Shigehisa Aoki

Saga University, Сага Япония, Saga, Japan

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Publications (55)181.92 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: : We describe a unique case of Merkel cell carcinoma (MCC) with a heterogeneous differentiation exhibiting distinct triphasic phenotypic differentiation features: small cells typical of MCC, sweat gland carcinoma (sweat gland Ca.) with possible decapitation secretion, and spindle cell carcinoma (spindle cell Ca.). The patient was an 84-year-old Japanese woman. We evaluated the present case immunohistochemically with various antibodies. The histological features showed a gradual transition from MCC to sweat gland Ca. and spindle cell Ca. For clarifying the histogenesis, immunophenotypic analysis of the 3 different components of the carcinoma was performed using hair follicle stem cell markers (eg, CK15, CK19, and CD200) that have been identified as biomarkers of human bulge cells. The triphasic components immunohistochemically shared the characteristic feature of CK19 and CD200 expression. We posit that the MCC arose from hair follicle stem cells residing within the bulge area where Merkel cells are preferentially situated. Based on our findings, we recommend adding this rare neoplasm to the expanding morphological spectrum of MCC.
    The American Journal of dermatopathology. 03/2015; 37(3):e31-e36.
  • CEN Case Reports. 11/2014; 3(2):172-177.
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    ABSTRACT: Stenosing flexor tenosynovitis, trigger finger, is a common clinical disorder causing painful locking or contracture of the involved digits, and most instances are idiopathic. This problem is generally caused by a size mismatch between the swollen flexor tendon and the thickened first annular pulley. Although hypertrophic pulleys have been histologically and ultrasonographically detected, little is known about the histopathology of the tenosynovium covering the tendons of trigger fingers. We identified chondrocytoid cells that produced hyaluronic acid in 23 (61%) fingers and hypocellular collagen matrix in 32 (84%) fingers around the tenosynovium among 38 specimens of tenosynovium from patients with trigger fingers. These chondrocytoid cells expressed the synovial B cell marker CD44, but not the chondrocyte marker S-100 protein. The incidence of these findings was much higher than that of conventional findings of synovitis, such as inflammatory infiltrate (37%), increased vascularity (37%), hyperplasia of synovial lining cells (21%), or fibrin exudation (5%). We discovered the following distinctive histopathological features of trigger finger: hyaluronic acid-producing chondrocytoid cells originated from fibroblastic synovial B cells, and a hypocellular collagen matrix surrounding the tenosynovium. Thus, an edematous extracellular matrix with active hyaluronic acid synthesis might increase pressure under the pulley and contribute to the progression of stenosis.
    Pathology International 06/2014; 64(6). · 1.59 Impact Factor
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    ABSTRACT: Severe burn patients lose wide areas of their skin and are confronted with a high risk of death because they lose an indispensable barrier against the invader, which in turn promotes water evaporation. Cultured skin is expected to be a promising technology for extensive skin defect patients, while faultless cultured skin has not been established. A skin sheet, tough and durable enough in clinical use, is urgently needed because typical cell sheets available now are fragile and difficult to handle at the time of surgery. Collagen vitrigel membrane is a novel biomaterial consisting of high-density collagen fibrils equivalent to connective tissues in vivo. With this novel collagen material utilized as a scaffold, we established a novel cultured skin sheet composed of keratinocytes and mesenchymal cell types. This cultured skin showed a fully differentiated epidermal layer, and could be handled with a tweezers. Interestingly, transplantation of a skin sheet revealed that acceleration of healing or inhibition against scarring depended on mesenchymal cell types in the skin sheet. Our findings suggest that the cultured skin sheet utilizing collagen vitrigel membrane cultured with keratinocytes and mesenchymal cell types will be a powerful tool for the wide skin defect and injury.
    Inflammation and Regeneration 01/2014; 34(3):117-123.
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    ABSTRACT: We present a rare case of Merkel cell carcinoma (MCC) with heterologous differentiation. The patient was an 86-year-old female patient with MCC who presented with a forearm skin tumor and left axillary lymph node swelling. Histopathologically, the malignant components of the primary and metastatic lesions showed the intermingled features of triphasic phenotype differentiation, which had distinct cell populations; MCC, sweat gland carcinoma (SGC) and malignant poorly differentiated spindle cells with myogenic differentiation were immunohistochemically showed. Moreover, an electron microscopic observation of the tumor cells revealed intracytoplasmic canaliculi and junctional structures that indicated ductal differentiation. To our knowledge, this is the first case of MCC admixed with SGC and sarcomatous components in both the primary and metastatic lesions. An immunohistochemical study, using several stem cell markers, indicated that the MCC arose from pluripotent epidermal stem cells.
    Journal of Cutaneous Pathology 12/2013; · 1.56 Impact Factor
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    ABSTRACT: Peritoneal dysfunction is a major factor leading to treatment failure of peritoneal dialysis (PD). However, the precise mechanism of the peritoneal diffusion changes related to PD remains to be elucidated. To this end, we have established a novel peritoneal diffusion model in vitro, which consists of a three-dimensional culture system using a collagen vitrigel membrane chamber and a fluid-stream generation system. This artificial peritoneal model revealed that high-glucose culture medium and fluid flow stress promoted the epithelial-mesenchymal transition (EMT) process of mesothelial cells, and that endothelial cells inhibited this mesothelial EMT process. Mesothelial cells in the EMT state showed high expression of connective tissue growth factor and low expression of bone morphogenic protein-7, while non-EMT mesothelial cells showed the opposite expression pattern of these two proteins. In addition, these protein expressions were dependent on the presence of endothelial cells in the model. Our model revealed that the endothelial slit function was predominantly dependent on the covering surface area, while the mesothelial layer possessed a specific barrier function against for small solutes independently of the surface area. Notably, a synergic barrier effect of mesothelial cells and endothelial cells was present with low glucose pretreatment, but high glucose pretreatment abolished this synergic effect. These findings suggest that the mesothelial slit function is not only regulated by the high-glucose-induced EMT process, but is also affected by an endothelial paracrine effect. This peritoneal diffusion model could be a promising tool for the development of PD.
    AJP Renal Physiology 11/2013; · 4.42 Impact Factor
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    ABSTRACT: Phosphaturic mesenchymal tumors of the mixed connective tissue type (PMT-MCTs) are rare neoplasms, most of which are benign and cause tumor-induced osteomalacia because of overproduction of a phosphaturic hormone, fibroblast growth factor 23 (FGF23). This entity may have been unrecognized or misdiagnosed as other mesenchymal tumors, such as giant cell tumor, hemangiopericytoma, and osteosarcoma. Ten percent of these tumors, without phosphaturia, were diagnosed only by their histologic features. We report here the first case of malignant PMT-MCT, nonphosphaturic variant, resulting in fatal multiple lung metastases. Chondromyxoid matrix with "grungy" calcification, multinucleated giant cell proliferation, and expression of FGF23 mRNA (reverse transcription-polymerase chain reaction) and fibroblast growth factor 23 protein (immunohistochemistry) were seen in the primary and recurrent tumors of the right foot. The lung metastases showed flocculent calcification and FGF23 protein expression as well as giant cell proliferation. This unique case highlights the need for careful histologic assessment of PMT-MCTs, especially the nonphosphaturic variant, and the need for recognition of its rare malignant behavior.
    Human pathology 08/2013; · 2.81 Impact Factor
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    ABSTRACT: Adipose tissue, together with the mesothelial layer and microvessels, is a major component of the mesenteric peritoneum, and the mesenterium is a target site for peritoneal fibrosis. Adipose tissue has been speculated to play a role in peritoneal dialysis (PD)-related fibrosis, but the precise cellular kinetics of adipose tissue during this process remain to be determined. To clarify this critical issue, we analyzed the kinetics of adipose tissue using a novel peritoneal reconstruction model in which the effects of mesothelial cells or endothelial cells could be identified. Adipose tissue was co-cultured with mesothelial cells or endothelial cells in a combined organ culture and fluid flow stress culture system. Spindle mesenchymal cells and immature adipocytes derived from adipose tissue were characterized by immunohistochemistry. Adipose tissue fragments cultured in this system yielded many spindle mesenchymal cells in non-co-culture conditions. However, the number of spindle mesenchymal cells emerging from adipose tissue was reduced in co-culture conditions with a covering layer of mesothelial cells. Mesothelial cells co-cultured in the separated condition did not inhibit the emergence of spindle mesenchymal cells from adipose tissue. Interestingly, endothelial cells promoted the emergence of lipid-laden immature adipocytes from adipose tissue under fluid flow stress. We have demonstrated that adipose tissue behavior is not only regulated by mesothelial cells and endothelial cells under fluid flow stress, but is also involved in fibrosis and fat mass production in the peritoneum. Our findings suggest that adipose tissue is a potential source of cells for peritoneal fibrosis caused by PD therapy.
    Journal of Artificial Organs 03/2013; · 1.39 Impact Factor
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    ABSTRACT: Systemic adipose tissue is involved in the pathophysiology of obesity-associated liver diseases. However, a method has not been established for analyzing the direct interaction between adipose tissue and hepatocytes. We describe a useful three-dimensional model comprising a collagen gel coculture system in which HepG2 hepatocytes are cultured on a gel layer with visceral adipose tissue fragments (VAT) or subcutaneous tissue samples (SAT). Male adipose tissues were obtained from 5-week-old Wistar rats and human autopsy cases. Cellular behavior was analyzed by electron microscopy, immunohistochemistry, Western blot, real-time reverse transcription plus the polymerase chain reaction and enzyme-linked immunosorbent assay. VAT significantly promoted lipid accumulation and apoptosis in HepG2 cells and suppressed their growth and differentiation compared with SAT. VAT produced higher concentrations of fatty acids (palmitate, oleate, linoleate) than SAT. HepG2 cells significantly decreased the production of these fatty acids in VAT. Only HepG2 cells treated with 250 μM palmitate replicated VAT-induced apoptosis. Neither VAT nor SAT affected lipotoxicity-associated signals of nuclear factor kappa B, c-Jun N-terminal kinase and inositol requiring enzyme-1α in HepG2 cells. HepG2 cells never affected adiponectin, leptin, or resistin production in VAT and SAT. The data indicate that our model actively creates adipose tissue and HepG2 hepatocyte interactions, suggesting that (1) VAT plays more critical roles in hepatocyte lipotoxicity than SAT; (2) palmitate but not adipokines, is partly involved in the mechanisms of VAT-induced lipotoxicity; (3) HepG2 cells might inhibit fatty acid production in VAT to protect themselves against lipotoxicity. Our model should serve in studies of interactions between adipose tissue and hepatocytes and of the mechanisms in obesity-related lipotoxicity and liver diseases.
    Cell and Tissue Research 03/2013; 352(3). · 3.33 Impact Factor
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    ABSTRACT: Abstract is missing (Letter).
    Acta Dermato-Venereologica 02/2013;
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    ABSTRACT: A 38-year-old female presenting with a high fever of 39 °C developed severe liver dysfunction and acute renal failure (ARF). In tests for a hepatitis associated virus, an Immunoglobulin M-anti-hepatitis B virus core antibody was the only positive finding. Moreover, the progression of ARF coincided with the pole period of liver damage and all the other assumed causes for the ARF were unlikely. Therefore, this case was diagnosed as ARF caused by acute hepatitis B. ARF associated with non-fulminant hepatitis has been infrequently reported, usually in association with acute hepatitis A. This case is considered to be an extremely rare and interesting case.
    World journal of hepatology. 02/2013; 5(2):82-5.
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    ABSTRACT: We report a case of a 33-year-old male with a mixed germ-cell testicular tumor. Postoperative follow-up FDG-PET revealed concentration of FDG in the left inguinal area which is not tumor metastasis or local recurrence but suture reactivity granuloma. In this paper, we reviewed suture granulomas associated with false-positive findings on FDG-PET after surgery. If FDG-PET will be used more frequently in the future, it will be necessary to refrain from using silk thread in order to prevent any unnecessary surgery.
    Case reports in urology. 01/2013; 2013:472642.
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    ABSTRACT: Osteoblasts are believed to differentiate into osteocytes, becoming embedded in bone, or to undergo apoptosis after the bone formation phase. The regulation of this terminal differentiation seems to be critical for bone homeostasis. However the mechanism remains unclear and there is no assay system currently available to analyze this process. To address this issue, we developed a new model in which osteoblasts are cultured on a type I collagen gel layer with osteogenic supplements β-glycerophosphate and ascorbic acid. Cellular behavior was analyzed by electron microscopy, immunohistochemistry and real-time RT-PCR. Osteoblasts gradually migrated into the gel, produced collagen fibrils, and differentiated to osteocytic cells with bone lacunae- and canaliculi-like mineralization. Osteocalcin, DMP-1 and SOST protein expression was mainly expressed in the migrated cells within the mid-layer of the gel. Osteoblastic (ALP and osteocalcin) and osteocytic (PHEX, DMP-1 and SOST) mRNA expression was significantly increased compared with those of the cells cultured on plastic dishes alone after 21days. The number of TUNEL-positive apoptotic cells gradually increased, reaching a maximum at 28days. The cells were distributed at the surface and in the mid-layer of the gel at 7days and after 14days of culture, respectively. These data indicate that our model reproduces transition from osteoblasts to osteocytes, suggesting the following: 1) migration of osteoblasts into collagen gel may play a critical role in osteocytic differentiation; and 2) spatiotemporal gene expression and apoptosis may be involved in the terminal differentiation of osteoblasts. Our model will make it possible to study the mechanism of transition from osteoblast to osteocyte, and both cell type-related diseases including osteoporosis and osteonecrosis.
    Bone 09/2012; 52(1):102-110. · 4.46 Impact Factor
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    ABSTRACT: Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease where Th2-type immune responses are dominant. Keratinocytes persistently secrete proinflammatory cytokines and chemokines, amplifying Th2-type responses in AD. We have recently reported that periostin, an extracellular matrix protein induced by Th2 cytokines, plays a critical role in AD. In the present study, we have further investigated the characteristics of our allergen-induced AD model mice and the role of periostin in the pathogenesis of AD. Methods: The ears of C57BL/6 mice, BALB/c mice, and Rag-2-/-γ(c)-/- mice (BALB/c background) were epicutaneously sensitized repeatedly with HDM. Mice were analyzed after the final sensitization. To examine the direct role of periostin, we reconstituted skin in vitro by coculture of keratinocytes with wild-type or periostin-deficient fibroblasts. Results: Epicutaneous sensitization with HDM induced AD-like phenotypes and accumulation of periostin in dermis in C57BL/6 mice but not in Rag-2-/-γ(c)-/- mice. In vitro organotypic coculture systems revealed that periostin promoted survival and proliferation of keratinocytes and directly induced production of thymic stromal lymphopoietin (TSLP). Conclusions: Our results suggest that periostin exacerbates the pathogenesis of AD through TSLP production from keratinocytes.
    Allergology International 08/2012;
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    ABSTRACT: Allergic inflammation triggered by exposure of an allergen frequently leads to the onset of chronic inflammatory diseases such as atopic dermatitis (AD) and bronchial asthma. The mechanisms underlying chronicity in allergic inflammation remain unresolved. Periostin, a recently characterized matricellular protein, interacts with several cell surface integrin molecules, providing signals for tissue development and remodeling. Here we show that periostin is a critical mediator for the amplification and persistence of allergic inflammation using a mouse model of skin inflammation. Th2 cytokines IL-4 and IL-13 stimulated fibroblasts to produce periostin, which interacted with αv integrin, a functional periostin receptor on keratinocytes, inducing production of proinflammatory cytokines, which consequently accelerated Th2-type immune responses. Accordingly, inhibition of periostin or αv integrin prevented the development or progression of allergen-induced skin inflammation. Thus, periostin sets up a vicious circle that links Th2-type immune responses to keratinocyte activation and plays a critical role in the amplification and chronicity of allergic skin inflammation.
    The Journal of clinical investigation 06/2012; 122(7):2590-600. · 15.39 Impact Factor
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    ABSTRACT: Encapsulating peritoneal sclerosis (EPS) often develops after transfer to hemodialysis and transplantation. Both termination of peritoneal dialysis (PD) and transplantation-related factors are risks implicated in post-PD development of EPS, but the precise mechanism of this late-onset peritoneal fibrosis remains to be elucidated. We previously demonstrated that fluid flow stress induced mesothelial proliferation and epithelial-mesenchymal transition via mitogen-activated protein kinase (MAPK) signaling. Therefore, we speculated that the prolonged bioactive effect of fluid flow stress may affect mesothelial cell kinetics after cessation of fluid streaming. To investigate how long mesothelial cells stay under the bioactive effect brought on by fluid flow stress after removal of the stress, we initially cultured mesothelial cells under fluid flow stress and then cultured the cells under static conditions. Mesothelial cells exposed to fluid flow stress for a certain time showed significantly high proliferative activity compared with static conditions after stoppage of fluid streaming. The expression levels of protein phosphatase 2A, which dephosphorylates MAPK, in mesothelial cells changed with time and showed a biphasic pattern that was dependent on the duration of exposure to fluid flow stress. There were no differences in the fluid flow stress-related bioactive effects on mesothelial cells once a certain time had passed. The present findings show that fluid flow stress exerts a prolonged bioactive effect on mesothelial cells after termination of fluid streaming. These findings support the hypothesis that a history of PD for a certain period could serve as a trigger of EPS after stoppage of PD.
    Biochemical and Biophysical Research Communications 11/2011; 416(3-4):391-6. · 2.28 Impact Factor
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    ABSTRACT: Airway remodeling in bronchial asthma is characterized by epithelial detachment and proliferation, subepithelial fibrosis, increased smooth muscle mass, and goblet cell hyperplasia. These features are mediated by T-helper type 2 (Th2) cytokines including interleukin (IL)-13. However, the direct effects of IL-13 on the functions of airway epithelial cells are not fully understood. Murine primary airway epithelial (MPAE) cells were cultured in an air-liquid interface (ALI) culture system. AG1478, a specific inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, was used to examine whether EGFR was involved in the IL-13-stimulated proliferation of MPAE cells. The expressions of EGFR ligands were investigated by reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemical analyses. The cell counting in cross-sections and [(3)H]thymidine incorporation assays revealed a significant increase in the number of MPAE cells cultured with IL-13 compared with a phosphate-buffered saline (PBS) control. AG1478 abolished the IL-13-stimulated proliferation of MPAE cells. The expression of epigen, one of the EGFR ligands, was enhanced in MPAE cells cultured with IL-13. The findings suggest that EGFR is involved in the IL-13-stimulated proliferation of MPAE cells, and that epigen is important for the proliferation process in airway remodeling.
    Experimental Lung Research 08/2011; 37(8):461-70. · 1.75 Impact Factor
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    ABSTRACT: The thyroid is composed of thyroid follicles supported by extracellular matrix, capillary network, and stromal cell types such as fibroblasts. The follicles consist of thyrocytes and C cells. In this microenvironment, thyrocytes are highly integrated in their specific structural and functional polarization, but monolayer and floating cultures cannot allow thyrocytes to organize the follicles with such polarity. In contrast, three-dimensional (3-D) collagen gel culture enables thyrocytes to form 3-D follicles with normal polarity. However, these systems never reconstruct the follicles consisting of both thyrocytes and C cells. Thyroid tissue-organotypic culture retains 3-D follicles with both thyrocytes and C cells. To create more appropriate experimental models, we here characterize four culture systems above and then introduce the models for studying thyroid biology and disorders. Finally, we propose a new approach to the cell type-specific culture systems on the basis of in vivo microenvironments of various cell types.
    ISRN endocrinology. 07/2011; 2011:275782.
    This article is viewable in ResearchGate's enriched format
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    Breakthroughs in Melanoma Research, 06/2011; , ISBN: 978-953-307-291-3
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    ABSTRACT: There is a histopathological similarity between cutaneous apocrine carcinoma (CAC) and breast carcinoma. Cutaneous histiocytoid or signet-ring cell (SRC) carcinoma is a rare neoplasm, which usually occurs on the eyelid, and less commonly on the axilla. The precise histogenesis of this carcinoma remains controversial. We report the case of a man with a cutaneous histiocytoid SRC carcinoma of the axilla having histopathological and immunohistochemical features that were quite similar to histiocytoid lobular carcinoma (histiocytoid LC) of the breast, which is a subtype of classic invasive lobular carcinoma of the breast with apocrine differentiation. We consider this case to be a type of CAC equivalent to histiocytoid LC of the breast, based on the features and the occurrence on the axilla. The patient was treated with adjuvant chemotherapy according to the general guidelines for the treatment of breast carcinoma.
    Clinical and Experimental Dermatology 06/2011; 36(8):874-7. · 1.23 Impact Factor

Publication Stats

394 Citations
181.92 Total Impact Points


  • 2004–2014
    • Saga University
      • • Department of Pathology & Microbiology
      • • Division of Dermatology
      • • Department of Pathology
      • • Faculty of Medicine
      Сага Япония, Saga, Japan
  • 2008
    • Takagi Hospital
      Ishinomachi, Miyagi, Japan