排序方式: 共有36条查询结果,搜索用时 0 毫秒
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Senderek J Krieger M Stendel C Bergmann C Moser M Breitbach-Faller N Rudnik-Schöneborn S Blaschek A Wolf NI Harting I North K Smith J Muntoni F Brockington M Quijano-Roy S Renault F Herrmann R Hendershot LM Schröder JM Lochmüller H Topaloglu H Voit T Weis J Ebinger F Zerres K 《Nature genetics》2005,37(12):1312-1314
SIL1 (also called BAP) acts as a nucleotide exchange factor for the Hsp70 chaperone BiP (also called GRP78), which is a key regulator of the main functions of the endoplasmic reticulum. We found nine distinct mutations that would disrupt the SIL1 protein in individuals with Marinesco-Sj?gren syndrome, an autosomal recessive cerebellar ataxia complicated by cataracts, developmental delay and myopathy. Identification of SIL1 mutations implicates Marinesco-Sj?gren syndrome as a disease of endoplasmic reticulum dysfunction and suggests a role for this organelle in multisystem disorders. 相似文献
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Astrid v. Lützow 《Cellular and molecular life sciences : CMLS》1966,22(4):215-216
Summary Theb-wave in the electroretinogram of the isolated retina of the rabbit can be completely preserved by addition of plasma to the perfusing fluid. The plasma factor is a non-protein (heat-stable, molecular size <24Å), and was found in the plasma of rabbit, man, and horse. 相似文献
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A microglial cell is both a glial cell of the central nervous system and a mononuclear phagocyte, which belongs to the haematopoietic system and is involved in inflammatory and immune responses. As such, microglia face a challenging task. The neurons of the central nervous system cannot divide and be replenished, and therefore need to be protected against pathogens, which is a key role of the immune system, but without collateral damage. In addition, after physical injury, neural cells need restorative support, which is provided by inflammatory responses. Excessive or chronic inflammatory responses can, however, be harmful. How microglia balance these demands, and how their behaviour can be modified to ameliorate disorders of the central nervous system, is becoming clear. 相似文献
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Svenja D. Steinbrink Carlo Pergola Ulrike Bühring Sven George Julia Metzner Astrid S. Fischer Ann-Kathrin Häfner Joanna M. Wisniewska Gerd Geisslinger Oliver Werz Dieter Steinhilber Thorsten J. Maier 《Cellular and molecular life sciences : CMLS》2010,67(5):797-806
Sulindac is a non-selective inhibitor of cyclooxygenases (COX) used to treat inflammation and pain. Additionally, non-COX targets may account for the drug’s chemo-preventive efficacy against colorectal cancer and reduced gastrointestinal toxicity. Here, we demonstrate that the pharmacologically active metabolite of sulindac, sulindac sulfide (SSi), targets 5-lipoxygenase (5-LO), the key enzyme in the biosynthesis of proinflammatory leukotrienes (LTs). SSi inhibited 5-LO in ionophore A23187- and LPS/fMLP-stimulated human polymorphonuclear leukocytes (IC50 ≈ 8–10 μM). Importantly, SSi efficiently suppressed 5-LO in human whole blood at clinically relevant plasma levels (IC50 = 18.7 μM). SSi was 5-LO-selective as no inhibition of related lipoxygenases (12-LO, 15-LO) was observed. The sulindac prodrug and the other metabolite, sulindac sulfone (SSo), failed to inhibit 5-LO. Mechanistic analysis demonstrated that SSi directly suppresses 5-LO with an IC50 of 20 μM. Together, these findings may provide a novel molecular basis to explain the COX-independent pharmacological effects of sulindac under therapy. 相似文献
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The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins 总被引:3,自引:0,他引:3
Veldhoen M Hirota K Westendorf AM Buer J Dumoutier L Renauld JC Stockinger B 《Nature》2008,453(7191):106-109
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H. Bornschein Renate Hanitzsch Astrid V. Lützow 《Cellular and molecular life sciences : CMLS》1966,22(2):98-99
Summary Barbiturates cause an increase of the ERG amplitude in the isolated perfused retina of the rabbit as well as in the eye of the intact animal. Therefore, this effect cannot be transmitted by centrifugal fibres in the optic nerve. 相似文献
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Chi Chiu Wang Ellen Billett Astrid Borchert Hartmut Kuhn Christoph Ufer 《Cellular and molecular life sciences : CMLS》2013,70(4):599-630
Monoamine oxidases (MAOs) are flavoproteins of the outer mitochondrial membrane that catalyze the oxidative deamination of biogenic and xenobiotic amines. In mammals there are two isoforms (MAO-A and MAO-B) that can be distinguished on the basis of their substrate specificity and their sensitivity towards specific inhibitors. Both isoforms are expressed in most tissues, but their expression in the central nervous system and their ability to metabolize monoaminergic neurotransmitters have focused MAO research on the functionality of the mature brain. MAO activities have been related to neurodegenerative diseases as well as to neurological and psychiatric disorders. More recently evidence has been accumulating indicating that MAO isoforms are expressed not only in adult mammals, but also before birth, and that defective MAO expression induces developmental abnormalities in particular of the brain. This review is aimed at summarizing and critically evaluating the new findings on the developmental functions of MAO isoforms during embryogenesis. 相似文献
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The DNA sequence and comparative analysis of human chromosome 5 总被引:1,自引:0,他引:1
Schmutz J Martin J Terry A Couronne O Grimwood J Lowry S Gordon LA Scott D Xie G Huang W Hellsten U Tran-Gyamfi M She X Prabhakar S Aerts A Altherr M Bajorek E Black S Branscomb E Caoile C Challacombe JF Chan YM Denys M Detter JC Escobar J Flowers D Fotopulos D Glavina T Gomez M Gonzales E Goodstein D Grigoriev I Groza M Hammon N Hawkins T Haydu L Israni S Jett J Kadner K Kimball H Kobayashi A Lopez F Lou Y Martinez D Medina C Morgan J Nandkeshwar R Noonan JP Pitluck S Pollard M Predki P 《Nature》2004,431(7006):268-274
Chromosome 5 is one of the largest human chromosomes and contains numerous intrachromosomal duplications, yet it has one of the lowest gene densities. This is partially explained by numerous gene-poor regions that display a remarkable degree of noncoding conservation with non-mammalian vertebrates, suggesting that they are functionally constrained. In total, we compiled 177.7 million base pairs of highly accurate finished sequence containing 923 manually curated protein-coding genes including the protocadherin and interleukin gene families. We also completely sequenced versions of the large chromosome-5-specific internal duplications. These duplications are very recent evolutionary events and probably have a mechanistic role in human physiological variation, as deletions in these regions are the cause of debilitating disorders including spinal muscular atrophy. 相似文献