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  • 1
    Keywords: Germany ; THERAPY ; CLASSIFICATION ; RISK ; PATIENT ; treatment ; LESIONS ; EXPERIENCE ; REPAIR ; HIGH-RISK ; SELECTION ; RECONSTRUCTION ; MANAGEMENT ; SURGICAL-TREATMENT ; ABDOMINAL AORTIC-ANEURYSM ; aneurysm ; ARTERY ANEURYSMS ; endograft ; endovascular ; ENDOVASCULAR TREATMENT ; GRAFTS ; iliac artery ; MIDTERM EXPERIENCE
    Abstract: Isolated iliac aneurysms (IIA) are uncommon lesions that require surgical repair to prevent rupture. The aim of this article is to give an update on the current surgical management of IIA. This report also evaluates the application of endovascular repair in IIA, based on a recent Pubmed search and on our own experience in the interventional field: Open reconstruction achieves good longterm results and still represents the golden standard in surgical treatment of IIA. Transluminally placed endovascular stent grafts can be successfully used to exclude isolated iliac aneurysms in selected high risk patients with suitable anatomy. A classification based on aneurysm morphology is useful for patient selection. The value of endovascular therapy has yet to be determined
    Type of Publication: Journal article published
    PubMed ID: 16485205
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  • 2
    Keywords: Germany ; RISK ; DISTINCT ; GENE ; GENES ; PATIENT ; MARKER ; ASSOCIATION ; DISORDER ; NO ; etiology ; MARKERS ; REGION ; SUSCEPTIBILITY GENE ; LEVEL ; analysis ; HAPLOTYPE ; PSYCHIATRIC-DISORDERS ; USA ; depression ; population-based ; comparison ; quantitative ; ANXIETY ; GENOME-WIDE ASSOCIATION ; VA ; HAPLOTYPE SHARING ANALYSIS ; MAJOR DEPRESSION ; AMINO-ACID OXIDASE ; BIPOLAR-AFFECTIVE-DISORDER ; DAOA/G30 LOCUS ; DIAGNOSTIC BOUNDARIES ; G72/G30 GENE LOCUS ; PERSECUTORY DELUSIONS
    Abstract: Objective: G72 is among the most frequently replicated vulnerability genes for schizophrenia and bipolar disorder. The authors previously found identical haplotypes of markers M23 and M24 to be associated with schizophrenia, bipolar disorder, and panic disorder. Given both the well-recognized familial clustering across these disorders and recent linkage findings implicating the region harboring G72 in the etiology of major depression and panic disorder, we can hypothesize that G72 should also be involved in the etiology of major depression. Neuroticism, measuring trait anxiety, may be the endophenotypic link underlying genetic associationswith G72 across diagnostic boundaries. The authors tested whether the previously observed risk haplotypes are also associated with major depression and neuroticism. Method: The authors performed a standard haplotype analysis in a group of 500 major depression patients and 1,030 population-based comparison subjects. The authors also performed an exploratory analysis on 10 additional G72 markers using a novel haplotype-sharing approach. They performed a quantitative trait haplotype analysis in an independent group of 907 individuals phenotyped for neuroticism. Results: The previously identified M23-M24 risk haplotype was significantly associated with major depression and high levels of neuroticism. The haplotype-sharing analysis also implicated the same region, whereas more proximal markers showed no association with major depression. Conclusions: This is the first study to the authors' knowledge to implicate the G72 locus in the etiology of major depression and neuroticism. The results strengthen the notion of a genetic overlap between diagnoses, commonly conceptualized as distinct entities. Neuroticism may constitute the common underlying endophenotypic link
    Type of Publication: Journal article published
    PubMed ID: 18346999
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  • 3
    Keywords: RECEPTOR ; ANGIOGENESIS ; APOPTOSIS ; CANCER ; CELLS ; ENDOTHELIAL-CELLS ; EXPRESSION ; GROWTH ; IN-VITRO ; carcinoma ; CELL ; ENDOTHELIAL GROWTH-FACTOR ; Germany ; human ; IN-VIVO ; MODEL ; MODELS ; VIVO ; ACTIVATION ; murine ; BINDING ; PHOSPHORYLATION ; BREAST ; breast cancer ; BREAST-CANCER ; MOUSE ; NEOPLASIA ; CARCINOMA CELLS ; CARCINOMA-CELLS ; MORPHOLOGY ; OVEREXPRESSION ; VEGF ; REGRESSION ; endothelial cells ; BLOOD-VESSELS ; angiopoietin ; TIE2 ; tumour growth ; CELL-CELL ; PROMOTES TUMOR ANGIOGENESIS ; vessel morphology
    Abstract: Sustained growth of solid tumours can rely on both the formation of new and the co-option of existing blood vessels. Current models suggest that binding of angiopoietin-2 (Ang-2) to its endothelial Tie2 receptor prevents receptor phosphorylation, destabilizes blood vessels, and promotes vascular permeability. In contrast, binding of angiopoietin-1 (Ang-1) induces Tie2 receptor activation and supports the formation of mature blood vessels covered by pericytes. Despite the intense research to decipher the role of angiopoietins during physiological neovascularization and tumour angiogenesis, a mechanistic understanding of angiopoietin function on vascular integrity and remodelling is still incomplete. We therefore assessed the vascular morphology of two mouse mammary carcinoma xenotransplants (M6378 and M6363) which differ in their natural angiopoietin expression. M6378 displayed Ang-1 in tumour cells but no Ang-2 in tumour endothelial cells in vivo. In contrast, M6363 tumours expressed Ang-2 in the tumour vasculature, whereas no Ang-1 expression was present in tumour cells. We stably transfected M6378 mouse mammary carcinoma cells with human Ang-1 or Ang-2 and investigated the consequences on the host vasculature, including ultrastructural morphology. Interestingly, M6378/Ang-2 and M6363 tumours displayed a similar vascular morphology, with intratumoural haemorrhage and non-functional and abnormal blood vessels. Pericyte loss was prominent in these tumours and was accompanied by increased endothelial cell apoptosis. Thus, overexpression of Ang-2 converted the vascular phenotype of M6378 tumours into a phenotype similar to M6363 tumours. Our results support the hypothesis that Ang-1/Tie2 signalling is essential for vessel stabilization and endothelial cell/pericyte interaction, and suggest that Ang-2 is able to induce a switch of vascular phenotypes within tumours. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd
    Type of Publication: Journal article published
    PubMed ID: 19116989
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  • 4
    Keywords: measurement ; CANCER ; SURVIVAL ; tumor ; carcinoma ; COMBINATION ; evaluation ; Germany ; MODEL ; THERAPY ; CLASSIFICATION ; imaging ; QUANTIFICATION ; LONG-TERM ; METABOLISM ; NUCLEAR-MEDICINE ; PATIENT ; prognosis ; CYCLE ; 5-FLUOROURACIL ; ACID ; colorectal cancer ; COLORECTAL-CANCER ; chemotherapy ; LONG-TERM SURVIVAL ; PARAMETERS ; POSITRON-EMISSION-TOMOGRAPHY ; PREDICTION ; PET ; FLUOROURACIL ; folinic acid ; KINETICS ; LIVER METASTASES ; OXALIPLATIN ; SERIES ; nuclear medicine ; FLUORODEOXYGLUCOSE ; FRACTION ; COLORECTAL-CARCINOMA ; colorectal tumor ; F-18-FDG ; fractal dimension ; THERAPY RESPONSE
    Abstract: We evaluated quantitative measurement series (MS) with F-18-FDG and PET and compared different quantification methods for prediction of individual survival in patients with metastatic colorectal cancer receiving chemotherapy with 5-fluorouracil, folinic acid, and oxaliplatin (FOLFOX). Methods: The study comprised 25 patients. All patients were examined before the onset of FOLFOX therapy and after completion of the first and fourth cycles. SUV, fractal dimension (ED), a 2-compartment model with computation of k1, k2, k3, and k4, and vascular fraction (VB) were used for data evaluation. Survival data served as a reference for the PET data. Discriminant analysis (DA), regression, and best-subset analysis were applied to the data. Results: Twenty of 25 patients died up to 801 d after the first PET study. A cutoff of 1 y (364 d) was used to classify the patients into 2 a priori groups, namely the short- and long-term survival groups. DA was used to predict the 2 categories using SUV and kinetic parameters of F-18-FDG metabolism as predictor variables. SUV provided a correct classification rate (CCR) ranging from 62% to 69%. SUV of the third MS resulted in a CCR of 69% as a single parameter. The best results were yielded by the use of kinetic parameters (k1, k3, VB, and FD) as predictor variables. CCR was 78% using kinetic F-18-FDG parameters of the first and third MS, in comparison with 69% for the corresponding SUVs. A multiple linear regression model was applied to the data to assess the relationship between individual survival and the PET data. The best-subset method revealed a correlation coefficient of 0.850 for the kinetic parameters of the first (k3, k4, VB, and FD) and third (k1, k2, k4, and VB) MS. Conclusion: The combination of kinetic parameters of the first and the third MS is acceptable for classification into a short or long survival class. Furthermore, even an individual prognosis of survival can be achieved using kinetic F-18-FDG parameters of the first and third MS
    Type of Publication: Journal article published
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  • 5
    Keywords: CELL ; Germany ; human ; NEW-YORK ; PROTEIN ; PROTEINS ; SACCHAROMYCES-CEREVISIAE ; FAMILY ; BINDING ; BIOLOGY ; MOLECULAR-BIOLOGY ; SIGNAL ; DELETION ; YEAST ; MEMBRANE ; LOCALIZATION ; RECRUITMENT ; GOLGI ; DOMAINS ; molecular biology ; molecular ; FAMILIES ; USA ; ARF ; TRANS-GOLGI NETWORK ; BINDING PROTEINS ; NUCLEOTIDE EXCHANGE FACTORS ; interactions ; CELL BIOLOGY ; PARTNER ; EFFECTORS ; membrane traffic ; ENDOSOMES ; Arf family ; clathrin coat ; flippase ; RETROGRADE TRANSPORT
    Abstract: The Gga proteins represent a family of ubiquitously expressed clathrin adaptors engaged in vesicle budding at the tubular endosomal network/trans Golgi network. Their membrane recruitment is commonly thought to involve interactions with Arf and signals in cargo through the so-called VHS domain. For yeast Gga proteins, however, partners binding to its VHS domain have remained elusive and Gga localization does not absolutely depend on Arf. Here, we demonstrate that yeast Gga recruitment relies on a network of interactions between the scaffold Ysl2p/Mon2p, the small GTPase Arl1p, and the flippase Neo1p. Deletion of either YSL2 or ARL1 causes mislocalization of Gga2p, whereas a neo1-69 mutant accumulates Gga2p on aberrant structures. Remarkably, Ysl2p directly interacts with human and yeast Ggas through the VHS domain, and binding to Gga proteins is also found for the human Ysl2p orthologue hMon2. Thus, Ysl2p represents an essential, evolutionarily conserved member of a network controlling direct binding and membrane docking of Ggas. Because activated Arl1p is part of the network that binds Gga2p, Arf and Arf-like GTPases may interact in a regulatory cascade
    Type of Publication: Journal article published
    PubMed ID: 18418388
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  • 6
    Keywords: RECEPTOR ; EXPRESSION ; CELL ; Germany ; imaging ; GENE ; GENE-EXPRESSION ; GENES ; microarray ; PROTEIN ; PROTEINS ; BREAST-CANCER ; TARGET ; gene expression ; genetics ; REQUIRES ; FUSION ; positron emission tomography ; tomography ; KINETICS ; TARGETS ; RECEPTORS ; REGRESSION ; PROGRAM ; RE ; ARRAY ; development ; analysis ; NUCLEAR ; EXPRESSION PROFILES ; technique ; USA ; function ; correlation ; gene array ; modeling ; EMISSION
    Abstract: The combined assessment of data obtained by positron emission tomography (PET) and gene array techniques provide new capabilities for the interpretation of kinetic tracer studies. The correlative analysis of the data helps to detect de pendencies of the kinetics of radiotracer on gene expression. Furthermore, gene expression may be predicted using regression functions if a significant correlation exists, which raises new aspects regarding the interpretation of dynamic PET examinations. The development of new radiopharmaceuticals requires the knowledge of the enhanced expression of genes, especially genes controlling receptors and cell surface proteins. The GenePET program facilitates an interactive approach together with the use of key words to identify possible targets for new radiopharmaceuticals
    Type of Publication: Journal article published
    PubMed ID: 17679331
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