Tatsuro Mutoh

Publications (79) View all

• Article: Potential therapeutic system for Alzheimer's disease: removal of blood Aβs by hemodialzyers and its effect on the cognitive functions of renal-failure patients.

  Masao Kato, Kazunori Kawaguchi, Sigeru Nakai, Kazutaka Murakami, Hideo Hori, Atsushi Ohashi, Yoshiyuki Hiki, Shinji Ito, Yasunobu Shimano, Nobuo Suzuki, Satoshi Sugiyama, Hiroshi Ogawa, Hiroko Kusimoto, Tatsuro Mutoh, Yukio Yuzawa, Nobuya Kitaguchi
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  ABSTRACT: The pathological changes of Alzheimer's disease include the deposition of amyloid β protein (Aβ) as senile plaques in the brain. We hypothesized that the rapid removal of Aβs from the blood may act as a peripheral Aβ drainage sink from the brain. In this study, the plasma Aβ concentrations and the cognitive functions were investigated for in 57 patients on hemodailysis (69.4 ± 3.8 years), 26 renal-failure patients without hemodialysis (66.6 ± 14.7 years), and 17 age-matched healthy controls (66.6 ± 4.1 years). The concentrations of plasma Aβs increased along with the decline of renal functions. Moreover, the renal-failure patients without hemodialysis and with poorer renal functions showed lower cognitive functions. The plasma concentrations of Aβ(1-42) correlated with serum creatinine (P < 0.001) and Mini-Mental-State Examination scores (P = 0.017). The dialyzers effectively removed Aβs in the blood during hemodialysis sessions. The plasma Aβ concentrations showed steady or slightly decreasing along with duration of hemodialysis. The total amount of Aβs removed during a hemodialysis session was calculated to be comparable to the Aβs dissolved in the blood and the cerebrospinal fluid. The MMSE scores of the hemodialysis patients showed no clear decrease in longer hemodialysis duration. Therefore, the therapeutic approach for Alzheimer's disease by removing Aβs from the blood is worthy of further investigation, including whether or not Aβs in the brain decrease.
  Acta Neurovegetativa 06/2012; · 2.73 Impact Factor
• Article: Winged scapula in patients with myotonic dystrophy type 1.

  Tadanori Hamano, Tatsuro Mutoh, Mikio Hirayama, Hidemasa Uematsu, Itsuro Higuchi, Hiroshi Koga, Fujio Umehara, Kiyonobu Komai, Masaru Kuriyama
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  ABSTRACT: We report two patients with myotonic dystrophy type 1 (DM1) showing winged scapula in a single family. Genomic analysis revealed a marked expansion of CTG repeats in the 3' untranslated region; 1100 in patient 1 and 667 in patient 2. Muscle MRI revealed marked atrophy in the serratus anterior muscle in both patients. Muscle biopsy findings showed central nuclei and variations in fiber size. One of the patients showed ragged red fibers in muscles of the biceps brachii. To our knowledge, this is the first report of typical winged scapula in DM1.
  Neuromuscular Disorders 06/2012; 22(8):755-8. · 2.80 Impact Factor
• Article: Novel therapeutic approach for Alzheimer’s disease by removing amyloid β protein from the brain with an extracorporeal removal system

  Kazunori Kawaguchi, Nobuya Kitaguchi, Shigeru Nakai, Kazutaka Murakami, Kunihiko Asakura, Tatsuro Mutoh, Yoshiro Fujita, Satoshi Sugiyama
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  ABSTRACT: The accumulation of amyloid beta (Aβ) protein in the brain reflects the cognitive impairment noted in Alzheimer’s disease. Recent studies have shown that brain Aβ disappeared and cognitive improvement occurred as a result of passive or active Aβ immunization. Peripheral administration of nonimmunization substances, such as GM1 ganglioside, also reduced brain Aβ. Therefore, we hypothesized that the rapid removal of Aβ from the blood by an extracorporeal system may act as a peripheral Aβ sink from the brain. In the present study, we investigated the Aβ removal activity of medical materials as a first step toward the design of an Aβ removal system. First, the removal activities of six materials were studied for Aβ1–40 and Aβ1–42 by batch analysis in albumin solution or in human plasma for 1–16h. Two of the six materials reduced the Aβ concentrations by 90–99% within 1h. Next, the two effective materials, hexadecyl-alkylated cellulose particles (HDC) and charcoal, were analyzed in a continuous single-pass system with minicolumns. Both materials showed around 81–90% removal activity for more than 2h, which corresponded to over 4l of plasma treatment in humans. In a human extracorporeal system, HDC also removed both Aβ1–40 and Aβ1–42 from whole blood circulation. In conclusion, biomedical materials were found that could remove Aβ1–40 and Aβ1–42 effectively in an extracorporeal system. It is now conceivable that further studies can be undertaken to reduce Aβ concentrations in the brain to improve cognitive function. KeywordsAlzheimer’s disease-Amyloid beta-Extracorporeal circulation-Adsorbent-Blood purification
  Journal of Artificial Organs 04/2012; 13(1):31-37. · 1.59 Impact Factor
• Article: Abnormal cross-talk between mutant presenilin 1 (I143T, G384A) and glycosphingolipid biosynthesis.

  Tatsuro Mutoh, Naoki Kawamura, Yoshio Hirabayashi, Sayuri Shima, Tadayuki Miyashita, Shinji Ito, Kunihiko Asakura, Wataru Araki, Emanuela Cazzaniga, Eri Muto, Massimo Masserini
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  ABSTRACT: Mutations in the presenilin 1 (PS1) gene are associated with early onset familial Alzheimer's disease (FAD). In this study, we found that the expression of mutant-PS1 in stable transfectants of SH-SY5Y neuroblastoma cells results in a reduction of the biosynthesis and steady-state levels of glucosylceramide. As an in vivo corroboration of these data, there was a significant reduction of brain glucosylceramide and gangliosides in an animal model of FAD. In mutant-PS1-transfectants (I143T, G384A), immunocytochemistry disclosed a remarkable reduction of glucosylceramide synthase (GlcT-1)-like immunoreactivity in the cells when compared with those of mock- and wild-PS1 transfectants. Immunoprecipitation of GlcT-1 protein from mutant-PS1 transfectants demonstrated a marked reduction in GlcT-1 protein, but there was no reduction in the levels of GlcT-1 mRNA. Both coprecipitation and γ-secretase inhibition experiments suggest that mutant-PS1 seems to form a complex with GlcT-1 protein and to be involved in GlcT-1 degradation, which was never found in other cell types. Thus, mutations in the PS1 gene result in profound glycosphingolipids abnormalities by abnormal molecular interaction with GlcT-1.
  The FASEB Journal 04/2012; 26(7):3065-74. · 5.71 Impact Factor
• Article: [Glycobiology and neurological disorders].

  Tatsuro Mutoh
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  ABSTRACT: Many researchers now recognize the importance of glycobiological research achievements. Glycoside-containing substances such as proteins (glycoproteins) and lipids (glycosphingolipids) have been involved in many important and essential events for normal life. The production of glycoside residues of the proteins is only partially regulated by the genes. In this talk, I will make a brief description of what glycobiology can influence the future of neurological research arena and how glycoproteins and glycolipids affect the normal biology of the neurons. Furthermore, I will introduce you some evidences that many neurological disorders such as Alzheimer's disease and immune-mediated encephalitis have special relationships with glycobiological abnormalities. I also explain the structures and functions of lipid rafts, caveolae, and glycosynapse and their roles in the intracellular signal transduction and cell motility.
  Rinshō shinkeigaku = Clinical neurology. 11/2011; 51(11):849-52.