小児急性リンパ性白血病のL-アスパラギナーゼを含む寛解導入療法ではトロンピン・プラスミン生成試験において著明な線溶抑制を主体とする凝固障害を示す。

Background: L-asparaginase (L-Asp)-associated thromboembolisms are serious complications in pediatrics patients with acute lymphoblastic leukemia (ALL), especially at ≥10.0 years old, but the pathogenesis remains to be clarified. Procedure: We conducted a multicenter, prospective study of 72 patients with ALL aged 1.0 to 15.2 years treated with either a Berlin-Frankfurt-Münster (BFM) 95-ALL oriented regimen or Japan Association of Childhood Leukemia Study ALL-02 protocol. We divided patients into each treatment protocol and investigated the dynamic changes in coagulation and fibrinolysis using simultaneous thrombin and plasmin generation assay. Patients' plasma samples were collected at the prephase (T0), intermittent phase (T1), and postphase of L-Asp therapy (T2), and postinduction phase (T3). Measurements of endogenous thrombin potential (T-EP) and plasmin peak height (P-Peak) were compared to normal plasma. Results: None of the cases developed thromboembolisms. Median ratios of T-EP and P-Peak for the controls in the JACLS group were 1.06 and 0.87 (T0), 1.04 and 0.71 (T1), 1.02 and 0.69 (T2), and 1.20 and 0.92 (T3), respectively, while those in the BFM group were 1.06 and 1.00 (T0), 1.04 and 0.64 (T1), 1.16 and 0.58 (T2), and 1.16 and 0.85 (T3), respectively. In particular, P-Peak ratios were depressed at T1 and T2 compared to T0 in the BFM group (P < .01). Moreover, P-Peak ratios in patients ≥10.0 years old were lower at T1 in the BFM group (P = .02). Conclusions: The results demonstrated that hemostatic dynamics appeared to shift to a hypercoagulable state with marked hypofibrinolysis associated with L-Asp therapy, especially in patients ≥10.0 years old following the BFM regimen.博士（医学）・甲第722号・令和元年12月5日© 2019 Wiley Periodicals, Inc.This is the pre-peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/full/10.1002/pbc.28016], which has been published in final form at [https://doi.org/10.1002/pbc.28016]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions

A mammalian enhancer trap resource for discovering and manipulating neuronal cell types

There is a continuing need for driver strains to enable cell-type-specific manipulation in the nervous system. Each cell type expresses a unique set of genes, and recapitulating expression of marker genes by BAC transgenesis or knock-in has generated useful transgenic mouse lines. However, since genes are often expressed in many cell types, many of these lines have relatively broad expression patterns. We report an alternative transgenic approach capturing distal enhancers for more focused expression. We identified an enhancer trap probe often producing restricted reporter expression and developed efficient enhancer trap screening with the PiggyBac transposon. We established more than 200 lines and found many lines that label small subsets of neurons in brain substructures, including known and novel cell types. Images and other information about each line are available online (enhancertrap.bio.brandeis.edu)

Association between periodontal condition and kidney dysfunction in Japanese adults : A cross‐sectional study

Recent studies have demonstrated that chronic kidney disease (CKD) may be associated with the progression of periodontal disease. Diabetes mellitus (DM) is a major risk factor for CKD. The objective of this study was to clarify the relationship between periodontal condition and kidney dysfunction in patients who had kidney failure with or without DM. One hundred sixty‐four patients with kidney dysfunction were enrolled (male: N = 105; female: N = 59), and the relationship between periodontal condition and kidney dysfunction was analyzed in a cross‐sectional study. The subjects were divided into three groups: (a) patients with DM, (b) dialysis patients with nephropathy due to various kidney diseases, and (c) dialysis patient with nephropathy due to DM (diabetic nephropathy). Then, the effect of DM on the periodontal condition was analyzed. The patients were also stratified by CKD stage (into G1–G5) using the estimated glomerular filtration rate (eGFR), and the G5 group was divided in patients with or without DM. Correlations between eGFR and parameters of periodontal condition were calculated in patients from G1 to G4. The number of missing teeth was significantly higher in dialysis patients with diabetic nephropathy than in patients with DM, whereas alveolar bone loss did not show a significant difference among the three groups. In addition, the G5 patients with DM had a significantly higher number of missing teeth than the other CKD groups, whereas alveolar bone loss did not show a significant difference. In G5 patients with DM, Community Periodontal Index and Oral Hygiene Index scores were significantly higher than in G1‐4 patients with DM. There was a significant negative correlation between eGFR and the number of missing teeth. Patients with diabetic nephropathy have a higher rate of periodontal problems such as missing teeth in Japanese adults

DNA polymerases ν and θ are required for efficient immunoglobulin V gene diversification in chicken

Polν and Polθ have specialized functions in immunoglobulin gene rearrangements and only contribute to DNA repair when other homologous recombination–related DNA polymerases are absent

Recombinant cyclin B-Cdk1-Suc1 capable of multi-site mitotic phosphorylation in vitro.

Cyclin-dependent kinase 1 (Cdk1) complexed with cyclin B phosphorylates multiple sites on hundreds of proteins during mitosis. However, it is not fully understood how multi-site mitotic phosphorylation by cyclin B-Cdk1 controls the structures and functions of individual substrates. Here we develop an easy-to-use protocol to express recombinant vertebrate cyclin B and Cdk1 in insect cells from a single baculovirus vector and to purify their complexes with excellent homogeneity. A series of in-vitro assays demonstrate that the recombinant cyclin B-Cdk1 can efficiently and specifically phosphorylate the SP and TP motifs in substrates. The addition of Suc1 (a Cks1 homolog in fission yeast) accelerates multi-site phosphorylation of an artificial substrate containing TP motifs. Importantly, we show that mitosis-specific multi-subunit and multi-site phosphorylation of the condensin I complex can be recapitulated in vitro using recombinant cyclin B-Cdk1-Suc1. The materials and protocols described here will pave the way for dissecting the biochemical basis of critical mitotic processes that accompany Cdk1-mediated large-scale phosphorylation