deposits with this antibody. The inclusions were not immunostained with antibodies against TGN46 and MG-160, markers of the trans-Golgi network and the medial cisternae of the Golgi apparatus, respectively, suggesting that they were not derived from the Golgi apparatus which was fragmented.
    Journal of the Neurological Sciences 07/2000; 176(2):109-13. DOI:10.1016/S0022-510X(00)00321-X · 2.47 Impact Factor

  • Journal of Cardiac Failure 09/1999; 5(3):55-55. DOI:10.1016/S1071-9164(99)91182-X · 3.05 Impact Factor
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    ABSTRACT: Type-1 hereditary motor and sensory neuropathy (HMSN I) is a slowly progressive disease resulting in distal muscle weakness with atrophy, and in sensory disturbance. Restrictive lung disease and respiratory muscle failure, common in many advanced neuromuscular disorders, is not a predominant feature of HMSN-I. Recently, there have been several reports of respiratory dysfunction in patients with HMSN I, complicated by diaphragmatic weakness. In five patients with HMSN I (3 men and 2 women, mean age 55.4 yrs), we measured spirometric variables, maximal inspiratory pressure, and maximal expiratory pressure, in both sitting and supine positions. We also studied phrenic nerve conduction by cutaneous stimulation at the posterior border of the sternocleidomastoid muscle. Four of five patients had low maximal inspiratory pressure and abnormally long phrenic nerve latency. Two patients showed evidence of a restrictive lung disorder and daytime alveolar hypoventilation. All-night polysomnography in those two patients revealed periodic decreases in arterial blood oxygen saturation, and episodes of central apnea. We conclude that diaphragmatic dysfunction is not rare in HMSN I, and that maximal inspiratory pressure and phrenic nerve conduction may be useful in the early detection of phrenic nerve involvement.
    Nihon Kyōbu Shikkan Gakkai zasshi 09/1996; 34(8):850-5.
  • H Aizawa · T Suzutani · O Yahara · R Gotoh · K Morita · H Minami · N Sasaki · K Tobise ·
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    ABSTRACT: Early diagnosis of neurological complications of varicella-zoster virus (VZV) is important because of its treatability. We performed polymerase chain reaction (PCR) to detect VZV-DNA from the cerebrospinal fluid (CSF) of a patient with myelopathy. A 69-year-old man developed sensory disturbances in the lower extremities and bladder-bowel disturbances, followed by cutaneous zoster on his left arm. Polymerase chain reaction was applied to identify the viral DNA in CSF. The increased antibody index of VZV and herpes simplex virus (HSV) in the CSF suggested intrathecal synthesis of IgG antibodies to these viruses. VZV-DNA was detected in the CSF by nested PCR, but neither HSV-1 nor HSV-2 DNA was detected in CSF. He was successfully treated with acyclovir and prednisolone. PCR may be a useful tool for the diagnosis of VZV myelopathy.
    Acta Neurologica Scandinavica 06/1996; 93(6):470-2. DOI:10.1111/j.1600-0404.1996.tb00028.x · 2.40 Impact Factor
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    ABSTRACT: A 52-year-old woman had a 14-year history of stridor attacks. Pulmonary function tests revealed reversible airway obstruction, and bronchial asthma was diagnosed. She also has bilateral ptosis, diplopia, and moderate weakness of all four limbs; a positive edrophonium test confirmed the diagnosis of myasthenia gravis. Although the parasympathetic system plays an important role in the regulation of bronchial tone, in this patient the edrophonium test did not provoke an asthmatic attack or exacerbate pulmonary function, except for increases in sputum production and in frequency of cough. The general weakness was usually worse in the afternoon. The decrease in grip strength and the shortening of arm elevation time also occurred after asthma attacks, which means that general muscle fatigue was caused by the work of breathing. Furthermore, dyspnea increased and pulmonary function worsened when an anti-cholinesterase inhibitor was discontinued, probably because of respiratory muscle weakness. Accordingly, the clinical status of bronchial asthma seemed to change in parallel with that of the myasthenia gravis.
    Nihon Kyōbu Shikkan Gakkai zasshi 05/1996; 34(4):449-53.

  • SEIBUTSU BUTSURI KAGAKU 01/1996; 40(1):13-20. DOI:10.2198/sbk.40.13

  • Journal of the Autonomic Nervous System 12/1995; 56(1):144-144. DOI:10.1016/0165-1838(96)80063-4