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排序方式: 共有109条查询结果,搜索用时 15 毫秒
81.
de Mattia F Savelkoul PJ Bichet DG Kamsteeg EJ Konings IB Marr N Arthus MF Lonergan M van Os CH van der Sluijs P Robertson G Deen PM 《Human molecular genetics》2004,13(24):3045-3056
Vasopressin regulates water homeostasis through insertion of homotetrameric aquaporin-2 (AQP2) water channels in the apical plasma membrane of renal cells. AQP2 mutations cause recessive and dominant nephrogenic diabetes insipidus (NDI), a disease in which the kidney is unable to concentrate urine in response to vasopressin. Until now, all AQP2 mutants in recessive NDI were shown to be misfolded, retained in the endoplasmic reticulum (ER) and unable to interact with wild-type (wt)-AQP2, whereas AQP2 mutants in dominant NDI are properly folded and interact with wt-AQP2, but, due to the mutation, cause missorting of the wt-AQP2/mutant complex. Here, patients of two families with recessive NDI appeared compound heterozygotes for AQP2-A190T or AQP2-R187C mutants, together with AQP2-P262L. As mutations in the AQP2 C-tail, where P262 resides, usually cause dominant NDI, the underlying cell-biological mechanism was investigated. Upon expression in oocytes, AQP2-P262L was a properly folded and functional aquaporin in contrast to the classical mutants, AQP2-R187C and AQP2-A190T. Expressed in polarized cells, AQP2-P262L was retained in intracellular vesicles and did not localize to the ER. Upon co-expression, however, AQP2-P262L interacted with wt-AQP2, but not with AQP2-R187C, resulting in a rescued apical membrane expression of AQP2-P262L. In conclusion, our study reveals a novel cellular phenotype in recessive NDI in that AQP2-P262L acts as a mutant in dominant NDI, except for that its missorting is overruled by apical sorting of wt-AQP2. Also, it demonstrates for the first time that the recessive inheritance of a disease involving a channel can be due to two cell-biological mechanisms. 相似文献
82.
Birgitta C. P. Hüsken Margreet B. Vroom Erik-Jan F. Timmenga Martin Pfaffendorf Pieter A. Van Zwieten 《European journal of pharmacology》1995,287(3):313-316
The effect of levcromakalim, an ATP-sensitive K+ channel opener, on isolated subcutaneous arteries from mammary tissues obtained from female patients undergoing reconstructive breast surgery was investigated. The small arteries were preserved in the University of Wisconsin (UW) solution. The contractile responses to K+ and 9,11-dideoxy-11,9-epoxy-methano-prostaglandin F2 (U46619) and the relaxant responses to levcromakalim and to the endothelium-dependent vasodilator, methacholine, in these arteries remained fully intact after preservation in UW solution for at least 5 days. The pD2 value and maximal relaxation obtained from the concentration-response curve of levcromakalim (n = 7) were 5.78 ± 0.23 and 81 ± 6%, respectively. The vasodilator effect of levcromakalim was significantly antagonised by the ATP-sensitive K+ channel blocker, glibenclamide (1 and 3 μM). In conclusion, isolated human arteries contain ATP-sensitive K+ channels, which can be modulated by K+ channel openers and blockers. Subcutaneous small arteries, as used in our experiments, appear to be very suitable for pharmacological experiments. 相似文献
83.
Nephrogenic diabetes insipidus (NDI) is a disease characterized by the inability of the kidney to concentrate urine upon stimulation with vasopressin. Mutations in the gene for aquaporin-2 (AQP2) are the cause of the autosomal recessive and autosomal dominant forms of NDI. Mutant AQP2 proteins, found in autosomal recessive NDI, were shown to be misfolded and retarded in the endoplasmic reticulum. One mutant protein leading to autosomal dominant NDI, E258K, has been analyzed in detail. It was shown that this mutant was not retarded in the endoplasmic reticulum but mainly retained in the Golgi network. Furthermore, this particular mutant was able to form heterotetramers with wild-type AQP2, in contrast to mutants found in autosomal recessive NDI. The subsequent misrouting of complexes containing wild-type and mutant AQP2 proteins explains dominant NDI. 相似文献
84.
Fleur J.A. van den Bogaart Kristl G. Claeys Rudolf A. Kley Benno Kusters Simone Schrading Erik J. Kamsteeg Nicol C. Voermans 《Neuromuscular disorders : NMD》2017,27(1):73-77
We report three patients with a predominantly proximal myopathy due to p.A193T mutation in the actin-binding domain of FLNC, which has so far only been associated with a distal myopathy. They presented with a late onset myopathy characterized by predominant limb-girdle and proximal weakness. We describe the clinical, electrophysiological, pathological, muscle imaging and genetic features. One of our patients did not have typical histological features for a myofibrillar myopathy in muscle biopsy. This observation is important for the recognition of the full clinical spectrum of filamin-C-related myopathies. Muscle imaging has an important role in distinguishing the different filamin-C myopathy types. 相似文献
85.
J��r?me Ruzzin Rasmus Petersen Emmanuelle Meugnier Lise Madsen Erik-Jan Lock Haldis Lillefosse Tao Ma Sandra Pesenti Si Brask Sonne Troels Torben Marstrand Marian Kjellevold Malde Zhen-Yu Du Carine Chavey Lluis Fajas Anne-Katrine Lundebye Christian Lehn Brand Hubert Vidal Karsten Kristiansen Livar Fr?yland 《Environmental health perspectives》2010,118(4):465-471
86.
Ghorbani Fatemeh de Boer-Bergsma Jelkje Verschuuren-Bemelmans Corien C. Pennings Maartje de Boer Eddy N. Kremer Berry Vanhoutte Els K. de Vries Jeroen J. van de Berg Raymond Kamsteeg Erik-Jan van Diemen Cleo C. Westers Helga van de Warrenburg Bart P. Verbeek Dineke S. 《Journal of neurology》2022,269(11):6086-6093
Journal of Neurology - Recently, an intronic biallelic (AAGGG)n repeat expansion in RFC1 was shown to be a cause of CANVAS and adult-onset ataxia in multiple populations. As the prevalence of the... 相似文献
87.
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89.
W. G. Leen M. Taher M. M. Verbeek E. J. Kamsteeg B. P. van de Warrenburg M. A. Willemsen 《Journal of neurology》2014,261(3):589-599
GLUT1 deficiency syndrome (GLUT1DS) is a treatable neurometabolic disorder in which glucose transport into the brain is disturbed. Besides the classic phenotype of intellectual disability, epilepsy, and movement disorders, other phenotypes are increasingly recognized. These include, for example, idiopathic generalized epilepsy and paroxysmal exercise-induced dyskinesia. Since the disorder has only been recognized for two decades and is mostly diagnosed in children, little is known about the disease course. Our purpose was to investigate the disease course of GLUT1DS patients with the classic, complex phenotype from infancy into adulthood. We performed a systematic literature review as well as a cohort study, including GLUT1DS patients aged 18 years and older. The literature search yielded a total of 91 adult GLUT1DS patients, of which 33 patients (one-third) had a complex phenotype. The cohort study included seven GLUT1DS patients with a complex phenotype who were prospectively followed up in our clinic from childhood into adulthood. Our results show that epilepsy is a prominent feature during childhood in classic GLUT1DS patients. During adolescence, however, epilepsy diminishes or even disappears, but new paroxysmal movement disorders, especially paroxysmal exercise-induced dyskinesia, either appear or worsen if already present in childhood. Intellectual disability was not systematically assessed, but cognitive functions appeared to be stabile throughout life. Like children, adolescents may benefit from a ketogenic diet or variants thereof. 相似文献
90.