Tadashi Yoshino

Japan Aerospace Exploration Agency, Chōfu, Tokyo, Japan

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Publications (488)

  • [Show abstract] [Hide abstract] ABSTRACT: “Objective” Although glucocorticoids are effective for patients with IgG4-related disease, the treatment has not yet been standardized. Therefore, the treatment strategy should be established. “Patients and methods” Patients who fulfilled the comprehensive diagnostic criteria for definite IgG4-related disease were started on prednisolone (0.6mg/kg body weight) with the dose reduced every 2 weeks. The subsequent maintenance dose and need for prednisolone were determined for individual patients. The primary endpoint was the complete remission (CR) rate at 1 year. Secondary endpoints included overall response rate (ORR), the maintenance dose, the relapse rate and adverse events. “Results” This study enrolled 61 patients. After clinicopathological review, three patients were excluded, and one, 13, and 44 patients were diagnosed with probable, possible, and definite IgG4-related disease, respectively. Of the 44 patients with definite IgG4-RD, 29 (65.9%) achieved CR, and the ORR was 93.2%. No patient was refractory to primary treatment. The most frequent adverse events were glucose intolerance. Six patients relapsed. “Conclusions” Glucocorticoid treatment is usually effective for patients with IgG4-RD, and we should examine the possibility of other disorders when a patient is glucocorticoid refractory. Some patients are misdiagnosed, making central clinicopathological review of diagnosis very important in conducting clinical studies.
    Article · Nov 2016 · Modern Rheumatology
  • Article · Nov 2016 · Pediatric Blood & Cancer
  • [Show abstract] [Hide abstract] ABSTRACT: Purpose: The purpose of the present study was to analyze the enhancement patterns of small bowel neoplasms on post-contrast multiphasic multidetector CT and to assess the diagnostic capacity for differentiating five tumor types. Methods: We performed a retrospective study of data on 92 small bowel neoplasms. The neoplasms were categorized into five groups according to pathology findings, not imaging findings (23 adenocarcinomas; 22 lymphomas; 19 metastases; 18 gastrointestinal stromal tumors [GIST]; 10 neuroendocrine tumors [NET]). Results: GIST and NET demonstrated a hypervascular pattern in the multiphasic dynamic study. Adenocarcinoma and lymphoma showed a delayed enhancement pattern. Metastasis was classified as an intermediate enhancement pattern. The receiver operating characteristic analyses revealed that attenuation thresholds could be set with acceptable accuracies for most of the small bowel neoplasms. Conclusions: Multiphasic dynamic studies may have the potential to improve the diagnostic capacity of multidetector CT for small bowel neoplasms.
    Article · Oct 2016
  • Xueyan Zhang · Katsuyoshi Takata · Wei Cui · [...] · Tadashi Yoshino
    [Show abstract] [Hide abstract] ABSTRACT: Protocadherin genes (PCDHs) have been suggested to act as tumor suppressor genes in various tumor types. Previous studies have demonstrated the upregulation of certain PCDH‑γ subfamily genes in nodal and duodenal follicular lymphoma (FL) using gene expression analyses. However, the mechanisms and associated molecular function of PCDH‑γ subfamily gene upregulation in FL remain to be elucidated. The present study examined the expression of PCDHGA3, an upregulated PCDH‑γ gene subfamily member, in B‑cell lymphoma 2 (BCL2)‑positive and ‑negative FL, and evaluated its association with tumor cell proliferation in an FL‑derived cell line. Immunohistochemical analysis demonstrated that the majority of FL grade 1‑2 samples (19/20; 95%) and over half of grade 3A FL samples (5/9; 56%) were PCDHGA3‑positive, whereas only 1/17 reactive lymphoid hyperplasia samples was positive. Notably, this positivity was widely observed in samples of BCL2‑negative FL (13/15; 87%) and FL with diffuse area (10/10; 100%). The FL‑derived cell line FL18 exhibited strong PCDHGA3 expression, similar to the patient samples, and its proliferation was suppressed by PCDHGA3 gene knockdown. Genes expressed concomitantly with PCDHGA3 were selected from gene expression data, and TNFRSF6B, a member of the tumor necrosis factor receptor superfamily, was among the top five most strongly correlated genes. Coexpression of TNFRSF6B and PCDHGA3 was observed immunohistochemically in FL18 cells, suggesting potential cooperation in tumor cell maintenance. In conclusion, the results of the present study indicated that PCDHGA3 was expressed in FL irrespective of BCL2 status and grading and was associated with cell proliferation. Further studies involving molecular genetic analyses are required to elucidate the mechanisms underlying the activity of PCDHGA3 in FL.
    Article · Oct 2016 · Molecular Medicine Reports
  • [Show abstract] [Hide abstract] ABSTRACT: The objective of this study was to observe the distribution of regulatory T cells (Tregs) in the development of tongue squamous cell carcinoma (SCC) and to determine the role of Tregs in the progression of tongue SCC. A mouse model of 4-nitroquinoline-1-oxide (4NQO)-induced-tongue SCC was established. The expression of Forkhead box P3 (Foxp3), interleukin 10, transforming growth factor-β, chemokine CC motif ligands 17, 20, and CC chemokine receptor 4 was determined using real-time quantitative polymerase chain reaction. Foxp3 expression was also analyzed using immunohistochemistry. The results were compared with those of control mice and of 4NQO-treated mice treated with a cyclooxygenase-2 (COX-2) inhibitor. Well to moderately differentiated tongue SCC was induced in all of the experimental mice. The amount of Tregs of the experimental mice was over 10 times as much as control mice at the early stage of tumor progression. COX-2 inhibitor did not prevent the progression of tongue SCC and did not reduce the total amount of Tregs. Tregs function at the early stage of the development of tongue SCC, and it may be effective to suppress Tregs at the early stage of tumor progression for the treatment and/or prevention of tongue SCC.
    Article · Sep 2016 · Cancer Immunology and Immunotherapy
  • [Show abstract] [Hide abstract] ABSTRACT: A 41-year-old man was diagnosed with immunoglobulin G4-related disease (IgG4-RD) in both eyelids 4 years ago and exhibited good response to steroid therapy. However, rapid swelling of the right eyelid lesion was recently observed. As IgG4-RD progression was suspected, biopsy was performed. Although the histology was consistent with IgG4-RD, the infiltrating large atypical lymphoid cells showed immunoglobulin light-chain restriction and IgH gene rearrangement. Consequently, he was diagnosed with extranodal marginal zone lymphoma with abundant IgG4-positive cells.
    Article · Aug 2016 · Modern Rheumatology
  • Nobuhiko Ohnishi · Katsuyoshi Takata · Tomoko Miyata-Takata · [...] · Tadashi Yoshino
    [Show abstract] [Hide abstract] ABSTRACT: Follicular lymphoma (FL) shows co-expression of BCL2 and CD10, whereas down-expression of CD10 is occasionally experienced in gastrointestinal (GI) FL with unknown significance. GI-FL is a rare variant of FL, and its similarity with mucosa-associated lymphoid tissue (MALT) lymphoma was reported. Here we investigated the clinicopathological and genetic features of CD10 down-expressed (CD10(down) ) GI-FL. The diagnosis of CD10(down) FL was conducted with a combination of pathological and molecular analyses. CD10(down) GI-FL was shown in 35/172 (20.3%) of cases, which was more frequent than nodal FL (3.5%, P < 0.001). The difference was additionally significant between GI-FL and nodal FL when we confined to primary GI-FL (55.2% vs. 3.5%, P < 0.001). In comparison with CD10 positive GI-FL, CD10(down) GI-FL significantly involved the stomach or large intestine (P = 0.015), and additionally showed the down-expression of BCL6 (P < 0.001). The follicular dendritic cell meshwork often showed a duodenal pattern in the CD10(down) group (P = 0.12). Furthermore, a lymphoepithelial lesion was observed in 5/12 (40%) of gastric FL cases, which indicated caution in the differentiation of MALT lymphoma. Further, molecular analyses were conducted in seven cases of CD10(down) GI-FL, and an identical clone was found between CD10(down) follicles and CD10+BCL2+neoplastic follicles. In the diagnosis of cases with CD10(down) BCL2+ follicles, careful examination with molecular studies should be performed. This article is protected by copyright. All rights reserved.
    Article · Aug 2016 · Cancer Science
  • [Show abstract] [Hide abstract] ABSTRACT: Plasma cell-type Castleman disease (PCD) is often encountered when differentiating IgG4-related disease (IgG4-RD). Given that serum IgA is often elevated in Castleman disease, we investigated whether IgA expression levels in histological specimens can be used to differentiate between the two diseases. Lymph node lesions obtained from 12 IgG4-RD and 11 PCD patients were analysed by immunohistochemistry with anti-IgG, -IgG4, and -IgA antibodies. In addition to all 12 cases of IgG4-RD, 8/11 cases (72.7 %) of PCD also met the diagnostic criteria of IgG4-RD (serum IgG4 ≥135 mg/dl and IgG4/IgG-positive cells ≥40 %). IgA-positive cells were sparsely and densely distributed in IgG4-RD and PCD cases, respectively. The median number of IgA-positive cells ± SD in all 12 cases of IgG4-RD was 31 ± 37 cells per three high-powered fields (3HPFs) (range 4-118 cells/3HPFs). In contrast, the median number of IgA-positive cells, which was significantly higher in all 11 cases of PCD, was 303 ± 238 cells/3HPFs (range 74-737 cells/3HPFs) (P < 0.001). In conclusion, our findings indicate that in cases where serum analysis-based data are unavailable, anti-IgA immunostaining can be used for differential diagnosis of IgG4-RD.
    Article · Jul 2016 · Medical Molecular Morphology
  • Keina Nagakita · Katsuyoshi Takata · Kohei Taniguchi · [...] · Tadashi Yoshino
    [Show abstract] [Hide abstract] ABSTRACT: The gastrointestinal (GI) tract is the most common primary site of extranodal diffuse large B-cell lymphoma (DLBCL), with approximately one-third of extranodal DLBCL occurring in the GI tract. We investigated the clinicopathological features and immunohistochemically-assessed cell-of-origin of 49 GI DLBCL cases (stomach, 24; small intestine, 10; colon, 15) and also examined the presence of MYD88 L265P as recently this mutation has been frequently identified in activated B-cell (ABC)-like DLBCL, particularly in extranodal sites. Small intestinal DLBCL was characterized by the preponderance of women (P = 0.041), elevated LDH (P = 0.002) and soluble interleukin-2 receptor (P = 0.033). Small intestinal DLBCL more frequently showed anemia (P = 0.031) and elevated CRP (P = 0.029) than gastric DLBCL. ABC-like phenotype was seen in 71.4 % cases (stomach, 79 %; small intestine, 70 %; colon, 60 %). MYD88 L265P was detected in 6.1 % cases; all were primary gastric DLBCL with ABC-like phenotype but had no distinct clinicopathological features. In conclusion, GI DLBCL had different clinicopathological features according to the primary site especially in the small intestine. Also, MYD88 L265P had little involvement in GI DLBCL compared with other extranodal DLBCLs, suggesting that its pathogenesis might be different from that of organs with a high frequency of MYD88 L265P.
    Article · Jul 2016 · Pathology International
  • Tetsuya Tabata · Katsuyoshi Takata · Tomoko Miyata-Takata · [...] · Tadashi Yoshino
    [Show abstract] [Hide abstract] ABSTRACT: Introduction: Histiocytic necrotizing lymphadenitis (or Kikuchi-Fujimoto disease) frequently occurs in Asian young adult females and typically presents as cervical lymphadenopathy with unknown etiology. Although large immunoblasts frequently appear in Kikuchi-Fujimoto disease, the diffuse infiltration of these cells can cause difficulty in establishing a differential diagnosis from lymphoma. In such cases, CD30 immunostaining may be used; however, the extent or distribution pattern of CD30-positive cells in Kikuchi-Fujimoto disease remains largely unknown. Here we investigated the expression of CD30 and its clinicopathologic significance. Materials and methods: We investigated 30 Kikuchi-Fujimoto disease and 16 control [6, systemic lupus erythematosus (SLE); 10, reactive lymphoid hyperplasia (RLH)] cases. Results: The number of CD30-positive cells in Kikuchi-Fujimoto disease was significantly more than that in SLE and RLH, and majority of these cells were located around necrotic areas. Moreover, double immunohistochemical staining showed these CD30-positive cells to be CD8-positive cytotoxic T cells, suggesting that activated cytotoxic T cells around necrotic areas are a characteristic feature of this disease. Clinicopathologic analysis showed that cases with abundant CD30-positive cells were predominantly female with only mild symptoms and normal laboratory data. Conclusions: In Kikuchi-Fujimoto disease cases, CD30-positive cytotoxic T cells were abundant around necrotic areas; this histologic feature may be helpful to differentiate this disease from SLE and RLH.
    Article · Jul 2016 · Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry
  • Lamia Abdalkader · Takashi Oka · Katsuyoshi Takata · [...] · Tadashi Yoshino
    [Show abstract] [Hide abstract] ABSTRACT: The Polycomb repressive complex-2 members (EZH2, EED, SUZ12 and EZH1) are important regulators of haematopoiesis, cell cycle and differentiation. Over-expression of EZH2 has been linked to cancer metastases and poor prognosis. Detailed information on the expression of other members in normal and neoplastic lymphoid tissue remains to be elucidated. Immunohistochemical and immunofluorescent analyses of 156 samples from haematopoietic neoplasms patients and 27 haematopoietic cell lines were used. B-cell neoplasms showed a significant over-expression of EZH2, EED and SUZ12 in the aggressive subtypes compared to the indolent subtypes and normal tissue (_p_ = 0.000–0.046) while expression of EZH1 was decreased in mantle cell lymphoma compared to normal tissue (_p_ = 0.011). T/NK-cell neoplasms also showed significant over-expression of EZH2, EED and SUZ12 (_p_ = 0.000–0.002) and decreased expression of EZH1 (_p_ = 0.001) compared to normal cells. EZH2 and EZH1 have opposite expression patterns both in normal and neoplastic lymphoid tissues as well as an opposite relation to Ki-67. These results were supported by western blotting analyses. Immunofluorescent staining revealed a difference in the intracellular localisation of EZH1 compared to other members. These evidences suggest that EZH2 and EZH1 are important in the counter-balancing mechanisms controlling proliferation/resting of lymphoid cells. The disruption of the balanced EZH2/EZH1 ratio may play important roles in the pathogenesis of lymphomas.
    Article · Jun 2016 · Pathology
  • [Show abstract] [Hide abstract] ABSTRACT: HRG's effects on the passage of CLP mouse blood through microchannels. Whole blood of CLP mice treated with PBS, HSA (20 mg/kg, i.v.), or HRG (20 mg/kg, i.v.) was withdrawn from the abdominal aorta 24 h after CLP and applied to a MC-FAN. The passage of blood cells was monitored by a CCD camera.
    File available · Data · Jun 2016
  • [Show abstract] [Hide abstract] ABSTRACT: In vivo imaging of circulating neutrophils and platelets in the venules in CLP sepsis mice. Alexa Fluor 594-labeled anti-Gr-1 antibody (10 μg/mouse) and DyLight488-labeled anti-CD42c antibody (2 μg/mouse) was injected i.v. to CLP mice treated with PBS, HSA, or HRG (20 mg/kg, i.v.). The immunostained neutrophils and platelets in the mesenteric venules were observed by a high-speed scan spinning-disk confocal microscopy system.
    File available · Data · Jun 2016
  • [Show abstract] [Hide abstract] ABSTRACT: HRG's effects on the passage of human neutrophils in microcapillaries. The purified human neutrophils were incubated with BSA, HSA, HRG, or fMLP at 1 μM for 1 h at 37 °C and applied to a MC-FAN. The passage of neutrophils through microcapillaries was monitored by microscope-CCD camera system in the apparatus.
    File available · Data · Jun 2016
  • [Show abstract] [Hide abstract] ABSTRACT: Supplementary material
    File available · Data · Jun 2016
  • [Show abstract] [Hide abstract] ABSTRACT: Effects of anti-HRG Ab on the passage of human whole blood in microcapillaries. The human whole blood was treated with anti-HRG Ab (40 μg/ml) or control IgG for 30 min at 37 °C and applied to MC-FAN. The passage of blood cells through the microcapillaries was monitored as described above.
    File available · Data · Jun 2016
  • [Show abstract] [Hide abstract] ABSTRACT: Sepsis is a major cause of death worldwide. We show that a plasma protein histidine-rich glycoprotein (HRG) was decreased significantly in septic mice with cecal ligation and puncture (CLP) and supplementary treatment of septic mice with exogenous HRG improved survival, with strong inhibition of tight attachment of neutrophils to pulmonary vasculatures, subsequent immunothrombosis, DIC state, lung inflammation, hypercytokinemia, and activation of vascular endothelial cells (VECs). In contrast, knockdown of HRG by siRNA exacerbated lethality. Purified human HRG reversibly induced morphological changes in human neutrophils in vitro; induction of spherical shape with reduced microvilli and adhesiveness to VECs. HRG maintained the passage of neutrophils through microcapillaries and abolished production of reactive oxygen species. These results suggested that the supplementary therapy with HRG may provide a novel strategy for the treatment of sepsis through suppression of excessive systemic inflammation and immunothrombosis by keeping circulating neutrophils quiescent and preventing uncontrolled activation of VECs.
    Article · Jun 2016 · EBioMedicine
  • [Show abstract] [Hide abstract] ABSTRACT: We herein report a case in which an IgG4-producing lymphoma arose in a patient with a previous diagnosis consistent with an IgG4-related disease. A 43-year-old man presented with enlarged cervical lymph nodes and was treated with steroids and radiation for what was initially assumed to be Kimura's disease, although the lesions were later histologically re-diagnosed as IgG4-related lymphadenopathy. Fourteen years later, when the patient was 58-years-old, he presented with retroperitoneal fibrosis and swollen lymph nodes. The suspicious lesions were not histologically examined as the patient did not give consent. However, the serum IgG4 concentration was high (1400 mg/dL) and he was clinically diagnosed with systemic IgG4-related disease. Although steroid administration reduced the size of the lesions, tapering the dose finally resulted in systemic, prominently enlarged lymph nodes. Analysis of the biopsy specimen revealed that these multiple lymph node lesions were marginal zone B cell lymphomas that themselves expressed IgG4. Complete remission was achieved after a total of six courses of chemotherapy including rituximab. This case suggests that the infiltrating IgG4-expressing cells observed in IgG4-related disease can clonally expand to malignant lymphomas.
    Article · Apr 2016 · Medical Molecular Morphology
  • [Show abstract] [Hide abstract] ABSTRACT: Conclusion: In Kikuchi-Fujimoto disease (KFD), a low ratio of blastic cells (<70%) in lymph node specimens and absence of atypical lymphocytes in peripheral blood are predictive of a protracted clinical course. Objectives: Since KFD is a self-limiting disorder that does not require any specific management, prognostic factors have received little attention. The present study identified clinical and pathological factors that may affect the period from onset to cure of KFD. Methods: This retrospective study investigated 43 KFD patients who underwent lymph node biopsy diagnosed by immunohistochemical staining at Okayama University Hospital and Okayama Medical Center from January 2001 to December 2013. Results: Mean total period from onset to cure was 6 months (median =9.4 months; range =1-37 months). Low ratios of blastic cell proliferation area (<70%) in lymph node specimens (p = 0.011) and absence of atypical lymphocytes in peripheral blood (p = 0.026) were associated with a relatively long duration of KFD.
    Article · Apr 2016 · Acta Oto-Laryngologica
  • [Show abstract] [Hide abstract] ABSTRACT: Esophagogastroduodenoscopy revealed small duodenal lesions in a 56-year-old Japanese man and a 92-year-old Japanese woman with stage IV follicular lymphoma. Magnifying endoscopy examination revealed tiny white deposits in the second duodenal portion of the former patient and slightly enlarged duodenal villi in the latter. In both cases, biopsy revealed infi ltration of follicular lymphoma cells and incipient formation of neoplastic follicles. Here, we discuss the usefulness of magnifying endoscopy and narrow-band imaging for the detection of small duodenal lesions in follicular lymphoma cases.
    Article · Apr 2016 · Acta medica Okayama

Publication Stats

10k Citations


  • 2009-2010
    • Japan Aerospace Exploration Agency
      • Institute of Space and Astronautical Science (ISAS)
      Chōfu, Tokyo, Japan
  • 2007
    • Kurume University
      Куруме, Fukuoka, Japan
  • 2002
    • Hiroshima City Hospital
      Hirosima, Hiroshima, Japan
  • 1985-2000
    • Okayama University
      • Department of Pathology and Oncology
      Okayama, Okayama, Japan