19 results on '"Keishi Mizuguchi"'
Search Results
2. Case report: Navigating treatment pathways for cardiac intimal sarcoma with PDGFRβ N666K mutation
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Akihiro Nishiyama, Shigeki Sato, Hiroyuki Sakaguchi, Hiroshi Kotani, Kaname Yamashita, Koushiro Ohtsubo, Keishi Mizuguchi, Hiroko Ikeda, Kenji Iino, Hirofumi Takemura, and Shinji Takeuchi
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intimal sarcoma ,PDGFRβ N666K mutation ,precision oncology ,MDM2 amplification ,CDK4 amplification ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
In the realm of rare cardiac tumors, intimal sarcoma presents a formidable challenge, often requiring innovative treatment approaches. This case report presents a unique instance of primary intimal sarcoma in the left atrium, underscoring the critical role of genomic profiling in guiding treatment. Initial genomic testing unveiled a somatic, active mutation in PDGFRβ (PDGFRβ N666K), accompanied by MDM2 and CDK4 amplifications. This discovery directed the treatment course toward pazopanib, a PDGFRβ inhibitor, following irradiation. The patient’s response was remarkable, with the therapeutic efficacy of pazopanib lasting for 16.3 months. However, the patient experienced a recurrence in the left atrium, where subsequent genomic analysis revealed the absence of the PDGFRβ N666K mutation and a significant reduction in PDGFRβ expression. This case report illustrates the complexities and evolving nature of cardiac intimal sarcoma treatment, emphasizing the potential of PDGFRβ signaling as a strategic target and highlighting the importance of adapting treatment pathways in response to genetic shifts.
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- 2024
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- View/download PDF
3. BMP signaling alters aquaporin-4 expression in the mouse cerebral cortex
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Kazuya Morita, Naoyuki Matsumoto, Kengo Saito, Toshihide Hamabe-Horiike, Keishi Mizuguchi, Yohei Shinmyo, and Hiroshi Kawasaki
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Medicine ,Science - Abstract
Abstract Aquaporin-4 (AQP4) is a predominant water channel expressed in astrocytes in the mammalian brain. AQP4 is crucial for the regulation of homeostatic water movement across the blood–brain barrier (BBB). Although the molecular mechanisms regulating AQP4 levels in the cerebral cortex under pathological conditions have been intensively investigated, those under normal physiological conditions are not fully understood. Here we demonstrate that AQP4 is selectively expressed in astrocytes in the mouse cerebral cortex during development. BMP signaling was preferentially activated in AQP4-positive astrocytes. Furthermore, activation of BMP signaling by in utero electroporation markedly increased AQP4 levels in the cerebral cortex, and inhibition of BMP signaling strongly suppressed them. These results indicate that BMP signaling alters AQP4 levels in the mouse cerebral cortex during development.
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- 2021
- Full Text
- View/download PDF
4. Tertiary lymphoid tissue in early‐stage IgG4-related tubulointerstitial nephritis incidentally detected with a tumor lesion of the ureteropelvic junction: a case report
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Tatsuhito Miyanaga, Keishi Mizuguchi, Satoshi Hara, Takeshi Zoshima, Dai Inoue, Ryo Nishioka, Ichiro Mizushima, Kiyoaki Ito, Hiroshi Fuji, Kazunori Yamada, Yuki Sato, Motoko Yanagita, and Mitsuhiro Kawano
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IgG4-related kidney disease ,IgG4-related tubulointerstitial nephritis ,Tertiary lymphoid tissue ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Abstract Background IgG4-related kidney disease causes renal impairment of unknown pathogenesis that may progress to kidney failure. Although ectopic germinal centers contribute to the pathogenesis of the head and neck lesions of IgG4-related disease, the presence of tertiary lymphoid tissue (TLT) containing germinal centers in IgG4-RKD has rarely been reported. Case presentation We report a 72-year-old Japanese man who had IgG4-related tubulointerstitial nephritis (TIN) with TLT formation incidentally detected in a resected kidney with mass lesion of IgG4-related ureteritis in the ureteropelvic junction. During follow-up for past surgical resection of a bladder tumor, renal dysfunction developed and a ureter mass was found in the right ureteropelvic junction, which was treated by nephroureterectomy after chemotherapy. Pathology revealed no malignancy but abundant IgG4-positive cell infiltration, obliterative phlebitis and storiform fibrosis, confirming the diagnosis of IgG4-related ureteritis. In the resected right kidney, lymphoplasmacytes infiltrated the interstitium with focal distribution in the renal subcapsule and around medium vessels without storiform fibrosis, suggesting the very early stage of IgG4-TIN. Lymphocyte aggregates were also detected at these sites and consisted of B, T, and follicular dendritic cells, indicating TLT formation. IgG4-positive cells infiltrated around TLTs. Conclusions Our case suggests that TLT formation is related with the development of IgG4-TIN and our analysis of distribution of TLT have possibility to elucidate IgG4-TIN pathophysiology.
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- 2021
- Full Text
- View/download PDF
5. The pronounced lung lesions developing in LATY136F knock-in mice mimic human IgG4-related lung disease.
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Yuko Waseda, Kazunori Yamada, Keishi Mizuguchi, Kiyoaki Ito, Satoshi Watanabe, Masahiko Zuka, Tamotsu Ishizuka, Marie Malissen, Bernard Malissen, Mitsuhiro Kawano, and Shoko Matsui
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Medicine ,Science - Abstract
RationaleImmunoglobulin (Ig) G4-related disease (IgG4-RD) is a novel clinical disease entity characterized by an elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells. Pathological changes are most frequently seen in the pancreas, lacrimal glands, and salivary glands, but pathological changes in the lung also exist. Linker for activation of T cell (LAT)Y136F knock-in mice show Th2-dominant immunoreactions with elevated serum IgG1 levels, corresponding to human IgG4. We have reported that LATY136F knock-in mice display several characteristic features of IgG4-RD and concluded that they constitute an appropriate model of human IgG4-RD in salivary glands, pancreas, and kidney lesions.ObjectivesThe aim of this study is to evaluate whether lung lesions in LATY136F knock-in mice can be a model of IgG4-related lung disease.MethodsLung tissue samples from LATY136F knock-in mice (LAT) and wild-type mice (WT) were immunostained for IgG1 and obtained for pathological evaluation, and cell fractions and cytokine levels in broncho-alveolar lavage fluid (BALF) were analyzed.ResultsIn the LAT group, IgG1-positive inflammatory cells increased starting at 4 weeks of age and peaked at 10 weeks of age. The total cell count and percentage of lymphocytes increased significantly in BALF in the LAT group compared to the WT group. In BALF, Th2-dominant cytokines and transforming growth factor-β were also increased. In the LAT group, marked inflammation around broncho-vascular bundles peaked at 10 weeks of age. After 10 weeks, fibrosis around broncho-vascular bundles and bronchiectasis were observed in LATY136F knock-in mice but not WT mice.ConclusionsLATY136F knock-in mice constitute an appropriate model of lung lesions in IgG4-RD.
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- 2021
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6. LatY136F knock-in mouse model for human IgG4-related disease.
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Kazunori Yamada, Masahiko Zuka, Kiyoaki Ito, Keishi Mizuguchi, Yasushi Kakuchi, Tamehito Onoe, Yasunori Suzuki, Masakazu Yamagishi, Shozo Izui, Marie Malissen, Bernard Malissen, and Mitsuhiro Kawano
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Medicine ,Science - Abstract
BACKGROUND:The adaptor protein Linker for activation of T cell (LAT) is a key signaling hub used by the T cell antigen receptor. Mutant mice expressing loss-of-function mutations affecting LAT and including a mutation in which tyrosine 136 is replaced by a phenylalanine (LatY136F) develop lymphoproliferative disorder involving T helper type 2 effector cells capable of triggering a massive polyclonal B cell activation that leads to hypergammaglobulinemia G1 and E and to non-resolving inflammation and autoimmunity. The purpose of this study was to evaluate whether the phenotypes of LatY136F knock-in mice resemble the immunohistopathological features of immunoglobulin G4-related disease (IgG4-RD). METHODS:LatY136F knock-in mice were sacrificed at 4-20 weeks of age, and pancreas, kidney, salivary gland and lung were obtained. All organs were stained with hematoxylin-eosin and with Azan for estimation of collagen in fibrosis, and the severity scores of inflammation and fibrosis were evaluated. Immunostainings were performed to analyze the types of infiltrating cells. In addition, the effects of corticosteroid treatment on the development of tissue lesions and serum levels of IgG1 were assessed. RESULTS:Tissue lesions characterized by inflammatory mononuclear cell infiltration and fibrosis were detected in pancreas, kidney, and salivary gland starting from 6 weeks of age. Immunostainings showed pronounced infiltration of plasma cells, CD4-positive T cells, and macrophages. Infiltrating plasma cells predominantly expressed IgG1. The extent of inflammation in pancreas and salivary glands was markedly reduced by corticosteroid treatment. CONCLUSIONS:LatY136F knock-in mice displayed increased production of Th2-type IgG1 (a homologue of human IgG4) and developed multiple organ tissue lesions reminiscent of those seen in patients with IgG4-RD. Moreover, the development of these tissue lesions was highly sensitive to corticosteroid treatment like in IgG4-RD. For these reasons we consider the LatY136F knock-in mouse strain to represent a promising model for human IgG4-RD.
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- 2018
- Full Text
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7. BMP signaling alters aquaporin-4 expression in the mouse cerebral cortex
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Kengo Saito, Naoyuki Matsumoto, Kazuya Morita, Yohei Shinmyo, Toshihide Hamabe-Horiike, Hiroshi Kawasaki, and Keishi Mizuguchi
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0301 basic medicine ,Science ,Molecular neuroscience ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Bmp signaling ,medicine ,Animals ,Aquaporin 4 ,Cerebral Cortex ,Multidisciplinary ,Chemistry ,Electroporation ,Development of the nervous system ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,In utero ,Cerebral cortex ,Astrocytes ,Bone Morphogenetic Proteins ,Mouse Cerebral Cortex ,Medicine ,sense organs ,030217 neurology & neurosurgery ,Homeostasis ,Signal Transduction - Abstract
Aquaporin-4 (AQP4) is a predominant water channel expressed in astrocytes in the mammalian brain. AQP4 is crucial for the regulation of homeostatic water movement across the blood–brain barrier (BBB). Although the molecular mechanisms regulating AQP4 levels in the cerebral cortex under pathological conditions have been intensively investigated, those under normal physiological conditions are not fully understood. Here we demonstrate that AQP4 is selectively expressed in astrocytes in the mouse cerebral cortex during development. BMP signaling was preferentially activated in AQP4-positive astrocytes. Furthermore, activation of BMP signaling by in utero electroporation markedly increased AQP4 levels in the cerebral cortex, and inhibition of BMP signaling strongly suppressed them. These results indicate that BMP signaling alters AQP4 levels in the mouse cerebral cortex during development.
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- 2021
8. Olfactory dysfunction in LATY136F knock-in mice
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Marie Malissen, Fumi Ozaki, Bernard Malissen, Keishi Mizuguchi, Tomokazu Yoshizaki, Kazunori Yamada, Sayaka Yagi-Nakanishi, Satoru Kondo, Mitsuhiro Kawano, Misako Kaneda, Kanazawa University Graduate School of Medical Sciences, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Kanazawa Medical University - Division of Hematology and Immunology
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Olfactory system ,medicine.medical_specialty ,Taste ,[SDV]Life Sciences [q-bio] ,Cycloheximide ,chemistry.chemical_compound ,Mice ,Olfaction Disorders ,Olfactory Mucosa ,Internal medicine ,Gene knockin ,Olfactory Marker Protein ,medicine ,Animals ,ComputingMilieux_MISCELLANEOUS ,business.industry ,Regeneration (biology) ,General Medicine ,Smell ,Endocrinology ,Behavioral test ,medicine.anatomical_structure ,Otorhinolaryngology ,chemistry ,Immunohistochemistry ,Surgery ,Immunoglobulin G4-Related Disease ,business ,Olfactory epithelium - Abstract
This study examined olfactory dysfunction in LATY136F knock-in mice and its pathogenic mechanism.The olfactory function of LATY136F knock-in mice was assessed by a behavioral test using cycloheximide solution, which has been used as a mice repellant because of its peculiar smell and unpleasant taste. The tests were administered to each group of LATY136F knock-in mice and WT mice at 8, 12, 16, 20, and 24 weeks of age. After the behavioral tests to evaluate olfactory function, the mice were sacrificed for evaluations by immunohistochemistry.Behavioral tests to evaluate olfactory function showed that the LATY136F knock-in mice had a statistically significant level of olfactory dysfunction (P0.05). Histological analysis showed that the thickness of the olfactory epithelium in these mice was thinner than that in the age-matched wild type mice. There was no IgG4-RD like lesion in the olfactory epithelium of LATY136F knock-in mice. Olfactory marker protein and growth-associated protein 43 expressions in the olfactory epithelium of the LATY136F knock-in mice were markedly lesser than those in the wild type mice (P0.05).The present study demonstrated that olfactory disturbances occurred in LATY136F knock-in mice. Furthermore, the mechanism was suggested to be reduced regeneration of the olfactory epithelium.
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- 2022
9. Tertiary lymphoid tissue in early‐stage IgG4-related tubulointerstitial nephritis incidentally detected with a tumor lesion of the ureteropelvic junction: a case report
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Kiyoaki Ito, Tatsuhito Miyanaga, Hiroshi Fuji, Takeshi Zoshima, Dai Inoue, Mitsuhiro Kawano, Ryo Nishioka, Motoko Yanagita, Keishi Mizuguchi, Ichiro Mizushima, Yuki Sato, Kazunori Yamada, and Satoshi Hara
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Male ,0301 basic medicine ,Nephrology ,Pathology ,medicine.medical_specialty ,Case Report ,Tertiary lymphoid tissue ,lcsh:RC870-923 ,Severity of Illness Index ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,Fibrosis ,Internal medicine ,parasitic diseases ,Humans ,Medicine ,Kidney Pelvis ,Aged ,030203 arthritis & rheumatology ,Incidental Findings ,Kidney ,Follicular dendritic cells ,integumentary system ,Ureteral Neoplasms ,business.industry ,fungi ,Germinal center ,Ureteritis ,medicine.disease ,lcsh:Diseases of the genitourinary system. Urology ,Kidney Neoplasms ,Tertiary Lymphoid Structures ,030104 developmental biology ,medicine.anatomical_structure ,Immunoglobulin G ,IgG4-related kidney disease ,Nephritis, Interstitial ,IgG4-related tubulointerstitial nephritis ,medicine.symptom ,business ,Kidney disease - Abstract
Background IgG4-related kidney disease causes renal impairment of unknown pathogenesis that may progress to kidney failure. Although ectopic germinal centers contribute to the pathogenesis of the head and neck lesions of IgG4-related disease, the presence of tertiary lymphoid tissue (TLT) containing germinal centers in IgG4-RKD has rarely been reported. Case presentation We report a 72-year-old Japanese man who had IgG4-related tubulointerstitial nephritis (TIN) with TLT formation incidentally detected in a resected kidney with mass lesion of IgG4-related ureteritis in the ureteropelvic junction. During follow-up for past surgical resection of a bladder tumor, renal dysfunction developed and a ureter mass was found in the right ureteropelvic junction, which was treated by nephroureterectomy after chemotherapy. Pathology revealed no malignancy but abundant IgG4-positive cell infiltration, obliterative phlebitis and storiform fibrosis, confirming the diagnosis of IgG4-related ureteritis. In the resected right kidney, lymphoplasmacytes infiltrated the interstitium with focal distribution in the renal subcapsule and around medium vessels without storiform fibrosis, suggesting the very early stage of IgG4-TIN. Lymphocyte aggregates were also detected at these sites and consisted of B, T, and follicular dendritic cells, indicating TLT formation. IgG4-positive cells infiltrated around TLTs. Conclusions Our case suggests that TLT formation is related with the development of IgG4-TIN and our analysis of distribution of TLT have possibility to elucidate IgG4-TIN pathophysiology.
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- 2021
10. Characterization of the Inner and Outer Fiber Layers in the Developing Cerebral Cortex of Gyrencephalic Ferrets
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Tung Anh Dinh Duong, Hiroshi Kawasaki, Keishi Mizuguchi, Yohei Shinmyo, Kengo Saito, and Toshihide Horiike
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Cerebral Cortex ,Mice, Inbred ICR ,Cognitive Neuroscience ,Electroporation ,05 social sciences ,Ferrets ,Biology ,Axons ,050105 experimental psychology ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,medicine.anatomical_structure ,Species Specificity ,Cerebral cortex ,Cortex (anatomy) ,medicine ,Animals ,0501 psychology and cognitive sciences ,Fiber ,Fiber layer ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Changes in the cerebral cortex of mammals during evolution have been of great interest. Ferrets, monkeys, and humans have more developed cerebral cortices compared with mice. Although the features of progenitors in the developing cortices of these animals have been intensively investigated, those of the fiber layers are still largely elusive. By taking the advantage of our in utero electroporation technique for ferrets, here we systematically investigated the cellular origins and projection patterns of axonal fibers in the developing ferret cortex. We found that ferrets have 2 fiber layers in the developing cerebral cortex, as is the case in monkeys and humans. Axonal fibers in the inner fiber layer projected contralaterally and subcortically, whereas those in the outer fiber layer sent axons to neighboring cortical areas. Furthermore, we performed similar experiments using mice and found unexpected similarities between ferrets and mice. Our results shed light on the cellular origins, the projection patterns, the developmental processes, and the evolution of fiber layers in mammalian brains.
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- 2018
11. The pronounced lung lesions developing in LATY136F knock-in mice mimic human IgG4-related lung disease
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Satoshi Watanabe, Masahiko Zuka, Keishi Mizuguchi, Kazunori Yamada, Marie Malissen, Shoko Matsui, Yuko Waseda, Bernard Malissen, Tamotsu Ishizuka, Mitsuhiro Kawano, Kiyoaki Ito, Fukui University of Technology, Kanazawa University (KU), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre d'Immunophénomique (CIPHE), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Toyama, and DUMENIL, Anita
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Lung Diseases ,0301 basic medicine ,Lung Development ,Pathology ,Physiology ,Organogenesis ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Salivary Glands ,White Blood Cells ,Mice ,0302 clinical medicine ,Animal Cells ,Fibrosis ,Immune Physiology ,Medicine and Health Sciences ,Lymphocytes ,skin and connective tissue diseases ,Immune Response ,Innate Immune System ,Kidney ,Multidisciplinary ,biology ,Animal Models ,3. Good health ,[SDV] Life Sciences [q-bio] ,Cytokine ,medicine.anatomical_structure ,Experimental Organism Systems ,Cytokines ,Medicine ,Anatomy ,Cellular Types ,Antibody ,medicine.symptom ,Research Article ,medicine.medical_specialty ,Immune Cells ,Science ,T cell ,Immunology ,Mutation, Missense ,Mouse Models ,Mice, Transgenic ,Inflammation ,Research and Analysis Methods ,03 medical and health sciences ,Model Organisms ,Signs and Symptoms ,Exocrine Glands ,medicine ,Animals ,Adaptor Proteins, Signal Transducing ,Blood Cells ,Lung ,Bronchiectasis ,business.industry ,Biology and Life Sciences ,Membrane Proteins ,Cell Biology ,Molecular Development ,medicine.disease ,respiratory tract diseases ,Disease Models, Animal ,030104 developmental biology ,Amino Acid Substitution ,Immune System ,Animal Studies ,Lesions ,biology.protein ,Immunoglobulin G4-Related Disease ,Clinical Medicine ,business ,Organism Development ,Digestive System ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Rationale Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a novel clinical disease entity characterized by an elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells. Pathological changes are most frequently seen in the pancreas, lacrimal glands, and salivary glands, but pathological changes in the lung also exist. Linker for activation of T cell (LAT)Y136F knock-in mice show Th2-dominant immunoreactions with elevated serum IgG1 levels, corresponding to human IgG4. We have reported that LATY136F knock-in mice display several characteristic features of IgG4-RD and concluded that they constitute an appropriate model of human IgG4-RD in salivary glands, pancreas, and kidney lesions. Objectives The aim of this study is to evaluate whether lung lesions in LATY136F knock-in mice can be a model of IgG4-related lung disease. Methods Lung tissue samples from LATY136F knock-in mice (LAT) and wild-type mice (WT) were immunostained for IgG1 and obtained for pathological evaluation, and cell fractions and cytokine levels in broncho-alveolar lavage fluid (BALF) were analyzed. Results In the LAT group, IgG1-positive inflammatory cells increased starting at 4 weeks of age and peaked at 10 weeks of age. The total cell count and percentage of lymphocytes increased significantly in BALF in the LAT group compared to the WT group. In BALF, Th2-dominant cytokines and transforming growth factor-β were also increased. In the LAT group, marked inflammation around broncho-vascular bundles peaked at 10 weeks of age. After 10 weeks, fibrosis around broncho-vascular bundles and bronchiectasis were observed in LATY136F knock-in mice but not WT mice. Conclusions LATY136F knock-in mice constitute an appropriate model of lung lesions in IgG4-RD.
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- 2021
12. A case report of SMARCA4/BRG1-deficient non-small cell lung cancer with a spindle cell component found by next-generation sequencing of a brain metastasis
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Hiroko Ikeda, Takashi Sone, Kazuo Kasahara, Satoko Nakada, Kaori Yoshimura, Maki Sakaguchi, Keishi Mizuguchi, Takayuki Nojima, Shinji Takeuchi, Seiji Yano, Kotaro Yoshida, and Toshifumi Gabata
- Abstract
Background: Several studies of different cancers have revealed mutations in switch/sucrose non-fermenting (SWI/SNF) complex genes. Brahma-related gene 1 (BRG1), which is encoded by SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4), is a member of this complex. SMARCA4/BRG-1-deficient non-small cell lung carcinoma (NSCLC) has been considered a subset of lung cancer that has distinct clinical, pathological, and molecular characteristics, which implies its relationship with SMARCA4/BRG1-deficient thoracic sarcoma. Case presentation: We experienced a case of SMARCA4/BRG1-deficient lung cancer in a 40-year-old female patient with a history of smoking. Magnetic resonance imaging revealed a large mass in the right lung apex with an extension to the extrapulmonary region and cerebral metastasis. Histological analysis showed poorly differentiated carcinoma with spindle cell components. She was diagnosed with NSCLC (stage IV) at that point. An EGFR mutation and ALK and ROS1 rearrangement were not detected, and then treated with chemoradiotherapy. Overall, the tumors were resistant to chemotherapy, and therefore, after 2 years, the brain tumor was excised for histological and molecular analysis. Histologically, the brain mass was an undifferentiated tumor with round cells and glandular components. The mutation in SMARCA4 in the brain specimen was identified by next-generation sequencing. Immunohistochemical examination revealed a complete loss of BRG1. SMARCA4/BRG1-deficient thoracic sarcoma had been raised as a differential diagnosis, collectively, she was diagnosed with SMARCA4/BRG1-deficient NSCLC considering for the result of positivity for cytokeratin AE1/AE3 and claudin-4, and negativity for Sal-like protein 4, CD34, and SRY-box 2 by immunohistochemical examination. Regrettably, a definitive diagnosis required approximately 2 years. She is alive with disease at 30 months after the presentation. Conclusions: The diagnosis of SMARCA4/BRG1-deficient NSCLC is frequently difficult because of no specific morphology and necessity of discrimination from SMARCA4/BRG1-deficient thoracic sarcoma, which is the practical reason this disease is sometimes missed. Immunohistochemistry for BRG1 should be encouraged for the pathological examination of NSCLC with any histology for the prompt and precise diagnosis of SMARCA4/BRG1-deficient NSCLC.
- Published
- 2020
13. ANCA-associated nephritis without crescent formation has atypical clinicopathological features: a multicenter retrospective study
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Hideki Nomura, Kazuyuki Suzuki, Takeshi Zoshima, Mitsuhiro Kawano, Fae Suzuki, Ichiro Mizushima, Hiroshi Fujii, Keishi Mizuguchi, Kiyoaki Ito, and Satoshi Hara
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Nephrology ,Male ,medicine.medical_specialty ,Physiology ,Urinary system ,Kidney Glomerulus ,030232 urology & nephrology ,Renal function ,Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Arteritis ,Aged ,Proportional Hazards Models ,Retrospective Studies ,Nephritis ,Sclerosis ,medicine.diagnostic_test ,Proportional hazards model ,business.industry ,Middle Aged ,medicine.disease ,Prognosis ,C-Reactive Protein ,Kidney Failure, Chronic ,Female ,Renal biopsy ,business ,Vasculitis ,Glomerular Filtration Rate - Abstract
Although crescentic glomerulonephritis is a hallmark of ANCA-associated nephritis, the clinicopathological features of ANCA-associated nephritis without crescent formation remain to be elucidated. We enrolled 146 Japanese ANCA-associated vasculitis (AAV) patients subjected to renal biopsy in 16 hospitals from 2001 to 2018, and compared those with and without crescent formation (C + and C− groups). The primary endpoint was end-stage renal disease (ESRD) and/or death. C− group comprised 25 (17.1%) subjects. They had better renal function at the time of renal biopsy [estimated glomerular filtration rate (eGFR); median 41.7 vs 27.5 ml/min/1.73 m2, p
- Published
- 2019
14. Solitary Gastric Metastasis from a Stage IA Serous Ovarian Carcinoma: A Case Report with Literature Review
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Isao Yoshida, Yuki Mitani, Junpei Iwadare, Kayo Kayahashi, Keishi Mizuguchi, Hiroshi Minato, and Kazuyoshi Watanabe
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Oncology ,medicine.medical_specialty ,Pathology ,endocrine system diseases ,Gastrointestinal Stromal Tumors ,gastric metastasis ,Case Report ,Ovarian Serous Adenocarcinoma ,gastrointestinal stromal tumor ,Diagnosis, Differential ,03 medical and health sciences ,Ovarian tumor ,micropapillary carcinoma ,0302 clinical medicine ,Stomach Neoplasms ,Internal medicine ,Ovarian carcinoma ,submucosal tumor ,Biopsy ,Internal Medicine ,medicine ,Humans ,Stage (cooking) ,Stromal tumor ,Aged ,Ovarian Neoplasms ,medicine.diagnostic_test ,business.industry ,General Medicine ,medicine.disease ,female genital diseases and pregnancy complications ,Cystadenocarcinoma, Serous ,Serous fluid ,ovarian cancer ,serous carcinoma ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,Ovarian cancer ,business - Abstract
Gastric metastasis from ovarian cancer is exceptionally rare and generally occurs in advanced stages. A 71-year-old woman presented with a solitary gastric submucosal mass 8 years after the diagnosis of a stage IA ovarian serous adenocarcinoma. Endoscopy showed a tumor covered with normal gastric mucosa. Initially, a gastrointestinal stromal tumor was suspected, but biopsy revealed a histology of invasive micropapillary carcinoma, similar to the histological findings of the previously resected ovarian tumor. Clinicians should consider that in patients with a submucosal tumor and a history of ovarian cancer, gastric lesions may be secondary metastases from ovarian cancer.
- Published
- 2017
15. A case of pancreatic mixed adenoneuroendocrine carcinoma and liver metastasis
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Hiroko Ikeda, Keishi Mizuguchi, Satoko Nakada, and Tsubasa Shimoda
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business.industry ,Mixed adenoneuroendocrine carcinoma ,Cancer research ,medicine ,medicine.disease ,business ,Metastasis - Published
- 2020
16. Cytopathological findings of primary pulmonary Ewing family of tumors with EWSR1 translocation: A case report
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Keishi Mizuguchi, Hitomi Onishi, Yuki Mitani, Hiroshi Minato, and Jun Kawai
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Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Ewing family of tumors ,CD99 ,Population ,Case Report ,Case Reports ,lung ,03 medical and health sciences ,0302 clinical medicine ,Biopsy ,medicine ,030212 general & internal medicine ,education ,education.field_of_study ,elderly man ,Lung ,medicine.diagnostic_test ,biology ,business.industry ,Chromogranin A ,General Medicine ,medicine.anatomical_structure ,Oncology ,EWSR1 ,030220 oncology & carcinogenesis ,biology.protein ,Aspiration cytology ,Immunohistochemistry ,business ,Fluorescence in situ hybridization - Abstract
Primary pulmonary neoplasms of the Ewing family of tumors (EFT) are extremely rare and usually occur in adolescents or young adults. Only about 40 cases of pulmonary EFT have been reported in English literature, and no cytological studies have been documented. In this report, we describe the cytopathological findings of a primary pulmonary EFT in an elderly patient. A 70-year-old man sought care because of a progressing cough and dyspnea. Chest computed tomography revealed a circumscribed mass of 6 cm in the left upper lobe. Fine needle aspiration cytology and core needle biopsy revealed uniform round cell proliferation. The predominant population consisted of cells with thickened nuclear membranes, finely dispersed chromatin, single distinct nucleoli, and indistinct cytoplasm. The other population consisted of smaller cells with darker chromatin. The cytoplasm stained positive for periodic acid–Schiff stain and was digested by diastase. Immunohistochemistry showed positivity for MIC2 (CD99), and focal positivity for neuron specific enolase, synaptophysin, and chromogranin A. Fluorescence in situ hybridization (FISH) revealed EWSR1 translocation. Although rare, pulmonary EFT cannot be disregarded, regardless of age. When two populations of uniform, round cells are observed, immunohistochemistry with MIC2 (CD99) and cytogenetic analysis by reverse transcription polymerase chain reaction or FISH should be considered. Cytological diagnosis may play an important role in the early diagnosis and treatment of pulmonary EFT.
- Published
- 2016
17. Lat(Y136F) knock-in mouse model for human IgG4-related disease
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Yasushi Kakuchi, Tamehito Onoe, Yasunori Suzuki, Bernard Malissen, Kiyoaki Ito, Shozo Izui, Masakazu Yamagishi, Masahiko Zuka, Kazunori Yamada, Mitsuhiro Kawano, Marie Malissen, Keishi Mizuguchi, Department of Molecular Biosciences [Lawrence], University of Kansas [Lawrence] (KU), Kanazawa University (KU), Human Information Processing Laboratory - Japanese Advances Institute of Science and Technology [Ishikawa] (HIP/JAIST), JAIST - Ishikawa - Japon, University of Geneva [Switzerland], Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Université de Genève = University of Geneva (UNIGE), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and DUMENIL, Anita
- Subjects
Pathology ,lcsh:Medicine ,Kidney ,Pathology and Laboratory Medicine ,medicine.disease_cause ,Mouse models ,Autoimmunity ,Mice ,White Blood Cells ,0302 clinical medicine ,Adrenal Cortex Hormones ,Animal Cells ,Fibrosis ,Medicine and Health Sciences ,Medicine ,Gene Knock-In Techniques ,lcsh:Science ,Lung ,Immune Response ,Plasma cells ,Multidisciplinary ,biology ,Salivary gland ,Animal Models ,3. Good health ,Phenotype ,medicine.anatomical_structure ,Experimental Organism Systems ,030220 oncology & carcinogenesis ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Anatomy ,Cellular Types ,medicine.symptom ,Antibody ,Research Article ,medicine.medical_specialty ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,Phenylalanine ,Immune Cells ,T cell ,Immunology ,Endocrine System ,Inflammation ,Salivary glands ,Research and Analysis Methods ,03 medical and health sciences ,Exocrine Glands ,Model Organisms ,Signs and Symptoms ,Diagnostic Medicine ,Animals ,Humans ,Pancreas ,Adaptor Proteins, Signal Transducing ,030203 arthritis & rheumatology ,Blood Cells ,business.industry ,lcsh:R ,Membrane Proteins ,Biology and Life Sciences ,Kidneys ,Renal System ,Cell Biology ,Phosphoproteins ,medicine.disease ,Disease Models, Animal ,Mononuclear cell infiltration ,Mutation ,Leukocytes, Mononuclear ,biology.protein ,Lesions ,Tyrosine ,lcsh:Q ,IgG4-related disease ,Immunoglobulin G4-Related Disease ,business ,Digestive System ,Developmental Biology - Abstract
International audience; Background The adaptor protein Linker for activation of T cell (LAT) is a key signaling hub used by the T cell antigen receptor. Mutant mice expressing loss-of-function mutations affecting LAT and including a mutation in which tyrosine 136 is replaced by a phenylalanine (Lat(Y136F)) develop lymphoproliferative disorder involving T helper type 2 effector cells capable of triggering a massive polyclonal B cell activation that leads to hypergammaglobulinemia G1 and E and to non-resolving inflammation and autoimmunity. The purpose of this study was to evaluate whether the phenotypes of Lat(Y136F) knock-in mice resemble the immunohistopathological features of immunoglobulin G4-related disease (IgG4-RD).Methods Lat(Y136F) knock-in mice were sacrificed at 4-20 weeks of age, and pancreas, kidney, salivary gland and lung were obtained. All organs were stained with hematoxylin-eosin and with Azan for estimation of collagen in fibrosis, and the severity scores of inflammation and fibrosis were evaluated. Immunostainings were performed to analyze the types of infiltrating cells. In addition, the effects of corticosteroid treatment on the development of tissue lesions and serum levels of IgG1 were assessed.Results Tissue lesions characterized by inflammatory mononuclear cell infiltration and fibrosis were detected in pancreas, kidney, and salivary gland starting from 6 weeks of age. Immunostainings showed pronounced infiltration of plasma cells, CD4-positive T cells, and macrophages. Infiltrating plasma cells predominantly expressed IgG1. The extent of inflammation in pancreas and salivary glands was markedly reduced by corticosteroid treatment.Conclusions Lat(Y136F) knock-in mice displayed increased production of Th2-type IgG1 (a homologue of human IgG4) and developed multiple organ tissue lesions reminiscent of those seen in patients with IgG4-RD. Moreover, the development of these tissue lesions was highly sensitive to corticosteroid treatment like in IgG4-RD. For these reasons we consider the Lat(Y136F) knock-in mouse strain to represent a promising model for human IgG4-RD.
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- 2018
18. Distribution and Morphological Features of Microglia in the Developing Cerebral Cortex of Gyrencephalic Mammals
- Author
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Toshihide Horiike, Naoyuki Matsumoto, Hiroshi Kawasaki, Keishi Mizuguchi, Yoshie Ichikawa, and Yohei Shinmyo
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0301 basic medicine ,Neurogenesis ,Subventricular zone ,Cell Count ,Biology ,Biochemistry ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Mice ,0302 clinical medicine ,Nerve Fibers ,Cortex (anatomy) ,Lateral Ventricles ,medicine ,Distribution (pharmacology) ,Animals ,Fiber layer ,Cerebral Cortex ,Mice, Inbred ICR ,Microglia ,Ferrets ,General Medicine ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Cerebral cortex ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Microglia have been attracting much attention because of their fundamental importance in both the mature brain and the developing brain. Though important roles of microglia in the developing cerebral cortex of mice have been uncovered, their distribution and roles in the developing cerebral cortex in gyrencephalic higher mammals have remained elusive. Here we examined the distribution and morphology of microglia in the developing cerebral cortex of gyrencephalic carnivore ferrets. We found that a number of microglia were accumulated in the germinal zones (GZs), especially in the outer subventricular zone (OSVZ), which is a GZ found in higher mammals. Furthermore, we uncovered that microglia extended their processes tangentially along inner fiber layer (IFL)-like fibers in the developing ferret cortex. The OSVZ and the IFL are the prominent features of the cerebral cortex of higher mammals. Our findings indicate that microglia may play important roles in the OSVZ and the IFL in the developing cerebral cortex of higher mammals.
- Published
- 2017
19. A case of mammary screlosing papilloma (ductal adenoma) interpreted as malignancy owing to the presence of multiple nuclear cytoplasmic inclusions and nuclear grooves
- Author
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Keishi MIZUGUCHI and Hiroshi MINATO
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medicine.medical_specialty ,business.industry ,Medicine ,Ductal Adenoma ,Radiology ,business ,Aspiration cytology - Published
- 2014
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