ホウシャセン タンドク リョウホウ ガ ソウコウ シタ Merkel サイボウガン ノ 1レイ

A ９１-year-old man was diagnosed with Merkel cell carcinoma after removal of a mass about １ cm in diameter from the right upper eyelid on August ５, ２０１X. Curative surgery was recommended, but the patient declined. Lymph node metastases to the right lateral angle of the eye and in front of the right ear, and cancer pain in the stump recurrence manifested. Accordingly, irradiation of the right upper eyelid was started from October ３ at ２．５Gy/fraction, and the right lateral corneal lymph nodes were included from October １１, ending at ３５ Gy in １４ fractions. From November ２２，irradiation of the lymph node metastasisin front of the right ear was started, ending at ３２. ５ Gy in １３ fractions. During irradiation, cancer pain was alleviated with opioids. Stump recurrence and lymph node metastases were decreased in size, and Computed Tomography indiated complete response. Radiation monotherapy of Merkel cell carcinoma appears to offer a treatment that should be proactively applied when curative surgery proves difficult or not desired by the patient. Use of opioids during radiotherapy may improve quality of life and enhance the therapeutic effect

ABO ケツエキガタ イッチ テキゴウ カン イショク ショウレイ ニ オケル C4d センショク ノ イギ ニ ツイテ

京都大学0048新制・課程博士博士(医学)甲第13331号医博第3143号新制||医||957(附属図書館)UT51-2007-M954京都大学大学院医学研究科内科系専攻(主査)教授 中畑 龍俊, 教授 稲垣 暢也, 教授 千葉 勉学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Genome-wide association study identifies HLA-DP as a susceptibility gene for pediatric asthma in Asian populations.

Asthma is a complex phenotype influenced by genetic and environmental factors. We conducted a genome-wide association study (GWAS) with 938 Japanese pediatric asthma patients and 2,376 controls. Single-nucleotide polymorphisms (SNPs) showing strong associations (P<1×10(-8)) in GWAS were further genotyped in an independent Japanese samples (818 cases and 1,032 controls) and in Korean samples (835 cases and 421 controls). SNP rs987870, located between HLA-DPA1 and HLA-DPB1, was consistently associated with pediatric asthma in 3 independent populations (P(combined) = 2.3×10(-10), odds ratio [OR] = 1.40). HLA-DP allele analysis showed that DPA1*0201 and DPB1*0901, which were in strong linkage disequilibrium, were strongly associated with pediatric asthma (DPA1*0201: P = 5.5×10(-10), OR = 1.52, and DPB1*0901: P = 2.0×10(-7), OR = 1.49). Our findings show that genetic variants in the HLA-DP locus are associated with the risk of pediatric asthma in Asian populations

ZNF384

Fusion genes involving ZNF384 have recently been identified in B-cell precursor acute lymphoblastic leukemia, and 7 fusion partners have been reported. We further characterized this type of fusion gene by whole transcriptome sequencing and/or polymerase chain reaction. In addition to previously reported genes, we identified BMP2K as a novel fusion partner for ZNF384. Including the EP300-ZNF384 that we reported recently, the total frequency of ZNF384-related fusion genes was 4.1% in 291 B-cell precursor acute lymphoblastic leukemia patients enrolled in a single clinical trial, and TCF3-ZNF384 was the most recurrent, with a frequency of 2.4%. The characteristic immunophenotype of weak CD10 and aberrant CD13 and/or CD33 expression was revealed to be a common feature of the leukemic cells harboring ZNF384-related fusion genes. The signature gene expression profile in TCF3-ZNF384-positive patients was enriched in hematopoietic stem cell features and related to that of EP300-ZNF384-positive patients, but was significantly distinct from that of TCF3-PBX1-positive and ZNF384-fusion-negative patients. However, clinical features of TCF3-ZNF384-positive patients are markedly different from those of EP300-ZNF384-positive patients, exhibiting higher cell counts and a younger age at presentation. TCF3-ZNF384-positive patients revealed a significantly poorer steroid response and a higher frequency of relapse, and the additional activating mutations in RAS signaling pathway genes were detected by whole exome analysis in some of the cases. Our observations indicate that ZNF384-related fusion genes consist of a distinct subgroup of B-cell precursor acute lymphoblastic leukemia with a characteristic immunophenotype, while the clinical features depend on the functional properties of individual fusion partners

FasL Expression in Hepatic Antigen-Presenting Cells and Phagocytosis of Apoptotic T Cells by FasL+ Kupffer Cells Are Indicators of Rejection Activity in Human Liver Allografts

Fas-Fas ligand (FasL) interaction and apoptosis are important in the mechanism of allograft rejection. However, the interaction between donor and recipient cells, specifically focusing on antigen-presenting cells (APCs), under various conditions is poorly understood in human liver allografts. FasL expression on APCs, its association with apoptosis, and the origin of apoptotic lymphocytes in human liver allografts were assessed by immunohistochemistry and in situ hybridization. We found increased expression of FasL on Kupffer cells (KCs) and endothelium in acute cellular rejection (n = 20) and to lesser extent in chronic rejection (n = 6) and septic cholangitis (n = 5) compared with stable grafts and normal controls. In addition, the graft specificity of infiltrating T cells was confirmed by polymerase chain reaction examination of T-cell receptor-γ loci. T-cell apoptosis occurred at a higher rate in acute cellular rejection than in chronic rejection or septic cholangitis. The number of apoptotic bodies derived from recipient lymphocytes correlated with the severity of rejection and was reversed by treatment. FasL+ KCs phagocytosed CD4+ interferon-γ+ T cells, rather than CD4+ interleukin-4+ T cells, suggesting a role of KCs in regulating CD4+ T-cell subset differentiation. In conclusion, our data suggest that FasL expression on APCs and phagocytosis of apoptotic T cells by FasL+ KCs are indicators of rejection activity in human liver allografts