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- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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- Yung, Diana E., et al.
(författare)
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Capsule endoscopy in young patients with iron deficiency anaemia and negative bidirectional gastrointestinal endoscopy
- 2017
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Ingår i: United European Gastroenterology Journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 5:7, s. 974-981
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent data imply young patients (age ≤50 years) undergoing small-bowel (SB) capsule endoscopy (CE) for iron deficiency anaemia (IDA) show higher diagnostic yield (DY) for sinister pathology. We aimed to investigate DY of CE in a large cohort of young IDA patients, and evaluate factors predicting significant SB pathology. Materials and methods: This was a retrospective, multicentre study (2010–2015) in consecutive, young patients (≤50 years) from 18 centres/12 countries, with negative bidirectional gastrointestinal (GI) endoscopy undergoing SBCE for IDA. Exclusion criteria: previous/ongoing obscure-overt GI bleeding; age <19 or >50 years; comorbidities associated with IDA. Data retrieved: SBCE indications; prior investigations; medications; SBCE findings; final diagnosis. Clinical and laboratory data were analysed by multivariate logistic regression. Results: Data on 389 young IDA patients were retrieved. In total, 169 (43.4%) were excluded due to incomplete clinical data; data from 220 (122F/98M; mean age 40.5 ± 8.6 years) patients were analysed. Some 71 patients had at least one clinically significant SBCE finding (DY: 32.3%). They were divided into two groups: neoplastic pathology (10/220; 4.5%), and non-neoplastic but clinically significant pathology (61/220; 27.7%). The most common significant but non-neoplastic pathologies were angioectasias (22/61) and Crohn’s disease (15/61). On multivariate analysis, weight loss and lower mean corpuscular volume(MCV) were associated with significant SB pathology (OR: 3.87; 95%CI: 1.3–11.3; p = 0.01; and OR: 0.96; 95%CI: 0.92–0.99; p = 0.03; respectively). Our model also demonstrates association between use of antiplatelets and significant SB pathology, although due to the small number of patients, definitive conclusions cannot be drawn. Conclusion: In IDA patients ≤50 years with negative bidirectional GI endoscopy, overall DY of SBCE for clinically significant findings was 32.3%. Some 5% of our cohort was diagnosed with SB neoplasia; lower MCV or weight loss were associated with higher DY for SB pathology.
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