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- 2019
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Journal article (peer-reviewed)
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- Ebefors, Kerstin, 1977, et al.
(author)
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Endothelin receptor-A mediates degradation of the glomerular endothelial surface layer via pathologic crosstalk between activated podocytes and glomerular endothelial cells
- 2019
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In: Kidney International. - : Elsevier BV. - 0085-2538. ; 96:4, s. 957-970
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Journal article (peer-reviewed)abstract
- Emerging evidence of crosstalk between glomerular cells in pathological settings provides opportunities for novel therapeutic discovery. Here we investigated underlying mechanisms of early events leading to filtration barrier defects of podocyte and glomerular endothelial cell crosstalk in the mouse models of primary podocytopathy (podocyte specific transforming growth factor-beta receptor 1 signaling activation) or Adriamycin nephropathy. We found that glomerular endothelial surface layer degradation and albuminuria preceded podocyte foot process effacement. These abnormalities were prevented by endothelin receptor-A antagonism and mitochondria! reactive oxygen species scavenging. Additional studies confirmed increased heparanase and hyaluronoglucosaminidase gene expression in glomerular endothelial cells in response to podocyte-released factors and to endothelin-1. Atomic force microscopy measurements showed a significant reduction in the endothelial surface layer by endothelin-1 and podocyte-released factors, which could be prevented by endothelin receptor-A but not endothelin receptor-B antagonism. Thus, our studies provide evidence of early crosstalk between activated podocytes and glomerular endothelial cells resulting in loss of endothelial surface layer, glomerular endothelial cell injury and albuminuria. Hence, activation of endothelin-1-endothelin receptor-A and mitochondrial reactive oxygen species contribute to the pathogenesis of primary podocytopathies in experimental focal segmental glomerulosclerosis.
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- Camara-Costa, H., et al.
(author)
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Quality of survival and cognitive performance in children treated for medulloblastoma in the PNET 4 randomized controlled trial
- 2017
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In: Neuro-Oncology Practice. - : Oxford University Press (OUP). - 2054-2577 .- 2054-2585. ; 4:3, s. 161-170
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Journal article (peer-reviewed)abstract
- Background. The relationship between direct assessments of cognitive performance and questionnaires assessing quality of survival (QoS) is reported to be weak-to-nonexistent. Conversely, the associations between questionnaires evaluating distinct domains of QoS tend to be strong. This pattern remains understudied. Methods. In the HIT-SIOP PNET4 randomized controlled trial, cognitive assessments, including Full Scale, Verbal and Performance IQ, Working Memory, and Processing Speed, were undertaken in 137 survivors of standard-risk medulloblastoma from 4 European countries. QoS questionnaires, including self-reports and/or parent reports of the Behavior Rating Inventory of Executive Function (BRIEF), the Health Utilities Index, the Strengths and Difficulties Questionnaire, and the Pediatric Quality of Life Inventory, were completed for 151 survivors. Correlations among direct cognitive assessments, QoS questionnaires, and clinical data were examined in participants with both assessments available (n = 86). Results. Correlations between direct measures of cognitive performance and QoS questionnaires were weak, except for moderate correlations between the BRIEF Metacognition Index (parent report) and working memory (r = .32) and between health status (self-report) and cognitive outcomes (r = .35-.44). Correlations among QoS questionnaires were moderate to strong both for parent and self-report (r = .39-.76). Principal Component Analysis demonstrated that questionnaires and cognitive assessments loaded on 2 separate factors. Conclusions. We hypothesize that the strong correlations among QoS questionnaires is partially attributable to the positive/negative polarity of all questions on the questionnaires, coupled with the relative absence of diseasespecific questions. These factors may be influenced by respondents' personality and emotional characteristics, unlike direct assessments of cognitive functioning, and should be taken into account in clinical trials.
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