| 41. |
- Lechman, Eric R, et al.
(författare)
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miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells.
- 2016
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Ingår i: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 29:2, s. 214-228
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Tidskriftsartikel (refereegranskat)abstract
- To investigate miRNA function in human acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated miRNA signature derived from functionally validated subpopulations of AML samples. For one signature miRNA, miR-126, high bioactivity aggregated all in vivo patient sample LSC activity into a single sorted population, tightly coupling miR-126 expression to LSC function. Through functional studies, miR-126 was found to restrain cell cycle progression, prevent differentiation, and increase self-renewal of primary LSC in vivo. Compared with prior results showing miR-126 regulation of normal hematopoietic stem cell (HSC) cycling, these functional stem effects are opposite between LSC and HSC. Combined transcriptome and proteome analysis demonstrates that miR-126 targets the PI3K/AKT/MTOR signaling pathway, preserving LSC quiescence and promoting chemotherapy resistance.
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| 42. |
- Lindqvist Appell, Malin, et al.
(författare)
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Nomenclature for alleles of the thiopurine methyltransferase gene
- 2013
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Ingår i: Pharmacogenetics & Genomics. - : Lippincott, Williams and Wilkins. - 1744-6872 .- 1744-6880. ; 23:4, s. 242-248
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Forskningsöversikt (refereegranskat)abstract
- The drug-metabolizing enzyme thiopurine methyltransferase (TPMT) has become one of the best examples of pharmacogenomics to be translated into routine clinical practice. TPMT metabolizes the thiopurines 6-mercaptopurine, 6-thioguanine, and azathioprine, drugs that are widely used for treatment of acute leukemias, inflammatory bowel diseases, and other disorders of immune regulation. Since the discovery of genetic polymorphisms in the TPMT gene, many sequence variants that cause a decreased enzyme activity have been identified and characterized. Increasingly, to optimize dose, pretreatment determination of TPMT status before commencing thiopurine therapy is now routine in many countries. Novel TPMT sequence variants are currently numbered sequentially using PubMed as a source of information; however, this has caused some problems as exemplified by two instances in which authors articles appeared on PubMed at the same time, resulting in the same allele numbers given to different polymorphisms. Hence, there is an urgent need to establish an order and consensus to the numbering of known and novel TPMT sequence variants. To address this problem, a TPMT nomenclature committee was formed in 2010, to define the nomenclature and numbering of novel variants for the TPMT gene. A website (http://www.imh.liu.se/tpmtalleles) serves as a platform for this work. Researchers are encouraged to submit novel TPMT alleles to the committee for designation and reservation of unique allele numbers. The committee has decided to renumber two alleles: nucleotide position 106 (Gandgt;A) from TPMT*24 to TPMT*30 and position 611 (Tandgt;C, rs79901429) from TPMT*28 to TPMT*31. Nomenclature for all other known alleles remains unchanged. Pharmacogenetics and Genomics 23: 242-248
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| 43. |
- Marsh, Gary M., et al.
(författare)
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Mortality Among Hardmetal Production Workers : Pooled Analysis of Cohort Data From an International Investigation
- 2017
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Ingår i: Journal of Occupational and Environmental Medicine. - Philadelphia, PA, USA : Lippincott Williams & Wilkins. - 1076-2752 .- 1536-5948. ; 59:12, s. e342-e364
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Based on a pooled analysis of data from an international study, evaluate total and cause-specific mortality among hardmetal production workers with emphasis on lung cancer.METHODS: Study members were 32,354 workers from three companies and 17 manufacturing sites in five countries. We computed standardized mortality ratios and evaluated exposure-response via relative risk regression analysis.RESULTS: Among long-term workers, we observed overall deficits or slight excesses in deaths for total mortality, all cancers, and lung cancer and found no evidence of any exposure-response relationships for lung cancer.CONCLUSIONS: We found no evidence that duration, average intensity, or cumulative exposure to tungsten, cobalt, or nickel, at levels experienced by the workers examined, increases lung cancer mortality risks. We also found no evidence that work in these facilities increased mortality risks from any other causes of death.
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| 44. |
- Hou, Song, et al.
(författare)
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Oxidation of 4-bromo-4'-chlorobiphenyl, model species for forming mixed halogenated aromatic compounds
- 2017
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Ingår i: International Journal of Environment and Pollution. - : InderScience Publishers. - 0957-4352 .- 1741-5101. ; 61:3-4, s. 243-260
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Tidskriftsartikel (refereegranskat)abstract
- This contribution reports results from the gas-phase oxidation of 4-bromo-4'-chlorobiphenyl (4,4'-BCB) in order to fathom the formation of toxic species produced during the combustion of mixed halogenated aromatics. In their own right, mixed polybrominated/polychlorinated biphenyls (PXBs) represent a new class of environmental contaminants, recently detected in food and human tissues. Gas chromatography-quadrupole mass spectrometry (GC-QMS), gas chromatography-quadrupole time of flight mass spectrometry (GC-QTOFMS), Fourier transform infrared spectroscopy (FTIR) and ion chromatography (IC) served to analyse the volatile and semi-volatile organic compounds (V/SVOCs), including mixed halogenated dibenzo-p-dioxins and dibenzofurans (PXDD/Fs), and gaseous products including HBr/HCl. The selection of non-ortho substituted PXB as a model species yields a large number of halogenated compounds, including monochloro- and monobromobenzene and higher halogenated benzenes and naphthalenes and derivatives of halogenated benzenes (such as 1-chloro-4-ethynylbenzene). We also detect small amounts of chlorinated and mixed halogenated dibenzofurans. The present study provides insights into the formation of several classes of halogenated and mixed-halogenated pollutants in combustion processes involving both bromine and chlorine sources, such as those of brominated flame retardants and PVC plastics.
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| 45. |
- Kane, Bridget, et al.
(författare)
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Multidisciplinary Team (MDT) experience in the incorporation of PACS and real-time electronic record-keeping at meetings
- 2011
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Ingår i: Health Informatics Society of Ireland (HISI). - : ICS HISI.
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Konferensbidrag (refereegranskat)abstract
- In tandem with the introduction of PACS and the adoption of an EPR system at St. James’s hospital, there has been a 237% increase in the number of patients being managed through Breast MDT meetings between 2005 and 2010.Methodology: This study forms part of a long-term ethnographic study at St. James's Hospital. Data are gathered at MDT meetings.Due to increased numbers of women attending breast triple assessment clinics, and awareness of breast complaints, coupled with new protocols and amended local hospital policies, new strategies were required to be implemented to cope effectively with the increased demand. Strategies include grouping and prioritizing of cases, increased formalisation, and the incorporation of real-time electronic record-keeping at meetings (as opposed to note-taking).The Electronic Patient Record (EPR) system allows access to all laboratory test results and the final written pathology report if required during discussion. PACS implementation facilitates direct access to digital radiological imaging such as Mammograms, Breast Ultrasound, Breast MRI, Body CT and Bone Scans. The increase in the number of patient presenting to the breast care services has resulted in more selective use of illustrating images. It is no longer practical to conduct a routine review of all images as may have happened in the past.In 2010 a ‘computer-on-wheels’, connected to the hospital wired-network, was introduced to enable real-time data entry of the decisions of the MDT. The lead clinician, at the end of the meeting, validates entries and the report from the MDT discussion is then available in the individual patient record.
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