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91.
Orietta D'Orlando Fang Zhao Brigitte Kasper Zane Orinska Jürgen Müller Irm Hermans‐Borgmeyer Gillian M. Griffiths Udo Zur Stadt Silvia Bulfone‐Paus 《European journal of immunology》2013,43(1):194-208
Syntaxin 11 (STX11) controls vesicular trafficking and is a key player in exocytosis. Since Stx11 mutations are causally associated with a familial hemophagocytic lymphohistio‐cytosis, we wanted to clarify whether STX11 is functionally important for key immune cell populations. This was studied in primary cells obtained from newly generated Stx11?/? mice. Our data revealed that STX11 is not only widely expressed in different immune cells, but also induced upon LPS or IFN‐γ treatment. However, Stx11 deficiency does not affect macrophage phagocytic function and cytokine secretion, mast cell activation, or antigen presentation by DCs. Instead, STX11 selectively controls lymphocyte cytotoxicity in NK and activated CD8+ T cells and degranulation in neutrophils. Stx11?/? NK cells and CTLs show impaired degranulation, despite a comparable activation, maturation and expression of the complex‐forming partners MUNC18–2 and VTI1B. In addition, Stx11?/? CTLs and NK cells produce abnormal levels of IFN‐γ. Since functional reconstitution rescues the defective phenotype of Stx11?/? CTLs, we suggest a direct, specific and key role of STX11 in controlling lymphocyte cytotoxicity, cytokine production and secretion. Finally, we show that these mice are a very useful tool for dissecting the role of STX11 in vesicular trafficking and secretion. 相似文献
92.
Michal Cohen‐Eliav Regina Golan‐Gerstl Zahava Siegfried Claus L Andersen Kasper Thorsen Torben F Ørntoft David Mu Rotem Karni 《The Journal of pathology》2013,229(4):630-639
An increasing body of evidence connects alterations in the process of alternative splicing with cancer development and progression. However, a direct role of splicing factors as drivers of cancer development is mostly unknown. We analysed the gene copy number of several splicing factors in colon and lung tumours, and found that the gene encoding for the splicing factor SRSF6 is amplified and over‐expressed in these cancers. Moreover, over‐expression of SRSF6 in immortal lung epithelial cells enhanced proliferation, protected them from chemotherapy‐induced cell death and converted them to be tumourigenic in mice. In contrast, knock‐down of SRSF6 in lung and colon cancer cell lines inhibited their tumourigenic abilities. SRSF6 up‐ or down‐regulation altered the splicing of several tumour suppressors and oncogenes to generate the oncogenic isoforms and reduce the tumour‐suppressive isoforms. Our data suggest that the splicing factor SRSF6 is an oncoprotein that regulates the proliferation and survival of lung and colon cancer cells. 相似文献
93.
Mads Damkjær Gustaf L. Isaksson Jane Stubbe Boye L. Jensen Kasper Assersen Peter Bie 《Pflügers Archiv : European journal of physiology》2013,465(1):153-165
The renin–angiotensin system is essential for body fluid homeostasis and blood pressure regulation. This review focuses on the homeostatic regulation of the secretion of active renin in the kidney, primarily in humans. Under physiological conditions, renin secretion is determined mainly by sodium intake, but the specific pathways involved and the relations between them are not well defined. In animals, renin secretion is a log-linear function of sodium intake. Close associations exist between sodium intake, total body sodium, extracellular fluid volume, and blood volume. Plasma volume increases by about 1.5 mL/mmol increase in daily sodium intake. Several lines of evidence indicate that central blood volume may vary substantially without measurable changes in arterial blood pressure. At least five intertwining feedback loops of renin regulation are identifiable based on controlled variables (blood volume, arterial blood pressure), efferent pathways to the kidney (nervous, humoral), and pathways operating via the macula densa. Taken together, the available evidence favors the notion that under physiological conditions (1) volume-mediated regulation of renin secretion is the primary regulator, (2) macula densa mediated mechanisms play a substantial role as co-mediator although the controlled variables are not well defined so far, and (3) regulation via arterial blood pressure is the exception rather than the rule. Improved quantitative analyses based on in vivo and in silico models are warranted. 相似文献
94.
Niki Antypa Raffaella Calati Daniel Souery Silvia Pellegrini Othman Sentissi Daniela Amital Ulrike Moser Stuart Montgomery Siegfried Kasper Joseph Zohar Diana De Ronchi Julien Mendlewicz Alessandro Serretti 《Journal of affective disorders》2013
Background
Social adjustment is impaired in depressed patients. The difficulty to adjust to social circumstances has been hypothesized to be one of the causes of depression, as well as a consequence of the disorder. Genetic variation in the serotonin transporter gene has been previously associated with social adjustment levels in patients with mood disorders.Methods
We investigated whether variations on the HTR1A (rs6295) and HTR2A (rs7997012) genes were associated with levels of social adjustment using the Social Adjustment Scale in two samples of depressed patients (total n=156).Results
Patients carrying the GG genotype of the HTR2A-rs7997012 showed better social adjustment in areas of work and family unit bonding.Limitations
These findings did not survive correction for multiple testing and should be interpreted with caution.Conclusion
Our finding is in line with previous observations that have associated the G allele of the HTR2A-rs7997012 with higher rate of antidepressant response. The HTR2A-rs7997012 is worthy of further investigation in studies examining factors that are related to depression course and outcome. 相似文献95.
SG Lindquist M Duno M Batbayli A Puschmann H Braendgaard S Mardosiene K Svenstrup LH Pinborg K Vestergaard LE Hjermind J Stokholm BB Andersen P Johannsen JE Nielsen 《Clinical genetics》2013,83(3):279-283
Recently, a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 was reported as the cause of chromosome 9p21‐linked frontotemporal dementia‐amyotrophic lateral sclerosis (FTD‐ALS). We here report the prevalence of the expansion in a hospital‐based cohort and associated clinical features indicating a wider clinical spectrum of C9ORF72 disease than previously described. We studied 280 patients previously screened for mutations in genes involved in early onset autosomal dominant inherited dementia disorders. A repeat‐primed polymerase chain reaction amplification assay was used to identify pathogenic GGGGCC expansions. As a potential modifier, confirmed cases were further investigated for abnormal CAG expansions in ATXN2. A pathogenic GGGGCC expansion was identified in a total of 14 probands. Three of these presented with atypical clinical features and were previously diagnosed with clinical olivopontocerebellar degeneration (OPCD), atypical Parkinsonian syndrome (APS) and a corticobasal syndrome (CBS). Further, the pathogenic expansion was identified in six FTD patients, four patients with FTD‐ALS and one ALS patient. All confirmed cases had normal ATXN2 repeat sizes. Our study widens the clinical spectrum of C9ORF72related disease and confirms the hexanucleotide expansion as a prevalent cause of FTD‐ALS disorders. There was no indication of a modifying effect of the ATXN2 gene. 相似文献
96.
97.
Louise Faurholt Obro Kasper Heiselberg Peter Gall Krogh Charlotte Handberg Jette Ammentorp Gitte Thybo Pihl Palle Jörn Sloth Osther 《Patient education and counseling》2021,104(4):680-688
BackgroundSelf-management approaches are widely used to improve chronic care. In this context, health care professionals call for efficient tools to engage patients in managing their illness. Mobile health (mHealth), defined by WHO as medical and public health practice supported by mobile devices, is demonstrated to enhance self-management and health-coaching as an engaging tool in supporting behaviour change. Nevertheless, it is unclear how health-coaching and mHealth can benefit from each other.ObjectiveWe conducted a scoping review to provide a literature-overview and identify any existing gaps in knowledge of mHealth in combination with health-coaching interventions for improving self-management in patients with chronic diseases.Patient involvementNo patients were involved in the review process.MethodsThe five-stage framework by Arksey and O'Malley was used. The review surveys; PubMed, CINAHL, Embase, Scopus, and PsycInfo. Two independent reviewers performed review selection and characterization.ResultsThe review points at two approaches; (i) coaching used to support mHealth and (ii) mHealth as support for coaching. The findings suggest that patients prefer physical interactions to telecommunication. mHealth was primarily used to facilitate telecommunication and to monitor disease aspects.DiscussionWe found that mHealth and health-coaching interventions benefit from each other. The review report on a considerable unclarity in the coaching-methods and that the patients were more satisfied with physical interactions than mHealth. We suggest to prioritize human contact and to explore more personalized health technology.Practical valueThis scoping review can provide a framework for researchers and care providers to support discussion and introduction of new approaches and technology in self-management for patients with chronic diseases, thereby improving patients’ quality of life. 相似文献
98.
Yael Lupu-Haber Oded Pinkas Stefanie Boehm Thomas Scheper Cornelia Kasper Marcelle Machluf 《Biomedical microdevices》2013,15(6):1055-1066
Bone tissue engineering is an alternative approach to bone grafts. In our study we aim to develop a composite scaffold for bone regeneration made of doped zirconium oxide (ZrO2) conjugated with poly(lactic-co-glycolic acid) (PLGA) particles for the delivery of growth factors. In this composite, the PLGA microspheres are designed to release a crucial growth factor for bone formation, bone morphogenetic protein-2 (BMP2). We found that by changing the polymer’s molecular weight and composition, we could control microsphere loading, release and size. The BMP2 released from PLGA microspheres retained its biological activity and increased osteoblastic marker expression in human mesenchymal stem cells (hMSCs). Uncapped PLGA microspheres were conjugated to ZrO2 scaffolds using carbodiimide chemistry, and the composite scaffold was shown to support hMSCs growth. We also demonstrated that human umbilical vein endothelial cells (HUVECs) can be co-cultured with hMSCs on the ZrO2 scaffold for future vascularization of the scaffold. The ZrO2 composite scaffold could serve as a bone substitute for bone grafting applications with the added ability of releasing different growth factors needed for bone regeneration. 相似文献
99.
100.
The predictive value of ERG protein expression for development of castration‐resistant prostate cancer in hormone‐naïve advanced prostate cancer treated with primary androgen deprivation therapy
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Kasper D. Berg Martin A. Røder Frederik B. Thomsen Ben Vainer Thomas A. Gerds Klaus Brasso Peter Iversen 《The Prostate》2015,75(14):1499-1509