Osamu Fujino

Nippon Medical School, Tokyo, Tokyo-to, Japan

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Publications (59)69.97 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background:In acute encephalopathy, deterioration of the condition can be rapid and early intervention is essential to prevent progression of the disease. However, in the acute period, differentiating acute encephalopathy from febrile seizures is difficult. Thus, an early diagnostic marker has been sought to enable early intervention. Proton nuclear magnetic resonance ((1)H NMR) spectroscopy is used to study the chemical characteristics of biological fluids such as cerebrospinal fluid (CSF). The purpose of this study was to ascertain if pattern recognition of (1)H NMR spectra could differentiate CSF obtained from patients with acute encephalopathy and febrile seizures.Methods:CSF was obtained from patients with acute encephalopathy (n = 4), complex febrile seizures (n = 9) and simple febrile seizures (n = 9).Results:NMR spectra of CSF did not visually differ across the three groups. Spectral data were analyzed by partial least squares discriminant analysis and visualized by plotting the partial least squares scores of each sample. The three patient groups clustered separately on the plots.Conclusion:In this preliminary study, we were able to visualize different characteristics of CSF obtained from patients with acute encephalopathy and simple and complex febrile seizures using pattern recognition analysis of (1)H NMR data.Pediatric Research (2014); doi:10.1038/pr.2014.141.
    Pediatric research. 09/2014;
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    ABSTRACT: We have reported that about half of children with chronic non-specific complaints were positive for antinuclear antibodies (ANA) and that the commonest complaint was fatigue in ANA-positive patients. Therefore, we have proposed a novel disease entity of autoimmune fatigue syndrome (AIFS). In order to investigate the relationship between AIFS and chronic fatigue syndrome (CFS) in children, all CFS patients seen in our clinic were immunologically assessed. Immunological examinations including ANA, autoantibody analysis by Western immunoblotting, lymphocyte subsets and NK activities were performed on 14 CFS patients. Clinical courses of these patients were reviewed retrospectively. None of the patients had fulfilled the CDC criteria for CFS at their first visit. They fulfilled the criteria in a relatively short time, with a 6 months to 6 years smoldering period. All patients had been diagnosed as school refusal by physicians or school teachers. Thirteen patients were positive for ANA and the other one was positive for rheumatoid factor. Twelve patients were positive for antibodies to the 62 kDa protein (anti-Sa) which had been detected in about 40% of AIFS patients. NK activity was not as low as reported in adult patients with CFS. Most of the children with CFS were positive for ANA, suggesting an autoimmune mechanism may play an important role in the pathogenesis of childhood CFS. AIFS patients should be carefully followed because of the possibility of later development of CFS.
    Modern Rheumatology 01/2014; 8(4):429-437. · 1.72 Impact Factor
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    ABSTRACT: We report on a 14-year-old girl with hydrocephalus that underwent spontaneous regression without any specific treatment, such as ventriculoperitoneal shunt surgery. A 14-year-old girl was referred to our hospital with severe headache, dizziness, nausea, and vomiting. Computed tomography and FLAIR-MRI findings on admission showed markedly dilated lateral, third and fourth ventricles with periventricular hyperintensity and downward displacement of the tonsils induced by dilatation of the fourth ventricle. We diagnosed hydrocephalus of unknown etiology. Although no specific treatment for hydrocephalus was performed, the symptoms gradually improved. One year after onset, the patient was completely free of neurological symptoms, and findings of physical examination and magnetic resonance imaging of the brain had returned to normal. The etiology of the spontaneous regression is unclear, but the following mechanisms are discussed: 1) rupture of ventricular diverticulum, 2) head injury causing skull-base fracture with leakage of cerebrospinal fluid, 3) extremely radiosensitive neoplasms diminished by X-p exploration, and 4) cerebrospinal fluid leakage due to lumbar puncture.
    01/2014; 81(5):337-9.
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    ABSTRACT: L-asparaginase (L-Asp) is an important reagent for acute lymphoblastic leukemia because asparagine is required for the malignant growth of tumor cells, especially lymphoblastic leukemia cells. An allergic response to L-Asp is not unusual because L-Asp is derived from Escherichia coli and is often recognized as a foreign protein. The hypersensitivity induced by L-Asp is of the immediate type in most cases. We report on a 5-year-old girl who was hospitalized for precursor T-cell lymphoblastic leukemia. She was treated according to a Tokyo Children's Cancer Study Group protocol (TCCSG ALL L09-1603 HEX/BFM). During the intensification phase, blisters with erythema developed on the arm proximal to the catheter insertion site owing to a delayed-type hypersensitivity reaction caused by intravenous L-Asp administration. She was treated with additional methylprednisolone, tapered dexamethasone, and an antihistamine for the allergic reaction. No asparaginases other than E. coli L-Asp have been approved for use in Japan. Other asparaginases, such as polyethylene glycol L-Asp and Erwinia L-Asp should be quickly approved for use as alternative chemotherapy reagents in Japan.
    Journal of Nippon Medical School 01/2012; 79(6):489-93.
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    ABSTRACT: Acute encephalopathy includes rapid deterioration and has a poor prognosis. Early intervention is essential to prevent progression of the disease and subsequent neurologic complications. However, in the acute period, true encephalopathy cannot easily be differentiated from febrile seizures, especially febrile seizures of the complex type. Thus, an early diagnostic marker has been sought in order to enable early intervention. The purpose of this study was to identify a novel marker candidate protein differentially expressed in the cerebrospinal fluid (CSF) of children with encephalopathy using proteomic analysis. For detection of biomarkers, CSF samples were obtained from 13 children with acute encephalopathy and 42 children with febrile seizure. Mass spectral data were generated by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) technology, which is currently applied in many fields of biological and medical sciences. Diagnosis was made by at least two pediatric neurologists based on the clinical findings and routine examinations. All specimens were collected for diagnostic tests and the remaining portion of the specimens were used for the SELDI-TOF MS investigations. In experiment 1, CSF from patients with febrile seizures (n = 28), patients with encephalopathy (n = 8) (including influenza encephalopathy (n = 3), encephalopathy due to rotavirus (n = 1), human herpes virus 6 (n = 1)) were used for the SELDI analysis. In experiment 2, SELDI analysis was performed on CSF from a second set of febrile seizure patients (n = 14) and encephalopathy patients (n = 5). We found that the peak with an m/z of 4810 contributed the most to the separation of the two groups. After purification and identification of the 4.8-kDa protein, a 4.8-kDa proteolytic peptide fragment from the neurosecretory protein VGF precursor (VGF4.8) was identified as a novel biomarker for encephalopathy. Expression of VGF4.8 has been reported to be decreased in pathologically degenerative changes such as Alzheimer's disease, amyotrophic lateral sclerosis (ALS), frontotemporal dementia, and encephalopathy. Thus, the VGF4.8 peptide might be a novel marker for degenerative brain conditions.
    BMC Neurology 08/2011; 11:101. · 2.56 Impact Factor
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    ABSTRACT: The present study aimed to elucidate the possible role of High Mobility Group Box 1 (HMGB1), which is a candidate prognostic marker in diseases that combine inflammation and tissue injury, in acute encephalopathy. HMGB1 in cerebrospinal fluid (CSF) obtained on admission from eight children with acute encephalopathy, and 16 children with febrile seizure, eight children with bacterial/aseptic meningitis, and eight children with fever without neurological symptoms were analyzed using enzyme-linked immunosorbent assay (ELISA). We found no increase in HMGB1 in CSF from acute encephalopathy or in CSF from febrile seizure or fever without neurological complications at early time points, while marked elevation of HMGB1 was seen in CSF from bacterial and aseptic meningitis. In conclusion, HMGB1 is a poor disease marker for acute encephalopathy.
    The International journal of neuroscience 06/2011; 121(8):480-4. · 0.86 Impact Factor
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    ABSTRACT:   The mumps virus is frequently the causative agent in aseptic meningitis and mumps has still prevailed in Japan. We compared data obtained from patients with mumps meningitis and patients with aseptic meningitis caused by other viruses in order to identify mumps meningitis-specific cytokine/chemokine alterations in cerebrospinal fluid (CSF).   We elucidated the cytokine/chemokine network based on the cytokine/chemokine profiles in CSF from children with mumps meningitis and meningitis due to other viral infections using multiplex cytokine measurement. Seventeen cytokines/chemokines, namely interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, granulocyte colony-stimulating factor (G-CSF), granulocyte monocyte colony-stimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1β (MIP-1β), were measured simultaneously in CSF supernatants from eight children with mumps meningitis, 11 children with other types of viral meningitis and eight children with fever without neurological complications such as convulsion.   We found that IL-8, IL-10, IL-12, IL-13 and IFN-γ showed a statistically significant increase in CSF from mumps meningitis when compared to other types of viral meningitis and fever without neurological complications.   Mumps meningitis may induce a distinct immunological response when compared with other types of viral meningitis.
    Pediatrics International 04/2011; 53(2):143-6. · 0.88 Impact Factor
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    ABSTRACT: Bacterial meningitis is characterized by a marked predominance of polymorphonuclear leukocytes (PMNs: segmented granulocytes or neutrophils) in the cerebrospinal fluid (CSF), whereas aseptic meningitis is characterized by a predominance of mononuclear leukocytes (MNs: lymphocytes or monocytes). However, the pathophysiology of this predominance of PMNs in the CSF of patients with bacterial meningitis has never, to our knowledge, been clearly described. To investigate the predominant cell components of CSF from pediatric patients with bacterial meningitis, we investigated cell death in association with levels of tumor necrosis factor-alpha (TNF-α) in the CSF, using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay and flow cytometry. The MTT assay of the CSF revealed that the PMNs had survived, while the MNs rapidly had undergone cell death. Although PMNs survived in CSF with high levels of TNF-α, PMN apoptosis was demonstrated with flow cytometry. The present study suggests that the pathophysiology of PMN predominance in the CSF of patients in the acute phase of bacterial meningitis is related to the rapid cell death of MNs and the survival of PMNs brought about by high levels of TNF-α.
    Journal of Nippon Medical School 01/2011; 78(6):360-6.
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    ABSTRACT: Cat-scratch disease is the most common form of Bartonella henselae infection. Although reports have shown that CSD is relatively common, they have not shown the prevalence of seropositivity for Bartonella henselae in cases of cervical lymphadenitis and Kawasaki disease, which are relatively common diseases in children. We evaluated the presence of immunoglobulin (Ig) G- and IgM-class antibodies against Bartonella henselae in children with cervical lymphadenitis, Kawasaki disease, and infectious diseases without lymphadenopathy in a semi-rural area in Japan. We found that the positivity rate for the IgG antibody against Bartonella henselae in patients with cervical lymphadenitis who owned cats or dogs was significantly higher than that in patients with Kawasaki disease and infectious diseases without lymphadenopathy. However, the average age of children with cervical lymphadenitis did not significantly differ when compared to those with other infectious diseases. Our serological study showed that Bartonella henselae infection may contribute to the etiology of cervical lymphadenitis in children.
    Pediatrics International 08/2010; 52(4):533-5. · 0.88 Impact Factor
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    ABSTRACT: We identify possible differences in the cytokine/chemokine profiles in cerebrospinal fluid (CSF) from children with encephalopathy and febrile seizure. Interleukin (IL)-1beta, 2, 4, 5, 6, 7, 8, 10, 12, 13, 17, interferon-gamma, tumour necrosis factor-alpha, granulocyte colony-stimulating factor, granulocyte monocyte colony-stimulating factor, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1beta were measured simultaneously in CSF supernatants from children with encephalopathy (n = 8), febrile seizure (n = 16) and fever without neurological complications (n = 8). IL-8 in CSF from children with encephalopathy was significantly elevated compared to that in CSF from children with febrile seizure and fever without neurological complications. IL-8 in CSF was also higher than serum IL-8, suggesting that increased IL-8 was generated from glia cells or astrocytes, not by leakage from serum. Increased IL-8 in CSF in encephalopathy may protect against severe brain damage.
    Scandinavian Journal of Immunology 06/2010; 71(6):447-51. · 2.20 Impact Factor
  • Pediatrics International 04/2010; 52(2):e98-e100. · 0.88 Impact Factor
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    ABSTRACT: Bacterial meningitis has a poor prognosis and neurologic complications. The present study aimed to investigate the cytokine/chemokine network in cerebrospinal fluid (CSF) from children with bacterial meningitis and aseptic meningitis. Interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, interferon-gamma, tumor necrosis factor-alpha, granulocyte colony-stimulating factor, granulocyte monocyte colony-stimulating factor, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1beta, were measured simultaneously in CSF supernatants. We found that, IL-17 was significantly elevated in CSF with bacterial meningitis. We believe that IL-17 plays a key role in neutrophil infiltration into CSF and neuronal protection in bacterial meningitis.
    Cytokine 03/2010; 51(1):101-6. · 2.52 Impact Factor
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    ABSTRACT: Fungal spondylodiskitis (inflammation of intervertebral disk tissue and adjacent vertebrae) is rare, particularly in immunocompetent patients. Here, we report a case of fungal and bacterial thoracic spondylodiskitis in a 14-year-old girl with abdominal and back pain. The spondylodiskitis was diagnosed on the basis of the presence of beta-D glucan and the unusual clinical course, although cultures for fungus were negative. We conclude spondylodiskitis must be considered in cases of abdominal pain without clear etiology and in cases of fungal infection with unexplainable findings after standard treatment for bacterial infection, even when fungal cultures are negative.
    Journal of Nippon Medical School 10/2009; 76(5):265-7.
  • Acta Paediatrica 10/2009; 99(2):164-5. · 1.97 Impact Factor
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    ABSTRACT: Although anemia frequently occurs in poststreptococcal acute glomerulonephritis (PSAGN), severe anemia is rare. We report severe normocytic, normochromic anemia (hematocrit, 19.8%) in PSAGN in a 6-year-old girl with edema, macrohematuria, and proteinuria for 1 month. The potential causes of severe anemia found in this case were: 1) longer duration of massive hematuria from onset of macrohemauria to treatment, 2) a level of erythropoietin much lower than that in cases of iron deficiency anemia, and 3) hemodilution. We speculate that these factors combined to cause an unusual case of severe anemia in PSAGN.
    Journal of Nippon Medical School 10/2009; 76(5):272-4.
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    ABSTRACT: We report an 8-year-old boy with left vertebral artery dissection featuring cerebellar ataxia in which congenital vertebral artery hypoplasia was suspected as a predisposing factor in the dissection. The patient suddenly suffered from vertigo and vomiting while swimming, and he was brought to our department. The initial brain Computed Tomography (CT) demonstrated no abnormalities, and his symptoms disappeared the next morning. However, one month after onset, brain Magnetic Resonance Imaging (MRI) revealed ischemic changes (infarction) in the left cerebellum. Transfemoral angiography showed complete occlusion at the C2 portion of the left vertebral artery, suggesting dissection and diffuse narrowing of the proximal segment of the occlusion site. Three-dimensional CT angiography also revealed diffuse narrowing of the left vertebral artery from the bifurcation of the subclavian artery. He has since been living daily life without any difficulties. The detailed etiology of cerebral artery dissection remains unknown, but arterial anomalies should be considered as a predisposing factor.
    Brain & development 09/2008; 31(4):326-30. · 1.74 Impact Factor
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    ABSTRACT: Pancreatitis represents an extremely rare complication of typhoid fever. Herein we report the case of a 4-year-old Bangladeshi girl with acute pancreatitis caused by Salmonella typhi.
    Pediatrics International 01/2008; 49(6):1004-6. · 0.88 Impact Factor
  • European Journal of Pediatrics 11/2007; 166(10):1065-6. · 1.98 Impact Factor
  • Pediatrics International 07/2007; 49(3):392-4. · 0.88 Impact Factor
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    ABSTRACT: We describe our treatment of two boys with continuous spikes and waves during slow wave sleep (CSWS). One of the boys was suffering from non-convulsive status epilepticus and the other from conscious disturbance with automatism. Their ictal EEG readings showed continuous diffuse spike and wave complexes, which were considered to show electrical status. The boys were diagnosed as having CSWS, and were later diagnosed with Landau-Kleffner syndrome (LKS). EEG readings returned to normal on intravenous injection of flunitazepam (FZP) at a dose of 0.02 mg/kg, suggesting that FZP is an effective treatment for CSWS.
    Seizure 04/2007; 16(2):190-2. · 2.00 Impact Factor

Publication Stats

126 Citations
69.97 Total Impact Points


  • 1991–2014
    • Nippon Medical School
      • Department of Pediatrics
      Tokyo, Tokyo-to, Japan
  • 2004–2005
    • National Hospital Organization Sagamihara Hospital
      Sagamihara, Kanagawa, Japan
  • 2003
    • Tokyo University of Science
      • Department of Pharmaceutical Sciences
      Edo, Tōkyō, Japan