HAPPEN TO BE FASHIONABLE? : NEW PRACTICE CREATION THROUGH THE SEQUENCE OF MULTIPLE ACTORS

In contrast to previous research, this paper illustrates a process in which institutional entrepreneurs play less significant roles in creating a new practice. We drew on a historical case study that deals with the emergence of a new practice of emphasizing fashionable design of a type of clothing known as meisen. In the historical case study, multiple actors played distinctive and essential roles, which, as a whole, led to the creation of a new practice.

A Sensitive New Method for Clinically Monitoring Cytarabine Concentrations at the DNA level in Leukemic Cells

Cytarabine (ara-C), a major antileukemic agent, is phosphorylated in the cell to cytarabine triphosphate (ara-CTP), which then is partly incorporated into DNA. The drug incorporation into DNA poisons the extending primer against further incorporation of deoxyribonucleotides including dCTP, ultimately inhibiting DNA synthesis. While intracellular ara-CTP concentration has been found to predict clinical outcome, cytotoxicity in vitro is determined primarily by the extent of drug incorporation into DNA. However, clinically appropriate quantitation methods for ara-C at the DNA level have not been available. We developed a sensitive new method for monitoring ara-C incorporated into DNA in vivo. After DNA from leukemic cells was fractionated using the Schmidt-Thannhauser-Schneider method, it was degraded to constituent nucleosides to release ara-C, which was isolated from the nucleosides using HPLC and then measured by radioimmunoassay. Recovery for DNA fractionation, ara-C release by degradation, and ara-C isolation were 92.0 ± 6.4%, 90.7 ± 9.4%, and 98.5 ± 1.4%, respectively. The method was found to determine ara-C incorporation into DNA of ara-C-treated HL60 cells in vitro with minimal interassay variation. The values determined were compatible with those determined by scintillation counting in parallel experiments using tritiated ara-C. Our method could be used to monitor DNA-incorporated ara-C concentrations during ara-C therapy, together with plasma ara-C and intracellular ara-CTP concentrations. ara-C incorporation into DNA appeared to be associated with intracellular retention of ara-CTP or persistence of plasma ara-C. Thus, the present method is sensitive, accurate, precise, and may permit therapeutic drug monitoring at the DNA level for better individualization of antileukemic regimens

Na+-Cl-共輸送体を介したクロライド輸送はアルドステロン投与ラットの血圧上昇と腎障害に関与する

広島大学(Hiroshima University)博士(医学)Doctor of Philosophy in Medical Sciencedoctora

Alkylator-Induced DNA Excision Repair in Human Leukemia CCRF-CEM Cells In Vitro, Measured Using the Single-Cell Gel Electrophoresis (Comet) Assay

The capacity to repair DNA damage is an important factor that affects the therapeutic outcome in cancer treatment. To clarify the cellular repair response, we investigated the kinetics of DNA excision repair initiated by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in human leukemia CCRF-CEM cells at an exponential growth phase in vitro. Using the alkaline single-cell gel electrophoresis (comet) assay, we quantitated the repair kinetics as the amount of DNA single-strand breaks that were generated from the incision and were diminished by the rejoining in the repair process. CEM cells could initiate DNA excision repair in response to BCNU by starting an incision reaction. However, the incision capacity came to a plateau at a concentration of 80 to 1003M or after an incubation time of 90 to 120 minutes. When the cells were pulsed with 403M BCNU, the maximal incision occurred at the end of the incubation period, and the repair process was completed within 4 hours.When cells were treated with 1003M BCNU, the incised DNA was not rejoined at 4 hours, suggesting that the repair was not completed. Higher concentrations might surpass the cellular capacity for repair and would be associated with increased cell death. Evaluation of the repair process may provide a clue for therapeutic strategies to improve clinical efficacy if accelerated DNA repair is responsible for the drug resistance

UCN-01 (7-hydroxystaurosporine) inhibits DNA repair and increases cytotoxicity in normal lymphocytes and chronic lymphocytic leukemia lymphocytes.

Elevated DNA repair processes represent resistance mechanisms to the treatment of malignancies with alkylating agents. Recently, the cell cycle checkpoint abrogator, UCN-01, was reported to inhibit nucleotide excision repair in cell-free systems. We hypothesized that if UCN-01 was combined with DNA-damaging agents, UCN-01 might inhibit the damage repair processes, thereby enhancing cytotoxicity in quiescent cells. Here, we investigated the effect of UCN-01 on DNA repair and viability of quiescent normal lymphocytes and chronic lymphocytic leukemia lymphocytes treated with UV or the cyclophosphamide prodrug 4-hydroperoxycyclophosphamide (4-HC). DNA damage repair kinetics were determined as DNA single strand breaks by the alkaline single cell gel electrophoresis (comet) assay and by [3H]thymidine incorporation. Pretreatment with UCN-01 inhibited DNA repair initiated by UV or 4-HC in normal lymphocytes as well as chronic lymphocytic leukemia lymphocytes in a concentration-dependent manner at clinically relevant levels (50-300 nM). This inhibition was demonstrated by the decreases in incision capability, DNA resynthesis, and in rejoining, suggesting that UCN-01 inhibits the multiple sites of the repair processes. The higher UCN-01 concentration (300 nM) maximized the inhibitory effects and enhanced the UV- or 4-HC-induced cytotoxicity, as determined by annexin V binding or Hoechst 33342 staining. This enhancement was not obtained by the lower concentrations that incompletely inhibited the repair, suggesting the close association between the inhibition of the repair and the enhancement of the cytotoxicity. Our findings suggest that UCN-01 may be a good candidate for combination strategies of cancer treatment

Theory of coevolution of cytoplasmic male-sterility, nuclear restorer and selfing

Gynodioecy is a sexual polymorphism in angiosperms, where hermaphroditic and female individuals coexist. This is often caused by a cytoplasmic genetic element (CGE) that destroys male functions, which is called cytoplasmic male-sterility (CMS). On the other hand, nuclear genes tend to evolve the ability to restore male function. The coevolutionary process of CMS and the restoration has been studied theoretically. Recently, a theoretical study suggested that these coevolutionary dynamics could be influenced by the rate of selfing within populations, although it assumed that the selfing rate of a population was a fixed parameter. Accordingly, we theoretically study the coevolution of three traits in this paper: CMS, nuclear restorer and selfing rate, in which we hypothesize that selfing evolution can suppress CMS evolution under some conditions. The analysis indicates three significant properties of the system; (1) CMS-restorer evolution can result in bistability under a given selfing rate, (2) the coevolution of three traits can realize intermediate levels of selfing, and (3) the evolution of high levels of selfing is conditionally associated with no CMS and/or no restoration, which may support our hypothesis

Open inflation in the landscape

Open inflation scenario is attracting a renewed interest in the context of string landscape. Since there are a large number of metastable de Sitter vacua in string landscape, tunneling transitions to lower metastable vacua through the bubble nucleation occur quite naturally. Although the deviation of Omega_0 from unity is small by the observational bound, we argue that the effect of this small deviation on the large angle CMB anisotropies can be significant for tensor-type perturbation in open inflation scenario. We consider the situation in which there is a large hierarchy between the energy scale of the quantum tunneling and that of the slow-roll inflation in the nucleated bubble. If the potential just after tunneling is steep enough, a rapid-roll phase appears before the slow-roll inflation. In this case the power spectrum is basically determined by the Hubble rate during the slow-roll inflation. If such rapid-roll phase is absent, the power spectrum keeps the memory of the high energy density there in the large angular components. The amplitude of large angular components can be enhanced due to the effects of the wall fluctuation mode if the bubble wall tension is small. Therefore, one can construct some models in which the deviation of Omega_0 from unity is large enough to produce measurable effects. We also consider a more general class of models, where the false vacuum decay may occur due to Hawking-Moss tunneling, as well as the models involving more than one scalar field. We discuss scalar perturbations in these models and point out that a large set of such models is already ruled out by observational data, unless there was a very long stage of slow-roll inflation after the tunneling. These results show that observational data allow us to test various assumptions concerning the structure of the string theory potentials and the duration of the last stage of inflation.Comment: 14 pages, 11 figures, v2:minor corrections and a reference added, v3:accepted for publication in PR

麹菌 Aspergillus oryzae RIB40由来のthiAリボスイッチの機能解析と応用に関する研究 [論文要旨及び審査の要旨]

関西大

Recombinant γY278H Fibrinogen Showed Normal Secretion from CHO Cells, but a Corresponding Heterozygous Patient Showed Hypofibrinogenemia

ArticleInternational journal of molecular sciences. 22(10): 5218(2021)journal articl

A novel variant fibrinogen, AαE11del, demonstrating the importance of AαE11 residue in thrombin binding

ArticleInternational journal of hematology. 114(5): 591-598. (2021)journal articl