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

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Language：Japanese   Publisher：(一社)日本造血・免疫細胞療法学会  

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Language：English  

The UK Myeloma Research Alliance Risk Profile (MRP) is a novel prognostic model for transplant-ineligible patients with multiple myeloma (MM). Since MRP was developed based on the results of clinical trials in which immunomodulatory drugs were used as induction regimens, its applicability to patients treated with bortezomib-based regimens remains elusive. The aim of this study is to assess the utility of MRP in patients treated with a representative bortezomib-based regimen of melphalan, prednisolone, and bortezomib (MPB) in JCOG1105, a randomized phase II trial comparing two modified MPB regimens. The patients (n=88) were categorized into MRP risk of low (59%), medium (18%), and high (23%). The median follow-up time was 3.9 years, and a higher MRP risk was not associated with poor overall survival (p=0.45). The 3-year OS of patients with low-, medium-, and high-risk of MRP was 84.3% (95% confidence interval [CI], 71.1-91.8%), 68.8% (95% CI, 40.5-85.6%), and 85.0% (95% CI, 60.4-94.9%), respectively. In conclusion, higher MRP risk groups were not significantly associated with poor prognosis in patients who received an MPB regimen in this supplementary analysis of JCOG1105. Large-scale studies which include patients treated with bortezomib-based regimens are required to further validate the significance of the MRP. This article is protected by copyright. All rights reserved.

DOI： 10.1002/hon.3103

PubMed

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Language：Japanese   Publisher：日本皮膚科学会-西部支部  

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Language：English   Publisher：CIG MEDIA GROUP, LP  

Web of Science

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Authorship：Lead author   Language：English  

DOI： 10.1007/s12185-021-03114-w

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Language：English   Publishing type：Research paper (scientific journal)  

Cancer immunotherapy using T cells redirected with chimeric antigen receptor (CAR) has shown a lot of promise. We have established a single-chain antibody (scFv) generation system in which scFv library-expressing CAR-T cells can be screened appropriately based on their antitumor functions. A variable region library containing the variable and J regions of the human immunoglobulin light or heavy chain was fused with the variable region of a heavy or light chain encoded by an existing tumor-specific antibody to generate a new scFv library. Then, scFv library-expressing CAR-T cells were generated and stimulated with target cells to concentrate the antigen-specific population. Using this system, target-specific recognition of CAR-T cells appeared to be finely tuned by selecting a new variable region. Importantly, we have demonstrated that the newly optimized scFv-expressing CAR-T cells had better proliferation capacity and durable phenotypes, enabling superior reactivity against advanced tumors in vivo in comparison with the original CAR-T cells. Therefore, the optimization of an scFv is needed to maximize the in vivo antitumor functions of CAR-T cells. This system may allow us to adjust an immunological synapse formed by an scFv expressed by CAR-T cells and a target antigen, representing an ideal form of CAR-T-cell immunotherapy.

DOI： 10.1038/s42003-021-01791-1

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

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Language：English  

DOI： 10.1007/s00277-020-04151-x

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Language：English  

DOI： 10.7326/L18-0610

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Language：English   Publishing type：Research paper (scientific journal)  

Cancer immunotherapy has been developed and established as a new treatment modality. Recently, adoptive transfer therapy using T cells redirected with antigen-specific antitumor receptors, such as T-cell receptor (TCR) and chimeric antigen receptor (CAR), has demonstrated clinical benefits even in patients with refractory malignancies. To advance this treatment modality, both generation of gene-modified T cells and evaluation of their reactivity with high quality in vitro are required. To achieve this, it is important to establish the ways (1) to generate optimal viral particle for T-cell transduction, (2) to transduce antitumor receptors into T cells and expand redirected T cells efficiently, and (3) to assess the functionality of antigen-specific gene-modified T cells precisely. Here, we summarize established protocols to generate and analyze antitumor receptor-transduced T cells. These procedures help to further assess characteristics of gene-modified T cells, resulting in promotion of translational research for cancer immunotherapy.

DOI： 10.1007/978-1-4939-9728-2_3

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Language：English   Publishing type：Research paper (scientific journal)  

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

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

Severe fever with thrombocytopenia syndrome (SFTS), a severe infectious disease caused by novel bunyavirus, SFTS virus (SFTSV), is endemic to China, Korea, and Japan. Most SFTS patients show abnormalities in consciousness. Pathological findings in the central nervous system (CNS) of SFTS patients are not reported. A 53-year-old Japanese man was admitted to Uwajima City Hospital with an 8-day history of fever and diarrhea. Laboratory tests revealed leukopenia, thrombocytopenia, and liver enzyme elevation. He was diagnosed as having severe fever with thrombocytopenia syndrome (SFTS) following detection of the SFTSV genome in his blood. Bone marrow aspiration revealed hemophagocytic lymphohistiocytosis. He suffered progressive CNS disturbance and died on day 13 from onset of first symptoms. The SFTSV genome load in blood and levels of certain cytokines increased over the disease course. Necrotizing lymphadenitis with systemic lymphoid tissues positive for nucleocapsid protein (NP) of SFTSV was revealed by immunohistochemical (IHC) analysis. SFTSV-NP-positive immunoblasts were detected in all organs examined, including the CNS, and in the vascular lumina of each organ. Parenchymal cells of all organs examined were negative for SFTSV-NP on IHC analysis. Microscopic examination of the pons showed focal neuronal cell degeneration with hemosiderin-laden macrophages around extended microvessels with perivascular inflammatory cell infiltration and intravascular fibrin deposition. Autopsy confirmed this patient with SFTS was positive for systemic hemophagocytic lymphohistiocytosis including in the CNS. This patient's neurological abnormalities may have been caused by both functional and organic abnormalities. These novel findings provide important insights into the pathophysiology of SFTS.

DOI： 10.1016/j.jiac.2017.10.016

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Severe fever with thrombocytopenia syndrome is an emerging infectious disease caused by a novel phlebovirus belonging to the family Bunyaviridate. Emergence of encephalitis/encephalopathy during severe fever with thrombocytopenia syndrome progression has been identified as a major risk factor associated with a poor prognosis. Here we report the case of a severely ill patient with severe fever with thrombocytopenia syndrome virus-associated encephalitis/encephalopathy characterized by a lesion of the splenium, which resolved later. CASE PRESENTATION: A 56-year-old Japanese man presented with fever and diarrhea, followed by dysarthria. Diffusion-weighted magnetic resonance imaging demonstrated high signal intensity in the splenium of the corpus callosum. The severe fever with thrombocytopenia syndrome virus genome was detected in our patient's serum, and the clinical course was characterized by convulsion, stupor, and hemorrhagic manifestations, with disseminated intravascular coagulation and hemophagocytic lymphohistiocytosis. Supportive therapy not including administration of corticosteroids led to gradual improvement of the clinical and laboratory findings, and magnetic resonance imaging demonstrated resolution of the splenial lesion. The serum severe fever with thrombocytopenia syndrome viral copy number, which was determined with the quantitative reverse-transcription polymerase chain reaction, rapidly decreased despite the severe clinical course. Our patient's overall condition improved, allowing him to be eventually discharged. CONCLUSIONS: Patients with encephalitis/encephalopathy due to severe fever with thrombocytopenia syndrome virus infection may have a favorable outcome, even if they exhibit splenial lesions and a severe clinical course; monitoring the serum viral load may be of value for prediction of outcome and potentially enables the avoidance of corticosteroids to intentionally cause opportunistic infection.

DOI： 10.1186/s13256-016-1192-0

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Language：English  

A 74-year-old woman visited our hospital because of right chest pain and fatigue. Laboratory examinations revealed pancytopenia and an elevated level of serum lactate dehydrogenase. Although bone lesions were detected by computed tomography, there was no lymphadenopathy. Blastoid cells were evident in the bone marrow. From the patient's medical history and results of immunohistological and chromosomal analysis, she was diagnosed as having diffuse large B-cell lymphoma, not otherwise specified. This form of presentation of diffuse large B-cell lymphoma is very rare, and emphasizes the need for careful evaluation of such cases, including bone marrow biopsy for accurate diagnosis.

DOI： 10.1007/s13691-016-0254-x

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

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Language：English   Publishing type：Research paper (scientific journal)  

Streptococcus pyogenes (group A streptococcus) is an aerobic gram-positive coccus that causes infections ranging from non-invasive pharyngitis to severely invasive necrotizing fasciitis. Mutations in csrS/csrR and rgg, negative regulator genes of group A streptococcus, are crucial factors in the pathogenesis of streptococcal toxic shock syndrome, which is a severe, invasive infection characterized by sudden onset of shock and multiorgan failure, resulting in a high mortality rate. Here we present a case of group A streptococcal bacteremia in a 28-year-old Japanese woman with no relevant previous medical history. The patient developed progressive abdominal symptoms that may have been due to spontaneous bacterial peritonitis, followed by a state of shock, which did not fulfill the proposed criteria for streptococcal toxic shock. The isolate was found to harbor a mutation in the negative regulator csrS gene, whereas the csrR and rgg genes were intact. It was noteworthy that this strain carrying a csrS mutation had caused group A streptococcal bacteremia characterized by acute abdomen as the presenting symptom in a young individual who had been previously healthy. This case indicates that group A streptococcus with csrS mutations has potential virulence factors that are associated with the onset of group A streptococcal bacteremia that does not meet the diagnostic criteria for streptococcal toxic shock syndrome.

DOI： 10.1016/j.jiac.2015.06.010

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Language：Japanese   Publishing type：Research paper (scientific journal)  

A 75-year-old man who had undergone subtotal gastrectomy for advanced gastric cancer 18 years previously with no signs of recurrence visited our hospital because of anemia detected by medical examination. Although no clinical abnormalities were evident, treatment with iron and vitamin B12 was started. However, because serum ALP was elevated, metastatic bone cancer was suspected. Subsequently, upper gastrointestinal endoscopy revealed findings suggestive of residual gastric cancer, and examination of a biopsy specimen demonstrated signet ring cell carcinoma. Furthermore, cells in a bone marrow biopsy sample showed morphology similar to that of cells obtained by stomach biopsy. FDG-PET demonstrated FDG accumulation only in the bone and residual stomach. The final diagnosis was bone metastasis from residual gastric cancer, and disseminated carcinomatosis of the bone marrow. Thereafter, pancytopenia progressed rapidly, and the patient died due to disseminated intravascular coagulation. When serum ALP is elevated in patients with a history of gastric cancer, bone marrow carcinomatosis should be suspected irrespective of symptoms, and imaging studies and bone marrow examination should be performed.

DOI： 10.11406/rinketsu.56.16

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

症例は75歳男性。18年前に進行胃がんに対して胃亜全摘術を行い,再発なく経過していた。健康診断で貧血を指摘され,当科を受診。無症状で,ビタミンB12と鉄の低下がみられたため補充を開始した。しかし,血清ALPが高値のため悪性腫瘍の骨転移を疑い精査したところ,上部消化管内視鏡検査で残胃がんを疑う所見を認め,同部からの生検の結果signet ring cell carcinomaと診断した。一方,骨髄検査でも胃生検と同様の組織所見を認めた。FDG-PET/CT検査で残胃と骨の他にFDGの集積を認めず,残胃がん骨転移,播種性骨髄癌腫症と診断した。その後,急速に血球減少が進行し,播種性血管内凝固症候群を併発して死亡した。胃がん手術歴のある患者で,血清ALPの上昇を認める場合は,無症状でも本症を疑い,速やかに骨髄検査や画像検査を行う必要があると考えられた。(著者抄録)

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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)日本病態栄養学会  

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Language：Japanese   Publisher：市立宇和島病院生活協同組合  

症例は78歳女性。再発マントル細胞リンパ腫に対し化学療法を行っていたが治療不応であり、局所コントロール目的で放射線療法を施行した。放射線療法開始翌日4Gy照射後に、せん妄、不穏行動、喘鳴、呼吸困難、腎機能障害などを認め腫瘍崩壊症候群(Tumor lysis syndrome:TLS)が生じたと判断した。利尿薬と補液でTLSから回復した。後日、補液、利尿薬、ラスブリカーゼの予防投与を行い放射線療法を再施行したところ、TLSは生じなかった。化学療法のみでなく、放射線療法においてもTLSを生じるリスクを評価することが重要と考えられた。(著者抄録)

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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

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

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Language：Japanese   Publisher：(一社)日本造血・免疫細胞療法学会  

症例は混合表現型急性白血病に対する非血縁者間同種骨髄移植の既往歴がある42歳男性で、COVID-19に罹患した。呼吸症状は改善し自覚症状無く退院したが、退院翌日(診断後11日目)の鼻咽頭拭い液でSARS-CoV-2高値を認めた。免疫抑制剤を緩徐に減量し、定期的にCt値および抗原定量値でウイルスの増減を評価した。SARS-CoV-2は126日目に抗原定量値が陰性となった。以上より、COVID-19を発症した重度の免疫不全患者はSARS-CoV-2感染が長期間持続する場合があるため、隔離解除前にウイルス検査を行う必要がある。今までに、SARS-CoV-2の長期間持続感染例に対し、定期的な抗原定量検査により陰性化するまでウイルス量の増減の推移を評価した報告は無い。

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J07578&link_issn=&doc_id=20230502380009&doc_link_id=10.7889%2Ftct-22-023&url=https%3A%2F%2Fdoi.org%2F10.7889%2Ftct-22-023&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(公社)日本医学放射線学会  

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Language：Japanese   Publisher：日本皮膚科学会-西部支部  

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

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J-GLOBAL

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Language：English   Publisher：(一社)日本血液学会  

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Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)   Publisher：American College of Physicians  

DOI： 10.7326/L18-0605

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Event date： 2014.5

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Language：Japanese   Presentation type：Poster presentation  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (general)  

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