Studies on creation of intracellularly active ribozymes

Thesis (Ph. D. in Science)--University of Tsukuba, (B), no. 2309, 2007.7.25Includes bibliographical references (leaves 57-70

Specificity of novel allosterically trans- and cis-activated connected maxizymes that are designed to suppress BCR-ABL expression

AbstractChronic myelogenous leukemia (CML) is associated with the presence of the Philadelphia chromosome, which is generated by the reciprocal translocation of chromosomes 9 and 22. In the case of L6 (b2a2) mRNA, it is difficult to cleave the abnormal mRNA specifically because the mRNA includes no sequences that can be cleaved efficiently by conventional hammerhead ribozymes near the BCR-ABL junction. We recently succeeded in designing a novel maxizyme, which specifically cleaves BCR-ABL fusion mRNA, as a result of the formation of a dimeric structure. As an extension of our molecular engineering of maxizymes, as well as to improve their potential utility, we examined whether an analogous conformational change could be induced within a single molecule when two maxizymes were connected via a linker sequence. An active conformation was achieved by binding of the construct to the BCR-ABL junction in trans, with part of the linker sequence then acting as an antisense modulator in cis (within the complex) to adjust the overall structure. Results of studies in vitro in the presence of cetyltrimethylammonium bromide (CTAB) (but not in its absence) suggested that a certain kind of connected maxizyme (cMzB) might be able to undergo a desired conformational change and, indeed, studies in vivo confirmed this prediction. Therefore, we successfully created a fully functional, connected maxizyme and, moreover, we found that the activity and specificity of catalytic RNAs in vivo might be better estimated if their reactions are monitored in vitro in the presence of CTAB

Influence of and Risk Factors for Axillary Web Syndrome Following Surgery for Breast Cancer

In this study, we examined whether axillary web syndrome (AWS) in patients with breast cancer following axil-lary lymph node dissection affects range of motion (ROM), upper extremity function, and quality of life (QOL). The risk factors for AWS were also evaluated in a total of 238 consecutive breast cancer patients follow-ing axillary lymph node dissection. At 1, 2, and 3 months after surgery, there were no significant differences between the AWS group and the non-AWS group in upper-limb function or QOL. At 2 months after surgery, shoulder flexion and abduction ROM were significantly higher in the AWS group than in the non-AWS group (p < 0.05). Self-training time at home was not significantly different between the groups at 1, 2, or 3 months. Only age was a significant predictor of AWS at 1 month after surgery (p < 0.05). The AWS group in the present study did not have worse results for shoulder joint ROM, upper-limb function, and QOL than the non-AWS group. Younger age should be useful for predicting the development of AWS in the early postoperative period

Factors Affecting Participation in Leisure Activities in Patients after Breast Cancer Surgery

Background: The purpose of this study was to investigate the factors related to patient's participation in leisure activity in breast cancer patients with axillary lymph node dissection at 3 months after surgery. Methods: In total, 160 women who were employed before their surgery were evaluated. Age, body mass index (BMI), employment, level of lymph node dissection, marital status, children, coresident household members, preoperative chemotherapy, postoperative chemotherapy, postoperative hormonal therapy, postoperative radiotherapy, shoulder range of motion test, upper limb function, quality of life, and patient's participation in leisure activity were evaluated. Results: Patients who undertook leisure activities constituted the leisure activity group, and patients who did not constituted the non-leisure activity group. Global health status, emotional function, social function, and dyspnea were significantly different between the leisure activity group and the non-leisure activity group at 3 months after surgery (p < 0.05). Regarding factors that affected participation in leisure activities, logistic regression analysis showed that only participation in leisure activities before surgery was significantly associated with participation in leisure activities at 3 months after surgery (p < 0.05). Conclusion: Patients who did not participate in leisure activities prior to surgery were unlikely to participate 3 months after surgery and thus require intervention to encourage their involvement

Investigation of Factors Affecting Early Quality of Life of Patients after Breast Cancer Surgery

Objective: The purpose of this study was to investigate factors related to early quality of life (QOL) three months after surgery in breast cancer patients with axillary lymph node dissection. Methods: The subjects of this study were 195 consecutive patients who underwent axillary lymph node dissection for breast cancer. Age, body mass index, level of lymph node dissection, marriage, children, co-resident household members, neoadjuvant chemotherapy, postoperative chemotherapy, postoperative hormonal therapy, postoperative radiotherapy, upper limb function (disabilities of the arm, shoulder, and hand (DASH)), and QOL (European Organization for the Treatment and Research of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)) were evaluated. For each item of the EORTC QLQ-C30, compared with preoperative status and three months after surgery, those who improved or remained unchanged in the three months after surgery were classified as the maintenance and improved groups, and those with worsening status were classified as the worsened group. Results: Age, level of lymph node dissection, DASH, neoadjuvant chemotherapy, postoperative chemotherapy, and postoperative radiotherapy were significantly associated with QOL (p < 0.05). Conclusions: The early QOL of postoperative patients with breast cancer is affected by multiple factors, such as upper limb function and postoperative chemotherapy, and thus comprehensive intervention is required

Using the Acropora digitifera genome to understand coral responses to environmental change

Despite the enormous ecological and economic importance of coral reefs, the keystone organisms in their establishment, the scleractinian corals, increasingly face a range of anthropogenic challenges including ocean acidification and seawater temperature rise1, 2, 3, 4. To understand better the molecular mechanisms underlying coral biology, here we decoded the approximately 420-megabase genome of Acropora digitifera using next-generation sequencing technology. This genome contains approximately 23,700 gene models. Molecular phylogenetics indicate that the coral and the sea anemone Nematostella vectensis diverged approximately 500 million years ago, considerably earlier than the time over which modern corals are represented in the fossil record (~240 million years ago)5. Despite the long evolutionary history of the endosymbiosis, no evidence was found for horizontal transfer of genes from symbiont to host. However, unlike several other corals, Acropora seems to lack an enzyme essential for cysteine biosynthesis, implying dependency of this coral on its symbionts for this amino acid. Corals inhabit environments where they are frequently exposed to high levels of solar radiation, and analysis of the Acropora genome data indicates that the coral host can independently carry out de novo synthesis of mycosporine-like amino acids, which are potent ultraviolet-protective compounds. In addition, the coral innate immunity repertoire is notably more complex than that of the sea anemone, indicating that some of these genes may have roles in symbiosis or coloniality. A number of genes with putative roles in calcification were identified, and several of these are restricted to corals. The coral genome provides a platform for understanding the molecular basis of symbiosis and responses to environmental changes

The Actual Conditions of creation and utilization of the Records of Children with Disabilities during the School Transition Period: A Survey of Early Childhood Facilities and Elementary Schools

The purpose of this study is to clarify the actual conditions of personal records such as “support files” and “transition support sheets” created by early childhood facilities (kindergartens and nursery schools) to provide transition support to children with disabilities. The study seeks to examine how these records are created by early childhood facilities and used by elementary schools. A nationwide questionnaire survey targeting public and private kindergartens, nursery schools, and elementary schools was carried out. The survey results show that about half of the early childhood facilities created these records and that the records were being effectively utilized by the elementary schools that received them. However, there were also differences based on the type of institution: for instance, the rate of record creation was high at public kindergartens and low at private kindergartens and nursery schools. In terms of record content, there is a possibility of a gap between the information recorded by early childhood facilities and that sought by elementary schools. Based on these actual conditions, this study identifies issues to be considered in the effective creation and utilization of records.本研究は平成28年度文科省委託「幼児期の教育内容等深化・充実調査研究」（調査研究課題：幼保小接続における学習機会の保障としての合理的配慮に関する研究，研究受託機関：名古屋市立大学）の助成を受けて行われた研究成果の一部である。なお，本稿の一部は日本教育心理学会第59回総会において発表した

A Survey on Cooperation between Early Childhood Facilities and Elementary Schools regarding Children with Disabilities

This survey aimed to reveal the current conditions of cooperation between early childhood facilities and elementary schools regarding children with disabilities. A nationwide questionnaire was administered to 172 nursery schools (public), 242 nursery schools (private), 200 kindergartens (public), 481 kindergartens (private), and 592 elementary schools. Overall, for cooperation with elementary school for children with disabilities, the percentage of practice with kindergarten (public) was highest among early childhood facilities. In particular, for “Exchange activities between early childhood facilities and elementary schools” and “Introduction of approach curriculum,” the percentage of practice with kindergarten (public) was higher when compared with that in other early childhood facilities. The newly found information in this survey was that nursery schools (public) were most likely to take advantage of the “Individual education program.” The major problem was that nursery school and kindergarten teachers were willing to cooperate on early childhood education and care with elementary school teachers, but elementary school teachers answered that it was difficult to cooperate with many of the early childhood facilities. The ideal method for cooperation between early childhood facilities and elementary schools needs to be considered within each community.本研究は平成26年度文部科学省委託「幼児教育の改善・充実調査研究」（研究代表者：山崎 晃）及び平成25～27年度科学研究費・基盤研究（C）（研究課題番号：25381325，研究代表者：山崎 晃）の助成を受けて行われた研究成果の一部である

Study protocol for a multi-center, randomized controlled trial to develop Japanese denture adhesive guidelines for patients with complete dentures : the Denture Adhesive Guideline trial : study protocol for a randomized controlled trial

Background: Denture adhesives, characterized as medical products in 1935 by the American Dental Association, have been considered useful adjuncts for improving denture retention and stability. However, many dentists in Japan are hesitant to acknowledge denture adhesives in daily practice because of the stereotype that dentures should be inherently stable, without the aid of adhesives. The aim of this study is to verify the efficacy of denture adhesives to establish guidelines for Japanese users. The null hypothesis is that the application of denture adhesives, including the cream and powder types, or a control (isotonic sodium chloride solution) would not produce different outcomes nor would they differentially improve the set outcomes between baseline and day 4 post-application. Methods: This ten-center, randomized controlled trial with parallel groups is ongoing. Three hundred edentulous patients with complete dentures will be allocated to three groups (cream-type adhesive, powder-type adhesive, and control groups). The participants will wear their dentures with the denture adhesive for 4 days, including during eight meals (three breakfasts, two lunches, and three dinners). The baseline measurements and final measurements for the denture adhesives will be performed on the first day and after breakfast on the fourth day. The primary outcome is a general satisfaction rating for the denture. The secondary outcomes are denture satisfaction ratings for various denture functions, occlusal bite force, resistance to dislodgement, masticatory performance, perceived chewing ability, and oral health-related quality of life. Between-subjects comparisons among the three groups and within-subjects comparisons of the pre- and post-intervention measurements will be performed. Furthermore, a multiple regression analysis will be performed. The main analyses will be based on the intention-to-treat principle. A sample size of 100 subjects per group, including an assumed dropout rate of 10 %, will be required to achieve 80 % power with a 5 % alpha level. Discussion: This randomized clinical trial will provide information about denture adhesives to complete denture wearers, prosthodontic educators, and dentists in Japan. We believe this new evidence on denture adhesive use from Japan will aid dentists in their daily practice even in other countries

Intention to return to the town of Tomioka in residents 7 years after the accident at Fukushima Daiichi Nuclear Power Station: a cross-sectional study

The aim of our study was to identify the factors associated with intention to return (ITR) in residents of Tomioka town, Fukushima Prefecture. We contacted approximated 8000 residents aged 20 years or older who lived in Tomioka. We invited them to take part in a written survey on ITR. In all, 1749 residents\u27 replies were included in the analysis. We asked about ITR in former residents of Tomioka town. We also asked about relevant factors and about risk perception in relation to the health effects of radiation exposure. Of those contacted, 469 (26.8%) had an ITR. Logistic regression analysis revealed that being male (OR = 1.6, 95% Cl: 1.24-1.96, P < 0.001),the anticipation of improving shopping in the town (OR = 1.5, 95% Cl: 1.26-1.67, P < 0.001) and requests for individual consultation with experts on the health effects of radiation (OR = 2.7, 95% Cl: 2.10-3.48, P <0.001) were associated with the ITR (+), and living with children under 18 years of age (OR = 0.7, 95% Cl: 0.51-0.95, P = 0.023), reluctance to drink tap water (OR = 0.5, 95% Cl: 0.36-0.69, P < 0.001) and anxiety regarding genetic effects of radiation in the next generation (OR = 0.6, 95% Cl: 0.45-079, P <0.001) were associated with the ITR (-) to Tomioka town, independent of other covariates. To allay the anxieties of residents who have an ITR to their hometown, careful risk communication, including information on the potential effects of radiation on health, is important