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Takeda H Takami M Oguni T Tsuji T Yoneda K Sato H Ihara N Itoh T Kata SR Mishina Y Womack JE Moritomo Y Sugimoto Y Kunieda T 《Proceedings of the National Academy of Sciences of the United States of America》2002,99(16):10549-10554
Chondrodysplastic dwarfism in Japanese brown cattle is an autosomal recessive disorder characterized by short limbs. Previously, we mapped the locus responsible for the disease on the distal end of bovine chromosome 6. Here, we narrowed the critical region to approximately 2 cM by using linkage analysis, constructed a BAC and YAC contig covering this region, and identified a gene, LIMBIN (LBN), that possessed disease-specific mutations in the affected calves. One mutation was a single nucleotide substitution leading to an activation of a cryptic splicing donor site and the other was a one-base deletion resulting in a frameshift mutation. Strong expression of the Lbn gene was observed in limb buds of developing mouse embryos and in proliferating chondrocytes and bone-forming osteoblasts in long bones. These findings indicate that LBN is responsible for bovine chondrodysplastic dwarfism and has a critical role in a skeletal development. 相似文献
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Marttila-Ichihara F Turja R Miiluniemi M Karikoski M Maksimow M Niemelä J Martinez-Pomares L Salmi M Jalkanen S 《Blood》2008,112(1):64-72
Macrophage mannose receptor (MR) participates in pathogen recognition, clearance of endogenous serum glycoproteins, and antigen presentation. MR is also present on lymphatic vessels, where its function is unknown. Here we show that migration of lymphocytes from the skin into the draining lymph nodes through the afferent lymphatics is reduced in MR-deficient mice, while the structure of lymphatic vasculature remains normal in these animals. Moreover, in a tumor model the primary tumors grow significantly bigger in MR–/– mice than in the wild-type (WT) controls, whereas the regional lymph node metastases are markedly smaller. Adhesion of both normal lymphocytes and tumor cells to lymphatic vessels is significantly decreased in MR-deficient mice. The ability of macrophages to present tumor antigens is indistinguishable between the 2 genotypes. Thus, MR on lymphatic endothelial cells is involved in leukocyte trafficking and contributes to the metastatic behavior of cancer cells. Blocking of MR may provide a new approach to controlling inflammation and cancer metastasis by targeting the lymphatic vasculature. 相似文献
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Sarfati M Mateo V Baudet S Rubio M Fernandez C Davi F Binet JL Delic J Merle-Beral H 《Blood》2003,101(1):265-269
Type 4 phosphodiesterase (PDE4) inhibitors reportedly induce apoptosis in chronic lymphocytic leukemia (CLL) cells. Following clinical improvement of one previously untreated CLL patient with sildenafil therapy, we evaluated the in vitro induction of apoptosis in CLL cells by 4 PDE5/6 inhibitors, including sildenafil, vardenafil, zaprinast, and methoxyquinazoline (MQZ). After 24 hours of culture, the various PDE inhibitors differed in their ability to induce apoptosis, with zaprinast displaying no killing effect. Normal B cells isolated from control donors were totally resistant to PDE-induced apoptosis. Vardenafil was 3 and 30 times more potent an inducer of apoptosis than sildenafil and MQZ, respectively. Both vardenafil and sildenafil failed to elevate adenosine 3'5' cyclic monophosphate (cAMP) levels, largely excluding an inhibitory effect on cAMP-PDE3, -PDE4, and -PDE7. Vardenafil- or sildenafil-treated B-CLL cells displayed up to 30% intracellular active caspase 3. Drug-induced apoptosis was inhibited by the caspase inhibitor z-VAD.fmk, prevented by interleukin-4 (IL-4), and significantly reduced by stromal-derived factor1-alpha (SDF-1alpha). We conclude that vardenafil and sildenafil induce caspase-dependent apoptosis of B-CLL cells in vitro and thus might be considered in the treatment of CLL patients. However, further in vivo investigations should be warranted. 相似文献
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Thierry Poynard Valentina Peta Olivier Deckmyn Mona Munteanu Joseph Moussalli Yen Ngo Marika Rudler Pascal Lebray Raluca Pais Luminita Bonyhay Frederic Charlotte Vincent Thibault Laetitia Fartoux Olivier Lucidarme Daniel Eyraud Olivier Scatton Eric Savier Marc Antoine Valantin An Ngo Fabienne Drane Olivier Rosmorduc Franoise Imbert‐Bismut Chantal Housset Dominique Thabut Vlad Ratziu 《Alimentary pharmacology & therapeutics》2019,49(3):308-320
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Brain networks disconnection in early multiple sclerosis cognitive deficits: An anatomofunctional study 下载免费PDF全文
Céline Louapre Vincent Perlbarg Daniel García‐Lorenzo Marika Urbanski Habib Benali Rana Assouad Damien Galanaud Léorah Freeman Benedetta Bodini Caroline Papeix Ayman Tourbah Catherine Lubetzki Bruno Stankoff 《Human brain mapping》2014,35(9):4706-4717
Severe cognitive impairment involving multiple cognitive domains can occur early during the course of multiple sclerosis (MS). We investigated resting state functional connectivity changes in large‐scale brain networks and related structural damage underlying cognitive dysfunction in patients with early MS. Patients with relapsing MS (3–5 years disease duration) were prospectively assigned to two groups based on a standardized neuropsychological evaluation: (1) cognitively impaired group (CI group, n = 15), with abnormal performances in at least 3 tests; (2) cognitively preserved group (CP group, n = 20) with normal performances in all tests. Patients and age‐matched healthy controls underwent a multimodal 3T magnetic resonance imaging (MRI) including anatomical T1 and T2 images, diffusion imaging and resting state functional MRI. Structural MRI analysis revealed that CI patients had a higher white matter lesion load compared to CP and a more severe atrophy in gray matter regions highly connected to networks involved in cognition. Functional connectivity measured by integration was increased in CP patients versus controls in attentional networks (ATT), while integration was decreased in CI patients compared to CP both in the default mode network (DMN) and ATT. An anatomofunctional study within the DMN revealed that functional connectivity was mostly altered between the medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC) in CI patients compared to CP and controls. In a multilinear regression model, functional correlation between MPFC and PCC was best predicted by PCC atrophy. Disconnection in the DMN and ATT networks may deprive the brain of compensatory mechanisms required to face widespread structural damage. Hum Brain Mapp 35:4706–4717, 2014. © 2014 Wiley Periodicals, Inc . 相似文献
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Lorenza Magliano Melania Patalano Alessandra Sagliocchi Marianna Scutifero Antonella Zaccaro Maria Grazia D’Angelo Federica Civati Erika Brighina Giuseppe Vita Gian Luca Vita Sonia Messina Maria Sframeli Marika Pane Maria Elena Lombardo Roberta Scalise Adele D’Amico Giulia Colia Michela Catteruccia Umberto Balottin Angela Berardinelli Maria Chiara Motta Corrado Angelini Alessandra Gaiani Claudio Semplicini Luca Bello Roberta Battini Guja Astrea Giulia Ricci Luisa Politano 《Journal of neurology》2014,261(1):188-195
This paper focuses on the psychological benefits of caregiving in key relatives of patients with muscular dystrophies (MD), a group of rare diseases characterized by progressive weakness and restriction of the patient’s functional abilities. We describe whether relatives perceived caregiving to be a positive experience and test whether relatives’ perceptions vary in relation to their view of the patient as a valued person, the degree of involvement in care, and the level of support provided by social network and professionals. The study sample included 502 key relatives of patients aged 4–25 years, suffering from Duchenne, Becker, or limb-girdle MD, in treatment for at least 6 months to one of the eight participating centers, living with at least one relative aged 18–80 years. Of key relatives, 88 % stated that they had gotten something positive out of the situation, 96 % considered their patients to be sensitive, and 94 % viewed their patients as talented. Positive aspects of caregiving were more recognized by key relatives who were more convinced that the patient was sensitive and who perceived that they received higher level of professional help and psychological social support. These results suggest that most key relatives consider that their caregiving experience has had a positive impact on their lives, despite the practical difficulties of caring for patients with MD. Professionals should help relatives to identify the benefits of caregiving without denying its difficulties. Clinicians themselves should develop positive attitudes towards family involvement in the care of patients with long-term diseases. 相似文献