Tokuhiro Kimura

Yamaguchi University, Yamaguti, Yamaguchi, Japan

Are you Tokuhiro Kimura?

Claim your profile

Publications (50)221.07 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Patent foramen ovale (PFO) can cause ischemic stroke because of paradoxical embolism. Autopsy studies have shown that the prevalence of PFO is 25% in whites or blacks. However, there is a paucity of data on the prevalence of PFO in Asians. The aim of this study was to clarify the prevalence of PFO in the Japanese population.Methods and Results:We reviewed 52,717 autopsy reports, which were collected and edited by the Japanese Society of Pathology from 2009 to 2012. Next, we inspected consecutive 103 formalin-fixed specimens that had already been examined by certified pathologists from 2009 to 2013 to find PFO and atrial septal aneurysm (ASA). ASA was defined as ≥10 mm protrusion of the septum into the left or the right atrium. In the database of the Japanese Society of Pathology, the incidence of PFO was 0.08% (43/52,717). Inspection of heart specimens disclosed that the prevalence of PFO was 13.6% (14/103). None of the PFO cases was reported at the original autopsy. PFO was more frequently found in the subjects with ASA (50%) than in those without ASA (9.7%) (P=0.004). PFO is under-reported in autopsy reports. Re-evaluation of heart specimens disclosed that theprevalence of PFO was 13.6%. The prevalence was lower than reported in the past.
    Circulation Journal 06/2015; DOI:10.1253/circj.CJ-15-0197 · 3.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Functional preservation is critical in glioma surgery, and the extent of resection influences survival outcome. Neoadjuvant chemotherapy is a promising option because of its potential to facilitate tumor shrinkage and maximum tumor resection. The object of this study was to assess the utility of the neoadjuvant strategy in a prospective series of gliomas with favorable molecular status. Twenty-six consecutive cases of diffuse gliomas of WHO grade II or III with either 1p19q codeletion or MGMT methylation were treated with upfront chemotherapy following maximal safe removal. In cases of incomplete initial surgery, second-look resection was intended after tumor volume decrease by chemotherapy. Among 22 evaluable cases, chemotherapy led to a median change in the sum of the product of perpendicular diameters of -35 %, and 14 out of the 22 cases (64 %) showed objective response. Second-look resection after tumor volume decrease was performed in 12 out of 19 cases of incomplete initial surgery (GTR/STR 9, removal of residual methionine PET uptake 3). The median progression-free survival among the 22 patients with grade II tumors was 57 months, with some cases showing durable progression-free survival after second-look resection. MIB-1 indices of the second-look resected tumors were lower than those of the initial tumors, and the methylation status of the MGMT gene was unchanged. Neoadjuvant chemotherapy based on molecular guidance often produces significant volume decrease of incompletely resected gliomas. Radical second-look resection is an optional advantage of upfront chemotherapy for chemosensitive gliomas compared with initial radiotherapy.
    Journal of Neuro-Oncology 05/2015; DOI:10.1007/s11060-015-1817-y · 2.79 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The prognostic significance of 1p19q loss in astrocytic gliomas has been inconclusive.We collected 57 gliomas with total 1p19q loss from among 218 cases of WHO grade-II/III gliomas operated at Keio University Hospital between 1990 and 2010. These tumors were classified as oligodendroglial or "astrocytic" by a WHO-criteria-based institutional diagnosis. Chromosomal copy number aberrations (CNAs), IDH 1/2 mutations, MGMT promoter methylation, and expression of p53 and ATRX were assessed. Survival outcome was compared between the two histological groups.Of the 57 codeleted gliomas, 37, 16, and four were classified as oligodendroglial, "astrocytic", and unclassified, respectively. Comparative genomic hybridization revealed that although chromosome 7q/7 gain was more frequent in "astrocytic" gliomas, other CNAs occurred at a similar frequency in both groups. None of the "astrocytic" gliomas showed p53 accumulation, and ATRX loss was found in three of the 15 "astrocytic" gliomas. The estimated overall survival (OS) curves in the patients with codeleted oligodendroglial and "astrocytic" gliomas overlapped, and the median OS was 187 and 184 months, respectively. Histopathological re-assessment by a single pathologist showed consistent results.Gliomas with total 1p19q loss with "astrocytic" features have molecular and biological characteristics comparable to those of oligodendroglial tumors.
    Oncotarget 05/2015; · 6.63 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective. ADAMTS4, also called aggrecanase-1, is considered to play a key role in aggrecan degradation in human osteoarthritic cartilage, but information about regulators of ADAMTS4 aggrecanase activity remains limited. We aimed to search for molecules that modulate ADAMTS4 activity. Methods. Molecules co-purified with ADAMTS4 from ADAMTS4-transfected chondrocytic cells were sequenced by nLC-MS/MS. Binding activity was determined by immunoprecipitation and solid-phase binding assay. Effects on ADAMTS4 activity were examined by aggrecan digestion assay. Expression of the binding molecule in osteoarthritic cartilage and chondrocytes was examined by immunohistochemistry and RT-PCR. Results. We identified CCN1 (Cyr61) as an ADAMTS4-binding protein and showed the specific binding to the ADAMTS4 cysteine-rich domain. Aggrecanase activity of ADAMTS4 was inhibited by interaction with CCN1. mRNA expression of CCN1 was significantly higher in human osteoarthritic cartilage than in normal cartilage. CCN1 was immunolocalized to chondrocytes in osteoarthritic cartilage, showing direct correlations of the immunoreactivity with Mankin score and chondrocyte cloning. CCN1 and ADAMTS4 were commonly co-expressed in clustered chondrocytes. CCN1 expression in osteoarthritic chondrocytes was down-regulated by IL-1α and up-regulated by TGF-β. ADAMTS4 expression was induced by treatment with IL-1α or TGF-β, but aggrecanase activity was detected only under the IL-1α stimulation. TGF-β-treated chondrocytes exhibited aggrecanase activity, when CCN1 expression was knocked down. Conclusion. Our findings provide the first evidence that CCN1 suppresses ADAMTS4 activity and is overexpressed with a direct correlation with chondrocyte cloning in osteoarthritic cartilage, and suggest that the TGF-β/CCN1 axis plays a role in chondrocyte cluster formation through inhibition of ADAMTS4. This article is protected by copyright. All rights reserved. © 2015 American College of Rheumatology.
    02/2015; 67(6). DOI:10.1002/art.39078
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Interleukin (IL)-23/Th17 axis plays an important role in the pathophysiology of asthma and eczema, however, there are some conflicting data about the effects of this system on allergic airway inflammation. In the present study, we aim to dissect the spatiotemporal differences in the roles of IL-23 in an epicutaneously-sensitized asthma model of mice. Methods: C57BL/6 mice were sensitized to ovalbumin (OVA) by patch application on the skin, followed by airway exposure to aerosolized OVA. During sensitization and/or challenge phase, either a specific neutralizing antibody (Ab) against IL-23 or control IgG was injected intraperitoneally. On days 1 and 8 after the final OVA exposure, airway inflammation and responsiveness to methacholine, immunoglobulin levels in serum, and cytokine release from splenocytes were evaluated. Skin Il23a mRNA levels were evaluated with quantitative RT-PCR. Results: Patch application time-dependently increased the expression of Il23a mRNA expression in the skin. Treatment with the anti-IL-23 Ab during sensitization phase alone significantly reduced the number of eosinophils in bronchoalveolar lavage fluids and peribronchial spaces after allergen challenge compared with treatment with control IgG. Anti-IL-23 Ab also reduced serum levels of OVA-specific IgG1. In contrast, treatment with the anti-IL-23 Ab during the challenge phase alone rather exacerbated airway hyperresponsiveness to methacholine with little effects on airway eosinophilia or serum IgG1 levels. Conclusions: IL-23 expressed in the skin during the sensitization phase plays an essential role in the development of allergic phenotypes, whereas IL-23 in the airways during the challenge phase suppresses airway hyperresponsiveness.
    Allergology International 05/2014; 63 Suppl 1(Supplement.1):13-22. DOI:10.2332/allergolint.13-OA-0632
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chordomas are invasive tumors that develop from notochordal remnants and frequently occur in the skull base. The T gene and its product (brachyury) have recently been suggested to play an important role in chordoma progression. To date, few studies have investigated the relationship between the molecular/genetic characteristics of chordoma and patient prognosis. We analyzed 37 skull base chordomas for chromosomal copy number aberrations using comparative genomic hybridization, brachyury expression by immunohistochemistry, and T gene copy number by fluorescence in situ hybridization. The results of these molecular analyses and clinical parameters were compared with the patients' clinical courses. Univariate analyses using the log-rank test demonstrated that losses on chromosome 1p and gains on 1q and 2p were negatively correlated with progression-free survival, as were factors such as female sex, partial tumor removal, lack of postoperative irradiation, and high MIB-1 index. Expression of brachyury and copy number gain of the T gene were also significantly associated with shorter progression-free survival. Multivariate analysis using the Cox hazards model showed that lack of irradiation, gain on chromosome 2p, and expression of brachyury were independently associated with a poor prognosis. Our results suggest that brachyury-negative chordomas are biologically distinct from brachyury-positive chordomas and that T/brachyury might be an appropriate molecular therapeutic target for chordoma.
    08/2013; DOI:10.1097/NEN.0b013e3182a065d0
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mycobacterial spindle cell pseudotumor (MSP) is a rare mass-forming lesion caused by mycobacterial infection, mostly in immunocompromised patients. Since it is composed of a proliferation of spindle-shaped fibrohistiocytic cells without forming epithelioid cell granulomas, histological distinction from other spindle cell lesions is often difficult and its pathophysiology is poorly understood. MSP arising in the nasal cavity is extremely rare, and only two cases have been reported previously. Here we report a case of MSP of the nasal cavity in an 83-year-old man with no evidence of immunodeficient state. The resected tumor consisted of spindle cells, which contained numerous acid-fast bacilli in the cytoplasm. By polymerase chain reaction and sequencing using DNA extracted from the paraffin sections, the bacilli were identified as Mycobacterium intracellulare. Immunohistochemistry revealed that the spindle cells were positive for CD68, CD11c and S100 protein, confirming the histiocytic nature of these cells. They were also positive for CD163 and CD204, suggesting that they showed a phenotype similar to alternatively activated (M2) macrophages and the phenotype might contribute to the maintenance of mycobacterial infection despite apparent immunocompetence of the host.
    Pathology International 05/2013; 63(5):266-271. DOI:10.1111/pin.12059 · 1.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: TNFα-converting enzyme (TACE) is a membrane-bound proteolytic enzyme with essential roles in the functional regulation of TNFα and epidermal growth factor receptor (EGFR) ligands. Previous studies have demonstrated critical roles for TACE in vivo, including epidermal development, immune response, and pathological neoangiogenesis, among others. However, the potential contribution of TACE to skeletal development is still unclear. In the present study, we generated a Tace mutant mouse in which Tace is conditionally disrupted in chondrocytes under the control of the Col2a1 promoter. These mutant mice were fertile and viable but all exhibited long bones that were approximately 10% shorter compared to those of wild-type animals. Histological analyses revealed that Tace mutant mice exhibited a longer hypertrophic zone in the growth plate, and there were fewer osteoclasts at the chondro-osseous junction in the Tace mutant mice than in their wild-type littermates. Of note, we found an increase in osteoprotegerin transcripts and a reduction in Rankl and Mmp-13 transcripts in the TACE-deficient cartilage, indicating that dysregulation of these genes is causally related to the skeletal defects in the Tace mutant mice. Furthermore, we also found that phosphorylation of EGFR was significantly reduced in the cartilage tissue lacking TACE, and that suppression of EGFR signaling increases osteoprotegerin transcripts and reduces Rankl and Mmp-13 transcripts in primary chondrocytes. In accordance, chondrocyte-specific abrogation of Egfr in vivo resulted in skeletal defects nearly identical to those observed in the Tace mutant mice. Taken together, these data suggest that TACE-EGFR signaling in chondrocytes is involved in the turnover of the growth plate during postnatal development via the transcriptional regulation of osteoprotegerin, Rankl, and Mmp-13.
    PLoS ONE 01/2013; 8(1):e54853. DOI:10.1371/journal.pone.0054853 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: TNFα-converting enzyme (TACE/ADAM17) is a membrane-bound proteolytic enzyme with a diverse set of target molecules. Most importantly, TACE is indispensable for the release and activation of pro-TNFα and the ligands for epidermal growth factor receptor in vivo. Previous studies suggested that the overproduction of TACE is causally related to the pathogenesis of inflammatory diseases and cancers. To test this hypothesis, we generated a transgenic line in which the transcription of exogenous Tace is driven by a CAG promoter. The Tace-transgenic mice were viable and exhibited no overt defects, and the quantitative RT-PCR and Western blot analyses confirmed that the transgenically introduced Tace gene was highly expressed in all of the tissues examined. The Tace-transgenic mice were further crossed with Tace(-/+) mice to abrogate the endogenous TACE expression, and the Tace-transgenic mice lacking endogenous Tace gene were also viable without any apparent defects. Furthermore, there was no difference in the serum TNFα levels after lipopolysaccharide injection between the transgenic mice and control littermates. These observations indicate that TACE activity is not necessarily dependent on transcriptional regulation and that excess TACE does not necessarily result in aberrant proteolytic activity in vivo.
    PLoS ONE 01/2013; 8(1):e54412. DOI:10.1371/journal.pone.0054412 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Coronary artery aneurysms are rare complications of autosomal dominant polycystic kidney disease (ADPKD), and their pathogenesis remains poorly understood. We report an autopsy case of a 64-year-old ADPKD patient with an asymptomatic, large (4 cm in diameter) saccular aneurysm arising from the left circumflex (LCX) branch of the coronary artery with only mild atherosclerotic changes. Autopsy also revealed small, focal defects of media with or without microaneurysm formation in the LCX, mesenteric and renal arteries, and a fibromuscular dysplasia-like lesion with microaneurysm in the common iliac artery. Since polycystin-1 and -2 are expressed in arterial smooth-muscle cells, these findings imply that abnormal polycystin expression in ADPKD initially causes the focal medial defects, some of which might later progress to microaneurysms and then overt aneurysms. To the best of our knowledge, this is the first description of the pathologic findings of an ADPKD-associated coronary aneurysm and its probable precursor lesions in arteries.
    Pathology International 11/2012; 62(11):758-62. DOI:10.1111/pin.12007 · 1.59 Impact Factor
  • Arthritis Research & Therapy 02/2012; 14(1). DOI:10.1186/ar3626 · 4.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies have revealed various extrinsic stimuli and factors involved in the regulation of hematopoiesis. Among these, Notch-mediated signaling has been suggested to be critically involved in this process. Herein, we show that conditional inactivation of ADAM10, a membrane-bound protease with a crucial role in Notch signaling (S2 cleavage), results in myeloproliferative disorder (MPD) highlighted by severe splenomegaly and increased populations of myeloid cells and hematopoietic stem cells. Reciprocal transfer of bone marrow cells between wild-type and ADAM10 mutant mice revealed that ADAM10 activity in both hematopoietic and nonhematopoietic cells is involved in the development of MPD. Notably, we found that MPD caused by lack of ADAM10 in nonhematopoietic cells was mediated by G-CSF, whereas MPD caused by ADAM10-deficient hematopoietic cells was not. Taken together, the present findings reveal previously undescribed nonredundant roles of cell-autonomous and non-cell-autonomous ADAM10 activity in the maintenance of hematopoiesis.
    Blood 12/2011; 118(26):6939-42. DOI:10.1182/blood-2011-06-357210 · 10.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hematopoietic stem cells (HSCs) are maintained in a specific bone marrow (BM) niche in cavities formed by osteoclasts. Osteoclast-deficient mice are osteopetrotic and exhibit closed BM cavities. Osteoclast activity is inversely correlated with hematopoietic activity; however, how osteoclasts and the BM cavity potentially regulate hematopoiesis is not well understood. To investigate this question, we evaluated hematopoietic activity in three osteopetrotic mouse models: op/op, c-Fos-deficient, and RANKL (receptor activator of nuclear factor kappa B ligand)-deficient mice. We show that, although osteoclasts and, by consequence, BM cavities are absent in these animals, hematopoietic stem and progenitor cell (HSPC) mobilization after granulocyte colony-stimulating factor injection was comparable or even higher in all three lines compared with wild-type mice. In contrast, osteoprotegerin-deficient mice, which have increased numbers of osteoclasts, showed reduced HSPC mobilization. BM-deficient patients and mice reportedly maintain hematopoiesis in extramedullary spaces, such as spleen; however, splenectomized op/op mice did not show reduced HSPC mobilization. Interestingly, we detected an HSC population in osteopetrotic bone of op/op mice, and pharmacological ablation of osteoclasts in wild-type mice did not inhibit, and even increased, HSPC mobilization. These results suggest that osteoclasts are dispensable for HSC mobilization and may function as negative regulators in the hematopoietic system.
    Journal of Experimental Medicine 10/2011; 208(11):2175-81. DOI:10.1084/jem.20101890 · 13.91 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pilocytic astrocytoma (PA) is a low-grade astrocytic tumor arising predominantly during the first two decades of life. Hemorrhagic onset of PAs is uncommon, and the etiology of hemorrhage remains unclear. Here we report a case of hemorrhagic onset of cerebellar PA in a 29-year-old man who presented with a week-long history of headache and gait instability. Computed tomography and magnetic resonance imaging revealed a hemorrhagic tumor located in the right cerebellar hemisphere, and total resection was performed. Histological examination showed bipolar glial cell proliferation in a biphasic pattern in a compact area and a loose microcystic area with Rosenthal fibers and eosinophilic granular bodies, indicating PA. Prominent changes in tumor vasculature, including aggregation of sclerotic thick-walled and ectatic thin-walled vessels, was observed, and nodules of thrombi containing complex vascular proliferation suggesting recanalized thrombi formed in partially ruptured vessels were also found. Thus, rupture of these abnormal vessels appeared to be the cause of hemorrhage. Review of the literature revealed that age distribution of patients with hemorrhagic PAs tends to be older than that of patients with general PAs. These findings imply a possibility that degenerative changes in blood vessels in long-standing PAs might be related to the mechanisms of spontaneous intratumoral hemorrhage.
    Brain Tumor Pathology 10/2011; 29(2):96-102. DOI:10.1007/s10014-011-0068-7 · 2.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Vascular endothelial growth factor 165 (VEGF165) and its receptors, including neuropilin 1 (NRP-1), are overexpressed in human osteoarthritic (OA) articular cartilage, although their functional roles in the cartilage are not fully understood. An axon-guidance molecule, semaphorin 3A (Sema3A), which binds to NRP-1, acts as an antagonist of VEGF signaling in endothelial cells. The aim of this study was to examine the expression of Sema3A and the functions of the VEGF165/Sema3A/NRP-1 axis in OA cartilage. The expression of Sema3A in OA and normal cartilage samples was examined by real-time polymerase chain reaction and immunohistochemical analyses. Functional analyses of VEGF165 and Sema3A were carried out using OA chondrocytes in culture. The migration activity of chondrocytes was examined in a monolayer wound assay. The effects of Sema3A on VEGF165-induced up-regulation of matrix metalloproteinases (MMPs) and intracellular signaling were also studied in cultured chondrocytes. Sema3A expression was significantly elevated in OA cartilage as compared to normal cartilage. Sema3A immunoreactivity directly correlated with the Mankin score and with chondrocyte cloning. VEGF165 promoted the migration of chondrocytes, and this activity was suppressed by VEGF receptor 2 tyrosine kinase inhibitors. Sema3A antagonized the chondrocyte migration promoted by VEGF165, and the activity was blocked by a selective inhibitor of, or small interfering RNA for, Sema3A. VEGF165-induced overexpression of MMPs and phosphorylation of ERK and focal adhesion kinase in chondrocytes were inhibited by Sema3A. Our findings provide the first evidence that Sema3A is overexpressed, with a direct correlation with cloning, in OA cartilage and that it suppresses the VEGF165-promoted migration of chondrocytes. Our findings also suggest that Sema3A plays a role in chondrocyte cloning through inhibition of cell migration in OA cartilage.
    Arthritis & Rheumatology 10/2011; 63(10):3000-9. DOI:10.1002/art.30482 · 7.87 Impact Factor
  • Tokuhiro Kimura, Masayoshi Komura, Yasuhiro Okubo
    [Show abstract] [Hide abstract]
    ABSTRACT: Giant cell arteritis involving intramural coronary artery branches is rare, and its clinical features remain poorly understood. We report a 56-year-old hemodialysed patient with a history of mitral valve replacement, who presented with "fever of unknown origin" and intractable hypotension. The antemortem diagnosis was very difficult and the autopsy revealed giant-cell-rich vasculitis in arteries in multiple organs. The heart was most severely involved, in which almost all of the intramural coronary artery branches were infiltrated by many multinucleated giant cells, macrophages, and lymphocytes with luminal narrowing, but the epicardial segments of the coronary arteries were spared. Superimposed on the preexisting valvular heart disease, the vasculitic lesions were thought to play a central role in severe cardiac dysfunction resulting in dialysis-related hypotension, which led to fatal non-occlusive mesenteric ischemia. This case highlights the possibility that giant cell arteritis of intramural coronary arteries could be an uncommon underlying cause of refractory dialysis-related hypotension.
    Heart and Vessels 06/2011; 27(2):216-20. DOI:10.1007/s00380-011-0158-9 · 2.11 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Extraventricular neurocytoma is an uncommon neuronal tumor, located outside the cerebral ventricles, which shows histological features similar to those of central neurocytoma. Most extraventricular neurocytomas are situated in the intraaxial regions of the central nervous system. We report a rare case of an extraaxial neurocytoma in the sphenocavernous-petroclival region that was successfully treated by radiation therapy following partial removal and pathological evaluation of the tumor.
    Brain Tumor Pathology 05/2011; 28(3):273-7. DOI:10.1007/s10014-011-0035-3 · 2.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The prostaglandin D(2) (PGD(2))/CRTH2 pathway is important for eosinophil trafficking in vitro; however, genetic deficiency of CRTH2 does not suppress in vivo eosinophilic airway inflammation in acute models of asthma, and the role of CRTH2 in the pathogenesis of asthma is still ambiguous. Therefore, in the present study we explored whether the PGD(2)/CRTH2 pathway could affect the phenotypes of chronic asthma. Either CRTH2-deficient (CRTH2-/-) or wild-type mice were sensitized and exposed to ovalbumin (OVA) for 3 days (acute model) or 6 weeks (chronic model). While the magnitude of the acute eosinophilic inflammation was equivalent between CRTH2-/- and wild-type mice, the number of inflammatory cells and eosinophils in bronchoalveolar lavage fluid after chronic OVA exposure was significantly reduced in CRTH2-/- mice (18.0 ± 2.6 × 10(4) cells and 2.0 ± 0.5 × 10(4) cells) compared to wild-type mice (27.9 ± 2.5 × 10(4) cells and 6.8 ± 1.1 × 10(4) cells, p < 0.001). On the contrary, no difference was observed between CRTH2-/- and wild-type mice in terms of airway hyperresponsiveness or remodeling (goblet cell hyperplasia) in the chronic model of asthma. In conclusion, CRTH2 that mediates PGD(2) activity is essential for sustained eosinophilic inflammation in the airways, and its antagonists could exert an anti-inflammatory effect in chronic asthma.
    International Archives of Allergy and Immunology 01/2011; 155 Suppl 1:6-11. DOI:10.1159/000327257 · 2.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Intracranial clear cell meningioma is very rare. We present 3 cases of intracranial clear cell meningiomas genetically characterized by comparative genomic hybridization with a review of the literature. Patient 1 is a 38-year-old woman with a petroclival tumor. Patient 2 is a 60-year-old man with a tumor at the foramen magnum. Patient 3 is a 60-year-old man with a tumor at the posterior clinoid process. Gross total resection was performed in patients 1 and 2. Patient 1 has been free from recurrence for 10 years. Patient 2 had a tumor recurrence at 14 months after the operation. After partial resection, conventional radiotherapy was given, and there was no tumor regrowth at 2 years after radiotherapy. Subtotal resection was performed in patient 3, and no regrowth was detected for 3 months. Histologically, all tumors were composed of cells with clear cytoplasm reactive for periodic acid-Schiff and diagnosed as clear cell meningioma. The MIB-1 and p53 staining indexes were 1.8, 1.7, and 5.6 and 1.1, 1.0, and 5.5, respectively. Comparative genomic hybridization revealed no chromosomal number aberrations in patient 1, numerous losses and gains including loss of chromosome 1 in patient 2, and loss of only 22q in patient 3. Because staining indexes of MIB-1 and p53 were equivalent in 2 patient (patients 1 and 2) with a long follow-up period, the contrary clinical courses are likely associated with genetic characteristics. To the best of our knowledge, this is the first report that suggests association between tumor behavior and genetic characteristics in clear cell meningiomas.
    Neurosurgery 09/2010; 67(3):E870-1; discussion E871. DOI:10.1227/01.NEU.0000374857.06732.CD · 3.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Skeletal fracture healing involves a variety of cellular and molecular events; however, the mechanisms behind these processes are not fully understood. In the current study, we investigated the potential involvement of the signal transducer and activator of transcription 1 (STAT1), a critical regulator for both osteoclastogenesis and osteoblast differentiation, in skeletal fracture healing. We used a fracture model and a cortical defect model in mice, and found that fracture callus remodeling and membranous ossification are highly accelerated in STAT1-deficient mice. Additionally, we found that STAT1 suppresses Osterix transcript levels and Osterix promoter activity in vitro, indicating the suppression of Osterix transcription as one of the mechanisms behind the inhibitory effect of STAT1 on osteoblast differentiation. Furthermore, we found that fludarabine, a potent STAT1 inhibitor, significantly increases bone formation in a heterotopic ossification model. These results reveal previously unknown functions of STAT1 in skeletal homeostasis and may have important clinical implications for the treatment of skeletal bone fracture.
    Journal of Orthopaedic Research 07/2010; 28(7):937-41. DOI:10.1002/jor.21086 · 2.97 Impact Factor

Publication Stats

819 Citations
221.07 Total Impact Points

Institutions

  • 2015
    • Yamaguchi University
      Yamaguti, Yamaguchi, Japan
  • 2005–2015
    • Keio University
      • • Department of Pathology
      • • School of Medicine
      • • Department of Cardiology
      • • Department of Pediatrics
      Edo, Tōkyō, Japan