1,838 research outputs found
Isolated familial pheochromocytoma as a variant of von Hippel-Lindau disease.
No full textInherited pheochromocytomas are often part of familial syndromes, especially multiple endocrine neoplasia type 2 (MEN 2), retinal cerebellar hemangioblastomatosis [von Hippel-Lindau (vHL) disease] or neurofibromatosis type 1. It is not clear whether isolated familial pheochromocytoma exists as a separate clinical entity. In a family with pheochromocytomas in three generations and with at least seven affected members, we investigated by clinical and genetic analyses the presence or absence of associated conditions. The clinical investigations included ophthalmological and radiological studies for von Hippel-Lindau disease (magnetic resonance imaging of the brain, computed tomography of the abdomen, and direct ophthalmoscopy after mydriasis) and annual calcitonin stimulation tests for C cell disease in five members who agreed to regular follow-up. Besides the pheochromocytomas (so far, these have been multiple in five of seven individuals) no definite second associated condition was found. Genetic analysis did not identify any MEN 2-specific RET protooncogene point mutations (which are present in 97% of MEN 2a families). However, despite the complete absence of other clinical manifestations of the vHL disease (besides pheochromocytomas), a previously undescribed germline missense mutation in the vHL tumor suppressor gene was found (C775G transversion with a predicted substitution of a leucine by a valine at codon 259 in the putative vHL protein). We conclude that in this family the sole occurrence of pheochromocytoma is a variant of vHL disease
Structure-guided design and optimization of small molecules targeting the protein-protein interaction between the von hippel-lindau (VHL) E3 ubiquitin ligase and the hypoxia inducible factor (HIF) alpha subunit with in vitro nanomolar affinities
No full textE3 ubiquitin ligases are attractive targets in the ubiquitin-proteasome system, however, the development of small-molecule ligands has been rewarded with limited success. The von Hippel-Lindau protein (pVHL) is the substrate recognition subunit of the VHL E3 ligase that targets HIF-1α for degradation. We recently reported inhibitors of the pVHL:HIF-1α interaction, however they exhibited moderate potency. Herein, we report the design and optimization, guided by X-ray crystal structures, of a ligand series with nanomolar binding affinities.</p
Gesammelte Aufsätze : Beiträge zur Literaturgeschichte der Gegenwart / Paul Lindau
No full textGESAMMELTE AUFSÄTZE : BEITRÄGE ZUR LITERATURGESCHICHTE DER GEGENWART / PAUL LINDAU
Gesammelte Aufsätze : Beiträge zur Literaturgeschichte der Gegenwart / Paul Lindau (1)
Cover (1)
Titelseite (4)
Druckvermerk (5)
Inhalt (6)
I. Roderich Bendix (8)
I. Eine Erinnerung an Hoffmann von Fallersleben (22)
I. Gustav Freytags neuester Roman "Die Ahnen" (36)
I. Erlebnisse einer Mannesseele (89)
I. Berthold Auerbach. "Waldfried" (101)
I. Neuere Erzählungen von Friedrich Spielhagen (130)
I. Paul Heyse. "Kinder der Welt" (163)
I. Fanny Lewald. "Benedikt" (191)
I. Daniel Spitzer, der Wiener Spaziergänger (202)
I. Johannes Scherr. "Hammerschläge und Historien" (217)
I. Robert Hamerling. "Teut" (228)
II. Goethes "Faust" in Frankreich (246)
II. Victor Hugo und seine letzten Werke (272)
II. Jules Janin, "Der Fürst des Feuilletons" (339)
II. Paul de Kock (355)
III. Unsere Classiker und unsere Universitäten (367)
III. Eine Kritik über Gustav Freytag (378)
III. Ein modernes Epos (388)
III. Patriotische Gedichte aus den Kriegsjahren (400)
III. Deutsche Poesie in den Vereinigten Staaten (411)
III. Ein deutscher Dichter (422)
III. Emile Maria Vacano. "Gräfin Katinka und ihre Nachbarn" (427)
III. Emerich Graf Stadion. "Rhapsodieen" (439)
III. Tartüffe in der Presse (451
Compound formation and bonding configuration at the Si-Cu interface
No full textJoint photoemission and Auger LVV line-shape spectroscopies on the Si-Cu interface show the existence of a silicidelike compound with bonding characteristics similar to those of the near-noble-metal silicides. This makes the Si-Cu interface different from the other noble-metal-Si interfaces where alloylike phases (Si-Au) or narrow interfaces with concentration gradients (Si-Ag) are formed. The Si-Cu compound is metal-rich with a stoichiometry close to the eutectic composition Cu3Si and is stable over a wide range of temperatures
Von Hippel-Lindau
No full textReview on Von Hippel-Lindau, with data on clinics, and the genes involved
The interaction of Notch signalling, haemodynamic flow and angiogenesis in Von Hippel-Lindau mutant zebrafish.
No full textIntroduction: There is increasing evidence that the endothelium is able to transduce circulatory force into signals which influence angiogenic behaviour. The Von Hippel-Lindau homozygous mutant zebrafish (vhl-/-) has increased HIF-1α signalling and aberrant angiogenesis. In this study I therefore set out to characterise the angiogenic phenotype of the vhl-/- mutant and examine the effect of manipulating blood flow. Both nitric oxide (NO) and Notch regulated intracellular signalling have been shown to influence endothelial angiogenic behaviour in development and disease, so I studied the role of these on development of the angiogenic phenotype in the vhl-/- mutant.
Hypothesis: Does angiogenesis stimulated by up-regulated hypoxic signalling require blood flow?
Methods: vhl mutant zebrafish were crossed with endothelial reporter transgenics to assess and quantify the angiogenic phenotype. Blood flow was manipulated using genetic and pharmacological manipulation in developing zebrafish embryos. To study the effect of flow on endothelial notch signalling I utilised a novel transgenic line Tg(CSL:venus), which expresses a fluorescent reporter upon activation of a Notch regulated transcription factor. The role of individual notch signalling components was investigated using reverse transcription quantitative polymerase chain reaction (RT-qPCR) for various ligands in developing zebrafish tissue during development in the absence of flow and in control embryos.
Results: The vhl-/- mutant showed early vessel changes including enlargement and sprouting. These angiogenic vessel changes were dependent on the presence of circulatory flow and are lost in mutant embryos treated with troponin t2 morpholino or 2,3-Butanedione monoxime (BDM). Imaging of aortic endothelium showed a significant up regulation of notch signalling in the Tg(CSL:venus) line in the absence of flow, induced by troponin t2 knockdown or BDM treatment. This increase in endothelial notch signalling in the absence of flow was mediated by increased expression of the notch ligand dll4 in RT-qPCR and whole mount in-situ hybridisation experiments.
Conclusion: The aberrant angiogenesis stimulated by increased HIF-1α signalling in the vhl-/- mutant is dependent on blood flow. My data suggests a novel flow dependent regulation of notch signalling in the developing vasculature mediated by the suppression of dll4 by blood flow
Von Hippel-Lindau
No full textReview on Von Hippel-Lindau, with data on clinics, and the genes involved
Erinnerungen aus Italien, England und Amerika / von F. A. von Chateaubriand. Aus dem Französischen übersetzt von W. A. Lindau
No full textERINNERUNGEN AUS ITALIEN, ENGLAND UND AMERIKA / VON F. A. VON CHATEAUBRIAND. AUS DEM FRANZÖSISCHEN ÜBERSETZT VON W. A. LINDAU
Erinnerungen aus Italien, England und Amerika / von F. A. von Chateaubriand. Aus dem Französischen übersetzt von W. A. Lindau (1)
Cover (1)
Titelseite (8)
Vorwort (9)
Erinnerungen aus Italien (12)
I. Rom und die Umgegend (13)
II. Reise auf den Vesuv (30)
III. Reise auf den Montblanc (35)
Erinnerungen aus England (46)
I. Ueber England und die Engländer (47)
II. Bemerkungen über die englische Literatur (56)
Erinnerungen aus Amerika (66)
I. Reise im Gebiete der Wilden (67)
II. Die Insel Gracioza (72)
III. Eine Nacht unter den Wilden (77)
IV. Der Niagara-Fall (83)
V. Der Franzose unter den Wilden (84)
VI. Bemerkungen über Mackenzie's Reise ... (86)
Zusätze und Berichtigungen (103)
Druckfehler (108
The Ge/Au interface investigated with photoemission at the Cooper minimum
No full textThe formation of the Au/Ge interface at room temperature is followed for increasing Au coverages and studied by energy dependent photoemission. The experimental EDC's are discussed and compared with density of states calculations for AuaGe. The evidence for Au 5d-Ge 4p mixed states indicates that the Au/Ge interface is similar to the near-noble metal germanides. A note on the photoemission branching ratio in semi-isolated Au and in thick Au layers is added
Exploiting energy-dependent photoemission in Si d-metal interfaces: the Si(111)-Pd case
No full textThe authors present a synchrotron radiation photoemission results from Si(111) with increasing Pd coverages theta (in monolayer units from 0. 5 to 23 monolayers). The authors have measured photoemission spectra in the Cooper minimum for the Pd 4d electrons (hv equals 130 ev) and outside this region (hv equals 80 ev) where the d emission is strong. By comparing the two cases, one obtains information on the Si(sp) and Pd(d) states. Making use of this, a discussion is presented regarding the coverage dependence of the spectra in connection with the nature of the chemical bond between Si and Pd and the structure of the Si-silicide interface
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