Clinical Features, ARIX and PHOX2B Nucleotide Changes in Three Families with Congenital Superior Oblique Muscle Palsy

We analyzed nucleotide changes in 3 genes, ARIX, PHOX2B, and KIF21A, in 6 patients of 3 families with congenital superior oblique muscle palsy. Three exons of ARIX, 3 exons of PHOX2B, and exons 8, 20, and 21 of KIF21A were amplified by polymerase chain reaction from genomic DNA isolated from the peripheral blood. The DNA fragments were directly sequenced in both directions. In 2 different families, a heterozygous nucleotide change, ARIX 153G&#62;A, in the 5’-untranslated region was found in common between a father and daughter with muscle palsy and between a mother and daughter with muscle palsy (Family No. 1 and No. 3). In the other family (Family No. 2), a heterozygous 15-nucleotide deletion, PHOX2B 1124del15, resulting in loss of 5 alanine residues in the alanine repeat of the protein, was found in the daughter with muscle palsy and her father with normal traits, but was not found in the mother with muscle palsy. No KIF21A nucleotide change was found in any patients. The ARIX 153G&#62;A polymorphism might be a genetic risk factor for the development of congenital superior oblique muscle palsy.</p

Pcdhβ deficiency affects hippocampal CA1 ensemble activity and contextual fear discrimination

Clustered protocadherins (Pcdhs), a large group of adhesion molecules, are important for axonal projections and dendritic spread, but little is known about how they influence neuronal activity. The Pcdhβ cluster is strongly expressed in the hippocampus, and in vivo Ca2+ imaging in Pcdhβ-deficient mice revealed altered activity of neuronal ensembles but not of individual cells in this region in freely moving animals. Specifically, Pcdhβ deficiency increased the number of large-size neuronal ensembles and the proportion of cells shared between ensembles. Furthermore, Pcdhβ-deficient mice exhibited reduced repetitive neuronal population activity during exploration of a novel context and were less able to discriminate contexts in a contextual fear conditioning paradigm. These results suggest that one function of Pcdhβs is to modulate neural ensemble activity in the hippocampus to promote context discrimination

Towards novel difluorinated sugar mimetrics; syntheses and conformational analyses of highly-functionalised difluorinated cyclooctenones

Highly-functionalised difluorinated cyclooctenones were synthesised from trifluoroethanol using either metallated difluoroenol acetal or carbamate chemistry, followed by a [2,3]-Wittig rearrangement or aldol reaction. Efficient RCM reactions afforded the title compounds which showed rather restricted fluxional behaviour by VT 19F NMR. Topological characterisation by molecular modelling and NOESY/ROESY experiments offered a number of challenges, but allowed the identification of two favoured boat-chair conformers which interconverted by pseudorotation with relatively large activation barriers

Feasibility of cord blood transplantation in chemosensitive adult T-cell leukemia/lymphoma: a retrospective analysis of the Nagasaki Transplantation Network

It has been reported that cord blood transplantation (CBT) for patients with aggressive adult T-cell leukemia/ lymphoma (ATL) results in poorer outcomes than transplantation using other stem cell sources. To identify a subset of ATL in which CBT is feasible, we retrospectively analyzed 27 patients treated with CBT at three institutions in Nagasaki Prefecture, Japan. The estimated overall survival (OS) rate at 3 years was 27.4 %. Of 16 patients who received CBT during remission (complete, CR, or partial, PR), the OS rate at 3 years was 50 %, while during refractory periods (non-CR or non-PR), the OS rate was 9.1 %. Reduced intensity conditioning (RIC) was given to 18 patients, and myeloablative conditioning (MAC) was used in nine, with 3-year OS of 50.0 and 0 %, respectively. Of the 19 deaths, nine were due to progressive disease, eight (five MAC and three RIC) to infection, and two to multiple organ failure. These results suggest that CBT provides similar results with those in other transplantation procedures for selected ATL patients, such as those in CR or PR. Further studies are needed to evaluate the use of CBT in aggressive ATL

小児がん患児の治療開始時のインフォームド・コンセントに同席した看護師が家族に実施している対応

京都府立医科大学大学院保健看護学研究科Department of Nursing for Health Care Science, Graduate School of Nursing for Health Care Science, Kyoto Prefectural University of Medicine子どもが小児がんと診断される際の家族の衝撃は大きい。本研究の目的は、小児がん患児の治療開始時のインフォームド・コンセントに同席した看護師が家族にどのような対応をしているのかを明らかにすることである。研究対象者は、小児がん拠点病院の小児科外来に通院する小児がん患児の家族9 名である。インタビューガイドに基づき半構成的面接を行い、質的記述的に分析した。対象者は全員母親であり、平均年齢は34.9 ± 6.1 歳であった。治療開始時のインフォームド・コンセントに同席した看護師が小児がん患児の家族である母親に実施している対応は分析した結果、【医師の説明を一緒に聞いて把握し落ち着くまで見守る】【頑張りに気づき言葉やタッチを用いて癒す】【感情の表出を促し、母親としての思いと希望を支える】【睡眠時間を確保しリフレッシュを促す】【入院生活に対する感じ方を把握し調整する】【家族の状況に応じた付き添いの調整と医療者と話しやすい雰囲気をつくる】が抽出された。　治療開始時の小児がん患児の家族に対して、看護師は医師の説明を一緒に聞くことで家族の複雑な心理状況を把握し、家族の頑張りを承認し言葉やタッチングを用いて癒し、母親のつらい思いを表出させ、希望を支える関わりをしていた。また、家族の健康面に配慮しながら、入院生活や家族の状況に応じた調整や医療者との良好な関係形成への支援を実施していた。以上から、看護師はインフォームド・コンセントに同席し、医師の説明後は家族を見守り、身体面と心理面の安楽を保持し、入院生活と人間関係の調整を行う重要性が示唆された

High-resolution melting analysis for a reliable and two-step scanning of mutations in the tyrosine kinase domain of the chimerical bcr-abl gene.

For relevant imatinib therapy against Philadelphia (Ph)-positive leukemias, it is essential to monitor mutations in the chimerical bcr-abl tyrosine kinase domain (TKD). However, there is no universally acceptable consensus on how to efficiently identify mutations in the target TKD. Recently, high-resolution melting (HRM) technology was developed, which allows gene scanning using an inexpensive generic heteroduplex-detecting dsDNA-binding dye. This study aimed to validate the introduction of HRM in a practical clinical setting for screening of mutations in sporadic sites of the chimerical bcr-abl TKD. All chimerical and wild-type abl TKD regions selectively amplified were used for HRM assays and direct sequencing. The HRM test had approximately 5-90% detection sensitivity for mutations. In contrast to mixture samples with mutant and wild-type cells, all mutant cell samples had indeterminate melting curves equivalent to those of the wild-type due to formation of only a homodulex. This issue was improved by the addition of exogenous wild-type DNA after PCR. Subsequently, HRM results gave a high accordance rate of 97.8% (44/45 samples) compared to the sequencing data. The discordant results in one appear to be due to unsuccessful amplification. Thus, HRM may be considered to be suitable for reliable scanning of mutations in the chimerical abl TKD in a clinical setting

Mitochonic Acid 5 (MA-5) Facilitates ATP Synthase Oligomerization and Cell Survival in Various Mitochondrial Diseases

Mitochondrial dysfunction increases oxidative stress and depletes ATP in a variety of disorders. Several antioxidant therapies and drugs affecting mitochondrial biogenesis are undergoing investigation, although not all of them have demonstrated favorable effects in the clinic. We recently reported a therapeutic mitochondrial drug mitochonic acid MA-5 (Tohoku J. Exp. Med., 2015). MA-5 increased ATP, rescued mitochondrial disease fibroblasts and prolonged the life span of the disease model “Mitomouse” (JASN, 2016). To investigate the potential of MA-5 on various mitochondrial diseases, we collected 25 cases of fibroblasts from various genetic mutations and cell protective effect of MA-5 and the ATP producing mechanism was examined. 24 out of the 25 patient fibroblasts (96%) were responded to MA-5. Under oxidative stress condition, the GDF-15 was increased and this increase was significantly abrogated by MA-5. The serum GDF-15 elevated in Mitomouse was likewise reduced by MA-5. MA-5 facilitates mitochondrial ATP production and reduces ROS independent of ETC by facilitating ATP synthase oligomerization and supercomplex formation with mitofilin/Mic60. MA-5 reduced mitochondria fragmentation, restores crista shape and dynamics. MA-5 has potential as a drug for the treatment of various mitochondrial diseases. The diagnostic use of GDF-15 will be also useful in a forthcoming MA-5 clinical trial

Successful cord blood transplantation for mycosis fungoides.

A 26-year-old female diagnosed as mycosis fungoides (MF, clinical stage IV) was treated with single-agent chemotherapy, multi-drug chemotherapy and unrelated bone marrow transplantation with reduced-intensity conditioning (engraftment failure), resulting in failure. Unrelated cord blood transplantation (CBT) as second transplantation following myeloablative conditioning brought complete remission (CR), but relapse of MF occurred 3 months after transplantation. However, discontinuation of immune suppressant led to the regression of MF regions and to second CR that continued for more than 23 months. This is the first report of successful CBT for MF, suggesting the graft-versus-MF effect in a setting of CBT.The original publication is available at www.springerlink.co

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1)漬け物を漬けている世帯は全体の80.8%であり,地域別では農村が最も多かった。高齢者のいる家庭では,いない家庭より漬けている比率が高かった。2)漬ける漬け物の種類は,塩漬けが78%と圧倒的に多く,ついで梅漬けであった。1世帯で漬ける漬け物の種類数は1～3種類が過半数を占め,5種類以上漬ける家庭も33.8%あった。3)塩漬けにする食品は,きゅうり,白菜が最も多く,何れも60%以上の家庭で漬けられていた。漬けておく期間は1～2日が71.4%と短期間のものが多く,長期間のものは僅かであった。4)梅漬けは毎年必ず漬ける家庭が60%前後あり,土用干しをする大梅・小梅が圧倒的に多かった。各年齢層別に梅を漬ける人の比率をみると61～65歳が75.0%で最も高かった。高齢者がいる家庭のうち約70%は梅を漬けており,高齢者のいない家庭よりその比率が高かった。1回に漬ける梅の分量は,大梅・小梅ともに1～4kgが多かった。塩分濃度は大梅・小梅(土用干し)とも,平均が約17%であり,塩分濃度の低いもの程焼酎を併用するものが多かった。5)漬け物を購入する家庭は全世帯の89.1%であり,漬ける・漬けないにかかわらず,ほとんどの家庭が購入していた。購入する漬け物の種類は,たくあん漬けが最も多く,ついで野菜類の塩漬け,福神漬け,梅干しの順であった。6)食事に漬け物が「必ず出る」は自宅で漬ける家庭では67.1%,漬けない家庭では31.2%であり,漬けているかいないかによって,その差が顕著であった。高齢者のいる家庭では,「必ず出る」が66.7%で,高齢者のいる家庭の方が漬け物が食事に出る頻度が高かった。7)漬け物の嗜好については「好き」と答えたものがほとんどであり,「嫌い」は僅かであった。年齢別では31歳以上はその70～80%のものが「好き」で,30歳以下との差が顕著であった。8)食べる頻度は「毎日必ず食べる」と「1日1回以上食べる」とで全体の半数を占め,「全く食べない」は僅かであった。嗜好別では「好き」と答えたものは「毎食必ず食べる」41.8%,「1日1回以上食べる」32.5%で,好きでないものより圧倒的によく食べている。即席漬けにしょう油をかけるものが約70%あった