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DOI： 10.1007/s00277-020-04185-1

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DOI： 10.1007/s00277-020-04151-x

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OBJECTIVES: The D-index is defined as the area over the neutrophil curve during neutropenia. The CEDMIC trial confirmed the noninferiority of D-index-guided early antifungal therapy (DET) using micafungin to empirical antifungal therapy (EAT). In this study, we evaluated the efficacy and safety of micafungin in these settings. METHODS: From the CEDMIC trial, we extracted 67 and 113 patients who received micafungin in the DET and EAT groups, respectively. Treatment success was defined as the fulfilment of all components of a five-part composite end point. Fever resolution was evaluated at seven days after the completion of therapy. RESULTS: The proportion of high-risk treatments including induction chemotherapy for acute leukemia and allogeneic hematopoietic stem cell transplantation was significantly higher in the DET group than in the EAT group (82.1% vs. 52.2%). The efficacy of micafungin was 68.7% (95%CI: 56.2-79.4) and 79.6% (71.0-86.6) in the DET and EAT groups, respectively. When we focused on high-risk treatments, the efficacy was 69.1% (55.2-80.9%) and 78.0% (65.3-87.7%), respectively (P = 0.30). There was no significant difference in any of the 5 components between the two groups. CONCLUSIONS: The efficacy of micafungin in patients undergoing high-risk treatment was not strongly impaired in DET compared to that in EAT.

DOI： 10.1016/j.ijid.2020.08.081

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PURPOSE: Empiric antifungal therapy (EAT) is recommended for persistent febrile neutropenia (FN), but in most patients, it is associated with overtreatment. The D-index, calculated as the area surrounded by the neutrophil curve and the horizontal line at a neutrophil count of 500/μL, reflects both the duration and depth of neutropenia and enables real-time monitoring of the risk of invasive fungal infection in individual patients at no cost. We investigated a novel approach for patients with persistent FN called D-index-guided early antifungal therapy (DET), in which antifungal treatment is postponed until a D-index reaches 5,500 or the detection of positive serum or imaging tests, and compared it with EAT in this multicenter open-label noninferiority randomized controlled trial. PATIENTS AND METHODS: We randomly assigned 423 patients who underwent chemotherapy or hematopoietic stem-cell transplantation for hematologic malignancies to the EAT or DET group. The prophylactic use of antifungal agents other than polyenes, echinocandins, or voriconazole was allowed. Micafungin at 150 mg per day was administered as EAT or DET. RESULTS: In an intent-to-treat analysis of 413 patients, the incidence of probable/proven invasive fungal infection was 2.5% in the EAT group and 0.5% in the DET group, which fulfilled the predetermined criterion of noninferiority of the DET group (-2.0%; 90% CI, -4.0% to 0.1%). The survival rate was 98.0% versus 98.6% at day 42 and 96.4% versus 96.2% at day 84. The use of micafungin was significantly reduced in the DET group (60.2% v 32.5%; P < .001). CONCLUSION: A novel strategy, DET, decreased the use and cost of antifungal agents without increasing invasive fungal infections and can be a reasonable alternative to empiric or preemptive antifungal therapy.

DOI： 10.1200/JCO.19.01916

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HIV-associated neurocognitive disorders (HAND) are characterized by cognitive, behavioral, and motor dysfunctions, which impact daily functioning and are predictive of poor survival among patients. The diagnosis of HAND is marked by clinically significant declines in multiple domains of neurocognitive functioning. Some patients diagnosed with HAND have social problem; however, higher brain dysfunction is not detected in general neuropsychological assessments and the intelligence quotient may remain unchanged. Impaired decision-making may reduce social and occupational qualities of life. The Iowa Gambling Task (IGT) has been developed as a task to evaluate risk predictions at the time of decision-making. In the present study, 38 HIV-infected patients enrolled in our hospital performed IGT and we investigated whether the results obtained are associated with HAND. The median net IGT score of all HIV-infected subjects was significantly lower than that of healthy controls. Patients diagnosed with HAND accounted for 43.8% of the negative net score group. We elucidated the relationship between the net IGT score and HAND for the first time. We think that IGT is a good tool to detect decision-making impairment for ANI and MND. Careful follow-ups of the progression of HAND and increased awareness among HIV-infected patients and medical care workers of the risk of social behavioral disorders, which negatively impact daily life before they are detected, are needed in order to prevent deteriorations in the quality of life of these patients.

DOI： 10.1016/j.jiac.2019.09.008

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DOI： 10.1097/MBC.0000000000000785

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INTRODUCTION: Cilostazol, an anti-platelet drug that inhibits phosphodiesterase 3, is beneficial for patients with atherothrombosis. In contrast to other anti-platelet drugs such as aspirin and thienopyridines, little information is available on the relationship between platelet responses to cilostazol and clinical outcomes. MATERIALS AND METHODS: We conducted a prospective study on patients with cerebral infarction who were treated with cilostazol. The platelet response to cilostazol was assessed with our new assay for the phosphorylation of vasodilator-stimulated phosphoprotein (VASP) subsequent to the pharmacological action of cilostazol. Patients were followed up for 2 years and the relationship between VASP assay results and the recurrence of thrombotic events was examined. We also investigated the effects of CYP3A5 and CYP2C19 genotypes involved in the metabolism of cilostazol on the platelet response to cilostazol. RESULTS: Among the 142 patients enrolled, 130 completed the 2-year follow-up and the recurrence of thrombotic events was noted in 8 (6.2%). VASP phosphorylation levels were significantly lower in patients with than in those without recurrence. The combined genotype of CYP3A5*1/*3 and CYP2C19*1/*1 was associated with a low level of VASP phosphorylation, while either genotype was not. A multivariate analysis showed that high residual platelet reactivity during the cilostazol treatment, which was defined by a low response of platelet VASP phosphorylation to cilostazol, was an independent risk factor for the recurrence of thrombotic events. CONCLUSION: A low platelet response to cilostazol determined by a new platelet assay was associated with the recurrence of thrombotic events in patients with cerebral infarction.

DOI： 10.1016/j.thromres.2018.10.003

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Mild hemophilia A is caused by a missense mutation in the FVIII gene that is responsible for a decrease in the FVIII:C to between 5% and 40%. The development of FVIII inhibitors has been reported in 3-13% of patients with mild hemophilia. Genetic risk factors for the development of inhibitors in mild hemophilia have been investigated. In the present study, we encountered a case of mild hemophilia with an FVIII inhibitor and identified the mutation responsible: a novel Phe595Cys mutation in the FVIII gene. In addition, this study showed that the inhibitor recognized exogenous wild-type FVIII and autologous mutant FVIII.

DOI： 10.2169/internalmedicine.1145-18

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Inherited antithrombin ( AT) deficiency is an autosomal dominant thrombotic disorder. We encountered a case of inherited type I AT deficiency and identified the mutation responsible; a novel 5406delA mutation in the SERPINC1 gene appeared to have caused a frameshift with premature termination at amino acid +283. The recombinant AT protein including 5406delA was not detected in cell lysates or culture supernatants. These results will contribute to the creation of an accurate database and define the molecular basis for AT deficiency. (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

DOI： 10.1097/MBC.0000000000000555

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Vancomycin-induced thrombocytopenia is a rare adverse reaction that may be overlooked because no specific diagnostic test is currently available. We herein report a patient with vancomycin-induced immune thrombocytopenia who was diagnosed by the detection of vancomycin-dependent anti-platelet antibody with flow cytometry. An IgG antibody in the patient's serum reacted with platelets only in the presence of vancomycin. Severe thrombocytopenia gave rise to life-threatening gastrointestinal bleeding, which was quickly resolved after effective platelet transfusion following the cessation of vancomycin administration. This report suggests that the flow cytometric test is useful for the differential diagnosis of thrombocytopenia and platelet transfusion should be performed after the cessation of vancomycin administration.

DOI： 10.2169/internalmedicine.55.6902

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DOI： 10.1155/2016/8751329

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DOI： 10.1007/s00277-015-2416-x

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DOI： 10.1007/s00277-014-2052-x

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DOI： 10.1007/s00277-013-1857-3

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Zinc finger protein 521 (ZFP521) regulates a number of cellular processes in a wide range of tissues, such as osteoblast formation and adipose commitment and differentiation. In the field of neurobiology, it is reported to be an essential factor for transition of epiblast stem cells into neural progenitors in vitro. However, the role of ZFP521 in the brain in vivo still remains elusive. To elucidate the role of ZFP521 in the mouse brain, we generated mice lacking exon 4 of the ZFP521 gene. The birth ratio of our ZFP521(Delta/Delta) mice was consistent with Mendel's laws. Although ZFP521(Delta/Delta) pups had no apparent defect in the body and were indistinguishable from ZFP521(+/+) and ZFP521(+/Delta) littermates at the time of birth, ZFP521(Delta/Delta) mice displayed significant weight reduction as they grew, and most of them died before 10 weeks of age. They displayed abnormal behavior, such as hyper-locomotion, lower anxiety and impaired learning, which correspond to the symptoms of schizophrenia. The border of the granular cell layer of the dentate gyrus in the hippocampus of the mice was indistinct and granular neurons were reduced in number. Furthermore, Sox1-positive neural progenitor cells in the dentate gyrus and cerebellum were significantly reduced in number. Taken together, these findings indicate that ZFP521 directly or indirectly affects the formation of the neuronal cell layers of the dentate gyrus in the hippocampus, and thus ZFP521(Delta/Delta) mice displayed schizophrenia-relevant symptoms. ZFP521(Delta/Delta) mice may be a useful research tool as an animal model of schizophrenia.

DOI： 10.1371/journal.pone.0092848

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Background Febrile neutropenia (FN) is one of the serious complications of chemotherapy. However, the hematological nadir after chemotherapy and the timing of prophylaxis for FN remain unclear, especially for outpatients.
Methods We prospectively analyzed laboratory data from outpatients treated with a single chemotherapy regimen, rituximab (R)-CHOP, on three consultation days (days 8, 10, and 15) after chemotherapy to identify any factors that might predict the onset of the hematological nadir and the optimal timing of G-CSF prophylaxis.
Results A total of 100 courses of chemotherapy (total 33 patients) were analyzed. Onset of the hematological nadir was not predictable in any of the patients who had a white blood cell count (WBC) of &gt;5,500 x 10(6)/L and/or monocyte count of &gt;80 x 10(6)/L on day 8, and thus there was little opportunity for G-CSF prophylaxis in each treatment course. Among patients who had a WBC count of 1,500-5,500 x 10(6)/L on day 8, the monocyte count on day 8 was significantly associated with the hematological nadir. Patients who had a monocyte count of &lt;5 x 10(6)/L on day 8, were identified as a high-risk group for neutropenia for whom G-CSF administration during the current treatment course should be considered.
Conclusion Our results indicate that, in outpatients receiving R-CHOP chemotherapy, the monocyte count on day 8 is a useful marker of the hematological nadir, allowing an opportunity for G-CSF prophylaxis.

DOI： 10.1007/s10147-013-0523-z

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An open-label, prospective, multicenter study was conducted between October 2006 and March 2010 to assess the efficacy and safety of intravenous voriconazole (VRCZ) as empirical therapy for antibiotic-refractory febrile neutropenia in Japanese patients with hematological disorders. In addition, to find the patient groups that may benefit from antifungal therapy, the definition of invasive fungal infection proposed by EORTC/MSG (2002) was assessed in this study. Plasma (1-3)-beta-d-glucan and Aspergillus PCR in blood were also measured to improve the diagnostic accuracy. A total of 103 patients (median age, 59 years), including 25 undergoing induction chemotherapies and 19 allogeneic hematopoietic cell transplants, were evaluable. Sixty-nine percent of the patients achieved resolution of clinical symptoms and 31 % achieved treatment success, defined as fulfilling the previously described five-part composite endpoint. Although VRCZ was discontinued in 9.7 % of the patients because of adverse effects, all the patients recovered soon after discontinuation of VRCZ. The treatment success rate of VRCZ appeared to be higher in patients categorized as "not classified" compared with "possible invasive fungal disease" according to the EORTC/MSG criteria. Moreover, six "not classified" patients were positive for either plasma (1-3)-beta-d-glucan (n = 5) or Aspergillus PCR in blood (n = 2). The present study demonstrates that empirical VRCZ therapy is safe and effective in Japanese patients. Additionally, (1-3)-beta-d-glucan and Aspergillus PCR tests were expected to provide additional information on the diagnosis of invasive fungal infections.

DOI： 10.1007/s10156-013-0634-5

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Aims: STAT3 is a key modulator of activation and differentiation of macrophages. But it is still unknown if deficiency of STAT3 activates macrophages to destroy erythrocytes by phagocytosis. We generated STAT3 conditional knockout mice by crossing foxed STAT3 mice with Tie2 promoter-driven Cre-recombinase transgenic mice and clarified that Stat3 plays a critical role in the formation and activation of macrophages.
Main methods: Blood cell count, reticulocyte count, serum lactate dehydrogenase, erythropoietin, iron and ferritin concentration, and life span of the erythrocytes in Tie2 promoter-driven STAT3 conditional knockout mice were analyzed. To explore the erythropoietic function of the mice, we subjected them to brief hemolytic anemia by injecting them intraperitoneally with phenylhydrazine. The fragility of erythrocytes was examined by scanning electron microscopy and osmotic tolerance test.
Key findings: The conditional knockout mice had mild normocytic anemia. They also displayed higher lactate dehydrogenase, ferritin and erythropoietin concentration, higher reticulocyte count, and a shorter lifespan of erythrocytes compared with wild-type controls. These data suggest that destruction of erythrocytes and secondary blood formation were accelerated in the STAT3 conditional knockout mice. It didn't appear due to the fragility of erythrocytes. A few of the conditional knockout mice suddenly developed acute severe anemia, high body temperature and massive splenomegaly, and died within 2 weeks after the onset of anemia.
Significance: This study provided evidence that STAT3 have a critical role in the destruction of erythrocytes by resident macrophages in the spleen. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.

DOI： 10.1016/j.lfs.2013.07.025

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DOI： 10.1016/j.thromres.2013.01.021

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Acute promyelocytic leukemia (APL) is characterized by t(15;17)(q22;q21), which results in the fusion of the promyelocytic leukemia (PML) gene at 15q22 with the retinoic acid alpha-receptor (RARA) at 17q21. We report a patient with APL carrying a new complex variant translocation (5;17;15;20). Spectral karyotyping analysis of bone marrow cells revealed t(5;17;15;20)(q33;q12;q22;q11.2). Fluorescence in situ hybridization with a PML/RARA dual-color DNA probe showed a single fusion signal, and RT-PCR analysis showed PML/RARA fusion transcripts. Complete remission was attained with a course of conventional chemotherapy with all-trans retinoic acid (ATRA). To our knowledge, this is the first report of a four-way translocation of 5q33 and 20q11 involvement in APL.

DOI： 10.1007/s12185-011-0929-1

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DOI： 10.1007/s12185-011-0895-7

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In order to analyze the clinical activity and cost-effectiveness of granulocyte colony-stimulating factors (G-CSF), the prophylactic usage of G-CSF in patients treated with a single chemotherapy regimen during early courses was prospectively evaluated.
Thirty patients with newly diagnosed non-Hodgkin lymphoma (NHL) treated with the first course of an R-CHOP regimen were enrolled randomly. After treatment with the first course of chemotherapy, a daily dose of G-CSF (lenograstim, 100 mu g) was administered to half (15 cases) of the patients, and a dose of G-CSF (100 mu g) was administered every other day to the other half of the patients when leukocytopenia (&lt; 1.5 x 10(9)/L) and/or neutropenia (&lt; 0.5 x 10(9)/L) occurred. Changes in leukocyte and neutrophil counts, prophylaxis, febrile neutropenia (FN) events, and cost performance between the two groups were analyzed.
No significant difference between the two groups was observed in recoveries of leukocyte and neutrophil counts and evidence of FN. The only difference was the total cost of G-CSF.
We concluded that every-other-day use of G-CSF was as clinically effective for the prophylaxis of FN as the daily use of G-CSF, and economically speaking, the administration of G-CSF every other day should be more beneficial for patients with NHL during early courses of R-CHOP chemotherapy.

DOI： 10.1007/s10147-010-0134-x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INFORMA HEALTHCARE  

Recent clinical trials have demonstrated that cilostazol, an antiplatelet drug competent to inhibit phosphodiesterase 3, is effective in secondary prevention of atherothrombosis including ischemic stroke, myocardial infarction, and peripheral arterial disease. However, there is no reliable assay for detection of the platelet response to cilostazol. We attempted to establish such an assay for clinical use. Phosphorylation of vasodilator-stimulated phosphoprotein (VASP) subsequent to the pharmacological action of cilostazol was measured by a platelet VASP assay kit that has been widely used for monitoring platelet response to ADP receptor antagonists in clinical settings. We modified the kit and found the optimal conditions for detection of cilostazol-dependent VASP phosphorylation. The assay could detect the in vitro and in vivo platelet responses to cilostazol effectively in the presence of 50 nM PGE1. ROC analysis showed that our assay had 97%% sensitivity and 75%% specificity when blood drawn between 3 and 9 h after cilostazol ingestion was subjected to the assay. The assay results were verified by immunoblotting specific for VASP phosphorylation. Standard light transmission platelet aggregometry could not detect significant inhibition of agonist-induced platelet aggregation by cilostazol except for the in vitro effect of high concentrations of cilostazol. These results demonstrate that the platelet VASP assay can detect the platelet response to cilostazol with high sensitivity and specificity.&lt;/.

DOI： 10.3109/09537104.2010.525976

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This study reports the association of the chromosomal abnormality derivative (1;18)(q10;q10) with essential thrombocythemia (ET) occurring in a 75-year-old woman. Allele-specific polymerase chain reaction also revealed a V617F mutation in the Janus Kinase 2 gene (JAK2) in the platelet compartment in this patient. The der(1;18)(q10;q10) abnormality has previously been reported in two cases of myeloid disorders. The etiological implications for ET of this combination of chromosomal abnormality and JAK2 mutation still remain elusive. This is a novel report of derivative (1;18)(q10;q10) abnormality in ET. (C) 2010 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.cancergencyto.2010.02.001

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DOI： 10.1007/s12185-009-0430-2

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

ZNF521 (zinc finger protein 521) is a transcription factor with an N-terminal transcriptional repressor motif and 30 zinc finger domains. Although a high expression level of ZNF521 in human CD34(+) progenitors and hematopoietic malignancies has been demonstrated, the functional role of ZNF521 in hematopoietic cell differentiation has not been clarified. In this study, we analyzed the role of ZNF521 in erythroid cell differentiation using the short hairpin RNA (shRNA)-mediated gene silencing method. Down-regulation of ZNF521 mediated by transient expression of shRNA for ZNF521 resulted in increased synthesis of hemoglobin in K562 and HEL cell lines as compared with control cells. K562-derived clones in which ZNF521 was constitutively silenced by shRNA also showed marked synthesis of hemoglobin and an increased expression level of glycophorin A. Since GATA-1 is the key regulator of erythroid differentiation, the effect of ZNF521 on transcription activity of GATA-1 was analyzed using a luciferase assay. GATA-1 activity was markedly inhibited by ZNF521 in a dose-dependent manner. Deletion analysis of ZNF521 showed that the repressive effect requires an N-terminal repression motif. Furthermore, the direct interaction of ZNF521 with GATA-1 was demonstrated. These results indicate that ZNF521 modulates erythroid cell differentiation through direct binding with GATA-1.

DOI： 10.1074/jbc.M805874200

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Integrin-mediated cell adhesion is essential for development of multicellular organisms. In worms, flies, and vertebrates, talin forms a physical link between integrin cytoplasmic domains and the actin cytoskeleton. Loss of either integrins or talin leads to similar phenotypes. In vertebrates, talin is also a key regulator of integrin affinity. We used a ligand-mimetic Fab fragment, TWOW-1, to assess talin's role in regulating Drosophila alpha PS2 beta PS affinity. Depletion of cellular metabolic energy reduced TWOW-1 binding, suggesting alpha PS2 beta PS affinity is an active process as it is for vertebrate integrins. In contrast to vertebrate integrins, neither talin knockdown by RNA interference nor talin head overexpression had a significant effect on TWOW-1 binding. Furthermore, replacement of the transmembrane or talin-binding cytoplasmic domains of alpha PS2 beta PS with those of human alpha IIb beta 3 failed to enable talin regulation of TWOW-1 binding. However, substitution of the extracellular and transmembrane domains of alpha PS2 beta PS with those of alpha IIb beta 3 resulted in a constitutively active integrin whose affinity was reduced by talin knockdown. Furthermore, wild-type alpha IIb beta 3 was activated by overexpression of Drosophila talin head domain. Thus, despite evolutionary conservation of talin's integrin/cytoskeleton linkage function, talin is not sufficient to regulate Drosophila alpha PS2 beta PS affinity because of structural features inherent in the alpha PS2 beta PS extracellular and/or transmembrane domains.

DOI： 10.1091/mbc.E08-01-0085

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

Integrin cytoplasmic tails regulate integrin activation that is required for high affinity binding with ligands. The interaction of the integrin beta subunit tail with a cytoplasmic protein, talin, largely contributes to integrin activation. Here we report the cooperative interaction of the beta 3 membrane-proximal and -distal residues in regulation of talin-mediated alpha IIb beta 3 activation. Because a chimeric integrin, alpha IIb beta 3/beta 1, in which the beta 3 tail was replaced with the beta 1 tail was constitutively active, we searched for the residues responsible for integrin activation among the residues that differed between the beta 3 and beta 1 tails. Single amino acid substitutions of Ile-719 and Glu-749 in the beta 3 membraneproximal and -distal regions, respectively, with the corresponding beta 1 residues or alanine rendered alpha IIb beta 3 constitutively active. The I719M/E749S double mutant had the same ligand binding activity as alpha IIb beta 3/beta 1. These beta 3 mutations also induced alpha V beta 3 activation. Conversely, substitution of Met-719 or Ser-749 in the beta 1 tail with the corresponding beta 3 tail residue (M7191 or S749E) inhibited alpha IIb beta 3/beta 1 activation, and the M719I/S749E double mutant inhibited ligand binding to a level comparable with that of the wild-type alpha IIb beta 3. Knock down of talin by short hairpin RNA inhibited the I719M- and E749S-induced alpha IIb beta 3 activation. These results suggest that the beta 3 membraneproximal and -distal residues cooperatively regulate talin-mediated alpha IIb beta 3 activation.

DOI： 10.1074/jbc.M707246200

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Adoptive transfer of CD4+ CD25+ regulatory T cells has been shown to have therapeutic effects in animal models of autoimmune diseases. Chemokines play an important role in the development of autoimmune diseases in animal models and humans. The present study was performed to investigate whether the progression of organ-specific autoimmune diseases could be reduced more markedly by accumulating chemokine receptor-expressing CD4+ CD25+ regulatory T cells efficiently in target organs in MRL/MpJ-lpr/lpr (MRL/lpr) mice. CD4+ CD25+ Foxp3+ T cells (Treg cells) and CD4+ CD25+ Foxp3+ CCR2-transfected T cells (CCR2-Treg cells) were transferred via retro-orbital injection into 12-week-old MRL/lpr mice at the early stage of pneumonitis and sialadenitis, and the pathological changes were evaluated. Expression of monocyte chemoattractant protein-1 (MCP-1)/ CCL2 was observed in the lung and submandibular gland of the mice and increased age-dependently. The level of CCR2 expression and MCP-1 chemotactic activity of CCR2-Treg cells were much higher than those of Treg cells. MRL/lpr mice to which CCR2-Treg cells had been transferred showed significantly reduced progression of pneumonitis and sialadenitis in comparison with MRL/lpr mice that had received Treg cells. This was due to more pronounced migration of CCR2-Treg cells and their localization for a longer time in MCP1- expressing lung and submandibular gland, resulting in stronger suppressive activity. We prepared chemokine receptor-expressing Treg cells and demonstrated their ability to ameliorate disease progression by accumulating in target organs. This method may provide a new therapeutic approach for organ-specific autoimmune diseases in which the target antigens remain undefined.

DOI： 10.1186/ar2122

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Imatinib mesylate and rituximab are molecularly targeted drugs against the BCR-ABL fusion protein and the CD20 antigen, respectively. Although these drugs have excellent anticancer effects, a major concern is drug resistance. We have investigated the case of a patient with Philadelphia chromosome-positive and CD20(+) acute lymphocytic leukemia who acquired resistance to imatinib and rituximab. Imatinib therapy resulted in prompt cytogenetic remission, but resistance developed shortly thereafter. Sequencing of the kinase domain of the ABL gene and allele-specific polymerase chain reaction analysis revealed a point mutation resulting in an E255V substitution that was present before the therapy. After the patient received mild chemotherapy followed by rituximab administration, hematologic and cytogenetic remission was sustained for 5.5 months. The recurrent leukemic cells after the rituximab therapy showed not only the E255V mutation in the ABL gene but also loss of the CD20 antigen due to impaired transcription of the CD20 gene. The results of 2-color flow cytometry analysis showed that a small population of CD20(-) leukemic cells existed before the imatinib therapy. These results suggest that leukemic subclones carrying a genetic perturbation of the targeted molecules for both imatimb and rituximab were present before the therapies. The preexistence of primary resistant clones suggests the inability of combination therapy with 2 molecularly targeted drugs to overcome drug resistance in leukemia. (C) 2004 The Japanese Society of Hematology.

DOI： 10.1532/ijh97.04033

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PORTLAND PRESS  

Integrin cytoplasmic tails regulate integrin activation including an increase in integrin affinity for ligands. Although there is ample evidence that the membrane-proximal regions of the alpha and beta tails interact with each other to maintain integrins in a low-affinity state, little is known about the role of the membrane-distal region of the alpha tail in regulation of integrin activation. We report a critical sequence for regulation of integrin activation in the membrane-distal region of the alphaIIb tail. Alanine substitution of the RPP residues in the alphaIIb tail rendered alphaIIbbeta3 constitutively active in a metabolic energy-dependent manner. Although an alphaIIb/alpha6Abeta3 chimaeric integrin, in which the alphaIIb tail was replaced by the alpha6A tail, was in an energy-dependent active state to bind soluble ligands, introduction of the RPP sequence into the alpha6A tail inhibited binding of an activation-dependent antibody PAC1. In alphaIIb/alpha6Abeta3, deleting the TSDA sequence from the alpha6A tail or single amino acid substitutions of the TSDA residues inhibited alphaIIb/alpha6Abeta3 activation and replacing the membrane-distal region of the alphaIIb tail with TSDA rendered alphaIIbbeta3 active, suggesting a stimulatory role of TSDA in energy-dependent integrin activation. However, adding TSDA to the alphaIIb tail containing the RPP sequence of the membrane-distal region failed to activate alphaIIbbeta3. These results suggest that the RPP sequence after the GFFKR motif of the alphaIIb tail suppresses energy-dependent alphaIIbbeta3 activation. These findings provide a molecular basis for the regulation of energy-dependent integrin activation by alpha subunit tails.

DOI： 10.1042/BJ20031753

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DOI： 10.1111/j.1538-7836.2004.0584b.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN  

Ligand binding to integrin alphaIIbbeta3 is a key event of thrombus formation.The propeller domain of the alphallb subunit has been implicated in ligand binding. Recently, the ligand binding site of the V propeller was, determined by crystal structure analysis. However, the structural basis of ligand recognition by the alphaIIb propeller remains to be determined. In this study, we conducted site-directed mutagenesis of all residues located in the loops extending above blades 2 and 4 of the alphaIIb propeller, which are spatially close to, but distinct from, the loops that contain the binding site for an RGD ligand in the crystal structure of the alphaV propeller. Replacement by alanine of Q111, H112 or N114 in the loop within the blade 2 (the W2:2-3 loop in the propeller
model) abolished binding of a ligand-mimetic antibody and fibrinogen to alphaIIbbeta3 induced by different types of integrin activation including activation of alphallbbeta3 by beta3 cytoplasmic mutation. CHO cells stably expressing recombinant alphallbbeta3 bearing Q111A, H112A or N114A mutation did not exhibit alphaIIbbeta3 mediated adhesion to fibrinogen. According to the crystal structure of alphaVbeta3, the aV residue corresponding to alphaIIbN 114 is exposed on the integrin surface and close to the RGD binding site.These results suggest that the Q111, H 112 and N 114 residues in the loop within blade 2 of the allb propeller are critical for ligand binding, possibly because of direct interaction with ligands or modulation of the RGD binding pocket.

DOI： 10.1160/TH03-06-0392

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PubMed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

A 39-year-old man with no significant medical history was admitted to our hospital with severe abdominal pain and melena. Computed tomographic (CT) scans demonstrated superior mesenteric venous thrombosis. Although thrombolysis and anticoagulant therapy was started immediately, symptoms of strangulation ileus developed. Laparotomy was therefore performed and revealed necrotic stenosis of the ileum. The patient, his father and sisters showed low protein C levels. Direct sequencing analysis of their protein C gene revealed a heterozygous mutation at codon 169 corresponding to the cleavage site of the activation peptide, which was referred to as protein C Tochigi.

DOI： 10.2169/internalmedicine.42.110

Web of Science

PubMed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN  

To define the structural basis of ligand recognition by alphaIIbbeta3, we conducted site-directed mutagenesis of residues located on the top surface of the beta3 I-domain that is homologous to the I-domain of several alpha subunits and contains a putative ligand binding site, Here we identify D158 and N215 in beta3 as novel residues critical for ligand binding. Alanine substitution of D 158 or N215 abolished binding of a ligand-mimetic antibody and fibrinogen to alphaIIbbeta3 induced by different types of integrin activation. CHO cells expressing recombinant alphaIIbbeta3 bearing D158A or N215A mutation did not adhere to fibrinogen. These mutations had the same effect on ligand binding to another beta3 integrin, alphaVbeta3. Compared to the alphaI-domain structure, the betaB-betaC loop containing D158 in the beta3 I-domain is quite different in length and sequence. These results suggest that the structure for ligand recognition is different in the betaI- and alphaI-domains.

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Language：Japanese   Publisher：(一社)日本血栓止血学会  

近年の血友病治療の進歩は目覚ましいものがあり,様々な特徴を持つ血液凝固因子製剤のほか,凝固第VIII因子の機能を代替する抗体製剤も日常診療で使用されている.その結果,血友病の出血/止血管理は従来の標準的治療から,一人ひとりの薬物動態やライフスタイルに合わせた個別化治療に進化している.日本血栓止血学会では,血友病患者が居住地近くの施設で引き続き治療を受けることができるという利便性を損なうことなく,最新の個別的包括的ケアを受けることができるようにするため2018年に血友病診療連携委員会を設置して,血友病診療連携体制を構築した.本体制は,血友病患者が血友病診療ブロック拠点病院あるいは地域中核病院を受診し,診療方針の提示を受けることを基本としているが,遠方に在住している患者にとっては,時間的経済的負担が大きい.今回,直接受診を補完するものとして,血友病における遠隔診療(オンライン診療)連携の可能性を考えた.(著者抄録)

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Language：Japanese   Publisher：医歯薬出版(株)  

後天性血小板機能異常症は血液疾患をはじめ,さまざまな基礎疾患,薬剤により血小板機能が障害され,出血症状を呈する.一般臨床で頻度が多い後天性血小板機能異常症は,血小板機能に影響を及ばす薬剤によるものである.抗血小板薬は日常診療において脳梗塞や心筋梗塞,狭心症を予防するために服用されているが,出血性副作用について考えておく必要がある.また,非ステロイド性消炎鎮痛薬(NSAIDs)も血小板機能が障害される.(著者抄録)

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Language：Japanese   Publisher：(一社)日本輸血・細胞治療学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J04824&link_issn=&doc_id=20231229310006&doc_link_id=10.3925%2Fjjtc.69.648&url=https%3A%2F%2Fdoi.org%2F10.3925%2Fjjtc.69.648&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

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Publishing type：Meeting report  

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Language：Japanese   Publisher：(株)文光堂  

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Language：Japanese   Publisher：(一社)愛媛県臨床検査技師会  

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Publishing type：Meeting report  

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Language：Japanese   Publisher：(一社)日本輸血・細胞治療学会  

症例は85歳、男性。非ホジキンリンパ腫の化学療法後の血小板減少症に対して血小板輸血を行ったところ、輸血開始20分後に喘鳴と呼吸困難が出現した。心エコーでEF27.3%と高度の心機能低下を認め、心基部の壁運動は正常に保たれているものの心尖部の壁運動が高度に低下していたことから、たこつぼ型心筋症と診断した。利尿薬等で加療を行い、症状は改善し、心エコー所見も正常化した。たこつぼ型心筋症は交感神経を介する何らかのストレスを誘因とし、突然、一過性の心機能障害を呈する病態である。本症例は血小板輸血後のアレルギー反応がストレスとなって、たこつぼ型心筋症を起こし、心不全症状が出現したのではないかと考えられた。輸血後に心不全を呈する疾患としてTACO(輸血関連循環負荷)が知られているが、本例はTACOの診断基準も満たしていた。TACOと診断されている症例の中にたこつぼ型心筋症の症例も含まれている可能性があり、またTACOの病態にたこつぼ型心筋症が関与している可能性も考えられ、多数例での解析が輸血後心不全の病態の解明に必要と思われる。(著者抄録)

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Language：Japanese   Publisher：(一社)日本内科学会  

72歳男。右背部の疼痛、腫脹を主訴とした。白血球・血小板の増加、幼若球の出現と好塩基球の増加、肝脾腫と背部の広範な皮下血腫を認めたため、精査加療目的で紹介受診した。骨髄生検で骨髄の線維化を認めたほか、Janus kinase 2(JAK2)V617F変異があり、白血球の著増、末梢血への赤芽球の出現、LD増加ならびに著明な脾腫があることから、骨髄線維症と診断した。また、皮下血腫に関しては血小板の著増、von Willebrand因子(vWF)活性22%、vWF抗原94%より、後天性von Willebrand症候群の合併によるものと考えられた。骨髄線維症に対してruxolitinib 40mg/日で治療を開始したところ、骨髄線維症の主症状である脾腫が改善するとともに、血小板数の低下とvWF活性の増加がみられ、皮下血腫は改善した。

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Language：Japanese   Publisher：日本医師会  

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Language：Japanese   Publisher：(一社)日本血栓止血学会  

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Language：Japanese   Publisher：(一社)愛媛県臨床検査技師会  

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Language：Japanese   Publisher：愛媛医学会  

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

DOI： 10.11406/rinketsu.57.869

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Language：Japanese   Publisher：(株)南江堂  

54歳男。労作時息切れ、全身倦怠感を主訴とした。血液検査で正球性正色素性貧血、網状赤血球の著減を認めた。血液生化学検査では総蛋白の増加、蛋白電気永動でモノクローナルな高γ-グロブリン血症を認めた。また、IgMの高値を認め、免疫電気永動検査でIgM κ typeのM蛋白を確認した。可溶性IL-2レセプターは上昇、エリスロポエチンも著明に上昇していた。骨髄検査では赤芽球の著明な低下を認め、小リンパ球から形質細胞にいたるB細胞が増加していた。以上より、原発性マクログロブリン血症に後天性慢性赤芽球癆を合併したものと判断した。赤芽球癆に対しciclospolinとrituximabによる化学療法を導入し、貧血は改善した。しかし、IgM値は低下せず横ばいであることから、原発性マクログロブリン血症の増悪は認めないものの寛解には至っていない。Ciclospolinによる維持療法を継続している。

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Language：Japanese   Publisher：愛媛医学会  

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：Japanese   Publisher：(一社)日本血栓止血学会  

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：Japanese   Publisher：(公社)日本化学療法学会  

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Language：Japanese   Publisher：(一社)愛媛県臨床検査技師会  

70歳代男。早期胃癌に対する内視鏡的粘膜下層剥離術(ESD)目的で入院した。心房細動があり、脳梗塞予防のためワーファリンコントロール中であった。ワーファリン内服を中止し、ビタミンK製剤投与を継続したが、プロトロンビン時間(PT)延長の改善は認めず、ESDは延期した。APTTは正常であったが、ワーファリンコントロールのためPTの延長を認めた。PIVKA-IIの著明な増加とフィブリノゲン(Fbg)の著減を認めた。FDPが存在しているにもかかわらず、FDP-Dダイマーは検出感度未満であった。トロンビン時間法におけるFbg測定の反応曲線により、Fbg分子構造に何らかの遺伝子異常が関与していると考えられた。遺伝子解析により、Fbgγ鎖R275Hのヘテロ異常症であることが判明した。

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Language：Japanese   Publisher：(一社)愛媛県臨床検査技師会  

60歳代男。右口腔粘膜潰瘍病変を指摘され、下顎歯肉癌と診断された。下顎歯肉癌の術前検査にて活性化部分トロンボプラスチン時間(APTT)延長を確認したが、出血傾向は認めなかった。手術のため新鮮凍結血漿を投与したところ一時的にAPTTが正常化した。手術後、創部に皮下血腫が出現し、再手術を施行した。APTT炎症の原因を確認するため混合試験を施行し、凝固因子欠損を疑った。プレカリクレイン欠損血漿を用いて患者血漿と混合試験を行い、プレカリクレインの欠乏が考えられた。さらにこの試験での患者血漿を用いたAPTTは、二重測定でバラつきを認めた。プレカリクレインの活性を測定し、検出感度以下であった。プレカリクレインの遺伝子検索において、220番目のアミノ酸フェニールアラニンをコードするコドンTTCがインフレームで欠失し、以後の配列にも両アレルによるずれは認められなかった。

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Language：Japanese   Publisher：(株)日本臨床社  

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Language：Japanese   Publisher：(株)日本臨床社  

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：Japanese   Publisher：(株)南江堂  

45歳男。検診で白血球増加を指摘され受診した。白血球数の著増、骨髄球や後骨髄球を認め、好塩基球および有核細胞数の増加を認めた。骨髄球系細胞の増加が顕著で、bcr/ablのFISH検査で融合遺伝子を認め、慢性骨髄性白血病と診断した。イマチニブで治療を開始し1ヵ月後には血液学的寛解に至ったが、5ヵ月目に白血球数が増加し、骨髄芽球を47.2%認め、LDHも高値を認めた。骨髄検査では骨髄芽球52.9%を認め、表面マーカはCD13、CD33、CD38が陽性で、慢性骨髄性白血病(CML)のmyeloid crisisと診断された。ABL遺伝子の遺伝子検査では、リン酸化酵素ドメインに変異は見つからなかった。dasatinib併用の化学療法を行ったところ、寛解に至った。第二慢性期となりdasatinibによる治療を継続した。2ヵ月目に腹部症状を伴わない発熱を認めた。精査の結果、大腸内視鏡で上行結腸からS状結腸にかけて小びらんが多発しており、同部位からの生検で封入体を認め、CMV免疫染色が陽性であったことからCMV腸炎と診断し、ガンシクロビルを投与した。その後は解熱し、1ヵ月後にはびらんは改善した。

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Other Link： http://search.jamas.or.jp/link/ui/2013133392

Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

血栓性血小板減少性紫斑病(TTP)の約20%は血漿交換抵抗性であり,そのような症例に対して,rituximabが有効であるとの報告が増加している。しかし,その適応基準や開始のタイミングはまだ定まっていない。私たちの施設では3例のTTPにrituximabの投与を行ったが,1例目は晩期投与で後遺症が残り,2例目は効果発現前に死亡し,3例目は早期投与にて完全回復した。このことからはrituximabの早期投与が望まれるが,その至適投与方法を確立していくためには,多くの症例を集積して検討する必要があると思われる。(著者抄録)

DOI： 10.11406/rinketsu.54.205

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Other Link： https://jlc.jst.go.jp/DN/JALC/10015802193?from=CiNii

Language：Japanese   Publisher：(一社)愛媛県臨床検査技師会  

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：Japanese   Publisher：(一社)日本内科学会  

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Language：Japanese   Publisher：(一社)日本血栓止血学会  

症例は82歳,男性.40年前から尋常性乾癬に罹患している.2008年11月に転倒し,右前腕,右下腿を受傷したが,受傷部位からの出血が持続するために近医を受診した.血小板数正常,PT&lt;5%,APTT&gt;200秒で,凝固第V因子活性を測定したところ3%未満で,インヒビターは7BethesdaU/mlであった.後天性凝固第V因子欠乏症と診断し,新鮮凍結血漿の投与を行い止血が得られた.その後,第V因子活性は徐々に増加してきたため経過をみていたが,2009年10月,下血をきたしたため再度受診した.第V因子活性の低下とインヒビター力価の上昇を認めた.この時,急性ラクナ梗塞を併発した.下血と梗塞後出血予防のためプレドニゾロンの投与を行ったところ,第V因子活性は速やかに正常となり,インヒビターも消失した.後天性第V因子インヒビターは,数ヵ月以内に自然消失することが多く,免疫抑制剤の効果は確立していない.本例は約1年にわたり凝固異常が持続したが,プレドニゾロンの投与で極めて速やかに改善し,免疫抑制療法の著効例と考えられたため報告する.(著者抄録)

DOI： 10.2491/jjsth.21.391

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

82歳男。四肢の皮下出血・腫脹が出現し、検査所見でPT正常、APTTは81.8秒と延長しており、第VIII因子活性が検出感度以下、第VIII因子インヒビターは30.4BU/mlと高値であった。後天性血友病と診断し、prednisolone(PSL)60mg/日を開始したところ、1ヵ月後には第VIII因子活性が150%まで増加し、第VIII因子インヒビターも消失し、皮下出血も消失した。しかし、PSL漸減により第VIII因子活性が低下し、第VIII因子インヒビターが出現するため、難治性と考えcyclosporine A 100mg/日を追加した。その結果、PSL減量による再燃はなくなったが、治療開始10ヵ月頃より右上腕と左大腿部に皮下腫瘤が出現し、次第に発赤と熱感を伴うようになった。超音波所見より筋膿瘍を疑い穿刺吸引を行ったところ、混濁した膿が採取された。グラム染色でグラム陽性桿菌が検出され、好酸性染色で陽性を示したことから、ノカルジア属であることが示唆された。ST合剤開始により速やかに改善し、後日起因菌はNocardia brasiliensisと同定された。

DOI： 10.11406/rinketsu.50.495

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Other Link： http://search.jamas.or.jp/link/ui/2009352399

Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

66歳女。1ヵ月前に右鎖骨部腫瘤が出現し、その後増悪した。CTでは右鎖骨に骨破壊を伴う6cm大の腫瘤を認め、内部に石灰化を伴っていた。生検でCD20陽性diffuse large B cell lymphomaとの診断が得られた。全身検索のGaシンチグラフィーでは右鎖骨、右大腿骨、右膝関節、左下腿に異常集積を認め、X線およびCTでは右大腿骨、左・右下腿に異常所見はなかったが、MRIでは右大腿骨にT1強調像で低信号、T2強調像で低信号域の中に一部高信号を認めた。CHOP療法を開始したところ腫瘤は速やかに縮小し、開始7日目にRituximabを投与したが、同日深夜にトイレで立ち上がった際に左脛骨、腓骨遠位部、右大腿骨転子部を骨折した。画像所見より病的骨折と考え、化学療法による骨髄抑制から回復した後に観血的接合術を施行した。その後、R-CHOP療法を繰り返し、現在は右鎖骨腫瘤は縮小して新たな骨形成も認め、Gaシンチでも異常集積は認めない。

DOI： 10.11406/rinketsu.50.187

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Language：Japanese   Publisher：(株)南江堂  

64歳男。39℃に及ぶ発熱と全身倦怠で近医受診し、上気道炎と診断され抗生物質の内服加療を受けたが改善しないため当科紹介受診となった。両側頸部リンパ節で5mm弱のものを数個触知し、扁桃腺炎による発熱と考え抗生物質の点滴を行なったが解熱せず、下部消化管内視鏡で回腸末端部に発赤を伴う小隆起性病変の散在を認めた。生検より異型リンパ球の浸潤が粘膜筋板部から粘膜下層に拡大し、血管内皮腫大が著明な血管増生と淡明な細胞質をもつ大型の異型細胞を多数認め、免疫染色でCD3とUCHL1は陽性、CD20とCD79の陰性であった。以上より、血管免疫芽球性T細胞リンパ腫(AILT)stageIV、IPI 2と診断してCHOP療法を施行した。1コース終了後に解熱、全身倦怠感の改善、頸部リンパ節腫大の改善を認め、2コース終了後には回腸末端部の隆起病変は消失した。6コース施行して現在寛解を維持した。

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Other Link： http://search.jamas.or.jp/link/ui/2009138560

Language：Japanese   Publisher：(株)南江堂  

64歳男。陰部に違和感を自覚し、近医で陰茎根部の硬結、左鼠径部のリンパ節腫大を指摘され、生検で悪性リンパ腫を疑われ当院紹介入院となった。CTでは陰茎根部に径3cmのややlow densityの陰影を、MRIのT2強調像では陰茎全体に低吸収域を認めた。Gaシンチグラフィーでは陰茎根部と左鼠径部リンパ節に加え、上方の骨盤内にも集積を認めた。生検組織標本では鼠径部リンパ節、陰茎根部ともびまん性にやや大型のリンパ腫細胞が浸潤しており、CD20染色は陽性であった。Stage IIEのnon-Hodgkin&#039;s lymphoma、diffuse large B-cell typeと診断し、R-CHOP療法を開始した。1コース終了時点で陰茎根部の硬結と鼠径部リンパ節の縮小を認め、以後化学療法を計8コース行い、寛解を維持している。

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2009072566

Language：Japanese   Publisher：(一社)日本内科学会  

47歳女。患者は全身倦怠感を主訴とし近医を受診、LDH高値を指摘され、著者らの施設へ紹介となった。所見では胸部CTで両肺野にび漫性のごく淡いスリガラス影が認められ、経過から過敏性肺臓炎を最も疑われたが、気管支鏡下肺生検の結果、血管内大細胞型B細胞性リンパ腫(ILV)と診断された。治療はび漫性肺浸潤を伴っていたため、初回化学療法としてプレドニゾロンを先行したCHOP療法を行い、LDHおよび低酸素血症の改善を確認した後に、rituximabの投与を行った。その結果、1コース終了後、LDHは正常化し、血液ガス所見も改善、更に両肺野のスリガラス影も著明に改善した。特に合併症は認めず経過は良好で、現在は8コースの化学療法終了後、完全寛解で外来経過観察中である。

DOI： 10.2169/naika.96.2783

CiNii Books

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Other Link： https://jlc.jst.go.jp/DN/JALC/00304871122?from=CiNii

Language：Japanese   Publisher：認定内科専門医会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

80歳女.下腹部痛および下血が出現した.大腸内視鏡で肝彎曲部に径2cmの2型進行大腸癌様腫瘤性病変を認め,生検で粘膜筋板から粘膜下層にかけて均質無構造なガラス様構造のアミロイド沈着を認めた.潰瘍周堤部では粘膜筋板が消失し,アミロイド集塊と粘膜が直接接する部位も見られたが,悪性所見は認めなかった.大腸癌や粘膜下腫瘍も否定できず,2ヵ月後に再度大腸内視鏡を行った.腫瘤病変は自壊による深い潰瘍形成を認め,3型進行大腸癌様の形態を呈し,易出血性であった.ただし比較的潰瘍底は整っており,周堤に相当する隆起は正常な粘膜で,悪性病変は示唆されなかった.生検でも悪性所見はなく,原発性アミロイドーシスによる消化管腫瘤病変と診断した.手術侵襲などを考慮して保存的治療を選択し,melphalan,prednisone,およびdimethyl sulfoxideの経口投与を行った.特有の口臭以外に副作用,検査値異常はなく,6ヵ月後の大腸内視鏡で腫瘤性病変の縮小,改善を認めた

DOI： 10.11280/gee1973b.46.2416

CiNii Books

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Language：Japanese   Publisher：愛媛医学会  

最近4年間の初回治療例において,高度の耐性例は認めなかったが,耐性基準濃度未満で耐性を示したものは高頻度であった.菌陰性化迄の期間は全例5ヵ月以内であり,治療に大きな支障を認めなかった

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Language：Japanese   Publisher：(株)南江堂  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

73歳男.1993年,頸部及び縦隔リンパ節腫大出現し,ホジキン病と診断され化学療法にて寛解.1994年,内視鏡検査にて胃体部小彎にIIc様の浅い陥凹性病変を認め,その生検組織は低分化型腺癌か悪性リンパ腫か鑑別が困難な組織像を呈した.前回のリンパ節と今回の胃病変の生検組織の再検討を行い,免疫組織染色にて,Ki-1(CD30)陽性,CD15陰性を示したことより,未分化大細胞型リンパ腫と診断した

DOI： 10.11280/gee1973b.40.2124

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

CiNii Books

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Language：Japanese   Publisher：愛媛医学会  

71歳女,64歳時に回腸末端部の腸間膜脂肪炎と診断され入院治療を受けた.下腹部膨満感,発熱を主訴とし,精査加療目的で入院となった.入院時,腹部には筋性防御,Blumberg&#039;s signを認めた.検査成績では,血沈1時間値42mm,白血球数12300/μlで好中球増加,CRP値の上昇があった.腹部CT像では,回腸末端部付近の腸間膜の脂肪のdensityが上昇し,一部に膿瘍状の低吸収域を認めた.腸間膜脂肪織炎の再発と診断した.補液,抗生物質の治療により,症状は改善し,1ヵ月後の腹部CT像では腸間膜の脂肪のdensityの上昇は軽快していた

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

症例は59歳女で,1994年,眼球乾燥感,口腔内乾燥感があり,抗SS-A抗体,抗SS-B抗体陽性よりシェーグレン症候群と診断した.1995年9月,肝機能異常を認めたため,腹腔鏡下肝生検を施行.正常胆管は減少し,殆どの胆管の変形を認める像であり,抗ミトコンドリア抗体陰性,抗平滑筋抗体陽性よりautoimmune cholangiopathy(AIC)と診断した.その後,外来で経過観察中,肝機能異常の増悪を認め,1996年9月入院.AICの増悪と診断し,プレドニゾロン40mgの投与を開始した.GOT,GPT値の改善を認めたが,T.Bilは47.6mg/dlまで上昇し,また,Hb4.6g/dl,LDH2875IU/l,ハプトグロビン&lt;9.5mg/dlと溶血性貧血を併発した

CiNii Books

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Language：Japanese   Publisher：(一社)日本感染症学会  

DOI： 10.11150/kansenshogakuzasshi1970.72.849

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

82歳男,嚥下困難と心拡大を主訴に入院した.理学的には第IV音とLevine III/VIの収縮期雑音を心尖部に聴取した.表在リンパ節は触知しなかった.検査所見ではLDH662IU/lがみられた.心エコーでは,3°の僧帽弁閉鎖不全がみられた.CTでは,後縦隔に大きな腫瘤がみられ,後方から心臓を圧迫していた.経過中,左胸水が出現したため,胸水穿刺を施行した.細胞診で,CD10,CD19陽性のリンパ球様細胞の集塊がみられ,t(8;14)(q24;q32)を含む多彩な染色体異常が認められた.以上より後縦隔原発のB cellリンパ腫と診断し,cyclophosphamide,THP-adriamycin,vincristine,prednisoloneによる化学療法を施行した.その結果,腫瘤はすみやかに消失し,僧帽弁閉鎖不全も改善した

DOI： 10.11406/rinketsu.39.606

CiNii Books

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

症例は81歳女で,1995年2月より38℃の発熱が出現した.次第に貧血の進行,LDHの上昇がみられるようになったため9月入院した.全身浮腫著明で,Roth斑を含む多彩な眼底異常を認めた.皮疹,精神神経症状はみられなかった.Hb7.6g/dl,Plt9.3×10^4/μl,WBC6,300/μl,LDH1,932IU/l.原因精査を行うと共に,抗生剤,抗結核薬,ステロイド剤を投与したが不明熱のまま経過し,10月心不全で死亡した.剖検では,肺,腎,膀胱,消化管粘膜の小血管内に大型の単核細胞が充満している像がみられた.これらは,LCA,L26陽性,UCHL-1陰性で,Bリンパ球由来と考えられ,Neoplastic angioendotheliosis(NAE)と最終診断された

DOI： 10.11406/rinketsu.39.227

CiNii Books

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Language：Japanese   Publisher：(株)南江堂  

64歳女.肺と皮膚にサルコイドーシス病変を認め,胃には潰瘍性病変がなく粘膜不整像のみで生検でサルコイドーシスの病変を認めた

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Language：Japanese   Publisher：愛媛医学会  

56歳女.四肢に腫脹,硬化を認め,末梢血好酸球増多,血沈亢進,高γ-グロブリン血症,皮膚生検所見等より好酸球性筋膜炎と診断した

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Language：Japanese   Publisher：大道学館出版部  

68歳女.腰痛の為受診.多発性骨髄腫(IgA-λ型)と診断され,経過観察中1992年12月及び1994年3月にIgMの上昇と共に胆道系酵素(ALP, LAP, γ-GTP)の上昇を認め,5〜7ヵ月で自然軽快した.1995年4月頃より全身倦怠感と共に骨髄での形質細胞の増加と尿中Bence Jones蛋白の増加を認め,再度IgMと胆道系酵素の上昇を認め入院した.肝生検で胆管壁内へのリンパ球の浸潤,胆管上皮細胞の配列不整,空胞変性を認める慢性非化膿性破裂性胆管炎及び肉芽腫を認め,Schener分類のI期に相当する原発性胆汁性肝硬変と診断した

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Event date： 2022.6

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Venue：名古屋市 WEB開催  

共催セミナー 共催：中外製薬株式会社

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誌上発表

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教育講演

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Venue：松山市  

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Venue：松山市  

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誌上

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Venue：松山市  

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2020年3月14日から4月29日に延期の後、中止。誌上発表。

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m3.com

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Venue：東京  

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2019.10.26-10.27

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厚生労働科学研究事業 HIV感染症の医療体制の整備に関する研究
分担研究「HIVカウンセリングの普及および充実化に関する研究」

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