排序方式: 共有62条查询结果,搜索用时 15 毫秒
31.
Oligosaccharides of hyaluronan are potent activators of dendritic cells 总被引:21,自引:0,他引:21
Termeer CC Hennies J Voith U Ahrens T Weiss JM Prehm P Simon JC 《Journal of immunology (Baltimore, Md. : 1950)》2000,165(4):1863-1870
The extracellular matrix component hyaluronan (HA) exists physiologically as a high m.w. polymer but is cleaved at sites of inflammation, where it will be contacted by dendritic cells (DC). To determine the effects of HA on DC, HA fragments of different size were established. Only small HA fragments of tetra- and hexasaccharide size (sHA), but not of intermediate size (m.w. 80, 000-200,000) or high m.w. HA (m.w. 1,000,000-600,000) induced immunophenotypic maturation of human monocyte-derived DC (up-regulation of HLA-DR, B7-1/2, CD83, down-regulation of CD115). Likewise, only sHA increased DC production of the cytokines IL-1beta, TNF-alpha, and IL-12 as well as their allostimulatory capacity. These effects were highly specific for sHA, because they were not induced by other glycosaminoglycans such as chondroitin sulfate or heparan sulfate or their fragmentation products. Interestingly, sHA-induced DC maturation does not involve the HA receptors CD44 or the receptor for hyaluronan-mediated motility, because DC from CD44-deficient mice and wild-type mice both responded similarly to sHA stimulation, whereas the receptor for hyaluronan-mediated motility is not detectable in DC. However, TNF-alpha is an essential mediator of sHA-induced DC maturation as shown by blocking studies with a soluble TNFR1. These findings suggest that during inflammation, interaction of DC with small HA fragments induce DC maturation. 相似文献
32.
Genetic variation in the human androgen receptor gene is the major determinant of common early-onset androgenetic alopecia 总被引:6,自引:0,他引:6
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Hillmer AM Hanneken S Ritzmann S Becker T Freudenberg J Brockschmidt FF Flaquer A Freudenberg-Hua Y Jamra RA Metzen C Heyn U Schweiger N Betz RC Blaumeiser B Hampe J Schreiber S Schulze TG Hennies HC Schumacher J Propping P Ruzicka T Cichon S Wienker TF Kruse R Nothen MM 《American journal of human genetics》2005,77(1):140-148
Androgenetic alopecia (AGA), or male-pattern baldness, is the most common form of hair loss. Its pathogenesis is androgen dependent, and genetic predisposition is the major requirement for the phenotype. We demonstrate that genetic variability in the androgen receptor gene (AR) is the cardinal prerequisite for the development of early-onset AGA, with an etiological fraction of 0.46. The investigation of a large number of genetic variants covering the AR locus suggests that a polyglycine-encoding GGN repeat in exon 1 is a plausible candidate for conferring the functional effect. The X-chromosomal location of AR stresses the importance of the maternal line in the inheritance of AGA. 相似文献
33.
Küchler S Henkes D Eckl KM Ackermann K Plendl J Korting HC Hennies HC Schäfer-Korting M 《Alternatives to laboratory animals : ATLA》2011,39(5):471-480
Loss-of-function mutations in the filaggrin gene (FLG) are a strong predisposing factor for atopic dermatitis, although their relevance to the disease pathomechanism needs further elucidation. The generation of an in vitro model of atopic skin would not only permit further evaluation of the underlying pathogenetic mechanisms and the testing of new treatment options, but would also allow toxicological studies to be performed in a simple, rapid and inexpensive manner. In this study, we have knocked down FLG expression in human keratinocytes and created three-dimensional skin models, which we used to investigate the impact of FLG on epidermal maturation and on skin absorption and its response to irritation. Histopathological evaluation of the skin models showed impaired epidermal differentiation in the FLG knock-down model. In addition, skin irritation induced by an application of sodium dodecyl sulphate resulted in significantly higher lactate dehydrogenase leakage, and interleukin (IL)-6 and IL-8 levels, than in the control model. To assess the effect of filaggrin deficiency on skin absorption of topically applied agents, we quantified the percutaneous absorption of lipophilic and hydrophilic model drugs, finding clinical relevance only for lipophilic drugs. This study clearly demonstrates that important clinical characteristics of atopic skin can be mimicked by using in vitro skin models. The FLG knock-down construct is the first step toward an in vitro model that allows clinical and toxicological studies of atopic-like skin. 相似文献
34.
Fatima A Xu G Shao K Papadopoulos S Lehmann M Arnáiz-Cot JJ Rosa AO Nguemo F Matzkies M Dittmann S Stone SL Linke M Zechner U Beyer V Hennies HC Rosenkranz S Klauke B Parwani AS Haverkamp W Pfitzer G Farr M Cleemann L Morad M Milting H Hescheler J Saric T 《Cellular physiology and biochemistry》2011,28(4):579-592
35.
Seifert W Kühnisch J Maritzen T Horn D Haucke V Hennies HC 《The Journal of biological chemistry》2011,286(43):37665-37675
Loss-of-function mutations in the gene COH1, also known as VPS13B, lead to autosomal recessive Cohen syndrome. However, the cellular distribution and function of the encoded protein COH1 (3997 amino acids), which lacks functional homologies to other mammalian proteins, have remained enigmatic. We show here that COH1 is a peripheral Golgi membrane protein that strongly co-localizes with the cis-Golgi matrix protein GM130. Consistent with its subcellular localization, COH1 depletion using RNAi causes fragmentation of the Golgi ribbon into ministacks. Disruption of Golgi organization observed in fibroblasts from Cohen syndrome patients suggests that Golgi dysfunction contributes to Cohen syndrome pathology. In conclusion, our findings establish COH1 as a Golgi-associated matrix protein required for Golgi integrity. 相似文献
36.
Hillmer AM Flaquer A Hanneken S Eigelshoven S Kortüm AK Brockschmidt FF Golla A Metzen C Thiele H Kolberg S Reinartz R Betz RC Ruzicka T Hennies HC Kruse R Nöthen MM 《American journal of human genetics》2008,82(3):737-743
Androgenetic alopecia (AGA, male pattern baldness) is the most common form of hair loss. The origin of AGA is genetic, with the X chromosome located androgen receptor gene (AR) being the only risk gene identified to date. We present the results of a genome-wide linkage study of 95 families and linkage fine mapping of the 3q21-q29, 11q14-q25, 18p11-q23, and 19p13-q13 regions in an extended sample of 125 families of German descent. The locus with strongest evidence for linkage was mapped to 3q26 with a nonparametric linkage (NPL) score of 3.97 (empirical p value = 0.00055). This is the first step toward the identification of new susceptibility genes in AGA, a process which will provide important insights into the molecular and cellular basis of scalp hair loss. 相似文献
37.
Identification and localization of a new human myotubularin-related protein gene, mtmr8, on 8p22-p23
Myotubularin and myotubularin-related proteins are dual-specificity phosphatases.Several myotubularin-related proteins have been identified in humans and mice. The members of the myotubularin protein family are highly conserved, from humans to yeast. Mutations in the human myotubularin gene (MTM1) lead to X-linked myotubular myopathy. Here we isolate and localize a novel putative myotubularin-related protein gene (MTMR8) on chromosome 8p22--p23,between the markers D8S550 and D8S265, by exon-trapping experiments and RT-PCR. Genomic sequencing revealed that the gene consists of 10 exons and spans approximately 43 kb. The corresponding cDNA is 7081 bp. The open reading frame predicts a protein of 549 amino acids and a calculated molecular mass of 63 kDa. Like myotubularin-related protein-5, MTMR8 has no dual-specificity phosphatase domain. It contains a double-helical motif similar to the SET interaction domain, which is thought to have a role in the control of cell proliferation. 相似文献
38.
Hennies HC Rauch A Seifert W Schumi C Moser E Al-Taji E Tariverdian G Chrzanowska KH Krajewska-Walasek M Rajab A Giugliani R Neumann TE Eckl KM Karbasiyan M Reis A Horn D 《American journal of human genetics》2004,75(1):138-145
Cohen syndrome is a rare autosomal recessive disorder with a variable clinical picture mainly characterized by developmental delay, mental retardation, microcephaly, typical facial dysmorphism, progressive pigmentary retinopathy, severe myopia, and intermittent neutropenia. A Cohen syndrome locus was mapped to chromosome 8q22 in Finnish patients, and, recently, mutations in the gene COH1 were reported in patients with Cohen syndrome from Finland and other parts of northern and western Europe. Here, we describe clinical and molecular findings in 20 patients with Cohen syndrome from 12 families, originating from Brazil, Germany, Lebanon, Oman, Poland, and Turkey. All patients were homozygous or compound heterozygous for mutations in COH1. We identified a total of 17 novel mutations, mostly resulting in premature termination codons. The clinical presentation was highly variable. Developmental delay of varying degree, early-onset myopia, joint laxity, and facial dysmorphism were the only features present in all patients; however, retinopathy at school age, microcephaly, and neutropenia are not requisite symptoms of Cohen syndrome. The identification of novel mutations in COH1 in an ethnically diverse group of patients demonstrates extensive allelic heterogeneity and explains the intriguing clinical variability in Cohen syndrome. 相似文献
39.
We report on the conventional cytogenetic and fluorescence in situ hybridization (FISH) results obtained for a 3.5-year-old girl with developmental and language delay and a supernumerary ring chromosome mosaicism in 8% of T-lymphocytes analyzed. Using different conventional and molecular cytogenetic techniques as YAC hybridization and comparative genomic hybridization, we could show that the extra tricentric ring chromosome consists of three heterochromatic blocks with inserted euchromatic material. Additionally, chromosome microdissection followed by FISH analysis demonstrated that the small tricentric ring chromosome consisted of material from the pericentromeric region of chromosome 1q21. Thus, the patient has a mosaic of normal cells and cells with partial pentasomy of the pericentromeric region of chromosome 1. So far, 19 cases with single supernumerary marker chromosome 1 have been published, but no tricentric ring chromosome 1 is, to our knowledge, reviewed in the literature. In this study, we compare the clinical features of our patient with cytogenetically comparable cases described in the literature. We introduce a hypothesis for the formation of a tricentric ring chromosome: starting with a monocentric ring, sister chromatid exchange leading to the formation of a tetracentric ring, which underwent intrastrand recombination generating the tricentric ring. 相似文献
40.
Hans Christian Hennies Michael Raghunath Victor Wiebe Melanie Vogel Florian Velten Heiko Traupe André Reis 《Human genetics》1998,102(3):314-318
Autosomal recessive lamellar ichthyosis is a clinically heterogeneous group of severe congenital keratinization disorders
that is characterized by generalized hyperkeratosis and variable erythema. About half of the patients have mutations in the
TGM1 gene, which encodes the keratinocyte transglutaminase. Linkage studies have shown that at least two further loci for
autosomal recessive lamellar ichthyosis must exist. We present here two patients with lamellar ichthyosis caused by mutations
in the TGM1 gene. The first patient is compound heterozygous for the novel missense mutation C53S and the splice mutation
A3447G. The second patient, a child of consanguineous parents from Tunisia, is homozygous for the unknown nonsense mutation
W263X. This is the first report of a mutation, C53S, that affects the region of the keratinocyte transglutaminase that is
essential for anchorage of the enzyme to the plasma membrane. A novel, rapid in situ transglutaminase activity assay revealed
the absence of keratinocyte transglutaminase activity in both patients. The mutations described are hence causative for the
ichthyosis phenotype.
Received: 27 October 1997 / Accepted: 24 November 1997 相似文献