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101.
T-cell-mediated autoimmunity: novel techniques to characterize autoreactive T-cell receptors 下载免费PDF全文
Dornmair K Goebels N Weltzien HU Wekerle H Hohlfeld R 《The American journal of pathology》2003,163(4):1215-1226
Histological samples of autopsy or biopsy tissue provide the best available evidence that autoreactive T cells are involved in the immunopathogenesis of many autoimmune diseases. However, morphology alone does not provide information on the antigen-specific T-cell receptor (TCR) of these cells, let alone on their antigen specificity. In this review article we discuss a number of emerging possibilities for identifying TCR sequences directly from biopsy tissue. We also review the methods for expressing presumably autoreactive TCR molecules and speculate on how the expressed TCR might be used to identify target antigens. Such information should eventually provide new insights into disease pathogenesis which lead to better therapies. 相似文献
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Kress W Schropp C Lieb G Petersen B Büsse-Ratzka M Kunz J Reinhart E Schäfer WD Sold J Hoppe F Pahnke J Trusen A Sörensen N Krauss J Collmann H 《European journal of human genetics : EJHG》2006,14(1):39-48
The Saethre-Chotzen syndrome (SCS) is an autosomal dominant craniosynostosis syndrome with uni- or bilateral coronal synostosis and mild limb deformities. It is caused by loss-of-function mutations of the TWIST 1 gene. In an attempt to delineate functional features separating SCS from Muenke's syndrome, we screened patients presenting with coronal suture synostosis for mutations in the TWIST 1 gene, and for the Pro250Arg mutation in FGFR3. Within a total of 124 independent pedigrees, 39 (71 patients) were identified to carry 25 different mutations of TWIST 1 including 14 novel mutations, to which six whole gene deletions were added. The 71 patients were compared with 42 subjects from 24 pedigrees carrying the Pro250Arg mutation in FGFR3 and 65 subjects from 61 pedigrees without a detectable mutation. Classical SCS associated with a TWIST 1 mutation could be separated phenotypically from the Muenke phenotype on the basis of the following features: low-set frontal hairline, gross ptosis of eyelids, subnormal ear length, dilated parietal foramina, interdigital webbing, and hallux valgus or broad great toe with bifid distal phalanx. Functional differences were even more important: intracranial hypertension as a consequence of early progressive multisutural fusion was a significant problem in SCS only, while mental delay and sensorineural hearing loss were associated with the Muenke's syndrome. Contrary to previous reports, SCS patients with complete loss of one TWIST allele showed normal mental development. 相似文献
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Honl M Rentzsch R Schwieger K Carrero V Dierk O Dries S Louis H Pude F Bishop N Hille E Morlock M 《Bio-medical materials and engineering》2003,13(4):317-325
In revision surgeries of endoprostheses, the interface between implant and bone cement or bone must be loosened. Conventional tools have many disadvantages because of their size and limited range. Taking advantage of the selective and athermic cutting process, a plain water jet is already used in order to cut soft tissues. This study investigates the possibilities of both a plain and an abrasive water jet as cutting tools for revision surgery. Samples of the mid-diaphysis of human femora and bone cement (CMW3) were cut with a plain water jet (PWJ) and an abrasive water jet (AWJ) at two different jet-to-surface angles (30 degrees,90 degrees ) and at five different pressure levels (30, 40, 50, 60, 70 MPa). For a PWJ a selective pressure range was identified, where only bone cement was cut. Injecting a bio-compatible abrasive (lactose) to the jet stream resulted in significantly higher cut depths in both materials. Material removal in bone was significantly less at the smaller jet-to-surface angle for both techniques. No clear selectivity between bone and bone cement was observed for application of the AWJ. However, the material removal rate was significantly higher for bone cement than for bone at all pressure levels. The results indicate that an AWJ might be an alternative tool for cement removal. The possibility for localised cutting at interfaces could be an advantage for revision of a non-cemented prosthesis. 相似文献
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Paige E. Cooper Heiko Reutter Joachim Woelfle Hartmut Engels Dorothy K. Grange Gijs van Haaften Bregje W. van Bon Alexander Hoischen Colin G. Nichols 《Human mutation》2014,35(7):809-813
ATP‐sensitive potassium (KATP) channels, composed of inward‐rectifying potassium channel subunits (Kir6.1 and Kir6.2, encoded by KCNJ8 and KCNJ11, respectively) and regulatory sulfonylurea receptor (SUR1 and SUR2, encoded by ABCC8 and ABCC9, respectively), couple metabolism to excitability in multiple tissues. Mutations in ABCC9 cause Cantú syndrome (CS), a distinct multiorgan disease, potentially via enhanced KATP channel activity. We screened KCNJ8 in an ABCC9 mutation‐negative patient who also exhibited clinical hallmarks of CS (hypertrichosis, macrosomia, macrocephaly, coarse facial appearance, cardiomegaly, and skeletal abnormalities). We identified a de novo missense mutation encoding Kir6.1[p.Cys176Ser] in the patient. Kir6.1[p.Cys176Ser] channels exhibited markedly higher activity than wild‐type channels, as a result of reduced ATP sensitivity, whether coexpressed with SUR1 or SUR2A subunits. Our results identify a novel causal gene in CS, but also demonstrate that the cardinal features of the disease result from gain of KATP channel function, not from a Kir6‐independent SUR2 function. 相似文献
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Sabina Kinder Hartmut Komber Dieter Jehnichen Liane Häussler Frank Böhme Mazen Garaleh Doris Pospiech Brigitte Voit Ulrich Schulze 《Macromolecular chemistry and physics.》2014,215(8):733-741
Comb‐like copolymers based on a polyolefin backbone of poly(10‐undecene‐1‐ol) (PUol) with poly(ε‐caprolactone) (PCL) side chains are synthesized in two steps. After synthesis of PUol by metallocene‐catalyzed polymerization, the side‐chain hydroxyl functionalities of this polar polyolefin are used as an initiator for the ring‐opening polymerization (ROP) of ε‐caprolactone (CL). In this context, copolymers with different lengths of PCL grafts are prepared. The chemical structure and the composition of the synthesized copolymers are characterized by 1H and 13C NMR spectroscopy. It is shown that the hydroxyl end groups of PUol act effectively as initiating sites for the CL ROP. Size‐exclusion chromatography (SEC) measurements confirm the absence of non‐attached PCL and the expected increase in molar mass after grafting. The thermal and decomposition behaviors are investigated by DSC and thermogravimetric analysis (TGA). The effect of the length of the PCL grafts on the crystallization behavior of the comb‐like copolymers is investigated by DSC and wide‐angle X‐ray scattering (WAXS).
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Michael Schädel-Höpfner Marta Marent-Huber Emre Gazyakan Karin Tanzer Klaus D. Werber Hartmut R. Siebert 《Archives of orthopaedic and trauma surgery》2010,130(9):1117-1127