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61.
Nyholm M Gullberg B Merlo J Lundqvist-Persson C Råstam L Lindblad U 《Obesity (Silver Spring, Md.)》2007,15(1):197-208
Objective: To validate self‐reported information on weight and height in an adult population and to find a useful algorithm to assess the prevalence of obesity based on self‐reported information. Research Methods and Procedures: This was a cross‐sectional survey consisting of 1703 participants (860 men and 843 women, 30 to 75 years old) conducted in the community of Vara, Sweden, from 2001 to 2003. Self‐reported weight, height, and corresponding BMI were compared with measured data. Obesity was defined as measured BMI ≥ 30 kg/m2. Information on education, self‐rated health, smoking habits, and physical activity during leisure time was collected by a self‐administered questionnaire. Results: Mean differences between measured and self‐reported weight were 1.6 kg (95% confidence interval, 1.4; 1.8) in men and 1.8 kg (1.6; 2.0) in women (measured higher), whereas corresponding differences in height were ?0.3 cm (?0.5; ?0.2) in men and ?0.4 cm (?0.5; ?0.2) in women (measured lower). Age and body size were important factors for misreporting height, weight, and BMI in both men and women. Obesity (measured) was found in 156 men (19%) and 184 women (25%) and with self‐reported data in 114 men (14%) and 153 women (20%). For self‐reported data, the sensitivity of obesity was 70% in men and 82% in women, and when adjusted for corrected self‐reported data and age, it increased to 81% and 90%, whereas the specificity decreased from 99% in both sexes to 97% in men and 98% in women. Discussion: The prevalence of obesity based on self‐reported BMI can be estimated more accurately when using an algorithm adjusted for variables that are predictive for misreporting. 相似文献
62.
The field of proteomics has gained considerable momentum over the last years as new technologies and better instrumentation allowed the field to mature from what resembled a cottage industry into a high-throughput means to identify, characterize and quantify hundreds of proteins. The identifications and (relative) quantitation values obtained are often controversial however, as various techniques and different software platforms are used in the many laboratories worldwide. This Opinion attempts to shed some light on some of the underlying issues, and proposes certain guidelines authors can adhere to in order to allow others to validate their findings. 相似文献
63.
High Performance Proteomics: 7th HUPO Brain Proteome Project Workshop March 7-9, 2007 Wellcome Trust Conference Centre, Hinxton, UK 总被引:1,自引:0,他引:1
Hamacher M Stephan C Eisenacher M Lewczuk P Wiltfang J Martens L Vizcaíno JA Kwon KH Yoo JS Park YM Beckers J Horsch M de Angelis MH Cho ZH Apweiler R Meyer HE 《Proteomics》2007,7(15):2490-2496
The Wellcome Trust Conference Centre at Hinxton, UK, was the meeting place of the 7th HUPO Brain Proteome Project Workshop entitled "High Performance Proteomics". It started on Wednesday, March 7, 2007 with a steering committee meeting followed by a two days series of talks dealing with the standardization and handling of tissues, body fluids as well as of proteomics data. The presentation and accompanying vivid discussions created a picture of actual strategies and standards in recent proteomics. 相似文献
64.
65.
Prasath Paramasivam Christian Franke Martin Stter Andreas Hijer Stefano Bartesaghi Alan Sabirsh Lennart Lindfors Marianna Yanez Arteta Anders Dahln Annette Bak Shalini Andersson Yannis Kalaidzidis Marc Bickle Marino Zerial 《The Journal of cell biology》2022,221(2)
Delivery of exogenous mRNA using lipid nanoparticles (LNPs) is a promising strategy for therapeutics. However, a bottleneck remains in the poor understanding of the parameters that correlate with endosomal escape versus cytotoxicity. To address this problem, we compared the endosomal distribution of six LNP-mRNA formulations of diverse chemical composition and efficacy, similar to those used in mRNA-based vaccines, in primary human adipocytes, fibroblasts, and HeLa cells. Surprisingly, we found that total uptake is not a sufficient predictor of delivery, and different LNPs vary considerably in endosomal distributions. Prolonged uptake impaired endosomal acidification, a sign of cytotoxicity, and caused mRNA to accumulate in compartments defective in cargo transport and unproductive for delivery. In contrast, early endocytic/recycling compartments have the highest probability for mRNA escape. By using super-resolution microscopy, we could resolve a single LNP-mRNA within subendosomal compartments and capture events of mRNA escape from endosomal recycling tubules. Our results change the view of the mechanisms of endosomal escape and define quantitative parameters to guide the development of mRNA formulations toward higher efficacy and lower cytotoxicity. 相似文献
66.
67.
M protein, a classical bacterial virulence determinant, forms complexes with fibrinogen that induce vascular leakage 总被引:10,自引:0,他引:10
Herwald H Cramer H Mörgelin M Russell W Sollenberg U Norrby-Teglund A Flodgaard H Lindbom L Björck L 《Cell》2004,116(3):367-379
Increased vascular permeability is a key feature of inflammatory conditions. In severe infections, leakage of plasma from the vasculature induces a life-threatening hypotension. Streptococcus pyogenes, a major human bacterial pathogen, causes a toxic shock syndrome (STSS) characterized by excessive plasma leakage and multi-organ failure. Here we find that M protein, released from the streptococcal surface, forms complexes with fibrinogen, which by binding to beta2 integrins of neutrophils, activate these cells. As a result, neutrophils release heparin binding protein, an inflammatory mediator inducing vascular leakage. In mice, injection of M protein or subcutaneous infection with S. pyogenes causes severe pulmonary damage characterized by leakage of plasma and blood cells. These lesions were prevented by treatment with a beta2 integrin antagonist. In addition, M protein/fibrinogen complexes were identified in tissue biopsies from a patient with necrotizing fasciitis and STSS, further underlining the pathogenic significance of such complexes in severe streptococcal infections. 相似文献
68.
Rehfeld JF Bundgaard JR Goetze JP Friis-Hansen L Hilsted L Johnsen AH 《Regulatory peptides》2004,120(1-3):177-183
The antral hormone gastrin continues to be in focus, because its hormonal and growth promoting effects are essential both for the function of the normal stomach and for the pathogenesis of major dyspeptic and neoplastic diseases. Deduction of the progastrin structure has improved the insight in the cellular synthesis of gastrin, but has also revealed that the biosynthetic machinery is complex, and, accordingly, that progastrin is processed to a multitude of more or less bioactive fragments. The naming of these fragments has, however, become inconsistent and confusing. Therefore, we propose a systematic nomenclature for progastrin-derived peptides of which there are three classes: (I) The gastrins with the evolutionary preserved tetrapeptide amide (Trp-Met-Asp-PheNH2) at the C-terminus, which ensures high-affinity binding to the gastrin (CCK-B) receptor. Among the gastrins, gastrin-34 and gastrin-17 constitute the primary forms. (II) Processing intermediates, which are early products of progastrin that contain the structure of the primary gastrins within their sequence, but still cannot bind the gastrin receptor due to insufficient processing at their C-terminus. (III) Flanking fragments from the N- and C-termini of progastrin that do not contain any primary gastrin in their sequence, but nevertheless may undergo posttranslational processing. Each fragment can be specified with suffixes corresponding to the derived sequence in progastrin. 相似文献
69.
J?Craig CohenEmail author Lennart?KA?Lundblad Jason?HT?Bates Michael?Levitzky Janet?E?Larson 《BMC genetics》2004,5(1):21
Background
Cystic Fibrosis is a pleiotropic disease in humans with primary morbidity and mortality associated with a lung disease phenotype. However, knockout in the mouse of cftr, the gene whose mutant alleles are responsible for cystic fibrosis, has previously failed to produce a readily, quantifiable lung phenotype. 相似文献70.
Dysfunction in various parts of immune defence, such as immune response, immune complex clearance, and inflammation, has an
impact on pathogenesis in systemic lupus erythematosus (SLE). We hypothesised that combinations of common variants of genes
involved in these immune functions are associated with susceptibility to SLE. The following variants were analysed: HLA DR3,
HLA DQ2, C4AQ0, Fcγ receptor IIa (FcγRIIa) genotype R/R, Fcγ receptor IIIa (FcRγIIIa) genotype F/F, mannan-binding lectin
(MBL) genotype conferring a low serum concentration of MBL (MBL-low), and interleukin-1 receptor antagonist (IL-1Ra) genotype
2/2. Polymorphisms were analysed in 143 Caucasian patients with SLE and 200 healthy controls. HLA DR3 in SLE patients was
in 90% part of the haplotype HLA DR3-DQ2-C4AQ0, which was strongly associated with SLE (odds ratio [OR] 2.8, 95% CI 1.7–4.5).
Analysis of combinations of gene variants revealed that the strong association with SLE for HLA DR3-DQ2-C4AQ0 remained after
combination with FcγRIIa R/R, FcγRIIIa F/F, and MBL-low (OR>2). Furthermore, the combination of the FcγRIIa R/R and IL-1Ra
2/2 genotypes yielded a strong correlation with SLE (OR 11.8, 95% CI 1.5–95.4). This study demonstrates that certain combinations
of gene variants may increase susceptibility to SLE, suggesting this approach for future studies. It also confirms earlier
findings regarding the HLA DR3-DQ2-C4AQ0 haplotype. 相似文献