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101.
102.
Renate Hochscheid Sven Heinrichs Stephan Kranz Holger Garn Bernd Müller 《Free radical research》2013,47(7):759-767
The lung is protected against oxidative stress by a variety of antioxidants and type II pneumocytes seem to play an important role in antioxidant defense. Previous studies have shown that inhalation of NO2 results in acute and chronic lung injury. How the expression and enzyme activity of antioxidant enzymes are influenced in type II cells of different inflammatory stages has yet not been studied. To elucidate this question, we exposed rats to 10 ppm NO2 for 3 or 20 days to induce acute or chronic lung injury. From these and air-breathing rats, type II pneumocytes were isolated. The mRNA expression and protein content of CuZnSOD and MnSOD as well as total SOD-specific enzyme activity were determined. For the acute lung injury (3 d NO2), the expression of CuZnSOD mRNA was significantly increased, while MnSOD expression was significantly reduced after 3 days of NO 2 exposure. For the chronic lung injury (20 d NO2), CuZnSOD expression was still enhanced, while MnSOD expression was comparable to control. In parallel to CuZnSOD mRNA expression, the protein amount was significantly increased in acute and chronic lung injury however MnSOD protein content exhibited no intergroup differences. Total SOD enzyme activity showed a significant decrease after 3 days of NO2 exposure and was similar to control after 20 days. We conclude that during acute and chronic lung injury in type II pneumocytes expression and protein synthesis of CuZnSOD and MnSOD are regulated differently. 相似文献
103.
Hereditary channelopathies, that is, mutations in channel genes that alter channel function
and are causal for the pathogenesis of the disease, have been described for several members
of the transient receptor potential channel family. Mutations in the TRPV4 gene,
encoding a polymodal Ca2+ permeable channel, are causative for several human
diseases, which affect the skeletal system and the peripheral nervous system, with highly
variable phenotypes. In this review, we describe the phenotypes of TRPV4 channelopathies and
overlapping symptoms. Putative mechanisms to explain the puzzle, and how mutations in the
same region of the channel cause different diseases, are discussed and experimental
approaches to tackle this surprising problem are suggested. 相似文献
104.
The lysosomal membrane was thought for a long time to primarily act as a physical barrier separating the luminal acidic milieu from the cytoplasmic environment. Meanwhile, it has been realized that unique lysosomal membranes play essential roles in a number of cellular events ranging from phagocytosis, autophagy, cell death, virus infection to membrane repair. This review provides an overview about the most interesting emerging functions of lysosomal membrane proteins and how they contribute to health and disease. Their importance is exemplified by their role in acidification, transport of metabolites and ions across the membrane, intracellular transport of hydrolases and the regulation of membrane fusion events. Studies in patient cells, non‐mammalian model organisms and knockout mice contributed to our understanding of how the different lysosomal membrane proteins affect cellular homeostasis, developmental processes as well as tissue functions. Because these proteins are central for the biogenesis of this compartment they are also considered as attractive targets to modulate the lysosomal machinery in cases where impaired lysosomal degradation leads to cellular pathologies. We are only beginning to understand the complex composition and function of these proteins which are tightly linked to processes occurring throughout the endocytic and biosynthetic pathways. 相似文献
105.
To investigate potential differences in stone composition with regard to the type of Primary Hyperoxaluria (PH), and in relation to the patient’s medical therapy (treatment naïve patients versus those on preventive medication) we examined twelve kidney stones from ten PH I and six stones from four PH III patients. Unfortunately, no PH II stones were available for analysis. The study on this set of stones indicates a more diverse composition of PH stones than previously reported and a potential dynamic response of morphology and composition of calculi to treatment with crystallization inhibitors (citrate, magnesium) in PH I. Stones formed by PH I patients under treatment are more compact and consist predominantly of calcium-oxalate monohydrate (COM, whewellite), while calcium-oxalate dihydrate (COD, weddellite) is only rarely present. In contrast, the single stone available from a treatment naïve PH I patient as well as stones from PH III patients prior to and under treatment with alkali citrate contained a wide size range of aggregated COD crystals. No significant effects of the treatment were noted in PH III stones. In disagreement with findings from previous studies, stones from patients with primary hyperoxaluria did not exclusively consist of COM. Progressive replacement of COD by small COM crystals could be caused by prolonged stone growth and residence times in the urinary tract, eventually resulting in complete replacement of calcium-oxalate dihydrate by the monohydrate form. The noted difference to the naïve PH I stone may reflect a reduced growth rate in response to treatment. This pilot study highlights the importance of detailed stone diagnostics and could be of therapeutic relevance in calcium-oxalates urolithiasis, provided that the effects of treatment can be reproduced in subsequent larger studies. 相似文献
106.
Judith Enders Matthias Rief Elke Zimmermann Patrick Asbach Gerd Diederichs Christoph Wetz Eberhard Siebert Moritz Wagner Bernd Hamm Marc Dewey 《PloS one》2013,8(12)
Background
The purpose of the present study was to compare the image quality of spinal magnetic resonance (MR) imaging performed on a high-field horizontal open versus a short-bore MR scanner in a randomized controlled study setup.Methods
Altogether, 93 (80% women, mean age 53) consecutive patients underwent spine imaging after random assignement to a 1-T horizontal open MR scanner with a vertical magnetic field or a 1.5-T short-bore MR scanner. This patient subset was part of a larger cohort. Image quality was assessed by determining qualitative parameters, signal-to-noise (SNR) and contrast-to-noise ratios (CNR), and quantitative contour sharpness.Results
The image quality parameters were higher for short-bore MR imaging. Regarding all sequences, the relative differences were 39% for the mean overall qualitative image quality, 53% for the mean SNR values, and 34–37% for the quantitative contour sharpness (P<0.0001). The CNR values were also higher for images obtained with the short-bore MR scanner. No sequence was of very poor (nondiagnostic) image quality. Scanning times were significantly longer for examinations performed on the open MR scanner (mean: 32±22 min versus 20±9 min; P<0.0001).Conclusions
In this randomized controlled comparison of spinal MR imaging with an open versus a short-bore scanner, short-bore MR imaging revealed considerably higher image quality with shorter scanning times.Trial Registration
ClinicalTrials.gov NCT00715806相似文献107.
Christina R?hr Martin Kerick Axel Fischer Alexander Kühn Karl Kashofer Bernd Timmermann Andriani Daskalaki Thomas Meinel Dmitriy Drichel Stefan T. B?rno Anja Nowka Sylvia Krobitsch Alice C. McHardy Christina Kratsch Tim Becker Andrea Wunderlich Christian Barmeyer Christian Viertler Kurt Zatloukal Christoph Wierling Hans Lehrach Michal R. Schweiger 《PloS one》2013,8(7)
MiRNAs are discussed as diagnostic and therapeutic molecules. However, effective miRNA drug treatments with miRNAs are, so far, hampered by the complexity of the miRNA networks. To identify potential miRNA drugs in colorectal cancer, we profiled miRNA and mRNA expression in matching normal, tumor and metastasis tissues of eight patients by Illumina sequencing. We validated six miRNAs in a large tissue screen containing 16 additional tumor entities and identified miRNA-1, miRNA-129, miRNA-497 and miRNA-215 as constantly de-regulated within the majority of cancers. Of these, we investigated miRNA-1 as representative in a systems-biology simulation of cellular cancer models implemented in PyBioS and assessed the effects of depletion as well as overexpression in terms of miRNA-1 as a potential treatment option. In this system, miRNA-1 treatment reverted the disease phenotype with different effectiveness among the patients. Scoring the gene expression changes obtained through mRNA-Seq from the same patients we show that the combination of deep sequencing and systems biological modeling can help to identify patient-specific responses to miRNA treatments. We present this data as guideline for future pre-clinical assessments of new and personalized therapeutic options. 相似文献
108.
Bernd Gröttrup Jens Wiltfang Helmut Heinsen Katrin Marcus Helmut E. Meyer Lea T. Grinberg Young Mok Park 《Proteomics》2013,13(20):2938-2941
The HUPO Brain Proteome Project (HUPO BPP) held its 19th workshop in Dortmund, Germany, from May 22 to 24, 2013. The focus of the spring workshop was on strategies and developments concerning early diagnosis of neurodegenerative diseases 相似文献
109.
Thomas B. Nicholson Anup K. Singh Hui Su Sarah Hevi Jing Wang Jeff Bajko Mei Li Reginald Valdez Margaret Goetschkes Paola Capodieci Joseph Loureiro Xiaodong Cheng En Li Bernd Kinzel Mark Labow Taiping Chen 《PloS one》2013,8(4)
Lysine-specific demethylase 1 (Lsd1/Aof2/Kdm1a), the first enzyme with specific lysine demethylase activity to be described, demethylates histone and non-histone proteins and is essential for mouse embryogenesis. Lsd1 interacts with numerous proteins through several different domains, most notably the tower domain, an extended helical structure that protrudes from the core of the protein. While there is evidence that Lsd1-interacting proteins regulate the activity and specificity of Lsd1, the significance and roles of such interactions in developmental processes remain largely unknown. Here we describe a hypomorphic Lsd1 allele that contains two point mutations in the tower domain, resulting in a protein with reduced interaction with known binding partners and decreased enzymatic activity. Mice homozygous for this allele die perinatally due to heart defects, with the majority of animals suffering from ventricular septal defects. Molecular analyses revealed hyperphosphorylation of E-cadherin in the hearts of mutant animals. These results identify a previously unknown role for Lsd1 in heart development, perhaps partly through the control of E-cadherin phosphorylation. 相似文献
110.
Anaerobic Co-Culture of Mesenchymal Stem Cells and Anaerobic Pathogens - A New In Vitro Model System