Zobrazení zdroje stránky Gatesdaugaard5242

BACKGROUND Currently, serum concentrations of sitosterol above 10&nbsp;μg/ml are considered to be one of the major diagnostic criteria of sitosterolemia. METHODS We retrospectively investigated consecutive 206 Japanese dyslipidemic subjects (mean age&nbsp;=&nbsp;46&nbsp;yr, male n&nbsp;=&nbsp;94) with the assessments of serum sitosterol level and the presence of ABCG5 or ABCG8 genetic mutations in our institute since 2009-2018. We divided the subjects into 3 groups based on the number of pathogenic mutations in ABCG5 or ABCG8 genes. We compared serum lipids and serum sitosterol among those groups, and tried to validate the cutoff value discriminating patients of sitosterolemia with double mutations from others. RESULTS We identified 8 individuals with sitosterolemia with double mutations (affected), 26 individuals with a single mutation (carrier), and 172 individuals without any mutations (wildtype control). Serum sitosterol level of patients with sitosterolemia with double mutations (affected) exhibited significantly higher than those of any other groups (45.2. vs. 7.9&nbsp;μg/ml, p&nbsp;=&nbsp;2.5&nbsp;×&nbsp;10-2, 45.2 vs. 3.1&nbsp;μg/ml, p&nbsp;=&nbsp;1.8&nbsp;×&nbsp;10-2). Under these conditions, a cutoff value of sitosterol 10&nbsp;μg/ml could discriminate the patients with sitosterolemia with double mutations in ABCG5 or ABCG8 gene from no mutation carrier (wildtype control) perfectly, although 6 heterozygous mutation carries exhibited sitosterol level greater than 10&nbsp;μg/ml. Receiver-operating characteristic (ROC) analysis predicting double mutation status showed that the best cut-off value was 14.81&nbsp;μg/ml. CONCLUSION We suggest a cutoff value of sitosterol 15&nbsp;μg/ml that shows higher positive predictive value than 10&nbsp;μg/ml. BACKGROUND Early detection of lung cancer significantly improves survival outcomes. Thus, lung cancer screening for high-risk individuals using low-dose CT scan (LDCT) is recommended. LDCT has several limitations, and often requires invasive follow up. Previously, we have developed an ELISA for measurement of Open Reading Frame 1 protein (ORF1p) in serum. We assessed whether ORF1p can be used as a risk assessment biomarker for patients at high risk for developing lung cancer. PATIENTS Patients with risk factors for lung cancer were enrolled in our study with consent under IRB approval. A total of 122 patients were included. The lung cancer cohort consisted of 38 patients with varying stages of cancer undergoing treatment. METHODS ORF1p quantification was performed using our ELISA assay on serum samples. RESULTS ORF1p was significantly increased in the serum of patients with identified lung nodules compared to those without nodules (P&nbsp;=&nbsp;0.0007). ORF1p was also significantly increased in patients who were recommended for follow up (P&nbsp;=&nbsp;0.0004). When comparing the at-risk cohort to patients with lung cancer, there was not a significant difference in ORF1p levels. CONCLUSION ORF1p can be used to identify patients at high risk of developing lung cancer and may provide an effective, non-invasive risk assessment marker to complement LDCT screening. V.Cell movement is crucial for morphogenesis in multicellular organisms. [https://www.selleckchem.com/products/e-7386.html E-7386 chemical structure] Growing embryos or tissues often expand isotropically, i.e., uniformly, in all dimensions. On the surfaces of these expanding environments, which we call "fields," cells are subjected to frictional forces and move passively in response. However, the potential roles of isotropically expanding fields in morphogenetic events have not been investigated well. Our previous mathematical simulations showed that a tissue was elongated on an isotropically expanding field (Imuta&nbsp;et&nbsp;al., 2014). However, the underlying mechanism remains unclarified, and how cells behave during tissue elongation was not investigated. In this study, we mathematically analyzed the effect of isotropically expanding fields using a vertex model, a standard type of multi-cellular model. We found that cells located on fields were elongated along a similar direction each other and exhibited a columnar configuration with nearly single-cell width. Simultaneously, it was confirmed that the cell clusters were also elongated, even though field expansion was absolutely isotropic. We then investigated the mechanism underlying these counterintuitive phenomena. In particular, we asked whether the dynamics of elongation was predominantly determined by the properties of the field, the cell cluster, or both. Theoretical analyses involving simplification of the model revealed that cell clusters have an intrinsic ability to asymmetrically deform, leading to their elongation. Importantly, this ability is effective only under the non-equilibrium conditions provided by field expansion. This may explain the elongation of the notochord, located on the surface of the growing mouse embryo. We established the mechanism underlying tissue elongation induced by isotropically expanding external environments, and its involvement in collective cell alignment with cell elongation, providing key insight into morphogenesis involving multiple adjacent tissues. Atherosclerosis starts with transmural (transwall) pressure-driven advective transport of blood-borne lipoprotein (LDL) cholesterol across rare endothelial cell (EC) monolayer leaks into the arterial subendothelial intima (SI) wall layer where they can spread, bind to extracellular matrix and seed lesions. The local SI LDL concentration, which governs LDL's binding kinetics, depends on the overall diluting transmural liquid flow. Transmural pressures typically compress the SI at physiological pressures, which keeps this flow low. Nguyen et&nbsp;al. (2015) showed that aortic ECs express the water channel protein aquaporin-1 (AQP1) and the transEC (δP) portion of the transmural (ΔP) pressure difference drives, in parallel, water across AQP1s and plasma across interEC junctions. Since the lumen is isotonic, selective AQP1-mediated water flow should quickly render the ECs' lumen side hypertonic and the SI hypotonic; resulting transEC oncotic pressure differences, δπ, should oppose δP and quickly halt transEC flow. Yetcantly increase SI thickness, flow and subsequently SI LDL dilution. This could retard LDL binding and delay preatherosclerotic lesion onset. The model also predicts that glycocalyx-degrading enzymes decrease overall transEC driving forces and thus lower, not raise, transmural water flux.