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

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

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

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

Molecular analysis of the BCR-ABL1 kinase domain in chronic-phase chronic myelogenous leukemia treated with tyrosine kinase inhibitors in practice: Study by the Nagasaki CML Study Group

An appropriate trigger for BCR-ABL1 mutation analysis has not yet been established in unselected cohorts of chronic-phase chronic myelogenous leukemia patients. We examined 92 patients after 12 months of tyrosine kinase inhibitor (TKI) treatment in Nagasaki Prefecture, Japan. Univariate analysis revealed that significant factors associated with not attaining a major molecular response (MMR) were the presence of the minor BCR-ABL1 fusion gene, a low daily dose of TKI, and the emergence of BCR-ABL1 kinase domain mutations conferring resistance to imatinib. Factors associated with the loss of sustained MMR were a low daily dose of TKI and the emergence of alternatively spliced BCR-ABL1 mRNA with a 35-nucleotide insertion. Taken together, our results suggest that the search for BCR-ABL1 mutations should be initiated if patients have not achieved MMR following 12 months of TKI treatment

「緩和ケアを推進する看護師教育プログラム」の評価 : 修了者およびその上司への調査から

京都府立医科大学医学部看護学科京都府立医科大学附属病院看護部京都府立医科大学看護実践キャリア開発センター京都府立医科大学附属病院地域医療推進部School of Nursing, Kyoto Prefectural University of MedicineDepartment of Nursing, University Hospital Kyoto Prefectural University of MedicineKyoto Prefectural University of Medicine, Career Development Center for NursingPromotion Division of Regional Medicine, University Hospital Kyoto Prefectural University of Medicine　本研究の目的は、「緩和ケア実践看護師養成コース（以下Aコース）」「在宅緩和ケア推進看護師養成コース（以下Bコース）」を受講した修了者とその上司への調査からプログラム評価および看護実践への活用状況を指標にしてプログラムを評価することである。【方法】平成27～31年度の間に京都府立医科大学看護実践キャリア開発センターが開催する「緩和ケアを推進する看護師教育プログラム」のAコースまたはBコースを受講した修了者25名のうち、調査時点で受講時と同じ施設・病院で就労を継続している21名（Aコース14名、Bコース7名）、とその上司21名（Aコース14名、Bコース7名）を研究対象者とした。修了生の施設・病院に質問紙を郵送し、令和3年7月～8月に無記名の自記式質問紙調査を行った。調査項目は、基本属性、カリキュラムについて、教育目標について、受講内容の適切性について、学習内容の臨床での活用について、とした。なお所属する大学の医学倫理審査委員会の承認を得て実施した（ERB-E-444）。【結果】回答者は、Aコース修了者9名、Aコース上司7名、Bコース修了者5名、Bコース上司3名であった。受講した修了者の評価においては、プログラムの内容についてAコースの8割以上が、Bコースの全員が（とても・まあまあ）適切としている。自己能力の発揮状況について、Aコースは4～6割、Bコースについては4～8割ができているとしている。　上司からの評価では、両コースとも受講した講義・演習・実習が7割程度現在の看護実践に役立っていると答えた。期待される能力については両コースとも8割以上が現在の看護活動に活きていると答えた。【結論】平成27年度から開始された「緩和ケアを推進する看護師教育プログラム」に対して、受講した修了者とその上司に，研修が有用であったかを問うたところ、受講した修了者はプログラムの内容が看護の実践で活かされていると実感していることが明らかとなった。さらに、上司は、受講した修了者が研修を踏まえた看護実践ができていると評価していることが明らかになった。修了者、上司の評価からプログラムの効果を評価することができた