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DOI： 10.3324/haematol.2021.279857

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DOI： 10.1007/s12185-021-03269-6

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DOI： 10.1002/pbc.29501

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BACKGROUND: Synovial sarcoma is a rare malignant soft-tissue tumor that is prevalent in adolescents and young adults, and poor prognosis has been reported in patients with metastatic lesions. Chimeric antigen receptor (CAR) T-cell therapy is an emerging novel therapy for solid tumors; however, its application in synovial sarcoma has not yet been explored. METHODS: A novel human epidermal growth factor receptor 2 (HER2)-targeted CAR containing scFv-FRP5, CD8α hinge and transmembrane domains as well as 4-1BB costimulatory and CD3ζ signaling domains was developed. Three synovial sarcoma cell lines that expressed the fusion transcript SS18-SSX1/2/4 were used in the study. Cytokine secretion assay, cytotoxicity assay, and real-time cell analysis experiments were conducted to confirm the function of T cells transduced with the CAR gene. RESULTS: High cell-surface expression of HER2 was observed in all the cell lines. HER2-targeted/4-1BB-costimulated CAR T cells specifically recognized the synovial sarcoma cells, secreted interferon gamma and tumor necrosis factor alpha, and exerted cytotoxic effects in these cells. CONCLUSION: To the best of our knowledge, this is the first study to indicate that HER2-targeted CAR T cells are directly effective against molecularly defined synovial sarcoma cells. Furthermore, our findings might set the basis for developing improved CAR T cell-based therapies for chemo-refractory or relapsed synovial sarcoma.

DOI： 10.1016/j.tranon.2021.101227

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

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

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Language：Japanese   Publisher：(株)日本小児医事出版社  

症例は12歳男児。両側の手指、足趾、手掌の肢端紅痛症で発症し、99.7万/μLの血小板増多を認め、骨髄所見やJAK2変異陽性から、本態性血小板血症(essential thrombocythemia;ET)と診断した。肢端紅痛症に対し少量アスピリン投与を開始したところ、症状は速やかに消失した。アスピリン投与開始後、血小板数は140万/μLへと増加傾向を示したため、後天性フォンウィルブランド症候群の検索を行い、合併が判明した。ガイドラインではアスピリンは原則禁忌となり細胞減少療法の適応となるが、本症例では出血症状は皆無であり、年齢や殺細胞薬使用に伴う白血病転化リスクを考慮した結果、アスピリン療法単独を継続し、6年経過した現在まで安全に管理できている。小児ETは非常に稀な疾患であり、治療アルゴリズムは確立していない。小児期特有の問題を加味した診療指針が作成されることが望まれる。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J00643&link_issn=&doc_id=20210427420011&doc_link_id=%2Fag1snrsd%2F2021%2F007405%2F012%2F0553-0558%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fag1snrsd%2F2021%2F007405%2F012%2F0553-0558%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本小児血液・がん学会  

症例は9ヵ月男児.繰り返す発熱,腋窩リンパ節腫大,全身の膿疱性皮疹を主訴に当院に紹介された.当初,前頭骨の骨融解像,臨床像,sIL-2R異常高値からランゲルハンス組織球症との鑑別を要し,皮膚生検を施行したが確定診断に至らず,腋窩リンパ節生検を施行した.生検組織からBCG菌が同定され,播種性BCG感染症と診断した.皮膚生検ではBCG菌は検出されず,BCG菌への過敏性反応による結核疹と考えられた.重症細菌感染,ウイルス感染の既往はなく,メンデル遺伝型マイコバクテリア易感染症を疑い精査した結果,IFNGR1遺伝子の既知のde-novoヘテロ変異が同定され,IFN-γR1部分欠損症と診断した.抗結核薬イソニアジド,リファンピシンの2剤による治療で症状は速やかに軽快した.18ヵ月間内服を継続し,終了後半年の現在も再燃なく経過している.ランゲルハンス組織球症として非典型的な皮疹や経過の場合にはBCG感染症を考える必要がある.(著者抄録)

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Language：Japanese   Publisher：(一社)日本小児血液・がん学会  

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In adoptive T-cell immunotherapy of cancer, expansion and persistence of effector cells is a key determinant of response. We tested whether T lymphocytes could be rendered sensitive to erythropoietin (Epo) through ectopic expression of its wild-type receptor or a truncated form (EpoRm), which augments Epo signaling in erythrocyte progenitors. Both receptors could be expressed in human T lymphocytes; Epo ligation induced STAT5 phosphorylation, which was abrogated by nontoxic concentrations of the JAK1/2 inhibitor ruxolitinib. EpoRm had higher expression and triggered more potent stimulation than its wild-type counterpart, including superior T-cell survival and proliferation. Using a bicistronic vector, we expressed EpoRm together with an anti-CD19-41BB-CD3ζ chimeric antigen receptor (CAR), while maintaining the functions of each receptor. In the presence of Epo, EpoRm-CAR T cells had greater ex vivo expansion than CAR T cells and killed CD19+ leukemic cells more effectively in long-term cultures. In immunodeficient mice, physiologic levels of murine Epo were sufficient to preferentially expand EpoRm-CAR T cells, yielding a significantly higher antileukemic activity. Thus, outfitting adoptive T cells with EpoRm should yield greater effector-to-target ratios with a smaller number of infused cells; Epo or ruxolitinib administration could be used to adjust their levels postinfusion, maximizing antitumor activity and minimizing toxicity.

DOI： 10.1182/blood.2019001645

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DOI： 10.1002/pbc.28052

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

Objectives: One of the reasons as to why chimeric antigen receptors (CAR)-T cell therapy for malignancies other than CD19- or BCMA-positive tumors has yet to produce remarkable progress is the paucity of targetable antigens. NKp44 is only expressed by activated natural killer cells and detects a variety of transformed cells, while it reportedly does not react with normal tissues. The aim of this study is to develop CAR-T cell that can target multiple types of tumor cells. Methods: We created a series of novel CAR constructs in first-generation (1G) and second-generation (2G) CAR format with the extracellular immunoglobulin-like domain of NKp44 (NKp44-CAR). Results: Transduction of the best 1G construct into human primary T cells led to specific cytotoxic effects and cytokine secretion upon encountering multiple types of neoplastic cells including AML, T-ALL and childhood solid tumors. Replacement of the extracellular hinge domain of NKp44 with that of CD8α resulted in diminished CAR function. The 1G NKp44-CAR-T cells exhibited significantly better tumor control in long-term co-culture assays compared with activated NK cells, as well as with NK cells transduced with identical NKp44-CAR. T cells transduced with the best 2G-CAR construct with 4-1BB co-stimulatory domain proliferated at significantly higher levels upon single antigen exposure and showed significantly better tumor control compared with the 1G-CAR and 2G-CAR with CD28 co-stimulatory domain. Conclusions: NKp44-based CAR endows T cells with NK cell-like anti-tumor specificity. The CAR gene created in this study will be useful for the development of novel gene-modified T-cell immunotherapy.

DOI： 10.1002/cti2.1147

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Chronic enteroviral meningoencephalitis is a well-known complication in patients with X-linked agammaglobulinemia (XLA). However, progressive neurodegenerative disorders or chronic neuroinflammatory diseases with no causative microorganisms have been recognized as rare central nervous system (CNS) complications in XLA. We herein report a family in which two of three members with XLA had developed progressive meningoencephalitis with an unknown etiology. A 15-month-old male infant presented with left-sided ptosis. Initially, the family denied any family history of inherited diseases, but later disclosed a family history of agammaglobulinemia previously diagnosed in two family members. In the early 1980s, one of the elder brothers of the index patient's mother who had been treated with intramuscular immunoglobulin [or later intravenous immunoglobulin (IVIG)] for agammaglobulinemia deceased at 10 years of age after showing progressive neurological deterioration during the last several years of his life. The index patient was diagnosed with XLA caused by Bruton tyrosine kinase deficiency (654delG; Val219Leufs*9), and chronic meningoencephalitis with an unknown infectious etiology. Magnetic resonance imaging of the brain demonstrated inflammatory changes in the basal ganglia, hypothalamus, midbrain, and pons, with multiple nodular lesions with ring enhancement, which showed impressive amelioration after the initiation of IVIG replacement therapy. Pleocytosis, which was characterized by an increase in CD4-positive and CD8-positive T cells expressing an activation marker and an elevation in inflammatory cytokines in the cerebrospinal fluid, was identified. No microorganism was identified as a cause of CNS complications. He thereafter developed brain infarction at 19 months of age and fatal status epilepticus at 5 years of age, despite regular IVIG with high trough levels and regular intraventricular immunoglobulin administration. The etiology of this rare CNS complication in XLA is currently unknown. Previous studies have suggested a possible association of IVIG, which was clearly denied in our index case because of the demonstration of his neurological disorder at presentation. In the future, extensive and unbiased molecular methods to detect causative microorganisms, as well as to investigate the possible role of autoimmunity are needed to clarify the etiology of CNS complications.

DOI： 10.3389/fped.2020.00579

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Language：Japanese   Publisher：(一社)日本小児神経外科学会  

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Language：Japanese   Publisher：(一社)日本小児神経外科学会  

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Language：Japanese   Publisher：(株)日本小児医事出版社  

繰り返す腸重積を契機に発見され、フローサイトメトリーでλ鎖優位のlight chain restriction(LCR)を認めた虫垂リンパ過形成の6歳女児例を経験した。腹部造影CTでは最大径2.5cmの全周性虫垂腫大を認め、迅速病理診断およびスタンプ標本からも成熟B細胞リンパ腫で矛盾のない所見を得たが、免疫グロブリン遺伝子やc-myc遺伝子の再構成は認めず、最終的に永久病理標本により虫垂リンパ過形成の診断となった。追加の治療介入は行わず経過観察の方針としたが、約12ヵ月を経過し再発は認めていない。文献上、LCRを認める虫垂リンパ過形成は極めて稀で、4〜6歳の4例が報告されているのみである(すべてλ鎖優位のLCR)。本例の経験から、反復性腸重積の稀な原因として虫垂リンパ過形成があること、そして、反応性の病態ながらもLCRを示す場合があることを念頭に置く必要があることが示された。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J00643&link_issn=&doc_id=20190124480010&doc_link_id=%2Fag1snrsd%2F2019%2F007202%2F010%2F0170-0174%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fag1snrsd%2F2019%2F007202%2F010%2F0170-0174%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本小児血液・がん学会  

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

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Language：Japanese   Publisher：(株)日本小児医事出版社  

急性リンパ性白血病(ALL)は腎腫大を含め様々な臓器浸潤を来すが、腎臓に結節性病変を呈することは少ない。症例は1歳4ヵ月の男児。発熱が持続し、血液検査でLDHの異常高値を指摘され、造影CTで両側腎腫大と多発結節性病変を認めた。末梢血中に芽球の出現があり、骨髄穿刺で前駆B細胞性急性リンパ性白血病と診断した。寛解導入療法後に両側腎腫大および腎多発結節性病変は消失し完全寛解に至った。腎の多発結節性病変の鑑別として造血器腫瘍も考慮すべきである。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00643&link_issn=&doc_id=20180724220012&doc_link_id=%2Fag1snrsd%2F2018%2F007108%2F013%2F1409-1414%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fag1snrsd%2F2018%2F007108%2F013%2F1409-1414%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：English   Publisher：WILEY  

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Language：English   Publisher：WILEY  

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Language：Japanese   Publisher：(一社)日本小児血液・がん学会  

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Language：Japanese   Publisher：(一社)日本小児血液・がん学会  

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Language：Japanese   Publisher：(一社)日本小児血液・がん学会  

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Histiocytic sarcoma, a rare hematopoietic neoplasm with evidence of histiocytic differentiation, is often refractory to conventional chemotherapy and radiotherapy, and its prognosis is generally dismal. The optimal management of this malignancy has not been established. We report a case of 8-year-old girl with histiocytic sarcoma involving the left femur. The tumor rapidly responded to a combination of cladribine and high-dose cytosine arabinoside, an aggressive salvage regimen for refractory Langerhans cell histiocytosis, and became impalpable during the first cycle. The patient has remained in complete remission more than 7 years from diagnosis.

DOI： 10.1007/s12185-017-2202-8

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Language：Japanese   Publisher：日本脳腫瘍病理学会  

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Language：Japanese   Publisher：新潟医学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00990&link_issn=&doc_id=20170929080007&doc_link_id=%2Fdg3nigta%2F2017%2Fs13105%2F002%2F0311-0312%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2017%2Fs13105%2F002%2F0311-0312%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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Perlman syndrome is a rare overgrowth syndrome characterized by polyhydramnios, macrosomia, distinctive facial appearance, renal dysplasia, and a predisposition to Wilms' tumor. The syndrome is often associated with a high neonatal mortality rate and there are few reports of long-term survivors. We studied a 6-year-old Japanese female patient, who was diagnosed with Perlman syndrome, with novel compound heterozygous mutations in DIS3L2 (c.[367-2A > G];[1328T > A]), who has survived long term. Most reported DIS3L2 mutations have been the homozygous deletion of exon 6 or exon 9, and these mutations would certainly have caused the loss of both RNA binding and degradation activity. We have identified new compound heterozygous mutations in the DIS3L2 of this long-term survivor of Perlman syndrome. The reason our patient has survived long-term would be a missense mutation (c.1328 T > A, p.Met443Lys) having retained RNA binding in both the cold-shock domains and the S1 domain, and through partial RNA degradation. If partial exonuclease functions remain in at least one allele, long-term survival may be possible. Further studies of Perlman syndrome patients with proven DIS3L2 mutations are needed to clarify genotype-phenotype correlation.

DOI： 10.1002/ajmg.a.38111

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：English   Publisher：(一社)日本小児血液・がん学会  

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Language：Japanese   Publisher：(一社)日本小児血液・がん学会  

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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：English   Publisher：(一社)日本小児血液・がん学会  

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Language：English   Publisher：(一社)日本小児血液・がん学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：English   Publisher：(一社)日本小児血液・がん学会  

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Language：Japanese   Publisher：(一社)日本小児血液・がん学会  

悪性脳腫瘍に対する全脳脊髄照射(CSI)では頭蓋骨及び全脊椎の骨髄組織が障害されるため、CSI後の強力な化学療法では骨髄抑制が著しく遷延し、結果的に治療全体の強度が低下することが大きな問題である。そこで我々は、CSI及び強力な化学療法を要する悪性脳腫瘍に対しG-CSF単独の末梢血幹細胞(PBSC)採取を試み、化学療法に自家末梢血幹細胞移植(aPBSCT)を併用することとした。早期にCSIを開始するため、術後2週以内の採取完了を目指した。初発未治療例6例では中央値12.6×10^6/kg(3.9-21.6×10^6/kg)のCD34陽性細胞採取が可能だったが、うち2例では複数回のaPBSCTに十分な細胞数に達しなかった。再発例の2例では少なくとも1回の移植に必要な量は採取できた。これら4例ではaPBSCT併用化学療法1コース終了後に再度PBSC採取を行い十分量が確保できた(13.7-42.1×10^6/kg)。術後2週以内のPBSC採取では白血球数が増加しやすい傾向にあったが、重篤な有害事象はみられなかった。全例で予定した複数回aPBSCTを実施でき、骨髄抑制の遷延をきたすことなく規定の間隔で化学療法を完遂できた。術後2週以内のG-CSF単独PBSC採取は安全に実施できたものの少数例の経験であり、術後早期にCSIを要する悪性脳腫瘍の集学的治療における有効性に関しては更なる検討を要する。(著者抄録)

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Language：Japanese   Publisher：(一社)日本小児血液・がん学会  

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Natural killer (NK) cell survival and, hence, cytotoxicity requires cytokine support. We determined whether expression of interleukin-15 (IL-15) in a nonsecretory, membrane-bound form could sustain NK cell growth. We linked the human IL15 gene to that encoding CD8α transmembrane domain (mbIL15). After retroviral transduction, human NK cells expressed mbIL15 on the cell surface; IL-15 secretion was negligible. Survival of mbIL15-NK cells without interleukin-2 (IL-2) after 7-day culture was vastly superior to that of mock-transduced NK cells (P < .001, n = 15) and of NK cells expressing nonmembrane-bound IL-15 (P = .025, n = 9); viable mbIL15-NK cells were detectable for up to 2 months. In immunodeficient mice, mbIL15-NK cells expanded without IL-2 and were detectable in all tissues examined (except brain) in much higher numbers than mock-transduced NK cells (P < .001). Expansion further increased with IL-2. The primary mechanism of mbIL15 stimulation was autocrine; it activated IL-15 signaling and antiapoptotic signaling. NK cells expressing mbIL15 had higher cytotoxicity against leukemia, lymphoma, and solid tumor cells in vitro and against leukemia and sarcoma cells in xenograft models. Thus, mbIL15 confers independent growth to NK cells and enhances their antitumor capacity. Infusion of mbIL15-NK cells would allow NK cell therapy without the potential adverse effects of cytokine administration.

DOI： 10.1182/blood-2014-02-556837

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会  

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

Secondary rhabdomyosarcoma (RMS) after treatment of osteosarcoma (OS) is rare. Reported here is the case of a metachronous RMS in the nasal cavity, developing 12 years after successful treatment of non-metastatic OS. The patient was diagnosed as having OS of the femur at 2 years of age. Chemotherapy for OS included doxorubicin (cumulative dose, 488 mg/m(2) ). No radiotherapy was given. There was no family history suggestive of cancer predisposition syndrome. At 14 years of age, alveolar RMS was diagnosed on histopathology. PAX3-FKHR fusion transcripts were detected on reverse transcription-polymerase chain reaction. Germline TP53 mutation was not seen on standard DNA sequencing. The occurrence of secondary sarcomas, in the Children's Cancer Survivor study conducted in North America, has been associated with high cumulative doses of anthracyclines, which may also have played a role in the development of RMS in the present case. In the future, novel molecular technologies might uncover genetic cancer predisposition in patients with metachronous cancers.

DOI： 10.1111/ped.12070

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

Philadelphia chromosome-positive acute lymphoblastic leukemia has a poor prognosis, even in pediatric patients. Although imatinib-containing chemotherapy can reportedly improve early event-free survival, allogeneic hematopoietic stem cell transplantation is still considered to be the main curative treatment option. Dasatinib, a novel abl tyrosine kinase inhibitor, is being used for the treatment of relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia and is reported to have excellent efficacy. We used dasatinib after bone marrow transplantation prior to the anticipated relapse for the purpose of prophylaxis against relapse. After discontinuation of dasatinib administration, molecular remission has lasted for 7 months. Although preventive use of dasatinib is as yet uncommon, we consider that dasatinib may eradicate the minimal residual disease and prevent recurrence, and it is feasible to administer and appears to be safe. Further studies are needed to confirm our experience in this case.

DOI： 10.1111/ped.12019

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Language：Japanese   Publisher：(NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会  

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Language：Japanese   Publisher：(一社)日本小児血液・がん学会  

先天性溶血性貧血の異常部位には赤血球膜、赤血球酵素、ヘモグロビンが知られている。遺伝性球状赤血球症(HS)は赤血球膜の異常に起因し、日本で最も高頻度の先天性溶血性貧血である。溶血性貧血を呈し、HSに矛盾しない背景を持つ場合では、他の稀な溶血性貧血が見逃される可能性も考えられる。Hb Koeln症はヘモグロビン異常症の一型で、稀な疾患である。今回、我々は複数の脾臓摘出者を認め、HSと考えられていた12歳男児のHb Koeln症を経験した。平均赤血球ヘモグロビン濃度(MCHC)は28.7%と低値、平時のSpO2は90%程と低値(高濃度酸素投与で92%)、HbA1cは2.0%と異常低値であった。これらの一般検査所見がHSとは矛盾したため、ヘモグロビン異常症を疑い精査を進めた。先天性溶血性貧血のような稀な疾患でも、日常的な検査の吟味が診断に重要と考えられた。(著者抄録)

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(公社)日本皮膚科学会  

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DOI： 10.1002/pbc.23228

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Language：Japanese   Publisher：(NPO)日本小児がん学会  

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Language：Japanese   Publisher：(NPO)日本小児がん学会  

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

BACKGROUND: Nuclear factor-κB essential modulator (NEMO) deficiency is a developmental and immunological disorder. The genetic and phenotypic correlation has been described. METHODS: We report a unique clinical presentation and the identification of a novel missense mutation in the NEMO gene in a 3-year-old boy with bacillus Calmette-Guerin (BCG) infection. RESULTS: The patient presented with fever, cervical lymphadenopathy, and abnormal anti-Epstein-Barr virus (EBV) antibody titers, suggestive of EBV-related diseases including chronic active EBV infection, X-linked lymphoproliferative syndrome, or nasopharyngeal carcinoma. Although the biopsy specimen from a nasopharyngeal lesion was initially diagnosed as squamous cell carcinoma, this was changed to disseminated BCG infection involving the nasopharynx, multiple systemic lymph nodes, and brain. A novel mutation (designated D311E) in the NEMO gene, located in the NEMO ubiquitin-binding (NUB) domain, was identified as the underlying cause of the immunodeficiency. Impaired immune responses which are characteristic of patients with NEMO deficiency were demonstrated. The patient underwent successful unrelated bone marrow transplantation at 4.9 years of age. CONCLUSION: This study suggests the importance of the NUB domain in host defense against mycobacteria. The unique presenting features in our patient indicate that a hypomorphic NEMO mutation can be associated with atypical pathological findings of the epithelial tissues in patients with BCG infection.

DOI： 10.1007/s10875-011-9568-9

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Language：Japanese   Publisher：日本小児血液学会  

3歳男児。B前駆細胞型小児急性リンパ性白血病(ALL)と診断し、超高危険群として寛解導入療法を開始した。治療開始42週目に2回目の再寛解導入療法に続く強化療法を開始した。一時解熱したが再度発熱し、発熱から10日後に全身強直性痙攣が出現した。頭部CTで右頭頂葉に輪状造影を伴う病変を認め、脳膿瘍が疑われた。接合菌症の可能性を考慮してliposomal amphotericin B(L-AMB)を開始したところ翌日には解熱し、発症2週後のDiffusion MRIでは右頭頂葉に膿瘍腔を示唆する高信号域を認めていたが、発症2ヵ月後には消失していた。しかし、CRPは0.3〜1.0mg/dl程度で著減していたため、L-AMB継続下にmercaptopurine(6MP)、methotrexate(MTX)内服による維持療法を開始した。発症4ヵ月後もDiffusion MRIの所見は変化を認めなかったが、血清クレアチニンは0.2mg/dlから0.5mg/dlへ上昇した。そのためL-AMBを5mg/kg/dayの隔日投与へ、さらに2週間後から週2回投与へ減量したが、CRPは増加傾向とはならなかった。Diffusion MRI所見の増悪もなく、週2回投与を2週間継続後にL-AMBを中止した。その後CRPは陰性化し、投与終了後約1年、脳膿瘍の再発は認めず、維持療法継続中である。

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J02258&link_issn=&doc_id=20110511060006&doc_link_id=%2Fex9syoke%2F2011%2F002502%2F006%2F0097-0101%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fex9syoke%2F2011%2F002502%2F006%2F0097-0101%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(公社)日本小児科学会  

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

We describe a 14-year-old boy who exhibited left palatine tonsillar enlargement after 6 cycles of aggressive chemotherapy for diffuse large B-cell lymphoma of the right palatine tonsil. The cervical computed tomography scan at 4 months after completion of chemotherapy revealed enlargement of the left palatine tonsil in addition to the thymus without any clinical symptoms. The F-fluorodeoxyglucose positron emission tomography indicated focal areas of strong F-fluorodeoxyglucose uptake in the left palatine tonsil. Histologic examination confirmed tonsillar hyperplasia with no evidence of recurrence. Reactive tonsillar hyperplasia after chemotherapy is rarely reported.

DOI： 10.1097/MPH.0b013e3181f69205

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(NPO)日本小児がん学会  

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Language：Japanese   Publisher：(NPO)日本小児がん学会  

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Language：Japanese   Publisher：(NPO)日本小児がん学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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

A major complication of retained testes is an occurrence of malignancy later in life. We, herein, report the case of a 2-year-old boy who presented with a huge yolk sac tumor with retroperitoneal lymph nodes metastasis that originated in a left intra-abdominal undescended testis. Computed tomography and magnetic resonance imaging showed a huge round tumor connecting to the left retroperitoneal lymph nodes with metastasis extending from the left pelvic region to the left renal hilum. The serum alpha-fetoprotein level was 36,528 ng/mL. The right abdominal tumor appeared to be a giant testis that had strangulated at the neck of the cord. The tumor had ruptured at the side of the left pelvic lymph node metastasis, and a yolk sac tumor was diagnosed from a histologic analysis of the resected specimens. Postoperative PEB chemotherapy was effective, and a complete surgical resection of the tumor was performed 3 months after the initial laparotomy. The pathologic findings showed fibrous tissue without any tumor cells. The patient has been doing well for 18 months after the radical operation. This case might be a coincidental association of a yolk sac tumor occurring in an undescended testis, which thus caused a delay in making an accurate diagnosis.

DOI： 10.1016/j.jpedsurg.2009.08.024

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(NPO)日本小児がん学会  

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Language：Japanese   Publisher：(NPO)日本小児がん学会  

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Language：Japanese   Publisher：(NPO)日本小児がん学会  

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Language：Japanese   Publisher：(NPO)日本小児がん学会  

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

We present a patient with Bernard-Soulier syndrome harboring a novel mutation. Flow cytometric analysis showed that the glycoprotein (GP) Ib/IX complex was absent from the platelet surface. By immunoblotting, GPIbalpha, GPIbbeta and GPIX were not detected in the platelet lysates. Glycocalicin, the soluble GPIbalpha fragment, was also absent in the plasma. Genetic analysis revealed a novel homozygous 8-base pair deletion in the GPIbalpha gene, 1136_1143delTTCACATG, which was predicted to cause a frame shift and the addition of 13 altered amino acids followed by premature termination. No mutation was found in the coding sequence of the GPIbbeta or GPIX genes. We demonstrated that the novel deletion mutation resulted in complete defectiveness of the GPIbalpha protein and null expression of the entire GPIb/IX complex, and was responsible for the Bernard-Soulier syndrome phenotype in this patient. Although the presence of a truncated GPIbalpha protein has been often documented, complete absence of the protein has been scarcely reported in Bernard-Soulier syndrome patients with a GPIbalpha mutation causing a premature stop codon. An underlying molecular mechanism to explain how the synthesis of a truncated protein is inhibited in selected cases remains to be elucidated.

DOI： 10.1097/MBC.0b013e32832b27fa

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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   Publishing type：Research paper (scientific journal)  

Liver X receptor (LXR) is a nuclear receptor that acts as a sterol sensor and metabolic regulator of cholesterol and lipid homeostasis. The foam cell transformation of macrophages (Mvarphi) is considered a critical process in atherosclerotic lesions. The relationship, however, of the foam cell transformation of Mvarphi and LXR is not fully understood. The purpose of the present study was to examine the expression of LXRalpha, retinoid X receptor (RXR)alpha, ATP-binding cassette transporter (ABCA1), and macrophage scavenger receptor A (MSR-A), and lipid accumulation in human monocyte-derived Mvarphi. The expression of LXRalpha, ABCA1, MSR-A in 7 day cultured granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced Mvarphi (GM-Mvarphi) was significantly higher than that in 7 day cultured M-CSF-induced Mvarphi (M-Mvarphi). The expression levels of LXRalpha, ABCA1 and MSR-A protein decreased from 48 h to 5 days after the addition of lipopolysaccharide (LPS) in GM-Mvarphi, but only MSR-A protein decreased at 5 days after the addition of LPS in M-Mvarphi. Intracellular lipid accumulation was clearly observed when GM-Mvarphi was pre-stimulated with LPS for 48 h and incubated with oxidized LDL for an additional 5 days. These findings suggest that the inhibitory activity of LXRalpha, ABCA1 and MSR-A by LPS may be related to the transformation of Mvarphis, especially GM-Mvarphi into foam cells.

DOI： 10.1111/j.1440-1827.2009.02343.x

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Language：Japanese   Publisher：(NPO)日本小児がん学会  

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Language：Japanese   Publisher：(NPO)日本小児がん学会  

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Language：English  

DOI： 10.1002/pbc.21626

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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)日本リンパ網内系学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JOHN WILEY & SONS LTD  

Pentraxin 3 (PTX3) and C-reactive protein (CRP) are members of the pentraxin superfamily. PTX3 expression is induced in response to inflammatory signals, and is produced at sites of inflammation by several types of cell, primarily monocytes/macrophages, dendritic cells (DCs), endothelial cells, smooth muscle cells (SMCs), and fibroblasts, but is not produced by hepatocytes, which are a major source of CRP. The aim of our study was to investigate the expression pattern of PTX3 in human atherosclerotic lesions using a novel monoclonal antibody against PTX3. We examined coronary arterial thrombi containing an atherosclerotic plaque component removed from patients with acute myocardial infarction and human aortic tissues with various degrees of atherosclerosis sampled from autopsy cases. Immunohistochemical study of paraffin and frozen sections indicated that macrophages, mainly foam cells, expressed PTX3 in advanced atherosclerotic lesions. Interestingly, we also clearly observed PTX3-positive neutrophils infiltrating into atherosclerotic plaques, suggesting that PTX3 derived from neutrophils as well as macrophages plays an important role in atherogenesis. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

DOI： 10.1002/path.2314

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Language：Japanese   Publisher：(NPO)日本小児がん学会  

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Language：Japanese   Publisher：(NPO)日本小児がん学会  

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

Pentraxin 3 (PTX3) is a prototype protein of long pentraxin. PTX3 is produced by various cells, such as monocytes/macrophages (Mphis) in response to lipopolysaccharide (LPS) and proinflammatory signals. We performed immunoblotting, immunohistochemical staining, reverse transcriptase-polymerase chain reaction (RT-PCR), quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA) of PTX3 in human monocyte-derived Mphis and neutrophils. PTX3 expression was observed in the cytoplasm of both GM-CSF induced monocyte-derived Mphi (GM-Mphi) and M-CSF induced monocyte-derived Mphi (M-Mphi). PTX3 level in both Mphis was up-regulated at 24 h after LPS stimulation. Moreover, we confirmed PTX3 expression in freshly isolated neutrophils, and PTX3 level was distinctly up-regulated at 6 and 24 h after LPS stimulation. These findings suggested that PTX3 expression, not only in Mphis, but also in neutrophils, may reflect the role of PTX3 in inflammation. We believe that PTX3 can contribute as a diagnostic tool to evaluate inflammation at peripheral sites.

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

We report on two sibs with partial 4q trisomy: dup (4)(q35.2-q31.22) and their renal biopsy findings. Both of them show renal hypoplasia, although their chromosomal aberration lacks the minimal duplicated region 4q22-q23 and/or 4q25-q31.3, which had been shown to be associated with urogenital abnormalities and thumb malformations in previous reports. From the renal biopsy findings, the two sibs were diagnosed as oligonephronia. We summarize the 13 having published cases of duplication of chromosome 4q, and examine which segments have a close relationship to renal hypoplasia. We suggest that renal hypoplasia may be female-prone, and may have a close relationship with duplication of 4q33-q34.

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

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

PubMed

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Language：Japanese   Publisher：(NPO)日本小児がん学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER SOC HEMATOLOGY  

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Language：Japanese   Publisher：新潟医学会  

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