Effects of constitutively active IKKβ on cardiac development

NF-κB is a major transcription factor regulating cell survival, organ development and inflammation, but its role in cardiac development has been inadequately explored. To examine this function, we generated mice in which IKKβ, an essential kinase for NF-κB activation, was constitutively activated in embryonic cardiomyocytes. For this purpose, we used smooth muscle-22α (SM22α)-Cre mice, which are frequently used for gene recombination in embryonic cardiomyocytes. Embryonic hearts of SM22αCre-CA (constitutively active) IKKβflox/flox mice revealed remarkably thin, spongy and hypoplastic myocardium. In exploring the mechanism, we found that the expression of bone morphogenetic protein 10 (BMP10) and T-box transcription factor 20 (Tbx20), major regulators of cardiac development, was significantly downregulated and upregulated, respectively, in the SM22αCre-CAIKKβflox/flox mice. We also generated NK2 homeobox 5 (Nkx2.5) Cre-CAIKKβflox/wt mice since Nkx2.5 is also expressed in embryonic cardiomyocytes and confirmed that the changes in these genes were also observed. These results implicated that the activation of NF-κB affects cardiac development

Fetal Goitrous Hypothyroidism due to Maternal Thyroid Stimulation-Blocking Antibody: A Case Report

Most fetal goitrous hypothyroidisms are reportedly caused by the maternal use of an antithyroid drug or fetal dyshormonogenesis. However, fetal goitrous hypothyroidism due to the transplacental passage of maternal thyroid stimulation-blocking antibody (TSBAb) is extremely rare. A woman at 28 weeks of gestation was found to have a fetal goiter by ultrasonography. Because the maternal serum showed hypothyroidism with an elevated titer of TSBAb, levothyroxine sodium was administered. The patient delivered a male infant, 3,412 g, with a goiter at term. Umbilical blood revealed primary hypothyroidism with increased TSBAb, and the infant was given levothyroxine sodium. After a month, neonatal thyroid function and TSBAb levels became normal. Attention should be paid to possible fetal hypothyroidism when a fetal goiter is observed to avoid impaired mental development of the neonate.ArticleFETAL DIAGNOSIS AND THERAPY. 28(4):220-224 (2010)journal articl

Fetal Goitrous Hypothyroidism due to Maternal Thyroid Stimulation-Blocking Antibody: A Case Report

Most fetal goitrous hypothyroidisms are reportedly caused by the maternal use of an antithyroid drug or fetal dyshormonogenesis. However, fetal goitrous hypothyroidism due to the transplacental passage of maternal thyroid stimulation-blocking antibody (TSBAb) is extremely rare. A woman at 28 weeks of gestation was found to have a fetal goiter by ultrasonography. Because the maternal serum showed hypothyroidism with an elevated titer of TSBAb, levothyroxine sodium was administered. The patient delivered a male infant, 3,412 g, with a goiter at term. Umbilical blood revealed primary hypothyroidism with increased TSBAb, and the infant was given levothyroxine sodium. After a month, neonatal thyroid function and TSBAb levels became normal. Attention should be paid to possible fetal hypothyroidism when a fetal goiter is observed to avoid impaired mental development of the neonate.ArticleFETAL DIAGNOSIS AND THERAPY. 28(4):220-224 (2010)journal articl

Overcoming minimal residual disease using intensified conditioning with medium-dose etoposide, cyclophosphamide and total body irradiation in allogeneic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in adults

BACKGROUND AIMS: An intensified conditioning regimen incorporating medium-dose etoposide (VP16) is an option for patients with acute lymphoblastic leukemia (ALL). However, the prognostic impacts of the addition of VP16 to cyclophosphamide (CY) and total body irradiation (TBI) in patients with Philadelphia chromosome-positive (Ph+) ALL with regard to minimal residual disease (MRD) status have not been elucidated. METHODS: The authors retrospectively compared the outcomes of patients with Ph+ ALL who underwent allogeneic transplantation following VP16/CY/TBI (n = 101) and CY/TBI (n = 563). RESULTS: At 4 years, the VP16/CY/TBI group exhibited significantly better disease-free survival (DFS) (72.6% versus 61.7%, P = 0.027) and relapse rate (11.5% versus 21.1%, P = 0.020) and similar non-relapse mortality (16.0% versus 17.2%, P = 0.70). In subgroup analyses, the beneficial effects of the addition of VP16 on DFS were more evident in patients with positive MRD status (71.2% versus 48.4% at 4 years, P = 0.022) than those with negative MRD status (72.8% versus 66.7% at 4 years, P = 0.24). Although MRD positivity was significantly associated with worse DFS in patients who received CY/TBI (48.4% versus 66.7%, P < 0.001), this was not the case in those who received VP16/CY/TBI (71.2% versus 72.8%, P = 0.86). CONCLUSIONS: This study demonstrated the benefits of the addition of VP16 in Ph+ ALL patients, especially those with positive MRD status. VP16/CY/TBI could be a potential strategy to overcome the survival risk of MRD positivity

「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

Collagenolytic Serine-Carboxyl Proteinase from Alicyclobacillus sendaiensis Strain NTAP-1: Purification, Characterization, Gene Cloning, and Heterologous Expression

Enzymatic degradation of collagen produces peptides, the collagen peptides, which show a variety of bioactivities of industrial interest. Alicyclobacillus sendaiensis strain NTAP-1, a slightly thermophilic, acidophilic bacterium, extracellularly produces a novel thermostable collagenolytic activity, which exhibits its optimum at the acidic region (pH 3.9) and is potentially applicable to the efficient production of such peptides. Here, we describe the purification to homogeneity, characterization, gene cloning, and heterologous expression of this enzyme, which we call ScpA. Purified ScpA is a monomeric, pepstatin-insensitive carboxyl proteinase with a molecular mass of 37 kDa which exhibited the highest reactivity toward collagen (type I, from a bovine Achilles tendon) among the macromolecular substrates examined. On the basis of the sequences of the peptides obtained by digestion of collagen with ScpA, the following synthetic peptides were designed as substrates for ScpA and kinetically analyzed: Phe-Gly-Pro-Ala(*)Gly-Pro-Ile-Gly (k(cat), 5.41 s(−1); K(m), 32 μM) and Met-Gly-Pro-Arg(*)Gly-Phe-Pro-Gly-Ser (k(cat), 351 s(−1); K(m), 214 μM), where the asterisks denote the scissile bonds. The cloned scpA gene encoded a protein of 553 amino acids with a calculated molecular mass of 57,167 Da. Heterologous expression of the scpA gene in the Escherichia coli cells yielded a mature 37-kDa species after a two-step proteolytic cleavage of the precursor protein. Sequencing of the scpA gene revealed that ScpA was a collagenolytic member of the serine-carboxyl proteinase family (the S53 family according to the MEROPS database), which is a recently identified proteinase family on the basis of crystallography results. Unexpectedly, ScpA was highly similar to a member of this family, kumamolysin, whose specificity toward macromolecular substrates has not been defined