Tadashi Yoshino

Okayama University, Okayama, Okayama, Japan

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Publications (534)1719.19 Total impact

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    ABSTRACT: Background: The purpose of this study is to determine the effects of anti-high mobility group box 1 (HMGB1) monoclonal antibody (mAb) on ischemia/reperfusion injury (IRI) and the mode of liver regeneration. Methods: Rats underwent 70% hepatectomy with IRI caused by clamping the hepatoduodenal ligament for 20 minutes, followed by the administration of anti-HMGB1 mAb immediately before declamping the hepatoduodenal ligament. Five animals were used for each time point. We then evaluated IRI, regeneration parameters and the status of HMGB1 in remnant livers. Results: The anti-HMGB1 mAb significantly ameliorated the degree of IRI in the remnant livers in association with the downregulation of HMGB1 protein. The ratio of Ki67-positive hepatocytes at 48 hours after 70% hepatectomy was significantly improved. Mean hepatocyte size was significantly reduced and cyclin-dependent kinase inhibitor 1 expression was significantly attenuated. Conclusions: Anti-HMGB1 mAb ameliorated IRI and improved the mode of liver regeneration after IRI followed by 70% hepatectomy in rats.
    American journal of surgery 09/2015; DOI:10.1016/j.amjsurg.2015.06.025 · 2.29 Impact Factor
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    ABSTRACT: Objective: There is no consensus regarding the best treatment for intestinal follicular lymphoma (FL). We used "watch and wait" for patients with intestinal FL with low-tumor-burden (LTB) criteria and without mass formation causing bowel obstruction. We investigated the overall survival (OS) and time to treatment required (TTR). Methods: Thirty-three intestinal FL patients [clinical stage (CS) I:16, II1:0, II2:7, IV:10; median observation period: 45.5 months, range: 13-110 months] were diagnosed via endoscopy. Detailed clinical and pathological examinations were performed, and neoplastic process behavior was monitored. Results: All of the 33 patients were WHO grade 1. FL lesions in the digestive tract were found frequently in the second-fourth portion of the duodenum in 91% of the patients; 87% of those patients had lesions in a broader area including the small intestine. Two patients had an enlargement of the area of the lesions and a worsening of the macroscopic findings. Three patients had CS progression; however, these remained within the indication for "watch and wait." Two patients with transformation into diffuse large B-cell lymphoma received rituximab and chemotherapy, which led to complete remission. The OS was 100%. The time to treatment required (TTR) was 49 months in one patient and 37 months in one patient. Conclusion: Intestinal FL in CS I-IV with broad infiltration of the digestive tract meeting the criteria for LTB had a remarkably slow course. This study suggests that "watch and wait" is appropriate for the treatment of LTB intestinal FL even in the era of rituximab.
    Scandinavian Journal of Gastroenterology 09/2015; DOI:10.3109/00365521.2015.1087589 · 2.36 Impact Factor
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    ABSTRACT: We previously suggested a relationship between ocular immunoglobulin (Ig)G4-related disease (IgG4-RD) and marginal zone lymphomas (MZLs). However, the cytokine background associated with these disorders and whether it differs between ocular adnexal MZLs with (IgG4-associated MZL) and without (IgG4-negative MZL) numerous IgG4(+) plasma cells are unknown. In this study, we identified the mRNA expression pattern of Th2 and regulatory T-cell (Treg) cytokines in IgG4-RD and in IgG4-associated MZL and IgG4-negative MZL using real-time polymerase chain reaction analysis. Ocular IgG4-RD and IgG4-associated MZL exhibited significantly higher expression ratios of interleukin (IL)-4/β-actin, IL-10/β-actin, IL-13/β-actin, transforming growth factor (TGF) β1/β-actin, and FOXP3/β-actin than did IgG4-negative MZL (p < 0.05). This finding further supports our prior observations that a significant subset of ocular MZLs arises in the setting of IgG4-RD. Furthermore, the presence of a different inflammatory background in IgG4-negative MZLs suggests that IgG4-associated MZLs may have a different pathogenesis.
    Scientific Reports 08/2015; 5:13539. DOI:10.1038/srep13539 · 5.58 Impact Factor
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    ABSTRACT: Enteropathy-associated T-cell lymphoma (EATL) is a rare primary T-cell lymphoma of the digestive tract. EATL is classified as either Type I, which is frequently associated with and thought to arise from celiac disease and is primarily observed in Northern Europe, and Type II, which occurs de novo and is distributed all over the world with predominance in Asia. The pathogenesis of EATL in Asia is unknown. We aimed to clarify the histological and genomic profiles of EATL in Japan in a homogeneous series of 20 cases. The cases were characterized by immunohistochemistry, high-resolution oligonucleotide microarray, and fluorescence in situ hybridization (FISH) at five different loci: 1q21.3 (CKS1B), 6q16.3 (HACE1), 7p22.3 (MAFK), 9q33.3 (PPP6C), and 9q34.3 (ASS1, CARD9) using formalin-fixed paraffin-embedded sections. The histological appearance of EATL ranged from medium- to large-sized cells in 13 cases (65%), small- to medium-sized cells in five cases (25%), and medium-sized in two cases (10%). The immunophenotype was CD2+ (60%), CD3ε+ (100%), CD4+ (10%), CD7+ (95%), CD8+ (80%), CD56+ (85%), TIA-1+ (100%), Granzyme B+ (25%), T-cell receptor (TCR)β+ (10%), TCRγ+ (35%), TCRγδ+ (50%), and double negative for TCR (six cases, 30%). All cases were EBER−. The genomic profile showed recurrent copy number gains of 1q32.3, 4p15.1, 5q34, 7q34, 8p11.23, 9q22.31, 9q33.2, 9q34.13, and 12p13.31, and losses of 7p14.1. FISH showed 15 patients (75%) with a gain of 9q34.3 with good correlation with array comparative genomic hybridization. EATL in Japan is characterized by non-monomorphic cells with a cytotoxic CD8+ CD56+ phenotype similar to EATL Type II. The genomic profile is comparable to EATL of Western countries, with more similarity to Type I (gain of 1q and 5q) rather than Type II (gain of 8q24, including MYC). The 9q34.3 gain was the most frequent change confirmed by FISH irrespective of the cell origin of αβ-T-cells and γδ-T-cells.
    Modern Pathology 07/2015; DOI:10.1038/modpathol.2015.85 · 6.19 Impact Factor
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    ABSTRACT: A 60-year-old Japanese man was diagnosed with systemic follicular lymphoma with duodenal, jejunal, and ileal involvement. The duodenal lesion showed typical endoscopic features with multiple whitish granules. Chemotherapy with bendamustine and rituximab was administered, and complete remission was confirmed by CT scanning and positron emission tomography scanning. Although the duodenal granular lesions did not completely disappear, magnifying observation for the remaining lesions showed no evidence of residual lymphoma. Complete remission was pathologically confirmed by biopsy examinations. This case suggests the usefulness of magnifying observation in evaluating the effects of treatment for duodenal follicular lymphoma lesions.
    Internal Medicine 07/2015; 54(14):1741-5. DOI:10.2169/internalmedicine.54.4390 · 0.90 Impact Factor
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    ABSTRACT: Langerhans cell histiocytosis (LCH) is a proliferative disorder in which abnormal Langerhans cell (LC)-like cells (LCH cells) intermingle with inflammatory cells. Whether LCH is reactive or neoplastic remains a controversial matter. We recently described Merkel cell polyomavirus (MCPyV) as a possible causative agent of LCH and proposed interleukin-1 loop model: LCH is a reactive disorder with an underlying oncogenic potential and we now propose to test this theory by looking for acute markers of inflammation. We detected MCPyV-DNA in the peripheral blood cells of patients with high-risk organ-type (LCH-risk organ (RO) (+)) but not those with non-high-risk organ-type LCH (LCH-RO (-)); this difference was significant. LCH-RO (-) is further classified by its involvement of either a single organ system (SS-LCH) or multiple organ systems (MS-LCH). In patients with LCH-RO (-), MCPyV-DNA sequences were present in LCH tissues, and significant differences were observed between LCH tissues and control tissues associated with conditions such as dermatopathic lymphadenopathy and reactive lymphoid hyperplasia. Although MCPyV causes subclinical infection in nearly all people and 22 % of healthy adults will harbor MCPyV in their buffy coats, circulating monocytes could serve as MCPyV reservoirs and cause disseminated skin lesions. Plasma sample from 12 patients with LCH-RO (-) (5 MS-LCH and 7 SS-LCH) and 5 non-LCH patients were analyzed by peptidomics. Mass spectrometry (MS) spectra were acquired and peptides exhibiting quantitative differences between MS-LCH and SS-LCH patients were targeted. One new candidate biomarker, m/z 3145 was selected and identified after obtaining a MS/MS fragmentation pattern using liquid chromatography-MS/MS. This peak was identified as a proteolytic fragment derived from inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4, [PDB: Q14624]). Peptidomics of LCH have revealed that the level of acute-phase ITIH4 distinguishes MS-LCH-RO (-) from SS-LCH-RO (-). Acute-phase proteins serve non-specific, physiological immune functions within the innate immune system. LCH may be a reactive disorder with both underlying neoplastic potential of antigen presenting cells harboring BRAF mutations and hyper-immunity of other inflammatory cells against MCPyV infection. Among LCH-RO (-), MCPyV-DNA sequences were present in both MS-LCH tissues and SS-LCH tissues without significant differences. ITIH4 may show that LCH activity or LCH subtypes correlates with the systemic or localized reactions of MCPyV infection.
    Clinical Proteomics 06/2015; 12(1). DOI:10.1186/s12014-015-9089-2
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    ABSTRACT: Background Central airway obstruction (CAO) may be caused by various etiologies. However, conventional chest X-rays are rarely diagnostic for patients with CAO. Case presentation We here described a 64-year-old asymptomatic female with tracheal mucosa-associated lymphoid tissue lymphoma discovered on spirometric findings during a complete physical examination. The plateau of forced expiratory flow was consistent with CAO. A decreased peak expiratory flow rate was noted at least 3 years before the diagnosis, and was attributed to an insufficient effort by the patient. Impulse oscillometric measurements, which were taken during quiet breathing and were effort-independent, suggested elevated respiratory resistance. These abnormalities completely disappeared after radiation therapy. Conclusion The addition of impulse oscillometry to spirometry may be useful for screening CAO in routine health examinations.
    BMC Research Notes 06/2015; 8(1). DOI:10.1186/s13104-015-1218-5
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    ABSTRACT: The importance of enteroscopy examinations to investigate the entire length of the small intestines has been emphasized in follicular lymphoma patients with intestinal involvement. The aim of the present study was to determine the current state of enteroscopy examinations, including the performance rate, and the prevalence of small intestinal lesions in a patient population in Japan. A retrospective multicenter survey of 17 institutions collected the case information of 110 follicular lymphoma patients with gastrointestinal involvement. The results of the enteroscopy examinations were reviewed, and in order to identify potential factors affecting the performance rate of enteroscopy, patient gender, age at lymphoma diagnosis, histopathological grade, clinical stage, the date of the initial diagnosis and the annual volume of enteroscopy at the institution were compared between the patients who underwent one or more enteroscopy procedures and the patients who did not undergo enteroscopy. A total of 34 patients (30.9%) underwent enteroscopy, and 24 of these (70.6%) presented with involvement in the jejunum and/or ileum. It was found that more patients diagnosed in recent years and more patients treated at an ultra-high volume institution (≥101 enteroscopy examinations/year) underwent an enteroscopy. In conclusion, although the prevalence of small intestinal lesions was high (70.6%) in the follicular lymphoma patients presenting with intestinal involvement, the performance rate of enteroscopy was only 30.9%, and thus the majority of the patients have not undergone enteroscopy examinations. Further investigation is required to define the clinical significance of enteroscopy at the initial diagnostic work-up and during the follow-up period of these patients.
    Oncology letters 05/2015; 10(1). DOI:10.3892/ol.2015.3251 · 1.55 Impact Factor
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    ABSTRACT: Hydroa vacciniforme (HV) is a rare photodermatosis that mainly affects children and manifests as vesiculopapular eruptions in sun-exposed areas without systemic symptoms. HV-like lymphoma (HVLL) is one of the Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPD) of childhood. Its diagnosis is based on monoclonal T-cell proliferation; however, its degree of malignancy is controversial owing to its variable prognosis. Elderly-onset cases of these diseases are extremely rare, and the clinical features remain unknown. It has been shown that late onset is closely associated with a severe phenotype in EBV-associated LPD including atypical HV. Here we describe a case of elderly-onset atypical HV accompanied by T-cell monoclonality, but with a very indolent clinical course. Our patient indicates a possible case with elderly-onset atypical HV manifesting a favorable course, and that T-cell monoclonality and age of onset cannot always predict the disease severity, and highlights the difficulty of prognosis prediction in elderly-onset atypical HV. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    British Journal of Dermatology 05/2015; DOI:10.1111/bjd.13893 · 4.28 Impact Factor
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    ABSTRACT: Acute lymphoblastic leukaemia/lymphoma (ALL/LBL) is an aggressive form of non-Hodgkin's lymphoma (NHL) affecting B-cells or T-cells, respectively. The serum level of soluble interleukin-2 receptor (sIL-2R) is known to reflect the immune activity and tumour volume in aggressive NHL; however, the release of sIL-2R in LBL has not been extensively studied. Further, the relationship between sIL-2R release and the expression level of IL-2R α subunit (CD25) remains unknown. In the present study, we examined the serum level of sIL-2R in 23 patients with T lymphoblactic lymphoma (T-LBL) and compared these with the levels in 20 patient with T acute lymphoblastic leukaemia (T-ALL), 40 patients with diffuse large B-cell lymphoma (DLBCL) and 40 patients with peripheral T-cell lymphoma (PTCL), not otherwise specified. The release of sIL-2R into the serum in patients with T-LBL was significantly lower than that for T-ALL, DLBCL and PTCL (p<0.001). Immunohistochemistry revealed that CD25 expression was correlated with the serum level of sIL-2R in T-LBL (p=0.0069), whereas no correlation was found to exist between serum sIL-2R levels and CD25 expression in patients with DLBCL (p=0.348) and PTCL (p=0.266). Furthermore, double immunohistochemical analysis revealed that CD25-positive cells were also found to be Foxp3-positive non-neoplastic T-cells. In conclusion, CD25-positive non-neoplastic T-cells in T-LBL are presumed to be the primary source of sIL-2R, and the low number of cells present results in a lower level of sIL-2R released into the serum compared with the other aggressive and highly aggressive lymphomas. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Journal of clinical pathology 05/2015; 68(8). DOI:10.1136/jclinpath-2015-202934 · 2.92 Impact Factor
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    ABSTRACT: Lymphomatoid gastropathy, which was first reported in 2010, is a rare NK-cell proliferation of cyCD3, CD4, CD5, CD8, CD56 phenotypes with unknown etiology. The diagnosis is challenging, as there is histopathologic similarity to malignant lymphoma. In the 2010 report on 10 cases, all lesions were located in the stomach, and all regressed without any therapy. In the present study, we analyzed 6 cases of lymphomatoid gastropathy by investigating the clinicopathologic, immunohistochemical, and molecular findings. Endoscopic and morphologic appearances of all cases were consistent with previous reports, but 2 cases showed previously unreported unique immunophenotypes of CD4CD8. Three of 6 patients underwent lower gastrointestinal examination (1 case underwent double-balloon endoscopic examination), but no patient had lesions in the lower gastrointestinal tract. No obvious difference of histology was found between the cases of CD4-CD8-typical phenotype and ones of CD4CD8 phenotype. Both cases had similar clinical behavior as the other 4 cases, implying that the spectrum of the disease is broader than initially thought. Careful clinical and endoscopic follow-up is required for the diagnosis of lymphomatoid gastropathy, and additional case studies and molecular studies are warranted to further investigate the pathophysiology of this peculiar benign mimic of lymphoma.
    The American journal of surgical pathology 04/2015; 39(9). DOI:10.1097/PAS.0000000000000443 · 5.15 Impact Factor
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    ABSTRACT: A 36-year-old Japanese woman presented with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in the stomach. The gastric lesions only partially improved after eradication therapy for Helicobacter pylori. A fluorescence in situ hybridization analysis revealed no fusion genes of API2-MALT1, although trisomy of chromosome 18 was identified. Radiation therapy was initiated to treat the gastric lymphoma lesions, resulting in complete remission. However, MALT lymphoma recurred in the stomach 16 months later. This case indicates that intensive follow-up is required for MALT lymphoma associated with chromosomal aberrations in order to detect early relapse.
    Internal Medicine 04/2015; 54(8):911-6. DOI:10.2169/internalmedicine.54.3784 · 0.90 Impact Factor
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    ABSTRACT: Fibroblastic reticular cell (FRC) neoplasms, which are one of the histiocyte tumor types, are very rare. Here we report a cytokeratin (CK)-positive FRC neoplasm having features of follicular dendritic cells in a 54-year-old woman with right axillary lymph node swelling. The resected lymph node showed multiple nodular aggregations simulating and replacing normal follicles. The tumor cells had a uniform, large and oval to polygonal shape, abundant cytoplasm, and various sizes of nuclei with central eosinophilic nucleoli and coarse nuclear chromatin. They were positive for CK AE1/AE3+CAM5.2, CK7, tenascin C, l-caldesomone, and CD21, weakly positive for S100, and negative for CD1a. Ultrastructurally, the tumor cells had long interdigitating microvillus-like cell processes and oval to elongated vesicular nuclei. In addition, the intercellular spaces contained accumulations of collagen, and some tumor cells had desmosomal-like junctions. These findings suggest that the present case is a CK-positive FRC tumor with follicular dendritic cell features.
    American Journal of Surgical Pathology 04/2015; 39(4):573-580. DOI:10.1097/PAS.0000000000000362 · 5.15 Impact Factor
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    ABSTRACT: We propose Langerhans cell histiocytosis (LCH) is an inflammatory process that is prolonged by mutations. We hypothesize that Merkel cell polyomavirus (MCPyV) infection triggers an interleukin-1 (IL-1) activation loop that underlies the pathogenesis of LCH. Langerhans cells (LCs) are antigen presenting cells in the skin. When LCs encounter exogenous antigens, they migrate from the epidermis into draining lymphoid tissues to initiate T-cell activity. It has been proposed that LC migration-related factors, including E-cadherin, matrix metalloproteinase, and Notch ligand induce LCH activity. We found that the tyrosine phosphatase SHP-1, which binds IL-1 receptor-associated kinase 1, is expressed at a significantly higher level in LCH affecting multiple organ systems (MS-LCH) than in LCH affecting a single organ system (SS-LCH). IL-1 stimulates T helper 17 cells and their signature cytokine IL-17 had been a matter of controversy. We detected higher levels of IL-17A receptor expression in MS-LCH than in SS-LCH and proposed an IL-17 endocrine model that could settle the controversy. IL-1 is the first cytokine secreted in response to sensitizers and promotes LC migration from sentinel tissues. Myeloid differentiation primary response 88 (MyD88), downstream of the IL-1 receptor, has functions in both RAS signaling and inflammation, leading to human cell transformation. In 2010, an activating mutation in the B-rapidly accelerated fibrosarcoma gene (BRAF) V600E was found in LCH. This BRAF mutation induces phosphorylation of the extracellular signal-regulated kinase (ERK) that may play an important role with MyD88 in LCH pathogenesis. However, phosphorylated ERK (pERK) is rapidly dephosphorylated by dual specificity phosphatase 6 (DUSP6), and limited proliferation is predicted in BRAF mutant cells. MyD88 binds pERK via its D-domain, thereby preventing pERK–DUSP6 interaction and maintaining ERK in an active, phosphorylated state. We detected MCPyV-DNA in the peripheral blood cells of two out of three patients with LCH in high-risk organs but not in those of patients with LCH in non–high-risk organs (0/12; P = .029). MCPyV infection can trigger precursor LCH cells with BRAF mutation to produce IL-1; the IL-1 loop is amplified in all LCH subclasses. Our model indicates both BRAF mutation and IL-1 loop regulation as potential therapeutic targets.
    Cell Communication and Signaling 02/2015; 13(1). DOI:10.1186/s12964-015-0092-z · 3.38 Impact Factor
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    ABSTRACT: The sensitivity and specificity of magnified endoscopic features for differentiating follicular lymphoma from other diseases with duodenal whitish lesions have never been investigated. Here we compared the magnified endoscopic features of duodenal follicular lymphoma with those of other whitish lesions. We retrospectively reviewed the cases of patients with follicular lymphoma (n=9), lymphangiectasia (n=7), adenoma (n=10), duodenitis (n=4), erosion (n=1), lymphangioma (n=1), and hyperplastic polyp (n=1). The magnified features of the nine follicular lymphomas included enlarged villi (n=8), dilated microvessels (n=5), and opaque white spots of various sizes (n=9). The lymphangiectasias showed enlarged villi, dilated microvessels, and white spots, but the sizes of the white spots were relatively homogeneous and their margin was clear. Observation of the adenoma and duodenitis revealed only whitish villi. Although the lymphangioma was indistinguishable from the follicular lymphomas by magnified features, it was easily diagnosed based on the macroscopic morphology. In conclusion, magnified endoscopic features, in combination with macroscopic features, are useful for differentiating follicular lymphomas from other duodenal diseases presenting whitish lesions.
    Acta medica Okayama 02/2015; 69(1):37-44. · 0.70 Impact Factor
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    ABSTRACT: In the adult hypothalamus and ependymal lining of the third ventricle, tanycytes function as multipotential progenitor cells that enable continuous neurogenesis, suggesting that tanycytes may be able to mediate the restoration of homeostatic function after stroke. Voluntary wheel running has been shown to alter neurochemistry and neuronal function and to increase neurogenesis in rodents. In the present study, we found that voluntary exercise improved the survival rate and energy balance of stroke-prone spontaneously hypertensive rats (SHRSP/Kpo). We also investigated the effect of exercise on the proliferation and differentiation of hypothalamic cells using immunoreactivity for tanycytes and neural markers. The proliferation of elongated cells, which may be the tanycytes, was enhanced in exercising SHRSP compared to sedentary rats before and after stroke. In addition, the proliferation of cells was correlated with the induction of fibroblast growth factor-2 in the subependymal cells of the third ventricle and in the cerebrospinal fluid. Some of the newborn cells of exercising SHRSP showed differentiation into mature neurons after stroke. Our results suggest that voluntary exercise correlates with hypothalamic neurogenesis, leading to recovery of homeostatic functions in the adult brain after stroke.
    Brain Structure and Function 01/2015; DOI:10.1007/s00429-015-0995-x · 5.62 Impact Factor
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    ABSTRACT: Interleukin (IL)-13 is a T helper 2 (Th2) cytokine that plays important roles in the pathogenesis of asthma. IL-13 induces hypersensitivity of the airways, increased mucous production, elevated serum immunoglobulin (Ig) E levels, and increased numbers of eosinophils. Many patients with IgG4-related disease have allergic backgrounds and show elevated serum IgE levels and an increase in the number of eosinophils. Upregulation of Th2/regulatory T (Treg) cytokines, including IL-13, has been detected in affected tissues of patients with IgG4-related disease. We previously reported that mast cells might be responsible for the production of the Th2/Treg cytokines IL-4, IL-10, and transforming growth factor (TGF)-β1 in IgG4-related disease. In this study, immunohistochemical analysis showed increased numbers of IL-13-positive mast cells in IgG4-related disease, which suggests that mast cells also produce IL-13 and contribute to elevation of serum IgE levels and eosinophil infiltration in IgG4-related disease.
    Scientific Reports 01/2015; 5:7696. DOI:10.1038/srep07696 · 5.58 Impact Factor
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    ABSTRACT: A 35-year-old man was referred to our hospital because of left supraclavicular and cervical lymphadenopathies. Histopathological examination of the lymph nodes revealed reactive lymphadenopathy. He visited our hospital three years after the initial diagnosis because of enlarged left cervical lymph nodes. Histopathologically, both Hodgkin/Reed-Sternberg (H/RS) and lymphocyte-predominant (LP) cells were found in the lymph node. We first suspected nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), because these cells were CD15(-) and CD30(-). However, the diagnosis of lymphocyte-rich classical Hodgkin lymphoma (LRCHL) was finally confirmed, because these cells were found to be CD20(-), Bob.1(+), Oct.2(-), and BCL6(-) by additional immunostaining. The patient was treated with six cycles of ABVD chemotherapy, and a complete response was achieved. However, he underwent autologous stem-cell transplantation after high-dose chemotherapy owing to a relapse 10 months after primary treatment. Distingushing LRCHL from NLPHL was difficult in this patient, because histopathological examination showed both H/RS and LP cells, and immunostaining revealed these cells to be triple negative (CD15(-), CD30(-) and CD20(-)). Accumulation of such cases are necessary to establish better criteria for the differential diagnosis and assessment of clinical behavior.
    Journal of Clinical and Experimental Hematopathology 01/2015; 55(1):23-8. DOI:10.3960/jslrt.55.23
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    Critical Care 12/2014; 18(Suppl 2):P23-P23. DOI:10.1186/cc14026 · 4.48 Impact Factor
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    ABSTRACT: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer, often associated with Merkel cell polyomavirus (MCPyV). Recently, immunoglobulin (Ig) expression was reported in MCC, thereby suggesting that B cells might be their cellular ancestors. We tested 30 MCCs (20 MCPyV-positive and 10 MCPyV-negative) using immunohistochemistry for the expressions of IgG, IgA, IgM, Igκ, Igλ, terminal desoxynucleotidyl transferase, paired box gene 5 (PAX5), octamer transcription factor-2 (Oct-2), and sex-determining region Y-box 11 (SOX11). We performed in situ hybridization for Igκ-mRNA or Igλ-mRNA and Ig heavy chain (IgH) gene rearrangement (IgH-R) analyses. The expressions of PAX5, TdT, Oct-2, and SOX11 were not significantly different between MCPyV-positive and MCPyV-negative MCCs. At least 1 of IgG, IgA, IgM, or Igκ was expressed in MCPyV-positive (14/20, 70%) and none in MCPyV-negative MCCs (P=0.0003). There was a higher tendency for Igκ-mRNA expression (7/19, using in situ hybridization) and IgH-R (10/20, using polymerase chain reaction) in MCPyV-positive than in MCPyV-negative MCCs (0/10 and 2/10, respectively), thus suggesting a different Ig production pattern and pathogenesis between the 2 types of MCC. Ig expression or IgH-R in MCPyV-positive MCCs might be associated with MCPyV gene integration or expression in cancer cells but do not necessarily suggest a B-cell origin for MCCs. IgH expression or IgH-R nonsignificantly correlated with improved prognosis. However, these might be important factors that influence the survival of neoplastic cells and might allow the development of novel therapies for patients with MCPyV-positive MCCs.
    American Journal of Surgical Pathology 12/2014; 38(12):1627-35. DOI:10.1097/PAS.0000000000000279 · 5.15 Impact Factor

Publication Stats

9k Citations
1,719.19 Total Impact Points


  • 1985–2015
    • Okayama University
      • • Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
      • • Medical School
      • • Department of Pharmacology
      • • Department of Pathology and Oncology
      Okayama, Okayama, Japan
  • 2013
    • Shujitsu Women's University
      Okayama, Okayama, Japan
  • 2009
    • Kurume University
      • School of Medicine
      Куруме, Fukuoka, Japan
    • Okayama City Hospital
      Okayama, Okayama, Japan
  • 2006
    • Novartis
      Bâle, Basel-City, Switzerland
    • Hiroshima City Hospital
      • Department of Surgery
      Hirosima, Hiroshima, Japan
  • 2005
    • The Ohio State University
      • Department of Microbiology
      Columbus, Ohio, United States
  • 2002
    • Aichi Cancer Center
      Nagoya, Aichi, Japan
  • 2001
    • Okayama University of Science
      Okayama, Okayama, Japan
  • 1987
    • Kochi Medical School
      Kôti, Kōchi, Japan