| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
- Namkoong, H, et al.
(författare)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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| 5. |
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| 6. |
- Wang, QBS, et al.
(författare)
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The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
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Tidskriftsartikel (refereegranskat)abstract
- Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.
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| 7. |
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| 8. |
- Armesto, N., et al.
(författare)
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Heavy-ion collisions at the LHC-Last call for predictions
- 2008
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 35:5, s. 054001-
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Forskningsöversikt (refereegranskat)abstract
- This writeup is a compilation of the predictions for the forthcoming Heavy Ion Program at the Large Hadron Collider, as presented at the CERN Theory Institute 'Heavy Ion Collisions at the LHC - Last Call for Predictions', held from 14th May to 10th June 2007.
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| 9. |
- Dahmen, J., et al.
(författare)
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Osteochondral Lesions of the Tibial Plafond and Ankle Instability With Ankle Cartilage Lesions: Proceedings of the International Consensus Meeting on Cartilage Repair of the Ankle
- 2022
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Ingår i: Foot & Ankle International. - : SAGE Publications. - 1071-1007 .- 1944-7876. ; 43:3, s. 448-452
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Tidskriftsartikel (refereegranskat)abstract
- Background: An international consensus group of experts was convened to collaboratively advance toward consensus opinions based on the best available evidence on key topics within cartilage repair of the ankle. The purpose of this article is to present the consensus statements on osteochondral lesions of the tibial plafond (OLTP) and on ankle instability with ankle cartilage lesions developed at the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. Methods: Forty-three experts in cartilage repair of the ankle were convened and participated in a process based on the Delphi method of achieving consensus. Questions and statements were drafted within 4 working groups focusing on specific topics within cartilage repair of the ankle, after which a comprehensive literature review was performed and the available evidence for each statement was graded. Discussion and debate occurred in cases where statements were not agreed on in unanimous fashion within the working groups. A final vote was then held. Results: A total of 11 statements on OLTP reached consensus. Four achieved unanimous support and 7 reached strong consensus (greater than 75% agreement). A total of 8 statements on ankle instability with ankle cartilage lesions reached consensus during the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. One achieved unanimous support, and seven reached strong consensus (greater than 75% agreement). Conclusions: These consensus statements may assist clinicians in the management of these difficult clinical pathologies.
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| 10. |
- Musso, G., et al.
(författare)
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Association of non-alcoholic fatty liver disease with chronic kidney disease : a systematic review and meta-analysis
- 2014
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Ingår i: PLoS Medicine. - : Public Library of Science. - 1549-1277 .- 1549-1676. ; 11:7, s. e1001680-
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Tidskriftsartikel (refereegranskat)abstract
- Background:Chronic kidney disease (CKD) is a frequent, under-recognized condition and a risk factor for renal failure and cardiovascular disease. Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to CKD. We conducted a meta-analysis to determine whether the presence and severity of NAFLD are associated with the presence and severity of CKD.Methods and Findings:English and non-English articles from international online databases from 1980 through January 31, 2014 were searched. Observational studies assessing NAFLD by histology, imaging, or biochemistry and defining CKD as either estimated glomerular filtration rate (eGFR) andlt;60 ml/min/1.73 m2 or proteinuria were included. Two reviewers extracted studies independently and in duplicate. Individual participant data (IPD) were solicited from all selected studies. Studies providing IPD were combined with studies providing only aggregate data with the two-stage method. Main outcomes were pooled using random-effects models. Sensitivity and subgroup analyses were used to explore sources of heterogeneity and the effect of potential confounders. The influences of age, whole-body/abdominal obesity, homeostasis model of insulin resistance (HOMA-IR), and duration of follow-up on effect estimates were assessed by meta-regression. Thirty-three studies (63,902 participants, 16 population-based and 17 hospital-based, 20 cross-sectional, and 13 longitudinal) were included. For 20 studies (61% of included studies, 11 cross-sectional and nine longitudinal, 29,282 participants), we obtained IPD. NAFLD was associated with an increased risk of prevalent (odds ratio [OR] 2.12, 95% CI 1.69-2.66) and incident (hazard ratio [HR] 1.79, 95% CI 1.65-1.95) CKD. Non-alcoholic steatohepatitis (NASH) was associated with a higher prevalence (OR 2.53, 95% CI 1.58-4.05) and incidence (HR 2.12, 95% CI 1.42-3.17) of CKD than simple steatosis. Advanced fibrosis was associated with a higher prevalence (OR 5.20, 95% CI 3.14-8.61) and incidence (HR 3.29, 95% CI 2.30-4.71) of CKD than non-advanced fibrosis. In all analyses, the magnitude and direction of effects remained unaffected by diabetes status, after adjustment for other risk factors, and in other subgroup and meta-regression analyses. In cross-sectional and longitudinal studies, the severity of NAFLD was positively associated with CKD stages. Limitations of analysis are the relatively small size of studies utilizing liver histology and the suboptimal sensitivity of ultrasound and biochemistry for NAFLD detection in population-based studies.Conclusion:The presence and severity of NAFLD are associated with an increased risk and severity of CKD.Please see later in the article for the Editors Summary. © 2014 Musso et al.
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| 11. |
- Frisoni, G. B., et al.
(författare)
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Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers
- 2017
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Ingår i: Lancet Neurology. - 1474-4422 .- 1474-4465. ; 16:8, s. 661-676
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Tidskriftsartikel (refereegranskat)abstract
- The diagnosis of Alzheimer's disease can be improved by the use of biological measures. Biomarkers of functional impairment, neuronal loss, and protein deposition that can be assessed by neuroimaging (ie, MRI and PET) or CSF analysis are increasingly being used to diagnose Alzheimer's disease in research studies and specialist clinical settings. However, the validation of the clinical usefulness of these biomarkers is incomplete, and that is hampering reimbursement for these tests by health insurance providers, their widespread clinical implementation, and improvements in quality of health care. We have developed a strategic five-phase roadmap to foster the clinical validation of biomarkers in Alzheimer's disease, adapted from the approach for cancer biomarkers. Sufficient evidence of analytical validity (phase 1 of a structured framework adapted from oncology) is available for all biomarkers, but their clinical validity (phases 2 and 3) and clinical utility (phases 4 and 5) are incomplete. To complete these phases, research priorities include the standardisation of the readout of these assays and thresholds for normality, the evaluation of their performance in detecting early disease, the development of diagnostic algorithms comprising combinations of biomarkers, and the development of clinical guidelines for the use of biomarkers in qualified memory clinics.
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| 12. |
- Murawski, Christopher D., et al.
(författare)
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Terminology for osteochondral lesions of the ankle: proceedings of the International Consensus Meeting on Cartilage Repair of the Ankle
- 2022
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Ingår i: JOURNAL OF ISAKOS JOINT DISORDERS & ORTHOPAEDIC SPORTS MEDICINE. - : Elsevier BV. - 2059-7754 .- 2059-7762. ; 7:2, s. 62-66
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Tidskriftsartikel (refereegranskat)abstract
- Background: The evidence supporting best practice guidelines in the field of cartilage repair of the ankle is based on both low quality and low levels of evidence. Therefore, an international consensus group of experts was convened to collaboratively advance toward consensus opinions based on the best available evidence on key topics within cartilage repair of the ankle. The purpose of this article is to report the consensus statements on "terminology for osteochondral lesions of the ankle" developed at the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. Methods: Forty-three international experts in cartilage repair of the ankle representing 20 countries were convened and participated in a process based on the Delphi method of achieving consensus. Questions and statements were drafted within four working groups focusing on specific topics within cartilage repair of the ankle, after which a comprehensive literature review was performed, and the available evidence for each state-ment was graded. Discussion and debate occurred in cases where statements were not agreed on in unanimous fashion within the working groups. A final vote was then held, and the strength of consensus was characterised as follows: consensus, 51%-74%; strong consensus, 75%-99%; unanimous, 100%. Results: A total of 11 statements on terminology and classification reached consensus during the 2019 Interna-tional Consensus Meeting on Cartilage Repair of the Ankle. Definitions are provided for osseous, chondral and osteochondral lesions, as well as bone marrow stimulation and injury chronicity, among others. An osteochondral lesion of the talus can be abbreviated as OLT. Conclusions: This international consensus derived from leaders in the field will assist clinicians with the appro-priate terminology for osteochondral lesions of the ankle.
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| 13. |
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| 14. |
- Baron, P., et al.
(författare)
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Observation of horizontal winds in the middle-atmosphere between 30 degrees S and 55 degrees N during the northern winter 2009-2010
- 2013
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 13:12, s. 6049-6064
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Tidskriftsartikel (refereegranskat)abstract
- Although the links between stratospheric dynamics, climate and weather have been demonstrated, direct observations of stratospheric winds are lacking, in particular at altitudes above 30 km. We report observations of winds between 8 and 0.01 hPa (similar to 35-80 km) from October 2009 to April 2010 by the Superconducting Submillimeter-Wave Limb-Emission Sounder (SMILES) on the International Space Station. The altitude range covers the region between 35-60 km where previous space-borne wind instruments show a lack of sensitivity. Both zonal and meridional wind components were obtained, though not simultaneously, in the latitude range from 30 degrees S to 55 degrees N and with a single profile precision of 7-9 ms(-1) between 8 and 0.6 hPa and better than 20 ms(-1) at altitudes above. The vertical resolution is 5-7 km except in the upper part of the retrieval range (10 km at 0.01 hPa). In the region between 1-0.05 hPa, an absolute value of the mean difference 5 ms(-1)). In the mesosphere, SMILES and ECMWF zonal winds exhibit large differences (>20 ms(-1)), especially in the tropics. We illustrate our results by showing daily and monthly zonal wind variations, namely the semi-annual oscillation in the tropics and reversals of the flow direction between 50-55 degrees N during sudden stratospheric warmings. The daily comparison with ECMWF winds reveals that in the beginning of February, a significantly stronger zonal westward flow is measured in the tropics at 2 hPa compared to the flow computed in the analysis (difference of similar to 20 ms(-1)). The results show that the comparison between SMILES and ECMWF winds is not only relevant for the quality assessment of the new SMILES winds, but it also provides insights on the quality of the ECMWF winds themselves. Although the instrument was not specifically designed for measuring winds, the results demonstrate that space-borne sub-mm wave radiometers have the potential to provide good quality data for improving the stratospheric winds in atmospheric models.
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| 15. |
- Baron, Phillippe, et al.
(författare)
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Observation of horizontal winds in the middle-atmosphere between 30° S and 55° N during the northern winter 2009–2010
- 2012
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 13, s. 6049-6064
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Tidskriftsartikel (refereegranskat)abstract
- Although the links between stratospheric dynamics, climate and weather have been demonstrated, direct observations of stratospheric winds are lacking. We report observations of winds between 8 and 0.01 hPa (~35–80 km) from October 2009 to April 2010 by the Superconducting Submillimeter-Wave Limb-Emission Sounder (SMILES) on the International Space Station. The altitude range covers the region between 35–60 km where previous space-borne wind instruments show a lack of sensitivity. Both zonal and meridional wind components were obtained, though not simultaneously, in the latitude range from 30° S to 55° N and with a single profile precision of 7–9 m s−1 between 8 and 0.6 hPa and better than 20 m s−1 at altitudes above. The vertical resolution is 5–7 km except in the upper part of the retrieval range (10 km at 0.01 hPa). In the region between 1–0.05 hPa, a mean difference <2 m s−1 is found between SMILES profiles retrieved from different spectroscopic lines and instrumental settings. Good agreement (mean difference of ~2 m s−1) is also found with the European Centre for Medium-Range Weather Forecasts (ECMWF) analysis in most of the stratosphere except for the zonal winds over the equator (mean difference of 5–10 m s−1). In the mesosphere, SMILES and ECMWF zonal winds exhibit large differences (> 20 m s−1), especially in the tropics. We illustrate our results by showing daily and monthly zonal wind variations, namely the semi-annual oscillation in the tropics and reversals of the flow direction between 50° N–55° N during sudden stratospheric warmings in the stratosphere. The daily comparison with ECMWF winds reveals that in the beginning of February, a significantly stronger zonal westward flow is measured in the tropics at 2 hPa compared to the flow computed in the analysis (difference of ~20 m s−1). The results show that the comparison between SMILES and ECMWF winds is not only relevant for the quality assessment of the new SMILES winds but it also provides insights on the quality of the ECMWF winds themselves. Although the instrument was not specifically designed for measuring winds, the results demonstrate that space-borne sub-mm wave radiometers have the potential to provide good quality data for improving the stratospheric winds in atmospheric models.
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| 16. |
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| 17. |
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| 18. |
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| 19. |
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| 20. |
- Kasai, Y., et al.
(författare)
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Validation of stratospheric and mesospheric ozone observed by SMILES from International Space Station
- 2013
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 6:9, s. 2311-2338
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Tidskriftsartikel (refereegranskat)abstract
- We observed ozone (O3) in the vertical region between 250 and 0.0005 hPa (~ 12–96 km) using the Superconducting Submillimeter-Wave Limb-Emission Sounder (SMILES) on the Japanese Experiment Module (JEM) of the International Space Station (ISS) between 12 October 2009 and 21 April 2010. The new 4 K superconducting heterodyne receiver technology of SMILES allowed us to obtain a one order of magnitude better signal-to-noise ratio for the O3 line observation compared to past spaceborne microwave instruments. The non-sun-synchronous orbit of the ISS allowed us to observe O3 at various local times. We assessed the quality of the vertical profiles of O3 in the 100–0.001 hPa (~ 16–90 km) region for the SMILES NICT Level 2 product version 2.1.5. The evaluation is based on four components: error analysis; internal comparisons of observations targeting three different instrumental setups for the same O3 625.371 GHz transition; internal comparisons of two different retrieval algorithms; and external comparisons for various local times with ozonesonde, satellite and balloon observations (ENVISAT/MIPAS, SCISAT/ACE-FTS, Odin/OSIRIS, Odin/SMR, Aura/MLS, TELIS). SMILES O3 data have an estimated absolute accuracy of better than 0.3 ppmv (3%) with a vertical resolution of 3–4 km over the 60 to 8 hPa range. The random error for a single measurement is better than the estimated systematic error, being less than 1, 2, and 7%, in the 40–1, 80–0.1, and 100–0.004 hPa pressure regions, respectively. SMILES O3 abundance was 10–20% lower than all other satellite measurements at 8–0.1 hPa due to an error arising from uncertainties of the tangent point information and the gain calibration for the intensity of the spectrum. SMILES O3 from observation frequency Band-B had better accuracy than that from Band-A. A two month period is required to accumulate measurements covering 24 h in local time of O3 profile. However such a dataset can also contain variation due to dynamical, seasonal, and latitudinal effects
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| 21. |
- Landier, Wendy, et al.
(författare)
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Surveillance for late effects in childhood cancer survivors
- 2018
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 36:21, s. 2216-2222
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Forskningsöversikt (refereegranskat)abstract
- Many childhood cancer survivors carry a significant risk for late morbidity and mortality, a consequence of the numerous therapeutic exposures that contribute to their cure. Focused surveillance for late therapy-related complications provides opportunities for early detection and implementation of health-preserving interventions. The substantial body of research that links therapeutic exposures used during treatment of childhood cancer to adverse outcomes among survivors enables the characterization of groups at the highest risk for developing complications related to specific therapies; however, methods available to optimize screening strategies to detect these therapy-related complications are limited. Moreover, the feasibility of conducting clinical trials to test screening recommendations for childhood cancer survivors is limited by requirements for large sample sizes, lengthy study periods, prohibitive costs, and ethical concerns. In addition, the harms of screening should be considered, including overdiagnosis and psychological distress. Experts in several countries have developed guideline recommendations for late effects surveillance and have collaborated to harmonize these recommendations internationally to enhance long-term follow-up care and quality of life for childhood cancer survivors. Methods used in these international efforts include systematic literature searches, development of evidence-based summaries, rigorous evaluation of the evidence, and formulation of consensus-based surveillance recommendations for each late complication. Alternate methods to refine recommendations, such as cumulative burden assessment and risk prediction and cost-effectiveness modeling, may provide novel approaches to guide survivorship care in this vulnerable population and, thus, represents a worthy objective for future international survivorship collaborations.
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| 22. |
- Lu, DH, et al.
(författare)
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Genome-wide association study of posttraumatic stress disorder among childhood cancer survivors: results from the Childhood Cancer Survivor Study and the St. Jude Lifetime Cohort
- 2022
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1, s. 342-
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Tidskriftsartikel (refereegranskat)abstract
- Genetic influence shapes who develops posttraumatic stress disorder (PTSD) after traumatic events. However, the genetic variants identified for PTSD may in fact be associated with traumatic exposures (e.g., interpersonal violence), which appear heritable as well. Childhood cancer survivors (CCS) are at risk for PTSD, but genetic influences affecting cancer are unlikely to overlap with those affecting PTSD. This offers a unique opportunity to identify variants specific to PTSD risk. In a genome-wide association study (GWAS), 3984 5-year survivors of childhood cancer of European-ancestry from the Childhood Cancer Survivor Study (CCSS) were evaluated for discovery and 1467 survivors from the St. Jude Lifetime (SJLIFE) cohort for replication. Childhood cancer-related PTSD symptoms were assessed using the Posttraumatic Stress Diagnostic Scale in CCSS. GWAS was performed in CCSS using logistic regression and lead markers were replicated/meta-analyzed using SJLIFE. Cross-associations of identified loci were examined between CCS and the general population. PTSD criteria were met for 671 participants in CCSS and 161 in SJLIFE. Locus 10q26.3 was significantly associated with PTSD (rs34713356, functionally mapped to ECHS1, P = 1.36 × 10–8, OR 1.57), and was replicated in SJLIFE (P = 0.047, OR 1.37). Variants in locus 6q24.3-q25.1 reached marginal significance (rs9390543, SASH1, P = 3.56 × 10–6, OR 0.75) in CCSS and significance when meta-analyzing with SJLIFE (P = 2.02 × 10–8, OR 0.75). Both loci were exclusively associated with PTSD in CCS rather than PTSD/stress-related disorders in general population (P-for-heterogeneity < 5 × 10–6). Our CCS findings support the role of genetic variation in PTSD development and may provide implications for understanding PTSD heterogeneity.
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| 23. |
- Mestre, Humberto, et al.
(författare)
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Aquaporin-4-dependent glymphatic solute transport in the rodent brain
- 2018
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Ingår i: eLife. - 2050-084X. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- The glymphatic system is a brain-wide clearance pathway; its impairment contributes to the accumulation of amyloid-β. Influx of cerebrospinal fluid (CSF) depends upon the expression and perivascular localization of the astroglial water channel aquaporin-4 (AQP4). Prompted by a recent failure to find an effect of Aqp4 knock-out (KO) on CSF and interstitial fluid (ISF) tracer transport, five groups re-examined the importance of AQP4 in glymphatic transport. We concur that CSF influx is higher in wild-type mice than in four different Aqp4 KO lines and in one line that lacks perivascular AQP4 (Snta1 KO). Meta-analysis of all studies demonstrated a significant decrease in tracer transport in KO mice and rats compared to controls. Meta-regression indicated that anesthesia, age, and tracer delivery explain the opposing results. We also report that intrastriatal injections suppress glymphatic function. This validates the role of AQP4 and shows that glymphatic studies must avoid the use of invasive procedures.
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| 24. |
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| 25. |
- Nishimoto, G, et al.
(författare)
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Arginine vasopressin stimulates phosphorylation of aquaporin-2 in rat renal tissue.
- 1999
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Ingår i: American Journal of Physiology. - 0002-9513 .- 2163-5773. ; 276:2 Pt 2, s. F254-9
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Tidskriftsartikel (refereegranskat)abstract
- Aquaporin-2 (AQP2), the protein that mediates arginine vasopressin (AVP)-regulated apical water transport in the renal collecting duct, possesses a single consensus phosphorylation site for cAMP-dependent protein kinase A (PKA) at Ser256. The aim of this study was to examine whether AVP, and other agents that increase cAMP levels, could stimulate the phosphorylation of AQP2 in intact rat renal tissue. Rat renal papillae were prelabeled with 32P and incubated with vehicle or drugs, and then AQP2 was immunoprecipitated. Two polypeptides corresponding to nonglycosylated (29 kDa) and glycosylated (35-48 kDa) AQP2 were identified by SDS-PAGE. AVP caused a time- and dose-dependent increase in phosphorylation of both glycosylated and nonglycosylated AQP2. The threshold dose for a significant increase in phosphorylation was 10 pM, which corresponds to a physiological serum concentration of AVP. Maximal phosphorylation was reached within 1 min of AVP incubation. This effect on AQP2 phosphorylation was mimicked by the vasopressin (V2) agonist, 1-desamino-[8-D-arginine]vasopressin (DDAVP), or forskolin. Two-dimensional phosphopeptide mapping indicated that AVP and forskolin stimulated the phosphorylation of the same site in AQP2. Immunoblot analysis using a phosphorylation state-specific antiserum revealed an increase in phosphorylation of Ser256 after incubation of papillae with AVP. The results indicate that AVP stimulates phosphorylation of AQP2 at Ser256 via activation of PKA, supporting the idea that this is one of the first steps leading to increased water permeability in collecting duct cells.
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| 26. |
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| 27. |
- Sato, T.O., et al.
(författare)
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Strato-mesospheric ClO observations by SMILES : error analysis and diurnal variation
- 2012
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 5:11, s. 2809-2825
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Tidskriftsartikel (refereegranskat)abstract
- Chlorine monoxide (ClO) is the key species for anthropogenic ozone losses in the middle atmosphere. We observed ClO diurnal variations using the Superconducting Submillimeter-Wave Limb-Emission Sounder (SMILES) on the International Space Station, which has a non-sun-synchronous orbit. This includes the first global observations of the ClO diurnal variation from the stratosphere up to the mesosphere. The observation of mesospheric ClO was possible due to 10–20 times better signal-to-noise (S/N) ratio of the spectra than those of past or ongoing microwave/submillimeter-wave limb-emission sounders. We performed a quantitative error analysis for the strato- and mesospheric ClO from the Level-2 research (L2r) product version 2.1.5 taking into account all possible contributions of errors, i.e. errors due to spectrum noise, smoothing, and uncertainties in radiative transfer model and instrument functions. The SMILES L2r v2.1.5 ClO data are useful over the range from 0.01 and 100 hPa with a total error estimate of 10–30 pptv (about 10%) with averaging 100 profiles. The SMILES ClO vertical resolution is 3–5 km and 5–8 km for the stratosphere and mesosphere, respectively. The SMILES observations reproduced the diurnal variation of stratospheric ClO, with peak values at midday, observed previously by the Microwave Limb Sounder on the Upper Atmosphere Research Satellite (UARS/MLS). Mesospheric ClO demonstrated an opposite diurnal behavior, with nighttime values being larger than daytime values. A ClO enhancement of about 100 pptv was observed at 0.02 to 0.01 hPa (about 70–80 km) for 50° N–65° N from January–February 2010. The performance of SMILES ClO observations opens up new opportunities to investigate ClO up to the mesopause.
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| 28. |
- Vaidyanathan, S, et al.
(författare)
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Recurrent vesical calculi, hypercalciuria, and biochemical evidence of increased bone resorption in an adult male with paraplegia due to spinal cord injury: is there a role for intermittent oral disodium etidronate therapy for prevention of calcium phosphate bladder stones?
- 2005
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Ingår i: Spinal Cord. - : Springer Science and Business Media LLC. - 1362-4393 .- 1476-5624. ; 43:5, s. 269-277
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Tidskriftsartikel (refereegranskat)abstract
- Study design: Clinical case report with comments by colleagues from Sweden, Poland, Spain, Brazil, Japan, Belgium and Switzerland. Objectives: To discuss the role of disodium etidronate therapy for prevention of calcium phosphate vesical calculi in persons with spinal cord injury, who have hypercalciuria and biochemical evidence of increased bone resorption. Setting: Regional Spinal Injuries Centre, Southport, UK. Methods: A 21-year-old male sustained paraplegia (T-10; ASIA scale: A) in a road traffic accident in June 2001. He had an indwelling urethral catheter until the end of August 2001, when he started self-catheterisation. He developed bladder stones and electrohydraulic lithotripsy (EHL) was performed in May 2002. All stone fragments were removed. Recurrence of vesical calculi was noted in October 2002. These stones were fragmented by lithoclast lithotripsy in two sessions, in December 2002 and February 2003; all stone fragments were removed at the end of the second session. This patient reverted to indwelling catheter drainage when vesical calculi recurred. In September 2003, X-ray of the abdomen showed recurrence of vesical calculi. By February 2004, the stones had increased in size and number. EHL of vesical calculi was again performed in April 2004. Complete clearance was achieved. Results: A 24-h urinalysis detected hypercalciuria – 18.7 mmol/day (reference range: 2.5–7.5). Biochemical analysis of vesical calculus revealed calcium phosphate (85%) and magnesium ammonium phosphate (15%). Plasma C-terminal telopeptide (CTX) was increased – 1.06 ng/ml (reference range: 0.1–0.5 ng/ml). Free deoxypyridinoline/creatinine ratio (fDPD/Cr) in urine was also increased – 20.2 (reference range: 2.3–5.4). In April 2004, this patient was prescribed disodium etidronate 400 mg day. Nearly 3 months after commencing therapy with etidronate, plasma CTX decreased to 0.87 ng/ml. fDPD/Cr in urine also decreased to 12.4. After 4 months of etidronate therapy, 24-h urinary calcium excretion had decreased to 6.1 mmol/day. Conclusion: Etidronate (400 mg daily) is a very effective inhibitor of calcium phosphate crystallisation. Etidronate decreased urinary excretion of calcium, an important factor in prevention of calcium phosphate bladder stones. Etidronate therapy is not a substitute for other well-established methods for prevention of vesical calculi in spinal cord injury patients, for example, large fluid intake, avoiding long-term catheter drainage. Intermittent therapy with etidronate may be considered in selected patients, in whom hypercalciuria persists after instituting nonpharmacological therapy for an adequate period, for example, early mobilisation, weight-bearing exercises, and functional electrical stimulation. However, possible side effects of etidronate, and the fact that etidronate is not licensed in United Kingdom for prevention of urolithiasis, should be borne in mind.
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