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Spontani govor govornika urednoga jezičnoga i govornoga statusa rijetko je potpuno tečan. Dvije su temeljne skupine netečnosti. Mucajuće netečnosti javljaju se unutar riječi i karakteristične su za govorne poremećaje. Normalne netečnosti pojavljuju se između riječi i nisu nužno povezane s govornim poremećajima. Većina istraživanja pokazuje da se u uobičajenomu spontanome govoru na 100 riječi javlja šest netečnosti. Mucajuće netečnosti mogu biti prisutne i kod tečnih govornika, iako su rjeđe od normalnih. Kao najčešće vrste normalnih netečnosti kod tečnih govornika navode se umetanja, revizije te, od mucajućih netečnosti, ponavljanje jednosložnih riječi. Cilj je ovoga istraživanja ponuditi opis netečnosti odraslih govornika hrvatskoga jezika pri pripovijedanju. Zanimao nas je ukupan broj netečnosti, vrste netečnosti te u kojim se omjerima pojavljuju. Rezultati su sukladni ranijim istraživanjima jer je prosječan broj 6,5 netečnosti na 100 riječi. Sudionici su najviše proizvodili normalne netečnosti, najčešće umetanja popunjivača te revizije fraza i revizije riječi. Od mucajućih netečnosti najviše je bilo duljenja glasova, a nešto manje ponavljanja jednosložnih riječi. Iako je mucajućih netečnosti puno manje, pojavile su se sve vrste osim zastoja ili bloka.

Summary Background Developmental processes are intimately tied to signaling events that integrate the dynamic reorganization of the actin cytoskeleton and membrane dynamics. The F-BAR-domain-containing proteins are prime candidates to couple actin dynamics and membrane trafficking in different morphogenetic processes. Results Here, we present the functional analysis of the Drosophila F-BAR protein Cip4/Toca1 (Cdc42-interacting protein 4/transducer of Cdc42-dependent actin assembly 1). Cip4 is able to form a complex with WASP and SCAR/WAVE and recruits both actin-nucleation-promoting factors to invaginating membranes and endocytic vesicles. Actin-comet-tail-based movement of these vesicles depends not only on WASP but largely on WAVE function. In vivo, loss of cip4 function causes multiple wing hairs. A similar phenotype is observed when vesicle scission is affected after Dynamin suppression. Gene dosage experiments show that Cip4 and WAVE functionally interact to restrict wing hair formation. Further rescue experiments confirm that Cip4 is able to act through WAVE and WASP in vivo. Biochemical and functional data support a model in which Cdc42 acts upstream of Cip4 and recruits not only WASP but also SCAR/WAVE via Abi to control Dynamin-dependent cell polarization in the wing. Conclusion Cip4 integrates membrane trafficking and actin dynamics through WASP and WAVE. First, Cip4 promotes membrane invaginations and triggers the vesicle scission by recruiting Dynamin to the neck of nascent vesicles. Second, Cip4 recruits WASP and WAVE proteins to induce actin polymerization, supporting vesicle scission and providing the force for vesicle movement.

One of the central regulators coupling tyrosine phosphorylation with cytoskeletal dynamics is the Abelson interactor (Abi). Its activity regulates WASP-/WAVE mediated F-actin formation and in addition modulates the activity of the Abelson tyrosine kinase (Abl). We have recently shown that the Drosophila Abi is capable of promoting bristle development in a wasp dependent fashion. Here, we report that Drosophila Abi induces sensory organ development by modulating EGFR signaling. Expression of a membrane-tethered activated Abi protein (Abi Myr ) leads to an increase in MAPK activity. Additionally, suppression of EGFR activity inhibits the induction of extra-sensory organs by Abi Myr , whereas co-expression of activated Abi Myr and EGFR dramatically enhances the neurogenic phenotype. In agreement with this observation Abi is able to associate with the EGFR in a common complex. Furthermore, Abi binds the Abl tyrosine kinase. A block of Abl kinase-activity reduces Abi protein stability and strongly abrogates ectopic sensory organ formation induced by Abi Myr . Concomitantly, we noted changes in tyrosine phosphorylation supporting previous reports that Abi protein stability is linked to tyrosine phosphorylation mediated by Abl.

Dynamic actin polymerization drives a variety of morphogenetic events during metazoan development. Members of the WASP/WAVE protein family are central nucleation-promoting factors. They are embedded within regulatory networks of macromolecular complexes controlling Arp2/3-mediated actin nucleation in time and space. WAVE (Wiskott-Aldrich syndrome protein family verprolin-homologous protein) proteins are found in a conserved pentameric heterocomplex that contains Abi, Kette/Nap1, Sra-1/CYFIP, and HSPC300. Formation of the WAVE complex contributes to the localization, activity, and stability of the various WAVE proteins. Here, we established the Bimolecular Fluorescence Complementation (BiFC) technique in Drosophila to determine the subcellular localization of the WAVE complex in living flies. Using different split-YFP combinations, we are able to visualize the formation of the WAVE-Abi complex in vivo. We found that WAVE also forms dimers that are capable of forming higher order clusters with endogenous WAVE complex components. The N-terminal WAVE homology domain (WHD) of the WAVE protein mediates both WAVE-Abi and WAVE-WAVE interactions. Detailed localization analyses show that formation of WAVE complexes specifically takes place at basal cell compartments promoting actin polymerization. In the wing epithelium, hetero- and homooligomeric WAVE complexes co-localize with Integrin and Talin suggesting a role in integrin-mediated cell adhesion. RNAi mediated suppression of single components of the WAVE and the Arp2/3 complex in the wing further suggests that WAVE-dependent Arp2/3-mediated actin nucleation is important for the maintenance of stable integrin junctions.

Keratoacanthoma is a fairly common, benign, usually self-resolving skin lesion that arises from the hair follicle. This nodular lesion shows a predilection for areas exposed to light, mainly for the face. We report on the intensive radiation therapy of 2 cases of a rare subset of keratoacanthoma which showed a locally aggressive, seriously destructive growth.Two female patients with previously treated, confluent-destructive growing keratoacanthoma were treated by multimodal, high-dose radiotherapy. Patient 1 showed a rapid progress of midfacial tumor with destructive infiltration of the left cheek, nasal cartilage, the cribriform plate of ethmoid and congestion of the conjunctiva close to the lacrimal caruncle. This could be shown in clinical and histopathological investigations and CT-scans. The coexistence of cutaneous and conjunctival lesions in locally rapidly enlarging keratoacanthoma of the face is unusual and unreported to our knowledge. One case of simultaneous conjunctival and multiple, eruptive keratoacanthoma of the body has been reported. Patient 2 had received soft X-ray pretreatment because of a large, relapsing keratoacanthoma of the left cheek.Patient 1 underwent a parallel, intensive treatment of the conjunctiva with 90Sr-contact therapy, percutaneous high-dose 60Co-gamma- and megavoltage electron treatment (10 and 18 MeV) of the midfacial lesions. Conjunctiva and caruncle showed a complete remission of keratoacanthoma. In the other facial areas no long-term regression could be reached, despite giving a fully cancericidal, total dose of more than 100 Gy in some regions. Patient 2: Further high dose radiotherapy using megavoltage electron treatment with a total dose of 50 Gy showed a complete remission of the lesion for 5 months. Another relapse of this keratoacanthoma could be operated successfully. There was no more relapse established in follow-up checks.The 2 case reports show that in treatment of locally destructive growing subsets of keratoacanthoma a sufficient therapy should be initiated in time. Keratoacanthoma and subsets of this lesion that do not respond well to initial treatment, recur early or show seriously aggressive growth should be treated early by combined therapy that takes previous experiences into consideration.

Image information obtained with different methods should be exactly transferable to profit fully from the single advantage the different imaging method has in localisation and for further treatment planning. Prominent anatomical points serve as reference structures (landmarks) for the transference of imaging information and details of situation. Aim of this study is the improvement of reproductability by comparing topographic relations, measurements and positioning in different imaging-procedures with supporting marking aids/surface markers.By using pharmacological capsules and plastic tubes filled with oily contrast medium containing iodine (Lipiodol; Byk Gulden), marking aids were developed which can be seen in similar definite limits within the framework of MRI-, CT- and conventional X-ray-Imaging.A method to view these new, artificial markers in combination with individual, anatomical landmarks is introduced. The marking aid/surface marker, fixed on anatomical reference structures on the skin, does not result in an additional burden for the patient.The new, artificial markers are also useful for making other structures recognizable, such as anatomical relation lines, center of the portal and edges in planning imaging for radiotherapy treatments and are used as leading and reference structures to compare localisation and extent of lesions in X-ray-, CT- and MRI. Marking aids/surface markers do not have to be changed in different imaging methods.

Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) belong to the same superfamily of neuropeptides which exert their effects by activating G-protein-coupled receptors defined as PACAP. So far, three receptor subtypes exist (PAC1R, VPACR-1 and VPACR-2). Because, PACAP appears to play a crucial role in cutaneous inflammation and vasoregulation, we examined the expression and biological effects of this peptide in primary human dermal microvascular endothelial cells (HDMECs). We detected the expression of PACAP and VPAC type 1 receptor at RNA and protein level by RT-PCR and immunohistochemistry, indicating an autocrine regulatory mechanism. cAMP assays revealed VPAC1R to be functional in these cells. RT-PCR showed upregulation of IL-8 in a time- and dose-dependent manner. ELISA experiments confirmed release of IL-8 by HDMEC cells. We also investigated cell adhesion molecule expression after stimulation with PACAP. ICAM-1 mRNA was upregulated at 3 and 6 h after treatment with PACAP, while VCAM was only upregulated maximally at 6 h after PACAP stimulation, indicating the regulation of cell adhesion molecule expression in human dermal endothelial cells via VPAC1R. Immunoreactivity for VPAC-1R was enhanced in microvascular endothelial cells of patients with atopic dermatitis and urticaria, indicating upregulation of this receptor in endothelial cells during cutaneous inflammation. In summary, VIP and PACAP may play an important role in cutaneous neurogenic inflammation by activating VPAC-1R on dermal microvascular endothelial cells.