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排序方式: 共有361条查询结果,搜索用时 15 毫秒
291.
Hematopoietic stem cells (HSCs) are responsible for the production of mature blood cells in bone marrow; peripheral pancytopenia is a common clinical presentation resulting from several different conditions, including hematological or extra-hematological diseases (mostly cancers) affecting the marrow function, as well as primary failure of hematopoiesis. Primary bone marrow failure syndromes are a heterogeneous group of diseases with specific pathogenic mechanisms, which share a profound impairment of the hematopoietic stem cell pool resulting in global or selective marrow aplasia. Constitutional marrow failure syndromes are conditions caused by intrinsic defects of HSCs; they are due to inherited germline mutations accounting for specific phenotypes, and often involve also organs and systems other than hematopoiesis. By contrast, in acquired marrow failure syndromes hematopoietic stem cells are thought to be intrinsically normal, but subjected to an extrinsic damage affecting their hematopoietic function. Direct toxicity by chemicals or radiation, as well as association with viruses and other infectious agents, can be sometimes demonstrated. In idiopathic Aplastic Anemia (AA) immunological mechanisms play a pivotal role in damaging the hematopoietic compartment, resulting in a depletion of the hematopoietic stem cell pool. Clinical and experimental evidences support the presence of a T cell-mediated immune attack, as confirmed by clonally expanded lymphocytes, even if the target antigens are still undefined. However, this simple model has to be integrated with recent data showing that, even in presence of an extrinsic damage, preexisting mutations or polymorphisms of genes may constitute a genetic propensity to develop marrow failure. Other recent data suggest that similar antigen-driven immune mechanisms may be involved in marrow failure associated with lymphoproliferative or autoimmune disorders characterized by clonal expansion of T lymphocytes, such as Large Granular Lymphocyte leukemia. In this wide spectrum, a unique and intriguing condition is Paroxysmal Nocturnal Hemoglobinuria (PNH); even in presence of a somatic mutation of the PIG-A gene carried by one or more HSCs and their progeny, the typical marrow failure in PNH is likely due to pathogenic mechanisms similar to those involved in AA, and not to the intrinsic abnormality conferred to the clonal population by the PIG-A mutation. The study of hematopoietic stem cell function in marrow failure syndromes provides hints for specific molecular pathways disturbed in many diseases of hematopoietic and non-hematopoietic stem cells. Beyond the specific interest of investigators involved in the field of these rare diseases, marrow failure syndromes represent a model that provides intriguing insight into quantity and function of normal hematopoietic stem cells, improving our knowledge on stem cell biology. 相似文献
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Anna Wojakowska ?ukasz Marczak Karol Jelonek Krzysztof Polanski Piotr Widlak Monika Pietrowska 《PloS one》2015,10(9)
Formalin-fixed paraffin-embedded (FFPE) tissue specimens constitute a highly valuable source of clinical material for retrospective molecular studies. However, metabolomic assessment of such archival material remains still in its infancy. Hence, there is an urgent need for efficient methods enabling extraction and profiling of metabolites present in FFPE tissue specimens. Here we demonstrate the methodology for isolation of primary metabolites from archival tissues; either fresh-frozen, formalin-fixed or formalin-fixed and paraffin-embedded specimens of mouse kidney were analysed and compared in this work. We used gas chromatography followed by mass spectrometry (GC/MS approach) to identify about 80 metabolites (including amino acids, saccharides, carboxylic acids, fatty acids) present in such archive material. Importantly, about 75% of identified compounds were detected in all three types of specimens. Moreover, we observed that fixation with formalin itself (and their duration) did not affect markedly the presence of particular metabolites in tissue-extracted material, yet fixation for 24h could be recommended as a practical standard. Paraffin embedding influenced efficiency of extraction, which resulted in reduced quantities of several compounds. Nevertheless, we proved applicability of FFPE specimens for non-targeted GS/MS-based profiling of tissue metabolome, which is of great importance for feasibility of metabolomics studies using retrospective clinical material. 相似文献
295.
Jaroslaw R Romaniuk Thomas E Dick Krzysztof E Kowalski Anthony F Dimarco 《Journal of applied physiology》2007,102(1):485-491
The effects of pulse lung inflation (LI) on expiratory muscle activity and phase duration (Te) were determined in anesthetized, spontaneously breathing dogs (n = 20). A volume syringe was used to inflate the lungs at various times during the expiratory phase. The magnitude of lung volume was assessed by the corresponding change in airway pressure (Paw; range 2-20 cmH(2)O). Electromyographic (EMG) activities were recorded from both thoracic and abdominal muscles. Parasternal muscle EMG was used to record inspiratory activity. Expiratory activity was assessed from the triangularis sterni (TS), internal intercostal (IIC), and transversus abdominis (TA) muscles. Lung inflations <7 cmH(2)O consistently inhibited TS activity but had variable effects on TA and IIC activity and expiratory duration. Lung inflations resulting in Paw values >7 cmH(2)O, however, inhibited expiratory EMG activity of each of the expiratory muscles and lengthened Te in all animals. The responses of expiratory EMG and Te were directly related to the magnitude of the lung inflation. The inhibition of expiratory motor activity was independent of the timing of pulse lung inflation during the expiratory phase. The inhibitory effects of lung inflation were eliminated by bilateral vagotomy and could be reproduced by electrical stimulation of the vagus nerve. We conclude that pulse lung inflation resulting in Paw between 7 and 20 cmH(2)O produces a vagally mediated inhibition of expiratory muscle activity that is directly related to the magnitude of the inflation. Lower inflation pressures produce variable effects that are muscle specific. 相似文献
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Macierzanka M Plotka M Pryputniewicz-Drobinska D Lewandowska A Lightowlers R Marszalek J 《Biochimica et biophysica acta》2008,1783(1):107-117
Mitochondrial DNA (mtDNA) is inherited as a protein-DNA complex (the nucleoid). Proteins associated with the nucleoid are not only components directly involved in maintenance and propagation of mtDNA but can also be bi-functional enzymes whose metabolic activities are not directly related to mtDNA stability. In the yeast Saccharomyces cerevisiae, one such enzyme, Ilv5p is required for branch chain amino acid biosynthesis but also associates with the nucleoid. Deletions of ILV5 lead not only to metabolic defects but also to destabilization of mtDNA. Further, minor overproduction of Ilv5p stabilizes mtDNA in strains lacking Abf2p, a major mtDNA binding and packaging protein. Here we show that Ilv5p binds double-stranded DNA in vitro and is unaffected by the presence of saturating concentrations of Abf2p. In cells lacking Abf2p the amount of Ilv5p associated with the nucleoid increases significantly and is proportional to the mitochondrial concentration of Ilv5p. Altogether, we conclude that direct binding of Ilv5p can aid in the maintenance and stabilization of mtDNA. 相似文献
298.
Zurawa-Janicka D Kobiela J Stefaniak T Wozniak A Narkiewicz J Wozniak M Limon J Lipinska B 《Acta biochimica Polonica》2008,55(1):9-19
Serine proteases HtrA1 and HtrA2 are involved in cellular stress response and development of several diseases, including cancer. Our aim was to examine the involvement of the HtrA proteins in acute oxidative stress response induced in hamster kidney by estrogen treatment, and in nephrocarcinogenesis caused by prolonged estrogenization of male Syrian hamster. We used semi-quantitative RT-PCR to estimate the HtrA1 and HtrA2 mRNA levels in kidney tissues, and Western blotting to monitor the amount of the HtrA proteins. Within the first five hours following estrogen administration both HtrA1 mRNA and the protein levels were increased significantly. No changes in the expression of HtrA2 were observed. This indicates that HtrA1 may be involved in the response against oxidative stress induced by estrogen treatment in hamster kidney. During prolonged estrogenization, a significant reduction of the HtrA1 mRNA and protein levels was observed after 6 months of estradiol treatment, while the expression of HtrA2 was significantly elevated starting from the third month. This suggests an involvement of the HtrA proteins in estrogen-induced nephrocarcinogenesis in hamster. Using fluorescence in situ hybridization we localized the HtrA1 gene at the qb3-4 region of Syrian hamster chromosome 2, the region known to undergo a nonrandom deletion upon prolonged estrogenization. It is possible that the reduced level of HtrA1 expression is due to this chromosomal aberration. A full-length cDNA sequence of the hamster HtrA1 gene was obtained. It codes for a 50 kDa protein which has 98 and 96% identity with mouse and human counterparts, respectively. 相似文献
299.
Skorupinska-Tudek K Poznanski J Wojcik J Bienkowski T Szostkiewicz I Zelman-Femiak M Bajda A Chojnacki T Olszowska O Grunler J Meyer O Rohmer M Danikiewicz W Swiezewska E 《The Journal of biological chemistry》2008,283(30):21024-21035
Plant isoprenoids are derived from two biosynthetic pathways, the cytoplasmic mevalonate (MVA) and the plastidial methylerythritol phosphate (MEP) pathway. In this study their respective contributions toward formation of dolichols in Coluria geoides hairy root culture were estimated using in vivo labeling with (13)C-labeled glucose as a general precursor. NMR and mass spectrometry showed that both the MVA and MEP pathways were the sources of isopentenyl diphosphate incorporated into polyisoprenoid chains. The involvement of the MEP pathway was found to be substantial at the initiation stage of dolichol chain synthesis, but it was virtually nil at the terminal steps; statistically, 6-8 isoprene units within the dolichol molecule (i.e. 40-50% of the total) were derived from the MEP pathway. These results were further verified by incorporation of [5-(2)H]mevalonate or [5,5-(2)H(2)]deoxyxylulose into dolichols as well as by the observed decreased accumulation of dolichols upon treatment with mevinolin or fosmidomycin, selective inhibitors of either pathway. The presented data indicate that the synthesis of dolichols in C. geoides roots involves a continuous exchange of intermediates between the MVA and MEP pathways. According to our model, oligoprenyl diphosphate chains of a length not exceeding 13 isoprene units are synthesized in plastids from isopentenyl diphosphate derived from both the MEP and MVA pathways, and then are completed in the cytoplasm with several units derived solely from the MVA pathway. This study also illustrates an innovative application of mass spectrometry for qualitative and quantitative evaluation of the contribution of individual metabolic pathways to the biosynthesis of natural products. 相似文献
300.
Izabela Szulc-Kielbik Jakub Pawelczyk Michal Kielbik Laurent Kremer Jaroslaw Dziadek Magdalena Klink 《Microbial cell factories》2017,16(1):217