WorldWideScience

Sample records for bcr providing biospecimen

  1. Knowledge and willingness to provide research biospecimens among foreign-born Latinos using safety-net clinics.

    Science.gov (United States)

    Loffredo, Christopher A; Luta, Gheorghe; Wallington, Sherrie; Makgoeng, Solomon B; Selsky, Claire; Mandelblatt, Jeanne S; Adams-Campbell, Lucile L

    2013-08-01

    Latinos tend to be under-represented in cancer research and in bio-repositories. We conducted a Spanish-language, interviewer-administered cross-sectional survey of 331 foreign-born Latinos from Central and South America attending safety-net clinics in order to describe factors associated with knowledge about and intention to provide bio-specimens for research purposes. We used logistic regression and multiple imputation methods to evaluate associations between socio-cultural measures, medical trust, demographics, as well as knowledge about and intentions to provide bio-specimens. Almost half (47 %) of respondents knew what bio-specimens were, and 67 % said that they would provide a specimen after being given information about what this involved; this increased to 72 % among those with prior knowledge. Controlling for covariates, Latinos with a high school education and above were more likely to know what a bio-specimen was and to say they would provide bio-specimens than were those with lower levels of education [adjusted OR (aOR) 2.85, 95 % CI 1.37-5.96; and 3.49, 95 % CI 1.41-8.63, p ≤ 0.01, respectively]. Those with greater social integration were more likely to know about bio-specimens than those with less integration (aOR 2.54, 95 % CI 1.45-4.46, p = 0.001). Higher endorsement of family values was independently associated with intent to give bio-specimens (aOR 1.11, 95 % CI 1.02-1.20, p = 0.017 per five-point increase in "familism" score). Medical mistrust was not related to intentions to provide specimens. Our results suggest that interventions to increase willingness to provide bio-specimens could leverage trusted clinics or social networks and should consider individuals' education and socio-cultural perspectives.

  2. Biospecimen Core Resource - Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The purpose of this notice is to notify the community that the National Cancer Institute's (NCI’s) Office of Cancer Clinical Proteomics Research (OCCPR) is seeking sources to establish a Biospecimen Core Resource (BCR), capable of receiving, qualifying, processing, and distributing annotated biospecimens.

  3. New Funding Opportunity: Biospecimen Core Resource - Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The purpose of this notice is to notify the community that the National Cancer Institute's (NCI’s) Office of Cancer Clinical Proteomics Research (OCCPR) is seeking sources to establish a Biospecimen Core Resource (BCR), capable of receiving, qualifying, processing, and distributing annotated biospecimens.

  4. Biospecimen Core Resource - TCGA

    Science.gov (United States)

    The Cancer Genome Atlas (TCGA) Biospecimen Core Resource centralized laboratory reviews and processes blood and tissue samples and their associated data using optimized standard operating procedures for the entire TCGA Research Network.

  5. Biotrust: a comprehensive system for acquiring and distributing biospecimens.

    Science.gov (United States)

    Anderson, Nicholas; Ponko, Stefan; Black, Tony; Prosser, Justin; Stein, Barbara; Tarczy-Hornoch, Peter; Porter, Peggy

    2013-01-01

    The Biotrust resource provides a web-accessible method to coordinate discovery and request of annotated biospecimens for research. The system is built on an open-source web-application framework, and has a modular approach to defining education on process, study registration and feasibility review, patient identification and cohort forwarding, consent tracking, and biospecimen processing/distribution. The architecture has been designed as a "pass through" system that provides annotated deidentified biospecimens for investigator use in a restricted time window of 4-7 days, and does not maintain biobanking facilities. As a core institutional resource, the system integrates seven vertical service arms, each of which can be accessed independently to support flexible and independent use in translational research. The system will be described in terms of requirements for use, metrics of evaluation, and lessons learned in integrating this into clinical and operational environments. PMID:24303285

  6. Review: The procurement, storage and quality assurance of frozen blood and tissue biospecimens

    Directory of Open Access Journals (Sweden)

    Manoj S. Charde

    2014-05-01

    Full Text Available The preserved frozen biospecimens are ideal for evaluating the genome, transcriptome, and proteome. Here we present a current overview of experimental data regarding procurement, storage, and quality assurance that can informthe handling of frozen biospecimens. Degradation of frozen biospecimens can be affected by collecting methodology, premortem agonal changes and warm ischemic time during surgery.  Tissue storage at− 80 °C can preserve DNA and protein but RNA show degradation at 5 years, therefore storage at − 150 °C provides significant advantages.  Histologic quality assurance of tissue biospecimens is typically performed at the time of surgery but should also be conducted on the aliquot to be distributed because of tissue heterogeneity.Additional qualityassurance testing should be dictated by the anticipated downstream applications.

  7. Biospecimen Reporting for Improved Study Quality (BRISQ)

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Ph.D., Helen M.; Kelly Ph.D., Andrea; Jewell Ph.D., Scott D.; McShane Ph.D., Lisa M.; Clark M.D., Douglas P.; Greenspan M.D., Renata; Hayes M.D., Daniel F.; Hainaut Ph.D.,, Pierre; Kim, Paula; Mansfield Ph.D., Elizabeth; Potapova Ph.D., Olga; Riegman Ph.D., Peter; Rubinstein Ph.D., Yaffa; Seijo M.S., Edward; Somiari Ph.D., Stella; Watson M.B., Peter; Weier Ph.D., Heinz-Ulrich; Zhu Ph.D., Claire; Vaught Ph.D., Jim

    2011-04-26

    Human biospecimens are subject to a number of different collection, processing, and storage factors that can significantly alter their molecular composition and consistency. These biospecimen preanalytical factors, in turn, influence experimental outcomes and the ability to reproduce scientific results. Currently, the extent and type of information specific to the biospecimen preanalytical conditions reported in scientific publications and regulatory submissions varies widely. To improve the quality of research utilizing human tissues it is critical that information regarding the handling of biospecimens be reported in a thorough, accurate, and standardized manner. The Biospecimen Reporting for Improved Study Quality (BRISQ) recommendations outlined herein are intended to apply to any study in which human biospecimens are used. The purpose of reporting these details is to supply others, from researchers to regulators, with more consistent and standardized information to better evaluate, interpret, compare, and reproduce the experimental results. The BRISQ guidelines are proposed as an important and timely resource tool to strengthen communication and publications around biospecimen-related research and help reassure patient contributors and the advocacy community that the contributions are valued and respected.

  8. Biospecimen Reporting for Improved Study Quality (BRISQ)

    Energy Technology Data Exchange (ETDEWEB)

    National Cancer Institute; Jewell, Ph.D., Scott D.; Seijo, M.S., Edward; Kelly, Ph.D., Andrea; Somiari, Ph.D., Stella; B.Chir., M.B.; McShane, Ph.D., Lisa M.; Clark, M.D., Douglas; Greenspan, M.D., Renata; Hayes, M.D., Daniel F.; Hainaut, Ph.D., M.S., Pierre; Kim, Paula; Mansfield, Ph.D., Elizabeth; Potapova, Ph.D., Olga; Riegman, Ph.D., Peter; Rubinstein, Ph.D., Yaffa; Weier, Ph.D., Heinz-Ulrich; Zhu, Ph.D., Claire; Moore, Ph.D., Helen M.; Vaught, Ph.D., Jim; Watson, Peter

    2010-09-02

    Human biospecimens are subjected to collection, processing, and storage that can significantly alter their molecular composition and consistency. These biospecimen preanalytical factors, in turn, influence experimental outcomes and the ability to reproduce scientific results. Currently, the extent and type of information specific to the biospecimen preanalytical conditions reported in scientific publications and regulatory submissions varies widely. To improve the quality of research that uses human tissues, it is crucial that information on the handling of biospecimens be reported in a thorough, accurate, and standardized manner. The Biospecimen Reporting for Improved Study Quality (BRISQ) recommendations outlined herein are intended to apply to any study in which human biospecimens are used. The purpose of reporting these details is to supply others, from researchers to regulators, with more consistent and standardized information to better evaluate, interpret, compare, and reproduce the experimental results. The BRISQ guidelines are proposed as an important and timely resource tool to strengthen communication and publications on biospecimen-related research and to help reassure patient contributors and the advocacy community that their contributions are valued and respected.

  9. Biospecimen Reporting for Improved Study Quality

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Ph.D., Helen M.; Kelly, Ph.D., Andrea B.; Jewell, Ph.D., Scott D.; McShane, Ph.D., Lisa M.; Clark, M.D., Douglas P.; Greenspan, M.D., Renata; Hayes, M.D., Daniel F.; Hainaut, Ph.D., Pierre; Kim, Paula; Mansfield, Ph.D., Elizabeth A.; Potapova, Ph.D., Olga; Riegman, Ph.D., Peter; Rubinstein, Ph.D., Yaffa; Seijo, M.S., Edward; Somiari, Ph.D., Stella; Chir., B; Weier, Ph.D., Heinz-Ulrich; Zhu, Ph.D., Claire; Vaught, Ph.D., Jim; Watson,M.B., Peter

    2010-12-27

    Human biospecimens are subjected to collection, processing, and storage that can significantly alter their molecular composition and consistency. These biospecimen preanalytical factors, in turn, influence experimental outcomes and the ability to reproduce scientific results. Currently, the extent and type of information specific to the biospecimen preanalytical conditions reported in scientific publications and regulatory submissions varies widely. To improve the quality of research that uses human tissues, it is crucial that information on the handling of biospecimens be reported in a thorough, accurate, and standardized manner. The Biospecimen Reporting for Improved Study Quality (BRISQ) recommendations outlined herein are intended to apply to any study in which human biospecimens are used. The purpose of reporting these details is to supply others, from researchers to regulators, with more consistent and standardized information to better evaluate, interpret, compare, and reproduce the experimental results. The BRISQ guidelines are proposed as an important and timely resource tool to strengthen communication and publications on biospecimen-related research and to help reassure patient contributors and the advocacy community that their contributions are valued and respected.

  10. Biospecimen Repository Access and Data Sharing (BRADS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — BRADS is a repository for data and biospecimens from population health research initiatives and clinical or interventional trials designed and implemented by...

  11. The Future of Biobanking: A Conceptual Look at How Biobanks Can Respond to the Growing Human Biospecimen Needs of Researchers.

    Science.gov (United States)

    Somiari, Stella B; Somiari, Richard I

    2015-01-01

    Biobanking of human biological specimens has evolved from the simple private collection of often poorly annotated residual clinical specimens, to well annotated and organized collections setup by commercial and not-for-profit organizations. The activities of biobanks is now the focus of international and government agencies in recognition of the need to adopt best practices and provide scientific, ethical and legal guidelines for the industry. The demand for more, high quality and clinically annotated biospecimens will increase, primarily due to the unprecedented level of genomic, post genomic and personalized medicine research activities going on. Demand for more biospecimens provides new challenges and opportunities for developing strategies to build biobanking into a business that is better able to supply the biospecimen needs of the future. A paradigm shift is required particularly in organization and funding, as well as in how and where biospecimens are collected, stored and distributed. New collection sites, organized as Research Ready Hospitals (RRHs) and new public-private partnership models are needed for sustainability and increased biospecimen availability. Biobanks will need to adopt industry-wide standard operating procedures, better and "non-destructive" methods for quality assessment, less expensive methods for sample storage/distribution, and objective methods to manage scarce biospecimens. Ultimately, the success of future biobanks will rely greatly on the success of public-private partnerships, number and diversity of available biospecimens, cost management and the realization that an effective biobank is one that provides high quality and affordable biospecimens to drive research that leads to better health and quality of life for all.

  12. A practical tool for modeling biospecimen user fees.

    Science.gov (United States)

    Matzke, Lise; Dee, Simon; Bartlett, John; Damaraju, Sambasivarao; Graham, Kathryn; Johnston, Randal; Mes-Masson, Anne-Marie; Murphy, Leigh; Shepherd, Lois; Schacter, Brent; Watson, Peter H

    2014-08-01

    The question of how best to attribute the unit costs of the annotated biospecimen product that is provided to a research user is a common issue for many biobanks. Some of the factors influencing user fees are capital and operating costs, internal and external demand and market competition, and moral standards that dictate that fees must have an ethical basis. It is therefore important to establish a transparent and accurate costing tool that can be utilized by biobanks and aid them in establishing biospecimen user fees. To address this issue, we built a biospecimen user fee calculator tool, accessible online at www.biobanking.org . The tool was built to allow input of: i) annual operating and capital costs; ii) costs categorized by the major core biobanking operations; iii) specimen products requested by a biobank user; and iv) services provided by the biobank beyond core operations (e.g., histology, tissue micro-array); as well as v) several user defined variables to allow the calculator to be adapted to different biobank operational designs. To establish default values for variables within the calculator, we first surveyed the members of the Canadian Tumour Repository Network (CTRNet) management committee. We then enrolled four different participants from CTRNet biobanks to test the hypothesis that the calculator tool could change approaches to user fees. Participants were first asked to estimate user fee pricing for three hypothetical user scenarios based on their biobanking experience (estimated pricing) and then to calculate fees for the same scenarios using the calculator tool (calculated pricing). Results demonstrated significant variation in estimated pricing that was reduced by calculated pricing, and that higher user fees are consistently derived when using the calculator. We conclude that adoption of this online calculator for user fee determination is an important first step towards harmonization and realistic user fees.

  13. Custodianship as an Ethical Framework for Biospecimen-Based Research

    OpenAIRE

    Yassin, Rihab; Lockhart, Nicole; Riego, Mariana González del; Pitt, Karen; Thomas, Jeffrey W.; Weiss, Linda; Compton, Carolyn

    2010-01-01

    Human biological specimens (biospecimens) are increasingly important for research that aims to advance human health. Yet, despite significant proliferation in specimen-based research and discoveries during the past decade, researchremains challenged by the inequitable access to high quality biospecimens that are collected under rigorous ethical standards. This is primarily caused by the complex level of control and ownership exerted by the myriad of stakeholders involved in the biospecimen re...

  14. International efforts to develop biospecimen best practices.

    Science.gov (United States)

    Vaught, Jimmie B; Caboux, Elodie; Hainaut, Pierre

    2010-04-01

    Variables introduced during the processes involved in biospecimen collection, processing, storage, and analysis are among the potential sources of bias in biomarker research. International efforts are under way to develop best practices to standardize biospecimen handling protocols. In general, documents on best practices address three major recurring themes: technical best practices on infrastructure and specimen handling, recommendations on informatics and data management, and recommendations on ethical, legal, and social issues. There are many areas of agreement among various international efforts, but no single set of practices has emerged as a unifying document. The ethical, legal, and social issues are particularly difficult to harmonize due to the many country-specific issues that are governed by a variety of local and federal rules and regulations. Given the increasingly international nature of research involving biomarkers and biospecimens, it will be necessary to continue to cooperate in the development of harmonized evidence-based best practices. Several international organizations including the International Cancer Genome Consortium are engaged in such efforts.

  15. Preanalytical Variables Affecting the Integrity of Human Biospecimens in Biobanking

    DEFF Research Database (Denmark)

    Ellervik, Christina; Vaught, Jim

    2015-01-01

    BACKGROUND: Most errors in a clinical chemistry laboratory are due to preanalytical errors. Preanalytical variability of biospecimens can have significant effects on downstream analyses, and controlling such variables is therefore fundamental for the future use of biospecimens in personalized...... medicine for diagnostic or prognostic purposes. CONTENT: The focus of this review is to examine the preanalytical variables that affect human biospecimen integrity in biobanking, with a special focus on blood, saliva, and urine. Cost efficiency is discussed in relation to these issues. SUMMARY: The quality...

  16. Biospecimen quality program in the biobank of the Norwegian Institute of Public Health

    Directory of Open Access Journals (Sweden)

    Liv Paltiel

    2012-04-01

    Full Text Available Background: The biological material collected, processed and stored in biobanks are important research tools and it is important to minimize preanalytical variations to provide researchers with high quality biological material that will give reproducible results. Methods: To minimize the preanalytical variations caused by sample collection, processing and storage, we have established a biospecimen quality program. It consists of quality assurance aspects as well as quality control programs to measure adherence to protocols and sample integrity. The quality control program includes measurements and evaluation of the DNA quality and quantity before storage, i.e. concentration, purity, fragmentation and PCR success, and long term storage programs for plasma, urine and RNA. Conclusions: The Biobank at the Norwegian Institute of Public Health has established a biospecimen quality program that ensures high quality specimens and provides the documentation required to use the biomaterial in a best possible way.

  17. Study of Womens Health Across the Nation (SWAN) Biospecimen Repository

    Data.gov (United States)

    U.S. Department of Health & Human Services — The SWAN Repository is the biospecimen bank of the SWAN study. All stored specimens are from the 3,302 SWAN participants, collected across the 14 clinic visits...

  18. Predictors of biospecimen donation in the Black Women’s Health Study

    Science.gov (United States)

    Adams-Campbell, Lucile L.; Dash, Chiranjeev; Palmer, Julie R.; Wiedemeier, Manuela V.; Russell, Cordelia W.; Rosenberg, Lynn; Cozier, Yvette C.

    2016-01-01

    Purpose Although African-Americans experience higher cancer morbidity and mortality rates compared to their White counterparts, their participation in biospecimen research is lower than that of their white peers. This study investigated the prevalence and predictors of biospecimen donation in a large, cohort study of Black women. Methods The BWHS is a follow-up study of U.S. Black women aged 21–69 years enrolled through postal health questionnaires. Between January 2004 and December 2007, participants were sent a consent form with a postage-paid return envelope, and a mouthwash collection kit. Univariate and age- and educational status-adjusted logistic regression models were used to estimate the association of socio-demographic, lifestyle and medical factors with donation of biospecimens. Results Buccal cells with consent forms were obtained from 26,790 women, for a response rate of 51 %. The strongest predictors of biospecimen donation were age: response increased from 48.6 % among those aged <40 to 63.1 % among those aged 60 and older [RR 1.30 (95 % CI 1.27, 1.34)]; multivitamin use [RR (95 % CI) 1.32 (1.30, 1.34)]; physician visit in the previous 2 years [RR (95 % CI) 1.61 (1.58, 1.65)], and a history of breast [RR (95 % CI) 1.59 (1.56, 1.63)], colon [RR (95 % CI) 1.18 (1.16, 1.20)], and cervical [RR (95 % CI) 1.63 (1.60, 1.67)] cancer screening. Conclusions We found that 51 % of women in the geographically-dispersed Black Women’s Health Study cohort were willing to provide mouthwash samples to be used for genetic analyses. The response in this study is encouraging given published findings of low overall participation rates of African-Americans in genetic studies. PMID:27106577

  19. A Federated Network for Translational Cancer Research Using Clinical Data and Biospecimens.

    Science.gov (United States)

    Jacobson, Rebecca S; Becich, Michael J; Bollag, Roni J; Chavan, Girish; Corrigan, Julia; Dhir, Rajiv; Feldman, Michael D; Gaudioso, Carmelo; Legowski, Elizabeth; Maihle, Nita J; Mitchell, Kevin; Murphy, Monica; Sakthivel, Mayurapriyan; Tseytlin, Eugene; Weaver, JoEllen

    2015-12-15

    Advances in cancer research and personalized medicine will require significant new bridging infrastructures, including more robust biorepositories that link human tissue to clinical phenotypes and outcomes. In order to meet that challenge, four cancer centers formed the Text Information Extraction System (TIES) Cancer Research Network, a federated network that facilitates data and biospecimen sharing among member institutions. Member sites can access pathology data that are de-identified and processed with the TIES natural language processing system, which creates a repository of rich phenotype data linked to clinical biospecimens. TIES incorporates multiple security and privacy best practices that, combined with legal agreements, network policies, and procedures, enable regulatory compliance. The TIES Cancer Research Network now provides integrated access to investigators at all member institutions, where multiple investigator-driven pilot projects are underway. Examples of federated search across the network illustrate the potential impact on translational research, particularly for studies involving rare cancers, rare phenotypes, and specific biologic behaviors. The network satisfies several key desiderata including local control of data and credentialing, inclusion of rich phenotype information, and applicability to diverse research objectives. The TIES Cancer Research Network presents a model for a national data and biospecimen network.

  20. A Federated Network for Translational Cancer Research Using Clinical Data and Biospecimens.

    Science.gov (United States)

    Jacobson, Rebecca S; Becich, Michael J; Bollag, Roni J; Chavan, Girish; Corrigan, Julia; Dhir, Rajiv; Feldman, Michael D; Gaudioso, Carmelo; Legowski, Elizabeth; Maihle, Nita J; Mitchell, Kevin; Murphy, Monica; Sakthivel, Mayurapriyan; Tseytlin, Eugene; Weaver, JoEllen

    2015-12-15

    Advances in cancer research and personalized medicine will require significant new bridging infrastructures, including more robust biorepositories that link human tissue to clinical phenotypes and outcomes. In order to meet that challenge, four cancer centers formed the Text Information Extraction System (TIES) Cancer Research Network, a federated network that facilitates data and biospecimen sharing among member institutions. Member sites can access pathology data that are de-identified and processed with the TIES natural language processing system, which creates a repository of rich phenotype data linked to clinical biospecimens. TIES incorporates multiple security and privacy best practices that, combined with legal agreements, network policies, and procedures, enable regulatory compliance. The TIES Cancer Research Network now provides integrated access to investigators at all member institutions, where multiple investigator-driven pilot projects are underway. Examples of federated search across the network illustrate the potential impact on translational research, particularly for studies involving rare cancers, rare phenotypes, and specific biologic behaviors. The network satisfies several key desiderata including local control of data and credentialing, inclusion of rich phenotype information, and applicability to diverse research objectives. The TIES Cancer Research Network presents a model for a national data and biospecimen network. PMID:26670560

  1. [Current modalities and concepts on access and use of biospecimen samples and associated data for research from human biobanks].

    Science.gov (United States)

    Siddiqui, Roman; Semler, Sebastian Claudius

    2016-03-01

    It is accepted worldwide that biospecimen and data sharing (BDS) play an essential role for the future of medical research to improve diagnostics and prognostics, e.g. by validated biomarkers. BDS is also pivotal to the development of new therapeutic treatments and for the improvement of population health. Human biobanks can generate an added value to this need by providing biospecimens and/or associated data to researchers. An inspection of several examples of epidemiological as well as clinical/disease-oriented biobanks in Germany shows that best practice procedures (BPP) that are internationally agreed on are being installed for biospecimen and/or data access. In general, fair access is aimed at requiring a written application by the requesting scientist, which is then peer-reviewed for scientific and ethical validity by the Biobank. Applied BPP take into account (i) patient education/agreement according to the informed consent model, (ii) privacy protection, (iii) intellectual property rights, the (iv) notification obligation of health-related findings (including incidental findings), the (v) use of material (MTA) and data transfer agreements (DTA) for mutual legal security, the avoidance of conflicts of interests, as well as for cost recovery/fee for service as a basis for sustainability of the biobank. BPP are rooted in the self-regulation efforts of life sciences and are supported by parent ethics committees in Germany. Central biobank registries displaying aggregated information on biospecimens stored and the research foci constitute an important tool to make biobanks that are scattered across the country visible to each other, and, can thus promote access to hitherto unknown biospecimen and data resources. PMID:26809822

  2. The CAS Bio-specimen Centers in Sound Progress

    Institute of Scientific and Technical Information of China (English)

    LI Liangqian; QIAO Gexia; YAO Yijian

    2010-01-01

    @@ Bio-specimen centers, including herbaria and zoological museums, are the most integrated places for the storage of specimens, which are real samples and the most important vouchers for taxonomic and biodiversity studies.The information carried by the specimens is of substantial reference for research on species distribution, history, status, phylogeny and evolution, etc.

  3. Evaluation of the BCR sequential extraction procedure applied for two unpolluted Spanish soils

    International Nuclear Information System (INIS)

    The procedure of BCR sequential extraction has been applied to five samples from two unpolluted soils in southern Spain. Total concentrations of different elements have been calculated as the sum of the three fractions of BCR and the residue has been measured for each. Also, a total analysis based on INAA or total-digestion techniques has been performed for the same samples. BCR and total analysis closely agreed for As, Pb and Cd. For Cu, Co, Cr and Zn the comparison of the results did not provide definitive conclusions concerning the capability of BCR in measuring total concentrations. On the other hand, in these cases, a certain correlation was found between the concentrations measured and some soil characteristics, especially the clay, organic-matter and CaCO3 contents. BCR proved incapable of providing accurate measurements for Ni

  4. Biobanking Comes of Age: The Transition to Biospecimen Science.

    Science.gov (United States)

    Vaught, Jim

    2016-01-01

    Biobanking involves the collection, processing, storage, and distribution of biological specimens and the policies and procedures necessary to accomplish those aims successfully. Although biobanking may also involve collections for environmental studies or museum archives, most efforts to standardize biobanking practices have been directed toward human biomedical research. Initially focused primarily on collecting samples for diagnostic purposes in pathology settings, biobanks have evolved into complex organizations engaged in advancing personalized (or precision) medicine and translational research. This evolution has involved the development of biobanking best practices and the transformation of a field driven by empirical approaches into the emerging area of biospecimen science. It has become increasingly important to develop evidence-based practices for collecting biospecimens and data that can be shared with confidence with international collaborators. Aside from these technical approaches, other factors play crucial roles, such as ethical and regulatory issues, business planning and sustainability, and approaches to data collection and sharing. PMID:26514206

  5. TRWG developmental pathway for biospecimen-based assessment modalities

    Energy Technology Data Exchange (ETDEWEB)

    Translational Research Working Group; Srivastava, Sudhir; Gray, Joe W.; Reid, Brian J.; Grad, Oren; Greenwood, Addison; Hawk, Ernest T.

    2008-09-03

    The Translational Research Working Group (TRWG) was created as a national initiative to evaluate the current status of NCI's investment in translational research and envision its future. The TRWG conceptualized translational research as a set of six developmental processes or pathways focused on various clinical goals. One of those pathways describes the development of biospecimen-based assays that utilize biomarkers for the detection, diagnosis, prognosis, and assessment of response to cancer treatment. The biospecimen-based assessment modality (BM) pathway was conceived not as comprehensive description of the corresponding real-world processes, but rather as a tool designed to facilitate movement of a candidate assay through the translational process to the point where it can be handed off for definitive clinical testing. This paper introduces the pathway in the context of prior work and discusses key challenges associated with the biomarker development process in light of the pathway.

  6. Factors associated with willingness to participate in biospecimen research among Chinese Americans.

    Science.gov (United States)

    Gao, Wanzhen; Ma, Grace X; Tan, Yin; Fang, Carolyn; Weaver, JoEllen; Jin, Ming; Lai, Philip

    2014-04-01

    A paucity of information exists on the recruitment of Asian Americans for biospecimen research. Although studies show that Chinese Americans are at high risk for hepatitis B virus (HBV) infection, little is known about their willingness to participate in HBV-related biospecimen research and how knowledge, attitudes, and cultural factors impact their willingness to participate. The study was guided by Community-Based Participatory Research principles. Data were derived from an assessment study on HBV-related biospecimen research participation among Chinese Americans in the Philadelphia region. The assessment was conducted with 415 Chinese Americans recruited from eight Chinese community-based organizations. Cultural beliefs, knowledge, and attitudes toward biospecimen research were examined for associations with their willingness to participate in biospecimen banking research. Overall, 192 (46.3%) of 415 participants who completed the assessment indicated they were willing to participate if they were invited to donate blood to be frozen and stored for future HBV biospecimen studies. Cultural variables significant in bivariate analysis included collectivism, knowledge about biospecimen research, and Yin-Yang beliefs. Fatalism and individualism were not associated with participation willingness. In multivariate analysis, age, health care attitudes, and trust were significantly associated with willingness to participate in biospecimen banking research. Asian American communities have little knowledge of biospecimen banking and will benefit from educational campaigns that emphasize collective benefits and attitudes towards and trust in the health care system. Understanding cultural factors is important for improving Chinese Americans' knowledge, awareness, and intentions of participation in biospecimen research. Similar efforts need to be undertaken to develop culturally appropriate educational intervention programs to increase participation in biospecimen research

  7. 75 FR 51830 - National Cancer Institute's Best Practices for Biospecimen Resources

    Science.gov (United States)

    2010-08-23

    ... HUMAN SERVICES National Institutes of Health National Cancer Institute's Best Practices for Biospecimen... best practices, the National Cancer Institute (NCI) is seeking public comment on a revised version of the NCI Best Practices for Biospecimen Resources. This revised version of the NCI Best Practices...

  8. BCR Routing for Intermittently Connected Mobile Ad hoc Networks

    Directory of Open Access Journals (Sweden)

    S. RAMESH

    2014-03-01

    Full Text Available The Wireless and the Mobile Networks appear to provide a wide range of applications. Following these, the Mobile Ad hoc Networks (MANET aid in wide development of many applications. The achievement of the real world applications are attained through effective routing. The Intermittently Connected Mobile Ad hoc Network (ICMANET is a sparse network where a full connectivity is never possible. ICMANET is a disconnected MANET and is also a Delay Tolerant Network (DTN that sustains for higher delays. The routing in a disseminated network is a difficult task. A new routing scheme called Bee Colony Routing (BCR is been proposed with a motto of achieving optimal result in delivering the data packet towards the destined node. BCR is proposed with the basis of Bee Colony Optimization technique (BCO. The routing in ICMNAET is done by means of Bee routing protocol. This paper enchants a novel routing methodology for data transmission in ICMANET.

  9. Comparative study of optimised BCR sequential extraction scheme and acid leaching of elements in the certified reference material NIST 2711

    International Nuclear Information System (INIS)

    The optimised BCR sequential extraction procedure and a 4 h 1 mol L-1 HCl partial extraction have been performed on the NIST 2711 reference material for a suite of 12 elements (Cd, Sb, Pb, Al, Cr, Mn, Fe, Co, Ni, Cu, Zn, As) using magnetic sector ICP-MS. A pseudo-total aqua regia digest of NIST 2711 has also been undertaken for quality assurance purposes, and comparison of the sum of the four BCR fractions, which included an aqua regia digest on the residue, with the pseudo-total aqua regia digest has been used to assess the accuracy of the BCR partitioning approach. As a result of this work, discrepancies between previous studies about BCR partitioning of elements in NIST 2711 have been discussed and an increase in confidence about the use of BCR partitioning scheme on seven elements (Cd, Pb, Al, Mn, Fe, Cu, Zn) in this standard material has been obtained. On the other hand, BCR partitioning for Sb, Cr, Co, Ni and As has been provided for the first time. Partial extraction results are also reported for the same 12 elements analysed by the optimised BCR procedure, with the partial extraction results exhibiting a strong correlation with the sum of the three labile steps of the BCR procedure

  10. 76 FR 38191 - New Proposed Collection; Comment Request; Biospecimen and Physical Measures Formative Research...

    Science.gov (United States)

    2011-06-29

    ... Physical Measures Formative Research Methodology Studies for the National Children's Study SUMMARY: In... comment questioned the cost and utility of the study and federally funded biomedical research in general...: Title: Biospecimen and Physical Measures Formative Research Methodology Studies for the...

  11. 76 FR 23609 - New Proposed Collection; Comment Request; Biospecimen and Physical Measures Formative Research...

    Science.gov (United States)

    2011-04-27

    ... questionnaires, storage and information management processes, and assay procedures, thereby informing data... formative research activities relating to the collection, storage, management, and assay of biospecimen and... Physical Measures Formative Research Methodology Studies for the National Children's Study SUMMARY:...

  12. BCR-ABL Translocation in Pediatric Acute Lymphoblastic Leukemia in Southern India.

    Science.gov (United States)

    Sugapriya, D; Preethi, S; Shanthi, P; Chandra, N; Jeyaraman, G; Sachdanandam, P; Thilagavathy, S; Venkatadesilalu, S

    2012-03-01

    Cytogenetics and polymerase chain reaction (PCR) based assays provide important information regarding biologically defined and prognostically relevant subgroups in acute leukemias. We utilized karyotyping and molecular analysis by reverse transcriptase PCR for the BCR-ABL translocation, in addition to morphological study, cytochemistry and immunophenotyping, to study 24 cases of pediatric acute lymphoblastic leukemia (ALL). Our objective was to determine the frequency of the BCRABL translocation in childhood ALL from southern India. Karyotyping showed one case of hyperdiploidy, one case of t (12; 21) translocation and one case of 46, XY-21+mar. The BCR-ABL translocation was found in 8.3% of these cases. One of these was a cryptic translocation, the karyotype being normal. BCR-ABL positivity in ALL is associated with aggressive disease and has been shown to be a poor prognostic factor, especially in children. PMID:23449388

  13. World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project: III. Fluid biospecimen collection, processing, and storage in endometriosis research

    DEFF Research Database (Denmark)

    Rahmioglu, Nilufer; Fassbender, Amelie; Vitonis, Allison F.;

    2014-01-01

    ObjectiveTo harmonize standard operating procedures (SOPs) and standardize the recording of associated data for collection, processing, and storage of fluid biospecimens relevant to endometriosis.......ObjectiveTo harmonize standard operating procedures (SOPs) and standardize the recording of associated data for collection, processing, and storage of fluid biospecimens relevant to endometriosis....

  14. Lessons from HeLa Cells: The Ethics and Policy of Biospecimens

    Science.gov (United States)

    Beskow, Laura M.

    2016-01-01

    Human biospecimens have played a crucial role in scientific and medical advances. Although the ethical and policy issues associated with biospecimen research have long been the subject of scholarly debate, the story of attention of a much broader audience. The story has been a catalyst for policy change, including major regulatory changes proposed in the United States surrounding informed consent. These proposals are premised in part on public opinion data, necessitating a closer look at what such data tell us. The development of biospecimen policy should be informed by many considerations—one of which is public input, robustly gathered, on acceptable approaches that optimize shared interests, including access for all to the benefits of research. There is a need for consent approaches that are guided by realistic aspirations and a balanced view of autonomy within an expanded ethical framework. PMID:26979405

  15. Expression of PTD-bcr/abl fusion oncoprotein fragment carrying protein transduction domain and its transmembrane transportation%PTD-bcr/abl融合癌蛋白片段的表达及其跨膜转运

    Institute of Scientific and Technical Information of China (English)

    梁英民; 孙强; 蒋姗姗; 陈萍; 王冀姝; 刘利; 韩骅

    2001-01-01

    Aim To explore the method of transfering oncoprotein bcr/abl, mediated by protein transduction domain (PTD), in order to provide the experimental basis for immune therapy. Methods DNA fragment encoding PTD was synthesized and fused with PCR-amplified bcr/abl gene fragment. The fusion protein was expressed in E.coli as His-tagged protein. The purified fusion protein was loaded to cultured HL-60 cells. Whether the fusion protein entered into HL-60 cells was determined by Western blot. Results It is shown that PTD could mediate transportation of bcr/abl protein to enter into cells. Conclusion These results may provide a new approach for loading exogenous proteins to antigen presenting cells.%目的探讨蛋白转导结构域 (PTD)介导的转导 bcr/abl癌蛋白片段的方法,为进行免疫治疗提供实验依据。方法合成编码 PTD的基因片段,并与 PCR扩增的慢性粒细胞白血病癌蛋白 bcr/abl基因片段融合 ,在大肠杆菌中表达。将纯化的融合蛋白 PTD-bcr/abl与 HL-60 细胞共孵育,用 Western blot分析融合蛋白的跨膜转运。结果 PTD基序可介导 bcr/abl蛋白由细胞外跨膜转导进入细胞内。结论这一结果可能为应用外源蛋白负载 (loading)抗原提呈细胞 (APC)提供新的途径。

  16. Molecular Detection of BCR-ABL in Chronic Myeloid Leukemia.

    Science.gov (United States)

    Qin, Ya-Zhen; Huang, Xiao-Jun

    2016-01-01

    All chronic myeloid leukemia (CML) patients have the BCR-ABL fusion gene. The constitutively activated BCR-ABL tyrosine kinase is a critical pathogenetic event in CML. Tyrosine kinase inhibitors (TKIs), such as imatinib, are synthesized small molecules that primarily target BCR-ABL tyrosine kinases and have become a first-line treatment for CML. Detection of BCR-ABL transcript level by real-time quantitative polymerase chain reaction (RQ-PCR) is a clinical routine for evaluating TKI treatment efficacy and predicting long-term response. Furthermore, because they are a main TKI resistance mechanism, the BCR-ABL tyrosine kinase domain (TKD) point mutations that are detected by Sanger sequencing can help clinicians make decisions on subsequent treatment selections. Here, we present protocols for the two abovementioned molecular methods for CML analysis. PMID:27581134

  17. Induction of autophagy by Imatinib sequesters Bcr-Abl in autophagosomes and down-regulates Bcr-Abl protein.

    LENUS (Irish Health Repository)

    Elzinga, Baukje M

    2013-06-01

    Chronic Myeloid Leukemia (CML) is a disease of hematopoietic stem cells which harbor the chimeric gene Bcr-Abl. Expression levels of this constitutively active tyrosine kinase are critical for response to tyrosine kinase inhibitor treatment and also disease progression, yet the regulation of protein stability is poorly understood. We have previously demonstrated that imatinib can induce autophagy in Bcr-Abl expressing cells. Autophagy has been associated with the clearance of large macromolecular signaling complexes and abnormal proteins, however, the contribution of autophagy to the turnover of Bcr-Abl protein in imatinib treated cells is unknown. In this study, we show that following imatinib treatment, Bcr-Abl is sequestered into vesicular structures that co-localize with the autophagy marker LC3 or GABARAP. This association is inhibited by siRNA mediated knockdown of autophagy regulators (Beclin 1\\/ATG7). Pharmacological inhibition of autophagy also reduced Bcr-Abl\\/LC3 co-localization in both K562 and CML patient cells. Bcr-Abl protein expression was reduced with imatinib treatment. Inhibition of both autophagy and proteasome activity in imatinib treated cells was required to restore Bcr-Abl protein levels to those of untreated cells. This ability to down-regulate Bcr-Abl protein levels through the induction of autophagy may be an additional and important feature of the activity of imatinib.

  18. Comparative study of DNA damage, cell cycle and apoptosis in human K562 and CCRF-CEM leukemia cells: role of BCR/ABL in therapeutic resistance.

    Science.gov (United States)

    Pytel, Dariusz; Wysocki, Tomasz; Majsterek, Ireneusz

    2006-09-01

    The Philadelphia translocation t(9;22) resulting in the bcr/abl fusion gene is the pathogenic principle of almost 95% of human chronic myelogenous leukemia (CML). Imatinib mesylate (STI571) is a specific inhibitor of the BCR/ABL fusion tyrosine kinase that exhibits potent antileukemic effects in CML. BCR/ABL-positive K562 and -negative CCRF-CEM human leukemia cells were investigated. MTT survival assay and clonogenic test of the cell proliferation ability were used to estimate resistance against idarubicin. DNA damage after cell treatment with the drug at the concentrations from 0.001 to 3 microM with or without STI571 pre-treatment were examined by the alkaline comet assay. We found that the level of DNA damages was lower in K562 cells after STI571 pre-treatment. It is suggested that BCR/ABL activity may promote genomic instability, moreover K562 cells were found to be resistant to the drug treatment. Further, we provided evidence of apoptosis inhibition in BCR/ABL-positive cells using caspase-3 activity colorimetric assay and DAPI nuclear staining for chromatin condensation. We suggest that these processes associated with cell cycle arrest in G2/M checkpoint detected in K562 BCR/ABL-positive compared to CCRF-CEM cells without BCR/ABL expression might promote clone selection resistance to drug treatment.

  19. Transferred BCR/ABL DNA from K562 extracellular vesicles causes chronic myeloid leukemia in immunodeficient mice.

    Directory of Open Access Journals (Sweden)

    Jin Cai

    Full Text Available Our previous study showed that besides mRNAs and microRNAs, there are DNA fragments within extracellular vesicles (EVs. The BCR/ABL hybrid gene, involved in the pathogenesis of chronic myeloid leukemia (CML, could be transferred from K562 EVs to neutrophils and decrease their phagocytic activity in vitro. Our present study provides evidence that BCR/ABL DNAs transferred from EVs have pathophysiological significance in vivo. Two months after injection of K562 EVs into the tail vein of Sprague-Dawley (SD rats, they showed some characteristics of CML, e.g., feeble, febrile, and thin, with splenomegaly and neutrophilia but with reduced neutrophil phagocytic activity. These findings were also observed in immunodeficient NOD/SCID mice treated with K562 EVs; BCR/ABL mRNA and protein were found in their neutrophils. The administration of actinomycin D, an inhibitor of de novo mRNA synthesis, prevented the abnormalities caused by K562 EVs in NOD/SCID mice related to CML, including neutrophilia and bone marrow hyperplasia. As a specific inhibitor of tyrosine kinases, imatinib blocked the activity of tyrosine kinases and the expression of phospho-Crkl, induced by the de novo BCR/ABL protein caused by K562 EVs bearing BCR/ABL DNA. Our current study shows the pathophysiological significance of transferred tumor gene from EVs in vivo, which may represent an important mechanism for tumorigenesis, tumor progression, and metastasis.

  20. Targeting Hedgehog signaling pathway and autophagy overcomes drug resistance of BCR-ABL-positive chronic myeloid leukemia.

    Science.gov (United States)

    Zeng, Xian; Zhao, Hui; Li, Yubin; Fan, Jiajun; Sun, Yun; Wang, Shaofei; Wang, Ziyu; Song, Ping; Ju, Dianwen

    2015-01-01

    The frontline tyrosine kinase inhibitor (TKI) imatinib has revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, drug resistance is the major clinical challenge in the treatment of CML. The Hedgehog (Hh) signaling pathway and autophagy are both related to tumorigenesis, cancer therapy, and drug resistance. This study was conducted to explore whether the Hh pathway could regulate autophagy in CML cells and whether simultaneously regulating the Hh pathway and autophagy could induce cell death of drug-sensitive or -resistant BCR-ABL(+) CML cells. Our results indicated that pharmacological or genetic inhibition of Hh pathway could markedly induce autophagy in BCR-ABL(+) CML cells. Autophagic inhibitors or ATG5 and ATG7 silencing could significantly enhance CML cell death induced by Hh pathway suppression. Based on the above findings, our study demonstrated that simultaneously inhibiting the Hh pathway and autophagy could markedly reduce cell viability and induce apoptosis of imatinib-sensitive or -resistant BCR-ABL(+) cells. Moreover, this combination had little cytotoxicity in human peripheral blood mononuclear cells (PBMCs). Furthermore, this combined strategy was related to PARP cleavage, CASP3 and CASP9 cleavage, and inhibition of the BCR-ABL oncoprotein. In conclusion, this study indicated that simultaneously inhibiting the Hh pathway and autophagy could potently kill imatinib-sensitive or -resistant BCR-ABL(+) cells, providing a novel concept that simultaneously inhibiting the Hh pathway and autophagy might be a potent new strategy to overcome CML drug resistance.

  1. BCR-ABL Promotes PTEN Downregulation in Chronic Myeloid Leukemia

    OpenAIRE

    Cristina Panuzzo; Sabrina Crivellaro; Giovanna Carrà; Angelo Guerrasio; Giuseppe Saglio; Alessandro Morotti

    2014-01-01

    Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the t(9;22) translocation coding for the chimeric protein p210 BCR-ABL. The tumor suppressor PTEN plays a critical role in the pathogenesis of CML chronic phase, through non genomic loss of function mechanisms, such as protein down-regulation and impaired nuclear/cytoplasmic shuttling. Here we demonstrate that BCR-ABL promotes PTEN downregulation through a MEK dependent pathway. Furthermore, we describe a novel n...

  2. Environment-mediated drug resistance in Bcr/Abl-positive acute lymphoblastic leukemia

    OpenAIRE

    Feldhahn, Niklas; Arutyunyan, Anna; Stoddart, Sonia; ZHANG Bin; Schmidhuber, Sabine; Yi, Sun-ju; Kim, Yong-Mi; Groffen, John; Heisterkamp, Nora

    2012-01-01

    Although cure rates for acute lymphoblastic leukemia (ALL) have increased, development of resistance to drugs and patient relapse are common. The environment in which the leukemia cells are present during the drug treatment is known to provide significant survival benefit. Here, we have modeled this process by culturing murine Bcr/Abl-positive acute lymphoblastic leukemia cells in the presence of stroma while treating them with a moderate dose of two unrelated drugs, the farnesyltransferase i...

  3. Leveraging a clinical research information system to assist biospecimen data and workflow management: a hybrid approach

    Science.gov (United States)

    2011-01-01

    Background Large multi-center clinical studies often involve the collection and analysis of biological samples. It is necessary to ensure timely, complete and accurate recording of analytical results and associated phenotypic and clinical information. The TRIBE-AKI Consortium http://www.yale.edu/tribeaki supports a network of multiple related studies and sample biorepository, thus allowing researchers to take advantage of a larger specimen collection than they might have at an individual institution. Description We describe a biospecimen data management system (BDMS) that supports TRIBE-AKI and is intended for multi-center collaborative clinical studies that involve shipment of biospecimens between sites. This system works in conjunction with a clinical research information system (CRIS) that stores the clinical data associated with the biospecimens, along with other patient-related parameters. Inter-operation between the two systems is mediated by an interactively invoked suite of Web Services, as well as by batch code. We discuss various challenges involved in integration. Conclusions Our experience indicates that an approach that emphasizes inter-operability is reasonably optimal in allowing each system to be utilized for the tasks for which it is best suited. PMID:21884570

  4. A critical role of CDKN3 in Bcr-Abl-mediated tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Qinghuang Chen

    Full Text Available CDKN3 (cyclin-dependent kinase inhibitor 3, a dual specificity protein phosphatase, dephosphorylates cyclin-dependent kinases (CDKs and thus functions as a key negative regulator of cell cycle progression. Deregulation or mutations of CDNK3 have been implicated in various cancers. However, the role of CDKN3 in Bcr-Abl-mediated chronic myelogenous leukemia (CML remains unknown. Here we found that CDKN3 acts as a tumor suppressor in Bcr-Abl-mediated leukemogenesis. Overexpression of CDKN3 sensitized the K562 leukemic cells to imanitib-induced apoptosis and dramatically inhibited K562 xenografted tumor growth in nude mouse model. Ectopic expression of CDKN3 significantly reduced the efficiency of Bcr-Abl-mediated transformation of FDCP1 cells to growth factor independence. In contrast, depletion of CDKN3 expression conferred resistance to imatinib-induced apoptosis in the leukemic cells and accelerated the growth of xenograph leukemia in mice. In addition, we found that CDKN3 mutant (CDKN3-C140S devoid of the phosphatase activity failed to affect the K562 leukemic cell survival and xenografted tumor growth, suggesting that the phosphatase of CDKN3 was required for its tumor suppressor function. Furthermore, we observed that overexpression of CDKN3 reduced the leukemic cell survival by dephosphorylating CDK2, thereby inhibiting CDK2-dependent XIAP expression. Moreover, overexpression of CDKN3 delayed G1/S transition in K562 leukemic cells. Our results highlight the importance of CDKN3 in Bcr-Abl-mediated leukemogenesis, and provide new insights into diagnostics and therapeutics of the leukemia.

  5. CD40 signaling synergizes with TLR-2 in the BCR independent activation of resting B cells.

    Science.gov (United States)

    Jain, Shweta; Chodisetti, Sathi Babu; Agrewala, Javed N

    2011-01-01

    Conventionally, signaling through BCR initiates sequence of events necessary for activation and differentiation of B cells. We report an alternative approach, independent of BCR, for stimulating resting B (RB) cells, by involving TLR-2 and CD40--molecules crucial for innate and adaptive immunity. CD40 triggering of TLR-2 stimulated RB cells significantly augments their activation, proliferation and differentiation. It also substantially ameliorates the calcium flux, antigen uptake capacity and ability of B cells to activate T cells. The survival of RB cells was improved and it increases the number of cells expressing activation induced deaminase (AID), signifying class switch recombination (CSR). Further, we also observed increased activation rate and decreased threshold period required for optimum stimulation of RB cells. These results corroborate well with microarray gene expression data. This study provides novel insights into coordination between the molecules of innate and adaptive immunity in activating B cells, in a BCR independent manner. This strategy can be exploited to design vaccines to bolster B cell activation and antigen presenting efficiency, leading to faster and better immune response. PMID:21674065

  6. CD40 signaling synergizes with TLR-2 in the BCR independent activation of resting B cells.

    Directory of Open Access Journals (Sweden)

    Shweta Jain

    Full Text Available Conventionally, signaling through BCR initiates sequence of events necessary for activation and differentiation of B cells. We report an alternative approach, independent of BCR, for stimulating resting B (RB cells, by involving TLR-2 and CD40--molecules crucial for innate and adaptive immunity. CD40 triggering of TLR-2 stimulated RB cells significantly augments their activation, proliferation and differentiation. It also substantially ameliorates the calcium flux, antigen uptake capacity and ability of B cells to activate T cells. The survival of RB cells was improved and it increases the number of cells expressing activation induced deaminase (AID, signifying class switch recombination (CSR. Further, we also observed increased activation rate and decreased threshold period required for optimum stimulation of RB cells. These results corroborate well with microarray gene expression data. This study provides novel insights into coordination between the molecules of innate and adaptive immunity in activating B cells, in a BCR independent manner. This strategy can be exploited to design vaccines to bolster B cell activation and antigen presenting efficiency, leading to faster and better immune response.

  7. BCR-ABL DERIVED PEPTIDE VACCINES FOR CHRONIC MYELOID LEUKAEMIA

    Directory of Open Access Journals (Sweden)

    M. Bocchia

    2012-01-01

    Full Text Available Chronic Myeloid Leukemia (CML is a myeloproliferative pluripotent stem cell disorder characterized by the presence of a cytogenetic hallmark, the Philadelphia (Ph chromosome, and accounts for 15% of adult leukemias. The disease progresses from a chronic phase through an accelerated phase to a blast phase and its natural course accounts for a median 4 years survival1. The Ph chromosome is derived by a reciprocal translocation termed t(9;22 in which the c-abl oncogene has moved from chromosome 9 into the breakpoint cluster region (bcr, within the bcr gene on chromosome 22, resulting in a chimeric bcr-abl fusion gene that encodes a 210 KD protein (p210 with constitutive tyrosine kinase activity. Two major alternative chimeric p210 can result from this fusion gene: p210-b2a2 where the junction occurs between bcr exon 2 (b2 and abl exon 2 (a2 and p210-b3a2 where the the junction occurs between bcr exon 3 (b3 and abl exon 2 (a2. About 40% of CML patients harbor the p210-b2a2 and about 60% of them show the p210-b3a2.

  8. INHIBITION OF APOPTOSIS BY bcr-abl FUSION GENE IN K562 CELLS

    Institute of Scientific and Technical Information of China (English)

    WANG Chun-hong; SUN Bing-zhong; YUAN Yue-chuan

    1999-01-01

    Objective: To investigate the effect of bcr-abl fusion gene on CML cell apoptosis. Methods: Apoptosis of exvivo cultured K562 cells were observed after exposure to synthetic 18 mer antisense oligodeoxynucleotide complementary to the bcr-abl junction (b3a2). Results: Apoptosis of K562 cells was significantly increased associated with inhibition of bcr-abl expression. Conclusion: bcr-abl fusion gene formation due to chromosome translocation may be the major mechanism of CML via inhibition of apoptosis.

  9. Imatinib-dependent tyrosine phosphorylation profiling of Bcr-Abl-positive chronic myeloid leukemia cells

    OpenAIRE

    Preisinger, C.; Schwarz, J. P.; Bleijerveld, O.B.; et al

    2012-01-01

    Bcr-Abl is the major cause and pathogenetic principle of chronic myeloid leukemia (CML). Bcr-Abl results from a chromosomal translocation that fuses the bcr and abl genes, thereby generating a constitutively active tyrosine kinase, which stimulates several signaling networks required for proliferation and survival. peer-reviewed

  10. Statistical design for biospecimen cohort size in proteomics-based biomarker discovery and verification studies.

    Science.gov (United States)

    Skates, Steven J; Gillette, Michael A; LaBaer, Joshua; Carr, Steven A; Anderson, Leigh; Liebler, Daniel C; Ransohoff, David; Rifai, Nader; Kondratovich, Marina; Težak, Živana; Mansfield, Elizabeth; Oberg, Ann L; Wright, Ian; Barnes, Grady; Gail, Mitchell; Mesri, Mehdi; Kinsinger, Christopher R; Rodriguez, Henry; Boja, Emily S

    2013-12-01

    Protein biomarkers are needed to deepen our understanding of cancer biology and to improve our ability to diagnose, monitor, and treat cancers. Important analytical and clinical hurdles must be overcome to allow the most promising protein biomarker candidates to advance into clinical validation studies. Although contemporary proteomics technologies support the measurement of large numbers of proteins in individual clinical specimens, sample throughput remains comparatively low. This problem is amplified in typical clinical proteomics research studies, which routinely suffer from a lack of proper experimental design, resulting in analysis of too few biospecimens to achieve adequate statistical power at each stage of a biomarker pipeline. To address this critical shortcoming, a joint workshop was held by the National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI), and American Association for Clinical Chemistry (AACC) with participation from the U.S. Food and Drug Administration (FDA). An important output from the workshop was a statistical framework for the design of biomarker discovery and verification studies. Herein, we describe the use of quantitative clinical judgments to set statistical criteria for clinical relevance and the development of an approach to calculate biospecimen sample size for proteomic studies in discovery and verification stages prior to clinical validation stage. This represents a first step toward building a consensus on quantitative criteria for statistical design of proteomics biomarker discovery and verification research.

  11. Factors that Affect Willingness to Donate Blood for the Purpose of Biospecimen Research in the Korean American Community

    OpenAIRE

    Yen, Glorian P.; Davey, Adam; Grace X. Ma

    2015-01-01

    Objective: Biorepositories have been key resources in examining genetically-linked diseases, particularly cancer. Asian Americans contribute to biorepositories at lower rates than other racial groups, but the reasons for this are unclear. We hypothesized that attitudes toward biospecimen research mediate the relationship between demographic and healthcare access factors, and willingness to donate blood for research purposes among individuals of Korean heritage.

  12. BCR and its mutants, the reciprocal t(9;22-associated ABL/BCR fusion proteins, differentially regulate the cytoskeleton and cell motility

    Directory of Open Access Journals (Sweden)

    Puccetti Elena

    2006-11-01

    Full Text Available Abstract Background The reciprocal (9;22 translocation fuses the bcr (breakpoint cluster region gene on chromosome 22 to the abl (Abelson-leukemia-virus gene on chromosome 9. Depending on the breakpoint on chromosome 22 (the Philadelphia chromosome – Ph+ the derivative 9+ encodes either the p40(ABL/BCR fusion transcript, detectable in about 65% patients suffering from chronic myeloid leukemia, or the p96(ABL/BCR fusion transcript, detectable in 100% of Ph+ acute lymphatic leukemia patients. The ABL/BCRs are N-terminally truncated BCR mutants. The fact that BCR contains Rho-GEF and Rac-GAP functions strongly suggest an important role in cytoskeleton modeling by regulating the activity of Rho-like GTPases, such as Rho, Rac and cdc42. We, therefore, compared the function of the ABL/BCR proteins with that of wild-type BCR. Methods We investigated the effects of BCR and ABL/BCRs i. on the activation status of Rho, Rac and cdc42 in GTPase-activation assays; ii. on the actin cytoskeleton by direct immunofluorescence; and iii on cell motility by studying migration into a three-dimensional stroma spheroid model, adhesion on an endothelial cell layer under shear stress in a flow chamber model, and chemotaxis and endothelial transmigration in a transwell model with an SDF-1α gradient. Results Here we show that both ABL/BCRs lost fundamental functional features of BCR regarding the regulation of small Rho-like GTPases with negative consequences on cell motility, in particular on the capacity to adhere to endothelial cells. Conclusion Our data presented here describe for the first time an analysis of the biological function of the reciprocal t(9;22 ABL/BCR fusion proteins in comparison to their physiological counterpart BCR.

  13. Naïve and memory B cells exhibit distinct biochemical responses following BCR engagement.

    Science.gov (United States)

    Moens, Leen; Kane, Alisa; Tangye, Stuart G

    2016-09-01

    Immunological memory is characterized by the rapid reactivation of memory B cells that produce large quantities of high-affinity antigen-specific antibodies. This contrasts the response of naïve B cells, and the primary immune response, which is much slower and of lower affinity. Memory responses are critical for protection against infectious diseases and form the basis of most currently available vaccines. Although we have known about the phenomenon of long-lived memory for centuries, the biochemical differences underlying these diverse responses of naïve and memory B cells is incompletely resolved. Here we investigated the nature of B-cell receptor (BCR) signaling in human splenic naïve, IgM(+) memory and isotype-switched memory B cells following multivalent BCR crosslinking. We observed comparable rapid and transient phosphorylation kinetics for proximal (phosphotyrosine and spleen tyrosine kinase) and propagation (B-cell linker, phospholipase Cγ2) signaling components in these different B-cell subsets. However, the magnitude of activation of downstream components of the BCR signaling pathway were greater in memory compared with naïve cells. Although no differences were observed in the magnitude of Ca(2+) mobilization between subsets, IgM(+) memory B cells exhibited a more rapid Ca(2+) mobilization and a greater depletion of the Ca(2+) endoplasmic reticulum stores, while IgG(+) memory B cells had a prolonged Ca(2+) uptake. Collectively, our findings show that intrinsic signaling features of B-cell subsets contribute to the robust response of human memory B cells over naïve B cells. This has implications for our understanding of memory B-cell responses and provides a framework to modulate these responses in the setting of vaccination and immunopathologies, such as immunodeficiency and autoimmunity. PMID:27101923

  14. A widefield fluorescence microscope with a linear image sensor for image cytometry of biospecimens: Considerations for image quality optimization

    Science.gov (United States)

    Hutcheson, Joshua A.; Majid, Aneeka A.; Powless, Amy J.; Muldoon, Timothy J.

    2015-09-01

    Linear image sensors have been widely used in numerous research and industry applications to provide continuous imaging of moving objects. Here, we present a widefield fluorescence microscope with a linear image sensor used to image translating objects for image cytometry. First, a calibration curve was characterized for a custom microfluidic chamber over a span of volumetric pump rates. Image data were also acquired using 15 μm fluorescent polystyrene spheres on a slide with a motorized translation stage in order to match linear translation speed with line exposure periods to preserve the image aspect ratio. Aspect ratios were then calculated after imaging to ensure quality control of image data. Fluorescent beads were imaged in suspension flowing through the microfluidics chamber being pumped by a mechanical syringe pump at 16 μl min-1 with a line exposure period of 150 μs. The line period was selected to acquire images of fluorescent beads with a 40 dB signal-to-background ratio. A motorized translation stage was then used to transport conventional glass slides of stained cellular biospecimens. Whole blood collected from healthy volunteers was stained with 0.02% (w/v) proflavine hemisulfate was imaged to highlight leukocyte morphology with a 1.56 mm × 1.28 mm field of view (1540 ms total acquisition time). Oral squamous cells were also collected from healthy volunteers and stained with 0.01% (w/v) proflavine hemisulfate to demonstrate quantifiable subcellular features and an average nuclear to cytoplasmic ratio of 0.03 (n = 75), with a resolution of 0.31 μm pixels-1.

  15. A widefield fluorescence microscope with a linear image sensor for image cytometry of biospecimens: Considerations for image quality optimization

    Energy Technology Data Exchange (ETDEWEB)

    Hutcheson, Joshua A.; Majid, Aneeka A.; Powless, Amy J.; Muldoon, Timothy J., E-mail: tmuldoon@uark.edu [Department of Biomedical Engineering, University of Arkansas, 120 Engineering Hall, Fayetteville, Arkansas 72701 (United States)

    2015-09-15

    Linear image sensors have been widely used in numerous research and industry applications to provide continuous imaging of moving objects. Here, we present a widefield fluorescence microscope with a linear image sensor used to image translating objects for image cytometry. First, a calibration curve was characterized for a custom microfluidic chamber over a span of volumetric pump rates. Image data were also acquired using 15 μm fluorescent polystyrene spheres on a slide with a motorized translation stage in order to match linear translation speed with line exposure periods to preserve the image aspect ratio. Aspect ratios were then calculated after imaging to ensure quality control of image data. Fluorescent beads were imaged in suspension flowing through the microfluidics chamber being pumped by a mechanical syringe pump at 16 μl min{sup −1} with a line exposure period of 150 μs. The line period was selected to acquire images of fluorescent beads with a 40 dB signal-to-background ratio. A motorized translation stage was then used to transport conventional glass slides of stained cellular biospecimens. Whole blood collected from healthy volunteers was stained with 0.02% (w/v) proflavine hemisulfate was imaged to highlight leukocyte morphology with a 1.56 mm × 1.28 mm field of view (1540 ms total acquisition time). Oral squamous cells were also collected from healthy volunteers and stained with 0.01% (w/v) proflavine hemisulfate to demonstrate quantifiable subcellular features and an average nuclear to cytoplasmic ratio of 0.03 (n = 75), with a resolution of 0.31 μm pixels{sup −1}.

  16. A widefield fluorescence microscope with a linear image sensor for image cytometry of biospecimens: Considerations for image quality optimization

    International Nuclear Information System (INIS)

    Linear image sensors have been widely used in numerous research and industry applications to provide continuous imaging of moving objects. Here, we present a widefield fluorescence microscope with a linear image sensor used to image translating objects for image cytometry. First, a calibration curve was characterized for a custom microfluidic chamber over a span of volumetric pump rates. Image data were also acquired using 15 μm fluorescent polystyrene spheres on a slide with a motorized translation stage in order to match linear translation speed with line exposure periods to preserve the image aspect ratio. Aspect ratios were then calculated after imaging to ensure quality control of image data. Fluorescent beads were imaged in suspension flowing through the microfluidics chamber being pumped by a mechanical syringe pump at 16 μl min−1 with a line exposure period of 150 μs. The line period was selected to acquire images of fluorescent beads with a 40 dB signal-to-background ratio. A motorized translation stage was then used to transport conventional glass slides of stained cellular biospecimens. Whole blood collected from healthy volunteers was stained with 0.02% (w/v) proflavine hemisulfate was imaged to highlight leukocyte morphology with a 1.56 mm × 1.28 mm field of view (1540 ms total acquisition time). Oral squamous cells were also collected from healthy volunteers and stained with 0.01% (w/v) proflavine hemisulfate to demonstrate quantifiable subcellular features and an average nuclear to cytoplasmic ratio of 0.03 (n = 75), with a resolution of 0.31 μm pixels−1

  17. A widefield fluorescence microscope with a linear image sensor for image cytometry of biospecimens: Considerations for image quality optimization.

    Science.gov (United States)

    Hutcheson, Joshua A; Majid, Aneeka A; Powless, Amy J; Muldoon, Timothy J

    2015-09-01

    Linear image sensors have been widely used in numerous research and industry applications to provide continuous imaging of moving objects. Here, we present a widefield fluorescence microscope with a linear image sensor used to image translating objects for image cytometry. First, a calibration curve was characterized for a custom microfluidic chamber over a span of volumetric pump rates. Image data were also acquired using 15 μm fluorescent polystyrene spheres on a slide with a motorized translation stage in order to match linear translation speed with line exposure periods to preserve the image aspect ratio. Aspect ratios were then calculated after imaging to ensure quality control of image data. Fluorescent beads were imaged in suspension flowing through the microfluidics chamber being pumped by a mechanical syringe pump at 16 μl min(-1) with a line exposure period of 150 μs. The line period was selected to acquire images of fluorescent beads with a 40 dB signal-to-background ratio. A motorized translation stage was then used to transport conventional glass slides of stained cellular biospecimens. Whole blood collected from healthy volunteers was stained with 0.02% (w/v) proflavine hemisulfate was imaged to highlight leukocyte morphology with a 1.56 mm × 1.28 mm field of view (1540 ms total acquisition time). Oral squamous cells were also collected from healthy volunteers and stained with 0.01% (w/v) proflavine hemisulfate to demonstrate quantifiable subcellular features and an average nuclear to cytoplasmic ratio of 0.03 (n = 75), with a resolution of 0.31 μm pixels(-1). PMID:26429450

  18. Allosteric inhibition enhances the efficacy of ABL kinase inhibitors to target unmutated BCR-ABL and BCR-ABL-T315I

    Directory of Open Access Journals (Sweden)

    Mian Afsar

    2012-09-01

    Full Text Available Abstract Background Chronic myelogenous leukemia (CML and Philadelphia chromosome-positive (Ph+ acute lymphatic leukemia (Ph + ALL are caused by the t(9;22, which fuses BCR to ABL resulting in deregulated ABL-tyrosine kinase activity. The constitutively activated BCR/ABL-kinase “escapes” the auto-inhibition mechanisms of c-ABL, such as allosteric inhibition. The ABL-kinase inhibitors (AKIs Imatinib, Nilotinib or Dasatinib, which target the ATP-binding site, are effective in Ph + leukemia. Another molecular therapy approach targeting BCR/ABL restores allosteric inhibition. Given the fact that all AKIs fail to inhibit BCR/ABL harboring the ‘gatekeeper’ mutation T315I, we investigated the effects of AKIs in combination with the allosteric inhibitor GNF2 in Ph + leukemia. Methods The efficacy of this approach on the leukemogenic potential of BCR/ABL was studied in Ba/F3 cells, primary murine bone marrow cells, and untransformed Rat-1 fibroblasts expressing BCR/ABL or BCR/ABL-T315I as well as in patient-derived long-term cultures (PDLTC from Ph + ALL-patients. Results Here, we show that GNF-2 increased the effects of AKIs on unmutated BCR/ABL. Interestingly, the combination of Dasatinib and GNF-2 overcame resistance of BCR/ABL-T315I in all models used in a synergistic manner. Conclusions Our observations establish a new approach for the molecular targeting of BCR/ABL and its resistant mutants using a combination of AKIs and allosteric inhibitors.

  19. Differential expression of Toll-like receptor (TLR) and B cell receptor (BCR) signaling molecules in primary diffuse large B-cell lymphoma of the central nervous system.

    Science.gov (United States)

    Akhter, Ariz; Masir, Noraidah; Elyamany, Ghaleb; Phang, Kean-Chang; Mahe, Etienne; Al-Zahrani, Ali Matar; Shabani-Rad, Meer-Taher; Stewart, Douglas Allan; Mansoor, Adnan

    2015-01-01

    Primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) is a distinct and aggressive lymphoma that is confined to CNS. Since, central nervous system is barrier-protected and immunologically silent; role of TLR/BCR signaling in pathogenesis and biology of CNS DLBCL is intriguing. Genomic mutations in key regulators of TLR/BCR signaling pathway (MYD88/CD79B/CARD11) have recently been reported in this disease. These observations raised possible implications in novel targeted therapies; however, expression pattern of molecules related to TLR/BCR pathways in this lymphoma remains unknown. We have analyzed the expression of 19 genes encoding TLR/BCR pathways and targets in CNS DLBCLs (n = 20) by Nanostring nCounter™ analysis and compared it with expression patterns in purified reactive B-lymphocytes and systemic diffuse large B cell lymphoma (DLBCL) (n = 20). Relative expression of TLR4, TLR5, TLR9, CD79B and BLNK was higher in CNS DLBCLs than in control B-lymphocytes; where as TLR7, MALT1, BCL10, CD79A and LYN was lower in CNS DLBCLs (P 1.5 fold change; P < 0.01). The B cell receptor molecules like BLNK and CD79B were also associated with higher expression of MYD88 dependent TLRs (TLR4/5/9). In conclusion, we have shown over expression of TLR/BCR related genes or their targets, where genomic mutations have commonly been identified in CNS DLBCL. We have also demonstrated that TLR over expression closely relate with up regulation of genes associated with BCR pathway like CD79B/BLNK and CARD11, which play an important role in NF-kB pathway activation. Our results provide an important insight into the possibility of TLR and/or B-cell receptor signaling molecules as possible therapeutic targets in CNS DLBCL. PMID:25391967

  20. Inverse regulation of bridging integrator 1 and BCR-ABL1 in chronic myeloid leukemia.

    Science.gov (United States)

    Trino, Stefania; De Luca, Luciana; Simeon, Vittorio; Laurenzana, Ilaria; Morano, Annalisa; Caivano, Antonella; La Rocca, Francesco; Pietrantuono, Giuseppe; Bianchino, Gabriella; Grieco, Vitina; Signorino, Elisabetta; Fragasso, Alberto; Bochicchio, Maria Teresa; Venturi, Claudia; Rosti, Gianantonio; Martinelli, Giovanni; Del Vecchio, Luigi; Cilloni, Daniela; Musto, Pellegrino

    2016-01-01

    Endocytosis is the major regulator process of tyrosine kinase receptor (RTK) functional activities. Bridging integrator 1 (BIN1) is a key protein involved in RTK intracellular trafficking. Here, we report, by studying 34 patients with chronic myeloid leukemia (CML) at diagnosis, that BIN1 gene is downregulated in CML as compared to healthy controls, suggesting an altered endocytosis of RTKs. Rab interactor 1 (RIN1), an activator of BIN1, displayed a similar behavior. Treatment of 57 patients by tyrosine kinase inhibitors caused, along with BCR-ABL1 inactivation, an increase of BIN1 and RIN1 expression, potentially restoring endocytosis. There was a significant inverse correlation between BIN1-RIN1 and BCR-ABL1 expression. In vitro experiments on both CML and nontumorigenic cell lines treated with Imatinib confirmed these results. In order to provide another proof in favor of BIN1 and RIN1 endocytosis function in CML, we demonstrated that Imatinib induced, in K562 cell line, BIN1-RIN1 upregulation accompanied by a parallel AXL receptor internalization into cytoplasmic compartment. This study shows a novel deregulated mechanism in CML patients, indicating BIN1 and RIN1 as players in the maintenance of the abnormal RTK signaling in this hematological disease.

  1. A review of room temperature storage of biospecimen tissue and nucleic acids for anatomic pathology laboratories and biorepositories

    OpenAIRE

    Lou, Jerry J.; Mirsadraei, Leili; Sanchez, Desiree E.; Wilson, Ryan W.; Shabihkhani, Maryam; Gregory M Lucey; Wei, Bowen; Singer, Elyse J.; Mareninov, Sergey; Yong, William H.

    2013-01-01

    Frozen biospecimens are crucial for translational research and contain well preserved nucleic acids and protein. However, the risk for catastrophic freezer failure as well as space, cost, and environmental concerns argue for evaluating long-term room temperature storage alternatives. Formalin-fixed paraffin embedded (FFPE) tissues have great value but their use is limited by cross-linking and fragmentation of nucleic acids, as well as loss of enzymatic activity. Stabilization solutions can no...

  2. Optimisation of beryllium-7 gamma analysis following BCR sequential extraction

    International Nuclear Information System (INIS)

    Graphical abstract: Showing decrease in analytical uncertainty using the optimal (combined preconcentrated sample extract) method. nv (no value) where extract activities were 7Be geochemical behaviour is required to support tracer studies. ► Sequential extraction with natural 7Be returns high analytical uncertainties. ► Preconcentrating extracts from a large sample mass improved analytical uncertainty. ► This optimised method can be readily employed in studies using low activity samples. - Abstract: The application of cosmogenic 7Be as a sediment tracer at the catchment-scale requires an understanding of its geochemical associations in soil to underpin the assumption of irreversible adsorption. Sequential extractions offer a readily accessible means of determining the associations of 7Be with operationally defined soil phases. However, the subdivision of the low activity concentrations of fallout 7Be in soils into geochemical fractions can introduce high gamma counting uncertainties. Extending analysis time significantly is not always an option for batches of samples, owing to the on-going decay of 7Be (t1/2 = 53.3 days). Here, three different methods of preparing and quantifying 7Be extracted using the optimised BCR three-step scheme have been evaluated and compared with a focus on reducing analytical uncertainties. The optimal method involved carrying out the BCR extraction in triplicate, sub-sampling each set of triplicates for stable Be analysis before combining each set and coprecipitating the 7Be with metal oxyhydroxides to produce a thin source for gamma analysis. This method was applied to BCR extractions of natural 7Be in four agricultural soils. The approach gave good counting statistics from a 24 h analysis period (∼10% (2σ) where extract activity >40% of total activity) and generated statistically useful sequential extraction profiles. Total recoveries of 7Be fell between 84 and 112%. The stable Be data demonstrated that the extraction

  3. Systems-wide analysis of BCR signalosomes and downstream phosphorylation and ubiquitylation

    DEFF Research Database (Denmark)

    Satpathy, Shankha; Wagner, Sebastian A; Beli, Petra;

    2015-01-01

    of the receptor-proximal signaling components, many of which are co-regulated by both the modifications. We illustrate the power of multilayered proteomic analyses for discovering novel BCR signaling components by demonstrating that BCR-induced phosphorylation of RAB7A at S72 prevents its association...

  4. Expression of BCR/ABL p210 from a Knockin Allele Enhances Bone Marrow Engraftment without Inducing Neoplasia

    Directory of Open Access Journals (Sweden)

    Samantha B. Foley

    2013-10-01

    Full Text Available Chronic myeloid leukemia (CML and some acute lymphoblastic leukemias are characterized by the t(9;22 chromosome, which encodes the BCR/ABL oncogene. Multiple mouse models of CML express BCR/ABL at high levels from non-Bcr promoters, resulting in the development of leukemias. In contrast, a significant fraction of healthy humans have been found to have BCR/ABL-positive hematopoietic cells. To bridge the gap between the information derived from current mouse models and nonleukemic humans with the BCR/ABL oncogene, we generated a knockin model with BCR/ABL p210 expressed from the Bcr locus. Unlike previous models, expression of BCR/ABL from the knockin allele did not induce leukemia. BCR/ABL mutant cells did exhibit favorable bone marrow engraftment compared to control cells. These data suggest that BCR/ABL expression alone is insufficient to induce disease. This model allows for inducible spatial and temporal control of BCR/ABL expression for analysis of early steps in the pathogenesis of BCR/ABL-expressing leukemias.

  5. Cytoprotective effect of imatinib mesylate in non-BCR-ABL-expressing cells along with autophagosome formation

    Energy Technology Data Exchange (ETDEWEB)

    Ohtomo, Tadashi [Department of Biochemistry, Tokyo Medical University, Tokyo (Japan); Miyazawa, Keisuke, E-mail: miyazawa@tokyo-med.ac.jp [Department of Biochemistry, Tokyo Medical University, Tokyo (Japan); Naito, Munekazu [Department of Anatomy, Tokyo Medical University, Tokyo (Japan); Moriya, Shota [Department of Biochemistry, Tokyo Medical University, Tokyo (Japan); Kuroda, Masahiko [Department of Molecular Pathology, Tokyo Medical University, Tokyo (Japan); Itoh, Masahiro [Department of Anatomy, Tokyo Medical University, Tokyo (Japan); Tomoda, Akio [Department of Biochemistry, Tokyo Medical University, Tokyo (Japan)

    2010-01-01

    Treatment with imatinib mesylate (IM) results in an increased viable cell number of non-BCR-ABL-expressing cell lines by inhibiting spontaneous apoptosis. Electron microscopy revealed an increase of autophagosomes in response to IM. IM attenuated the cytotoxic effect of cytosine arabinoside, as well as inhibiting cell death with serum-deprived culture. Cytoprotection with autophagosome formation by IM was observed in various leukemia and cancer cell lines as well as normal murine embryonic fibroblasts (MEFs). Complete inhibition of autophagy by knockdown of atg5 in the Tet-off atg5{sup -/-} MEF system attenuated the cytoprotective effect of IM, indicating that the effect is partially dependent on autophagy. However, cytoprotection by IM was not mediated through suppression of ROS production via mitophagy, ER stress via ribophagy, or proapoptotic function of ABL kinase. Although the target tyrosine kinase(s) of IM remains unclear, our data provide novel therapeutic possibilities of using IM for cytoprotection.

  6. BCR/ABL stimulates WRN to promote survival and genomic instability

    Science.gov (United States)

    Slupianek, Artur; Poplawski, Tomasz; Jozwiakowski, Stanislaw K.; Cramer, Kimberly; Pytel, Dariusz; Stoczynska, Ewelina; Nowicki, Michal O.; Blasiak, Janusz; Skorski, Tomasz

    2010-01-01

    BCR/ABL-transformed chronic myeloid leukemia (CML) cells accumulate numerous DNA double-strand breaks (DSBs) induced by reactive oxygen species (ROS) and genotoxic agents. To repair these lesions BCR/ABL stimulate unfaithful DSB repair pathways, homologous recombination repair (HRR), non-homologous end-joining (NHEJ) and single-strand annealing (SSA). Here we show that BCR/ABL enhances the expression and increase nuclear localization of WRN (mutated in Werner syndrome), which is required for processing DSB ends during the repair. Other fusion tyrosine kinases (FTKs) such as TEL/ABL, TEL/JAK2, TEL/PDGFβR, and NPM/ALK also elevate WRN. BCR/ABL induces WRN mRNA and protein expression in part by c-MYC -mediated activation of transcription and Bcl-xL –dependent inhibition of caspase-dependent cleavage, respectively. WRN is in complex with BCR/ABL resulting in WRN tyrosine phosphorylation and stimulation of its helicase and exonuclease activities. Activated WRN protects BCR/ABL-positive cells from the lethal effect of oxidative and genotoxic stresses, which causes DSBs. In addition, WRN promotes unfaithful recombination-dependent repair mechanisms HRR and SSA, and enhances the loss of DNA bases during NHEJ in leukemia cells. In summary, we postulate that BCR/ABL-mediated stimulation of WRN modulates the efficiency and fidelity of major DSB repair mechanisms to protect leukemia cells from apoptosis and to facilitate genomic instability. PMID:21123451

  7. BCR/ABL stimulates WRN to promote survival and genomic instability.

    Science.gov (United States)

    Slupianek, Artur; Poplawski, Tomasz; Jozwiakowski, Stanislaw K; Cramer, Kimberly; Pytel, Dariusz; Stoczynska, Ewelina; Nowicki, Michal O; Blasiak, Janusz; Skorski, Tomasz

    2011-02-01

    BCR/ABL-transformed chronic myeloid leukemia (CML) cells accumulate numerous DNA double-strand breaks (DSB) induced by reactive oxygen species (ROS) and genotoxic agents. To repair these lesions BCR/ABL stimulate unfaithful DSB repair pathways, homologous recombination repair (HRR), nonhomologous end-joining (NHEJ), and single-strand annealing (SSA). Here, we show that BCR/ABL enhances the expression and increase nuclear localization of WRN (mutated in Werner syndrome), which is required for processing DSB ends during the repair. Other fusion tyrosine kinases (FTK), such as TEL/ABL, TEL/JAK2, TEL/PDGFβR, and NPM/ALK also elevate WRN. BCR/ABL induces WRN mRNA and protein expression in part by c-MYC-mediated activation of transcription and Bcl-xL-dependent inhibition of caspase-dependent cleavage, respectively. WRN is in complex with BCR/ABL resulting in WRN tyrosine phosphorylation and stimulation of its helicase and exonuclease activities. Activated WRN protects BCR/ABL-positive cells from the lethal effect of oxidative and genotoxic stresses, which causes DSBs. In addition, WRN promotes unfaithful recombination-dependent repair mechanisms HRR and SSA, and enhances the loss of DNA bases during NHEJ in leukemia cells. In summary, we postulate that BCR/ABL-mediated stimulation of WRN modulates the efficiency and fidelity of major DSB repair mechanisms to protect leukemia cells from apoptosis and to facilitate genomic instability.

  8. The Study on BCR/ABL Fusion Gene in Adult Acute Lymphoblastic Leukemia

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In order to assess the significance of BCR/ABC fusion gene in adult acute lymphoblastic Leukemia (ALL), 28 patients who were diagnosed as ALL were enrolled to detect BCR/ABC gene using nested-RT PCR. The results showed that 9 cases (31.25%) were BCR/ABL positive ,and expressed P210 subtype. A mong them 7 cases were B-ALL, and one was T-ALL. The diagnosis was proved by monoclonal antibodies recognition by indirect immunofluorescence. Adult patients with BCR/ABL positive ALL were significantly older (p<0. 01) and had higher WBC count (p<0. 01) as compared with BCR/ABL-negative patients. There was no significant difference in sex, hemoglobin and splenomegaly between two group (p>0. 05). The induc tion failure rate was high in BCR/ABL positive patients and those who achieved complete remission usually relapsed earlier. In conclusion, adult ALL patients with BCR/ABL-positive have poorer prognosis.

  9. Gads (Grb2-related adaptor downstream of Shc) is required for BCR-ABL-mediated lymphoid leukemia

    Science.gov (United States)

    Gillis, LC; Berry, DM; Minden, MD; McGlade, CJ; Barber, DL

    2016-01-01

    Philadelphia chromosome-positive leukemias, including chronic myeloid leukemia and B-cell acute lymphoblastic leukemia (B-ALL), are driven by the oncogenic BCR-ABL fusion protein. Animal modeling experiments utilizing retroviral transduction and subsequent bone marrow transplantation have demonstrated that BCR-ABL generates both myeloid and lymphoid disease in mice receiving whole bone marrow transduced with BCR-ABL. Y177 of BCR-ABL is critical to the development of myeloid disease, and phosphorylation of Y177 has been shown to induce GRB2 binding to BCR-ABL, followed by activation of the Ras and phosphoinositide 3 kinase signaling pathways. We show that the GRB2-related adapter protein, GADS, also associates with BCR-ABL, specifically through Y177 and demonstrate that BCR-ABL-driven lymphoid disease requires Gads. BCR-ABL transduction of Gads(−/−) bone marrow results in short latency myeloid disease within 3–4 weeks of transplant, while wild-type mice succumb to both a longer latency lymphoid and myeloid diseases. We report that GADS mediates a unique BCR-ABL complex with SLP-76 in BCR-ABL-positive cell lines and B-ALL patient samples. These data suggest that GADS mediates lymphoid disease downstream of BCR-ABL through the recruitment of specific signaling intermediates. PMID:23399893

  10. A Requirement for SOCS-1 and SOCS-3 Phosphorylation in Bcr-Abl-Induced Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Xiaoxue Qiu

    2012-06-01

    Full Text Available Suppressors of cytokine signaling 1 and 3 (SOCS-1 and SOCS-3 are inhibitors of the Janus tyrosine kinase (JAK/signal transducers and activators of transcription (STAT pathway and function in a negative feedback loop during cytokine signaling. Abl transformation is associated with constitutive activation of JAK/STAT-dependent signaling. However, the mechanism by which Abl oncoproteins bypass SOCS inhibitory regulation remains poorly defined. Here, we demonstrate that coexpression of Bcr-Abl with SOCS-1 or SOCS-3 results in tyrosine phosphorylation of these SOCS proteins. Interestingly, SOCS-1 is highly tyrosine phosphorylated in one of five primary chronic myelogenous leukemia samples. Bcr-Abl-dependent tyrosine phosphorylation of SOCS-1 and SOCS-3 occurs mainly on Tyr 155 and Tyr 204 residues of SOCS-1 and on Tyr 221 residue of SOCS-3. We observed that phosphorylation of these SOCS proteins was associated with their binding to Bcr-Abl. Bcr-Abl-dependent phosphorylation of SOCS-1 and SOCS-3 diminished their inhibitory effects on the activation of JAK and STAT5 and thereby enhanced JAK/STAT5 signaling. Strikingly, disrupting the tyrosine phosphorylation of SOCS-1 or SOCS-3 impaired the expression of Bcl-XL protein and sensitized K562 leukemic cells to undergo apoptosis. Moreover, selective mutation of tyrosine phosphorylation sites of SOCS-1 or SOCS-3 significantly blocked Bcr-Abl-mediated tumorigenesis in nude mice and inhibited Bcr-Abl-mediated murine bone marrow transformation. Together, these results reveal a mechanism of how Bcr-Abl may overcome SOCS-1 and SOCS-3 inhibition to constitutively activate the JAK/STAT-dependent signaling, and suggest that Bcr-Abl may critically requires tyrosine phosphorylation of SOCS-1 and SOCS-3 to mediate tumorigenesis when these SOCS proteins are present in cells.

  11. Lack of bcr and abr promotes hypoxia-induced pulmonary hypertension in mice.

    Directory of Open Access Journals (Sweden)

    Min Yu

    Full Text Available BACKGROUND: Bcr and Abr are GTPase activating proteins that specifically downregulate activity of the small GTPase Rac in restricted cell types in vivo. Rac1 is expressed in smooth muscle cells, a critical cell type involved in the pathogenesis of pulmonary hypertension. The molecular mechanisms that underlie hypoxia-associated pulmonary hypertension are not well-defined. METHODOLOGY/PRINCIPAL FINDINGS: Bcr and abr null mutant mice were compared to wild type controls for the development of pulmonary hypertension after exposure to hypoxia. Also, pulmonary arterial smooth muscle cells from those mice were cultured in hypoxia and examined for proliferation, p38 activation and IL-6 production. Mice lacking Bcr or Abr exposed to hypoxia developed increased right ventricular pressure, hypertrophy and pulmonary vascular remodeling. Perivascular leukocyte infiltration in the lungs was increased, and under hypoxia bcr-/- and abr-/- macrophages generated more reactive oxygen species. Consistent with a contribution of inflammation and oxidative stress in pulmonary hypertension-associated vascular damage, Bcr and Abr-deficient animals showed elevated endothelial leakage after hypoxia exposure. Hypoxia-treated pulmonary arterial smooth muscle cells from Bcr- or Abr-deficient mice also proliferated faster than those of wild type mice. Moreover, activated Rac1, phosphorylated p38 and interleukin 6 were increased in these cells in the absence of Bcr or Abr. Inhibition of Rac1 activation with Z62954982, a novel Rac inhibitor, decreased proliferation, p38 phosphorylation and IL-6 levels in pulmonary arterial smooth muscle cells exposed to hypoxia. CONCLUSIONS: Bcr and Abr play a critical role in down-regulating hypoxia-induced pulmonary hypertension by deactivating Rac1 and, through this, reducing both oxidative stress generated by leukocytes as well as p38 phosphorylation, IL-6 production and proliferation of pulmonary arterial smooth muscle cells.

  12. Essential role for telomerase in chronic myeloid leukemia induced by BCR-ABL in mice

    OpenAIRE

    Vicente-Dueñas, Carolina; Barajas-Diego, Marcos; Romero-Camarero, Isabel; González-Herrero, Inés; Flores, Teresa; Sánchez García, Isidro

    2012-01-01

    The telomerase protein is constitutively activated in malignant cells from many patients with cancer, including the chronic myeloid leukemia (CML), but whether telomerase is essential for the pathogenesis of this disease is not known. Here, we used telomerase deficient mice to determine the requirement for telomerase in CML induced by BCR-ABL in mouse models of CML. Loss of one telomerase allele or complete deletion of telomerase prevented the development of leukemia induced by BCR-ABL. Howev...

  13. Role of Bcr1-activated genes Hwp1 and Hyr1 in Candida albicans oral mucosal biofilms and neutrophil evasion.

    Science.gov (United States)

    Dwivedi, Prabhat; Thompson, Angela; Xie, Zhihong; Kashleva, Helena; Ganguly, Shantanu; Mitchell, Aaron P; Dongari-Bagtzoglou, Anna

    2011-01-25

    Candida albicans triggers recurrent infections of the oropharyngeal mucosa that result from biofilm growth. Prior studies have indicated that the transcription factor Bcr1 regulates biofilm formation in a catheter model, both in vitro and in vivo. We thus hypothesized that Bcr1 plays similar roles in the formation of oral mucosal biofilms and tested this hypothesis in a mouse model of oral infection. We found that a bcr1/bcr1 mutant did not form significant biofilm on the tongues of immunocompromised mice, in contrast to reference and reconstituted strains that formed pseudomembranes covering most of the tongue dorsal surface. Overexpression of HWP1, which specifies an epithelial adhesin that is under the transcriptional control of Bcr1, partly but significantly rescued the bcr1/bcr1 biofilm phenotype in vivo. Since HWP1 overexpression only partly reversed the biofilm phenotype, we investigated whether additional mechanisms, besides adhesin down-regulation, were responsible for the reduced virulence of this mutant. We discovered that the bcr1/bcr1 mutant was more susceptible to damage by human leukocytes when grown on plastic or on the surface of a human oral mucosa tissue analogue. Overexpression of HYR1, but not HWP1, significantly rescued this phenotype. Furthermore a hyr1/hyr1 mutant had significantly attenuated virulence in the mouse oral biofilm model of infection. These discoveries show that Bcr1 is critical for mucosal biofilm infection via regulation of epithelial cell adhesin and neutrophil function.

  14. Evaluation of Morpholino Antisense Oligos’ Role on BCR-ABL Gene Silencing in the K562 Cell Line

    Directory of Open Access Journals (Sweden)

    Bahman Delalat

    2010-01-01

    Full Text Available Objective: Chronic myeloid leukemia (CML develops when a hematopoietic stem cellacquires the BCR/ABL fusion gene. This causes these transformed hematopoietic cellsto have a greater than normal proliferation rate. Scientists attempt to improve the CMLtreatment process by silencing the BCR/ABL oncogene. In this work, we used morpholinoantisense oligos to silence the BCR/ABL oncogene.Materials and Methods: In this study, the K562 was used as a BCR/ABL fusion-genepositive cell line and the Jurkat cell line as a control. We explored the inhibiting capacityof morpholino antisense oligos in the the expression of the BCR/ABL oncogene andstudied their p210 BCR/ABL suppression, inhibition of cell proliferation and stimulation ofapoptosis in the K562 cells after 24 and 48 hours. Endo-Porter was used for delivery ofmorpholino antisense oligos into cell cytosols. Meanwhile, flow cytometric analysis wasperformed in order to determine the appropriate concentration of morpholino antisenseoligos.Results: Prolonged exposure of the K562 cell line to the morpholino antisense oligostargeted against the BCR-ABL gene showed proliferation inhibition as its main feature.After western blotting, we found that complete silencing of BCR/ABL was achieved, butflow cytometric analysis showed no broad apoptosis.Conclusion: The results indicate that the Morpholino antisense oligo is able to inhibitp210 BCR/ABL; however, it cannot induce broad apoptosis due to co-silencing of BCR.

  15. Elucidation of tonic and activated B-cell receptor signaling in Burkitt's lymphoma provides insights into regulation of cell survival.

    Science.gov (United States)

    Corso, Jasmin; Pan, Kuan-Ting; Walter, Roland; Doebele, Carmen; Mohr, Sebastian; Bohnenberger, Hanibal; Ströbel, Philipp; Lenz, Christof; Slabicki, Mikolaj; Hüllein, Jennifer; Comoglio, Federico; Rieger, Michael A; Zenz, Thorsten; Wienands, Jürgen; Engelke, Michael; Serve, Hubert; Urlaub, Henning; Oellerich, Thomas

    2016-05-17

    Burkitt's lymphoma (BL) is a highly proliferative B-cell neoplasm and is treated with intensive chemotherapy that, because of its toxicity, is often not suitable for the elderly or for patients with endemic BL in developing countries. BL cell survival relies on signals transduced by B-cell antigen receptors (BCRs). However, tonic as well as activated BCR signaling networks and their relevance for targeted therapies in BL remain elusive. We have systematically characterized and compared tonic and activated BCR signaling in BL by quantitative phosphoproteomics to identify novel BCR effectors and potential drug targets. We identified and quantified ∼16,000 phospho-sites in BL cells. Among these sites, 909 were related to tonic BCR signaling, whereas 984 phospho-sites were regulated upon BCR engagement. The majority of the identified BCR signaling effectors have not been described in the context of B cells or lymphomas yet. Most of these newly identified BCR effectors are predicted to be involved in the regulation of kinases, transcription, and cytoskeleton dynamics. Although tonic and activated BCR signaling shared a considerable number of effector proteins, we identified distinct phosphorylation events in tonic BCR signaling. We investigated the functional relevance of some newly identified BCR effectors and show that ACTN4 and ARFGEF2, which have been described as regulators of membrane-trafficking and cytoskeleton-related processes, respectively, are crucial for BL cell survival. Thus, this study provides a comprehensive dataset for tonic and activated BCR signaling and identifies effector proteins that may be relevant for BL cell survival and thus may help to develop new BL treatments. PMID:27155012

  16. Biospecimen Retrieval from NASA's Rodent Research-1: Maximizing Science Return from Flight Missions

    Science.gov (United States)

    Choi, S. Y.; Chen, Y.- C.; Reyes, A.; Verma, V.; Dinh, M.; Globus, R. K.

    2016-01-01

    Rodent Research (RR)-1 was conducted to validate flight hardware, operations, and science capabilities that were developed to support long duration missions on the International Space Station. After 37 days in microgravity twenty mice were euthanized and frozen on orbit. Upon return to Earth the carcasses were dissected and yielded 32 different types of tissues from each mouse and over 3200 tissue aliquots. Many tissues were distributed to the Space Life and Physical Sciences (SLPS) Biospecimen Sharing Program (BSP) Principal Investigators (PIs) through the Ames Life Science Data Archive (ALSDA). A second round of dissections was performed to collect additional tissues from the remaining carcasses thawed for a second time for additional BSP PIs. Tissues retrieved included vaginal walls, aorta, pelvis, brown adipose tissue, tail, spine and forearms. Although the analyses are still in progress, some of the PIs have reported that the quality of the tissues was acceptable for their study. In a separate experiment we tested the RNA quality of the tissues that were dissected from frozen carcasses that were subjected to euthanasia, freezing, first and second thaw dissections. Timelines simulated the on-orbit RR-1 procedures to assess the quality of the tissues retrieved from the second thaw dissections. We analyzed the RIN values of select tissues including kidney, brain, white adipose tissue (WAT) and brown adipose tissue (BAT). Overall the RIN values from the second thaw were lower compared to those from the first by about a half unit; however, the tissues yielded RNA that are acceptable quality for some quantitative gene expression assays. Interestingly, RIN values of brain tissues were 8.4+/-0.6 and 7.9+/-0.7 from first and second round dissections, respectively (n=5). Kidney and WAT yielded RIN values less than 8 but they can still be used for qPCR. BAT yielded higher quality RNA (8.2+/-0.5) than WAT (5.22+/-0.9), possibly due to the high fat content. Together, these

  17. BCR-ABL transcript variations in chronic phase chronic myelogenous leukemia patients on imatinib first-line: Possible role of the autologous immune system.

    Science.gov (United States)

    Clapp, Geoffrey D; Lepoutre, Thomas; Nicolini, Franck E; Levy, Doron

    2016-05-01

    Many chronic myelogenous leukemia (CML) patients in chronic phase who respond well to imatinib therapy show fluctuations in their leukemic loads in the long-term. We developed a mathematical model of CML that incorporates the intervention of an autologous immune response. Our results suggest that the patient's immune system plays a crucial role in imatinib therapy in maintaining disease control over time. The observed BCR-ABL/ABL oscillations in such patients provide a signature of the autologous immune response. PMID:27467931

  18. Reciprocal t(9;22 ABL/BCR fusion proteins: leukemogenic potential and effects on B cell commitment.

    Directory of Open Access Journals (Sweden)

    Xiaomin Zheng

    Full Text Available BACKGROUND: t(9;22 is a balanced translocation, and the chromosome 22 breakpoints (Philadelphia chromosome--Ph+ determine formation of different fusion genes that are associated with either Ph+ acute lymphatic leukemia (Ph+ ALL or chronic myeloid leukemia (CML. The "minor" breakpoint in Ph+ ALL encodes p185(BCR/ABL from der22 and p96(ABL/BCR from der9. The "major" breakpoint in CML encodes p210(BCR/ABL and p40(ABL/BCR. Herein, we investigated the leukemogenic potential of the der9-associated p96(ABL/BCR and p40(ABL/BCR fusion proteins and their roles in the lineage commitment of hematopoietic stem cells in comparison to BCR/ABL. METHODOLOGY: All t(9;22 derived proteins were retrovirally expressed in murine hematopoietic stem cells (SL cells and human umbilical cord blood cells (UCBC. Stem cell potential was determined by replating efficiency, colony forming--spleen and competitive repopulating assays. The leukemic potential of the ABL/BCR fusion proteins was assessed by in a transduction/transplantation model. Effects on the lineage commitment and differentiation were investigated by culturing the cells under conditions driving either myeloid or lymphoid commitment. Expression of key factors of the B-cell differentiation and components of the preB-cell receptor were determined by qRT-PCR. PRINCIPAL FINDINGS: Both p96(ABL/BCR and p40(ABL/BCR increased proliferation of early progenitors and the short term stem cell capacity of SL-cells and exhibited own leukemogenic potential. Interestingly, BCR/ABL gave origin exclusively to a myeloid phenotype independently from the culture conditions whereas p96(ABL/BCR and to a minor extent p40(ABL/BCR forced the B-cell commitment of SL-cells and UCBC. CONCLUSIONS/SIGNIFICANCE: Our here presented data establish the reciprocal ABL/BCR fusion proteins as second oncogenes encoded by the t(9;22 in addition to BCR/ABL and suggest that ABL/BCR contribute to the determination of the leukemic phenotype through their

  19. Modeling the influence of stromal microenvironment in the selection of ENU-induced BCR-ABL1 mutants by tyrosine kinase inhibitors.

    Science.gov (United States)

    Aggoune, Djamel; Tosca, Lucie; Sorel, Nathalie; Bonnet, Marie-Laure; Dkhissi, Fatima; Tachdjian, Gérard; Bennaceur-Griscelli, Annelise; Chomel, Jean-Claude; Turhan, Ali G

    2014-01-01

    Tyrosine kinase inhibitors (TKIs) have profoundly changed the natural history of chronic myeloid leukemia (CML). However, acquired resistance to imatinib, dasatinib or nilotinib (1(st) and 2(nd) generation TKIs), due in part to BCR-ABL1 kinase mutations, has been largely described. These drugs are ineffective on the T315I gatekeeper substitution, which remains sensitive to 3(rd) generation TKI ponatinib. It has recently been suggested that the hematopoietic niche could protect leukemic cells from targeted therapy. In order to investigate the role of a stromal niche in mutation-related resistance, we developed a niche-based cell mutagenesis assay. For this purpose, ENU (N-ethyl-N-nitrosourea)-exposed UT-7 cells expressing non-mutated or T315I-mutated BCR-ABL1 were cultured with or without murine MS-5 stromal cells and in the presence of imatinib, dasatinib, nilotinib, or ponatinib. In the assays relative to 1(st) and 2(nd) generation TKIs, which were performed on non-mutated BCR-ABL1 cells, our data highlighted the increasing efficacy of the latter, but did not reveal any substantial effect of the niche. In ponatinib assays performed on both non-mutated and T315I-mutated BCR-ABL1 cells, an increased number of resistant clones were observed in the presence of MS-5. Present data suggested that T315I mutants need either compound mutations (e.g. E255K/T315I) or a stromal niche to escape from ponatinib. Using array-comparative genomic hybridization experiments, we found an increased number of variations (involving some recurrent chromosome regions) in clones cultured on MS-5 feeder. Overall, our study suggests that the hematopoietic niche could play a crucial role in conferring resistance to ponatinib, by providing survival signals and favoring genetic instability.

  20. Targeting the SH2-Kinase Interface in Bcr-Abl Inhibits Leukemogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Grebien, Florian; Hantschel, Oliver; Wojcik, John; Kaupe, Ines; Kovacic, Boris; Wyrzucki, Arkadiusz M.; Gish, Gerald D.; Cerny-Reiterer, Sabine; Koide, Akiko; Beug, Hartmut; Pawson, Tony; Valent, Peter; Koide, Shohei; Superti-Furga, Giulio (AAS); (Mount Sinai Hospital); (Med U. Vienna); (UC); (IMP-CNRS)

    2012-10-25

    Chronic myelogenous leukemia (CML) is caused by the constitutively active tyrosine kinase Bcr-Abl and treated with the tyrosine kinase inhibitor (TKI) imatinib. However, emerging TKI resistance prevents complete cure. Therefore, alternative strategies targeting regulatory modules of Bcr-Abl in addition to the kinase active site are strongly desirable. Here, we show that an intramolecular interaction between the SH2 and kinase domains in Bcr-Abl is both necessary and sufficient for high catalytic activity of the enzyme. Disruption of this interface led to inhibition of downstream events critical for CML signaling and, importantly, completely abolished leukemia formation in mice. Furthermore, disruption of the SH2-kinase interface increased sensitivity of imatinib-resistant Bcr-Abl mutants to TKI inhibition. An engineered Abl SH2-binding fibronectin type III monobody inhibited Bcr-Abl kinase activity both in vitro and in primary CML cells, where it induced apoptosis. This work validates the SH2-kinase interface as an allosteric target for therapeutic intervention.

  1. Arsenic fractionation in sediments of different origins using BCR sequential and single extraction methods

    International Nuclear Information System (INIS)

    The arsenic (As) contaminated sediment serves as a long-term source of arsenic because its mobility and transport in the environment are strongly influenced to associated solid phase. A single extraction method based on the reagents employed in the BCR three steps sequential extraction scheme (BCR-SES) for partitioning of arsenic (As) in sediment samples has been developed. The single-step extraction enabled a reduction of extraction times, yielding extractable contents in accordance with those obtained by application of the BCR-SES, which can be regarded as a standard method and validated by using certified reference material BCR 701. The extractable As content associated with different phases in sediment samples were analysed by electrothermal atomic absorption spectrophotometer. The extraction efficiency of As by single-step extraction was slightly higher than BCR-SES, ranged (100-104%), while difference was not significant at 95% confidence limit with <10% precision. The sediment samples from different origins varied in their physico-chemical properties and total As content. The relative mobility of As obtained from different origins was found in increasing order as: acid soluble fraction < oxidizable fraction < reducible fraction. The acid soluble fraction of As was higher in lake sediment samples as compared to those of canal and river sediments, indicating the contamination of lake ecosystem.

  2. INTERNAL RATING – AN ACTIVE INSTRUMENT IN THE MANAGEMENT OF BANKING RISKS. CASE STUDY BCR

    Directory of Open Access Journals (Sweden)

    PhD Gabriela Cornelia Piciu

    2013-06-01

    Full Text Available This paper aims to clarify some aspects regarding the banking activity in general, of crediting, in particular, because it involves a risk by the very elements of anticipation underlying the decision of the banking specialists. For the bank it is very important to know this risk, to make an evaluation as close as possible to reality, and to reject or accept it in full awareness. The contribution of the internal rating in terms of efficiency and stability of a bank is shown via a case study – the Romanian Commercial Bank. The internal rating used by BCR is an active instrument for making credit decisions it provides valuable indicators to the banking analysts that can be used to develop de risk management policies and the prudential measures for the balanced risk dispersion. Given the fact that the credit rating contributes to the objective, professional analysis, the system must be continuously improved and developed by categories of clients and types of risk, so that the included criteria and the resulting conclusions are relevant.

  3. Deletion of ABL/BCR on der(9 associated with severe basophilia

    Directory of Open Access Journals (Sweden)

    Shantashri Vaidya

    2011-01-01

    Full Text Available Chronic basophilic leukemia is a rare form in chronic myeloid leukemia patients. Only limited number of reports are available. Herein, we describe a patient who presented with fatigue, weight loss, leucocytosis, prominent basophilia, and mild eosinophilia. On biopsy, bone marrow was hypercellular with marked basophils. The immunophenotype showed abnormal expression of CD7, which is suggestive of basophilic maturation. Chromosomal analysis from GTG-banded metaphases revealed Ph positivity, and fluorescence in situ hybridization (FISH with BCR/ABL dual color, dual fusion probe showed single fusion on the der(22 chromosome and ABL/BCR fusion was deleted on the der(9 chromosome. The deletion (ABL/BCR on der(9 may be associated with basophilia which may be also indicative of the transformation of CML to acute myeloid leukemia.

  4. Nilotinib treatment in mouse models of P190 Bcr/Abl lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Groffen John

    2007-10-01

    Full Text Available Abstract Background Ph-positive leukemias are caused by the aberrant fusion of the BCR and ABL genes. Nilotinib is a selective Bcr/Abl tyrosine kinase inhibitor related to imatinib, which is widely used to treat chronic myelogenous leukemia. Because Ph-positive acute lymphoblastic leukemia only responds transiently to imatinib therapy, we have used mouse models to test the efficacy of nilotinib against lymphoblastic leukemia caused by the P190 form of Bcr/Abl. Results After transplant of 10,000 highly malignant leukemic cells into compatible recipients, untreated mice succumbed to leukemia within 21 days, whereas mice treated with 75 mg/kg nilotinib survived significantly longer. We examined cells from mice that developed leukemia while under treatment for Bcr/Abl kinase domain point mutations but these were not detected. In addition, culture of such cells ex vivo showed that they were as sensitive as the parental cell line to nilotinib but that the presence of stromal support allowed resistant cells to grow out. Nilotinib also exhibited impressive anti-leukemia activity in P190 Bcr/Abl transgenic mice that had developed overt leukemia/lymphoma masses and that otherwise would have been expected to die within 7 days. Visible lymphoma masses disappeared within six days of treatment and leukemic cell numbers in peripheral blood were significantly reduced. Treated mice survived more than 30 days. Conclusion These results show that nilotinib has very impressive anti-leukemia activity but that lymphoblastic leukemia cells can become unresponsive to it both in vitro and in vivo through mechanisms that appear to be Bcr/Abl independent.

  5. Expression patterns of WT-1 and Bcr-Abl measured by TaqMan quantitative real-time RT-PCR during follow-up of leukemia patients with the Ph chromosome

    Institute of Scientific and Technical Information of China (English)

    CHEN Zi-xing陈子兴; Jaspal Kaeda; Sue Saunders; John M Goldman

    2004-01-01

    Background This study was designed to quantitatively measure WT-1 expression levels in patients with chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL) during follow-up and to clarify the value of WT-1 as a molecular marker in minimal residual disease monitoring.Methods The TaqMan quantitative real-time RT-PCR method was established by using cloned WT-1 cDNA or synthesized oligonucleotides resembling WT-1 cDNA fragments in limit dilution as template until a stable and reliable standard curve was obtained. In a 25-month follow-up, the transcriptional levels of WT-1, Bcr-Abl, and Abl gene, were quantitatively measured in bone marrow cells from 25 CML or acute lymphoblastic leukemia (ALL) patients with the Ph chromosome. In addition, the expression of these genes in 40 samples of normal peripheral blood was also examined using the same method. The ratios of WT-1/Abl and Bcr-Abl/Abl were both plotted, and the two expression patterns were compared as well as their clinical significance.Results The levels of WT-1 expression in normal peripheral blood were detectable. In CML and Ph positive ALL patients, WT-1 expression levels changed in parallel with the Bcr-Abl expression pattern as the disease progressed or responded to effective treatment.Conclusion WT-1 expression provides a novel molecular marker in addition to Bcr-Abl for monitoring minimal residual disease (MRD) and targeting therapy in Ph chromosome-positive leukemia patients.

  6. Altered BCR signalling quality predisposes to autoimmune disease and a pre-diabetic state

    OpenAIRE

    Königsberger, Sebastian; Prodöhl, Jan; Stegner, David; Weis, Vanessa; Andreas, Martin; Stehling, Martin; Schumacher, Theresa; Böhmer, Ruben; Thielmann, Ina; van Eeuwijk, Judith M M; Nieswandt, Bernhard; Kiefer, Friedemann

    2012-01-01

    The related tyrosine kinases Syk and Zap-70 are key signalling proteins downstream of antigen receptors. A knock-in strategy reveals that the two kinases differentially affect BCR signalling, leading to aberrant B cell section and increased risk of autoimmune disease.

  7. Prospective molecular monitoring of BCR/ABL transcript in children with Ph+ acute lymphoblastic leukaemia unravels differences in treatment response.

    Science.gov (United States)

    Cazzaniga, Giovanni; Lanciotti, Marina; Rossi, Vincenzo; Di Martino, Daniela; Aricò, Maurizio; Valsecchi, Maria Grazia; Basso, Giuseppe; Masera, Giuseppe; Micalizzi, Concetta; Biondi, Andrea

    2002-11-01

    Children with Philadelphia-chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) represent a subgroup at very high risk for treatment failure, despite intensive chemotherapy. However, recent retrospective studies showed that Ph+ childhood ALL is a heterogeneous disease with regard to treatment response. We have prospectively monitored, by reverse transcription polymerase chain reaction (RT-PCR) during follow-up, the presence of the BCR/ABL fusion transcript in Ph+ ALL children diagnosed in the Italian multicentre Associazione Italiana Ematologia Oncologia Pediatrica ALL-AIEOP-95 therapy protocol. To our knowledge, this is the first report on the evaluation of minimal residual disease (MRD) in childhood Ph+ ALL prospectively enrolled in an intensive, Berlin-Frankfurt-Munster (BFM)-type treatment protocol. Twenty-seven of 36 (75.0%) Ph+ patients consecutively enrolled into the high-risk group of the AIEOP-ALL protocol between May 1995 and October 1999 were successfully analysed. Twenty were good responders to the pre-phase of prednisone/intrathecal methotrexate treatment (PGR) and seven were poor responders (PPR). Within the PPR group, the RT-PCR monitoring constantly showed positivity for the BCR/ABL fusion transcript and all the patients died of disease progression. In contrast, highly sensitive qualitative RT-PCR monitoring revealed heterogeneity within the PGR group of Ph+ childhood ALL patients. Three different subgroups could be defined, according to the clearance of Ph+ cells within the first 5 months of treatment. This provides useful information on the capability of chemotherapy to reduce the leukaemic clone, with prognostic implications.

  8. MicroRNA-320a acts as a tumor suppressor by targeting BCR/ABL oncogene in chronic myeloid leukemia.

    Science.gov (United States)

    Xishan, Zhu; Ziying, Lin; Jing, Du; Gang, Liu

    2015-01-01

    Accumulating evidences demonstrated that the induction of epithelial-mesenchymal transition (EMT) and aberrant expression of microRNAs (miRNAs) are associated with tumorigenesis, tumor progression, metastasis and relapse in cancers, including chronic myeloid leukemia (CML). We found that miR-320a expression was reduced in K562 and in CML cancer stem cells. Moreover, we found that miR-320a inhibited K562 cell migration, invasion, proliferation and promoted apoptosis by targeting BCR/ABL oncogene. As an upstream regulator of BCR/ABL, miR-320a directly targets BCR/ABL. The enhanced expression of miR-320a inhibited the phosphorylation of PI3K, AKT and NF-κB; however, the expression of phosphorylated PI3K, AKT and NF-κB were restored by the overexpression of BCR/ABL. In K562, infected with miR-320a or transfected with SiBCR/ABL, the protein levels of fibronectin, vimentin, and N-cadherin were decreased, but the expression of E-cadherin was increased. The expression of mesenchymal markers in miR-320a-expressing cells was restored to normal levels by the restoration of BCR/ABL expression. Generally speaking, miR-320a acts as a novel tumor suppressor gene in CML and miR-320a can decrease migratory, invasive, proliferative and apoptotic behaviors, as well as CML EMT, by attenuating the expression of BCR/ABL oncogene.

  9. A BCR/ABL-hIL-2 DNA Vaccine Enhances the Immune Responses in BALB/c Mice

    Directory of Open Access Journals (Sweden)

    Yanan Qin

    2013-01-01

    Full Text Available The use of a DNA vaccine encoding the BCR/ABL fusion gene is thought to be a promising approach for patients with chronic myeloid leukemia (CML to eradicate minimal residual disease after treatment with chemotherapy or targeted therapy. In this study, our strategy employs genetic technology to create a DNA vaccine encoding the BCR/ABL fusion and human interleukin-2 (hIL-2 genes. The successfully constructed plasmids BCR/ABL-pIRES-hIL-2, BCR/ABL-pIRES, and pIRES-hIL-2 were delivered intramuscularly to BALB/c mice at 14-day intervals for three cycles. The transcription and expression of the BCR/ABL and hIL-2 genes were found in the injected muscle tissues. The interferon-γ (IFN-γ serum levels were increased, and the splenic CD4+/CD8+ T cell ratio was significantly decreased in the BCR/ABL-pIRES-hIL-2-injected mice. Furthermore, specific antibodies against K562 cells could be detected by indirect immunofluorescence. These results indicate that a DNA vaccine containing BCR/ABL and hIL-2 together may elicit increased in vivo humoral and cellular immune responses in BALB/c mice.

  10. Expression of p190 BCR-ABL fusion gene in a patient with chronic myeloid leukemia Expressão do rearranjo gênico BCR-ABL com ponto de quebra na região menor do gene BCR em um paciente com leucemia mielóide crônica

    Directory of Open Access Journals (Sweden)

    P. V. B. Carvalho

    2003-01-01

    Full Text Available A minority of chronic myeloid leukemia cases have breakpoints in the minor cluster region (m-bcr of the BCR-ABL gene. We report on a patient with Ph-positive and m-bcr breakpoint at diagnosis. She was treated with hydroxyurea and interferon-alpha. Two years later, she developed a lymphoid blast crisis and died shortly after. We discuss herein the different forms of the BCR-ABL oncogene, its products, and the possible influence of them on the clinical outcome of patients with the disease.A leucemia mielóide crônica (LMC é uma doença mieloproliferativa clonal e caracteriza-se pela presença da translocação cromossômica entre os braços longos dos cromossomos 9 e 22, o denominado cromossomo Ph. Esta translocação determina a fusão dos genes BCR e ABL. Os diferentes pontos de quebra no gene BCR determinam a síntese de proteínas com diferentes pesos moleculares pelo gene BCR-ABL. Nós relatamos o caso de uma paciente portadora de LMC com ponto de quebra cromossômico na região menor do gene BCR. Foi tratada com hidroxiuréia e interferon alfa. Dois anos após o diagnóstico desenvolveu crise blástica linfóide e evoluiu rapidamente para o óbito. Nós discutimos nesta apresentação as diferentes formas do gene BCR-ABL e seus produtos e a possível influência dos mesmos na evolução clínica dos pacientes com a doença.

  11. Allogeneic stem cell transplantation for patients harboring T315I BCR-ABL mutated leukemias

    DEFF Research Database (Denmark)

    Nicolini, Franck Emmanuel; Basak, Grzegorz W; Soverini, Simona;

    2011-01-01

    T315I(+) Philadelphia chromosome-positive leukemias are inherently resistant to all licensed tyrosine kinase inhibitors, and therapeutic options remain limited. We report the outcome of allogeneic stem cell transplantation in 64 patients with documented BCR-ABL(T315I) mutations. Median follow...... myeloid leukemia. The occurrence of chronic GVHD had a positive impact on overall survival (P = .047). Transplant-related mortality rates were low. Multivariate analysis identified only blast phase at transplantation (hazard ratio 3.68, P = .0011) and unrelated stem cell donor (hazard ratio 2.98, P = .011......) as unfavorable factors. We conclude that allogeneic stem cell transplantation represents a valuable therapeutic tool for eligible patients with BCR-ABL(T315I) mutation, a tool that may or may not be replaced by third-generation tyrosine kinase inhibitors....

  12. Susceptibility of Ph-positive all to TKI therapy associated with Bcr-Abl rearrangement patterns: a retrospective analysis.

    Directory of Open Access Journals (Sweden)

    Yu Jing

    Full Text Available BACKGROUND: Tyrosine kinase inhibitors (TKIs have demonstrated success in the treatment of acute lymphoblastic leukemia (ALL in patients that express BCR-ABL rearrangements (Philadelphia chromosome [Ph]. The current study aimed to assess the efficacy of TKIs and prognostic factors in the treatment of adults with Ph+-ALL. METHODS: In this multicenter retrospective study, the relationship between Ph+-ALL and treatment outcomes among Chinese patients receiving TKI-containing induction/consolidation chemotherapy was examined. A total of 86 Ph+-ALL patients were included and followed for 3.85 (0.43-9.30 years. Overall survival (OS and event-free survival (EFS were analyzed. RESULTS: A total of 86 Ph+-ALL patients (40 females and 46 males; median age: 34.0 years were enrolled, including those with BCR/ABL transcripts 190 (n = 52, 210 (n = 25, and 230 (n = 2; BCR/ABL isoform determination was not available for 7 patients. Mortality was influenced by variable BCR/ABL transcripts and TKI administration, and BCR/ABL transcripts, hematopoietic stem cell transplantation (HSCT, and TKI administration were associated with the occurrence of events. The OS rate in the TKI administration group during steady state was significantly higher compared with those patients who did not receive TKI administration (P = 0.008, the EFS rate in the TKI administration group during steady state was significantly higher compared with those patients who did not receive TKIs (P = 0.012, and also higher than those with TKI salvage administration (P = 0.004. BCR/ABL transcripts 210 showed preferable OS and EFS compared with BCR/ABL transcripts 190 and 230 (P<0.05 for each. CONCLUSIONS: The susceptibility of Ph+-ALL to TKI associated with the patterns of BCR-ABL rearrangement is demonstrated for the first time, thus adding another risk-stratifying molecular prognostic tool for the management of patients with Ph+-ALL.

  13. The BTK Inhibitor Ibrutinib (PCI-32765) Blocks Hairy Cell Leukaemia Survival, Proliferation and BCR Signalling: A New Therapeutic Approach

    OpenAIRE

    Sivina, Mariela; Kreitman, Robert J.; Arons, Evgeny; Ravandi, Farhad; Burger, Jan A.

    2014-01-01

    B cell receptor (BCR) signalling plays a critical role in the progression of several B-cell malignancies, but its role in hairy cell leukaemia (HCL) is ambiguous. Bruton tyrosine kinase (BTK), a key player in BCR signalling, migration and adhesion, can be targeted with ibrutinib, a selective, irreversible BTK inhibitor. We analysed BTK expression and function in HCL and analysed the effects of ibrutinib on HCL cells. We demonstrated uniform BTK protein expression in HCL cells. Ibrutinib signi...

  14. Detection of BCR-ABL Fusion mRNA Using Reverse Transcriptase Loop-mediated Isothermal Amplification

    Energy Technology Data Exchange (ETDEWEB)

    Dugan, L C; Hall, S; Kohlgruber, A; Urbin, S; Torres, C; Wilson, P

    2011-12-08

    RT-PCR is commonly used for the detection of Bcr-Abl fusion transcripts in patients diagnosed with chronic myelogenous leukemia, CML. Two fusion transcripts predominate in CML, Br-Abl e13a2 and e14a2. They have developed reverse transcriptase isothermal loop-mediated amplification (RT-LAMP) assays to detect these two fusion transcripts along with the normal Bcr transcript.

  15. Death by a thousand knives: Multiple BH3-only proteins are required for maximal apoptosis triggered through the BCR.

    Science.gov (United States)

    Carter, Matthew J; Cragg, Mark S

    2016-03-01

    The B-cell receptor (BCR) represents a key driver of B-cell development. Consequently, multiple mechanisms link inappropriate BCR signaling to apoptosis. Recently, we characterized the molecular regulators involved in lymphoma cells, confirming a major role for Bcl-2 interacting mediator of cell death (Bim) and supplementary roles for Bcl-2 interacting killer (Bik) and Noxa, and showing that all 3 proteins are required for maximal apoptosis. PMID:27308607

  16. On Tachyons in Generic Orbifolds of $\\BC^r$ and Gauged Linear Sigma Models

    OpenAIRE

    Sarkar, Tapobrata

    2006-01-01

    We study some aspects of Gauged Linear Sigma Models corresponding to orbifold singularities of the form $\\BC^r/\\Gamma$, for $r=2,3$ and $\\Gamma = \\BZ_n$ and $\\BZ_n\\times \\BZ_m$. These orbifolds might be tachyonic in general. We compute expressions for the multi parameter sigma model Lagrangians for these orbifolds, in terms of their toric geometry data. Using this, we analyze some aspects of the phases of generic orbifolds of $\\BC^r$.

  17. B Cells Regulate CD4+ T cell Responses to Papain Following BCR-Independent Papain Uptake

    OpenAIRE

    Dwyer, Daniel F.; Woodruff, Matthew C.; Carroll, Michael C.; Austen, K. Frank; Gurish, Michael F.

    2014-01-01

    Papain, a cysteine protease allergen with inherent adjuvant activity, induces potent IL4 expression by T cells in the popliteal lymph nodes (PLN) of mice following footpad immunization. Here we identify a novel, non-BCR mediated capacity for B cells to rapidly bind and internalize papain. B cells subsequently regulate the adaptive immune response by enhancing Inducible T cell Costimulator (ICOS) expression on CD4+ T cells and amplifying Th2 and T follicular helper induction. Antibody blockade...

  18. Mutations in the BCR-ABL1 Kinase Domain and Elsewhere in Chronic Myeloid Leukemia.

    Science.gov (United States)

    Soverini, Simona; de Benedittis, Caterina; Mancini, Manuela; Martinelli, Giovanni

    2015-06-01

    Chronic myeloid leukemia (CML) has been the first human malignancy to be associated, more than 50 years ago, with a consistent chromosomal abnormality--the t(9;22)(q34;q11) chromosomal translocation. The resulting BCR-ABL1 fusion gene, encoding a tyrosine kinase with deregulated activity, has a central role in the pathogenesis of CML. Ancestral or additional genetic events necessary for CML to develop have long been hypothesized but never really demonstrated. CML can successfully be treated with tyrosine kinase inhibitors (TKIs). Mutations in the BCR-ABL1 kinase domain might arise, however, that confer resistance to 1 or more of the currently available TKIs. Hence, the critical role of BCR-ABL1 mutation screening for optimal therapeutic management, with the current gold standard technique, conventional sequencing, likely to be replaced soon by ultra-deep sequencing. Mutations in genes other than BCR-ABL1 include ASXL1, TET2, RUNX1, DNMT3A, EZH2, and TP53 in chronic phase patients and RUNX1, ASXL1, IKZF1, WT1, TET2, NPM1, IDH1, IDH2, NRAS, KRAS, CBL, TP53, CDKN2A, RB1, and GATA-2 mutations in advanced phase patients. The latter also display additional cytogenetic abnormalities, including submicroscopic regions of gain or loss that only single nucleotide polymorphism arrays or array comparative genomic hybridization can detect. Whether whole genome/exome sequencing studies will uncover novel mutations relevant for pathogenesis, progression, and risk-adapted therapy is still unclear. PMID:26297264

  19. Autophagy induction by Bcr-Abl-expressing cells facilitates their recovery from a targeted or nontargeted treatment.

    LENUS (Irish Health Repository)

    Crowley, Lisa C

    2012-01-31

    Although Imatinib has transformed the treatment of chronic myeloid leukemia (CML), it is not curative due to the persistence of resistant cells that can regenerate the disease. We have examined how Bcr-Abl-expressing cells respond to two mechanistically different therapeutic agents, etoposide and Imatinib. We also examined Bcr-Abl expression at low and high levels as elevated expression has been associated with treatment failure. Cells expressing low levels of Bcr-Abl undergo apoptosis in response to the DNA-targeting agent (etoposide), whereas high-Bcr-Abl-expressing cells primarily induce autophagy. Autophagic populations engage a delayed nonapoptotic death; however, sufficient cells evade this and repopulate following the withdrawal of the drug. Non-Bcr-Abl-expressing 32D or Ba\\/F3 cells induce both apoptosis and autophagy in response to etoposide and can recover. Imatinib treatment induces both apoptosis and autophagy in all Bcr-Abl-expressing cells and populations rapidly recover. Inhibition of autophagy with ATG7 and Beclin1 siRNA significantly reduced the recovery of Imatinib-treated K562 cells, indicating the importance of autophagy for the recovery of treated cells. Combination regimes incorporating agents that disrupt Imatinib-induced autophagy would remain primarily targeted and may improve response to the treatment in CML.

  20. Identification of drug combinations containing imatinib for treatment of BCR-ABL+ leukemias.

    Directory of Open Access Journals (Sweden)

    Yunyi Kang

    Full Text Available The BCR-ABL translocation is found in chronic myeloid leukemia (CML and in Ph+ acute lymphoblastic leukemia (ALL patients. Although imatinib and its analogues have been used as front-line therapy to target this mutation and control the disease for over a decade, resistance to the therapy is still observed and most patients are not cured but need to continue the therapy indefinitely. It is therefore of great importance to find new therapies, possibly as drug combinations, which can overcome drug resistance. In this study, we identified eleven candidate anti-leukemic drugs that might be combined with imatinib, using three approaches: a kinase inhibitor library screen, a gene expression correlation analysis, and literature analysis. We then used an experimental search algorithm to efficiently explore the large space of possible drug and dose combinations and identified drug combinations that selectively kill a BCR-ABL+ leukemic cell line (K562 over a normal fibroblast cell line (IMR-90. Only six iterations of the algorithm were needed to identify very selective drug combinations. The efficacy of the top forty-nine combinations was further confirmed using Ph+ and Ph- ALL patient cells, including imatinib-resistant cells. Collectively, the drug combinations and methods we describe might be a first step towards more effective interventions for leukemia patients, especially those with the BCR-ABL translocation.

  1. Association of HLA antigens and BCR-ABL transcripts in leukemia patients with the Philadelphia chromosome

    Directory of Open Access Journals (Sweden)

    Daiana Landenberger de Carvalho

    2012-01-01

    Full Text Available OBJECTIVE: This study aimed to verify the association between human leukocyte antigens and the bcr-abl fusion protein resulting from t(9;22(q34;q11 in chronic leukemia myeloid and acute lymphoblastic leukemia patients. METHODS: Forty-seven bcr-abl positive individuals were evaluated. Typing was performed bymicrolymphocytotoxicity and molecular biological methods (human leukocyte antigens Class I and Class II. A control group was obtained from the data of potential bone marrow donors registered in the Brazilian Bone Marrow Donor Registry (REDOME. RESULTS: Positive associations with HLA-A25 and HLA-B18 were found for the b2a2 transcript, as well as a tendency towards a positive association with HLA-B40 and a negative association with HLA-A68. The b3a2 transcript showed positive associations with HLA-B40 and HLA-DRB1*3. CONCLUSION: The negative association between human leukocyte antigens and the BCR-ABL transcript suggests that binding and presentation of peptides derived from the chimeric protein are effective to increase a cytotoxic T lymphocyte response appropriate for the destruction of leukemic cells.

  2. Biodegradable charged polyester-based vectors (BCPVs) as an efficient non-viral transfection nanoagent for gene knockdown of the BCR-ABL hybrid oncogene in a human chronic myeloid leukemia cell line

    Science.gov (United States)

    Yang, Chengbin; Panwar, Nishtha; Wang, Yucheng; Zhang, Butian; Liu, Maixian; Toh, Huiting; Yoon, Ho Sup; Tjin, Swee Chuan; Chong, Peter Han Joo; Law, Wing-Cheung; Chen, Chih-Kuang; Yong, Ken-Tye

    2016-04-01

    First-line therapy of chronic myelogenous leukemia (CML) has always involved the use of BCR-ABL tyrosine-kinase inhibitors which is associated with an abnormal chromosome called Philadelphia chromosome. Although the overall survival rate has been improved by the current therapeutic regime, the presence of resistance has resulted in limited efficacy. In this study, an RNA interference (RNAi)-based therapeutic regime is proposed with the aim to knockdown the BCR-ABL hybrid oncogene using small interfering RNA (siRNA). The siRNA transfection rates have usually been limited due to the declining contact probability among polyplexes and the non-adherent nature of leukemic cells. Our work aims at addressing this limitation by using a biodegradable charged polyester-based vector (BCPV) as a nanocarrier for the delivery of BCR-ABL-specific siRNA to the suspension culture of a K562 CML cell line. BCR-ABL siRNAs were encapsulated in the BCPVs by electrostatic force. Cell internalization was facilitated by the BCPV and assessed by confocal microscopy and flow cytometry. The regulation of the BCR-ABL level in K562 cells as a result of RNAi was analyzed by real-time polymerase chain reaction (RT-PCR). We observed that BCPV was able to form stable nanoplexes with siRNA molecules, even in the presence of fetal bovine serum (FBS), and successfully assisted in vitro siRNA transfection in the non-adherent K562 cells. As a consequence of downregulation of BCR-ABL, BCPV-siRNA nanoplexes inhibited cell proliferation and promoted cell apoptosis. All results were compared with a commercial transfection reagent, Lipofectamine2000™, which served as a positive control. More importantly, this class of non-viral vector exhibits biodegradable features and negligible cytotoxicity, thus providing a versatile platform to deliver siRNA to non-adherent leukemia cells with high transfection efficiency by effectively overcoming extra- and intra-cellular barriers. Due to the excellent in vitro

  3. BCR-701: A review of 10-years of sequential extraction analyses

    International Nuclear Information System (INIS)

    A detailed quantitative analysis was performed on data presented in the literature that focused on the sequential extraction of cadmium (Cd), chromium (Cr), copper (Cu), nickel (Ni), lead (Pb) and zinc (Zn) from the certified reference material BCR-701 (lake sediment) using the three-step harmonized BCR procedure. The accuracy of data reported in the literature, including precision and different measures of trueness, was assessed relative to the certified values for BCR-701. Forty data sets were accepted following extreme outlier removal, and statistically summarized with measures of central tendency, dispersion, and distribution form. In general, literature data were similar in their measurement precision to the expert laboratories used to certify the trace element contents in BCR-701. The overall median precision for literature reported data was 10% (range 6-19%), compared to certifying laboratories of 9% (range 4-33%). One measure of literature data trueness was assessed via a confirmatory approach using a robust bootstrap method. Only 22% of the comparisons indicated significantly different (all were lower) concentrations reported in the literature compared to certified values. The question of whether the differences are practically significant for environmental studies is raised. Bias was computed as a measure of trueness, and literature data were more frequently negatively biased, indicating lower concentrations reported in the literature for the six trace elements for the three-step sequential procedure compared to the certified values. However, 95% confidence intervals about the average bias for the 18 comparisons indicated only four instances when a mean bias of 0 (i.e., measured = certified) was not incorporated-suggesting statistical difference. Finally, Z-scores incorporating a Horwitz-type function were used to assess the general trueness of laboratory data. Of the 468 laboratory Z-score values computed, 92% were considered to be satisfactory, 5% were

  4. AP24534, a Pan-BCR-ABL Inhibitor for Chronic Myeloid Leukemia, Potently Inhibits the T315I Mutant and Overcomes Mutation-Based Resistance

    Energy Technology Data Exchange (ETDEWEB)

    O’Hare, Thomas; Shakespeare, William C.; Zhu, Xiaotian; Eide, Christopher A.; Rivera, Victor M.; Wang, Frank; Adrian, Lauren T.; Zhou, Tianjun; Huang, Wei-Sheng; Xu, Qihong; Metcalf, III, Chester A.; Tyner, Jeffrey W.; Loriaux, Marc M.; Corbin, Amie S.; Wardwell, Scott; Ning, Yaoyu; Keats, Jeffrey A.; Wang, Yihan; Sundaramoorthi, Raji; Thomas, Mathew; Zhou, Dong; Snodgrass, Joseph; Commodore, Lois; Sawyer, Tomi K.; Dalgarno, David C.; Deininger, Michael W.N.; Druker, Brian J.; Clackson, Tim; (OHSU- Cancer Instit.); (ARIAD)

    2010-09-07

    Inhibition of BCR-ABL by imatinib induces durable responses in many patients with chronic myeloid leukemia (CML), but resistance attributable to kinase domain mutations can lead to relapse and a switch to second-line therapy with nilotinib or dasatinib. Despite three approved therapeutic options, the cross-resistant BCR-ABL{sup T315I} mutation and compound mutants selected on sequential inhibitor therapy remain major clinical challenges. We report design and preclinical evaluation of AP24534, a potent, orally available multitargeted kinase inhibitor active against T315I and other BCR-ABL mutants. AP24534 inhibited all tested BCR-ABL mutants in cellular and biochemical assays, suppressed BCR-ABL{sup T315I}-driven tumor growth in mice, and completely abrogated resistance in cell-based mutagenesis screens. Our work supports clinical evaluation of AP24534 as a pan-BCR-ABL inhibitor for treatment of CML.

  5. Acute progression of BCR-FGFR1 induced murine B-lympho/myeloproliferative disorder suggests involvement of lineages at the pro-B cell stage.

    Directory of Open Access Journals (Sweden)

    Mingqiang Ren

    Full Text Available Constitutive activation of FGFR1, through rearrangement with various dimerization domains, leads to atypical myeloproliferative disorders where, although T cell lymphoma are common, the BCR-FGFR1 chimeric kinase results in CML-like leukemia. As with the human disease, mouse bone marrow transduction/transplantation with BCR-FGFR1 leads to CML-like myeloproliferation as well as B-cell leukemia/lymphoma. The murine disease described in this report is virtually identical to the human disease in that both showed bi-lineage involvement of myeloid and B-cells, splenomegaly, leukocytosis and bone marrow hypercellularity. A CD19(+ IgM(- CD43(+ immunophenotype was seen both in primary tumors and two cell lines derived from these tumors. In all primary tumors, subpopulations of these CD19(+ IgM(- CD43(+ were also either B220(+ or B220(-, suggesting a block in differentiation at the pro-B cell stage. The B220(- phenotype was retained in one of the cell lines while the other was B220(+. When the two cell lines were transplanted into syngeneic mice, all animals developed the same B-lymphoblastic leukemia within 2-weeks. Thus, the murine model described here closely mimics the human disease with bilineage myeloid and B-cell leukemia/lymphoma which provides a representative model to investigate therapeutic intervention and a better understanding of the etiology of the disease.

  6. A Tissue Retrieval and Postharvest Processing Regimen for Rodent Reproductive Tissues Compatible with Long-Term Storage on the International Space Station and Postflight Biospecimen Sharing Program

    Directory of Open Access Journals (Sweden)

    Vijayalaxmi Gupta

    2015-01-01

    Full Text Available Collection and processing of tissues to preserve space flight effects from animals after return to Earth is challenging. Specimens must be harvested with minimal time after landing to minimize postflight readaptation alterations in protein expression/translation, posttranslational modifications, and expression, as well as changes in gene expression and tissue histological degradation after euthanasia. We report the development of a widely applicable strategy for determining the window of optimal species-specific and tissue-specific posteuthanasia harvest that can be utilized to integrate into multi-investigator Biospecimen Sharing Programs. We also determined methods for ISS-compatible long-term tissue storage (10 months at −80°C that yield recovery of high quality mRNA and protein for western analysis after sample return. Our focus was reproductive tissues. The time following euthanasia where tissues could be collected and histological integrity was maintained varied with tissue and species ranging between 1 and 3 hours. RNA quality was preserved in key reproductive tissues fixed in RNAlater up to 40 min after euthanasia. Postfixation processing was also standardized for safe shipment back to our laboratory. Our strategy can be adapted for other tissues under NASA’s Biospecimen Sharing Program or similar multi-investigator tissue sharing opportunities.

  7. A tissue retrieval and postharvest processing regimen for rodent reproductive tissues compatible with long-term storage on the international space station and postflight biospecimen sharing program.

    Science.gov (United States)

    Gupta, Vijayalaxmi; Holets-Bondar, Lesya; Roby, Katherine F; Enders, George; Tash, Joseph S

    2015-01-01

    Collection and processing of tissues to preserve space flight effects from animals after return to Earth is challenging. Specimens must be harvested with minimal time after landing to minimize postflight readaptation alterations in protein expression/translation, posttranslational modifications, and expression, as well as changes in gene expression and tissue histological degradation after euthanasia. We report the development of a widely applicable strategy for determining the window of optimal species-specific and tissue-specific posteuthanasia harvest that can be utilized to integrate into multi-investigator Biospecimen Sharing Programs. We also determined methods for ISS-compatible long-term tissue storage (10 months at -80°C) that yield recovery of high quality mRNA and protein for western analysis after sample return. Our focus was reproductive tissues. The time following euthanasia where tissues could be collected and histological integrity was maintained varied with tissue and species ranging between 1 and 3 hours. RNA quality was preserved in key reproductive tissues fixed in RNAlater up to 40 min after euthanasia. Postfixation processing was also standardized for safe shipment back to our laboratory. Our strategy can be adapted for other tissues under NASA's Biospecimen Sharing Program or similar multi-investigator tissue sharing opportunities.

  8. Contrasting the ethical perspectives of biospecimen research among individuals with familial risk for hereditary cancer and biomedical researchers: implications for researcher training.

    Science.gov (United States)

    Quinn, Gwendolyn P; Koskan, Alexis; Sehovic, Ivana; Pal, Tuya; Meade, Cathy; Gwede, Clement K

    2014-07-01

    While ethical concerns about participating in biospecimen research have been previously identified, few studies have reported the concerns among individuals with familial risk for hereditary cancer (IFRs). At the same time, biomedical researchers often lack training in discussing such concerns to potential donors. This study explores IFRs' and biomedical researchers' perceptions of ethical concerns about participating in biobanking research. In separate focus groups, IFRs and biomedical researchers participated in 90-min telephone focus groups. Focus group questions centered on knowledge about laws that protect the confidentiality of biospecimen donors, understanding of informed consent and study procedures, and preferences for being recontacted about potential incidental discovery and also study results. A total of 40 IFRs and 32 biomedical researchers participated in the focus groups. Results demonstrated discrepancies between the perceptions of IFRs and researchers. IFRs' concerns centered on health information protection; potential discrimination by insurers and employers; and preferences for being recontacted upon discovery of gene mutations or to communicate study results. Researchers perceived that participants understood laws protecting donors' privacy and (detailed study information outlined in the informed consent process), study outcomes were used to create a training tool kit to increase researchers' understanding of IFRs' concerns about biobanking.

  9. SGX393 inhibits the CML mutant Bcr-Abl[superscript T315I] and preempts in vitro resistance when combined with nilotinib or dasatinib

    Energy Technology Data Exchange (ETDEWEB)

    O' Hare, Thomas; Eide, Christopher A.; Tyner, Jeffrey W.; Corbin, Amie S.; Wong, Matthew J.; Buchanan, Sean; Holme, Kevin; Jessen, Katayoun A.; Tang, Crystal; Lewis, Hal A.; Romero, Richard D.; Burley, Stephen K.; Deininger, Michael W. (OHSU- Cancer Instit.); (SGX)

    2010-01-12

    Imatinib inhibits Bcr-Abl, the oncogenic tyrosine kinase that causes chronic myeloid leukemia. The second-line inhibitors nilotinib and dasatinib are effective in patients with imatinib resistance resulting from Bcr-Abl kinase domain mutations. Bcr-Abl{sup T315I}, however, is resistant to all Abl kinase inhibitors in clinical use and is emerging as the most frequent cause of salvage therapy failure. SGX393 is a potent inhibitor of native and T315I-mutant Bcr-Abl kinase that blocks the growth of leukemia cell lines and primary hematopoietic cells expressing Bcr-Abl{sup T315I}, with minimal toxicity against Bcr-Abl-negative cell lines or normal bone marrow. A screen for Bcr-Abl mutants emerging in the presence of SGX393 revealed concentration-dependent reduction in the number and range of mutations. Combining SGX393 with nilotinib or dasatinib preempted emergence of resistant subclones, including Bcr-Abl{sup T315I}. These findings suggest that combination of a T315I inhibitor with the current clinically used inhibitors may be useful for reduction of Bcr-Abl mutants in Philadelphia chromosome-positive leukemia.

  10. Inhibitory Effects of Omacetaxine on Leukemic Stem Cells and BCR-ABL-Induced Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia in Mice

    OpenAIRE

    Chen, Yaoyu; Hu, Yiguo; Michaels, Shawnya; Segal, David; Brown, Dennis; Li, Shaoguang

    2009-01-01

    Omacetaxine mepesuccinate (formerly homoharringtonine) is a molecule with a mechanism of action that is different from tyrosine kinase inhibitors and its activity in chronic myeloid leukemia (CML) seems to be independent of BCR-ABL mutation status. Using BCR-ABL-expressing myelogenous and lymphoid cell lines and mouse models of CML and B cell acute lymphoblastic leukemia (B-ALL) induced by wild type BCR-ABL or T315I mutant-BCR-ABL, we evaluated the inhibitory effects of omacetaxine on CML and...

  11. Development of an Integrated Biospecimen Database among the Regional Biobanks in Korea

    OpenAIRE

    Park, Hyun Sang; Cho, Hune; Kim, Hwa Sun

    2016-01-01

    Objectives This study developed an integrated database for 15 regional biobanks that provides large quantities of high-quality bio-data to researchers to be used for the prevention of disease, for the development of personalized medicines, and in genetics studies. Methods We collected raw data, managed independently by 15 regional biobanks, for database modeling and analyzed and defined the metadata of the items. We also built a three-step (high, middle, and low) classification system for cla...

  12. BCR-ABL1 kinase inhibits uracil DNA glycosylase UNG2 to enhance oxidative DNA damage and stimulate genomic instability

    Science.gov (United States)

    Slupianek, Artur; Falinski, Rafal; Znojek, Pawel; Stoklosa, Tomasz; Flis, Sylwia; Doneddu, Valentina; Pytel, Dariusz; Synowiec, Ewelina; Blasiak, Janusz; Bellacosa, Alfonso; Skorski, Tomasz

    2013-01-01

    Tyrosine kinase inhibitors (TKIs) revolutionized the treatment of CML-CP. Unfortunately, 25% of TKI-naive patients and 50–90% of TKI-responding patients carry CML clones expressing TKI resistant BCR-ABL1 kinase mutants. We reported that CML-CP leukemia stem and progenitor cell populations accumulate high amounts of reactive oxygen species (ROS), which may result in accumulation of uracil derivatives in genomic DNA. Unfaithful and/or inefficient repair of these lesions generates TKI resistant point mutations in BCR-ABL1 kinase. Using an array of specific substrates and inhibitors/blocking antibodies we found that uracil-DNA glycosylase UNG2 were inhibited in BCR-ABL1 –transformed cell lines and CD34+ CML cells. The inhibitory effect was not accompanied by downregulation of nuclear expression and/or chromatin association of UNG2. The effect was BCR-ABL1 kinase-specific because several other fusion tyrosine kinases did not reduce UNG2 activity. Using UNG2-specific inhibitor UGI we found that reduction of UNG2 activity increased the number of uracil derivatives in genomic DNA detected by modified comet assay and facilitated accumulation of ouabain-resistant point mutations in reporter gene Na+/K+ATPase. In conclusion, we postulate that BCR-ABL1 kinase-mediated inhibition of UNG2 contributes to accumulation of point mutations responsible for TKI-resistance causing the disease relapse, and perhaps also other point mutations facilitating malignant progression of CML. PMID:23047475

  13. The impact of multiple low-level BCR-ABL1 mutations on response to ponatinib

    Science.gov (United States)

    Yeung, David T. O.; Yeoman, Alexandra L.; Altamura, Haley K.; Jamison, Bronte A.; Field, Chani R.; Hodgson, J. Graeme; Lustgarten, Stephanie; Rivera, Victor M.; Hughes, Timothy P.; Branford, Susan

    2016-01-01

    The third-generation tyrosine kinase inhibitor (TKI) ponatinib shows activity against all common BCR-ABL1 single mutants, including the highly resistant BCR-ABL1-T315I mutant, improving outcome for patients with refractory chronic myeloid leukemia (CML). However, responses are variable, and causal baseline factors have not been well-studied. The type and number of low-level BCR-ABL1 mutations present after imatinib resistance has prognostic significance for subsequent treatment with nilotinib or dasatinib as second-line therapy. We therefore investigated the impact of low-level mutations detected by sensitive mass-spectrometry before ponatinib initiation (baseline) on treatment response in 363 TKI-resistant patients enrolled in the PONATINIB for Chronic Myeloid Leukemia Evaluation and Ph+ Acute Lymphoblastic Leukemia trial, including 231 patients in chronic phase (CP-CML). Low-level mutations were detected in 53 patients (15%, including low-level T315I in 14 patients); most, however, did not undergo clonal expansion during ponatinib treatment and, moreover, no specific individual mutations were associated with inferior outcome. We demonstrate however, that the number of mutations detectable by mass spectrometry after TKI resistance is associated with response to ponatinib treatment and could be used to refine the therapeutic approach. Although CP-CML patients with T315I (63/231, 27%) had superior responses overall, those with multiple mutations detectable by mass spectrometry (20, 32%) had substantially inferior responses compared with those with T315I as the sole mutation detected (43, 68%). In contrast, for CP-CML patients without T315I, the inferior responses previously observed with nilotinib/dasatinib therapy for imatinib-resistant patients with multiple mutations were not seen with ponatinib treatment, suggesting that ponatinib may prove to be particularly advantageous for patients with multiple mutations detectable by mass spectrometry after TKI resistance

  14. Infrared matrix-assisted laser desorption electrospray ionization mass spectrometry imaging analysis of biospecimens.

    Science.gov (United States)

    Bokhart, M T; Muddiman, D C

    2016-09-21

    Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry imaging (MSI) is a technique well suited for analysis of biological specimens. This tutorial review focuses on recent advancements and applications of IR-MALDESI MSI to better understand key biological questions. Through optimization of user-defined source parameters, comprehensive and quantitative MSI data can be obtained for a variety of analytes. The effect of an ice matrix layer is well defined in the context of desorption dynamics and resulting ion abundance. Optimized parameters and careful control of conditions affords quantitative MSI data which provides valuable information for targeted, label-free drug distribution studies and untargeted metabolomic datasets. Challenges and limitations of MSI using IR-MALDESI are addressed in the context of the bioimaging field. PMID:27484166

  15. Evaluating CO2 mineralization capacity of sedimentary rock Using BCR sequential extraction procedures

    Science.gov (United States)

    Yang, Gang-Ting; Yu, Chi-Wen; Yang, Hsiao-Ming; Chiao, Chung-Hui; Yang, Ming-Wei

    2015-04-01

    To relief the high concentration of carbon dioxide in the atmosphere, carbon capture and storage (CCS) is gradually becoming an important concept to reduce greenhouse gas emissions. In IPCC Special Report on CCS, the storage mechanisms for geological formations are categorized into structural/stratigraphic, hydrodynamic and geochemical trappings. Geochemical trapping is considered as a storage mechanism, which can further increase storage capacity, effectiveness and security in terms of permanent CO2 sequestration. The injected CO2 can have geochemical interactions with pore fluid and reservoir rocks and transform into minerals. It is important to evaluate the capacity of reservoir rock for sequestrating CO2. In this study, sedimentary rock samples were collected from a 2-km-deep well in Midwestern Taiwan; and, the BCR sequential extraction experiments developed by European Union Measurement and Testing Programme were conducted. BCR was designed for extracting three major phases from soil, including exchangeable phase and carbonates (the first stage), reducible phase (the second stage) and oxidizable phase (the third stage). The chemistry of extracted solutions and rock residues were measured with ICP-MS and XRF, respectively. According to the results of XRF, considerable amounts of calcium and iron can be extracted by BCR procedures but other cations are negligible. In general, shale has a higher capacity of CO2 sequestration than sandstone. The first stage of extraction can release about 6 (sandstone) to 18.5 (shale) g of calcium from 1 kg rock, which are equivalent to 6.6 and 20.4 g CO2/kg rock, respectively. In the second stage extraction, 0.71 (sandstone) to 1.38 (shale) g/kg rock of iron can be released and can mineralized 0.56 to 1.08 g CO2/kg rock. However, there are no considerable cations extracted in the third stage of BCR as shown by the XRF analysis. In addition, the results of ICP-MS show that Mg can be released in the order of 10-3 g from 1 kg rock

  16. Molecular Imaging of Bcr-Abl Phosphokinase in a Xenograft Model*

    OpenAIRE

    Wu, Ji Yuan; David J. Yang; Angelo, Laura S.; Kohanim, Saady; Kurzrock, Razelle

    2009-01-01

    The purpose of this study was to determine whether the Bcr-Abl tyrosine kinase can be assessed by gamma imaging using an 111Indium-labeled anti-phosphotyrosine antibody, and if the response to treatment with imatinib could be detected using this imaging technique. Anti-phosphotyrosine antibody (APT) was labeled with indium (111In) using ethylenedicysteine (EC) as a chelator. To determine if 111In-EC-APT could assess a non-receptor tyrosine kinase, xenografts of the human chronic myelogenous l...

  17. Distinct GAB2 signaling pathways are essential for myeloid and lymphoid transformation and leukemogenesis by BCR-ABL1.

    Science.gov (United States)

    Gu, Shengqing; Chan, Wayne W; Mohi, Golam; Rosenbaum, Joel; Sayad, Azin; Lu, Zhibin; Virtanen, Carl; Li, Shaoguang; Neel, Benjamin G; Van Etten, Richard A

    2016-04-01

    Tyrosine kinase inhibitors (TKIs) directed against BCR-ABL1, the product of the Philadelphia (Ph) chromosome, have revolutionized treatment of patients with chronic myeloid leukemia (CML). However, acquired resistance to TKIs is a significant clinical problem in CML, and TKI therapy is much less effective against Ph(+)B-cell acute lymphoblastic leukemia (B-ALL). BCR-ABL1, via phosphorylated Tyr177, recruits the adapter GRB2-associated binding protein 2 (GAB2) as part of a GRB2/GAB2 complex. We showed previously that GAB2 is essential for BCR-ABL1-evoked myeloid transformation in vitro. Using a genetic strategy and mouse models of CML and B-ALL, we show here that GAB2 is essential for myeloid and lymphoid leukemogenesis by BCR-ABL1. In the mouse model, recipients of BCR-ABL1-transducedGab2(-/-)bone marrow failed to develop CML-like myeloproliferative neoplasia. Leukemogenesis was restored by expression of GAB2 but not by GAB2 mutants lacking binding sites for its effectors phosphatidylinositol 3-kinase (PI3K) or SRC homology 2-containing phosphotyrosine phosphatase 2 (SHP2). GAB2 deficiency also attenuated BCR-ABL1-induced B-ALL, but only the SHP2 binding site was required. The SHP2 and PI3K binding sites were differentially required for signaling downstream of GAB2. Hence, GAB2 transmits critical transforming signals from Tyr177 to PI3K and SHP2 for CML pathogenesis, whereas only the GAB2-SHP2 pathway is essential for lymphoid leukemogenesis. Given that GAB2 is dispensable for normal hematopoiesis, GAB2 and its effectors PI3K and SHP2 represent promising targets for therapy in Ph(+)hematologic neoplasms. PMID:26773044

  18. Microstructure and Wear Analysis of FeBCr Based Coating Deposited by HVOF Method

    Directory of Open Access Journals (Sweden)

    M.S. Priyan

    2014-06-01

    Full Text Available Thermally sprayed coatings that are based on FeBCr-related alloy powders are widely used to improve properties such as the surface hardness and wear resistance of a variety of coated metal substrate materials. Gray cast iron is widely used in the automobile industry due to its low cost and performance. In this work Gray cast iron substrate is coated with FeBCr alloy powder to improve its performance. The microstructure and micro abrasive wear performance of both the uncoated substrates and the coated substrates were characterized by optical microscopy as well as by Scanning Electron Microscope (SEM. In addition, X-ray Diffraction (XRD was undertaken in the partial characterization of the coating. The densely layered coating had porosity levels that were below 2.5 % and a high surface hardness, of the order of 980 HV0.1. The coating exhibited excellent wear resistance when subjected to the ball-cratering test method. The low coefficients of friction of hard coating on the substrate were recorded. The wear performance of the coating was nearly 82 % better than that of the substrate, with a 0.05 N load, even under severe three body abrasive conditions.

  19. The Role of MEK Kinase 1 in Bcr-Abl-Induced Self-Renewal Activity of Embryonic Stem Cells

    OpenAIRE

    NAKAMURA, Yukinori; Yujiri, Toshiaki; Tanizawa, Yukio

    2006-01-01

    BCR-ABL oncogene, the moecular hallmark of chronic mylogenous leukemia, arises in a promitive hematopoietic stem cell that has the capacity for both differentiation and self-renewal. Its product, Bcr-Abl protein, has been shown to sctivate signal transducers and activators of transcription 3 (STAT3) and to promote self-renewal in embryonic stem (ES)cells, even in the absencs of leukemia in hibitory factor (LIF). MEK kinase 1 (MEKK1) is a 196-kDa mitogen-activated protein kinase (MAPK) kinase ...

  20. DMPD: Mechanisms of selection mediated by interleukin-7, the preBCR, and hemokinin-1during B-cell development. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 14962188 Mechanisms of selection mediated by interleukin-7, the preBCR, and hemokin...ng) (.svg) (.html) (.csml) Show Mechanisms of selection mediated by interleukin-7, the preBCR, and hemokinin...-1during B-cell development. PubmedID 14962188 Title Mechanisms of selection media

  1. Association of HLA Class I and Class II genes with bcr-abl transcripts in leukemia patients with t(9;22 (q34;q11

    Directory of Open Access Journals (Sweden)

    Cano Pedro

    2004-06-01

    Full Text Available Abstract Background Based on the site of breakpoint in t(9;22 (q34;q11, bcr-abl fusion in leukemia patients is associated with different types of transcript proteins. In this study we have seen the association of HLA genes with different types of bcr-abl transcripts. The association could predict the bcr-abl peptide presentation by particular HLA molecules. Methods The study included a total of 189 patients of mixed ethnicity with chronic myelogenous leukemia and acute lymphocytic leukemia who were being considered for bone marrow transplantation. Typing of bcr-abl transcripts was done by reverse transcriptase PCR method. HLA typing was performed by molecular methods. The bcr-abl and HLA association was studied by calculating the relative risks and chi-square test. Results Significant negative associations (p Conclusions The negative associations of a particular bcr-abl transcript with specific HLA alleles suggests that these alleles play a critical role in presenting peptides derived from the chimeric proteins and eliciting a successful T-cell cytotoxic response. Knowledge of differential associations between HLA phenotypes and bcr-abl fusion transcript types would help in developing better strategies for immunization with the bcr-abl peptides against t(9;22 (q34;q11-positive leukemia.

  2. A multiple reaction monitoring (MRM method to detect Bcr-Abl kinase activity in CML using a peptide biosensor.

    Directory of Open Access Journals (Sweden)

    Tzu-Yi Yang

    Full Text Available The protein kinase Bcr-Abl plays a major role in the pathogenesis of chronic myelogenous leukemia (CML, and is the target of the breakthrough drug imatinib (Gleevec™. While most patients respond well to imatinib, approximately 30% never achieve remission or develop resistance within 1-5 years of starting imatinib treatment. Evidence from clinical studies suggests that achieving at least 50% inhibition of a patient's Bcr-Abl kinase activity (relative to their level at diagnosis is associated with improved patient outcomes, including reduced occurrence of resistance and longer maintenance of remission. Accordingly, sensitive assays for detecting Bcr-Abl kinase activity compatible with small amounts of patient material are desirable as potential companion diagnostics for imatinib. Here we report the detection of Bcr-Abl activity and inhibition by imatinib in the human CML cell line K562 using a cell-penetrating peptide biosensor and multiple reaction monitoring (MRM on a triple quadrupole mass spectrometer. MRM enabled reproducible, selective detection of the peptide biosensor at fmol levels from aliquots of cell lysate equivalent to ~15,000 cells. This degree of sensitivity will facilitate the miniaturization of the entire assay procedure down to cell numbers approaching 15,000, making it practical for translational applications in patient cells in which the limited amount of available patient material often presents a major challenge.

  3. WT1-mediated repression of the proapoptotic transcription factor ZNF224 is triggered by the BCR-ABL oncogene.

    Science.gov (United States)

    Montano, Giorgia; Vidovic, Karina; Palladino, Chiara; Cesaro, Elena; Sodaro, Gaetano; Quintarelli, Concetta; De Angelis, Biagio; Errichiello, Santa; Pane, Fabrizio; Izzo, Paola; Grosso, Michela; Gullberg, Urban; Costanzo, Paola

    2015-09-29

    The Kruppel-like protein ZNF224 is a co-factor of the Wilms' tumor 1 protein, WT1. We have previously shown that ZNF224 exerts a specific proapoptotic role in chronic myelogenous leukemia (CML) K562 cells and contributes to cytosine arabinoside-induced apoptosis, by modulating WT1-dependent transcription of apoptotic genes. Here we demonstrate that ZNF224 gene expression is down-regulated both in BCR-ABL positive cell lines and in primary CML samples and is restored after imatinib and second generation tyrosine kinase inhibitors treatment. We also show that WT1, whose expression is positively regulated by BCR-ABL, represses transcription of the ZNF224 gene. Finally, we report that ZNF224 is significantly down-regulated in patients with BCR-ABL positive chronic phase-CML showing poor response or resistance to imatinib treatment as compared to high-responder patients. Taken as a whole, our data disclose a novel pathway activated by BCR-ABL that leads to inhibition of apoptosis through the ZNF224 repression. ZNF224 could thus represent a novel promising therapeutic target in CML. PMID:26320177

  4. Transcription Factors Efg1 and Bcr1 Regulate Biofilm Formation and Virulence during Candida albicans-Associated Denture Stomatitis.

    Science.gov (United States)

    Yano, Junko; Yu, Alika; Fidel, Paul L; Noverr, Mairi C

    2016-01-01

    Denture stomatitis (DS) is characterized by inflammation of the oral mucosa in direct contact with dentures and affects a significant number of otherwise healthy denture wearers. The disease is caused by Candida albicans, which readily colonizes and form biofilms on denture materials. While evidence for biofilms on abiotic and biotic surfaces initiating Candida infections is accumulating, a role for biofilms in DS remains unclear. Using an established model of DS in immunocompetent animals, the purpose of this study was to determine the role of biofilm formation in mucosal damage during pathogenesis using C. albicans or mutants defective in morphogenesis (efg1-/-) or biofilm formation (bcr1-/-). For in vivo analyses, rats fitted with custom dentures, consisting of fixed and removable parts, were inoculated with wild-type C. albicans, mutants or reconstituted strains and monitored weekly for fungal burden (denture and palate), body weight and tissue damage (LDH) for up to 8 weeks. C. albicans wild-type and reconstituted mutants formed biofilms on dentures and palatal tissues under in vitro, ex vivo and in vivo conditions as indicated by microscopy demonstrating robust biofilm architecture and extracellular matrix (ECM). In contrast, both efg1-/- and bcr1-/- mutants exhibited poor biofilm growth with little to no ECM. In addition, quantification of fungal burden showed reduced colonization throughout the infection period on dentures and palates of rats inoculated with efg1-/-, but not bcr1-/-, compared to controls. Finally, rats inoculated with efg1-/- and bcr1-/- mutants had minimal palatal tissue damage/weight loss while those inoculated with wild-type or reconstituted mutants showed evidence of tissue damage and exhibited stunted weight gain. These data suggest that biofilm formation is associated with tissue damage during DS and that Efg1 and Bcr1, both central regulators of virulence in C. albicans, have pivotal roles in pathogenesis of DS.

  5. BCR-ABL1 kinase inhibits uracil DNA glycosylase UNG2 to enhance oxidative DNA damage and stimulate genomic instability.

    Science.gov (United States)

    Slupianek, A; Falinski, R; Znojek, P; Stoklosa, T; Flis, S; Doneddu, V; Pytel, D; Synowiec, E; Blasiak, J; Bellacosa, A; Skorski, T

    2013-03-01

    Tyrosine kinase inhibitors (TKIs) revolutionized the treatment of chronic myeloid leukemia in chronic phase (CML-CP). Unfortunately, 25% of TKI-naive patients and 50-90% of patients developing TKI-resistance carry CML clones expressing TKI-resistant BCR-ABL1 kinase mutants. We reported that CML-CP leukemia stem and progenitor cell populations accumulate high amounts of reactive oxygen species, which may result in accumulation of uracil derivatives in genomic DNA. Unfaithful and/or inefficient repair of these lesions generates TKI-resistant point mutations in BCR-ABL1 kinase. Using an array of specific substrates and inhibitors/blocking antibodies we found that uracil DNA glycosylase UNG2 were inhibited in BCR-ABL1-transformed cell lines and CD34(+) CML cells. The inhibitory effect was not accompanied by downregulation of nuclear expression and/or chromatin association of UNG2. The effect was BCR-ABL1 kinase-specific because several other fusion tyrosine kinases did not reduce UNG2 activity. Using UNG2-specific inhibitor UGI, we found that reduction of UNG2 activity increased the number of uracil derivatives in genomic DNA detected by modified comet assay and facilitated accumulation of ouabain-resistant point mutations in reporter gene Na(+)/K(+)ATPase. In conclusion, we postulate that BCR-ABL1 kinase-mediated inhibition of UNG2 contributes to accumulation of point mutations responsible for TKI resistance causing the disease relapse, and perhaps also other point mutations facilitating malignant progression of CML.

  6. Transcription Factors Efg1 and Bcr1 Regulate Biofilm Formation and Virulence during Candida albicans-Associated Denture Stomatitis.

    Directory of Open Access Journals (Sweden)

    Junko Yano

    Full Text Available Denture stomatitis (DS is characterized by inflammation of the oral mucosa in direct contact with dentures and affects a significant number of otherwise healthy denture wearers. The disease is caused by Candida albicans, which readily colonizes and form biofilms on denture materials. While evidence for biofilms on abiotic and biotic surfaces initiating Candida infections is accumulating, a role for biofilms in DS remains unclear. Using an established model of DS in immunocompetent animals, the purpose of this study was to determine the role of biofilm formation in mucosal damage during pathogenesis using C. albicans or mutants defective in morphogenesis (efg1-/- or biofilm formation (bcr1-/-. For in vivo analyses, rats fitted with custom dentures, consisting of fixed and removable parts, were inoculated with wild-type C. albicans, mutants or reconstituted strains and monitored weekly for fungal burden (denture and palate, body weight and tissue damage (LDH for up to 8 weeks. C. albicans wild-type and reconstituted mutants formed biofilms on dentures and palatal tissues under in vitro, ex vivo and in vivo conditions as indicated by microscopy demonstrating robust biofilm architecture and extracellular matrix (ECM. In contrast, both efg1-/- and bcr1-/- mutants exhibited poor biofilm growth with little to no ECM. In addition, quantification of fungal burden showed reduced colonization throughout the infection period on dentures and palates of rats inoculated with efg1-/-, but not bcr1-/-, compared to controls. Finally, rats inoculated with efg1-/- and bcr1-/- mutants had minimal palatal tissue damage/weight loss while those inoculated with wild-type or reconstituted mutants showed evidence of tissue damage and exhibited stunted weight gain. These data suggest that biofilm formation is associated with tissue damage during DS and that Efg1 and Bcr1, both central regulators of virulence in C. albicans, have pivotal roles in pathogenesis of DS.

  7. MEK kinase 1 is essential for Bcr-Abl-induced STAT3 and self-renewal activity in embryonic stem cells.

    Science.gov (United States)

    Nakamura, Yukinori; Yujiri, Toshiaki; Nawata, Ryouhei; Tagami, Kozo; Tanizawa, Yukio

    2005-11-17

    BCR-ABL oncogene, the molecular hallmark of chronic myelogenous leukemia, arises in a primitive hematopoietic stem cell that has the capacity for both differentiation and self-renewal. Its product, Bcr-Abl protein, has been shown to activate signal transducers and activators of transcription 3 (STAT3) and to promote self-renewal in embryonic stem (ES) cells, even in the absence of leukemia inhibitory factor (LIF). MEK kinase 1 (MEKK1) is a 196-kDa mitogen-activated protein kinase (MAPK) kinase kinase involved in Bcr-Abl signal transduction. To investigate the role of MEKK1 in Bcr-Abl-induced transformation of stem cells, p210 Bcr-Abl was stably transfected into wild-type (WT(p210)) and MEKK1-/- (MEKK1-/-(p210)) ES cells. Bcr-Abl enhanced MEKK1 expression in ES transfectants, as it does in other Bcr-Abl-transformed cells. In the absence of LIF, WT(p210) cells showed constitutive STAT3 activation and formed rounded, compact colonies having strong alkaline phosphatase activity, a characteristic phenotype of undifferentiated ES cells. MEKK1-/-(p210) cells, by contrast, showed less STAT3 activity than WT(p210) cells and formed large, flattened colonies having weak alkaline phosphatase activity, a phenotype of differentiated ES cells. These results indicate that MEKK1 plays a key role in Bcr-Abl-induced STAT3 activation and in ES cells' capacity for LIF-independent self-renewal, and may thus be involved in Bcr-Abl-mediated leukemogenesis in stem cells. PMID:16044153

  8. Structure-Activity Relationship Studies of Mitogen Activated Protein Kinase Interacting Kinase (MNK) 1 and 2 and BCR-ABL1 Inhibitors Targeting Chronic Myeloid Leukemic Cells.

    Science.gov (United States)

    Cherian, Joseph; Nacro, Kassoum; Poh, Zhi Ying; Guo, Samantha; Jeyaraj, Duraiswamy A; Wong, Yun Xuan; Ho, Melvyn; Yang, Hai Yan; Joy, Joma Kanikadu; Kwek, Zekui Perlyn; Liu, Boping; Wee, John Liang Kuan; Ong, Esther H Q; Choong, Meng Ling; Poulsen, Anders; Lee, May Ann; Pendharkar, Vishal; Ding, Li Jun; Manoharan, Vithya; Chew, Yun Shan; Sangthongpitag, Kanda; Lim, Sharon; Ong, S Tiong; Hill, Jeffrey; Keller, Thomas H

    2016-04-14

    Clinically used BCR-ABL1 inhibitors for the treatment of chronic myeloid leukemia do not eliminate leukemic stem cells (LSC). It has been shown that MNK1 and 2 inhibitors prevent phosphorylation of eIF4E and eliminate the self-renewal capacity of LSCs. Herein, we describe the identification of novel dual MNK1 and 2 and BCR-ABL1 inhibitors, starting from the known kinase inhibitor 2. Initial structure-activity relationship studies resulted in compound 27 with loss of BCR-ABL1 inhibition. Further modification led to orally bioavailable dual MNK1 and 2 and BCR-ABL1 inhibitors 53 and 54, which are efficacious in a mouse xenograft model and also reduce the level of phosphorylated eukaryotic translation initiation factor 4E in the tumor tissues. Kinase selectivity of these compounds is also presented. PMID:27011159

  9. Time saving modified BCR sequential extraction procedure for the fraction of Cd, Cr, Cu, Ni, Pb and Zn in sediment samples of polluted lake

    International Nuclear Information System (INIS)

    The mobility, availability and persistence of heavy metals (Cd, Cr, Cu, Ni, Pb and Zn) in contaminated lake sediment samples were evaluated by means of sequential extraction scheme, proposed by the Community Bureau of Reference protocol (BCR). The metal content in the extracts was measured by atomic absorption spectrometry. The precision and accuracy of the proposed procedure were evaluated by using a certified reference material BCR 701. The maximum recoveries for heavy metals (HMs) were observed for all three steps of BCR protocol at 32 h total shaking period instead of previously reported 51 h, with p > 0.05. The lixiviation tests (DIN 38414-S4) were used to evaluate the leaching of HMs from sediment samples and it was observed that levels of water extractable HMs were low as compared to those values obtained by acid-soluble fraction of the BCR protocol

  10. Ability of 3 extraction methods (BCR, Tessier and protease K) to estimate bioavailable metals in sediments from Huelva estuary (Southwestern Spain).

    Science.gov (United States)

    Rosado, Daniel; Usero, José; Morillo, José

    2016-01-15

    The bioavailable fraction of metals (Zn, Cu, Cd, Mn, Pb, Ni, Fe, and Cr) in sediments of the Huelva estuary and its littoral of influence has been estimated carrying out the most popular methods of sequential extraction (BCR and Tessier) and a biomimetic approach (protease K extraction). Results were compared to enrichment factors found in Arenicola marina. The linear correlation coefficients (R(2)) obtained between the fraction mobilized by the first step of the BCR sequential extraction, by the sum of the first and second steps of the Tessier sequential extraction, and by protease K, and enrichment factors in A. marina, are at their highest for protease K extraction (0.709), followed by BCR first step (0.507) and the sum of the first and second steps of Tessier (0.465). This observation suggests that protease K represents the bioavailable fraction more reliably than traditional methods (BCR and Tessier), which have a similar ability.

  11. Ibrutinib inhibits BCR and NF-κB signaling and reduces tumor proliferation in tissue-resident cells of patients with CLL

    OpenAIRE

    Herman, Sarah E. M.; Mustafa, Rashida Z.; Gyamfi, Jennifer A.; Pittaluga, Stefania; Chang, Stella; Chang, Betty; Farooqui, Mohammed; Wiestner, Adrian

    2014-01-01

    Ibrutinib inhibits both BCR and NF-κB signaling in lymph node and bone marrow resident CLL cells.Rapid and sustained reduction of cellular activation and tumor proliferation was achieved in all anatomic compartments.

  12. Kriging analysis of geochemical data obtained by sequential extraction procedure (BCR)

    Science.gov (United States)

    Fajkovic, Hana; Pitarević Svedružić, Lovorka; Prohić, Esad; Rončević, Sanda; Nemet, Ivan

    2015-04-01

    Field examination and laboratory analysis were performed to establish whether nonsanitary landfill Bastijunski brig has a negative influence on Vransko Lake, situated only 1500 m away. Vransko Lake is Croatia's largest natural lake, and it is a part of the Nature Park and ornithological reserve, which indicates its high biodiversity. Therefore it is necessary to understand the environmental processes and complex sediment/water interface. Lake sediments are considered to be a good "sinkhole'and are often the final recipients of anthropogenic and natural pollutants through adsorption onto the organic or clay fraction in sediments. Geochemical investigation were obtained throughout more than 50 lake sediments cores situated in different parts of the lake Speciation of heavy metals by modified BCR sequential extraction procedure with the addition of a first step of sequential extraction procedure by Tessier and analysis of residual by aqua regia were used to determine the amounts of selected elements (Al, Cd, Cr, Co, Cu, Fe, Mn, Ni, Pb, Zn) in different fractions. With such approach it is possible to determine which element will be extracted from sediment/soil in a different environmental conditions and can be valuable tool for interpretation of the mobile fraction of the elements, considered bioavailability, that present threat to biota in a case of a contaminant concentration magnification. All sediment and soil samples were analyzed by inductively coupled plasma atomic emission spectrometry. More accurate interpretation of data is an advantage of BCR sequential extraction procedure while high number of the data together with point data type could be considered as a drawback. Due to high amount of data, graphical presentation is advisable while interpolation tool is a first choice for point type of data, as it makes predictions for defined area based on the measurements. Distribution maps of analysed elements were obtained by kriging as a geostatistical method and

  13. Association of HLA Class I and Class II genes with bcr-abl transcripts in leukemia patients with t(9;22) (q34;q11)

    International Nuclear Information System (INIS)

    Based on the site of breakpoint in t(9;22) (q34;q11), bcr-abl fusion in leukemia patients is associated with different types of transcript proteins. In this study we have seen the association of HLA genes with different types of bcr-abl transcripts. The association could predict the bcr-abl peptide presentation by particular HLA molecules. The study included a total of 189 patients of mixed ethnicity with chronic myelogenous leukemia and acute lymphocytic leukemia who were being considered for bone marrow transplantation. Typing of bcr-abl transcripts was done by reverse transcriptase PCR method. HLA typing was performed by molecular methods. The bcr-abl and HLA association was studied by calculating the relative risks and chi-square test. Significant negative associations (p < 0.05) were observed with HLA-A*02 (b2a2, e1a2), -A*68 (b2a2, b3a2, e1a2), -B*14 (b2a2, b3a2, e1a2), -B*15 (b2a2, b3a2), -B*40 (b2a2), -DQB1*0303 (b2a2, b3a2), -DQB1*0603 (b2a2), -DRB1*0401 (e1a2), -DRB1*0701 (b3a2), and -DRB1*1101 (b2a2). The negative associations of a particular bcr-abl transcript with specific HLA alleles suggests that these alleles play a critical role in presenting peptides derived from the chimeric proteins and eliciting a successful T-cell cytotoxic response. Knowledge of differential associations between HLA phenotypes and bcr-abl fusion transcript types would help in developing better strategies for immunization with the bcr-abl peptides against t(9;22) (q34;q11)-positive leukemia

  14. A clinical and laboratory study of chronic myeloid leukemia with atypical BCR-ABL fusion gene subtypes

    Institute of Scientific and Technical Information of China (English)

    桂晓敏

    2014-01-01

    Objective To explore the clinical and laboratory features of chronic myeloid leukemia(CML)with atypical e14a3 and e19a2 BCR-ABL fusion gene subtypes.Methods We retrospectively analyzed a cohort of CML patients with Ph chromosome positive confirmed by cytogenetic and FISH but classical e13a3(b2a2),e14a2(b3a2)and e1a2 fusion transcripts negative identified by

  15. Curcumin synergistically augments bcr/abl phosphorethieate antisense oligonucleotides to inhibit growth of chronic myelogenous leukemia cells

    Institute of Scientific and Technical Information of China (English)

    Kun-zhong ZHANG; Jian-hua XU; Xiu-wang HUANG; Li-xian WU; Yu SU; Yuan-zhong CHEN

    2007-01-01

    Aim: To investigate the growth inhibition effect of the combination of bcr/abl phosphorothioate antisense oligonucleotides (PS-ASODN) and curcumin (cur), and the possible mechanisms of cur on the chronic myelogenous leukemia cell line K562. Methods: The K562 cell line was used as a P210bcr/abl-positive cell model in vitro and was exposed to different concentrations of PS-ASODN (0-20 μmol/L), cur (0-20 μmol/L), or a combination of both. Growth inhibition and apoptosis of K562 cells were assessed by MTT assay and AO/EB fluorescent staining, respec-tively. The expression levels of P210bct/abl, NF-κB and heat shock protein 90 (Hsp90) were assessed by Western blot. Results: Exposure to cur (5-20 μmol/L) and PS-ASODN (5-20 μmol/L) resulted in a synergistic inhibitory effect on cell growth.Growth inhibition was associated with the inhibition of the proliferation and in-duction of apoptosis. Western blot analysis showed that the drugs synergisti-cally downregulated the level of P210bcr/abl and NF-κB. Cur downregulated Hsp90,whereas no synergism was observed when cur was combined with PS-ASODN.Conclusion: PS-ASODN and cur exhibited a synergistic inhibitory effect on the cell growth of K562. The synergistic growth inhibition was mediated through different mechanisms that involved the inhibition of P210bcr/abl.

  16. BCR Signaling Inhibitors: an Overview of Toxicities Associated with Ibrutinib and Idelalisib in Patients with Chronic Lymphocytic Leukemia

    OpenAIRE

    Falchi, Lorenzo; Baron, Jessica M.; Orlikowski, Carrie Anne; Ferrajoli, Alessandra

    2016-01-01

    The B-cell receptor (BCR) signaling inhibitors ibrutinib and idelalisib are revolutionizing the treatment of chronic lymphocytic leukemia (CLL) and other B-cell malignancies. These oral agents, both alone and in combination with other drugs, have shown remarkable clinical activity in relapsed or refractory CLL across all risk groups, and have been approved by the Food and Drug Administration for this indication. Preliminary data suggest that an even greater benefit can be expected in treatmen...

  17. Quantification of BCR-ABL mRNA in Plasma/Serum of Patients with Chronic Myelogenous Leukemia

    Directory of Open Access Journals (Sweden)

    Miwako Narita, Anri Saito, Aya Kojima, Minami Iwabuchi, Naoya Satoh, Takayoshi Uchiyama, Akie Yamahira, Tatsuo Furukawa, Hirohito Sone, Masuhiro Takahashi

    2012-01-01

    Full Text Available Quantification of tumor-associated mRNA extracted from blood cells/tissues containing tumor cells is used for evaluation of treatment efficacy or residual tumor cell burden in tumors including leukemia. However, this method using tumor cell-containing blood/tissue is difficult to evaluate the whole tumor cell burden in the body. In order to establish an efficient method to evaluate the whole tumor cell burden in the body, we tried to quantify tumor-associated mRNA existing in plasma/serum instead of leukemia cell-containing blood cells in patients with chronic myelogenous leukemia (CML and compared the levels of BCR-ABL mRNA between plasma/serum and peripheral blood cells. mRNA of BCR-ABL, WT1 or GAPDH (control molecule was detected by real-time RT-PCR using RNA extracted from plasma/serum of almost all the patients with CML. Copy numbers of BCR-ABL mRNA were significantly correlated between plasma/serum and peripheral blood cells. However, levels of BCR-ABL mRNA extracted from serum were low compared with those extracted with peripheral blood cells. The present findings suggest that although real-time RT-PCR of mRNA existing in plasma/serum could be used for evaluating the whole tumor cell burden in the body, it's required to establish an efficient method to quantify plasma/serum mRNA by nature without degrading during the procedure.

  18. Additive antileukemia effects by GFI1B- and BCR-ABL-specific siRNA in advanced phase chronic myeloid leukemic cells.

    Science.gov (United States)

    Koldehoff, M; Zakrzewski, J L; Beelen, D W; Elmaagacli, A H

    2013-07-01

    Previous studies demonstrated selective inhibition of the BCR-ABL (breakpoint cluster region-Abelson murine leukemia oncogene) tyrosine kinase by RNA interference in leukemic cells. In this study, we evaluated the effect of BCR-ABL small interfering RNA (siRNA) and GFI1B siRNA silencing on chronic myeloid leukemia (CML) cells in myeloid blast crises. The GFI1B gene was mapped to chromosome 9 and is, therefore, located downstream of the BCR-ABL translocation in CML cells. Co-transfection of BCR-ABL siRNA and GFI1B siRNA dramatically decreased cell viability and significantly induced apoptosis and inhibited proliferation in K562 cells (P<0.0001) and primary advanced phase CML cells (P<0.0001) versus controls. Furthermore, combining of BCR-ABL siRNA and GFI1B siRNA significantly modified the expression of several relevant genes including Myc, MDR1, MRP1 and tyrosyl-phosphoproteins in primary CML cells. Our data suggest that silencing of both BCR-ABL siRNA and GFI1B siRNA is associated with an additive antileukemic effect against K562 cells and primary advanced CML cells, further validating these genes as attractive therapeutic targets. PMID:23788109

  19. Structural Mechanism of the Pan-BCR-ABL Inhibitor Ponatinib (AP24534): Lessons for Overcoming Kinase Inhibitor Resistance

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Tianjun; Commodore, Lois; Huang, Wei-Sheng; Wang, Yihan; Thomas, Mathew; Keats, Jeff; Xu, Qihong; Rivera, Victor M.; Shakespeare, William C.; Clackson, Tim; Dalgarno, David C.; Zhu, Xiaotian (ARIAD)

    2012-01-20

    The BCR-ABL inhibitor imatinib has revolutionized the treatment of chronic myeloid leukemia. However, drug resistance caused by kinase domain mutations has necessitated the development of new mutation-resistant inhibitors, most recently against the T315I gatekeeper residue mutation. Ponatinib (AP24534) inhibits both native and mutant BCR-ABL, including T315I, acting as a pan-BCR-ABL inhibitor. Here, we undertook a combined crystallographic and structure-activity relationship analysis on ponatinib to understand this unique profile. While the ethynyl linker is a key inhibitor functionality that interacts with the gatekeeper, virtually all other components of ponatinib play an essential role in its T315I inhibitory activity. The extensive network of optimized molecular contacts found in the DFG-out binding mode leads to high potency and renders binding less susceptible to disruption by single point mutations. The inhibitory mechanism exemplified by ponatinib may have broad relevance to designing inhibitors against other kinases with mutated gatekeeper residues.

  20. Investigation of trace elements in agricultural Edirne soils by BCR sequential extraction method and its transfer to wheat plants

    International Nuclear Information System (INIS)

    Complete text of publication follows. In this study, soil samples were collected from Edirne-Turkey and subjected to a sequential procedure in order to evaluate the precision of the procedure and determine metal partitioning and concentrations of elements and to investigate the predictability of trace element on plant uptake. The samples were subjected to a three stage extraction procedure proposed by the Community Bureau of Reference (BCR) (G. Rauret et al., J. Environ. Monit., 1 (1999) 57-61.) .The three phases that were separated out were (1) carbonate, exchangeable, (2) Fe-Mn oxides and (3) organic matter. Metal concentrations were determined by ICP-OES. The wheat samples were prepared to analysis using microwave acid digestion procedure (E.P. Nardi et al., food Chem., 112 (2009) 727-732.). The pseudo-total concentrations of metals were determinated after aqua regia digestion (S. Melaku et al., Anal. Chim. Acta, 543 (2005) 117-123.). The analytical accuracy of the method was determinated by using the Standard Reference Materials ( BCR 142R Light Sandy Soil, NIST 2711 Montana Soil, NIST 2704 Buffalo River Sediment) The sum of the metal contents obtained from the modified BCR sequential extraction procedure and pseudo-total metal contents for soil samples were used to calculate recovery values (a. Tokalioglu et al., Intern. J. Environ. Anal. Chem., 86 (2006) 417-430.). In order to evaluate the bioavailability of metals, the relationships between the wheat-metal and soil-extractable metal concentrations were examined.

  1. 血液病患者bcr/abl融合基因、Ph染色体异同浅谈

    Institute of Scientific and Technical Information of China (English)

    王旭萍

    2011-01-01

    @@ CML特异性费城染色体(Philadephia,Ph)是由t(9:22)(q34:11)易位形成.9号染色体原癌基因abl(Abelson protooncogene)易位至22号染色体的断裂点簇集区(breakpoint duster region,ber),发生重排,产生bcr/abl融合基因,引起CML的始动突变.融合基因bcr/abl几乎见于所有的慢性粒细胞性白血病、25%-50%的急性B系淋巴细胞性白血病(ALL)和约5%的急性粒细胞性白血病中J,本文统计了进行染色体和bcr/abl融合基因检查的初诊血液病66例,对其骨髓细胞染色体核型及ber/~1融合基因进行分析.

  2. Migration of antibody secreting cells towards CXCL12 depends on the isotype that forms the BCR

    Science.gov (United States)

    Achatz-Straussberger, Gertrude; Zaborsky, Nadja; Königsberger, Sebastian; Luger, Elke O.; Lamers, Marinus; Crameri, Reto; Achatz, Gernot

    2010-01-01

    Truncation of the cytoplasmic tail of membrane-bound IgE in vivo results in lower serum IgE levels, decreased numbers of IgE-secreting plasma cells and the abrogation of specific secondary immune responses. Here we present mouse strain KN1 that expresses a chimeric ε-γ1 BCR, consisting of the extracellular domains of the ε gene and the trans-membrane and cytoplasmic domains of the γ1 gene. Thus, differences in the IgE immune response of KN1 mice reflect the influence of the “γ1-mediated signalling” of mIgE bearing B cells. KN1 mice show an increased serum IgE level, resulting from an elevated number of IgE-secreting cells. Although the primary IgE immune response in KN1 mice is inconspicuous, the secondary response is far more robust. Most strikingly, IgE-antibody secreting cells with “γ1-signalling history” migrate more efficiently towards the chemokine CXCL12, which guides plasmablasts to plasma cell niches, than IgE-antibody secreting cells with WT “ε-signalling history”. We conclude that IgE plasmablasts have an intrinsic, lower chance to contribute to the long-lived plasma cell pool than IgG1 plasmablasts. PMID:18925577

  3. Arsenic Mobility and Availability in Sediments by Application of BCR Sequential Extractions Method

    International Nuclear Information System (INIS)

    Arsenic is a metalloid found in nature, both naturally and due to anthropogenic activities. Among them, mining works are an important source of arsenic release to the environment. Asturias is a region where important mercury mines were exploited, and in them arsenic occurs in para genesis with mercury minerals. The toxicity and mobility of this element depends on the chemical species it is found. Fractionation studies are required to analyze the mobility of this metalloid in soils and sediments. Among them, the proposed by the Bureau Community of Reference (BCR) is one of the most employed. This method attempts to divide up, by operationally defined stages, the amount of this element associated with carbonates (fraction 1), iron and manganese oxy hydroxides (fraction 2), organic matter and sulphides (fraction 3), and finally as the amount associated residual fraction to primary and secondary minerals, that is, from the most labile fractions to the most refractory ones. Fractionation of arsenic in sediments from two mines in Asturias were studied, La Soterrana and Los Rueldos. Sediments from La Soterrana showed high levels of arsenic in the non-residual phases, indicating that the majority of arsenic has an anthropogenic origin. By contrast, in sediments from Los Rueldos most of the arsenic is concentrated in the residual phase, indicating that this element remains bound to very refractory primary minerals, as is also demonstrated by the strong correlation of arsenic fractionation and the fractionation of elements present in refractory minerals, such as iron, aluminum and titanium. (Author) 51 refs.

  4. Expression of P190 and P210 BCR/ABL1 in normal human CD34(+) cells induces similar gene expression profiles and results in a STAT5-dependent expansion of the erythroid lineage

    DEFF Research Database (Denmark)

    Järås, Marcus; Johnels, Petra; Agerstam, Helena;

    2009-01-01

    and systematically compared the effects of retroviral P190 BCR/ABL1 and P210 BCR/ABL1 expression on cell proliferation, differentiation, and global gene expression in human CD34(+) cells from cord blood. RESULTS: Expression of either P190 BCR/ABL1 or P210 BCR/ABL1 resulted in expansion of erythroid cells...... and stimulated erythropoietin-independent burst-forming unit-erythroid colony formation. By using a lentiviral anti-signal transducer and activator of transcription 5 (STAT5) short-hairpin RNA, we found that both P190 BCR/ABL1- and P210 BCR/ABL1-induced erythroid cell expansion were STAT5-dependent. Under...... that the early cellular and transcriptional effects of P190 BCR/ABL1 and P210 BCR/ABL1 expression are very similar when they are expressed in the same human progenitor cell population, and that STAT5 is an important regulator of BCR/ABL1-induced erythroid cell expansion....

  5. Outcomes of Children With BCR-ABL1–Like Acute Lymphoblastic Leukemia Treated With Risk-Directed Therapy Based on the Levels of Minimal Residual Disease

    Science.gov (United States)

    Roberts, Kathryn G.; Pei, Deqing; Campana, Dario; Payne-Turner, Debbie; Li, Yongjin; Cheng, Cheng; Sandlund, John T.; Jeha, Sima; Easton, John; Becksfort, Jared; Zhang, Jinghui; Coustan-Smith, Elaine; Raimondi, Susana C.; Leung, Wing H.; Relling, Mary V.; Evans, William E.; Downing, James R.; Mullighan, Charles G.; Pui, Ching-Hon

    2014-01-01

    Purpose BCR-ABL1–like acute lymphoblastic leukemia (ALL) is a recently identified B-cell ALL (B-ALL) subtype with poor outcome that exhibits a gene expression profile similar to BCR-ABL1-positive ALL but lacks the BCR-ABL1 fusion protein. We examined the outcome of children with BCR-ABL1–like ALL treated with risk-directed therapy based on minimal residual disease (MRD) levels during remission induction. Patients and Methods Among 422 patients with B-ALL enrolled onto the Total Therapy XV study between 2000 and 2007, 344 had adequate samples for gene expression profiling. Next-generation sequencing and/or analysis of genes known to be altered in B-ALL were performed in patients with BCR-ABL1–like ALL who had available material. Outcome was compared between patients with and those without BCR-ABL1–like ALL. Results Forty (11.6%) of the 344 patients had BCR-ABL1–like ALL. They were significantly more likely to be male, have Down syndrome, and have higher MRD levels on day 19 and at the end of induction than did other patients with B-ALL. Among 25 patients comprehensively studied for genetic abnormalities, 11 harbored a genomic rearrangement of CRLF2, six had fusion transcripts responsive to ABL tyrosine kinase inhibitors or JAK inhibitors, and seven had mutations involving the Ras signaling pathway. There were no significant differences in event-free survival (90.0% ± 4.7% [SE] v 88.4% ± 1.9% at 5 years; P = .41) or in overall survival (92.5% ± 4.2% v 95.1% ± 1.3% at 5 years; P = .41) between patients with and without BCR-ABL1–like ALL. Conclusion Patients who have BCR-ABL1–like ALL with poor initial treatment response can be salvaged with MRD-based risk-directed therapy and may benefit from identification of kinase-activating lesions for targeted therapies. PMID:25049327

  6. Frequency of p190 and p210 BCR-ABL rearrangements and survival in Brazilian adult patients with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Ilana de França Azevedo

    2014-10-01

    Full Text Available Objective: This study investigated the occurrence of the p190 and p210 break point clusterregion-Abelson (BCR-ABL rearrangements in adults with acute lymphoblastic leukemia and possible associations with clinical and laboratory characteristics and survival. Methods: Forty-one over 18-year-old patients with acute lymphoblastic leukemia of both genders followed-up between January 2008 and May 2012 were included in this study. Clinical and laboratory data were obtained from the medical charts of the patients. Reverse transcription polymerase chain reaction (RT-PCR using specific primers was employed to identify molecular rearrangements. Results: At diagnosis, the median age was 33 years, and there was a predominance of males (61%. The most common immunophenotype was B lineage (76%. BCR-ABL rearrangements was detected in 14 (34% patients with the following distribution: p190 (28%, p210 (50% and double positive (22%. Overall survival of patients with a mean/median of 331/246 days of follow up was 39%, respectively, negative BCR-ABL (44% and positive BCR-ABL (28%. Conclusion: These results confirm the high frequency of BCR-ABL rearrangements and the low survival rate of adult Brazilian patients with acute lymphoblastic leukemia.

  7. Potentiation of antileukemic therapies by the dual PI3K/PDK-1 inhibitor, BAG956: effects on BCR-ABL– and mutant FLT3-expressing cells

    Science.gov (United States)

    Weisberg, Ellen; Banerji, Lolita; Wright, Renee D.; Barrett, Rosemary; Ray, Arghya; Moreno, Daisy; Catley, Laurence; Jiang, Jingrui; Hall-Meyers, Elizabeth; Sauveur-Michel, Maira; Stone, Richard; Galinsky, Ilene; Fox, Edward; Kung, Andrew L.

    2008-01-01

    Mediators of PI3K/AKT signaling have been implicated in chronic myeloid leukemia (CML) and acute myeloid leukemia (AML). Studies have shown that inhibitors of PI3K/AKT signaling, such as wortmannin and LY294002, are able to inhibit CML and AML cell proliferation and synergize with targeted tyrosine kinase inhi-bitors. We investigated the ability of BAG956, a dual PI3K/PDK-1 inhibitor, to be used in combination with inhibitors of BCR-ABL and mutant FLT3, as well as with the mTOR inhibitor, rapamycin, and the rapamycin derivative, RAD001. BAG956 was shown to block AKT phosphorylation induced by BCR-ABL–, and induce apoptosis of BCR-ABL–expressing cell lines and patient bone marrow cells at concentrations that also inhibit PI3K signaling. Enhancement of the inhibitory effects of the tyrosine kinase inhibitors, imatinib and nilotinib, by BAG956 was demonstrated against BCR-ABL expressing cells both in vitro and in vivo. We have also shown that BAG956 is effective against mutant FLT3-expressing cell lines and AML patient bone marrow cells. Enhancement of the inhibitory effects of the tyrosine kinase inhibitor, PKC412, by BAG956 was demonstrated against mutant FLT3-expressing cells. Finally, BAG956 and rapamycin/RAD001 were shown to combine in a nonantagonistic fashion against BCR-ABL– and mutant FLT3-expressing cells both in vitro and in vivo. PMID:18184863

  8. Speciation of heavy metals by modified BCR sequential extraction procedure in different depths of sediments from Sungai Buloh, Selangor, Malaysia

    International Nuclear Information System (INIS)

    Highlights: → A BCR sequential extraction procedure was applied for measurement of heavy metals in Sungai Buloh sediments in different depths. → The amounts of CF and percentage of RAC was measured in this study too. → Highest CF was obtained for Cd, Co, Pb and Zn in these samples. → Zn at S3 and Cd at S3-S7 showed a high risk for the sediment samples. There were no elements of very high risk conditions in the selected samples. - Abstract: The sequential extraction procedure proposed by the European Standard, Measurements and Testing (SM and T) program, formerly the Community Bureau of Reference (BCR), was applied for partitioning of heavy metals (HMs) in river sediments collected along the course of Sungai Buloh and the Straits of Malacca in Selangor, Malaysia. Eight elements (V, Pb, Cd, Cr, Co, Ni, Cu and Zn) from seven stations (S1-S7) and at different depths were analyzed using the modified BCR Sequential Extraction Procedure (SEP) in combination with ICP-MS to obtain the metal distribution patterns in this region. The results showed that heavy metal contaminations at S2 and S3 was more severe than at other sampling sites, especially for Zn, Cu, Ni and Pb. Nevertheless, the element concentrations from top to bottom layers decreased predominantly. The samples from the Straits of Malacca (S4-S7) the highest contamination factors obtained were for Co, Zn and Pb while the lowest were found for V and Cr, similar to Sungai Buloh sediments. The sediments showed a low risk for V, Cr, Cu and Pb with RAC values of less than 10%, but medium risk for Co, Zn (except S3), Cd at S1 and S2 and Ni at S1, S3 and S5. Zn at S3 and Cd at S3-S7 showed high risk to our sediment samples. There is not any element of very high risk conditions in the selected samples.

  9. Molecular monitoring of BCR-ABL transcripts in patients with chronic myelogenous leukemia: is high sensitivity of clinical value?

    Science.gov (United States)

    Norkin, Maxim; Schiffer, Charles A

    2010-04-01

    Monitoring of disease response during treatment with tyrosine kinase inhibitors of patients with chronic myelogenous leukemia dramatically changed after the introduction of real-time PCR, which allows quantification of BCR-ABL transcript levels with high sensitivity and precision. However, its role in patients who have achieved complete cytogenetic response is not entirely clear; incorrect interpretation of results could lead to unnecessary changes from an effective treatment. This review discusses the current evidence regarding the benefits, uncertainties, and potential drawbacks of molecular monitoring in patients with chronic myelogenous leukemia in chronic phase.

  10. Application of methods (sequential extraction procedures and high-pressure digestion method) to fly ash particles to determine the element constituents: A case study for BCR 176

    International Nuclear Information System (INIS)

    Sequential extraction procedures and the high-pressure digestion method were selected to determine the element constituents of fly ash samples. Sequential extraction is one of the most useful methods used to measure the various elements from municipal solid waste incineration ash and contaminated soils. The extract from each step is analyzed using various techniques and equipments, and the results are then evaluated. In this work, a six-step extraction procedure modified from that of Tessier et al. and Wang et al. was performed and applied to the certified reference material BCR 176 (city waste incineration ash). Analyses were carried out by various techniques such as inductively coupled plasma atomic emission spectrometry (ICP-AES), inductively coupled plasma-mass spectrometry (ICP-MS), scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDX), and X-ray powder diffraction (XRPD) to evaluate the characteristics of fly ash. The extraction efficiency of many elements was higher than 80%, and the relative standard deviations (RSD) for recovery of most elements were within 10%. In addition, an H2O2 + HNO3 + HF mixed acid digestion solution processed using a low-temperature evaporation procedure was selected as the optimal process for fly ash digestion. The results of this work provide information on the chemical composition, distribution, and potential mobility of the investigated elements

  11. Involvement of primary mesenchymal precursors and hematopoietic bone marrow cells from chronic myeloid leukemia patients by BCR-ABL1 fusion gene.

    Science.gov (United States)

    Chandia, Mauricio; Sayagués, José-María; Gutiérrez, María-Laura; Chillón, María-Laura; Aristizábal, José-Alejandro; Corrales, Alejandro; Castellanos, Marta; Melón, Alberto; Sánchez, María-Luz; Bárcena, Paloma; Matarraz, Sergio; González-González, María; Barrena, Susana; López, Antonio; Cañizo, María-Consuelo; Sánchez-Guijo, Fermín; Orfao, Alberto

    2014-03-01

    For decades now, it is well established that chronic myeloid leukemia (CML) is a hematopoietic stem cell(HPC) disorder. However, it remains to be determined whether BCR-ABL1 gene rearrangement occurs in a HPC or at an earlier stem cell and whether the degree of involvement of hematopoiesis by the BCR-ABL1 fusion gene relates to the response to therapy. Here, we have investigated by interphase fluorescence in situ hybridization (iFISH) the distribution of BCR-ABL1 fusion gene in FACS-sorted bone marrow (BM) populations of mesenchymal precursor cells (MPC) and other hematopoietic cell populations from 18 newly diagnosed CML patients. Overall, our results showed systematic involvement at relatively high percentages of BM maturing neutrophils (97%615%), basophils (95%612%), eosinophils (90%68%), CD341 precursors cells (90%67%),monocytes (84%630%), nucleated red blood cells (87%624%), and mast cells (77%633%). By contrast, MPC(30%634%), B-cells (15%627%), T-lymphocytes (50%626%), and NK-cells (35%634%) were involved at lower percentages. In 8/18 CML patients, 2 tumor BCR-ABL11 subclones were detected by iFISH. Of note, all tumor cell subclones were systematically detected in CD341 cells, whereas MPC were only involved by the ancestral tumor cell subclone. In summary, here we confirm the presence at diagnosis of the BCR-ABL1 fusion gene inMPC, CD341 precursors, and other different BM hematopoietic myeloid cell lineages from CML patients,including also in a significant fraction of cases, a smaller percentage of T, B, and NK lymphocytes.Interestingly, involvement of MPC was restricted to the ancestral BCR-ABL11 subclone. PMID:24779036

  12. Reactive Oxygen Species and Mitochondrial DNA Damage and Repair in BCR-ABL1 Cells Resistant to Imatinib.

    Science.gov (United States)

    Blasiak, Janusz; Hoser, Grazyna; Bialkowska-Warzecha, Jolanta; Pawlowska, Elzbieta; Skorski, Tomasz

    2015-01-01

    Imatinib revolutionized the therapy of chronic myeloid leukemia (CML), but the resistance to it became an emerging problem. We reported previously that CML cells expressing the BCR/ABL1 fusion gene, accumulated a high level of reactive oxygen species (ROS) due to deregulated mitochondrial electron transport chain, which in turn led to genomic instability, resulting in imatinib resistance. In the present work, we hypothesize that imatinib-resistant cells may show higher instability of mitochondrial DNA (mtDNA) than their sensitive counterparts. To verify this hypothesis, we checked the ROS level and mtDNA damage and repair in model CML cells sensitive and resistant to imatinib and exposed to doxorubicin (DOX), a DNA-damaging agent. The extent of endogenous ROS in imatinib-resistant cells was higher than in their sensitive counterparts and DOX potentiated this relationship. ROS level in cells with primary resistance, which resulted from the T315I mutation in BCR/ABL1, was higher than in cells with acquired resistance. DOX-induced mtDNA damage in T315I imatinib-resistant cells was more pronounced than in imatinib-sensitive cells. All kinds of cells were repairing mtDNA damage with similar kinetics. In conclusion, imatinib-resistant cells can show increased instability of mtDNA, which can result from increased ROS production. PMID:26309809

  13. Speciation of heavy metals by modified BCR sequential extraction procedure in different depths of sediments from Sungai Buloh, Selangor, Malaysia.

    Science.gov (United States)

    Nemati, Keivan; Abu Bakar, Nor Kartini; Abas, Mhd Radzi; Sobhanzadeh, Elham

    2011-08-15

    The sequential extraction procedure proposed by the European Standard, Measurements and Testing (SM&T) program, formerly the Community Bureau of Reference (BCR), was applied for partitioning of heavy metals (HMs) in river sediments collected along the course of Sungai Buloh and the Straits of Malacca in Selangor, Malaysia. Eight elements (V, Pb, Cd, Cr, Co, Ni, Cu and Zn) from seven stations (S1-S7) and at different depths were analyzed using the modified BCR Sequential Extraction Procedure (SEP) in combination with ICP-MS to obtain the metal distribution patterns in this region. The results showed that heavy metal contaminations at S2 and S3 was more severe than at other sampling sites, especially for Zn, Cu, Ni and Pb. Nevertheless, the element concentrations from top to bottom layers decreased predominantly. The samples from the Straits of Malacca (S4-S7) the highest contamination factors obtained were for Co, Zn and Pb while the lowest were found for V and Cr, similar to Sungai Buloh sediments. The sediments showed a low risk for V, Cr, Cu and Pb with RAC values of less than 10%, but medium risk for Co, Zn (except S3), Cd at S1 and S2 and Ni at S1, S3 and S5. Zn at S3 and Cd at S3-S7 showed high risk to our sediment samples. There is not any element of very high risk conditions in the selected samples.

  14. Allelic expression imbalance of JAK2 V617F mutation in BCR-ABL negative myeloproliferative neoplasms.

    Directory of Open Access Journals (Sweden)

    Hye-Ran Kim

    Full Text Available The discovery of a single point mutation in the JAK2 gene in patients with BCR/ABL-negative myeloproliferative neoplasms (MPNs has not only brought new insights and pathogenesis, but also has made the diagnosis of MPNs much easier. Although, to date, several mechanisms for the contribution of single JAK2V617F point mutation to phenotypic diversity of MPNs have been suggested in multiple studies, but it is not clear how a unique mutation can cause the phenotypic diversity of MPNs. In this study, our results show that allelic expression imbalance of JAK2 V617F mutant frequently occurs and contributes to phenotypic diversity of BCR-ABL-negative MPNs. The proportion of JAK2 V617F mutant allele was significantly augmented in RNA levels as compared with genomic DNA differently by distinct MPNs subtypes. In detail, preferential expression of JAK2 mutant allele showed threefold increase from the cDNA compared with the genomic DNA from patients with essential thrombocythemia and twofold increase in polycythemia vera. In conclusion, allelic expression imbalance of JAK2 V617F mutant proposes another plausible mechanism for the contribution of single JAK2 point mutation to phenotypic diversity of MPNs.

  15. Biosensing of BCR/ABL fusion gene using an intensity-interrogation surface plasmon resonance imaging system

    Science.gov (United States)

    Wu, Jiangling; Huang, Yu; Bian, Xintong; Li, DanDan; Cheng, Quan; Ding, Shijia

    2016-10-01

    In this work, a custom-made intensity-interrogation surface plasmon resonance imaging (SPRi) system has been developed to directly detect a specific sequence of BCR/ABL fusion gene in chronic myelogenous leukemia (CML). The variation in the reflected light intensity detected from the sensor chip composed of gold islands array is proportional to the change of refractive index due to the selective hybridization of surface-bound DNA probes with target ssDNA. SPRi measurements were performed with different concentrations of synthetic target DNA sequence. The calibration curve of synthetic target sequence shows a good relationship between the concentration of synthetic target and the change of reflected light intensity. The detection limit of this SPRi measurement could approach 10.29 nM. By comparing SPRi images, the target ssDNA and non-complementary DNA sequence are able to be distinguished. This SPRi system has been applied for assay of BCR/ABL fusion gene extracted from real samples. This nucleic acid-based SPRi biosensor therefore offers an alternative high-effective, high-throughput label-free tool for DNA detection in biomedical research and molecular diagnosis.

  16. A target-disease network model of second-generation BCR-ABL inhibitor action in Ph+ ALL.

    Directory of Open Access Journals (Sweden)

    Uwe Rix

    Full Text Available Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL is in part driven by the tyrosine kinase bcr-abl, but imatinib does not produce long-term remission. Therefore, second-generation ABL inhibitors are currently in clinical investigation. Considering different target specificities and the pronounced genetic heterogeneity of Ph+ ALL, which contributes to the aggressiveness of the disease, drug candidates should be evaluated with regard to their effects on the entire Ph+ ALL-specific signaling network. Here, we applied an integrated experimental and computational approach that allowed us to estimate the differential impact of the bcr-abl inhibitors nilotinib, dasatinib, Bosutinib and Bafetinib. First, we determined drug-protein interactions in Ph+ ALL cell lines by chemical proteomics. We then mapped those interactions along with known genetic lesions onto public protein-protein interactions. Computation of global scores through correlation of target affinity, network topology, and distance to disease-relevant nodes assigned the highest impact to dasatinib, which was subsequently confirmed by proliferation assays. In future, combination of patient-specific genomic information with detailed drug target knowledge and network-based computational analysis should allow for an accurate and individualized prediction of therapy.

  17. BCR translocation to derivative chromosome 2: a new case of chronic myeloid leukemia with a complex variant translocation and Philadelphia chromosome

    OpenAIRE

    Al-Achkar, Walid; Wafa, Abdulsamad; ALMEDANI, SUHER

    2010-01-01

    The well-known typical fusion gene BCR/ABL is observed in connection with a complex translocation event in 5–8% of cases of chronic myeloid leukemia (CML). The present study described an exceptional CML case with complex chromosomal aberrations not previously observed. Aberrations included a translocated BCR to the derivative chromosome 2 [der(2)] that also involved a four-chromosome translocation, implying chromosomal regions 1p32 and 2q21, besides 9q34 and 22q11.2, which were characterized ...

  18. Role of the three-dimensional distribution of abl and bcr genes in the formation of bcr/abl fusion gene in interphase neucleus%间期细胞核中abl和bcr基因的三维空间分布在bcr/abl融合基因形成中的作用

    Institute of Scientific and Technical Information of China (English)

    张青; 周淑芸; 刘晓力; 牛超; 徐岚; 陈赛娟

    2002-01-01

    目的从生物体视学角度分析bcr/abl融合基因的形成机制.方法应用荧光原位杂交和激光共聚焦扫描显微镜技术,观察γ-射线对IM9细胞中的bcr和abl基因在间期核内三维空间分布的影响.结果abl和bcr基因在间期核内有其特定的分布区域,且该分布区域在细胞周期中呈规律性的动态变化.放射性照射会使abl和bcr基因之间的距离缩短.结论abl和bcr基因在间期细胞核内的易接近性是bcr/abl融合基因形成的因素之一.

  19. Detection of BCR/ABL Fusion Gene in Interphase Cens with Bi-labelling Hybridization in Situ%双标记原位杂交法检测间期细胞BCR/ABL融合基因

    Institute of Scientific and Technical Information of China (English)

    袁长吉; 王建伟; 李舜华; 易永林

    2003-01-01

    目的:应用双标记原位杂交方法检测BCR/ABL融合基因.方法:BCR基因探针用地高辛标记,碱性磷酸酶显色;ABL基因用3H-dATP标记,核子乳胶放射自显影.结果:检测9例初治的慢性粒细胞白血病(CML)病人均为阳性,阳性细胞比例为93%;检测CML来源的K562细胞株阳性细胞占98.8%;正常人假阳性率为0.75%.结论:该方法简便、快速,适用于CML微小残留病的检测.

  20. Rapid Evolution to Blast Crisis Associated with a Q252H ABL1 Kinase Domain Mutation in e19a2 BCR-ABL1 Chronic Myeloid Leukaemia

    Directory of Open Access Journals (Sweden)

    Sarah L. McCarron

    2013-01-01

    Full Text Available A minority of chronic myeloid leukaemia (CML patients express variant transcripts of which the e19a2 BCR-ABL1 fusion is the most common. Instances of tyrosine kinase inhibitor (TKI resistance in e19a2 BCR-ABL1 CML patients have rarely been reported. A case of e19a2 BCR-ABL1 CML is described in whom imatinib resistance, associated with a Q252H ABL1 kinase domain mutation, became apparent soon after initiation of TKI therapy. The patient rapidly transformed to myeloid blast crisis (BC with considerable bone marrow fibrosis and no significant molecular response to a second generation TKI. The clinical course was complicated by comorbidities with the patient rapidly succumbing to advanced disease. This scenario of Q252H-associated TKI resistance with rapid BC transformation has not been previously documented in e19a2 BCR-ABL1 CML. This case highlights the considerable challenges remaining in the management of TKI-resistant BC CML, particularly in the elderly patient.

  1. A novel Lyn-protein kinase Cδ/ε-protein kinase D axis is activated in B cells by signalosome-independent alternate pathway BCR signaling.

    Science.gov (United States)

    Guo, Benchang; Rothstein, Thomas L

    2013-06-01

    BCR signaling initiates multiple activities critical for B-cell function. Recently, we identified an alternate BCR signaling pathway, induced by IL-4, that is signalosome-independent, unlike the classical signalosome-dependent pathway, and that leads to activation of the MAP kinase, ERK. Here we questioned whether alternate pathway signaling extends to other key downstream events, especially protein kinase D (PKD) activation. We found that in murine spleen-derived B cells the IL-4-induced alternate pathway for BCR signaling results in PKD and PKD substrate phosphorylation, and that alternate pathway phosphorylation of HDAC5/7 and other key substrates requires PKD. Furthermore, we found that tyrosine phosphorylation of PKCδ/ε occurs as a result of alternate but not classical pathway signaling and is required for phosphorylation of PKD and PKD substrates. This result identifies PKCδ/ε tyrosine phosphorylation as a unique outcome of the alternate pathway. The alternate pathway is mediated by Lyn that is not required for classical pathway signaling and we found that Lyn associates directly with PKCδ/ε and is required for phosphorylation of PKCδ/ε and of PKD. These findings indicate that IL-4 influences B-cell activation by inducing a novel signaling pathway from BCR to Lyn to PKCδ/ε to PKD.

  2. Clonality Analysis of Immunoglobulin Gene Rearrangement by Next-Generation Sequencing in Endemic Burkitt Lymphoma Suggests Antigen Drive Activation of BCR as Opposed to Sporadic Burkitt Lymphoma

    Science.gov (United States)

    Amato, Teresa; Abate, Francesco; Piccaluga, Pierpaolo; Iacono, Michele; Fallerini, Chiara; Renieri, Alessandra; De Falco, Giulia; Ambrosio, Maria Raffaella; Mourmouras, Vaselious; Ogwang, Martin; Calbi, Valeria; Rabadan, Roul; Hummel, Michael; Pileri, Stefano; Bellan, Cristiana

    2016-01-01

    Objectives: Recent studies using next-generation sequencing (NGS) analysis disclosed the importance of the intrinsic activation of the B-cell receptor (BCR) pathway in the pathogenesis of sporadic Burkitt lymphoma (sBL) due to mutations of TCF3/ID3 genes. Since no definitive data are available on the genetic landscape of endemic Burkitt (eBL), we first assessed the mutation frequency of TCF3/ID3 in eBL compared with sBL and subsequently the somatic hypermutation status of the BCR to answer whether an extrinsic activation of BCR signaling could also be demonstrated in Burkitt lymphoma. Methods: We assessed the mutations of TCF3/ID3 by RNAseq and the BCR status by NGS analysis of the immunoglobulin genes (IGs). Results: We detected mutations of TCF3/ID3 in about 30% of the eBL cases. This rate is significantly lower than that detected in sBL (64%). The NGS analysis of IGs revealed intraclonal diversity, suggesting an active targeted somatic hypermutation process in eBL compared with sBL. Conclusions: These findings support the view that the antigenic pressure plays a key role in the pathogenetic pathways of eBL, which may be partially distinct from those driving sBL development. PMID:26712879

  3. 66例血液病患者bcr/abl融合基因、Ph染色体结果分析

    Institute of Scientific and Technical Information of China (English)

    刘永林; 虞玉群; 陈益民; 张丽; 彭来君; 施丽华; 谈潘莉; 钱丽丽; 胡正军; 陈婷停

    2011-01-01

    @@ CML特异性费城染色体(Philadephia,Ph)是由t(9:22)(q34:11)易位形成.9号染色体原癌基因abl(Abelson protooncogene)易位至22号染色体的断裂点簇集区(breakpointcluster region,bcr),发生重排,产生ber/abl融合基因,引起CML的始动突变.融合基因bcr/abl几乎见于所有的慢性粒细胞性白血病、25%~50%的急性B系淋巴细胞性白血病(ALL)和约5%的急性粒细胞性白血病中,本文统计了进行染色体和bcr/abl融合基因检查的初诊血液病66例,对其骨髓细胞染色体核型及bcr/abl融合基因进行分析.

  4. Sensitive detection of pre-existing BCR-ABL kinase domain mutations in CD34+ cells of newly diagnosed chronic-phase chronic myeloid leukemia patients is associated with imatinib resistance: implications in the post-imatinib era.

    Directory of Open Access Journals (Sweden)

    Zafar Iqbal

    Full Text Available BACKGROUND: BCR-ABL kinase domain mutations are infrequently detected in newly diagnosed chronic-phase chronic myeloid leukemia (CML patients. Recent studies indicate the presence of pre-existing BCR-ABL mutations in a higher percentage of CML patients when CD34+ stem/progenitor cells are investigated using sensitive techniques, and these mutations are associated with imatinib resistance and disease progression. However, such studies were limited to smaller number of patients. METHODS: We investigated BCR-ABL kinase domain mutations in CD34+ cells from 100 chronic-phase CML patients by multiplex allele-specific PCR and sequencing at diagnosis. Mutations were re-investigated upon manifestation of imatinib resistance using allele-specific PCR and direct sequencing of BCR-ABL kinase domain. RESULTS: Pre-existing BCR-ABL mutations were detected in 32/100 patients and included F311L, M351T, and T315I. After a median follow-up of 30 months (range 8-48, all patients with pre-existing BCR-ABL mutations exhibited imatinib resistance. Of the 68 patients without pre-existing BCR-ABL mutations, 24 developed imatinib resistance; allele-specific PCR and BCR-ABL kinase domain sequencing detected mutations in 22 of these patients. All 32 patients with pre-existing BCR-ABL mutations had the same mutations after manifestation of imatinib-resistance. In imatinib-resistant patients without pre-existing BCR-ABL mutations, we detected F311L, M351T, Y253F, and T315I mutations. All imatinib-resistant patients except T315I and Y253F mutations responded to imatinib dose escalation. CONCLUSION: Pre-existing BCR-ABL mutations can be detected in a substantial number of chronic-phase CML patients by sensitive allele-specific PCR technique using CD34+ cells. These mutations are associated with imatinib resistance if affecting drug binding directly or indirectly. After the recent approval of nilotinib, dasatinib, bosutinib and ponatinib for treatment of chronic myeloid

  5. MicroRNA-1301-Mediated RanGAP1 Downregulation Induces BCR-ABL Nuclear Entrapment to Enhance Imatinib Efficacy in Chronic Myeloid Leukemia Cells.

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    Tsung-Yao Lin

    Full Text Available Chronic myeloid leukemia (CML is a myeloproliferative disease. Imatinib (IM, the first line treatment for CML, is excessively expensive and induces various side effects in CML patients. Therefore, it is essential to investigate a new strategy for improving CML therapy. Our immunoblot data revealed that RanGTPase activating protein 1 (RanGAP1 protein levels increased by approximately 30-fold in K562 cells compared with those in normal cells. RanGAP1 is one of the important components of RanGTPase system, which regulates the export of nuclear protein. However, whether RanGAP1 level variation influences BCR-ABL nuclear export is still unknown. In this report, using shRNA to downregulate RanGAP1 expression level augmented K562 cell apoptosis by approximately 40% after treatment with 250 nM IM. Immunofluorescence assay also indicated that three-fold of nuclear BCR-ABL was detected. These data suggest that BCR-ABL nuclear entrapment induced by RanGAP1 downregulation can be used to improve IM efficacy. Moreover, our qRT-PCR data indicated a trend of inverse correlation between the RanGAP1 and microRNA (miR-1301 levels in CML patients. MiR-1301, targeting the RanGAP1 3' untranslated region, decreased by approximately 100-fold in K562 cells compared with that in normal cells. RanGAP1 downregulation by miR-1301 transfection impairs BCR-ABL nuclear export to increase approximately 60% of cell death after treatment of 250 nM IM. This result was almost the same as treatment with 1000 nM IM alone. Furthermore, immunofluorescence assay demonstrated that Tyr-99 of nuclear P73 was phosphorylated accompanied with nuclear entrapment of BCR-ABL after transfection with RanGAP1 shRNA or miR-1301 in IM-treated K562 cells. Altogether, we demonstrated that RanGAP1 downregulation can mediate BCR-ABL nuclear entrapment to activate P73-dependent apoptosis pathway which is a novel strategy for improving current IM treatment for CML.

  6. The L-amino acid oxidase from Calloselasma rhodostoma snake venom modulates apoptomiRs expression in Bcr-Abl-positive cell lines.

    Science.gov (United States)

    Burin, Sandra Mara; Berzoti-Coelho, Maria Gabriela; Cominal, Juçara Gastaldi; Ambrosio, Luciana; Torqueti, Maria Regina; Sampaio, Suely Vilela; de Castro, Fabíola Attié

    2016-09-15

    Anti-apoptotic genes and apoptomiRs deregulated expression contribute to apoptosis resistance in chronic myeloid leukemia (CML) Bcr-Abl(+) cells. Here, the L-amino acid oxidase from Calloselasma rhodostoma (CR-LAAO) venom altered the apoptotic machinery regulation by modulating the expression of the miR-145, miR-26a, miR-142-3p, miR-21, miR-130a, and miR-146a, and of the apoptosis-related proteins Bid, Bim, Bcl-2, Ciap-2, c-Flip, and Mcl-1 in Bcr-Abl(+) cells. CR-LAAO is a potential tool to instigate apoptomiRs regulation that contributes to drive CML therapy. PMID:27421670

  7. Conventional and fluorescence in situ hybridization analysis of three-way complex BCR-ABL rearrangement in a chronic myeloid leukemia patient

    Directory of Open Access Journals (Sweden)

    Ganguly Bani

    2007-01-01

    Full Text Available Chromosomal analysis was carried out in bone marrow sample of an 11-year-old girl suspected of myeloproliferative disorder. Conventional G-banding study detected a complex three-way translocation involving 7, 9 and 22, which has resulted in the formation of a variant Philadelphia chromosome causing rearrangement of abl and bcr genes in 87% cells. Fluorescence in situ hybridization (FISH confirmed the fusion of bcr-abl oncogene. Thus the bone marrow karyotype was observed as 46,XX (13% / 46,XX,t(7;9;22(q11;q34;q11 (87%. Hyperdiploidy was present in two cells. In this study, both conventional cytogenetic and FISH diagnosis proved to be significant to identify the variant nature of the Philadelphia chromosome and hyperdiploid condition for introduction of a suitable treatment regimen and estimation of life expectancy of the young girl.

  8. The chimeric ubiquitin ligase SH2-U-box inhibits the growth of imatinib-sensitive and resistant CML by targeting the native and T315I-mutant BCR-ABL.

    Science.gov (United States)

    Ru, Yi; Wang, Qinhao; Liu, Xiping; Zhang, Mei; Zhong, Daixing; Ye, Mingxiang; Li, Yuanchun; Han, Hua; Yao, Libo; Li, Xia

    2016-01-01

    Chronic myeloid leukemia (CML) is characterized by constitutively active fusion protein tyrosine kinase BCR-ABL. Although the tyrosine kinase inhibitor (TKI) against BCR-ABL, imatinib, is the first-line therapy for CML, acquired resistance almost inevitably emerges. The underlying mechanism are point mutations within the BCR-ABL gene, among which T315I is notorious because it resists to almost all currently available inhibitors. Here we took use of a previously generated chimeric ubiquitin ligase, SH2-U-box, in which SH2 from the adaptor protein Grb2 acts as a binding domain for activated BCR-ABL, while U-box from CHIP functions as an E3 ubiquitin ligase domain, so as to target the ubiquitination and degradation of both native and T315I-mutant BCR-ABL. As such, SH2-U-box significantly inhibited proliferation and induced apoptosis in CML cells harboring either the wild-type or T315I-mutant BCR-ABL (K562 or K562R), with BCR-ABL-dependent signaling pathways being repressed. Moreover, SH2-U-box worked in concert with imatinib in K562 cells. Importantly, SH2-U-box-carrying lentivirus could markedly suppress the growth of K562-xenografts in nude mice or K562R-xenografts in SCID mice, as well as that of primary CML cells. Collectively, by degrading the native and T315I-mutant BCR-ABL, the chimeric ubiquitin ligase SH2-U-box may serve as a potential therapy for both imatinib-sensitive and resistant CML. PMID:27329306

  9. Arsenic Mobility and Availability in Sediments by Application of BCR Sequential Extractions Method; Movilidad y Disponibilidad de Arsenico en Sedimentos Mediante la Aplicacion del Metodo de Extracciones Secuenciales BCR

    Energy Technology Data Exchange (ETDEWEB)

    Larios, R.; Fernandez, R.; Rucandio, M. I.

    2011-05-13

    Arsenic is a metalloid found in nature, both naturally and due to anthropogenic activities. Among them, mining works are an important source of arsenic release to the environment. Asturias is a region where important mercury mines were exploited, and in them arsenic occurs in para genesis with mercury minerals. The toxicity and mobility of this element depends on the chemical species it is found. Fractionation studies are required to analyze the mobility of this metalloid in soils and sediments. Among them, the proposed by the Bureau Community of Reference (BCR) is one of the most employed. This method attempts to divide up, by operationally defined stages, the amount of this element associated with carbonates (fraction 1), iron and manganese oxy hydroxides (fraction 2), organic matter and sulphides (fraction 3), and finally as the amount associated residual fraction to primary and secondary minerals, that is, from the most labile fractions to the most refractory ones. Fractionation of arsenic in sediments from two mines in Asturias were studied, La Soterrana and Los Rueldos. Sediments from La Soterrana showed high levels of arsenic in the non-residual phases, indicating that the majority of arsenic has an anthropogenic origin. By contrast, in sediments from Los Rueldos most of the arsenic is concentrated in the residual phase, indicating that this element remains bound to very refractory primary minerals, as is also demonstrated by the strong correlation of arsenic fractionation and the fractionation of elements present in refractory minerals, such as iron, aluminum and titanium. (Author) 51 refs.

  10. Voltammetric behaviour at gold electrodes immersed in the BCR sequential extraction scheme media Application of underpotential deposition-stripping voltammetry to determination of copper in soil extracts

    International Nuclear Information System (INIS)

    The development of mercury-free electroanalytical systems for in-field analysis of pollutants requires a foundation on the electrochemical behaviour of the chosen electrode material in the target sample matrices. In this work, the behaviour of gold working electrodes in the media employed in the BCR sequential extraction protocol, for the fractionation of metals in solid environmental matrices, is reported. All three of the BCR sequential extraction media are redox active, on the basis of acidity and oxygen content as well as the inherent reducing or oxidising nature of some of the reagents employed: 0.11 M acetic acid, 0.1 M hydroxylammonium chloride (adjusted to pH 2) and 1 M ammonium acetate (adjusted to pH 2) with added trace hydrogen peroxide. The available potential ranges together with the demonstrated detection of target metals in these media are presented. Stripping voltammetry of copper or lead in the BCR extract media solutions reveal a multi-peak behaviour due to the stripping of both bulk metal and underpotential metal deposits. A procedure based on underpotential deposition-stripping voltammetry (UPD-SV) was evaluated for application to determination of copper in 0.11 M acetic acid soil extracts. A preliminary screening step in which different deposition times are applied to the sample enables a deposition time commensurate with UPD-SV to be selected so that no bulk deposition or stripping occurs thus simplifying the shape and features of the resulting voltammograms. Choice of the suitable deposition time is then followed by standards addition calibration. The method was validated by the analysis of a number of BCR 0.11 M acetic acid soil extracts. Good agreement was obtained been the UPD-SV method and atomic spectroscopic results

  11. Fractionation of metals in street sediment samples by using the BCR sequential extraction procedure and multivariate statistical elucidation of the data

    International Nuclear Information System (INIS)

    The concentrations of metals (Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, and Zn) in street sediment samples were determined by flame atomic absorption spectrometry (FAAS) using the modified BCR (the European Community Bureau of Reference) sequential extraction procedure. According to the BCR protocol for extracting the metals from the relevant target phases, 1.0 g of specimen of the sample was treated with 0.11 M acetic acid (exchangeable and bound to carbonates), 0.5 M hydroxylamine hydrochloride (bound to iron- and manganese-oxides), and 8.8 M hydrogen peroxide plus 1 M ammonium acetate (bound to sulphides and organics), sequentially. The residue was treated with aqua regia solution for recovery studies, although this step is not part of the BCR procedure. The mobility sequence based on the sum of the BCR sequential extraction stages was: Cd ∼ Zn (∼90%) > Pb (∼84%) > Cu (∼75%) > Mn (∼70%) > Co (∼57%) > Ni (∼43%) > Cr (∼40%) > Fe (∼17%). Enrichment factors as the criteria for examining the impact of the anthropogenic emission sources of heavy metals were calculated, and it was observed that the highest enriched elements were Cd, Pb, and Zn in the dust samples, average 190, 111, and 20, respectively. Correlation analysis (CA) and principal component analysis (PCA) were applied to the data matrix to evaluate the analytical results and to identify the possible pollution sources of metals. PCA revealed that the sampling area was mainly influenced from three pollution sources, namely; traffic, industrial, and natural sources. The results show that chemical sequential extraction is a precious operational tool. Validation of the analytical results was checked by both recovery studies and analysis of the standard reference material (NIST SRM 2711 Montana Soil)

  12. UV Differentially Induces Oxidative Stress, DNA Damage and Apoptosis in BCR-ABL1-Positive Cells Sensitive and Resistant to Imatinib

    Directory of Open Access Journals (Sweden)

    Ewelina Synowiec

    2015-08-01

    Full Text Available Chronic myeloid leukemia (CML cells express the active BCR-ABL1 protein, which has been targeted by imatinib in CML therapy, but resistance to this drug is an emerging problem. BCR-ABL1 induces endogenous oxidative stress promoting genomic instability and imatinib resistance. In the present work, we investigated the extent of oxidative stress, DNA damage, apoptosis and expression of apoptosis-related genes in BCR-ABL1 cells sensitive and resistant to imatinib. The resistance resulted either from the Y253H mutation in the BCR-ABL1 gene or incubation in increasing concentrations of imatinib (AR. UV irradiation at a dose rate of 0.12 J/(m2·s induced more DNA damage detected by the T4 pyrimidine dimers glycosylase and hOGG1, recognizing oxidative modifications to DNA bases in imatinib-resistant than -sensitive cells. The resistant cells displayed also higher susceptibility to UV-induced apoptosis. These cells had lower native mitochondrial membrane potential than imatinib-sensitive cells, but UV-irradiation reversed that relationship. We observed a significant lowering of the expression of the succinate dehydrogenase (SDHB gene, encoding a component of the complex II of the mitochondrial respiratory chain, which is involved in apoptosis sensing. Although detailed mechanism of imatinib resistance in AR cells in unknown, we detected the presence of the Y253H mutation in a fraction of these cells. In conclusion, imatinib-resistant cells may display a different extent of genome instability than their imatinib-sensitive counterparts, which may follow their different reactions to both endogenous and exogenous DNA-damaging factors, including DNA repair and apoptosis.

  13. Multidimensional single-cell analysis of BCR signaling reveals proximal activation defect as a hallmark of chronic lymphocytic leukemia B cells.

    Directory of Open Access Journals (Sweden)

    M Lia Palomba

    Full Text Available PURPOSE: Chronic Lymphocytic Leukemia (CLL is defined by a perturbed B-cell receptor-mediated signaling machinery. We aimed to model differential signaling behavior between B cells from CLL and healthy individuals to pinpoint modes of dysregulation. EXPERIMENTAL DESIGN: We developed an experimental methodology combining immunophenotyping, multiplexed phosphospecific flow cytometry, and multifactorial statistical modeling. Utilizing patterns of signaling network covariance, we modeled BCR signaling in 67 CLL patients using Partial Least Squares Regression (PLSR. Results from multidimensional modeling were validated using an independent test cohort of 38 patients. RESULTS: We identified a dynamic and variable imbalance between proximal (pSYK, pBTK and distal (pPLCγ2, pBLNK, ppERK phosphoresponses. PLSR identified the relationship between upstream tyrosine kinase SYK and its target, PLCγ2, as maximally predictive and sufficient to distinguish CLL from healthy samples, pointing to this juncture in the signaling pathway as a hallmark of CLL B cells. Specific BCR pathway signaling signatures that correlate with the disease and its degree of aggressiveness were identified. Heterogeneity in the PLSR response variable within the B cell population is both a characteristic mark of healthy samples and predictive of disease aggressiveness. CONCLUSION: Single-cell multidimensional analysis of BCR signaling permitted focused analysis of the variability and heterogeneity of signaling behavior from patient-to-patient, and from cell-to-cell. Disruption of the pSYK/pPLCγ2 relationship is uncovered as a robust hallmark of CLL B cell signaling behavior. Together, these observations implicate novel elements of the BCR signal transduction as potential therapeutic targets.

  14. 自身淬灭荧光定量PCR检测慢性粒细胞白血病bcr/abl mRNA%Quantification of bcr/abl mRNA in patients with chronic myeloid leukemia by using real-time quantitative fluorescence PCR with self-quenched primer

    Institute of Scientific and Technical Information of China (English)

    彭辉; 冯文莉; 王小中; 曾建明; 肖青; 潘健; 曹唯希; 罗云萍; 黄宗干

    2007-01-01

    目的 利用自身淬灭探针技术建立一种能检测慢性粒细胞白血病(CML)bcr/abl融合基因mRNA的实时荧光定量PCR方法,为CML的诊断、疗效观察以及微量残留白血病(MRD)的监测提供有效手段.方法 用逆转录PCR方法(RT-PCR)扩增K562细胞的bcr/abl融合基因,A-T克隆法构建定量标准模板;设计自身淬灭荧光引物(探针),建立自身淬灭荧光定量逆转录PCR方法(FQRT-PCR),并对该方法的线性检测范围、灵敏度、重复性、稳定性进行检测;然后检测临床白血病患者骨髓标本bcr/abl mRNA.结果 建立的FQ-RT-PCR方法可检测10 copies/μl的bcr/abl重组质粒,并能从105个正常细胞中检出1个白血病细胞,该方法的批内、批间变异系数(CV)分别为2.1%、6.1%,线性检测范围为102~109 copies/μl.25例CML患者bcr/abl融合基因mRNA表达量中位数为4.50×104[(0.45~89.00)×104]copies/μg RNA,其中11例慢性期初诊患者bcr/abl mRNA表达量中位数为5.45×104[(2.95~19.30)×104]copies/μg RNA,6例急变期患者bcr/abl mRNA表达量中位数为13.00×104[(4.10~89.00)×104]copies/μg RNA,8例慢性期治疗后复查患者bcr/ablmRNA表达量中位数为2.35×104[(0.45~5.12)×104]copies/μg RNA,CML急变期患者bcr/abl融合基因表达水平与慢性期患者之间差异有统计学意义(q=3.41,P<0.05).PCR产物经电泳分析,其中21例CML患者为b3a2型,4例CML患者为b2a2型;3例急性淋巴细胞白血病(ALL)患者中,1例有bcr/abl mRNA表达,为b2a2型.结论 所建立的基于自身淬灭探针技术的实时荧光定量PCR检测方法灵敏、特异、重复性好,结果用拷贝数表示,准确可靠,利于标准统一.可广泛用于CML的诊断、疗效观察以及MRD的监测.

  15. Use of the modified BCR three-step sequential extraction procedure for the study of trace element dynamics in contaminated soils

    International Nuclear Information System (INIS)

    The modified BCR three-step sequential extraction procedure was used to examine the temporal dynamics of trace elements in soils contaminated by an accidental spill from an opencast mine in south-west Spain. Soils were mainly contaminated with pyritic sludge and acidic wastewater, whereas some soils were affected only by acidic wastewater. The distributions obtained for both some major (Ca, Fe and Mn) and trace elements (As, Cd, Cu, Pb and Zn) in the sludge and soil samples taken at different times after the accident, 1-3 months and 21 months, were compared. Sequential extractions were useful in identifying different sources of contamination, and in obtaining additional information on the solubility of secondary minerals formed by pyrite oxidation. Thus, the effectiveness of the BCR procedure has proved to be a useful tool for predicting short- and long-term mobility of trace elements, even in complex environmental scenarios. - The modified BCR three-step sequential extraction procedure has proved a useful prediction tool for short- and long-term mobility of trace elements in contaminated soils

  16. Low expression of miR-196b enhances the expression of BCR-ABL1 and HOXA9 oncogenes in chronic myeloid leukemogenesis.

    Directory of Open Access Journals (Sweden)

    Yue Liu

    Full Text Available MicroRNAs (miRNAs can function as tumor suppressors or oncogene promoters during tumor development. In this study, low levels of expression of miR-196b were detected in patients with chronic myeloid leukemia. Bisulfite genomic sequencing PCR and methylation-specific PCR were used to examine the methylation status of the CpG islands in the miR-196b promoter in K562 cells, patients with leukemia and healthy individuals. The CpG islands showed more methylation in patients with chronic myeloid leukemia compared with healthy individuals (P<0.05, which indicated that low expression of miR-196b may be associated with an increase in the methylation of CpG islands. The dual-luciferase reporter assay system demonstrated that BCR-ABL1 and HOXA9 are the target genes of miR-196b, which was consistent with predictions from bioinformatics software analyses. Further examination of cell function indicated that miR-196b acts to reduce BCR-ABL1 and HOXA9 protein levels, decrease cell proliferation rate and retard the cell cycle. A low level of expression of miR-196b can cause up-regulation of BCR-ABL1 and HOXA9 expression, which leads to the development of chronic myeloid leukemia. MiR-196b may represent an effective target for chronic myeloid leukemia therapy.

  17. Coupling a universal DNA circuit with graphene sheets/polyaniline/AuNPs nanocomposites for the detection of BCR/ABL fusion gene

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Xueping [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China); Wang, Li [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China); Department of Medical Laboratory, Chongqing Emergency Medical Center (Chongqing The Fourth Hospital), Chongqing, 400016 (China); Sheng, Shangchun [The No.2 Peoples' Hospital of Yibin, Sichuan, 644000 (China); Wang, Teng; Yang, Juan [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China); Xie, Guoming, E-mail: guomingxie@cqmu.edu.cn [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China); Feng, Wenli, E-mail: fengwlcqmu@sina.com [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China)

    2015-08-19

    This article described a novel method by coupling a universal DNA circuit with graphene sheets/polyaniline/AuNPs nanocomposites (GS/PANI/AuNPs) for highly sensitive and specific detection of BCR/ABL fusion gene (bcr/abl) in chronic myeloid leukemia (CML). DNA circuit known as catalyzed hairpin assembly (CHA) is enzyme-free and can be simply operated to achieve exponential amplification, which has been widely employed in biosensing. However, application of CHA has been hindered by the need of specially redesigned sequences for each single-stranded DNA input. Herein, a transducer hairpin (HP) was designed to obtain a universal DNA circuit with favorable signal-to-background ratio. To further improve signal amplification, GS/PANI/AuNPs with excellent conductivity and enlarged effective area were introduced into this DNA circuit. Consequently, by combining the advantages of CHA and GS/PANI/AuNPs, bcr/abl could be detected in a linear range from 10 pM to 20 nM with a detection limit of 1.05 pM. Moreover, this protocol showed excellent specificity, good stability and was successfully applied for the detection of real sample, which demonstrated its great potential in clinical application. - Highlights: • A transducer hairpin was designed to improve the versatility of DNA circuit. • GS/PANI/AuNPs were introduced to the DNA circuit for further signal amplification. • The established biosensor displayed high sensitivity and good specificity.

  18. Coupling a universal DNA circuit with graphene sheets/polyaniline/AuNPs nanocomposites for the detection of BCR/ABL fusion gene

    International Nuclear Information System (INIS)

    This article described a novel method by coupling a universal DNA circuit with graphene sheets/polyaniline/AuNPs nanocomposites (GS/PANI/AuNPs) for highly sensitive and specific detection of BCR/ABL fusion gene (bcr/abl) in chronic myeloid leukemia (CML). DNA circuit known as catalyzed hairpin assembly (CHA) is enzyme-free and can be simply operated to achieve exponential amplification, which has been widely employed in biosensing. However, application of CHA has been hindered by the need of specially redesigned sequences for each single-stranded DNA input. Herein, a transducer hairpin (HP) was designed to obtain a universal DNA circuit with favorable signal-to-background ratio. To further improve signal amplification, GS/PANI/AuNPs with excellent conductivity and enlarged effective area were introduced into this DNA circuit. Consequently, by combining the advantages of CHA and GS/PANI/AuNPs, bcr/abl could be detected in a linear range from 10 pM to 20 nM with a detection limit of 1.05 pM. Moreover, this protocol showed excellent specificity, good stability and was successfully applied for the detection of real sample, which demonstrated its great potential in clinical application. - Highlights: • A transducer hairpin was designed to improve the versatility of DNA circuit. • GS/PANI/AuNPs were introduced to the DNA circuit for further signal amplification. • The established biosensor displayed high sensitivity and good specificity

  19. Effects of modified zeolite on the removal and stabilization of heavy metals in contaminated lake sediment using BCR sequential extraction.

    Science.gov (United States)

    Wen, Jia; Yi, Yuanjie; Zeng, Guangming

    2016-08-01

    Sediment can be applied on land as a soil conditioner. However, toxic substances such as heavy metals within the sediment often lead to soil contamination if no proper management is conducted prior to land application. In order to reduce the bioavailable portion of heavy metals such as Pb, Cu, Zn and Cd, zeolite as a kind of stabilizer was investigated on the effect of metal stabilization in sediment. Zeolite was firstly modified and screened to get the best condition for removal of heavy metals. Results showed that the granulated zeolite with NaCl conditioning had the highest CEC and metal sorption. Using BCR sequential extraction, the selected modified zeolite effectively stabilized Pb, Cu, Zn and Cd in sediment to different extents. It was most suitable for Cd stabilization by reducing its acid exchangeable fraction while increasing the contents of the reducible and residual fractions. Modified zeolite also immobilized Cu, Zn and Pb in sediment by enhancing one stable fraction while decreasing the acid exchangeable fraction. PMID:27136618

  20. Speciation of Heavy Metals by Modified BCR Sequential Extraction in Soils Contaminated by Phosphogypsum in Sfax, Tunisia

    Directory of Open Access Journals (Sweden)

    Ahmed Wali

    2015-01-01

    Full Text Available The accumulation of trace metals in soil is a serious environmental problem that creates a hazard when metals are transferred to water or plants. To understand the mobility and bioavailability of trace metals, the concentrations and distributions of trace metals must be established for different physical and chemical phases of the soil. We determined the concentrations of trace metals (Zn, Pb, Cu, Cr, Co, Ni, Mn, and Fe in soil using the sequential extraction method recommended by Community Bureau of Reference (BCR and analysed chemical properties, such as the pH, cation exchange capacity, total organic carbon, electrical conductivity, and calcium carbonate. Our results revealed higher concentrations of trace metals in topsoil samples (0–20 cm than in subsoil samples (20–40 cm and 40–60 cm for most metals at four sites. Zn in the topsoil was mostly associated with the non-resistant fraction at all sites. Approximately 60% more Pb was bound to the non-residual, exchangeable and reducible fractions at all sites, and soil depths. Cr, Cu, Ni and Fe were mainly in the residual fraction, whereas Mn was largely present in the non-resistant fraction. The global contamination factor of trace metals decreased with soil depth. The mobility and bioavailability were greatest for Zn, followed by Cu and Pb. DOI: http://dx.doi.org/10.5755/j01.erem.70.4.7807

  1. Myeloproliferative neoplasms (BCR-ABL1 negative) and myelodysplastic/myeloproliferative neoplasms: current diagnostic principles and upcoming updates.

    Science.gov (United States)

    Geyer, J T; Orazi, A

    2016-05-01

    Since the publication of the latest World Health Organization (WHO) classification in 2008, there has been a significant effort for clarification of unresolved questions, especially with the help of the rapidly developing field of molecular genetic studies, next-generation sequencing in particular. Numerous entities within the WHO categories of myeloproliferative neoplasms (MPNs) and myelodysplastic (MDS)/MPNs have been extensively studied, with large published series attempting to characterize and better define their morphologic and molecular genetic features. This emerging genetic landscape maintains a robust correlation with the various disease entities recognized by the WHO classification scheme based on a careful integration of detailed clinical information, bone marrow and peripheral blood morphology, immunohistology, and genomics. This brief review summarizes the current guidelines as they apply to diagnosing both the classical BCR-ABL1 negative MPN (polycythemia vera, essential thrombocythemia, and primary myelofibrosis) and the more common subtypes of MDS/MPN overlap syndromes. The more important recent molecular updates as well as the upcoming changes to the current WHO classification, expected to be published in late 2016, will also be briefly reviewed. PMID:27161873

  2. Evaluation of mobility, bioavailability and toxicity of Pb and Cd in contaminated soil using TCLP, BCR and earthworms.

    Science.gov (United States)

    Kede, Maria Luiza F M; Correia, Fabio V; Conceição, Paulo F; Junior, Sidney F Salles; Marques, Marcia; Moreira, Josino C; Pérez, Daniel V

    2014-11-01

    The objective of the present study was to investigate the reduction of mobility, availability and toxicity found in soil contaminated with lead (Pb) and cadmium (Cd) from Santo Amaro Municipality, Bahia, Brazil using two combined methods, commonly tested separately according to the literature: metal mobilization with phosphates and phytoextraction. The strategy applied was the treatment with two sources of phosphates (separately and mixed) followed by phytoremediation with vetiver grass (Vetiveria zizanioides (L.)). The treatments applied (in triplicates) were: T1-potassium dihydrogen phosphate (KH2PO4); T2-reactive natural phosphate fertilizer (NRP) and; T3-a mixture 1:1 of KH2PO4 and NRP. After this step, untreated and treated soils were planted with vetiver grass. The extraction procedures and assays applied to contaminated soil before and after the treatments included metal mobility test (TCLP); sequential extraction with BCR method; toxicity assays with Eisenia andrei. The soil-to-plant transfer factors (TF) for Pb and Cd were estimated in all cases. All treatments with phosphates followed by phytoremediation reduced the mobility and availability of Pb and Cd, being KH2PO4 (T1) plus phytoremediation the most effective one. Soil toxicity however, remained high after all treatments. PMID:25386955

  3. Evaluation of Mobility, Bioavailability and Toxicity of Pb and Cd in Contaminated Soil Using TCLP, BCR and Earthworms

    Directory of Open Access Journals (Sweden)

    Maria Luiza F. M. Kede

    2014-11-01

    Full Text Available The objective of the present study was to investigate the reduction of mobility, availability and toxicity found in soil contaminated with lead (Pb and cadmium (Cd from Santo Amaro Municipality, Bahia, Brazil using two combined methods, commonly tested separately according to the literature: metal mobilization with phosphates and phytoextraction. The strategy applied was the treatment with two sources of phosphates (separately and mixed followed by phytoremediation with vetiver grass (Vetiveria zizanioides (L.. The treatments applied (in triplicates were: T1—potassium dihydrogen phosphate (KH2PO4; T2—reactive natural phosphate fertilizer (NRP and; T3—a mixture 1:1 of KH2PO4 and NRP. After this step, untreated and treated soils were planted with vetiver grass. The extraction procedures and assays applied to contaminated soil before and after the treatments included metal mobility test (TCLP; sequential extraction with BCR method; toxicity assays with Eisenia andrei. The soil-to-plant transfer factors (TF for Pb and Cd were estimated in all cases. All treatments with phosphates followed by phytoremediation reduced the mobility and availability of Pb and Cd, being KH2PO4 (T1 plus phytoremediation the most effective one. Soil toxicity however, remained high after all treatments.

  4. Effects of modified zeolite on the removal and stabilization of heavy metals in contaminated lake sediment using BCR sequential extraction.

    Science.gov (United States)

    Wen, Jia; Yi, Yuanjie; Zeng, Guangming

    2016-08-01

    Sediment can be applied on land as a soil conditioner. However, toxic substances such as heavy metals within the sediment often lead to soil contamination if no proper management is conducted prior to land application. In order to reduce the bioavailable portion of heavy metals such as Pb, Cu, Zn and Cd, zeolite as a kind of stabilizer was investigated on the effect of metal stabilization in sediment. Zeolite was firstly modified and screened to get the best condition for removal of heavy metals. Results showed that the granulated zeolite with NaCl conditioning had the highest CEC and metal sorption. Using BCR sequential extraction, the selected modified zeolite effectively stabilized Pb, Cu, Zn and Cd in sediment to different extents. It was most suitable for Cd stabilization by reducing its acid exchangeable fraction while increasing the contents of the reducible and residual fractions. Modified zeolite also immobilized Cu, Zn and Pb in sediment by enhancing one stable fraction while decreasing the acid exchangeable fraction.

  5. A report case of mixed phenotype acute leukemia with BCR - ABL positive and literature review%BCR - ABL 融合基因阳性的急性混合细胞白血病1例并文献复习

    Institute of Scientific and Technical Information of China (English)

    符爽; 张男; 陈芳; 刘璇; 胡延平; 张旻昱; 张继红

    2014-01-01

    Objective:To investigate the clinical characteristics,biological features,clinical curative effect and out-come of mixed PhenotyPe acute leukemia(MPAL). Methods:Results of clinical data,cell morPhology,immunoPheno-tyPe,cytogenetics and molecular genetics of the MPAL Patient with BCR - ABL Positive were analyzed with literature reviews. Results:The clinical and hematological findings were comPatible with the diagnosis of MPAL. LymPhoid and myeloid markers were Positive on the leukemia cells. KaryotyPe analysis showed that the Patient had t(9;22)(q34;q11)translocation. Quantitative reverse transcriPtion PCR results showed that BCR - ABL(P210)exPressed 100% . And no deletion,Point or insert mutation was found among C - Kit(8,17 exon),FLT3 - ITD/ TKD,NPM1 and CEBPα. Conclusion:Primary MPAL with BCR - ABL Positive is rarely rePorted which have a Poor Prognosis. Some of them are cases of chronic myeloid leukemia blast crisis. BCR - ABL gene exPression is closely related to Patients' Prognosis.%目的:探讨 BCR - ABL 融合基因阳性表达的急性混合细胞白血病(MPAL)的临床特点、生物学特性、临床疗效及预后。方法:对1例 BCR - ABL 融合基因阳性的急性混合细胞白血病患者的临床资料、细胞形态学、免疫分型、细胞遗传学及分子生物学的检测结果进行综合分析。结果:患者的临床表现和实验室检测结果均符合急性混合细胞白血病诊断标准,免疫表型分析白血病细胞同时表达髓系和淋系抗原,染色体核型为46,XX,t(9;22)(q34;q11),荧光定量 PCR 检测结果示 BCR - ABL(P210)融合基因表达100%,白血病预后基因检测结果示患者 C - Kit(8、17 exon)、FLT3- ITD/ TKD、NPM1和 CEBPα基因均为野生型。结论:初发的 BCR - ABL 融合基因阳性的急性混合细胞白血病病例罕见,部分病例由慢性粒细胞白血病急变而来,预后差。BCR - ABL 基因阳性与患者预后密切相关。

  6. STUDY ON QUANTITATIVE SPECIATION, BY BCR METHOD, OF ZINC CONTENT FROM RIVER SEDIMENTS

    Directory of Open Access Journals (Sweden)

    Georgiana Vasile

    2008-06-01

    Full Text Available The present work presents the results obtained during investigation of the zinc content of the water and river sediments in an area polluted by mining activities, to provide information on the mobility and availability of this element. Sediment and water samples have been collected from significant sites in a former mining area in which with some sterile pits, which represent a major environmental hazard.

  7. Assessing of distribution, mobility and bioavailability of exogenous Pb in agricultural soils using isotopic labeling method coupled with BCR approach

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Zhi-Yong, E-mail: zhyhuang@jmu.edu.cn [College of Bioengineering, Jimei University, Xiamen 361021 (China); Xie, Hong [College of Bioengineering, Jimei University, Xiamen 361021 (China); Shandong Vocational Animal Science and Veterinary College, Weifang 261061 (China); Cao, Ying-Lan [College of Bioengineering, Jimei University, Xiamen 361021 (China); Cai, Chao [Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021 (China); Zhang, Zhi [College of Bioengineering, Jimei University, Xiamen 361021 (China)

    2014-02-15

    Highlights: • Large amounts of exogenous Pb were found to distribute in reducible fractions. • Very few of exogenous Pb were found to distribute in acid-extractable fractions. • More than 60% of exogenous Pb in rhizosphere soils lost after planting. • Isotopic labeling method and SEP enable to explore Pb bioavailability in soil. -- Abstract: The contamination of Pb in agricultural soils is one of the most important ecological problems, which potentially results in serious health risk on human health through food chain. Hence, the fate of exogenous Pb contaminated in agricultural soils is needed to be deeply explored. By spiking soils with the stable enriched isotopes of {sup 206}Pb, the contamination of exogenous Pb{sup 2+} ions in three agricultural soils sampled from the estuary areas of Jiulong River, China was simulated in the present study, and the distribution, mobility and bioavailability of exogenous Pb in the soils were investigated using the isotopic labeling method coupled with a four-stage BCR (European Community Bureau of Reference) sequential extraction procedure. Results showed that about 60–85% of exogenous Pb was found to distribute in reducible fractions, while the exogenous Pb in acid-extractable fractions was less than 1.0%. After planting, the amounts of exogenous Pb presenting in acid-extractable, reducible and oxidizable fractions in rhizospheric soils decreased by 60–66%, in which partial exogenous Pb was assimilated by plants while most of the metal might transfer downward due to daily watering and applying fertilizer. The results show that the isotopic labeling technique coupled with sequential extraction procedures enables us to explore the distribution, mobility and bioavailability of exogenous Pb contaminated in soils, which may be useful for the further soil remediation.

  8. miR-29b suppresses CML cell proliferation and induces apoptosis via regulation of BCR/ABL1 protein

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yajuan; Wang, Haixia; Tao, Kun [Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated of Ministry of Education, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing 400016 (China); Xiao, Qing [Department of Hematology, The First Affiliated Hospital, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing 400016 (China); Huang, Zhenglan; Zhong, Liang; Cao, Weixi [Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated of Ministry of Education, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing 400016 (China); Wen, Jianping [Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5 (Canada); Feng, Wenli, E-mail: fengwlcqmu@sina.com [Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated of Ministry of Education, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing 400016 (China)

    2013-05-01

    MicroRNAs (miRNAs) are small RNAs that regulate gene expression posttranscriptionally and are critical for many cellular pathways. Recent evidence has shown that aberrant miRNA expression profiles and unique miRNA signaling pathways are present in many cancers. Here, we demonstrate that miR-29b is markedly lower expressed in CML patient samples. Bioinformatics analysis reveals a conserved target site for miR-29b in the 3′-untranslated region (UTR) of ABL1. miR-29b significantly suppresses the activity of a luciferase reporter containing ABL1-3′UTR and this activity is not observed in cells transfected with mutated ABL1-3′UTR. Enforced expression of miR-29b in K562 cells inhibits cell growth and colony formation ability thereby inducing apoptosis through cleavage of procaspase 3 and PARP. Furthermore, K562 cells transfected with a siRNA targeting ABL1 show similar growth and apoptosis phenotypes as cells overexpression of miR-29b. Collectively, our results suggest that miR-29b may function as a tumor suppressor by targeting ABL1 and BCR/ABL1. - Highlights: ► miR-29b expression was downregulated in CML patients. ► ABL1 was identified as a direct target gene of miR-29b. ► Enforced expression of miR-29b inhibits cell proliferation and induces apoptosis. ► miR-29b might be a therapeutic target to CML.

  9. Molecular approach to diagnose BCR/ABL negative chronic myeloproliferative neoplasms

    Directory of Open Access Journals (Sweden)

    Michelle Maccarini Barcelos

    2011-01-01

    Full Text Available Chronic myeloproliferative neoplasms arise from clonal proliferation of hematopoietic stem cells. According to the World Health Organization myeloproliferative neoplasms are classified as: chronic myelogenous leukemia, polycythemia vera, essential thrombocythemia, primary myelofibrosis, chronic neutrophilic leukemia, chronic eosinophilic leukemia, hypereosinophilic syndrome, mast cell disease, and unclassifiable myeloproliferative neoplasms. In the revised 2008 WHO diagnostic criteria for myeloproliferative neoplasms, mutation screening for JAK2V617F is considered a major criterion for polycythemia vera diagnosis and also for essential thrombocythemia and primary myelofibrosis, the presence of this mutation represents a clonal marker. There are currently two hypotheses explaining the role of the JAK2V617F mutation in chronic myeloproliferative neoplasms. According to these theories, the mutation plays either a primary or secondary role in disease development. The discovery of the JAK2V617F mutation has been essential in understanding the genetic basis of chronic myeloproliferative neoplasms, providing some idea on how a single mutation can result in three different chronic myeloproliferative neoplasm phenotypes. But there are still some issues to be clarified. Thus, studies are still needed to determine specific molecular markers for each subtype of chronic myeloproliferative neoplasm.

  10. Modeling the low-LET dose-response of BCR-ABL formation: predicting stem cell numbers from A-bomb data.

    Science.gov (United States)

    Radivoyevitch, T; Hoel, D G

    1999-01-01

    Formation of the BCR-ABL chromosomal translocation t(9;22)(q34;q11) is essential to the genesis of chronic myeloid leukemia (CML). An interest in the dose-response of radiation induced CML therefore leads naturally to an interest in the dose-response of BCR-ABL formation. To predict the BCR-ABL dose-response to low-linear energy transfer (LET) ionizing radiation, three models valid over three different dose ranges are examined: the first for doses greater than 80 Gy, the second for doses less than 5 Gy and the third for doses greater than 2 Gy. The first of the models, due to Holley and Chatterjee, ignores the accidental binary eurejoining of DNA double-strand break (DSB) free ends ('eurejoining' refers to the accidental restitution of DSB free ends with their own proper mates). As a result, the model is valid only in the limit of high doses. The second model is derived directly from cytogenetic data. This model has the attractive feature that it implicitly accounts for single-track effects at low doses. The third model, based on the Sax-Markov binary eurejoining/misrejoining (SMBE) algorithm, does not account for single-track effects and is therefore limited to moderate doses greater than approximately 2 Gy. Comparing the second model to lifetime excess CML risks expected after 1 Gy, estimates of the number of hematopoietic stem cells capable of causing CML were obtained for male and female atomic bomb survivors in Hiroshima and Nagasaki. The stem cell number estimates lie in the range of 5 x 10(7)-3 x 10(8) cells. PMID:10616282

  11. In-silico identification of inhibitors against mutated BCR-ABL protein of chronic myeloid leukemia: a virtual screening and molecular dynamics simulation study.

    Science.gov (United States)

    Kumar, Himansu; Raj, Utkarsh; Gupta, Saurabh; Varadwaj, Pritish Kumar

    2016-10-01

    Aberrant and proliferative expression of the oncogene BCR-ABL in the bone marrow cells had been proven as the prime cause of chronic myeloid leukemia (CML). It has been established that tyrosine kinase domain of BCR-ABL protein is a potential therapeutic target for the treatment of CML. Imatinib is considered as a first-generation drug that can inhibit the enzymatic action by inhibiting the ATP binding with BCR-ABL protein. Later on, insensitivity of CML cells towards Imatinib has been observed may be due to mutation in tyrosine kinase domain of the ABL receptor. Subsequently, some other second-generation drugs have also been reported viz. Baustinib, Nilotinib, Dasatinib, Ponatinib, Bafetinib, etc., which can able to combat against mutated domain of ABL tyrosine kinase protein. By taking into account of bioavailability and resistance developed, there is an utmost need to find some more inhibitors for the mutated ABL tyrosine kinase protein. For virtual screening, a data-set has been generated by collecting the all available drug like natural compounds from ZINC and Drug Bank databases. Comparative docking analysis was also carried out on the active site of ABL tyrosine kinase receptor with reported reference inhibitors. Molecular dynamics simulation of the best screened interacting complex was done for 50 ns to validate the stability of the system. These selected inhibitors were further validated and analyzed through pharmacokinetics properties and series of ADMET parameters by in silico methods. Considering the above said parameters proposed molecules are concluded as potential leads for drug designing pipeline against CML. PMID:26479578

  12. Comparative quantitative analysis of BCR-ABL transcripts with the T315I mutant clone by polymerase chain reaction (PCR)-Invader method.

    Science.gov (United States)

    Tadokoro, Kenichi; Ishikawa, Maho; Suzuki, Makoto; Saito, Tomoyoshi; Suzuki, Yoshie; Yamaguchi, Toshikazu; Yagasaki, Fumiharu

    2011-09-01

    Drug resistance is a serious complication in the treatment of chronic myeloid leukemia (CML). The most common and best-characterized mechanism of secondary imatinib resistance in CML is the development of kinase domain mutations in the BCR-ABL gene. Second-generation tyrosine kinase inhibitors, such as dasatinib or nilotinib, overcome most of these mutations, but they are not effective against the T315I mutant. To determine whether these mutations contribute to clinical resistance, it is necessary to monitor the ratio of the mutant and wild-type forms. Here, we developed a polymerase chain reaction (PCR)-Invader assay for comparative quantitative analysis (qPI assay) of BCR-ABL transcripts with the T315I mutant clone. T315I ratios were calculated for the wild-type and mutant fold-over-zero (FOZ) values. In examination with 2 kinds of plasmids containing wild-type or T315I mutant PCR amplicons, mutant FOZ values were detected down to 1% of the total. The results of 12 serial samples from 2 patients (case A: Philadelphia-positive acute lymphoblastic leukemia and case B: CML) with the T315I mutant clone were compared with those of direct sequencing or 2 kinds of allele-specific oligonucleotide (ASO)-PCR. All samples showed the T315I mutation by qPI assay and ASO-PCR, and 10 samples showed it by direct sequencing. Significant correlation (correlation coefficient; r2 = 0.951) was noted between the qPI assay and quantitative ASO-PCR to analyze T315I mutant ratios. Thus, the qPI assay is a useful method for evaluating the T315I mutant clone in BCR-ABL transcripts.

  13. Down-regulation of Thanatos-associated protein 11 by BCR-ABL promotes CML cell proliferation through c-Myc expression.

    Science.gov (United States)

    Nakamura, Satoki; Yokota, Daisuke; Tan, Lin; Nagata, Yasuyuki; Takemura, Tomonari; Hirano, Isao; Shigeno, Kazuyuki; Shibata, Kiyoshi; Fujisawa, Shinya; Ohnishi, Kazunori

    2012-03-01

    Bcr-Abl activates various signaling pathways in chronic myelogenous leukemia (CML) cells. The proliferation of Bcr-Abl transformed cells is promoted by c-Myc through the activation of Akt, JAK2 and NF-κB. However, the mechanism by which c-Myc regulates CML cell proliferation is unclear. In our study, we investigated the role of Thanatos-associated protein 11 (THAP11), which inhibits c-Myc transcription, in CML cell lines and in hematopoietic progenitor cells derived from CML patients. The induction of THAP11 expression by Abl kinase inhibitors in CML cell lines and in CML-derived hematopoietic progenitor cells resulted in the suppression of c-Myc. In addition, over-expression of THAP11 inhibited CML cell proliferation. In colony forming cells derived from CML-aldehyde dehydrogenase (ALDH)(hi) /CD34(+) cells, treatment with Abl kinase inhibitors and siRNA depletion of Bcr-Abl induced THAP11 expression and reduced c-Myc expression, resulting in inhibited colony formation. Moreover, overexpression of THAP11 significantly decreased the colony numbers, and also inhibited the expression of c-myc target genes such as Cyclin D1, ODC and induced the expression of p21(Cip1) . The depletion of THAP11 inhibited JAK2 or STAT5 inactivation-mediated c-Myc reduction in ALDH(hi) /CD34(+) CML cells. Thus, the induced THAP11 might be one of transcriptional regulators of c-Myc expression in CML cell. Therefore, the induction of THAP11 has a potential possibility as a target for the inhibition of CML cell proliferation. PMID:21400515

  14. Stat5 Exerts Distinct, Vital Functions in the Cytoplasm and Nucleus of Bcr-Abl+ K562 and Jak2(V617F)+ HEL Leukemia Cells

    International Nuclear Information System (INIS)

    Signal transducers and activators of transcription (Stats) play central roles in the conversion of extracellular signals, e.g., cytokines, hormones and growth factors, into tissue and cell type specific gene expression patterns. In normal cells, their signaling potential is strictly limited in extent and duration. The persistent activation of Stat3 or Stat5 is found in many human tumor cells and contributes to their growth and survival. Stat5 activation plays a pivotal role in nearly all hematological malignancies and occurs downstream of oncogenic kinases, e.g., Bcr-Abl in chronic myeloid leukemias (CML) and Jak2(V617F) in other myeloproliferative diseases (MPD). We defined the mechanisms through which Stat5 affects growth and survival of K562 cells, representative of Bcr-Abl positive CML, and HEL cells, representative for Jak2(V617F) positive acute erythroid leukemia. In our experiments we suppressed the protein expression levels of Stat5a and Stat5b through shRNA mediated downregulation and demonstrated the dependence of cell survival on the presence of Stat5. Alternatively, we interfered with the functional capacities of the Stat5 protein through the interaction with a Stat5 specific peptide ligand. This ligand is a Stat5 specific peptide aptamer construct which comprises a 12mer peptide integrated into a modified thioredoxin scaffold, S5-DBD-PA. The peptide sequence specifically recognizes the DNA binding domain (DBD) of Stat5. Complex formation of S5-DBD-PA with Stat5 causes a strong reduction of P-Stat5 in the nuclear fraction of Bcr-Abl-transformed K562 cells and a suppression of Stat5 target genes. Distinct Stat5 mediated survival mechanisms were detected in K562 and Jak2(V617F)-transformed HEL cells. Stat5 is activated in the nuclear and cytosolic compartments of K562 cells and the S5-DBD-PA inhibitor most likely affects the viability of Bcr-Abl+ K562 cells through the inhibition of canonical Stat5 induced target gene transcription. In HEL cells, Stat5 is

  15. Stat5 Exerts Distinct, Vital Functions in the Cytoplasm and Nucleus of Bcr-Abl+ K562 and Jak2(V617F)+ HEL Leukemia Cells.

    Science.gov (United States)

    Weber, Axel; Borghouts, Corina; Brendel, Christian; Moriggl, Richard; Delis, Natalia; Brill, Boris; Vafaizadeh, Vida; Groner, Bernd

    2015-01-01

    Signal transducers and activators of transcription (Stats) play central roles in the conversion of extracellular signals, e.g., cytokines, hormones and growth factors, into tissue and cell type specific gene expression patterns. In normal cells, their signaling potential is strictly limited in extent and duration. The persistent activation of Stat3 or Stat5 is found in many human tumor cells and contributes to their growth and survival. Stat5 activation plays a pivotal role in nearly all hematological malignancies and occurs downstream of oncogenic kinases, e.g., Bcr-Abl in chronic myeloid leukemias (CML) and Jak2(V617F) in other myeloproliferative diseases (MPD). We defined the mechanisms through which Stat5 affects growth and survival of K562 cells, representative of Bcr-Abl positive CML, and HEL cells, representative for Jak2(V617F) positive acute erythroid leukemia. In our experiments we suppressed the protein expression levels of Stat5a and Stat5b through shRNA mediated downregulation and demonstrated the dependence of cell survival on the presence of Stat5. Alternatively, we interfered with the functional capacities of the Stat5 protein through the interaction with a Stat5 specific peptide ligand. This ligand is a Stat5 specific peptide aptamer construct which comprises a 12mer peptide integrated into a modified thioredoxin scaffold, S5-DBD-PA. The peptide sequence specifically recognizes the DNA binding domain (DBD) of Stat5. Complex formation of S5-DBD-PA with Stat5 causes a strong reduction of P-Stat5 in the nuclear fraction of Bcr-Abl-transformed K562 cells and a suppression of Stat5 target genes. Distinct Stat5 mediated survival mechanisms were detected in K562 and Jak2(V617F)-transformed HEL cells. Stat5 is activated in the nuclear and cytosolic compartments of K562 cells and the S5-DBD-PA inhibitor most likely affects the viability of Bcr-Abl+ K562 cells through the inhibition of canonical Stat5 induced target gene transcription. In HEL cells, Stat5 is

  16. Epidemiologic study on survival of chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia patients with BCR-ABL T315I mutation

    DEFF Research Database (Denmark)

    Nicolini, Franck E; Mauro, Michael J; Martinelli, Giovanni;

    2009-01-01

    ), or blastic-phase (BP) and Philadelphia chromosome-positive (Ph)(+) acute lymphoblastic leukemia (ALL) patients with T315I mutation. Medical records of 222 patients from 9 countries were reviewed; data were analyzed using log-rank tests and Cox proportional hazard models. Median age at T315I mutation......The BCR-ABL T315I mutation represents a major mechanism of resistance to tyrosine kinase inhibitors (TKIs). The objectives of this retrospective observational study were to estimate overall and progression-free survival for chronic myeloid leukemia in chronic-phase (CP), accelerated-phase (AP...

  17. Stat5 Exerts Distinct, Vital Functions in the Cytoplasm and Nucleus of Bcr-Abl+ K562 and Jak2(V617F+ HEL Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Axel Weber

    2015-03-01

    Full Text Available Signal transducers and activators of transcription (Stats play central roles in the conversion of extracellular signals, e.g., cytokines, hormones and growth factors, into tissue and cell type specific gene expression patterns. In normal cells, their signaling potential is strictly limited in extent and duration. The persistent activation of Stat3 or Stat5 is found in many human tumor cells and contributes to their growth and survival. Stat5 activation plays a pivotal role in nearly all hematological malignancies and occurs downstream of oncogenic kinases, e.g., Bcr-Abl in chronic myeloid leukemias (CML and Jak2(V617F in other myeloproliferative diseases (MPD. We defined the mechanisms through which Stat5 affects growth and survival of K562 cells, representative of Bcr-Abl positive CML, and HEL cells, representative for Jak2(V617F positive acute erythroid leukemia. In our experiments we suppressed the protein expression levels of Stat5a and Stat5b through shRNA mediated downregulation and demonstrated the dependence of cell survival on the presence of Stat5. Alternatively, we interfered with the functional capacities of the Stat5 protein through the interaction with a Stat5 specific peptide ligand. This ligand is a Stat5 specific peptide aptamer construct which comprises a 12mer peptide integrated into a modified thioredoxin scaffold, S5-DBD-PA. The peptide sequence specifically recognizes the DNA binding domain (DBD of Stat5. Complex formation of S5-DBD-PA with Stat5 causes a strong reduction of P-Stat5 in the nuclear fraction of Bcr-Abl-transformed K562 cells and a suppression of Stat5 target genes. Distinct Stat5 mediated survival mechanisms were detected in K562 and Jak2(V617F-transformed HEL cells. Stat5 is activated in the nuclear and cytosolic compartments of K562 cells and the S5-DBD-PA inhibitor most likely affects the viability of Bcr-Abl+ K562 cells through the inhibition of canonical Stat5 induced target gene transcription. In HEL

  18. The validation of Kayzero-assisted NAA in Budapest, Rez, and Ljubljana via the analysis of three BCR certified reference materials.

    Science.gov (United States)

    De Corte, F; van Sluijs, R; Simonits, A; Kucera, J; Smodis, B; Byrne, A R; De Wispelaere, A; Bossus, D; Frána, J; Horák, Z; Jaćimović, R

    2001-05-01

    After installation and calibration of k0-assisted NAA in three Central European research institutes (AEKI-Budapest, NPI-Rez, and IJS, Ljubljana), its validation was established via the analysis of three BCR certified reference materials. The matrices of choice were: CRM 277 estuarine sediment, CRM 038 coal fly ash from pulverized coal, and CRM 101 spruce needles. For some elements, e.g. Zn, Cd, and Hg, the analyses were not only performed instrumentally (INAA), but also in the radiochemical mode (RNAA). The work was performed in the framework of a European Copernicus Project. PMID:11393234

  19. Recent advances in the bcr-abl negative chronic myeloproliferative diseases

    Directory of Open Access Journals (Sweden)

    Stroncek David F

    2006-10-01

    Full Text Available Abstract The chronic myeloproliferative disorders are clonal hematopoietic stem cell disorders of unknown etiology. In one of these (chronic myeloid leukemia, there is an associated pathognomonic chromosomal abnormality known as the Philadelphia chromosome. This leads to constitutive tyrosine kinase activity which is responsible for the disease and is used as a target for effective therapy. This review concentrates on the search in the other conditions (polycythemia vera, essential thrombocythemia and idiopathic mylofibrosis for a similar biological marker with therapeutic potential. There is no obvious chromosomal marker in these conditions and yet evidence of clonality can be obtained in females by the use of X-inactivation patterns. PRV-1mRNA over expression, raised vitamin B12 levels and raised neutrophil alkaline phosphatase scores are evidence that cells in these conditions have received excessive signals for proliferation, maturation and reduced apoptosis. The ability of erythroid colonies to grow spontaneously without added external erythropoietin in some cases, provided a useful marker and a clue to this abnormal signaling. In the past year several important discoveries have been made which go a long way in elucidating the involved pathways. The recently discovered JAK2 V617F mutation which occurs in the majority of cases of polycythemia vera and in about half of the cases with the two other conditions, enables constitutive tyrosine kinase activity without the need for ligand binding to hematopoietic receptors. This mutation has become the biological marker for these conditions and has spurred the development of a specific therapy to neutralize its effects. The realization that inherited mutations in the thrombopoietin receptor (c-Mpl can cause a phenotype of thrombocytosis such as in Mpl Baltimore (K39N and in a Japanese family with S505A, has prompted the search for acquired mutations in this receptor in chronic myeloproliferative

  20. A combination of STI571 and BCR-ABL1 siRNA with overexpressed p15INK4B induced enhanced proliferation inhibition and apoptosis in chronic myeloid leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Xia, D.Y.; Liu, L.; Hao, M.W.; Liu, Q.; Chen, R.A.; Liang, Y.M. [Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi' an (China)

    2014-10-14

    p15INK4B, a cyclin-dependent kinase inhibitor, has been recognized as a tumor suppressor. Loss of or methylation of the p15INK4B gene in chronic myeloid leukemia (CML) cells enhances myeloid progenitor formation from common myeloid progenitors. Therefore, we examined the effects of overexpressed p15INK4B on proliferation and apoptosis of CML cells. Overexpression of p15INK4B inhibited the growth of K562 cells by downregulation of cyclin-dependent kinase 4 (CDK4) and cyclin D1 expression. Overexpression of p15INK4B also induced apoptosis of K562 cells by upregulating Bax expression and downregulating Bcl-2 expression. Overexpression of p15INK4B together with STI571 (imatinib) or BCR-ABL1 small interfering RNA (siRNA) also enhanced growth inhibition and apoptosis induction of K562 cells. The enhanced effect was also mediated by reduction of cyclin D1 and CDK4 and regulation of Bax and Bcl-2. In conclusion, our study may provide new insights into the role of p15INK4B in CML and a potential therapeutic target for overcoming tyrosine kinase inhibitor resistance in CML.

  1. 伴不典型BCR-ABL融合基因的慢性髓性白血病的临床和实验研究%A clinical and laboratory study of chronic myeloid leukemia with atypical BCR-ABL fusion gene subtypes

    Institute of Scientific and Technical Information of China (English)

    桂晓敏; 潘金兰; 仇惠英; 岑建农; 薛永权; 陈苏宁; 沈宏杰; 姚利; 张俊

    2014-01-01

    目的 探讨伴不典型BCR-ABL融合基因亚型el4a3和e19a2型慢性髓性白血病(CML)的临床和实验室特点.方法 对2004至2012年染色体核型分析有t(9;22) (q34;q11),荧光原位杂交(FISH)证实为BCR-ABL融合基因阳性,而常规实时定量PCR(RQ-PCR)检测常见BCR-ABL融合基因(b3a2、b2a2和e1a2)阴性的6例CML患者,重新设计引物进行PCR扩增,并将扩增产物测序,以明确不典型BCR-ABL融合基因类型.对BCR-ABL融合基因扩增产物进行突变检测.对患者的临床资料进行回顾性分析.结果 6例患者PCR扩增产物经测序分析,其中5例为e14a3型,1例为e19a2型.5例e14a3型CML患者中,男4例,女1例,中位年龄48岁,慢性期4例,加速期1例;1例e19a2型患者为女性,40岁,CML慢性期,PLT>1 000× 109/L.5例e14a3型CML患者中4例在羟基脲或IFN治疗无效后予以伊马替尼(IM)治疗,1例行造血干细胞移植(HSCT).前4例患者中1例因有E255K突变而对IM耐药,改用达沙替尼后获完全细胞遗传学反应(CCyR);1例在IM治疗获CCyR后3个月复发并急变,最终死亡;2例IM治疗后获CCyR,目前状态稳定,仍处于CCyR,尽管其中1例伴有I293T突变.行HSCT治疗患者目前处于CCyR.1例e19a2型CML患者羟基脲治疗后获得完全血液学反应,后改用IM治疗,很快获得CCyR.结论 伴不典型BCR-ABL融合基因的CML发病率极低,酪氨酸激酶抑制剂或HSCT都可以取得疗效,常规RQ-PCR可能漏检少见的不典型BCR-ABL融合基因亚型.%Objective To explore the clinical and laboratory features of chronic myeloid leukemia (CML) with atypical e14a3 and e19a2 BCR-ABL fusion gene subtypes.Methods We retrospectively analyzed a cohort of CML patients with Ph chromosome positive confirmed by cytogenetic and FISH but classical el3a3 (b2a2),e14a2 (b3a2)and ela2 fusion transcripts negative identified by conventional realtime quantification RT-PCR (RQ-PCR).Further RQ-PCR was done with the forward primer and reverse primer designed to

  2. Standardization of real-time quantitative polymerase chain reaction for detection of the JAK2V617F mutation in BCR-ABL1 negative myeloproliferative neoplasms: A tertiary care centre experience

    Directory of Open Access Journals (Sweden)

    Tathagat Chatterjee

    2015-01-01

    Full Text Available Background: Identification of JAK2V617F mutations has led to a significant development in our understanding of the pathogenesis and therapy of BCR-ABL1 negative myeloproliferative neoplasms (MPNs. However, not all cases of BCR-ABL1 negative MPNs carry JAK2V617F mutations. The present study was undertaken with an aim to standardize the real-time quantitative polymerase chain reaction (PCR for the detection of JAK2V617F mutations and to find the prevalence of Janus kinase 2 (JAK2 mutations in MPNs in the Indian scenario. Materials and Methods: Real-time quantitative PCR was used to detect the JAK2V617F mutation. Standardization of the detection procedure was carried out using recommended guidelines to ensure the accuracy and reproducibility of results. Forty-nine patients of BCR-ABL1 negative MPNs were included in the study. Results: The JAK2V617F mutation was detected in 63.3% patients of BCR-ABL1 negative MPNs. On classification of these BCR-ABL1 negative MPNs, JAK2V617F mutation was detected in 78.3% patients with polycythemia vera (PV, 62.5% patients with essential thrombocythemia (ET, and 44.4% patients with Primary myelofibrosis (PMF. Conclusion: Role of detection of JAK2 mutations in BCR-ABL1 negative MPN has begun to be described and can be used in the diagnosis of PV, ET, and PMF along with other criterias. In future, it may be suitable for treatment monitoring and prognostication.

  3. 荧光原位杂交在慢性粒细胞白血病细胞BCR/ABL融合基因检测中的应用及其意义%The detection of BCR/ABL fusion gene by interphase fluorescence in situ hybridization in patients with chronic myeloid leukemia and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    张济; 李君君; 颜家运; 邹礼衡; 刘静

    2012-01-01

    目的:探讨荧光原位杂交(FISH)技术检测慢性粒细胞白血病(CML)骨髓和外周血细胞的BCR /ABL融合基因的临床价值.方法:应用FISH 对正常对照组及CML患者骨髓和外周血细胞BCR/ ABL融合基因进行检测和分析.结果:慢性期CML 患者骨髓和外周血细胞该融合基因阳性细胞率分别为(61.9 ± 22.3)%和(68.4 ± 19.8)%,加速期为(77.2 ± 16.7)% 和(86.8 ± 12.1)%,急变期为(80.6 ± 17.5)%和(81.4 ± 18.0)%,两者细胞中BCR/ABL 基因的阳性率未见统计学差异(P>0.05),且骨髓和外周血细胞之间融合基因阳性细胞比率呈直线正相关.同时发现在完全临床缓解患者中,经伊马替尼治疗的CML 患者(71.4%)较经干扰素和羟基脲联合治疗者(10.0%)有更高的分子生物学缓解(P 0.05). A significant correlation was found between the BCR/ABL positive cells in peripheral blood and in bone marrow samples. Moreover, the higher rate of complete molecular remission was achieved by treating with imatinib than with interferon and hydroxyurea during complete remission phase (P < 0.05). Conclusions Detecting BCR/ABL fusion gene in peripheral blood and bone marrow samples by FISH are beneficial to diagnosis, treatment and minimal residual disease monitor in CML.

  4. The diagnosis of BCR/ABL-negative chronic myeloproliferative diseases (CMPD): a comprehensive approach based on morphology, cytogenetics, and molecular markers.

    Science.gov (United States)

    Haferlach, Torsten; Bacher, Ulrike; Kern, Wolfgang; Schnittger, Susanne; Haferlach, Claudia

    2008-01-01

    Recent years showed significant progress in the molecular characterization of the chronic myeloproliferative disorders (CMPD) which are classified according to the WHO classification of 2001 as polycythemia vera (PV), chronic idiopathic myelofibrosis (CIMF), essential thrombocythemia (ET), CMPD/unclassifiable (CMPD-U), chronic neutrophilic leukemia, and chronic eosinophilic leukemia (CEL)/hypereosinophilic syndrome, all to be delineated from BCR/ABL-positive chronic myeloid leukemia (CML). After 2001, the detection of the high frequency of the JAK2V617F mutation in PV, CIMF, and ET, and of the FIP1L1-PDGFRA fusion gene in CEL further added important information in the diagnosis of CMPD. These findings also enhanced the importance of tyrosine kinase mutations in CMPD and paved the way to a more detailed classification and to an improved definition of prognosis using also novel minimal residual disease (MRD) markers. Simultaneously, the broadening of therapeutic strategies in the CMPD, e.g., due to reduced intensity conditioning in allogeneic hematopoietic stem cell transplantation and the introduction of tyrosine kinase inhibitors in CML, in CEL, and in other ABL and PDGRFB rearrangements, increased the demands to diagnostics. Therefore, today, a multimodal diagnostic approach combining cytomorphology, cytogenetics, and individual molecular methods is needed in BCR/ABL-negative CMPD. A stringent diagnostic algorithm for characterization, choice of treatment, and monitoring of MRD will be proposed in this review. PMID:17938925

  5. Functionally deregulated AML1/RUNX1 cooperates with BCR-ABL to induce a blastic phase-like phenotype of chronic myelogenous leukemia in mice.

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    Kiyoko Yamamoto

    Full Text Available Patients in the chronic phase (CP of chronic myelogenous leukemia (CML have been treated successfully following the advent of ABL kinase inhibitors, but once they progress to the blast crisis (BC phase the prognosis becomes dismal. Although mechanisms underlying the progression are largely unknown, recent studies revealed the presence of alterations of key molecules for hematopoiesis, such as AML1/RUNX1. Our analysis of 13 BC cases revealed that three cases had AML1 mutations and the transcript levels of wild-type (wt. AML1 were elevated in BC compared with CP. Functional analysis of representative AML1 mutants using mouse hematopoietic cells revealed the possible contribution of some, but not all, mutants for the BC-phenotype. Specifically, K83Q and R139G, but neither R80C nor D171N mutants, conferred upon BCR-ABL-expressing cells a growth advantage over BCR-ABL-alone control cells in cytokine-free culture, and the cells thus grown killed mice upon intravenous transfer. Unexpectedly, wt.AML1 behaved similarly to K83Q and R139G mutants. In a bone marrow transplantation assay, K83Q and wt.AML1s induced the emergence of blast-like cells. The overall findings suggest the roles of altered functions of AML1 imposed by some, but not all, mutants, and the elevated expression of wt.AML1 for the disease progression of CML.

  6. INFLUENCE OF CHEMOTHERAPEUTANTS AND CYTOKINES ON GROWTH AND TRANSGENE EXPRESSION OF BONE MARROW CELLS FROM MT/P210bcr-ab1 TRANSGENIC MICE

    Institute of Scientific and Technical Information of China (English)

    CHEN Hanchun; Andrew Pierce; Tony Whetton

    1999-01-01

    Objective: To investigate the influence of chemotherapeutic agents and cytokines on growth of bone marrow cells from MT/p210 bcr-ab1 transgenic mice.Methods: The bone marrow cells of transgenic chronic myelogenous leukemia (CML) model mice carrying metallothionein (MT) promoter/enhancer, bcr-abl (p210)cDNA and SV40 splicing/poly (A) signal sequences were cultured in liquid and soft agar with hydroxyurea (Hu),5-fluorouracil (5-Fu), mouse stem cell factor (mSCF)and mouse interleukin-3 (mIL-3) independently or collectively. The cells and colonies were counted. The levels of transgene expression were detected by reverse transcriptase-polymerase chain reaction (RT-PCR).Results: The cell proliferation, colony formation and transgene expression of the bone marrow cells were stimulated with mSCF and mIL-3, but there was little growth without any growth factors, or when mSCF,mIL-3 and Hu or 5-Fu were added. Conclusion: The combined utilization of chemotherapeutants and cytokines is a potentially effective strategy of clinical treatment for CML.

  7. Comparison between BCR sequential extraction and geo-accumulation method to evaluate metal mobility in sediments of Dongting Lake, Central China

    Science.gov (United States)

    Yao, Zhigang

    2008-02-01

    The form in which a metal exists strongly influences its mobility and thus, the effects on the environment. Operational methods of speciation analysis, such as the use of sequential extraction procedures, are commonly applied. The Dongting Lake, the second largest fresh-water lake in China, contains three China wetlands of international importance, the East Dongting Lake, South Dongting Lake, and West Dongting Lake. In this work, an optimized BCR sequential extraction procedure was used to assess the environmental risk of Cd, Cr, Cu, Ni, Pb and Zn in contaminated sediment of the Dongting Lake. The procedure was evaluated by using a certified reference material, BCR701. The results of the partitioning study indicated that in the lake sediments, more easily mobilized forms (acid exchangeable) were predominant for Cd, particularly in the samples from the East Dongting Lake. In contrast, the largest amount of Pb was associated with the iron and manganese oxide fractions and Cu, Zn, Cr, and Ni analyzed were mainly distributed in residual phase at an average percentage greater than 60% of the total metals. The potential risk to the lake’s water contamination was highest in the East Dongting Lake based on the calculated contamination factors. On the other hand, the total metal content was determined as well by inductively coupled plasma and mass spectrometry (ICP-MS) and assessed by using geo-accumulation index. The assessment results using geo-accumulation index were compared with the information on metal speciation. Both were correspondent with each other.

  8. GENE THERAPY USING RETROVIRAL VECTOR OF bcr-abl SPECIFIC MULTI-UNIT RIBOZYMES COULD INHIBIT CML CELL GROWTH AND INDUCE APOPTOSIS

    Institute of Scientific and Technical Information of China (English)

    冯琦; 孙凯; 赵永同; 张涛; 尚振川; 王莎; 王玮; 赵宁; 颜真; 韩苇; 张英起; 孙秉中

    2003-01-01

    Objective: To investigate the in vitro cleavage ability and effects on apoptosis and cell growth of the bcr-abl fusion gene specific multi-unit ribozymes. Methods: Three fusion point specific ribozymes were designed and the multi-unit ribozymes' in vitro transcription vector and retroviral vector were constructed. The in vitro cleavage ability was tested. The retroviral vector was transfected into K562 cell and the effects on proliferation, apoptosis, cell cycle and cell structure were observed. Results: Multi-unit ribozymes had in vitro cleavage efficiency of 70.8%, which was more efficient than single-unit and double-unit ribozymes. Transfection of the retroviral vector of the ribozyme into K562 cells, induced inhibition of cell growth and apoptosis. The incorporation rate of DNA in ribozymes transfected K562 cells was greatly decreased along with time passed, with an inhibition rate of more than 50% after 96 h of transfection. Under FCM, 18.4% of the cells underwent apoptosis 72 h after transfection and more cells were blocked in G phase, with the ratio in S phase greatly decreased (41.9%). Under electron microscope, compaction of nuclear chromatin and apoptosis bodies were observed.Conclusion: Multi-unit ribozymes specific to bcr-abl fusion gene can be used to treat CML and to purge bone marrow for self-grafting.

  9. Estandarización de la TR-PCR para la detección de las fusiones génicas BCR-ABL en pacientes con leucemia Mieloide Crónica (LMC y Linfoide Aguda (LLA provenientes de HUSVP y Clíncia León XIII

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    Gonzálo Vásquez Palacio

    2006-04-01

    Full Text Available La translocación recíproca t(9:22(q34;q11 involucra el proto-oncogen ABL y el gen BCR, originando un gen de fusión BCR-ABL, que codifica una proteína con elevada actividad tirosina quinasa, implicada en la leucemogénesis.

  10. Which method better evaluates the molecular response in newly diagnosed chronic phase chronic myeloid leukemia patients with imatinib treatment, BCR-ABL(IS) or log reduction from the baseline level?

    Science.gov (United States)

    Qin, Ya-Zhen; Jiang, Qian; Jiang, Hao; Li, Jin-Lan; Li, Ling-Di; Zhu, Hong-Hu; Lai, Yue-Yun; Lu, Xi-Jing; Liu, Yan-Rong; Jiang, Bin; Huang, Xiao-Jun

    2013-09-01

    The molecular response of chronic myeloid leukemia (CML) patients to tyrosine kinase inhibitor treatment can be evaluated either by BCR-ABL mRNA levels on international scale (IS) or by log reduction from the baseline level of the laboratory. Both methods were compared in 248 newly diagnosed chronic phase CML patients treated with imatinib. The major molecular responses (MMR) obtained by both methods predict progression-free survival (PFS, all Plog reduction method, had the same PFS as MMR patients identified by both methods. The molecular responses of patients at 3 and 6 months, as evaluated by the two methods, have similar predictive values on their cytogenetic responses at 12 months and on their molecular responses at 18 months. Both ≤ 10%(IS) and ≥ 1 log reduction at 3 months and ≤ 1%(IS) at 6 months were significantly associated with PFS (P=0.0011, 0.0090, and 0.0064). The percentages of patients with BCR-ABL(IS) of ≤ 1%, >1-10%, and of >10% at 3 months and 6 months in the German CML Study IV were similar with those with corresponding BCR-ABL(IS) in our center, but was significantly different with those evaluated by the log reduction method. Therefore, the molecular response evaluated by BCR-ABL(IS) has similar trends in PFS and in response prediction, but can better differentiate patients than that by the log reduction method. Furthermore, the IS method allows comparison among molecular response results from different laboratories.

  11. Increased acetylation of lysine 317/320 of p53 caused by BCR-ABL protects from cytoplasmic translocation of p53 and mitochondria-dependent apoptosis in response to DNA damage

    NARCIS (Netherlands)

    Kusio-Kobialka, Monika; Wolanin, Kamila; Podszywalow-Bartnicka, Paulina; Sikora, Ewa; Skowronek, Krzysztof; McKenna, Sharon L.; Ghizzoni, Massimo; Dekker, Frank J.; Piwocka, Katarzyna

    2012-01-01

    Chronic myeloid leukemia (CML) is a disorder of hematopoietic stem cells caused by the expression of BCR-ABL. Loss of p53 has not been implicated as important for the development of CML. Mutations in p53 protein are infrequent, however they correlate with the disease progression. The absence of p53

  12. Determination of lactate dehydrogenase (LDH and Bcr-Abl transcript in the follow-up of patients with chronic myeloid leukemia = Determinação da lactate desidrogenase (LDH e do transcrito Bcr-Abl em pacientes com leucemia mielóide crônica

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    Roberto Iemitsu Tatakihara

    2010-07-01

    Full Text Available Chronic myeloid leukemia (CML is a malignant myeloproliferative disorder that originates from a pluripotent stem cell characterized by abnormal release of the expanded, malignant stem cell clone from the bone marrow into the bloodstream. The vast majority of patients with CML present Bcr-Abl transcripts. Lactate dehydrogenase (LDH is considered a biochemical marker common for tumor growth, anaerobic glycolysis and has been considered a poor prognostic factor for acute myeloid leukemia. Therefore, this study aimed to evaluate the concentration of LDH in plasma and the detection of the Bcr-Abl transcripts in patients with CML and healthy donors. We analyzed 22 patients demonstrably diagnosed with CML and 56 healthy donors. LDH concentration in plasma was higher in patients with CML. All patients with CML in this study were under treatment, but even so four patients had the Bcr-Abl (b3a2 transcript in peripheral blood. Two out of the four patients with b3a2 showed higher LDH (486 U L-1 and 589 U L-1. Thus, although the study was conducted with small numbers of samples, it is possible to suggest therapy alteration for two patients who presented transcript b3a2 in the peripheral blood samples and whose LDH concentration was high, in order to improve the disease. Leucemia mieloide crônica (LMC é uma desordem mieloproliferativa maligna que é originada de célula-tronco pluripotente caracterizada por expansão anormal, maligna de clones de células tronco da medula óssea na circulação. A grande maioria dos pacientes com LMC apresentam transcritos Bcr-Abl. Lactato desidrogenase (LDH,considerado um marcador bioquímico para crescimento tumoral, glicólise anaeróbica, e tem sido considerado um fator de pior prognóstico da LMC. Portanto, este estudo visa avaliar a concentraçãode LDH no plasma e a detecção do transcrito Bcr-Abl em 22 pacientes com LMC e 56 indivíduos saudáveis. Foram avaliados 22 pacientes com LMC e 56 doadores saudáveis. A

  13. SPR Detection and Discrimination of the Oligonucleotides Related to the Normal and the Hybrid bcr-abl Genes by Two Stringency Control Strategies

    Science.gov (United States)

    Matsishin, M. J.; Ushenin, Iu. V.; Rachkov, A. E.; Solatkin, A. P.

    2016-01-01

    In this study, we applied two stringency control strategies for surface plasmon resonance (SPR) detection of DNA hybridization and discrimination of completely and partially complementary 24-mer sequences. These sequences are specific to the human normal bcr and the hybrid bcr-abl genes, protein products of which are responsible for some leukemia. SPR sensors based on resonance phenomena in nanoscale gold films are well suited for label-free, real-time investigations of the macromolecule interactions. Thermodynamic parameters obtained using the web server DINAMelt allowed supposing the possibility for realization (a) stringency control based on the ionic strength of the hybridization buffer and (b) stringency control based on the temperature elevation. The first one resulted in that the discrimination index of completely complementary and partially complementary oligonucleotides depending on the target concentration varied from 1.3 to 1.8 in 2 × SSC and from 2.0 to 2.9 in 0.5 × SSC. For implementation of the second stringency control strategy, SPR spectrometer measuring flow cell with built-in high-precision temperature control and regulation as well as corresponding software was created. It is shown that the duplexes formed by the immobilized probes mod-Ph and completely complementary oligonucleotides P1 remained without significant changes until ~50 °C, while the duplexes formed with partially complementary oligonucleotide Bcrex14 almost entirely disrupted at 40 °C. Thus, the absolutely effective thermodiscrimination of this pair of oligonucleotides was achieved in this temperature range (40-50 °C).

  14. Next-generation sequencing for sensitive detection of BCR-ABL1 mutations relevant to tyrosine kinase inhibitor choice in imatinib-resistant patients

    Science.gov (United States)

    Soverini, Simona; De Benedittis, Caterina; Polakova, Katerina Machova; Linhartova, Jana; Castagnetti, Fausto; Gugliotta, Gabriele; Papayannidis, Cristina; Mancini, Manuela; Klamova, Hana; Salvucci, Marzia; Crugnola, Monica; Iurlo, Alessandra; Albano, Francesco; Russo, Domenico; Rosti, Gianantonio; Cavo, Michele; Baccarani, Michele; Martinelli, Giovanni

    2016-01-01

    In chronic myeloid leukemia (CML) and Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) patients who fail imatinib treatment, BCR-ABL1 mutation profiling by Sanger sequencing (SS) is recommended before changing therapy since detection of specific mutations influences second-generation tyrosine kinase inhibitor (2GTKI) choice. We aimed to assess i) in how many patients who relapse on second-line 2GTKI therapy next generation sequencing (NGS) may track resistant mutations back to the sample collected at the time of imatinib resistance, before 2GTKI start (switchover sample) and ii) whether low level mutations identified by NGS always undergo clonal expansion. To this purpose, we used NGS to retrospectively analyze 60 imatinib-resistant patients (CML, n = 45; Ph+ ALL, n = 15) who had failed second-line 2GTKI therapy and had acquired BCR-ABL1 mutations (Group 1) and 25 imatinib-resistant patients (CML, n = 21; Ph+ ALL, n = 4) who had responded to second-line 2GTKI therapy, for comparison (Group 2). NGS uncovered that in 26 (43%) patients in Group 1, the 2GTKI-resistant mutations that triggered relapse were already detectable at low levels in the switchover sample (median mutation burden, 5%; range 1.1%–18.4%). Importantly, none of the low level mutations detected by NGS in switchover samples failed to expand whenever the patient received the 2GTKI to whom they were insensitive. In contrast, no low level mutation that was resistant to the 2GTKI the patients subsequently received was detected in the switchover samples from Group 2. NGS at the time of imatinib failure reliably identifies clinically relevant mutations, thus enabling a more effective therapeutic tailoring. PMID:26980736

  15. SPR Detection and Discrimination of the Oligonucleotides Related to the Normal and the Hybrid bcr-abl Genes by Two Stringency Control Strategies.

    Science.gov (United States)

    Matsishin, M J; Ushenin, Iu V; Rachkov, A E; Solatkin, A P

    2016-12-01

    In this study, we applied two stringency control strategies for surface plasmon resonance (SPR) detection of DNA hybridization and discrimination of completely and partially complementary 24-mer sequences. These sequences are specific to the human normal bcr and the hybrid bcr-abl genes, protein products of which are responsible for some leukemia. SPR sensors based on resonance phenomena in nanoscale gold films are well suited for label-free, real-time investigations of the macromolecule interactions. Thermodynamic parameters obtained using the web server DINAMelt allowed supposing the possibility for realization (a) stringency control based on the ionic strength of the hybridization buffer and (b) stringency control based on the temperature elevation. The first one resulted in that the discrimination index of completely complementary and partially complementary oligonucleotides depending on the target concentration varied from 1.3 to 1.8 in 2 × SSC and from 2.0 to 2.9 in 0.5 × SSC. For implementation of the second stringency control strategy, SPR spectrometer measuring flow cell with built-in high-precision temperature control and regulation as well as corresponding software was created. It is shown that the duplexes formed by the immobilized probes mod-Ph and completely complementary oligonucleotides P1 remained without significant changes until ~50 °C, while the duplexes formed with partially complementary oligonucleotide Bcrex14 almost entirely disrupted at 40 °C. Thus, the absolutely effective thermodiscrimination of this pair of oligonucleotides was achieved in this temperature range (40-50 °C). PMID:26759355

  16. 用COLD-PCR方法提高BCR-ABL1激酶区耐药突变检测灵敏度%Application of COLD-PCR for improved detection of BCR-ABL1 kinase domain drug-resistant mutation

    Institute of Scientific and Technical Information of China (English)

    李庆; 刘红星; 孙慧; 王倩; 张之芬; 武焕玲; 李元堂; 陈永金; 田文君

    2013-01-01

    Objective To evaluate the feasibility of the co-amplification using a low denaturation temperature PCR (COLD-PCR) method in improving the detection of BCR-ABL1 fusion gene kinase domain drug-resistant mutation.Methods Conventional nested PCR (CN-PCR) and COLD-PCR protocol were designed to amplify full-length of BCR-ABL1 kinase domain.PCR products were purified and then Sanger sequenced to detect BCR-ABL1 kinase domain mutation (KDM).20 newly diagnosed CML patients and 32 Imatinib (IM) resistant patients were chosen and peripheral blood or bone marrow samples were collected.PCR products of the clinical specimens were purified and then cloned to evaluate the proportion of the KDM allele.Standard samples with different proportion of KDMs were prepared using T-A vectors with KDM and wild type BCR-ABL1 kinase domain sequence,and then CN-PCR,COLD-PCR and Sanger sequencing were performed to compare the detection sensitivity.Results In the 32 IM-resistant patients,23 were identified KDM-positive using CN-PCR and 28 KDM-positive using COLD-PCR.In the 20 newly diagnosed CML patients,none was identified KDM-positive using CN-PCR and 1 was identified carrying a lower proportion of KDM using COLD-PCR.For 16 different types of KDMs,COLD-PCR method could improve the detection sensitivity 4-12 times.Conclusion Detection sensitivity of BCR-ABL1 drug-resistant kinase domain mutation can be effectively improved by using COLD-PCR method and may contribute to early detection of resistance KDMs.%目的 探讨用低变性温度共扩增PCR(COLD-PCR)方法提高BCR-ABL1融合基因激酶区耐药突变检测灵敏度的可行性.方法 本研究为实验诊断研究.设计常规巢式PCR(CN-PCR)和COLD-PCR方案扩增BCR-ABL1激酶区全长,扩增产物纯化后用Sanger测序法检测激酶区突变(KDM).采集32例经伊马替尼(IM)治疗并出现耐药的慢性粒细胞性白血病(CML)患者和20例初诊CML患者外周血或骨髓标本,用上述2种方案检测标本中的KDM.

  17. B cell TLR1/2, TLR4, TLR7 and TLR9 interact in induction of class switch DNA recombination: modulation by BCR and CD40, and relevance to T-independent antibody responses.

    Science.gov (United States)

    Pone, Egest J; Lou, Zheng; Lam, Tonika; Greenberg, Milton L; Wang, Rui; Xu, Zhenming; Casali, Paolo

    2015-02-01

    Ig class switch DNA recombination (CSR) in B cells is crucial to the maturation of antibody responses. It requires IgH germline IH-CH transcription and expression of AID, both of which are induced by engagement of CD40 or dual engagement of a Toll-like receptor (TLR) and B cell receptor (BCR). Here, we have addressed cross-regulation between two different TLRs or between a TLR and CD40 in CSR induction by using a B cell stimulation system involving lipopolysaccharides (LPS). LPS-mediated long-term primary class-switched antibody responses and memory-like antibody responses in vivo and induced generation of class-switched B cells and plasma cells in vitro. Consistent with the requirement for dual TLR and BCR engagement in CSR induction, LPS, which engages TLR4 through its lipid A moiety, triggered cytosolic Ca2+ flux in B cells through its BCR-engaging polysaccharidic moiety. In the presence of BCR crosslinking, LPS synergized with a TLR1/2 ligand (Pam3CSK4) in CSR induction, but much less efficiently with a TLR7 (R-848) or TLR9 (CpG) ligand. In the absence of BCR crosslinking, R-848 and CpG, which per se induced marginal CSR, virtually abrogated CSR to IgG1, IgG2a, IgG2b, IgG3 and/or IgA, as induced by LPS or CD154 (CD40 ligand) plus IL-4, IFN-γ or TGF-β, and reduced secretion of class-switched Igs, without affecting B cell proliferation or IgM expression. The CSR inhibition by TLR9 was associated with the reduction in AID expression and/or IgH germline IH-S-CH transcription, and required co-stimulation of B cells by CpG with LPS or CD154. Unexpectedly, B cells also failed to undergo CSR or plasma cell differentiation when co-stimulated by LPS and CD154. Overall, by addressing the interaction of TLR1/2, TLR4, TLR7 and TLR9 in the induction of CSR and modulation of TLR-dependent CSR by BCR and CD40, our study suggests the complexity of how different stimuli cross-regulate an important B cell differentiation process and an important role of TLRs in inducing

  18. Overexpression or knock-down of runt-related transcription factor 1 affects BCR-ABL-induced proliferation and migration in vitro and leukemogenesis in vivo in mice

    Institute of Scientific and Technical Information of China (English)

    YANG Li-jun; YU Wei-dong; DU Jun-bao; CHAO Shuang; CHEN Min-xia; ZHAO He-hua; GUO Jing-zhu

    2009-01-01

    Background Runt-related transcription factor 1 (Runx1) plays a crucial role in hematogenesis and its dysfunction may contribute to leukemogenesis. However, it is not clear whether or not abnormal expression of Runx1 will induce leukemia and how the change of Runx1 expression level could affect BCR-ABL-induced leukemogenesis. In the present study, we aimed to analyze if abnormal expression of Runx1 in BaF3 cells alone would induce leukemogenesis. And we also wanted to know if abnormal expression of Runx1 in leukemic cells would affect leukemogenesis. Furthermore, we investigated whether overexpression or knock-down of Runx1 in BaF3 cells would induce leukemogenesis.Methods Plasmids containing full-length Runx1 cDNA were transduced into BaF3 cells and BaF3-P185wt cells (BCR-ABL transformed BaF3 cells) by electroporation. Plasmids containing a short hairpin RNA of Runx1 were transduced into BaF3 cells and BaF3-P185wt cells by electroporation. Runx1 expression level was quantified by Western blotting and quantitative real-time PCR. The effects of overexpression or knock-down of Runx1 on proliferation, apoptosis and migration of cells were detected in vitro. Then, using MSCV-P185wt-FGFP as a control, we transplanted MSCV-P185wt-Runx1 cells or MSCV-P185wt-shRNA cells into Balb/c mice through tail vein and observed tumorgenesis of the different phenotypes.Results In vitro analysis revealed that overexpression of Runx1 in P185wt cells could inhibit cell proliferation and slow down cell migration; while knock-down of Runx1 could promote cell proliferation and speed up cell migration. In vivo analysis indicated that mice transplanted with MSCV-P185wt-Runx1 survived longer than controls. In contrast, mice transplanted with MSCV-P185wt-shRNA survived shorter than the control group. Gross pathological analysis revealed that the MSCV-P185wt-Runx1 group had less severe splenomegaly and hepatomegaly compared to the control group, and the MSCV-P185wt-shRNA group had more severe

  19. Therapy Provider Phase Information

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Therapy Provider Phase Information dataset is a tool for providers to search by their National Provider Identifier (NPI) number to determine their phase for...

  20. Synthesis and characterization of a BODIPY conjugate of the BCR-ABL kinase inhibitor Tasigna® (Nilotinib): Evidence for transport of Tasigna® and its fluorescent derivative by ABC drug transporters

    OpenAIRE

    Shukla, Suneet; Skoumbourdis, Amanda P.; Walsh, Martin J.; Hartz, Anika M. S.; Fung, King Leung; Wu, Chung-pu; Gottesman, Michael M.; Bauer, Björn; Thomas, Craig J.; Suresh V Ambudkar

    2011-01-01

    Tasigna® (Nilotinib) is a recently approved BCR-ABL kinase inhibitor by the Food and Drug Administration, which is indicated for the treatment of drug-resistant chronic myelogenous leukemia (CML). The efflux of tyrosine kinase inhibitors by ATP-binding cassette (ABC) drug transporters, which actively pump these drugs out of cells utilizing ATP as an energy source, has been linked to the development of drug resistance in CML patients. We report here synthesis and characterization of a fluoresc...

  1. Provide, provide: the economics of aging.

    Science.gov (United States)

    1998-06-26

    Most older persons face two potentially serious economic problems: (a) declining earning power and (b) declining health that can be partly offset by increased utilization of health care. The decline in earning power is largely attributable to physiological changes and to obsolescence of skills and knowledge. These adverse effects are exacerbated by public and private policies that reduce the incentives of older persons to continue work and increase the cost to employers of employing older workers. The problems of earnings replacement and health care payment are usually discussed separately, but there are several reasons why they should be considered together. First, there are often tradeoffs between the two. Money is money, and for most people there is never enough to go around. This is self-evident where private funds are concerned. Low-income elderly, for instance, frequently must choose between expensive prescription drugs and an adequate diet. For middle-income elderly, the choice may be between saving on medigap insurance or forgoing an airplane trip to a grandchild's graduation. Difficult choices are also inherent in the allocation of public funds. The same tax receipts that could be used to maintain or increase retirement benefits could be used to fund additional care, and vice versa. In discussing these tradeoffs, some analysts assert that people will gladly give up other goods and services for medical care that cures illness, relieves pain, or restores function. Others believe that some people would forgo some health insurance in order to maintain access to other goods and services. A second reason for looking at the two problems together is that they pose similar questions for public policy. How much should each generation provide for its own needs in old age, and how much should be provided by the generations that follow? How much provision should be voluntary, how much compulsory? How much intra-generational redistribution is appropriate after age 65

  2. Establishment and characterization of A novel Philadelphia-chromosome positive chronic myeloid leukemia cell line, TCC-S, expressing P210 and P190 BCR/ABL transcripts but missing normal ABL gene.

    Science.gov (United States)

    Van, Phan Nguyen Thanh; Xinh, Phan Thi; Kano, Yasuhiko; Tokunaga, Katsushi; Sato, Yuko

    2005-03-01

    A novel Philadelphia-chromosome positive (Ph+) cell line, TCC-S, has been established from a patient with Ph+ chronic myeloid leukemia (CML) in the blastic crisis. TCC-S cells were shown to express both P210 and P190 BCR/ABL transcripts by reverse transcriptase-polymerase chain reaction (PCR), although quantitative-PCR revealed that TCC-S cells mainly expressed P210 BCR/ABL transcript. Karyotype analysis revealed several triploid clones which constantly harbored two der(9)del(9) (p12)t(9;22) (q34;qll)s and two del(9) (q21)s. The der(9)del(9) (p12)t(9;22) (q34;q11) is rarely found in other CML cell lines. Moreover, to the best of our knowledge, del(9) (q21) resulting in missing of a restrict region including normal ABL gene has not been found among CML cell lines previously described. Thus, TCC-S cells with only BCR/ABL gene and no normal ABL gene may be a useful tool for functional study of ABL in Ph+ CML.

  3. Doxorubicin Differentially Induces Apoptosis, Expression of Mitochondrial Apoptosis-Related Genes, and Mitochondrial Potential in BCR-ABL1-Expressing Cells Sensitive and Resistant to Imatinib

    Directory of Open Access Journals (Sweden)

    Ewelina Synowiec

    2015-01-01

    Full Text Available Imatinib resistance is an emerging problem in the therapy of chronic myeloid leukemia (CML. Because imatinib induces apoptosis, which may be coupled with mitochondria and DNA damage is a prototype apoptosis-inducing factor, we hypothesized that imatinib-sensitive and -resistant CML cells might differentially express apoptosis-related mitochondrially encoded genes in response to genotoxic stress. We investigated the effect of doxorubicin (DOX, a DNA-damaging anticancer drug, on apoptosis and the expression of the mitochondrial NADH dehydrogenase 3 (MT-ND3 and cytochrome b (MT-CYB in model CML cells showing imatinib resistance caused by Y253H mutation in the BCR-ABL1 gene (253 or culturing imatinib-sensitive (S cells in increasing concentrations of imatinib (AR. The imatinib-resistant 253 cells displayed higher sensitivity to apoptosis induced by 1 μM DOX and this was confirmed by an increased activity of executioner caspases 3 and 7 in those cells. Native mitochondrial potential was lower in imatinib-resistant cells than in their sensitive counterparts and DOX lowered it. MT-CYB mRNA expression in 253 cells was lower than that in S cells and 0.1 μM DOX kept this relationship. In conclusion, imatinib resistance may be associated with altered mitochondrial response to genotoxic stress, which may be further exploited in CML therapy in patients with imatinib resistance.

  4. Induction of apoptosis by shikonin through a ROS/JNKmediated process in Bcr/Abl-positive chronic myelogenous leukemia (CML) cells

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    This study examined the signaling events induced by shikonin that lead to the induction of apoptosis in Bcr/ Abl-positive chronic myelogenous leukemia (CML) cells (e.g., K562, LAMA84). Treatment of K562 cells with shikonin (e.g., 0.5 μM) resulted in profound induction of apoptosis accompanied by rapid generation of reactive oxygen species (ROS), striking activation of c-Jun-N-terminai kinase (JNK) and p38, marked release of the mitochondrial proteins cytochrome c and Smac/DIABLO, activation of caspase-9 and -3, and cleavage of PARP. Scavenging of ROS completely blocked all of the above-mentioned events (i.e., JNK and p38 phosphorylation, cytochrome c and Smac/DIABLO release, caspase and PARP cleavage, as well as the induction of apoptosis) following shikonin treatment. Inhibition of JNK and knock-down of JNKI significantly attenuated cytochrome c release, caspase cleavage and apoptosis, but did not affect shikonin-mediated ROS production. Additionally, inhibition of caspase activation completely blocked shikonin-induced apoptosis, but did not appreciably modify shikonin-mediated cytochrome c release or ROS generation. Altogether, these findings demonstrate that shikonin-induced oxidative injury operates at a proximal point in apoptotic signaling cascades, and subsequently activates the stress-related JNK pathway, triggers mitochondrial dysfunction, cytochrome c release, and caspase activation, and leads to apoptosis. Our data also suggest that shikonin may be a promising agent for the treatment of CML, as a generator of ROS.

  5. Cell sorting enables interphase fluorescence in situ hybridization detection of low BCR-ABL1 producing stem cells in chronic myeloid leukaemia patients beyond deep molecular remission

    DEFF Research Database (Denmark)

    van Kooten Niekerk, Peter Buur; Petersen, Charlotte Christie; Nyvold, Charlotte Guldborg;

    2014-01-01

    The exact disease state of chronic myeloid leukaemia (CML) patients in deep molecular remission is unknown, because even the most sensitive quantitative reverse transcription polymerase chain reaction (qPCR) methods cannot identify patients prone to relapse after treatment withdrawal. To elucidate......) ), n = 11) using both sensitive qPCR and interphase fluorescence in situ hybridization (iFISH). Despite evaluating fewer cells, iFISH proved superior to mRNA-based qPCR in detecting residual Ph(+) stem cells (P = 0·005), and detected Ph(+) stem- and progenitor cells in 9/10 patients at frequencies of 2......-14%. Moreover, while all qPCR(+) samples also were iFISH(+) , 9/33 samples were qPCR-/iFISH(+) , including all positive samples from MR(4) patients. Our findings show that residual Ph(+) cells are low BCR-ABL1 producers, and that DNA-based methods are required to assess the content of persisting Ph(+) stem...

  6. MAX Provider Characteristics

    Data.gov (United States)

    U.S. Department of Health & Human Services — The MAX Provider Characteristics (PC) File Implementation Report describes the design, implementation, and results of the MAXPC prototype, which was based on three...

  7. Multivariate Analyses and Evaluation of Heavy Metals by Chemometric BCR Sequential Extraction Method in Surface Sediments from Lingdingyang Bay, South China

    Directory of Open Access Journals (Sweden)

    Linglong Cao

    2015-04-01

    Full Text Available Sediments in estuary areas are recognized as the ultimate reservoirs for numerous contaminants, e.g., toxic metals. Multivariate analyses by chemometric evaluation were performed to classify metal ions (Cu, Zn, As, Cr, Pb, Ni and Cd in superficial sediments from Lingdingyang Bay and to determine whether or not there were potential contamination risks based on the BCR sequential extraction scheme. The results revealed that Cd was mainly in acid-soluble form with an average of 75.99% of its total contents and thus of high potential availability, indicating significant anthropogenic sources, while Cr, As, Ni were enriched in the residual fraction which could be considered as the safest ingredients to the environment. According to the proportion of secondary to primary phases (KRSP, Cd had the highest bioavailable fraction and represented high or very high risk, followed by Pb and Cu with medium risks in most of samples. The combined evaluation of the Pollution Load Index (PLI and the mean Effect Range Median Quotient (mERM-Q highlighted that the greatest potential environmental risk area was in the northwest of Lingdingyang Bay. Almost all of the sediments had a 21% probability of toxicity. Additionally, Principal Component Analysis (PCA revealed that the survey region was significantly affected by two main sources of anthropogenic contributions: PC1 showed increased loadings of variables in acid-soluble and reducible fractions that were consistent with the input from industrial wastes (such as manufacturing, metallurgy, chemical industry and domestic sewages; PC2 was characterized by increased loadings of variables in residual fraction that could be attributed to leaching and weathering of parent rocks. The results obtained demonstrated the need for appropriate remediation measures to alleviate soil pollution problem due to the more aggregation of potentially risky metals. Therefore, it is of crucial significance to implement the targeted

  8. Relationship between JAK2 gene V617F mutation and clinical characteristics in patients with BCR-ABL-negative myeloproliferative neoplasms%BCR-ABL阴性的骨髓增殖性肿瘤JAK2基因V617F突变分析

    Institute of Scientific and Technical Information of China (English)

    张燕香; 魏蓉

    2013-01-01

    目的:探讨BCR-ABL阴性的骨髓增殖性肿瘤(myeloproliferative neoplasms,MPN)患者蛋白质酪氨酸激酶基因(JAK2)V617F突变的发生率及其与患者临床特征的关系.方法:抽提65例MPN患者骨髓细胞DNA(其中真性红细胞增多症28例,特发性血小板增多症30例,特发性骨髓纤维化7例),应用等位基因特异性PCR技术(allele specific PCR,AS-PCR)分析JAK2基因V617F突变的发生率,并分析此突变与外周血细胞计数及血栓发生率等临床特征的关系.结果:65例MPN患者的V617F突变阳性率为64.62% (42/65).其中真性红细胞增多症患者的阳性率为75.00% (21/28),其白细胞及血小板计数较非突变者均显著增高(P<0.001);特发性血小板增多症患者该突变的阳性率为56.67% (17/30),其白细胞计数和血红蛋白水平均较非突变者显著增高(P<0.05);而7例特发性骨髓纤维化患者中4例被检出此突变阳性,其白细胞、血小板计数及血红蛋白水平与非突变者比较,差异则无统计学意义.同时,携带V617F突变的MPN患者血栓发生率明显高于非突变者(P<0.05).结论:JAK2基因V617F突变是我国BCR-ABL阴性MPN患者主要的分子遗传标志,可作为临床诊断的指标之一,而此突变对临床特征有一定影响.%Objective:To investigate the relationship between V617F mutation in JAK2 gene and clinical characteristics in patients with BCR-ABL-negative myeloproliferative neoplasms (MPN).Methods:Sixty-five patients with MPN,including 28 subjects with polycythemia vera (PV),30 subjects with essential thrombocythemia (ET) and 7 subjects with idiopathic myelofibrosis (IMF) were enrolled in this study.Bone marrow cell DNA was extracted from MPN patients,and V617F mutation in JAK2 gene was identified by allele specific PCR (AS-PCR).The correlation between V617F mutation and clinical characteristics such as peripheral blood cell count and incidence of thrombosis were analyzed.Results:Of the 65 patients

  9. Provider of Services File

    Data.gov (United States)

    U.S. Department of Health & Human Services — The POS file consists of two data files, one for CLIA labs and one for 18 other provider types. The file names are CLIA and OTHER. If downloading the file, note it...

  10. What HERA may provide?

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Hannes [DESY, Hamburg (Germany); De Roeck, Albert [CERN, Genf (Switzerland); Bartles, Jochen [Univ. Hamburg (DE). Institut fuer Theoretische Physik II] (and others)

    2008-09-15

    More than 100 people participated in a discussion session at the DIS08 workshop on the topic What HERA may provide. A summary of the discussion with a structured outlook and list of desirable measurements and theory calculations is given. (orig.)

  11. The Provident Principal.

    Science.gov (United States)

    McCall, John R.

    This monograph offers leadership approaches for school principals. Discussion applies the business leadership theory of Warren Bennis and Burt Nanus to the role of the principal. Each of the booklet's three parts concludes with discussion questions. Part 1, "Visions and Values for the Provident Principal," demonstrates the importance of…

  12. Achieving Provider Engagement

    Science.gov (United States)

    Greenfield, Geva; Pappas, Yannis; Car, Josip; Majeed, Azeem; Harris, Matthew

    2014-01-01

    The literature on integrated care is limited with respect to practical learning and experience. Although some attention has been paid to organizational processes and structures, not enough is paid to people, relationships, and the importance of these in bringing about integration. Little is known, for example, about provider engagement in the organizational change process, how to obtain and maintain it, and how it is demonstrated in the delivery of integrated care. Based on qualitative data from the evaluation of a large-scale integrated care initiative in London, United Kingdom, we explored the role of provider engagement in effective integration of services. Using thematic analysis, we identified an evolving engagement narrative with three distinct phases: enthusiasm, antipathy, and ambivalence, and argue that health care managers need to be aware of the impact of professional engagement to succeed in advancing the integrated care agenda. PMID:25212855

  13. Providence Their Guide

    Directory of Open Access Journals (Sweden)

    A.D. Naudé

    2012-02-01

    Full Text Available In his preface to this book the author quotes from Milton's Paradise lost, from which the title of this book is derived: 'Som natural tears they drop'd, but wip'd them soon; The World was all before them, where to choose Thir place of rest, and Providence thir guide; They hand in hand, with wand ring steps and slow, Through Eden took thir solitarie way.

  14. Why healthcare providers merge.

    Science.gov (United States)

    Postma, Jeroen; Roos, Anne-Fleur

    2016-04-01

    In many OECD countries, healthcare sectors have become increasingly concentrated as a result of mergers. However, detailed empirical insight into why healthcare providers merge is lacking. Also, we know little about the influence of national healthcare policies on mergers. We fill this gap in the literature by conducting a survey study on mergers among 848 Dutch healthcare executives, of which 35% responded (resulting in a study sample of 239 executives). A total of 65% of the respondents was involved in at least one merger between 2005 and 2012. During this period, Dutch healthcare providers faced a number of policy changes, including increasing competition, more pressure from purchasers, growing financial risks, de-institutionalisation of long-term care and decentralisation of healthcare services to municipalities. Our empirical study shows that healthcare providers predominantly merge to improve the provision of healthcare services and to strengthen their market position. Also efficiency and financial reasons are important drivers of merger activity in healthcare. We find that motives for merger are related to changes in health policies, in particular to the increasing pressure from competitors, insurers and municipalities. PMID:26055501

  15. 利用 BCR法和 Maiz法提取蔗田土壤中重金属的研究%Study on Extraction of Heavy Metals from Soil of Sugarcane Field by BCR Method and Maiz Method

    Institute of Scientific and Technical Information of China (English)

    王晓飞; 许桂苹; 洪欣; 陈丽君; 梁晓曦

    2015-01-01

    分别采用BCR法和Maiz法两种连续提取法,对蔗田土壤样品中重金属元素Cu、Zn、Pb、Cd和Ni进行了形态分析。结果表明:Cu、Zn、Pb、Cd和Ni均主要以残渣态的形式赋存,具有较低的潜在生物有效性;Pb主要以可还原态或螯合态的形式存在,具有一定的潜在生物有效性;BCR法得到的重金属回收率高于Maiz法的,但是Maiz法测得的有效态Cu、Zn、Pb、Cd和Ni的量均高于BCR法测得的弱酸提取态的量。%The occurrence characteristics of heavy metals Cu, Zn, Pb, Cd and Ni in the soil samples of sugarcane fields in Guangxi were analyzed by using BCR and Maiz sequential extraction procedures respectively.The results showed that Cu, Zn, Pb, Cd and Ni existed mainly in residual fraction, and they had a lower potential bioavailability.Pb existed mainly in reducible fraction or chelated fraction, and it possessed a certain potential bioavailability.In addition, BCR method acquired higher recovery rate of heavy metal than Maiz method, but the quantity of effective-state Cu, Zn, Pb, Cd and Ni measured by Maiz method was all higher than that of weak-acid-extractable-state Cu, Zn, Pb, Cd and Ni measured by BCR method.

  16. MPT0B169, a New Antitubulin Agent, Inhibits Bcr-Abl Expression and Induces Mitochondrion-Mediated Apoptosis in Nonresistant and Imatinib-Resistant Chronic Myeloid Leukemia Cells.

    Science.gov (United States)

    Wong, Shuit-Mun; Liu, Fu-Hwa; Lee, Yueh-Lun; Huang, Huei-Mei

    2016-01-01

    Chronic myeloid leukemia (CML) is a clonal disorder of hematopoietic stem/progenitor cells that is caused by the Bcr-Abl oncoprotein. Clinical resistance to the Bcr-Abl inhibitor imatinib is a critical problem in treating CML. This study investigated the antitumor effect and mechanism of MPT0B169, a new antitubulin agent, in K562 CML cells and their derived imatinib-resistant cells, IMR2 and IMR3. IMR2 and IMR3 cells showed complete resistance to imatinib-induced growth inhibition and apoptosis. Resistance involved ERK1/2 overactivation and MDR1 overexpression. MPT0B169 inhibited the growth of K562, IMR2, and IMR3 cells in a dose- and time-dependent manner. MPT0B169 substantially inhibited the mRNA and protein levels of Bcr-Abl, followed by its downstream pathways including Akt, ERK1/2, and STAT3 in these cells. MPT0B169 treatment resulted in a decrease in the polymer form of tubulin according to Western blot analysis. It triggered cell cycle arrest at the G2/M phase before apoptosis, which was related to the upregulation of the mitotic marker MPM2 and the cyclin B1 level, and a change in the phosphorylation of Cdk1. MPT0B169 induced apoptosis in nonresistant and imatinib-resistant cells via a mitochondrion-mediated caspase pathway. Further study showed that the agent led to a decrease in the antiapoptotic proteins Bcl-2, Bcl-xL, and Mcl-1 and an increase in the apoptotic protein Bax. Taken together, our results suggest that MPT0B169 might be a promising agent for overcoming imatinib resistance in CML cells. PMID:26815740

  17. MPT0B169, a New Antitubulin Agent, Inhibits Bcr-Abl Expression and Induces Mitochondrion-Mediated Apoptosis in Nonresistant and Imatinib-Resistant Chronic Myeloid Leukemia Cells.

    Directory of Open Access Journals (Sweden)

    Shuit-Mun Wong

    Full Text Available Chronic myeloid leukemia (CML is a clonal disorder of hematopoietic stem/progenitor cells that is caused by the Bcr-Abl oncoprotein. Clinical resistance to the Bcr-Abl inhibitor imatinib is a critical problem in treating CML. This study investigated the antitumor effect and mechanism of MPT0B169, a new antitubulin agent, in K562 CML cells and their derived imatinib-resistant cells, IMR2 and IMR3. IMR2 and IMR3 cells showed complete resistance to imatinib-induced growth inhibition and apoptosis. Resistance involved ERK1/2 overactivation and MDR1 overexpression. MPT0B169 inhibited the growth of K562, IMR2, and IMR3 cells in a dose- and time-dependent manner. MPT0B169 substantially inhibited the mRNA and protein levels of Bcr-Abl, followed by its downstream pathways including Akt, ERK1/2, and STAT3 in these cells. MPT0B169 treatment resulted in a decrease in the polymer form of tubulin according to Western blot analysis. It triggered cell cycle arrest at the G2/M phase before apoptosis, which was related to the upregulation of the mitotic marker MPM2 and the cyclin B1 level, and a change in the phosphorylation of Cdk1. MPT0B169 induced apoptosis in nonresistant and imatinib-resistant cells via a mitochondrion-mediated caspase pathway. Further study showed that the agent led to a decrease in the antiapoptotic proteins Bcl-2, Bcl-xL, and Mcl-1 and an increase in the apoptotic protein Bax. Taken together, our results suggest that MPT0B169 might be a promising agent for overcoming imatinib resistance in CML cells.

  18. Providing Compassion through Flow

    Directory of Open Access Journals (Sweden)

    Lydia Royeen

    2015-07-01

    Full Text Available Meg Kral, MS, OTR/L, CLT, is the cover artist for the Summer 2015 issue of The Open Journal of Occupational Therapy. Her untitled piece of art is an oil painting and is a re-creation of a photograph taken while on vacation. Meg is currently supervisor of outpatient services at Rush University Medical Center. She is lymphedema certified and has a specific interest in breast cancer lymphedema. Art and occupational therapy serve similar purposes for Meg: both provide a sense of flow. She values the outcomes, whether it is a piece of art or improved functional status

  19. Pharmacophore Modeling of Nilotinib as an Inhibitor of ATP-Binding Cassette Drug Transporters and BCR-ABL Kinase Using a Three-Dimensional Quantitative Structure–Activity Relationship Approach

    OpenAIRE

    Shukla, Suneet; Kouanda, Abdul; Silverton, Latoya; Talele, Tanaji T.; Suresh V Ambudkar

    2014-01-01

    Nilotinib (Tasigna) is a tyrosine kinase inhibitor approved by the FDA to treat chronic phase chronic myeloid leukemia patients. It is also a transport substrate of the ATP-binding cassette (ABC) drug efflux transporters ABCB1 (P-glycoprotein, P-gp) and ABCG2 (BCRP), which may have an effect on the pharmacokinetics and toxicity of this drug. The goal of this study was to identify pharmacophoric features of nilotinib in order to potentially develop specific inhibitors of BCR-ABL kinase with mi...

  20. BCR/ABL-negative primitive progenitors suitable for transplantation can be selected from the marrow of most early-chronic phase but not accelerated-phase chronic myelogenous leukemia patients

    OpenAIRE

    Verfaillie, Catherine; R Bhatia; Miller, W.; F. Mortari; Van Roy, V.; Burger, S.; Mccullough, J; Stieglbauer, K; Dewald, G; Heimfeld, S; Miller, J. S.; McGlave, P B

    1996-01-01

    We have previously reported that selection of marrow cells on the basis of the CD34+HLA-DR- phenotype (34+DR-) may result in the recovery of Philadelphia chromosome (Ph)- and BCR/ABL-negative long-term culture-initiating cells (LTC-IC) in selected patients with chronic myelogenous leukemia (CML). We now present data on 27 early chronic-phase ([ECP] studied within 1 year after diagnosis) and 23 advanced-phase ([AP] late chronic phase, ie, studied >1 year from diagnosis, or accelerated phase) C...

  1. Stat5 Exerts Distinct, Vital Functions in the Cytoplasm and Nucleus of Bcr-Abl{sup +} K562 and Jak2(V617F){sup +} HEL Leukemia Cells

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Axel [Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main 60596 (Germany); Borghouts, Corina [Ganymed Pharmaceuticals AG, Mainz 55131 (Germany); Brendel, Christian [Boston Children’s Hospital, Division of Hematology/Oncology, Boston, MA 02115 (United States); Moriggl, Richard [Ludwig Boltzmann Institute for Cancer Research (LBI-CR), Vienna 1090 (Austria); Delis, Natalia; Brill, Boris; Vafaizadeh, Vida; Groner, Bernd, E-mail: Groner@em.uni-frankfurt.de [Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main 60596 (Germany)

    2015-03-19

    Signal transducers and activators of transcription (Stats) play central roles in the conversion of extracellular signals, e.g., cytokines, hormones and growth factors, into tissue and cell type specific gene expression patterns. In normal cells, their signaling potential is strictly limited in extent and duration. The persistent activation of Stat3 or Stat5 is found in many human tumor cells and contributes to their growth and survival. Stat5 activation plays a pivotal role in nearly all hematological malignancies and occurs downstream of oncogenic kinases, e.g., Bcr-Abl in chronic myeloid leukemias (CML) and Jak2(V617F) in other myeloproliferative diseases (MPD). We defined the mechanisms through which Stat5 affects growth and survival of K562 cells, representative of Bcr-Abl positive CML, and HEL cells, representative for Jak2(V617F) positive acute erythroid leukemia. In our experiments we suppressed the protein expression levels of Stat5a and Stat5b through shRNA mediated downregulation and demonstrated the dependence of cell survival on the presence of Stat5. Alternatively, we interfered with the functional capacities of the Stat5 protein through the interaction with a Stat5 specific peptide ligand. This ligand is a Stat5 specific peptide aptamer construct which comprises a 12mer peptide integrated into a modified thioredoxin scaffold, S5-DBD-PA. The peptide sequence specifically recognizes the DNA binding domain (DBD) of Stat5. Complex formation of S5-DBD-PA with Stat5 causes a strong reduction of P-Stat5 in the nuclear fraction of Bcr-Abl-transformed K562 cells and a suppression of Stat5 target genes. Distinct Stat5 mediated survival mechanisms were detected in K562 and Jak2(V617F)-transformed HEL cells. Stat5 is activated in the nuclear and cytosolic compartments of K562 cells and the S5-DBD-PA inhibitor most likely affects the viability of Bcr-Abl{sup +} K562 cells through the inhibition of canonical Stat5 induced target gene transcription. In HEL cells

  2. B cell TLR1/2, TLR4, TLR7 and TLR9 interact in induction of class switch DNA recombination: modulation by BCR and CD40, and relevance to T-independent antibody responses

    OpenAIRE

    Pone, Egest J; Lou, Zheng; Lam, Tonika; Greenberg, Milton L.; Wang, Rui; Xu, Zhenming; Casali, Paolo

    2015-01-01

    Ig class switch DNA recombination (CSR) in B cells is crucial to the maturation of antibody responses. It requires IgH germline IH-CH transcription and expression of AID, both of which are induced by engagement of CD40 or dual engagement of a Toll-like receptor (TLR) and B cell receptor (BCR). Here, we have addressed cross-regulation between two different TLRs or between a TLR and CD40 in CSR induction by using a B cell stimulation system involving lipopolysaccharides (LPS). LPS mediated long...

  3. The Provident Sea

    Science.gov (United States)

    Cushing, David H.

    1988-09-01

    The Provident Sea describes the history of fish stock management (including whales and seals). The book traces, on the basis of the original scientific material, the history of the management of "the provident sea" up to recent times when problems of over-exploitation have had dramatic effects upon stocks. The need for management arose mainly from the increasing industrialization of capture. Hence the preindustrial fisheries are covered, in particular the old cod fishery on the Grand Bank and the herring fishery in the North Sea, as an essential background to current problems. The origins of fisheries and whaling science are described, as is the development up to 1965 of the science and institution in fisheries, whaling, and sealing. In the sixties and seventies, certain major fishing nations took a heavy harvest of fish stocks using sophisticated and efficient gathering methods. This in turn led to conflict and one consequence was the "Law of the Sea" conference set up to try and resolve these issues.

  4. Polymorphism Analysis of 5′ Promotor Region of BCR Gene%BCR基因5′启动子区多态性分析

    Institute of Scientific and Technical Information of China (English)

    田红; 郑维扬; 付永贵; 林蒋海; 吕凤娟; 周淑芸

    2004-01-01

    背景与目的:bcr-abl融合基因被认为是慢性髓系白血病(chronic myelogenous leukemia,CML)的分子标志,该融合基因的表达受 bcr基因启动子的调控.本实验目的是研究 bcr基因启动子区的多态性,并探讨其与 CML之间可能存在的联系.方法:采用 PCR方法扩增 bcr基因 5′启动子区 1.13 kb的序列范围,通过测序获得了 30例 CML和 19例对照的启动子区序列.应用软件和在线工具对启动子序列进行转录因子结合位点分析和重复序列分析.结果:在所研究片段范围内共发现 4处新的单核苷酸多态性(single nucleotide polymorphism,SNP)和 3处与参考序列不一致的碱基变异.其中 2处 SNPs和 1处碱基插入位于转录因子结合位点中或邻近几个碱基内.各多态性基因频率在 CML和对照人群中无统计学差异.结论:bcr基因的 5′启动子区存在一定的序列多态性,主要为 SNPs,未能证实其与 CML之间存在相关性,但部分 SNPs的定位使其有可能对基因的转录和表达产生影响.

  5. What HERA May Provide?

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Hannes; /DESY; De Roeck, Albert; /CERN; Bartels, Jochen; /Hamburg U., Inst. Theor. Phys. II; Behnke, Olaf; Blumlein, Johannes; /DESY; Brodsky, Stanley; /SLAC /Durham U., IPPP; Cooper-Sarkar, Amanda; /Oxford U.; Deak, Michal; /DESY; Devenish, Robin; /Oxford U.; Diehl, Markus; /DESY; Gehrmann, Thomas; /Zurich U.; Grindhammer, Guenter; /Munich, Max Planck Inst.; Gustafson, Gosta; /CERN /Lund U., Dept. Theor. Phys.; Khoze, Valery; /Durham U., IPPP; Knutsson, Albert; /DESY; Klein, Max; /Liverpool U.; Krauss, Frank; /Durham U., IPPP; Kutak, Krzysztof; /DESY; Laenen, Eric; /NIKHEF, Amsterdam; Lonnblad, Leif; /Lund U., Dept. Theor. Phys.; Motyka, Leszek; /Hamburg U., Inst. Theor. Phys. II /Birmingham U. /Southern Methodist U. /DESY /Piemonte Orientale U., Novara /CERN /Paris, LPTHE /Hamburg U. /Penn State U.

    2011-11-10

    More than 100 people participated in a discussion session at the DIS08 workshop on the topic What HERA may provide. A summary of the discussion with a structured outlook and list of desirable measurements and theory calculations is given. The HERA accelerator and the HERA experiments H1, HERMES and ZEUS stopped running in the end of June 2007. This was after 15 years of very successful operation since the first collisions in 1992. A total luminosity of {approx} 500 pb{sup -1} has been accumulated by each of the collider experiments H1 and ZEUS. During the years the increasingly better understood and upgraded detectors and HERA accelerator have contributed significantly to this success. The physics program remains in full swing and plenty of new results were presented at DIS08 which are approaching the anticipated final precision, fulfilling and exceeding the physics plans and the previsions of the upgrade program. Most of the analyses presented at DIS08 were still based on the so called HERA I data sample, i.e. data taken until 2000, before the shutdown for the luminosity upgrade. This sample has an integrated luminosity of {approx} 100 pb{sup -1}, and the four times larger statistics sample from HERA II is still in the process of being analyzed.

  6. What HERA May Provide?

    International Nuclear Information System (INIS)

    More than 100 people participated in a discussion session at the DIS08 workshop on the topic What HERA may provide. A summary of the discussion with a structured outlook and list of desirable measurements and theory calculations is given. The HERA accelerator and the HERA experiments H1, HERMES and ZEUS stopped running in the end of June 2007. This was after 15 years of very successful operation since the first collisions in 1992. A total luminosity of ∼ 500 pb-1 has been accumulated by each of the collider experiments H1 and ZEUS. During the years the increasingly better understood and upgraded detectors and HERA accelerator have contributed significantly to this success. The physics program remains in full swing and plenty of new results were presented at DIS08 which are approaching the anticipated final precision, fulfilling and exceeding the physics plans and the previsions of the upgrade program. Most of the analyses presented at DIS08 were still based on the so called HERA I data sample, i.e. data taken until 2000, before the shutdown for the luminosity upgrade. This sample has an integrated luminosity of ∼ 100 pb-1, and the four times larger statistics sample from HERA II is still in the process of being analyzed.

  7. BCR-ABL1: Test

    Science.gov (United States)

    ... Complete Blood Count ; Bone Marrow Aspiration and Biopsy ; Blood Smear ; WBC Differential At a Glance Test Sample The ... are often evaluated as part of the initial diagnosis, but the majority of follow-up monitoring is performed on blood samples. There is significant test variability among laboratories ...

  8. Stepwise effects of the BCR sequential chemical extraction procedure on dissolution and metal release from common ferromagnesian clay minerals: A combined solution chemistry and X-ray powder diffraction study

    International Nuclear Information System (INIS)

    Sequential extraction procedures (SEPs) are commonly used to determine speciation of trace metals in soils and sediments. However, the non-selectivity of reagents for targeted phases has remained a lingering concern. Furthermore, potentially reactive phases such as phyllosilicate clay minerals often contain trace metals in structural sites, and their reactivity has not been quantified. Accordingly, the objective of this study is to analyze the behavior of trace metal-bearing clay minerals exposed to the revised BCR 3-step plus aqua regia SEP. Mineral quantification based on stoichiometric analysis and quantitative powder X-ray diffraction (XRD) documents progressive dissolution of chlorite (CCa-2 ripidolite) and two varieties of smectite (SapCa-2 saponite and SWa-1 nontronite) during steps 1-3 of the BCR procedure. In total, 8 (± 1) % of ripidolite, 19 (± 1) % of saponite, and 19 (± 3) % of nontronite (% mineral mass) dissolved during extractions assumed by many researchers to release trace metals from exchange sites, carbonates, hydroxides, sulfides and organic matter. For all three reference clays, release of Ni into solution is correlated with clay dissolution. Hydrolysis of relatively weak Mg-O bonds (362 kJ/mol) during all stages, reduction of Fe(III) during hydroxylamine hydrochloride extraction and oxidation of Fe(II) during hydrogen peroxide extraction are the main reasons for clay mineral dissolution. These findings underscore the need for precise mineral quantification when using SEPs to understand the origin/partitioning of trace metals with solid phases

  9. Frequency of the ETV6-RUNX1, BCR-ABL1, TCF3-PBX1, and MLL-AFF1 fusion genes in Guatemalan pediatric acute lymphoblastic leukemia patients and their ethnic associations.

    Science.gov (United States)

    Carranza, Claudia; Granados, Lilian; Morales, Oneida; Jo, Wendy; Villagran, Swuanny; Tinti, Damaris; Villegas, Mauricio; Antillón, Federico; Torselli, Silvana; Silva, Gabriel

    2013-06-01

    Fusion genes involved in acute lymphoblastic leukemia (ALL) occur mostly due to genetic and environmental factors, and only a limited number of studies have reported any ethnic influence. This study assesses whether an ethnic influence has an effect on the frequency of any of the four fusion genes: BCR-ABL1, ETV6-RUNX1, TCF3-PBX1, and MLL-AFF1 found in ALL. To study this ethnic influence, mononuclear cells were obtained from bone marrow samples from 143 patients with ALL. We performed RNA extraction and reverse transcription, then assessed the quality of the cDNA by amplifying the ABL1 control gene, and finally evaluated the presence of the four transcripts by multiplex polymerase chain reaction. We found 10 patients who had the BCR-ABL1 fusion gene (7%); 3 patients (2%) were TCF3-PBX1 positive; and 6 patients (4.5%) were ETV6-RUNX1 positive. The incidence of this last fusion gene is quite low when compared to the values reported in most countries. The low incidence of the ETV6-RUNX1 fusion gene found in Guatemala matches the incidence rates that have been reported in Spain and Indian Romani. Since it is known that an ethnic resemblance exists among these three populations, as shown by ancestral marker studies, the ALL data suggests an ethnic influence on the occurrence and frequency of this particular fusion gene.

  10. Stepwise effects of the BCR sequential chemical extraction procedure on dissolution and metal release from common ferromagnesian clay minerals: A combined solution chemistry and X-ray powder diffraction study

    Energy Technology Data Exchange (ETDEWEB)

    Ryan, P.C. [Geology Department, Middlebury College, Middlebury, Vermont 05753 (United States)], E-mail: pryan@middlebury.edu; Hillier, S. [Macaulay Institute, Aberdeen, AB15 8QH UK (United Kingdom); Wall, A.J. [Department of Geosciences, Penn State University, University Park, Pennsylvania, 16802 (United States)

    2008-12-15

    Sequential extraction procedures (SEPs) are commonly used to determine speciation of trace metals in soils and sediments. However, the non-selectivity of reagents for targeted phases has remained a lingering concern. Furthermore, potentially reactive phases such as phyllosilicate clay minerals often contain trace metals in structural sites, and their reactivity has not been quantified. Accordingly, the objective of this study is to analyze the behavior of trace metal-bearing clay minerals exposed to the revised BCR 3-step plus aqua regia SEP. Mineral quantification based on stoichiometric analysis and quantitative powder X-ray diffraction (XRD) documents progressive dissolution of chlorite (CCa-2 ripidolite) and two varieties of smectite (SapCa-2 saponite and SWa-1 nontronite) during steps 1-3 of the BCR procedure. In total, 8 ({+-} 1) % of ripidolite, 19 ({+-} 1) % of saponite, and 19 ({+-} 3) % of nontronite (% mineral mass) dissolved during extractions assumed by many researchers to release trace metals from exchange sites, carbonates, hydroxides, sulfides and organic matter. For all three reference clays, release of Ni into solution is correlated with clay dissolution. Hydrolysis of relatively weak Mg-O bonds (362 kJ/mol) during all stages, reduction of Fe(III) during hydroxylamine hydrochloride extraction and oxidation of Fe(II) during hydrogen peroxide extraction are the main reasons for clay mineral dissolution. These findings underscore the need for precise mineral quantification when using SEPs to understand the origin/partitioning of trace metals with solid phases.

  11. RT-PCR ANALYSIS OF E2A-PBX1, TEL-AML1, BCR-ABL AND MLL-AF4 FUSION GENE TRANSCRIPTS IN B-LINEAGE ACUTE LYMPHOBLASTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Iuliu-Cristian Ivanov

    2013-11-01

    Full Text Available Acute lymphoblastic leukemia represents a heterogeneous group of hematological malignancies, defined by clonal proliferation of lymphoid cells. Immunophenotyping by flow cytometry and molecular analysis for the detection of genetic anomalies are clinical standard procedures for diagnosis, sub-classification and post-therapeutic evaluation. Samples from 105 patients diagnosed with acute lymphoblastic leukemia were immunophenotyped at diagnosis and were investigated by molecular analysis in order to identify the occurrence of four fusion genes: MLL-AF4, TEL-AML-1, BCR-ABL-p190, E2A-PBX-1. There were no associations found between the immunophenotype and the presence of any fusion genes evaluated. Both methods in combination remain a prerequisite for an improved subclassification of hematological malignancies, therapeutic decision, and evaluation of treatment response.

  12. Modeling the presentation of C3d-coated antigen by B lymphocytes: enhancement by CR1/2-BCR co-ligation is selective for the co-ligating antigen.

    Science.gov (United States)

    Prechl, József; Baiu, Dana C; Horváth, Attila; Erdei, Anna

    2002-03-01

    We have used a set of single-chain variable fragment antibodies (sc) genetically fused with an influenza hemagglutinin-derived peptide as a means to investigate the role of CR1 and CR2 in antigen presentation by B cells. When incubated with the B cell lymphoma 2PK3, peptide-containing sc specific for either CR1 or CR1/2 mediated activation of the hemagglutinin peptide-specific T cell line IP-12-7, as assessed by IL-2 production. Efficient presentation was dependent on the binding of the constructs to CR1/2, implying that receptor-mediated endocytosis is responsible for the effect. Cross-linkage of CR1/2 or CD19 by mAb did not increase the extent of T cell activation. However, when CR1/2 was co-ligated with the BCR--using either polyclonal goat anti-mouse IgG or recombinant protein LA--the antigen concentration required to activate T cells decreased by two orders of magnitude. Moreover, this enhancement was selective for the antigen included in these complexes and did not affect the presentation of a free peptide or of antigen bound to CR1/2 excluded from the complexes. These results suggest that B cells may bind various C3d-coated antigens at a time, but only the one which reacts with the BCR will be processed with high efficiency. This mechanism may ensure the specificity of cognate T cell help. PMID:11867560

  13. Internet Provider Facilities, Published in Not Provided, US Army.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Internet Provider Facilities dataset as of Not Provided. Data by this publisher are often provided in Not Applicable coordinate system; in a Not Applicable...

  14. Monitoring of bcr/abl Fusion Gene by Interphase-Dual-Color and Dual-Fusion Fluorescence in situ Hybridization in CML after Allo-HSCT%间期双色双融合荧光原位杂交监测慢性髓系白血病异基因造血干细胞移植后bcr/abl融合基因

    Institute of Scientific and Technical Information of China (English)

    钱思轩; 李建勇; 张闰; 洪鸣; 仇海荣; 李丽; 徐卫; 盛瑞兰; 吴汉新

    2006-01-01

    本研究探讨bcr/abl双色双融合荧光原位杂交(DD-FISH)的敏感性及临床应用价值.对19例慢性髓细胞白血病(CML)异基因造血干细胞移植(allo-HSCT)后微小残留病灶(MRD)用DD-FISH进行监测,同时与常规细胞遗传学(CC)、逆转录-聚合酶链反应(RT-PCR)结果相比较.样本取自骨髓,少数来源于骨髓片或外周血.结果表明:14例CML患者在Allo-HSCT后CC显示持续正常供者核型,RT-PCR转为阴性,移植2月后均为完全供者嵌合(DC),DD-FISH检测结果持续为阴性,平均随访11.25月,MRD无增加.1例CC及RT-PCR阴性,而性染色体FISH为混合嵌合,DD-FISH阳性,监测无MRD增加,临床未治疗,疾病稳定.3例骨髓复发患者的DD-FISH及性染色体FISH均提示MRD明显增加,RT-PCR转为阳性,却只有1例CC异常,供者淋巴细胞输注(DLI)及甲磺酸伊马替尼治疗后均为DC,DD-FISH阴性,RT-PCR阴性.1例骨活检证实髓外复发患者骨髓或外周血样本的DD-FISH、CC及PCR均阴性,供受者完全嵌合.结论:间期双色双融合FISH可应用于CML异基因造血干细胞移植后MRD的监测,其操作简易快速,灵敏度高,且骨髓或外周血均可采用.动态监测能及时发现扩大的白血病细胞克隆.

  15. BCR-ABL融合基因T315I突变的白血病行异基因HSCT的疗效及复发后的治疗分析%Curative effectiveness of allogeneic stem cell transplantation and treatment of recurrence in patients harboring T315I BCR-ABL mutated leukemias

    Institute of Scientific and Technical Information of China (English)

    桂晓敏; 仇惠英; 潘金兰; 周敏; 鲍协炳; 陈苏宁; 孙爱宁; 吴德沛; 岑建农

    2014-01-01

    Objective To retrospectively analyze the curative effectiveness of allogeneic stem cell transplantation (allo-SCT) for the leukemia patients with the T315I mutation,and to discuss the treatments for the relapsing patients after allo-SCT.Method Through observing 10 leukemia patients harboring a T315I BCR-ABL mutation who underwent allo-SCT,we analyzed the remission rate,recurrence rate and long-term survival situation of these patients and explored the treatments for relapsing patients after allo-SCT.Result Of 10 patients,4 patients were female and 6 were male.The median age was 29 years (range,18-49).Before HSCT,5 were given imatinib,3 nilotinib and 2 dasatinib,respectively.Ten patients (100%) obtained complete remission (CR) and the median remission time was 23 days (range,14-56).During the follow-up period,1 case of CML and 3 cases of Ph+-ALL (40%) obtained CR.The survival time was 75 to 741 days.In the 6 dead patients,1 died of upper gastrointestinal hemorrhage on the day 137 after allo-SCT; 2 died of graft versus host disease on the day 53 and 617 respectively after allo-SCT; 1 case of CML and 2 cases of Ph+ ALL relapsed on the day 27,50 and 130 respectively after allo-SCT,and 2 of them died on the day 5 and 40 respectively after relapse,and 1 recurrent case did not obtain remission after chemotherapy and died on the day 97 after relapse.Conclusion The allo-SCT can be used to treat the leukemia patients with T315I mutation,and high remission rate can be obtained,tut there is the high risk of recurrence.The patients with recurrent leukemia can take further relevant treatment to prolong survival time.%目的 分析BCR-ABL融合基因T315I突变的白血病患者接受异基因造血干细胞移植(HSCT)的资料,探讨移植疗效及复发后的治疗.方法 观察10例伴T315I突变的费城染色体阳性(Ph+)的急性淋巴细胞白血病(ALL)和慢性粒细胞白血病(CML)接受异基因HSCT后缓解率、复发率以及长期存活情况,分析这

  16. Querying Data Providing Web Services

    OpenAIRE

    Sabesan, Manivasakan

    2010-01-01

    Web services are often used for search computing where data is retrieved from servers providing information of different kinds. Such data providing web services return a set of objects for a given set of parameters without any side effects. There is need to enable general and scalable search capabilities of data from data providing web services, which is the topic of this Thesis. The Web Service MEDiator (WSMED) system automatically provides relational views of any data providing web service ...

  17. Choosing Your Prenatal Care Provider

    Science.gov (United States)

    ... care provider is. These kinds of providers can take care of you during pregnancy and deliver your baby: ... doctor who has special education and training to take care of pregnant women and deliver babies. About 8 ...

  18. Babesiosis for Health Care Providers

    Centers for Disease Control (CDC) Podcasts

    2012-04-25

    This podcast will educate health care providers on diagnosing babesiosis and providing patients at risk with tick bite prevention messages.  Created: 4/25/2012 by Center for Global Health, Division of Parasitic Diseases and Malaria.   Date Released: 4/25/2012.

  19. Interferon-α Revisited: Individualized Treatment Management Eased the Selective Pressure of Tyrosine Kinase Inhibitors on BCR-ABL1 Mutations Resulting in a Molecular Response in High-Risk CML Patients.

    Science.gov (United States)

    Polivkova, Vaclava; Rohon, Peter; Klamova, Hana; Cerna, Olga; Divoka, Martina; Curik, Nikola; Zach, Jan; Novak, Martin; Marinov, Iuri; Soverini, Simona; Faber, Edgar; Machova Polakova, Katerina

    2016-01-01

    Bone marrow transplantation or ponatinib treatment are currently recommended strategies for management of patients with chronic myeloid leukemia (CML) harboring the T315I mutation and compound or polyclonal mutations. However, in some individual cases, these treatment scenarios cannot be applied. We used an alternative treatment strategy with interferon-α (IFN-α) given solo, sequentially or together with TKI in a group of 6 cases of high risk CML patients, assuming that the TKI-independent mechanism of action may lead to mutant clone repression. IFN-α based individualized therapy decreases of T315I or compound mutations to undetectable levels as assessed by next-generation deep sequencing, which was associated with a molecular response in 4/6 patients. Based on the observed results from immune profiling, we assumed that the principal mechanism leading to the success of the treatment was the immune activation induced with dasatinib pre-treatment followed by restoration of immunological surveillance after application of IFN-α therapy. Moreover, we showed that sensitive measurement of mutated BCR-ABL1 transcript levels augments the safety of this individualized treatment strategy. PMID:27214026

  20. Interferon-α Revisited: Individualized Treatment Management Eased the Selective Pressure of Tyrosine Kinase Inhibitors on BCR-ABL1 Mutations Resulting in a Molecular Response in High-Risk CML Patients.

    Directory of Open Access Journals (Sweden)

    Vaclava Polivkova

    Full Text Available Bone marrow transplantation or ponatinib treatment are currently recommended strategies for management of patients with chronic myeloid leukemia (CML harboring the T315I mutation and compound or polyclonal mutations. However, in some individual cases, these treatment scenarios cannot be applied. We used an alternative treatment strategy with interferon-α (IFN-α given solo, sequentially or together with TKI in a group of 6 cases of high risk CML patients, assuming that the TKI-independent mechanism of action may lead to mutant clone repression. IFN-α based individualized therapy decreases of T315I or compound mutations to undetectable levels as assessed by next-generation deep sequencing, which was associated with a molecular response in 4/6 patients. Based on the observed results from immune profiling, we assumed that the principal mechanism leading to the success of the treatment was the immune activation induced with dasatinib pre-treatment followed by restoration of immunological surveillance after application of IFN-α therapy. Moreover, we showed that sensitive measurement of mutated BCR-ABL1 transcript levels augments the safety of this individualized treatment strategy.

  1. First Case of Biphenotypic/bilineal (B/myeloid, B/monocytic) Mixed Phenotype Acute Leukemia with t(9;22)(q34;q11.2);BCR-ABL1.

    Science.gov (United States)

    Kim, Hyeong Nyeon; Hur, Mina; Kim, Hanah; Ji, Misuk; Moon, Hee-Won; Yun, Yeo-Min; Lee, Mark Hong

    2016-07-01

    Mixed phenotype acute leukemia (MPAL) includes biphenotypic leukemia, bilineal leukemia, or its combination by the 2008 WHO classification. A few cases of combined biphenotypic/bilineal MPAL have been reported so far; they all had biphenotypic expressions in only one of the two distinct leukemic populations. A 43-year-old female presented with leukocytosis and bicytopenia. Her complete blood counts were: hemoglobin, 6.9 g/dL; white blood cells, 62.8×10(9)/L; and platelets, 83×10(9)/L. Neither lymphadenopathy nor organomegaly was observed. Blasts and promonocytes/monoblasts were increased in her peripheral blood (42%) and bone marrow (60.1%). Flow cytometric analysis revealed two distinct populations of leukemic cells, which expressed CD11c, CD19, and cytoplasmic CD79a in common. Additionally, the first population expressed CD10 and CD117 (B/myeloid), and the second one expressed CD14 and CD20 (B/monocytic). She had a karyotype of 46,XX,inv(9)(p12q13),t(9;22)(q34;q11.2)[20] and BCR/ABL1 rearrangement. To the best of our knowledge, this is the first reported case of biphenotypic/bilineal MPAL with B/myeloid and B/monocytic expressions.

  2. Switching to second-generation tyrosine kinase inhibitor improves the response and outcome of frontline imatinib-treated patients with chronic myeloid leukemia with more than 10% of BCR-ABL/ABL ratio at 3 months

    Science.gov (United States)

    Casado, Luis-Felipe; García-Gutiérrez, José-Valentín; Massagué, Isabel; Giraldo, Pilar; Pérez-Encinas, Manuel; de Paz, Raquel; Martínez-López, Joaquín; Bautista, Guiomar; Osorio, Santiago; Requena, María-José; Palomera, Luis; Peñarrubia, María-Jesús; Calle, Carmen; Hernández-Rivas, José-Ángel; Burgaleta, Carmen; Maestro, Begoña; García-Ormeña, Nuria; Steegmann, Juan-Luis

    2015-01-01

    Chronic myeloid leukemia patients display heterogeneous responses to imatinib. Survival depends on baseline clinical characteristics (including prognostic scoring systems) and on early response (such as >10% BCR-ABL/ABL ratio at 3 months of therapy). The results of switching to second-generation tyrosine kinase inhibitors (2GTKIs) may contain a bias since, in the majority of these studies, patients who switch treatment due to intolerance or failure are censored or excluded. We analyzed the Spanish Registry data on switching in an intention-to-treat analysis of patients in standard clinical practice. Switching to 2GTKIs improves responses from 45% to 75% of complete cytogenetic response (CCyR) and from 15% to 45% of major molecular response (MMR) in the group without molecular response 1 (MR1) at 3 months and from 70% to 87% in CCyR and from 52% to 87% in MMR in the group with MR1. The final response rate is poorer in the group with no MR1 at 3 months. Nevertheless, the differences in the rates of response were not translated into differences in major events (transformations or deaths), and the final progression-free survival and overall survival were similar. PMID:25756742

  3. TERRAIN, PROVIDENCE COUNTY, RHODE ISLAND

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — The Providence AOI consists of the costal portion of the county, and meshes up seamlessly with the Kent county AOI directly south. Ground Control is collected...

  4. Types of health care providers

    Science.gov (United States)

    Physicians; Nurses; Health care providers; Doctors; Pharmacists ... with a Doctor of Medicine (MD) or a Doctor of Osteopathic Medicine (DO). NURSING CARE Registered nurses (RNs) have graduated from a nursing program, have ...

  5. Medicare Referring Provider DMEPOS PUF

    Data.gov (United States)

    U.S. Department of Health & Human Services — This dataset, which is part of CMSs Medicare Provider Utilization and Payment Data, details information on Durable Medical Equipment, Prosthetics, Orthotics and...

  6. Ecosystem services provided by waterbirds.

    Science.gov (United States)

    Green, Andy J; Elmberg, Johan

    2014-02-01

    Ecosystem services are ecosystem processes that directly or indirectly benefit human well-being. There has been much recent literature identifying different services and the communities and species that provide them. This is a vital first step towards management and maintenance of these services. In this review, we specifically address the waterbirds, which play key functional roles in many aquatic ecosystems, including as predators, herbivores and vectors of seeds, invertebrates and nutrients, although these roles have often been overlooked. Waterbirds can maintain the diversity of other organisms, control pests, be effective bioindicators of ecological conditions, and act as sentinels of potential disease outbreaks. They also provide important provisioning (meat, feathers, eggs, etc.) and cultural services to both indigenous and westernized societies. We identify key gaps in the understanding of ecosystem services provided by waterbirds and areas for future research required to clarify their functional role in ecosystems and the services they provide. We consider how the economic value of these services could be calculated, giving some examples. Such valuation will provide powerful arguments for waterbird conservation. PMID:23786594

  7. Ecosystem services provided by waterbirds.

    Science.gov (United States)

    Green, Andy J; Elmberg, Johan

    2014-02-01

    Ecosystem services are ecosystem processes that directly or indirectly benefit human well-being. There has been much recent literature identifying different services and the communities and species that provide them. This is a vital first step towards management and maintenance of these services. In this review, we specifically address the waterbirds, which play key functional roles in many aquatic ecosystems, including as predators, herbivores and vectors of seeds, invertebrates and nutrients, although these roles have often been overlooked. Waterbirds can maintain the diversity of other organisms, control pests, be effective bioindicators of ecological conditions, and act as sentinels of potential disease outbreaks. They also provide important provisioning (meat, feathers, eggs, etc.) and cultural services to both indigenous and westernized societies. We identify key gaps in the understanding of ecosystem services provided by waterbirds and areas for future research required to clarify their functional role in ecosystems and the services they provide. We consider how the economic value of these services could be calculated, giving some examples. Such valuation will provide powerful arguments for waterbird conservation.

  8. Enstore with Chimera namespace provider

    International Nuclear Information System (INIS)

    Enstore is a mass storage system developed by Fermilab that provides distributed access and management of data stored on tapes. It uses a namespace service, PNFS, developed by DESY to provide a filesystem-like view of the stored data. PNFS is a legacy product and is being replaced by a new implementation, called Chimera, which is also developed by DESY. Chimera offers multiple advantages over PNFS in terms of performance and functionality. The Enstore client component, encp, has been modified to work with Chimera, as well as with any other namespace provider. We performed high load end-to-end acceptance test of Enstore with the Chimera namespace. This paper describes the modifications to Enstore, the test procedure and the results of the acceptance testing.

  9. Knudsen Gas Provides Nanobubble Stability

    NARCIS (Netherlands)

    Seddon, James R.T.; Zandvliet, Harold J.W.; Lohse, Detlef

    2011-01-01

    We provide a model for the remarkable stability of surface nanobubbles to bulk dissolution. The key to the solution is that the gas in a nanobubble is of Knudsen type. This leads to the generation of a bulk liquid flow which effectively forces the diffusive gas to remain local. Our model predicts th

  10. Twitter for travel medicine providers.

    Science.gov (United States)

    Mills, Deborah J; Kohl, Sarah E

    2016-03-01

    Travel medicine practitioners, perhaps more so than medical practitioners working in other areas of medicine, require a constant flow of information to stay up-to-date, and provide best practice information and care to their patients. Many travel medicine providers are unaware of the popularity and potential of the Twitter platform. Twitter use among our travellers, as well as by physicians and health providers, is growing exponentially. There is a rapidly expanding body of published literature on this information tool. This review provides a brief overview of the ways Twitter is being used by health practitioners, the advantages that are peculiar to Twitter as a platform of social media, and how the interested practitioner can get started. Some key points about the dark side of Twitter are highlighted, as well as the potential benefits of using Twitter as a way to disseminate accurate medical information to the public. This article will help readers develop an increased understanding of Twitter as a tool for extracting useful facts and insights from the ever increasing volume of health information. PMID:26988200

  11. Providing Southern Perspectives on CSR

    OpenAIRE

    Jeppesen, Søren; Kothuis, Bas

    2014-01-01

    The article seeks to contribute to the SMEs and CSR literature in developing countries by providing; a) a ‘Southern’ SME perspective, which includes the voices of managers and workers, b) a perspective of CSR, which opens up to informal CSR practices that SMEs undertake, and c) an analysis of the key institutional issues affecting the CSR practices of SMEs. It presents perceptions of CSR practices among 21 SMEs in the garment industry in South Africa, based on 40 interviews with managers and ...

  12. Providing cleaner air to Canadians

    International Nuclear Information System (INIS)

    This booklet is designed to explain salient aspects of the Ozone Annex, negotiated and signed recently by Canada and the United States, in a joint effort to improve air quality in North America. By significantly reducing the transboundary flows of air pollutants that cause smog, the Ozone Annex will benefit some 16 million people in central and eastern Canada and provide an example for a future round of negotiations to address concerns of the millions of Canadians and Americans who live in the border area between British Columbia and Washington State. The brochure provide summaries of the Canadian and American commitments, focusing on transportation, monitoring and reporting. The Ozone Annex complements other air quality initiatives by the Government of Canada enacted under the Environmental Protection Act, 1999. These measures include regulations to reduce sulphur content to 30 parts per million by Jan 1, 2005; proposing to restrict toxic particulate matter (PM) to less than 10 microns; establishing daily smog forecasts in the Maritimes and committing to a national program built upon existing smog advisories and forecasts in Quebec, Ontario and British Columbia; and investing in more clean air research through the newly created Canadian Foundation for Climate and Atmospheric Sciences

  13. Providing Southern Perspectives on CSR

    DEFF Research Database (Denmark)

    Jeppesen, Søren; Kothuis, Bas

    The article seeks to contribute to the SMEs and CSR literature in developing countries by providing; a) a ‘Southern’ SME perspective, which includes the voices of managers and workers, b) a perspective of CSR, which opens up to informal CSR practices that SMEs undertake, and c) an analysis of the...... are found to be important factors in explaining the CSR perceptions and level of practices. It is suggested that future research investigate the role of informal practices further and explore the role of institutional theory.......The article seeks to contribute to the SMEs and CSR literature in developing countries by providing; a) a ‘Southern’ SME perspective, which includes the voices of managers and workers, b) a perspective of CSR, which opens up to informal CSR practices that SMEs undertake, and c) an analysis...... of the key institutional issues affecting the CSR practices of SMEs. It presents perceptions of CSR practices among 21 SMEs in the garment industry in South Africa, based on 40 interviews with managers and 19 interviews with workers through the use of qualitative and quantitative interview frameworks...

  14. Expression of p89c-Mybex9b, an alternatively spliced form of c-Myb, is required for proliferation and survival of p210BCR/ABL-expressing cells

    International Nuclear Information System (INIS)

    The c-Myb gene encodes the p75c-Myb isoform and less-abundant proteins generated by alternatively spliced transcripts. Among these, the best known is pc-Mybex9b, which contains 121 additional amino acids between exon 9 and 10, in a domain involved in protein–protein interactions and negative regulation. In hematopoietic cells, expression of pc-Mybex9b accounts for 10–15% of total c-Myb; these levels may be biologically relevant because modest changes in c-Myb expression affects proliferation and survival of leukemic cells and lineage choice and frequency of normal hematopoietic progenitors. In this study, we assessed biochemical activities of pc-Mybex9b and the consequences of perturbing its expression in K562 and primary chronic myeloid leukemia (CML) progenitor cells. Compared with p75c-Myb, pc-Mybex9b is more stable and more effective in transactivating Myb-regulated promoters. Ectopic expression of pc-Mybex9b enhanced proliferation and colony formation and reduced imatinib (IM) sensitivity of K562 cells; conversely, specific downregulation of pc-Mybex9b reduced proliferation and colony formation, enhanced IM sensitivity of K562 cells and markedly suppressed colony formation of CML CD34+ cells, without affecting the levels of p75c-Myb. Together, these studies indicate that expression of the low-abundance pc-Mybex9b isoform has an important role for the overall biological effects of c-Myb in BCR/ABL-transformed cells

  15. Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intolerance to imatinib

    Science.gov (United States)

    Shah, Neil P.; Kim, Dong-Wook; Kantarjian, Hagop; Rousselot, Philippe; Llacer, Pedro Enrique Dorlhiac; Enrico, Alicia; Vela-Ojeda, Jorge; Silver, Richard T.; Khoury, Hanna Jean; Müller, Martin C.; Lambert, Alexandre; Matloub, Yousif; Hochhaus, Andreas

    2010-01-01

    Background Dasatinib 100 mg once daily achieves intermittent BCR-ABL kinase inhibition and is approved for chronic-phase chronic myeloid leukemia patients resistant or intolerant to imatinib. To better assess durability of response to and tolerability of dasatinib, data from a 2-year minimum follow-up for a dose-optimization study in chronic-phase chronic myeloid leukemia are reported here. Design and Methods In a phase 3 study, 670 chronic-phase chronic myeloid leukemia patients with resistance, intolerance, or suboptimal response to imatinib were randomized to dasatinib 100 mg once-daily, 50 mg twice-daily, 140 mg once-daily, or 70 mg twice-daily. Results Data from a 2-year minimum follow-up demonstrate that dasatinib 100 mg once daily achieves major cytogenetic response and complete cytogenetic response rates comparable to those in the other treatment arms, and reduces the frequency of key side effects. Comparable 2-year progression-free survival and overall survival rates were observed (80% and 91%, respectively, for 100 mg once daily, and 75%–76% and 88%–94%, respectively, in other arms). Complete cytogenetic responses were achieved rapidly, typically by 6 months. In patients treated with dasatinib 100 mg once daily for 6 months without complete cytogenetic response, the likelihood of achieving such a response by 2 years was 50% for patients who had achieved a partial cytogenetic response, and only 8% or less for patients with minor, minimal, or no cytogenetic response. Less than 3% of patients suffered disease transformation to accelerated or blast phase. Conclusions Intermittent kinase inhibition can achieve rapid and durable responses, indistinguishable from those achieved with more continuous inhibition. PMID:20139391

  16. Wind Turbine Providing Grid Support

    DEFF Research Database (Denmark)

    2011-01-01

    A variable speed wind turbine is arranged to provide additional electrical power to counteract non-periodic disturbances in an electrical grid. A controller monitors events indicating a need to increase the electrical output power from the wind turbine to the electrical grid. The controller...... is arranged to control the wind turbine as follows: after an indicating event has been detected, the wind turbine enters an overproduction period in which the electrical output power is increased, wherein the additional electrical output power is taken from kinetic energy stored in the rotor and without...... changing the operation of the wind turbine to a more efficient working point.; When the rotational speed of the rotor reaches a minimum value, the wind turbine enters a recovery period to re-accelerate the rotor to the nominal rotational speed while further contributing to the stability of the electrical...

  17. Biospecimen Solicitation - Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    A funding opportunity in support of the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) seeks to prospectively procure tumor samples, collected for proteomics investigation.

  18. Providing global WLCG transfer monitoring

    International Nuclear Information System (INIS)

    The WLCG[1] Transfers Dashboard is a monitoring system which aims to provide a global view of WLCG data transfers and to reduce redundancy in monitoring tasks performed by the LHC experiments. The system is designed to work transparently across LHC experiments and across the various technologies used for data transfer. Currently each LHC experiment monitors data transfers via experiment-specific systems but the overall cross-experiment picture is missing. Even for data transfers handled by FTS, which is used by 3 LHC experiments, monitoring tasks such as aggregation of FTS transfer statistics or estimation of transfer latencies are performed by every experiment separately. These tasks could be performed once, centrally, and then served to all experiments via a well-defined set of APIs. In the design and development of the new system, experience accumulated by the LHC experiments in the data management monitoring area is taken into account and a considerable part of the code of the ATLAS DDM Dashboard is being re-used. The paper describes the architecture of the Global Transfer monitoring system, the implementation of its components and the first prototype.

  19. Identifiable Data Files - Medicare Provider Analysis and ...

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Medicare Provider Analysis and Review (MEDPAR) File contains data from claims for services provided to beneficiaries admitted to Medicare certified inpatient...

  20. Dairies, Published in Not Provided, US Army.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Dairies dataset as of Not Provided. Data by this publisher are often provided in Not Applicable coordinate system; in a Not Applicable projection; The extent...

  1. Discussing Diabetes with Your Healthcare Provider

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Diabetes Discussing Diabetes with Your Healthcare Provider Past Issues / Fall 2009 Table of Contents Diabetes Medicines—Always Discuss Them with Your Healthcare Provider ...

  2. Internet Provider Facilities, Published in 2006, Farmer.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Internet Provider Facilities dataset, was produced all or in part from Field Survey/GPS information as of 2006. Data by this publisher are often provided in...

  3. Institutional Provider and Beneficiary Summary PUF

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CMS IPBS PUFs are aggregated files in which each record summarizes information for a particular institutional provider. An institutional provider refers to a...

  4. Insure Kids Now (IKN) (Dental Care Providers)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Insure Kids Now (IKN) Dental Care Providers in Your State locator tool is provided, in accordance with the Children's Health Insurance Program Reauthorization...

  5. An analysis of healthcare providers' online ratings

    OpenAIRE

    Erik Black; Lindsay Thompson; Heidi Saliba; Kara Dawson; Nicole Paradise Black

    2009-01-01

    Background Many websites allow consumers to evaluate their healthcare experience yet scant data exist that explore the type and content of reviews. Objective To evaluate and describe online healthcare provider reviews. Methods We analysed 16 703 ratings on 6101 providers from four US cities. Ratings spanned five categories and an overall provider score. We also performed text analyses of narrative commentary (n = 15 952). Results Providers had a high mean score for each category (3.7...

  6. 5 CFR 890.910 - Provider information.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Provider information. 890.910 Section 890.910 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS..., and FEHB Benefit Payments § 890.910 Provider information. The hospital provider information used...

  7. Competition of Wireless Providers for Atomic Users

    CERN Document Server

    Gajić, Vojislav; Rimoldi, Bixio

    2010-01-01

    We study a problem where wireless service providers compete for heterogenous wireless users. The users differ in their utility functions as well as in the perceived quality of service of individual providers. We model the interaction of an arbitrary number of providers and users as a two-stage multi-leader-follower game. We prove existence and uniqueness of the subgame perfect Nash equilibrium for a generic channel model and a wide class of users' utility functions. We show that the competition of resource providers leads to a globally optimal outcome under mild technical conditions. Most users will purchase the resource from only one provider at the unique subgame perfect equilibrium. The number of users who connect to multiple providers at the equilibrium is always smaller than the number of providers. We also present a decentralized algorithm that globally converges to the unique system equilibrium with only local information under mild conditions on the update rates.

  8. Data Service Provider Cost Estimation Tool

    Science.gov (United States)

    Fontaine, Kathy; Hunolt, Greg; Booth, Arthur L.; Banks, Mel

    2011-01-01

    The Data Service Provider Cost Estimation Tool (CET) and Comparables Database (CDB) package provides to NASA s Earth Science Enterprise (ESE) the ability to estimate the full range of year-by-year lifecycle cost estimates for the implementation and operation of data service providers required by ESE to support its science and applications programs. The CET can make estimates dealing with staffing costs, supplies, facility costs, network services, hardware and maintenance, commercial off-the-shelf (COTS) software licenses, software development and sustaining engineering, and the changes in costs that result from changes in workload. Data Service Providers may be stand-alone or embedded in flight projects, field campaigns, research or applications projects, or other activities. The CET and CDB package employs a cost-estimation-by-analogy approach. It is based on a new, general data service provider reference model that provides a framework for construction of a database by describing existing data service providers that are analogs (or comparables) to planned, new ESE data service providers. The CET implements the staff effort and cost estimation algorithms that access the CDB and generates the lifecycle cost estimate for a new data services provider. This data creates a common basis for an ESE proposal evaluator for considering projected data service provider costs.

  9. Home Care Providers to the Rescue

    DEFF Research Database (Denmark)

    Hansen, Steen M; Brøndum, Stig; Thomas, Grethe;

    2015-01-01

    AIM: To describe the implementation of a novel first-responder programme in which home care providers equipped with automated external defibrillators (AEDs) were dispatched in parallel with existing emergency medical services in the event of a suspected out-of-hospital cardiac arrest (OHCA......). METHODS: We evaluated a one-year prospective study that trained home care providers in performing cardiopulmonary resuscitation (CPR) and using an AED in cases of suspected OHCA. Data were collected from cardiac arrest case files, case files from each provider dispatch and a survey among dispatched...... providers. The study was conducted in a rural district in Denmark. RESULTS: Home care providers were dispatched to 28 of the 60 OHCAs that occurred in the study period. In ten cases the providers arrived before the ambulance service and subsequently performed CPR. AED analysis was executed in three cases...

  10. 78 FR 71476 - Health Insurance Providers Fee

    Science.gov (United States)

    2013-11-29

    ... provides health insurance under Medicare Advantage, Medicare Part D, or Medicaid; or (5) a non-fully... under subchapter L, an entity providing health insurance under Medicare Advantage, Medicare Part D, or... net premiums written. Medicare Advantage and Medicare Part D Plans Some employers or unions...

  11. Organizational culture associated with provider satisfaction

    Science.gov (United States)

    Scammon, Debra L.; Tabler, Jennifer; Brunisholz, Kimberly; Gren, Lisa H.; Kim, Jaewhan; Tomoaia-Cotisel, Andrada; Day, Julie; Farrell, Timothy W.; Waitzman, Norman J.; Magill, Michael K.

    2014-01-01

    Objectives Assess 1) provider satisfaction with specific elements of PCMH; 2) clinic organizational cultures; 3) associations between provider satisfaction and clinic culture. Methods Cross sectional study with surveys conducted in 2011 with providers and staff in 10 primary care clinics implementing their version of a PCMH: Care by Design™. Measures included the Organizational Culture Assessment Instrument (OCAI) and the American Medical Group Association provider satisfaction survey. Results Providers were most satisfied with quality of care (M=4.14; scale=1–5) and interactions with patients (M=4.12) and least satisfied with time spent working (M=3.47), paper work (M =3.45) and compensation (M=3.35). Culture profiles differed across clinics with family/clan and hierarchical the most common. Significant correlations (p ≤ 0.05) between provider satisfaction and clinic culture archetypes included: family/clan negatively correlated with administrative work; entrepreneurial positively correlated with the Time Spent Working dimension; market/rational positively correlated with how practices were facing economic and strategic challenges; and hierarchical negatively correlated with Relationships with Staff and Resource dimensions. Discussion Provider satisfaction is an important metric for assessing experiences with features of a PCMH model. Conclusions Identification of clinic-specific culture archetypes and archetype associations with provider satisfaction can help inform practice redesign. Attention to effective methods for changing organizational culture is recommended. PMID:24610184

  12. Providing Career Counseling to Lesbian Women.

    Science.gov (United States)

    McVannel, Martha Erwin

    The literature on career counseling and lesbian women was reviewed resulting in the identification of 10 maxims regarding providing career counseling to lesbian women. The maxims are as follows: (1) sexual orientation is essential information when providing career counseling; (2) it is important that the workplace be lesbian-affirming; (3) lesbian…

  13. 75 FR 6839 - Technical Service Provider Assistance

    Science.gov (United States)

    2010-02-12

    ... provider (TSP) provisions under the Food Security Act of 1985. The Food, Conservation, and Energy Act of.... Specifically, under section 1244 of the Food Security Act of 1985, each of the NRCS conservation programs makes... Conservation Service 7 CFR Part 652 RIN 0578-AA48 Technical Service Provider Assistance AGENCY:...

  14. Identifying Mentors' Observations for Providing Feedback

    Science.gov (United States)

    Hudson, Peter

    2016-01-01

    Mentors' feedback can assist preservice teachers' development; yet feedback tends to be variable from one mentor to the next. What do mentors observe for providing feedback? In this study, 24 mentors observed a final-year preservice teacher through a professionally video-recorded lesson and provided written notes for feedback. They observed the…

  15. Concussion management by primary care providers

    Science.gov (United States)

    Pleacher, M D; Dexter, W W

    2006-01-01

    Objective To assess current concussion management practices of primary care providers. Methods An 11 item questionnaire was mailed to primary care providers in the state of Maine, with serial mailings to non‐respondents. Results Over 50% of the questionnaires were completed, with nearly 70% of primary care providers indicating that they routinely use published guidelines as a tool in managing patients with concussion. Nearly two thirds of providers were aware that neuropsychological tests could be used, but only 16% had access to such tests within a week of injury. Conclusions Primary care providers are using published concussion management guidelines with high frequency, but many are unable to access neuropsychological testing when it is required. PMID:16371479

  16. Compassion fatigue in pediatric palliative care providers.

    Science.gov (United States)

    Rourke, Mary T

    2007-10-01

    The experience of compassion fatigue is an expected and common response to the professional task of routinely caring for children at the end of life. Symptoms of compassion fatigue often mimic trauma reactions. Implementing strategies that span personal, professional, and organizational domains can help protect health care providers from the damaging effects of compassion fatigue. Providing pediatric palliative care within a constructive and supportive team can help caregivers deal with the relational challenges of compassion fatigue. Finally, any consideration of the toll of providing pediatric palliative care must be balanced with a consideration of the parallel experience of compassion satisfaction. PMID:17933615

  17. Medicare Provider Analysis and Review (MEDPAR)

    Data.gov (United States)

    U.S. Department of Health & Human Services — MEDPAR files contain information on Medicare beneficiaries using hospital inpatient services. The data is provided by the state and the Diagnosis Related Groups...

  18. Medicare Referring Provider DMEPOS PUF CY2013

    Data.gov (United States)

    U.S. Department of Health & Human Services — This dataset, which is part of CMSs Medicare Provider Utilization and Payment Data, details information on Durable Medical Equipment, Prosthetics, Orthotics and...

  19. Provider Customer Service Program - Performance Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — CMS is continuously analyzing performance and quality of the Provider Customer Service Programs (PCSPs) of the contractors and will be identifying trends and making...

  20. Medicare Provider Utilization and Payment Data - Inpatient

    Data.gov (United States)

    U.S. Department of Health & Human Services — The data provided here include hospital-specific charges for the more than 3,000 U.S. hospitals that receive Medicare Inpatient Prospective Payment System (IPPS)...

  1. Topological Trends of Internet Content Providers

    CERN Document Server

    Shavitt, Yuval

    2012-01-01

    The Internet is constantly changing, and its hierarchy was recently shown to become flatter. Recent studies of inter-domain traffic showed that large content providers drive this change by bypassing tier-1 networks and reaching closer to their users, enabling them to save transit costs and reduce reliance of transit networks as new services are being deployed, and traffic shaping is becoming increasingly popular. In this paper we take a first look at the evolving connectivity of large content provider networks, from a topological point of view of the autonomous systems (AS) graph. We perform a 5-year longitudinal study of the topological trends of large content providers, by analyzing several large content providers and comparing these trends to those observed for large tier-1 networks. We study trends in the connectivity of the networks, neighbor diversity and geographical spread, their hierarchy, the adoption of IXPs as a convenient method for peering, and their centrality. Our observations indicate that co...

  2. Medicare Referring Provider (DMEPOS) Data CY2013

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Centers for Medicare and Medicaid Services (CMS) released a new dataset, the Referring Provider Durable Medical Equipment, Prosthetics, Orthotics and Supplies...

  3. Medicare Provider Utilization and Payment Data - Outpatient

    Data.gov (United States)

    U.S. Department of Health & Human Services — The data provided here include estimated hospital-specific charges for 30 Ambulatory Payment Classification (APC) Groups paid under the Medicare Outpatient...

  4. National Provider Identifier Standard - Data Dissemination

    Data.gov (United States)

    U.S. Department of Health & Human Services — The National Plan and Provider Enumeration System, NPPES, downloadable file, also referred to as the NPI Downloadable File, contains FOIA disclosable NPPES health...

  5. Concrete "Waffle" Provides Laser Beam Accuracy

    Science.gov (United States)

    Building Design and Construction, 1978

    1978-01-01

    A massive concrete "waffle," riding on a bed of specially treated gravel and sand inside another building, provides the structural rigidity needed by the University of Rochester's Laboratory for Laser Energetics. (Author)

  6. Extensive IT outsourcing: advice from providers.

    Science.gov (United States)

    Smith, Mike; Whiting, Stacilee

    2007-01-01

    In summary, providers are reporting some benefits related to resources and knowledge, improved service levels/performance and stronger IT staff/leadership. Also, on average, providers are reporting satisfactory experiences with application support and CIO outsourcing. However, not all of their expectations are being met, and some providers have discontinued outsourcing due to unmet expectations. Clearly, outsourcing is an option one must research in depth--it is not for everyone. When one evaluates the results of extensive IT outsourcing, it becomes easier to see what outsourcing mix and firm may be a good match for your organization's needs and expected outcomes. As you decide upon the outsourcing mix and firm that is right for you, providers advise you to pay special attention to contractual arrangements. With adequate research and contractual provisions, organizations can find the outsourcing mix that is right for them.

  7. Capitated contracting of integrated health provider organizations.

    Science.gov (United States)

    Bazzoli, G J; Dynan, L; Burns, L R

    This paper examines global capitation of integrated health provider organizations that link physicians and hospitals, such as physician-hospital organizations and management service organizations. These organizations have proliferated in recent years, but their contracting activity has not been studied. We develop a conceptual model to understand the capitated contracting bargaining process. Exploratory multivariate analysis suggests that global capitation of these organizations is more common in markets with high health maintenance organization (HMO) market share, greater numbers of HMOs, and fewer physician group practices. Additionally, health provider organizations with more complex case mix, nonprofit status, more affiliated physicians, health system affiliations, and diversity in physician organizational arrangements are more likely to have global capitation. Finally, state regulation of provider contracting with self-insured employers appears to have spillover effects on health plan risk contracting with health providers. PMID:10711318

  8. Providing Service Using A Virtualization Infrastructure

    OpenAIRE

    Young R. Park; Srinarayan Sharma

    2011-01-01

    Services could be designed to be simple, atomic, and transparent to potential consumers who interact with providers to attain desired outcome. Providing the desired service, though, may involve a series of complex operations such as accessing multiples databases owned by multiple parties residing in multiple locations, complex queries to obtain desired outcome, transforming these queries for proper display, displaying the outcome in a format comprehensible to the consumer, et cetera. The deve...

  9. Providing driving rain data for hygrothermal calculations

    DEFF Research Database (Denmark)

    Kragh, Mikkel Kristian

    1996-01-01

    Due to a wish for driving rain data as input for hygrothermal calculations, this report deals with utilizing commonly applied empirical relations and standard meteorological data, in an attempt to provide realistic estimates rather than exact correlations.......Due to a wish for driving rain data as input for hygrothermal calculations, this report deals with utilizing commonly applied empirical relations and standard meteorological data, in an attempt to provide realistic estimates rather than exact correlations....

  10. Competition in bank-provided payment services

    OpenAIRE

    Bolt, Wilko; Humphrey, David

    2013-01-01

    Banks supply payment services that underpin the smooth operation of the economy. To ensure an efficient payment system, it is important to maintain competition among payment service providers but data available to gauge the degree of competition are quite limited. We propose and implement a frontierbased method to assess relative competition in bank-provided payment services. Billion dollar banks account for around ninety percent of assets in the US and those with around to billion in assets ...

  11. Quality Business Service Provider in Community Enterprise

    OpenAIRE

    Chalard Chantarasombat; Tantawan Singkeaw

    2012-01-01

    Problem statement: The development of community enterprises focuses on the development of service providers for commercial industries and community enterprises and it is necessary to create and extend the development according to the changing global conditions. The department of industrial promotion and industry promotion center region 5, Khon Kaen must create and develop the quality of service providers in community enterprises as an exclusive course to find a model and development guideline...

  12. Net neutrality at internet backbone provider level

    OpenAIRE

    Baglioni, Laura; Calabrese, Armando; Ghiron, Nathan Levialdi

    2013-01-01

    This paper analysis the Internet interconnection market and combine the main technical (i.e. service quality) and economic aspects (i.e. profits and utility) characterizing relations between market players (end users, EUs; Internet Service Providers, ISPs; Internet Backbone Providers, IBPs) in order to determine possible economic outcomes in the strategic interaction between them. The proposed model enables a comparison to be made between expected values of social welfare (i.e. EU utility and...

  13. Obstetric Provider Maldistribution: Georgia, USA, 2011.

    Science.gov (United States)

    Spelke, Bridget; Zertuche, Adrienne D; Rochat, Roger

    2016-07-01

    Objectives In 2010, Georgia had the nation's highest maternal mortality rate, sixteenth highest infant mortality rate, and a waning obstetrician/gynecologist (ob/gyn) workforce. Statewide ob/gyn workforce data, however, masked obstetric-specific care shortages and regional variation in obstetric services. The Georgia Maternal and Infant Health Research Group thereby assessed each Georgia region's obstetric provider workforce to identify service-deficient areas. Methods We identified 63 birthing facilities in the 82 Primary Care Service Areas (PCSAs) outside metropolitan Atlanta and interviewed nurse managers and others to assess the age, sex, and expected departure year of each delivering professional. Using accepted annual delivery rates of 155 per obstetrician (OB), 100 per certified nurse midwife (CNM), and 70 per family medicine physician (FP) we converted obstetric providers into "OB equivalents" to standardize obstetric services available in any given area. Using facility births and computed OB equivalents (contemporary and 2020 estimates), we calculated current and projected average annual births per provider (AABP) for each PCSA, categorizing its obstetric provider workforce as "adequate" (AABP  166). We mapped results using ArcGIS. Results Of 82 surveyed PCSAs, 52 % (43) were deficient in obstetric care; 16 % (13) had a shortage and 37 % (30) lacked obstetric providers entirely. There were no delivering FPs in 89 % (73) of PCSAs and no CNMs in 70 % (56). If Georgia fails to recruit delivering providers, 72 % (58/77) of PCSAs will have deficient or no obstetric care by 2020. Conclusions Obstetric provider shortages in Georgia hinder access to prenatal and delivery services. Care-deficient areas will expand if recruitment and retention of delivering professionals does not improve.

  14. Quality Business Service Provider in Community Enterprise

    Directory of Open Access Journals (Sweden)

    Chalard Chantarasombat

    2012-01-01

    Full Text Available Problem statement: The development of community enterprises focuses on the development of service providers for commercial industries and community enterprises and it is necessary to create and extend the development according to the changing global conditions. The department of industrial promotion and industry promotion center region 5, Khon Kaen must create and develop the quality of service providers in community enterprises as an exclusive course to find a model and development guideline in effective operations that is efficient and appropriate according to the particular community. Approach: The objectives of this research were: (1 to recruit and select at least 15 individuals to participate in the training of service providers in community enterprise in Kalasin province. (2 To define the structure, content, create a curriculum and development of service providers in community enterprise. (3 To develop the participants basic skills training, create motivation, learning experience through on the job training and business management and capability in the diagnosing the cause of problems. (4 To develop the participants understanding of community product standards and provide advice and consultation on the preparation and application of manufacturing standard certification of community products, community enterprise management and provide advice in the implementation of management standards of community enterprises. (5 Satisfaction of the participants training in service providers in community enterprise. Results: 29 people applied for the training program and 26 passed evaluation which was higher than the target of 15 individuals. The theoretical training courses prior to the training had an overall average of 5.06 and after the training had an average of 15.80, the average progress was 10.74. The exercise training through on the job training was regarded as a vocational skill and hand an average of 5.27 before the training. After the

  15. Logistic service providers and sustainable physical distribution

    Directory of Open Access Journals (Sweden)

    Stef Weijers

    2012-06-01

    Full Text Available Background: Logistic Service Providers main concern was to ensure reliability for a low price (Christopher, 2005. Dutch Logistic Service Providers still have these two aspects at the top of their list, but also have to take in a new aspect: sustainability. 88% Of the investigated Logistic Service Providers have included sustainability in the company's goals. These Logistic Service Providers have developed different strategies to achieve a higher level of sustainability. This paper presents the results of a study into what Logistic Service Providers say what they are doing, or intend to do, to improve sustainability for their transport services. In this way insight is given in the attitude of Dutch Logistic Service Providers towards sustainability and how they intend to translate this into business practise: internal solutions or new methods incorporating external partners. Methods: Various methods of the investigations were used, among which the analysis of the statements about the sustainabilityon the websites of various companies as well as the questionnaire per Internet. The research covered 50 largest logistics companies operating in the Netherlands and 60 companies that competed for the award "Lean and Green" advertised in the Netherlands. In addition, the Internet survey was answered by 41 companies that belong to the network of our university. Results: The investigation has shown that sustainability is handled by the logistics company as an integral part of the corporate strategy. In contrast, shippers depend in the choice of logistics services primarily on such classical aspects as the reliability or the price and the sustainability play a minor role. Conclusions: Trying to find methods to improve the sustainability, Dutch logistics service providers, in the first place, look for solutions that increase the efficiency and therefore the cost reduction potential. Solutions, which require the involvement of clients, were less often

  16. Social Attention and the Provider's Dilemma

    CERN Document Server

    Aperjis, Christina

    2010-01-01

    While attracting attention is one of the prime goals of content providers, the conversion of that attention into revenue is by no means obvious. Given that most users expect to consume web content for free, a provider with an established audience faces a dilemma. Since the introduction of advertisements or subscription fees will be construed by users as an inconvenience which may lead them to stop using the site, what should the provider do in order to maximize revenues? We address this question through the lens of adaptation theory, which states that even though a change affects a person's utility initially, as time goes on people tend to adapt and become less aware of past changes. We establish that if the likelihood of continuing to attend to the provider after an increase in inconvenience is log-concave in the magnitude of the increase, then the provider faces a tradeoff between achieving a higher revenue per user sooner and maximizing the number of users in the long term. On the other hand, if the likeli...

  17. Providing Service Using A Virtualization Infrastructure

    Directory of Open Access Journals (Sweden)

    Young R. Park

    2011-05-01

    Full Text Available Services could be designed to be simple, atomic, and transparent to potential consumers who interact with providers to attain desired outcome. Providing the desired service, though, may involve a series of complex operations such as accessing multiples databases owned by multiple parties residing in multiple locations, complex queries to obtain desired outcome, transforming these queries for proper display, displaying the outcome in a format comprehensible to the consumer, et cetera. The development of service-oriented architecture (SOA or service-oriented computing (SOC allows organizations to exploit the services that may or may not belong to them to provide customized services to potential customers. Virtualization, viewed as the separation of a service request from the underlying physical delivery of that service, allows such services to be provided in a flexible and cost-effective manner.  Virtualization is also seen as one of the green ITs which can help reduce infrastructure and maintenance cost especially for the organizations that may not be able to afford big capital investment upfront. In this paper we make a case for integrating SOA and virtualization technologies to provide desired services to the consumer in highly a flexible and cost effective manner.

  18. Liability of intermediary service providers in Romania

    Directory of Open Access Journals (Sweden)

    Mihaela GIURANIUC (TUDORACHE

    2011-12-01

    Full Text Available The purpose of this paper is to analyze the legislation, doctrinal opinions and relevant case law regarding the liability of intermediary service providers in Romania and to contribute to the current stage of knowledge in this matter. The objectives pursued by the author are: identification of the peculiarities of the transposition of the E-Commerce Directive into Romanian legislation; identification of problems that could arise from law’s interpretation; issuing of the de lege ferenda proposals. According to Romanian Law, the rule is the liability of the intermediary service provider. The liability limitations apply to certain clearly delimited activities carried out by service providers, precisely defined by art. 12-15 from Law no. 362/2002, as: mere conduit, caching, hosting, search engines and hyperlinks. Romanian Law does not offer the possibility to impose on service provider an obligation to monitor the information they transmit or store or an obligation to actively seek out facts and circumstances, even if it could be only for specific, clearly defined individual case. The notice and take down procedures for illegal content is not a legal obligation according to Romanian Law. The Romanian Law is mandatory only for service providers established in Romania.

  19. Providing Group Anonymity Using Wavelet Transform

    CERN Document Server

    Chertov, Oleg

    2010-01-01

    Providing public access to unprotected digital data can pose a threat of unwanted disclosing the restricted information. The problem of protecting such information can be divided into two main subclasses, namely, individual and group data anonymity. By group anonymity we define protecting important data patterns, distributions, and collective features which cannot be determined through analyzing individual records only. An effective and comparatively simple way of solving group anonymity problem is doubtlessly applying wavelet transform. It's easy-to-implement, powerful enough, and might produce acceptable results if used properly. In the paper, we present a novel method of using wavelet transform for providing group anonymity; it is gained through redistributing wavelet approximation values, along with simultaneous fixing data mean value and leaving wavelet details unchanged (or proportionally altering them). Moreover, we provide a comprehensive example to illustrate the method.

  20. International nurse education: implications for providers.

    Science.gov (United States)

    Cecchin, M

    1998-12-01

    This exploratory study conducted in 1996 described the profiles, roles and preparation of twelve South Australian registered nurses in relation to their provision of education programs for nurses from South East Asia. The research showed respondents were well qualified and highly experienced educators whose roles were complex. Their preparation for providing education programs for nurse from South East Asia had been haphazard and inadequate. Consequently respondents considered they were not fully prepared for the providing this specialised education. Career planning and a more strategic approach to the development of specific expertise are essential to support an international approach to nurse education. Nurse education that values intercultural awareness, and is multicultural and global would benefit both local and international students. Development of germane knowledge, skill, attitudes and behaviours is recommended to ensure excellence in the provision of international nurse education. An action research model is proposed as an alternative to traditional professional development to prepare providers of international education. PMID:10095500

  1. Patients Provide Recommendations for Improving Patient Satisfaction.

    Science.gov (United States)

    Moore, Angelo D; Hamilton, Jill B; Krusel, Jessica L; Moore, LeeAntoinette G; Pierre-Louis, Bosny J

    2016-04-01

    National Committee for Quality Assurance recommends patient-centered medical homes incorporate input from patient populations; however, many health care organizations do not. This qualitative study used two open-ended questions from 148 active duty Army Soldiers and their family members to illicit recommendations for primary care providers and clinic leadership that would improve their health care experiences. Content analysis and descriptive statistics were used to analyze responses. Participant responses were related to four major themes: Access to Care, Interpersonal Interaction, Satisfaction of Care, and Quality of Care. Participants were overall satisfied with their care; however, spending less time waiting for appointments and to see the provider or specialist were the most frequently requested improvements related to Access to Care. For Interpersonal Interaction, 82% of the responses recommended that providers be more attentive listeners, courteous, patient, caring, and respectful. Decreasing wait times and improving interpersonal skills would improve health care experiences and patient satisfaction. PMID:27046182

  2. Teaching antenatal counseling skills to neonatal providers.

    Science.gov (United States)

    Stokes, Theophil A; Watson, Katie L; Boss, Renee D

    2014-02-01

    Counseling a family confronted with the birth of a periviable neonate is one of the most difficult tasks that a neonatologist must perform. The neonatologist's goal is to facilitate an informed, collaborative decision about whether life-sustaining therapies are in the best interest of this baby. Neonatologists are trained to provide families with a detailed account of the morbidity and mortality data they believe are necessary to facilitate a truly informed decision. Yet these complicated and intensely emotional conversations require advanced communication and counseling skills that our current fellowship-training strategies are not adequately providing. We review educational models for training neonatology fellows to provide antenatal counseling at the threshold of viability. We believe that training aimed at teaching these skills should be incorporated into the neonatal-perinatal medicine fellowship. The optimal approaches for teaching these skills remain uncertain, and there is a need for continued innovation and outcomes-based research.

  3. Care for the Health Care Provider.

    Science.gov (United States)

    Kunin, Sharon Brown; Kanze, David Mitchell

    2016-03-01

    Pretravel care for the health care provider begins with an inventory, including the destination, length of stay, logistical arrangements, type of lodging, food and water supply, team members, personal medical needs, and the needs of the community to be treated. This inventory should be created and processed well in advance of the planned medical excursion. The key thing to remember in one's planning is to be a health care provider during one's global health care travel and not to become a patient oneself. This article will help demonstrate the medical requirements and recommendations for such planning. PMID:26900113

  4. Homeless women's experiences of service provider encounters.

    Science.gov (United States)

    Biederman, Donna J; Nichols, Tracy R

    2014-01-01

    Service providers are gatekeepers to health-sustaining services and resources, although little is known about service encounters from the perspective of homeless women. We conducted in-depth semistructured interviews with 15 homeless women to better understand their experiences of service encounters. Using a phenomenological method, 160 significant statements were extracted from participant transcripts; more positive than negative interactions were reported. The 10 themes that emerged fall along a dehumanizing/humanizing continuum primarily separated by the power participants experienced in the interaction and the trust they felt in the service provider. Implications for nursing practice and research are offered. PMID:24528122

  5. Outpatient provider concentration and commercial colonoscopy prices.

    Science.gov (United States)

    Pozen, Alexis

    2015-01-01

    The objective was to evaluate the magnitude of various contributors to outpatient commercial colonoscopy prices, including market- and provider-level factors, especially market share. We used adjudicated fee-for-service facility claims from a large commercial insurer for colonoscopies occurring in hospital outpatient department or ambulatory surgery center from October 2005 to December 2012. Claims were matched to provider- and market-level data. Linear fixed effects regressions of negotiated colonoscopy price were run on provider, system, and market characteristics. Markets were defined as counties. There were 178,433 claims from 169 providers (104 systems). The mean system market share was 76% (SD = 0.34) and the mean real (deflated) price was US$1363 (SD = 374), ranging from US$169 to US$2748. For every percentage point increase in a system or individual facility's bed share, relative price increased by 2 to 4 percentage points; this result was stable across a number of specifications. Market population and price were also consistently positively related, though this relation was small in magnitude. No other factor explained price as strongly as market share. Price variation for colonoscopy was driven primarily by market share, of particular concern as the number of mergers increases in wake of the recession and the Affordable Care Act. Whether variation is justified by better quality care requires further research to determine whether quality is subsumed in prices.

  6. Providing Access to Justice through Service Learning

    Science.gov (United States)

    Kubichek, Mary

    2010-01-01

    In the Casper College Legal Service (CCLS) program, Casper College paralegal students, under supervision of pro bono attorneys, use paralegal skills to provide legal services and work product. CCLS is different from other legal clinics; it is not law school based, bar based, or court based. CCLS is paralegal based.

  7. 42 CFR 410.134 - Provider qualifications.

    Science.gov (United States)

    2010-10-01

    ... Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Medical Nutrition Therapy § 410.134 Provider qualifications. For Medicare Part B coverage of MNT, only a registered dietitian or nutrition professional...

  8. Management services organizations: providing economies of scale.

    Science.gov (United States)

    Schaffer, C L

    1998-09-01

    Effective information management and other shared costs can reduce agencies' operating expenses as well as make new products available while providing opportunities to gain a competitive advantage. By taking a close look at ways of controlling documentation, such as the use of a management services organization for information system/computer-based management, agencies can prepare for the challenges of the next century.

  9. Providing Career Guidance for Young Women.

    Science.gov (United States)

    Colby, Pamela G.

    This module is directed at personnel working or planning to work in the areas of guidance, counseling, placement and follow-through in junior and senior high school settings, grades 7-12. The module topic is career guidance for young women of junior and senior high school age, aand the focus will be on providing nonbiased career guidance which…

  10. SYSTEM ORGANIZATION OF MATERIAL PROVIDING OF BUILDING

    Directory of Open Access Journals (Sweden)

    A. V. Rаdkеvich

    2014-04-01

    Full Text Available Purpose. Development of scientific-methodical bases to the design of rational management of material streams in the field of building providing taking into account intersystem connections with the enterprises of building industry. Methodology. The analysis of last few years of functioning of building industry in Ukraine allows distinguishing a number of problems that negatively influence the steady development of building, as the component of the state economics system. Therefore the research of existent organization methods of the system of building objects providing with material resources is extremely necessary. In connection with this the article justifies the use of method of hierarchies analysis (Saati method for finding the optimal task solution of fixing the enterprises of building industry after building objects. Findings. Results give an opportunity to guidance of building organization to estimate and choose advantageous suppliers - enterprises of building industry, to conduct their rating, estimation taking into account basic descriptions, such as: quality, price, reliability of deliveries, specialization, financial status etc. Originality. On the basis of Saati method the methodologies of organization are improved, planning and managements of the reliable system of providing of building necessary material resources that meet the technological requirements of implementation of building and installation works. Practical value. Contribution to the decisions of many intricate organizational problems that are accompanied by the problems of development of building, provided due to organization of the reliable system of purchase of material resources.

  11. Training To Provide for Healthy Rural Aging.

    Science.gov (United States)

    Troisi, Joseph

    2001-01-01

    Most of the world's rapidly expanding aging population is in rural areas of developing countries. Geriatric training programs should include social, economic, and psychological aspects of aging as well as medical, and should focus on enabling primary health caregivers to care for older people in their environments. Efforts to provide rural…

  12. Providing nursing care in a children's hospice.

    Science.gov (United States)

    Day, Alison

    Children who are admitted to hospices need specialist treatment that enables them to enjoy their childhood as much as possible while they receive the care they require. Their parents also have particular needs. During Children's Hospice Week, which started on September 21, the Association of Children's Hospices aims to raise awareness of the work done by children's hospices and the services they provide.

  13. Wholistic Health Care: Challenge to Health Providers.

    Science.gov (United States)

    McKay, Susan

    1980-01-01

    Due to the increasing influence of the holistic health movement, health providers will increasingly be challenged to reexamine their roles in patient relationships, increase the extent of interdisciplinary teamwork, emphasize health education and positive health behaviors, examine the usefulness of various alternative therapies, and consider the…

  14. Outpatient Provider Concentration and Commercial Colonoscopy Prices

    Directory of Open Access Journals (Sweden)

    Alexis Pozen PhD

    2015-04-01

    Full Text Available The objective was to evaluate the magnitude of various contributors to outpatient commercial colonoscopy prices, including market- and provider-level factors, especially market share. We used adjudicated fee-for-service facility claims from a large commercial insurer for colonoscopies occurring in hospital outpatient department or ambulatory surgery center from October 2005 to December 2012. Claims were matched to provider- and market-level data. Linear fixed effects regressions of negotiated colonoscopy price were run on provider, system, and market characteristics. Markets were defined as counties. There were 178 433 claims from 169 providers (104 systems. The mean system market share was 76% (SD = 0.34 and the mean real (deflated price was US$1363 (SD = 374, ranging from US$169 to US$2748. For every percentage point increase in a system or individual facility’s bed share, relative price increased by 2 to 4 percentage points; this result was stable across a number of specifications. Market population and price were also consistently positively related, though this relation was small in magnitude. No other factor explained price as strongly as market share. Price variation for colonoscopy was driven primarily by market share, of particular concern as the number of mergers increases in wake of the recession and the Affordable Care Act. Whether variation is justified by better quality care requires further research to determine whether quality is subsumed in prices.

  15. Messer to provide helium for LHC

    CERN Document Server

    2008-01-01

    Over the course of the next few years, industrial gas specialist The Messer Group, through its Swiss subsidiary Messer Schweiz AG, is to provide a 160,000kg supply of helium to the European Organisation for Nuclear Research (CERN) for the operation of the world's largest particle accelerator.

  16. Messer to provide helium for LHC project

    CERN Multimedia

    2008-01-01

    Over the course of the next few years, industrial gas specialist The Messer Group, through its Swiss subsidiary Messer Schweiz AG, is to provide a 160,000kg supply of helium to the European Organisation for Nuclear Research (CERN) for the operation of the world's largest particle accelerator.

  17. Estate Planning: Providing for Your Child's Future.

    Science.gov (United States)

    Beyer, Henry A.

    1986-01-01

    Parents who wish their handicapped offspring to be financially provided for after their own deaths need to explore several ways of managing and distributing their assets, including: creating a will; disinheritance (to avoid loss of benefits; joint property and life insurance; and trusts and trustees. (CB)

  18. The $500,000 deduction limitation for remuneration provided by certain health insurance providers. Final regulations.

    Science.gov (United States)

    2014-09-23

    This document contains final regulations on the application of the $500,000 deduction limitation for remuneration provided by certain health insurance providers under section 162(m)(6) of the Internal Revenue Code (Code). These regulations affect certain health insurance providers providing remuneration that exceeds the deduction limitation.

  19. Providing Scalable Data Services in Ubiquitous Networks

    CERN Document Server

    Malik, Tanu; Patil, Sanket; Chaudhary, Amitabh; Venkatasubramanian, Venkat

    2010-01-01

    Topology is a fundamental part of a network that governs connectivity between nodes, the amount of data flow and the efficiency of data flow between nodes. In traditional networks, due to physical limitations, topology remains static for the course of the network operation. Ubiquitous data networks (UDNs), alternatively, are more adaptive and can be configured for changes in their topology. This flexibility in controlling their topology makes them very appealing and an attractive medium for supporting "anywhere, any place" communication. However, it raises the problem of designing a dynamic topology. The dynamic topology design problem is of particular interest to application service providers who need to provide cost-effective data services on a ubiquitous network. In this paper we describe algorithms that decide when and how the topology should be reconfigured in response to a change in the data communication requirements of the network. In particular, we describe and compare a greedy algorithm, which is of...

  20. The EU as an international security provider

    DEFF Research Database (Denmark)

    Rodt, Annemarie Peen; Wolff, Stefan; Whitman, Richard

    2015-01-01

    that will emerge from this analysis will then be tested and applied empirically in the following contributions that focus on how particular policies are formulated and implemented, and that analyse, in single and comparative case studies, the impact and effectiveness of the EU as an international security provider.......This contribution develops a framework of analysis that covers the actors involved in the policy making process of international security provision, the dynamics of this process itself, its outcomes (concrete strategies and policies) and their impact. Our efforts to establish such a framework...... of analysis, which could serve as the foundation for a mid-range theory of the EU as an international security provider, will examine the relevance of, and apply, existing theories of international relations/international security and foreign policy analysis to the specific case of the EU. The framework...

  1. Challenges in conceptualizing and providing human security

    OpenAIRE

    Prezelj, Iztok

    2015-01-01

    Changes in the security environment after the end of Cold War have seriously affected our security concepts and paradigms. Human security was finally conceptualized and presented to the global public in a Human Development Report in 1994. The concept has evolved since then and, today, we can identify quite a number of seriously conceptualized definitions and theoretical approaches that have led to the formation of a number of practical attempts to provide it. This concept is theoretically rat...

  2. Service Providers Rush to Capital Markets

    Institute of Scientific and Technical Information of China (English)

    ISABELDING

    2004-01-01

    Chinese Service Providers (SPs) are finding it hard to resist the lure of the overseas capital market and many are rushing towards listing. On March 4, Shanghai-based Linktone Ltd,under the trading name LTON, became the first Chinese SP to list on the Nasdaq stock market. Through its IPO, the company offered a total of 6.14 million American Depositary Receipts and raised US$84.7 million.

  3. Management Standards Integration in Service Providing Organizations

    OpenAIRE

    Anton Persic; Mirko Markic

    2012-01-01

    The purpose of the paper is to define key leadership models, to recognize advantages and benefits, and define influence factors of business success on leadership systems integration in service providing organizations in Slovenia. We use quantitative research with frequent analysis complex questions to present and analyse some factors of leadership standards and build a new regression leadership model of organization. We have sent the questionnaire to 89 organizations, all with certificate sys...

  4. The Next Generation of ABA Providers.

    Science.gov (United States)

    Dixon, Mark R

    2014-10-01

    The imbalance of supply and demand for behavior analytic services will change in the near future. Behavior analysts, who want to survive in an increasing competitive marketplace, will need to show quality results and better results than the next behavior analyst. Trumpet Behavioral Health is a company designed to infuse scientific research with clinical practices. In the years ahead, look to companies like Trumpet as role models of the next generation of autism service providers. PMID:27471663

  5. Providing emergency supply of nuclear power plants

    OpenAIRE

    ROZMILER, Jiří

    2013-01-01

    Work "Providing emergency power nuclear power plant" describes how solving their own consumption nuclear power plant, as emergency power supply is designed and how it should be a solution of known states of emergency, having an immediate impact on the power consumption of their own nuclear power plants. The aim of this thesis is to propose options to strengthen its own emergency power consumption of nuclear power plants, one might say-more resistant to harsh extremes, which could lead to loss...

  6. Providing Real Research Opoportunities to Undergraduates

    Science.gov (United States)

    Ragozzine, Darin

    2016-01-01

    The current approach to undergraduate education focuses on teaching classes which provide the foundational knowledge for more applied experiences such as scientific research. Like most programs, Florida Institute of Technology (Florida Tech or FIT) strongly encourages undergraduate research, but is dominated by content-focused courses (e.g., "Physical Mechanics"). Research-like experiences are generally offered through "lab" classes, but these are almost always reproductions of past experiments: contrived, formulaic, and lacking the "heart" of real (i.e., potentially publishable) scientific research. Real research opportunities 1) provide students with realistic insight into the actual scientific process; 2) excite students far more than end-of-chapter problems; 3) provide context for the importance of learning math, physics, and astrophysics concepts; and 4) allow unique research progress for well-chosen problems. I have provided real research opportunities as an "Exoplanet Lab" component of my Introduction to Space Science (SPS1020) class at Florida Tech, generally taken by first-year majors in our Physics, Astronomy & Astrophysics, Planetary Science, and Astrobiology degree programs. These labs are a hybrid between citizen science (e.g., PlanetHunters) and simultaneously mentoring ~60 undergraduates in similar small research projects. These projects focus on problems that can be understood in the context of the course, but which benefit from "crowdsourcing". Examples include: dividing up the known planetary systems and developing a classification scheme and organizing them into populations (Fall 2013); searching through folded light curves to discover new exoplanets missed by previous pipelines (Fall 2014); and fitting n-body models to all exoplanets with known Transit Timing Variations to estimate planet masses (Fall 2015). The students love the fact that they are doing real potentially publishable research: not many undergraduates can claim to have discovered

  7. Providing research infrastructures with data publishing

    OpenAIRE

    Assante, Massimiliano; Candela, Leonardo; Manghi, Paolo; Pagano, Pasquale (ISTI-CNR); Castelli, Donatella

    2015-01-01

    The purpose of data publishing is to release research data for others to use. However, its implementation remains an open issue. 'Science 2.0 Repositories' (SciRepos) address the publishing requirements arising in Science 2.0 by blurring the distinction between research life-cycle and research publishing. SciRepos interface with the ICT services of research infrastructures to intercept and publish research products while providing researchers with social networking tools for discovery, notifi...

  8. Employer Provided Health Insurance and Retirement Behavior

    OpenAIRE

    1993-01-01

    This paper analyzes the effects on retirement of employer provided health benefits to workers and retirees. Retiree health benefits delay retirement until age of eligibility, and then accelerate it. With a base case of no retiree health coverage, granting retiree health coverage to all those with employer coverage while working accelerates retirement age by less than one month. Valuing benefits at costs of private health insurance to unaffiliated individuals, rather than at group rates, incre...

  9. ACCOUNTING TREATMENTS USED FOR ACCOUNTING SERVICES PROVIDERS

    OpenAIRE

    ŢOGOE GRETI DANIELA; AVRAM MARIOARA; AVRAM COSTIN DANIEL

    2014-01-01

    The theme of our research is the ways of keeping accounting entities that are the object of the provision of services in the accounting profession. This paper aims to achieve a parallel between the ways of organizing financial records - accounting provided by freelancers and companies with activity in the financial - accounting. The first step in our scientific research is to establish objectives chosen area of scientific knowledge. Our scientific approach seeks to explain thr...

  10. Logistics Service Providers in the Czech Republic

    OpenAIRE

    HRNEČKOVÁ, Kateřina

    2010-01-01

    The main purpose of the thesis is to analyze the developement of providing logistics services in the Czech Republic and analyze the current situation and expected trends in the near future. The thesis presents the implementation process of logistics outsourcing and follows up the influence of the outsourcing at the level of logistics costs. Manufacturing companies see in logistics the potential tool to improve the efficiency in their operations and they include the logistics in their strategi...

  11. Mobile application to provide personalized sightseeing tours

    OpenAIRE

    Anacleto, Ricardo; Figueiredo, Lino; Almeida, Ana; Novais, Paulo

    2014-01-01

    Tourist recommendation systems have been growing over the last few years, mainly because of the use of mobile devices to obtain user context. This work discusses some of the most relevant systems on the field and presents PSiS Mobile, which is a mobile recommendation and planning application designed to support a tourist during his vacations. It provides recommendations about points of interest to visit based on tourist preferences and on user and sight context. Also, it suggests a visit plan...

  12. Supercomputing Centers and Electricity Service Providers

    DEFF Research Database (Denmark)

    Patki, Tapasya; Bates, Natalie; Ghatikar, Girish;

    2016-01-01

    Supercomputing Centers (SCs) have high and variable power demands, which increase the challenges of the Electricity Service Providers (ESPs) with regards to efficient electricity distribution and reliable grid operation. High penetration of renewable energy generation further exacerbates...... (LRZ). We conclude that perspectives on demand management are dependent on the electricity market and pricing in the geographical region and on the degree of control that a particular SC has in terms of power-purchase negotiation....

  13. Airborne Internet Providing Tethered Balloon System

    Directory of Open Access Journals (Sweden)

    Suvriti Dhawan1

    2015-12-01

    Full Text Available In this paper we shall introduce a new system for providing wireless network communication over a specified area using ’lighter than air’ balloons. This technology will replace the existing fiber optic network system. This will be done by using a tethered balloon along with the payload (containing a receiver, a transmitter and a radio communication device.This payload will be suspended from the ground at an altitude (depending on the area of coverage required. Users under this area will be able to access this system directly for internet connectivity. This system can be used over large areas like universities, companies and societies to provide internet facility to their users through Wi-Fi or over an area where the user is specified (commercial purposes. Currently Google is working on similar idea called the ’Google Loon’ in which they use high altitude balloons which float at an altitude twice as high as air planes and the weather. They recently tested this system over New-Zealand by providing internet to their pilot testers on ground. Their balloons not being stationary, move with directional winds and have to be replaced one after the other to maintain consistency. This can be a huge problem over the areas where upper atmospheric winds are not in favorable direction. We can resolve this problem by using our stationary tethered balloon system which can communicate with the loon balloons to provide internet facility over a desired area. Moreover when our balloon will communicate with the loon balloon it will increase the coverage area as the loon balloon has to communicate to a point which is above the ground. Our system will not only replace the existing fiber optic system but it will also be selfsustaining i.e. It will generate its own power using solar panels.

  14. Provider volume and outcomes for oncological procedures.

    LENUS (Irish Health Repository)

    Killeen, S D

    2012-02-03

    BACKGROUND: Oncological procedures may have better outcomes if performed by high-volume providers. METHODS: A review of the English language literature incorporating searches of the Medline, Embase and Cochrane collaboration databases was performed. Studies were included if they involved a patient cohort from 1984 onwards, were community or population based, and assessed health outcome as a dependent variable and volume as an independent variable. The studies were also scored quantifiably to assess generalizability with respect to any observed volume-outcome relationship and analysed according to organ system; numbers needed to treat were estimated where possible. RESULTS: Sixty-eight relevant studies were identified and a total of 41 were included, of which 13 were based on clinical data. All showed either an inverse relationship, of variable magnitude, between provider volume and mortality, or no volume-outcome effect. All but two clinical reports revealed a statistically significant positive relationship between volume and outcome; none demonstrated the opposite. CONCLUSION: High-volume providers have a significantly better outcome for complex cancer surgery, specifically for pancreatectomy, oesphagectomy, gastrectomy and rectal resection.

  15. INNOVATIVE ASPECTS OF THE PROVIDING COMPETITIVENESS OFENTERPRISES

    Directory of Open Access Journals (Sweden)

    Н. Yamnenko

    2016-01-01

    Full Text Available The world experience of economic development shows that innovations are the catalyst of modernization and restructuring of the economy, which contributedthe strengthening of the competitiveness, profitability and innovative development of enterprisesand help to conquer new and retain existing markets. The decision of problems of activation of innovative activity of enterprises becomes the main guarantee of providing of success of market reforms. The purpose of this article is to determine of features of intercommunication between innovative activity and competitive advantages of an enterprise. The study identified the competitive advantages related to innovative activity. It is proved that the maintenance of sustainable competition position at the market depends on determination and maintenance of key success factors. It is determined the basic stages of providing of competitiveness of an enterprise through the use of its innovative capabilities. It is shown that only through developing existing and creating new competitive advantages an enterprise will be able to attain the desired state of competitiveness in the modern realities. It has suggested forming an effective competitive strategy through extensive use of innovative decisions on the basis of knowledge for providing of competitiveness of enterprises. The basis to competitive advantages should be considered the process of stimulation innovations.

  16. ACCOUNTING TREATMENTS USED FOR ACCOUNTING SERVICES PROVIDERS

    Directory of Open Access Journals (Sweden)

    ŢOGOE GRETI DANIELA

    2014-08-01

    Full Text Available The theme of our research is the ways of keeping accounting entities that are the object of the provision of services in the accounting profession. This paper aims to achieve a parallel between the ways of organizing financial records - accounting provided by freelancers and companies with activity in the financial - accounting. The first step in our scientific research is to establish objectives chosen area of scientific knowledge. Our scientific approach seeks to explain through a thorough and detailed approach as different sides (conceptual and practical looking projections of accounting issues related to regulatory developments and practices in the field. This paper addresses various concepts, accounting treatments, and books and accounting documents used both freelancers in providing accounting services and legal persons authorized accounting profession. In terms of methodology and research perspective, the whole scientific approach combined with quantitative and qualitative research theoretical perspective (descriptive-conceptual with practice perspective (empirical analyzing the main contributions of various authors (Romanian and foreign to knowledge in the field. Following the survey believe that the amendments to the national legislation will support entities providing accounting services, by cutting red tape on Administrative Burdens, and consequently will increase profitability and increase service quality.

  17. Threatened corals provide underexplored microbial habitats.

    Directory of Open Access Journals (Sweden)

    Shinichi Sunagawa

    Full Text Available Contemporary in-depth sequencing of environmental samples has provided novel insights into microbial community structures, revealing that their diversity had been previously underestimated. Communities in marine environments are commonly composed of a few dominant taxa and a high number of taxonomically diverse, low-abundance organisms. However, studying the roles and genomic information of these "rare" organisms remains challenging, because little is known about their ecological niches and the environmental conditions to which they respond. Given the current threat to coral reef ecosystems, we investigated the potential of corals to provide highly specialized habitats for bacterial taxa including those that are rarely detected or absent in surrounding reef waters. The analysis of more than 350,000 small subunit ribosomal RNA (16S rRNA sequence tags and almost 2,000 nearly full-length 16S rRNA gene sequences revealed that rare seawater biosphere members are highly abundant or even dominant in diverse Caribbean corals. Closely related corals (in the same genus/family harbored similar bacterial communities. At higher taxonomic levels, however, the similarities of these communities did not correlate with the phylogenetic relationships among corals, opening novel questions about the evolutionary stability of coral-microbial associations. Large proportions of OTUs (28.7-49.1% were unique to the coral species of origin. Analysis of the most dominant ribotypes suggests that many uncovered bacterial taxa exist in coral habitats and await future exploration. Our results indicate that coral species, and by extension other animal hosts, act as specialized habitats of otherwise rare microbes in marine ecosystems. Here, deep sequencing provided insights into coral microbiota at an unparalleled resolution and revealed that corals harbor many bacterial taxa previously not known. Given that two of the coral species investigated are listed as threatened under

  18. Intraoperative patient information handover between anesthesia providers

    Science.gov (United States)

    Choromanski, Dominik; Frederick, Joel; McKelvey, George Michael; Wang, Hong

    2014-01-01

    Abstract Currently, no reported studies have evaluated intraoperative handover among anesthesia providers. Studies on anesthetic handover in the US recovery room setting observed that handover processes are insufficient and, in many instances, significant intraoperative events are disregarded. An online survey tool was sent to anesthesia providers at US anesthesia residency programs nationwide (120 out of the 132 US programs encompassing around 4500 residents and their academic MDAs) and a smaller survey selection of CRNAs (10 institutions about 300 CRNAs in the metropolitan area of Detroit, MI, USA) to collect information on handover practices. The response rate to this survey (n = 216) was comprised of approximately 5% (n = 71) of the resident population in US anesthesia programs, 5% (n = 87) of MDAs , and 20% (n = 58) of the CRNAs. Out of all respondents (n = 212), 49.1 % had no hand-over protocol at their institution and 88% of respondents who did have institutional handover protocols believed them insufficient for effective patient handover. In addiiton, 84.8% of all responders reported situations where there was insufficient information received during a patient handover. Only 7% of the respondents reported never experiencing complications or mismanagement due to poor or incomplete hand-overs. In contrast, 60% reported rarely having complications, 31% reported sometimes having complications, and 3% reported frequent complications. In conclusion, handover transition of patient care is a vulnerable and potentially life-threatening event in the operating room. Our preliminary study suggests that current intraoperatvive handover practices among anesthesia providers are suboptimal and that national patient handover guidelines are required to improve patient safety. PMID:25332710

  19. Esourcing capability model for service providers

    CERN Document Server

    Hefley, Keith M Heston and Bill; Hyder, Elaine

    2010-01-01

    The eSourcing Capability Model for Service Providers (eSCM-SP) is the best practices model that supports sourcing organizations successfully manage and reduce their risks and improve their capabilities across the entire sourcing life-cycle. It addresses the critical issues related to IT-enabled sourcing (eSourcing) for both outsourced and in-sourced (shared services) agreements. Each of the Model's 84 Practice is distributed along three easy to follow dimensions: Sourcing Life-cycle, Capability Area, and Capability Level, and have been applied in IT, BPO, and KPO settings.The eSCM-SP has been

  20. Power beaming providing a space power infrastructure

    International Nuclear Information System (INIS)

    This paper, based on two levels of technology maturity, applied the power beaming concept to four panned satellite constellations. The analysis shows that with currently available technology, power beaming can provide mass savings to constellations in orbits ranging from low-Earth orbit to geosynchronous orbit. Two constellations, space surveillance and tracking system and space-based radar, can be supported with current technology. The other two constellations, space-based laser array and boost surveillance and tracking system, will require power and transmission system improvements before their breakeven specific mass is achieved. A doubling of SP-100 conversion efficiency from 10 to 20% would meet or exceed breakeven for these constellations

  1. Zika Virus: Critical Information for Emergency Providers.

    Science.gov (United States)

    Shastry, Siri; Koenig, Kristi L; Hirshon, Jon Mark

    2016-08-01

    Zika virus is an arbovirus of the Flaviviridae family. It is primarily a minimally symptomatic mosquito-borne infection. However, with Zika's 2015 to 2016 introduction into the Western Hemisphere and its dramatic and rapid spread, it has become a public health concern, in large part due to congenital abnormalities associated with infection in pregnant women. In early 2016, the World Health Organization declared the microcephaly and other neurologic conditions associated with Zika virus infection a public health emergency of international concern. This article discusses the current epidemiologic and clinical understanding of Zika virus, focusing on critical information needed by emergency providers.

  2. Zika Virus: Critical Information for Emergency Providers.

    Science.gov (United States)

    Shastry, Siri; Koenig, Kristi L; Hirshon, Jon Mark

    2016-08-01

    Zika virus is an arbovirus of the Flaviviridae family. It is primarily a minimally symptomatic mosquito-borne infection. However, with Zika's 2015 to 2016 introduction into the Western Hemisphere and its dramatic and rapid spread, it has become a public health concern, in large part due to congenital abnormalities associated with infection in pregnant women. In early 2016, the World Health Organization declared the microcephaly and other neurologic conditions associated with Zika virus infection a public health emergency of international concern. This article discusses the current epidemiologic and clinical understanding of Zika virus, focusing on critical information needed by emergency providers. PMID:27475021

  3. Identity federation using shibboleth identity provider

    OpenAIRE

    Kankaala, Laura

    2015-01-01

    The employer of this thesis is a global company called KPMG. In addition to KPMG’s primary accounting services, the company has also expanded its expertise to the field of information security. The purpose of this thesis was to construct an environment for KPMG to showcase identity federation solutions, using Shibboleth Identity Provider. The research method used in this thesis is constructive and it is based on a real life use case. Some of the references used in this thesis are from the...

  4. Will British weather provide reliable electricity?

    International Nuclear Information System (INIS)

    There has been much academic debate on the ability of wind to provide a reliable electricity supply. The model presented here calculates the hourly power delivery of 25 GW of wind turbines distributed across Britain's grid, and assesses power delivery volatility and the implications for individual generators on the system. Met Office hourly wind speed data are used to determine power output and are calibrated using Ofgem's published wind output records. There are two main results. First, the model suggests that power swings of 70% within 12 h are to be expected in winter, and will require individual generators to go on or off line frequently, thereby reducing the utilisation and reliability of large centralised plants. These reductions will lead to increases in the cost of electricity and reductions in potential carbon savings. Secondly, it is shown that electricity demand in Britain can reach its annual peak with a simultaneous demise of wind power in Britain and neighbouring countries to very low levels. This significantly undermines the case for connecting the UK transmission grid to neighbouring grids. Recommendations are made for improving 'cost of wind' calculations. The authors are grateful for the sponsorship provided by The Renewable Energy Foundation

  5. Green roofs provide habitat for urban bats

    Directory of Open Access Journals (Sweden)

    K.L. Parkins

    2015-07-01

    Full Text Available Understanding bat use of human-altered habitat is critical for developing effective conservation plans for this ecologically important taxon. Green roofs, building rooftops covered in growing medium and vegetation, are increasingly important conservation tools that make use of underutilized space to provide breeding and foraging grounds for urban wildlife. Green roofs are especially important in highly urbanized areas such as New York City (NYC, which has more rooftops (34% than green space (13%. To date, no studies have examined the extent to which North American bats utilize urban green roofs. To investigate the role of green roofs in supporting urban bats, we monitored bat activity using ultrasonic recorders on four green and four conventional roofs located in highly developed areas of NYC, which were paired to control for location, height, and local variability in surrounding habitat and species diversity. We then identified bat vocalizations on these recordings to the species level. We documented the presence of five of nine possible bat species over both roof types: Lasiurus borealis, L. cinereus, L. noctivagans, P. subflavus,andE. fuscus. Of the bat calls that could be identified to the species level, 66% were from L. borealis. Overall levels of bat activity were higher over green roofs than over conventional roofs. This study provides evidence that, in addition to well documented ecosystem benefits, urban green roofs contribute to urban habitat availability for several North American bat species.

  6. Private provider participation in statewide immunization registries

    Directory of Open Access Journals (Sweden)

    Cowan Anne E

    2006-02-01

    Full Text Available Abstract Background Population-based registries have been promoted as an effective method to improve childhood immunization rates, yet rates of registry participation in the private sector are low. We sought to describe, through a national overview, the perspectives of childhood immunization providers in private practice regarding factors associated with participation or non-participation in immunization registries. Methods Two mailed surveys, one for 264 private practices identified as registry non-participants and the other for 971 identified as registry participants, from 15 of the 31 states with population-based statewide immunization registries. Frequency distributions were calculated separately for non-participants and participants regarding the physician-reported factors that influenced decisions related to registry participation. Pearson chi-square tests of independence were used to assess associations among categorical variables. Results Overall response rate was 62% (N = 756. Among non-participants, easy access to records of vaccines provided at other sites (N = 101, 68% and printable immunization records (N = 82, 55% were most often cited as "very important" potential benefits of a registry, while the most commonly cited barriers to participation were too much cost/staff time (N = 36, 38% and that the practice has its own system for recording and monitoring immunizations (N = 35, 37%. Among registry participants, most reported using the registry to input data on vaccines administered (N = 326, 87% and to review immunization records of individual patients (N = 302, 81%. A minority reported using it to assess their practice's immunization coverage (N = 110, 29% or generate reminder/recall notices (N = 54, 14%. Few participants reported experiencing "significant" problems with the registry; the most often cited was cost/staff time to use the registry (N = 71, 20%. Conclusion Most registry participants report active participation with few

  7. Multiagency Initiative to Provide Greenhouse Gas Information

    Science.gov (United States)

    Boland, Stacey W.; Duren, Riley M.

    2009-11-01

    Global Greenhouse Gas Information System Workshop; Albuquerque, New Mexico, 20-22 May 2009; The second Greenhouse Gas Information System (GHGIS) workshop brought together 74 representatives from 28 organizations including U.S. government agencies, national laboratories, and members of the academic community to address issues related to the understanding, operational monitoring, and tracking of greenhouse gas emissions and carbon offsets. The workshop was held at Sandia National Laboratories and organized by an interagency collaboration among NASA centers, Department of Energy laboratories, and the U.S. National Oceanic and Atmospheric Administration. It was motivated by the perceived need for an integrated interagency, community-wide initiative to provide information about greenhouse gas sources and sinks at policy-relevant temporal and spatial scales. Such an initiative could significantly enhance the ability of national and regional governments, industry, and private citizens to implement and evaluate effective climate change mitigation policies.

  8. Multicultural Nursing: Providing Better Employee Care.

    Science.gov (United States)

    Rittle, Chad

    2015-12-01

    Living in an increasingly multicultural society, nurses are regularly required to care for employees from a variety of cultural backgrounds. An awareness of cultural differences focuses occupational health nurses on those differences and results in better employee care. This article explores the concept of culturally competent employee care, some of the non-verbal communication cues among cultural groups, models associated with completing a cultural assessment, and how health disparities in the workplace can affect delivery of employee care. Self-evaluation of the occupational health nurse for personal preferences and biases is also discussed. Development of cultural competency is a process, and occupational health nurses must develop these skills. By developing cultural competence, occupational health nurses can conduct complete cultural assessments, facilitate better communication with employees from a variety of cultural backgrounds, and improve employee health and compliance with care regimens. Tips and guidelines for facilitating communication between occupational health nurses and employees are also provided. PMID:26199294

  9. Generational considerations in providing critical care education.

    Science.gov (United States)

    Paterson, Tricia

    2010-01-01

    With the current and predicted nursing shortage, much emphasis is placed on recruitment and retention. With an aging workforce, we must recruit, educate, and retain nurses from many different generations. As leaders and educators, we must be aware of generational differences and work with staff to appreciate potential preferences in communication, approach to learning and motivational factors. We are aware that over the next 15 years, many experienced nurses will retire. We must do all we can to recruit and retain nurses from all generations in order to provide a workforce able to meet the needs of our patients and families. Generational preferences should be considered when developing nursing education and in welcoming and accepting new staff into the culture of the nursing unit. PMID:20019512

  10. Providing Virtual Execution Environments: A Twofold Illustration

    CERN Document Server

    Grehant, Xavier

    2008-01-01

    Platform virtualization helps solving major grid computing challenges: share resource with flexible, user-controlled and custom execution environments and in the meanwhile, isolate failures and malicious code. Grid resource management tools will evolve to embrace support for virtual resource. We present two open source projects that transparently supply virtual execution environments. Tycoon has been developed at HP Labs to optimise resource usage in creating an economy where users bid to access virtual machines and compete for CPU cycles. SmartDomains provides a peer-to-peer layer that automates virtual machines deployment using a description language and deployment engine from HP Labs. These projects demonstrate both client-server and peer-to-peer approaches to virtual resource management. The first case makes extensive use of virtual machines features for dynamic resource allocation. The second translates virtual machines capabilities into a sophisticated language where resource management components can b...

  11. International Entry Modes for Digital Product Providers

    DEFF Research Database (Denmark)

    Rask, Morten

    Often internationalization of the firm refers to the process of increasing involvement in international operations. In relation to e-business many authors have argued that e-business will change the internationalization processes. E-business is about digitalization of processes, products and actors...... and many think that because these digitalisations, the importance of localization diminish, especially for what we call digital product providers that sells digitized products and services. The empirical foundation of this paper consists of an inductive explorative case-study that serves as a challenger...... (Fredsted, 2003). The case study gives insight into one of the few international marketplaces. Scanmarket has expanded to the English, German, American and Swedish markets. Essentially the case raises the question: "To what extent does the Internet supersede firms' need for local, physical presence?"...

  12. Impact of Regulation on Financial Services Providers

    Directory of Open Access Journals (Sweden)

    Ketharaman Swaminathan

    2012-08-01

    Full Text Available Digital pundits and research analysts regularly gush about the slew of innovative financial products launched by nonbanking financial services providers almost daily. They’d have us believe that unless traditional banks match the new players with equal degree of innovation, they face extinction. In this paper, we present the counterview that banks have little to fear from these new kids on the block. We then explain how, contrary to popular misconception, most nonbanking players will vanish overnight if banks were to stop operating the rails on top of which most of these new products are built. We go on to examine how regulations restrain banks. In conclusion, we expose a graver threat to banks that’s unconnected to regulation. Good news is, banks can overcome this internal challenge without facing any roadblocks from regulators.

  13. Providing better indoor environmental quality brings economicbenefits

    Energy Technology Data Exchange (ETDEWEB)

    Fisk, William; Seppanen, Olli

    2007-06-01

    This paper summarizes the current scientific evidence that improved indoor environmental quality can improve work performance and health. The review indicates that work and school work performance is affected by indoor temperature and ventilation rate. Pollutant source removal can sometimes improve work performance. Based on formal statistical analyses of existing research results, quantitative relationships are provided for the linkages of work performance with indoor temperature and outdoor air ventilation rate. The review also indicates that improved health and related financial savings are obtainable from reduced indoor tobacco smoking, prevention and remediation of building dampness, and increased ventilation. Example cost-benefit analyses indicate that many measures to improve indoor temperature control and increase ventilation rates will be highly cost effective, with benefit-cost ratios as high as 80 and annual economic benefits as high as $700 per person.

  14. New consumer services provided by smart metering

    Directory of Open Access Journals (Sweden)

    Daminov Ildar

    2015-01-01

    Full Text Available This paper focuses on the issues of smart metering market and considers different services provided by smart metering from consumer point of view. Firstly, smart metering deployment challenges emerging and conventional tariffs, which modify a consumer behavior and thus, the entire electric energy market can be optimized since the customer is motivated to consume less energy. Secondly, the authors illustrate changes in electricity quality, which have an impact on consumer relations with utility. Additionally, two main indices of grid resilience – SAIDI and SAIFI – are exemplified to reveal the improvement potential of smart metering implementation in certain regions of Russia that also influence the consumer. Finally, in-home display and privacy problem directly reflect the consumer’s behavior, thus the private life rights should not be violated as they are guaranteed by law.

  15. Perioperative Care of Prisoners: Providing Safe Care.

    Science.gov (United States)

    Smith, Francis Duval

    2016-03-01

    Correctional nurses are trained to care for prisoners in a controlled security environment; however, when a convict is transferred to a noncorrectional health care facility, the nurses there are often unfamiliar with custody requirements or how to safely care for these patients. The care of prisoners outside of prison has not been adequately investigated, and a gap exists between research and nursing education and practice. Nurses rarely have to consider how providing care for a prisoner in custody affects their practice, the potential dissonance between routine nursing care and the requirements to maintain security, or that care of prisoners in unsecured clinical areas places the nurse and other personnel at risk for physical assault or prisoner escape. Educating perioperative nurses in the care of prisoners in a public hospital environment is important for the provision of safe care and prevention of physical and emotional repercussions to personnel.

  16. caTissue Suite 1.2 released —

    Science.gov (United States)

    caTissue Suite 1.2 is an open-source, web and programmatically accessible tool for managing biospecimens collected in support of basic and clinical research. Building on the capabilities of previous releases the application helps users manage biospecimen inventory, annotation and sample tracking. It also supports clinical and pathology report annotation and provides query capabilities for researchers to identify and find biospecimens for their research projects. In addition, it features "Dynamic Extensions", allowing Biorepositories to extend the caTissue data model and develop annotations customized for their institution.

  17. PROVIDING R-TREE SUPPORT FOR MONGODB

    Directory of Open Access Journals (Sweden)

    L. Xiang

    2016-06-01

    Full Text Available Supporting large amounts of spatial data is a significant characteristic of modern databases. However, unlike some mature relational databases, such as Oracle and PostgreSQL, most of current burgeoning NoSQL databases are not well designed for storing geospatial data, which is becoming increasingly important in various fields. In this paper, we propose a novel method to provide R-tree index, as well as corresponding spatial range query and nearest neighbour query functions, for MongoDB, one of the most prevalent NoSQL databases. First, after in-depth analysis of MongoDB’s features, we devise an efficient tabular document structure which flattens R-tree index into MongoDB collections. Further, relevant mechanisms of R-tree operations are issued, and then we discuss in detail how to integrate R-tree into MongoDB. Finally, we present the experimental results which show that our proposed method out-performs the built-in spatial index of MongoDB. Our research will greatly facilitate big data management issues with MongoDB in a variety of geospatial information applications.

  18. Providing R-Tree Support for Mongodb

    Science.gov (United States)

    Xiang, Longgang; Shao, Xiaotian; Wang, Dehao

    2016-06-01

    Supporting large amounts of spatial data is a significant characteristic of modern databases. However, unlike some mature relational databases, such as Oracle and PostgreSQL, most of current burgeoning NoSQL databases are not well designed for storing geospatial data, which is becoming increasingly important in various fields. In this paper, we propose a novel method to provide R-tree index, as well as corresponding spatial range query and nearest neighbour query functions, for MongoDB, one of the most prevalent NoSQL databases. First, after in-depth analysis of MongoDB's features, we devise an efficient tabular document structure which flattens R-tree index into MongoDB collections. Further, relevant mechanisms of R-tree operations are issued, and then we discuss in detail how to integrate R-tree into MongoDB. Finally, we present the experimental results which show that our proposed method out-performs the built-in spatial index of MongoDB. Our research will greatly facilitate big data management issues with MongoDB in a variety of geospatial information applications.

  19. Dental practice satisfaction with preferred provider organizations

    Directory of Open Access Journals (Sweden)

    Schilling Elizabeth A

    2007-11-01

    Full Text Available Abstract Background Despite their increasing share of the dental insurance market, little is known about dental practices' satisfaction with preferred provider organizations (PPOs. This analysis examined practice satisfaction with dental PPOs and the extent to which satisfaction was a function of communications from the plan, claims handling and compensation. Methods Data were collected through telephone surveys with dental practices affiliated with MetLife between January 2002 and December 2004. Each respondent was asked a series of questions related to their satisfaction with a systematically selected PPO with which they were affiliated. Six different PPO plans had sufficient observations to allow for comparative analysis (total n = 4582. Multiple imputation procedures were used to adjust for item non-response. Results While the average level of overall satisfaction with the target plan fell between "very satisfied" and "satisfied," regression models revealed substantial differences in overall satisfaction across the 6 PPOs (p Conclusion Results demonstrate the importance of compensation to dental practice satisfaction with PPOs. However, these results also highlight the critical role of service-related factors in differentiating plans and suggest that there are important non-monetary dimensions of PPO performance that can be used to recruit and retain practices.

  20. Family benefits - Obligation to provide information

    CERN Multimedia

    HR Department

    2015-01-01

    Pursuant to Article R V 1.38 of the Staff Regulations, members of the personnel are reminded that they are required to inform the Organization in writing, within 30 calendar days, of any change in their family situation (marriage, partnership, birth of a child, etc.) and of the amount of any financial benefit of a similar nature to those provided for in the Staff Regulations (e.g. family allowance, child allowance, infant allowance, non-resident allowance or international indemnity) to which they or a member of their family may be entitled from a source other than CERN.   The procedures to be followed are available in the Admin e-guide: https://admin-eguide.web.cern.ch/en/procedure/change-family-situation Members of the personnel are also reminded that any false declaration or failure to make a declaration with a view to deceiving others or achieving a gain resulting in a loss of funds or reputation for CERN constitutes fraud and may lead to disciplinary action in accordance with Article S ...

  1. Contingency management: perspectives of Australian service providers.

    Science.gov (United States)

    Cameron, Jacqui; Ritter, Alison

    2007-03-01

    Given the very positive and extensive research evidence demonstrating efficacy and effectiveness of contingency management, it is important that Australia explore whether contingency management has a role to play in our own treatment context. Qualitative interviews were conducted with 30 experienced alcohol and drug practitioners, service managers and policy-makers in Victoria. Interviewees were selected to represent the range of drug treatment services types and included rural representation. A semi-structured interview schedule, covering their perceptions and practices of contingency management was used. All interviews were transcribed verbatim and analysed using N2 qualitative data analysis program. The majority of key informants were positively inclined toward contingency management, notwithstanding some concerns about the philosophical underpinnings. Concerns were raised in relation to the use of monetary rewards. Examples of the use of contingency management provided by key informants demonstrated an over-inclusive definition: all the examples did not adhere to the key principles of contingency management. This may create problems if a structured contingency management were to be introduced in Australia. Contingency management is an important adjunctive treatment intervention and its use in Australia has the potential to enhance treatment outcomes. No unmanageable barriers were identified in this study. PMID:17364854

  2. Are Anesthesia Providers Ready for Hypnosis? Anesthesia Providers' Attitudes Toward Hypnotherapy.

    Science.gov (United States)

    Stone, Alexander B; Sheinberg, Rosanne; Bertram, Amanda; Seymour, Anastasia Rowland

    2016-04-01

    This study sought to measure current attitudes toward hypnosis among anesthesia providers using an in-person survey distributed at a single grand rounds at a single academic teaching hospital. One hundred twenty-six anesthesia providers (anesthesiologists and nurse anesthetists) were included in this study. A 10-question Institutional Review Board (IRB)-approved questionnaire was developed. One hundred twenty-six (73% of providers at the meeting) anesthesia providers completed the survey. Of the respondents, 54 (43%) were anesthesiologists, 42 (33%) were trainees (interns/residents/fellows) in anesthesia, and 30 (24%) were nurse anesthetists. Over 70% of providers, at each level of training, rated their knowledge of hypnosis as either below average or having no knowledge. Fifty-two (42%) providers agreed or strongly agreed that hypnotherapy has a place in the clinical practice of anesthesia, while 103 (83%) believed that positive suggestion has a place in the clinical practice of anesthesia (p hypnosis were that it is too time consuming (41%) and requires special training (34%). Only three respondents (2%) believed that there were no reasons for using hypnosis in their practice. These data suggest that there is a self-reported lack of knowledge about hypnosis among anesthesia providers, although many anesthesia providers are open to the use of hypnosis in their clinical practice. Anesthesia providers are more likely to support the use of positive suggestion in their practice than hypnosis. Practical concerns should be addressed if hypnosis and therapeutic verbal techniques are to gain more widespread use.

  3. Parenting provided by adults with mental retardation.

    Science.gov (United States)

    Dowdney, L; Skuse, D

    1993-01-01

    Studies assessing the quality of parenting provided by adults with mental retardation present conflicting conclusions. Some consider the majority to be doing reasonably well, whilst others report frequently unsatisfactory caretaking. There are a number of reasons for such different views. First, inconsistent selection criteria make it hard to compare across studies. In particular, sample composition will be influenced by the recruitment source. For example, if parents have been chosen from voluntary educational programmes a rather different picture is likely to be found than if they have been selected from individuals known to, or referred by, statutory agencies. On the whole, authors working with subjects from the former source have been rather more optimistic than those working with parents referred because there were already serious concerns about parenting difficulties or about delayed child development. Secondly, the majority of studies have used poorly defined global measures of parenting, with variable criteria of what constitutes adequate care. Some have concentrated on physical care and hygiene, whilst others have looked for the presence of affection and warmth. A child's reception into care as the sole measure of the quality of parenting is an unsatisfactory criterion because parental retardation has itself occasionally been used as the basis for removal of a child into care, even in the absence of other evidence of neglect or abuse. Thirdly, methodological flaws are found in studies that have used observational assessments of parenting. Such studies have suggested mothers with mental retardation tend to lack interactive skills (such as high levels of praise and imitation, and low restrictiveness) which are known to be associated with optimal child development. Control groups have often not been matched on social and other variables which might be expected to exert a significant influence upon parenting practices. In addition, the generalisability of

  4. Providing nuclear pharmacy education via the internet

    International Nuclear Information System (INIS)

    Aim: (1) Increase the nuclear pharmacy education opportunities across the United States and the around the world. (2) Establish collaborative educational agreements between colleges of pharmacy and local nuclear pharmacy preceptors. (3) Decrease the shortage of radio pharmacists. 4) Provide nuclear education courses to supplement existing educational programs. Materials and Methods: Nuclear Education Online (www.nuclearonline.org) is an educational consortium between the University of Arkansas for Medical Sciences and the University of New Mexico. The faculty members from each institution have collaborated to design an online didactic curriculum and experiential training materials. The didactic portion is delivered via WebCT (www.webct.com) and involves interactive studies with faculty from UNM and UAMS. The student-centered curriculum is based on the APhA Syllabus for Nuclear Pharmacy Training and includes interactive web-based course materials, discussion groups, preceptor-led activities and problem-based learning (PBL) case studies based upon actual clinical studies and real-life pharmacy situations. Individual units of study include Nuclear Physics, Radiation Biology, Radiation Safety, Instrumentation, and Radiochemistry/Radiopharmacology. Students can begin the program at anytime. Once a cohort of students is established, the students proceed through the PBL cases, working interactively as a group. Results: Since June 2001, over 26 students have completed the 10-week certificate program. These students have been located across the U.S. and in Saudi Arabia. Fifteen students have completed individual courses in nuclear physics and instrumentation through colleges of pharmacy course offerings using the NEO faculty as instructors. Student evaluations revealed that 78% of the students thought that the NEO program was a 'great way to learn' (highest rating). When comparing PBL to a traditional classroom setting, two thirds of students preferred problem

  5. Parenting provided by adults with mental retardation.

    Science.gov (United States)

    Dowdney, L; Skuse, D

    1993-01-01

    Studies assessing the quality of parenting provided by adults with mental retardation present conflicting conclusions. Some consider the majority to be doing reasonably well, whilst others report frequently unsatisfactory caretaking. There are a number of reasons for such different views. First, inconsistent selection criteria make it hard to compare across studies. In particular, sample composition will be influenced by the recruitment source. For example, if parents have been chosen from voluntary educational programmes a rather different picture is likely to be found than if they have been selected from individuals known to, or referred by, statutory agencies. On the whole, authors working with subjects from the former source have been rather more optimistic than those working with parents referred because there were already serious concerns about parenting difficulties or about delayed child development. Secondly, the majority of studies have used poorly defined global measures of parenting, with variable criteria of what constitutes adequate care. Some have concentrated on physical care and hygiene, whilst others have looked for the presence of affection and warmth. A child's reception into care as the sole measure of the quality of parenting is an unsatisfactory criterion because parental retardation has itself occasionally been used as the basis for removal of a child into care, even in the absence of other evidence of neglect or abuse. Thirdly, methodological flaws are found in studies that have used observational assessments of parenting. Such studies have suggested mothers with mental retardation tend to lack interactive skills (such as high levels of praise and imitation, and low restrictiveness) which are known to be associated with optimal child development. Control groups have often not been matched on social and other variables which might be expected to exert a significant influence upon parenting practices. In addition, the generalisability of

  6. Providing Data Access for Interdisciplinary Research

    Science.gov (United States)

    Hooper, R. P.; Couch, A.

    2012-12-01

    Developing an interdisciplinary understanding of human and environmental interactions with water requires access to a variety of data kinds collected by various organizations. The CUAHSI Hydrologic Information System (HIS) is a standards-based, services-oriented architecture designed for time-series data. Such data represents an important type of data in water studies. Through the efforts of HIS, a standard transmission language, WaterML2, has been adopted by the Open Geospatial Consortium and is under consideration by the World Meteorologic Organization as an international standards. Web services have also been developed to retrieve data and metadata. HIS is completed with a metadata catalog, hosted by San Diego Supercomputing Center, which indexes more than 20 million time series provided from over 90 different services. This catalog is supported through a hierarchically organized controlled vocabulary that is open for community input and mediation. Data publishers include federal agencies, universities, state agencies, and non-profit organizations such as watershed associations. Accessing data from such a broad spectrum of sources through a uniform service standard promises to truly transform the way in which hydrologic research is done. CUAHSI HIS is a large-scale prototype at this time, but a proposal is under consideration by the National Science Foundation to operationalize HIS through a data facility, tentatively called the CUAHSI Water Data Center. Establishing HIS is an important step to enable research into human-environment interactions with water, but it is only one step. Other data structures will need to be made accessible and interoperable to support this research. Some data—such as two-dimensional GIS coverages—already have widely used standards for transmission and sharing. The US Federal government has long operated a clearinghouse for federal geographic data that is now being augmented with other services such as ArcGIS OnLine. Other data

  7. Attitudes of Healthcare Providers towards Providing Contraceptives for Unmarried Adolescents in Ibadan, Nigeria.

    Directory of Open Access Journals (Sweden)

    Ezihe Loretta Ahanonu

    2014-03-01

    Full Text Available This study sought to assess the attitude of Healthcare Providers towards providing contraceptives for unmarried adolescents in four Local Government Areas in Ibadan, Nigeria.A cross-sectional descriptive study was conducted among 490 Healthcare Providers in 24 randomly selected healthcare facilities using self-administered, pre-tested questionnaires.More than half (57.5% of the respondents perceived the provision of contraceptives for unmarried adolescents as promoting sexual promiscuity. The attitude of 42.7% of them was informed by the Nigerian culture which does not support premarital sex. About half (51.7%, reported that unmarried adolescents should be asked to abstain from sex rather than providing them with contraceptives. Over a third (44.2% reported that providers should not provide services for both married and unmarried adolescents.Many healthcare providers have unfavourable attitudes towards the provision of contraceptives for unmarried adolescents. There is a need for further training of Healthcare Providers to address this situation.

  8. Are Anesthesia Providers Ready for Hypnosis? Anesthesia Providers' Attitudes Toward Hypnotherapy.

    Science.gov (United States)

    Stone, Alexander B; Sheinberg, Rosanne; Bertram, Amanda; Seymour, Anastasia Rowland

    2016-04-01

    This study sought to measure current attitudes toward hypnosis among anesthesia providers using an in-person survey distributed at a single grand rounds at a single academic teaching hospital. One hundred twenty-six anesthesia providers (anesthesiologists and nurse anesthetists) were included in this study. A 10-question Institutional Review Board (IRB)-approved questionnaire was developed. One hundred twenty-six (73% of providers at the meeting) anesthesia providers completed the survey. Of the respondents, 54 (43%) were anesthesiologists, 42 (33%) were trainees (interns/residents/fellows) in anesthesia, and 30 (24%) were nurse anesthetists. Over 70% of providers, at each level of training, rated their knowledge of hypnosis as either below average or having no knowledge. Fifty-two (42%) providers agreed or strongly agreed that hypnotherapy has a place in the clinical practice of anesthesia, while 103 (83%) believed that positive suggestion has a place in the clinical practice of anesthesia (p hypnosis were that it is too time consuming (41%) and requires special training (34%). Only three respondents (2%) believed that there were no reasons for using hypnosis in their practice. These data suggest that there is a self-reported lack of knowledge about hypnosis among anesthesia providers, although many anesthesia providers are open to the use of hypnosis in their clinical practice. Anesthesia providers are more likely to support the use of positive suggestion in their practice than hypnosis. Practical concerns should be addressed if hypnosis and therapeutic verbal techniques are to gain more widespread use. PMID:27003489

  9. Provider practice models in ambulatory oncology practice: analysis of productivity, revenue, and provider and patient satisfaction.

    Science.gov (United States)

    Buswell, Lori A; Ponte, Patricia Reid; Shulman, Lawrence N

    2009-07-01

    Physicians, nurse practitioners, and physician assistants often work in teams to deliver cancer care in ambulatory oncology practices. This is likely to become more prevalent as the demand for oncology services rises, and the number of providers increases only slightly.

  10. Providing Services to Survivors of Domestic Violence: A Comparison of Rural and Urban Service Provider Perceptions

    Science.gov (United States)

    Eastman, Brenda J.; Bunch, Shelia Grant

    2007-01-01

    Although there is a considerable body of knowledge about domestic violence, a limited proportion focuses on domestic violence in rural settings. Using a nonprobability purposive sampling technique, 93 providers of domestic violence services from rural and urban localities in North Carolina and Virginia were located and asked to complete a…

  11. Health service providers in Somalia: their readiness to provide malaria case-management

    Directory of Open Access Journals (Sweden)

    Moonen Bruno

    2009-05-01

    Full Text Available Abstract Background Studies have highlighted the inadequacies of the public health sector in sub-Saharan African countries in providing appropriate malaria case management. The readiness of the public health sector to provide malaria case-management in Somalia, a country where there has been no functioning central government for almost two decades, was investigated. Methods Three districts were purposively sampled in each of the two self-declared states of Puntland and Somaliland and the south-central region of Somalia, in April-November 2007. A survey and mapping of all public and private health service providers was undertaken. Information was recorded on services provided, types of anti-malarial drugs used and stock, numbers and qualifications of staff, sources of financial support and presence of malaria diagnostic services, new treatment guidelines and job aides for malaria case-management. All settlements were mapped and a semi-quantitative approach was used to estimate their population size. Distances from settlements to public health services were computed. Results There were 45 public health facilities, 227 public health professionals, and 194 private pharmacies for approximately 0.6 million people in the three districts. The median distance to public health facilities was 6 km. 62.3% of public health facilities prescribed the nationally recommended anti-malarial drug and 37.7% prescribed chloroquine as first-line therapy. 66.7% of public facilities did not have in stock the recommended first-line malaria therapy. Diagnosis of malaria using rapid diagnostic tests (RDT or microscopy was performed routinely in over 90% of the recommended public facilities but only 50% of these had RDT in stock at the time of survey. National treatment guidelines were available in 31.3% of public health facilities recommended by the national strategy. Only 8.8% of the private pharmacies prescribed artesunate plus sulphadoxine/pyrimethamine, while 53

  12. Obstetric Provider Trainees in Georgia: Characteristics and Attitudes About Practice in Obstetric Provider Shortage Areas.

    Science.gov (United States)

    Smulian, Elizabeth A; Zahedi, Leilah; Hurvitz, Julie; Talbot, Abigail; Williams, Audra; Julian, Zoë; Zertuche, Adrienne D; Rochat, Roger

    2016-07-01

    Objectives In Georgia, 52 % of the primary care service areas outside metropolitan Atlanta have a deficit of obstetric providers. This study was designed to identify factors associated with the likelihood of Georgia's obstetric trainees (obstetrics and gynecology (OB/GYN) residents and certified nurse midwifery (CNM) students) to practice in areas of Georgia that lack obstetric providers and services, i.e. rural Georgia. Methods Pilot-tested electronic and paper surveys were distributed to all of Georgia's OB/GYN residents (N = 95) and CNM students (N = 28). Mixed-methods survey questions assessed characteristics, attitudes, and incentives that might be associated with trainee desire to practice in areas of Georgia that lack obstetric providers and services. Surveys also gathered information about concerns that may prevent trainees from practicing in shortage areas. Univariate and bivariate analyses were performed, and qualitative themes were abstracted from open-ended questions. Results The survey response rate was 87.8 % (108/123). Overall, 24.4 % (19/78) of residents and 53.6 % (15/28) of CNM students expressed interest in practicing in rural Georgia, and both residents and CNM students were more likely to desire to practice in rural Georgia with the offer of any of six financial incentives (P < 0.001). Qualitative themes highlighted trainees' strong concerns about Georgia's political environment as it relates to reproductive healthcare. Conclusions Increasing state-level, rurally-focused financial incentive programs and emphasizing the role of CNMs may alleviate obstetric provider shortages in Georgia.

  13. Provider portrayals and patient-provider communication in drama and reality medical entertainment television shows.

    Science.gov (United States)

    Jain, Parul; Slater, Michael D

    2013-01-01

    Portrayals of physicians on medical dramas have been the subject of research attention. However, such research has not examined portrayals of interactions between physicians and patients, has not compared physician portrayals on medical dramas versus on medical reality programs, and has not fully examined portrayals of physicians who are members of minority groups or who received their education internationally. This study content-analyzes 101 episodes (85 hours) of such programs broadcast during the 2006-2007 viewing season. Findings indicate that women are underrepresented as physicians on reality shows, though they are no longer underrepresented as physicians on dramas. However, they are not as actively portrayed in patient-care interactions as are male physicians on medical dramas. Asians and international medical graduates are underrepresented relative to their proportion in the U.S. physician population, the latter by almost a factor of 5. Many (but certainly not all) aspects of patient-centered communication are modeled, more so on reality programs than on medical dramas. Differences in patient-provider communication portrayals by minority status and gender are reported. Implications for public perception of physicians and expectations regarding provider-patient interaction are discussed. PMID:23581602

  14. Research and Practice Communications Between Oral Health Providers and Prenatal Health Providers: A Bibliometric Analysis.

    Science.gov (United States)

    Skvoretz, John; Dyer, Karen; Daley, Ellen; Debate, Rita; Vamos, Cheryl; Kline, Nolan; Thompson, Erika

    2016-08-01

    Objectives We aimed to examine scholarly collaboration between oral health and prenatal providers. Oral disease is a silent epidemic with significant public health implications for pregnant women. Evidence linking poor oral health during pregnancy to adverse pregnancy and birth outcomes requires oral health and prenatal providers to communicate on the prevention, treatment and co-management matters pertaining to oral health issues among their pregnant patients. The need for inter-professional collaboration is highlighted by guidelines co-endorsed by the American College of Obstetricians and Gynecologists and the American Dental Association, stressing the importance of oral health care during pregnancy. Methods To assess if interdisciplinary communication occurs between oral health and prenatal disciplines, we conducted a network analysis of research on pregnancy-related periodontal disease. Results Social Network analysis allowed us to identify communication patterns between communities of oral health and prenatal professionals via scientific journals. Analysis of networks of citations linking journals in different fields reveals a core-periphery pattern dominated by oral health journals with some participation from medicine journals. However, an analysis of dyadic ties of citation reveals statistically significant "inbreeding" tendencies in the citation patterns: both medical and oral health journals tend to cite their own kind at greater-than-chance levels. Conclusions Despite evidence suggesting that professional collaboration benefits patients' overall health, findings from this research imply that little collaboration occurs between these two professional groups. More collaboration may be useful in addressing women's oral-systemic health concerns that result in adverse pregnancy outcomes.

  15. Research and Practice Communications Between Oral Health Providers and Prenatal Health Providers: A Bibliometric Analysis.

    Science.gov (United States)

    Skvoretz, John; Dyer, Karen; Daley, Ellen; Debate, Rita; Vamos, Cheryl; Kline, Nolan; Thompson, Erika

    2016-08-01

    Objectives We aimed to examine scholarly collaboration between oral health and prenatal providers. Oral disease is a silent epidemic with significant public health implications for pregnant women. Evidence linking poor oral health during pregnancy to adverse pregnancy and birth outcomes requires oral health and prenatal providers to communicate on the prevention, treatment and co-management matters pertaining to oral health issues among their pregnant patients. The need for inter-professional collaboration is highlighted by guidelines co-endorsed by the American College of Obstetricians and Gynecologists and the American Dental Association, stressing the importance of oral health care during pregnancy. Methods To assess if interdisciplinary communication occurs between oral health and prenatal disciplines, we conducted a network analysis of research on pregnancy-related periodontal disease. Results Social Network analysis allowed us to identify communication patterns between communities of oral health and prenatal professionals via scientific journals. Analysis of networks of citations linking journals in different fields reveals a core-periphery pattern dominated by oral health journals with some participation from medicine journals. However, an analysis of dyadic ties of citation reveals statistically significant "inbreeding" tendencies in the citation patterns: both medical and oral health journals tend to cite their own kind at greater-than-chance levels. Conclusions Despite evidence suggesting that professional collaboration benefits patients' overall health, findings from this research imply that little collaboration occurs between these two professional groups. More collaboration may be useful in addressing women's oral-systemic health concerns that result in adverse pregnancy outcomes. PMID:27029538

  16. Quality assessment and preservation of RNA from biobank tissue specimens: a systematic review.

    Science.gov (United States)

    Caixeiro, Nicole Joaquim; Lai, Ken; Lee, Cheok Soon

    2016-03-01

    It is well recognised that genomic, proteomic and biomarker studies require properly annotated and well-characterised biospecimens. Consequently, this necessitates biobanks to collect, store and distribute biospecimens under stringent quality control and assurance measures. However, despite this realisation, there remains a lack of standardisation in quality management among biobanks and consensus as to which quality indicators provide the optimal molecular diagnostic performance tools and information for biospecimens. In an attempt to identify key factors that predict tissue specimen integrity and quality, this systematic review investigated the measures reported in the literature, which characterised the collection, processing and storage of high-quality tissue specimens. Our findings demonstrated RNA integrity, alone, may not be an effective measure of tissue quality. Furthermore, the frequently reported parameters related to biospecimen integrity, such as storage time, temperature, time to cryopreservation and tissue morphology were also not effective indicators of quality control and assurance. These findings suggest that it is unlikely that a single marker will provide the optimal diagnostic and performance information for biospecimens, but rather, a panel of markers assessing the molecular integrity of the lifespan of the biospecimen is required. Further work is needed to identify which factors predict specimen integrity and quality in biobanked tissue specimens. PMID:26598626

  17. Cable Provider Facilities, Cable Provider Facilities, Published in Not Provided, 1:4800 (1in=400ft) scale, Warren County Emergency Services.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Cable Provider Facilities dataset, published at 1:4800 (1in=400ft) scale, was produced all or in part from Hardcopy Maps information as of Not Provided. It is...

  18. 76 FR 54474 - Submission for OMB Review; Comment Request New proposed collection, Biospecimen and Physical...

    Science.gov (United States)

    2011-09-01

    ...) investigate basic mechanisms of developmental disorders and environmental factors, both risk and protective... study of environmental influences (including physical, chemical, biological, and psychosocial) on... complete assessment of the physical, chemical, biological, and psychosocial environmental influences...

  19. Improving diversity in cancer research trials: the story of the Cancer Disparities Research Network.

    Science.gov (United States)

    Simon, Melissa A; de la Riva, Erika E; Bergan, Raymond; Norbeck, Carrie; McKoy, June M; Kulesza, Piotr; Dong, XinQi; Schink, Julian; Fleisher, Linda

    2014-06-01

    The participation of racial and ethnic minorities and underserved populations in clinical trials is a critical link between scientific innovation and improvements in health care delivery and health outcomes. However, these population groups continue to be underrepresented in research. We describe the development of the Cancer Disparities Research Network (CDRN) to improve minority and underserved populations' participation in biobanking research. Between February and October 2011, we conducted a regional assessment to identify challenges and opportunities for cancer trials and biobanking research across the CDRN. Representatives from ten CDRN biorepository facilities completed an online survey assessing their facilities' minority biospecimen collection, biobanking practices, and education/outreach initiatives. Representatives of eight facilities also participated in stakeholder interviews. The majority (70%) of facilities reported that specimens were available for research, although only one tenth of these specimens were from non-White patients. Most facilities collected a patient's age, gender, race, medical history, and ethnicity with samples; however, less than half also collected family health history, education level, household income, or primary language spoken. In addition, few institutions collected Asian or Hispanic subgroup information. Only a few reported biospecimen collection outreach programs specifically targeting minority and underserved populations. Biospecimen directors and administrators indicated that funding, biospecimen sharing procedures, and standardization barriers limited their facilities from collaborating in biospecimen collection programs, despite their great interest. These findings suggest that the CDRN can provide opportunities for collaboration, resource sharing, and fostering of research ideas to address cancer disparities in biospecimen research. PMID:24519744

  20. 22 CFR 96.12 - Authorized adoption service providers.

    Science.gov (United States)

    2010-04-01

    ... provider; or (3) An exempted provider, if the exempted provider's home study or child background study will... has been provided consistently with the Convention, the IAA, or the regulations implementing the IAA... agency, temporarily accredited agency, or approved person is providing adoption services...

  1. Road and Street Centerlines, Published in Not Provided, Embarq.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — , was produced all or in part from Not Provided information as of Not Provided. Data by this publisher are often provided in State Plane coordinate system; in a Not...

  2. Correct Diagnosis Provides Relief for Those with Dry Mouth

    Science.gov (United States)

    ... Correct Diagnosis Provides Relief for Those with Dry Mouth Article Chapters Correct Diagnosis Provides Relief for Those ... dentist regularly Reviewed: January 2012 Related Articles: Dry Mouth (Xerostomia) Acupuncture May Provide Relief from Dry Mouth ...

  3. 34 CFR 300.138 - Equitable services provided.

    Science.gov (United States)

    2010-07-01

    ... standards as personnel providing services in the public schools, except that private elementary school and... of services than children with disabilities in public schools. (b) Services provided in...

  4. 78 FR 19949 - The $500,000 Deduction Limitation for Remuneration Provided by Certain Health Insurance Providers

    Science.gov (United States)

    2013-04-02

    ... Deduction Limitation for Remuneration Provided by Certain Health Insurance Providers; Proposed Rule #0;#0... Remuneration Provided by Certain Health Insurance Providers AGENCY: Internal Revenue Service (IRS), Treasury... application of the $500,000 deduction limitation for remuneration provided by certain health...

  5. Attitudes regarding the safety of health care provider attire.

    Science.gov (United States)

    Garvin, Kanishka W; Lipira, Lauren; Neradilek, Moni; Fox, Anna; Ali, Fatima; Pottinger, Paul S

    2014-11-01

    The majority of medical providers, nurses, and patients agree that appearance is important for patient care. However, at our institution, concerns regarding providers' white coats as fomites are expressed primarily by providers and nurses, not by patients. We provide a framework for approaching this important issue through a structured quality-improvement process.

  6. Childcare Providers: Work Stress and Personal Well-Being

    Science.gov (United States)

    Faulkner, Monica; Gerstenblatt, Paula; Lee, Ahyoung; Vallejo, Viana; Travis, Dnika

    2016-01-01

    Childcare providers face multiple work-related stressors. Small studies of childcare providers have suggested that providers have high levels of depression compared to the general population. However, unlike other caregiving professions, the research examining childcare providers is sparse, and there is little information to inform practices and…

  7. Synthesis and Characterization of Five New F-bearing Basalt Reference Materials (Fba Glasses): Quantifying the Fluorine Content of the Basaltic Glass Standards BCR-2G, BHVO-2G. GSA-1G, GSC-1G, GSD-1G, GSE-1G, ML3B-G, KL2-G, and ALV-519-4

    Science.gov (United States)

    Guggino, S. N.; Hervig, R. L.

    2011-12-01

    -, detection of low-energy negative secondary ions (-5 kV), and a mass resolution that resolved 18OH. Homogeneity of the Fba glasses was established by both SIMS and EPMA. Glasses labeled Fba-2, -3. -4, and -5 pass statistical tests for homogeneity and may be used as EPMA or SIMS standards. SIMS calibration curves were constructed using the Fba glasses and other F standards of varying silica, iron, and sodium content, including Bt-3, F-phlog, NIST 610, KE-12, and UTR-2. The calibration curves revealed large matrix effects for the analysis of F by SIMS (~ 50%) between an Fba:Bt-3 curve and a high-silica glass:F-phlog curve. The Fba:Bt-3 calibration curve was used to determine the F contents (ppm ± 1 σ) of the following nine commonly used basaltic glass standards: BCR-2G (321 ± 15), BHVO-2G (297 ± 14), GSA-1G (7 ± 0.1), GSC-1G (9 ± 0.5), GSD-1G (18 ± 1), GSE-1G (154 ± 7), ML3B-G (47 ± 2), KL2-G (82 ± 4), ALV-519-4 (76 ± 4).

  8. Indian Reservations, Published in Not Provided, NC Emergency Management.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Indian Reservations dataset as of Not Provided. Data by this publisher are often provided in Not Applicable coordinate system; in a Not Applicable projection;...

  9. Address Points, Published in Not Provided, Shield Engineering, Inc..

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Address Points dataset as of Not Provided. Data by this publisher are often provided in Not Applicable coordinate system; in a Not Applicable projection; The...

  10. Hydrography, Published in Not Provided, Chautauqua County/Elk County.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Hydrography dataset as of Not Provided. Data by this publisher are often provided in State Plane coordinate system; in a Lambert Conformal-conic projection;...

  11. Poultry Houses, Published in Not Provided, US Army.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Poultry Houses dataset as of Not Provided. Data by this publisher are often provided in Not Applicable coordinate system; in a Not Applicable projection; The...

  12. State Boundaries, Published in Not Provided, Hubie's School of Learning.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This State Boundaries dataset as of Not Provided. Data by this publisher are often provided in Not Applicable coordinate system; in a Not Applicable projection; The...

  13. Pest Locations, Published in Not Provided, US Army.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Pest Locations dataset as of Not Provided. Data by this publisher are often provided in Not Applicable coordinate system; in a Not Applicable projection; The...

  14. Hog and Pig Houses, Published in Not Provided, US Army.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Hog and Pig Houses dataset as of Not Provided. Data by this publisher are often provided in Not Applicable coordinate system; in a Not Applicable projection;...

  15. Television Stations, Published in Not Provided, US Army.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Television Stations dataset as of Not Provided. Data by this publisher are often provided in Not Applicable coordinate system; in a Not Applicable projection;...

  16. Television Transmitter Locations, Published in Not Provided, US Army.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Television Transmitter Locations dataset as of Not Provided. Data by this publisher are often provided in Not Applicable coordinate system; in a Not Applicable...

  17. Broadcast Service Areas, Cable, Published in Not Provided, US Army.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Broadcast Service Areas, Cable dataset as of Not Provided. Data by this publisher are often provided in Not Applicable coordinate system; in a Not Applicable...

  18. Provider Specific Data for Public Use in SAS Format

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Fiscal Intermediary maintains the Provider Specific File (PSF). The file contains information about the facts specific to the provider that affects computations...

  19. How Do Health Care Providers Diagnose Fragile X Syndrome?

    Science.gov (United States)

    ... and Publications How do health care providers diagnose Fragile X syndrome? Skip sharing on social media links Share this: ... information helps families and providers to prepare for Fragile X syndrome and to intervene as early as possible. Possible ...

  20. Government Buildings, Owned, Published in Not Provided, The Keith Corporation.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Government Buildings, Owned dataset as of Not Provided. Data by this publisher are often provided in Not Sure coordinate system; in a Not Sure projection; The...

  1. Talk with Your Health Care Provider about High Cholesterol

    Science.gov (United States)

    ... you do? Always ask your provider what your cholesterol numbers are and write them down. Discuss these ... provider may prescribe medicine to help lower your cholesterol. y y Take your medicine every day, or ...

  2. Agriculture, Fruit and Orchards, Published in Not Provided, US Army.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Agriculture, Fruit and Orchards dataset as of Not Provided. Data by this publisher are often provided in Not Applicable coordinate system; in a Not Applicable...

  3. Government Buildings, Leased, Published in Not Provided, The Keith Corporation.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Government Buildings, Leased dataset as of Not Provided. Data by this publisher are often provided in Not Sure coordinate system; in a Not Sure projection; The...

  4. On Fair Network Cache Allocation to Content Providers

    OpenAIRE

    Hoteit, Sahar; El Chamie, Mahmoud; Saucez, Damien; Secci, Stefano

    2016-01-01

    International audience In-network caching is an important solution for content offloading from content service providers. However despite a rather high maturation in the definition of caching techniques, minor attention has been given to the strategic interaction among the multiple content providers. Situations involving multiple Content Providers (CPs) and one Internet Service Provider (ISP) having to give them access to its caches are prone to high cache contention, in particular at the ...

  5. Outsourcing customer support : The role of provider customer focus

    NARCIS (Netherlands)

    Wuyts, S.H.K.; Rindfleisch, A.; Citrin, A.

    2015-01-01

    An increasing number of firms are outsourcing customer support to external service providers. This creates a triadic setting in which an outsourcing provider serves end customers on behalf of its clients. While outsourcing presents an opportunity to serve customers, service providers differ in their

  6. Lessons from VET Providers Delivering Degrees: Case Studies. Support Document

    Science.gov (United States)

    Callan, Victor J.; Bowman, Kaye

    2015-01-01

    The recent growth in the number of registered vocational education and training (VET) providers delivering associate degrees and bachelor degrees in their own right has been well publicized. However, little is known about why these VET providers have made this transition, what support is being provided to their staff and students, and how the…

  7. 20 CFR 220.45 - Providing evidence of disability.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Providing evidence of disability. 220.45... DETERMINING DISABILITY Evidence of Disability § 220.45 Providing evidence of disability. (a) General. The claimant for a disability annuity is responsible for providing evidence of the claimed disability and...

  8. 7 CFR 400.406 - Insurance provider responsibilities.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Insurance provider responsibilities. 400.406 Section 400.406 Agriculture Regulations of the Department of Agriculture (Continued) FEDERAL CROP INSURANCE... Insurance provider responsibilities. The insurance provider is required to collect and record the SSN or...

  9. Provider-sponsored HMOs: make, buy, or joint venture?

    Science.gov (United States)

    Clay, S B

    1997-03-01

    Providers can sponsor their own HMOs in one of three ways: by creating their own HMO, by joint venturing with an existing HMO, or by purchasing an existing HMO. When selecting the best option, providers must consider various market conditions. Managed care penetration in the area, potential competitive responses of existing HMOs, market demand, provider reputation, and provider marketing ability will all influence the feasibility of each option. Providers also must examine their own organizational identity, their ability to raise the necessary capital to start an HMO, their managed care expertise and risk contracting experience, and their information systems capabilities.

  10. Are Private Providers more Productive and Efficient than Public Providers of International Education? Evidence from New Zealand

    Directory of Open Access Journals (Sweden)

    Dayal TALUKDER

    2011-10-01

    Full Text Available This study has investigated the productivity growth and efficiency of private and public providers of international education in New Zealand. It has used secondary data to calculate the DEA-based Malmquist productivity index for measuring Total Factor Productivity (TFP-growth and efficiency of both public and private providers of international education during 1999-2010. The study has found that private providers experienced a larger TFP-growth than that of public providers during 1999-2004. However, they experienced a sharp decline in TFP-growth since 2005 through to 2010 and experienced a much smaller TFP-growth than that of public providers during this period. Conversely, public providers experienced a positive TFP-growth during 1999-2004 but they experienced a negative TFP-growth since 2005 through to 2010. Considering efficiency, both private and public providers experienced almost a constant Technical Efficiency Change (TEC having a same level of efficiency of one. Both private and public providers exhibited a constant return to scale during 1999-2010. This study argues that on an average, private providers are more productive than public providers of international education. However, they are not more efficient than public providers as both types of providers exhibited a constant return to scale during 1999-2010. This study also argues that TFP-growth of New Zealand’s international education was determined by Technological Change (TC, not by TEC during this period.

  11. The perspective of rural physicians providing abortion in Canada: qualitative findings of the BC Abortion Providers Survey (BCAPS.

    Directory of Open Access Journals (Sweden)

    Jennifer Dressler

    Full Text Available BACKGROUND: An increasing proportion of Canadian induced abortions are performed in large urban areas. For unknown reasons the number of rural abortion providers in Canadian provinces, such as British Columbia (BC, has declined substantially. This study explored the experiences of BC rural and urban physicians providing abortion services. METHODS: The mixed methods BC Abortion Providers Survey employed self-administered questionnaires, distributed to all known current and some past BC abortion providers in 2011. The optional semi-structured interviews are the focus of this analysis. Interview questions probed the experiences, facilitators and challenges faced by abortion providers, and their future intentions. Interviews were transcribed and analyzed using cross-case and thematic analysis. RESULTS: Twenty interviews were completed and transcribed, representing 13/27 (48.1% rural abortion providers, and 7/19 (36.8% of urban providers in BC. Emerging themes differed between urban and rural providers. Most urban providers worked within clinics and reported a supportive environment. Rural physicians, all providing surgical abortions within hospitals, reported challenging barriers to provision including operating room scheduling, anesthetist and nursing logistical issues, high demand for services, professional isolation, and scarcity of replacement abortion providers. Many rural providers identified a need to "fly under the radar" in their small community. DISCUSSION: This first study of experiences among rural and urban abortion providers in Canada identifies addressable challenges faced by rural physicians. Rural providers expressed a need for increased support from hospital administration and policy. Further challenges identified include a desire for continuing professional education opportunities, and for available replacement providers.

  12. Development of an educational module on provider self-care.

    Science.gov (United States)

    Meadors, Patrick; Lamson, Angela; Sira, Natalia

    2010-01-01

    Intensive care providers who care for traumatized populations often face multiple traumas for extended periods and are vulnerable to developing lasting symptoms of compassion fatigue and secondary traumatization. Symptoms are often not recognizable until compassion fatigue or secondary traumatization negatively affects the providers' ability to care for their patients. More attention needs to be given to the care of the provider to ensure high-quality patient care, decrease turnover in the profession, and increase productivity. This article provides a framework for the development of an educational module for healthcare providers' self-care. This educational module created the opportunity to share with providers (a) how to explore their own professional experience; (b) how to recognize the different symptoms of compassion fatigue, primary traumatization, and secondary traumatization; (c) factors related to grief reactions; and (d) personal and professional strategies to decrease compassion fatigue and secondary traumatization. PMID:20683299

  13. Management of behavioral health provider networks in private health plans.

    Science.gov (United States)

    Garnick, Deborah W; Horgan, Constance M; Reif, Sharon; Merrick, Elizabeth L; Hodgkin, Dominic

    2008-01-01

    We explored the techniques used by private health plans or by their contracted managed behavioral healthcare organizations (MBHOs) to maintain networks of behavioral health providers. In particular, we focused on differences by health plans' product types (health maintenance organization, point-of-service plan, or preferred provider organization) and contracting arrangements (MBHO contracts, comprehensive contracts, or no contracts). More than 94% of products selected providers using credentialing standards, particular specialists, or geographic coverage. To retain providers viewed as high quality, 54% offer reduced administrative burden and 44% higher fees. Only 16% reported steerage to a core group of highest-quality providers and few reported an annual bonus or guaranteed volume of referrals. Some standard activities are common, but some health plans are adopting other approaches to retain higher-quality providers.

  14. Provider attributes correlation analysis to their referral frequency and awards

    OpenAIRE

    Wiley, Matthew T.; Rivas, Ryan L.; Hristidis, Vagelis

    2016-01-01

    Background There has been a recent growth in health provider search portals, where patients specify filters—such as specialty or insurance—and providers are ranked by patient ratings or other attributes. Previous work has identified attributes associated with a provider’s quality through user surveys. Other work supports that intuitive quality-indicating attributes are associated with a provider’s quality. Methods We adopt a data-driven approach to study how quality indicators of providers ar...

  15. 22 CFR 96.44 - Acting as primary provider.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Acting as primary provider. 96.44 Section 96.44... Approval Service Planning and Delivery § 96.44 Acting as primary provider. (a) When required by § 96.14(a), the agency or person acts as primary provider and adheres to the provisions in § 96.14(b) through...

  16. Human Trafficking: The Role of the Health Care Provider

    OpenAIRE

    Dovydaitis, Tiffany

    2010-01-01

    Human trafficking is a major public health problem, both domestically and internationally. Health care providers are often the only professionals to interact with trafficking victims who are still in captivity. The expert assessment and interview skills of providers contribute to their readiness to identify victims of trafficking. The purpose of this article is to provide clinicians with knowledge on trafficking and give specific tools that they may use to assist victims in the clinical setti...

  17. Effective Patient-Provider Communication in Pediatric Obesity.

    Science.gov (United States)

    Carcone, April Idalski; Jacques-Tiura, Angela J; Brogan Hartlieb, Kathryn E; Albrecht, Terrance; Martin, Tim

    2016-06-01

    Effective patient-provider communication is not a primary focus of medical school curricula. Motivational interviewing (MI) is a patient-centered, directive communication framework appropriate for in health care. Research on MI's causal mechanisms has established patient change talk as a mediator of behavior change. Current MI research focuses on identifying which provider communication skills are responsible for evoking change talk. MI recommends informing, asking, and listening. Research provides evidence that asking for and reflecting patient change talk are effective communication strategies, but cautions providers to inform judiciously. Supporting a patient's decision making autonomy is an important strategy to promote health behaviors. PMID:27261548

  18. Full amnesty could encourage provider self-disclosure.

    Science.gov (United States)

    Mustokoff, M M; Nagele, R L; Swichar, J L

    2000-07-01

    The Federal government's current policy toward healthcare providers that voluntarily disclose improprieties has been ineffective because it offers no guarantee of immunity from prosecution. To be successful, a self-disclosure program must offer real incentives to providers to come forward. The government's self-disclosure programs with respect to tax, environmental, and antitrust laws provide models for an effective amnesty program. The success of these three programs, and particularly of the antitrust program, suggests that healthcare providers would be encouraged to come forward and disclose improprieties if, under certain specific conditions, the OIG and DOJ offered a guarantee of full amnesty to the entity and its officers, directors, and employees.

  19. External Service Providers to the National Security Technology Incubator

    Energy Technology Data Exchange (ETDEWEB)

    None

    2008-02-28

    This report documents the identification and assessment of external service providers to the National Security Technology Incubator (NSTI) program for southern New Mexico. The NSTI is being developed as part of the National Security Preparedness Project (NSPP), funded by a Department of Energy (DOE)/National Nuclear Security Administration (NNSA) grant to Arrowhead Center, New Mexico State University. This report contains 1) a summary of the services to be provided by NSTI; 2) organizational descriptions of external service providers; and 3) a comparison of NSTI services and services offered by external providers.

  20. Consumer satisfaction with primary care provider choice and associated trust

    Directory of Open Access Journals (Sweden)

    Balkrishnan Rajesh

    2006-10-01

    Full Text Available Abstract Background Development of managed care, characterized by limited provider choice, is believed to undermine trust. Provider choice has been identified as strongly associated with physician trust. Stakeholders in a competitive healthcare market have competing agendas related to choice. The purpose of this study is to analyze variables associated with consumer's satisfaction that they have enough choice when selecting their primary care provider (PCP, and to analyze the importance of these variables on provider trust. Methods A 1999 randomized national cross-sectional telephone survey conducted of United States residential households, who had a telephone, had seen a medical professional at least twice in the past two years, and aged ≥ 20 years was selected for secondary data analyses. Among 1,117 households interviewed, 564 were selected as the final sample. Subjects responded to a core set of questions related to provider trust, and a subset of questions related to trust in the insurer. A previously developed conceptual framework was adopted. Linear and logistic regressions were performed based on this framework. Results Results affirmed 'satisfaction with amount of PCP choice' was significantly (p Conclusion This study confirmed the association of 'satisfaction with amount of PCP choice' with provider trust. Results affirmed 'enough PCP choice' was a strong predictor of provider trust. 'Second opinion on PCP' may indicate distrust in the provider. Data such as 'trust in providers in general' and 'the role of provider performance information' in choice, though import in PCP choice, were not available for analysis and should be explored in future studies. Results have implications for rethinking the relationships among consumer choice, consumer behaviors in making trade-offs in PCP choice, and the role of healthcare experiences in 'satisfaction with amount of PCP choice' or 'provider trust.'

  1. Providing Culturally Competent Services to Visually Impaired Persons.

    Science.gov (United States)

    Bau, Angela M.

    1999-01-01

    Discusses providing culturally competent services to individuals with visual impairments and seven cultural values: communication, health beliefs and practice, family structure, attitudes toward authority, etiquette, expectations of "helping," and time orientation. Provides suggestions for meeting cross-cultural challenges through skills used in…

  2. Providers' response to child eating behaviors: A direct observation study.

    Science.gov (United States)

    Tovar, Alison; Vaughn, Amber E; Fallon, Megan; Hennessy, Erin; Burney, Regan; Østbye, Truls; Ward, Dianne S

    2016-10-01

    Child care providers play an important role in feeding young children, yet little is known about children's influence on providers' feeding practices. This qualitative study examines provider and child (18 months -4 years) feeding interactions. Trained data collectors observed 200 eating occasions in 48 family child care homes and recorded providers' responses to children's meal and snack time behaviors. Child behaviors initiating provider feeding practices were identified and practices were coded according to higher order constructs identified in a recent feeding practices content map. Analysis examined the most common feeding practices providers used to respond to each child behavior. Providers were predominately female (100%), African-American (75%), and obese (77%) and a third of children were overweight/obese (33%). Commonly observed child behaviors were: verbal and non-verbal refusals, verbal and non-verbal acceptance, being "all done", attempts for praise/attention, and asking for seconds. Children's acceptance of food elicited more autonomy supportive practices vs. coercive controlling. Requests for seconds was the most common behavior, resulting in coercive controlling practices (e.g., insisting child eat certain food or clean plate). Future interventions should train providers on responding to children's behaviors and helping children become more aware of internal satiety and hunger cues. PMID:27328098

  3. Residents provide feedback to their clinical teachers: Reflection through dialogue

    NARCIS (Netherlands)

    Fluit, C.R.; Bolhuis, S.M.; Klaassen, T.; Visser, M. de; Grol, R.P.T.M.; Laan, R.F.; Wensing, M.

    2013-01-01

    Background: Physicians play a crucial role in teaching residents in clinical practice. Feedback on their teaching performance to support this role needs to be provided in a carefully designed and constructive way. Aims: We investigated an evaluation system for evaluating supervisors and providing fo

  4. Understanding Emotional Development: Helping Early Childhood Providers Better Support Families

    Science.gov (United States)

    Edwards, Nicole Megan

    2012-01-01

    This article is intended to provide early childhood providers with a concise overview of emerging emotional development in young children (birth-5), the important role of primary caregivers, and the link between parenting, emotional development, and behavior. Specific suggestions that have been shared with urban Head Start mothers are offered,…

  5. The Role of Child Care Providers in Child Abuse Prevention

    Science.gov (United States)

    Seibel, Nancy L.; Gillespie, Linda G.; Temple, Tabitha

    2008-01-01

    Child care providers are likely to be the professionals who most frequently interact with families with young children. Thus, infant and toddler child care providers are uniquely positioned to recognize and respond to families' needs for information and support. This article describes knowledge, skills, and strategies that support child care…

  6. 7 CFR 1788.55 - Providing RUS evidence.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Providing RUS evidence. 1788.55 Section 1788.55... AGRICULTURE (CONTINUED) RUS FIDELITY AND INSURANCE REQUIREMENTS FOR ELECTRIC AND TELECOMMUNICATIONS BORROWERS Insurance for Contractors, Engineers, and Architects, Telecommunications Borrowers § 1788.55 Providing...

  7. Responding to discriminatory requests for a different healthcare provider.

    Science.gov (United States)

    Anstey, Kyle; Wright, Linda

    2014-02-01

    Patient requests for a healthcare provider of a particular race or sexual orientation create a conflict of obligations. On the one hand, providers have a duty to deliver clinically indicated care consistent with patient preferences. On the other hand, providers have legal, professional, and organizational assurances that they should not suffer workplace discrimination. Protecting healthcare providers from harm while maintaining obligations to patients requires unambiguous messaging to both parties. Providers need to be clear that their organization will not be complicit in discrimination against them, instead supporting their needs and preferences for management of the situation. In a context of patient-centered care, harm principle-based boundaries of respect for autonomy must be defined. A Caregiver preference guideline developed and used at University Health Network, Toronto provides a standardized way for the organization to decide when it will honor patient requests for providers of a particular background. This process stresses dialogue, assessment of clinical feasibility, and empowerment and support for affected care providers. PMID:23801379

  8. 7 CFR 272.9 - Approval of homeless meal providers.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false Approval of homeless meal providers. 272.9 Section 272... AGENCIES § 272.9 Approval of homeless meal providers. The State food stamp agency, or another appropriate... does in fact serve meals to homeless persons. Where the State food stamp agency identifies...

  9. A joint venture in providing home care and community service.

    Science.gov (United States)

    Reifsteck, S

    1987-01-01

    General discussion of a joint venture providing home care and community service including future possibilities, business and financial aspects and demand is presented. The author then provides a group practice joint venture model including descriptions of operating structure, contract arrangements and management.

  10. 22 CFR 96.46 - Using providers in Convention countries.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Using providers in Convention countries. 96.46... AND APPROVAL OF PERSONS UNDER THE INTERCOUNTRY ADOPTION ACT OF 2000 (IAA) Standards for Convention Accreditation and Approval Service Planning and Delivery § 96.46 Using providers in Convention countries....

  11. Return on Investment Point of Service Computerized Provider Charge Entry

    OpenAIRE

    Kiepek, Wendy; Fitzhenry, Fern1; Shultz, Edward K.

    2003-01-01

    Provider charge entry systems offer many benefits to users and organizations. At Vanderbilt University Medical Center, a web-based provider charge entry system promises to deliver benefits in reducing days in accounts receivable, reducing labor required for claims and edit processing, and implementing business rules that deliver both strategic and financial benefits.

  12. "If Only Someone Had Told Me ...": Lessons from Rural Providers

    Science.gov (United States)

    Chipp, Cody; Dewane, Sarah; Brems, Christiane; Johnson, Mark E.; Warner, Teddy D.; Roberts, Laura W.

    2011-01-01

    Purpose: Health care providers face challenges in rural service delivery due to the unique circumstances of rural living. The intersection of rural living and health care challenges can create barriers to care that providers may not be trained to navigate, resulting in burnout and high turnover. Through the exploration of experienced rural…

  13. How Childcare Providers Interpret "Reasonable Suspicion" of Child Abuse

    Science.gov (United States)

    Levi, Benjamin H.; Crowell, Kathryn; Walsh, Kerryann; Dellasega, Cheryl

    2015-01-01

    Background: Childcare providers are often "first responders" for suspected child abuse, and how they understand the concept of "reasonable suspicion" will influence their decisions regarding which warning signs warrant reporting. Objective: The purpose of this study was to investigate how childcare providers interpret the…

  14. Statistics Report on TEQSA Registered Higher Education Providers

    Science.gov (United States)

    Australian Government Tertiary Education Quality and Standards Agency, 2014

    2014-01-01

    This report is the first release of selected data held and analysed by The Tertiary Education Quality Standards Agency (TEQSA) for its regulatory purposes that provides a complete view of the sector that has not previously been disseminated. As the national regulator of all Australian higher education providers, TEQSA is in a unique position in…

  15. Communicating Effectively with Non-Indian Service Providers.

    Science.gov (United States)

    Manuelito, Jeannie; Johnson, Martha

    This paper provides Indian parents of children with disabilities with information from the Education for Parents of Indian Children with Special Needs Project concerning communication between Indian parents and non-Indian service providers. Five basic strategies for effective communication are reviewed: (1) when you do not understand, ask for…

  16. 20 CFR 404.1662 - What support we will provide.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false What support we will provide. 404.1662 Section 404.1662 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND... support we will provide. Performance support may include, but is not limited to, any or all of...

  17. 20 CFR 416.1062 - What support we will provide.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false What support we will provide. 416.1062 Section 416.1062 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE... What support we will provide. Performance support may include, but is not limited to, any or all of...

  18. 8 CFR 204.302 - Role of service providers.

    Science.gov (United States)

    2010-01-01

    ... facilitator that is not authorized under 8 CFR part 292 to engage in representation before USCIS. (c... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Role of service providers. 204.302 Section... PETITIONS Intercountry Adoption of a Convention Adoptee § 204.302 Role of service providers. (a) Who...

  19. Arbitration clauses in contracts between providers and patients.

    Science.gov (United States)

    Buckner, F

    1998-01-01

    Arbitration clauses in contracts between health care providers and their patients can offer benefits to both parties. However, practitioners need to ensure that their contracts will not be judged unenforceable by a court. This article outlines the contractual and constitutional issues involved in arbitration agreements and provides advice to practitioners on drafting such an agreement. PMID:10662267

  20. 14 CFR 1263.110 - Intention to provide guidance.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Intention to provide guidance. 1263.110 Section 1263.110 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION DEMAND FOR INFORMATION OR TESTIMONY SERVED ON AGENCY EMPLOYEES; PROCEDURES § 1263.110 Intention to provide guidance....

  1. 39 CFR 501.2 - Postage Evidencing System provider authorization.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Postage Evidencing System provider authorization... MANUFACTURE AND DISTRIBUTE POSTAGE EVIDENCING SYSTEMS § 501.2 Postage Evidencing System provider authorization. (a) The Postal Service considers Postage Evidencing Systems and their respective infrastructure to...

  2. 39 CFR 501.3 - Postage Evidencing System provider qualification.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Postage Evidencing System provider qualification... MANUFACTURE AND DISTRIBUTE POSTAGE EVIDENCING SYSTEMS § 501.3 Postage Evidencing System provider qualification. Any person or entity seeking authorization to manufacture and/or distribute Postage Evidencing...

  3. A Novel Trust Service Provider for Internet Based Commerce Applications.

    Science.gov (United States)

    Siyal, M. Y.; Barkat, B.

    2002-01-01

    Presents a framework for enhancing trust in Internet commerce. Shows how trust can be provided through a network of Trust Service Providers (TSp). Identifies a set of services that should be offered by a TSp. Presents a distributed object-oriented implementation of trust services using CORBA, JAVA and XML. (Author/AEF)

  4. Rolls-Royce Becomes Provider for West-East Pipeline

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ Rolls-Royce, a leading provider of gas turbines for global energy markets, announced on February that it has won the contract to provide Rolls-Royce pipeline compression equipment for China's West-East Gas Pipeline Project (WEPP). The contract is valued at over US$150 million.

  5. 25 CFR 47.4 - When does OIEP provide funding?

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false When does OIEP provide funding? 47.4 Section 47.4 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION UNIFORM DIRECT FUNDING AND SUPPORT FOR BUREAU-OPERATED SCHOOLS § 47.4 When does OIEP provide funding? By July 1 of each year OIEP will...

  6. Early Intervention Provider Use of Child Caregiver-Teaching Strategies

    Science.gov (United States)

    Campbell, Philippa H.; Coletti, Catherine Ehret

    2013-01-01

    The purpose of this study was to identify the extent to which multidiscipline early intervention providers identified and demonstrated caregiver-teaching strategies. A total of 78 providers submitted 205 videotaped segments to illustrate 1 of 5 caregiver-teaching strategies (i.e., demonstration; caregiver practice with feedback; guided practice;…

  7. Using Turnitin to Provide Feedback on L2 Writers' Texts

    Science.gov (United States)

    Kostka, Ilka; Maliborska, Veronika

    2016-01-01

    Second language (L2) writing instructors have varying tools at their disposal for providing feedback on students' writing, including ones that enable them to provide written and audio feedback in electronic form. One tool that has been underexplored is Turnitin, a widely used software program that matches electronic text to a wide range of…

  8. Providers' Perceptions of Challenges in Obstetrical Care for Somali Women

    Directory of Open Access Journals (Sweden)

    Jalana N. Lazar

    2013-01-01

    Full Text Available Background. This pilot study explored health care providers’ perceptions of barriers to providing health care services to Somali refugee women. The specific aim was to obtain information about providers’ experiences, training, practices and attitudes surrounding the prenatal care, delivery, and management of women with Female Genital Cutting (FGC. Methods. Individual semi-structured interviews were conducted with 14 obstetricians/gynecologists and nurse midwives in Columbus, Ohio. Results. While providers did not perceive FGC as a significant barrier in itself, they noted considerable challenges in communicating with their Somali patients and the lack of formal training or protocols guiding the management of circumcised women. Providers expressed frustration with what they perceived as Somali patients' resistance to obstetrical interventions and disappointment with a perception of mistrust from patients and their families. Conclusion. Improving the clinical encounter for both patients and providers entails establishing effective dialogue, enhancing clinical and cultural training of providers, improving health literacy, and developing trust through community engagement.

  9. Employee motivation in Product-Service-System providers

    DEFF Research Database (Denmark)

    Kreye, Melanie

    2016-01-01

    This research investigates how intrinsic and extrinsic motivation factors contribute to employee motivation in providers of Product-Service Systems (PSS). Employee motivation determines the quality of the delivered service and is thus an area of great importance for PSS providers. We present rich...... case-based data collected through semi-structured interviews, a survey and secondary sources. The analysis showed the particularly high importance of intrinsic and individual motivation factors such as the fulfilling nature of the work and skill development showing the ownership and pride service...... employees took in their work. Further, the organisation needs to set the context of high employee motivation by enabling flexibility and performance feedback. Our research contributes to the literature by providing a first empirical study of employee motivation in PSS providers and thus providing important...

  10. Enhancing genomic laboratory reports: A qualitative analysis of provider review

    Science.gov (United States)

    Rahm, Alanna Kulchak; Stuckey, Heather; Green, Jamie; Feldman, Lynn; Zallen, Doris T.; Bonhag, Michele; Segal, Michael M.; Fan, Audrey L.; Williams, Marc S.

    2016-01-01

    This study reports on the responses of physicians who reviewed provider and patient versions of a genomic laboratory report designed to communicate results of whole genome sequencing. Semi‐structured interviews addressed concept communication, elements, and format of example genome reports. Analysis of the coded transcripts resulted in recognition of three constructs around communication of genome sequencing results: (1) Providers agreed that whole genomic sequencing results are complex and they welcomed a report that provided supportive interpretation information to accompany sequencing results; (2) Providers strongly endorsed a report that included active clinical guidance, such as reference to practice guidelines, if available; and (3) Providers valued the genomic report as a resource that would serve as the basis to facilitate communication of genome sequencing results with their patients and families. Providers valued both versions of the report, though they affirmed the need for a provider‐oriented report. Critical elements of the report included clear language to explain the result, as well as consolidated yet comprehensive prognostic information with clear guidance over time for the clinical care of the patient. Most importantly, it appears a report with this design has the potential not only to return results but also serves as a communication tool to help providers and patients discuss and coordinate care over time. © 2016 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc. PMID:26842872

  11. Trust Your Cloud Service Provider: User Based Crypto Model. Sitanaboina

    Directory of Open Access Journals (Sweden)

    Sri Lakshmi Parvathi

    2014-10-01

    Full Text Available In Data Storage as a Service (STaaS cloud computing environment, the equipment used for business operations can be leased from a single service provider along with the application, and the related business data can be stored on equipment provided by the same service provider. This type of arrangement can help a company save on hardware and software infrastructure costs, but storing the company’s data on the service provider’s equipment raises the possibility that important business information may be improperly disclosed to others [1]. Some researchers have suggested that user data stored on a service-provider’s equipment must be encrypted [2]. Encrypting data prior to storage is a common method of data protection, and service providers may be able to build firewalls to ensure that the decryption keys associated with encrypted user data are not disclosed to outsiders. However, if the decryption key and the encrypted data are held by the same service provider, it raises the possibility that high-level administrators within the service provider would have access to both the decryption key and the encrypted data, thus presenting a risk for the unauthorized disclosure of the user data. we in this paper provides an unique business model of cryptography where crypto keys are distributed across the user and the trusted third party(TTP with adoption of such a model mainly the CSP insider attack an form of misuse of valuable user data can be treated secured.

  12. Privately Provided Accommodation Service Quality and Customer Satisfaction

    Directory of Open Access Journals (Sweden)

    Joshua Mugambwa

    2016-04-01

    Full Text Available Privately provided accommodation is a growing service in Uganda’s higher education sector due to education liberalization and demand for education. This research took a case study of Nsamizi Training Institute of Social Development (NTISD to determine the relationship between privately provided accommodation service quality and customer satisfaction. Specifically, the objectives of the study were (a to find out the relationship between security and NTISD students’ satisfaction with privately provided accommodation, and (b to find out the hierarchical level of importance of NTISD student satisfaction of the three service quality dimensions (reliability, security, and tangibles with privately provided accommodation. Using quantitative and qualitative modes of data analysis and a sample of 300 students from 20 private hostels, this study established a strong positive significant relationship between security and satisfaction regarding privately provided accommodation. This implies that accommodation service providers should increase the quality of security so as to increase the satisfaction of students regarding privately provided accommodation. The study established the hierarchical order of importance from the most important service quality dimension, respectively, as follows: reliability, security, and tangibles. Therefore, private accommodation service managers should pay extra attention to the dimensions in the same order.

  13. Clinical trial participant characteristics and saliva and DNA metrics

    Directory of Open Access Journals (Sweden)

    Richards Julie

    2009-10-01

    Full Text Available Abstract Background Clinical trial and epidemiological studies need high quality biospecimens from a representative sample of participants to investigate genetic influences on treatment response and disease. Obtaining blood biospecimens presents logistical and financial challenges. As a result, saliva biospecimen collection is becoming more frequent because of the ease of collection and lower cost. This article describes an assessment of saliva biospecimen samples collected through the mail, trial participant demographic and behavioral characteristics, and their association with saliva and DNA quantity and quality. Methods Saliva biospecimens were collected using the Oragene® DNA Self-Collection Kits from participants in a National Cancer Institute funded smoking cessation trial. Saliva biospecimens from 565 individuals were visually inspected for clarity prior to and after DNA extraction. DNA samples were then quantified by UV absorbance, PicoGreen®, and qPCR. Genotyping was performed on 11 SNPs using TaqMan® SNP assays and two VNTR assays. Univariate, correlation, and analysis of variance analyses were conducted to observe the relationship between saliva sample and participant characteristics. Results The biospecimen kit return rate was 58.5% among those invited to participate (n = 967 and 47.1% among all possible COMPASS participants (n = 1202. Significant gender differences were observed with males providing larger saliva volume (4.7 vs. 4.5 ml, p = 0.019, samples that were more likely to be judged as cloudy (39.5% vs. 24.9%, p 0.21, P Conclusion Findings from this study show that demographic and behavioral characteristics of smoking cessation trial participants have significant associations with saliva and DNA metrics, but not with the performance of TaqMan® SNP or VNTR genotyping assays. Trial registration COMPASS; registered as NCT00301145 at clinicaltrials.gov.

  14. Conditions of Caregiving, Provider Nurturance, and Quality Care

    OpenAIRE

    Austin, Ann Marie Berghout; Lindauer, Shelley L. Knudsen; Rodriquez, Ariel; Nortion, Maria L.; Nelson, Farol A. Groutage

    1997-01-01

    Participants included 36 licensed family day care providers from six rural counties who had been providing care for a mean of 8.3 years (SO = 6.8 years). Fourteen of the providers had earned high school diplomas; twenty‐two had some post high school education. At least one child from an economically strained home (as measured by AFDC receipt) was present in 44.4% of the FDC homes. Dependent measures included: The Caregiver Interaction Scale (Arnett, 1989); Elaboration Scale from The Family Da...

  15. AN ADAPTIVE AQM TO PROVIDE DELAY GUARANTEES FOR DIFFERENTIATED SERVICES

    Institute of Scientific and Technical Information of China (English)

    Yang Zongkai; Liu Wei; He Jianhua; Chou Chuntung

    2005-01-01

    RIO(RED with IN and OUT) is the primary queue management mechanism proposed for assured forwarding in the DiffServ (Differentiated Service) framework. Although RIO can generally provide bandwidth guarantees, its queuing delay is sensitive to the traffic load. This paper presents a qualitative explanation for its origin. As a solution, an Adaptive RIO for Delay (ARIO-D) is proposed to provide guaranteed delay for multimedia traffic. Simulation results show that by trading loss for delay, ARIO-D can effectively improve the robustness of RIO under different and dynamic traffic, and provide stable and differentiated performance of queuing delay without any degradation in performance of throughput.

  16. Find Ryan White HIV/AIDS Medical Care Providers

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Find Ryan White HIV/AIDS Medical Care Providers tool is a locator tool designed to make data and information concerning HIV/AIDS resources more easily available...

  17. How Do Health Care Providers Diagnose Rett Syndrome?

    Science.gov (United States)

    ... and Publications How do health care providers diagnose Rett syndrome? Skip sharing on social media links Share this: ... would rule out a Rett syndrome diagnosis. Atypical Rett Syndrome Genetic mutations causing some atypical variants of Rett ...

  18. NPS Team Provides Emergency Wireless Communications to Haiti

    OpenAIRE

    Naval Postgraduate School Public Affairs Office

    2010-01-01

    The Naval Postgraduate School is providing a critical component of humanitarian assistance and disaster relief to the people of Haiti struggling in the wake of the devastating 7.0 earthquake – desperately needed emergency communications.

  19. Rural and Urban Hospitals' Role in Providing Inpatient Care, 2010

    Science.gov (United States)

    ... National Technical Information Service NCHS Rural and Urban Hospitals' Role in Providing Inpatient Care, 2010 Recommend on ... Survey, inpatient hospital utilization What share of inpatient hospital care was delivered in rural compared with urban ...

  20. Increasing the marketability and recognition of provider network joint ventures.

    Science.gov (United States)

    Sjobeck, S J

    1998-08-01

    Physicians have been developing provider network joint ventures to market their services jointly to managed care plans, employers, and other purchasers. Over the past few years, external market factors have produced a growing impact on these joint ventures. These external market factors include the Federal government's revised antitrust guidelines, National Committee for Quality Assurance activities, and state and Federal consumer protection laws. Simply responding to these forces may not increase a provider network's marketability unless the network can demonstrate its value in the terms and measurements accepted by the consumer, managed care plans, and provider networks. By doing so, a provider network can not only increase its marketability, but also increase its recognition in the market, improve its competitive advantage, and enhance its return on investment.

  1. NIH scientists provide new insight into rare kidney cancer

    Science.gov (United States)

    NIH scientists have discovered a unique feature of a rare, hereditary form of kidney cancer that may provide a better understanding of its progression and metastasis, possibly laying the foundation for the development of new targeted therapies.

  2. Systems approach provides management control of complex programs

    Science.gov (United States)

    Dudek, E. F., Jr.; Mc Carthy, J. F., Jr.

    1970-01-01

    Integrated program management process provides management visual assistance through three interrelated charts - system model that identifies each function to be performed, matrix that identifies personnel responsibilities for these functions, process chart that breaks down the functions into discrete tasks.

  3. Identifying tools and strategies to provide quality oncology care

    OpenAIRE

    Ganz, PA

    2013-01-01

    This session of the ASCO Quality Symposium provided an opportunity to examine a variety of research and quality improvement strategies aimed at improving the quality of cancer care along the continuum.

  4. Choosing the right health care provider for pregnancy and childbirth

    Science.gov (United States)

    ... Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Choosing the right health care provider for pregnancy and childbirth URL of this page: //medlineplus.gov/ency/patientinstructions/ ...

  5. How Do Health Care Providers Diagnose Spina Bifida?

    Science.gov (United States)

    ... and Publications How do health care providers diagnose spina bifida? Skip sharing on social media links Share this: Page Content Doctors diagnose spina bifida before or after the infant is born. Spina ...

  6. How Do Health Care Providers Diagnose Turner Syndrome?

    Science.gov (United States)

    ... and Publications How do health care providers diagnose Turner syndrome? Skip sharing on social media links Share this: ... the X chromosomes is partially or completely missing. Turner syndrome also can be diagnosed during pregnancy by testing ...

  7. Broadcast Service Areas, Other, Published in Not Provided, CPMC Mortgage.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Broadcast Service Areas, Other dataset, was produced all or in part from Published Reports/Deeds information as of Not Provided. The extent of these data is...

  8. Athena: Providing Insight into the History of the Universe

    Science.gov (United States)

    Murphy, Gloria A.

    2010-01-01

    The American Institute for Aeronautics and Astronautics has provided a Request for Proposal which calls for a manned mission to a Near-Earth Object. It is the goal of Team COLBERT to respond to their request by providing a reusable system that can be implemented as a solid stepping stone for future manned trips to Mars and beyond. Despite Team COLBERT consisting of only students in Aerospace Engineering, in order to achieve this feat, the team must employ the use of Systems Engineering. Tools and processes from Systems Engineering will provide quantitative and semi-quantitative tools for making design decisions and evaluating items such as budgets and schedules. This paper will provide an in-depth look at some of the Systems Engineering processes employed and will step through the design process of a Human Asteroid Exploration System.

  9. Integration between manufacturers and third party logistics providers?

    DEFF Research Database (Denmark)

    Mortensen, Ole; Lemoine, Olga W.

    2008-01-01

    , more segmented markets for the various services and more intense competition, the manufacturers do not expect increased dependence on the TPL providers. Research limitations/implications - Managerial and behavioural components are not part of this study and their effect on integration will require......Purpose - The purpose of this study is to analyse the extent of the integration between manufacturers and third party logistics (TPL) providers at present and how the integration is expected to develop in the near future. The focus is on studying what tasks are part of the cooperation, what...... information and communications technology (ICT) tools are used for support, and what types of services are supplied and are expected to be supplied by TPL providers in the future. Design/methodology/approach - A multiple case study of seven manufacturers and TPL providers is conducted. As the basis...

  10. Shared Savings Program ACO Provider-level RIF

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Centers for Medicare (CM) has created a set of standard analytical files that contain Shared Savings Program Accountable Care Organizations. Provider-level RIF...

  11. Ecosystem services provided by pacific NW Estuaries: State of knowledge

    Science.gov (United States)

    Coastal regions in the United States are rapidly developing areas, with increasing urbanization and growing populations. Estuarine and nearshore coastal marine waters provide valuable ecosystem services to resident and transient human communities. In the Pacific Northwest (PNW)...

  12. Diarrhea - what to ask your health care provider - adult

    Science.gov (United States)

    What to ask your health care provider about diarrhea - adult; Loose stools - what to ask your health ... medicines, vitamins, herbs, or supplements I take cause diarrhea? Should I stop taking any of them? What ...

  13. Modeling Market Shares of Competing (e)Care Providers

    Science.gov (United States)

    van Ooteghem, Jan; Tesch, Tom; Verbrugge, Sofie; Ackaert, Ann; Colle, Didier; Pickavet, Mario; Demeester, Piet

    In order to address the increasing costs of providing care to the growing group of elderly, efficiency gains through eCare solutions seem an obvious solution. Unfortunately not many techno-economic business models to evaluate the return of these investments are available. The construction of a business case for care for the elderly as they move through different levels of dependency and the effect of introducing an eCare service, is the intended application of the model. The simulation model presented in this paper allows for modeling evolution of market shares of competing care providers. Four tiers are defined, based on the dependency level of the elderly, for which the market shares are determined. The model takes into account available capacity of the different care providers, in- and outflow distribution between tiers and churn between providers within tiers.

  14. The role of written provider communication in external client participation.

    Science.gov (United States)

    Dellande, Stephanie; Taylor, Gail Ayala

    2004-01-01

    In certain classes of services, the client's role in the service delivery process often extends beyond the face-to-face exchange. With compliance dependent services (CDS), the client is expected to continue to perform for him or herself once away from the service provider in order to ensure positive outcomes and customer satisfaction (Dellande and Gilly, 1998). This study examined the effectiveness of written provider communication in influencing client motivation and role clarity in CDS. Two exploratory investigations examining written provider communication were conducted. In study 1, written material of three different types of health care related CDS (dialysis, prenatal care and weight loss) were examined; in study 2, dialysis written material was further examined. The findings suggest that, in the majority of the materials examined, written provider communication does not seem to clearly communicate the consequences of noncompliance (a source of customer motivation). However, the materials examined were effective in clarifying the client's external service roles. PMID:15774368

  15. Customer-Provider Strategic Alignment: A Maturity Model

    Science.gov (United States)

    Luftman, Jerry; Brown, Carol V.; Balaji, S.

    This chapter presents a new model for assessing the maturity of a ­customer-provider relationship from a collaborative service delivery perspective: the Customer-Provider Strategic Alignment Maturity (CPSAM) Model. This model builds on recent research for effectively managing the customer-provider relationship in IT service outsourcing contexts and a validated model for assessing alignment across internal IT service units and their business customers within the same organization. After reviewing relevant literature by service science and information systems researchers, the six overarching components of the maturity model are presented: value measurements, governance, partnership, communications, human resources and skills, and scope and architecture. A key assumption of the model is that all of the components need be addressed to assess and improve customer-provider alignment. Examples of specific metrics for measuring the maturity level of each component over the five levels of maturity are also presented.

  16. Challenging RSD clients’ preferences for foreign service providers

    Directory of Open Access Journals (Sweden)

    Christian Pangilinan

    2012-12-01

    Full Text Available Organisations that provide legal services to refugees and asylumseekers face the challenge of responding ethically to clients’ requeststo be assisted by foreigners as opposed to by nationals in countryoffices.

  17. IPPS Provider Summary for the Top 100 DRGs - FY2011

    Data.gov (United States)

    U.S. Department of Health & Human Services — A provider level summary of Inpatient Prospective Payment System (IPPS) discharges, average charges and average Medicare payments for the Top 100 Diagnosis-Related...

  18. Using the National Provider Identifier for Health Care...

    Data.gov (United States)

    U.S. Department of Health & Human Services — The establishment in recent years of a National Provider Identifier (NPI) offers a new method for counting and categorizing physicians and other health care...

  19. How Do Health Care Providers Diagnose Pregnancy Loss or Miscarriage?

    Science.gov (United States)

    ... do health care providers diagnose pregnancy loss or miscarriage? Skip sharing on social media links Share this: ... pregnant woman experiences any of the symptoms of miscarriage, such as crampy abdominal or back pain, light ...

  20. Establishment of Pediatric Cardiac Intensive Care Advanced Practice Provider Services.

    Science.gov (United States)

    Gilliland, Jill; Donnellan, Amy; Justice, Lindsey; Moake, Lindy; Mauney, Jennifer; Steadman, Page; Drajpuch, David; Tucker, Dawn; Storey, Jean; Roth, Stephen J; Koch, Josh; Checchia, Paul; Cooper, David S; Staveski, Sandra L

    2016-01-01

    The addition of advanced practice providers (APPs; nurse practitioners and physician assistants) to a pediatric cardiac intensive care unit (PCICU) team is a health care innovation that addresses medical provider shortages while allowing PCICUs to deliver high-quality, cost-effective patient care. APPs, through their consistent clinical presence, effective communication, and facilitation of interdisciplinary collaboration, provide a sustainable solution for the highly specialized needs of PCICU patients. In addition, APPs provide leadership, patient and staff education, facilitate implementation of evidence-based practice and quality improvement initiatives, and the performance of clinical research in the PCICU. This article reviews mechanisms for developing, implementing, and sustaining advance practice services in PCICUs. PMID:26714997