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41.
42.
Pernille Mathiesen Tørring Martin Jakob Larsen Charlotte Brasch-Andersen Lotte Nylandsted Krogh Maria Kibæk Lone Laulund Niels Illum Ulrike Dunkhase-Heinl Antje Wiesener Bernt Popp Giuseppe Marangi Tina Duelund Hjortshøj Jakob Ek Ida Vogel Naja Becher Laura Roos Marcella Zollino Christina Ringmann Fagerberg 《European journal of medical genetics》2019,62(2):129-136
Introduction
MED13L-related intellectual disability is characterized by moderate intellectual disability (ID), speech impairment, and dysmorphic facial features. We present 8 patients with MED13L-related intellectual disability and review the literature for phenotypical and genetic aspects of previously described patients.Materials and methods
In the search for genetic aberrations in individuals with ID, two of the patients were identified by chromosomal microarray analysis, and five by exome sequencing. One of the individuals, suspected of MED13L-related intellectual disability, based on clinical features, was identified by Sanger sequencing.Results
All 8 individuals had de novo MED13L aberrations, including two intragenic microdeletions, two frameshift, three nonsense variants, and one missense variant. Phenotypically, they all had intellectual disability, speech and motor delay, and features of the mouth (open mouth appearance, macroglossia, and/or macrostomia). Two individuals were diagnosed with autism, and one had autistic features. One had complex congenital heart defect, and one had persistent foramen ovale. The literature was reviewed with respect to clinical and dysmorphic features, and genetic aberrations.Conclusions
Even if most clinical features of MED13L-related intellectual disability are rather non-specific, the syndrome may be suspected in some individuals based on the association of developmental delay, speech impairment, bulbous nasal tip, and macroglossia, macrostomia, or open mouth appearance. 相似文献43.
Gambichler T Moussa G Sand M Sand D Orlikov A Altmeyer P Hoffmann K 《Journal of biomedical optics》2005,10(6):064030
Noninvasive imaging techniques might be of particular diagnostic value for studying and monitoring cutaneous inflammatory conditions such as contact dermatitis. We evaluate acute allergic contact dermatitis (AACD) by means of optical coherence tomography (OCT) and correlate the clinical grading of patch test reactions with the findings obtained from OCT. Twenty positive patch test reactions (+, n = 6; ++, n = 7; +++, n = 7) are investigated using a conventional OCT scanner. In comparison to the control sites, OCT of AACD showed pronounced skin folds, thickened and/or disrupted entrance signals, and a significant increase in epidermal thickness. Moreover, clearly demarcated signal-free cavities within the epidermis and considerable reduction of dermal reflectivity are demonstrated by OCT. Notably, the latter findings strongly correlate with the clinical patch test grading. OCT may be a useful tool for visualization of micromorphological features of AACD. However, before OCT can be employed as an objective parameter in grading severity of patch test reactions, larger studies are required that correlate clinical patch test readings and OCT findings with histopathology. 相似文献
44.
Mouse models of atopic eczema critically evaluated 总被引:2,自引:0,他引:2
Gutermuth J Ollert M Ring J Behrendt H Jakob T 《International archives of allergy and immunology》2004,135(3):262-276
Atopic eczema (AE) is a chronic relapsing inflammatory skin disorder with increasing prevalence in Western societies. Even though we have made considerable progress in understanding the cellular and molecular nature of cutaneous inflammation, the precise pathomechanisms of AE still remain elusive. Experimental animal models are indispensable tools to study the pathogenic mechanisms and to test novel therapeutic approaches in vivo. For AE a considerable number of mouse models have been proposed and have been used to study specific aspects of the disease, such as genetics, skin barrier defects, immune deviations, bacteria-host interactions or the role of cytokines or chemokines in the inflammatory process. While some models closely resemble human AE, others appear to reflect only specific aspects of the disease. Here we review the currently available mouse models of AE in light of the novel World Allergy Organization classification of eczematous skin diseases and evaluate them according to their clinical, histopathological and immunological findings. The pathogenetic analogies between mice and men will be discussed. 相似文献
45.
Reliable detection of macrolide-resistant Helicobacter pylori via fluorescence in situ hybridization in formalin-fixed tissue. 总被引:2,自引:0,他引:2
Stefan Jüttner Michael Vieth Stephan Miehlke Wulf Schneider-Brachert Christian Kirsch Thilo Pfeuffer Norbert Lehn Manfred Stolte 《Modern pathology》2004,17(6):684-689
Macrolide-resistant Helicobacter (H.) pylori represent an increasing therapeutic problem. Macrolide resistance is usually determined phenotypically in vitro with methods such as E-test or agar dilution test. A prerequisite for those tests, however, is bacterial culture that is not routinely set up in the course of gastroscopy. In contrast, formalin-fixed, paraffin-embedded biopsies are regularly available from patients who have undergone gastroscopy. In such biopsies macrolide-resistant H. pylori can be detected by the genotype-based technique of fluorescence in situ hybridization (FISH). Experience gained by this new method, however, is still extremely limited, especially in formalin-fixed tissue. Therefore, we retrospectively investigated formalin-fixed, paraffin-embedded biopsy specimens by FISH in 104 patients suffering from therapy-resistant H. pylori gastritis. To test the accuracy of FISH, we initially examined specimens from 53 patients for whom results of the E-test were available. Next we analyzed biopsies from another 51 patients that had been selected since phenotypical resistance testing had failed despite documented culturing attempts. In all 104 patients, H. pylori was detected by FISH and could thus be investigated for macrolide resistance. Overall, macrolide-resistant bacteria were found in 71 patients (68.3%). In 49 of 53 patients (92.4%), FISH and E-test returned identical results (no significant discordance according to McNemar's chi(2)-test). Taken together, our study demonstrates that FISH is a highly sensitive and reliable method for detecting macrolide-resistant H. pylori in formalin-fixed, paraffin-embedded biopsy specimens, which represents the routine method of processing tissue obtained upon gastroscopy. 相似文献
46.
Members of the tumor necrosis factor (TNF) superfamily are crucially involved in the regulation of T cell activation, homeostasis and cytotoxicity. In particular, Fas ligand (FasL), expressed by activated T lymphocytes, induces cell-mediated cytotoxicity and may also be responsible for apoptotic suicide. Tight regulation of this death-inducing ligand is a prerequisite for proper immune defense and homeostasis. In this review, we will discuss various aspects of FasL regulation in cell-mediated cytotoxicity, immune homeostasis and the immunopathology of diseases. 相似文献
47.
Enzymatic digestion of adult human articular cartilage yields a small fraction of the total available cells 总被引:1,自引:0,他引:1
Jakob M Démarteau O Schäfer D Stumm M Heberer M Martin I 《Connective tissue research》2003,44(3-4):173-180
We investigated whether different protocols for the digestion of adult human articular cartilage influence the cell yield and capacity to attach and proliferate in culture dishes. Chondrocyte yields were expressed as a percentage of the total number of cells in the tissue, determined both histologically (using the dissector method) and biochemically (measuring the DNA content of tissue digests). Human cartilage specimens (n = 79) were digested using different protocols based on combinations of collagenase II (CGN), trypsin/EDTA, hyaluronidase, and tosyllysylchloromethane (TLCM). Yields of viable chondrocytes were the highest within a specific range of CGN concentrations and digestion times, but always < 22% of the total available cells. The combination of CGN with trypsin/EDTA or TLCM accelerated the digestion process but did not significantly increase cell yields. The percentage of viable cells that attached to culture dishes ranged 75-85% (< 19% of the total) and was reduced by TLCM. Doubling times of attached cells were comparable in all experimental groups. Our results indicate that chondrocyte yields and capacity to attach and proliferate are not highly sensitive to the specific isolation protocol used. However, typically used cartilage digestion protocols yield only a small fraction of the total available cells, possibly introducing an uncontrolled selection of certain chondrocyte subpopulations. 相似文献
48.
49.
Hans-Jürgen Rode Joachim Jakob Bugert Michaela Handermann Paul Schnitzler Roland Kehm Waltraud Janssen Hajo Delius Gholamreza Darai 《Virus genes》1994,9(1):61-75
The complete DNA nucleotide sequence of theEcoRI DNA fragment N (0.235 to 0.258 viral map units) of equine herpes virus type 2 (EHV-2) strain T400/3 was determined. This DNA fragment comprises 4237 bp with a base composition of 55.23% G+C and 44.77% A+T. Nineteen open reading frames (ORFs) of 50-287 amino acid (aa) residues were detected. ORF number 10 is located between the nucleotide position 2220 and 2756 coding for a protein of 179 amino acid residues. This protein shows significant homology to the cytokine synthesis inhibitory factor (CSIF; interleukin 10) of human (76.4%) and mouse (68.5%), and to the Epstein-Barr virus (EBV) protein BCRF1 (70.6%). The existence of an interleukin 10 (IL-10) analogous gene within the genome of the EHV-2 was confirmed by screening the genome of nine EHV-2 strains using specific oligonucleotide primers corresponding to the 5 and 3 region of this particular gene by polymerase chain reaction. In all experiments an 870 bp DNA product was amplified. The specifity of the amplified DNA fragments obtained from individual EHV-2 strains was confirmed by DNA-DNA hybridization experiments. The DNA sequence analysis of the amplified DNA products of the EHV-2 strain LK was carried out. This analysis revealed the identity of the corresponding IL-10 gene (540 bp) of this strain to the IL-10 gene of EHV-2 strain T400/3. The presented data indicate that the EHV-2 genome harbors a viral interleukin 10-like gene. This is further evidence that the IL-10 gene can be present in the genomes of members of the Herpesviridae family. 相似文献
50.
Sørensen JB Nielsen MS Gudme CN Larsen EH Nielsen R 《Pflügers Archiv : European journal of physiology》2001,442(1):1-11
The primary secretion formed in various exocrine glands has a [K+] 2-5 times that of plasma. In this study we measured the transepithelial flux of 36Cl-, 22Na+ and 42K+ across the frog skin and applied the single-channel patch-clamp technique to the apical membrane of frog skin gland acini to investigate the pathway taken by K+ secreted by the glands. Transepithelial K+ secretion was active and was driven by a larger force than the secretion of Na+. When driving Na+ through the epithelium by clamping the transepithelial potential to 100 mV (apical solution reference), blockers of cellular secretion (apical 5-nitro-2-(3-phenylpropylamino)benzoate or basolateral quinine or furosemide) decreased K+ secretion but left Na+ secretion unaffected. We conclude that K+ follows a transcellular pathway across the epithelium. Patch-clamp analysis of the apical membrane of microdissected gland acini revealed a population of voltage- and calcium-activated K+ channels of the maxi K+ type. In cell-attached patches these channels were activated by membrane potential depolarisation or exposure to prostaglandin E2 and had a permeability of 3.6 +/- 0.3 x 10(-13) cm3 s-1, giving a calculated conductance of 170 pS with 125 mM K+ on both sides of the membrane. In inside-out patches the channels were activated by increasing intracellular [Ca2+] from 10(-7) to 10(-6) M and were blocked by Ba2+ added to the cytoplasmic side. Exposure of inside-out patches containing the maxi K+ channel to ATP on the inside activated cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels, confirming that both channels are co-localised to the apical membrane. We interpret these findings in terms of a model where transepithelial NaCl secretion can be supported in part by an apical K+ conductance. 相似文献