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  1. Article ; Online: mTORC1 signaling in primary central nervous system lymphoma

    Naoki Nitta / Satoshi Nakasu / Ayako Shima / Kazuhiko Nozaki

    Surgical Neurology International, Vol 7, Iss 18, Pp 475-

    2016  Volume 480

    Abstract: Background: Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) acts as a downstream effector of phosphatidyl-inositol-3 kinase, which is frequently hyperactivated in glioblastoma multiforme and links to cell signaling in cellular proliferation, ... ...

    Abstract Background: Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) acts as a downstream effector of phosphatidyl-inositol-3 kinase, which is frequently hyperactivated in glioblastoma multiforme and links to cell signaling in cellular proliferation, differentiation, metabolism, and survival. Although many studies have suggested the importance of mTORC1 in tumorigenesis, its role remains unclear in brain tumors other than glioblastoma. Methods: In the present study, we evaluated the activation of mTORC1 in 24 cases of primary central nervous system lymphoma (PCNSL). Results: Immunohistochemical analysis showed overexpression of Rheb, which is immediately upstream of mTORC1, in 20 cases of PCNSL. Immunohistochemical analysis also showed overexpression of phospho-4E-BP1 (Thr37/46) and phospho-S6 (Ser235/236), which are increased after mTORC1 activation as mTORC1 downstream effectors in 17 and 21 cases, respectively. Conclusion: Our data suggest that abnormal activation of the mTORC1 signaling pathway may cause tumor growth in patients with PCNSL.
    Keywords mTOR ; phospho-4E-BP1 ; phospho-S6 ; primary central nervous system lymphoma ; Rheb ; Medicine ; R ; Surgery ; RD1-811 ; Internal medicine ; RC31-1245 ; Neurosciences. Biological psychiatry. Neuropsychiatry ; RC321-571 ; Neurology. Diseases of the nervous system ; RC346-429
    Subject code 570
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Medknow Publications
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Straight sinus thrombosis during neurosurgical operation

    Hiroto Kawano / Naoki Nitta / Kazuhiko Nozaki

    Surgical Neurology International, Vol 7, Iss 1, Pp 50-

    2016  Volume 50

    Abstract: Background: Perioperative straight sinus thrombosis is extremely rare. Case Description: A 59-year-old female was admitted to our department because of incidentally found small anterior cerebral artery (A1) aneurysm with microbleeding. After clipping the ...

    Abstract Background: Perioperative straight sinus thrombosis is extremely rare. Case Description: A 59-year-old female was admitted to our department because of incidentally found small anterior cerebral artery (A1) aneurysm with microbleeding. After clipping the cerebral aneurysm, she had delayed emergence from anesthesia, total aphasia, and right hemiparesis. Fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) of the head showed hyperintensity in the bilateral caudate nuclei, putamina, and thalami, and computed tomography of the head showed a hyperdense straight sinus, suggesting straight sinus thrombosis. Her neurologic symptoms improved gradually, and she achieved a full clinical recovery, with radiological evidence of recanalization of the straight sinus at follow-up. Conclusion: The possibility of straight sinus thrombosis should be considered in postoperative patients with unexplained postoperative deficits when MRI demonstrates hyperintensity in the bilateral basal ganglia and thalami on FLAIR signal images.
    Keywords Basal ganglia ; bilateral ; postoperative ; straight sinus thrombosis ; thalamus ; Medicine ; R ; Surgery ; RD1-811 ; Internal medicine ; RC31-1245 ; Neurosciences. Biological psychiatry. Neuropsychiatry ; RC321-571 ; Neurology. Diseases of the nervous system ; RC346-429
    Subject code 610
    Publishing date 2016-01-01T00:00:00Z
    Publisher Medknow Publications
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Recurrent subdural hematoma secondary to headbanging

    Naoki Nitta / Junya Jito / Kazuhiko Nozaki

    Surgical Neurology International, Vol 6, Iss 19, Pp 448-

    A case report

    2015  Volume 450

    Abstract: Background: "Headbanging" is the slang term used to denote violent shaking of one′s head in time with the music. This abrupt flexion-extension movement of the head to rock music extremely rarely causes a subdural hematoma. Case Description: A 24-year-old ...

    Abstract Background: "Headbanging" is the slang term used to denote violent shaking of one′s head in time with the music. This abrupt flexion-extension movement of the head to rock music extremely rarely causes a subdural hematoma. Case Description: A 24-year-old female was admitted to our department because of right sided partial seizure and acute or subacute subdural hematoma over the left cerebral convexity. She had no history of recent head trauma but performed headbanging at a punk rock concert at 3 days before admission. Since, she had a previous acute subdural hematoma on the same side after an accidental fall from a baby buggy when she was 11 months old, the present was recurrent subdural hematoma probably due to headbanging. Conclusions: Headbanging has the hazardous potential to cause a subdural hematoma.
    Keywords Headbanging ; punk rock ; recurrence ; subdural hematoma ; Medicine ; R ; Surgery ; RD1-811 ; Internal medicine ; RC31-1245 ; Neurosciences. Biological psychiatry. Neuropsychiatry ; RC321-571 ; Neurology. Diseases of the nervous system ; RC346-429
    Subject code 780
    Publishing date 2015-01-01T00:00:00Z
    Publisher Medknow Publications
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Primary pericranial Ewing′s sarcoma on the temporal bone

    Hiroto Kawano / Naoki Nitta / Mitsuaki Ishida / Tadateru Fukami / Kazuhiko Nozaki

    Surgical Neurology International, Vol 7, Iss 16, Pp 444-

    A case report

    2016  Volume 448

    Abstract: Background: Primary Ewing′s sarcoma originating in the pericranium is an extremely rare disease entity. Case Description: A 9-year-old female patient was admitted to our department due to a left temporal subcutaneous mass. The mass was localized under ... ...

    Abstract Background: Primary Ewing′s sarcoma originating in the pericranium is an extremely rare disease entity. Case Description: A 9-year-old female patient was admitted to our department due to a left temporal subcutaneous mass. The mass was localized under the left temporal muscle and attached to the surface of the temporal bone. Head computed tomography revealed a mass with bony spicule formation on the temporal bone, however, it did not show bone destruction or intracranial invasion. F-18 fluorodeoxyglucose positron emission tomography showed no lesions other than the mass on the temporal bone. Magnetic resonance imaging showed that the mass was located between the temporal bone and the pericranium. The mass was completely resected with the underlying temporal bone and the overlying deep layer of temporal muscle, and was diagnosed as primary Ewing′s sarcoma. Because the tumor was located in the subpericranium, we created a new classification, "pericranial Ewing′s sarcoma," and diagnosed the present tumor as pericranial Ewing′s sarcoma. Conclusion: We herein present an extremely rare case of primary pericranial Ewing′s sarcoma that developed on the temporal bone.
    Keywords Ewing′s sarcoma ; pericranium ; skull ; temporal bone ; Medicine ; R ; Surgery ; RD1-811 ; Internal medicine ; RC31-1245 ; Neurosciences. Biological psychiatry. Neuropsychiatry ; RC321-571 ; Neurology. Diseases of the nervous system ; RC346-429
    Subject code 616
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Medknow Publications
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Statins as a Candidate of Drugs for Intracranial Aneurysm Treatment

    Keiichi Tsuji / Tomohiro Aoki / Miyuki Fukuda / Kazuhiko Nozaki

    Health, Vol 06, Iss 12, Pp 1459-

    2014  Volume 1466

    Abstract: The treatment for intracranial aneurysm (IA) is socially important because of poor outcome posed by subarachnoid hemorrhage after rupture. Further, the incidence of IAs in general public is high and, indeed, in developed countries many IAs are ... ...

    Abstract The treatment for intracranial aneurysm (IA) is socially important because of poor outcome posed by subarachnoid hemorrhage after rupture. Further, the incidence of IAs in general public is high and, indeed, in developed countries many IAs are incidentally found through brain check. However, to date, options for treatment of IAs to prevent rupture are quite limited only to surgical procedures such as microsurgical clipping and endovascular coiling. Taking into account unavoidable risks of complication from surgical interventions and numerous aneurysm careers without treatment, less invasive medical therapies should be established. In human IA lesions, the presence of inflammatory responses, such as expressions of pro-inflammatory mediators and infiltration of inflammatory cells, have been reported, which suggests the involvement of inflammatory responses in the pathogenesis of IA. Recent experimental studies using rodent models have revealed the crucial role of inflammatory responses mediated by NF- κ B activation in IA formation and progression and supported the notion that IA is an inflammatory disease affected intracranial arteries. To find out a candidate drug for IA treatments, the effect of several drugs with anti-inflammatory and anti-NF- κ B actions on IA progression has been examined using rodent models and revealed the excellent inhibitory effect of statins (HMG-CoA reductase inhibitors) on IA progression. Based on these findings, the case-control study was recently carried out enrolling patients with unruptured or ruptured IAs to examine the effect of statin usage on rupture. This study revealed the significant differences in the ratio of statin usage between two groups and notably the remarkable reduction of risk of rupture of pre-existing IAs under statin usage at the adjusted odds ratio of 0.30. Recent laboratory and clinical studies make considerable achievement toward the future development of drugs for IA treatment and especially suggest the potential of statins as a candidate.
    Keywords Inflammation ; Intracranial Aneurysm ; NF- κ B ; Statin ; Subarachnoid Hemorrhage ; Medicine (General) ; R5-920 ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2014-06-01T00:00:00Z
    Publisher Scientific Research Publishing
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Cerebral aneurysms and inflammation

    Toshihiro Yokoi / Makoto Saito / Yayoi Yoshimura / Keiichi Tsuji / Kazuhiko Nozaki

    Neuroimmunology and Neuroinflammation, Vol 2, Iss 2, Pp 55-

    2015  Volume 58

    Abstract: Multiple inflammatory factors, playing a crucial role in cerebral aneurysm formation, have been identified. tumor necrosis factor-alpha (TNF-α) has been revealed to have a close connection with several risk factors that affect aneurysm formation. ... ...

    Abstract Multiple inflammatory factors, playing a crucial role in cerebral aneurysm formation, have been identified. tumor necrosis factor-alpha (TNF-α) has been revealed to have a close connection with several risk factors that affect aneurysm formation. Remarkable expression in aneurysm walls of mRNA for TNF-α has been observed in humans. Possible therapeutic interventions to reduce the formation of cerebral aneurysms may include the inhibition of mediators of inflammation.
    Keywords Cerebral aneurysm ; inflammation ; molecular biology ; Neurosciences. Biological psychiatry. Neuropsychiatry ; RC321-571
    Language English
    Publishing date 2015-06-01T00:00:00Z
    Publisher Hongkong Partner Publishing Co. Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: T cell function is dispensable for intracranial aneurysm formation and progression.

    Haruka Miyata / Hirokazu Koseki / Katsumi Takizawa / Hidetoshi Kasuya / Kazuhiko Nozaki / Shuh Narumiya / Tomohiro Aoki

    PLoS ONE, Vol 12, Iss 4, p e

    2017  Volume 0175421

    Abstract: Given the social importance of intracranial aneurysm as a major cause of a lethal subarachnoid hemorrhage, clarification of mechanisms underlying the pathogenesis of this disease is essential for improving poor prognosis once after rupture. Previous ... ...

    Abstract Given the social importance of intracranial aneurysm as a major cause of a lethal subarachnoid hemorrhage, clarification of mechanisms underlying the pathogenesis of this disease is essential for improving poor prognosis once after rupture. Previous histopathological analyses of human aneurysm walls have revealed the presence of T cells in lesions suggesting involvement of this type of cell in the pathogenesis. However, it remains unclear whether T cell actively participates in intracranial aneurysm progression. To examine whether T cell is involved in aneurysm progression, intracranial aneurysm model of rat was used. In this model, aneurysm is induced by increase in hemodynamic force loaded on bifurcation site of intracranial arteries where aneurysms are developed. Deficiency in T cells and pharmacological inhibition of T cell function were applied to this model. CD3-positive T cells were present in human aneurysm walls, whose number was significantly larger compared with that in control arterial walls. Deficiency in T cells in rats and pharmacological inhibition of T cell function by oral administration of Cyclosporine A both failed to affect intracranial aneurysm progression, degenerative changes of arterial walls and macrophage infiltration in lesions. Although T cells are detectable in intracranial aneurysm walls, their function is dispensable for macrophage-mediated inflammation and degenerative changes in arterial walls, which presumably leads to intracranial aneurysm progression.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: RNA sequencing analysis revealed the induction of CCL3 expression in human intracranial aneurysms

    Tomohiro Aoki / Hirokazu Koseki / Haruka Miyata / Masayoshi Itoh / Hideya Kawaji / Katsumi Takizawa / Akitsugu Kawashima / Hiroshi Ujiie / Takashi Higa / Kenzo Minamimura / Toshikazu Kimura / Hidetoshi Kasuya / Kazuhiko Nozaki / Akio Morita / Hirotoshi Sano / Shuh Narumiya

    Scientific Reports, Vol 9, Iss 1, Pp 1-

    2019  Volume 8

    Abstract: Abstract Intracranial aneurysm (IA) is a socially important disease as a major cause of subarachnoid hemorrhage. Recent experimental studies mainly using animal models have revealed a crucial role of macrophage-mediated chronic inflammatory responses in ... ...

    Abstract Abstract Intracranial aneurysm (IA) is a socially important disease as a major cause of subarachnoid hemorrhage. Recent experimental studies mainly using animal models have revealed a crucial role of macrophage-mediated chronic inflammatory responses in its pathogenesis. However, as findings from comprehensive analysis of unruptured human IAs are limited, factors regulating progression and rupture of IAs in humans remain unclear. Using surgically dissected human unruptured IA lesions and control arterial walls, gene expression profiles were obtained by RNA sequence analysis. RNA sequencing analysis was done with read count about 60~100 million which yielded 6~10 billion bases per sample. 79 over-expressed and 329 under-expressed genes in IA lesions were identified. Through Gene Ontology analysis, ‘chemokine activity’, ‘defense response’ and ‘extracellular region’ were picked up as over-represented terms which included CCL3 and CCL4 in common. Among these genes, quantitative RT-PCR analysis using another set of samples reproduced the above result. Finally, increase of CCL3 protein compared with that in control arterial walls was clarified in IA lesions. Findings of the present study again highlight importance of macrophage recruitment via CCL3 in the pathogenesis of IA progression.
    Keywords Medicine ; R ; Science ; Q
    Subject code 572
    Language English
    Publishing date 2019-07-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Correction

    Yayoi Yoshimura / Akihiko Shiino / Kazue Muraki / Tadateru Fukami / Shigeki Yamada / Takeshi Satow / Miyuki Fukuda / Masaaki Saiki / Masato Hojo / Susumu Miyamoto / Nobuyuki Onishi / Hideyuki Saya / Toshiro Inubushi / Kazuhiko Nozaki / Kenji Tanigaki

    PLoS ONE, Vol 11, Iss 2, p e

    Arsenic Trioxide Sensitizes Glioblastoma to a Myc Inhibitor.

    2016  Volume 0149826

    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Arsenic trioxide sensitizes glioblastoma to a myc inhibitor.

    Yayoi Yoshimura / Akihiko Shiino / Kazue Muraki / Tadateru Fukami / Shigeki Yamada / Takeshi Satow / Miyuki Fukuda / Masaaki Saiki / Masato Hojo / Susumu Miyamoto / Nobuyuki Onishi / Hideyuki Saya / Toshiro Inubushi / Kazuhiko Nozaki / Kenji Tanigaki

    PLoS ONE, Vol 10, Iss 6, p e

    2015  Volume 0128288

    Abstract: Glioblastoma multiforme (GBM) is associated with high mortality due to infiltrative growth and recurrence. Median survival of the patients is less than 15 months, increasing requirements for new therapies. We found that both arsenic trioxide and 10058F4, ...

    Abstract Glioblastoma multiforme (GBM) is associated with high mortality due to infiltrative growth and recurrence. Median survival of the patients is less than 15 months, increasing requirements for new therapies. We found that both arsenic trioxide and 10058F4, an inhibitor of Myc, induced differentiation of cancer stem-like cells (CSC) of GBM and that arsenic trioxide drastically enhanced the anti-proliferative effect of 10058F4 but not apoptotic effects. EGFR-driven genetically engineered GBM mouse model showed that this cooperative effect is higher in EGFRvIII-expressing INK4a/Arf-/- neural stem cells (NSCs) than in control wild type NSCs. In addition, treatment of GBM CSC xenografts with arsenic trioxide and 10058F4 resulted in significant decrease in tumor growth and increased differentiation with concomitant decrease of proneural and mesenchymal GBM CSCs in vivo. Our study was the first to evaluate arsenic trioxide and 10058F4 interaction in GBM CSC differentiation and to assess new opportunities for arsenic trioxide and 10058F4 combination as a promising approach for future differentiation therapy of GBM.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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