1,048 research outputs found
Identifizierung VHL-assoziierter Veränderungen im klarzelligen Nierenzellkarzinom: Anwendung von kombinierten Genom- und Expressionsanalysen
Zusammenfassung: Das sporadische Nierenzellkarzinom (NZK) ist ein heterogener solider Tumor, der traditionell basierend auf morphologischen Kriterien in weitere Subtypen unterteilt wird. In den letzten Jahren konnten unter Anwendung molekularer Hochdurchsatzanalysen genetische, transkriptionelle und translationale Alterationen identifiziert werden. Diese Marker eignen sich zum einen für die molekulare Klassifizierung des NZK und haben zum anderen prognostische Wertigkeit. Die isolierte Betrachtung genetischer, transkriptioneller und translationaler Veränderungen verhindert jedoch ein tieferes Verständnis für die komplexen Vorgänge der Karzinogenese. Wir fassen hier aktuelle Forschungsergebnisse zur molekularen Charakterisierung des NZK zusammen und stellen ein systembiologisches Konzept zur Identifizierung neuer Tumormarker vor. Diese könnten zukünftig Einsatz in der Diagnostik und Therapie des sporadischen NZK finde
Von-Hippel-Lindau-Gen-Mutationstypen: Assoziation mit Genexpressionssignaturen in klarzelligen Nierenzellkarzinomen
Zusammenfassung: Fragestellung: Der Von-Hippel-Lindau- (VHL-)Tumorsuppressor ist ein multifunktionelles Protein. VHL-Mutationen treten häufig auf im klarzelligen Nierenzellkarzinom (kNZK). Verschiedene Mutationstypen führen vermutlich zu spezifischen pVHL-Funktionsveränderungen, die wiederum einen signifikanten Einfluss auf die Genexpression und schließlich auf den Krankheitsverlauf haben dürften. Ziel der vorliegenden Studie ist die Korrelation von Genexpressionssignaturen mit spezifischen VHL-Mutationstypen im kNZK. Methodik: Transkriptomanalyse wurde für 94 kNZK und 21 papilläre NZK (pNZK) mittels Affymetrix HG U133A Genchips durchgeführt. Alle 94 kNZK wurden auf VHL-Mutationen analysiert. Ergebnisse: Ein "hierarchical clustering" anhand der zwischen kNZK und pNZK differenziell regulierten Gene zeigt eine deutliche Stratifizierung der beiden histologischen Subtypen. 186 Gene wurden zwischen VHL-Wildtyp kNZK und kNZK mit mutiertem VHL-Gen differenziell exprimiert. Schlussfolgerung: Unsere Resultate weisen auf eine signifikante Auswirkung von VHL-Mutationen auf die Genexpression im NZK hi
PRS35 The Economic Burden of HAE: Findings From the HAE Burden of Illness Study in Europe (HAE-BOIS-Europe)
Natural killer cells in afferent lymph express an activated phenotype and readily produce IFN-γ
Natural killer (NK) cells are motile cells that migrate between peripheral blood (PB), lymph nodes (LNs) and various organs. Domestic animals have frequently been used to study cellular migration, and offer unique opportunities for such studies. The aim of this study was to characterize the phenotype and cytokine producing capacity of NK cells in bovine skin-draining lymph. NKp46/NCR1+ CD3- cells constituted 2-11 % of mononuclear cells in afferent lymph (AL), a majority of cells were CD16+, CD8α+ and CD2-/low, and elevated CD25 and CD44 expression indicated an activated phenotype. Interestingly, significantly fewer AL NK cells expressed the early activation marker CD69 compared to PB NK cells. A large proportion of lymph and blood NK cells produced interferon (IFN)-γ following stimulation with IL-2 and IL-12. Notably, in AL, but not blood, a similar amount of IFN-γ+ NK cells was observed when cells were stimulated with IL-12 alone. Overall, AL NK cells were more similar to LN-residing NK cells than those circulating in PB. We conclude that AL appears to be an important migration route for tissue-activated NK cells, and may represent an alternative route for NK cell traffic to LNs. These findings may have important implications in the development of adjuvant strategies that aim to target NK cells in a vaccine response
WAO guideline for the management of hereditary angioedema
Hereditary Angioedema (HAE) is a rare disease and for this reason proper diagnosis and appropriate therapy are often unknown or not available for physicians and other health care providers. For this reason we convened a group of specialists that focus upon HAE from around the world to develop not only a consensus on diagnosis and management of HAE, but to also provide evidence based grades, strength of evidence and classification for the consensus. Since both consensus and evidence grading were adhered to the document meets criteria as a guideline. The outcome of the guideline is to improve diagnosis and management of patients with HAE throughout the world and to help initiate uniform care and availability of therapies to all with the diagnosis no matter where the residence of the individual with HAE exists
Condensation of a tetrahedra rigid-body libration mode in HoBaCo4O7 : the origin of phase transition at 355 K
Rietveld profiles, Moessbauer spectra and x-ray absorption fine structure
(XAFS) were analyzed through the structural phase transition at Ts = 355 K in
HoBaCo4O7. Excess of the oxygen content over O7 was avoided via annealing the
samples in argon flow at 600 degree C. Space groups (S.G.) Pbn21c and P63mc
were used to refine the structure parameters in the low- and high-temperature
phases, respectively. Additionally, the Cmc21 symmetry was considered as a
concurrent model of structure of the low-temperature phase. In the
high-temperature phase, severe anisotropy of thermal motion of the major part
of the oxygen atoms was observed. This anisotropic motion turns to be quenched
as the sample is cooled below Ts. The variation of quadrupole splitting near Ts
is not similar to a steplike anomaly frequently seen at the charge-ordering
transition. We observe instead a dip-like anomaly of the average quadrupole
splitting near Ts. Narrow distribution of the electric field gradient (EFG)
over different cobalt sites is observed and explained on the basis of
point-charge model. XAFS spectra show no evidence of significant difference
between YBaCo4O7 (T > Ts) and HoBaCo4O7 (T < Ts). The origin of the transition
at Ts is ascribed to the condensation of the libration phonon mode associated
with the rigid-body rotational movements of the starlike tetrahedral units, the
building blocks of kagome network. It is shown that the condensation of the
libration mode is not compatible with translation symmetry for the hexagonal
S.G., but compatible for the orthorhombic S.G. The orthorhombic lattice
parameters and EFG components (Vxx, Vyy, Vzz) vary smoothly with temperature at
approaching Ts and closely follow each other.Comment: 13 figure
- …