68 results on '"Kidoguchi, K."'
Search Results
2. DNA demethylating agents for chemoprevention of oncovirus-associated leukemogenesis.
- Author
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Yamamoto Y, Watanabe T, Ureshino H, Kurahashi Y, Fukuda-Kurahashi Y, Kamachi K, Kawasoe K, Kidoguchi K, Yamashita S, Hattori N, Ushijima T, and Kimura S
- Subjects
- Humans, Animals, Leukemia, Mice, Chemoprevention methods, Azacitidine therapeutic use, Azacitidine pharmacology, Carcinogenesis drug effects, DNA Methylation drug effects
- Published
- 2024
- Full Text
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3. Reprogramming of pyrimidine nucleotide metabolism supports vigorous cell proliferation of normal and malignant T cells.
- Author
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Watanabe T, Yamamoto Y, Kurahashi Y, Kawasoe K, Kidoguchi K, Ureshino H, Kamachi K, Yoshida-Sakai N, Fukuda-Kurahashi Y, Nakamura H, Okada S, Sueoka E, and Kimura S
- Subjects
- Adult, Humans, Uridine metabolism, Cell Proliferation, Cytidine, Pyrimidine Nucleotides, Receptors, Antigen, T-Cell, T-Lymphocytes metabolism, Pyrimidines, Human T-lymphotropic virus 1
- Abstract
Abstract: Adult T-cell leukemia/lymphoma (ATL) is triggered by infection with human T-cell lymphotropic virus-1 (HTLV-1). Here, we describe the reprogramming of pyrimidine biosynthesis in both normal T cells and ATL cells through regulation of uridine-cytidine kinase 2 (UCK2), which supports vigorous proliferation. UCK2 catalyzes the monophosphorylation of cytidine/uridine and their analogues during pyrimidine biosynthesis and drug metabolism. We found that UCK2 was overexpressed aberrantly in HTLV-1-infected T cells but not in normal T cells. T-cell activation via T-cell receptor (TCR) signaling induced expression of UCK2 in normal T cells. Somatic alterations and epigenetic modifications in ATL cells activate TCR signaling. Therefore, we believe that expression of UCK2 in HTLV-1-infected cells is induced by dysregulated TCR signaling. Recently, we established azacitidine-resistant (AZA-R) cells showing absent expression of UCK2. AZA-R cells proliferated normally in vitro, whereas UCK2 knockdown inhibited ATL cell growth. Although uridine and cytidine accumulated in AZA-R cells, possibly because of dysfunction of pyrimidine salvage biosynthesis induced by loss of UCK2 expression, the amount of UTP and CTP was almost the same as in parental cells. Furthermore, AZA-R cells were more susceptible to an inhibitor of dihydroorotic acid dehydrogenase, which performs the rate-limiting enzyme of de novo pyrimidine nucleotide biosynthesis, and more resistant to dipyridamole, an inhibitor of pyrimidine salvage biosynthesis, suggesting that AZA-R cells adapt to UCK2 loss by increasing de novo pyrimidine nucleotide biosynthesis. Taken together, the data suggest that fine-tuning pyrimidine biosynthesis supports vigorous cell proliferation of both normal T cells and ATL cells., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2024
- Full Text
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4. A Combination of Alectinib and DNA-Demethylating Agents Synergistically Inhibits Anaplastic-Lymphoma-Kinase-Positive Anaplastic Large-Cell Lymphoma Cell Proliferation.
- Author
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Kawasoe K, Watanabe T, Yoshida-Sakai N, Yamamoto Y, Kurahashi Y, Kidoguchi K, Ureshino H, Kamachi K, Fukuda-Kurahashi Y, and Kimura S
- Abstract
The recent evolution of molecular targeted therapy has improved clinical outcomes in several human malignancies. The translocation of anaplastic lymphoma kinase (ALK) was originally identified in anaplastic large-cell lymphoma (ALCL) and subsequently in non-small cell lung carcinoma (NSCLC). Since ALK fusion gene products act as a driver of carcinogenesis in both ALCL and NSCLC, several ALK tyrosine kinase inhibitors (TKIs) have been developed. Crizotinib and alectinib are first- and second-generation ALK TKIs, respectively, approved for the treatment of ALK-positive ALCL (ALK
+ ALCL) and ALK+ NSCLC. Although most ALK+ NSCLC patients respond to crizotinib and alectinib, they generally relapse after several years of treatment. We previously found that DNA-demethylating agents enhanced the efficacy of ABL TKIs in chronic myeloid leukemia cells. Moreover, aberrant DNA methylation has also been observed in ALCL cells. Thus, to improve the clinical outcomes of ALK+ ALCL therapy, we investigated the synergistic efficacy of the combination of alectinib and the DNA-demethylating agent azacytidine, decitabine, or OR-2100 (an orally bioavailable decitabine derivative). As expected, the combination of alectinib and DNA-demethylating agents synergistically suppressed ALK+ ALCL cell proliferation, concomitant with DNA hypomethylation and a reduction in STAT3 (a downstream target of ALK fusion proteins) phosphorylation. The combination of alectinib and OR-2100 markedly altered gene expression in ALCL cells, including that of genes implicated in apoptotic signaling, which possibly contributed to the synergistic anti-ALCL effects of this drug combination. Therefore, alectinib and OR-2100 combination therapy has the potential to improve the outcomes of patients with ALK+ ALCL.- Published
- 2023
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5. HHV-8 negative PEL-like lymphoma follicular helper T type in a non-HIV infected elderly.
- Author
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Kidoguchi K, Uchino M, Tokushima E, Monji M, Yamasaki F, Shimasaki Y, and Ohshima K
- Subjects
- Aged, 80 and over, Female, HIV Infections complications, Herpesviridae Infections complications, Herpesvirus 8, Human isolation & purification, Humans, Lymphoma, Follicular virology, Lymphoma, Primary Effusion virology, Lymphoma, Follicular diagnosis, Lymphoma, Primary Effusion diagnosis
- Published
- 2021
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6. Oral Azacitidine in Patients With Myelodysplastic Syndrome.
- Author
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Shibusawa M, Kidoguchi K, and Tanimoto T
- Subjects
- Antimetabolites, Azacitidine adverse effects, Humans, Myelodysplastic Syndromes drug therapy
- Abstract
Competing Interests: Tetsuya TanimotoConsulting or Advisory Role: Medical Network Systems, MNES Inc, Bionics Co LtdNo other potential conflicts of interest were reported.
- Published
- 2021
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7. Efficacy and safety of ponatinib for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: a case series from a single institute.
- Author
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Kidoguchi K, Ureshino H, Kizuka-Sano H, Yamaguchi K, Katsuya H, Kubota Y, Ando T, Miura M, Takahashi N, and Kimura S
- Subjects
- Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Combined Modality Therapy, Disease Management, Female, Fusion Proteins, bcr-abl genetics, Humans, Imidazoles administration & dosage, Imidazoles adverse effects, Male, Middle Aged, Molecular Targeted Therapy methods, Philadelphia Chromosome, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Protein Kinase Inhibitors administration & dosage, Protein Kinase Inhibitors adverse effects, Pyridazines administration & dosage, Pyridazines adverse effects, Retrospective Studies, Treatment Outcome, Fusion Proteins, bcr-abl antagonists & inhibitors, Imidazoles therapeutic use, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Protein Kinase Inhibitors therapeutic use, Pyridazines therapeutic use
- Abstract
Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) is an aggressive leukemia that occurs in 20-40% of adult patients. Ph + ALL is caused by the Philadelphia chromosome (Ph), which consists of a t(9;22)(q34;q11) reciprocal translocation leading to the formation of a BCR-ABL1 fusion gene. The disease is treated with targeted therapy comprising ABL1 tyrosine kinase inhibitors (TKIs). Ponatinib is a third generation TKI that demonstrates higher binding affinity for ABL1 than first/second generation TKIs. Although intensive combined immunotherapy with ponatinib greatly improves the prognosis of Ph + ALL, the safety and efficacy profiles of ponatinib in Japanese patients are unclear. This retrospective study investigated five cases of Ph + ALL at a single institute to evaluate safety and efficacy profiles. Three patients achieved a deep molecular response (DMR) following combined intensive treatment with ponatinib as induction chemotherapy. Four patients received consolidative allogenic stem cell transplantation (allo-SCT) during their first complete response. Three of the four experienced early relapse within 100 days; they subsequently received ponatinib, and one of the three achieved a DMR. No patient experienced severe cardiovascular events. This case series suggests that ponatinib at a concentration of least 30 mg exhibits anti-leukemia effects in Japanese patients with Ph + ALL., (© 2021. Japanese Society of Hematology.)
- Published
- 2021
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8. Blinatumomab vs Chemotherapy Among Children With Relapsed Acute Lymphoblastic Leukemia.
- Author
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Shibusawa M, Kidoguchi K, and Tanimoto T
- Subjects
- Child, Humans, Antibodies, Bispecific therapeutic use, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Published
- 2021
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9. Does the order of busulfan and cyclophosphamide affect allogeneic stem cell transplantation related liver toxicity?
- Author
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Kidoguchi K, Kuniyoshi Y, and Kataoka Y
- Subjects
- Cyclophosphamide adverse effects, Liver, Busulfan adverse effects, Hematopoietic Stem Cell Transplantation adverse effects
- Published
- 2021
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10. Idecabtagene Vicleucel in Relapsed Myeloma.
- Author
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Kidoguchi K, Mori J, and Tanimoto T
- Subjects
- Humans, Neoplasm Recurrence, Local, Multiple Myeloma drug therapy
- Published
- 2021
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11. PET-guided omission of radiotherapy in Hodgkin lymphoma.
- Author
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Shibusawa M, Kidoguchi K, Mori J, and Tanimoto T
- Subjects
- Humans, Positron-Emission Tomography, Vinblastine, Hodgkin Disease diagnostic imaging, Hodgkin Disease drug therapy, Hodgkin Disease radiotherapy
- Abstract
Competing Interests: TT reports personal fees from Medical Network Systems, and Bionics, outside of the submitted work. All other authors declare no competing interests.
- Published
- 2021
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12. Ibrutinib-Induced Cardiac Tamponade in Chronic Lymphocytic Leukemia
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Kidoguchi K, Kubato Y, Nishimura Y, Kizuka-Sano H, and Kimura S
- Subjects
- Adenine adverse effects, Adenine therapeutic use, Aged, Biomarkers, Biopsy, Echocardiography, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Piperidines therapeutic use, Protein Kinase Inhibitors therapeutic use, Radiography, Thoracic, Symptom Assessment, Adenine analogs & derivatives, Cardiac Tamponade diagnosis, Cardiac Tamponade etiology, Leukemia, Lymphocytic, Chronic, B-Cell complications, Piperidines adverse effects, Protein Kinase Inhibitors adverse effects
- Published
- 2021
- Full Text
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13. Aplastic Anemia in a Patient with Cronkhite-Canada Syndrome.
- Author
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Kidoguchi K, Kubota Y, Fujimoto S, Sakata Y, Kizuka-Sano H, Yamaguchi K, Ureshino H, Katsuya H, Ando T, Esaki M, and Kimura S
- Subjects
- Histocompatibility Antigens Class I, Humans, Male, Mesalamine, Middle Aged, Anemia, Aplastic complications, Anemia, Aplastic diagnosis, Hemoglobinuria, Paroxysmal complications, Hemoglobinuria, Paroxysmal diagnosis, Intestinal Polyposis complications, Intestinal Polyposis diagnosis
- Abstract
Cronkhite-Canada syndrome (CCS) is a rare polyposis disorder accompanied by alopecia and onychodystrophy. A 63-year-old man with a history of CCS and repeated embolism developed progressive thrombocytopenia and mild anemia. Laboratory testing, a bone marrow examination, and magnetic resonance imaging of the spine resulted in a diagnosis of concurrent aplastic anemia (AA). Paroxysmal nocturnal hemoglobinuria (PNH)-type cells were detected in a peripheral blood specimen. In addition, human leukocyte antigen (HLA) included DRB1*15:01 and DRB1*15:02. Mesalazine was discontinued in consideration of possible drug-induced pancytopenia. Immunosuppressive therapy ameliorated both the gastrointestinal symptoms of CCS and pancytopenia. A common autoimmune abnormality might underlie both CCS and AA.
- Published
- 2021
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14. Concomitant Nephrotic Syndrome with Diffuse Large B-cell Lymphoma: A Case Report.
- Author
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Kidoguchi K, Katsuya H, Ureshino H, Kizuka-Sano H, Yamaguchi K, Nagata A, Rikitake S, Aikawa K, Naito S, Aoki S, Kubota Y, Ando T, and Kimura S
- Subjects
- Aged, Basement Membrane pathology, Combined Modality Therapy, Diabetes Complications, Humans, Immunotherapy, Inflammation, Lymphoma, Large B-Cell, Diffuse complications, Lymphoma, Large B-Cell, Diffuse pathology, Lymphoma, Large B-Cell, Diffuse therapy, Male, Nephrotic Syndrome complications, Nephrotic Syndrome pathology, Nephrotic Syndrome therapy, Pancreatic Neoplasms complications, Pancreatic Neoplasms diagnostic imaging, Pancreatic Neoplasms pathology, Pancreatic Neoplasms therapy, Receptors, Phospholipase A2 immunology, Rituximab pharmacology, Tomography, X-Ray Computed, Lymphoma, Large B-Cell, Diffuse diagnostic imaging, Nephrotic Syndrome diagnostic imaging
- Abstract
Membranous nephropathy (MN) is a common glomerular disease that is characterized by diffuse thickening of the glomerular basement membrane, and a common cause of nephrotic syndrome (NS). MN is often accompanied with malignant disease; The solid tumors are commonly associated with MN, whereas hematological malignancies are rarely found in patients with MN. A 68-year-old man with a history of diabetes mellitus visited a hospital with a chief complaint of general fatigue. He was previously not diagnosed with any complications of diabetes. Computed tomography revealed a pancreatic tumor, and the pathological findings of the biopsied tumor revealed the tumor was diffuse large B-cell lymphoma (DLBCL). Concurrently, he developed severe proteinuria, hypoalbuminemia, systemic edema and hyperlipidemia, consistent with the diagnosis of NS. The biopsied renal specimen revealed minute spike lesions of glomerular basement membrane, and abnormal lymphocytes infiltrated in the kidney interstitially. Anti-glomerular basement membrane antibody, proteinase-3-/myeloperoxidase antineutrophil cytoplasmic antibody and hepatitis B antigenemia, are absent in the patient. Serum anti-phospholipase A2 receptor (PLA2R) antibody (marker for primary MN) was not detected. A diagnosis of secondary MN induced by DLBCL was made. He received rituximab containing chemotherapy for DLBCL, resulting in amelioration of both DLBCL and MN. We report the rare case of a patient co-existing NS and DLBCL. DLBCL might be pathogenesis of NS; the findings are supported by the presence of MN, an underlying malignancy (DLBCL), and the lack of anti-PLA2R antibodies. Although further investigation is warranted, our case suggests that DLBCL is a possible cause of secondary MN.
- Published
- 2020
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15. A methotrexate-associated lymphoproliferative disorder expressing CD10 and BCL6 with the IGH/CCND1 translocation.
- Author
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Katsuya H, Kizuka-Sano H, Yokoo M, Kidoguchi K, Yamaguchi K, Nishioka A, Ureshino H, Kubota Y, Ando T, Naito S, Ohshima K, and Kimura S
- Subjects
- Aged, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Arthritis, Rheumatoid complications, Arthritis, Rheumatoid drug therapy, Chromosomes, Human, Pair 11 genetics, Chromosomes, Human, Pair 14 genetics, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Female, Humans, Immunosuppressive Agents therapeutic use, Lymph Nodes pathology, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse genetics, Methotrexate therapeutic use, Neoplasm Proteins genetics, Oncogene Proteins, Fusion genetics, Prednisolone administration & dosage, Remission Induction, Rituximab administration & dosage, Vincristine administration & dosage, Chromosomes, Human, Pair 11 ultrastructure, Chromosomes, Human, Pair 14 ultrastructure, Immunosuppressive Agents adverse effects, Lymphoma, Large B-Cell, Diffuse chemically induced, Methotrexate adverse effects, Neoplasm Proteins analysis, Neprilysin analysis, Oncogene Proteins, Fusion analysis, Proto-Oncogene Proteins c-bcl-6 analysis, Translocation, Genetic
- Published
- 2020
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16. Durable remission of post-transplant relapsed FLT3-ITD AML in response to gilteritinib administration after a second transplant from the same donor.
- Author
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Ando T, Sano H, Yokoo M, Kusaba K, Kidoguchi K, Yamaguchi K, Katsuya H, Yoshihara S, Kubota Y, Kojima K, and Kimura S
- Subjects
- Aniline Compounds pharmacology, Female, Graft vs Leukemia Effect drug effects, Humans, Leukemia, Myeloid, Acute immunology, Mutation, Pyrazines pharmacology, Remission Induction, Reoperation, Treatment Outcome, fms-Like Tyrosine Kinase 3 antagonists & inhibitors, Aniline Compounds administration & dosage, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute surgery, Pyrazines administration & dosage, Recurrence, Tandem Repeat Sequences genetics, Tissue Donors, fms-Like Tyrosine Kinase 3 genetics
- Abstract
Patients with FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) acute myeloid leukemia (AML) respond to conventional induction chemotherapy, with remission rates similar to those seen in other subtypes; however, they are much more likely to relapse and relapse is rapid. For this reason, eligible patients receive consolidation therapy with early allogenic transplantation, but the recurrence rate remains high, even after transplantation. Moreover, the optimal therapy for patients with FLT3-ITD AML who relapse after allogeneic hematopoietic stem cell transplantation remains unclear. Here, we report a case in which graft-versus-leukemia (GVL) effects were induced by gilteritinib administration after a second transplant from the same donor, resulting in sustained remission of early FLT3-ITD AML relapse after allogeneic transplantation. Several studies suggest that the benefits of FLT3 tyrosine kinase inhibitors (FLT3-TKI) after allogeneic transplantation are attributable to GVL induction, as well as direct effects on FLT3 mutation-positive leukemia cells. With this in mind, we induced lymphodepletion using L-PAM to further enhance GVL induction by donor lymphocytes and FLT3-TKI. We believe that enhancement of GVL induction by lymphodepletion should be considered before FLT3-TKI use, if the prognosis is very poor, such as in patients with recurrence following allogeneic transplantation.
- Published
- 2020
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17. Ventriculitis with aqueduct stenosis.
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Kidoguchi K and Yoshioka F
- Subjects
- Cerebral Ventriculitis surgery, Humans, Hydrocephalus etiology, Hydrocephalus surgery, Magnetic Resonance Imaging, Male, Middle Aged, Tomography, X-Ray Computed, Cerebral Ventriculitis diagnosis, Constriction, Pathologic etiology, Hydrocephalus diagnosis
- Published
- 2020
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18. Accelerated Phase of Atypical Chronic Myeloid Leukemia with Severe Disseminated Intravascular Coagulation at Initial Presentation.
- Author
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Fujita M, Kamachi K, Yokoo M, Kidoguchi K, Kusaba K, Kizuka-Sano H, Yamaguchi K, Nishioka A, Yoshimura M, Kubota Y, Ando T, Kojima K, and Kimura S
- Subjects
- Adult, Antineoplastic Agents therapeutic use, Humans, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative drug therapy, Leukocytosis complications, Male, Disseminated Intravascular Coagulation complications, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative complications, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative pathology
- Abstract
Patients with myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) are often asymptomatic and thus can remain undiagnosed until they become symptomatic due to progression to the accelerated phase (AP) or transformation to acute leukemia (leukemic transformation; LT). We herein report the case of a previously healthy 38-year-old man who had hyperleukocytosis with dysplastic myeloid precursor cells and severe disseminated intravascular coagulation. Hematopoietic recovery with features of atypical chronic myeloid leukemia (aCML) after induction chemotherapy was a diagnostic clue. Although rare, this case highlights the limitation of the diagnostic approach for aCML with AP or LT at the initial presentation.
- Published
- 2020
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19. Successful Anti-TNF-Alpha Therapy for Crohn's Disease After Allogeneic Stem Cell Transplantation: A Case Report.
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Kamachi K, Ando T, Tsuruoka N, Hashiguchi M, Kidoguchi K, Kusaba K, Sano H, Sano H, Yamaguchi K, Nishioka A, Yoshimura M, Yokoo M, Kubota Y, Kojima K, and Kimura S
- Subjects
- Adalimumab administration & dosage, Combined Modality Therapy, Female, Graft vs Host Disease etiology, Graft vs Host Disease therapy, Humans, Immunotherapy methods, Infliximab administration & dosage, Remission Induction, Transplantation, Homologous adverse effects, Treatment Outcome, Tumor Necrosis Factor-alpha antagonists & inhibitors, Tumor Necrosis Factor-alpha immunology, Young Adult, Antibodies, Monoclonal administration & dosage, Cord Blood Stem Cell Transplantation adverse effects, Crohn Disease etiology, Crohn Disease therapy, Hodgkin Disease therapy
- Abstract
Graft-versus-host disease (GVHD) is a potentially life-threatening complication of allogeneic stem cell transplantation (Allo-SCT). Chronic GVHD, which typically presents more than 100 days after Allo-SCT, can resemble manifestations of autoimmune disease; however, there are only a few reports on the development of Crohn's disease (CD) after Allo-SCT. Here, we report a case of steroid-refractory CD after umbilical cord blood transplantation (CBT), which was dramatically improved with administration of anti-tumor necrosis factor-alpha (anti-TNF-alpha) antibodies. A 21-year-old woman with refractory Hodgkin lymphoma underwent CBT and achieved complete remission. About 1 year after CBT, she complained of intermittent abdominal pain and bloody diarrhea, and colonoscopy revealed multiple longitudinal colonic ulcers with a cobblestone appearance; thus, based on the colonoscopy findings, she was diagnosed with CD. We considered a CD-like manifestation of gastrointestinal GVHD and initially administered steroids, but the therapeutic effect was poor. Then, we administered anti-TNF-alpha antibodies, infliximab, and then adalimumab, which resulted in rapid improvement of abdominal symptoms, with no recurrence despite discontinuation of this therapy. Anti-TNF-alpha antibodies are effective for CD after Allo-SCT, which can be considered as a subsequent complication of GVHD.
- Published
- 2020
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20. Reconstitution of NK cells expressing KIR3DL1 is associated with reduced NK cell activity and relapse of CML after allogeneic hematopoietic stem cell transplantation.
- Author
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Ureshino H, Shindo T, Sano H, Kubota Y, Ando T, Kidoguchi K, Kusaba K, Itamura H, Kojima H, Kusunoki Y, Miyazaki Y, Kojima K, Tanaka H, Saji H, Oshima K, and Kimura S
- Subjects
- Allografts, Genes, abl genetics, Graft vs Leukemia Effect genetics, Graft vs Leukemia Effect immunology, HLA Antigens, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Neoplasm Recurrence, Local, Transcription, Genetic, Treatment Outcome, Gene Expression, Hematopoietic Stem Cell Transplantation, Killer Cells, Natural immunology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive immunology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Receptors, KIR3DL1 genetics
- Abstract
Although the prognosis of chronic myeloid leukemia (CML) in blastic crisis remains poor, some patients achieve long-term remission after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This may be attributable to graft-versus-leukemia (GVL) effects by donor lymphocytes, but their regulating mechanisms are unclear. Antitumor natural killer (NK) cell immunity is assumed to be important in CML, and we have previously shown that allelic polymorphisms of killer immunoglobulin-like receptors (KIRs) and histocompatibility leukocyte antigens (HLAs) are associated with the response of CML to tyrosine kinase inhibitors. Here, we report a case of CML in blastic phase who received HLA-matched but KIR3DL1 allelic-mismatched allo-HSCT. After transplant, decreased BCR-ABL transcript levels and enhanced NK cell activity were transiently observed. However, reconstitution of KIR3DL1-expressing NK cells occurred, which was associated with diminished NK cell activity and increased BCR-ABL. This case indicates the potential significance of KIR3DL1 in NK cell-mediated GVL activity following allo-HSCT. To the best of our knowledge, this is the first report to analyze the association between sequential KIR3DL1 expression and activity of NK cells after allo-HSCT. Selecting donors with KIR3DL1-null alleles may maintain competent GVL effects and provide improved outcomes in allo-HSCT for CML.
- Published
- 2020
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21. Severe infusion reaction, anti-rituximab antibodies and lymphoma.
- Author
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Kidoguchi K, Kubota Y, Kusaba K, Kizuka-Sano H, Yamaguchi K, Nishioka A, Yokoo M, Ando T, Kojima K, and Kimura S
- Subjects
- Antibodies, Monoclonal, Murine-Derived, Antigens, CD20 immunology, Cytokines blood, Cytokines immunology, Humans, Injection Site Reaction drug therapy, Lymphoma, Follicular pathology, Male, Middle Aged, Prednisolone therapeutic use, Rituximab, Shock immunology, Treatment Outcome, Antibodies, Monoclonal adverse effects, Antineoplastic Agents, Immunological adverse effects, Injection Site Reaction etiology, Lymphoma, Follicular drug therapy, Shock physiopathology
- Published
- 2020
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22. Terminal deoxynucleotidyl transferase (TdT) negative early T cell precursor acute lymphoblastic leukemia (ETP-ALL) with spontaneous acute kidney injury.
- Author
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Kidoguchi K, Yokoo M, Umino A, Aoki S, and Kimura S
- Subjects
- Acute Kidney Injury therapy, Fatal Outcome, Humans, Male, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma therapy, Young Adult, Acute Kidney Injury blood, Acute Kidney Injury diagnosis, DNA Nucleotidylexotransferase blood, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma blood, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma diagnosis
- Published
- 2020
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23. Epstein-Barr virus-positive diffuse large B cell lymphoma, not otherwise specified, carrying a t(19;22)(q13;q11) translocation.
- Author
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Yamaguchi K, Kubota Y, Kishimori C, Ohno H, Kidoguchi K, Kizuka-Sano H, Nishioka A, Katsuya H, Ando T, and Kimura S
- Subjects
- Abnormal Karyotype, Aged, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, B-Lymphocytes chemistry, B-Lymphocytes virology, Chromosomes, Human, Pair 19 ultrastructure, Chromosomes, Human, Pair 22 ultrastructure, Cisplatin administration & dosage, Cyclophosphamide administration & dosage, Cytarabine administration & dosage, Doxorubicin administration & dosage, Etoposide administration & dosage, Humans, Lymphoma, Large B-Cell, Diffuse virology, Male, Methylprednisolone administration & dosage, Prednisone administration & dosage, RNA, Neoplasm analysis, RNA, Viral analysis, Rituximab administration & dosage, Vincristine administration & dosage, Chromosomes, Human, Pair 19 genetics, Chromosomes, Human, Pair 22 genetics, Epstein-Barr Virus Infections genetics, Translocation, Genetic
- Published
- 2020
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24. Clinical impact of the CONUT score in patients with multiple myeloma.
- Author
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Okamoto S, Ureshino H, Kidoguchi K, Kusaba K, Kizuka-Sano H, Sano H, Nishioka A, Yamaguchi K, Kamachi K, Itamura H, Yoshimura M, Yokoo M, Shindo T, Kubota Y, Ando T, Kojima K, Kawaguchi A, Sueoka E, and Kimura S
- Subjects
- Adult, Aged, Aged, 80 and over, Autografts, Disease-Free Survival, Female, Follow-Up Studies, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Survival Rate, Multiple Myeloma mortality, Multiple Myeloma pathology, Multiple Myeloma physiopathology, Multiple Myeloma therapy, Nutritional Status, Peripheral Blood Stem Cell Transplantation
- Abstract
Novel anti-myeloma drugs have significantly improved the overall survival (OS) of patients with multiple myeloma (MM). However, not all MM patients treated with these drugs show survival benefits, and biologic and genetic prognostic factors are insufficient to predict the response to treatment. Decreasing treatment-related complications is important to improve the efficacy of treatment in patients with MM. The Controlling Nutritional Status (CONUT) score is a screening method for poor nutritional status, which is associated with poor prognosis in several cancers because it increases the rate of treatment-related complications. We retrospectively analyzed the OS of 64 patients with symptomatic MM and evaluated the correlation between the CONUT score and patient prognosis in MM. The median age at diagnosis was 66 years, and multivariate analysis showed that a high CONUT score (≥ 5; hazard ratio, 3.937; 95% confidence interval, 1.214-12.658; P = 0.022) was an independent prognostic risk factor. Subgroup analysis was performed according to patient age because the choice of treatment strategy, particularly autologous peripheral blood stem cell transplantation (auto-PBSCT), can vary depending on age in MM patients. Younger patients (< 65 years old) who received auto-PBSCT and had a lower CONUT score (0-3) showed a significantly better survival outcome than those with a higher CONUT score (≥ 4) (median OS, not reached vs. 64.1 months; P = 0.011). The CONUT score is simple to calculate and provides a useful prognostic indicator in patients with MM, especially transplant-eligible patients.
- Published
- 2020
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25. BCR-ABL1- and CBFB-MYH11-positive chronic myeloid leukemia presenting with primary blast crisis and marrow fibrosis.
- Author
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Kidoguchi K, Kojima K, Yokoo M, and Kimura S
- Subjects
- Aged, Blast Crisis diagnostic imaging, Female, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnostic imaging, Blast Crisis genetics, Fusion Proteins, bcr-abl genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Oncogene Proteins, Fusion genetics
- Published
- 2019
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- View/download PDF
26. Primary Chest Wall MYC/BCL6 Double-hit Lymphoma with t (3;7) (q27;p12) and t (8;14) (q24;q32) Translocations.
- Author
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Kamachi K, Kubota Y, Nagaie T, Yamaguchi K, Ogusu S, Kidoguchi K, Kusaba K, Kizuka-Sano H, Nishioka A, Yoshimura M, Yokoo M, Ando T, Kai K, Kojima K, Ohshima K, Sueoka E, and Kimura S
- Subjects
- Humans, Lymphoma, B-Cell pathology, Male, Middle Aged, Treatment Outcome, Antineoplastic Agents therapeutic use, Lymphoma, B-Cell drug therapy, Lymphoma, B-Cell genetics, Proto-Oncogene Proteins c-bcl-6 genetics, Thoracic Wall pathology, Translocation, Genetic
- Abstract
Primary chest wall lymphoma is rare and typically associated with chronic pleural inflammation. Double-hit lymphoma (DHL), which is defined as aggressive mature B-cell lymphoma with MYC and BCL2 or BCL6 rearrangements, is a highly aggressive malignancy that tends to have extranodal involvement and is resistant to standard immunochemotherapy. We herein report a 55-year-old man with no history of chronic pleural inflammation, diagnosed with primary chest wall DHL with MYC/BCL6 rearrangement, and harboring a unique BCL6 translocation, t (3;7) (q27;p12). After six courses of intensive chemotherapy, he has achieved complete remission. To our knowledge, this is the first case report of primary chest wall DHL.
- Published
- 2019
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27. Oral ulceration: an unusual manifestation of lymphomatoid granulomatosis.
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Kidoguchi K, Yoshimura M, Kojima K, Ureshino H, Egashira R, Yokoo M, Kai K, Egashira Y, Ohshima K, Ando T, and Kimura S
- Subjects
- Aged, Female, Humans, Male, Lymphomatoid Granulomatosis diagnostic imaging, Lymphomatoid Granulomatosis drug therapy, Oral Ulcer diagnostic imaging, Oral Ulcer drug therapy, Tomography, X-Ray Computed
- Published
- 2019
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- View/download PDF
28. Is clinicopathological distinction of mucosa-associated lymphoid tissue lymphoma from Waldenström macroglobulinemia essential in MYD88 L265P mutation-positive cases?
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Kidoguchi K, Kojima K, Seki R, Nagafuji K, Ohshima K, and Kimura S
- Subjects
- Amino Acid Substitution, Humans, Male, Middle Aged, Lymphoma, B-Cell, Marginal Zone diagnostic imaging, Lymphoma, B-Cell, Marginal Zone genetics, Lymphoma, B-Cell, Marginal Zone metabolism, Mutation, Missense, Myeloid Differentiation Factor 88 genetics, Myeloid Differentiation Factor 88 metabolism, Waldenstrom Macroglobulinemia diagnostic imaging, Waldenstrom Macroglobulinemia genetics, Waldenstrom Macroglobulinemia metabolism
- Published
- 2019
- Full Text
- View/download PDF
29. Clinical impact of the CONUT score and mogamulizumab in adult T cell leukemia/lymphoma.
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Ureshino H, Kusaba K, Kidoguchi K, Sano H, Nishioka A, Itamura H, Yoshimura M, Yokoo M, Shindo T, Kubota Y, Ando T, Kojima K, Sueoka E, and Kimura S
- Subjects
- Aged, Aged, 80 and over, Allografts, Antibodies, Monoclonal, Humanized adverse effects, Disease-Free Survival, Female, Follow-Up Studies, Humans, Male, Middle Aged, Risk Assessment, Survival Rate, Antibodies, Monoclonal, Humanized administration & dosage, Hematopoietic Stem Cell Transplantation, Leukemia-Lymphoma, Adult T-Cell mortality, Leukemia-Lymphoma, Adult T-Cell therapy
- Abstract
Accurate risk assessment to determine the eligibility for allogeneic hematopoietic stem cell transplantation (allo-HCT) in patients with adult T cell leukemia (ATL) is necessary to improve survival outcomes. The controlling nutritional status (CONUT) score predicts prognosis in several tumors; however, the prognostic significance of the CONUT score in ATL remains unclear. The present study investigated the correlation between the CONUT score and the survival outcomes of transplant-eligible ATL patients. Mogamulizumab, a humanized monoclonal antibody against C-C chemokine receptor 4, was recently identified as a promising salvage chemotherapy agent for transplant-ineligible ATL patients. We therefore evaluated the efficacy of mogamulizumab in transplant-ineligible ATL patients. Patients diagnosed with aggressive ATL (acute lymphoma of unfavorable chronic type) between January 2008 and March 2017 at Saga University Hospital, Japan, were retrospectively enrolled. Of 54 patients, 25 were < 70 years of age and 14 received allo-HCT. The median overall survival (OS) and non-relapse mortality (NRM) rate at 1 year among patients receiving allo-HCT were 1685.5 days and 30% in those with a CONUT score 0-3 (n = 10) and 184.5 days and 100% in those with a score ≥ 4 (n = 4) (p = 0.017, OS; p = 0.064, NRM). Older patients who received mogamulizumab had a significantly longer OS (n = 12, median 432 days) than those who did not receive mogamulizumab (n = 17, median 199 days) (p = 0.018). The CONUT score was identified as a prognostic tool for transplant-eligible ATL patients, and mogamulizumab improved OS in transplant-ineligible ATL patients.
- Published
- 2019
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- View/download PDF
30. Successful treatment of post-transplant relapsed adult T cell leukemia after cord blood transplantation with low-dose, short-term lenalidomide.
- Author
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Ando T, Kojima K, Sano H, Kidoguchi K, Kusaba K, Yoshimura M, Yokoo M, Kubota Y, Nakamura H, Takase Y, Aishima S, and Kimura S
- Subjects
- Humans, Leukemia-Lymphoma, Adult T-Cell immunology, Leukemia-Lymphoma, Adult T-Cell pathology, Male, Middle Aged, Neoplasm Recurrence, Local immunology, Neoplasm Recurrence, Local pathology, Treatment Outcome, Cord Blood Stem Cell Transplantation, Immunologic Factors therapeutic use, Lenalidomide therapeutic use, Leukemia-Lymphoma, Adult T-Cell therapy, Neoplasm Recurrence, Local drug therapy
- Published
- 2018
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- View/download PDF
31. Strategy for patients with co-existence of meningioma and intracerebral aneurysm, especially unruptured aneurysm (-seven cases and review of the literature-).
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Takeda N, Nishihara M, Yamanishi S, Kidoguchi K, and Hashimoto K
- Subjects
- Aged, Aged, 80 and over, Female, Humans, Intracranial Aneurysm therapy, Male, Middle Aged, Neurosurgical Procedures methods, Intracranial Aneurysm complications, Meningeal Neoplasms complications, Meningeal Neoplasms surgery, Meningioma complications, Meningioma surgery
- Abstract
Background: Intracerebral aneurysms co-existing with meningiomas are rare. Treatment strategies for intracerebral aneurysms co-existing with meningiomas have not yet been established., Methods: We studied 62 patients with intracerebral aneurysms co-existing with meningiomas in the literature including our seven cases, evaluated the various managements and outcomes, and discussed the strategy for intracerebral aneurysms, especially unruptured cases, co-existing with meningiomas. The aim of this study was to develop a guide for the management of non-subarachnoid hemorrhage (SAH) intracerebral aneurysms co-existing with meningiomas., Results: Most intracerebral aneurysms co-existing with meningiomas are unruptured. Of course, aneurysms presenting with SAH should be treated first followed by the resection of meningiomas. In addition, intracerebral aneurysms inside or adjacent to meningiomas have a high risk of intraoperative rupture during the surgery for meningiomas, and it may be necessary to treat them first followed by the resection of meningiomas with one or two-step surgery. In nine out of 62 patients, ten intracerebral unruptured aneurysms were not treated; however, no intracerebral aneurysms ruptured during the follow-up period, and outcomes of these patients were good in eight and poor in only one., Conclusions: Intracerebral unruptured aneurysms remote from meningiomas may be treated according to the guidelines for unruptured aneurysms. In advance of microsurgery and endovascular techniques, both lesions should be treated, if possible., (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Published
- 2017
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32. Supratentorial extraventricular WHO grade III (anaplastic) ependymoma 17 years after total removal of WHO grade II ependymoma of the fourth ventricle.
- Author
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Takeda N, Nishihara M, Harada T, Kidoguchi K, and Hashimoto K
- Subjects
- Adult, Cerebral Ventricle Neoplasms diagnostic imaging, Ependymoma diagnostic imaging, Female, Fourth Ventricle diagnostic imaging, Humans, Magnetic Resonance Imaging, Neoplasm Recurrence, Local, Neurosurgical Procedures methods, Supratentorial Neoplasms diagnostic imaging, Cerebral Ventricle Neoplasms pathology, Cerebral Ventricle Neoplasms surgery, Ependymoma pathology, Ependymoma surgery, Fourth Ventricle pathology, Fourth Ventricle surgery, Supratentorial Neoplasms pathology, Supratentorial Neoplasms surgery
- Abstract
We report a WHO grade III ependymoma of the supratentorial interhemispheric fissure and grew to form a large mass with anaplastic transformation without local recurrence 17 years after the total removal of a fourth ventricular WHO grade II ependymoma. We emphasize the necessity of long-term follow-up, even in benign ependymomas.
- Published
- 2017
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33. Diagnostic yield and morbidity by neuronavigation-guided frameless stereotactic biopsy using magnetic resonance imaging and by frame-based computed tomography-guided stereotactic biopsy.
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Nishihara M, Takeda N, Harada T, Kidoguchi K, Tatsumi S, Tanaka K, Sasayama T, and Kohmura E
- Abstract
Background: We compared the diagnostic yield and morbidity by frame-based computed tomography-guided stereotactic biopsy (CTSTB) with Brown-Roberts-Wells (BRW) unit and by neuronavigation-guided frameless stereotactic biopsy (NSTB) using magnetic resonance imaging (MRI)., Methods: The subjects' age range was 15-83 years. CTSTB with BRW unit was performed for 59 tumors (58 cases, 1988-2007). NSTB was performed for 38 tumors (35 cases, 2007-2013) with the needle sheath attached to the head holder. By NSTB, target locations of sampling points and trajectories were confirmed by using MRI. Diffusion tensor imaging-based fiber tractography was used to achieve safe trajectories. STB by using BRW did not visualize the trajectory virtually; however, the planning images for NSTB were able to show the trajectory virtually before the procedure., Results: Histological diagnoses were established for 93 tumors at the first biopsy. The diagnostic yield was 94.9% by CTSTB and 97.4% by NSTB (P = 0.944). The morbidity rate was 5.1% by CTSTB and 0% by NSTB (P = 0.417). The absolute risk reduction was 23.1% by NSTB when the targets were basal ganglia (putamen, globus pallidus) or thalamus. In the cases of glioma for which the targets were basal ganglia (putamen, globus pallidus) or thalamus, the absolute risk reduction by NSTB was 30%., Conclusions: There was no significant difference between CTSTB and NSTB concerning the diagnostic yield and morbidity. However, when the target is the basal ganglia (putamen, globus pallidus) or thalamus and glioma is suspected, NSTB by using MRI with virtual trajectory is preferable to CTSTB concerning morbidity.
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- 2014
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34. Skull metastasis as initial manifestation of pulmonary epithelial-myoepithelial carcinoma: a case report of an unusual case.
- Author
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Nishihara M, Takeda N, Tatsumi S, Kidoguchi K, Hayashi S, Sasayama T, Kohmura E, and Hashimoto K
- Abstract
Epithelial-myoepithelial carcinoma (EMC) of the lung is rare and is considered to be low-grade malignancy. Intracranial metastasis of pulmonary EMC has not previously been reported according to our search of the literature. We report a case of skull metastasis as the initial manifestation of pulmonary EMC. An 81-year-old man complained of left leg motor weakness. Neurological examination showed left hemiparesis. Computed tomography and magnetic resonance imaging revealed an osteolytic tumor in the right frontal bone with invasion to the dura and subdural space, attached to the superior sagittal sinus. Subtotal removal of the tumor was performed, and the left hemiparesis showed improvement. Histopathological study revealed the tumor to consist of epithelial and myoepithelial cells. Pulmonary EMC was diagnosed. The MIB-1 index in primary lesion was approximately 10%. The skull and dura are possible sites for metastasis from pulmonary EMC. The MIB-1 index is a predictive marker of malignant potential.
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- 2011
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35. [Spinal subdural abscess in the cervical region: a case report].
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Akiyama H, Kidoguchi K, Hayashi S, Katayama S, and Takeda N
- Subjects
- Abscess diagnosis, Abscess microbiology, Humans, Male, Middle Aged, Neck, Staphylococcus aureus isolation & purification, Subdural Space, Abscess surgery
- Abstract
The authors present a patient with a spinal subdural abscess (SSA) in the cervical region and review the relevant literature. A 48-year-old man suffering from intractable high fever and back pain was admitted to our hospital with a diagnosis of meningitis. Despite antibiotic therapy, his condition deteriorated and he developed neurological deficits including left hemiparesis, sensory disturbance and bladder dysfunction. MR images of the cervical spine with gadolinium contrast revealed a circumferentially enhancing lesion anterior to the spinal cord that extended from the C4 to C6 level and compressed the spinal cord. After an urgent laminectomy extending from C4 to C6, the subdural abscess that consisted of purulent material and a thick capsule was irrigated and drained. Staphylococcus aureus was cultured from the abscess and he received antibiotic therapy postoperatively for 14 weeks. The high fever and the back pain subsided immediately and his neurologic condition gradually recovered. The majority of SSA cases involve the thoracic or lumbar region and are rarely found in the cervical region. Because they are associated with a high morbidity, early diagnosis with MRI and urgent surgical interventions including decompressive laminectomy, copious irrigation and drainage followed by appropriate antibiotic therapy are vital.
- Published
- 2009
36. In vivo cerebral artery microangiography in rat and mouse using synchrotron radiation imaging system.
- Author
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Umetani K, Kidoguchi K, Morishita A, Oizumi XS, Tamaki M, Yamashita H, Sakurai T, and Kondoh T
- Subjects
- Animals, Carotid Arteries diagnostic imaging, Cerebrovascular Circulation drug effects, Data Compression methods, Hemorrhage diagnostic imaging, Hypercapnia diagnostic imaging, Hypotension diagnostic imaging, Mice, Rats, Vasoconstriction drug effects, Vasoconstrictor Agents pharmacology, Angiography methods, Brain blood supply, Brain diagnostic imaging, Synchrotrons
- Abstract
Microangiography with spatial resolution in the micrometer range was carried out to depict vascular responses of the cerebral artery and arterioles in rats and mice using a real-time imaging system and a third generation synchrotron radiation source at SPring-8. An X-ray direct-conversion type detector with 6 microm spatial resolution was developed for real-time biomedical imaging. The X-ray image is converted directly into an electrical signal in the photoconductive layer without image blurring. In synchrotron radiation radiography, a long source-to-object distance and a small source spot can produce high-resolution images. Microangiographic images were obtained without image blurring and were stored in a digital frame memory system with a 1024 x 1024-pixel, 10-bit format. In imaging experiments, vasoconstriction and vasodilatation of small cerebral arteries were visualized in response to hypercapnia, hemorrhagic hypotension, and vasoactive agents after iodine contrast agent injection into the carotid artery.
- Published
- 2007
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37. In vivo X-ray angiography in the mouse brain using synchrotron radiation.
- Author
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Kidoguchi K, Tamaki M, Mizobe T, Koyama J, Kondoh T, Kohmura E, Sakurai T, Yokono K, and Umetani K
- Subjects
- 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine administration & dosage, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine analogs & derivatives, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine pharmacology, Adenosine Triphosphate administration & dosage, Adenosine Triphosphate pharmacology, Animals, Carotid Arteries diagnostic imaging, Carotid Arteries drug effects, Carotid Artery, External, Cerebral Angiography instrumentation, Cerebral Angiography methods, Cerebral Arteries drug effects, Contrast Media administration & dosage, Hypercapnia pathology, Image Processing, Computer-Assisted, Injections, Intra-Arterial, Male, Mice, Papaverine administration & dosage, Papaverine pharmacology, Species Specificity, Vasodilation drug effects, Vasodilator Agents administration & dosage, Vasodilator Agents pharmacology, Carotid Arteries ultrastructure, Cerebral Angiography veterinary, Cerebral Arteries ultrastructure, Mice, Inbred C57BL anatomy & histology, Synchrotrons
- Abstract
Background and Purpose: We, for the first time, performed in vivo x-ray angiography in the mouse brain using SPring-8, a third-generation synchrotron radiation facility., Methods: A thin PE-50 tube was placed in the unilateral external carotid artery in adult male C57BL/6J mice. While maintaining the blood flow in the internal carotid artery, 33 muL of contrast agent was injected and then selective angiography of the hemisphere was performed., Results: The average diameters of cerebral artery were as follows: 142.5+/-7.90 microm in middle cerebral artery, 138.3+/-9.35 microm in anterior cerebral artery, 120.5+/-5.53 microm in posterior cerebral artery, and 162.6+/-10.87 microm in internal carotid artery (n=5). To demonstrate the changes in diameter, we induced hypercapnia and detected the dilatation of the vessels between 121% and 124% of the original diameters (n=5). We also repeated angiography in the mice before and after intracarotid injection of vasodilatation drugs papaverine hydrochloride, ATP disodium, and fasudil hydrochloride hydrate and demonstrated the chronological changes in the diameters in each artery at 1, 5, 15, and 30 minutes after injection (n=1 for each drug)., Conclusions: Using only a minimum volume of the contrast agent, synchrotron radiation enables us to study x-ray angiography in the mouse brain. The morphology of the vessels can be clearly observed under physiological conditions. The diameters and their changes can also be successfully studied in vivo.
- Published
- 2006
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38. Sca-1 and Thy-1 accelerate neuron-like differentiation in bone marrow stromal cells.
- Author
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Mizobe T, Kidoguchi K, Tamaki M, Sasayama T, Kondoh T, and Kohmura E
- Subjects
- Animals, Antigens, Ly biosynthesis, Antigens, Ly genetics, Bone Marrow Cells metabolism, Cells, Cultured, Coculture Techniques, Genes, Reporter, Membrane Proteins biosynthesis, Membrane Proteins genetics, Mice, Neurons metabolism, Stromal Cells cytology, Stromal Cells metabolism, Thy-1 Antigens biosynthesis, Thy-1 Antigens genetics, Antigens, Ly physiology, Bone Marrow Cells cytology, Cell Differentiation physiology, Membrane Proteins physiology, Neurons cytology, Thy-1 Antigens physiology
- Abstract
Bone marrow stromal cells taken from EGFP transgenic mice were sorted by magnetic beads with surface markers for Sca-1 and Thy-1. The cells were then co-cultured on organotypic hippocampal slice or with neuronal cell feeder in dish. On hippocampus, both Sca-1 and Thy-1 positive cells showed 4- 8 folds higher potential to show neuron-like morphology than negative cells. In dish, negative cells fewly survived but each positive cells survived and showed neuron-like differentiation. In both culture condition, retinoic acid supplement accelerate differentiation. Differentiated Sca-1 and Thy-1 positive cells were immunohistochemically GFAP- and NeuN-negative but nestin-, neurofilament- and NSE-positive. Neuron-like differentiation of bone marrow cells can be enhanced by selection using cell surface proteins.
- Published
- 2006
39. Carotid artery occlusion and collateral circulation in C57Black/6J mice detected by synchrotron radiation microangiography.
- Author
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Tamaki M, Kidoguchi K, Mizobe T, Koyama J, Kondoh T, Sakurai T, Kohmura E, Yokono K, and Umetani K
- Subjects
- Angiography, Animals, Arterial Occlusive Diseases physiopathology, Arterial Occlusive Diseases surgery, Carotid Stenosis physiopathology, Carotid Stenosis surgery, Collateral Circulation physiology, Male, Mice, Mice, Inbred C57BL, Microcirculation, Neovascularization, Pathologic physiopathology, Neovascularization, Pathologic surgery, Pilot Projects, Synchrotrons, Arterial Occlusive Diseases diagnostic imaging, Carotid Arteries diagnostic imaging, Carotid Arteries physiopathology, Carotid Stenosis diagnostic imaging, Neovascularization, Pathologic diagnostic imaging
- Abstract
Using monochromatic synchrotron radiation, we performed microangiography in C57BL/6J mice and investigated their vasculature after unilateral and bilateral carotid artery occlusion. Bilateral occlusion of the carotid artery was made by a ligation of the left common carotid artery followed by a ligation of the right internal carotid artery (ICA) two days later (n=12). Five days after the second surgery, angiography was performed. Unilateral occlusion was made by clipping the right ICA and then angiography was performed immediately (n=5). The control mice did not undergo any occlusion (n=5). We removed the brain of the bilateral occlusion mice after angiography and examined the infarction area. The cerebral microvessels in all animals were clearly visualized. In the control mice, the posterior communicating artery (Pcom) was not visualized. In the unilateral occlusion mice, the anastomosis of the pterygopalatine artery (PPA) and the external carotid artery (ECA) were recognized. The PPA is thus considered to play a role in the collateral vessel between the ICA and the ECA. The Pcom was not visualized. In the bilateral occlusion mice, the Pcom was observed either unilaterally (n=5) or bilaterally (n=5). The Pcom supplied blood flow to the anterior circulation from the vertebrobasilar arteries. The bilateral occlusion mice that had at least one visualized Pcom did not have any infarction. We could successfully visualize the cerebral vasculature of normal mice and carotid artery occluded mice in an in vivo study. Microangiography can demonstrate the development of vasculature and the blood flow dynamics in mice.
- Published
- 2006
40. Direct surgical removal of the dural arteriovenous fistulas involving transverse-sigmoid sinuses.
- Author
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Kawaguchi T, Hosoda K, Shibata Y, Kidoguchi K, Koyama J, and Tamaki N
- Subjects
- Aged, Central Nervous System Vascular Malformations classification, Central Nervous System Vascular Malformations diagnostic imaging, Cerebral Angiography methods, Cerebral Veins diagnostic imaging, Cerebral Veins surgery, Cerebrovascular Circulation, Dura Mater blood supply, Dura Mater diagnostic imaging, Female, Humans, Male, Middle Aged, Transverse Sinuses diagnostic imaging, Transverse Sinuses surgery, Central Nervous System Vascular Malformations surgery, Central Nervous System Vascular Malformations therapy, Embolization, Therapeutic methods, Vascular Surgical Procedures methods
- Abstract
We investigated the operative methods and the angiographical classification in eight patients with dural arteriovenous fistulas involving transverse-sigmoid sinuses. There were two men and six women with a mean age of 68.3 (range 61-73) years. The initial symptoms were focal neurological deficits (aphasia, hemiparesis, hemianopsia) because of intracranial haematoma in four patients, dementia in two, headache in one and pulsatile tinnitus in one. Preoperatively, transarterial coil embolisaton was performed in four patients and transvenous coil embolisation in three. Finally total removal was performed in all patients. In all patients angiogram showed the presence of sinus occlusion diagnosed in the late venous phase and retrograde flow from the sinuses to the cortical veins. According to Borden's classification, three patients were classified as Type II-C (or C'), four patients as Type III-D and one patient as Type E. The volume of blood loss did not change either with or without preoperative transarterial coil embolisation. There was no new procedure-related morbidity. The presence of sinus occlusion diagnosed in the late venous phase and retrograde flow from the sinuses to the cortical veins indicate that total removal is possible.
- Published
- 2002
41. Cerebral vasoreactivity and internal carotid artery flow help to identify patients at risk for hyperperfusion after carotid endarterectomy.
- Author
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Hosoda K, Kawaguchi T, Shibata Y, Kamei M, Kidoguchi K, Koyama J, Fujita S, and Tamaki N
- Subjects
- Acetazolamide, Aged, Brain diagnostic imaging, Carotid Artery, Internal diagnostic imaging, Female, Humans, Intraoperative Period, Male, Middle Aged, Reperfusion Injury diagnostic imaging, Risk Factors, Syndrome, Brain blood supply, Carotid Artery, Internal physiology, Cerebrovascular Circulation, Endarterectomy, Carotid adverse effects, Reperfusion Injury etiology, Tomography, Emission-Computed, Single-Photon methods
- Abstract
Background and Purpose: Hyperperfusion syndrome is a rare but potentially devastating complication after carotid endarterectomy (CEA). The aim of this study was to investigate whether preoperative measurement of cerebral vasoreactivity (CVR) and intraoperative measurement of internal carotid artery (ICA) flow could identify patients at risk for hyperperfusion after CEA., Methods: For 26 patients with unilateral ICA stenosis >/=70%, cerebral blood flow (CBF) and CVR were investigated before and 1 month after CEA, with resting and acetazolamide-challenge single-photon emission CT. CBF on the first postoperative day was also measured. ICA flow was measured before and after reconstruction by electromagnetic flowmeter during surgery., Results: Ipsilateral CBF on the first postoperative day significantly increased relatively (56.6+/-53.2%) as well as absolutely (37.9+/-8.8 to 57.7+/-18.0 mL/100 g per minute) in the reduced CVR group (CVR <12%) but not in the normal CVR group (CVR >/=12%) (10.3+/-15.5% and 40.6+/-7.9 to 43.9+/-5.7 mL/100 g per minute, respectively). One month later, this difference almost disappeared. Two patients showed ipsilateral CBF increase of >/=100%. A significant association of intracerebral steal with hyperperfusion (CBF increase >/=100%) on the first postoperative day was also observed. ICA flow increase after reconstruction significantly correlated with CBF increase on the first postoperative day in the reduced CVR group but not in the normal CVR group. The threshold of ICA flow increase for hyperperfusion was estimated to be 330 mL/min in the reduced CVR group., Conclusions: Single-photon emission CT with acetazolamide challenge and ICA flow measurement during surgery could identify patients at risk for hyperperfusion after CEA, in whom careful monitoring and control of blood pressure should be initiated even intraoperatively.
- Published
- 2001
- Full Text
- View/download PDF
42. Neonatal lupus erythematosus: results of maternal corticosteroid therapy.
- Author
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Shinohara K, Miyagawa S, Fujita T, Aono T, and Kidoguchi K
- Subjects
- Adult, Autoantibodies blood, Autoantigens immunology, Female, Heart Block congenital, Humans, Infant, Newborn, Infant, Newborn, Diseases, Pregnancy immunology, Ribonucleoproteins immunology, SS-B Antigen, Adrenal Cortex Hormones therapeutic use, Heart Block prevention & control, Lupus Erythematosus, Cutaneous prevention & control, RNA, Small Cytoplasmic
- Abstract
Objective: To assess the possibility of preventing cardiac or cutaneous manifestations of neonatal lupus erythematosus or treating the fetus with congenital heart block by administering corticosteroid therapy to the mother., Methods: Eighty-seven offspring of 40 anti-Ro/SSA-positive mothers, followed up from 1979 to 1996, were evaluated. Autoantibodies against Ro/SSA and La/SSB antigens were detected by immunodiffusion and enzyme-linked immunosorbent assay., Results: None of 26 neonates whose mothers received corticosteroid maintenance therapy initiated before 16 weeks' gestation demonstrated congenital heart block, whereas 15 of 61 neonates whose mothers received no corticosteroids during pregnancy or began receiving steroid therapy after 16 weeks' gestation had congenital heart block. Complete congenital heart block, once developed, did not respond to corticosteroid treatment in utero. Four infants whose mothers received steroid treatment before 16 weeks' gestation had skin lesions of neonatal lupus erythematosus., Conclusion: Once established, complete congenital heart block was irreversible and maternal corticosteroid therapy did not effectively prevent cutaneous lupus erythematosus. However, prenatal maintenance therapy with prednisolone or betamethasone given to the mother starting early in pregnancy (before 16 weeks' gestation) might reduce the risk of developing antibody-mediated congenital heart block in the offspring.
- Published
- 1999
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- View/download PDF
43. Neonatal lupus erythematosus: analysis of HLA class I genes in Japanese child/mother pairs.
- Author
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Miyagawa S, Kidoguchi K, Kaneshige T, and Shirai T
- Subjects
- Adolescent, Autoantibodies immunology, Child, Child, Preschool, Female, Humans, Infant, Lupus Erythematosus, Systemic congenital, Lupus Erythematosus, Systemic immunology, Male, Maternal-Fetal Exchange immunology, Pregnancy, Histocompatibility Antigens Class I genetics, Lupus Erythematosus, Systemic genetics
- Abstract
Neonatal lupus erythematosus (NLE), characterized by two major symptoms of congenital heart block (CHB) and transient cutaneous lesions, is an antibody mediated disorder due to placentally transmitted maternal autoantibodies to Ro/SSA and/or La/SSB. We genotyped 14 mothers, 9 children with CHB, 8 with cutaneous NLE only and 5 asymptomatic siblings at HLA class I loci, by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) combined with sequence-specific amplification. Mothers of children with NLE exhibited a very high polymorphism of HLA class I genes. Significant increases of HLA-B*1501 (B62) and Cw*0303 (Cw9) with absence of HLA-A1/B8 haplotype in Japanese mothers differed from the serologically defined HLA class I profiles among NLE mothers in white and North American black populations. Child/mother heterozygous HLA-A/B/C haplotype identity, which extended to HLA-class II DR/DQ loci, was observed in only one of 9 cases with CHB. No association was found between HLA class I alleles of children and the symptoms of NLE. These findings provide for the opportunity to investigate the primary genetic associations with NLE/CHB in different ethnic groups.
- Published
- 1999
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- View/download PDF
44. Neonatal lupus erythematosus: maternal IgG antibodies bind to a recombinant NH2-terminal fusion protein encoded by human alpha-fodrin cDNA.
- Author
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Miyagawa S, Yanagi K, Yoshioka A, Kidoguchi K, Shirai T, and Hayashi Y
- Subjects
- Autoantibodies blood, Autoantigens isolation & purification, Binding Sites, Antibody, Carrier Proteins genetics, Carrier Proteins immunology, DNA, Complementary genetics, Female, Humans, Immunoglobulin G immunology, Infant, Newborn, Lupus Erythematosus, Cutaneous immunology, Microfilament Proteins genetics, Microfilament Proteins immunology, Mothers, Recombinant Proteins immunology, Sjogren's Syndrome immunology, Lupus Erythematosus, Systemic immunology
- Abstract
IgG antibodies to a cleavage product of alpha-fodrin (120 kDa alpha-fodrin) have recently been identified as organ-specific autoantibodies in primary Sjögren's syndrome. In this study, we examined seroreactivity of mothers and infants with neonatal lupus erythematosus (NLE) to a recombinant NH2-terminal protein (120 kDa alpha-fodrin) of human alpha-fodrin. Serum samples were collected during the perinatal period in seven pregnancies of five mothers delivering offspring with NLE. Anti-120 kDa alpha-fodrin antibodies were identified by immunoblotting in six of seven perinatal maternal sera of offspring with NLE: one of two congenital heart block offspring and all five offspring with cutaneous NLE. These antibodies were placentally transmitted to infants. One of the five mothers had primary Sjögren's syndrome, and four were asymptomatic. One asymptomatic mother did not demonstrate anti-120 kDa alpha-fodrin activity at the time of the first delivery of a congenital heart block infant, but was found to be positive at the time of subsequent delivery of a second child with cutaneous NLE. We propose that maternal antibodies to 120 kDa alpha-fodrin may be an additional serologic marker for the risk of NLE in anti-Ro/SS-A positive women.
- Published
- 1998
- Full Text
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45. Polymorphisms of HLA class II genes and autoimmune responses to Ro/SS-A-La/SS-B among Japanese subjects.
- Author
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Miyagawa S, Shinohara K, Nakajima M, Kidoguchi K, Fujita T, Fukumoto T, Yoshioka A, Dohi K, and Shirai T
- Subjects
- Adolescent, Adult, Amino Acid Sequence, Female, Genotype, HLA-DQ Antigens genetics, HLA-DR Antigens genetics, Humans, Japan, Lupus Erythematosus, Systemic genetics, Middle Aged, Molecular Sequence Data, Polymerase Chain Reaction, Polymorphism, Genetic, Sjogren's Syndrome genetics, SS-B Antigen, Autoantibodies analysis, Autoantigens immunology, Genes, MHC Class II genetics, Lupus Erythematosus, Systemic immunology, RNA, Small Cytoplasmic, Ribonucleoproteins immunology, Sjogren's Syndrome immunology
- Abstract
Objective: To investigate HLA class II allele associations with autoantibody responses to Ro/SS-A and La/SS-B among Japanese subjects., Methods: Haplotype and allele distributions, along with molecular polymorphisms, of HLA class II genes were analyzed by polymerase chain reaction-restriction fragment length polymorphism in 41 Japanese women with precipitating autoantibodies to Ro/SS-A and/or La/SS-B., Results: Among women with both Ro/SS-A and La/SS-B antibodies, the HLA class II haplotype DRB1*08032/DQA1*0103/DQB1*0601 and DRB1*08032 allele showed significantly increased frequencies compared with patients with anti-Ro/SS-A alone or with normal controls. All women with both anti-Ro/SS-A and anti-La/SS-B, but not those with anti-Ro/SS-A alone, carried DRB1 alleles that shared the same amino acid residues at positions 14-31 and 71 of the hypervariable regions of the DRB1 chain. All anti-Ro/SS-A positive women carried 1 or 2 alleles of DQB1*06 and DQB1*03 subtypes that shared the same amino acid residues at positions 71-77 of the DQB1 chain. HLA class II allele distributions did not differ among 3 anti-Ro/SS-A positive groups with different disease expressions, i.e., patients with systemic lupus erythematosus, patients with primary Sjögren's syndrome, and women with no apparent symptoms of rheumatic disease., Conclusion: HLA class II allele distributions differ among anti-Ro/SS-A positive subjects according to the presence or absence of coexisting anti-La/SS-B antibodies, but not according to disease expression. Our findings suggest that different HLA class II molecules might control the development of anti-Ro/SS-A and/or anti-La/SS-B antibodies in the autoimmune response to the Ro/SS-A-La/SS-B complex.
- Published
- 1998
- Full Text
- View/download PDF
46. [A case of congenital complete heart block in a mother with anti-52 kD SS-A/Ro antibodies].
- Author
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Yahara T, Noda C, Miyano A, Miyamichi T, Nakayama M, Shinohara K, and Kidoguchi K
- Subjects
- Adult, Female, Humans, Infant, Newborn, Male, Pregnancy, Antibodies, Antinuclear blood, Heart Block congenital, Maternal-Fetal Exchange
- Abstract
We report a case of congenital complete heart block (CCHB). A 38-year-old woman was admitted our hospital because of fetal bradycardia at 21 weeks 3 days of gestational age. She had no symptom of collagen disease. On admission, laboratory data showed positive anti-nuclear antibodies, anti-SS-A/Ro antibodies and anti-52 kD SS-A/Ro antibodies. But anti-60 kD SS-A/Ro and anti-SS-B/La antibodies were negative. Consequently anti-52 kD SS-A/Ro antibodies positive woman had an infant with CCHB. The baby was equipped with pacemaker at the age of 2 months. This report suggests that anti-52 kD SS-A/Ro antibodies may play an important role in the development of CCHB.
- Published
- 1997
- Full Text
- View/download PDF
47. Neonatal lupus erythematosus: HLA-DR and -DQ distributions are different among the groups of anti-Ro/SSA-positive mothers with different neonatal outcomes.
- Author
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Miyagawa S, Shinohara K, Kidoguchi K, Fujita T, Fukumoto T, Yamashina Y, Hashimoto K, Yoshioka A, Sakurai S, Nishihara O, and Shirai T
- Subjects
- Adult, Alleles, Amino Acids analysis, Antibodies, Antinuclear blood, Autoimmunity, Causality, Female, Gene Frequency, HLA-DQ Antigens genetics, HLA-DR Antigens genetics, Haplotypes, Heart Block congenital, Heart Block epidemiology, Heart Block immunology, Humans, Incidence, Infant, Newborn, Lupus Erythematosus, Cutaneous epidemiology, Lupus Erythematosus, Cutaneous pathology, Maternal-Fetal Exchange, Middle Aged, Skin chemistry, Skin pathology, Antibodies, Antinuclear analysis, HLA-DQ Antigens analysis, HLA-DR Antigens analysis, Lupus Erythematosus, Cutaneous immunology, Pregnancy immunology, Pregnancy Outcome
- Abstract
Neonatal lupus erythematosus (NLE) is an antibody-mediated disorder of infants characterized by two major clinical manifestations; cutaneous lupus lesions and congenital heart block (CHB). The disease is associated with placentally transferred maternal anti-Ro/SSA and/or La/SSB antibodies. There is a tendency for the same disease expression to occur within a sibship. To reveal a possible association of class II MHC genes with maternal anti-Ro/SSA autoimmune responses and neonatal outcomes in NLE with a relatively homogeneous ethnic background, haplotype, and allele distributions were analyzed based on the PCR-RFLP results in 26 Japanese anti-Ro/SSA-positive mothers from three groups defined by neonatal outcomes. The results were as follows: (i) maternal HLA-DR5 haplotype DRB1*1101-DQA1*0501-DQB1*0301 and individual class II alleles making up this haplotype were significantly associated with neonatal cutaneous lupus but not CHB. Conversely, maternal HLA-DQB1*0602 carried on HLA-DR2 haplotypes was associated with CHB but not cutaneous NLE; (ii) HLA-DQA1 alleles with glutamine at position 34 of the first domain, which have reportedly been associated with the autoimmune responses to Ro/SSA antigens in other ethnic groups, were increased in the mothers of infants with cutaneous involvement; and (iii) there was no particular class II HLA profile that distinguished the disease manifestations in infants. These findings suggest that specific maternal MHC class II genes might correlate with specific neonatal outcomes in NLE.
- Published
- 1997
- Full Text
- View/download PDF
48. Neonatal lupus erythematosus: haplotypic analysis of HLA class II alleles in child/mother pairs.
- Author
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Miyagawa S, Fukumoto T, Hashimoto K, Yoshioka A, Shirai T, Shinohara K, Kidoguchi KI, and Fujita T
- Subjects
- Adolescent, Alleles, Child, Child, Preschool, Female, Haplotypes, Humans, Infant, Infant, Newborn, Male, Maternal-Fetal Exchange genetics, Pregnancy, Genes, MHC Class II genetics, Lupus Erythematosus, Cutaneous congenital
- Published
- 1997
- Full Text
- View/download PDF
49. Neonatal lupus erythematosus: analysis of HLA class II alleles in mothers and siblings from seven Japanese families.
- Author
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Miyagawa S, Shinohara K, Fujita T, Kidoguchi K, Fukumoto T, Hashimoto K, Yoshioka A, and Shirai T
- Subjects
- Disease Susceptibility, Female, Gene Frequency, Haplotypes, Humans, Infant, Newborn, Male, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Genes, MHC Class II genetics, Lupus Erythematosus, Cutaneous genetics
- Abstract
Background: Neonatal lupus erythematosus (NLE) is a syndrome characterized by dermatitis and congenital heart block. The disease is mostly associated with transplacental passage of maternal anti-Ro(SS-A) or anti-La(SS-B) antibodies. Maternal HLA-DR3 and DQ2 alleles are associated with NLE in white and North American black populations., Objective: We sought evidence of a potential genetic disposition to NLE in mothers with a relatively homogeneous ethnic background., Methods: Class II human major histocompatibility complex HLA-DRB1, DQA1, DQB1, and DPB1 alleles were determined by polymerase chain reaction-restriction fragment length polymorphism in anti-Ro(SS-A)-positive mothers as well as in infants from seven Japanese families with siblings concordant or discordant for disease expression of NLE., Results: All seven mothers had two or three DQ alleles of DQA1 and DQB1 possessing specific amino acid residues, which are reportedly associated with anti-Ro(SS-A) autoantibody response in white and black populations. There was no class II HLA profile that distinguished disease manifestations of NLE in infants., Conclusion: The HLA class II allele associations with anti-Ro(SS-A) autoantibodies that have been noted in other ethnic groups were also found in Japanese anti-Ro(SS-A)-positive mothers whose infants had NLE, suggesting shared susceptibility factors across racial barriers in maternal predisposition to Ro(SS-A) autoimmune response.
- Published
- 1997
- Full Text
- View/download PDF
50. Neonatal lupus erythematosus: studies on HLA class II genes and autoantibody profiles in Japanese mothers.
- Author
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Miyagawa S, Shinohara K, Kidoguchi K, Fujita T, Fukumoto T, Hashimoto K, Yoshioka A, and Shirai T
- Subjects
- Animals, Antibodies, Antinuclear analysis, DNA blood, Enzyme-Linked Immunosorbent Assay, Female, Gene Frequency, Genes, MHC Class II immunology, Genotype, HLA-DQ Antigens chemistry, HLA-DQ Antigens genetics, HLA-DR Antigens chemistry, HLA-DR Antigens genetics, Haplotypes, Heart Block congenital, Humans, Infant, Newborn, Japan, Lupus Erythematosus, Cutaneous genetics, Lupus Erythematosus, Cutaneous immunology, Lupus Erythematosus, Systemic genetics, Mothers, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Rabbits, Sjogren's Syndrome immunology, Autoantibodies classification, Genes, MHC Class II genetics, Lupus Erythematosus, Systemic immunology
- Abstract
Neonatal lupus erythematosus (NLE) is a rare disorder of neonates characterized by two major clinical manifestations: congenital heart block and cutaneous lupus lesions. The disease is associated with placentally transferred maternal anti-Ro/SSA and/or La/SSB antibodies. To clarify possible class II HLA associations with maternal autoantibody responses, haplotypic and allelic distributions, along with the polymorphism of the MHC class II HLA alleles, were analyzed based on PCR-RFLP results in 25 Japanese mothers of two groups defined by precipitating autoantibody profiles. Among mothers with both anti-Ro/SSA and anti-La/SSB antibodies, but not those with anti-Ro/SSA alone, the class II haplotypes DRB1*1101-DQA1*0501-DQB1*0301 and DRB1*08032-DQA1*0103-DQB1*0601 as well as individual class II alleles DRB1*1101, DRB1*08032 and DQB1*0301 showed significantly increased frequencies compared to those in normal controls. All anti-Ro/SSA and anti-La/SSB positive mothers carried DRB1 alleles that shared the same amino acid residues at positions 14-31 and 71 of the DRB1 chain. These mothers also carried homozygous or heterozygous DQ6 and DQ3 alleles that shared the same amino acid residues at positions 27-36 and 71-77 of hypervariable regions of the DQB1 chain. Furthermore, all mothers with both anti-Ro/SSA and anti-La/SSB were homozygous for DPB1*0501. Nine of 10 anti-Ro/SSA and anti-La/SSB-positive mothers, but only 6 of 15 mothers with anti-Ro/SSA alone, had affected infants. Thus, our findings suggest that there may be immunogenetic differences among mothers according to their autoantibody profiles, and that mothers with both anti-Ro/SSA and anti-La/SSB are more likely to have infants with NLE than mothers with anti-Ro/SSA alone.
- Published
- 1997
- Full Text
- View/download PDF
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