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排序方式: 共有461条查询结果,搜索用时 234 毫秒
151.
Nybo M Nielsen LB Nielsen SJ Lindegaard M Damm P Rehfeld JF Goetze JP 《Regulatory peptides》2007,141(1-3):135-139
BACKGROUND: Maternal diabetes increases the risk of hypertrophic cardiomyopathy in the fetus. As signaling via the C-type natriuretic peptide (CNP) specific receptor protects against cardiac hypertrophy, we examined whether maternal type 1 diabetes affects the plasma concentrations of proCNP-derived peptides in newborn infants. METHODS: Plasma concentrations of proCNP-derived peptides were measured in umbilical cord plasma and human placental tissue extracts using sequence-specific radioimmunoassays raised against N-terminal and C-terminal proCNP regions, respectively. RESULTS: The median proCNP concentrations were similar in umbilical cord plasma from pregnant women with and without type 1 diabetes (17 pmol/L vs. 19 pmol/L, P not significant) and did not correlate with the proBNP concentrations in the same samples. However, the molar ratio between the proCNP and the CNP peptide was increased in umbilical cord plasma compared to adult plasma (4.6 vs. 1.1), which parallels our earlier findings for proBNP and BNP peptides. CONCLUSIONS: There is a discordant expression of CNP and BNP peptides in newborn infants of mothers with diabetes. Moreover, fetal metabolism of proCNP and CNP appears to differ from healthy adults. The precise mechanism underlying these differences warrants further investigation. 相似文献
152.
Sørensen RB Hadrup SR Køllgaard T Svane IM thor Straten P Andersen MH 《Cancer immunology, immunotherapy : CII》2007,56(4):527-533
Based on the detection of spontaneous immune responses in cancer patients with cancer of different origin, Bcl-X(L) was recently
described as a highly interesting tumor antigen recognized by CD8 positive cytotoxic T lymphocytes. To further characterize
Bcl-X(L) as a tumor antigen we isolated and expanded Bcl-X(L) specific T cells from the peripheral blood of a breast cancer
patient hosting a strong Bcl-X(L) specific T cell response. We describe that HLA-A2 restricted Bcl-X(L) specific T cell clones
very efficiently lyse peptide pulsed T2 cells. Furthermore, tumor cell lines of different origin, i.e., breast cancer, colon
cancer, and melanoma, are efficiently lysed in an HLA-dependent manner. Finally, ex vivo-isolated leukemia cells, but not
non-malignant B and T cells are killed by Bcl-X(L) specific T cells. Our data underline Bcl-X(L) as an universal tumor antigen
widely applicable in specific anticancer immunotherapy. 相似文献
153.
Mads T. S?ndergaard Xixi Tian Yingjie Liu Ruiwu Wang Walter J. Chazin S. R. Wayne Chen Michael T. Overgaard 《The Journal of biological chemistry》2015,290(43):26151-26162
The intracellular Ca2+ sensor calmodulin (CaM) regulates the cardiac Ca2+ release channel/ryanodine receptor 2 (RyR2), and mutations in CaM cause arrhythmias such as catecholaminergic polymorphic ventricular tachycardia (CPVT) and long QT syndrome. Here, we investigated the effect of CaM mutations causing CPVT (N53I), long QT syndrome (D95V and D129G), or both (CaM N97S) on RyR2-mediated Ca2+ release. All mutations increased Ca2+ release and rendered RyR2 more susceptible to store overload-induced Ca2+ release (SOICR) by lowering the threshold of store Ca2+ content at which SOICR occurred and the threshold at which SOICR terminated. To obtain mechanistic insights, we investigated the Ca2+ binding of the N- and C-terminal domains (N- and C-domain) of CaM in the presence of a peptide corresponding to the CaM-binding domain of RyR2. The N53I mutation decreased the affinity of Ca2+ binding to the N-domain of CaM, relative to CaM WT, but did not affect the C-domain. Conversely, mutations N97S, D95V, and D129G had little or no effect on Ca2+ binding to the N-domain but markedly decreased the affinity of the C-domain for Ca2+. These results suggest that mutations D95V, N97S, and D129G alter the interaction between CaM and the CaMBD and thus RyR2 regulation. Because the N53I mutation minimally affected Ca2+ binding to the C-domain, it must cause aberrant regulation via a different mechanism. These results support aberrant RyR2 regulation as the disease mechanism for CPVT associated with CaM mutations and shows that CaM mutations not associated with CPVT can also affect RyR2. A model for the CaM-RyR2 interaction, where the Ca2+-saturated C-domain is constitutively bound to RyR2 and the N-domain senses increases in Ca2+ concentration, is proposed. 相似文献
154.
Christoph Biesemann Mads Grønborg Elisa Luquet Sven P Wichert Véronique Bernard Simon R Bungers Ben Cooper Frédérique Varoqueaux Liyi Li Jennifer A Byrne Henning Urlaub Olaf Jahn Nils Brose Etienne Herzog 《The EMBO journal》2014,33(2):157-170
For decades, neuroscientists have used enriched preparations of synaptic particles called synaptosomes to study synapse function. However, the interpretation of corresponding data is problematic as synaptosome preparations contain multiple types of synapses and non‐synaptic neuronal and glial contaminants. We established a novel Fluorescence Activated Synaptosome Sorting (FASS) method that substantially improves conventional synaptosome enrichment protocols and enables high‐resolution biochemical analyses of specific synapse subpopulations. Employing knock‐in mice with fluorescent glutamatergic synapses, we show that FASS isolates intact ultrapure synaptosomes composed of a resealed presynaptic terminal and a postsynaptic density as assessed by light and electron microscopy. FASS synaptosomes contain bona fide glutamatergic synapse proteins but are almost devoid of other synapse types and extrasynaptic or glial contaminants. We identified 163 enriched proteins in FASS samples, of which FXYD6 and Tpd52 were validated as new synaptic proteins. FASS purification thus enables high‐resolution biochemical analyses of specific synapse subpopulations in health and disease. 相似文献
155.
Mads F. Hjorth Jean-Philippe Chaput Camilla T. Damsgaard Stine-Mathilde Dalskov Rikke Andersen Arne Astrup Kim F. Michaelsen Inge Tetens Christian Ritz Anders Sj?din 《PloS one》2014,9(8)
Background
As cardio-metabolic risk tracks from childhood to adulthood, a better understanding of the relationship between movement behaviors (physical activity, sedentary behavior and sleep) and cardio-metabolic risk in childhood may aid in preventing metabolic syndrome (MetS) in adulthood.Objective
To examine independent and combined cross-sectional and longitudinal associations between movement behaviors and the MetS score in 8-11 year old Danish children.Design
Physical activity, sedentary time and sleep duration (seven days and eight nights) were assessed by accelerometer and fat mass index (fat mass/height2) was assessed using Dual-energy X-ray absorptiometry. The MetS-score was based on z-scores of waist circumference, mean arterial blood pressure, homeostatic model assessment of insulin resistance, triglycerides and high density lipoprotein cholesterol. All measurements were taken at three time points separated by 100 days. Average of the three measurements was used as habitual behavior in the cross-sectional analysis and changes from first to third measurement was used in the longitudinal analysis.Results
723 children were included. In the cross-sectional analysis, physical activity was negatively associated with the MetS-score (P<0.03). In the longitudinal analysis, low physical activity and high sedentary time were associated with an increased MetS-score (all P<0.005); however, after mutual adjustments for movement behaviors, physical activity and sleep duration, but not sedentary time, were associated with the MetS-score (all P<0.03). Further adjusting for fat mass index while removing waist circumference from the MetS-score rendered the associations no longer statistically significant (all P>0.17). Children in the most favorable tertiles of changes in moderate-to-vigorous physical activity, sleep duration and sedentary time during the 200-day follow-up period had an improved MetS-score relative to children in the opposite tertiles (P = 0.005).Conclusion
The present findings indicate that physical activity, sedentary time and sleep duration should all be targeted to improve cardio-metabolic risk markers in childhood; this is possibly mediated by adiposity. 相似文献156.
157.
Chenjie Xu Yuk Kee C. Poh Isaac Roes Eoin D. O'Cearbhaill Mads Emil Matthiesen Luye Mu Seung Yun Yang David Miranda-Nieves Daniel Irimia Jeffrey M. Karp 《PloS one》2012,7(9)
Flow-based microfluidic systems have been widely utilized for cell migration studies given their ability to generate versatile and precisely defined chemical gradients and to permit direct visualization of migrating cells. Nonetheless, the general need for bulky peripherals such as mechanical pumps and tubing and the complicated setup procedures significantly limit the widespread use of these microfluidic systems for cell migration studies. Here we present a simple method to power microfluidic devices for chemotaxis assays using the commercially available ALZET® osmotic pumps. Specifically, we developed a standalone chemotaxis platform that has the same footprint as a multiwell plate and can generate well-defined, stable chemical gradients continuously for up to 7 days. Using this platform, we validated the short-term (24 hours) and long-term (72 hours) concentration dependent PDGF-BB chemotaxis response of human bone marrow derived mesenchymal stem cells. 相似文献
158.
159.
160.
M Rosenkilde P Auerbach MH Reichkendler T Ploug BM Stallknecht A Sjödin 《American journal of physiology. Regulatory, integrative and comparative physiology》2012,303(6):R571-R579
The amount of weight loss induced by exercise is often disappointing. A diet-induced negative energy balance triggers compensatory mechanisms, e.g., lower metabolic rate and increased appetite. However, knowledge about potential compensatory mechanisms triggered by increased aerobic exercise is limited. A randomized controlled trial was performed in healthy, sedentary, moderately overweight young men to examine the effects of increasing doses of aerobic exercise on body composition, accumulated energy balance, and the degree of compensation. Eighteen participants were randomized to a continuous sedentary control group, 21 to a moderate-exercise (MOD; 300 kcal/day), and 22 to a high-exercise (HIGH; 600 kcal/day) group for 13 wk, corresponding to ~30 and 60 min of daily aerobic exercise, respectively. Body weight (MOD: -3.6 kg, P < 0.001; HIGH: -2.7 kg, P = 0.01) and fat mass (MOD: -4.0 kg, P < 0.001 and HIGH: -3.8 kg, P < 0.001) decreased similarly in both exercise groups. Although the exercise-induced energy expenditure in HIGH was twice that of MOD, the resulting accumulated energy balance, calculated from changes in body composition, was not different (MOD: -39.6 Mcal, HIGH: -34.3 Mcal, not significant). Energy balance was 83% more negative than expected in MOD, while it was 20% less negative than expected in HIGH. No statistically significant changes were found in energy intake or nonexercise physical activity that could explain the different compensatory responses associated with 30 vs. 60 min of daily aerobic exercise. In conclusion, a similar body fat loss was obtained regardless of exercise dose. A moderate dose of exercise induced a markedly greater than expected negative energy balance, while a higher dose induced a small but quantifiable degree of compensation. 相似文献