670 research outputs found
Significance of Autologous Tissues in the Treatment of Complicated, Large, and Eventrated Abdominal Wall Hernias
Repair of complicated, large, or eventrated abdominal wall hernias poses a considerable challenge. Not infrequently, synthetic grafts implanted earlier become infected, entero- or subcutaneous fistulas appear, or emergency conditions like mechanical ileus or peritonitis develop. In such cases, direct closure of the abdominal wall with sutures or reinforcement with synthetic grafts is not recommended. Not many surgical techniques are capable of creating a low tension state. One is bridging of the abdominal wall defects; another is mobilization of the musculo-aponeurotic elements of the abdominal wall (components separation). In this chapter, the use of autologous double-layer dermal grafts and the technique of bilateral rectus muscle turnover allowing reconstruction of eventrated hernias in a tension-free way are discussed. In both procedures, only autologous tissues are used for reconstruction. With autologous dermal grafts, the rate of surgical complications is 4%, recurrence in the first 24 months is 11%, and the quality of life is significantly improved. With bilateral rectus muscle turnover, surgical complications occur at a rate of less than 2%, 24-month recurrence is 0%, and the quality of life is significantly improved. The technique of the interventions, their indications and contraindications, as well as their feasibility, advantages and disadvantages are described
Activation dependent clustering of the erbB2 receptor tyrosine kinase detected by scanning near-field optical microscopy
ErbB2 (HER2, Neu), a member of the epidermal growth factor (EGF) receptor tyrosine kinase family, is often overexpressed in breast cancer and other malignancies, ErbB2 homodimerizes but also presents as a common auxiliary subunit of the EGF and heregulin receptors (erbB1 or EGFR; and erbB3-4, respectively), with which it heteroassociates, ErbB2 is generally regarded as an orphan (ligand-less) receptor with a very potent kinase domain activated either via its associated partners or constitutively as a consequence of discrete mutations. It follows that the extent and regulation of its cell surface interactions are of central importance. We have studied the large-scale association pattern of erbB2 in quiescent and activated cells labeled with fluorescent anti-erbB2 monoclonal antibodies using scanning near-field optical microscopy (SNOM), ErbB2 was found to be concentrated in irregular membrane patches with a mean diameter of approx. 0.5 mu m in nonactivated SKBR3 and MDA453 human breast tumor cells. The average number of erbB2 proteins in a single cluster on nonactivated SKBR3 cells was about 10(3). Activation of SKBR3 cells with EGF, heregulin as well as a partially agonistic anti-erbB2 monoclonal antibody led to an increase in the mean cluster diameter to 0.6-0.9 mu m, irrespective of the ligand, The EGF-induced increase in the erbB2 cluster size was inhibited by the EGFR-specific tyrosine kinase inhibitor PD153035, The average size of erbB2 clusters on the erbB2-transfected line of CHO cells (CB2) was similar to that of activated SKBR3 cells, a finding correlated with the increased base-line tyrosine phosphorylation of erbB2 in cells expressing only erbB2, We conclude that an increase in cluster size may constitute a general phenomenon in the activation of erbB2
SejtfelszĂni Ă©s magreceptorok többszörös asszociáciĂłjának Ă©s dinamikájának vizsgálata fluoreszcencia korreláciĂłs spektroszkĂłpia Ă©s energia transzfer segĂtsĂ©gĂ©vel = Examination of the multiple association and dynamics of cell surface and nuclear receptors by fluorescence correlation spectroscopy and energy transfer
Az interleukin-2 Ă©s -15 citokinek fontos szerepet játszanak a T sejtek funkciĂłjának Ă©s homeosztázisának szabályozásában. A pályázat keretĂ©ben az IL-2/15R komplex összeszerelĹ‘dĂ©sĂ©t, sejtfelszĂni elrendezĹ‘dĂ©sĂ©t Ă©s más membránfehĂ©rjĂ©kkel kialakĂtott kölcsönhatásait tanulmányoztuk humán T sejtek felszĂnĂ©n. Igazoltuk, hogy az MHC I glikoproteinek szervezĹ‘ szerepet játszanak az IL-2/15R klaszterek összeszerelĹ‘dĂ©sĂ©ben. Az IL-2/15R Ă©s az MHC I/II glikoproteinek által alkotott klaszterek stabilitása nem fĂĽgg jelentĹ‘s mĂ©rtĂ©kben a citoszkeletontĂłl, az asszociáciĂłk apoptotikus blebek felszĂnĂ©n is megmaradnak. JellemeztĂĽk az ILRAP - egy IL-2R-rel asszociálĂłdĂł fehĂ©rje molekuláris kölcsönhatásait, ami hozzájárulhat az IL-2/IL-15 eltĂ©rĹ‘ hatásspektrumának magyarázatához. Közvetlen bizonyĂtĂ©kát adtuk az IL-15 transz prezentáciĂłjának kĂ©t T limfĂłma sejttĂpus között. Kidolgoztunk egy megbĂzhatĂł mĂłdszert, mellyel GFP Ă©s mRFP között lehet FRET mĂ©rĂ©seket vĂ©gezni. FRET, FCCS Ă©s modellezĂ©s segĂtsĂ©gĂ©vel leĂrtuk a Jun-Fos komplex C terminális konformáciĂłját, ami a működĂ©sre vonatkozĂł felvetĂ©seket is eredmĂ©nyezett. RXR Ă©s RAR magreceptorok Ă©s funkcionális mutánsaik mobilitását vizsgálva megállapĂtottuk, hogy a magreceptorok ligand hiányában ? ellentĂ©tben a jelenleg elfogadott molekuláris kapcsolĂł modellel ? nagyrĂ©szt szabad állapotban vannak. Agonista hatására rĂ©szleges átrendezĹ‘dĂ©s törtĂ©nik egy alacsony mobilitásĂş állapotba, amelyben a receptor feltehetĹ‘en koaktivátort köt, Ă©s DNS-kötĹ‘ affinitása megnĹ‘. | Interleukin-2 and -15 play an important role in regulating the function and homeostasis of T cell function. In our research we investigated the assembly, cell surface organization and interactions of the IL-2/15R complex with other membrane proteins in human T cells. We showed that MHC I glycoproteins play an organizing role in the assembly of IL-2/15R clusters. The stability of clusters formed by IL-2/15R and MHCI/II proteins does not critically depend on the cytoskeleton, associations remain stable on the surface of apoptotic blebs as well. We characterized the interactions of ILRAP, an IL-2R-associated protein, which may contribute to understanding the distinct effects of IL-2 and IL-15. We gave direct evidence of the trans presentation of IL-15 between two T lymphoma cell types. We elaborated a method for the measurement of FRET between GFP and mRFP. By using FRET, FCCS and MD-modeling the C terminal conformation of the Jun-Fos complex was characterized, which yielded implications for their mode of action. By measuring the mobility of RXR and RAR nuclear receptors and their functional mutants we demonstrated that receptors are in a freely diffusing state in the absence of ligand, which is in contrast to expectations of the molecular switch model. Agonist treatment yields a shift to a less mobile state, in which the receptor probably binds coactivator and has an increased DNA-binding affinity
SejtfelszĂni receptor minták mint lehetsĂ©ges diagnosztikai eszközök = Cell surface receptor patterns as potential diagnostic tools
Modern biofizikai mĂłdszerek kombinált alkalmazásával (FRET, konfokális mikroszkĂłpia, fluoreszcencia korreláciĂłs spektroszkĂłpia, stb.) a T sejtes immunválaszban rĂ©sztvevĹ‘ kulcsfontosságĂş membránfehĂ©rjĂ©k sejtfelszĂni elrendezĹ‘dĂ©sĂ©t, asszociáciĂłs mintázatait, kölcsönhatásait tanulmányoztuk. A kialakulĂł mintázatok a jelátvitel egyes lĂ©pĂ©seinek szervezĂ©se rĂ©vĂ©n alapvetĹ‘en befolyásolják a sejtek fiziolĂłgiás működĂ©sĂ©t, másrĂ©szrĹ‘l potenciális terápiás cĂ©lpontok lehetnek. Megalkottuk az IL-2/15R rendszer dinamikus heterotetramer modelljĂ©t: a releváns citokin kötĹ‘dĂ©se a receptor alegysĂ©gek átrendezĂ©sĂ©vel alakĂtja ki a megfelelĹ‘ nagy affinitásĂş heterotrimert. Kimutattuk, hogy az IL-2/15R Ă©s az MHC molekulák közös szuperklasztereket alkotnak a T sejtek lipid tutajaiban. Jurkat T sejteken Ă©s aktivált CTL-eken kimutattuk a Kv1.3 káliumcsatornák Ă©s a TCR kolokalizáciĂłját. A CTL-target sejt kölcsönhatás során a CTL-ek Kv1.3 csatornái feldĂşsulnak a kĂ©t sejt közötti immunolĂłgiai szinapszisban, felvetve a TCR Ă©s a Kv1.3 kölcsönös szabályozásának lehetĹ‘sĂ©gĂ©t. A korábban limfoid Ă©s kolorektális karcinĂłma sejteken feltárt, az MHC I, II Ă©s az ICAM-1 rĂ©szvĂ©telĂ©vel kialakulĂł asszociáciĂłs mintázatok jelenlĂ©tĂ©t uveális melanĂłma sejteken is kimutattuk. RNS interferencia felhasználásával igazoltuk, hogy a kolorektális karcinĂłma sejteken az MHC I Ă©s ICAM-1 klasztereit Ă©s domĂ©n szintű elrendezĹ‘dĂ©sĂ©t e kĂ©t fehĂ©rje relatĂv expressziĂłs szintje dinamikus mĂłdon szabályozza. | We investigated the cell surface distribution, association motifs and interactions of key membrane proteins involved in T cell mediated immune responses by applying modern biophysical techniques (FRET, confocal microscopy, fluorescence correlation spectroscopy, etc.). The studied protein patterns have a profound influence on the physiological function of the cells via organizing certain signaling steps, and may serve as potential therapeutic targets. We proposed a dynamic heterotetrameric model for the IL-2/15R system: binding of the cytokine rearranges the receptor subunits to form the relevant heterotrimeric high affinity receptor. We demonstrated that IL-2/15 receptors and MHC glycoproteins form superclusters in lipid rafts of T cells. We showed that Kv1.3 K+ channels and TCR are colocalized on Jurkat T cells and CTLs. Kv1.3 channels are enriched in the immune synapse formed between the CTL and the target cell, raising the possibility of reciprocal regulation of TCR and Kv1.3. We identified association patterns of MHC I, II and ICAM-1 on uveal melanoma cells similar to those previously found on lymphoid and colorectal carcinoma cells. By using RNA interference we demonstrated that the clusterization and interaction of MHC I and ICAM-1 are dynamically regulated by the relative expression levels of these proteins
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