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Sample records for von hippel-lindau peptide

  1. [Von Hippel-Lindau syndrome].

    Science.gov (United States)

    Reich, H; Hollwich, F

    1984-06-01

    The von Hippel-Lindau syndrome is an autosomal dominant condition that comprises, apart from angiomas of the retina, the cerebellum, the spinal cord, and the cerebrum, also cystic and blastomatous dysplasias resulting from maldevelopment, namely cystic kidney and pancreas, hypernephroma, and pheochromocytoma. Early observers of the syndrome were the English neurologist John Hughlings Jackson (1872) and the German ophthalmologist Hugo Magnus (1874). The typical association of angiomas of the retina with the cerebellum was first described in 1905 by the Prague ophthalmologist Wilhelm Czermak, long before Lindau (1926). The fact that hypernephromas and pheochromocytomas may form parts of it characterizes the syndrome as a polyneoplastic hereditary disease and the sufferers as members of families at risk. Since the ophthalmologist is often the first to recognize this disease by direct inspection of the fundi, he is responsible for ensuring proper medical care for the affected person and his or her entire family.

  2. von Hippel-Lindau development in children and adolescents

    DEFF Research Database (Denmark)

    Launbjerg, Karoline; Bache, Iben; Galanakis, Michael

    2017-01-01

    The autosomal dominant von Hippel-Lindau disease (vHL) is associated with a lifelong risk of tumor development, especially retinal and CNS hemangioblastomas, pheochromocytoma, and renal cell carcinoma. Knowledge of paediatric vHL development is limited, and current surveillance guidelines are based...

  3. Von Hippel-Lindau disease (vHL)

    DEFF Research Database (Denmark)

    Binderup, Marie Louise Mølgaard; Bisgaard, Søs Marie Luise; Harbud, Vibeke

    2013-01-01

    These clinical guidelines outline the criteria and recommendations for diagnostic and genetic work-up of families suspected of von Hippel-Lindau disease (vHL), as well as recommendations for prophylactic surveillance for vHL patients. The guideline has been composed by the Danish Coordination Gro...

  4. Von Hippel-Lindau disease: MRI of abdominal manifestations

    Energy Technology Data Exchange (ETDEWEB)

    Tattersall, Deborah J.; Moore, Niall R

    2002-02-01

    The cranial and spinal manifestations of von Hippel-Lindau disease are well known. Less attention has been given to the varied abdominal manifestations. We present a pictorial review of the cystic and solid tumours involving the kidneys, pancreas and adrenal glands as demonstrated by magnetic resonance imaging. We highlight the advantages of this non-ionizing technique in the assessment of this young group of patients with a protracted screening future. Tattersall, D.J. and Moore N.R. (2002)

  5. Multifocal spinal hemangioblastoma in von Hippel-Lindau syndrome: A case report and literature review

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ok Hwa [Dept. of Radiology, Inje University College of Medicine, Haeundae Paik Hospital, Busan (Korea, Republic of)

    2015-03-15

    Hemangioblastoma is a benign vascular neoplasm of the central nervous system that occurs frequently in the cerebellum and other areas of the central nervous system including spinal cord and brainstem. Spinal hemangioblastoma can present as a sporadic isolated lesion or as a component of von Hippel-Lindau syndrome. The author presents a case of 32-year-old man with von Hippel-Lindau syndrome and spinal hemangioblastomas represented by multiple small spinal lesions, with an emphasis on the magnetic resonance imaging findings and clinical characteristics of von Hippel-Lindau syndrome-associated spinal hemangioblastomas.

  6. Von Hippel-Lindau disease (vHL)

    DEFF Research Database (Denmark)

    Binderup, Marie Louise Mølgaard; Bisgaard, Søs Marie Luise; Harbud, Vibeke;

    2013-01-01

    These clinical guidelines outline the criteria and recommendations for diagnostic and genetic work-up of families suspected of von Hippel-Lindau disease (vHL), as well as recommendations for prophylactic surveillance for vHL patients. The guideline has been composed by the Danish Coordination Group...... for vHL which is comprised of Danish doctors and specialists interested in vHL. The recommendations are based on longstanding clinical experience, Danish original research, and extensive review of the international literature. vHL is a hereditary multi-tumour disease caused by germline mutations...... of the disease, and/or in individuals with a vHL-associated manifestation; i.e. a hemangioblastoma in the retina or the central nervous system, familial or bilateral pheochromocytomas, familial, multiple, or early onset renal cell carcinomas, and in individuals with an endolymphatic sac tumour in the inner ear...

  7. Von Hippel-Lindau disease (vHL)

    DEFF Research Database (Denmark)

    Binderup, Marie Louise Mølgaard; Bisgaard, Søs Marie Luise; Harbud, Vibeke

    2013-01-01

    These clinical guidelines outline the criteria and recommendations for diagnostic and genetic work-up of families suspected of von Hippel-Lindau disease (vHL), as well as recommendations for prophylactic surveillance for vHL patients. The guideline has been composed by the Danish Coordination Group...... for vHL which is comprised of Danish doctors and specialists interested in vHL. The recommendations are based on longstanding clinical experience, Danish original research, and extensive review of the international literature. vHL is a hereditary multi-tumour disease caused by germline mutations...... of the disease, and/or in individuals with a vHL-associated manifestation; i.e. a hemangioblastoma in the retina or the central nervous system, familial or bilateral pheochromocytomas, familial, multiple, or early onset renal cell carcinomas, and in individuals with an endolymphatic sac tumour in the inner ear...

  8. Pancreatic cyst development: insights from von Hippel-Lindau disease

    Directory of Open Access Journals (Sweden)

    van Asselt Sophie J

    2013-02-01

    Full Text Available Abstract Pancreatic cysts are a heterogeneous group of lesions, which can be benign or malignant. Due to improved imaging techniques, physicians are more often confronted with pancreatic cysts. Little is known about the origin of pancreatic cysts in general. Von Hippel-Lindau (VHL disease is an atypical ciliopathy and inherited tumor syndrome, caused by a mutation in the VHL tumor suppressor gene encoding the VHL protein (pVHL. VHL patients are prone to develop cysts and neuroendocrine tumors in the pancreas in addition to several other benign and malignant neoplasms. Remarkably, pancreatic cysts occur in approximately 70% of VHL patients, making it the only hereditary tumor syndrome with such a discernible expression of pancreatic cysts. Cellular loss of pVHL due to biallelic mutation can model pancreatic cystogenesis in other organisms, suggesting a causal relationship. Here, we give a comprehensive overview of various pVHL functions, focusing on those that can potentially explain pancreatic cyst development in VHL disease. Based on preclinical studies, cilia loss in ductal cells is probably an important early event in pancreatic cyst development.

  9. Von Hippel-Lindau disease: clinical and genetic investigations in the Netherlands

    NARCIS (Netherlands)

    Hes, Frederik Jan

    2001-01-01

    Von Hippel-Lindau (VHL) disease is an autosomal, dominant inherited tumour syndrome. The disease is named after the German ophthalmologist Eugen von Hippel, who described retinal haemangioblastoma in 1904, and the Swedish pathologist Arvid Lindau who associated retinal and CNS haemangioblastom

  10. von Hippel-Lindau disease: surveillance strategy for endolymphatic sac tumors

    DEFF Research Database (Denmark)

    Poulsen, Marie Louise Mølgaard; Gimsing, Steen; Kosteljanetz, Michael

    2011-01-01

    : Up to 16% of patients with the hereditary von Hippel-Lindau disease develop endolymphatic sac tumors of the inner ear. Early diagnosis and treatment of endolymphatic sac tumors can prevent audiovestibular morbidity, but optimal endolymphatic sac tumor surveillance strategy has yet...... to be determined. We aimed to evaluate endolymphatic sac tumor surveillance to determine the best surveillance strategy....

  11. Von Hippel-Lindau Disease : Genetics and role of genetic counseling in a multiple neoplasia syndrome

    NARCIS (Netherlands)

    Nielsen, Sarah M; Rhodes, Lindsay; Blanco, Ignacio; Chung, Wendy K; Eng, Charis; Maher, Eamonn R; Richard, Stéphane; Giles, Rachel H

    2016-01-01

    Von Hippel-Lindau disease (VHL) is one of the most common inherited neoplasia syndromes and is characterized by highly vascular tumors of the eyes, brain, and spine, as well as benign and malignant tumors and/or cysts of the kidneys, adrenal medullae and sympathetic paraganglia, endolymphatic sac, e

  12. Mobility of the von Hippel-Lindau tumour suppressor protein is regulated by kinesin-2.

    NARCIS (Netherlands)

    Mans, D.A.; Lolkema, M.P.; Beest, M van; Daenen, L.G.; Voest, E.E.; Giles, R.H.

    2008-01-01

    The von Hippel-Lindau tumour suppressor protein (pVHL) participates in many cellular processes including oxygen sensing, microtubule stability and primary cilia regulation. Recently, we identified ATP-dependent motor complex kinesin-2 to endogenously bind the full-length variant of VHL (pVHL30) in p

  13. The von Hippel-Lindau tumor suppressor protein influences microtubule dynamics at the cell periphery.

    NARCIS (Netherlands)

    Lolkema, M.P.; Mehra, N.; Jorna, A.S.; Beest, M. van; Giles, R.H.; Voest, E.E.

    2004-01-01

    The von Hippel-Lindau (VHL) protein protects microtubules (MTs) from destabilization by nocodazole treatment. Based on this fixed-cell assay with static end points, VHL has been reported to directly stabilize the MT cytoskeleton. To investigate the dynamic changes in MTs induced by VHL in living cel

  14. Pregnancy-related hemangioblastoma progression and complications in von Hippel-Lindau disease.

    NARCIS (Netherlands)

    Frantzen, C.; Kruizinga, R.C.; Asselt, S.J. van; Zonnenberg, B.A.; Lenders, J.W.M.; Herder, W.W. de; Walenkamp, A.M.; Giles, R.H.; Hes, F.J.; Sluiter, W.J.; Pampus, M.G. van; Links, T.P.

    2012-01-01

    OBJECTIVE: We studied the reciprocal effect of pregnancy and von Hippel-Lindau (VHL) disease by analyzing the influence of pregnancy on VHL disease-related lesions and VHL disease on pregnancy outcome. METHODS: Medical charts and imaging reports from the VHL disease expertise centers in the Netherla

  15. The von Hippel-Lindau tumour suppressor interacts with microtubules through kinesin-2

    NARCIS (Netherlands)

    Lolkema, M.P.J.K.; Mans, D.A.; Snijckers, C.M.J.T.; Noort, Mascha van; Beest, M. van; Voest, E.E.; Giles, R.H.

    2007-01-01

    Synthesis and maintenance of primary cilia are regulated by the von Hippel-Lindau (VHL) tumour suppressor protein. Recent studies indicate that this regulation is linked to microtubule-dependent functions of pVHL such as orienting microtubule growth and increasing plus-end microtubule stability, how

  16. Allele-specific regulation of primary cilia function by the von Hippel-Lindau tumor suppressor

    NARCIS (Netherlands)

    Lolkema, M.P.; Mans, D.A.; Ulfman, L.H.; Volpi, S.; Voest, E.E.; Giles, R.H.

    2008-01-01

    Patients with von Hippel-Lindau (VHL) disease often develop VHL-/- kidney cysts, which possibly progress into clear-cell renal carcinomas (ccRCCs). Recent data link the VHL gene product to formation of the primary cilium, an organelle that extends apically into the renal lumen. Exactly how VHL induc

  17. Von Hippel Lindau disease with metastatic pancreatic neuroendocrine tumor causing ectopic Cushing's syndrome.

    Science.gov (United States)

    Hatipoglu, Esra; Kepicoglu, Hasan; Rusen, Elif; Kabasakal, Levent; Gundogdu, Sadi; Kadioglu, Pinar

    2013-01-01

    We present a 39-year-old woman who was previously diagnosed with Von Hippel Lindau Disease (VHLD). She had surgery and radiotherapy for cranial hemangioblastoma (HA) 11 years ago and had unilateral adrenalectomy for pheochromocytoma in another hospital 6 month prior to her admission to our center. Moon face, buffalo hump, central obesity, progressive weight gain and menstrual irregularities persisted after adrenalectomy. Her laboratory results were consistent with ectopic Cushing's syndrome (ECS). A pancreatic solid mass with a nodule on the left lung were revealed upon computed tomography. In addition, Gallium-68 Somatostatin Receptor PET confirmed the pancreatic involvement and demonstrated additional lesions on the left lung and in the aortocaval lymphatic system on the right side, suggesting metastatic pancreatic neuroendocrine tumor (PNET). Peptide receptor radionuclide therapy (PRRT) with [177Lutetium-DOTA0,Tyr3] octreotate was performed on the patient, with no side effects observed. She was discharged from the hospital 10 days after the first cycle.

  18. Prenatal exclusion of von Hippel-Lindau syndrome in a Mexican family carrying a novel VHL gene mutation

    National Research Council Canada - National Science Library

    Chacón-Camacho, Oscar Francisco; Benitez-Granados, Jesús; Zenteno, Juan Carlos

    2013-01-01

    Von Hippel-Lindau syndrome is an autosomal dominant and familial multisystemic syndrome that is caused by the inactivation of the VHL gene and it is characterized by diverse types of high vasculated...

  19. Prenatal exclusion of von Hippel-Lindau syndrome in a Mexican family carrying a novel VHL gene mutation

    National Research Council Canada - National Science Library

    Chacón-Camacho, Oscar Francisco; Benitez-Granados, Jesús; Zenteno, Juan Carlos

    2014-01-01

    von Hippel-Lindau (VHL) disease is an autosomal dominant and familial multisystemic syndrome that is caused by the inactivation of the VHL gene and it is characterized by diverse types of high vasculated tumours of benign and malign nature...

  20. Hodgkin's disease in a patient with Von Hippel-Lindau disease. A case report.

    Science.gov (United States)

    D'hondt, R; Thomas, J; Van Oosterom, A T; Dewolf-Peeters, C

    2000-01-01

    Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited disorder with a predisposition to develop a wide variety of lesions: retinal, cerebellar, spinal and medullar hemangioblastomas, renal cell carcinomas, phaeochromocytomas, and renal, pancreatic and epididymal cysts are the most frequent manifestations of the disease. The prevalence of VHL disease has been estimated to be 1 per 36,000 persons. We report the case of a 68-year-old woman with Von Hipple-Lindau disease who developed high fever with pulmonary and hepatic lesions proven to be Hodgkin's disease on biopsy. To our knowledge, this is the first report of Hodgkin's disease in a patient with Von Hippel-Lindau.

  1. Neuroregeneration of Induced Pluripotent Stem Cells in Polyacrylamide-Chitosan Inverted Colloidal Crystal Scaffolds with Poly(lactide-co-glycolide) Nanoparticles and Transactivator of Transcription von Hippel-Lindau Peptide.

    Science.gov (United States)

    Kuo, Yung-Chih; Chen, Chun-Wei

    2017-04-01

    Polyacrylamide (PAAM) and chitosan were fabricated by inverted colloidal crystal (ICC) method for scaffolds comprising regular pores. The hybrid PAAM-chitosan ICC scaffolds were grafted with poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) for a rougher pore surface and grafted with transactivator of transcription von Hippel-Lindau (TATVHL) peptide for a better differentiation of induced pluripotent stem (iPS) cells toward neural lineage. By scanning electron microscopy, we found that iPS cells cultured in PAAM-chitosan ICC scaffolds with PLGA NPs at 1.0 mg/mL and TATVHL peptide at 15 μg/mL elongated the axonal length to 15 μm. A combination of PLGA NPs and TATVHL peptide favored the adhesion of iPS cells, reduced the embryonic phenotype after cultivation, and guided the production of βIII tubulin-positive cells in PAAM-chitosan ICC scaffolds. In addition to the differentiation toward neurite-like cells, an increase in the content of TATVHL peptide in PAAM-chitosan ICC scaffolds inhibited the differentiation of iPS cells toward astrocytes. ICC scaffolds composed of PAAM, chitosan, PLGA NPs, and TATVHL peptide can be an efficacious matrix to differentiate iPS cells toward neurons and retard the glial formation for nerve regeneration.

  2. Epididymal Cystadenomas in von Hippel-Lindau Disease Showing Increased Activity on 68Ga DOTATATE PET/CT.

    Science.gov (United States)

    Papadakis, Georgios Z; Millo, Corina; Sadowski, Samira M; Bagci, Ulas; Patronas, Nicholas J

    2016-10-01

    von Hippel-Lindau (VHL) disease is a familial cancer syndrome characterized by the development of a variety of malignant and benign tumors, including epididymal cystadenomas. We report a case of a VHL patient with bilateral epididymal cystadenomas who was evaluated with Ga DOTATATE PET/CT, showing intensely increased activity (SUVmax, 21.6) associated with the epididymal cystadenomas, indicating cell-surface overexpression of somatostatin receptors. The presented case supports the usefulness of somatostatin receptor imaging using Ga DOTA-conjugated peptides for detection and follow-up of VHL manifestations, as well as surveillance of asymptomatic gene carriers.

  3. A case of von Hippel-Lindau disease with exudative maculopathy

    Directory of Open Access Journals (Sweden)

    Basel T Ba′arah

    2009-01-01

    Full Text Available Von Hippel-Lindau (VHL disease is a rare multisystem familial tumor syndrome of autosomal dominant inheritance. Hallmark lesions include retinal, cerebellum and spinal cord hemangioblastomas, renal cell carcinomas, adrenal pheochromocytomas, angiomatous or cystic lesions of the kidneys, pancreas, and epididymis. We report a case of VHL disease in a 26-year-old patient who presented with exudative macular edema. Ocular and systemic studies revealed the presence of retinal and central nervous system hemangioblastomas, adrenal pheochromocytoma, multiple pancreatic, and kidney cysts. The retinal angiomas were successfully treated with argon laser photocoagulation and cryotherapy.

  4. Imaging manifestations of von Hippel-Lindau disease: a report of 3 cases

    Institute of Scientific and Technical Information of China (English)

    GONG Jing-shan; XU Jian-min

    2005-01-01

    @@ Von Hippel-Lindau (VHL) disease is an autosomal-dominant hereditary familial neoplasm syndrome characterized by development of a variety of benign and malignant tumors in multiple organ systems, such as the brain, kidney, pancreas, adrenal gland, and epididymis, with a prevalence of one in 39000-53000.1-4 Hallmarks of the condition include retinal angiomas, hemangioblastomas of the cerebellum and the spinal cord, renal cell carcinoma and cysts, and pheochromocytomas. In this article, we report imaging findings in three cases of VHL disease.

  5. Nervous system involvement in von Hippel-Lindau disease: pathology and mechanisms.

    Science.gov (United States)

    Vortmeyer, Alexander O; Falke, Eric A; Gläsker, Sven; Li, Jie; Oldfield, Edward H

    2013-03-01

    Patients with von Hippel-Lindau disease carry a germline mutation of the Von Hippel-Lindau (VHL) tumor-suppressor gene. We discuss the molecular consequences of loss of VHL gene function and their impact on the nervous system. Dysfunction of the VHL protein causes accumulation and activation of hypoxia inducible factor (HIF) which can be demonstrated in earliest stages of tumorigenesis and is followed by expression of VEGF, erythropoietin, nitric oxide synthase and glucose transporter 1 in VHL-deficient tumor cells. HIF-independent functions of VHL, epigenetic inactivation of VHL, pVHL proteostasis, and links between loss of VHL function and developmental arrest are also described. A most intriguing feature in VHL disease is the occurrence of primary hemangioblastic tumors in the nervous system, the origin of which has not yet been entirely clarified, and current hypotheses are discussed. Endolymphatic sac tumors may extend into the brain, but originally arise from proliferation of endolymphatic duct/sac epithelium; the exact nature of the proliferating epithelial cell, however, also has remained unclear, as well as the question why tumors almost consistently develop in the intraosseous portion of the endolymphatic sac/duct only. The epitheloid clear cell morphology of both advanced hemangioblastoma and renal clear cell carcinoma can make the differential diagnosis challenging, recent developments in immunohistochemical differentiation are discussed. Finally, metastasis to brain may not only be caused by renal carcinoma, but may derive from VHL disease-associated pheochromocytoma/paraganglioma, or pancreatic neuroendocrine tumor.

  6. Targeted therapy for genetic cancer syndromes: Von Hippel-Lindau disease, Cowden syndrome, and Proteus syndrome.

    Science.gov (United States)

    Agarwal, Rishi; Liebe, Sarah; Turski, Michelle L; Vidwans, Smruti J; Janku, Filip; Garrido-Laguna, Ignacio; Munoz, Javier; Schwab, Richard; Rodon, Jordi; Kurzrock, Razelle; Subbiah, Vivek

    2015-02-01

    Von Hippel-Lindau disease, Cowden syndrome, and Proteus syndrome are cancer syndromes which affect multiple organs and lead to significant decline in quality of life in affected patients. These syndromes are rare and typically affect the adolescent and young adult population, resulting in greater cumulative years of life lost. Improved understanding of the underpinnings of the genetic pathways underlying these syndromes and the rapid evolution of targeted therapies in general have made it possible to develop therapeutic options for these patients and other genetic cancer syndromes. Targeted therapies especially antiangiogenics and inhibitors of the PIK3CA/AKT/mTOR signaling pathway have shown activity in selected group of patients affected by these syndromes or in patients harboring specific sporadic mutations which are otherwise characteristic of these syndromes. Unfortunately due to the rare nature, patients with these syndromes are not the focus of clinical trials and unique results seen in these patients can easily go unnoticed. Most of the data suggesting benefits of targeted therapies are either case reports or small case series. Thus, a literature review was indicated. In this review we explore the use of molecularly targeted therapy options in Von Hippel-Lindau disease, Cowden syndrome, and Proteus syndrome.

  7. von Hippel-Lindau tumor suppressor mutants faithfully model pathological hypoxia-driven angiogenesis and vascular retinopathies in zebrafish

    NARCIS (Netherlands)

    van Rooijen, E.; Voest, E.E.; Logister, I.; Bussmann, J.; Korving, J.; van Eeden, F.J.; Giles, R.H.; Schulte-Merker, S.

    2010-01-01

    Biallelic inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene predisposes human patients to the development of highly vascularized neoplasms in multiple organ systems. We show that zebrafish vhl mutants display a marked increase in blood vessel formation throughout the embryo, starting

  8. Characterization of endolymphatic sac tumors and von Hippel-Lindau disease in the International Endolymphatic Sac Tumor Registry

    NARCIS (Netherlands)

    Bausch, Birke; Wellner, Ulrich; Peyre, Mathieu; Boedeker, Carsten C.; Hes, Frederik J.; Anglani, Mariagiulia; de Campos, Jose M.; Kanno, Hiroshi; Maher, Eamonn R.; Krauss, Tobias; Sanso, Gabriela; Barontini, Marta; Letizia, Claudio; Hader, Claudia; Schiavi, Francesca; Zanoletti, Elisabetta; Suarez, Carlos; Offergeld, Christian; Malinoc, Angelica; Zschiedrich, Stefan; Glasker, Sven; Bobin, Serge; Sterkers, Olivier; Huy, Patrice Tran Ba; Giraud, Sophie; Links, Thera; Eng, Charis; Opocher, Giuseppe; Richard, Stephane; Neumann, Hartmut P. H.

    Background. Endolymphatic sac tumors (ELSTs) are, with a prevalence of up to 16%, a component of von Hippel-Lindau (VHL) disease. Data from international registries regarding heritable fraction and characteristics, germline VHL mutation frequency, and prevalence are lacking. Methods. Systematic

  9. Diagnostic Genetics at a Distance: Von Hippel-Lindau Disease and a Novel Mutation

    Directory of Open Access Journals (Sweden)

    Clare Brookes

    2013-01-01

    Full Text Available Genetic testing at a distance is commonplace where members of a family with a segregating germline mutation are geographically separated. For the most part, this challenge is addressed through the intervention of health professionals in taking and/or processing blood samples for subsequent couriering of DNA to a referral laboratory. In some circumstances, however, the collecting of pivotal clinical material may involve direct patient involvement. We describe such a situation where noninvasive saliva samples were provided by members of a family manifesting Von Hippel-Lindau (VHL disease. The analysis identified a novel mutation in the VHL gene that was used to exclude other family members as being at risk of VHL disease.

  10. Pathology of the Nervous System in Von Hippel-Lindau Disease

    Directory of Open Access Journals (Sweden)

    Alexander O. Vortmeyer

    2015-06-01

    Full Text Available Von Hippel-Lindau (VHL disease is a tumor syndrome that frequently involves the central nervous system (CNS. It is caused by germline mutation of the VHL gene. Subsequent VHL inactivation in selected cells is followed by numerous well-characterized molecular consequences, in particular, activation and stabilization of hypoxia-inducible factors HIF1 and HIF2. The link between VHL gene inactivation and tumorigenesis remains poorly understood. Hemangioblastomas are the most common manifestation in the CNS; however, CNS invasion by VHL disease-associated endolymphatic sac tumors or metastatic renal cancer also occur, and their differentiation from primary hemangioblastoma may be challenging. Finally, in this review, we present recent morphologic insights on the developmental concept of VHL tumorigenesis which is best explained by pathologic persistence of temporary embryonic progenitor cells. 

  11. Familial pheochromocytoma associated with a novel mutation in the von Hippel-Lindau gene

    Energy Technology Data Exchange (ETDEWEB)

    Gross, D.J.; Avishai, N.; Meiner, V.; Abeliovich, D.; Filon, D. [Hadassah Univ. Hospital and the Hebrew Univ.-Hadassah Medical School, Jerusalem (Israel)] [and others

    1996-01-01

    We report a three generation, 25 member kindred with familial pheochromocytoma. Seven subjects of generations I and II had pheochromocytoma, in five of the seven, the tumors were bilateral, and in two of the seven, the tumors were both adrenal and extraadrenal. One patient also had a carotid body chemodectoma, and one patient had a malignant adrenal tumor and abdominal paraganglioma. In the patient with the chemodectoma, a cerebellar hemagioblastoma became manifest 25 yr after his initial diagnosis with pheochromocytoma, leading only then to a clinical diagnosis of von Hippel-Lindau disease (VHL). A mutational analysis of the VHL gene revealed a novel nucleotide 709 G{r_arrow}T transversion present in all affected subjects and in four presymptomatic children. In familial pheochromocytoma the diagnosis of VHL should be considered, even when the formal criteria for diagnosis of the syndrome are lacking. 16 refs., 2 figs.

  12. Treatment options for von Hippel-Lindau's haemangioblastomatosis: the role of gamma knife stereotactic radiosurgery.

    Science.gov (United States)

    Rajaraman, C; Rowe, J G; Walton, L; Malik, I; Radatz, M; Kemeny, A A

    2004-08-01

    Haemangioblastomas secondary to von Hippel-Lindau (VHL) disease can be difficult to manage surgically, which has lead to an interest in the use of stereotactic radiosurgery. Retrospectively reviewed here are 30 tumours treated in 14 patients with a mean +/- SD follow-up of 34 +/- 24 months. During this time, three of the 14 patients (21%) died, two of generalized progressive disease. Before radiosurgery, the median time between interventions for cranial haemangioblastomas was 3 years (mean 3.9 +/- 5.0 years). After radiosurgery, the tendency for cranial disease progression was similar, 50% of patients developing further disease by 5 years. Local tumour control was achieved in the majority of cases and estimates of this are included. Radiosurgery is a useful palliative measure controlling the majority of haemangioblastomas, although its efficacy in these patients is limited by the tendency of further disease to develop or progress intracranially.

  13. Survival and causes of death in patients with von Hippel-Lindau disease

    DEFF Research Database (Denmark)

    Binderup, Marie Louise Mølgaard; Jensen, Annette Møller; Budtz-Jørgensen, Esben;

    2016-01-01

    without vHL. vHL life expectancy was compared with the general population using a relative survival model. Results The estimated mean life expectancies for male and female patients born in 2000 were 67 and 60 years, respectively. Survival is influenced by the sex and genotype of the patient. Female......Background Historically, the survival of patients with von Hippel-Lindau disease (vHL) has been poorer than that of the general population. We aimed to determine whether the survival of VHL mutation carriers and their risk of vHL-related death has changed over time and how it has been affected...... by sex, genotype and surveillance attendance. Methods In a retrospective cohort study, we included all known Danish vHL families with a VHL mutation. We assessed the survival and causes of death for 143 VHL mutation carriers using Cox regression models and compared vHL survival with that of 137 siblings...

  14. 68Ga-DOTA-NOC PET/CT detects somatostatin receptors expression in von hippel-lindau cerebellar disease.

    Science.gov (United States)

    Ambrosini, Valentina; Campana, Davide; Allegri, Vincenzo; Opocher, Giuseppe; Fanti, Stefano

    2011-01-01

    A case of Von-Hippel Lindau (VHL) disease has been studied using 68Ga-DOTA-NOC PET/CT. PET/CT demonstrated the presence of somatostatin receptors within 2 focal areas in the cerebellum corresponding to the lesions detected by MRI. Considering the heterogeneous lesions localizations in VHL disease, PET/CT may be a useful imaging modality for diagnosing lesions of central nervous system and neuroendocrine lesions and for direct demonstration of somatostatin receptors for targeted treatment.

  15. Sporadically second localization of cerebellar hemangioblastoma in sella turcica mimicking a meningioma with no associated von Hippel-Lindau disease.

    Science.gov (United States)

    Amelot, Aymeric; Bouazza, Schaharazad; Polivka, Marc; George, Bernard; Bresson, Damien

    2015-01-01

    A 72-year-old man presented with a gradual bilateral decrease in visual acuity. Imaging showed lesion in the sella turcica diagnosed as meningioma but proving secondarily to be a hemangioblastoma. His neurosurgical history included a resection of a cerebellar hemangioblastoma 30 years ago. To our knowledge, such a hemangioblastoma second localization from the infratentorial to supratentorial has not been reported in the literature for patients not presenting with von Hippel-Lindau disease.

  16. von Hippel-Lindau gene plays a role during zebrafish pronephros development.

    Science.gov (United States)

    Chen, Yau-Hung; Chang, Chiung-Fang; Lai, Yen-Yu; Sun, Chiao-Yin; Ding, Yu-Ju; Tsai, Jen-Ning

    2015-11-01

    von Hippel-Lindau (pVHL)-mediated ubiquitination of HIF-1α plays a central role in the cellular responses to changes in oxygen availability. In the present study, using zebrafish as a model, we showed that specific knockdown of endogenous vhl leads to pronephros malformation and renal failure. Knockdown of vhl resulted in abnormal kidney development, including curved and cystic pronephric tubule or/and cystic and atrophic glomerulus. Co-injecting capped vhl messenger RNA (mRNA) partially rescued pronephros morphant phenotype, confirming the specificity of the morpholino oligonucleotide (MO)-induced pronephric defects. In keeping with the pronephros phenotype, renal function was affected as well in vhl morphants. Dextran clearance abilities of vhl morphants were significantly reduced as compared with those of control embryos. Further analysis indicated that glomerular integrity is impaired in vhl morphants, while the organization of pronephric duct was minimally affected. Vhl morphants display global increased vegf signaling and angiogenesis. In addition, we found that vhl morphants displayed elevated expression of vegfa in podocytes and increased angiogenesis at pronephric glomerulus and the nearby vessels. Treatment of vegf inducer to embryos also caused pronephros phenotype resembling vhl morphants, further supporting that increased vegfa signaling contribute to the pronephros morphant phenotype. Our study establishes the zebrafish as an alternative vertebrate model system for studying Vhl function during kidney development.

  17. Melatonin and the von Hippel-Lindau/HIF-1 oxygen sensing mechanism: A review.

    Science.gov (United States)

    Vriend, Jerry; Reiter, Russel J

    2016-04-01

    There are numerous reports that melatonin inhibits the hypoxia-inducible factor, HIF-1α, and the HIF-1α-inducible gene, VEGF, both in vivo and in vitro. Through the inhibition of the HIF-1-VEGF pathway, melatonin reduces hypoxia-induced angiogenesis. Herein we discuss the interaction of melatonin with HIF-1α and HIF-1α-inducible genes in terms of what is currently known concerning the HIF-1α hypoxia response element (HIF-1α-HRE) pathway. The von Hippel-Lindau protein (VHL), also known as the VHL tumor suppressor, functions as part of a ubiquitin ligase complex which recognizes HIF-1α as a substrate. As such, VHL is part of the oxygen sensing mechanism of the cell. Under conditions of hypoxia, HIF-1α stimulates the transcription of numerous HIF-1α-induced genes, including EPO, VEGF, and PFKFB3; the latter is an enzyme which regulates glycolysis. Data from several studies show that ROS generated in mitochondria under conditions of hypoxia stimulate HIF-1α. Since melatonin acts as an antioxidant and reduces ROS, these data suggest that the antioxidant action of melatonin could account for reduced HIF-1, less VEGF, and reduced glycolysis in cancer cells (Warburg effect). A direct or indirect inhibitory action (via the reduction in ROS) of melatonin on proteasome activity would account for much of the published data.

  18. Development of Database and Genomic Medicine for von Hippel-Lindau Disease in Japan

    Science.gov (United States)

    TAKAYANAGI, Shunsaku; MUKASA, Akitake; NAKATOMI, Hirofumi; KANNO, Hiroshi; KURATSU, Jun-ichi; NISHIKAWA, Ryo; MISHIMA, Kazuhiko; NATSUME, Atushi; WAKABAYASHI, Toshihiko; HOUKIN, Kiyohiro; TERASAKA, Shunsuke; YAO, Masahiro; SHINOHARA, Nobuo; SHUIN, Taro; SAITO, Nobuhito

    2017-01-01

    von Hippel-Lindau (VHL) disease is a hereditary tumor disease in which tumors develop in multiple organs, not only as hemangioblastomas (HBs) in the central nervous system, but also as kidney tumors, pheochromocytomas, and so on. Much about the epidemiology of VHL disease remained unknown until fairly recently in Japan, leading to calls for the establishment of a VHL disease epidemiological database in Japanese. To elucidate its epidemiology in Japan, the Japanese Ministry of Health, Labour and Welfare created the VHL Disease Study Group, which was put in charge of carrying out a nationwide epidemiological survey. The survey found close to 400 Japanese VHL disease patients throughout the country. Based on those results, the VHL Disease Study Group created the VHL Disease Treatment Guideline and also a severity classification. It is thought that the prognosis of VHL disease patients can be improved by performing genetic diagnosis and careful follow-up. Accordingly, the University of Tokyo Hospital put in place an in-hospital system for implementing genomic medicine for VHL disease based on genetic diagnosis. For that system, it was especially important to establish (I) accurate genetic diagnostic techniques, (II) genetic counseling capabilities for the patients and their families, and (III) a system of cooperation among multiple departments, including urology departments, and so on. Further elucidation of the epidemiology and the development of genomic medicine are needed to improve the treatment results of VHL disease in Japan. PMID:28070114

  19. Germline mutation screening and predictive testing in families with von Hippel-Lindau disease

    Energy Technology Data Exchange (ETDEWEB)

    Brauch, H.; Glavac, D.; Pausch, F. [Univ. of Munich (Germany)] [and others

    1994-09-01

    von Hippel-Lindau (VHL) disease is an autosomal inheritable disease that predisposes gene carriers to develop tumors in the eyes, central nervous system, kidney, adrenal gland, pancreas and epididymis. VHL type 1 is without phenochromocytoma (P); VHL type 2 is with P. Screening for germline mutations and preclinical diagnosis in families with VHL disease has become feasible since the VHL gene was isolated. We applied Southern blotting and hybridization with g7cDNA to detect rearrangements, PCR-SSCP and sequencing to detect missense, nonsense and splice mutations, and primer-specified restriction map modification to detect a P-specific missense mutation. In 48 apparently unrelated VHL families mainly from Germany, we identified 20/48 (42%) VHL mutations: 7 (14.5%) rearrangements, 9/48 (19%) missense mutations affecting nt505, 1/48 (2%) splice site mutation, 2/48 (4%) other missense mutations, and 1/48 (2%) nonsense mutation. The predominance of the nt505 mutation in 9 German families with VHL type 2 suggests that this genotype expresses the VHL/P disease pattern. Predictive testing for VHL gene carriers in families with specific mutations identified 7 asymptomatic gene carriers. VHL manifestations have been confirmed by clinical examination in two individuals. Early molecular diagnosis may result in a successful management of VHL disease and prolong survival of VHL patients.

  20. Implications of Von Hippel-Lindau Syndrome and Renal Cell Carcinoma

    Science.gov (United States)

    Ashouri, Kenan; Mohseni, Sophia; Tourtelot, John; Sharma, Pranav

    2015-01-01

    Von Hippel-Lindau syndrome (VHLS) is a rare hereditary neoplastic disorder caused by mutations in the vhl gene leading to the development of tumors in several organs including the central nervous system, pancreas, kidneys, and reproductive organs. Manifestations of VHLS can present at different ages based on the affected organ and subclass of disease. In the subclasses of VHLS that cause renal disease, renal involvement typically begins closer to the end of the second decade of life and can present in different ways ranging from simple cystic lesions to solid tumors. Mutations in vhl are most often associated with clear cell renal carcinoma, the most common type of renal cancer, and also play a major role in sporadic cases of clear cell renal carcinoma. The recurrent, multifocal nature of this disease presents difficult challenges in the long-term management of patients with VHLS. Optimization of renal function warrants the use of several different approaches common to the management of renal carcinoma such as nephron sparing surgery, enucleation, ablation, and targeted therapies. In VHLS, renal lesions of 3 cm or bigger are considered to have metastatic potential and even small lesions often harbor malignancy. Many of the aspects of management revolve around optimizing both oncologic outcome and long-term renal function. As new surgical strategies and targeted therapies develop, the management of this complex disease evolves. This review will discuss the key aspects of the current management of VHLS.

  1. Implications of Von Hippel-Lindau Syndrome and Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Kenan Ashouri

    2015-09-01

    Full Text Available Von Hippel-Lindau syndrome (VHLS is a rare hereditary neoplastic disorder caused by mutations in the vhl gene leading to the development of tumors in several organs including the central nervous system, pancreas, kidneys, and reproductive organs. Manifestations of VHLS can present at different ages based on the affected organ and subclass of disease. In the subclasses of VHLS that cause renal disease, renal involvement typically begins closer to the end of the second decade of life and can present in different ways ranging from simple cystic lesions to solid tumors. Mutations in vhl are most often associated with clear cell renal carcinoma, the most common type of renal cancer, and also play a major role in sporadic cases of clear cell renal carcinoma. The recurrent, multifocal nature of this disease presents difficult challenges in the long-term management of patients with VHLS. Optimization of renal function warrants the use of several different approaches common to the management of renal carcinoma such as nephron sparing surgery, enucleation, ablation, and targeted therapies. In VHLS, renal lesions of 3 cm or bigger are considered to have metastatic potential and even small lesions often harbor malignancy. Many of the aspects of management revolve around optimizing both oncologic outcome and long-term renal function. As new surgical strategies and targeted therapies develop, the management of this complex disease evolves.  This review will discuss the key aspects of the current management of VHLS.

  2. Managing Renal Cell Carcinoma Associated Paraneoplastic Syndrome with Nephron-sparing Surgery in a Patient with von Hippel-Lindau

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    John M. DiBianco

    2017-07-01

    Full Text Available A patient with germline von Hippel-Lindau (VHL gene alteration and history of multiple tumors present with classical paraneoplastic syndrome (PNS associated with renal cell carcinoma (RCC. She underwent open nephron sparing surgery with resolution of symptoms. She remained without recurrence of RCC for the initial 2 years of her follow-up. To the best of our knowledge, this case represents the first in which PNS was specifically resolved using a partial nephrectomy in a patient with VHL. This case report provides initial evidence for the potential role of nephron sparing surgery in the management of paraneoplastic symptoms associated with hereditary RCC.

  3. Isoform-specific interactions of the von Hippel-Lindau tumor suppressor protein

    Science.gov (United States)

    Minervini, Giovanni; Mazzotta, Gabriella M.; Masiero, Alessandro; Sartori, Elena; Corrà, Samantha; Potenza, Emilio; Costa, Rodolfo; Tosatto, Silvio C. E.

    2015-01-01

    Deregulation of the von Hippel-Lindau tumor suppressor protein (pVHL) is considered one of the main causes for malignant renal clear-cell carcinoma (ccRCC) insurgence. In human, pVHL exists in two isoforms, pVHL19 and pVHL30 respectively, displaying comparable tumor suppressor abilities. Mutations of the p53 tumor suppressor gene have been also correlated with ccRCC insurgence and ineffectiveness of treatment. A recent proteomic analysis linked full length pVHL30 with p53 pathway regulation through complex formation with the p14ARF oncosuppressor. The alternatively spliced pVHL19, missing the first 53 residues, lacks this interaction and suggests an asymmetric function of the two pVHL isoforms. Here, we present an integrative bioinformatics and experimental characterization of the pVHL oncosuppressor isoforms. Predictions of the pVHL30 N-terminus three-dimensional structure suggest that it may exist as an ensemble of structured and disordered forms. The results were used to guide Yeast two hybrid experiments to highlight isoform-specific binding properties. We observed that the physical pVHL/p14ARF interaction is specifically mediated by the 53 residue long pVHL30 N-terminal region, suggesting that this N-terminus acts as a further pVHL interaction interface. Of note, we also observed that the shorter pVHL19 isoform shows an unexpected high tendency to form homodimers, suggesting an additional isoform-specific binding specialization. PMID:26211615

  4. Von Hippel-Lindau Disease: Genetics and Role of Genetic Counseling in a Multiple Neoplasia Syndrome.

    Science.gov (United States)

    Nielsen, Sarah M; Rhodes, Lindsay; Blanco, Ignacio; Chung, Wendy K; Eng, Charis; Maher, Eamonn R; Richard, Stéphane; Giles, Rachel H

    2016-06-20

    Von Hippel-Lindau disease (VHL) is one of the most common inherited neoplasia syndromes and is characterized by highly vascular tumors of the eyes, brain, and spine, as well as benign and malignant tumors and/or cysts of the kidneys, adrenal medullae and sympathetic paraganglia, endolymphatic sac, epididymis, and broad ligament. Since the discovery of the VHL gene in 1993, more than 900 families with VHL have been identified and examined. Genetic testing for VHL is widely available and will detect a disease-causing mutation in rate 95% to 100% of individuals who have a clinical diagnosis of VHL, making it the standard of care for diagnosis of VHL. Furthermore, genetic testing for VHL is indicated in some individuals with seemingly sporadic VHL-related tumor types, as ≤ 10% of pheochromocytoma or early-onset renal cell carcinoma and ≤ 40% of CNS hemangioblastoma harbor germline VHL mutations without a family history or additional features of VHL disease. The majority of VHL mutations are private, but there are also well-characterized founder mutations. VHL is a complex, multiorgan disease that spans the breadth of oncology subspecialties, and, as such, providers in these subspecialties should be aware of when to consider a diagnosis of VHL, when to refer a patient to a genetics specialist for consideration of gene testing, and, perhaps most importantly, how to communicate this sensitive information in an age-appropriate manner to at-risk families. This review will provide state-of-the-art information regarding the genetics of VHL and will serve as a key reference for nongenetics professionals who encounter patients with VHL.

  5. Von Hippel-Lindau disease associated with myasthenia gravis not related to thymoma

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    Paolo Pozzato

    2013-04-01

    Full Text Available BACKGROUND Von Hippel-Lindau disease (VHL is a rare autosomal dominant inherited disorder characterized by an increased risk of tumours in a number of locations (eyes, brain, adrenal gland, pancreas, liver, kidneys, or other areas of the body. It is caused by germline mutation in the VHL gene. The VHL gene is a tumour suppressor gene that has been identified on the short arm of chromosome 3. CASE REPORT We report a case of a 60 year-old female with the clinical diagnosis of VHL type 1 (cerebellar haemangioblastoma, pancreatic cysts with subsequent steatorrhoea, and bilateral renal carcinoma who developed weakness and fatigability of skeletal muscles, left lid ptosis, snarling expression and nasal timbre speech. Acetylcholine receptor antibodies were negative in serum, while the electrodiagnostic test demonstrated an alteration of neuromuscolar junction which was consistent with the diagnosis of myasthenia gravis. Contrast-enhanced TC scan of the anterior mediastinum was performed, which excluded thymus enlargement. VHL gene evaluation in this patient identified a new mutation (c279delC9 and polymorphism c291C>G. At present the patient still suffers from ataxia and dysmetria due to cerebellar involvement in VHL, while fatigue and lid ptosis improved after the treatment with oral pyridostigmine 60 mg tid. DISCUSSION AND CONCLUSIONS To our knowledge this is the first report of a case of VHL associated with myasthenia gravis without thymoma. A case of VHL associated with a form of myasthenia gravis related to thymoma has been recently reported. In our case the absence of acetylcholine receptor antibodies may suggest a genetic origin also for the myasthenia gravis.

  6. Pheochromocytoma Screening Initiation and Frequency in von Hippel-Lindau Syndrome

    Science.gov (United States)

    Aufforth, Rachel D.; Ramakant, Pooja; Sadowski, Samira M.; Mehta, Amit; Trebska-McGowan, Katarzyna; Nilubol, Naris; Pacak, Karel

    2015-01-01

    Context: Patients with von Hippel-Lindau (VHL) syndrome have a 25–30% chance of developing pheochromocytoma. Although practice guidelines recommend biochemical and radiological screening every 1–2 years for pheochromocytoma in patients with VHL, there are limited data on the optimal age and frequency for screening. Objective: Our objective was to determine the earliest age of onset and frequency of contralateral and recurrent pheochromocytomas in patients with VHL syndrome. Methods: This is a retrospective analysis of a prospective cohort of patients with VHL enrolled in a natural history study. Results: A total of 273 patients diagnosed with VHL were enrolled in a natural history clinical study. Thirty-one percent (84) were diagnosed with pheochromocytoma. The mean age of diagnosis was 28.8 ± 13.9 years. The earliest age at diagnosis was 5.5 years. Median follow-up for the cohort was 116.6 months (range, 0.1–613.2). Ninety-nine percent (83) of patients underwent adrenalectomy. Fifty-eight and 32% of patients had metanephrines and/or catecholamines elevated more than two times and more than four times the upper limit of normal, respectively. Twenty-five percent (21) of pheochromocytomas were diagnosed in pediatric patients younger than 19 years of age, and 86% and 57% of pediatric patients had an elevation more than two times and more than four times upper limit of normal, respectively. Eight patients had a total of nine recurrences. The median age at recurrence was 33.5 years (range, 8.8–51.9). Recurrences occurred as short as 0.5 years and as long as 39.7 years after the initial operation. Conclusions: Our findings among VHL pediatric patients supports the need for biochemical screening starting at age 5 with annual lifelong screening. PMID:26451910

  7. Disseminated cerebellar hemangioblastoma in two patients without von Hippel-Lindau disease

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    Jiro Akimoto

    2014-01-01

    Full Text Available Background: Two patients who had received a total resection of cerebellar hemangioblastoma developed cerebrospinal fluid dissemination during a long-term follow-up period. We present this rare disease with discussion based on the literature. Case Description: The patients were two women aged 45 and 57 years. In the cerebellar hemisphere, one patient had cystic hemangioblastoma of mural nodule type and the other had solid type. Both the patients successfully underwent total resection by craniotomy. They presented no mutations in the von Hippel-Lindau disease (VHL gene or lesions in the other organs. One patient developed local recurrence 38 months after the initial surgery, and received stereotactic radiosurgery. Three spinal cord tumors developed 91 months later, and the tumors were disseminated to the entire cerebrospinal cavity 107 months later. The other patient developed hydrocephalus 53 months after the initial surgery with tumor tissues disseminated in the intracranial subarachnoid space. The conditions of the two patients gradually aggravated despite treatment with ventriculo-peritoneal shunt and irradiation to the whole brain and whole spinal cord. Conclusion: Cerebrospinal fluid dissemination of cerebellar hemangioblastoma was found dominantly in non-VHL patients. The diagnosis was made 10 years after the initial surgery. Irradiation therapy was performed, but the patients died about 2 years after the diagnosis was given. Molecular targeted therapies including vascular proliferation suppression have been attempted lately, but no effective therapy has been established. Early diagnosis of dissemination as well as combination of aggressive excision and stereotactic radiosurgery are considered to be appropriate for current interventions.

  8. Mutation of von Hippel-Lindau tumour suppressor and human cardiopulmonary physiology.

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    Thomas G Smith

    2006-07-01

    Full Text Available BACKGROUND: The von Hippel-Lindau tumour suppressor protein-hypoxia-inducible factor (VHL-HIF pathway has attracted widespread medical interest as a transcriptional system controlling cellular responses to hypoxia, yet insights into its role in systemic human physiology remain limited. Chuvash polycythaemia has recently been defined as a new form of VHL-associated disease, distinct from the classical VHL-associated inherited cancer syndrome, in which germline homozygosity for a hypomorphic VHL allele causes a generalised abnormality in VHL-HIF signalling. Affected individuals thus provide a unique opportunity to explore the integrative physiology of this signalling pathway. This study investigated patients with Chuvash polycythaemia in order to analyse the role of the VHL-HIF pathway in systemic human cardiopulmonary physiology. METHODS AND FINDINGS: Twelve participants, three with Chuvash polycythaemia and nine controls, were studied at baseline and during hypoxia. Participants breathed through a mouthpiece, and pulmonary ventilation was measured while pulmonary vascular tone was assessed echocardiographically. Individuals with Chuvash polycythaemia were found to have striking abnormalities in respiratory and pulmonary vascular regulation. Basal ventilation and pulmonary vascular tone were elevated, and ventilatory, pulmonary vasoconstrictive, and heart rate responses to acute hypoxia were greatly increased. CONCLUSIONS: The features observed in this small group of patients with Chuvash polycythaemia are highly characteristic of those associated with acclimatisation to the hypoxia of high altitude. More generally, the phenotype associated with Chuvash polycythaemia demonstrates that VHL plays a major role in the underlying calibration and homeostasis of the respiratory and cardiovascular systems, most likely through its central role in the regulation of HIF.

  9. Importância do exame oftalmológico na doença de von Hippel-Lindau The importance of the ophthalmological examination in von Hippel-Lindau disease

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    Ricardo Evangelista Marrocos de Aragão

    2009-08-01

    Full Text Available Von Hippel-Lindau (VHL é uma síndrome tumoral autossômica dominante. Esses tumores incluem hemangioblastoma da retina e sistema nervoso central (CSN, carcinoma de células renais, feocromocitoma, tumores de pâncreas, cistoadenoma de rins, pâncreas e epidídimo. Os sintomas mais comuns são perda da visão, aumento da pressão intracraniana, déficits neurológicos, aumento da pressão arterial sistêmica paradoxal e dor local. Relatamos o caso de um paciente com perda de visão e história de hemangiomas cerebelares cujo diagnóstico de VHL foi feito após exame oftalmológico.Von Hippel-Lindau (VHL disease is an autossomical, dominant inherited tumour syndrom. These tumours may include haemangioblastoma in the retina and central nervous system (CNS, renal cell carcinoma, phaeochromocytoma, islet cell tumours of the pancreas, cystadenoma in the kidney, pancreas, and epididymis. The most common symptoms include: loss of vision, raised intracranial pressure, neurological deficits, paroxysmal raised blood pressure and local pain. We report herein a 29-year-old man with visual loss and cerebellar haemangioblastoma that despite neurological manifestations the diagnosis of VHL was established after the ophthalmological examanination.

  10. Kidney Tumor in a von Hippel-Lindau (VHL) Patient With Intensely Increased Activity on 68Ga-DOTA-TATE PET/CT.

    Science.gov (United States)

    Papadakis, Georgios Z; Millo, Corina; Sadowski, Samira M; Bagci, Ulas; Patronas, Nicholas J

    2016-12-01

    Renal and pancreatic cysts and tumors are the most common visceral manifestations of von Hippel-Lindau (VHL) disease, a heritable multisystem cancer syndrome characterized by development of a variety of malignant and benign tumors. We report a case of a VHL patient with multiple renal cystic and complex cystic/solid lesions. The patient underwent Ga-DOTA-TATE-PET/CT showing intensely increased activity by a solid lesion which demonstrated enhancement on both CT and MRI scans, raising high suspicion for malignancy. The presented case indicates application of SSTR-imaging using Ga-DOTA-conjugated peptides in VHL-patients and emphasizes the need for cautious interpretation of renal parenchyma Ga-DOTATATE activity.

  11. 18F-FDG and 68Ga-DOTATATE PET/CT in von Hippel-Lindau Disease-Associated Retinal Hemangioblastoma.

    Science.gov (United States)

    Papadakis, Georgios Z; Millo, Corina; Jassel, Inderbir S; Bagci, Ulas; Sadowski, Samira M; Karantanas, Apostolos H; Patronas, Nicholas J

    2017-03-01

    Retinal hemangioblastomas are highly vascular benign tumors that can be encountered either sporadically or within the von Hippel-Lindau (VHL) syndrome. We report a case of a VHL patient with retinal hemangioblastoma who underwent PET/CT scans using F-FDG and Ga-DOTATATE. The tumor showed low-level F-FDG and increased Ga-DOTATATE activity, suggesting cell-surface overexpression of somatostatin receptors. The presented case indicates the clinical applications of somatostatin receptor imaging with Ga-DOTA-conjugated peptides in detection and follow-up of VHL manifestations, screening of asymptomatic gene carriers, and in diagnosis of sporadic retinal hemangioblastomas, which may have similar features on MRI with other retinal tumors.

  12. Von Hippel-Lindau status influences phenotype of liver cancers arising from PTEN loss

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    Sendor AB

    2015-02-01

    aggressive tumor formation and widespread steatosis in mouse livers. Co-deletion of Vhl and Pten results in lower tumor burden with gene expression profiling suggesting a switch from a profile of lipid deposition to an expression profile more consistent with upregulation of the hypoxia response pathway. A relationship between tumor hypoxia signaling and altered hepatic steatotic response suggests that competing influences may alter tumor phenotypes.Keywords: Von Hippel-Lindau (VHL, phosphatase and tension homologue deleted on chromosome 10 (PTEN, cholangiocarcinoma (CC, hepatocellular-cholangiocarcinoma (HCC

  13. Clinical features of patients bearing central nervous system hemangioblastoma in von Hippel-Lindau disease.

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    Kanno, Hiroshi; Kuratsu, Jun-ichi; Nishikawa, Ryo; Mishima, Kazuhiko; Natsume, Atushi; Wakabayashi, Toshihiko; Houkin, Kiyohiro; Terasaka, Shunsuke; Shuin, Taro

    2013-01-01

    Central nervous system (CNS) hemangioblastoma (HB) is one of the most common manifestations in von Hippel-Lindau disease (VHL), but large-scale studies on clinical features of CNS HB in VHL are scarce. On the basis of the results of a questionnaire, we collected data of VHL patients with CNS HB. The total number of CNS HBs in 111 VHL patients (male 59, female 52) was 264 with the following distributions: cerebellar, 65.4 %; brainstem, 9.9 %; spinal cord, 23.9 %; and pituitary, 1. 1 %. The follow-up period was 0.6 to 39.2 years, with the mean 12.5 years. Patients bearing brainstem or spinal cord HB also had another HB significantly more frequently than those bearing cerebellar HBs (P < 0.05). The mean onset age of CNS HB was 29.1 years, and that of patients bearing a single HB (mean 34.4 years) was significantly greater than that of multiple HBs (mean 25.7 years). Patients with multiple HBs under 40 years are more dominant than those with a single HB. The distribution rate of brainstem HB is significantly smaller in patients below 30 years than patients above 29 years. Although ECOG PS score increased along with number of operations, the onset age decreased with increasing number of operations. The mean ECOG PS score of patients below 20 years is significantly smaller than patients above 19 years. When the onset age of CNS HB is under 40 years, and CNS HB is located at the brainstem or spinal cord HB, the probability of multiple occurrence can be predicted. Since patients with an onset age under 20 years old preserve a high performance status, early detection of CNS HB would be important. In addition, since a multiple operations aggravate performance status, number of operations should be reduced.

  14. Uptake of genetic testing and long-term tumor surveillance in von Hippel-Lindau disease

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    Chávez Mireya

    2010-01-01

    Full Text Available Abstract Background von Hippel-Lindau (VHL disease is a hereditary cancer syndrome caused by germline mutations in the VHL gene. Patients have significant morbidity and mortality secondary to vascular tumors. Disease management is centered on tumor surveillance that allows early detection and treatment. Presymptomatic genetic testing is therefore recommended, including in at-risk children. Methods We tested 17 families (n = 109 individuals for VHL mutations including 43 children under the age of 18. Personalized genetic counseling was provided pre and post-test and the individuals undergoing presymptomatic testing filled out questionnaires gathering socio-demographic, psychological and psychiatric data. Mutation analysis was performed by direct sequencing of the VHL gene. Mutation-carriers were screened for VHL disease-related tumors and were offered follow-up annual examinations. Results Mutations were identified in 36 patients, 17 of whom were asymptomatic. In the initial screening, we identified at least one tumor in five of 17 previously asymptomatic individuals. At the end of five years, only 38.9% of the mutation-carriers continued participating in our tumor surveillance program. During this time, 14 mutation carriers developed a total of 32 new tumors, three of whom died of complications. Gender, education, income, marital status and religiosity were not found to be associated with adherence to the surveillance protocol. Follow-up adherence was also independent of pre-test depression, severity of disease, or number of affected family members. The only statistically significant predictor of adherence was being symptomatic at the time of testing (OR = 5; 95% CI 1.2 - 20.3; p = 0.02. Pre-test anxiety was more commonly observed in patients that discontinued follow-up (64.7% vs. 35.3%; p = 0.01. Conclusions The high initial uptake rate of genetic testing for VHL disease, including in minors, allowed the discontinuation of unnecessary screening

  15. Novel three missense mutations observed in Von Hippel-Lindau gene in a patient reported with renal cell carcinoma

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    Pasupuleti Santhosh Kumar

    2013-01-01

    Full Text Available Von Hippel-Lindau (VHL disease is an autosomal dominant hereditary cancer syndrome that predisposes to the development of a variety of benign and malignant tumors, especially cerebellar hemangioblastomas, retinal angiomas and clear-cell renal cell carcinomas (RCC. We have identified of VHL gene using immunohistochemistry in a patient who was diagnosed for RCC. In order to understand the involvement of mutation in the VHL gene exon 1 was amplified and sequenced (accession number: JX 401534. The sequence analysis revealed the presence of novel missense mutations c.194 C>T, c.239 G>A, c.278 G>A, c.319 C>G, c. 337 C > G leading to the following variations p.Ala 65 Val, p.Gly 80 Asp, p.Gly 93 Glu, p.Gln 107 Glu, p.Gln 113 Glu in the protein.

  16. Carcinoid tumor of the common bile duct: A rare complication of von Hippel-Lindau syndrome

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Van Hippel-Lindau syndrome (VHL) is a rare autosomal dominant, inherited familial cancer syndrome. Hemangioblastomas, pheochromocytomas and renal carcinoma are the frequent reported VHL tumors. Neuroendocrine tumors have also been described, mostly in the pancreas and rarely in the biliary trees. We report the second case of bile duct carcinoid in a 31-year-old VHL woman. She underwent right adrenalectomy for a pheochromocytoma in the past. She also had a positive family history of phenotypic expression of VHL syndrome. The patient presented with biliary colic. Endoscopic retrograde cholangio-pancreatography showed intra luminal bile duct mass. Surgical exploration identified a beige nodular lesion that was a carcinoid tumor on histology. This new association should be clarified by further genetic investigations.

  17. Hemangioblastoma cereberoloso en el síndrome de von Hippel-Lindau, como causa de muerte: Reporte de un caso

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    Kennette Villalobos León

    2015-12-01

    Full Text Available El síndrome de von Hippel-Lindau es una enfermedad caracterizada por el desarrollo de tumores como hemangioblastomas del sistema nervioso central y de la retina, quistes renales, hepáticos y pancreáticos; carcinoma renal de células claras, feocromocitoma, así como adenomas en el oído interno, la nariz y la laringe. En la mayoría de los casos hay un antecedente familiar positivo del síndrome 8. A continuación se presenta el caso de una femenina de 35 años de edad, sin antecedentes personales patológicos conocidos, con antecedente familiar positivo por la enfermedad de von Hippel-Lindau. Según la historia de sus familiares, la mujer presentaba “ataques de rigidez” de dos semanas de evolución, posterior a uno de estos ataques fue atendida por paramédicos quienes la declararon fallecida. Según la autopsia médico legal se diagnosticó una hidrocefalia obstructiva secundaria a hemangioma cerebeloso y hallazgos compatibles con el Síndrome de von Hippel-Lindau. El objetivo de este artículo es resaltar los hallazgos postmortem de esta entidad y su relación con la causa de la muerte.

  18. Perioperative outcomes of syndromic paraganglioma and pheochromocytoma resection in patients with von Hippel-Lindau disease, multiple endocrine neoplasia type 2, or neurofibromatosis type 1.

    Science.gov (United States)

    Butz, James J; Yan, Qi; McKenzie, Travis J; Weingarten, Toby N; Cavalcante, Alexandre N; Bancos, Irina; Young, William F; Schroeder, Darrell R; Martin, David P; Sprung, Juraj

    2017-09-14

    Pheochromocytoma and/or paraganglioma associated with neurofibromatosis type 1, multiple endocrine neoplasia type 2A, and von Hippel-Lindau disease have different catecholamine biochemical phenotypes. We examined perioperative outcomes of pheochromocytoma/paraganglioma resection in 3 syndromic forms. Retrospective review of patients undergoing resection of syndromic pheochromocytoma/paraganglioma from 2000 through 2016. Eighty-one patients underwent pheochromocytoma/paraganglioma resection (multiple endocrine neoplasia type 2A, n = 36; neurofibromatosis type 1, n = 26; von Hippel-Lindau disease, n = 19). Tumor size differed across groups; patients with neurofibromatosis type 1 and von Hippel-Lindau disease had the largest tumors (P = .017). Larger tumor volumes correlated with higher urine 24-hour total metanephrine (r = 0.94, P < .001; r = 0.67, P = .033; and r = 0.89, P < .001 for multiple endocrine neoplasia type 2A, von Hippel-Lindau disease, and neurofibromatosis type 1, respectively). High adrenergic secretion (24-hour urine metanepinephrine) was found in neurofibromatosis type 1 (median, 861 μg/24 h), similar to that found in multiple endocrine neoplasia type 2A (median, 809 μg/24 h). The highest noradrenergic secretion (24-hour urine normetanephrine) occurred with von Hippel-Lindau disease (median, 4,598 μg/24 h), followed by neurofibromatosis type 1 and multiple endocrine neoplasia type 2A (median, 1,607 and 923 μg/24 h, respectively). The highest graded complications occurred among patients with neurofibromatosis type 1 (P = .036). However, when comparing postoperative outcomes across 3 groups in those who had laparoscopic resection, there was no significant difference (P = .955). Patients with neurofibromatosis type 1 had the most volatile intraoperative hemodynamic course and more severe postoperative complications. These complications are related to large tumors associated with abundant catecholamine secretion and the fact that a high

  19. Preimplantation genetic diagnosis of Von Hippel-Lindau disease cancer syndrome by combined mutation and segregation analysis

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    Denilce R. Sumita

    2007-03-01

    Full Text Available Von Hippel-Lindau (VHL disease is an autosomal dominant cancer syndrome, associated with the development of tumors and cysts in multiple organ systems, whose expression and age of onset are highly variable. The VHL disease tumor suppressor gene (VHL maps to 3p25-p26 and mutations ranging from a single base change to large deletions have been detected in patients with VHL disease. We developed a single cell PCR protocol for preimplantation genetic diagnosis (PGD of VHL disease to select unaffected embryos on the basis of the detection of the specific mutation and segregation analysis of polymorphic linked markers. Multiplex-nested PCR using single buccal cells of an affected individual were performed in order to test the accuracy and reliability of this single-cell protocol. For each locus tested, amplification efficiency was 83% to 87% and allelic drop-out rates ranged from 12% to 8%. Three VHL disease PGD cycles were performed on cells from a couple with paternal transmission of a 436delC mutation in exon 2 of the VHL gene, leading to the identification of three unaffected embryos. Independent of the mutation present, this general PGD protocol for the diagnosis of VHL disease can be used in families informative for either the D3S1038 or D3S1317 microsatellite markers.

  20. Pathological and Clinical Features and Management of Central Nervous System Hemangioblastomas in von Hippel-Lindau Disease

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    Hiroshi Kanno

    2014-08-01

    Full Text Available Central nervous system (CNS hemangioblastoma is the most common manifestation of von Hippel-Lindau (VHL disease. It is found in 70-80% of VHL patients. Hemangioblastoma is a rare form of benign vascular tumor of the CNS, accounting for 2.0% of CNS tumors. It can occur sporadically or as a familial syndrome. CNS hemangioblastomas are typically located in the posterior fossa and the spinal cord. VHL patients usually develop a CNS hemangioblastoma at an early age. Therefore, they require a special routine for diagnosis, treatment and follow-up. The surgical management of symptomatic tumors depends on many factors such as symptom, location, multiplicity, and progression of the tumor. The management of asymptomatic tumors in VHL patients is controversial since CNS hemangioblastomas grow with intermittent quiescent and rapid-growth phases. Preoperative embolization of large solid hemangioblastomas prevents perioperative hemorrhage but is not necessary in every case. Radiotherapy should be reserved for inoperable tumors. Because of complexities of VHL, a better understanding of the pathological and clinical features of hemangioblastoma in VHL is essential for its proper management.

  1. Quantifying the Binding Interaction between the Hypoxia-Inducible Transcription Factor and the von Hippel-Lindau Suppressor.

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    Domene, Carmen; Jorgensen, Christian; Vanommeslaeghe, Kenno; Schofield, Christopher J; MacKerell, Alexander

    2015-08-11

    The hypoxia-inducible transcription factors (HIF) play a central role in the human oxygen sensing signaling pathway. The binding of the von Hippel-Lindau tumor suppressor protein (pVHL)-ElonginC-ElonginB complex (VCB) to HIF-1α is highly selective for the trans-4-hydroxylation form of when Pro564 in the C-terminal oxygen-dependent degradation domain (ODDD) of HIF-1α. The binding of HIFα for VCB is increased by ∼1000-fold upon addition of a single hydroxyl group to either of two conserved proline-residues. Here, we address how this addition governs selective recognition and characterizes the strength of the interaction of this "switch-like" signaling event. A new set of molecular mechanics parameters for 4-hydroxyproline has been developed following the CHARMM force field philosophy. Using the free energy perturbation (FEP) formalism, the difference in the binding free energies between HIF-1α in the nonhydroxylated and hydroxylated forms with the VCB complex was estimated using over 3 μs of MD trajectories. These results can favorably be compared to an experimental value of ∼4 kcal mol(-1). It is observed that the optimized hydrogen bonding network to the buried hydroxyprolyl group confers precise discrimination between hydroxylated and unmodified prolyl residues. These observations provide insight that will aid in developing therapeutic agents that block HIF-α recognition by pVHL.

  2. Design and analysis of a Petri net model of the Von Hippel-Lindau (VHL tumor suppressor interaction network.

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    Giovanni Minervini

    Full Text Available Von Hippel-Lindau (VHL syndrome is a hereditary condition predisposing to the development of different cancer forms, related to germline inactivation of the homonymous tumor suppressor pVHL. The best characterized function of pVHL is the ubiquitination dependent degradation of Hypoxia Inducible Factor (HIF via the proteasome. It is also involved in several cellular pathways acting as a molecular hub and interacting with more than 200 different proteins. Molecular details of pVHL plasticity remain in large part unknown. Here, we present a novel manually curated Petri Net (PN model of the main pVHL functional pathways. The model was built using functional information derived from the literature. It includes all major pVHL functions and is able to credibly reproduce VHL syndrome at the molecular level. The reliability of the PN model also allowed in silico knockout experiments, driven by previous model analysis. Interestingly, PN analysis suggests that the variability of different VHL manifestations is correlated with the concomitant inactivation of different metabolic pathways.

  3. von Hippel-Lindau protein induces hypoxia-regulated arrest of tyrosine hydroxylase transcript elongation in pheochromocytoma cells.

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    Kroll, S L; Paulding, W R; Schnell, P O; Barton, M C; Conaway, J W; Conaway, R C; Czyzyk-Krzeska, M F

    1999-10-15

    Rat pheochromocytoma (PC12) cells were stably transfected with either wild type or mutated human von Hippel-Lindau tumor suppressor protein (hpVHL). These proteins have opposing effects on regulating expression of the gene encoding tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. Whereas wild type hpVHL represses levels of TH mRNA and protein 5-fold, a truncated pVHL mutant, pVHL(1-115), induces accumulation of TH mRNA and protein 3-fold. hpVHL-induced inhibition of TH gene expression does not involve either a decrease in TH mRNA stability or repression of TH promoter activity. However, repression results from inhibition of RNA elongation at a downstream region of the TH gene. This elongation pause is accompanied by hpVHL sequestration in the nuclear extracts of elongins B and C, regulatory components of the transcription elongation heterotrimer SIII (elongin A/B/C). Hypoxia, a physiological stimulus for TH gene expression, alleviates the elongation block. A truncated pVHL mutant, pVHL(1-115), stimulates TH gene expression by increasing the efficiency of TH transcript elongation. This is the first report showing pVHL-dependent regulation of specific transcript elongation in vivo, as well as dominant negative activity of pVHL mutants in pheochromocytoma cells.

  4. A patient with bilateral pheochromocytoma as part of a Von Hippel-Lindau (VHL syndrome type 2C

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    Rinkes Inne

    2007-10-01

    Full Text Available Abstract Background Von Hippel-Lindau (VHL disease is an autosomal dominant inherited disease. It is relatively recent that type 2C was identified as a separate group solely presenting with pheochromocytomas. As an illustration, an interesting case is presented of a pregnant woman with refractory hypertension. It proved to be the first manifestation of bilateral pheochromocytomas. The family history may indicate the diagnosis, but only identification of a germ line mutation in the DNA of a patient will confirm carriership. Case presentation A 27 year pregnant patient with intra uterine growth retardation presented with hypertension and pre-eclampsia. Magnetic resonance imaging revealed bilateral adrenal pheochromocytoma. She underwent laparoscopic adrenelectomy and a missense mutation (Gly93Ser in exon 1 of the VHL gene on chromosome 3 (p25 – p26 was shown in the patient, her father and her daughter confirming the diagnosis of VHL. Conclusion In almost all VHL families molecular genetic analysis of DNA will demonstrate an inherited mutation. Because of the involvement in several organs, periodic clinical evaluation should take place in a well coordinated, multidisciplinary setting. VHL disease can be classified into several subtypes. VHL type 2C patients present with pheochromocytomas without evidence of haemangioblastomas in the central nervous system and/or retina and a low risk of renal cell carcinoma. Therefore, in such families, periodic clinical screening can be focussed on pheochromocytomas.

  5. Infratentorial craniospinal irradiation for von Hippel-Lindau: a retrospective study supporting a new treatment for patients with CNS hemangioblastomas.

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    Simone, Charles B; Lonser, Russell R; Ondos, John; Oldfield, Edward H; Camphausen, Kevin; Simone, Nicole L

    2011-09-01

    Patients with von Hippel-Lindau (VHL) syndrome with diffuse CNS hemangioblastomas have morbidity related to their disease and require a lifetime of surgical resections. Ninety-seven percent of tumors progress, and 5-year surgery rates are 20%-60%. Stereotactic radiosurgery and fractionated radiotherapy have had limited success. For the first time, we have used infratentorial craniospinal radiation therapy (ICSRT) for VHL patients with CNS hemangioblastomas. Consecutive VHL patients treated at the National Institutes of Health with radiographic evidence of hemangioblastomas were included if they received ICSRT. Patients underwent neurologic examinations and imaging at 3- to 12-month intervals. Seven patients with 84 hemangioblastomas met eligibility criteria. ICSRT was commonly administered to 43.2 Gy in 24 fractions. Mean pre-ICSRT tumor volume was 5.48 cm(3). At a mean follow-up of 73.8 months, mean post-ICSRT tumor volume was 6.87 cm(3), and 91 tumors were identified. Complete radiographic resolution was achieved in 17.9% of lesions. Although many patients were no longer optimal surgical candidates, only 4 surgeries were needed for symptomatic lesions after ICSRT, compared with 33 prior. Acute toxicity was mild and no patient developed grade ≥1 late spinal cord toxicity according to the criteria of the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer, despite the high dose that the entire spinal cord received. Clinical and radiographic stability or resolution was demonstrated in the majority of tumors. Tumor growth rate in this study was less than reported in natural history studies, and the rate of surgical intervention was reduced. ICSRT was well tolerated, can decrease hemangioblastoma growth rate, and is a potential therapeutic option for VHL patients that warrants further investigation.

  6. Differing von Hippel Lindau genotype in paired primary and metastatic tumors in patients with clear cell renal cell carcinoma

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    Susan A.J. Vaziri

    2012-05-01

    Full Text Available In sporadic clear cell renal cell carcinoma (CCRCC, the von Hippel Lindau (VHL gene is inactivated by mutation or methylation in the majority of primary (P tumors. Due to differing effects of wild-type (WT and mutant (MT VHL gene on downstream signaling pathways regulating angiogenesis, VHL gene status could impact clinical outcome. In CCRCC, comparative genomic hybridization (CGH analysis studies have reported genetic differences between paired P and metastatic (M tumors. We thus sequenced the VHL gene in paired tumor specimens from 10 patients to determine a possible clonal relationship between the P tumor and M lesion(s in patients with CCRCC. Using paraffin embedded specimens, genomic DNA from microdissected samples (>80% tumor of paired P tumor and M lesions from all 10 patients, as well as in normal tissue from 6 of these cases, was analyzed. The DNA was used for PCR-based amplification of each of the 3 exons of the VHL gene. Sequences derived from amplified samples were compared to the wild-type VHL gene sequence (GeneBank Accession No. AF010238. Methylation status of the VHL gene was determined using VHL methylation-specific PCR primers after DNA bisulfite modification. In 4/10 (40% patients the VHL gene status differed between the P tumor and the M lesion. As expected, when the VHL gene was mutated in both the P tumor and M lesion, the mutation was identical. Further, while the VHL genotype differed between the primary tumor in different kidneys or multiple metastatic lesions in the same patient, the VHL germline genotype in the normal adjacent tissue was always wild-type irrespective of the VHL gene status in the P tumor. These results demonstrate for the first time that the VHL gene status can be different between paired primary and metastatic tissue in patients with CCRCC.

  7. Long-term follow-up clinical courses of cerebellar hemangioblastoma in von hippel-lindau disease : two case reports and a literature review.

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    Lee, Seung Hwan; Park, Bong Jin; Kim, Tae Sung; Lim, Young Jin

    2010-09-01

    Although cerebellar hemangioblastomas are histopathologically benign, they yield a degree of malignant clinical behavior in long-term follow-up. We present two cases of long-term progression of renal cell carcinoma, which had been diagnosed as renal cysts during treatment for cerebellar hemangioblastoma. A 14-year-old male with von Hippel-Lindau disease was admitted for a cerebellar hemangioblastoma with multiple spinal hemangioblastomas and a renal cyst. After primary total resection of the cerebellar hemangioblastoma, the patient required two further surgeries after 111 and 209 months for a recurrent cerebellar hemangioblastoma. Furthermore, he underwent radical nephrectomy as his renal cyst had progressed to renal cell carcinoma 209 months after initial diagnosis. A 26-year-old male presented with multiple cerebellar hemangioblastomas associated with von Hippel-Lindau disease and accompanied by multiple spinal hemangioblastomas and multiple cystic lesions in the liver, kidney, and pancreas. He underwent primary resection of the cerebellar hemangioblastoma in association with craniospinal radiation for multiple intracranial/spinal masses. Unexpectedly, a malignant glioma developed 83 months after discovery of the cerebellar hemangioblastoma. At the same time, renal cell carcinoma, which had developed from an initial renal cyst, was diagnosed, and a radical nephrectomy was performed. In the view of long term clinical course, cerebellar hemangioblastoma associated with von Hipple-Lindau disease may redevelop even after primary total resection. In addition, associated lesions such as renal cysts may also progress to malignancy after the passing of a sufficient length of time.

  8. Mutation screening of VHL gene in a family with malignant bilateral pheochromocytoma: from isolated familial pheochromocytoma to von Hippel-Lindau disease.

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    Hasani-Ranjbar, Shirin; Amoli, Mahsa M; Ebrahim-Habibi, Azadeh; Haghpanah, Vahid; Hejazi, Maryam; Soltani, Akbar; Larijani, Bagher

    2009-01-01

    von Hippel-Lindau (vHL) disease is an inherited, autosomal dominant syndrome manifested by a variety of benign and malignant tumors. More than 300 germline VHL mutations have been identified that are involved in VHL disease. A large family (four generations) was evaluated. In this paper we report the presence of a single nucleotide mutation in exon 3 of VHL gene c499 C>T causing substitution of Arginine by Tryptophan at position 167 (R 167 W). It was detected in a family with bilateral malignant pheochromocytoma who has been followed for at least 9 years as RET negative isolated familial pheochromocytoma, finally diagnosed as von Hipple-Lindau disease according to retinal angioma and VHL gene mutation. VHL type 2 presenting with both pheochromocytoma and retinal angioma in this family found to be associated with the new missense mutation (c499 C>T) of VHL gene.

  9. Clinical and molecular characteristics of East Asian patients with von Hippel-Lindau syndrome

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    Meihua Wong; YingHsia Chu; Hwei Ling Tan; Hideharu Bessho; Joanne Ngeow; Tiffany Tang; MinHan Tan

    2016-01-01

    Background: Von Hippel–Lindau (VHL) syndrome is a dominantly inherited multisystem cancer syndrome caused by a heterozygous mutation in the VHL tumor suppressor gene. Previous studies suggested that similar populations of Caucasian and Japanese patients have similar genotype or phenotype characteristics. In this comprehensive study of East Asian patients, we investigated the genetic and clinical characteristics of patients with VHL syndrome. Methods: To create a registry of clinical characteristics and mutations reported in East Asian patients with VHL syndrome, we conducted a comprehensive review of English language and non‑English language articles identi‑fied through a literature search. Publications in Japanese or Chinese language were read by native speakers of the language, who then performed the data extraction. Results: Of 237 East Asian patients with VHL syndrome, 154 unique kindreds were identified for analysis. Analyzed by kindred, missense mutations were the most common (40.9%, 63/154), followed by large/complete deletions (32.5%, 50/154) and nonsense mutations (11.7%, 18/154). Compared with a previously reported study of both East Asian and non‑East Asian patients, we found several key differences. First, missense and frameshift mutations in the VHL gene occurred less commonly in our population of East Asian patients (40.9% vs. 52.0%; P = 0.012 and 8.4% vs.13.0%; P < 0.001, respectively). Second, large/complete deletions were more common in our population of East Asian patients (32.5% vs. 10.5%; P < 0.001). Third, phenotypically, we observed that, in our population of East Asian patients with VHL syndrome, the incidence of retinal capillary hemangioblastoma was lower, whereas the incidence of renal cell carcinoma was higher. Conclusions: Evidence suggests that the genotypic and phenotypic characteristics of East Asian patients with VHL syndrome differ from other populations. This should be considered when making screening recommendations for

  10. p.N78S and p.R161Q germline mutations of the VHL gene are present in von Hippel-Lindau syndrome in two pedigrees.

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    Qi, Xiao-Ping; Liu, Wen-Ting; Li, Jin-Yu; Dai, Yun; Ma, Ju-Ming; Zhao, Yan; Fei, Jun; Li, Feng; Shen, Mao; Jin, Hang-Yang; Chen, Zhen-Guang; Du, Zhen-Fang; Chen, Xiao-Ling; Zhang, Xian-Ning

    2013-09-01

    Von Hippel-Lindau (VHL) disease is an autosomal dominant familial cancer syndrome. VHL is characterized by the development of renal cell carcinoma (RCC), hemangioblastomas of the central nervous system or retina and pheochromocytoma (PCC). RCC and PCC are known to be caused by germline mutations of six and ten genes, respectively. In the present study, 30 individuals from two unrelated pedigrees with type 2A and 2C VHL syndrome were investigated. The patients were clinically examined and treated by radical nephrectomy [or nephron‑sparing surgery (NSS)] and cortical-sparing adrenalectomy (CSA), and all members of the two families underwent genetic screening. Two members from the first family were diagnosed with PCC and RCC, and three individuals from the second family who had only hypertension were diagnosed with PCC. Heterozygous variants of the VHL gene, c.A233G (p.N78S) within exon 1 and c.G482A (p.R161Q) within exon 3, were verified, respectively. Surgery was performed on all the patients, with the exception of an asymptomatic 5-year-old p.N78S male in family 1, in addition to genetic testing and genetic counseling. Further patient follow-up was warranted with regard to blood pressure and health, although normal blood pressure and no local recurrence and distant metastasis of VHL were observed previously. The present study suggests that molecular genetic testing may aid the diagnosis and clinical management of VHL syndrome.

  11. Novel interactions of the von Hippel-Lindau (pVHL) tumor suppressor with the CDKN1 family of cell cycle inhibitors

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    Minervini, Giovanni; Lopreiato, Raffaele; Bortolotto, Raissa; Falconieri, Antonella; Sartori, Geppo; Tosatto, Silvio C. E.

    2017-01-01

    Germline inactivation of the von Hippel-Lindau (VHL) tumor suppressor predisposes patients to develop different highly vascularized cancers. pVHL targets the hypoxia-inducible transcription factor (HIF-1α) for degradation, modulating the activation of various genes involved in hypoxia response. Hypoxia plays a relevant role in regulating cell cycle progression, inducing growth arrest in cells exposed to prolonged oxygen deprivation. However, the exact molecular details driving this transition are far from understood. Here, we present novel interactions between pVHL and the cyclin-dependent kinase inhibitor family CDKN1 (p21, p27 and p57). Bioinformatics analysis, yeast two-hybrid screening and co-immunoprecipitation assays were used to predict, dissect and validate the interactions. We found that the CDKN1 proteins share a conserved region mimicking the HIF-1α motif responsible for pVHL binding. Intriguingly, a p27 site-specific mutation associated to cancer is shown to modulate this novel interaction. Our findings suggest a new connection between the pathways regulating hypoxia and cell cycle progression. PMID:28425505

  12. Molecular Characterization of a Novel Germline VHL Mutation by Extensive In Silico Analysis in an Indian Family with Von Hippel-Lindau Disease

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    Gautham Arunachal

    2016-01-01

    Full Text Available Von Hippel-Lindau [VHL] disease, an autosomal dominant hereditary cancer syndrome, is well known for its complex genotype-phenotype correlations. We looked for germline mutations in the VHL gene in an affected multiplex family with Type 1 VHL disease. Real-Time quantitative PCR for deletions and Sanger sequencing of coding regions along with flanking intronic regions were performed in two affected individuals and one related individual. Direct sequencing identified a novel heterozygous single nucleotide base substitution in both the affected members tested, segregating with VHL phenotype in this family. This variant in exon 3, c.473T>A, results in substitution of leucine, a highly conserved acid, to glutamine at position 158 [p.L158Q] and has not been reported thus far as a variant associated with disease causation. Further, this variant was not observed in 50 age and ethnicity matched healthy individuals. Extensive in silico prediction analysis along with molecular dynamics simulation revealed significant deleterious nature of the substitution L158Q on pVHL. The results of this study when collated support the view that the missense variation p.L158Q in the Elongin C binding domain of pVHL may be disease causing.

  13. Treatment of multiple synchronous misdiagnosed renal cell cancers in a young patient affected by a "de novo" Von Hippel-Lindau syndrome.

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    Allasia, Marco; Battaglia, Antonino; Pasini, Barbara; Gazzera, Carlo; Calandri, Marco; Bosio, Andrea; Gontero, Paolo; Destefanis, Paolo

    2017-02-28

    Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited syndrome occurring in one out of 36,000 live births. Diagnosis could be a challenge in patients with no familial VHL history. Renal cancer (RCC) represents one of the most important manifestations. RCC is usually recurrent and multifocal. Actually treating RCC in VHL patients represent a clinical dilemma: the oncological outcomes must be balanced against renal function preservation. A young man with a negative familial history was referred to our department with seven misdiagnosed renal masses. VHL disease was determined through genetic test. The multiple RCCs were treated by surgery and percutaneous thermal ablation by radiofrequency ablation (RFA) with complete control of RCC and no impairment of renal function. This case history confirms that VHL disease has to be suspected in young patients with evidence of synchronous multiple renal masses and in presence of specific clinical criteria.RFA appears to be safe in terms of oncological radicalism and in renal function preservation.In hereditary RCC, we should purpose, whenever it is possible, minimally invasive treatment in terms of low hospital stay and a minimal loss of renal tissue.

  14. Ser80Ile mutation and a concurrent Pro25Leu variant of the VHL gene in an extended Hungarian von Hippel-Lindau family

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    Fazakas Ferenc

    2008-04-01

    Full Text Available Abstract Von Hippel-Lindau disease (VHL is a rare autosomal dominant disease characterized by development of cystic and tumorous lesions at multiple sites, including the brain, spinal cord, kidneys, adrenals, pancreas, epididymis and eyes. The clinical phenotype results from molecular abnormalities of the VHL tumor suppressor gene, mapped to human chromosome 3p25-26. The VHL gene encodes two functionally active VHL proteins due to the presence of two translational initiation sites separated by 53 codons. The majority of disease-causing mutations have been detected downstream of the second translational initiation site, but there are conflicting data as to whether few mutations located in the first 53 codons, such as the Pro25Leu could have a pathogenic role. In this paper we report a large Hungarian VHL type 2 family consisting of 32 members in whom a disease-causing AGT80AAT (Ser80Ile c.239G>A, p.Ser80Ile mutation, but not the concurrent CCT25CTT (Pro25Leu c.74C>T, p.Pro25Leu variant co-segregated with the disease. To our knowledge, the Ser80Ile mutation has not been previously described in VHL type 2 patients with high risk of pheochromocytoma and renal cell cancer. Therefore, this finding represents a novel genotype-phenotype association and VHL kindreds with Ser80Ile mutation will require careful surveillance for pheochromocytoma. We concluded that the Pro25Leu variant is a rare, neutral variant, but the presence such a rare gene variant may make genetic counseling difficult.

  15. Through the looking glass: an exploratory study of the lived experiences and unmet needs of families affected by Von Hippel-Lindau disease.

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    Kasparian, Nadine A; Rutstein, Alison; Sansom-Daly, Ursula M; Mireskandari, Shab; Tyler, Janet; Duffy, Jessica; Tucker, Katherine M

    2015-01-01

    Despite well-established protocols for the medical management of Von Hippel-Lindau disease (VHL), families affected by this rare tumour syndrome continue to face numerous psychological, social, and practical challenges. To our knowledge, this is one of the first qualitative studies to explore the psychosocial difficulties experienced by families affected by VHL. A semi-structured interview was developed to explore patients' and carers' experiences of VHL along several life domains, including: self-identity and self-esteem, interpersonal relationships, education and career opportunities, family communication, physical health and emotional well-being, and supportive care needs. Quantitative measures were also used to examine the prevalence of anxiety, depression, and disease-specific distress in this sample. Participants were recruited via the Hereditary Cancer Clinic at the Prince of Wales Hospital in Sydney, Australia. A total of 23 individual telephone interviews were conducted (15 patients, 8 carers), yielding a response rate of 75%. A diverse range of experiences were reported, including: sustained uncertainty about future tumour development, frustration regarding the need for lifelong medical screening, strained family relationships, difficulties communicating with others about VHL, perceived social isolation and limited career opportunities, financial and care-giving burdens, complex decisions in relation to childbearing, and difficulties accessing expert medical and psychosocial care. Participants also provided examples of psychological growth and resilience, and voiced support for continued efforts to improve supportive care services. More sophisticated systems for connecting VHL patients and their families with holistic, empathic, and person-centred medical and psychosocial care are urgently needed.

  16. Von Hippel-Lindau (VHL inactivation in sporadic clear cell renal cancer: associations with germline VHL polymorphisms and etiologic risk factors.

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    Lee E Moore

    2011-10-01

    Full Text Available Renal tumor heterogeneity studies have utilized the von Hippel-Lindau VHL gene to classify disease into molecularly defined subtypes to examine associations with etiologic risk factors and prognosis. The aim of this study was to provide a comprehensive analysis of VHL inactivation in clear cell renal tumors (ccRCC and to evaluate relationships between VHL inactivation subgroups with renal cancer risk factors and VHL germline single nucleotide polymorphisms (SNPs. VHL genetic and epigenetic inactivation was examined among 507 sporadic RCC/470 ccRCC cases using endonuclease scanning and using bisulfite treatment and Sanger sequencing across 11 CpG sites within the VHL promoter. Case-only multivariate analyses were conducted to identify associations between alteration subtypes and risk factors. VHL inactivation, either through sequence alterations or promoter methylation in tumor DNA, was observed among 86.6% of ccRCC cases. Germline VHL SNPs and a haplotype were associated with promoter hypermethylation in tumor tissue (OR = 6.10; 95% CI: 2.28-16.35, p = 3.76E-4, p-global = 8E-5. Risk of having genetic VHL inactivation was inversely associated with smoking due to a higher proportion of wild-type ccRCC tumors [former: OR = 0.70 (0.20-1.31 and current: OR = 0.56 (0.32-0.99; P-trend = 0.04]. Alteration prevalence did not differ by histopathologic characteristics or occupational exposure to trichloroethylene. ccRCC cases with particular VHL germline polymorphisms were more likely to have VHL inactivation through promoter hypermethylation than through sequence alterations in tumor DNA, suggesting that the presence of these SNPs may represent an example of facilitated epigenetic variation (an inherited propensity towards epigenetic variation in renal tissue. A proportion of tumors from current smokers lacked VHL alterations and may represent a biologically distinct clinical entity from inactivated cases.

  17. Congenital polycythemia with homozygous and heterozygous mutations of von Hippel-Lindau gene: five new Caucasian patients.

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    Bento, Maria Celeste; Chang, Ko Tung; Guan, Yongli; Liu, Enli; Caldas, Gabriela; Gatti, Richard A; Prchal, Josef T

    2005-01-01

    We report on five Caucasian patients with congenital polycythemia and mutations of the von Hipple-Lindau (VHL) gene: a compound heterozygote for the novel exon 1 (VHL 235C->T) and previously reported VHL 562C->G mutations; three homozygotes for Chuvash VHL 598C->T mutation; and a heterozygote for VHL 523->G mutation who also has ataxia-telangiectasia; a rare autosomal disease of childhood onset.

  18. Bilateral optic nerve head hemangioma in Von Hippel Lindau disease: Report of a case with severe visual loss

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    Abdollahi A

    2001-06-01

    Full Text Available A 22 year-old woman presented with gradual visual loss in her right eye since 1990. Medical and family histories were unremarkable. Her visual acuity was 20/80 and 20/20 in right and left eyes respectively. Slit lamp examination was quite normal with no relative afferent papillary defect.Fundi of both eyes revealed subretinal lesion with optic nerve head involvement and subretinal fluid in papillomacular bundle with macular pucker in right eye. Whole body MRI revealed a large hemangioma in the spinal canal. In 1998 the patient ahsd significant visual loss at both eyes. This is the first report of Von hippel disease with bilateral optic nerve hemangioma in Iran.

  19. Juxtapapillary hemangioma: a case report and review of clinical features and management of von Hippel-Lindau disease.

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    Aumiller, Mira Silbert

    2005-08-01

    The phakomatose von Hipple-Lindau (VHL) disease is a multisystem disorder characterized by hemangioblastomas of the central nervous system (CNS), retinal angiomas, and multiple cysts and tumors of the viscera. Retinal capillary hemangiomas are the most common manifestation of VHL disease, which can occur in the optic nerve, where it may simulate disc edema, or in the retinal periphery, which is characterized by massive retinal exudation. Both locations can result in progressive accumulation of exudates leading to a decrease in visual acuity and potentially to a serous retinal detachment. A juxtapapillary hemangioma was observed in a 72-year-old man who presented for a routine examination. The patient was asymptomatic, despite the presence of a trace afferent papillary defect. This finding had to be carefully differentiated from sectoral disc edema. Blood tests, computed tomography (CT), and magnetic resonance imaging (MRI) all had normal results. Fluorescein angiography was a valuable secondary test showing early filling of the vascular network overlying the nerve head and characteristic late hyperfluorescence. There are 2 distinct forms of capillary hemangiomas--the juxtapapillary tumor or the peripheral capillary hemangioma. Although both types are similar histologically, they do vary in their appearance, differential diagnosis, and treatment. In both types, fluorescein angiography is an extremely helpful ancillary test in making the initial diagnosis. This case report reviews the ocular manifestations and systemic findings associated with VHL disease.

  20. Potential role of {sup 68}Ga-DOTATOC PET/CT in screening for pancreatic neuroendocrine tumour in patients with von Hippel-Lindau disease

    Energy Technology Data Exchange (ETDEWEB)

    Prasad, Vikas; Brenner, Winfried [Charite Universitaetsmedizin Berlin, Department of Nuclear Medicine, Campus Virchow-Klinikum, Berlin (Germany); Tiling, Nikolaus; Ploeckinger, Ursula [Charite Universitaetsmedizin Berlin, Interdisziplinaeren Stoffwechsel-Centrum, Campus Virchow Klinikum, Berlin (Germany); Denecke, Timm [Charite Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany)

    2016-10-15

    Neuroendocrine tumours of the pancreas (pNET) are observed in 8 - 17 % of patients with von Hippel-Lindau disease (vHLD), and 11 - 20 % of these patients develop metastatic disease. MRI and CT have a very high resolution; however, their sensitivity and specificity for the detection of pNET amongst cystic lesions in the pancreas of vHLD patients are generally considered insufficient. In contrast, {sup 68}Ga-DOTATOC PET/CT demonstrates a high sensitivity for the diagnosis and staging of neuroendocrine tumours. In this study we investigated the potential role of {sup 68}Ga-DOTATOC PET/CT in screening of patients with vHLD. {sup 68}Ga-DOTATOC PET/three-phase contrast-enhanced CT was performed according to guidelines in all consecutive vHLD patients between January 2012 and November 2015. All patients underwent additional MRI imaging of the abdomen, spine, and head. Chromogranin A (CgA) was determined at the time of the PET/CT examination. A lesion seen on {sup 68}Ga-DOTATOC PET in the pancreas was defined as positive if the uptake was visually higher than in the surrounding tissues. Lesions were quantified using maximum SUV. Overall, 20 patients (8 men, 12 women; mean age 44.7 ± 11.1 years) were prospectively examined. Genetically, 12 patients had type 1 vHLD and 8 had type 2 vHLD. {sup 68}Ga-DOTATOC PET/CT detected more pNET than morphological imaging (CT or MRI): 11 patients (55 %; 8 type 1, 3 type 2) vs. 9 patients (45 %; 6 type 1, 3 type 2). The concentration of CgA was mildly elevated in 2 of 11 patients with pNET. The mean SUVmax of the pancreatic lesions was 18.9 ± 21.9 (range 5.0 - 65.6). Four patients (36.4 %) had multiple pNETs. The mean size of the lesions on CT and/or MRI was 10.4 ± 8.3 mm (range 4 - 38 mm), and 41.1 % were larger than 10 mm. In addition, somatostatin receptor-positive cerebellar and spinal haemangioblastomas were detected in three patients (SUVmax 2.1 - 10.1). One patient presented with a solitary somatostatin receptor-positive lymph

  1. von Hippel-Lindau disease

    DEFF Research Database (Denmark)

    Binderup, Marie Louise Mølgaard; Gimsing, Steen; Kosteljanetz, Michael;

    2013-01-01

    HL patient who became deaf in one ear due to a radiologically undetectable ELST. Results: Despite annual MRIs, the ELST was not visible until four months after onset of deafness when it appeared as a 1.4 × 1.4 mm tumor mass. Although his hearing was objectively within normal limits for the first 14 years...

  2. Von Hippel-Lindau Syndrome

    Science.gov (United States)

    ... which is a specific type of kidney cancer; pheochromocytoma , which is a tumor of the adrenal gland ; ... hemangioblastoma and clear cell kidney cancer, pancreatic cysts, pheochromocytoma, endolymphatic sac tumor, or epididymal cyst In young ...

  3. [A Case of Von Hippel-Lindau Disease with Nonfunctioning Pancreatic Neuroendocrine Tumors Treated by Duodenum-Preserving Resection of the Head of the Pancreas and Spleen-Preserving Resection of the Tail of the Pancreas].

    Science.gov (United States)

    Umehara, Yutaka; Umehara, Minoru; Tokura, Tomohisa; Yachi, Takafumi; Takahashi, Kenichi; Morita, Takayuki; Hakamada, Kenichi

    2015-10-01

    A 26-year-old woman presented to our department with a diagnosis of multiple nonfunctioning pancreatic neuroendocrine tumors. She had a family history of pheochromocytoma and a medical history of bilateral adrenalectomy for pheochromocytoma at the age of 25 years. During follow-up treatment for adrenal insufficiency after the surgery, highly enhanced tumors in the pancreas were detected on contrast-enhanced CT. Other examinations found that the patient did not satisfy the clinical criteria for von Hippel-Lindau (VHL) disease. Considering her age and risk of developing multiple heterotopic and heterochronous tumors, we performed a duodenum-preserving resection of the head of the pancreas and spleen-preserving resection of the tail of the pancreas with informed consent. The histopathological findings revealed that all of the tumors were NET G1. She underwent genetic testing postoperatively and was diagnosed with VHL disease. This diagnosis meant that we were able to create an optimal treatment plan for the patient. If a tumor predisposition syndrome is suspected, VHL disease should be borne in mind and genetic testing after genetic counseling should be duly considered.

  4. Hypoglycemia in Von Hippel-Lindau Syndrome and Literature Review%以低血糖症为主要表现的Von Hippel-Lindau综合征并文献复习

    Institute of Scientific and Technical Information of China (English)

    聂川; 吕黄勇; 陈晓敏; 韩峰; 肖萧

    2016-01-01

    Objective To investigate the diagnosis and treatment of Von Hippel-Lindau syndrome. Methods The clinical data of one patient of VHL Syndrome was retrospectively analyzed and the related literature was reviewed. Results A 37-year-old male patient was admitted for recurrent hypoglycemia, abdominal pain, headache, and vertigo for 1 year. He had been diagnosed with hypoglycemia at several local hospitals, and the symptoms mostly occurred in the morning but were relieved after eating or tak-ing oral glucose. In spite of this, the symptoms reoccurred. His fasting blood glucose fluctuated between 2. 2~4. 0 mmol/L upon admission to our hospital. Abdominal CT, head and neck MRI examination confirmed VHL syndrome. The patient was transferred to a specialized hospital and after symptomatic treatment, the patient's condition turned stable and the patient survived in one year fol-low-up. Conclusion VHL syndrome is a rare autosomal dominant genetic disease with multi organ involvement and clinical mani-festations. The key to reduce the misdiagnosis and missed diagnosis rates is to raise awareness.%目的 探讨Von Hippel-Lindau综合征(VHL综合征)的诊治要点.方法 回顾性分析VHL综合征1例的临床资料并复习相关文献.结果 本例为37岁男性,因反复发作的低血糖症伴上腹痛、头痛、眼花1年入院.曾在当地医院多次就诊,诊断为低血糖症,进食或口服葡萄糖后病情可缓解,但此后又反复发作,发作时间多为清晨.入我院后查空腹血糖在2.2~4.0 mmol/L,后结合腹部CT、头颈部MRI检查诊断为VHL综合征.转专科医院仅予对症支持治疗后病情稳定,随访1年仍存活.结论 VHL综合征是一种临床少见的常染色体显性遗传性疾病,常多器官受累,临床表现多样,提高对本病的认识是降低误诊及漏诊的关键.

  5. A mutation at IVS1 + 5 of the von Hippel-Lindau gene resulting in intron retention in transcripts is not pathogenic in a patient with a tongue cancer?: case report

    Directory of Open Access Journals (Sweden)

    Asakawa Takeshi

    2012-03-01

    Full Text Available Abstract Background Von Hippel-Lindau disease (VHL is a dominantly inherited familial cancer syndrome predisposing the patient to a variety of malignant and benign neoplasms, most frequently hemangioblastoma, renal cell carcinoma, pheochromocytoma, and pancreatic tumors. VHL is caused by mutations of the VHL tumor suppressor gene on the short arm of chromosome 3, and clinical manifestations develop if both alleles are inactivated according to the two-hit hypothesis. VHL mutations are more frequent in the coding region and occur occasionally in the splicing region of the gene. Previously, we reported that the loss of heterozygosity (LOH of the VHL gene is common in squamous cell carcinoma tissues of the tongue. Case Presentation We describe a case of squamous cell carcinoma in the tongue caused by a point mutation in the splicing region of the VHL gene and discuss its association with VHL disease. Sequence analysis of DNA extracted from the tumor and peripheral blood of the patient with squamous cell carcinoma revealed a heterozygous germline mutation (c. 340 + 5 G > C in the splice donor sequence in intron 1 of the VHL gene. RT-PCR analysis of the exon1/intron1 junction in RNA from tumor tissue detected an unspliced transcript. Analysis of LOH using a marker with a heterozygous mutation of nucleotides (G or C revealed a deletion of the mutant C allele in the carcinoma tissues. Conclusions The fifth nucleotide G of the splice donor site of the VHL gene is important for the efficiency of splicing at that site. The development of tongue cancer in this patient was not associated with VHL disease because the mutation occurred in only a single allele of the VHL gene and that allele was deleted in tumor cells.

  6. Prolyl hydroxylase 2 dependent and Von-Hippel-Lindau independent degradation of Hypoxia-inducible factor 1 and 2 alpha by selenium in clear cell renal cell carcinoma leads to tumor growth inhibition

    Directory of Open Access Journals (Sweden)

    Chintala Sreenivasulu

    2012-07-01

    Full Text Available Abstract Background Clear cell renal cell carcinoma (ccRCC accounts for more than 80% of the cases of renal cell carcinoma. In ccRCC deactivation of Von-Hippel-Lindau (VHL gene contributes to the constitutive expression of hypoxia inducible factors 1 and 2 alpha (HIF-α, transcriptional regulators of several genes involved in tumor angiogenesis, glycolysis and drug resistance. We have demonstrated inhibition of HIF-1α by Se-Methylselenocysteine (MSC via stabilization of prolyl hydroxylases 2 and 3 (PHDs and a significant therapeutic synergy when combined with chemotherapy. This study was initiated to investigate the expression of PHDs, HIF-α, and VEGF-A in selected solid cancers, the mechanism of HIF-α inhibition by MSC, and to document antitumor activity of MSC against human ccRCC xenografts. Methods Tissue microarrays of primary human cancer specimens (ccRCC, head & neck and colon were utilized to determine the incidence of PHD2/3, HIF-α, and VEGF-A by immunohistochemical methods. To investigate the mechanism(s of HIF-α inhibition by MSC, VHL mutated ccRCC cells RC2 (HIF-1α positive, 786–0 (HIF-2α positive and VHL wild type head & neck cancer cells FaDu (HIF-1α were utilized. PHD2 and VHL gene specific siRNA knockdown and inhibitors of PHD2 and proteasome were used to determine their role in the degradation of HIF-1α by MSC. Results We have demonstrated that ccRCC cells express low incidence of PHD2 (32%, undetectable PHD3, high incidence of HIF-α (92%, and low incidence of VEGF-A compared to head & neck and colon cancers. This laboratory was the first to identify MSC as a highly effective inhibitor of constitutively expressed HIF-α in ccRCC tumors. MSC did not inhibit HIF-1α protein synthesis, but facilitated its degradation. The use of gene knockdown and specific inhibitors confirmed that the inhibition of HIF-1α was PHD2 and proteasome dependent and VHL independent. The effects of MSC treatment on HIF-α were associated with

  7. Von Hippel-Lindau Disease (VHL)

    Science.gov (United States)

    ... may include headaches, problems with balance and walking, dizziness, weakness of the limbs, vision problems, deafness in ... may include headaches, problems with balance and walking, dizziness, weakness of the limbs, vision problems, deafness in ...

  8. Von Hippel-Lindau syndrome-2B accompanied with leukocytoclastic vasculitis: a case report and lirerature review%von Hippel-Lindau综合征2B型合并白细胞破碎性血管炎一例报告并文献复习

    Institute of Scientific and Technical Information of China (English)

    邓建华; 李汉忠; 严维刚; 徐维锋

    2012-01-01

    Objective To explore clinicopathologic features,diagnosis,treatment and prognosis of von Hippel-Lindau (VHL) type 2B mixed cutaneous leukocytoclastic vasculitis. Methods A 22-Year-Old Man who presented with constitutional symptoms,severe hypertension,and purpuric lesions over the knees.Clinical features,histopathological,IHC and anti-angiogenesis therapy of this case with VHL syndrome-2B mixed cutaneous leukocytoclastic vasculitis was studied based on the available follow-up data.He underwent laparoscopic adrenalectomy and nephron sparing nephrectomy.Clinical evaluation included ophthalmologic examination as well as imaging exams and endocrinal hormone test for tumors markers ; molecular analysis consisted of PCR amplification of the complete VHL gene coding sequence (three exons) and automated nucleotide sequencing. Results 24 h urine Norepinephrine was 295.84 μg and octreotide scan was positive.The VHL-2B patient suffered from leukocytoclastic vasculitis,a retinal hole,pancroatic tumors (endocrine tumor and microcystic cystadenoma),bilateral pheochromocyoma,clear renal cell carcinoma,renal cysts,hepatic hemangioma and epididymal cyst.The patient developed 5 different tumors related to VHL within a period of 6 years.The cutaneous vasculitis persisted despite treatment with high-dose systemic corticosteroids,but rapidly resolved after treatment with phenoxybenzamine and removal of bilateral pheochromocytomas.Tumor cells of resected PHEO samples stained positive for CgA and S-100,but negative for Melan-A.,and with less than 1% Ki-67. Conclusions Cutaneous leukocytoclastic vasculitis is one of paraneoplastic syndrome of pheochromocytoma.Because new lesions may develop during the patient's lifetime,regular clinical inspection is recommended in order to check up the development of any new lesions.%目的 探讨合并白细胞破碎性血管炎(leukocytoclastic vasculitis,LV)的von HippelLindau综合征2B型(VHL-2B)的临床特点、诊治方法和预后. 方法 2010

  9. Genetics Home Reference: von Hippel-Lindau syndrome

    Science.gov (United States)

    ... in the inner ear . These growths can cause hearing loss in one or both ears, as well as ringing in the ears (tinnitus) and problems with balance. Without treatment, these tumors can cause sudden profound deafness. Related Information What does it mean ...

  10. Surveillance in von Hippel-Lindau disease (vHL)

    DEFF Research Database (Denmark)

    Poulsen, Marie Louise Mølgaard; Budtz-Jørgensen, E; Bisgaard, M L

    2010-01-01

    for the patient. Also, pre-symptomatic surveillance increased cumulative incidence of clinical vHL diagnosis from 46% to 72% and from 89% to 94% by age 30 and 50 years, respectively. The present results promote optimization of surveillance, expectantly improving clinical vHL outcomes....

  11. Von Hippel-Lindau disease (vHL)

    DEFF Research Database (Denmark)

    Binderup, Marie Louise Mølgaard; Bisgaard, Søs Marie Luise; Harbud, Vibeke

    2013-01-01

    cell carcinoma), the adrenal glands (pheochromocytoma), the pancreas, as well as in other organs. As many different organs can be affected, several medical specialities often take part in both diagnosis and treatment of manifestations. vHL should be suspected in individuals with a family history...... of the disease, and/or in individuals with a vHL-associated manifestation; i.e. a hemangioblastoma in the retina or the central nervous system, familial or bilateral pheochromocytomas, familial, multiple, or early onset renal cell carcinomas, and in individuals with an endolymphatic sac tumour in the inner ear...

  12. New von Hippel-Lindau manifestations develop at the same or decreased rates in pregnancy

    DEFF Research Database (Denmark)

    Binderup, Marie Louise Mølgaard; Budtz-Jørgensen, Esben; Bisgaard, Søs Marie Luise

    2015-01-01

    diagnosed throughout their lifetimes. We analyzed age-dependent manifestation rates using Poisson regression. We compared the women's rates in intervals where they had been pregnant with their age-matched nonpregnant intervals. We investigated possible long-term effects using pregnancy intervals...... pregnancies. Manifestation rates in women's pregnant intervals were lower compared with their age-matched nonpregnant intervals (1 year: hazard ratio [HR] = 0.439, 95% confidence interval [CI] 0.131-1.474, p = 0.18; 3 years: HR = 0.412, 95% CI 0.214-0.796, p = 0.0083; and 5 years: HR = 0.450, 95% CI 0.......136-1.489, p = 0.19). Men and women had similar manifestation rates, both increasing from their 20s. CONCLUSIONS: Pregnancy does not aggravate vHL tumor development, and we neither discourage pregnancy in VHL mutation carriers nor recommend intensified surveillance during pregnancy. The pregnancy effect...

  13. Prevalence, birth incidence, and penetrance of von Hippel-Lindau disease (vHL) in Denmark

    DEFF Research Database (Denmark)

    Binderup, Marie Louise Mølgaard; Galanakis, Michael Carter Bisgaard; Budtz-Jørgensen, Esben

    2017-01-01

    . We further used national health registers to identify individuals who fulfilled the clinical diagnostic vHL criteria based on their registered diagnostic codes, but had not been diagnosed with vHL. We also assessed the medical histories of first-degree relatives to identify familial cases. This study...... gives the first national estimates of vHL prevalence (1 in 46 900 individuals) and birth incidence (1 in 27 300 live births). vHL has been underdiagnosed in Denmark, and as many as 25% of the overall vHL cohort (diagnosed+undiagnosed patients) have a missed diagnosis in spite of fulfilling...

  14. MicroRNA-150 regulates glycolysis by targeting von Hippel-Lindau in glioma cells

    OpenAIRE

    Li, Shi-Jie; Liu, Hong-Lin; Tang, Shi-Lei; Li, Xiao-Juan; Wang, Xiao-yin

    2017-01-01

    Warburg effect, characterized by enhanced glycolysis and lactate production, even under aerobic conditions, is one of the hallmarks of cancer cells. However, the mechanism underlying this phenomenon remains poorly understood. Previous studies have shown that microRNA-150 (miR-150) is significantly up-regulated in various malignancies and represents a putative onco-miRNA in human cancers. In the present study, we aim to investigate the functional significance and molecular target of miR-150 in...

  15. Chemokine receptor CXCR4 downregulated by von Hippel-Lindau tumour suppressor pVHL

    DEFF Research Database (Denmark)

    Staller, Peter; Sulitkova, Jitka; Lisztwan, Joanna

    2003-01-01

    Organ-specific metastasis is governed, in part, by interactions between chemokine receptors on cancer cells and matching chemokines in target organs. For example, malignant breast cancer cells express the chemokine receptor CXCR4 and commonly metastasize to organs that are an abundant source...... regulates CXCR4 expression owing to its capacity to target hypoxia-inducible factor (HIF) for degradation under normoxic conditions. This process is suppressed under hypoxic conditions, resulting in HIF-dependent CXCR4 activation. An analysis of clear cell renal carcinoma that manifests mutation of the VHL...

  16. Sindrom Von Hippel–Lindau

    Directory of Open Access Journals (Sweden)

    E V Ershova

    2011-06-01

    Full Text Available Von Hippel-Lindau syndrome - a systemic disease manifesting with multiple tumor growth, inherited by autosomal-dominant type with high penetrance. Understanding the pathogenesis of the disease is important for determining the start time of screening for the presence of the tumors and adequate treatment, including metabolic disorders.

  17. The von Hippel-Lindau Chuvash mutation in mice causes carotid-body hyperplasia and enhanced ventilatory sensitivity to hypoxia.

    Science.gov (United States)

    Slingo, Mary E; Turner, Philip J; Christian, Helen C; Buckler, Keith J; Robbins, Peter A

    2014-04-01

    The hypoxia-inducible factor (HIF) family of transcription factors coordinates diverse cellular and systemic responses to hypoxia. Chuvash polycythemia (CP) is an autosomal recessive disorder in humans in which there is impaired oxygen-dependent degradation of HIF, resulting in long-term systemic elevation of HIF levels at normal oxygen tensions. CP patients demonstrate the characteristic features of ventilatory acclimatization to hypoxia, namely, an elevated baseline ventilation and enhanced acute hypoxic ventilatory response (AHVR). We investigated the ventilatory and carotid-body phenotype of a mouse model of CP, using whole-body plethysmography, immunohistochemistry, and electron microscopy. In keeping with studies in humans, CP mice had elevated ventilation in euoxia and a significantly exaggerated AHVR when exposed to 10% oxygen, with or without the addition of 3% carbon dioxide. Carotid-body immunohistochemistry demonstrated marked hyperplasia of the oxygen-sensing type I cells, and the cells themselves appeared enlarged with more prominent nuclei. This hypertrophy was confirmed by electron microscopy, which also revealed that the type I cells contained an increased number of mitochondria, enlarged dense-cored vesicles, and markedly expanded rough endoplasmic reticulum. The morphological and ultrastructural changes seen in the CP mouse carotid body are strikingly similar to those observed in animals exposed to chronic hypoxia. Our study demonstrates that the HIF pathway plays a major role, not only in regulating both euoxic ventilatory control and the sensitivity of the response to hypoxia, but also in determining the morphology of the carotid body.

  18. The von Hippel-Lindau Chuvash mutation in mice alters cardiac substrate and high-energy phosphate metabolism.

    Science.gov (United States)

    Slingo, Mary; Cole, Mark; Carr, Carolyn; Curtis, Mary K; Dodd, Michael; Giles, Lucia; Heather, Lisa C; Tyler, Damian; Clarke, Kieran; Robbins, Peter A

    2016-09-01

    Hypoxia-inducible factor (HIF) appears to function as a global master regulator of cellular and systemic responses to hypoxia. HIF pathway manipulation is of therapeutic interest; however, global systemic upregulation of HIF may have as yet unknown effects on multiple processes. We used a mouse model of Chuvash polycythemia (CP), a rare genetic disorder that modestly increases expression of HIF target genes in normoxia, to understand what these effects might be within the heart. An integrated in and ex vivo approach was employed. Compared with wild-type controls, CP mice had evidence (using in vivo magnetic resonance imaging) of pulmonary hypertension, right ventricular hypertrophy, and increased left ventricular ejection fraction. Glycolytic flux (measured using [(3)H]glucose) in the isolated contracting perfused CP heart was 1.8-fold higher. Net lactate efflux was 1.5-fold higher. Furthermore, in vivo (13)C-magnetic resonance spectroscopy (MRS) of hyperpolarized [(13)C1]pyruvate revealed a twofold increase in real-time flux through lactate dehydrogenase in the CP hearts and a 1.6-fold increase through pyruvate dehydrogenase. (31)P-MRS of perfused CP hearts under increased workload (isoproterenol infusion) demonstrated increased depletion of phosphocreatine relative to ATP. Intriguingly, no changes in cardiac gene expression were detected. In summary, a modest systemic dysregulation of the HIF pathway resulted in clear alterations in cardiac metabolism and energetics. However, in contrast to studies generating high HIF levels within the heart, the CP mice showed neither the predicted changes in gene expression nor any degree of LV impairment. We conclude that the effects of manipulating HIF on the heart are dose dependent.

  19. The von Hippel-Lindau Chuvash mutation in mice alters cardiac substrate and high energy phosphate metabolism

    OpenAIRE

    Slingo, Mary; Cole, Mark; Carr, Carolyn; Curtis, Mary K.; Dodd, Michael; Giles, Lucia; Heather, Lisa C; Tyler, Damian; CLARKE, KIERAN; Robbins, Peter A.

    2016-01-01

    Hypoxia-inducible factor (HIF) appears to function as a global master regulator of cellular and systemic responses to hypoxia. HIF-pathway manipulation is of therapeutic interest, however global, systemic upregulation of HIF may have as yet unknown effects on multiple processes. We utilized a mouse model of Chuvash polycythemia (CP), a rare genetic disorder which modestly increases expression of HIF target genes in normoxia, to understand what these effects might be within the heart.\\ud \\ud A...

  20. The von Hippel-Lindau Chuvash mutation in mice alters cardiac substrate and high energy phosphate metabolism.

    OpenAIRE

    Slingo, Mary; Cole, Mark A.; Carr, Carolyn; Curtis, Mary K.; Dodd, Michael S.; Giles, Lucia; Heather, Lisa; Tyler, Damian; CLARKE, KIERAN; Robbins, Peter

    2016-01-01

    Hypoxia-inducible factor (HIF) appears to function as a global master regulator of cellular and systemic responses to hypoxia. HIF-pathway manipulation is of therapeutic interest, however global, systemic upregulation of HIF may have as yet unknown effects on multiple processes. We utilized a mouse model of Chuvash polycythemia (CP), a rare genetic disorder which modestly increases expression of HIF target genes in normoxia, to understand what these effects might be within the heart. An i...

  1. Expression of von Hippel-Lindau tumor suppressor and tumor-associated carbonic anhydrases Ⅸ and Ⅻ in normal and neoplastic colorectal mucosa

    Institute of Scientific and Technical Information of China (English)

    Antti J. Kivela; Abdul Waheed; William S. Sly; Hannu Rajaniemi; Silvia Pastorekova; Jaromir Pastorek; Seppo Parkkila; Juha Saarnio; Tuomo J. Karttunen; Jyrki Kivela; Anna-Kaisa Parkkila; Maria Bartosova; Vojtech Mucha; Michal Novak

    2005-01-01

    AIM: To analyze possible relationships between CA Ⅸ/ CA Ⅻ and pVHL expression in normal and neoplastic colorectal mucosa.METHODS: Immunohistochemical staining of 42 tissue specimens obtained from 17 cancer patients was performed to evaluate the distribution and semi-quantitatively assess the levels of CA Ⅸ, CA Ⅻ and pVHL. VHL mRNAs from 14fresh-frozen tumors was amplified by RT-PCR and subjected to sequencing. CA9 and CA12 mRNA levels were analyzed by semi-quantitative RT-PCR in comparison with VEGF as an indicator of hypoxia that uncouples the pVHL control.RESULTS: Tumor tissues were associated with a borderline increase of CA Ⅸ staining signal and slight but significant decrease of CA Ⅻ immunoreactivity, whereas no association was found for pVHL. Sequence analysis of RT-PCR-amplified VHL mRNAs revealed no deletions/ mutations, suggesting that they were VHL-competent. We did not observe any correlation between pVHL andCA Ⅸ/CA Ⅻ proteins as well as between VEGF and CA9mRNAs, but the tumor-associated changes in mRNA levels of VEGF and CA12showed a significant inverse relationship. CONCLUSION: Our results indicate that CA9 and CA12 are regulated by different intratumoral factors and that lack of apparent relationship between the levels of CA Ⅸ/CA Ⅻ and pVHL cannot be fully assigned to uncoupling of negative regulatory function of pVHL by tumor hypoxia signified by induced VEGF transcription. The interplay between the functional pVHL and CA Ⅸ/CA Ⅻ in colorectal tumors seems rather complex and is not evident merely at the expression levels.

  2. Genetic screening for von Hippel-Lindau gene mutations in non-syndromic pheochromocytoma: low prevalence and false-positives or misdiagnosis indicate a need for caution.

    NARCIS (Netherlands)

    Eisenhofer, G.; Vocke, C.D.; Elkahloun, A.; Huynh, T.T.; Prodanov, T.; Lenders, J.W.M.; Timmers, H.J.L.M.; Benhammou, J.N.; Linehan, W.M.; Pacak, K.

    2012-01-01

    Genetic testing of tumor susceptibility genes is now recommended in most patients with pheochromocytoma or paraganglioma (PPGL), even in the absence of a syndromic presentation. Once a mutation is diagnosed there is rarely follow-up validation to assess the possibility of misdiagnosis. This study

  3. {sup 68}Ga-labelled peptides in the management of neuroectodermal tumours

    Energy Technology Data Exchange (ETDEWEB)

    Naji, Meeran [Maidstone and Tunbridge Wells NHS Trust, Departments of Nuclear Medicine and Radiology, Maidstone (United Kingdom); Al-Nahhas, Adil [Hammersmith Hospital, Imperial College NHS Trust, Department of Nuclear Medicine, London (United Kingdom)

    2012-02-15

    Neuroectodermal tumours arise from chromaffin cells and possess the ability to secrete catecholamines. They are generally rare and may occur in association with a variety of hereditary syndromes such as MEN-2A and 2B, neurofibromatosis type 1 and von Hippel-Lindau disease. The most common types are phaeochromocytoma arising from the adrenal medulla and paraganglioma of extra-adrenal origin. Phaeochromocytomas tend to be benign and are often associated with a gene mutation if the disease is bilateral, while paragangliomas are often malignant, have a more aggressive nature and tend to metastasize. There are no specific histological or immunohistochemical features that indicate the malignant potential and the diagnosis of malignancy can only be established by the presence of distant metastases. Therefore, imaging can play a vital role in the diagnosis, localization, staging and assessment of spread. Traditionally, this is achieved with a combination of cross-sectional (CT and MRI) and functional ({sup 123}I-MIBG or {sup 111}In-octreotide) imaging. However, these modalities are not adequate and achieve moderate sensitivity. The introduction of {sup 68}Ga-DOTA peptide in PET/CT imaging has led to improved receptor targeting and superb PET resolution, as well as accurate localization of lesions. The use of this technique in neuroectodermal tumours has been shown to be superior to all available modalities, but the available data are limited and larger studies are awaited to establish its role in the management of these tumours. (orig.)

  4. BASED TO CLINICAL CASE. VON HIPLEA-LINDAU SYNDROME

    Directory of Open Access Journals (Sweden)

    Brzeziński Piotr

    2011-01-01

    Full Text Available von Hippel-Lindau syndrome (VHL is a rare, genetic multi-system disorder characterized by the abnormal growth of tumors in certain parts of the body (angiomatosis. The tumors of the central nervous system (CNS are benign and are comprised of a nest of blood vessels and are called hemangioblastomas. Hemangioblastomas may develop in the brain, the retina of the eyes, and other areas of the nervous system. Other types of tumors develop in the adrenal glands, the kidneys, or the pancreas. Symptoms of VHL vary among patients and depend on the size and location of the tumors. Symptoms may include headaches, problems with balance and walking, dizziness, weakness of the limbs, vision problems, and high blood pressure. Cysts (fluid-filled sacs and/or tumors (benign or cancerous may develop around the hemangioblastomas and cause the symptoms listed above. Individuals with VHL are also at a higher risk than normal for certain types of cancer, especially kidney cancer. Based on the case of 30-year old patient with characteristics of von Hippel-Lindau syndrome as phakomatosis.

  5. Von hippel-lindaus disease: Report of three cases and review of the literature Doença de von Hippel-Lindau: relato de três casos e revisão da literatura

    Directory of Open Access Journals (Sweden)

    Luiz F. Bleggi-Torres

    1995-12-01

    Full Text Available The authors present the autopsy findings of two related patients and the biopsy findings of a thrid member of the family. The oldest member was 34 years old at death and on postmortem examination he had haemangioblastomas in the retina, cerebellum, medulla and spinal cord. Other findings were renal cell carcinoma, phaechromocytoma, cysts of kidney and pancreas, hydromyelia and atypical meningiomas. His brother died when 30 years old. The autopsy revealed haemangioblastomas of cerebellum, renal cell carcinoma and a clear cell cystadenoma of epididymus. The third patient was the daughter of the first and presented with headache and dizziness. CT-scan showed a cerebellar haemangioblastoma. Epidemiological considerations on the commonest visceral and CNS lesions and a review of current diagnostic criteria are discussed.Os autores relatam os achados de autópsia de dois pacientes de uma mesma família e o diagnóstico por biópsia de hemangioblastoma de um terceiro membro desta mesma família. O primeiro paciente tinha 34 anos por ocasião do óbito e os achados de necrópsia mostraram hemangioblastoma de retina, cerebelo, bulbo e medula espinhal, além de carcinoma renal, feocromocitoma, lesões císticas de rim e pâncreas, hidromielia e meningiomas atípicos. Seu irmão morreu com 30 anos de idade e a autópsia revelou hemangioblastomas de cerebelo, carcinoma renal e cistoadenoma de células claras de epididimo. A terceira paciente era filha do primeiro paciente e apresentou cefaléia e ataxia. A tomografia computadorizada mostrou lesão cerebelar cística e a biópsia confirmou tratar-se de hemangioblastoma. São feitas considerações epidemiológicas sobre lesões viscerais e do sistema nervoso mais comumente encontradas, além de discutir critérios diagnósticos.

  6. Dicty_cDB: VSE765 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available :none) Xenopus laevis von Hippel-Lindau b... 127 3e-28 BC092334_1( BC092334 |pid:...32169_1( BC132169 |pid:none) Mus musculus von Hippel-Lindau bin... 124 2e-27 EF087700_1( EF087700 |pid:none)

  7. Dicty_cDB: VSE760 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available |pid:none) Xenopus laevis von Hippel-Lindau b... 127 2e-28 BC092334_1( BC092334 ...7 BC132169_1( BC132169 |pid:none) Mus musculus von Hippel-Lindau bin... 124 2e-27 EF087700_1( EF087700 |pid:

  8. Disease: H00559 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available description, gene) Maher ER, Neumann HP, Richard S von Hippel-Lindau disease: a clinical and scientific revi...amasaki I, Tamura K, Okuda H, Furihata M, Ashida S Von Hippel-Lindau disease: molecular pathological basis, clinical... criteria, genetic testing, clinical features of tumors and treatment. Jpn J Clin Oncol 36:337-43 (2

  9. von Willebrand factor binds to the surface of dendritic cells and modulates peptide presentation of factor VIII.

    Science.gov (United States)

    Sorvillo, Nicoletta; Hartholt, Robin B; Bloem, Esther; Sedek, Magdalena; ten Brinke, Anja; van der Zwaan, Carmen; van Alphen, Floris P; Meijer, Alexander B; Voorberg, Jan

    2016-03-01

    It has been proposed that von Willebrand factor might affect factor VIII immunogenicity by reducing factor VIII uptake by antigen presenting cells. Here we investigate the interaction of recombinant von Willebrand factor with immature monocyte-derived dendritic cells using flow cytometry and confocal microscopy. Surprisingly, von Willebrand factor was not internalized by immature dendritic cells, but remained bound to the cell surface. As von Willebrand factor reduces the uptake of factor VIII, we investigated the repertoire of factor VIII presented peptides when in complex with von Willebrand factor. Interestingly, factor VIII-derived peptides were still abundantly presented on major histocompatibility complex class II molecules, even though a reduction of factor VIII uptake by immature dendritic cells was observed. Inspection of peptide profiles from 5 different donors showed that different core factor VIII peptide sequences were presented upon incubation with factor VIII/von Willebrand factor complex when compared to factor VIII alone. No von Willebrand factor peptides were detected when immature dendritic cells were pulsed with different concentrations of von Willebrand factor, confirming lack of von Willebrand factor endocytosis. Several von Willebrand factor derived peptides were recovered when cells were pulsed with von Willebrand factor/factor VIII complex, suggesting that factor VIII promotes endocytosis of small amounts of von Willebrand factor by immature dendritic cells. Taken together, our results establish that von Willebrand factor is poorly internalized by immature dendritic cells. We also show that von Willebrand factor modulates the internalization and presentation of factor VIII-derived peptides on major histocompatibility complex class II.

  10. Gclust Server: 158408 [Gclust Server

    Lifescience Database Archive (English)

    Full Text Available 158408 DME_CG13221_17864658 Cluster Sequences - 178 Vhl: von Hippel-Lindau CG13221-...o cluster sequences Cluster Sequences Link to related sequences - Sequence length 178 Representative annotation Vhl: von Hippel-Linda

  11. Identification of 3 novel VHL germ-line mutations in Danish VHL patients

    DEFF Research Database (Denmark)

    Dandanell, Mette; Friis-Hansen, Lennart Jan; Sunde, Lone

    2012-01-01

    von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome in which the patients develop retinal and central nervous system hemangioblastomas, pheochromocytomas and clear-cell renal tumors. The autosomal dominant disease is caused by mutations in the VHL gene.......von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome in which the patients develop retinal and central nervous system hemangioblastomas, pheochromocytomas and clear-cell renal tumors. The autosomal dominant disease is caused by mutations in the VHL gene....

  12. Tissue expression and plasma levels of adrenomedullin in renal cancer patients

    DEFF Research Database (Denmark)

    Michelsen, Jens; Thiesson, Helle; Walter, Steen;

    2006-01-01

    The peptide AM (adrenomedullin) is stimulated by hypoxia through HIF-1 (hypoxia-inducible factor-1). The majority of human CC-RCCs (clear cell renal cell carcinomas) display mutations in the tumour suppressor protein von Hippel-Lindau, which leads to constitutively elevated HIF-1. We hypothesized......RNA and peptide expression in tissue and AM plasma concentration were determined. HIF-1alpha was localized in tissue by immunohistochemistry. AM mRNA was elevated in CC-RCC compared with adjacent renal cortex (6-fold, n=18; P

  13. Endolymphatic Sac Tumor Showing Increased Activity on 68Ga DOTATATE PET/CT.

    Science.gov (United States)

    Papadakis, Georgios Z; Millo, Corina; Sadowski, Samira M; Bagci, Ulas; Patronas, Nicholas J

    2016-10-01

    Endolymphatic sac tumors (ELSTs) are rare tumors arising from the epithelium of the endolymphatic sac and duct that can be either sporadic or associated with von Hippel-Lindau (VHL) disease. We report a case of a VHL patient with histologically proven residual ELST who underwent Ga DOTATATE PET/CT showing increased activity (SUVmax, 6.29) by the ELST. The presented case of a VHL-associated ELST with increased Ga DOTATATE uptake indicates cell-surface expression of somatostatin receptors by this tumor, suggesting the potential application of somatostatin receptor imaging using Ga DOTA-conjugated peptides in the workup and management of these patients.

  14. Vasoactive intestinal peptide induces oxidative stress and suppresses metastatic potential in human clear cell renal cell carcinoma.

    Science.gov (United States)

    Vacas, Eva; Bajo, Ana M; Schally, Andrew V; Sánchez-Chapado, Manuel; Prieto, Juan C; Carmena, María J

    2013-01-30

    Molecular mechanisms involved in progression of clear-cell renal-cell carcinomas (ccRCCs) are poorly understood. A common genetic mutation found in ccRCC is the loss of the von Hippel-Lindau (VHL) gene, which contributes to cancer progression and metastasis. We investigated VIP effects on metastatic and angiogenic factors in human VHL-null A498 ccRCC and HK2 renal cells. VIP increased adhesion but decreased expression of metalloproteinases, MMP2 and MMP9, as well as cell migration and VEGF expression and secretion in A498 but not in HK2 cells. VIP enhanced ROS levels and decreased nuclear levels of β-catenin and NFκB p50-subunit in A498 cells, suggesting neuropeptide involvement in the observed decrease of metastatic ability in clear-cell carcinoma. VIP effects in A498 cells were blocked by the VPAC(1/2)-receptor antagonist JV-1-53. In conclusion, present data point to a role of VIP in preventing invasion and metastasis in ccRCCs and support its potential therapeutic usefulness in this disease.

  15. Dicty_cDB: SSE728 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available cromonas sp. RCC299 chromosome... 131 2e-29 BC054252_1( BC054252 |pid:none) Xenopus laevis von Hippel-Lind...4 2e-27 BC132169_1( BC132169 |pid:none) Mus musculus von Hippel-Lindau bin... 124 2e-27 protein update 2009.

  16. Measurements of plasma methoxytyramine, normetanephrine, and metanephrine as discriminators of different hereditary forms of pheochromocytoma

    NARCIS (Netherlands)

    Eisenhofer, G.; Lenders, J.W.M.; Timmers, H.; Mannelli, M.; Grebe, S.K.; Hofbauer, L.C.; Bornstein, S.R.; Tiebel, O.; Adams, K.; Bratslavsky, G.; Linehan, W.M.; Pacak, K.

    2011-01-01

    BACKGROUND: Pheochromocytomas are rare catecholamine-producing tumors derived in more than 30% of cases from mutations in 9 tumor-susceptibility genes identified to date, including von Hippel-Lindau tumor suppressor (VHL); succinate dehydrogenase complex, subunit B, iron sulfur (Ip) (SDHB); and succ

  17. Potential value of EUS in pancreatic surveillance of VHL patients

    NARCIS (Netherlands)

    van Asselt, Sophie Josephien; Brouwers, Adrienne H; van Dullemen, Hendrik M; van der Jagt, Eric J; Bongaerts, Alfons H; Koopmans, Klaas P; Kema, Ido; Zonnenberg, Bernard A; Timmers, Henri Jlm; de Herder, Wouter; Sluiter, Wim; de Vries, Elisabeth G E; Links, T P

    2016-01-01

    Background: Patients with von Hippel-Lindau (VHL) disease are prone to develop pancreatic neuroendocrine tumors (pNETs). However, the best imaging technique for early detection of pNETs in VHL is currently unknown. In a head-to-head comparison, we evaluated endoscopic ultrasound (EUS) and C-11-5-hyd

  18. A Zebrafish Model to Study and Therapeutically Manipulate Hypoxia Signaling in Tumorigenesis

    NARCIS (Netherlands)

    Santhakumar, Kirankumar; Judson, Emma C.; Elks, Philip M.; McKee, Sarah; Elworthy, Stone; van Rooijen, Ellen; Walmsley, Sarah S.; Renshaw, Stephen A.; Cross, Simon S.; van Eeden, Fredericus J. M.

    2012-01-01

    Hypoxic signaling is a central modulator of cellular physiology in cancer. Core members of oxygen-sensing pathway including the von Hippel-Lindau tumor suppressor protein (pVHL) and the hypoxia inducible factor (HIF) transcription factors have been intensively studied, but improved organismal models

  19. Coexistence of intracranial aneurysm and hemangioblastoma: A case report and literature review.

    Science.gov (United States)

    Lü, J; Quan, Y; Xu, G; Gong, S-P

    2016-08-01

    The association of intracranial aneurysm and hemangioblastoma is extremely rare. This report regards a patient affected by Von Hippel-Lindau syndrome with multiple hemangioblastoma and two intracranial aneurysms, of which one was on a hemangioblastoma feeder vessel and the other on an unrelated vessel. Review of the literature revealed 13 other previously reported cases. Possible mechanisms to explain the association are discussed.

  20. MR imaging findings od supratentorail meningeal hemangioblastoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Gi Hong; Lee, Ho Kyu; Koh, Myeong Ju; Maeng, Young Hee [Jeju National University Hospital, Jeju (Korea, Republic of)

    2016-07-15

    Hemangioblastomas account for 1.1-2.5% of intracranial neoplasms. These tumors most commonly occur in the cerebellum. A 77-year-old woman had a hemangioblastoma, which showed the supratentorial meningeal mass without any history of von Hippel-Lindau disease.

  1. Genotype and tumor locus determine expression profile of pseudohypoxic pheochromocytomas and paragangliomas

    NARCIS (Netherlands)

    Shankavaram, U.; Fliedner, S.M.; Elkahloun, A.G.; Barb, J.J.; Munson, P.J.; Huynh, T.T.; Matro, J.C.; Turkova, H.; Linehan, W.M.; Timmers, H.J.L.M.; Tischler, A.S.; Powers, J.F.; Krijger, R. de; Baysal, B.E.; Takacova, M.; Pastorekova, S.; Gius, D.; Lehnert, H.; Camphausen, K.; Pacak, K.

    2013-01-01

    Pheochromocytomas (PHEOs) and paragangliomas (PGLs) related to mutations in the mitochondrial succinate dehydrogenase (SDH) subunits A, B, C, and D, SDH complex assembly factor 2, and the von Hippel-Lindau (VHL) genes share a pseudohypoxic expression profile. However, genotype-specific differences

  2. Interplay between VHL/HIF1alpha and Wnt/beta-catenin pathways during colorectal tumorigenesis.

    NARCIS (Netherlands)

    Giles, R.H.; Lolkema, M.P.; Snijckers, C.M.; Belderbos, M.; Groep, P. van der; Mans, D.A.; Beest, M. van; Noort, M. van; Goldschmeding, R.; Diest, P.J. van; Clevers, H.; Voest, E.E.

    2006-01-01

    Activation of the Wnt signaling pathway initiates the transformation of colorectal epithelial cells, although the transition to metastatic cancer requires angiogenesis. We have investigated the expression of the von Hippel-Lindau (VHL) tumor suppressor in the intestines from humans and mice. Here, w

  3. Fibronectin is a hypoxia-independent target of the tumor suppressor VHL.

    NARCIS (Netherlands)

    Bluyssen, H.A.; Lolkema, M.P.; Beest, M. van; Boone, M.; Snijckers, C.M.; Los, M.; Gebbink, M.F.; Braam, B.; Holstege, F.C.; Giles, R.H.; Voest, E.E.

    2004-01-01

    The von Hippel-Lindau (VHL) tumor suppressor gene regulates the extracellular matrix by controlling fibronectin deposition. To identify novel VHL target genes, we subjected mRNA from VHL-deficient RCC cells (786-0-pRC) and a transfectant re-expressing wildtype VHL (786-0-VHL) to differential express

  4. Dicty_cDB: Contig-U04465-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 01333 |pid:none) Micromonas sp. RCC299 chromosome... 114 5e-24 BC054252_1( BC054252 |pid:none) Xenopus laevis von Hippel-Linda...ein-1 (VBP-1) mR... 110 7e-23 BC132169_1( BC132169 |pid:none) Mus musculus von Hippel-Linda...70_1( BC095370 |pid:none) Danio rerio von Hippel-Lindau bind... 105 1e-21 ( O1805

  5. Cauda equina hemangioblastoma: case report Hemangioblastoma da cauda equina: relato de caso

    Directory of Open Access Journals (Sweden)

    Leodante Batista da Costa Jr

    2003-06-01

    Full Text Available Hemangioblastomas of the spinal cord are rare lesions, and those located at the cauda equina are even rarer. Most commonly these tumors are present in patients with von Hippel-Lindau (VHL syndrome. We describe here the case of a 48 years old woman with a pure radicular hemangioblastoma, not associated with VHL, presenting with radicular pain, diagnosed with magnetic ressonance imaging (MRI and submitted to total resection with a very good outcome. To our knownledge, this is the second report to describe the MRI aspect of histologically proved hemangioblastoma of the cauda equina in a patient without clinical criteria for VHL.Hemangioblastomas da medula espinhal são lesões raras, sendo sua localização na cauda equina ainda mais incomum. Estes tumores são diagnosticados com mais frequência em pacientes portadores da síndrome de Von Hippel-Lindau. Descrevemos o caso mulher de 48 anos hemangioblastoma radicular na cauda equina, diagnosticado com ressonância nuclear magnética, não associado à síndrome de Von Hippel-Lindau, tratado cirurgicamente com ótimo resultado. Em nossa revisão, este é o segundo relato de diagnóstico com ressonância nuclear magnética de hemangioblastoma da cauda equina em paciente sem critérios clínicos da síndrome de Von Hipppel-Lindau.

  6. Laparoscopic Cortical Sparing Adrenalectomy for Pediatric Bilateral Pheochromocytoma: Anesthetic Management

    OpenAIRE

    Rajappa, Geetha Chamanhalli; Anandaswamy, Tejesh Channasandra

    2014-01-01

    Introduction: Pheochromocytoma is a catecholamine-secreting tumor, which is seen rarely in children. These tumors predominantly secrete norepinephrine and epinephrine. They might be familial and associated with hereditary tumors such as Von Hippel-Lindau syndrome and multiple endocrine neoplasia type II. Case Presentation: The child might present with a spectrum of clinical manifestation including hypertension, headache, visual disturbances, and behavioral problems. A meticulous preoperative ...

  7. Primary gastric hemangioblastoma: report of a case

    OpenAIRE

    Horacio N. López Basave; Flavia Morales-Vasquez; Juan Carlos Tenorio Monterrubio; Angel Herrera Gomez; Juan Manuel Ruiz Molina; Gonzalo Montalvo Esquivel; Leonardo Saúl Lino Silva

    2015-01-01

    Capillary hemangioblastoma (CHB) is a benign, highly vascularized tumor that generally occurs in central nervous system either in the setting of von Hippel-Lindau (VHL) disease or, more often, as a solitary sporadic lesion that is increasingly recognized in extraneural sites. We present the case of a 18 year-old man with abdominal pain, nausea and hematemesis, the endoscopy showed polypoid tumor bleeding of 5 cm in gastric antrum. The patients had not signs of VHL disease and was subjected to...

  8. ERK5/BMK1 is a novel target of the tumor suppressor VHL: Implication in clear cell renal carcinoma

    OpenAIRE

    Arias-González, Laura; Moreno-Gimeno, Inmaculada; del Campo, Antonio Rubio; Leticia, Serrano-Oviedo; Valero, María Llanos; Esparís-Ogando, Azucena; de la Cruz-Morcillo, Miguel Ángel; Melgar-Rojas, Pedro; García-Cano, Jesús; Cimas, Francisco José; Hidalgo, María José Ruiz; Prado, Alfonso; Callejas-Valera, Juan Luis; Nam-Cha, Syong Hyun; Giménez-Bachs, José Miguel

    2013-01-01

    Extracellular signal-regulated kinase 5 (ERK5), also known as big mitogen-activated protein kinase (MAPK) 1, is implicated in a wide range of biologic processes, which include proliferation or vascularization. Here, we show that ERK5 is degraded through the ubiquitin-proteasome system, in a process mediated by the tumor suppressor von Hippel-Lindau (VHL) gene, through a prolyl hydroxylation-dependent mechanism. Our conclusions derive from transient transfection assays in Cos7 cells, as well a...

  9. ERK5/BMK1 Is a Novel Target of the Tumor Suppressor VHL: Implication in Clear Cell Renal Carcinoma12

    OpenAIRE

    Arias-González, Laura; Moreno-Gimeno, Inmaculada; del Campo, Antonio Rubio; Serrano-Oviedo, Leticia; Valero, María Llanos; Esparís-Ogando, Azucena; de la Cruz-Morcillo, Miguel Ángel; Melgar-Rojas, Pedro; García-Cano, Jesús; Cimas, Francisco José; Hidalgo, María José Ruiz; Prado, Alfonso; Callejas-Valera, Juan Luis; Nam-Cha, Syong Hyun; Giménez-Bachs, José Miguel

    2013-01-01

    Extracellular signal-regulated kinase 5 (ERK5), also known as big mitogen-activated protein kinase (MAPK) 1, is implicated in a wide range of biologic processes, which include proliferation or vascularization. Here, we show that ERK5 is degraded through the ubiquitin-proteasome system, in a process mediated by the tumor suppressor von Hippel-Lindau (VHL) gene, through a prolyl hydroxylation-dependent mechanism. Our conclusions derive from transient transfection assays in Cos7 cells, as well a...

  10. Decreased serum glucose and glycosylated hemoglobin levels in patients with Chuvash polycythemia: a role for HIF in glucose metabolism

    OpenAIRE

    McClain, Donald A.; Abuelgasim, Khadega A; Nouraie, Mehdi; Salomon-Andonie, Juan; Niu, Xiaomei; Miasnikova, Galina; Polyakova, Lydia A.; Sergueeva, Adelina; Okhotin, Daniel J.; Cherqaoui, Rabia; Okhotin, David; Cox, James E.; Swierczek, Sabina; Song, Jihyun; Simon, M. Celeste

    2012-01-01

    In Chuvash polycythemia, a homozygous 598C>T mutation in the von Hippel-Lindau gene (VHL) leads to an R200W substitution in VHL protein, impaired degradation of α-subunits of hypoxia inducible factor (HIF)-1 and HIF-2, and augmented hypoxic responses during normoxia. Chronic hypoxia of high altitude is associated with decreased serum glucose and insulin concentrations. Other investigators reported that HIF-1 promotes cellular glucose uptake by increased expression of GLUT1 and increased glyco...

  11. Modulation of STAT3 folding and function by TRiC/CCT chaperonin.

    Directory of Open Access Journals (Sweden)

    Moses Kasembeli

    2014-04-01

    Full Text Available Signal transducer and activator of transcription 3 (Stat3 transduces signals of many peptide hormones from the cell surface to the nucleus and functions as an oncoprotein in many types of cancers, yet little is known about how it achieves its native folded state within the cell. Here we show that Stat3 is a novel substrate of the ring-shaped hetero-oligomeric eukaryotic chaperonin, TRiC/CCT, which contributes to its biosynthesis and activity in vitro and in vivo. TRiC binding to Stat3 was mediated, at least in part, by TRiC subunit CCT3. Stat3 binding to TRiC mapped predominantly to the β-strand rich, DNA-binding domain of Stat3. Notably, enhancing Stat3 binding to TRiC by engineering an additional TRiC-binding domain from the von Hippel-Lindau protein (vTBD, at the N-terminus of Stat3, further increased its affinity for TRiC as well as its function, as determined by Stat3's ability to bind to its phosphotyrosyl-peptide ligand, an interaction critical for Stat3 activation. Thus, Stat3 levels and function are regulated by TRiC and can be modulated by manipulating its interaction with TRiC.

  12. [Multiple endocrine neoplasia type 1 (MEN 1): clinical, biochemical and molecular diagnosis and treatment of the associated disturbances].

    Science.gov (United States)

    Hoff, Ana Oliveira; Hauache, Omar Magid

    2005-10-01

    Multiple endocrine neoplasia (MEN) syndromes include types 1 (MEN 1) and 2 (MEN 2), von Hippel-Lindau syndrome, neurofibromatosis type 1 and Carney complex. These are complex genetic syndromes caused by activation or inactivation of different types of genes known to be involved in the regulation of cell proliferation. In this review we will discuss the clinical manifestations and management of the MEN 1 syndrome as well as the genetic screening of potential MEN 1 gene carriers. MEN 1 is a hereditary syndrome, transmitted in an autosomic dominant fashion and caused by an inactivating mutation of the MEN 1 gene, characterized by the development of primary hyperparathyroidism, islet cell tumors and pituitary adenomas. In addition, these patients can present with cutaneous manifestations such as angiofibromas and collagenomas, and can develop other neoplastic manifestations including carcinoids, thyroid tumors, adrenal adenomas, lipomas, pheochromocytomas and meningiomas. The MEN 1 gene encodes a peptide which is a tumor suppressor gene called menin. Several studies have demonstrated its importance in regulation of cell proliferation and have confirmed its role in the pathogenesis of the MEN 1 syndrome. The discovery of the MEN 1 gene and the genetic analysis of MEN 1 patients have resulted in earlier diagnosis and treatment of asymptomatic carriers which can potentially result in a longer survival of these patients. Further investigation of the function and signaling pathways of the menin protein will hopefully offer therapeutic alternatives to patients with malignant progression of MEN 1-related tumors and also result in improved survival.

  13. von Neumann Morgenstern Preferences

    DEFF Research Database (Denmark)

    Vind, Karl

    von Neumann Morgenstern utility is generalized to von Neumann Morgenstern preferences. The proof is an application of simple hyperplane theorems......von Neumann Morgenstern utility is generalized to von Neumann Morgenstern preferences. The proof is an application of simple hyperplane theorems...

  14. von Neumann Morgenstern Preferences

    DEFF Research Database (Denmark)

    Vind, Karl

    2000-01-01

    von Neumann Morgenstern utility is generalized to von Neumann Morgenstern preferences. The proof is an application of simple hyperplane theorems......von Neumann Morgenstern utility is generalized to von Neumann Morgenstern preferences. The proof is an application of simple hyperplane theorems...

  15. A factor VIII-derived peptide enables von Willebrand factor (VWF)-binding of artificial platelet nanoconstructs without interfering with VWF-adhesion of natural platelets.

    Science.gov (United States)

    Haji-Valizadeh, Hassan; Modery-Pawlowski, Christa L; Sen Gupta, Anirban

    2014-05-01

    There is substantial clinical interest in synthetic platelet analogs for potential application in transfusion medicine. To this end, our research is focused on self-assembled peptide-lipid nanoconstructs that can undergo injury site-selective adhesion and subsequently promote site-directed active platelet aggregation, thus mimicking platelet's primary hemostatic actions. For injury site-selective adhesion, we have utilized a coagulation factor FVIII-derived VWF-binding peptide (VBP). FVIII binds to VWF's D'-D3 domain while natural platelet GPIbα binds to VWF's A1 domain. Therefore, we hypothesized that the VBP-decorated nanoconstructs will adhere to VWF without mutual competition with natural platelets. We further hypothesized that the adherent VBP-decorated constructs can enhance platelet aggregation when co-decorated with a fibrinogen-mimetic peptide (FMP). To test these hypotheses, we used glycocalicin to selectively block VWF's A1 domain and, using fluorescence microscopy, studied the binding of fluorescently labeled VBP-decorated nanoconstructs versus platelets to ristocetin-treated VWF. Subsequently, we co-decorated the nanoconstructs with VBP and FMP and incubated them with human platelets to study construct-mediated enhancement of platelet aggregation. Decoration with VBP resulted in substantial construct adhesion to ristocetin-treated VWF even if the A1-domain was blocked by glycocalicin. In comparison, such A1-blocking resulted in significant reduction of platelet adhesion. Without A1-blocking, the VBP-decorated constructs and natural platelets could adhere to VWF concomitantly. Furthermore, the constructs co-decorated with VBP and FMP enhanced active platelet aggregation. The results indicate significant promise in utilizing the FVIII-derived VBP in developing synthetic platelet analogs that do not interfere with VWF-binding of natural platelets but allow site-directed enhancement of platelet aggregation when combined with FMP.

  16. Neuro image in neuroectodermal disorders. Part III: angiomatous and melanotic syndromes. Neuroimagen en los transtornos neuroectodermicos. Parte III: sindromes angiomatosos y melanoticos

    Energy Technology Data Exchange (ETDEWEB)

    Marti-Bonmati, L.; Menor, F.; Poyatos, C.; Cortina, H.; Esteban, M.J.; Vilar, J. (Hospital La Fe Valencia. (Spain))

    1994-01-01

    Twenty-eight consecutive patients affected by these rare angiomatous melanotic neuroectodermal disorders are assessed. The diagnostics value and clinical correlation of neuroimaging methods, both CT and MR, are established. Patients with Sturge-Weber syndrome (15 cases), Klippel-Trenaunay syndrome (1 case), Rendu-Osler disease (3 cases), multiple hemangiomatosis (4 cases), von Hippel-Lindau syndrome (3 cases), neuro cutaneous melanosis (1 case) and hypo melanosis of Ito (1 case) are included. In vascular phacomatosis, neuroimaging methods usually contribute to the positive diagnosis. In melanotic disorders, the neuroradiological findings most often are unspecific and do not contribute to the diagnosis of the disease.

  17. ANATOMÍA PATOLÓGICA Y TUMORES HEREDITARIOS

    Directory of Open Access Journals (Sweden)

    Dra. M. Teresa Vial

    2017-07-01

    Nos referiremos desde el punto de vista patológico a algunas de las neoplasias malignas incluidas en síndromes de cáncer hereditario causados por los principales y más frecuentes genes de predisposición genética. Cáncer de Mama (BRCA1/2, Cáncer Colorectal no Polipósico/Síndrome de Lynch (MMR, Cáncer Gástrico Hereditario, Poliposis adenomatosa familiar (PAF, Cáncer Renal y Síndrome de von Hippel Lindau (VHL y Cáncer Medular de Tiroides (RET.

  18. Laparoscopic cortical sparing adrenalectomy for pediatric bilateral pheochromocytoma: anesthetic management.

    Science.gov (United States)

    Rajappa, Geetha Chamanhalli; Anandaswamy, Tejesh Channasandra

    2014-05-01

    Pheochromocytoma is a catecholamine-secreting tumor, which is seen rarely in children. These tumors predominantly secrete norepinephrine and epinephrine. They might be familial and associated with hereditary tumors such as Von Hippel-Lindau syndrome and multiple endocrine neoplasia type II. The child might present with a spectrum of clinical manifestation including hypertension, headache, visual disturbances, and behavioral problems. A meticulous preoperative preparation is essential for a stable intraoperative and postoperative outcome. We described successful perioperative management of a child who underwent bilateral laparoscopic cortical sparing adrenalectomy and a repeated surgery for the residual tumor removal.

  19. Kinase requirements in human cells: III. Altered kinase requirements in VHL−/− cancer cells detected in a pilot synthetic lethal screen

    OpenAIRE

    Bommi-Reddy, Archana; Almeciga, Ingrid; Sawyer, Jacqueline; Geisen, Christoph; Li, Wenliang; Harlow, Ed; Kaelin, William G.; Grueneberg, Dorre A.

    2008-01-01

    Clear cell renal carcinomas are the most common form of kidney cancer and frequently are linked to biallelic inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene. The VHL gene product, pVHL, has multiple functions including directing the polyubiquitylation of the HIF transcription factor. We screened 100 shRNA vectors, directed against 88 kinases, for their ability to inhibit the viability of VHL−/− renal carcinoma cells preferentially compared with isogenic cells in which pVHL f...

  20. Diagnosis and Management of Hereditary Renal Cell Cancer.

    Science.gov (United States)

    Menko, Fred H; Maher, Eamonn R

    2016-01-01

    Renal cell cancer (RCC) is the common denominator for a heterogeneous group of diseases. The subclassification of these tumours is based on histological type and molecular pathogenesis. Insight into molecular pathogenesis has led to the development of targeted systemic therapies. Genetic susceptibility is the principal cause of RCC in about 2-4% of cases. Hereditary RCC is the umbrella term for about a dozen different conditions, the most frequent of which is von Hippel-Lindau disease . Here, we describe the main hereditary RCC syndromes, consider criteria for referral of RCC patients for clinical genetic assessment and discuss management options for patients with hereditary RCC and their at-risk relatives.

  1. Synthetic lethality-based targets for discovery of new cancer therapeutics.

    Science.gov (United States)

    Weidle, Ulrich H; Maisel, Daniela; Eick, Dirk

    2011-01-01

    Synthetic lethality is based on the incompatibility of cell survival with the loss of function of two or more genes, not with loss of function of a single gene. If targets of synthetic lethality are deregulated or mutated in cancer cells, the strategy of synthetic lethality can result in significant increase of therapeutic efficacy and a favourable therapeutic window. In this review, we discuss synthetic lethality based on deficient DNA repair mechanisms, activating mutations of RAS, loss of function mutations of the tumor suppressor genes p53, Rb and von Hippel-Lindau, and disruption of interactive protein kinase networks in the context of development of new anticancer agents.

  2. Malignant pheochromocytomas and paragangliomas - the importance of a multidisciplinary approach

    DEFF Research Database (Denmark)

    Andersen, Kim Francis; Altaf, Rahim; Krarup-Hansen, Anders;

    2011-01-01

    Approximately 10% of the pheochromocytomas and 20% of the paragangliomas are malignant with poor survival. As the biological behaviour of these tumours cannot be predicted with certainty from pathology the diagnosis of malignancy is difficult. Genetic testing is gaining impact as mutations...... in the tumour suppressor gene Von Hippel-Lindau and the mitochondrial succinate dehydrogenase enzyme complex subunit B (SDHB) are associated with malignancy. Excess release of catecholamines is characteristic for pheochromocytomas. High levels of chromogranin A, that is co-stored and co...

  3. Primary gastric hemangioblastoma: report of a case

    Directory of Open Access Journals (Sweden)

    Horacio N. López Basave

    2015-03-01

    Full Text Available Capillary hemangioblastoma (CHB is a benign, highly vascularized tumor that generally occurs in central nervous system either in the setting of von Hippel-Lindau (VHL disease or, more often, as a solitary sporadic lesion that is increasingly recognized in extraneural sites. We present the case of a 18 year-old man with abdominal pain, nausea and hematemesis, the endoscopy showed polypoid tumor bleeding of 5 cm in gastric antrum. The patients had not signs of VHL disease and was subjected to subtotal gastrectomy and referred to our institution. To our knowledge this is the first reported case of CHB occurring in stomach.

  4. Clinical use of photodynamic therapy in ocular tumors.

    Science.gov (United States)

    Cerman, Eren; Çekiç, Osman

    2015-01-01

    Although the introduction of intravitreal anti-vascular endothelial growth factor drugs reduced the indications for photodynamic therapy in ophthalmology, it may still be used in various ocular tumors. Although many studies have shown that photodynamic therapy is effective in ocular tumors, the literature consists of case reports and series. In this review, we systematically performed a meta-analysis for the use of photodynamic therapy in circumscribed choroidal hemangioma, diffuse choroidal hemangioma, retinal capillary hemangioma, von Hippel-Lindau angiomatosis, choroidal melanoma, retinal astrocytoma, retinoblastoma, eyelid tumors, conjunctival tumors, and choroidal metastasis. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Hemangioblastoma of the optic nerve--case report.

    Science.gov (United States)

    Higashida, Tetsuhiro; Sakata, Katsumi; Kanno, Hiroshi; Kawasaki, Takashi; Tanabe, Yutaka; Yamamoto, Isao

    2007-05-01

    A 64-year-old man presented with a rare sporadic hemangioblastoma arising in the left optic nerve manifesting as left visual disturbance gradually progressive over 5 years. Magnetic resonance imaging revealed a well-enhanced mass in the left optic nerve. Partial resection of the tumor was performed via the frontoorbital approach. The histological diagnosis was optic nerve hemangioblastoma. Hemangioblastoma must be considered in the differential diagnosis of optic nerve tumors even in the absence of other lesions associated with von Hippel-Lindau disease.

  6. Odonaten von Sumatra, gesammelt von Edward Jacobson

    NARCIS (Netherlands)

    Ris, F.

    1927-01-01

    Die folgende Bearbeitung sumatranischer Libellen schliesst sich an zwei frühere Aufsätze über Libellen von Java und von Simalur an, die mir Herr Jacobson anvertraute. Die hier beschriebene wesentlich grössere Sammlung aus den Jahren 1913—15 kam gegen Ende 1920 in meine Hände, sie hätte also längst e

  7. Rheologie von Beschichtungen

    Science.gov (United States)

    Schäffler, Michael

    Die Rheologie beschreibt die Fließ- und Deformationseigenschaften von Materialien. Der Begriff Rheologie ist aus dem Griechischen abgeleitet: rhein - fließen. Erst im Jahre 1930 entwickelte E.C. Bingham und M. Reiner in Easton (USA) die Rheologie zu einer eigenständigen Wissenschaft. Aber bereits seit dem 17. Jahrhundert wurden wesentliche Einzelbeiträge zu Fließphänomenen veröffentlich, so z.B. 1676 von R. Hooke (Hookesches Gesetz) und 1687 von I. Newton (Newtonsches Gesetz). Die Rheologie hat sich bis heute immer mehr zu einer interdisziplinären Wissenschaft entwickelt, die die mechanischen Eigenschaften von Materialien charakterisiert.

  8. Von Triers kristendom

    DEFF Research Database (Denmark)

    Søndergaard, Leif

    2009-01-01

    Lars von Trier er i hans film Antichrist i sin negation af kristendommen stærkt bundet til kristendommens dualistiske verdensbillede. Samtidig er filmen kvindefjendsk. Udgivelsesdato: 2. september......Lars von Trier er i hans film Antichrist i sin negation af kristendommen stærkt bundet til kristendommens dualistiske verdensbillede. Samtidig er filmen kvindefjendsk. Udgivelsesdato: 2. september...

  9. Planung von Hochschulbibliotheken - Tagungsbericht

    Directory of Open Access Journals (Sweden)

    Felicitas Hundhausen

    2015-07-01

    Full Text Available Am 18. November 2014 veranstalteten das HIS-Institut für Hochschulentwicklung und die beiden Herausgeber des "Handbuchs Hochschulbibliothekssysteme", Konstanze Söllner und Wilfried Sühl-Strohmenger, in Hannover eine Tagung zum Thema "Planung von Hochschulbibliotheken". Hier ging es um ausgewählte Aspekte der Planung und Steuerung von Hochschulbibliotheken.

  10. Oligocaene Gastropoden von Buton

    NARCIS (Netherlands)

    Martin, K.

    1935-01-01

    Vor einiger Zeit besehrieb ich eine kleine, eigenartige Molluskenfauna aus tertiären Asphaltkalken von der unbedeutenden Insel Buton, im Südosten von Celebes¹). Seither empfing Herr Prof. Ir. Chr. K. Visser in Delft weitere Versteinerungen aus den Asphaltkalken des Eilands, die nach ihm wahrscheinli

  11. Bevacizumab for the treatment of surgically unresectable cervical cord hemangioblastoma: a case report

    Directory of Open Access Journals (Sweden)

    Omar Ayman I

    2012-08-01

    Full Text Available Abstract Introduction Hemangioblastomas are highly vascular tumors that can arise within the central nervous system as well as other organ systems within the body. They can arise sporadically or as part of von Hippel-Lindau syndrome. Those arising in critical locations within the central nervous system can be difficult to resect surgically and therefore pose a significant challenge and result in morbidity and even mortality. Hemangioblastomas express high levels of vascular endothelial growth factor that drives angiogenesis and tumor progression. We hypothesized that bevacizumab through its inhibitory effect on vascular endothelial growth factor will result in hemangioblastoma tumor regression as well as a meaningful clinical response. Case presentation We present the case of a 51-year-old Caucasian man with surgically unresectable cervical cord hemangioblastoma presenting with progressive weakness leading to quadriparesis. He was treated with bevacizumab and his follow up magnetic resonance imaging scans showed marked tumor regression. After only six cycles of intravenous bevacizumab (10mg/kg every two weeks, he started ambulating after being wheelchair bound. He is currently still receiving treatment almost two years after initiation of bevacizumab. Conclusions We have shown for the first time that bevacizumab can result in significant tumor regression and a sustained clinical improvement in a patient with an otherwise unresectable spinal cord hemangioblastoma. This novel approach can be immensely useful for patients with difficult to resect hemangioblastomas or those with multiple lesions such as in von Hippel-Lindau syndrome.

  12. Interaction between Mnk2 and CBCVHL ubiquitin ligase E3 complex

    Institute of Scientific and Technical Information of China (English)

    WANG Pingzhang; WANG Xin; WANG Feng; CAI Tianjing; LUO Ying

    2006-01-01

    MAP kinase-interacting kinase-2 (Mnk2) is one of the downstream kinases activated by MAP kinases. It phosphorylates the eukaryotic initiation factor 4E (eIF4E), although the role of eIF4E phosphorylation and the role of Mnk2 in the process of protein translation are not well understood. Except for eIF4E, other physiological substrates of Mnk2 are still unidentified. To look for these unidentified substrates and to reveal the physiological function of Mnk2, we performed a yeast two-hybrid screening with Mnk2 as the bait. The results demonstrated Mnk2 could interact with VHL (von Hippel-Lindau tumor suppressor), Rbx1 (ring-box 1) and Cul2 (Cullin2) proteins in yeast cells. Furthermore, we validated the interaction between Mnk2 and VHL proteins in mammalian cells by co-immunoprecipitation analysis. Because the three proteins VHL, Rbx1 and Cul2 are all components of the CBCVHL ubiquitin ligase E3 complex, it has been shown that Mnk2 can interact with CBCVHL complex, and is probably one of the new substrates of the CBCVHL complex. Furthermore, during the interaction of Mnk2 with von Hippel-Lindau (VHL) tumor suppressor- binding protein 1 (VBP1), it appears that Mnk2 also joins to modulate cell shape as VBP1 plays an important role in the process of the maturation of the cytoskeleton and in the process of morphogenesis.

  13. Molecular genetics of pediatric renal cell carcinoma%青少年肾细胞癌分子遗传学研究进展

    Institute of Scientific and Technical Information of China (English)

    饶秋

    2012-01-01

    青少年肾细胞癌少见,占青少年肾肿瘤的2%~6%.该类肿瘤可能与希佩尔-林道(von Hippel-Lindau,VHL)病相关,但大多数为散发性,表现Xp11.2易位/转录因子E3(transcription factor E3,TFE3)基因融合相关性肾癌和t(6;11)(p21;q12) 转录因子EB(transcription factor EB,TFEB)基因融合相关性肾癌.文中就青少年肾细胞癌的分子遗传学研究进展作一综述.%Pediatric renal cell carcinoma ( RCC ) is relatively rare and represent approximately 2% -6% of all renal neoplasms in children and young adults. RCC may be associated with von Hippel-Lindau (VHL) disease, mostly sporadic and correlated with Xp11.2 translocation/TFE3 gene fusion and t(6;11 )( p21 ;ql2 )/Alpha-TFEB gene fusion. This article focuses on the molecular genetics of pediatric RCC.

  14. An Update on the Ophthalmologic Features in the Phakomatoses

    Directory of Open Access Journals (Sweden)

    Solmaz Abdolrahimzadeh

    2016-01-01

    Full Text Available Neurofibromatosis type 1, tuberous sclerosis complex, and Von Hippel-Lindau disease, historically classified as the phakomatoses, are hereditary multisystem disorders characterized by the presence of hamartoma, which carry the risk of malignant transformation. The alteration of tumor suppressor genes seems to be at the basis of their pathophysiogenetic mechanism. Lisch and choroidal nodules in neurofibromatosis type 1, retinal astrocytomas in tuberous sclerosis complex, and retinal capillary hemangioma in Von Hippel-Lindau disease are the principal ophthalmic hamartomatous manifestations. The advent of novel imaging techniques such as near infrared reflectance and optical coherence tomography has provided unprecedented insight on the choroidal and retinal features of these diseases. These methods have improved early diagnosis and the ongoing surveillance in these conditions. Among an array of treatment modalities, antivascular endothelial growth factor therapy has been used in the management of retinal hamartomas but results have been varied. This review is an update on the pathophysiogenetic mechanisms, ophthalmic manifestations, and novel treatment strategies in the phakomatoses with emphasis on the role of imaging techniques.

  15. Untersuchungen ueber den Bau von Orbitolina (Patellina auct.) von Borneo

    NARCIS (Netherlands)

    Martin, K.

    1884-01-01

    Vor einer Reihe von Jahren (1856—57) entdeckte Everwijn am Seberoeang, linken Nebenflusse des Kapoeas, in der West-Abtheilung von Borneo, Schichten mit Versteinerungen, welche von ihm für Nummuliten gehalten wurden. Der Fundort befand sich am rechten Ufer, 4—5 Kilometer von der Mündung des

  16. Ellis Von Creveld Syndrome

    Directory of Open Access Journals (Sweden)

    Afshar H

    1999-01-01

    Full Text Available One patient with Ellis Von Creveld syndrome contains: dwarfism, congenital heart"ndisease, ectodermal dysplasia, polyductyly, an abnormally wide labial frenum and maxillary"nmolars with single root.

  17. Lars von Triers film

    DEFF Research Database (Denmark)

    Nielsen, Lisbeth Overgaard

    2007-01-01

    Afhandlingen undersøger Lars von Triers filmæstetik, som den kommer til udtryk i spillefilmene fra perioden 1984-2007. Afhandlingen analyserer de enkelte films stil, virkningsstrategi og betydningsdannelse.......Afhandlingen undersøger Lars von Triers filmæstetik, som den kommer til udtryk i spillefilmene fra perioden 1984-2007. Afhandlingen analyserer de enkelte films stil, virkningsstrategi og betydningsdannelse....

  18. Energetisches Verhalten von Doppelfassaden

    OpenAIRE

    2002-01-01

    Durch die Forderung nach einer natürlichen Lüftung von Bürogebäuden und einem effektiven Sonnenschutz in Hochhäusern haben Doppelfassaden einen hohen Stellenwert erreicht. Das energetische Verhalten von Doppelfassaden ist Gegenstand zahlreicher Veröffentlichungen. Bisher liegen jedoch nur wenige Messungen in ausgeführten Gebäuden vor.Im Rahmen dieser Arbeit wurden drei Gebäude mit Doppelfassaden detailliert vermessen. Die Langzeitmessungen erfassten über mindestens ein Jahr unter anderem die ...

  19. Kontextualisierung von Queer Theory

    Directory of Open Access Journals (Sweden)

    Anna Voigt

    2008-03-01

    Full Text Available Christine M. Klapeer legt in diesem Einführungsband dar, aus welchen politischen und theoretischen Kontexten heraus sich ‚queer‘ zu einem Begriff mit besonderem politischem und theoretischem Gehalt entwickelt hat. Wesentlich zielt sie dabei auf eine kritische Kontextualisierung von „queer theory”. Die Autorin geht zunächst auf das Gay Liberation Movement ein, grenzt die Queer Theory vom Poststrukturalismus, von feministischen Theorien und den Lesbian and Gay Studies ab, beleuchtet Eckpunkte queeren Denkens und zeichnet schließlich die Entwicklungen in Österreich sowohl politisch-rechtlich als auch bewegungsgeschichtlich und in der Wissenschaftslandschaft nach.

  20. Energetische Verwertung von Biomasse

    Science.gov (United States)

    Zahoransky, Richard; Allelein, Hans-Josef; Bollin, Elmar; Oehler, Helmut; Schelling, Udo

    Etwa 0,1% der Solarenergie wandeln sich durch Photosynthese aus dem Kohlendioxid der Luft in Biomasse um. Die Biomassen sind als Festbrennstoff nutzbar oder zu gasförmigen Brennstoffen weiterverarbeitbar. Zwei Arten von Biomassen sind zu unterscheiden: Anfallende Biomasse

  1. Rhizostomeen von Manila

    NARCIS (Netherlands)

    Stiasny, G.

    1924-01-01

    Die hier beschriebene kleine Scyphomedusen-Sammlung wurde von Herrn Director P. B. Sivickis, Dept. of Zoology, University of Philippines, Manila, dem Rijksmuseum van Natuurlijke Historie in Leiden überwiesen. Das Material wurde im December 1922 in Manila-bay gefischt und befindet sich in bestem Erha

  2. Abschied von Ingeborg Pomp

    OpenAIRE

    Hänsel, Rosemarie

    2007-01-01

    Am 4. Juni 2007 erhielten wir die traurige Nachricht, dass Ingeborg Barbara Pomp, Leiterin i. R. der Stenografischen Sammlung von 1996 bis 2006 nach kurzer schwerer Krankheit verstorben ist. Die Mitarbeiterinnen und Mitarbeiter der Sächsischen Landesbibliothek – Staats- und Universitätsbibliothek trauern um eine liebenswerte Kollegin, die sich immer mit einem Höchstmaß an persönlichem Einsatz für die Weiterentwicklung der Stenografischen Sammlung engagiert hat.

  3. [Genetic tests in oncology practice with emphasis on the RET oncogene and VHL tumor suppressor gene].

    Science.gov (United States)

    Nesković, Gorana; Stanojević, Boban; Palmar, Ivan; Dimitrijević, Bogomir

    2002-07-01

    Molecular oncogenetics is the study of two distinct gene classes participating in the pathogenesis of malignant diseases: proto-oncogenes and tumour suppressors genes. Stepwise alterations in their structure are the basis of malignancy. Structural abnormalities range widely: gross genetic rearrangements including insertions, deletions, gene amplifications and single nucleotide deleotide deletions and substitutions. These gene alterations are determined by gene testing that increasingly are part of clinical diagnosis. Among many applications of oncogene testing is detection of hereditary forms of malignant disease with outstanding prophylactic and therapeutic importance. Along this line, gene testing provided for effective prevention of specific hereditary tumour types. Analysis of hereditary pheochromocytoma two gene tests are established: detection of multiple endocrine neoplasia type 2 (MEN 2) using mutational analysis of RET gene and detection of von Hippel-Lindau syndrome using mutational analysis of VHL gene. These genes were characterized about a decade ago and their structure determined in detail. Numerous studies focus on expression of these genes in different tissues and the function of respective proteins. In extensive epidemiology the following facts are established: hereditary mutations in the RET gene in > 92% of cases with MEN 2 syndrome while in patients with von Hippel-Lindau syndrome hereditary mutations were detected in VHL gene in > 95% of cases. Such a high genotype--phenotype correlation forms the basis for clinical applications. Gene testing in oncology offers numerous advantages. If a patient with pheochromocytoma presents with hereditary mutation in the RET or VHL gene, family gene testing is recommended. Family member with hereditary gene mutation is indicative of the risk level of nearly 100% for MEN 2 or von Hippel-Lindau syndrome. In such cases surgery is warranted (e.g. in MEN 2 total thyroidectomy by the age of (6). Negative findings

  4. Nutzerorientiertes Management von materiellen und immateriellen Informationsobjekten

    OpenAIRE

    Hübsch, Chris

    2001-01-01

    Schaffung einer stabilen, erweiterbaren und skalierbaren Infrastruktur für die Bereitstellung von Diensten im Umfeld von Bibliotheken und ähnlichen wissensanbietenden Einrichtungen unter Verwendung von XML-RPC und Python.

  5. Nutzerorientiertes Management von materiellen und immateriellen Informationsobjekten

    OpenAIRE

    Hübsch, Chris

    2001-01-01

    Schaffung einer stabilen, erweiterbaren und skalierbaren Infrastruktur für die Bereitstellung von Diensten im Umfeld von Bibliotheken und ähnlichen wissensanbietenden Einrichtungen unter Verwendung von XML-RPC und Python.

  6. Theodore von Karman

    Science.gov (United States)

    1950-01-01

    Dr. Theodore von Karman, co-founder of the Jet Propulsion Laboratory (JPL) Pasadena, California was an aeronautical theoretician. His contributions in the fields of aerodynamics and aeronautical engineering are well documented and well known to every aerospace engineer. He was the first winner of the prestigious U.S. Medal of Science presented to him by President John F. Kennedy. As well as being co-founder of JPL, he also was principal founder of a major rocket propulsion firm (Aerojet-General Corp.), the top science advisor to the U.S. Air Force during its transition to jet propulsion aircraft and the top science advisor to NATO. He was, during much of this time, the fountainhead of aerodynamic thought as head of the Guggenheim Aeronautical Laboratory at the California Institute of Technology (GALCIT) in Pasadena, California. In the May 1956 issue of the Journal of Aeronautical Sciences, it was said of him that 'No other man has had so great an impact on the development of aeronautical science in this country. Hundreds of young men became his students and scientific collaborators and were inspired to greater effort.' Dr. William H. Pickering, then director of JPL said in 1960 'We wouldn't have an aeronautical science as we know it today, if it weren't for Dr. Thoedore von Karman.' Under his guidance, Caltech's 10 foot wind tunnel was designed, built and operated. Industry firms such as Douglas, Northrop, Hughes, Lockheed, North American, Vultee and Consolidated all tested new aeronautical designs and concepts in GALCIT's tunnel. Even Boeing's own high-speed wind tunnel was heavily influenced by suggestions from von Karman. The National Advisory Committee for Aeronautics (NACA) became so concerned about GALCIT's growing influence over West coast aviation, it erected the Ames Laboratory in Sunnyvale, California in part to deter an ever widening aeronautical gap that had formed between NACA and GALCIT. From 1936 to 1940, Caltech stood alone as the only university

  7. Acquired von Willebrand Syndrome

    Institute of Scientific and Technical Information of China (English)

    郭涛

    2005-01-01

    @@ Acquired von Willebrand syndrome (AvWS) is kind of bleeding disorder with laboratory findings similar to those in congenital yon Willebrand disease (vWD).AvWS doesn's have any personal or family history of bleeding, but is associated with certain diseases or abnormal conditions or drugs. Although AvWS is being stated as a rare disease, it has gained more and more attention during the past years. Not because of the severity of the disease, but it is more common than we thought and most patients don' t have a proper diagnosis.

  8. Struktur von ABCE1

    OpenAIRE

    Karcher, Annette

    2007-01-01

    ABCE1 ist ein Mitglied der ATP Binding Cassette (ABC) Superfamilie. ABC Proteine binden und hydrolysieren ATP und verändern dabei ihre Konformation. Dadurch können sie mechanochemische Arbeit leisten. Durch drei zusätzliche Domänen unterscheidet sich ABCE1 von allen bislang bekannten und charakterisierten Mitgliedern dieser Familie. Neben den ATP-bindenden Regionen enthält ABCE1 eine cysteinreiche, N-terminale Domäne, welche zwei Eisen-Schwefel-Cluster bindet. Diese Domäne hat hohe s...

  9. Arginine and Tryptophan rich antimicrobial peptides (AMPs) : modifications, application and mode of action

    OpenAIRE

    Penkova, Maya

    2010-01-01

    Da multiresistente Bakterienstämme ein häufiges Problem darstellen, besteht Bedarf an neuen Verbindungen, die keine Resistenzen hervorrufen. Eine solche Verbindungsklasse stellen die kationischen antimikrobiellen Peptide dar (cationic antimicrobial peptides, AMPs). Mithilfe von Festphasenpeptidsynthese wurden Peptide und deren Metallocenanaloga (Ferrocen- und Ruthenocenbiokonjugate) hergestellt und auf ihre biologische Aktivität untersucht. Alle hergestellten Verbindungen zeigten ...

  10. Alejandro Von Humboldt

    Directory of Open Access Journals (Sweden)

    Gerardo Paz Otero

    1965-09-01

    Full Text Available Diverso fue y sigue siéndolo, el destino de los dos hermanos Humboldt, Guillermo y Alejandro. Sino que se inicia con el nacimiento: Guillermo, el mayor, nace el 22 de junio de 1767 en Potsdam, residencia de los emperadores prusianos, la ciudad de los palacios imperiales, el imperio del militarismo germano; su cuna se meció cerca al palacete de Sans-Soussi, donde Federico el Grande forja ba el poderío de Prusia, cultivaba las ciencias y las artes, anfitrionaba a los intelectuales de Europa, y era "vasallo espiritual de Volta ire", según la aguda frase de Goethe. Alejandro viene al mundo dos años después (14 de septiembre de 1769 en Berlín, en la casa burguesa de la Jagerstrasse (calle del cazador que su madre Elizabeth von Humboldt heredara de su primer esposo.

  11. Mikrochirurgische Entfernung von Hirnstammkavernomen

    Directory of Open Access Journals (Sweden)

    Pfisterer W

    2002-01-01

    Full Text Available Der Anteil der Kavernome an allen intrakraniellen vaskulären Malformationen beträgt 14 %. Davon liegen etwa 20 % im Hirnstamm. Bei einer Rezidivblutungsrate von 21 % jährlich ist auch eine Exstirpation im Hirnstamm indiziert. Wir berichten über 3 Patienten mit Hirnstammkavernomen, die in mikrochirurgischer Technik bei geringer Morbidität und ohne Mortalität an unserer Abteilung total exstirpiert wurden. Wir halten die subakute Phase für den besten Zeitpunkt zur Entfernung des Kavernoms, wenn dies der klinisch-neurologische Zustand des Patienten erlaubt. Die mikrochirurgische Exstirpation wurde durch Elektrophysiologie (akustisch und somatosensorisch evozierte Potentiale, Endoskopie und Neuronavigation unterstützt.

  12. Clinical and genetic aspects of phaeochromocytoma.

    Science.gov (United States)

    Opocher, Giuseppe; Schiavi, Francesca; Conton, Pierantonio; Scaroni, Carla; Mantero, Franco

    2003-01-01

    Phaeochromocytoma is a tumour of the adrenal medulla, which, although rare, is a major cause of correctable hypertension with a prevalence of 0.1-0.5% in the hypertensive population. Clinical symptoms include attacks of paroxysmal headache, sweating, palpitations, stress and a sense of imminent death. Often associated with the above is an increase in blood pressure. Despite the fact that the underlying genetic mechanisms of phaeochromocytoma have been well investigated, they are still incompletely understood. In approximately 80% of cases the tumour occurs sporadically, but it may occur in association with type 2 multiple endocrine neoplasia, type 1 neurofibromatosis or von Hippel-Lindau disease. Molecular evidence suggests that other genes such as SDHD or SDHB may control its development; the possibility of other putative phaeochromocytoma genes is currently being investigated.

  13. [Molecular biology of renal cancer: bases for genetic directed therapy in advanced disease].

    Science.gov (United States)

    Maroto Rey, José Pablo; Cillán Narvaez, Elena

    2013-06-01

    There has been expansion of therapeutic options in the management of metastatic renal cell carcinoma due to a better knowledge of the molecular biology of kidney cancers. There are different tumors grouped under the term renal cell carcinoma, being clear cell cancer the most frequent and accounting for 80% of kidney tumors. Mutations in the Von Hippel-Lindau gene can be identified in up to 80% of sporadic clear cell cancer, linking a genetically inheritable disease where vascular tumors are frequent, with renal cell cancer. Other histologic types present specific alterations in molecular pathways, like c-MET in papillary type I tumors, and Fumarase Hydratase in papillary type II tumors. Identification of the molecular alteration for a specific tumor may offer an opportunity for treatment selection based on biomarkers, and, in the future, for developing an engineering designed genetic treatment.

  14. Advances of Hypoxia and Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xuebing LI

    2013-04-01

    Full Text Available Lung cancer is one of the malignant tumors with fastest growing rates in incidence and mortality in our country, also with largest threat to human health and life. However, the exact mechanisms underlying lung cancer development remain unclear. The microenvironment of tumor hypoxia was discovered in 1955, but hypoxia in lung cancer tissues had not been successfully detected till 2006. Further studies show that hypoxia not only functions through the resistance to radiotherapy, but also regulates lung cancer development, invasion, metastasis, chemotherapy resistance and prognosis through an important oncogene HIF (hypoxia inducible factor, with its regulators PHD (prolyl hydroxylase domain and pVHL (product of von Hippel-Lindau gene. Therefore, hypoxia, HIF, PHD and pVHL should be considered as potential therapeutic targets for lung cancer pathogenesis and progression.

  15. RNA Sequencing Reveals Upregulation of RUNX1-RUNX1T1 Gene Signatures in Clear Cell Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Zuquan Xiong

    2014-01-01

    Full Text Available In the past few years, therapies targeted at the von Hippel-Lindau (VHL and hypoxia-inducible factor (HIF pathways, such as sunitinib and sorafenib, have been developed to treat clear cell renal cell carcinoma (ccRCC. However, the majority of patients will eventually show resistance to antiangiogenesis therapies. The purpose of our study was to identify novel pathways that could be potentially used as targets for new therapies. Whole transcriptome sequencing (RNA-Seq was conducted on eight matched tumor and adjacent normal tissue samples. A novel RUNX1-RUNX1T1 pathway was identified which was upregulated in ccRCC through gene set enrichment analysis (GSEA. We also confirmed the findings based on previously published gene expression microarray data. Our data shows that upregulated of the RUNX1-RUNX1T1 gene set maybe an important factor contributing to the etiology of ccRCC.

  16. Lipid-rich variant of pancreatic endocrine tumour with inhibin positivity and microscopic foci of microcystic adenoma-like areas: emphasis on histopathology.

    Science.gov (United States)

    Rao, Anuradha Calicut Kini; Monappa, Vidya; Shetty, Prashanth

    2013-02-01

    Pancreatic endocrine tumours (PETs) are uncommon tumours with typical morphology characterised by relatively uniform cuboidal cells arranged in nests and festoons, with distinctive nuclear salt-and-pepper chromatin. A lipid-rich variant poses diagnostic difficulties in the midst of other pancreatic tumours and metastatic goblet cell carcinoid. A 22-year-old man presented with symptoms of abdominal pain and jaundice. His liver function test and blood glucose level were normal, but computed tomography of the abdomen suggested the presence of a tumour in the head of the pancreas. Specimen obtained by pancreaticoduodenectomy revealed an infiltrating yellow-tan tumour composed of nests and a cribriform arrangement of polygonal vacuolated cells with pyknotic nuclei, along with focal classical areas of PET. Two foci of early serous microcystic adenoma were seen. Immunohistochemistry contributed to the arrival of a conclusive diagnosis. Von Hippel-Lindau disease was excluded in our patient, as other supportive classical features of the syndrome were absent.

  17. 双侧肾癌的诊治进展

    Institute of Scientific and Technical Information of China (English)

    邓国贤

    2011-01-01

    @@ 双侧肾癌临床较少见,发病率约占同时散发肾癌的2%~4%,但在一些家族遗传病中发病率却高达83%,常见的家族遗传病包括:遗传性乳头状肾癌、林道(Von Hippel-Lindau,VHL)病、家族性透明细胞癌和家族性肾腺瘤伴发Birt-Hogg-Dub综合征[1].双侧肾癌主要分同时性双侧肾癌和异时性双侧肾癌.

  18. Structural basis for oxygen degradation domain selectivity of the HIF prolyl hydroxylases

    Science.gov (United States)

    Chowdhury, Rasheduzzaman; Leung, Ivanhoe K. H.; Tian, Ya-Min; Abboud, Martine I.; Ge, Wei; Domene, Carmen; Cantrelle, François-Xavier; Landrieu, Isabelle; Hardy, Adam P.; Pugh, Christopher W.; Ratcliffe, Peter J.; Claridge, Timothy D. W.; Schofield, Christopher J.

    2016-08-01

    The response to hypoxia in animals involves the expression of multiple genes regulated by the αβ-hypoxia-inducible transcription factors (HIFs). The hypoxia-sensing mechanism involves oxygen limited hydroxylation of prolyl residues in the N- and C-terminal oxygen-dependent degradation domains (NODD and CODD) of HIFα isoforms, as catalysed by prolyl hydroxylases (PHD 1-3). Prolyl hydroxylation promotes binding of HIFα to the von Hippel-Lindau protein (VHL)-elongin B/C complex, thus signalling for proteosomal degradation of HIFα. We reveal that certain PHD2 variants linked to familial erythrocytosis and cancer are highly selective for CODD or NODD. Crystalline and solution state studies coupled to kinetic and cellular analyses reveal how wild-type and variant PHDs achieve ODD selectivity via different dynamic interactions involving loop and C-terminal regions. The results inform on how HIF target gene selectivity is achieved and will be of use in developing selective PHD inhibitors.

  19. International workshop on chromosome 3. Final report, April 15, 1991--April 14, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Gemmill, R.M.

    1992-07-01

    The Second Workshop on Human Chromosome 3 was held on April 4--5, 1991 at Denver, Colorado. There were 43 participants representing 8 nations. The workshop participants reviewed the current state of the chromosome 3 map, both physical and genetic, and prepared lists of markers and cell lines to be made commonly available. These markers and cell lines should be incorporated into the mapping efforts of diverse groups to permit the integration of data and development of consensus maps at future workshops. Region specific efforts were described for sections of the chromosome harboring genes thought to be involved in certain diseases including Von Hippel-Lindau disease, 3p-syndrome, lung cancer and renal cancer. Selected papers have been processed separately for inclusion in the Energy Science and Technology Database.

  20. Myelopathy and sciatica induced by an extradural S1 root haemangioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Hermier, M.; Cotton, F.; Froment, J.C. [Department of Radiology, Hopital Neurologique et Neurochirurgical, Lyon (France); Saint-Pierre, G.; Jouvet, A. [Department of Neuropathology, Hopital Neurologique et Neurochirurgical, Lyon (France); Ongolo-Zogo, P. [Department of Radiology, Hopital Neurologique et Neurochirurgical, Lyon (France); Department of Radiology, Hopital Central, Yaounde (Cameroon); Fischer, G. [Department of Neurosurgery, Hopital Neurologique et Neurochirurgical, Lyon (France)

    2002-06-01

    Haemangioblastomas are vascular tumours which mainly involve the central nervous system and retina, often in the setting of von Hippel-Lindau disease. Haemangioblastomas occurring outside the central nervous system are uncommon. Wherever it is, recognising this tumour prior to surgery is desirable, as preoperative embolisation may be considered. We report the clinical, imaging and pathological features of a sporadic sacral root haemangioblastoma in a 58-year-old man with chronic sciatica and myelopathy. The diagnosis was questioned preoperatively because an enlarged sacral foramen, seen to be filled by a highly vascular, enhancing mass and dilated vessels. Myelopathy was attributed to the presumed high venous pressure resulting from increased flow in veins draining the vascular tumour. Microneurosurgical excision was performed after endovascular embolisation and led to persistent clinical improvement. (orig.)

  1. Complete remission with sunitinib in a poor-risk patient with metastatic renal cell carcinoma: the fine balance between toxicity and efficacy.

    Science.gov (United States)

    Massari, Francesco; Ciccarese, Chiara; Bimbatti, Davide; Fantinel, Emanuela; Modena, Alessandra; Simbolo, Michele; Brunelli, Matteo; Artibani, Walter; Martignoni, Guido; Scarpa, Aldo; Tortora, Giampaolo

    2015-04-01

    Sunitinib represents a reasonable therapeutic option for first-line treatment of poor-risk metastatic renal cell carcinoma and the treatment should aim at the delicate balance between managing side effects to improve the toxicity profile and patient compliance to treatment while maintaining anticancer efficacy. Achievement of a complete response, although rare, is possible, even in poor-risk patients. Treatment discontinuation represents a viable alternative for both tumour biology and patients' quality of life. To date, no molecular markers have been identified with prognostic and/or predictive value for guiding therapeutic decisions. Further research should aim at gaining in-depth knowledge of renal cell carcinoma biology for a tailored personalized therapy. We report a case of poor-risk metastatic renal cell carcinoma, with Von Hippel-Lindau loss of function, which achieved and maintained a complete remission after first-line therapy with sunitinib by using a reduced dosage and a modified schedule of treatment.

  2. Multiple cysts in kidneys: A case report

    Directory of Open Access Journals (Sweden)

    K. V. S. Hari Kumar

    2014-01-01

    Full Text Available Von Hippel-Lindau (VHL disease, which is an autosomal dominant inherited disease, is characterized by highly vascularized tumors in different organs. We report a 42-year-old male who presented to our hospital with diarrhea and weight loss of six months′ duration. Ultrasonography of the abdomen revealed bilateral polycystic kidneys with multiple cystic and solid com-ponents as well as polycystic pancreas. A computerized tomography scan of the abdomen revealed bilateral multiple simple and complex renal cysts, cystic lesions in the head and body of the pancreas and a non-enhancing lesion in the left adrenal gland. The features raised the possibility of VHL syndrome and a biopsy of the kidney revealed atypical cells with a suspicion of malignancy. He underwent bilateral nephrectomy and is on maintenance dialysis since then.

  3. Carbonic anhydrases in normal gastrointestinal tract and gastrointestinal tumours

    Institute of Scientific and Technical Information of China (English)

    Antti J. Kivel(a); Jyrki Kivel(a); Juha Saarnio; Seppo Parkkila

    2005-01-01

    Carbonic anhydrases (CAs) catalyse the hydration of CO2to bicarbonate at physiological pH. This chemical interconversion is crucial since HCO3- is the substrate for several biosynthetic reactions. This review is focused on the distribution and role of CA isoenzymes in both normal and pathological gastrointestinal (GI) tract tissues. It has been known for many years that CAs are widely present in the GI tract and play important roles in several physiological functions such as production of saliva, gastric acid, bile, and pancreatic juice as well as in absorption of salt and water in intestine. New information suggests that these enzymes participate in several processes that were not envisioned earlier. Especially, the recent reports on plasma membranebound isoenzymes Ⅸ and Ⅻ have raised considerable interest since they were reported to participate in cancer invasion and spread. They are induced by tumour hypoxia and may also play a role in von Hippel-Lindau (VHL)-mediated carcinogenesis.

  4. [Current strategies in the treatment of renal-cell cancer: targeted therapies].

    Science.gov (United States)

    Trigo, José Manuel; Bellmunt, Joaquim

    2008-03-22

    Renal-cell carcinoma represents 95% of all renal tumours. The Von Hippel-Lindau (VHL) tumor-suppressor gene is mutated or silenced in most clear cell renal carcinomas. pVHL loss results in the stabilization of the heterodimeric transcription factor hypoxia-inducible factor (HIF) and enhanced transactivation of HIF target genes. HIF itself has been difficult to inhibit with drug-like molecules although a number of agents that indirectly inhibit HIF, including mTOR (mammalian target of rapamycin) inhibitors, have been identified. Moreover, a number of drugs have been developed that target HIF-responsive gene products, such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), implicated in tumor angiogenesis. Many of these targeted therapies, especially sunitinib, have demonstrated significant activity in kidney cancer clinical trials and represent a substantive advance in the treatment of this disease.

  5. CASE REPORT: Papillary Adenoma of Kidney- An Incidental Autopsy Finding: Report of Two Cases

    Directory of Open Access Journals (Sweden)

    Bhakti D. Deshmukh

    2012-01-01

    Full Text Available Background: Renal papillary adenoma is usually an incidental finding at autopsy with an incidence of 7% to 23%. The frequency of small papillary tumours of kidney increases with age to approximately 40% of the population over the age of 65. These tumours occur morefrequently in scarred kidneys, acquired renal cystic disease and in children with von Hippel-Lindau syndrome. Case history: In this report we describe renal papillary adenoma incidentally detected during autopsies of two elderly males. Gross examination of kidneyshowed two tiny subcapsular yellowish nodules in one case and single nodule with similar morphology in the other. Microscopic examination in both the cases showed a well circumscribed tumour composed of densely packed tubules and papillae lined by small cuboidal to columnar cells with rounded uniform nuclei. However there was no nuclear atypia, mitosis or necrosis.

  6. Familial Investigations of Childhood Cancer Predisposition

    Science.gov (United States)

    2017-10-11

    Acute Leukemia; Adenomatous Polyposis; Adrenocortical Carcinoma; AML; BAP1 Tumor Predisposition Syndrome; Carney Complex; Choroid Plexus Carcinoma; Constitutional Mismatch Repair Deficiency Syndrome; Diamond-Blackfan Anemia; DICER1 Syndrome; Dyskeratosis Congenita; Emberger Syndrome; Familial Acute Myeloid Leukaemia; Familial Adenomatous Polyposis; Fanconi Anemia; Familial Cancer; Familial Wilms Tumor; Familial Neuroblastoma; GIST; Hereditary Breast and Ovarian Cancer; Hereditary Paraganglioma-Pheochromocytoma Syndrome; Hodgkin Lymphoma; Juvenile Polyposis; Li-Fraumeni Syndrome; Lynch Syndrome; MDS; Melanoma Syndrome; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2; Neuroblastoma; Neurofibromatosis Type 1; Neurofibromatosis Type II; Nevoid Basal Cell Carcinoma Syndrome; Non Hodgkin Lymphoma; Noonan Syndrome and Other Rasopathy; Overgrowth Syndromes; Pancreatic Cancer; Peutz-Jeghers Syndrome; Pheochromocytoma/Paraganglioma; PTEN Hamartoma Tumor Syndrome; Retinoblastoma; Rhabdoid Tumor Predisposition Syndrome; Rhabdomyosarcoma; Rothmund-Thomson Syndrome; Tuberous Sclerosis; Von Hippel-Lindau Disease

  7. Systematic genetic screening in a prospective group of Danish patients with pheochromocytoma

    DEFF Research Database (Denmark)

    Hansen, Morten Steen Svarer; Jacobsen, Niels; Frederiksen, Anja Lisbeth

    2017-01-01

    Recent guidelines recommend consideration of genetic screening in all newly diagnosed patients with pheochromocytoma. Patients diagnosed with pheochromocytoma in the Region of Southern Denmark during 2006-2013 without previously recognized monogenetic etiology were offered genetic screening...... for mutations in the VHL, RET, SDHB, SDHC, and SDHD genes. A total of 41 patients were included, and genetic data were available in 35. In four of the 35 patients, a pathogenic variant was identified prior to the diagnosis of pheochromocytoma (von Hippel-Lindau disease, n=2; neurofibromatosis type 1, n=2......). The patients carrying a genetic mutation were all younger than 45 years at time of diagnosis of pheochromocytoma, two patients presented with bilateral tumors, and one patient had a positive family history of pheochromocytoma. Genetic screening of the remaining 31 patients did not identify any mutations...

  8. A Rare Case of Endolymphatic Sac Tumour: Clinicopathologic Study and Surgical Management

    Directory of Open Access Journals (Sweden)

    Emanuele Ferri

    2014-01-01

    Full Text Available Objective. Endolymphatic sac tumor (ELST is a rare neoplasm arising from the intrapetrous portion of the endolymphatic sac, either isolated or in association with the von Hippel-Lindau disease. We report a sporadic case of ELST with an overview of the literature and a discussion of clinic-radiological, histopathologic, and surgical findings. Case Report. A young woman presented with a progressive hearing loss in the left ear. Otoscopy showed a reddish, bleeding hypotympanic mass. CT demonstrated an expansile lytic mastoid lesion extending to the middle ear, with bone erosion. MRI confirmed a lesion of increased signal on T1-weighted sequences. The patient underwent a canal wall-down tympanoplasty with complete removal of the tumor. Histopathology was consistent with a papillary ELST. Immunohistochemistry was positive for cytokeratin and chromogranin A. Conclusion. This paper highlights the rarity of ELST, the need for an accurate neuroradiological and immunohistochemical study at the early stages, and the timeliness of surgical treatment.

  9. Genetic testing by cancer site: endocrine system.

    Science.gov (United States)

    Pilarski, Robert; Nagy, Rebecca

    2012-01-01

    Numerous hereditary syndromes, caused by mutations in multiple tumor suppressor genes and oncogenes, can cause tumors in organs of the endocrine system. The primary syndromes (and genes) addressed here include multiple endocrine neoplasia types 1 and 2 (MEN1 and RET genes), Cowden syndrome (PTEN), hereditary pheochromocytoma/paraganglioma syndromes (multiple genes), and von Hippel-Lindau disease (VHL). Clinical genetic testing is available for each of these syndromes and is generally directed to individuals with endocrine or other tumors and additional features suggestive of a hereditary syndrome. However, for some endocrine tumors, the proportion because of heredity is so high that genetic testing may be appropriate for all affected individuals. Management for hereditary cases typically involves aggressive screening and/or surgical protocols, starting at young ages to minimize morbidity and mortality. Endocrine tumors can be less commonly seen in a number of other hereditary syndromes (eg, neurofibromatosis), which are not reviewed in this section.

  10. The Oxygen Sensor PHD2 Controls Dendritic Spines and Synapses via Modification of Filamin A

    Directory of Open Access Journals (Sweden)

    Inmaculada Segura

    2016-03-01

    Full Text Available Neuronal function is highly sensitive to changes in oxygen levels, but how hypoxia affects dendritic spine formation and synaptogenesis is unknown. Here we report that hypoxia, chemical inhibition of the oxygen-sensing prolyl hydroxylase domain proteins (PHDs, and silencing of Phd2 induce immature filopodium-like dendritic protrusions, promote spine regression, reduce synaptic density, and decrease the frequency of spontaneous action potentials independently of HIF signaling. We identified the actin cross-linker filamin A (FLNA as a target of PHD2 mediating these effects. In normoxia, PHD2 hydroxylates the proline residues P2309 and P2316 in FLNA, leading to von Hippel-Lindau (VHL-mediated ubiquitination and proteasomal degradation. In hypoxia, PHD2 inactivation rapidly upregulates FLNA protein levels because of blockage of its proteasomal degradation. FLNA upregulation induces more immature spines, whereas Flna silencing rescues the immature spine phenotype induced by PHD2 inhibition.

  11. 经瞳孔温热疗法在眼科的应用

    Institute of Scientific and Technical Information of China (English)

    傅扬; 俞素勤; 张皙

    2001-01-01

    @@ 经瞳孔温热疗法(transpupillary thermotherapy,TTT)是近年来国外应用于眼科治疗的一种新方法,主要应用于脉络膜黑色素瘤(choroidal melanoma)、视网膜母细胞瘤(retinoblastoma,Rb)、脉络膜血管瘤(circumscribed choroidal hemangiomas)、视网膜血管瘤(von-Hippel-Lindau disease)以及年龄相关性黄斑变性(age-related macular degeneration,AMD)引起的脉络膜新生血管(choroidal neovaseularizationCNV)等疾病,在国内也已受到重视并开始应用.本文就此作一综述.

  12. von Willebrand Disease (For Parents)

    Science.gov (United States)

    ... to classify the type of von Willebrand disease platelet function tests, which determine how well the platelets work ... for pain or fever. These drugs interfere with platelet function and can increase the risk of bleeding. It ...

  13. Kleben von Kunststoff mit Metall

    CERN Document Server

    Brockmann, W; Käufer, H

    1989-01-01

    Das Buch behandelt das Kleben von Kunststoffen mit Metallen in einer fur den Praktiker verstandlichen und umsetzbaren Form. Es leitet zu Klebeverfahren an, die optimale Ergebnisse hinsichtlich Qualitat, Dauerhaftigkeit und Wirtschaftlichkeit liefern.

  14. Planung und Bewertung von Montagesystemen

    Science.gov (United States)

    Hartel, Marko; Lotter, Bruno

    Die Gestaltung von Montagesystemen ist eine wesentliche Aufgabenstellung an die planenden Bereiche eines Unternehmens. Anhand von Praxis-beispielen werden Planungssystematiken and Bewertungsverfahren — sei es fur die Effizienzsteigerung einer bestehenden Montage oder die Entscheidung zwischen Varianten eines geplanten Montagesystems — aufzeigt. Die folgende Planungssystematik nach REFA wird für Produktionssysteme im Allgemeinen angewandt; die Planungssystematik nach Lotter ist speziell auf Montagesysteme ausgelegt.

  15. Theorie und Praxis von Hochschulrankings

    OpenAIRE

    Hornbostel, Stefan

    2007-01-01

    Der Beitrag gibt einen Überblick über die theoretische Grundlage von Hochschulrankings, welche in der qualitativ stark differenzierten Hochschullandschaft in Deutschland entscheidend für öffentliche Reputationsurteile sein können. Ausgehend von einem formal gleichrangigen Institutionengefüge der Hochschullandschaft in Deutschland haben die Stichworte Profilbildung, Exzellenz und Wettbewerb in den letzten Jahren zunehmend an Bedeutung gewonnen. Der daraus resultierende große Informationsbedarf...

  16. Hemangioblastomas: achados clínicos, epidemiológicos e anatomopatológicos em 14 casos Haemangioblastomas: clinical, epidemiological and pathological findings in 14 cases

    Directory of Open Access Journals (Sweden)

    EMERSON LEANDRO GASPARETTO

    2000-06-01

    Full Text Available Relatamos os achados clínicos, epidemiológicos e anatomopatológicos de 14 casos de hemangioblastoma. Sessenta e quatro por cento ocorreram em pacientes do sexo masculino, com idades variando de 16 a 60 anos, com média de 34,4 anos. Nove localizaram-se no cerebelo. Os sintomas mais comuns foram cefaléia (n=7 e tontura (n=7, com período médio de evolução de 70 dias. O diagnóstico de síndrome de von Hippel-Lindau (vHL foi feito em 3 pacientes. Onze pacientes foram submetidos a ressecção cirúrgica total e 3 a exérese parcial. Evidenciou-se recidiva em 28% dos casos, em 3 anos de acompanhamento. Os pacientes com vHL apresentaram recidiva em 66% dos casos. Estes achados aproximam-se dos encontrados na literatura, enfatizando a morbidade deste tumor quando associado à vHL.We report the clinical, epidemiological and pathological findings of 14 patients with haemangioblastoma. Sixty-four percent occurred in males, with ages ranging from 16 to 60 years, with an average of 34,4 years. Most of the tumours were confined to the cerebellum (n=9. The most frequent symptoms were headache (n=7 and dizziness (n=7, with a mean duration of 70 days. Von Hippel-Lindau syndrome (vHL was diagnosed in 3 patients. Eleven patients were submitted to total surgical removal and in 3 the tumour was partially ressected. A relapse rate of 28% in 3 years of follow-up was found. The patients with vHL showed recurrence in 66% of the cases. These findings corroborate those in current medical literature, showing an increased morbidity of this tumor when associated with vHL.

  17. Erythrocytosis-associated HIF-2α Mutations Demonstrate a Critical Role for Residues C-terminal to the Hydroxylacceptor Proline*

    Science.gov (United States)

    Furlow, Paul W.; Percy, Melanie J.; Sutherland, Scott; Bierl, Charlene; McMullin, Mary Frances; Master, Stephen R.; Lappin, Terence R. J.; Lee, Frank S.

    2009-01-01

    A classic physiologic response to hypoxia in humans is the up-regulation of the ERYTHROPOIETIN (EPO) gene, which is the central regulator of red blood cell mass. The EPO gene, in turn, is activated by hypoxia inducible factor (HIF). HIF is a transcription factor consisting of an α subunit (HIF-α) and a β subunit (HIF-β). Under normoxic conditions, prolyl hydroxylase domain protein (PHD, also known as HIF prolyl hydroxylase and egg laying-defective nine protein) site specifically hydroxylates HIF-α in a conserved LXXLAP motif (where underlining indicates the hydroxylacceptor proline). This provides a recognition motif for the von Hippel Lindau protein, a component of an E3 ubiquitin ligase complex that targets hydroxylated HIF-α for degradation. Under hypoxic conditions, this inherently oxygen-dependent modification is arrested, thereby stabilizing HIF-α and allowing it to activate the EPO gene. We previously identified and characterized an erythrocytosis-associated HIF2A mutation, G537W. More recently, we reported two additional erythrocytosis-associated HIF2A mutations, G537R and M535V. Here, we describe the functional characterization of these two mutants as well as a third novel erythrocytosis-associated mutation, P534L. These mutations affect residues C-terminal to the LXXLAP motif. We find that all result in impaired degradation and thus aberrant stabilization of HIF-2α. However, each exhibits a distinct profile with respect to their effects on PHD2 binding and von Hippel Lindau interaction. These findings reinforce the importance of HIF-2α in human EPO regulation, demonstrate heterogeneity of functional defects arising from these mutations, and point to a critical role for residues C-terminal to the LXXLAP motif in HIF-α. PMID:19208626

  18. Prognostic and predictive value of VHL gene alteration in renal cell carcinoma: a meta-analysis and review.

    Science.gov (United States)

    Kim, Bum Jun; Kim, Jung Han; Kim, Hyeong Su; Zang, Dae Young

    2017-01-17

    The von Hippel-Lindau (VHL) gene is often inactivated in sporadic renal cell carcinoma (RCC) by mutation or promoter hypermethylation. The prognostic or predictive value of VHL gene alteration is not well established. We conducted this meta-analysis to evaluate the association between the VHL alteration and clinical outcomes in patients with RCC. We searched PUBMED, MEDLINE and EMBASE for articles including following terms in their titles, abstracts, or keywords: 'kidney or renal', 'carcinoma or cancer or neoplasm or malignancy', 'von Hippel-Lindau or VHL', 'alteration or mutation or methylation', and 'prognostic or predictive'. There were six studies fulfilling inclusion criteria and a total of 633 patients with clear cell RCC were included in the study: 244 patients who received anti-vascular endothelial growth factor (VEGF) therapy in the predictive value analysis and 419 in the prognostic value analysis. Out of 663 patients, 410 (61.8%) had VHL alteration. The meta-analysis showed no association between the VHL gene alteration and overall response rate (relative risk = 1.47 [95% CI, 0.81-2.67], P = 0.20) or progression free survival (hazard ratio = 1.02 [95% CI, 0.72-1.44], P = 0.91) in patients with RCC who received VEGF-targeted therapy. There was also no correlation between the VHL alteration and overall survival (HR = 0.80 [95% CI, 0.56-1.14], P = 0.21). In conclusion, this meta-analysis indicates that VHL gene alteration has no prognostic or predictive value in patients with clear cell RCC.

  19. Vergleich von simulierten und reellen Schleppkurven von Landmaschinen

    Directory of Open Access Journals (Sweden)

    Steffen Hürter

    2014-02-01

    Full Text Available An das landwirtschaftliche Wegenetz werden durch die kontinuierliche Größenentwicklung von Landmaschinen neue Anforderungen gestellt. Die Maschinen werden breiter und länger und besitzen mehr Achsen und komplexere Lenksysteme als in der Vergangenheit. Beim landwirtschaftlichen Wegebau hat dies insbesondere Auswirkungen auf die Planung der Kurven. In der Untersuchung wurden die Schleppkurven aktueller Landmaschinen aufgenommen und es wurde geprüft, ob sie mithilfe einer Software simuliert werden können. Dabei zeigt sich, dass die verwendete Simulationssoftware für die Bestimmung von Schleppkurven für Landmaschinen mit komplexen Lenksystemen hinreichend genau ist.

  20. Ethnographische Filme und die Darstellung von Frauen

    Directory of Open Access Journals (Sweden)

    Judith Keilbach

    2002-03-01

    Full Text Available In dieser Filmographie werden ethnographische und koloniale Filme aus dem Bestand des Nederlands Filmmuseum kommentiert, die für die Frage nach der Darstellung von Frauen und Geschlechterverhältnissen von Interesse sind.

  1. Bibliographie der Werke von Herbert Spencer

    OpenAIRE

    Schmid, Michael (Prof.)

    1991-01-01

    Bibliographie der Werke von Herbert Spencer / bearb., hrsg., mit e. Einl. u. e. Kurzbiogr. vers. von Michael Schmid u. Margit Weihrich. - München : Inst. für Soziologie u. Gesellschaftspolitik, Univ. d. Bundeswehr, 1991. - 159 S.

  2. Diskriminierung von Enantiomeren mit chiralen Selektoren

    OpenAIRE

    Würthner, Stefan

    2007-01-01

    Die vorliegende Dissertation befasst sich mit der systematischen Aufklärung von zwischenmolekularen Wirt-Gast-Wechselwirkungen von Arzneistoffen mit Cyclodextrinen. In einem sich trichterförmig verengenden Erkenntnisprozeß wird im ersten Schritt eine breite Datenbasis von Kapillarelektrophorese-Daten von 86 chiralen Arzneistoffen mit 3 nativen CDs (alpha, beta und gamma) sowie 11 CD-Derivaten gewonnen. Sowohl die Trennfaktoren der Enantiomeren (alpha_m) als auch die Retardierungsfaktoren (R_m...

  3. [Pheochromocytoma and von Recklinghausen's disease].

    Science.gov (United States)

    Rabii, R; Fekak, H; Moufid, K; Joual, A; Bennani, S; el Mrini, M; Benjelloun, S

    2002-07-01

    The association between von Recklinghausen's disease and pheochromocytoma is present about 10% of cases. We report a case of 49 years old women who presented with elevated blood pressure and von Recklinghausen's neurofibromatosis. Laboratory examination showed a marked level in the urinary excretion of cathecholamine. The computed tomography showed a right adrenal tumor suggesting a pheochromocytoma. The adrenalectomy was realised by transabdominal approach and the histological examination confirmed a benign pheochromocytoma. The authors discuss the pathogenetic hypothesis of this rare pathological association, the diagnostic methods and the therapeutic procedure.

  4. An Invitation from Lars von Trier

    DEFF Research Database (Denmark)

    Skadhauge, Troels; Tønder, Lars

    2015-01-01

    Translation of Martin Krasnik interview with Lars von Trier broadcast on DR2, January 12, 2015. The following is an interview of Lars von Trier (LvT) by the Danish journalist Martin Krasnik (MK). The interview took place in Lars von Trier’s home in Brede, a small town just outside Copenhagen...

  5. Kardiale Wirkungen von authentischem PTHrP und dessen N-terminalen Peptidfragmenten

    OpenAIRE

    Katzer, Christian

    2003-01-01

    Parathormone (PTH) und PTH-related Peptide (PTHrP) vermitteln Wirkungen an das kardiovaskuläre System, die physiologische Rollen dabei sind noch weitestgehend unbekannt. Die Verlängerung des PTHrP im Vergleich zum PTH am COOH-terminalen Ende des Moleküls weist auf die Existenz spezieller PTHrP-Rezeptoren hin. PTHrP vermittelt so über die Aktivierung der Adenylatzyklase oder der Phospholipase C Wirkungen, die sich von denen des PTH unterscheiden. Kardiovaskuläre Effekte von PTHrP auf adulte...

  6. Homopteren von Java, gesammelt von Herrn Edw. Jacobson

    NARCIS (Netherlands)

    Melichar, L.

    1914-01-01

    Herr Edw. Jacobson hat auf Java in den Jahren 1908— 1910 Homopteren gesammelt und mir die Bearbeitung des gesammelten Materiales übertragen. Die Jacobson’sche Ausbeute ist insoferne bemerkenswert, als dieselbe viele Mikrohomopteren enthält, welche von nichtfachkundigen Sammlern gewöhnlich nicht

  7. Homopteren von Java, gesammelt von Herrn Edw. Jacobson

    NARCIS (Netherlands)

    Melichar, L.

    1914-01-01

    Herr Edw. Jacobson hat auf Java in den Jahren 1908— 1910 Homopteren gesammelt und mir die Bearbeitung des gesammelten Materiales übertragen. Die Jacobson’sche Ausbeute ist insoferne bemerkenswert, als dieselbe viele Mikrohomopteren enthält, welche von nichtfachkundigen Sammlern gewöhnlich nicht beac

  8. Integration von Erkennung und Interpretation von gesprochener Sprache

    OpenAIRE

    Fink, Gernot A.; Kummert, Franz; Sagerer, Gerhard; Kunze, Jürgen

    1994-01-01

    Die Mehrzahl der heutigen sprachverstehenden Systeme sind aus zwei sehr unterschiedlichen Verarbeitungskomponenten aufgebaut, einer meist statistischen Spracherkennungskomponente und einer in der Regel wissensbasiert arbeitenden Komponente zur Interpretation. Die Kommunikation zwischen diesen Verarbeitungseinheiten ist stark eingeschränkt. In der Regel werden von der Spracherkennung nur Worthypothesenmengen berechnet und an die Interpretationskomponente weitergereicht ohne weitere Interaktion...

  9. Zur Soziologie von Ctenidium molluscum

    NARCIS (Netherlands)

    Zijlstra, Gea

    1979-01-01

    Bei einer Untersuchung in einer Anzahl von niederländischen „blauwgraslanden“ (d. h. „blaue Wiesen“, Cirsio-Molinietum, Junco-Molinion) wurde Ctenidium molluscum angetroffen, eine Art, welche in den Niederlanden mehr oder weniger zum Mesobromion gerechnet wird. Untersuchungen an altem Herbarmaterial

  10. [Friedrich Ludwig von Maydelli pildid Baltimaade ajaloost = Friedrich Ludwig von Maydells Baltische Geschichte in Bildern = Friedrich Ludwig von Maydell ́s Baltic history in images] / Ulrike Plath

    Index Scriptorium Estoniae

    Plath, Ulrike, 1972-

    2014-01-01

    Arvustus: Friedrich Ludwig von Maydelli pildid Baltimaade ajaloost = Friedrich Ludwig von Maydells Baltische Geschichte in Bildern = Friedrich Ludwig von Maydell ́s Baltic history in images. Eesti kunstimuuseum, Kadrioru kunstimuuseum. Tallinn 2013

  11. [Friedrich Ludwig von Maydelli pildid Baltimaade ajaloost = Friedrich Ludwig von Maydells Baltische Geschichte in Bildern = Friedrich Ludwig von Maydell ́s Baltic history in images] / Ulrike Plath

    Index Scriptorium Estoniae

    Plath, Ulrike, 1972-

    2014-01-01

    Arvustus: Friedrich Ludwig von Maydelli pildid Baltimaade ajaloost = Friedrich Ludwig von Maydells Baltische Geschichte in Bildern = Friedrich Ludwig von Maydell ́s Baltic history in images. Eesti kunstimuuseum, Kadrioru kunstimuuseum. Tallinn 2013

  12. Schätzung von Vegetationsparametern aus multispektralen Fernerkundungsdaten

    OpenAIRE

    2007-01-01

    In der vorliegenden Arbeit wird ein Verfahren zur Schätzung von Vegetationsparametern aus multispektralen Fernerkundungsdaten unter Verwendung von physikalischen Strahlungstransfer-Modellen und einer geringen Anzahl von Bodenmessungen vorgestellt. Dieses Verfahren wurde über einen Zeitraum von zwei Jahren exemplarisch an verschiedenen Winterweizenfeldern getestet, die mit einem Daedalus ATM Multispektralscanner aufgenommen wurden. Von besonderem Interesse sind hierbei die Schwankungen der Veg...

  13. Shock, diaschisis and von Monakow

    Directory of Open Access Journals (Sweden)

    Eliasz Engelhardt

    2013-07-01

    Full Text Available The concept of shock apparently emerged in the middle of the 18th century (Whyett as an occurrence observed experimentally after spinal cord transection, and identified as "shock" phenomenon one century later (Hall. The concept was extended (Brown-Séquard and it was suggested that brain lesions caused functional rupture in regions distant from the injured one ("action à distance". The term "diaschisis" (von Monakow, proposed as a new modality of shock, had its concept broadened, underpinned by observations of patients, aiming at distinguishing between symptoms of focal brain lesions and transitory effects they produced, attributable to depression of distant parts of the brain connected to the injured area. Presently, diaschisis is related mainly to cerebrovascular lesions and classified according to the connection fibers involved, as proposed by von Monakow. Depression of metabolism and blood flow in regions anatomically separated, but related by connections with the lesion, allows observing diaschisis with neuroimaging.

  14. Moose von Inselbergen in Benin

    OpenAIRE

    Frahm, Jan-Peter; Porembski, Stefan

    1998-01-01

    Acht Leber- und zehn Laubmoosarten werden von Inselbergen aus Benin angegeben. Fünf der Lebermoose (Acrolejeunea emergens, Riccia atropurpurea, R. congoana, R. discolor, R. moenkemeyeri) und alle Laubmoose (Archidium ohioense, Brachymenium acuminatum, B. exile, Bryum arachnoideum, B. argenteum, Bryum deperssum, Garckea moenkemeyeri, Hyophila involuta, Philonotis mniobryoides und Weissia cf. edentula) werden neu für Benin angegeben. Eight liverworts and ten mosses are reported from inselber...

  15. An integumentary mucin (FIM-B.1) from Xenopus laevis homologous with von Willebrand factor.

    Science.gov (United States)

    Probst, J C; Gertzen, E M; Hoffmann, W

    1990-07-03

    We present a new protein from X. laevis skin termed "frog integumentary mucin B.1" (FIM-B.1) with a general structure similar to FIM-A.1 (formerly "spasmolysin"). The central region consisting of tandem repeats of 11 amino acid residues is probably a target for extensive O-glycosylation, whereas the C-terminal cysteine-rich domain shows pronounced homology with the C1-C2 domains and the C-terminal end of von Willebrand factor. Furthermore, we describe homology with antistasin, an anticoagulant peptide from a leech. We also discuss some implications concerning the evolutionary origin of von Willebrand factor. In situ hybridization studies revealed the expression of FIM-B.1 exclusively in mucous glands of the skin. This is comparable with FIM-A.1 but is in contrast to all other physiologically active peptides, which are synthesized in granular glands.

  16. Bioactive Peptides

    Directory of Open Access Journals (Sweden)

    Eric Banan-Mwine Daliri

    2017-04-01

    Full Text Available The increased consumer awareness of the health promoting effects of functional foods and nutraceuticals is the driving force of the functional food and nutraceutical market. Bioactive peptides are known for their high tissue affinity, specificity and efficiency in promoting health. For this reason, the search for food-derived bioactive peptides has increased exponentially. Over the years, many potential bioactive peptides from food have been documented; yet, obstacles such as the need to establish optimal conditions for industrial scale production and the absence of well-designed clinical trials to provide robust evidence for proving health claims continue to exist. Other important factors such as the possibility of allergenicity, cytotoxicity and the stability of the peptides during gastrointestinal digestion would need to be addressed. This review discusses our current knowledge on the health effects of food-derived bioactive peptides, their processing methods and challenges in their development.

  17. Bioactive Peptides.

    Science.gov (United States)

    Daliri, Eric Banan-Mwine; Oh, Deog H; Lee, Byong H

    2017-04-26

    The increased consumer awareness of the health promoting effects of functional foods and nutraceuticals is the driving force of the functional food and nutraceutical market. Bioactive peptides are known for their high tissue affinity, specificity and efficiency in promoting health. For this reason, the search for food-derived bioactive peptides has increased exponentially. Over the years, many potential bioactive peptides from food have been documented; yet, obstacles such as the need to establish optimal conditions for industrial scale production and the absence of well-designed clinical trials to provide robust evidence for proving health claims continue to exist. Other important factors such as the possibility of allergenicity, cytotoxicity and the stability of the peptides during gastrointestinal digestion would need to be addressed. This review discusses our current knowledge on the health effects of food-derived bioactive peptides, their processing methods and challenges in their development.

  18. Didaktische Konzeption von Serious Games: Zur Verknüpfung von Spiel- und Lernangeboten

    Directory of Open Access Journals (Sweden)

    Michael Kerres

    2009-08-01

    Full Text Available Serious Games versuchen Spielen mit Lernen zu verbinden. Der Beitrag problematisiert die Machbarkeit einer solchen Verknüpfung in digitalen Welten und diskutiert verschiedene didaktische Konzepte einer Nutzbarmachung digitaler Spiele für das Lernen und Lehren. Ausgehend von einer Analyse des Erlernens von Spielen werden drei didaktische Konzepte von Serious Games im Hinblick auf ihre didaktischen Potenziale untersucht: (1 der unmittelbare Transfer von Wissen, das im Spiel erworben wird (keine zusätzliche Didaktisierung, (2 Didaktisierung durch Einbettung des Spiels in einer Lernsituation oder (3 Didaktisierung durch Einbettung von Lernaufgaben in ein Spiel. Ergebnisse zur Nutzung von Spielen, bei denen Lernaufgaben in eine Spielwelt eingebettet sind, zeigen, dass Personen die Aufnahme von Wissen in einem expliziten Lernmodus eher zu reduzieren versuchen, um möglichst zügig wieder in den Spielmodus zu wechseln. Diskutiert werden die Konsequenzen dieser Problematik für die didaktische Konzeption von Serious Games.

  19. Dr. von Braun Briefing Walt Disney

    Science.gov (United States)

    1965-01-01

    Dr. von Braun began his association with Walt Disney in the 1950s when the rocket scientist appeared in three Disney television productions related to the exploration of space. Years later, Dr. von Braun invited Disney and his associates to tour the Marshall Space Flight Center (MSFC) in Huntsville, Alabama. This photograph is dated April 13, 1965. From left are R.J. Schwinghamer from the MSFC, Disney, B.J. Bernight, and Dr. von Braun.

  20. Reflexionseigenschaften von Windenergieanlagen im Funkfeld von Funknavigations- und Radarsystemen

    Science.gov (United States)

    Sandmann, S.; Divanbeigi, S.; Garbe, H.

    2015-11-01

    Die hier behandelte Untersuchung befasst sich mit den Störungen des elektrischen Feldes einer Doppler Very High Frequency Omnidirectional Radio Range Navigationsanlage (DVOR) in der Gegenwart von Windenergieanlagen (WEA). Hierfür wird die Feldstärke auf 25 konzentrischen Kreisbahnen, sog. Orbit Flights verschiedener Höhen und mit verschiedenen Radien rund um die DVOR-Anlage numerisch simuliert. Insbesondere werden die Einflüsse diverser Parameter der WEA wie deren Anzahl, Position, Rotorwinkel, Turmhöhe und Rotordurchmesser auf die Feldverteilung herausgestellt, sowie die Anwendbarkeit der Simulationsmethode Physical Optics (PO) durch Vergleich der Simulationsergebnisse mit denen der Multi Level Fast Multipol Method (MLFMM) untersucht.

  1. Peptide identification

    Science.gov (United States)

    Jarman, Kristin H [Richland, WA; Cannon, William R [Richland, WA; Jarman, Kenneth D [Richland, WA; Heredia-Langner, Alejandro [Richland, WA

    2011-07-12

    Peptides are identified from a list of candidates using collision-induced dissociation tandem mass spectrometry data. A probabilistic model for the occurrence of spectral peaks corresponding to frequently observed partial peptide fragment ions is applied. As part of the identification procedure, a probability score is produced that indicates the likelihood of any given candidate being the correct match. The statistical significance of the score is known without necessarily having reference to the actual identity of the peptide. In one form of the invention, a genetic algorithm is applied to candidate peptides using an objective function that takes into account the number of shifted peaks appearing in the candidate spectrum relative to the test spectrum.

  2. Planung von CLIL-Unterricht

    Directory of Open Access Journals (Sweden)

    Josef Leisen

    2015-10-01

    Full Text Available Der Beitrag formuliert die Sprachlernbedingungen und die Leitlinien des Sprachlernens im Fach und nennt Merkmale des guten integrierten Fach- und Sprachlehrens. Ausgehend von den Sprachproblemen, die sich im CLIL-Unterricht auftun, wird der sprachsensible CLIL-Unterricht definiert, und es werden Anregungen zur Gestaltung gegeben. Sprachliche Standardsituationen umfassen die kommunikativen Situationen im CLIL-Unterricht, die beim fachlichen Lernen auftreten und von der CLIL-Lehrkraft professionell bewältigt werden müssen. Im Beitrag wird ein Lehr-Lern-Modell ausführlich beschrieben und erläutert. Die Steuerungen von Sprachlernprozessen im CLIL durch Aufgabenstellungen, Methoden-Werkzeuge, Moderation und Diagnose/Rückmeldung werden ausführlich beschrieben. Die Planung einer Lernlinie in sechs Schritten wird dargestellt und erläutert. Planungsraster für CLIL-Lernlinien schließen den Beitrag ab. The article sets out the conditions for language learning in general as well as guiding principles of language learning in the subject and puts forward criteria for successfully integrated content and language learning. Based on typical language problems arising in CLIL-classrooms, the language-sensitive CLIL-classroom is defined and organisational suggestions are given. Linguistic standard situations comprise the communicative situations in the CLIL-classroom which are encountered in subject-related learning and have to be professionally mastered by the CLIL-teacher. The article extensively describes and explains a model of teaching and learning that can be used for the CLIL-classroom. It gives detailed information on managing language learning processes in CLIL by means of tasks, resources and methods as well as discourse facilitation, evaluation and feedback. In addition, a six-step lesson unit is outlined and explained. The article concludes by giving a planning matrix for CLIL lesson units.

  3. Walt Disney and Dr. Wernher von Braun

    Science.gov (United States)

    1954-01-01

    Dr. Werhner von Braun, then Chief, Guided Missile Development Operation Division at Army Ballistic Missile Agency (ABMA) in Redstone Arsenal, Alabama, was visited by Walt Disney in 1954. In the 1950's, von Braun worked with Disney Studio as a technical director, making three films about space exploration for television. A model of the V-2 rocket is in background.

  4. Von Neumann Was Not a Quantum Bayesian

    CERN Document Server

    Stacey, Blake C

    2014-01-01

    Wikipedia has claimed for over two years now that John von Neumann was the "first quantum Bayesian." In context, this reads as stating that von Neumann inaugurated QBism, the approach to quantum theory promoted by Fuchs, Mermin and Schack. This essay explores how such a claim is, historically speaking, unsupported.

  5. Kultuuriakadeemias saab kaeda Von Krahli ime tabamist

    Index Scriptorium Estoniae

    2006-01-01

    Marianne Kõrver, Jaak Kilmi, Andres Maimik, Marko Raat, Rainer Sarnet ja Arbo Tammiksaar tegid Eduard Vilde näidendist "Tabamata ime" kuus lühimängufilmi Von Krahli teatris ettekandmiseks. 25. mail tuleb Von Krahli Teater Viljandisse ja näitab teatrifilmi Kultuuriakadeemias

  6. Mixing subalgebras of finite von Neumann algebras

    CERN Document Server

    Cameron, Jan; Mukherjee, Kunal

    2010-01-01

    Jolissaint and Stalder introduced the definitions of mixing and weak mixing for von Neumann subalgebras of finite von Neumann algebras. In this paper, we study various algebraic and analytical properties of mixing and weakly mixing von Neumann subalgebras. We prove some basic results about mixing inclusions of von Neumann algebras and establish a connection between mixing properties and normalizers of von Neumann subalgebras. The special case of mixing subalgebras arising from inclusions of group von Neumann algebras finds applications to ergodic theory. For a finite von Neumann algebra $M$ and von Neumann subalgebras $A$, $B$ of $M$, we introduce a notion of weak mixing of $B\\subseteq M$ relative to $A$. If $B$ is abelian and $A\\subset B$, we show that weak mixing of $B \\subset M$ relative to $A$ is equivalent to the following property: if $x\\in M$ and $xAx^*\\subset B$ then $x\\in B$. In the general case, we show that weak mixing of $B\\subset M$ relative to $A$ is equivalent to the following property: if $x\\i...

  7. Ludwig von Mises: An Annotated Bibliography.

    Science.gov (United States)

    Gordon, David

    A 117-item annotated bibliography of books, articles, essays, lectures, and reviews by economist Ludwig von Mises is presented. The bibliography is arranged chronologicaly, and is followed by an alphabetical listing of the citations, excluding books. An index and information on the Ludwig von Mises Institute at Auburn University (Alabama) are…

  8. Jacob Stael von Holstein ja palladionism eesti arhitektuuris / Ants Hein

    Index Scriptorium Estoniae

    Hein, Ants, 1952-

    2005-01-01

    Sõjaväeinsenerist ja arhitektist Jacob Stael von Holsteinist (1628, Pärnu-1679), tema kavandatud hoonetest ja rollist 17. sajandi II poole arhitektuuris. Fabian von Ferseni Toompeal Lossiplatsil asunud elamust (lammutati 1894) ja Maardu mõisahoonest, Hans von Ferseni Mäo mõisahoonest Järvamaal, Otto Wilhelm von Ferseni majast Toompeal, Axel von Roseni majast Tallinnas Pikk t. 28 (1670-74), Otto Reinhold von Taube majast Tartus (hävinud), J. S. von Holsteini enda hoonetest: majast Tallinnas Toompea 1, Anija mõisahoonest, elamust Riias jm. Bibliograafia lk. 452

  9. Jacob Stael von Holstein ja palladionism eesti arhitektuuris / Ants Hein

    Index Scriptorium Estoniae

    Hein, Ants, 1952-

    2005-01-01

    Sõjaväeinsenerist ja arhitektist Jacob Stael von Holsteinist (1628, Pärnu-1679), tema kavandatud hoonetest ja rollist 17. sajandi II poole arhitektuuris. Fabian von Ferseni Toompeal Lossiplatsil asunud elamust (lammutati 1894) ja Maardu mõisahoonest, Hans von Ferseni Mäo mõisahoonest Järvamaal, Otto Wilhelm von Ferseni majast Toompeal, Axel von Roseni majast Tallinnas Pikk t. 28 (1670-74), Otto Reinhold von Taube majast Tartus (hävinud), J. S. von Holsteini enda hoonetest: majast Tallinnas Toompea 1, Anija mõisahoonest, elamust Riias jm. Bibliograafia lk. 452

  10. C-Peptide Test

    Science.gov (United States)

    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities C-peptide Share this page: Was this page helpful? Also known as: Insulin C-peptide; Connecting Peptide Insulin; Proinsulin C-peptide Formal ...

  11. The Digital Von Fahrenheid Pyramid

    Science.gov (United States)

    Bura, M.; Janowski, J.; Wężyk, P.; Zięba, K.

    2017-08-01

    3D Scanners Lab from Digital Humanities Laboratory at the University of Warsaw initiated the scientific project, the purpose of which was to call attention to systematically penetrated and devastated pyramid-shaped tomb from the XVIII/XIX century, of family von Fahrenheid in Rapa in Banie Mazurskie commune (NE Poland). By conducting a series of non-invasive studies, such as 3D inventory using terrestrial laser scanning (TLS), thermal imaging, georadar measurements (around and inside the tomb) and anthropological research of mummified remains as well - the complete dataset was collected. Through the integration of terrestrial (TLS) and airborne laser scanning (ALS) authors managed to analyse the surroundings of Fahrenheid pyriamid and influence of some objects (like trees) on the condition and visibility of the Pyramids in the landscape.

  12. Neues über das Tertiär von Java und die mesozoischen Schichten von West-Borneo

    NARCIS (Netherlands)

    Martin, K.

    1888-01-01

    Die Monographie, welche unter dem Titel Die Fossilien von Java herausgegeben wird ¹), ist so weit fortgeschritten, dass sich aus den in ihr beschriebenen Gastropoden bereits eine Anzahl von Schlussfolgerungen ableiten lässt, welche für die in Bearbeitung begriffene, geologische Karte von Java von

  13. Neues über das Tertiär von Java und die mesozoischen Schichten von West-Borneo

    NARCIS (Netherlands)

    Martin, K.

    1888-01-01

    Die Monographie, welche unter dem Titel Die Fossilien von Java herausgegeben wird ¹), ist so weit fortgeschritten, dass sich aus den in ihr beschriebenen Gastropoden bereits eine Anzahl von Schlussfolgerungen ableiten lässt, welche für die in Bearbeitung begriffene, geologische Karte von Java von Be

  14. Einfluss der Koordination von Spurenelementen in Silikatschmelzen auf Verteilungsprozesse

    OpenAIRE

    Sebastian Simon

    2016-01-01

    Das Wissen um die lokale Struktur von Seltenen Erden Elementen (SEE) in silikatischen und aluminosilikatischen Schmelzen ist von fundamentalem Interesse für die Geochemie der magmatischen Prozesse, speziell wenn es um ein umfassendes Verständnis der Verteilungsprozesse von SEE in magmatischen Systemen geht. Es ist allgemein akzeptiert, dass die SEE-Verteilungsprozesse von Temperatur, Druck, Sauerstofffugazität (im Fall von polyvalenten Kationen) und der Kristallchemie kontrolliert werden. All...

  15. Charakterisierung von Radiolyseprodukten in gammabestrahlten Polyamiden Thermodesorption-Gaschromatographie Massenspekroskopie

    OpenAIRE

    Selmi, Hany

    2008-01-01

    Der Verbrauch von Polyamiden in allen technischen Bereichen, darunter im Bereich der Verpackung von Lebensmitteln sowie im Bereich der Herstellung von medizinischen Artikeln und Geräten steigt stetig an. Dies beruht auf ihren Eigenschaften wie hohe Festigkeit, ausgezeichnete Thermoformbarkeit, hohe Wärmeformbeständigkeit, Sterilisierbarkeit und sehr gute Barriereeigenschaften gegen Gase, insbesondere gegenüber Sauerstoff und Aromen. Die Anwendung von Gammastrahlen zur Sterilisation von Verpac...

  16. Von Laue's theorem and its applications

    CERN Document Server

    Wang, Changbiao

    2012-01-01

    Von Laue's theorem is strictly proved in detail to clarify confusions in textbook and literature. This theorem is used to analyze the classical electron and the static electric field confined in a finite region of space.

  17. Arbeit von Frauen in Zeiten der Globalisierung

    NARCIS (Netherlands)

    D. Grunow

    2010-01-01

    Hohe Erwerbsquote, Dienstleistungsberufe und Minijobs: Die weibliche Erwerbstätigkeit hat sich in den letzten Jahrzehnten in Deutschland stark verändert. Wie hängen die Prozesse zusammen mit der Globalisierung von Wirtschaft und Arbeit?

  18. Titanisierung von Implantatoberflächen

    Science.gov (United States)

    Zimmermann, Hanngörg; Heinlein, Markus; Guldner, Norbert W.

    Titan gilt seit Jahrzehnten als einer der wichtigsten Implantatwerkstoffe in der Medizin. Neben den guten mechanischen Eigenschaften (Leichtigkeit, hohe Festigkeit etc.), besitzen Titanimplantate vor allem eine hervorragende Körperverträglichkeit, so dass die Implantate optimal in den humanen Organismus integriert werden [1]. Ist jedoch aufgrund der Anforderungen an das Implantat eine hohe Flexibilität und/ oder Elastizität gefragt, so scheidet der Werkstoff Titan aufgrund seiner spröden und unflexiblen Materialeigenschaften aus. Die Folge ist der Einsatz von Implantatmaterialien, sowohl künstlichen als auch biologischen Ursprungs, welche nicht selten eine unzureichende Biokompatibilität aufweisen und somit zu Fremdköper- und immunologischen Reaktionen und Einkapselung des Implantates führen können. Die Erhöhung der Körperverträglichkeit, eine Adaption an das biologische Umfeld und eine hohe Biokompatibilität sind demzufolge die wichtigsten Eigenschaften bei der bedarfsgerechten Herstellung von Implantaten und Implantatoberflächen. Zur Gestaltung von innovativen, biokompatiblen Oberflächen stehen unterschiedliche technische Lösungsansätze zur Verfügung. Zum einen besteht die Möglichkeit, geeignete Oberflächeneigenschaften aus dem Grundmaterial selbst zu optimieren. Dies geschieht unter anderem durch Modifikation der Werkstoffoberflächen in Form von Texturierungen und Oberflächenrauhigkeiten. Zum anderen können die Oberflächeneigenschaften unabhängig von denen des Trägermaterials gestaltet werden. Durch Funktionalisierung der Oberflächen mit geeigneten Beschichtungen oder der Zugabe von Medikamenten (Drug Eluting) werden die Kunststoffimplantate dahingehend verändert, dass eine Steigerung der Körperakzeptanz erreicht wird. Die Titanbeschichtung von Implantatoberflächen kombiniert die positiven Materialeigenschaften von Titan und Polymer.

  19. Beschichtung von Kohlenstofffasern durch Chemische Gasphasenabscheidung (CVD)

    OpenAIRE

    Schmidt, Stephan

    2005-01-01

    Der Einsatz faserverstärkter Verbundwerkstoffe mit metallischer und keramischer Matrix bietet den Vorteil von Kombination und optimaler Ausnutzung verschiedenster Werkstoffeigenschaften. Die Verwendung einer durch Kohlenstofffasern verstärkten keramischen Matrix erlangte dabei in der kürzeren Vergangenheit vermehrtes Interesse. Grundlegend für den erfolgreichen Einsatz von Faserverbundwerkstoffen ist dabei ein optimiertes Faser-Matrix-Interface, also eine "optimale" Haftung der Fasern innerha...

  20. Studien zur didaktischen Nutzung von Concept Maps

    OpenAIRE

    Jüngst, Karl Ludwig

    1995-01-01

    In einer ersten Studie wurde geprüft, ob elaborierendes Durcharbeiten von Concept Maps lerneffektiver ist als elaborierendes Durcharbeiten von analogen Texten. Es wurden 13 Exemplare in unterschiedlichen Schulfächern im Sekundarschulwesen durchgeführt. Die Versuchs- Klassen arbeiten Concept Maps zu einem bestimmten Begriff durch, die Kontrollklassen analoge Texte. Die Behaltensleistung auf einfacherem Anforderungsniveau war in den Klassen mit Concept Maps besser als in den Klassen mit Texten....

  1. Hullud päevad von Krahlis

    Index Scriptorium Estoniae

    2006-01-01

    Von Krahli Teatris mängitakse neil päevi neli korda Peeter Jalaka lavastuses Tõnu Kõrvitsa kammeroopereid "Tuliaed" ja "Mu luiged, mu mõtted", mille aluseks on luuletaja Marie Heibergi saatus. Libreto autor on Maarja Kangro. Kammerooperid tulevad lavale Von Krahli Teatri ja Nargen Opera koostöös. Esitavad Kädy Plaas, Helen Lokuta, Nargen Opera koor ja Tallinna Kammerorkester, dirigent Tõnu Kaljuste

  2. 50th birthday of Christian von Ferber

    Directory of Open Access Journals (Sweden)

    2011-06-01

    Full Text Available On May 15, 2011 Christian von Ferber - member of the Editorial Board of "Condensed Matter Physics" and renowned expert in the fields of soft matter physics and complex systems - celebrated his 50th birthday. The Editorial board of CMP, colleagues and friends warmy congratulate Christian von Ferber and wish him and his family continuing good health and to enjoy many adventures and discoveries in his future scientific travels!

  3. Charakterisierung von Wechselwirkungsprozessen in sensitiven Schichten

    OpenAIRE

    Rathgeb, Frank

    1999-01-01

    Die vorliegende Arbeit soll verschiedene Strategien aufzeigen, um eine selektive Anreicherung gasförmiger Analytmoleküle in sensitiven Schichten zu erzielen. Im Mittelpunkt des Interesses lagen hierbei pH-responsive Polymere, mikroporöse Schichten und Cyclohexapeptide. Mit den pH-responsiven Polymeren konnte eine selektive und sensitive Detektion von Ammoniak mit Nachweisgrenzen von 150 ppb erreicht werden. Die Stabilität der sensitiven Schicht konnte im Vergleich zu farbstoffdotie...

  4. Hullud päevad von Krahlis

    Index Scriptorium Estoniae

    2006-01-01

    Von Krahli Teatris mängitakse neil päevi neli korda Peeter Jalaka lavastuses Tõnu Kõrvitsa kammeroopereid "Tuliaed" ja "Mu luiged, mu mõtted", mille aluseks on luuletaja Marie Heibergi saatus. Libreto autor on Maarja Kangro. Kammerooperid tulevad lavale Von Krahli Teatri ja Nargen Opera koostöös. Esitavad Kädy Plaas, Helen Lokuta, Nargen Opera koor ja Tallinna Kammerorkester, dirigent Tõnu Kaljuste

  5. Peptide arrays for screening cancer specific peptides.

    Science.gov (United States)

    Ahmed, Sahar; Mathews, Anu Stella; Byeon, Nara; Lavasanifar, Afsaneh; Kaur, Kamaljit

    2010-09-15

    In this paper, we describe a novel method to screen peptides for specific recognition by cancer cells. Seventy peptides were synthesized on a cellulose membrane in an array format, and a direct method to study the peptide-whole cell interaction was developed. The relative binding affinity of the cells for different peptides with respect to a lead 12-mer p160 peptide, identified by phage display, was evaluated using the CyQUANT fluorescence of the bound cells. Screening allowed identification of at least five new peptides that displayed higher affinity (up to 3-fold) for MDA-MB-435 and MCF-7 human cancer cells compared to the p160 peptide. These peptides showed very little binding to the control (noncancerous) human umbilical vein endothelial cells (HUVECs). Three of these peptides were synthesized separately and labeled with fluorescein isothiocyanate (FITC) to study their uptake and interaction with the cancer and control cells using confocal laser scanning microscopy and flow cytometry. The results confirmed the high and specific affinity of an 11-mer peptide 11 (RGDPAYQGRFL) and a 10-mer peptide 18 (WXEAAYQRFL) for the cancer cells versus HUVECs. Peptide 11 binds different receptors on target cancer cells as its sequence contains multiple recognition motifs, whereas peptide 18 binds mainly to the putative p160 receptor. The peptide array-whole cell binding assay reported here is a complementary method to phage display for further screening and optimization of cancer targeting peptides for cancer therapy and diagnosis.

  6. An MRI Von Economo - Koskinas atlas.

    Science.gov (United States)

    Scholtens, Lianne H; de Reus, Marcel A; de Lange, Siemon C; Schmidt, Ruben; van den Heuvel, Martijn P

    2016-12-28

    The cerebral cortex displays substantial variation in cellular architecture, a regional patterning that has been of great interest to anatomists for centuries. In 1925, Constantin von Economo and George Koskinas published a detailed atlas of the human cerebral cortex, describing a cytoarchitectonic division of the cortical mantle into over 40 distinct areas. Von Economo and Koskinas accompanied their seminal work with large photomicrographic plates of their histological slides, together with tables containing for each described region detailed morphological layer-specific information on neuronal count, neuron size and thickness of the cortical mantle. Here, we aimed to make this legacy data accessible and relatable to in vivo neuroimaging data by constructing a digital Von Economo - Koskinas atlas compatible with the widely used FreeSurfer software suite. In this technical note we describe the procedures used for manual segmentation of the Von Economo - Koskinas atlas onto individual T1 scans and the subsequent construction of the digital atlas. We provide the files needed to run the atlas on new FreeSurfer data, together with some simple code of how to apply the atlas to T1 scans within the FreeSurfer software suite. The digital Von Economo - Koskinas atlas is easily applicable to modern day anatomical MRI data and is made publicly available online.

  7. Positive Effekte von NSAR auf den Gastrointestinaltrakt

    Directory of Open Access Journals (Sweden)

    Lang M

    2015-01-01

    Full Text Available Ein protektiver Effekt von nichtsteroidalen Antirheumatika (NSAR auf die Tumorentstehung im Kolon wird in diversen präklinischen, epidemiologischen und auch randomisierten Arbeiten postuliert. Der Hauptwirkungsmechanismus von NSAR wird der Hemmung der Prostaglandinsynthese über die Cyclooxygenasen (COX zugeschrieben. Es existieren aber auch COX-unabhängige Mechanismen. Hier wollen wir einen Überblick über die Studienlage mit Aspirin, Sulindac und COX-2-Hemmern im Hinblick auf die Entstehung von Adenomen und Kolorektalkarzinomen geben. Die Wirkung dieser Substanzen ist besonders für Patienten mit familiärer Disposition relevant, aber auch für Patienten, die NSAR oder Aspirin aufgrund anderer Indikationen einnehmen. Es bestehen Abhängigkeiten von Dosis und Zeit sowie Interaktionen mit speziellen Mutationen (BRAF, PI3K und der zellulären COX-2-Expression. Beim Lynch-Syndrom ist die Wirksamkeit von Aspirin letztlich nicht sicher und eine multinationale klinische Studie mit 5-Aminosalizylsäure (Mesalazin wurde vom europäischen TRANSCAN-Programm gefördert.

  8. Doença de von Willebrand e anestesia Enfermedad de von Willebrand y anestesia Von Willebrand's disease and anesthesia

    Directory of Open Access Journals (Sweden)

    Fabiano Timbó Barbosa

    2007-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A doença de von Willebrand ocorre devido à mutação no cromossomo 12 e é caracterizada por deficiência qualitativa ou quantitativa do fator de von Willebrand. A diversidade de mutações leva ao aparecimento das mais variadas manifestações clínicas possibilitando a divisão dos pacientes em vários tipos e subtipos clínicos. A coagulopatia se manifesta basicamente através da disfunção plaquetária associada à diminuição dos níveis séricos do fator VIII coagulante. O objetivo dessa revisão foi mostrar os cuidados relacionados aos pacientes portadores da doença de von Willebrand durante o período perioperatório. CONTEÚDO: Foram definidas as características da doença de von Willebrand quanto à fisiopatologia, à classificação, ao diagnóstico laboratorial, ao tratamento atual e aos cuidados com o manuseio do paciente no período perioperatório. CONCLUSÕES: A doença de von Willebrand é o distúrbio hemorrágico hereditário mais comum, porém ela é subdiagnosticada pela complexidade da própria doença. A correta classificação do paciente, o uso apropriado da desmopressina e a transfusão do fator de von Willebrand são medidas fundamentais para a realização do procedimento anestésico bem-sucedido.JUSTIFICATIVA Y OBJETIVOS: La enfermedad de von Willebrand ocurre debido a la mutación en el cromosoma 12 y se caracteriza por la deficiencia cualitativa o cuantitativa del factor de von Willebrand. La diversidad de mutaciones conlleva al aparecimiento de las más variadas manifestaciones clínicas posibilitando la división de los pacientes en varios tipos y subtipos clínicos. La coagulopatía se manifiesta básicamente a través de la disfunción plaquetaria asociada con la disminución de los niveles séricos del factor VIII coagulante. El objetivo de esa revisión fue mostrar los cuidados relacionados con las pacientes portadoras de la enfermedad de von Willebrand durante el per

  9. Kerttu Wagner. Die historischen romane von Jaan Kross / Wolfgang Drechsler

    Index Scriptorium Estoniae

    Drechsler, Wolfgang, 1963-

    2001-01-01

    Arvustus: Wagner, Kerttu. Die historischen Romane von Jaan Kross : am Beispiel einer Untersuchung der deutschen und englischen Übersetzungen von "Professor Martensi ärasõit" (1984). Frankfurt am Main [etc.] : P. Lang, 2001.

  10. Kerttu Wagner. Die historischen romane von Jaan Kross / Wolfgang Drechsler

    Index Scriptorium Estoniae

    Drechsler, Wolfgang, 1963-

    2001-01-01

    Arvustus: Wagner, Kerttu. Die historischen Romane von Jaan Kross : am Beispiel einer Untersuchung der deutschen und englischen Übersetzungen von "Professor Martensi ärasõit" (1984). Frankfurt am Main [etc.] : P. Lang, 2001.

  11. Von Willebrand's disease: case report and review of literature ...

    African Journals Online (AJOL)

    Abstract. Von Willebrand Disease (VWD) is the most common human ... The most bleeding forms of VWD usually do not concern type 1 patients with the ... and collagen binding test and genanalysis allow diagnosing the different types of von.

  12. Gemeinsam hilfreich oder einsam lästig? Beurteilung von praktikumsbegleitenden Weblogs von angehenden Lehrpersonen

    Directory of Open Access Journals (Sweden)

    Nives Egger

    2017-02-01

    Full Text Available Weblogs werden an Hochschulen vermehrt zur Unterstützung von Lern- und Reflexionsprozessen eingesetzt, in der Lehrer/innenbildung auch zunehmend während der berufspraktischen Ausbildung. Die Studierenden beurteilen den Einsatz von Weblogs jedoch unterschiedlich. Dabei ist wenig bekannt, welchen Einfluss die Vergabe und das Erhalten von Peerfeedback auf den Beurteilungsprozess von praktikumsbegleitenden Weblogs sowie auf den Umfang von Blogpostings haben. Im folgenden Beitrag wird dieser Frage mittels einer Befragung von 74 angehenden Lehrpersonen nachgegangen, die praktikumsbegleitende Weblogs mit oder ohne Peerfeedback nutzten, um über herausfordernde Ereignisse im Praktikum zu reflektieren. Die Ergebnisse zeigen, dass Studierende, die Peerfeedback erhielten und andere Blogbeiträge kommentierten, den Weblogeinsatz nützlicher einschätzen sowie eine höhere Motivation und positivere Einstellung gegenüber den Einsatz von Weblogs aufweisen als Studierende, die ohne Peerfeedback bloggen. Keinen Einfluss hat Peerfeedback auf den Umfang der Blogbeiträge und auf die dafür aufgewendete Zeit.

  13. Liouville-von Neumann molecular dynamics

    Science.gov (United States)

    Jakowski, Jacek; Morokuma, Keiji

    2009-06-01

    We present a novel first principles molecular dynamics scheme, called Liouville-von Neumann molecular dynamics, based on Liouville-von Neumann equation for density matrices propagation and Magnus expansion of the time-evolution operator. The scheme combines formally accurate quantum propagation of electrons represented via density matrices and a classical propagation of nuclei. The method requires a few iterations per each time step where the Fock operator is formed and von Neumann equation is integrated. The algorithm (a) is free of constraint and fictitious parameters, (b) avoids diagonalization of the Fock operator, and (c) can be used in the case of fractional occupation as in metallic systems. The algorithm is very stable, and has a very good conservation of energy even in cases when a good quality conventional Born-Oppenheimer molecular dynamics trajectories is difficult to obtain. Test simulations include initial phase of fullerene formation from gaseous C2 and retinal system.

  14. Gasification of liquid manure; Vergasung von Guelle

    Energy Technology Data Exchange (ETDEWEB)

    Gudenau, H.W.; Hoberg, H.; Hirsch, U. [Technische Hochschule Aachen (Germany). Inst. fuer Eisenhuettenkunde

    1996-12-31

    The potential of thermal use of liquid manure is investigated. It is recommended to separate the liquid and solid fraction. While the liquid fraction can be used as fertilizer, the solid fraction can be used for generating a fuel gas for combined heat and power generation. (orig) [Deutsch] Die Untersuchungen haben ergeben, dass in der thermischen Verwertung von Guelle ein bisher nur wenig genutztes Potential vorliegt. Die zum Anbau von Getreide notwendige Duengung kann durch Separation von Guelle in Fest- und Duennfraktion effektiver und kostenguenstiger durchgefuehrt werden. Der Naehrstoffgehalt des Guellefeststoffs sollte durch thermische Aufbereitung aufkonzentriert werden, so dass eine Vermarktung auch mit laengeren Transpoertwegen darstellbar ist. Die bei der thermischen Behandlung gewonnene Waerme kann prozessintern genutzt und ueberschuessige Waerme an Abnehmer in der naeheren Umgebung geliefert werden. Genauso besteht die Moeglichkeit, ein Brenngas zu erzeugen und die Energie mit Kraft-Waerme-Kopplung zu nutzen. (orig)

  15. Multivariate Herkunftsanalyse von Marmor auf petrographischer und geochemischer Basis

    OpenAIRE

    Cramer, Thomas

    2004-01-01

    Am Beispiel von aus Kleinasien stammenden Grabungsfunden in der Antikensammlung Berlin wird die Methodik der Herkunftsanalyse von Marmoren, d.h. der Zuordnung zu ihren Lagerstätten, weiterentwickelt und erprobt. Dazu wird der aktuelle Forschungsstand kritisch gewürdigt, die Voraussetzungen, Bedingungen und Grenzen der Provenienzbestimmung werden systematisiert und von den zahlreichen Gesteinsmerkmalen und Untersuchungsmethoden die geeignetsten ausgewählt. Marmore von 38 Sammlungsobjekten, die...

  16. Experimentelle Untersuchung von Konzentrations- und Verweilzeiteffekten in Membranreaktoren

    OpenAIRE

    Tota, A.; Hamel, C.; Thomas, S.; Joshi, M.; Klose, F.; Seidel-Morgenstern, A.

    2003-01-01

    Heterogen katalysierte Oxidationsreaktionen von kurzkettigen Kohlenwasserstoffen werden in der Industrie zur Erzeugung von Ausgangsmaterialien für wertvollere Syntheseprodukte (selektive Oxidation) oder zur Entsorgung von Abgasen eingesetzt. Bei selektiven Oxidationen ist das gewünschte Produkt gewöhnlich ein thermodynamisch instabiles Zwischenprodukt. Mit dem Einsatz von Membranreaktoren verspricht man sich hohe Selektivitäten. bei gleichzeitig hohen Ausbeuten. Als Modellreaktion für systema...

  17. Approximate equivalence in von Neumann algebras

    Institute of Scientific and Technical Information of China (English)

    DING; Huiru; Don; Hadwin

    2005-01-01

    One formulation of D. Voiculescu's theorem on approximate unitary equivalence is that two unital representations π and ρ of a separable C*-algebra are approximately unitarily equivalent if and only if rank o π = rank o ρ. We study the analog when the ranges of π and ρ are contained in a von Neumann algebra R, the unitaries inducing the approximate equivalence must come from R, and "rank" is replaced with "R-rank" (defined as the Murray-von Neumann equivalence of the range projection).

  18. Von Mumien, Cyborgs und Röntgenbildern

    Directory of Open Access Journals (Sweden)

    Regina Schleicher

    2004-03-01

    Full Text Available Unter dem Titel Techniken der Reproduktion liegt ein Sammelband vor, der die Beiträge einer Tagung an der Universität Paderborn vom Dezember 2001 enthält. In enger Verknüpfung verschiedener disziplinärer Perspektiven werden Schlaglichter auf eine Vielzahl von Themen geworfen, die sich mit dem Begriff „Reproduktion“ verbinden. Dabei wird deutlich, wie eng die Geschichte der Medien und die Entwicklung von Technologien der biologischen Fortpflanzung miteinander verzahnt sind.

  19. Verwertung von Prozessbieren in der Brauerei

    OpenAIRE

    Schneeberger, Mark

    2007-01-01

    Die betriebsinterne Verwertung von Prozessbieren (PB) zur Minimierung des Bierschwandes stellt den Kern der Arbeit dar. Als mengenmäßig bedeutsamste PB haben sich Hefebiere (HB), Vor-, Zwischen- und Nachläufe (VZNL) aus der Filtration, Biere aus unterfüllten bzw. falsch etikettierten Flaschen aus der Abfüllung sowie Rückbiere herausgestellt. Verschiedene Indikatoren in Hefezellen und im HB wurden zur Kontrolle von Hefebierrückgewinnungsanlagen ermittelt. Um eine hohe Qualität der wiedergewinn...

  20. [Anja Wilhelmi. Lebensweltlen von Frauen der deutschen Oberschicht im Baltikum (1800-1939). Eine Untersuchung anhand von Autobiographien] / Alexander Ewig

    Index Scriptorium Estoniae

    Ewig, Alexander, 1980-

    2011-01-01

    Arvustus: Wilhelmi, Anja. Lebenswelten von Frauen der deutschen Oberschicht im Baltikum (1800-1939). Eine Untersuchung anhand von Autobiographien. (Veröffentlichungen des Nordost-Instituts, 10.) (Wiesbaden : HArrassowitz 2008)

  1. [Anja Wilhelmi. Lebensweltlen von Frauen der deutschen Oberschicht im Baltikum (1800-1939). Eine Untersuchung anhand von Autobiographien] / Alexander Ewig

    Index Scriptorium Estoniae

    Ewig, Alexander, 1980-

    2011-01-01

    Arvustus: Wilhelmi, Anja. Lebenswelten von Frauen der deutschen Oberschicht im Baltikum (1800-1939). Eine Untersuchung anhand von Autobiographien. (Veröffentlichungen des Nordost-Instituts, 10.) (Wiesbaden : HArrassowitz 2008)

  2. Cerebellar Hemangioblastoma: Four Case Reports and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Sevgi Bakaris

    2015-03-01

    Full Text Available Hemangioblastoma (HB is a benign, slow-growing, highly vascular tumour of not well defined histological origin. These tumors make up about 1 to 2 percent of all intracranial neoplasms and occur primarily in the posterior fossa. Hemangioblastomas can occur sporadically but in about 20% to 30% cases, it is associated with von Hippel-Lindau (VHL disease. Four cases of cerebellar haemangioblastoma, not associated with von Hippel-Lindau disease (sporadic haemangioblastomas, were presented and reviewed the relevant literature.Four hemangioblastomas of the central nervous system were examined with haematoxylin and eosin (H and E, reticulin stain and with a panel of antibodies including CD34, vimentin, NSE, S-100, CD99, CD56, GFAP, cytoceratin, epithelial membrane antigen (EMA, CD10. Of the 4 patients in this study 1 was male and 3 were female. Their ages ranged from 46 years to 60 years with a mean age of 54.75 years. All of them were as cystic nodules about 2-3 cm in diameter. In the histopathological examination, the tumors sections showed large and vacuolated stromal cells and numerous arborizing capillary-size blood vessels. Some tumors showed atypical nuclei. Vimentin was strongly positive both stromal cells and blood veessels in all tumors. In 4 cases of HB, some stromal cells were positive for NSE and CD99. Three tumors were positive for S-100 and CD56, two tumors were focally positive for glial fibrillary acidic protein (GFAP. CD34 immunostaining highlighted the arborizing and complex vascular network, whereas the tumor stromal cells were negative. The stromal cells were negative for epithelial markers such as cytokeratin, EMA and CD10. Ki-67 index was less than 1% of the tumor cells. Hemangioblastoma, a rare, benign tumors of uncertain histogenesis, is characterized histologically by the presence of vacuolated, lipid containing cells and a well developed, fine capillary network. The main histological differential diagnosis of HB is metastatic

  3. Identification of the Lipodepsipeptide MDN-0066, a Novel Inhibitor of VHL/HIF Pathway Produced by a New Pseudomonas Species

    Science.gov (United States)

    Cautain, Bastien; de Pedro, Nuria; Schulz, Christian; Pascual, Javier; da S. Sousa, Thiciana; Martin, Jesús; Pérez-Victoria, Ignacio; Asensio, Francisco; González, Ignacio; Bills, Gerald F.; Reyes, Fernando; Genilloud, Olga; Vicente, Francisca

    2015-01-01

    Throughout recent history, metabolites of microbial origin have had an extraordinary impact on the welfare of humanity. In fact, natural products have largely been –and still are– considered an exceedingly valuable platform for the discovery of new drugs against diverse pathologies. Such value is partly due to their higher complexity and chemical diversity as compared to those of synthetic and combinatorial compounds. Mutations in the Von Hippel-Lindau (vhl) gene are responsible for VHL disease, congenital polycythemia, and are found in many sporadic tumor types. The primary cause of morbidity and mortality for these patients arises from progression of Renal Cell Carcinoma (RCC) or end-stage renal disease. Inactivation of the Von Hippel-Lindau (vhl) tumor suppressor gene arises in the majority of Renal Cell Carcinoma (RCC) as well as in other types of cancer and is associated with a high degree of vascularization and poor prognosis. Loss of pVHL function thus represents a pathognomonic molecular defect for therapeutic exploitation. In this study, renal carcinoma cell lines with naturally occurring vhl mutations (RCC4 VA) and their genetically matched wild-type vhl (RCC4 VHL) counterparts were seeded onto 96-well plates and treated with a collection of 1,040 organic extracts obtained from 130 bacterial strains belonging to at least 25 genera of the phyla Actinobacteria, Firmicutes, Proteobacteria and Bacteroidetes. This strategy allowed us to identify several extracts obtained from bacterial strain F-278,770T, the type strain of the recently proposed new species Pseudomonas granadensis, showing biological activities not associated with previously known bioactive metabolites. The fractionation and structural elucidation of one of these extracts led to the discovery of a new lipodepsipeptide (MDN-0066) with specific toxicity in pVHL deficient cells that is not detectable in cells with pVHL expression rescue. This specific toxicity is associated with apoptosis

  4. Die Verteilung und Eigenschaften von Bodenformen in der Deutschen Bucht, eine Rekonstruktion der Karten von Ulrich (1973)

    DEFF Research Database (Denmark)

    Winter, Christian; Lefebvre, Alice; Benninghoff, Markus

    2015-01-01

    Entstehung, Gestalt und Dynamik von Bodenformen in vergleichsweise kleinen Untersuchungsgebieten ist die Arbeit von ULRICH (1973) über die Verteilung von Bodenformen in der Deutschen Bucht bis heute die einzige verfügbare zusammenhängende Darstellung für die deutsche Nordseeküste. Die analogen Karten und die...

  5. Herstellung von Bio-Fleisch- und Wurstwaren ohne Einsatz von Pökelstoffen

    OpenAIRE

    2008-01-01

    Bei der ökologischen Herstellung von Fleisch- und Wurstwaren werden vielfach auf die in der konventionellen Wurstherstellung verwendeten Konservierungsstoffe E 250 (Natriumnitrit) bzw. E 252 (Kaliumnitrat) verzichtet oder reduzierte Zugabemengen der Zusatzstoffe verwendet.

  6. Der Briefwechsel zwischen Alexander von Humboldt und Karl Ernst von Baer

    Directory of Open Access Journals (Sweden)

    Thomas Schmuck

    2012-10-01

    Full Text Available Zusammenfassung Der kurze, nicht vollständig erhaltene Briefwechsel zwischen Alexander von Humboldt und Karl Ernst von Baer behandelt sehr verschiedene Themen: Politik, Kriegsgefahr, den Wissenschaftsbetrieb, Auszeichnungen und Tagungen, Embryologie und Cholera. Gemeinsam mit Briefen und Reden ergibt sich dabei ein differenziertes Bild der Beurteilung der beiden Wissenschaftler durch den jeweils anderen. Während Baer sich als Bewunderer Humboldts erweist, erscheint umgekehrt Humboldts Einschätzung Baers als ambivalent. Abstract The short, not completely preserved correspondence between Alexander von Humboldt and Karl Ernst von Baer deals with a wide range of subjects: politics and the danger of war, academic activities, scientific awards and conferences, aspects of embryology and the cholera. Letters to third persons and speeches, together with the correspondence between Humboldt and Baer show a differentiated pattern of mutual appraisal: While Baer always remained an admirer of the elder naturalist, Humboldt’s estimation was characterized by ambivalence.

  7. Von der Medienwirkungsbehauptung zur erziehungswissenschaftlichen Medienrezeptionsforschung. Vorschlag zur Analyse von Filmkommunikaten

    Directory of Open Access Journals (Sweden)

    Barbara Drinck

    2001-04-01

    Full Text Available Im Hinblick auf die Erforschung spezifischer Zusammenhänge von Medienkonsum und der Herausbildung von Einstellungen und Handlungen wird eine konstruktivistische Theorieorientierung plausibilisiert, indem zunächst auf den Stand der Medienwirkungsforschung eingegangen und vor dem Hintergrund einer begründeten Kritik des Wirkungsverständnisses auf die Notwendigkeit einer medienrezeptionswissenschaftlichen Forschungsalternative hingewiesen wird. Weiterhin wird der Stand der (erziehungswissenschaftlichen Medienrezeptionsforschung erörtert. Sodann werden Elemente einer konstruktivistischen Methodologie von Medienrezeptionsforschung beschrieben, die am Beispiel der Rezeption von Filmen konkretisiert werden. Dabei wird das Konzept des Kommunikates (S.J. Schmidt als Ausgangspunkt genommen, ein Vorschlag für eine Beschreibungssprache für (Film- Kommunikate entwickelt und eine Adaption des Ansatzes filmischer Narration zur Sprache gebracht.

  8. Auswirkung von Umweltchemikalien auf die Biologie von Chironomiden und Fischen als deren Prädatoren

    OpenAIRE

    Langer-Jaesrich, Miriam

    2012-01-01

    Im Rahmen der Dissertation wurden in mehreren Teilprojekten die Auswirkungen von Umweltchemikalien auf Chironomiden als Schlüsselorganismen in aquatisch-benthischen Lebensräumen untersucht. Dabei lag der Fokus besonders auf der Erfassung von nicht-standardisierten Endpunkten und Bioindikatoren sowie auf der Bearbeitung einer weiterführenden ökologisch relevanten Fragestellung zum Räuber-Beute-Verhältnis unter Schadstoffeinfluss. Im ersten Teil der Dissertation wurde das herkömmliche Standa...

  9. Synthese von grenzflächenaktiven Monomeren zur Herstellung von funktionalen Metall-Chalkogenid/Polymer-Hybridnanopartikeln

    OpenAIRE

    Fischer, V.

    2013-01-01

    In dieser Arbeit wurde gezeigt, wie oberflächenfunktionalisierte Polystyrolnanopartikel zur Herstellung von Metallchalkogenid/Polymer-Hybridnanopartikeln eingesetzt werden können. Dazu wurden zunächst phosphonsäure- und phosphorsäurefunktionalisierte Surfmere synthetisiert, die anschließend bei der Miniemulsionspolymerisation von Styrol verwendet wurden. Die Surfmere dienten dabei zugleich zur Stabilisierung und als Comonomer. Die oberflächenfunktionalisierten Polystyrolnanopartikel wurden an...

  10. Untersuchung der Rolle von Rhodopsin 7 und Cryptochrom im Sehprozess von Drosophila melanogaster

    OpenAIRE

    Grebler, Rudi

    2015-01-01

    Ausgangspunkt für die Detektion von Licht ist im gesamten Tierreich die Absorption von Photonen durch photorezeptive Proteine, die sogenannten Opsine und in geringerem Ausmaß die Typ 1 Cryptochrome. Die Taufliege Drosophila melanogaster besitzt sechs eingehend charakterisierte, auch als Rhodopsine bezeichnete Opsine (Rh1-Rh6) und ein Cryptochrom (CRY). Neben den Ocellen und den Hofbauer-Buchner Äuglein werden die Rhodopsine in erster Linie in den Photorezeptorzellen der Komplexaugen, den Haup...

  11. Untersuchungen zur Trockenentschwefelung von Brenngasen durch Partialoxidation von H2S an Herdofenkoks

    OpenAIRE

    Bauersfeld, Dirk

    2009-01-01

    Die vorliegende Arbeit befasst sich mit Untersuchungen zur Trockenentschwefelung von Brenngasen durch Partialoxidation von H2S an Herdofenkoks. Hierzu wurden Versuche in der Technikumsanlage VTE 2004 mit einem simulierten PHTW Gas durchgeführt. Es zeigte sich, dass der COS-Abbau nicht wie bisher angenommen durch die COS-Partialoxidation sondern durch die COS-Hydrolyse erfolgt. Die COS-Hydrolyse gewinnt dabei mit abnehmender Raumbelastung an Bedeutung. Der Entschwefelungsgrad erhöht sich mit s...

  12. Dentinhaftung von Zementen. Der Haftverbund von Zementen mit Dentin in Kombination mit verschiedenen indirekten Restaurationsmaterialien

    OpenAIRE

    Peutzfeldt, Anne; Sahafi, Alireza; Flury, Simon

    2011-01-01

    Einleitung: Die Anzahl zahnärztlicher Zemente sowie Restaurationsmaterialien steigt stetig. Die richtige Zementwahl für einen zuverlässigen Haftverbund zwischen Restaurationsmaterial und Zahnsubstanz ist von Interesse für den Kliniker. Ziel der vorliegenden in vitro-Studie war es daher, den Dentinhaftverbund von verschiedenen Zementen in Kombination mit verschiedenen indirekten Restaurationsmaterialien zu untersuchen. Material und Methoden: Zylindrische Probekörper aus sechs Restaurations...

  13. [The Costantin Von Economo's lethargic encefalitis

    Science.gov (United States)

    Pistacchio, E.

    1998-01-01

    Starting from the Constantin Von Economo's description of a "new" disease, the lethargic encephalitis, the author delineates the history of an infectious sleeping sickness that caused epidemics in Europe from 1917 to 1928 and led to create, in Italy, the "Institutes for Encephalitis".

  14. Die larvale Entwicklung von Chirocentrus dorab (Forsk.)

    NARCIS (Netherlands)

    Delsman, H.C.

    1922-01-01

    Wer sich mit dem Studium der Lebensweise indischer Fische befassen will, hat dabei den grossen Vorteil, sich beim Bestimmen der Species auf die zahlreichen Arbeiten BLEEKER’S stützen zu können, während ihm das Determinieren ganz besonders erleichtert wird durch das von dichotomischen Tabellen

  15. Soolopartiid Von Krahli katuse all / Kristi Eberhart

    Index Scriptorium Estoniae

    Eberhart, Kristi

    2007-01-01

    Von Krahli Teatri kolmest lavastusest: "Erki ja Tiina" (lavastaja Mart Kangro, tantsivad Erki Laur ja Tiina Tauraite), "Faust" (J. W. Goethe ainetel tekst ja lavastus Taavi Eelmaa, muusika ja laulud Chalice, osades Jarek Kasar ja Rein Pakk), "Hamletid" (William Shakespeare'i ainetel kontseptsiooni, lavastuse, koreograafia, kujunduse, valguse autor Sasha Pepeljajev, video- ja helikunstnik Taavet Jansen. Esitaja Juhan Ulfsak)

  16. Drei neue Chelonarium-Arten von Sumatra

    NARCIS (Netherlands)

    Reitter, Edm.

    1886-01-01

    Die Arten dieser Gattung kommen vorherschend in Central- und Süd-Amerika vor, doch sind in neuerer Zeit auch drei Arten: Ch. orientale Reitt. 1), conspersum Reitt. 2) und adspersum Chevrl.3) von den grossen Sunda-Inseln und Malakka bekannt geworden, zu denen nun weitere 3 Arten treten, die ich nachf

  17. Ueber eine Anomalie von Acromitus flagellatus (Stiasny)

    NARCIS (Netherlands)

    Stiasny, G.

    1934-01-01

    Bei erneuter Durchsicht des reichhaltigen Materiales von Acromitus flagellatus (Stiasny) in der Scyphomedusen-Sammlung des Rijksmuseum van Natuurlijke Historie in Leiden (vergl. meine Mitteilungen daruber, 1920, Uebersichtstabelle III und 1921, p. 131/136) fand ich ein Exemplar, das eine

  18. Ueber zwei neue Vogelarten von Java

    NARCIS (Netherlands)

    Finsch, O.

    1902-01-01

    Die beiden nachstehend beschriebenen Vögel wurden mir von Herrn Max Bartels als muthmasslich neu zugesandt. Die genaue Untersuchung hat dies bestätigt. Ich freue mich daher eine der Arten zu Ehren des Entdeckers benennen zu können. Seit einigen Jahren als Leiter der Plantage Pangerango bei Pasir Dat

  19. Active Von Willebrand Factor, thrombocytopenia and thrombosis

    NARCIS (Netherlands)

    Hulstein, J.J.J.

    2006-01-01

    Platelets and von Willebrand factor (VWF) are unable to interact in circulation. To induce an interaction, a conversion of VWF to a platelet-binding conformation is required. At higher shear stresses, the first step in thrombus formation is binding of VWF to the subendothelium. This results in expos

  20. The von Bertalanffy growth model for horticulture

    NARCIS (Netherlands)

    Tijskens, L.M.M.; Schouten, R.E.; Unuk, T.; Šumak, D.

    2017-01-01

    Traditionally, crop load and fruit yield from previous seasons are used as indicators for prediction of fruit size. Disregarding the inevitable biological variation between fruit, von Bertalanffy (1938) described the growth, expressed as length, of virtually any living organism. The model is here

  1. Von Kalifornien nach Taxham / Katri Soe

    Index Scriptorium Estoniae

    Soe, Katri, 1971-

    2005-01-01

    Neljas osa magistritööst "Von Kalifornien nach Taxham: Formen und Strukturen der Kommunikation in Peter Handkes Romanen "Der kurze Brief zum langen Abschied" und "In einer dunklen Nacht ging ich aus meinem stillen Haus"" (Tartu, 2000. Juhendaja: Claus Sommerhage)

  2. Ueber eine Anomalie von Acromitus flagellatus (Stiasny)

    NARCIS (Netherlands)

    Stiasny, G.

    1934-01-01

    Bei erneuter Durchsicht des reichhaltigen Materiales von Acromitus flagellatus (Stiasny) in der Scyphomedusen-Sammlung des Rijksmuseum van Natuurlijke Historie in Leiden (vergl. meine Mitteilungen daruber, 1920, Uebersichtstabelle III und 1921, p. 131/136) fand ich ein Exemplar, das eine bemerkenswe

  3. Zustandsschätzung von aktiven Fahrwerkregelsystemen

    NARCIS (Netherlands)

    Leenen, R.; Maurice, J.P.

    2010-01-01

    Eine Weiterentwicklung von Fahrdynamikregelung, Überroll- und Seitenaufprallschutz sowie Pre-Crash-Funktionen und Kollisionsminderung verspricht TNO. Mit einem System zur Beobachtung des aktuellen Fahrzeugzustands (Vehicle State Estimator – VSE) bietet der niederländische Zulieferer ein zentrales Mo

  4. Ueberreste vorweltlicher Proboscidier von Java und Banka

    NARCIS (Netherlands)

    Martin, K.

    1884-01-01

    Junghuhn führte in seinem Werke über Java nur einen einzigen Wirbelthierrest, Carcharias megalodon, an (7, IV, pag. 97); es war ihm nicht gelungen bei seinem ersten Aufenthalte auf der Insel Reste von Säugethieren zu finden, so eifrig er auch darnach in den Höhlen des Tertiaergebirges suchte (7, IV,

  5. Entendendo a entropia de von Neumann

    OpenAIRE

    Maziero, Jonas

    2015-01-01

    Revisamos os postulados da mecânica quântica necessários para discutir a entropia de von Neumann, que é introduzida como uma generalização da entropia de Shannon e propomos um jogo simples que facilita o entendimento do seu significado físico.

  6. Das Haarkleid eines Fetus von Schimpanse

    NARCIS (Netherlands)

    Bolk, L.

    1919-01-01

    In seiner ausführlichen Arbeit über die Richtung der Haare bei den Affenembryonen nebst allgemeinen Erörterungen über die Ursachen der Haarrichtungen, hat Schwalbe eine Fülle von Tatsachen und eine wertvolle kritische Betrachtung über das Problem der Haarrichtungen geliefert. Leider war der Autor ni

  7. Human peptide transporters

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Brodin, Birger; Jørgensen, Flemming Steen

    2002-01-01

    Peptide transporters are epithelial solute carriers. Their functional role has been characterised in the small intestine and proximal tubules, where they are involved in absorption of dietary peptides and peptide reabsorption, respectively. Currently, two peptide transporters, PepT1 and PepT2, wh...

  8. Human peptide transporters

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Brodin, Birger; Jørgensen, Flemming Steen;

    2002-01-01

    Peptide transporters are epithelial solute carriers. Their functional role has been characterised in the small intestine and proximal tubules, where they are involved in absorption of dietary peptides and peptide reabsorption, respectively. Currently, two peptide transporters, PepT1 and PepT2...

  9. Inherited pancreatic endocrine tumor syndromes: advances in molecular pathogenesis, diagnosis, management and controversies

    Science.gov (United States)

    Jensen, Robert T.; Berna, Marc J.; Bingham, David B; Norton, Jeffrey A.

    2008-01-01

    Pancreatic endocrine tumors (PETs) can occur in as part of four inherited disorders including: Multiple Endocrine Neoplasia type 1 (MEN1), von Hippel-Lindau disease (VHL), neurofibromatosis 1(NF-1) [von Recklinghausen’s disease] and the tuberous sclerosis complex (TSC). The relative frequency with which patients with these disorders develop PETs is MEN1>VHL>NF-1>TSC. Over the last few years there have been major advances in the understanding of the genetics and molecular pathogenesis of these disorders as well in the localization, medical and surgical treatment of the PETs in these patients. The study of the PETs in these disorders has not only provided insights into the possible pathogenesis of sporadic PETs, but have also presented a number of unique management and treatment issues, some of which are applicable to patients with sporadic PETs. Therefore the study of PETs in these uncommon disorders has provided valuable insights that in many cases are applicable to the general group of patients with sporadic PETs. In this article these areas are briefly reviewed as well as the current state of knowledge of the PETs in these disorders and the controversies that exist in their management are briefly summarized and discussed. PMID:18798544

  10. Nuclear molecular imaging of paragangliomas; Imagerie moleculaire nucleaire des paragangliomes

    Energy Technology Data Exchange (ETDEWEB)

    Taieb, D.; Tessonnier, L.; Mundler, O. [Service central de biophysique et de medecine nucleaire, CHU de la Timone, 13 - Marseille (France)

    2010-08-15

    Paragangliomas (PGL) are relatively rare neural crest tumors originating in the adrenal medulla (usually called pheochromocytoma), chemoreceptors (i.e., carotid and aortic bodies) or autonomic ganglia. These tumors are highly vascular, usually benign and slow-growing. PGL may occur as sporadic or familial entities, the latter mostly in association with germline mutations of the succinate dehydrogenase (SDH) B, SDHC, SDHD, SDH5, von Hippel-Lindau (VHL), ret proto-oncogene (RET), neurofibromatosis 1 (NF1) (von Recklinghausen's disease), prolyl hydroxylase domain protein 2 (PHD2) genes and TMEM127. Molecular nuclear imaging has a central role in characterization of PGL and include: somatostatin receptor imaging ({sup 111}In, {sup 68}Ga), MIBG scintigraphy ({sup 131}I, {sup 123}I), {sup 18}F-dihydroxy-phenylalanine ({sup 18}F-DOPA) positron emission tomography (PET), and {sup 18}F-deoxyglucose ({sup 18}F-FDG) PET. The choice of the tracer is not yet fully established but the work-up of familial forms often require the combination of multiple approaches. (authors)

  11. Doença de von Willebrand e anestesia Enfermedad de von Willebrand y anestesia Von Willebrand's disease and anesthesia

    OpenAIRE

    Fabiano Timbó Barbosa; Rafael Martins da Cunha; Luciano Timbó Barbosa

    2007-01-01

    JUSTIFICATIVA E OBJETIVOS: A doença de von Willebrand ocorre devido à mutação no cromossomo 12 e é caracterizada por deficiência qualitativa ou quantitativa do fator de von Willebrand. A diversidade de mutações leva ao aparecimento das mais variadas manifestações clínicas possibilitando a divisão dos pacientes em vários tipos e subtipos clínicos. A coagulopatia se manifesta basicamente através da disfunção plaquetária associada à diminuição dos níveis séricos do fator VIII coagulante. O objet...

  12. Wir zeigen andere Bilder von Frauen ...

    Directory of Open Access Journals (Sweden)

    Bettina Rulofs

    2010-03-01

    Full Text Available Der vorliegende Beitrag beleuchtet die Bedeutung der Geschlechterordnung im Prozess der sportmedialen Kommunikation. Im Kern geht es um die Frage, inwiefern im Prozess der medialen Vermittlung von Sport traditionelle Geschlechterstereotype aufrechterhalten werden oder Möglichkeiten der Irritation solcher Stereotype bestehen. Dazu werden verschiedene Ebenen des massenmedialen Kommunikationsprozesses in den Blick genommen: die Medienprodukte, die Öffentlichkeitsarbeit und Selbst-Präsentation der Sportler/innen, die Medienrezeption und die Herstellungsprozesse von Medien in den Sportredaktionen. This article illustrates the relevance of gender in processes of sports media communication. The question in focus is in what way traditional gender stereotypes are perpetuated in the process of media communication in sport and how such stereotypes can be irritated. Therefore different levels of mass media communication are considered: the media products, the public relations of athletes and the presentation of themselves as athletes, the media-reception and the production processes in sport departments of media institutions.

  13. Von Neumann's Quantization of General Relativity

    CERN Document Server

    Arbuzov, A B; Cirilo-Lombardo, D J; Nazmitdinov, R G; Han, Nguyen Suan; Pavlov, A E; Pervushin, V N; Zakharov, A F

    2015-01-01

    Von Neumann's procedure is applied for quantization of General Relativity. We quantize the initial data of dynamical variables at the Planck epoch, where the Hubble parameter coincides with the Planck mass. These initial data are defined via the Fock simplex in the tangent Minkowskian space-time, the Dirac conformal interval. The Einstein cosmological principle is applied for the average of the spatial metric determinant logarithm over the spatial volume of the visible Universe. We derive the splitting of the general coordinate transformations into the diffeomorphisms (as the object of the second Noether theorem) and the initial data transformations (as objects of the first Noether theorem). Following von Neumann, we suppose that the vacuum state is a quantum ensemble. The vacuum state is degenerated with respect to quantum numbers of non-vacuum states with the distribution function that yields the Casimir effect in gravidynamics in analogy to the one in electrodynamics. The generation functional of the pertu...

  14. Integrales Lernen in und von Organisationen

    Directory of Open Access Journals (Sweden)

    Wendelin Kupers

    2006-06-01

    Full Text Available Bezogen auf das integrale Models von Ken Wilber untersucht der Beitrag die Bedeutung des Lernens in und von Organisationen. Nach einer Darstellung der Relevanz und des Grundverständnisses des Lernens im Organisationskontext, werden integrale Dimensionen des Lernens dargestellt. Im Einzelnen werden die verschiedenen Sphären eines inneren-subjektiven und äusseren-„objektiven“ Lernens des Einzelnen als auch ein gemeinschaftliches Lernen und Lernen im System auf der kollektiven Ebene dargestellt sowie deren interrelationaler Zusammenhang diskutiert. Schließlich beschreibt der Beitrag noch integrale Lernprozesse sowie integrale Gestaltungsfelder zur Förderung des Lernens in den verschiedenen Bereichen. Abschließend spricht der Artikel noch Schwierigkeiten und Probleme an sowie nimmt im Fazit ein perspektivischen Ausblick vor.

  15. NOTIZ USER EIN GNETUM VON BORNEO

    Directory of Open Access Journals (Sweden)

    Fr. Markgraf

    2015-11-01

    Full Text Available Diese Varietat, die ich friiher nach unvollstandigem Material zu G. diminutum gerechnet habe, besitzt in beiden Geschlechtern verzweigte Blutenstande. Dieses Merkmal kommt in der Gruppe mit sitzenden Fruch-ten (Subsection Sessiles nur bei G. leptostachyum, vor, zu dem auch die Friichte der neuen Varietat gut passen. Sie ist eine Nebelwaldpflanze grosserer Hohen und hat bei reduzierten Massen der Blatter und Bliitenstande die schmalen, kurzen mannlichen Katzchen der Tieflands-Varietat leptostachyum mit den kurzgliedrigen, grossfriichtigen weiblichen Bluten-standen der Tieflands-Varietat robustum vereinigt. In Indochina und Siam lebt eine zweite Berg-Varietat — entsprechend der weiteren Ent-fernung vom Aquator in etwas geringeren Hohen die umgekehrt die dicken mannlichen Katzchen von der Varietat robustum mit den lang-gliedrigen weiblichen Bliitenstanden von der Varietat leptostachyum vereinigt. In beiden Fallen sind die Verkiirzungs- und Verlangerungs-Tenden-zen bei den Berg-Varietaten starker als bei denen des Tieflandes.

  16. Evolution equations of von Karman type

    CERN Document Server

    Cherrier, Pascal

    2015-01-01

    In these notes we consider two kinds of nonlinear evolution problems of von Karman type on Euclidean spaces of arbitrary even dimension. Each of these problems consists of a system that results from the coupling of two highly nonlinear partial differential equations, one hyperbolic or parabolic and the other elliptic. These systems take their name from a formal analogy with the von Karman equations in the theory of elasticity in two dimensional space. We establish local (respectively global) results for strong (resp., weak) solutions of these problems and corresponding well-posedness results in the Hadamard sense. Results are found by obtaining regularity estimates on solutions which are limits of a suitable Galerkin approximation scheme. The book is intended as a pedagogical introduction to a number of meaningful application of classical methods in nonlinear Partial Differential Equations of Evolution. The material is self-contained and most proofs are given in full detail. The interested reader will gain a ...

  17. Metabolisierung von Lebensmittelinhaltsstoffen im simulierten Verdauungsmodell

    OpenAIRE

    Hageböck, Martin

    2013-01-01

    Mit Hilfe eines in vitro Modells, basierend auf 4 hintereinander geschalteten Bioreaktoren, war es möglich, komplexe Vorgänge der Verdauung modellhaft nachzustellen. Somit konnte die stufenweise Metabolisierung von ausgewählten Lebensmittelinhaltsstoffen unter definierten physikochemischen, enzymatischen und mikrobiellen Bedingungen der einzelnen Verdauungsstufen verfolgt werden. Beim Einsatz der polyphenolischen Reinsubstanzen wurden zunächst charakteristische Abbaureaktionen wie Hydrolyse v...

  18. La Medea de Lars von Trier

    Directory of Open Access Journals (Sweden)

    Iratxe Fresneda Delgado

    2013-04-01

    Full Text Available El presente artículo analiza el modo en el que Lars von Trier recrea para el cine el estereotipo de Medea. Mediante el análisis fílmico de la película y apoyándose en los estudios culturales, el texto se interroga acerca de la importancia y el poder potencial del cine a la hora recuperar el antiguo mito y demostrar su vigencia. El análisis amplía horizontes para la compresión de los mecanismos que articulan el entramado de significados de la película, donde Von Trier aporta una nueva visión del arquetipo de Medea uniéndola, a la tradición pictórica del Romanticismo. Una influencia que habita en las posteriores obras del director danés, donde el paisaje, la naturaleza, se erige en elemento catalizador de las pulsiones humanas, en su cómplice y testigo.This paper explores the way that Lars von Trier’s film recreates the stereotype of Medea. Using film analysis and based on cultural studies the article asks about the importance and potential power of cinema to recover the ancient myth and show their effects. The analysis expands horizons for the understanding of the mechanisms that link the network of meanings of the film, where the author offers a new vision of Medea's archetype attaching it to the pictorial tradition tied to the Romanticism. An influence that can be seen in the later works of Lars von Trier, where the landscape, the nature, stands as a catalyst of human drives, as his accomplice and witness.

  19. Diskretfrequente Synthese von Nachhall-Prozessen

    OpenAIRE

    Boesnecker, Robert

    2008-01-01

    Die Arbeit verfolgt einen neuartigen Ansatz zur digitalen Nachhallsynthese. Es wird dabei von folgender Beobachtung ausgegangen: Ruft man in ein Klavier, dessen Saiten unbedämpft sind, so antwortet das Instrument mit einem aus diskreten Einzeltönen bestehenden Nachklang, der ähnlich wie ein raumakustischer Nachhall klingt. Verbreitert man bei einer diskretfrequenten Synthese nun die spektrale Breite eines jeden "Klaviertons" auf einen schmalbandigen Bandpass, so dass nicht 12 Töne, sondern 12...

  20. Von Medien, Übertragungen und Automaten

    Directory of Open Access Journals (Sweden)

    Alessandro Barberi

    2013-12-01

    Full Text Available Im Zuge der Debatten zum Medialen Habitus wurde vielfach betont, dass die >Theorie der Praxispraxeologischen Medientheorie< des Medialen Habitus avant la lettre gesprochen werden kann. Dieser Artikel untersucht – ausgehend von den Debatten zur "Medienkompetenz" – wie Bourdieu Sprache, Sprechen und Diskurs, sowie Akteure, Felder und Habitus als Medien begreift und betont dabei die Nützlichkeit der Bourdieuschen Bildungssoziologie im Rahmen einer sozialwissenschaftlichen Grundlegung der Medienpädagogik.

  1. Bettina von Zwehl: Made up Love Song

    OpenAIRE

    Brown, Camilla

    2012-01-01

    This article considers an exhibition of work made whilst the artist Bettina von Zwehl was on a residency at the Victoria and Albert Museum London. Influenced by their miniature collection she made a new series of work and for the first time made one longer series of work with the same person. This essay considers how this development evolved from the artist's previous practice over a period of 10 years.

  2. Herstellung von Chitosan und einige Anwendungen

    Science.gov (United States)

    Struszczyk, Marcin Henryk

    2001-05-01

    1. Die Deacetylierung von crabshell - Chitosan führte gleichzeitig zu einem drastischen Abfall der mittleren viscosimetrischen Molmasse ( Mv), insbesondere wenn die Temperatur und die Konzentration an NaOH erhöht werden. Diese Parameter beeinflussten jedoch nicht den Grad der Deacetylierung (DD). Wichtig ist jedoch die Quelle des Ausgangsmaterials: Chitin aus Pandalus borealis ist ein guter Rohstoff für die Herstellung von Chitosan mit niedrigem DD und gleichzeitig hoher mittlerer Mv, während Krill-Chitin (Euphausia superba) ein gutes Ausgangsmaterial zur Herstellung von Chitosan mit hohem DD und niedrigem Mv ist. Chitosan, das aus Insekten (Calliphora erythrocephala), unter milden Bedingungen (Temperatur: 100°C, NaOH-Konzentration: 40 %, Zeit: 1-2h ) hergestellt wurde, hatte die gleichen Eigenschaften hinsichtlich DD und Mv wie das aus Krill hergestellte Chitosan. Der Bedarf an Zeit, Energie und NaOH ist für die Herstellung von Insekten-Chitosan geringer als für crabshell-Chitosan vergleichbare Resultaten für DD und Mv. 2. Chitosan wurde durch den Schimmelpilz Aspergillus fumigatus zu Chitooligomeren fermentiert. Die Ausbeute beträgt 25%. Die Chitooligomere wurden mit Hilfe von HPLC und MALDI-TOF-Massenspektrmetrie identifiziert. Die Fermentationsmischung fördert die Immunität von Pflanzen gegen Bakterien und Virusinfektion. Die Zunahme der Immunität schwankt jedoch je nach System Pflanze-Pathogen. Die Fermentation von Chitosan durch Aspergillus fumigatus könnte eine schnelle und billige Methode zur Herstellung von Chitooligomeren mit guter Reinheit und Ausbeute sein. Eine partiell aufgereinigte Fermentationsmischung dieser Art könnte in der Landwirtschaft als Pathogeninhibitor genutzt werden. Durch kontrollierte Fermentation, die Chitooligomere in definierter Zusammensetzung (d.h. definierter Verteilung des Depolymerisationsgrades) liefert, könnte man zu Mischungen kommen, die für die jeweilige Anwendung eine optimale Bioaktivität besitzen. 3

  3. Optimierung von Mehrkörpersystemen

    OpenAIRE

    Theis, Winfried; Räbiger, Klaus

    2009-01-01

    Auf Grund der ständig steigenden Anforderungen während der Entwicklung neuartiger Produkte ist es oftmals schwierig einen optimalen Entwurf zu finden. Die vorliegende Arbeit soll deshalb einen Einblick in die Welt der mathematischen Optimierung geben und anhand von ausgewählten Beispielen aus der Mehrkörperdynamik die nötigen Schritte einer Optimierungsrechnung genauer erklären. Spezielle Aufmerksamkeit wird hierbei der Ermittlung der Bewegungsgleichungen, der Formulierung der Optimierungsauf...

  4. Katheterablation von Vorhofflimmern - Neue Technologien und Strategien

    Directory of Open Access Journals (Sweden)

    Rolf S

    2011-01-01

    Full Text Available Die Katheterablation von symptomatischem Vorhofflimmern hat sich zu einem Therapieverfahren mit reproduzierbaren Erfolgsraten und überschaubarem Risiko bei selektierten Patientenkollektiven entwickelt. Hinsichtlich der Effektivität ist sie der Antiarrhythmika-Therapie schon heute überlegen. Die Verfahrenstechnik wird stetig weiterentwickelt, um die langfristige Erfolgsrate zu erhöhen, die Rate an Re-Interventionen zu reduzieren, die Komplikationsraten zu senken, die Prozedur selber zu vereinfachen und die Prozedurzeit zu verkürzen. Beispiele für solche Neuerungen sind die zielorientierte CT-Integration in elektro-anatomische Mappingsysteme, die optimierte Schaffung und Validierung linearer Läsionen mit der Pace-and-Ablate-Strategie, der effizientere Energietransfer ins Gewebe durch Verwendung steuerbarer transseptaler Schleusen und Berücksichtigung des elektrischen Kontaktes, sowie die strategische Planung von Linienkonzepten bei atrialen Makro-Reentry-Tachykardien durch Erstellung farbkodierter Entrainment- Maps. Diese Behandlungsinnovationen haben sich als wirkungsvoll erwiesen und in den vergangenen Jahren Einzug in den klinischen Alltag der Katheterablation von Vorhofflimmern im Herzzentrum Leipzig gefunde

  5. Engagement und Beanspruchung von Lehrpersonen in der Phase des Berufseintritts

    OpenAIRE

    Affolter-Huber, Benita Barbara

    2017-01-01

    Die Dissertation untersucht die Entstehung von Engagement und Beanspruchung von Lehrpersonen am Übergang von der Ausbildung in den Beruf. Das Job Demands-Resources Modell wird durch die Lern- und Vermeidungsleistungszielorientierung, die allgemeine Selbstwirksamkeits- sowie die Lehrerselbstwirksamkeitserwartung, die Extraversion und den Neurotizismus ergänzt und empirisch mittels Pfadanalysen geprüft. Aus den Befunden geht hervor, dass das Engagement und die Beanspruchung durch unterschiedlic...

  6. Studien zur Kinetik der Fehlfaltung un Aggregation von Proteinen

    OpenAIRE

    Modler, Andreas Johannes

    2003-01-01

    Diese Arbeit befasst sich mit der Kinetik der Fehlfaltung und Aggregation von Proteinen. Anhand dreier Beispiele, der Phosphoglyceratkinase (PGK) aus Hefe, einer Variante von Barstar und des Prion-Proteins des Syrischen Hamsters (SHaPrP(90-232)) wurde insbesondere die Kinetik der Bildung von Amyloidfibrillen und deren kinetischer Vorläuferstrukturen mittels dynamischer und statischer Lichtstreuung, Circulardichroismus, Infrarotspektroskopie, Elektronenmikroskopie und teilweise analytischer Ch...

  7. From regular modules to von Neumann regular rings via coordinatization

    Directory of Open Access Journals (Sweden)

    Leonard Daus

    2014-07-01

    Full Text Available In this paper we establish a very close link (in terms of von Neu- mann's coordinatization between regular modules introduced by Zel- manowitz, on one hand, and von Neumann regular rings, on the other hand: we prove that the lattice L^{fg}(M of all finitely generated submodules of a finitely generated regular module M, over an arbitrary ring, can be coordinatized as the lattice of all principal right ideals of some von Neumann regular ring S.

  8. Thomas-Fermi-von Weizsaecker theory of atoms and molecules

    Energy Technology Data Exchange (ETDEWEB)

    Benguria, R.; Brezis, H.; Lieb, E.H.

    1981-11-02

    We place the Thomas-Fermi-von Weizsaecker model of atoms on a firm mathematical footing. We prove existence and uniqueness of solutions of the Thomas-Fermi-von Weizsaecker equation as well as the fact that they minimize the Thomas-Fermi-von Weizsaecker energy functional. Moreover, we prove the existence of bindings for two very dissimilar atoms in the frame of this model.

  9. Portrait of Dr. Von Braun with Walt Disney, 1954.

    Science.gov (United States)

    1954-01-01

    Marshall Center Director Dr. Wernher Von Braun is pictured with Walt Disney during a visit to the Marshall Space Flight Center in 1954. In the 1950s, Dr. Von Braun while working in California on the Saturn project, also worked with Disney studios as a technical director in making three films about Space Exploration for television. Disney's tour of Marshall in 1965 was Von Braun's hope for a renewed public interest in the future of the Space Program at NASA.

  10. Saage tuttavaks : Elisabeth ja Karl von Hoerschelmann / Mai Levin

    Index Scriptorium Estoniae

    Levin, Mai, 1942-

    2004-01-01

    Kuraator M. Levin kuni 10. X 2004 Adamson-Ericu muuseumis avatud näitusest "Tuntud ja tundmatud Elisabeth von Rosendorff-Hoerschelmann ja Karl von Hoerschelmann". Enamik töid on kunstnike laste Konstantin Hoerschelmanni ja Anna Röder-Hoerschelmanni omand. Elisabeth Rosendorff (1898-1984) sündis Virumaal Maidlas eesti perekonnas, Karl von Hoerschelmann (1899-1951) Sevastoopolis saksa perekonnas

  11. Saage tuttavaks : Elisabeth ja Karl von Hoerschelmann / Mai Levin

    Index Scriptorium Estoniae

    Levin, Mai, 1942-

    2004-01-01

    Kuraator M. Levin kuni 10. X 2004 Adamson-Ericu muuseumis avatud näitusest "Tuntud ja tundmatud Elisabeth von Rosendorff-Hoerschelmann ja Karl von Hoerschelmann". Enamik töid on kunstnike laste Konstantin Hoerschelmanni ja Anna Röder-Hoerschelmanni omand. Elisabeth Rosendorff (1898-1984) sündis Virumaal Maidlas eesti perekonnas, Karl von Hoerschelmann (1899-1951) Sevastoopolis saksa perekonnas

  12. Sicherheitskriterien bei der Auswahl von ERP-Systemen

    OpenAIRE

    Wollersheim, Jan;Konstantinidis, Christos;Krcmar, Helmut

    2014-01-01

    Bei Auswahl und Anpassung von Software as a Service (SaaS) basierten ERP-Systemen (SaaS-ERP) kann auf bew?hrte und erprobte Kriterien zur?ckgegriffen werden. Dieser Beitrag strukturiert exemplarisch ausgew?hlte Sicherheits- und Risiko-Kriterien (S&R-Kriterien) anhand von f?nf Perspektiven. Dabei wird zuerst die Auswahl und im Folgenden die Anpassung von SaaS basierten ERP-Systemen betrachtet.

  13. Preiswettbewerb im deutschen Lebensmitteleinzelhandel: Empirische Analysen anhand von Scannerdaten

    OpenAIRE

    Hoffmann, Angela

    2012-01-01

    Der deutsche Lebensmitteinzelhandel ist durch eine hohe Konzentration und einen intensiven Preiswettbewerb gekennzeichnet. Ziel dieser Arbeit ist es, die Preissetzung von Discountern, Super- und Verbrauchermärkten unter Beachtung von Sonderangeboten und den daraus resultierenden Preiswettbewerb zu analysieren. Vier empirische Studien anhand von Scannerdaten werden durchgeführt. Es zeigt sich, dass das Ausmaß der Preissynchronisation bei Milchprodukten im deutschen Handel deutlich größer i...

  14. PeptideAtlas

    Data.gov (United States)

    U.S. Department of Health & Human Services — PeptideAtlas is a multi-organism, publicly accessible compendium of peptides identified in a large set of tandem mass spectrometry proteomics experiments. Mass...

  15. Solares Recyceln von Aluminium in einem direkt bestrahlten Drehrohrofen

    OpenAIRE

    Neises-von Puttkamer, Martina; Roeb, Martin; Beyer, T.; Reinhold, Jan Philipp; Willsch, Christian; Thelen, Martin; Raeder, Christian; Oliveira,Lamark de; TESCARI, Stefania; Breuer, Stefan; Sattler, Christian

    2016-01-01

    Das Aufschmelzen von Metallen ist ein energieintensiver Prozess, da hier hohe Temperaturen benötigt werden. Konventionell wird diese Energie mit fossilen Energieträgern zur Verfügung gestellt. Mit einem solaren Schmelzverfahren von Metallen können der Ausstoß von CO2 und die Energiekosten der Gießereien erheblich gesenkt werden. Insbesondere Länder mit hoher direkter Solarstrahlung wie Südafrika, können ein solches Verfahren zum Schmelzen und Wiederverwerten von Metallschrott einsetzten. ...

  16. Peptide Nucleic Acids (PNA)

    DEFF Research Database (Denmark)

    2002-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  17. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    1998-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  18. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2003-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  19. Antimicrobial Peptides in 2014

    Directory of Open Access Journals (Sweden)

    Guangshun Wang

    2015-03-01

    Full Text Available This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release its cargo. Proline-rich peptides, previously known to bind to heat shock proteins, are shown to inhibit protein synthesis. A model antimicrobial peptide is demonstrated to have multiple hits on bacteria, including surface protein delocalization. While cell surface modification to decrease cationic peptide binding is a recognized resistance mechanism for pathogenic bacteria, it is also used as a survival strategy for commensal bacteria. The year 2014 also witnessed continued efforts in exploiting potential applications of antimicrobial peptides. We highlight 3D structure-based design of peptide antimicrobials and vaccines, surface coating, delivery systems, and microbial detection devices involving antimicrobial peptides. The 2014 results also support that combination therapy is preferred over monotherapy in treating biofilms.

  20. Peptide Nucleic Acid Synthons

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  1. Peptide-Carrier Conjugation

    DEFF Research Database (Denmark)

    Hansen, Paul Robert

    2015-01-01

    To produce antibodies against synthetic peptides it is necessary to couple them to a protein carrier. This chapter provides a nonspecialist overview of peptide-carrier conjugation. Furthermore, a protocol for coupling cysteine-containing peptides to bovine serum albumin is outlined....

  2. PH dependent adhesive peptides

    Science.gov (United States)

    Tomich, John; Iwamoto, Takeo; Shen, Xinchun; Sun, Xiuzhi Susan

    2010-06-29

    A novel peptide adhesive motif is described that requires no receptor or cross-links to achieve maximal adhesive strength. Several peptides with different degrees of adhesive strength have been designed and synthesized using solid phase chemistries. All peptides contain a common hydrophobic core sequence flanked by positively or negatively charged amino acids sequences.

  3. Zielgerechte Logistikkonzepte in Betrachtung von LNG- Umschlageplätzen unter Berücksichtigung von Industrie 4.0

    OpenAIRE

    Jenne, Christian; Noche, Bernd

    2016-01-01

    Logistikkonzepte in der Spedition und Transportgewerbe spielen heutzutage eine immer wichtigere Rolle, um Lohnnebenkosten so niedrig wie möglich zu halten. Gerade in der Spedition entsteht ein Zusammenspiel aus zeitnaher Lieferung von Konsumgütern und Optimierung der Lagerhaltungskosten bei dem die modulare Integration von Logistik, Informationstechnischen Systemen und vernetzter Kommunikation eine ganz spezifische Rolle hat. Anbindung von der Industrie zum Kunden wird dadurch immer mehr vers...

  4. WIE PREISSENSIBEL REAGIEREN DEUTSCHE VERBRAUCHER? AKTUELLE SCHÄTZUNGEN VON PREIS- UND AUSGABENELASTIZITÄTEN AUF DER BASIS VON HAUSHALTSPANELDATEN

    OpenAIRE

    2012-01-01

    Der Beitrag untersucht das Nachfrageverhalten der deutschen Privathaushalte anhand von Daten zweier Haushaltspanels der Gesellschaft für Konsumforschung. Es wird ein Almost Ideal Demand System (AIDS) mit 13 Lebensmittelgruppen für den Zeitraum von 2004 bis 2008 geschätzt. Der Fokus der Analyse liegt auf den geschätzten Eigenpreis- und Ausga-benelastizitäten und deren Einordnung in die Literatur. Mit Ausnahme von Kaffee und Eiern zeigt sich die Nachfrage in allen Lebensmittelgruppen, darunter ...

  5. Produktion von pharmakologischen Sekundärmetabolite - Am Beispiel von mikrobiellen β-Lactam-Antibiotika und pflanzlichen Triterpenen

    OpenAIRE

    Ludwig, Benjamin

    2015-01-01

    Durch das Entstehen von neuen Infektionskrankheiten und das Auftreten von Resistenzen können bisher verwendete Medikamente ihren pharmazeutischen Nutzen verlieren. Daher ist eine konstante Weiterentwicklung von bioaktiven Pharmazeutika lebensrettend. Viele pflanzli-che und mikrobielle Sekundärmetabolite besitzen gesundheitsfördernde Wirkungen und kön-nen als Ressourcen für die Entwicklung neuer Arzneimittel herangezogen werden. Da Pflan-zen und Mikroorganismen ein sehr umfangreiches Repertoir...

  6. Assoziation des arteriellen Sauerstoffpartialdrucks mit dem Auftreten von Erythroblasten im peripheren Blut von Patienten einer chirurgischen Intensivstation

    OpenAIRE

    Kuert, Sandra

    2012-01-01

    Erythroblasten (EBL) treten im peripheren Blut eines gesunden Erwachsenen gewöhnlich nicht auf. Studien zeigten, dass das Auftreten von EBL bei hospitalisierten Patienten auf ein erhöhtes Mortalitätsrisiko hinweist. Die zugrundeliegenden Mechanismen sind bisher unbekannt. Es ergaben sich Hinweise, dass EBL bei Zuständen von Hypoxie und Inflammation auftreten. Die vorliegende Studie untersucht den Einfluss des arteriellen Sauerstoffpartialdruckes (pO2) auf das Auftreten von EBL ...

  7. Philologie im Horizont der Geschichtlichkeit von Sprache und Text: zum Tagungsband von Wulf Oesterreicher und Maria Selig

    Directory of Open Access Journals (Sweden)

    Olaf Müller

    2016-03-01

    Full Text Available Wulf Oesterreicher und Maria Selig, Hrsg., Geschichtlichkeit von Sprache und Text: Philologien – Disziplingenese – Wissenschaftshistoriographie (Paderborn: Wilhelm Fink, 2014, 332 S.

  8. Unterschiedliche beta-blockierende Wirkungen von Carvedilol, Metoprolol und Bisoprolol

    Directory of Open Access Journals (Sweden)

    Stoschitzky K

    2001-01-01

    Full Text Available Metoprolol und Bisoprolol sind beta1-selektive Beta-Blocker, Carvedilol ist ein nicht-selektiver Beta-Blocker mit zusätzlicher alpha1-blockierender Wirkung. Wir verglichen die Wirkungen von klinisch empfohlenen Dosen von Carvedilol (25, 50 und 100 mg, Metoprolol (50, 100 und 200 mg und Bisoprolol (2,5, 5 und 10 mg mit Placebo in einer randomisierten, überkreuzten, placebokontrollierten Doppelblind-Studie an 12 gesunden männlichen Freiwilligen. Zwei Stunden (Bisoprolol: drei Stunden nach oraler Applikation der jeweiligen Substanzen wurden arterieller Blutdruck und Herzfrequenz in Ruhe, nach 10 Minuten Belastung und nach weiteren 15 Minuten Erholung gemessen. Verglichen mit Placebo führten ansteigende Dosen von Metoprolol und Bisoprolol in Ruhe zu ansteigenden Wirkungen auf die Herzfrequenz (jeweils -13 %, -15 % und -18 % während ansteigende Dosen von Carvedilol abfallende Wirkungen zeigten (-13 %, -7 % und -3 %. Die Herzfrequenz unter Belastung wurde von Metoprolol (-21 %, -25 % und -24 %, Bisoprolol (-17 %, -21 % und -25 % und Carvedilol gesenkt (-16 %, -16 % und -18 %, die Wirkung von Metoprolol erschien dabei etwas ausgeprägter als jene von Carvedilol. Der systolische Blutdruck wurde sowohl von Metoprolol (-9 %, -16 %, -16 % unter Belastung und -7 %, -7 %, -9 % nach 15 min Erholung, Bisoprolol (-8 %, -12 %, -15 % unter Belastung als auch von Carvedilol (-7 %, -17 %, -20 % unter Belastung und -8 %, -11 %, -14 % nach 15 min Erholung deutlich gesenkt. Auf den diastolischen Blutdruck zeigten die Substanzen (mit Ausnahme von 50 und 100 mg Carvedilol in Ruhe jedoch keine signifikanten Wirkungen. Wir schließen aus unseren Ergebnissen, daß klinisch empfohlene Dosen von Carvedilol bei gesunden Freiwilligen klinisch relevante beta-blockierende Wirkungen nur unter Belastung zeigen, während die von Carvedilol bewirkte Beta-Blockade in Ruhe bestenfalls als schwach zu bezeichnen ist. Auf der anderen Seite zeigen Metoprolol und Bisoprolol sowohl in

  9. Von den Liven von Oesel / August Ludwig Schlözer

    Index Scriptorium Estoniae

    Schlözer, August Ludwig

    2008-01-01

    Avaldatud Eberhard Winkleri initsiatiivil A. L. Schlözeri teose põhjal: Gesammelte Nachrichten von den Ueberresten der Liven, in Livland und Kurland. (1770), mis moodustab osa teosest: Schlözer, August Ludwig. M. Johann Joseph Haigold's Beylagen zum Neuveränderten Russland. Zweiter Theil. Riga und Leipzig, 1770

  10. Ööklubi Club von Überlingen = Club von Überlingen

    Index Scriptorium Estoniae

    2008-01-01

    Ööklubi Club von Überlingen (Madara 22A, Tallinn) sisekujundusest. Sisearhitekt: Taavi Aunre (Boom.ee OÜ). Taavi Aunrest, tema tähtsamad tööd. I-II korruse plaan, 11 värv. vaadet, foto T. Aunrest

  11. Aino Lepik von Wiren / Aino Lepik von Wiren ; interv. Kadi Alatalu

    Index Scriptorium Estoniae

    Lepik von Wirén, Aino, 1961-

    2007-01-01

    Heinrich Marga eksiilvalitsuse (20.06.1990-7.10.1992) kohtuminister Aino Lepik von Wiren pagulaslapse elust Rootsis, haridusest ja elukutse valikust, tööst eksiilvalitsuses, tööleasumisest Eestisse 1992. aastal, seadusandlikust tegevusest ning aluse panekust välismaalaste- ja kodakondsuspoliitikale, naiste võimalustest poliitilisse tippu tõusmiseks, kodu- ja väliseestlaste vastandamisest

  12. Von den Liven von Oesel / August Ludwig Schlözer

    Index Scriptorium Estoniae

    Schlözer, August Ludwig

    2008-01-01

    Avaldatud Eberhard Winkleri initsiatiivil A. L. Schlözeri teose põhjal: Gesammelte Nachrichten von den Ueberresten der Liven, in Livland und Kurland. (1770), mis moodustab osa teosest: Schlözer, August Ludwig. M. Johann Joseph Haigold's Beylagen zum Neuveränderten Russland. Zweiter Theil. Riga und Leipzig, 1770

  13. Simultaneous adrenal pheochromocytoma and carotid body paraganglioma in a woman

    Energy Technology Data Exchange (ETDEWEB)

    Han, Eun Ji; Lee, Sang Hoon; Song, In Uk; Chung, Yong An; Maeng, Lee So [The Catholic Univ. of Korea, Incheon (Korea, Republic of)

    2012-03-15

    Simultaneous occurrence of carotid body tumor and pheochromocytoma is rare. Most pheochromocytomas have grown on adrenal medulla, but some of the pheochromocytoma patients have multifocal paragangliomas arising from extraaderenal tissues. Pheochromocytomas and paragangliomas occur as sporadic tumors or they can be associated with several hereditary syndromes such as (1) multiple endocrine neoplasia type 2 (MEN 2), (2) Von Hippel Lindau disease (VHL) and (3) neurofibromatosis type 1 as an unusual genetic cause of pheochromocytomas. Genetic testing is recommended for patients with an apparently sporadic pheochromocytoma under the age of 20 years with a family history or features suggestive of hereditary pheochromocytoma or for patients with sympathetic paragangliomas. For individuals who do not meet these criteria, genetic testing is optional. Discovery of pheochromocytoma or paraganglioma in a patient should lead to a careful search to rule out multifocal lesions and/or hereditary syndromes. The diagnosis of pheochromocytoma and paraganglioma is made by biochemical testing, and imaging is done to localize the tumor for surgical planning. F 18 FDG PET has proved to be an effective tool in the localization of pheochromocytomas and paragangliomas.

  14. HIF-2α downregulation in the absence of functional VHL is not sufficient for renal cell differentiation

    Directory of Open Access Journals (Sweden)

    Burk Robert D

    2007-06-01

    Full Text Available Abstract Background Mutational inactivation of the von Hippel-Lindau (VHL tumor suppressor gene has been linked to hereditary as well as sporadic clear cell renal carcinomas. The product of the VHL gene, pVHL, acts to target hypoxia-inducible factor alpha (HIF-α subunits for ubiquitination and subsequent degradation. Using an RNA interference approach to lower levels of HIF-2α in two different renal cell lines that lack functional pVHL, we have tested the contribution of HIF-2α toward cellular pVHL activities. Results Knockdown of HIF-2α resulted in cell cycle arrest of renal cells that were grown on collagen I, indicating that this pVHL function is dependent on HIF-2α regulation. However, cellular morphological changes and downregulation of integrins α5 and β1, which were seen upon pVHL replacement, were not faithfully phenocopied by HIF-2α reduction. Moreover, fibronectin deposition and expression of renal cell differentiation markers were observed in cells containing replaced pVHL, but not in HIF-2α knockdown cells, indicating that these pVHL functions may occur independently of HIF-2α downregulation. Conclusion These results indicate that HIF-2α regulation is not sufficient for pVHL-induced renal cell differentiation. We hypothesize that in addition to HIF-2α dysregulation, abrogation of additional pVHL functions is required for the initiation of renal carcinogenesis.

  15. Identification of 3 novel VHL germ-line mutations in Danish VHL patients

    Directory of Open Access Journals (Sweden)

    Dandanell Mette

    2012-07-01

    Full Text Available Abstract Background von Hippel-Lindau (VHL disease is a hereditary cancer syndrome in which the patients develop retinal and central nervous system hemangioblastomas, pheochromocytomas and clear-cell renal tumors. The autosomal dominant disease is caused by mutations in the VHL gene. Methods VHL mutational analysis was carried out by sequencing of the coding sequence and by multiplex ligation-dependent probe amplification analysis. The functional consequence of the variants was investigated using in silico prediction tools. Results A total of 289 probands suspected of having VHL syndrome have been screened for mutations in the VHL gene. Twenty-six different VHL mutations were identified in 36 families including one in-frame duplication, two frame-shift mutations, four nonsense mutations, twelve missense mutations, three intronic mutations and four large genomic rearrangements. Three of these mutations (c.319 C > T, c.342_343dupGGT and c.520_521dupAA were novel. Conclusions In this study we report the VHL germ-line mutations found in Danish families. We found three novel VHL mutations where two were classified as pathogenic and the latter was classified as a variant of unknown significance. Together, our findings contribute to the interpretation of the potential pathogenicity of VHL germ-line mutations.

  16. ERK5/BMK1 Is a Novel Target of the Tumor Suppressor VHL: Implication in Clear Cell Renal Carcinoma12

    Science.gov (United States)

    Arias-González, Laura; Moreno-Gimeno, Inmaculada; del Campo, Antonio Rubio; Serrano-Oviedo, Leticia; Valero, María Llanos; Esparís-Ogando, Azucena; de la Cruz-Morcillo, Miguel Ángel; Melgar-Rojas, Pedro; García-Cano, Jesús; Cimas, Francisco José; Hidalgo, María José Ruiz; Prado, Alfonso; Callejas-Valera, Juan Luis; Nam-Cha, Syong Hyun; Giménez-Bachs, José Miguel; Salinas-Sánchez, Antonio S; Pandiella, Atanasio; del Peso, Luis; Sánchez-Prieto, Ricardo

    2013-01-01

    Extracellular signal-regulated kinase 5 (ERK5), also known as big mitogen-activated protein kinase (MAPK) 1, is implicated in a wide range of biologic processes, which include proliferation or vascularization. Here, we show that ERK5 is degraded through the ubiquitin-proteasome system, in a process mediated by the tumor suppressor von Hippel-Lindau (VHL) gene, through a prolyl hydroxylation-dependent mechanism. Our conclusions derive from transient transfection assays in Cos7 cells, as well as the study of endogenous ERK5 in different experimental systems such as MCF7, HMEC, or Caki-2 cell lines. In fact, the specific knockdown of ERK5 in pVHL-negative cell lines promotes a decrease in proliferation and migration, supporting the role of this MAPK in cellular transformation. Furthermore, in a short series of fresh samples from human clear cell renal cell carcinoma, high levels of ERK5 correlate with more aggressive and metastatic stages of the disease. Therefore, our results provide new biochemical data suggesting that ERK5 is a novel target of the tumor suppressor VHL, opening a new field of research on the role of ERK5 in renal carcinomas. PMID:23730213

  17. Introduction of a PCR-RFLP method for the detection of two mutations in VHL gene

    Directory of Open Access Journals (Sweden)

    Antonio Alejandro Esperón

    2013-07-01

    Full Text Available Background: Von Hippel-Lindau disease is an inherited neoplastic disorder caused by germline mutations in the VHL gene. In Cuba, molecular diagnosis is performed by the method of single-strand conformation polymorphism of DNA of the three exons of the gene followed by sequencing. This method is expensive, complicated and time-consuming. Objective: to describe the introduction of the molecular diagnosis of mutations c.362A>G and c.481C> in the VHL gene by PCR-RFLP. Methods: computer software CLC Sequence viewer 6.5.1 was used to identify restriction enzymes with cleavage sites modified by mutation c.362A>G in the exon 2 and c.481C>T in exon 3 in the VHL gene. DNA samples of patients already diagnosed through SSCP-sequencing were used. Such samples were amplified by PCR method followed by the enzymatic digestion with SfaNI and BtgZI restriction enzymes. Amplified fragments were analyzed by agarose gel electrophoresis. Results obtained using both methods were compared. Results: effectiveness of the PRC-RFLP method for the diagnosis of c.362A>G and c.481C>T mutations in the VHL gene was standardized and proved. Conclusions: PCR-RFLP method has advantages over SSCP-sequencing strategy for establishing a fast, reproducible and reliable diagnosis of VHL disease in family cases molecularly characterized.

  18. Uptake of prenatal diagnostic testing for retinoblastoma compared to other hereditary cancer syndromes in the Netherlands.

    Science.gov (United States)

    Dommering, Charlotte J; Henneman, Lidewij; van der Hout, Annemarie H; Jonker, Marianne A; Tops, Carli M J; van den Ouweland, Ans M W; van der Luijt, Rob B; Mensenkamp, Arjen R; Hogervorst, Frans B L; Redeker, Egbert J W; de Die-Smulders, Christine E M; Moll, Annette C; Meijers-Heijboer, Hanne

    2017-04-01

    Since the 1980s the genetic cause of many hereditary tumor syndromes has been elucidated. As a consequence, carriers of a deleterious mutation in these genes may opt for prenatal diagnoses (PND). We studied the uptake of prenatal diagnosis for five hereditary cancer syndromes in the Netherlands. Uptake for retinoblastoma (Rb) was compared with uptake for Von Hippel-Lindau disease (VHL), Li-Fraumeni syndrome (LFS), familial adenomatous polyposis (FAP), and hereditary breast ovarian cancer (HBOC). A questionnaire was completed by all nine DNA-diagnostic laboratories assessing the number of independent mutation-positive families identified from the start of diagnostic testing until May 2013, and the number of PNDs performed for these syndromes within these families. Of 187 families with a known Rb-gene mutation, 22 had performed PND (11.8%), this was significantly higher than uptake for FAP (1.6%) and HBOC (<0.2%). For VHL (6.5%) and LFS (4.9%) the difference was not statistically significant. PND for Rb started 3 years after introduction of diagnostic DNA testing and remained stable over the years. For the other cancer syndromes PND started 10-15 years after the introduction and uptake for PND showed an increase after 2009. We conclude that uptake of PND for Rb was significantly higher than for FAP and HBOC, but not different from VHL and LFS. Early onset, high penetrance, lack of preventive surgery and perceived burden of disease may explain these differences.

  19. Polymorphism and genetic mapping of the human oxytocin receptor gene on chromosome 3

    Energy Technology Data Exchange (ETDEWEB)

    Michelini, S.; Urbanek, M.; Goldman, D. [National Institute of Health-National Institute of Alcohol Abuse and Alcoholism, Rockville, MD (United States)] [and others

    1995-06-19

    Centrally administered oxytocin has been reported to facilitate affiliative and social behaviors, in functional harmony with its well-known peripheral effects on uterine contraction and milk ejection. The biological effects of oxytocin could be perturbed by mutations occurring in the sequence of the oxytocin receptor gene, and it would be of interest to establish the position of this gene on the human linkage map. Therefore we identified a polymorphism at the human oxytocin receptor gene. A portion of the 3{prime} untranslated region containing a 30 bp CA repeat was amplified by polymerase chain reaction (PCR), revealing a polymorphism with two alleles occurring with frequencies of 0.77 and 0.23 in a sample of Caucasian CEPH parents (n = 70). The CA repeat polymorphism we detected was used to map the human oxytocin receptor to chromosome 3p25-3p26, in a region which contains several important genes, including loci for Von Hippel-Lindau disease (VHL) and renal cell carcinoma. 53 refs., 2 figs., 1 tab.

  20. P53 mutations and cancer: a tight linkage.

    Science.gov (United States)

    Perri, Francesco; Pisconti, Salvatore; Della Vittoria Scarpati, Giuseppina

    2016-12-01

    P53 is often mutated in solid tumors, in fact, somatic changes involving the gene encoding for p53 (TP53) have been discovered in more than 50% of human malignancies and several data confirmed that p53 mutations represent an early event in cancerogenesis. Main p53 functions consist in cell cycle arrest, DNA repair, senescence and apoptosis induction in response to mutagenic stimuli, and, to exert those functions, p53 acts as transcriptional factor. Recent data have highlighted another very important role of p53, consisting in regulate cell metabolism and cell response to oxidative stress. Majority of tumor suppressor genes, such as adenomatous polyposis coli (APC), retinoblastoma-associated protein (RB) and Von-Hippel-Lindau (VHL) are inactivated by deletion or early truncation mutations in tumors, resulting in the decreased or loss of expression of their proteins. Differently, most p53 mutations in human cancer are missense mutations, which result in the production of full-length mutant p53 proteins. It has been reported that mutant p53 proteins and wild type p53 proteins often regulate same cellular biological processes with opposite effects. So, mutant p53 has been reported to supply the cancer cells of glucose and nutrients, and, to avoid reactive oxygen species (ROS) mediated damage during oxidative stress. These last features are able to render tumor cells resistant to ionizing radiations and chemotherapy. A future therapeutic approach in tumors bearing p53 mutations may be to deplete cancer cells of their energy reserves and antioxidants.

  1. A systems approach reveals distinct metabolic strategies among the NCI-60 cancer cell lines

    Science.gov (United States)

    Aurich, Maike K.; Fleming, Ronan M. T.; Thiele, Ines

    2017-01-01

    The metabolic phenotype of cancer cells is reflected by the metabolites they consume and by the byproducts they release. Here, we use quantitative, extracellular metabolomic data of the NCI-60 panel and a novel computational method to generate 120 condition-specific cancer cell line metabolic models. These condition-specific cancer models used distinct metabolic strategies to generate energy and cofactors. The analysis of the models’ capability to deal with environmental perturbations revealed three oxotypes, differing in the range of allowable oxygen uptake rates. Interestingly, models based on metabolomic profiles of melanoma cells were distinguished from other models through their low oxygen uptake rates, which were associated with a glycolytic phenotype. A subset of the melanoma cell models required reductive carboxylation. The analysis of protein and RNA expression levels from the Human Protein Atlas showed that IDH2, which was an essential gene in the melanoma models, but not IDH1 protein, was detected in normal skin cell types and melanoma. Moreover, the von Hippel-Lindau tumor suppressor (VHL) protein, whose loss is associated with non-hypoxic HIF-stabilization, reductive carboxylation, and promotion of glycolysis, was uniformly absent in melanoma. Thus, the experimental data supported the predicted role of IDH2 and the absence of VHL protein supported the glycolytic and low oxygen phenotype predicted for melanoma. Taken together, our approach of integrating extracellular metabolomic data with metabolic modeling and the combination of different network interrogation methods allowed insights into the metabolism of cells. PMID:28806730

  2. VHL type 2B mutations retain VBC complex form and function.

    Directory of Open Access Journals (Sweden)

    Kathryn E Hacker

    Full Text Available BACKGROUND: von Hippel-Lindau disease is characterized by a spectrum of hypervascular tumors, including renal cell carcinoma, hemangioblastoma, and pheochromocytoma, which occur with VHL genotype-specific differences in penetrance. VHL loss causes a failure to regulate the hypoxia inducible factors (HIF-1alpha and HIF-2alpha, resulting in accumulation of both factors to high levels. Although HIF dysregulation is critical to VHL disease-associated renal tumorigenesis, increasing evidence points toward gradations of HIF dysregulation contributing to the degree of predisposition to renal cell carcinoma and other manifestations of the disease. METHODOLOGY/PRINCIPAL FINDINGS: This investigation examined the ability of disease-specific VHL missense mutations to support the assembly of the VBC complex and to promote the ubiquitylation of HIF. Our interaction analysis supported previous observations that VHL Type 2B mutations disrupt the interaction between pVHL and Elongin C but maintain partial regulation of HIF. We additionally demonstrated that Type 2B mutant pVHL forms a remnant VBC complex containing the active members ROC1 and Cullin-2 which retains the ability to ubiquitylate HIF-1alpha. CONCLUSIONS: Our results suggest that subtypes of VHL mutations support an intermediate level of HIF regulation via a remnant VBC complex. These findings provide a mechanism for the graded HIF dysregulation and genetic predisposition for cancer development in VHL disease.

  3. Small Intestinal Tumours: An Overview on Classification, Diagnosis, and Treatment

    Directory of Open Access Journals (Sweden)

    Chiara Notaristefano

    2014-12-01

    Full Text Available The small intestinal neoplasia group includes different types of lesions and are a relatively rare event, accounting for only 3-6% of all gastrointestinal (GI neoplasms and 1-3% of all GI malignancies. These lesions can be classified as epithelial and mesenchymal, either benign or malignant. Mesenchymal tumours include stromal tumours (GIST and other neoplasms that might arise from soft tissue throughout the rest of the body (lipomas, leiomyomas and leiomyosarcomas, fibromas, desmoid tumours, and schwannomas. Other lesions occurring in the small bowel are carcinoids, lymphomas, and melanomas. To date, carcinoids and GIST are reported as the most frequent malignant lesions occurring in the small bowel. Factors that predispose to the development of malignant lesions are different, and they may be hereditary (Peutz-Jeghers syndrome, familial adenomatous polyposis, hereditary non-polyposis colorectal cancer, neuroendocrine neoplasia Type 1, von Hippel-Lindau disease, and neurofibromatosis Type 1, acquired (sporadic colorectal cancer and small intestine adenomas, coeliac disease, Crohn’s disease, or environmental (diet, tobacco, and obesity. Small bowel tumours present with different and sometimes nonspecific symptoms, and a prompt diagnosis is not always so easily performed. Diagnostic tools, that may be both radiological and endoscopic, possess specificity and sensitivity, as well as different roles depending on the type of lesion. Treatment of these lesions may be different and, in recent years, new therapies have enabled an improvement in life expectancy.

  4. Mitochondrial Sirt3 supports cell proliferation by regulating glutamine-dependent oxidation in renal cell carcinoma

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    Choi, Jieun; Koh, Eunjin; Lee, Yu Shin; Lee, Hyun-Woo; Kang, Hyeok Gu [Department of Biochemistry and Molecular Biology, Brain Korea 21 PLUS Project for Medical Sciences, Institute of Genetic Science, Integrated Genomic Research Center for Metabolic Regulation, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Yoon, Young Eun; Han, Woong Kyu [Department of Urology, Urological Science Institute, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Choi, Kyung Hwa [Department of Urology, CHA Bundang Medical Center, CHA University, Seongnam 463-712 (Korea, Republic of); Kim, Kyung-Sup, E-mail: KYUNGSUP59@yuhs.ac [Department of Biochemistry and Molecular Biology, Brain Korea 21 PLUS Project for Medical Sciences, Institute of Genetic Science, Integrated Genomic Research Center for Metabolic Regulation, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of)

    2016-06-03

    Clear cell renal carcinoma (RCC), the most common malignancy arising in the adult kidney, exhibits increased aerobic glycolysis and low mitochondrial respiration due to von Hippel-Lindau gene defects and constitutive hypoxia-inducible factor-α expression. Sirt3 is a major mitochondrial deacetylase that mediates various types of energy metabolism. However, the role of Sirt3 as a tumor suppressor or oncogene in cancer depends on cell types. We show increased Sirt3 expression in the mitochondrial fraction of human RCC tissues. Sirt3 depletion by lentiviral short-hairpin RNA, as well as the stable expression of the inactive mutant of Sirt3, inhibited cell proliferation and tumor growth in xenograft nude mice, respectively. Furthermore, mitochondrial pyruvate, which was used for oxidation in RCC, might be derived from glutamine, but not from glucose and cytosolic pyruvate, due to depletion of mitochondrial pyruvate carrier and the relatively high expression of malic enzyme 2. Depletion of Sirt3 suppressed glutamate dehydrogenase activity, leading to impaired mitochondrial oxygen consumption. Our findings suggest that Sirt3 plays a tumor-progressive role in human RCC by regulating glutamine-derived mitochondrial respiration, particularly in cells where mitochondrial usage of cytosolic pyruvate is severely compromised. -- Highlights: •Sirt3 is required for the maintenance of RCC cell proliferation. •Mitochondrial usage of cytosolic pyruvate is severely compromised in RCC. •Sirt3 supports glutamine-dependent oxidation in RCC.

  5. Folliculin contributes to VHL tumor suppressing activity in renal cancer through regulation of autophagy.

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    Prabhat Bastola

    Full Text Available Von Hippel-Lindau tumor suppressor (VHL is lost in the majority of clear cell renal cell carcinomas (ccRCC. Folliculin (FLCN is a tumor suppressor whose function is lost in Birt-Hogg-Dubé syndrome (BHD, a disorder characterized by renal cancer of multiple histological types including clear cell carcinoma, cutaneous fibrofolliculoma, and pneumothorax. Here we explored whether there is connection between VHL and FLCN in clear cell renal carcinoma cell lines and tumors. We demonstrate that VHL regulates expression of FLCN at the mRNA and protein levels in RCC cell lines, and that FLCN protein expression is decreased in human ccRCC tumors with VHL loss, as compared with matched normal kidney tissue. Knockdown of FLCN results in increased formation of tumors by RCC cells with wild-type VHL in orthotopic xenografts in nude mice, an indication that FLCN plays a role in the tumor-suppressing activity of VHL. Interestingly, FLCN, similarly to VHL, is necessary for the activity of LC3C-mediated autophagic program that we have previously characterized as contributing to the tumor suppressing activity of VHL. The results show the existence of functional crosstalk between two major tumor suppressors in renal cancer, VHL and FLCN, converging on regulation of autophagy.

  6. Epidemiology, molecular epidemiology, and risk factors for renal cell carcinoma

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    Chiara Paglino

    2011-12-01

    Full Text Available Despite only accounting for approximately 2% of all new primary cancer cases, renal cell carcinoma (RCC incidence has dramatically increased over time. Incidence rates vary greatly according to geographic areas, so that it is extremely likely that exogenous risk factors could play an important role in the development of this cancer. Several risk factors have been linked with RCC, including cigarette smoking, obesity, hypertension (and antihypertensive drugs, chronic kidney diseases (also dialysis and transplantation, as well as the use of certain analgesics. Furthermore, although RCC has not generally been considered an occupational cancer, several types of occupationally-derived exposures have been implicated in its pathogenesis. These include exposure to asbestos, chlorinated solvents, gasoline, diesel exhaust fumes, polycyclic aromatic hydrocarbons, printing inks and dyes, cadmium and lead. Finally, families with a predisposition to the development of renal neoplasms were identified and the genes involved discovered and characterized. Therefore, there are now four well-characterized, genetically determined syndromes associated with an increased incidence of kidney tumors, i.e., Von Hippel Lindau (VHL, Hereditary Papillary Renal Carcinoma (HPRC, Birt-Hogg-Dubé Syndrome (BHD, and Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC. This review will address present knowledge about the epidemiology, molecular epidemiology and risk factors of RCC.

  7. RENAL TUMOR QUANTIFICATION AND CLASSIFICATION IN TRIPLE-PHASE CONTRAST-ENHANCED ABDOMINAL CT

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    Gautam, Rabindra; Peterson, James; Yao, Jianhua; Linehan, W. Marston; Summers, Ronald M.

    2009-01-01

    It is estimated that a quarter of a million people in the USA are living with kidney cancer. In clinical practice, the response to treatment is monitored by manual measurements of tumor size, which are time consuming and show high intra- and inter-operator variability. We propose a computer-assisted radiology tool to assess renal tumors in contrast-enhanced CT for the management of tumor diagnoses and treatments. The algorithm employs anisotropic diffusion, a combination of fast-marching and geodesic level-sets, and a novel statistical refinement step to adapt to the shape of the lesions. It also quantifies the 3D size, volume and enhancement of the lesion and allows serial management of tumors. The comparison between manual and semi-automated quantifications shows disparity within the limits of inter-observer variability. The automated tumor classification shows great separation between cysts, von Hippel-Lindau syndrome (VHL) lesions and hereditary papillary renal carcinomas (HPRC) (p < 0.004). PMID:20383290

  8. Physapubescin selectively induces apoptosis in VHL-null renal cell carcinoma cells through down-regulation of HIF-2α and inhibits tumor growth

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    Chen, Lixia; Xia, Guiyang; Qiu, Feng; Wu, Chunli; Denmon, Andria P.; Zi, Xiaolin

    2016-01-01

    We have purified physapubescin, a predominant steroidal lactone, from medicinal plant Physalis pubescens L., commonly named as “hairy groundcherry” in English and “Deng-Long-Cao” in Chinese. Von Hippel-Lindau (VHL)-null 786-O, RCC4 and A498 Renal Cell Carcinoma (RCC) cell lines expressing high levels of Hypoxia Inducible Factor (HIF)-2α are more sensitive to physapubescin-mediated apoptosis and growth inhibitory effect than VHL wild-type Caki-2 and ACHN RCC cell lines. Restoration of VHL in RCC4 cells attenuated the growth inhibitory effect of physapubescin. Physapubescin decreases the expression of HIF-2α and increases the expression of CCAAT/enhancer-binding protein homologus protein (CHOP), which leads to up-regulation of death receptor 5 (DR5), activation of caspase-8 and -3, cleavage of poly (ADP-Ribose) polymerase (PARP) and apoptosis. Under hypoxia conditions, the apoptotic and growth inhibitory effects of physapubescin are further enhanced. Additionally, physapubescin synergizes with TNF-related apoptosis-inducing ligand (TRAIL) for markedly enhanced induction of apoptosis in VHL-null 786-O cells but not in VHL wild-type Caki-2 cells. Physapubescin significantly inhibited in vivo angiogenesis in the 786-O xenograft. Physapubescin as a novel agent for elimination of VHL-null RCC cells via apoptosis is warranted for further investigation. PMID:27581364

  9. Transcriptional activation of hypoxia-inducible factor-1 (HIF-1) in myeloid cells promotes angiogenesis through VEGF and S100A8.

    Science.gov (United States)

    Ahn, G-One; Seita, Jun; Hong, Beom-Ju; Kim, Young-Eun; Bok, Seoyeon; Lee, Chan-Ju; Kim, Kwang Soon; Lee, Jerry C; Leeper, Nicholas J; Cooke, John P; Kim, Hak Jae; Kim, Il Han; Weissman, Irving L; Brown, J Martin

    2014-02-18

    Emerging evidence indicates that myeloid cells are essential for promoting new blood vessel formation by secreting various angiogenic factors. Given that hypoxia-inducible factor (HIF) is a critical regulator for angiogenesis, we questioned whether HIF in myeloid cells also plays a role in promoting angiogenesis. To address this question, we generated a unique strain of myeloid-specific knockout mice targeting HIF pathways using human S100A8 as a myeloid-specific promoter. We observed that mutant mice where HIF-1 is transcriptionally activated in myeloid cells (by deletion of the von Hippel-Lindau gene) resulted in erythema, enhanced neovascularization in matrigel plugs, and increased production of vascular endothelial growth factor (VEGF) in the bone marrow, all of which were completely abrogated by either genetic or pharmacological inactivation of HIF-1. We further found that monocytes were the major effector producing VEGF and S100A8 proteins driving neovascularization in matrigel. Moreover, by using a mouse model of hindlimb ischemia we observed significantly improved blood flow in mice intramuscularly injected with HIF-1-activated monocytes. This study therefore demonstrates that HIF-1 activation in myeloid cells promotes angiogenesis through VEGF and S100A8 and that this may become an attractive therapeutic strategy to treat diseases with vascular defects.

  10. Paragangliomas/Pheochromocytomas: Clinically Oriented Genetic Testing

    Directory of Open Access Journals (Sweden)

    Rute Martins

    2014-01-01

    Full Text Available Paragangliomas are rare neuroendocrine tumors that arise in the sympathetic or parasympathetic nervous system. Sympathetic paragangliomas are mainly found in the adrenal medulla (designated pheochromocytomas but may also have a thoracic, abdominal, or pelvic localization. Parasympathetic paragangliomas are generally located at the head or neck. Knowledge concerning the familial forms of paragangliomas has greatly improved in recent years. Additionally to the genes involved in the classical syndromic forms: VHL gene (von Hippel-Lindau, RET gene (Multiple Endocrine Neoplasia type 2, and NF1 gene (Neurofibromatosis type 1, 10 novel genes have so far been implicated in the occurrence of paragangliomas/pheochromocytomas: SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX, EGLN1, HIF2A, and KIF1B. It is currently accepted that about 35% of the paragangliomas cases are due to germline mutations in one of these genes. Furthermore, somatic mutations of RET, VHL, NF1, MAX, HIF2A, and H-RAS can also be detected. The identification of the mutation responsible for the paraganglioma/pheochromocytoma phenotype in a patient may be crucial in determining the treatment and allowing specific follow-up guidelines, ultimately leading to a better prognosis. Herein, we summarize the most relevant aspects regarding the genetics and clinical aspects of the syndromic and nonsyndromic forms of pheochromocytoma/paraganglioma aiming to provide an algorithm for genetic testing.

  11. Pheochromocytomas and secreting paragangliomas

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    Gimenez-Roqueplo Anne-Paule

    2006-12-01

    Full Text Available Abstract Catecholamine-producing tumors may arise in the adrenal medulla (pheochromocytomas or in extraadrenal chromaffin cells (secreting paragangliomas. Their prevalence is about 0.1% in patients with hypertension and 4% in patients with a fortuitously discovered adrenal mass. An increase in the production of catecholamines causes symptoms (mainly headaches, palpitations and excess sweating and signs (mainly hypertension, weight loss and diabetes reflecting the effects of epinephrine and norepinephrine on α- and β-adrenergic receptors. Catecholamine-producing tumors mimic paroxysmal conditions with hypertension and/or cardiac rhythm disorders, including panic attacks, in which sympathetic activation linked to anxiety reproduces the same signs and symptoms. These tumors may be sporadic or part of any of several genetic diseases: familial pheochromocytoma-paraganglioma syndromes, multiple endocrine neoplasia type 2, neurofibromatosis 1 and von Hippel-Lindau disease. Familial cases are diagnosed earlier and are more frequently bilateral and recurring than sporadic cases. The most specific and sensitive diagnostic test for the tumor is the determination of plasma or urinary metanephrines. The tumor can be located by computed tomography, magnetic resonance imaging and metaiodobenzylguanidine scintigraphy. Treatment requires resection of the tumor, generally by laparoscopic surgery. About 10% of tumors are malignant either at first operation or during follow-up, malignancy being diagnosed by the presence of lymph node, visceral or bone metastases. Recurrences and malignancy are more frequent in cases with large or extraadrenal tumors. Patients, especially those with familial or extraadrenal tumors, should be followed-up indefinitely.

  12. The genetic basis of myeloproliferative disorders.

    Science.gov (United States)

    Skoda, Radek

    2007-01-01

    For many decades, myeloproliferative disorders (MPD) were largely neglected orphan diseases. The conceptual work of William Dameshek in 1951 provided the basis for understanding MPD as a continuum of related syndromes, possibly with a common pathogenetic cause. Recognition of the clonal origin of peripheral blood cells in MPD in 1976 and the ability to grow erythroid colonies in vitro in the absence of added growth factors in 1974 initiated the search for genetic alterations that might be responsible for myeloproliferation. Mutations in the genes for the erythropoietin receptor, thrombopoietin and the von Hippel-Lindau protein were found to cause familial syndromes resembling MPD, but despite their phenotypic similarities, none of these mutations were later found in patients with the sporadic form of MPD. The discovery of activating mutations in the Janus kinase 2 (JAK2) in most patients with MPD has fully transformed and energized the MPD field. Sensitive assays for detecting the JAK2-V617F mutation have become an essential part of the diagnostic work-up, and JAK2 now constitutes a prime target for developing specific inhibitors for the treatment of patients with MPD. Despite this progress, many questions remain unsolved, including how a single JAK2 mutation causes three different MPD phenotypes, what other genes might be involved in the pathogenesis, and what are the factors determining the progression to acute leukemia.

  13. (1)H NMR metabolomics analysis of renal cell carcinoma cells: Effect of VHL inactivation on metabolism.

    Science.gov (United States)

    Cuperlovic-Culf, Miroslava; Cormier, Kevin; Touaibia, Mohamed; Reyjal, Julie; Robichaud, Sarah; Belbraouet, Mehdi; Turcotte, Sandra

    2016-05-15

    Von Hippel-Lindau (VHL) is an onco-suppressor involved in oxygen and energy-dependent promotion of protein ubiquitination and proteosomal degradation. Loss of function mutations of VHL (VHL-cells) result in organ specific cancers with the best studied example in renal cell carcinomas. VHL has a well-established role in deactivation of hypoxia-inducible factor (HIF-1) and in regulation of PI3K/AKT/mTOR activity. Cell culture metabolomics analysis was utilized to determined effect of VHL and HIF-1α or HIF-2α on metabolism of renal cell carcinomas (RCC). RCC cells were stably transfected with VHL or shRNA designed to silence HIF-1α or HIF-2α genes. Obtained metabolic data was analysed qualitatively, searching for overall effects on metabolism as well as quantitatively, using methods developed in our group in order to determine specific metabolic changes. Analysis of the effect of VHL and HIF silencing on cellular metabolic footprints and fingerprints provided information about the metabolic pathways affected by VHL through HIF function as well as independently of HIF. Through correlation network analysis as well as statistical analysis of significant metabolic changes we have determined effects of VHL and HIF on energy production, amino acid metabolism, choline metabolism as well as cell regulation and signaling. VHL was shown to influence cellular metabolism through its effect on HIF proteins as well as by affecting activity of other factors.

  14. Clinical and Genetic Aspects of Sporadic Non-Medullar Thyroid Cancer

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    U Rumjanzeva

    2006-03-01

    Full Text Available The role of somatic mutations in sporadic thyroid cancer is unclear today. Probably they coming out as aetiological factors in carcinogenesis as well as, respectfully to many authors, can to participate in TC pathogenesis and to determine the clinical course and prognosis of the disease. For today as main oncogenes taking part in initiation of thyroid malignant tumors are considered: RET/PTC, TRK, PTEN, P53, RAS, MET, PPARγ. By means of genetic investigations scientists are trying to solve problems with thyroid cancer differentiated diagnostics (cytokeratin-19, cytokeratin-20, mesothelial cells antigen (Hector Battifora MEsotelial (cell or HBME-1, loss of heterozigitoty (LOH in short arm of 3 chromosome (gene VHL -von Hippel Lindau, 3р26. Recently in foreign literature appeared reports of activated mutations in gene BRAF which most frequently are occurred in melanoma and papillary TC. Prognosis of thyroid cancer may reflected by the LOH as a biological breakage as well as changes of tumor suppressive gene P53 which fraught with decrease of disease prognosis. Thus, both researchers and clinicians have many questions concerning the role of genome, particularly in order to precise of genetic abnormality influence on tumor growth and therefore for assessment of clinical prognosis and with aim to chose adequate treatment tactic in each case.

  15. Surgical Management of Ampullary Somatostatinoma

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    Nicholas Phillips

    2016-07-01

    Full Text Available Introduction Somatostatinomas of the ampulla are rare neuroendocrine tumours with limited studies in the literature. These are often associated with familial genetic predisposition e.g. NF 1 and Von Hippel-Lindau Syndrome. Histology commonly shows classical features such as Psammoma bodies. The classical presentation with inhibitory syndrome is rare, but ampullary mass effects can cause an earlier presentation with potentially better outcomes with earlier intervention and treatment. Case series We report three cases of ampullary somatostatisnomas: one sporadic and two familial, associated with neurofibromatosis type 1. The first patient presented with pruritus, the second with recurrent pancreatitis and the third, with elevated CA19-9 levels. Various preoperative localisation techniques were employed and one had an attempted endoscopic resection yielding involved margins. All patients underwent pancreaticoduodenectomy, of which one was laparoscopic assisted. The median size of the tumour was 10 mm and one patient had nodal involvement. All 3 patients have remained disease free at most recent follow up ranging from 1.5 to 11 years. Discussion Ampullary somatostatinomas can present early with mass related effects while inhibitory syndrome is rare. Early detection and intervention in ampullary somatostatinoma may contribute to better outcomes than pancreatic somatostatinomas. Long-term survival is achievable through pancreaticoduodenectomy for resectable ampullary somatostatinoma and laparoscopic approach is a feasible and viable option.

  16. [Prophylactic pancreas surgery].

    Science.gov (United States)

    Langer, P; Rothmund, M; Bartsch, D K

    2006-01-01

    The goal of prophylactic surgery is to prevent malignant growth in patients with hereditary tumor predisposition. The pancreas presents as particularly challenging, due to the difficulty of operation and comparatively high risk of morbidity and even mortality. In addition, partial operative procedures and, more significantly, total resection lead to exocrine pancreas insufficiency and secondary diabetes, with grave consequences for the patient. Hereditary tumor predisposition syndromes that can result in pancreaticoduodenal endocrine tumors (PET) include multiple endocrine neoplasia type 1 syndrome and von Hippel-Lindau syndrome. As penetrance is maximally 70-80% and the 10-year survival rate over 80%, prophylactic pancreatic resection without evidence of a tumor is not indicated. However, prophylactic extension of a resection would be advised, should a PET be diagnosed. Patients predisposed to developing ductal pancreatic carcinoma (PC) are at risk of familial pancreatic cancer syndrome (FPC), hereditary pancreatitis, and other hereditary tumor predisposition syndromes such as Peutz-Jeghers syndrome and familial atypical multiple mole-melanoma syndrome. As the gene defect responsible for FPC has yet to be identified and the penetrance of PC in the other tumor predisposition syndromes is low or unknown, a prophylactic pancreatectomy based on today's knowledge is not indicated. Prophylactic extension of the resection is advisable should PC or high-grade PanIN lesions be diagnosed, as these patients often present with multifocal dysplasia and even carcinoma.

  17. Genetic aspects of pheochromocytoma.

    Science.gov (United States)

    Kolačkov, Katarzyna; Tupikowski, Krzysztof; Bednarek-Tupikowska, Grażyna

    2012-01-01

    Pheochromocytomas are derived from chromaffin cells of the adrenal medulla which synthesize and secrete catecholamines, thus affecting the cardiovascular system and metabolic processes. Pheochromocytoma is a tumor of the following multicarcinoma hereditary syndromes: type 2 multiple endocrine neoplasia, von Hippel-Lindau disease, type 1 neurofibromatosis and the pheochromocytomas/paragangliomas syndrome. Pheochromocytomas are relatively rare, and because of non-specific manifestation of these tumors and the possible lack of signs and symptoms for extended periods of time, the diagnosis may be delayed, which may, in turn, lead to death. Pheochromocytomas may occur sporadically. However, due to the frequent incidence of hereditary forms of these cancers, the presymptomatic genetic testing of family members with a positive family history is indicated, thus allowing for selecting people with higher risk of cancer. Early detection of the syndrome and the coexisting tumors (which may be malignant) may lead to a correct diagnosis, regular surveillance, preventive examinations and implementation of appropriate early treatment. Recent examinations have shown significant involvement of RET, VHL, NF1, SDHB and SDHD as well as the newly discovered KIF1Bβ, TMEM127 and MAX genes in pathogenesis of these tumors. The microarray-gene expression studies, based on the analysis of cellular pathways, have revealed two distinct clusters indicating two different routes of tumorgenesis. The genotype-phenotype correlations are still being studied and future research can give us clearer information about the function of these genes, which may prove crucial from the clinical point of view.

  18. Intermittent hypoxia regulates RNA polymerase II in hippocampus and prefrontal cortex

    Science.gov (United States)

    Ignacak, Monika L.; Harbaugh, Svetlana V.; Dayyat, Ehab; Row, Barry W.; Gozal, David; Czyzyk-Krzeska, Maria F.

    2009-01-01

    Intermittent hypoxia (IH) is a major pathological factor in the development of neural deficits associated with sleep-disordered breathing. Here we demonstrate that IH lasting 2 or 30 days, but not sustained hypoxia (SH) of the same duration, was accompanied by several posttranslational modifications of the large subunit of RNA Polymerase II, Rpb1, including hydroxylation of proline 1465, phosphorylation of serine 5 residues within the C-terminal domain, and nondegradative ubiquitylation. These modifications were found to occur in two regions of the brain, hippocampal region CA1 and the prefrontal cortex, but not in neocortex, brainstem and CA3 region of hippocampus. We also found that mice exposed to 14 or 30 days of IH, but not SH, demonstrated cognitive deficits in behavioral assays. Furthermore, by using the pheochromocytoma-derived PC12 cell line, we showed that, under in vitro IH conditions, induction of Rpb1 hydroxylation, phosphorylation, and ubiquitylation required that the von Hippel-Lindau protein be present. We hypothesize that the observed modifications of Rpb1 participate in regulating the expression of genes involved in mediating cognitive deficits evoked by chronic IH. PMID:19095046

  19. Pheochromocytoma and paraganglioma: understanding the complexities of the genetic background.

    Science.gov (United States)

    Fishbein, Lauren; Nathanson, Katherine L

    2012-01-01

    Pheochromocytomas and paragangliomas (PCC/PGL) are tumors derived from the adrenal medulla or extra-adrenal ganglia, respectively. They are rare and often benign tumors that are associated with high morbidity and mortality due to mass effect and high circulating catecholamines. Although most PCCs and PGLs are thought to be sporadic, over one third are associated with 10 known susceptibility genes. Mutations in three genes causing well characterized tumor syndromes are associated with an increased risk of developing PCCs and PGLs, including VHL (von Hippel-Lindau disease), NF1 (Neurofibromatosis Type 1), and RET (Multiple Endocrine Neoplasia Type 2). Mutations in any of the succinate dehydrogenase (SDH) complex subunit genes (SDHA, SDHB, SDHC, SDHD) can lead to PCCs and PGLs with variable penetrance, as can mutations in the subunit cofactor, SDHAF2. Recently, two additional genes have been identified, TMEM127 and MAX. Although these tumors are rare in the general population, occurring in two to eight per million people, they are more commonly associated with an inherited mutation than any other cancer type. This review summarizes the known germline and somatic mutations leading to the development of PCC and PGL, as well as biochemical profiling for PCCs/PGLs and screening of mutation carriers.

  20. Update on iron metabolism and molecular perspective of common genetic and acquired disorder, hemochromatosis.

    Science.gov (United States)

    Yun, Seongseok; Vincelette, Nicole D

    2015-07-01

    Iron is an essential component of erythropoiesis and its metabolism is tightly regulated by a variety of internal and external cues including iron storage, tissue hypoxia, inflammation and degree of erythropoiesis. There has been remarkable improvement in our understanding of the molecular mechanisms of iron metabolism past decades. The classical model of iron metabolism with iron response element/iron response protein (IRE/IRP) is now extended to include hepcidin model. Endogenous and exogenous signals funnel down to hepcidin via wide range of signaling pathways including Janus Kinase/Signal Transducer and Activator of Transcription 3 (JAK/STAT3), Bone Morphogenetic Protein/Hemojuvelin/Mothers Against Decapentaplegic Homolog (BMP/HJV/SMAD), and Von Hippel Lindau/Hypoxia-inducible factor/Erythropoietin (VHL/HIF/EPO), then relay to ferroportin, which directly regulates intra- and extracellular iron levels. The successful molecular delineation of iron metabolism further enhanced our understanding of common genetic and acquired disorder, hemochromatosis. The majority of the hereditary hemochromatosis (HH) patients are now shown to have mutations in the genes coding either upstream or downstream proteins of hepcidin, resulting in iron overload. The update on hepcidin centered mechanisms of iron metabolism and their clinical perspective in hemochromatosis will be discussed in this review.

  1. VHL loss causes spindle misorientation and chromosome instability.

    Science.gov (United States)

    Thoma, Claudio R; Toso, Alberto; Gutbrodt, Katrin L; Reggi, Sabina P; Frew, Ian J; Schraml, Peter; Hergovich, Alexander; Moch, Holger; Meraldi, Patrick; Krek, Wilhelm

    2009-08-01

    Error-free mitosis depends on fidelity-monitoring checkpoint systems that ensure correct temporal and spatial coordination of chromosome segregation by the microtubule spindle apparatus. Defects in these checkpoint systems can lead to genomic instability, an important aspect of tumorigenesis. Here we show that the von Hippel-Lindau (VHL) tumour suppressor protein, pVHL, which is inactivated in hereditary and sporadic forms of renal cell carcinoma, localizes to the mitotic spindle in mammalian cells and its functional inactivation provokes spindle misorientation, spindle checkpoint weakening and chromosomal instability. Spindle misorientation is linked to unstable astral microtubules and is supressed by the restoration of wild-type pVHL in pVHL-deficient cells, but not in naturally-occurring VHL disease mutants that are defective in microtubule stabilization. Impaired spindle checkpoint function and chromosomal instability are the result of reduced Mad2 (mitotic arrest deficient 2) levels actuated by pVHL-inactivation and are rescued by re-expression of either Mad2 or pVHL in VHL-defective cells. An association between VHL inactivation, reduced Mad2 levels and increased aneuploidy was also found in human renal cancer, implying that the newly identified functions of pVHL in promoting proper spindle orientation and chromosomal stability probably contribute to tumour suppression.

  2. 15-Deoxy-Delta(12,14)-prostaglandin-J(2) reveals a new pVHL-independent, lysosomal-dependent mechanism of HIF-1alpha degradation.

    Science.gov (United States)

    Olmos, Gemma; Arenas, María I; Bienes, Raquel; Calzada, María Jose; Aragonés, Julián; Garcia-Bermejo, Maria Laura; Landazuri, Manuel O; Lucio-Cazaña, Javier

    2009-07-01

    Hypoxia-inducible factor-1alpha (HIF-1alpha) protein is degraded under normoxia by its association to von Hippel-Lindau protein (pVHL) and further proteasomal digestion. However, human renal cells HK-2 treated with 15-deoxy-Delta(12,14)-prostaglandin-J(2) (15d-PGJ(2)) accumulate HIF-1alpha in normoxic conditions. Thus, we aimed to investigate the mechanism involved in this accumulation. We found that 15d-PGJ(2) induced an over-accumulation of HIF-1alpha in RCC4 cells, which lack pVHL and in HK-2 cells treated with inhibitors of the pVHL-proteasome pathway. These results indicated that pVHL-proteasome-independent mechanisms are involved, and therefore we aimed to ascertain them. We have identified a new lysosomal-dependent mechanism of HIF-1alpha degradation as a target for 15d-PGJ(2) based on: (1) HIF-1alpha colocalized with the specific lysosomal marker Lamp-2a, (2) 15d-PGJ(2) inhibited the activity of cathepsin B, a lysosomal protease, and (3) inhibition of lysosomal activity did not result in over-accumulation of HIF-1alpha in 15d-PGJ(2)-treated cells. Therefore, expression of HIF-1alpha is also modulated by lysosomal degradation.

  3. Multiple Components of the VHL Tumor Suppressor Complex Are Frequently Affected by DNA Copy Number Loss in Pheochromocytoma

    Science.gov (United States)

    Rowbotham, David A.; Enfield, Katey S. S.; Martinez, Victor D.; Thu, Kelsie L.; Vucic, Emily A.; Stewart, Greg L.; Bennewith, Kevin L.; Lam, Wan L.

    2014-01-01

    Pheochromocytomas (PCC) are rare tumors that arise in chromaffin tissue of the adrenal gland. PCC are frequently inherited through predisposing mutations in genes such as the von Hippel-Lindau (VHL) tumor suppressor. VHL is part of the VHL elongin BC protein complex that also includes CUL2/5, TCEB1, TCEB2, and RBX1; in normoxic conditions this complex targets hypoxia-inducible factor 1 alpha (HIF1A) for degradation, thus preventing a hypoxic response. VHL inactivation by genetic mechanisms, such as mutation and loss of heterozygosity, inhibits HIF1A degradation, even in the presence of oxygen, and induces a pseudohypoxic response. However, the described <10% VHL mutation rate cannot account for the high frequency of hypoxic response observed. Indeed, little is known about genetic mechanisms disrupting other complex component genes. Here, we show that, in a panel of 171 PCC tumors, 59.6% harbored gene copy number loss (CNL) of at least one complex component. CNL significantly reduced gene expression and was associated with enrichment of gene targets controlled by HIF1. Interestingly, we show that VHL-related renal clear cell carcinoma harbored disruption of VHL alone. Our results indicate that VHL elongin BC protein complex components other than VHL could be important for PCC tumorigenesis and merit further investigation. PMID:25298778

  4. Multiple Components of the VHL Tumor Suppressor Complex Are Frequently Affected by DNA Copy Number Loss in Pheochromocytoma

    Directory of Open Access Journals (Sweden)

    David A. Rowbotham

    2014-01-01

    Full Text Available Pheochromocytomas (PCC are rare tumors that arise in chromaffin tissue of the adrenal gland. PCC are frequently inherited through predisposing mutations in genes such as the von Hippel-Lindau (VHL tumor suppressor. VHL is part of the VHL elongin BC protein complex that also includes CUL2/5, TCEB1, TCEB2, and RBX1; in normoxic conditions this complex targets hypoxia-inducible factor 1 alpha (HIF1A for degradation, thus preventing a hypoxic response. VHL inactivation by genetic mechanisms, such as mutation and loss of heterozygosity, inhibits HIF1A degradation, even in the presence of oxygen, and induces a pseudohypoxic response. However, the described <10% VHL mutation rate cannot account for the high frequency of hypoxic response observed. Indeed, little is known about genetic mechanisms disrupting other complex component genes. Here, we show that, in a panel of 171 PCC tumors, 59.6% harbored gene copy number loss (CNL of at least one complex component. CNL significantly reduced gene expression and was associated with enrichment of gene targets controlled by HIF1. Interestingly, we show that VHL-related renal clear cell carcinoma harbored disruption of VHL alone. Our results indicate that VHL elongin BC protein complex components other than VHL could be important for PCC tumorigenesis and merit further investigation.

  5. Role of the NEDD8 Modification of Cul2 in the Sequential Activation of ECV Complex

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    Roxana I. Sufan

    2006-11-01

    Full Text Available ECV is an E3 ubiquitin ligase complex, which is composed of elongins B and C, Rbxi, Cul2, the substrate-conferring von Hippel-Lindau (VHL tumorsuppressor protein that targets the catalytic α subunit of hypoxia-inducible factor (HI F for oxygen-dependent ubiquitin-mediated destruction. Mutations in VHL that compromise proper HIFα regulation through ECV have been documented in the majority of renal cell carcinomas, underscoring the significance of the VHL-HIF pathway in renal epithelial oncogenesis. Recent evidence has shown that the modification of Cul2 by the ubiquitin-like molecule NEDD8 increases the activity of ECV to ubiquitylate HIFα. However, the underlying mechanism responsible for the NEDD8-mediated induction of ECV function is unknown. Here, we demonstrate that oxygen-dependent recognition of HIFα by VHL triggers Rbxi-dependent neddylation of Cul2, which preferentially engages the E2 ubiquitin-conjugating enzyme UbcH5a. These events establish a central role for the neddylation of Cul2 in a previously unrecognized, temporally coordinated activation of ECV with the recruitment of its substrate HIFα.

  6. Premalignant Lesions in the Kidney

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    Ziva Kirkali

    2001-01-01

    Full Text Available Renal cell carcinoma (RCC is the most malignant urologic disease. Different lesions, such as dysplasia in the tubules adjacent to RCC, atypical hyperplasia in the cyst epithelium of von Hippel-Lindau syndrome, and adenoma have been described for a number of years as possible premalignant changes or precursor lesions of RCC. In two recent papers, kidneys adjacent to RCC or removed from other causes were analyzed, and dysplastic lesions were identified and defined in detail. Currently renal intraepithelial neoplasia (RIN is the proposed term for classification. The criteria for a lesion to be defined as premalignant are (1 morphological similarity; (2 spatial association; (3 development of microinvasive carcinoma; (4 higher frequency, severity, and extent then invasive carcinoma; (5 progression to invasive cancer; and (6 similar genetic alterations. RIN resembles the neoplastic cells of RCC. There is spatial association. Progression to invasive carcinoma is described in experimental cancer models, and in some human renal tumors. Similar molecular alterations are found in some putative premalignant changes. The treatment for RCC is radical or partial nephrectomy. Preneoplastic lesions may remain in the renal remnant in patients treated by partial nephrectomy and may be the source of local recurrences. RIN seems to be a biologic precursor of some RCCs and warrants further investigation. Interpretation and reporting of these lesions would reveal important resources for the biological nature and clinical significance. The management of RIN diagnosed in a renal biopsy and partial nephrectomy needs to be answered.

  7. LXY6090 - a novel manassantin A derivative - limits breast cancer growth through hypoxia-inducible factor-1 inhibition.

    Science.gov (United States)

    Lai, Fangfang; Liu, Qian; Liu, Xiaoyu; Ji, Ming; Xie, Ping; Chen, Xiaoguang

    2016-01-01

    Hypoxia-inducible factor-1 (HIF-1) represents a novel antitumor target owing to its involvement in vital processes considered hallmarks of cancer phenotypes. Manassantin A (MA) derived from Saururus cernuus has been reported as a selective HIF-1 inhibitor. Herein, the structure of MA was optimized to achieve new derivatives with simple chemical properties while retaining its activity. LXY6090 was designed to replace the central tetrahydrofuran moiety of MA with a cyclopentane ring and was identified as a potent HIF-1 inhibitor with an IC50 value of 4.11 nM. It not only inhibited the activity of HIF-1 in breast cancer cells but also downregulated the protein level of HIF-1α, which depended on von Hippel-Lindau for proteasome degradation. The related biological evaluation showed that the activity of HIF-1 target genes, VEGF and IGF-2, was decreased by LXY6090 in breast cancer cell lines. LXY6090 presented potent antitumor activity in vitro. Furthermore, LXY6090 showed in vivo anticancer efficacy by decreasing the HIF-1α expression in nude mice bearing MX-1 tumor xenografts. In conclusion, our data provide a basis for the future development of the novel compound LXY6090 as a potential therapeutic agent for breast cancer.

  8. Multiple Components of the VHL Tumor Suppressor Complex Are Frequently Affected by DNA Copy Number Loss in Pheochromocytoma.

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    Rowbotham, David A; Enfield, Katey S S; Martinez, Victor D; Thu, Kelsie L; Vucic, Emily A; Stewart, Greg L; Bennewith, Kevin L; Lam, Wan L

    2014-01-01

    Pheochromocytomas (PCC) are rare tumors that arise in chromaffin tissue of the adrenal gland. PCC are frequently inherited through predisposing mutations in genes such as the von Hippel-Lindau (VHL) tumor suppressor. VHL is part of the VHL elongin BC protein complex that also includes CUL2/5, TCEB1, TCEB2, and RBX1; in normoxic conditions this complex targets hypoxia-inducible factor 1 alpha (HIF1A) for degradation, thus preventing a hypoxic response. VHL inactivation by genetic mechanisms, such as mutation and loss of heterozygosity, inhibits HIF1A degradation, even in the presence of oxygen, and induces a pseudohypoxic response. However, the described complex component genes. Here, we show that, in a panel of 171 PCC tumors, 59.6% harbored gene copy number loss (CNL) of at least one complex component. CNL significantly reduced gene expression and was associated with enrichment of gene targets controlled by HIF1. Interestingly, we show that VHL-related renal clear cell carcinoma harbored disruption of VHL alone. Our results indicate that VHL elongin BC protein complex components other than VHL could be important for PCC tumorigenesis and merit further investigation.

  9. Heterogeneous Effects of Direct Hypoxia Pathway Activation in Kidney Cancer.

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    Rafik Salama

    Full Text Available General activation of hypoxia-inducible factor (HIF pathways is classically associated with adverse prognosis in cancer and has been proposed to contribute to oncogenic drive. In clear cell renal carcinoma (CCRC HIF pathways are upregulated by inactivation of the von-Hippel-Lindau tumor suppressor. However HIF-1α and HIF-2α have contrasting effects on experimental tumor progression. To better understand this paradox we examined pan-genomic patterns of HIF DNA binding and associated gene expression in response to manipulation of HIF-1α and HIF-2α and related the findings to CCRC prognosis. Our findings reveal distinct pan-genomic organization of canonical and non-canonical HIF isoform-specific DNA binding at thousands of sites. Overall associations were observed between HIF-1α-specific binding, and genes associated with favorable prognosis and between HIF-2α-specific binding and adverse prognosis. However within each isoform-specific set, individual gene associations were heterogeneous in sign and magnitude, suggesting that activation of each HIF-α isoform contributes a highly complex mix of pro- and anti-tumorigenic effects.

  10. Inhibition of endogenous hydrogen sulfide production in clear-cell renal cell carcinoma cell lines and xenografts restricts their growth, survival and angiogenic potential.

    Science.gov (United States)

    Sonke, Eric; Verrydt, Megan; Postenka, Carl O; Pardhan, Siddika; Willie, Chantalle J; Mazzola, Clarisse R; Hammers, Matthew D; Pluth, Michael D; Lobb, Ian; Power, Nicholas E; Chambers, Ann F; Leong, Hon S; Sener, Alp

    2015-09-15

    Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel-Lindau (VHL)-deficiency, resulting in pseudohypoxic, angiogenic and glycolytic tumours. Hydrogen sulfide (H2S) is an endogenously-produced gasotransmitter that accumulates under hypoxia and has been shown to be pro-angiogenic and cytoprotective in cancer. It was hypothesized that H2S levels are elevated in VHL-deficient ccRCC, contributing to survival, metabolism and angiogenesis. Using the H2S-specific probe MeRhoAz, it was found that H2S levels were higher in VHL-deficient ccRCC cell lines compared to cells with wild-type VHL. Inhibition of H2S-producing enzymes could reduce the proliferation, metabolism and survival of ccRCC cell lines, as determined by live-cell imaging, XTT/ATP assay, and flow cytometry respectively. Using the chorioallantoic membrane angiogenesis model, it was found that systemic inhibition of endogenous H2S production was able to decrease vascularization of VHL-deficient ccRCC xenografts. Endogenous H2S production is an attractive new target in ccRCC due to its involvement in multiple aspects of disease.

  11. The pleckstrin homology domain of phospholipase D1 accelerates EGFR endocytosis by increasing the expression of the Rab5 effector, rabaptin-5.

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    Park, Mi Hee; Choi, Kang-Yell; Min, Do Sik

    2015-12-18

    Endocytosis is differentially regulated by hypoxia-inducible factor-1α (HIF-1α) and phospholipase D (PLD). However, the relationship between HIF-1α and PLD in endocytosis is unknown. HIF-1α is degraded through the prolyl hydroxylase (PHD)/von Hippel-Lindau (VHL) ubiquitination pathway in an oxygen-dependent manner. Here, we show that PLD1 recovers the decrease in epidermal growth factor receptor (EGFR) endocytosis induced by HIF-1α independent of lipase activity via the Rab5-mediated endosome fusion pathway. EGF-induced interaction of PLD1 with HIF-1α, PHD and VHL may contribute to EGFR endocytosis. The pleckstrin homology domain (PH) of PLD1 itself promotes degradation of HIF-1α, then accelerates EGFR endocytosis via upregulation of rabaptin-5 and suppresses tumor progression. These findings reveal a novel role of the PLD1-PH domain as a positive regulator of endocytosis and provide a link between PLD1 and HIF-1α in the EGFR endocytosis pathway.

  12. ELR510444 inhibits tumor growth and angiogenesis by abrogating HIF activity and disrupting microtubules in renal cell carcinoma.

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    Jennifer S Carew

    Full Text Available BACKGROUND: Hypoxia-inducible factor (HIF is an attractive therapeutic target for renal cell carcinoma (RCC as its high expression due to the loss of von Hippel-Lindau (VHL promotes RCC progression. Considering this, we hypothesized that ELR510444, a novel orally available small molecule inhibitor of HIF activity, would reduce angiogenesis and possess significant activity in RCC. The mechanism of action and therapeutic efficacy of ELR510444 were investigated in in vitro and in vivo models of RCC. PRINCIPAL FINDINGS: ELR510444 decreased HIF-1α and HIF-2α levels, reduced RCC cell viability and clonogenic survival, and induced apoptosis. VHL-deficient RCC cells were more sensitive to ELR510444-mediated apoptosis and restoration of VHL promoted drug resistance. Higher concentrations of ELR51044 promoted apoptosis independently of VHL status, possibly due to the microtubule destabilizing properties of this agent. ELR510444 significantly reduced tumor burden in the 786-O and A498 RCC xenograft models. These effects were associated with increased necrosis and apoptosis and inhibition of angiogenesis. CONCLUSIONS: ELR510444 is a promising new HIF inhibitor that reduced RCC cell viability, induced apoptosis, and diminished tumor burden in RCC xenograft models. ELR510444 also destabilized microtubules suggesting that it possesses vascular disrupting and anti-angiogenic properties. Further investigation of ELR510444 for the therapy of RCC is warranted.

  13. Differential regulation of LncRNA-SARCC suppresses VHL-mutant RCC cell proliferation yet promotes VHL-normal RCC cell proliferation via modulating androgen receptor/HIF-2α/C-MYC axis under hypoxia.

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    Zhai, W; Sun, Y; Jiang, M; Wang, M; Gasiewicz, T A; Zheng, J; Chang, C

    2016-09-15

    It is well established that hypoxia contributes to tumor progression in a hypoxia inducible factor-2α (HIF-2α)-dependent manner in renal cell carcinoma (RCC), yet the role of long noncoding RNAs (LncRNAs) involved in hypoxia-mediated RCC progression remains unclear. Here we demonstrate that LncRNA-SARCC (Suppressing Androgen Receptor in Renal Cell Carcinoma) is differentially regulated by hypoxia in a von Hippel-Lindau (VHL)-dependent manner both in RCC cell culture and clinical specimens. LncRNA-SARCC can suppress hypoxic cell cycle progression in the VHL-mutant RCC cells while derepress it in the VHL-restored RCC cells. Mechanism dissection reveals that LncRNA-SARCC can post-transcriptionally regulate androgen receptor (AR) by physically binding and destablizing AR protein to suppress AR/HIF-2α/C-MYC signals. In return, HIF-2α can transcriptionally regulate the LncRNA-SARCC expression via binding to hypoxia-responsive elements on the promoter of LncRNA-SARCC. The negative feedback modulation between LncRNA-SARCC/AR complex and HIF-2α signaling may then lead to differentially modulated RCC progression in a VHL-dependent manner. Together, these results may provide us a new therapeutic approach via targeting this newly identified signal from LncRNA-SARCC to AR-mediated HIF-2α/C-MYC signals against RCC progression.

  14. VHL genetic alteration in CCRCC does not determine de-regulation of HIF, CAIX, hnRNP A2/B1 and osteopontin.

    LENUS (Irish Health Repository)

    Nyhan, Michelle J

    2012-01-31

    BACKGROUND: von Hippel-Lindau (VHL) tumour suppressor gene inactivation is associated with clear cell renal cell carcinoma (CCRCC) development. The VHL protein (pVHL) has been proposed to regulate the expression of several proteins including Hypoxia Inducible Factor-alpha (HIF-alpha), carbonic anhydrase (CA)IX, heterogeneous nuclear ribonucleoprotein (hnRNP) A2\\/B1 and osteopontin. pVHL has been characterized in vitro, however, clinical studies are limited. We evaluated the impact of VHL genetic alterations on the expression of several pVHL protein targets in paired normal and tumor tissue. METHODS: The VHL gene was sequenced in 23 CCRCC patients and VHL transcript levels were evaluated by real-time RT-PCR. Expression of pVHL\\'s protein targets were determined by Western blotting in 17 paired patient samples. RESULTS: VHL genetic alterations were identified in 43.5% (10\\/23) of CCRCCs. HIF-1alpha, HIF-2alpha and CAIX were up-regulated in 88.2% (15\\/17), 100% (17\\/17) and 88.2% (15\\/17) of tumors respectively and their expression is independent of VHL status. hnRNP A2\\/B1 and osteopontin expression was variable in CCRCCs and had no association with VHL genetic status. CONCLUSION: As expression of these proposed pVHL targets can be achieved independently of VHL mutation (and possibly by hypoxia alone), these data suggests that other pVHL targets may be more crucial in renal carcinogenesis.

  15. Manifestation of a sellar hemangioblastoma due to pituitary apoplexy: a case report

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    Sahli Rahel

    2011-10-01

    Full Text Available Abstract Introduction Hemangioblastomas are rare, benign tumors occurring in any part of the nervous system. Most are found as sporadic tumors in the cerebellum or spinal cord. However, these neoplasms are also associated with von Hippel-Lindau disease. We report a rare case of a sporadic sellar hemangioblastoma that became symptomatic due to pituitary apoplexy. Case presentation An 80-year-old, otherwise healthy Caucasian woman presented to our facility with severe headache attacks, hypocortisolism and blurred vision. A magnetic resonance imaging scan showed an acute hemorrhage of a known, stable and asymptomatic sellar mass lesion with chiasmatic compression accounting for our patient's acute visual impairment. The tumor was resected by a transnasal, transsphenoidal approach and histological examination revealed a capillary hemangioblastoma (World Health Organization grade I. Our patient recovered well and substitutional therapy was started for panhypopituitarism. A follow-up magnetic resonance imaging scan performed 16 months postoperatively showed good chiasmatic decompression with no tumor recurrence. Conclusions A review of the literature confirmed supratentorial locations of hemangioblastomas to be very unusual, especially within the sellar region. However, intrasellar hemangioblastoma must be considered in the differential diagnosis of pituitary apoplexy.

  16. Low VHL mRNA expression is associated with more aggressive tumor features of papillary thyroid carcinoma.

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    Boban Stanojevic

    Full Text Available Alterations of the von Hippel-Lindau (VHL tumor suppressor gene can cause different hereditary tumors associated with VHL syndrome, but the potential role of the VHL gene in papillary thyroid carcinoma (PTC has not been characterized. This study set out to investigate the relationship of VHL expression level with clinicopathological features of PTC in an ethnically and geographically homogenous group of 264 patients from Serbia, for the first time. Multivariate logistic regression analysis showed a strong correlation between low level of VHL expression and advanced clinical stage (OR = 5.78, 95% CI 3.17-10.53, P<0.0001, classical papillary morphology of the tumor (OR = 2.92, 95% CI 1.33-6.44, P = 0.008 and multifocality (OR = 1.96, 95% CI 1.06-3.62, P = 0.031. In disease-free survival analysis, low VHL expression had marginal significance (P = 0.0502 by the log-rank test but did not appear to be an independent predictor of the risk for chance of faster recurrence in a proportion hazards model. No somatic mutations or evidence of VHL downregulation via promoter hypermethylation in PTC were found. The results indicate that the decrease of VHL expression associates with tumor progression but the mechanism of downregulation remains to be elucidated.

  17. CUL2-mediated clearance of misfolded TDP-43 is paradoxically affected by VHL in oligodendrocytes in ALS

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    Uchida, Tsukasa; Tamaki, Yoshitaka; Ayaki, Takashi; Shodai, Akemi; Kaji, Seiji; Morimura, Toshifumi; Banno, Yoshinori; Nishitsuji, Kazuchika; Sakashita, Naomi; Maki, Takakuni; Yamashita, Hirofumi; Ito, Hidefumi; Takahashi, Ryosuke; Urushitani, Makoto

    2016-01-01

    The molecular machinery responsible for cytosolic accumulation of misfolded TDP-43 in amyotrophic lateral sclerosis (ALS) remains elusive. Here we identified a cullin-2 (CUL2) RING complex as a novel ubiquitin ligase for fragmented forms of TDP-43. The von Hippel Lindau protein (VHL), a substrate binding component of the complex, preferentially recognized misfolded TDP-43 at Glu246 in RNA-recognition motif 2. Recombinant full-length TDP-43 was structurally fragile and readily cleaved, suggesting that misfolded TDP-43 is cleared by VHL/CUL2 in a step-wise manner via fragmentation. Surprisingly, excess VHL stabilized and led to inclusion formation of TDP-43, as well as mutant SOD1, at the juxtanuclear protein quality control center. Moreover, TDP-43 knockdown elevated VHL expression in cultured cells, implying an aberrant interaction between VHL and mislocalized TDP-43 in ALS. Finally, cytoplasmic inclusions especially in oligodendrocytes in ALS spinal cords were immunoreactive to both phosphorylated TDP-43 and VHL. Thus, our results suggest that an imbalance in VHL and CUL2 may underlie oligodendrocyte dysfunction in ALS, and highlight CUL2 E3 ligase emerges as a novel therapeutic potential for ALS. PMID:26751167

  18. Chromosome 3p loss of heterozygosity is associated with a unique metabolic network in clear cell renal carcinoma

    Science.gov (United States)

    Gatto, Francesco; Nookaew, Intawat; Nielsen, Jens

    2014-01-01

    Several common oncogenic pathways have been implicated in the emergence of renowned metabolic features in cancer, which in turn are deemed essential for cancer proliferation and survival. However, the extent to which different cancers coordinate their metabolism to meet these requirements is largely unexplored. Here we show that even in the heterogeneity of metabolic regulation a distinct signature encompassed most cancers. On the other hand, clear cell renal cell carcinoma (ccRCC) strongly deviated in terms of metabolic gene expression changes, showing widespread down-regulation. We observed a metabolic shift that associates differential regulation of enzymes in one-carbon metabolism with high tumor stage and poor clinical outcome. A significant yet limited set of metabolic genes that explained the partial divergence of ccRCC metabolism correlated with loss of von Hippel-Lindau tumor suppressor (VHL) and a potential activation of signal transducer and activator of transcription 1. Further network-dependent analyses revealed unique defects in nucleotide, one-carbon, and glycerophospholipid metabolism at the transcript and protein level, which contrasts findings in other tumors. Notably, this behavior is recapitulated by recurrent loss of heterozygosity in multiple metabolic genes adjacent to VHL. This study therefore shows how loss of heterozygosity, hallmarked by VHL deletion in ccRCC, may uniquely shape tumor metabolism. PMID:24550497

  19. ERK5/BMK1 Is a Novel Target of the Tumor Suppressor VHL: Implication in Clear Cell Renal Carcinoma

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    Laura Arias-González

    2013-06-01

    Full Text Available Extracellular signal-regulated kinase 5 (ERK5, also known as big mitogen-activated protein kinase (MAPK 1, is implicated in a wide range of biologic processes, which include proliferation or vascularization. Here, we show that ERK5 is degraded through the ubiquitin-proteasome system, in a process mediated by the tumor suppressor von Hippel-Lindau (VHL gene, through a prolyl hydroxylation-dependent mechanism. Our conclusions derive from transient transfection assays in Cos7 cells, as well as the study of endogenous ERK5 in different experimental systems such as MCF7, HMEC, or Caki-2 cell lines. In fact, the specific knockdown of ERK5 in pVHL-negative cell lines promotes a decrease in proliferation and migration, supporting the role of this MAPK in cellular transformation. Furthermore, in a short series of fresh samples from human clear cell renal cell carcinoma, high levels of ERK5 correlate with more aggressive and metastatic stages of the disease. Therefore, our results provide new biochemical data suggesting that ERK5 is a novel target of the tumor suppressor VHL, opening a new field of research on the role of ERK5 in renal carcinomas.

  20. Confounding of the Association between Radiation Exposure from CT Scans and Risk of Leukemia and Brain Tumors by Cancer Susceptibility Syndromes.

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    Meulepas, Johanna M; Ronckers, Cécile M; Merks, Johannes; Weijerman, Michel E; Lubin, Jay H; Hauptmann, Michael

    2016-01-01

    Recent studies linking radiation exposure from pediatric computed tomography (CT) to increased risks of leukemia and brain tumors lacked data to control for cancer susceptibility syndromes (CSS). These syndromes might be confounders because they are associated with an increased cancer risk and may increase the likelihood of CT scans performed in children. We identify CSS predisposing to leukemia and brain tumors through a systematic literature search and summarize prevalence and risk estimates. Because there is virtually no empirical evidence in published literature on patterns of CT use for most types of CSS, we estimate confounding bias of relative risks (RR) for categories of radiation exposure based on expert opinion about the current and previous patterns of CT scans among CSS patients. We estimate that radiation-related RRs for leukemia are not meaningfully confounded by Down syndrome, Noonan syndrome, or other CSS. In contrast, RRs for brain tumors may be overestimated due to confounding by tuberous sclerosis complex (TSC) while von Hippel-Lindau disease, neurofibromatosis type 1, or other CSS do not meaningfully confound. Empirical data on the use of CT scans among CSS patients are urgently needed. Our assessment indicates that associations with leukemia reported in previous studies are unlikely to be substantially confounded by unmeasured CSS, whereas brain tumor risks might have been overestimated due to confounding by TSC. Future studies should identify TSC patients in order to avoid overestimation of brain tumor risks due to radiation exposure from CT scans. ©2015 American Association for Cancer Research.

  1. Correlation analysis of VHL and Jade-1 gene expression in human renal cell carcinoma

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    Xiao-fen Wu

    2016-01-01

    Full Text Available The aim of this study was to investigate the correlation of von Hippel-Lindau tumor suppressor (VHL mRNA expression and jade family PHD finger 1 (Jade-1 gene expression in patients with renal cell carcinoma (RCC. Another aim of this study was to analyze the relationship of these two genes with clinicalpathological features of the RCC patients. Methods: A total of 75 RCC patients who received surgically therapy in our hospital were included. All patients had complete pathological data. The expression of VHL/Jade-1 was determined by real-time polymerase chain reaction (RT-PCR. Results: VHL and Jade-1 were both obviously downregulated in RCC tissues than that of the matched normal tissues, and both negatively correlated with tumor size as well as tumor grade. And we found a fine association of VHL gene expression with Jade-1. Conclusion: VHL/Jade-1 exhibited significantly decreased expression in RCC tissues and was closely related to the clinical prognosis of patients. The finding of VHL expression positively correlated with Jade-1 expression shed light and provided crucial evidence on the connection of VHL protein with Wnt/b-catenin pathway.

  2. Oxygen-dependent ATF-4 stability is mediated by the PHD3 oxygen sensor.

    Science.gov (United States)

    Köditz, Jens; Nesper, Jutta; Wottawa, Marieke; Stiehl, Daniel P; Camenisch, Gieri; Franke, Corinna; Myllyharju, Johanna; Wenger, Roland H; Katschinski, Dörthe M

    2007-11-15

    The activating transcription factor-4 (ATF-4) is translationally induced under anoxic conditions, mediates part of the unfolded protein response following endoplasmic reticulum (ER) stress, and is a critical regulator of cell fate. Here, we identified the zipper II domain of ATF-4 to interact with the oxygen sensor prolyl-4-hydroxylase domain 3 (PHD3). The PHD inhibitors dimethyloxalylglycine (DMOG) and hypoxia, or proteasomal inhibition, all induced ATF-4 protein levels. Hypoxic induction of ATF-4 was due to increased protein stability, but was independent of the ubiquitin ligase von Hippel-Lindau protein (pVHL). A novel oxygen-dependent degradation (ODD) domain was identified adjacent to the zipper II domain. Mutations of 5 prolyl residues within this ODD domain or siRNA-mediated down-regulation of PHD3, but not of PHD2, was sufficient to stabilize ATF-4 under normoxic conditions. These data demonstrate that PHD-dependent oxygen-sensing recruits both the hypoxia-inducible factor (HIF) and ATF-4 systems, and hence not only confers adaptive responses but also cell fate decisions.

  3. E2F1 in renal cancer: Mr Hyde disguised as Dr Jekyll?

    Science.gov (United States)

    Tian, Weihua; Cui, Fenggong; Esteban, Miguel A

    2013-10-01

    The transcription factor E2F1 has both oncogenic and tumour suppressor properties, depending on the context. Clarifying the function of E2F1 in different types of cancer is relevant because in those situations in which it acts as an oncogene there may be a route for therapeutic interference. Renal cell carcinoma is the most frequent form of kidney cancer in adults and inactivation of the von Hippel-Lindau (VHL) gene underlies most cases. This malignancy represents a challenge for standard therapies due to drug- and radio-resistance, effects that fit well within the scope of functions of E2F1. A new report by Mans et al postulates that up-regulation of E2F1 in VHL-defective renal cell carcinoma induces cell senescence and can thus be considered a good prognostic factor. Here we discuss these findings in a wider context and propose that E2F1 may actually not play a uniform role in renal cell carcinoma but rather an ambiguous one whose deeper understanding could have practical implications. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  4. The Nephrologist's Tumor: Basic Biology and Management of Renal Cell Carcinoma.

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    Hu, Susie L; Chang, Anthony; Perazella, Mark A; Okusa, Mark D; Jaimes, Edgar A; Weiss, Robert H

    2016-08-01

    Kidney cancer, or renal cell carcinoma (RCC), is a disease of increasing incidence that is commonly seen in the general practice of nephrology. However, RCC is under-recognized by the nephrology community, such that its presence in curricula and research by this group is lacking. In the most common form of RCC, clear cell renal cell carcinoma (ccRCC), inactivation of the von Hippel-Lindau tumor suppressor is nearly universal; thus, the biology of ccRCC is characterized by activation of hypoxia-relevant pathways that lead to the associated paraneoplastic syndromes. Therefore, RCC is labeled the internist's tumor. In light of this characterization and multiple other metabolic abnormalities recently associated with ccRCC, it can now be viewed as a metabolic disease. In this review, we discuss the basic biology, pathology, and approaches for treatment of RCC. It is important to distinguish between kidney confinement and distant spread of RCC, because this difference affects diagnostic and therapeutic approaches and patient survival, and it is important to recognize the key interplay between RCC, RCC therapy, and CKD. Better understanding of all aspects of this disease will lead to optimal patient care and more recognition of an increasingly prevalent nephrologic disease, which we now appropriately label the nephrologist's tumor.

  5. Endolymphatic sac tumor: case report and review of the literature

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    Sun Yan-Hua

    2012-04-01

    Full Text Available Abstract Endolymphatic sac tumor (ELST is a rare neoplasm which can be encountered sporadically or in Von Hippel-Lindau (VHL disease. Here we report a sporadic case of ELST in 31-year-old man. Neither the symptoms nor a family history of VHL disease were found in the patient. CT imaging demonstrated an expansile lytic lesion of the mastoid process of the left petrous bone. MR scanning revealed a 5.2 cm × 4.7 cm × 4.2 cm mass which showed hyperintensity on T1- and T2-weighted images. Histologic sections showed a papillary, cystic or glandular architecture. The papillary and glandular structures were lined by a single layer of flattened cuboidal-to-columnar cells. The stroma of the papillary fronds was richly vascularized and chronically inflamed. The tumor showed diffusely positive reactivity with cytokeratin (Pan, cytokeratin 19, cytokeratin 5/6, cytokeratin 7, EMA, vimentin, CD56, and NSE and also showed variable reactivity with glial fibrillary acidic protein (GFAP and VEGF. The Ki-67 immunostain showed a proliferation index of Virtual Slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7973320646763012

  6. Stereotactic radiosurgery in hemangioblastoma: Experience over 14 years

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    Nishant Goyal

    2016-01-01

    Full Text Available Background: Although gamma knife has been advocated for hemangioblastomas, it is not used widely by neurosurgeons. Objective: We review our experience over 14 years in an attempt to define the role of stereotactic radiosurgery (SRS in the management of hemangioblastomas. Patients and Methods: A retrospective study was conducted on all patients of hemangioblastoma who underwent SRS at our institute over a period of 14 years (1998–2011. Gamma knife plans, clinical history, and radiology were reviewed for all patients. Results: A total of 2767 patients underwent gamma knife during the study period. Of these, 10 (0.36% patients were treated for 24 hemangioblastomas. Eight patients (80% had von Hippel-Lindau disease while two had sporadic hemangioblastomas. The median peripheral dose (50% isodose delivered to the tumors was 29.9 Gy. Clinical and radiological follow-up data were available for eight patients. Of these, two were re-operated for persisting cerebellar symptoms. The remaining six patients were recurrence-free at a mean follow-up of 48 months (range 19–108 months. One patient had an increase in cyst volume along with a decrease in the size of the mural nodule. Conclusions: SRS should be the first option for asymptomatic hemangioblastomas. Despite the obvious advantages, gamma knife is not widely used as an option for hemangioblastomas.

  7. Radiation promotes malignant progression of glioma cells through HIF-1alpha stabilization.

    Science.gov (United States)

    Kim, Young-Heon; Yoo, Ki-Chun; Cui, Yan-Hong; Uddin, Nizam; Lim, Eun-Jung; Kim, Min-Jung; Nam, Seon-Young; Kim, In-Gyu; Suh, Yongjoon; Lee, Su-Jae

    2014-11-01

    Given its contribution to malignant phenotypes of cancer, tumor hypoxia has been considered as a potential therapeutic problem. In the stressful microenvironment condition, hypoxia inducible factor 1 (HIF1) is well known to mediate the transcriptional adaptation of cells to hypoxia and acts as a central player for the process of hypoxia-driven malignant cancer progression. Here, we found that irradiation causes the HIF1α protein to stabilize, even in normoxia condition through activation of p38 MAPK, thereby promoting angiogenesis in tumor microenvironment and infiltrative property of glioma cells. Notably, irradiation reduced hydroxylation of HIF1α through destabilization of prolyl hydroxylases (PHD)-2. Moreover, radiation also decreased the half-life of protein von Hippel-Lindau (pVHL), which is a specific E3 ligase for HIF1α. Of note, inhibition of p38 MAPK attenuated radiation-induced stabilization of HIF1α through destabilization of PHD-2 and pVHL. In agreement with these results, targeting of either p38 MAPK, HIF1α, pVHL or PHD-2 effectively mitigated the radiation-induced tube formation of human brain-derived micro-vessel endothelial cells (HB-MEC) and infiltration of glioma cells. Taken together, our findings suggest that targeting HIF1α in combination with ionizing radiation might increase the efficacy of radiotherapy for glioma treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. Accumulation of Krebs cycle intermediates and over-expression of HIF1alpha in tumours which result from germline FH and SDH mutations.

    Science.gov (United States)

    Pollard, P J; Brière, J J; Alam, N A; Barwell, J; Barclay, E; Wortham, N C; Hunt, T; Mitchell, M; Olpin, S; Moat, S J; Hargreaves, I P; Heales, S J; Chung, Y L; Griffiths, J R; Dalgleish, A; McGrath, J A; Gleeson, M J; Hodgson, S V; Poulsom, R; Rustin, P; Tomlinson, I P M

    2005-08-01

    The nuclear-encoded Krebs cycle enzymes, fumarate hydratase (FH) and succinate dehydrogenase (SDHB, -C and -D), act as tumour suppressors. Germline mutations in FH predispose individuals to leiomyomas and renal cell cancer (HLRCC), whereas mutations in SDH cause paragangliomas and phaeochromocytomas (HPGL). In this study, we have shown that FH-deficient cells and tumours accumulate fumarate and, to a lesser extent, succinate. SDH-deficient tumours principally accumulate succinate. In situ analyses showed that these tumours also have over-expression of hypoxia-inducible factor 1alpha (HIF1alpha), activation of HIF1alphatargets (such as vascular endothelial growth factor) and high microvessel density. We found no evidence of increased reactive oxygen species in our cells. Our data provide in vivo evidence to support the hypothesis that increased succinate and/or fumarate causes stabilization of HIF1alpha a plausible mechanism, inhibition of HIF prolyl hydroxylases, has previously been suggested by in vitro studies. The basic mechanism of tumorigenesis in HPGL and HLRCC is likely to be pseudo-hypoxic drive, just as it is in von Hippel-Lindau syndrome.

  9. VHL Frameshift Mutation as Target of Nonsense-Mediated mRNA Decay in Drosophila melanogaster and Human HEK293 Cell Line

    Directory of Open Access Journals (Sweden)

    Lucia Micale

    2009-01-01

    Full Text Available There are many well-studied examples of human phenotypes resulting from nonsense or frameshift mutations that are modulated by Nonsense-Mediated mRNA Decay (NMD, a process that typically degrades transcripts containing premature termination codons (PTCs in order to prevent translation of unnecessary or aberrant transcripts. Different types of germline mutations in the VHL gene cause the von Hippel-Lindau disease, a dominantly inherited familial cancer syndrome with a marked phenotypic variability and age-dependent penetrance. By generating the Drosophila UAS:Upf1D45B line we showed the possible involvement of NMD mechanism in the modulation of the c.172delG frameshift mutation located in the exon 1 of Vhl gene. Further, by Quantitative Real-time PCR (QPCR we demonstrated that the corresponding c.163delG human mutation is targeted by NMD in human HEK 293 cells. The UAS:Upf1D45B line represents a useful system to identify novel substrates of NMD pathway in Drosophila melanogaster. Finally, we suggest the possible role of NMD on the regulation of VHL mutations.

  10. pVHL mediates K63-linked ubiquitination of nCLU.

    Directory of Open Access Journals (Sweden)

    Jing Xue

    Full Text Available pVHL, product of von Hippel-Lindau (VHL tumor suppressor gene, functions as the substrate recognition component of an E3-ubiquitin ligase that targets proteins for ubiquitination and proteasomal degradation. Hypoxia-inducible factor α (HIFα is the well-known substrate of pVHL. Besides HIFα, pVHL also binds to many other proteins and has multiple functions. In this manuscript, we report that the nuclear clusterin (nCLU is a target of pVHL. We found that pVHL had a direct interaction with nCLU. nCLU bound to pVHL at pVHL's β domain, the site for recognition of substrate, indicating that nCLU might be a substrate of pVHL. Interestingly, pVHL bound to nCLU but did not lead to nCLU destruction. Further studies indicated that pVHL mediated K63-linked ubiquitination of nCLU and promoted nCLU nuclear translocation. In summary, our results disclose a novel function of pVHL that mediates K63-linked ubiquitination and identify nCLU as a new target of pVHL.

  11. VEGF Spliced Variants: Possible Role of Anti-Angiogenesis Therapy

    Directory of Open Access Journals (Sweden)

    Caroline Hilmi

    2012-01-01

    Full Text Available Angiogenesis has been targeted in retinopathies, psoriasis, and a variety of cancers (colon, breast, lung, and kidney. Among these tumour types, clear cell renal cell carcinomas (RCCs are the most vascularized tumours due to mutations of the von Hippel Lindau gene resulting in HIF-1 alpha stabilisation and overexpression of Vascular Endothelial Growth Factor (VEGF. Surgical nephrectomy remains the most efficient curative treatment for patients with noninvasive disease, while VEGF targeting has resulted in varying degrees of success for treating metastatic disease. VEGF pre-mRNA undergoes alternative splicing generating pro-angiogenic isoforms. However, the recent identification of novel splice variants of VEGF with anti-angiogenic properties has provided some insight for the lack of current treatment efficacy. Here we discuss an explanation for the relapse to anti-angiogenesis treatment as being due to either an initial or acquired resistance to the therapy. We also discuss targeting angiogenesis via SR (serine/arginine-rich proteins implicated in VEGF splicing.

  12. Reproductive disturbances in multiple neuroendocrine tumor syndromes.

    Science.gov (United States)

    Lytras, Aristides; Tolis, George

    2009-12-01

    In the context of multiple neuroendocrine tumor syndromes, reproductive abnormalities may occur via a number of different mechanisms, such as hyperprolactinemia, increased GH/IGF-1 levels, hypogonadotropic hypogonadism, hypercortisolism, hyperandrogenism, hyperthyroidism, gonadotropin hypersecretion, as well as, tumorigenesis or functional disturbances in gonads or other reproductive organs. Precocious puberty and/or male feminization is a feature of McCune-Albright syndrome (MAS), neurofibromatosis type 1 (NF1), Carney complex (CNC), and Peutz-Jeghers syndrome (PJS), while sperm maturation and ovulation defects have been described in MAS and CNC. Although tumorigenesis of reproductive organs due to a multiple neuroendocrine tumor syndrome is very rare, certain lesions are characteristic and very unusual in the general population. Awareness leading to their recognition is important especially when other endocrine abnormalities coexist, as occasionally they may even be the first manifestation of a syndrome. Lesions such as certain types of ovarian cysts (MAS, CNC), pseudogynecomastia due to neurofibromas of the nipple-areola area (NF1), breast disease (CNC and Cowden disease (CD)), cysts and 'hypernephroid' tumors of the epididymis or bilateral papillary cystadenomas (mesosalpinx cysts) and endometrioid cystadenomas of the broad ligament (von Hippel-Lindau disease), testicular Sertoli calcifying tumors (CNC, PJS) monolateral or bilateral macroochidism and microlithiasis (MAS) may offer diagnostic clues. In addition, multiple neuroendocrine tumor syndromes may be complicated by reproductive malignancies including ovarian cancer in CNC, breast and endometrial cancer in CD, breast malignancies in NF1, and malignant sex-cord stromal tumors in PJS.

  13. Utilization of ancillary studies in the cytologic diagnosis of biliary and pancreatic lesions: The Papanicolaou Society of Cytopathology Guidelines

    Directory of Open Access Journals (Sweden)

    Lester J. Layfield

    2014-01-01

    Full Text Available The Papanicolaou Society of Cytopathology has developed a set of guidelines for pancreatobiliary cytology including indications for endoscopic ultrasound guided fine needle aspiration, terminology and nomenclature of pancreatobiliary disease, ancillary testing and post-biopsy management. All documents are based on the expertise of the authors, a review of the literature, discussion of the draft document at several national and international meetings and synthesis of selected online comments of the draft document. This document presents the results of these discussions regarding the use of ancillary testing in the cytologic diagnosis of biliary and pancreatic lesions. Currently, fluorescence in-situ hybridization (FISH appears to be the most clinically relevant ancillary technique for cytology of bile duct strictures. The addition of FISH analysis to routine cytologic evaluation appears to yield the highest sensitivity without loss in specificity. Loss of immunohistochemical staining for the protein product of the SMAD4 gene and positive staining for mesothelin support a diagnosis of ductal adenocarcinoma. Immunohistochemical markers for endocrine and exocrine differentiation are sufficient for a diagnosis of endocrine and acinar tumors. Nuclear staining for beta-catenin supports a diagnosis of solid-pseudopapillary neoplasm. Cyst fluid analysis for amylase and carcinoembryonic antigen aids in the pre-operative classification of pancreatic cysts. A number of gene mutations (KRAS, GNAS, von Hippel-Lindau, RNF43 and CTNNB1 may be of aid in the diagnosis of cystic neoplasms. Other ancillary techniques do not appear to improve diagnostic sensitivity sufficiently to justify their increased costs.

  14. Die Felsfassadengräber von Kyrene

    OpenAIRE

    Greve, Anika

    2006-01-01

    Die griechische Kolonie Kyrene wurde im letzten Drittel des 7. Jhs. v. Chr. einige Kilometer vom Mittelmeer entfernt im libyschen Innenland gegründet. Die Siedler waren dorische Griechen aus Thera im Süden der Kykladen. Nicht nur die erhaltenen innerstädtischen Gebäude zeugen von einem einstigen Wohlstand, auch die Nekropole nahm im Laufe der Zeit gewaltige Ausmaße mit aufwendig gestalteten Grabanlagen an, die sich rund um die urbane Bebauung entlang der Ausfallstraßen ausbreitete. Viele Ruhe...

  15. Authentifizierung von Bio-Milch im Labor

    OpenAIRE

    2008-01-01

    In Deutschland ist die Nachfrage nach Bio-Lebensmitteln in den letzten Jahren stetig gestiegen. So erhöhte sich der Absatz von Bio-Trinkmilch in 2007 im Vergleich zum Vorjahr erneut kräftig um 34 Prozent (ZMP, Bonn) und der Bio-Anteil beträgt inzwischen bei Frischmilch knapp elf Prozent. Aufgrund sporadisch resultierender Lieferengpässe bei Bio-Milch sowie der vorhandenen Handelspreisdifferenz besteht zunehmend ein potenzielles Risiko der Falschdeklaration konventionell erzeugter Milch als Bi...

  16. Key contributors: Ernst von Glasersfeld's radical constructivism

    Science.gov (United States)

    Tobin, Kenneth

    2007-07-01

    This article reviews the significance of the contributions of Ernst von Glasersfeld to research in science education, especially through his theoretical contributions on radical constructivism. As a field shaper, Glasersfeld's subversive ideas catalyzed debate in the science education community and fuelled transformation of many facets including research methods, ways of thinking about teaching and learning, curriculum, and science teacher education. Perturbations emanating from the debates on constructivism forged new pathways that led to the development and use of many of the sociocultural frameworks employed by authors in Cultural Studies of Science Education.

  17. Synthese und Applikation von magnetisch verformbaren Hydrogelkompositen

    OpenAIRE

    Bolle, Jens

    2011-01-01

    Als „intelligent“ bezeichnete Materialien sind in der Lage, mit steuerbaren Form- oder Eigenschaftsänderungen auf Zielreize zu reagieren, ohne dafür einen zusätzlichen Sensor zu benötigen. Man bezeichnet sie daher auch als Sensor-Aktor-Systeme. Da sie ohne äußere Sensorsysteme auskommen, können diese Werkstoffe als kleine, einfach anwendbare und preisgünstige Bauteile für eine Vielzahl von Applikationen dienen. Ihre Entwicklung gestattet sowohl die fortschreitende Miniaturisierung tech-nische...

  18. Homology modeling and molecular dynamics simulation of the HIF2α degradation-related HIF2α-VHL complex.

    Science.gov (United States)

    Dong, Xiaotian; Su, Xiaoru; Yu, Jiong; Liu, Jingqi; Shi, Xiaowei; Pan, Qiaoling; Yang, Jinfeng; Chen, Jiajia; Li, Lanjuan; Cao, Hongcui

    2017-01-01

    Hypoxia-inducible factor 2 alpha (HIF2α), prolyl hydroxylase domain protein 2 (PHD2), and the von Hippel Lindau tumor suppressor protein (pVHL) are three principal proteins in the oxygen-sensing pathway. Under normoxic conditions, a conserved proline in HIF2α is hydroxylated by PHD2 in an oxygen-dependent manner, and then pVHL binds and promotes the degradation of HIF2α. However, the crystal structure of the HIF2α-pVHL complex has not yet been established, and this has limited research on the interaction between HIF and pVHL. Here, we constructed a structural model of a 23-residue HIF2α peptide (528-550)-pVHL-ElonginB-ElonginC complex by using homology modeling and molecular dynamics simulations. We also applied these methods to HIF2α mutants (HYP531PRO, F540L, A530 V, A530T, and G537R) to reveal structural defects that explain how these mutations weaken the interaction with pVHL. Homology modeling and molecular dynamics simulations were used to construct a three-dimensional (3D) structural model of the HIF2α-VHL complex. Subsequently, MolProbity, an active validation tool, was used to analyze the reliability of the model. Molecular mechanics energies combined with the generalized Born and surface area continuum solvation (MM-GBSA) and solvated interaction energy (SIE) methods were used to calculate the binding free energy between HIF2a and pVHL, and the stability of the simulation system was evaluated by using root mean square deviation (RMSD) analysis. We also determined the secondary structure of the system by using the definition of secondary structure of proteins (DSSP) algorithm. Finally, we investigated the structural significance of specific point mutations known to have clinical implications. We established a reliable structural model of the HIF2α-pVHL complex, which is similar to the crystal structure of HIF1α in 1LQB. Furthermore, we compared the structural model of the HIF2α-pVHL complex and the HIF2α (HYP531P, F540L, A530V, A530T, and G537

  19. Von Krahli Teater hakkab koolitama näitlejaid

    Index Scriptorium Estoniae

    2007-01-01

    Von Krahli Teater hakkab osalema järgmisel sügisel TÜ Viljandi Kultuuriakadeemia teatrikunsti erialale õppima asuvate tudengite koolitamises. Tudengeid hakkavad juhendama Von Krahli juht Peeter Jalakas, näitlejad Taavi Eelmaa ja Juhan Ulfsak, vene tantsija ja koreograaf Sasha Pepeljajev ning soome lavastaja Kristian Smeds

  20. On the miscellaneous aspects of von Willebrand factor

    NARCIS (Netherlands)

    Groeneveld, Dafna Jordana

    2015-01-01

    Von Willebrand disease is the most common inherited bleeding disorder and is characterized by reduced plasma von Willebrand factor (VWF) levels or functionally abnormal VWF. VWF is best known for its three classical hemostatic functions: (i) as a carrier protein for coagulation factor VIII, (ii)

  1. von Willebrand disease and aging : an evolving phenotype

    NARCIS (Netherlands)

    Sanders, Y. V.; Giezenaar, M. A.; Laros-van Gorkom, B. A. P.; Meijer, K.; van der Bom, J. G.; Cnossen, M. H.; Nijziel, M. R.; Ypma, P. F.; Fijnvandraat, K.; Eikenboom, J.; Mauser-Bunschoten, E. P.; Leebeek, F. W. G.

    2014-01-01

    Background: Because the number of elderly von Willebrand disease (VWD) patients is increasing, the pathophysiology of aging in VWD has become increasingly relevant. Objectives: To assess age-related changes in von Willebrand factor (VWF) and factor VIII (FVIII) levels and to compare age-related diff

  2. Von Krahli teatris etenduvad Tõnu Kõrvitsa kammerooperid / Esme Kassak

    Index Scriptorium Estoniae

    Kassak, Esme

    2006-01-01

    20. apr. esietenduvad Von Krahli Teatris Peeter Jalaka lavastuses Tõnu Kõrvitsa uued kammerooperid "Tuleaed" ja "Mu luiged, mu mõtted", mille aluseks on luuletaja Marie Heibergi saatus. Libretode autor on Maarja Kangro. Kammerooperid tulevad lavale Von Krahli Teatri ja Nargen Opera koostöös. Esitavad Kädy Plaas, Helen Lokuta, Nargen Opera koor ja Tallinna Kammerorkester, dirigent Tõnu Kaljuste

  3. Von Krahli teater mängib Kõrvitsa kammeroopereid

    Index Scriptorium Estoniae

    2006-01-01

    20. apr. esietenduvad Von Krahli Teatris Peeter Jalaka lavastuses Tõnu Kõrvitsa uued kammerooperid "Tuleaed" ja "Mu luiged, mu mõtted", mille aluseks on luuletaja Marie Heibergi saatus. Libretode autor on Maarja Kangro. Kammerooperid tulevad lavale Von Krahli Teatri ja Nargen Opera koostöös. Esitavad Kädy Plaas, Helen Lokuta, Nargen Opera koor ja Tallinna Kammerorkester, dirigent Tõnu Kaljuste

  4. Von Krahli teatris etenduvad Tõnu Kõrvitsa kammerooperid / Esme Kassak

    Index Scriptorium Estoniae

    Kassak, Esme

    2006-01-01

    20. apr. esietenduvad Von Krahli Teatris Peeter Jalaka lavastuses Tõnu Kõrvitsa uued kammerooperid "Tuleaed" ja "Mu luiged, mu mõtted", mille aluseks on luuletaja Marie Heibergi saatus. Libretode autor on Maarja Kangro. Kammerooperid tulevad lavale Von Krahli Teatri ja Nargen Opera koostöös. Esitavad Kädy Plaas, Helen Lokuta, Nargen Opera koor ja Tallinna Kammerorkester, dirigent Tõnu Kaljuste

  5. Victor or Villain? Wernher von Braun and the Space Race

    Science.gov (United States)

    O'Brien, Jason L.; Sears, Christine E.

    2011-01-01

    Set during the Cold War and space race, this historical role-play focuses on Wernher von Braun's involvement in and culpability for the use of slave laborers to produce V-2 rockets for Nazi Germany. Students will grapple with two central questions. Should von Braun have been allowed to emigrate to the United States given his affiliation with the…

  6. Die baltischen Kapitulationen von 1710 : Kontext, Wirkungen, Interpretationen / Marten Seppel

    Index Scriptorium Estoniae

    Seppel, Marten, 1979-

    2015-01-01

    Arvustus: Die baltischen Kapitulationen von 1710 : Kontext, Wirkungen, Interpretationen, hrsg. von Karsten Brüggemann, Mati Laur und Pärtel Piirimäe, Queleln und Studien zur baltischen Geschichte, Bd 23 (Köln u.a: Böhlau Verlag, 2014)

  7. Von Krahli teater mängib Kõrvitsa kammeroopereid

    Index Scriptorium Estoniae

    2006-01-01

    20. apr. esietenduvad Von Krahli Teatris Peeter Jalaka lavastuses Tõnu Kõrvitsa uued kammerooperid "Tuleaed" ja "Mu luiged, mu mõtted", mille aluseks on luuletaja Marie Heibergi saatus. Libretode autor on Maarja Kangro. Kammerooperid tulevad lavale Von Krahli Teatri ja Nargen Opera koostöös. Esitavad Kädy Plaas, Helen Lokuta, Nargen Opera koor ja Tallinna Kammerorkester, dirigent Tõnu Kaljuste

  8. Diurnal variation of von Willebrand factor in plasma

    DEFF Research Database (Denmark)

    Timm, Annette; Fahrenkrug, Jan; Jørgensen, Henrik L;

    2014-01-01

    BACKGROUND: Quantitation of von Willebrand factor (VWF) in plasma is a central element in assessing von Willebrand disease (VWD). VWF activity is known to vary, which has partly been ascribed to biological and preanalytical variation. However, a possible diurnal expression of VWF has not been tho...

  9. Entwicklung eines amperometrischen Biosensors zur Erfassung von Polyphenolen

    OpenAIRE

    2013-01-01

    In der durchgeführten Arbeit wurden neue Immobilisierungsstrategien zur Etablierung eines amperometrischen Biosensors, welcher Polyphenole erfasst, untersucht. Ziel war es eine „Handheld-Unit“ unter Verwendung einer Dickschichtelektrode (Thick-Film Technology, TFT) zu entwickeln. Zur Erfassung von Polyphenolen wurde das Enzym Laccase ausgewählt, welche die Oxidation von Phenolen zu Chinonen katalysiert. Dabei wurden in dieser Arbe...

  10. Von Stryk : halb oli nii aadlikel kui talupoegadel / Margus Haav

    Index Scriptorium Estoniae

    Haav, Margus, 1969-

    2007-01-01

    Rets. rmt.: Stryk, Wolf Dietmar von. Morsel-Podrigel, das Stammhaus der familie von Stryk in Livland/Estland 1562-1919-2003. : die Geschichte eines Gutes im Wandel der Zeiten der Jahrhunderte bis zur Gegenwart. Viljandi : W. Stryk, 2006. Artikkel ilmunud ka: Valgamaalane, 3. märts 2007, lk 4

  11. Erfahrungen an der Schnittstelle von Medienarbeit und Praxisforschung

    Directory of Open Access Journals (Sweden)

    Peter Holzwarth

    2007-11-01

    Full Text Available Der Beitrag reflektiert die Verbindung von praktischer Medienarbeit und Forschung am Beispiel eines internationalen EU-Forschungsprojekts zum Thema Medien und Migration. Neben didaktischen Prinzipien und Konzepten für die aktive Medienarbeit im Forschungskontext geht es um die Kooperation von medienpädagogischer Begleitung (MB und wissenschaftlicher Begleitung (WB sowie um deren spezifische Kompetenzen.

  12. Auf den Schultern von Riesen und Zwergen Einsteins unvollendete Revolution

    CERN Document Server

    Renn, Jürgen

    2006-01-01

    Dies ist die Geschichte von Einsteins unvollendeter Revolution, einer tiefgreifenden Veränderung unserer Begriffe von Raum, Zeit, Materie und Strahlung. Diese Revolution begann in Einsteins Wunderjahr 1905, wurde durch seine allgemeine Relativitätstheorie aus dem Jahre 1915 fortgesetzt und wirkt in den heutigen Versuchen der Wissenschaft, die Entstehung und das Schicksal des Universums zu verstehen, weiter. Vor dem Hintergrund einer historischen Theorie des wissenschaftlichen Fortschritts wird Einsteins bis heute nicht abgeschlossene Revolution als das Ergebnis einer langfristigen Entwicklung des Wissens verständlich. Anhand der spannenden Geschichte von Einsteins Entdeckungen wird nachvollziehbar, warum große Denker wie Einstein weiter gesehen haben als ihre Vorgänger. Sie standen nicht nur auf den Schultern von Riesen, also den wissenschaftlichen Leistungen einzelner großer Vorgänger wie Newton, sondern auch auf den Schultern von "Zwergen", dem wissenschaftlichen Wissen, dem technischen Wissen, und d...

  13. Suitability of tracers; Eignung von Tracern

    Energy Technology Data Exchange (ETDEWEB)

    Klotz, D. [GSF - Forschungszentrum fuer Umwelt und Gesundheit GmbH, Neuherberg (Germany). Inst. fuer Hydrologie

    1999-02-01

    Hydrological tracer techniques are a means of making statements on the direction and speed of underground water. One of the simpler tasks is to find out whether there is hydrological communication between two given points. This requires a determination of the direction of flow, which places less exacting demands on the properties of the tracer than does the task of determining the flow velocity of underground water. Tracer methods can serve to infer from flow velocity the distance (flow) velocity, which is defined as the ratio between the distance between two points located in flow direction and the actual time it takes water to flow from one to the other. [Deutsch] Mit Hilfe der hydrologischen Markierungstechniken koennen Aussagen ueber die Richtung und die Geschwindigkeit von Bewegungen des unterirdischen Wassers gemacht werden. Der einfachere Fall liegt vor, wenn festgestellt werden soll, ob zwischen zwei Punkten eine hydrologische Verbindung besteht. Bei dieser Fliessrichtungsbestimmung sind die Forderungen an die Eigenschaften der einzusetzenden Tracer geringer als bei der Bestimmung der Geschwindigkeit des unterirdischen Wassers. Von den Geschwindigkeiten des unterirdischen Wassers ist die Abstands-(Fliess)geschwindigkeit, die definiert ist durch das Verhaeltnis aus dem Abstand und der wahren Fliesszeit zwischen zwei in Bewegungsrichtung gelegenen Punkten, durch Tracermethoden zu bestimmen. (orig.)

  14. Guy von Dardel 1919-2009

    CERN Multimedia

    2009-01-01

    Guy von Dardel, a well-known figure at CERN and in the international particle physics community, passed away on 28 August. Guy von Dardel came to CERN when it was founded in 1954 and was a full-time staff member until 1964, performing several experiments and working on technical developments. These included the first measurement of the neutral pion’s life-time. Called to Lund University in 1964, he became professor there in 1965 and director of the 1.2 GeV electron accelerator. In the late 1960s, he performed an experiment at CERN’s PS that measured the decays of the Λ. Then, in the early 1970s, he involved the Lund group in a series of experiments at the Intersecting Storage Rings (ISR), where he measured the production of various types of particles. In particular, he participated in a series of experiments that observed the production of a high abundance of particles with large transverse momenta. This required an explanation...

  15. Approximate von Neumann entropy for directed graphs.

    Science.gov (United States)

    Ye, Cheng; Wilson, Richard C; Comin, César H; Costa, Luciano da F; Hancock, Edwin R

    2014-05-01

    In this paper, we develop an entropy measure for assessing the structural complexity of directed graphs. Although there are many existing alternative measures for quantifying the structural properties of undirected graphs, there are relatively few corresponding measures for directed graphs. To fill this gap in the literature, we explore an alternative technique that is applicable to directed graphs. We commence by using Chung's generalization of the Laplacian of a directed graph to extend the computation of von Neumann entropy from undirected to directed graphs. We provide a simplified form of the entropy which can be expressed in terms of simple node in-degree and out-degree statistics. Moreover, we find approximate forms of the von Neumann entropy that apply to both weakly and strongly directed graphs, and that can be used to characterize network structure. We illustrate the usefulness of these simplified entropy forms defined in this paper on both artificial and real-world data sets, including structures from protein databases and high energy physics theory citation networks.

  16. Kontextualisierung von Queer Theory Contextualizing Queer Theory

    Directory of Open Access Journals (Sweden)

    Anna Voigt

    2008-03-01

    Full Text Available Christine M. Klapeer legt in diesem Einführungsband dar, aus welchen politischen und theoretischen Kontexten heraus sich ‚queer‘ zu einem Begriff mit besonderem politischem und theoretischem Gehalt entwickelt hat. Wesentlich zielt sie dabei auf eine kritische Kontextualisierung von „queer theory”. Die Autorin geht zunächst auf das Gay Liberation Movement ein, grenzt die Queer Theory vom Poststrukturalismus, von feministischen Theorien und den Lesbian and Gay Studies ab, beleuchtet Eckpunkte queeren Denkens und zeichnet schließlich die Entwicklungen in Österreich sowohl politisch-rechtlich als auch bewegungsgeschichtlich und in der Wissenschaftslandschaft nach.Christine M. Klapeer’s introductory volume demonstrates the manner in which ‘queer’ grew out of various political and theoretical contexts to become a term with special political and theoretical content. She focuses primarily on a critical contextualization of “queer theory.” The author begins by approaching the Gay Liberation Movement and then distinguishes Queer Theory from poststructuralism, from feminist theories, and from Lesbian and Gay Studies. She continues on to illuminate the key aspects of queer thought and concludes by sketching the development in Austria in terms of politics and the law, the history of movements, and within the landscape of knowledge.

  17. Integrales Lernen in und von Organisationen

    Directory of Open Access Journals (Sweden)

    Wendelin Küpers

    2006-06-01

    Full Text Available Bezogen auf das integrale Models von Ken Wilber untersucht der Beitrag die Bedeutung des Lernens in und von Organisationen. Nach einer Darstellung der Relevanz und des Grundverständnisses des Lernens im Organisationskontext, werden integrale Dimensionen des Lernens dargestellt. Im Einzelnen werden die verschiedenen Sphären eines inneren-subjektiven und äusseren-„objektiven“ Lernens des Einzelnen als auch ein gemeinschaftliches Lernen und Lernen im System auf der kollektiven Ebene dargestellt sowie deren interrelationaler Zusammenhang diskutiert. Schließlich beschreibt der Beitrag noch integrale Lernprozesse sowie integrale Gestaltungsfelder zur Förderung des Lernens in den verschiedenen Bereichen. Abschließend spricht der Artikel noch Schwierigkeiten und Probleme an sowie nimmt im Fazit ein perspektivischen Ausblick vor. Abstract: Related to the integral model of Ken Wilber, this paper investigates the role of learning in and of organisations. After describing the relevance and basic understanding of learning in the context of organisations, integral dimensions of learning will be outlined. In particular learning in the sphere of an inner-subjective and exterior-objective learning of the individual and a communal learning and learning within a system on the collective level as well as its interrelations will be discussed. Afterwards integral learning processes and various measurements for enhancing integral learning in the different sphere will be discussed. Finally, difficulties and problems will be addressed and in conclusion some perspectives and implications are presented.

  18. Katheterablation von supraventrikulären Tachykardien

    Directory of Open Access Journals (Sweden)

    Strohmer S

    2011-01-01

    Full Text Available Supraventrikuläre Tachykardien (SVT spielen in der klinischen Praxis aufgrund ihrer Häufigkeit und Symptomatik eine große Rolle. Obwohl diese Arrhythmien im Allgemeinen nicht lebensbedrohlich sind, führen sie aufgrund ihres unvorhersehbaren Auftretens zu einer beträchtlichen Unsicherheit und Einschränkung der Lebensqualität. Die elektrophysiologische Untersuchung inklusive Katheterablation hat sich in den vergangenen 20 Jahren als kurative und sichere Erstlinientherapie für Patienten mit hochsymptomatischen bzw. wiederholten Anfällen etabliert. Heutzutage liegen die Erfolgsraten für die Radiofrequenzablation der regulären SVT über 95 % bei einer sehr niedrigen Rezidivrate von weniger als 5 %. Eine antiarrhythmische Therapie für das Langzeitmanagement ist aufgrund der geringen Effektivität und Gefahr von ernsthaften Nebenwirkungen weitgehend obsolet und nur in Ausnahmefällen erforderlich. Der folgende Artikel gibt eine aktuelle Übersicht über die häufigsten rhythmischen Schmalkomplextachykardien, die verschiedenen Mechanismen und moderne nicht-pharmakologische Therapieansätze.

  19. Die Krakauer Kirche von Karmeliten und Karmelitaninnen

    Directory of Open Access Journals (Sweden)

    Józef Szymon Wronski

    2004-12-01

    Full Text Available 1. Die Klosterkirche der unbeschuhten Karmelitinnen Zum Heiligen Josef. Ein glücklicher Auftakt und somit die charakteristische Einführung in das 20. Jh. für den Kirchenbau von Krakau war die Errichtung der Karmeliterinnen St. Josephs-Kirche an der Lobzowska-Straße 40, in der die Architekten (Tadeusz Stryjeński (1849-1943 - Projektant der Kirche und Franciszek Mączyński (1874-1947 - Ausführer des Bauprojektes mit eigenen Verbesserungen die historisch- eklektizistischen Formen d.h. die mittelalterlichen Formen vor allem des sog. Übergangsstils vereinfachten. Die Kirche, die in den Jahren 1903-1905 errichtet wurde, steht inmitten vom Baukomplex des Klosters, dessen Grundriss das Quadrat ist49. Der Kirchenbau ist ein dem Gesamtbau des Klosters eingefügter Längsraum. Hinter dem Chor liegt das Oratorium des Konvents. Das Material Backstein (mit Verwendung von Stein erinnert an die Baukunst eines der besten Architekten jener Zeit, nämlich Teodor Talowskis (1857-1910, der viele Kirchen in Südpolen, aber auch viele Bürgerhäuser nicht nur in Krakau im ausgehenden 19. Jh. baute. Die Architektur der Karmeliterinnen St. Josephs-Kirche ist immer noch im Malerischen begriffen. Aber die Vereinfachung der historischen Formen führt zu ihrer „Beruhigung” und dadurch zur Wuchtigkeit des Ausdrucks. Bemerkenswert ist die in dieser Zeit (in der Anlage noch seltene ausgewogene Proportionierung des Baukörpers. Das methodische Prinzip jener Zeit ist der Kontrast. Im Kontrast zu den gedrungenen und wuchtigen Formen des Baukörpers stehen z.B. die sich verjüngenden obeliskenförmigen und pylonenartigen Türmchen, die nicht nur die Eingangsfassade der Kirche flankieren, sondern auch an den Ecken des Querhauses der Kirche stehen. Die ingravierten weißen Steine an der Fassade in der Zahl von Zehn erinnern an das Gebot des Karmelterinnenordens: Bete täglich den Rosenkranz und sind zugleich ein Vanitativmotiv. 2. Die Klosterkirche der unbeschuhten

  20. Rethinking the diagnosis of von Willebrand disease.

    Science.gov (United States)

    Favaloro, Emmanuel J

    2011-01-01

    von Willebrand disease (VWD) is the most common inherited bleeding disorder and arises from deficiencies and/or defects in the plasma protein von Willebrand factor (VWF). VWD is classified into 6 different types, with type 1 identified as a (partial) quantitative deficiency of VWF, type 3 defined by a (virtual) total deficiency of VWF, and type 2 identifying four separate types (2A, 2B, 2M, 2N) characterised by qualitative defects. The classification is based on phenotypic assays including FVIII, VWF:Ag and VWF activity, typically by ristocetin cofactor (VWF:RCo), but also increasingly by collagen binding (VWF:CB). Phenotypic testing may be supplemented by multimer analysis, RIPA, and VWF:FVIII binding. Although genetic analysis is not required to diagnose VWD or to define a classification type, it may be useful in discrete situations. The current review briefly covers this diagnostic process, with a focus on newer approaches, including extended test panels and the use of data from desmopressin challenges as a diagnostic tool. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. [Heinz von zur Mühlen. Das Bürgertum Fordert Blut. Ein Bolschewistiches Flugblatt von 1918] / Paul Kaegbein

    Index Scriptorium Estoniae

    Kaegbein, Paul

    2007-01-01

    Arvustus: Heinz von zur Mühlen. Das Bürgertum Fordert Blut. Ein Bolschewistiches Flugblatt von 1918. In : Ostseeprovinzen, baltische Staaten und das Nationale. Münster : LIT, 2005, lk. 403-414. 1918. aastast pärit lendlehest, mille käekirja järgi otsustades on kirjutanud Viktor Kingissepp

  2. [Heinz von zur Mühlen. Das Bürgertum Fordert Blut. Ein Bolschewistiches Flugblatt von 1918] / Paul Kaegbein

    Index Scriptorium Estoniae

    Kaegbein, Paul

    2007-01-01

    Arvustus: Heinz von zur Mühlen. Das Bürgertum Fordert Blut. Ein Bolschewistiches Flugblatt von 1918. In : Ostseeprovinzen, baltische Staaten und das Nationale. Münster : LIT, 2005, lk. 403-414. 1918. aastast pärit lendlehest, mille käekirja järgi otsustades on kirjutanud Viktor Kingissepp

  3. Alexander von Humboldt in Daniel Kehlmanns Welt

    Directory of Open Access Journals (Sweden)

    Ottmar Ette

    2012-12-01

    Full Text Available Zusammenfassung Wie stark sich im Verlauf des zurückliegenden Vierteljahrhunderts der Bekanntheitsgrad Alexander von Humboldts in der deutschsprachigen Öffentlichkeit verändert hat, zeigen nicht nur Fernsehumfragen zu den berühmtesten Deutschen, in denen Alexander von Humboldt mittlerweile figuriert, oder Fernsehserien, die über aktuelle Expeditionen berichten und auf Humboldts Namen zurückgreifen. Am deutlichsten vielleicht belegt dies der enorme Erfolg von Daniel Kehlmanns Roman Die Vermessung der Welt, der ohne die zuvor skizzierte Entwicklung nicht denkbar gewesen wäre. Es ist vor diesem Hintergrund nicht nur reizvoll, sondern aufschlußreich, sich mit dem großen Erfolg dieses kleinen Romans zu beschäftigen. Worum geht es in Die Vermessung der Welt? Und wie läßt sich das „Phänomen Kehlmann“ aus etwas größerer Distanz erklären? Abstract In the last 25 years, Alexander von Humboldt‘s popularity has radically changed in the german-speaking public opinion. Proof of this are not only television surveys about the most famous germans - in which Alexander von Humboldt now regularly figures - or television series about contemporary expeditions, which constantly refer to Humboldt‘s name; perhaps what most clearly verifies this change is the great success of Daniel Kehlmann‘s novel Die Vermessung der Welt. Without the recent developments outlined above, this novel‘s degree of impact would have been unimaginable. To study the great success of this text against this backdrop is not only attractive, but also revealing. What is Die Vermessung der Welt really about? And how can we explain the „Kehlmann phenomenon“ from a greater distance? Resumen La popularidad de Alejandro de Humboldt ha cambiado profundamente dentro del último cuarto de siglo en la opinión pública de habla alemana. Prueba de esto son no sólo las encuestas televisivas sobre los alemanes más famosos, dentro de las cuales figura en estos momentos Alejandro

  4. Ludwig Leichhardt und Alexander von Humboldt

    Directory of Open Access Journals (Sweden)

    Aliya-Katarina Südfels

    2012-10-01

    Full Text Available Zusammenfassung Im Juli des Jahres 1841 kommt es zu einem Treffen zwischen zwei Männern, das zunächst belanglos erscheint, sich aber Jahre später als wichtige historische Begebenheit herausstellen wird. In seinem Pariser Büro empfängt der 71jährige Naturforscher Alexander von Humboldt den jungen Preußen Ludwig Leichhardt. Der angehende Naturwissenschaftler erhofft sich Zuspruch und Empfehlung des berühmten Alexander von Humboldts. Die Unterredung ist kurz und verläuft für Leichhardt ergebnislos. Es wird das einzige Treffen der beiden Naturwissenschaftler bleiben. Aus heutiger Sicht unverständlich, da Ludwig Leichhardt und Alexander von Humboldt mehr verband, als ihre Leidenschaft für die Naturwissenschaften. Viel zu wenig ist sich bis jetzt den biographischen Analogien und den vergleichbaren geographischen Leistungen der beiden Preußen gewidmet worden. Abstract During July 1841 a meeting between two men takes place, which seems to have been extraneous, but turns out to be a significant historical incident. 71 year old natural scientist Alexander von Humboldt welcomes young Ludwig Leichhardt from Prussia in his office in Paris. The prospective young scientist expects help and references from famous Alexander von Humboldt. The conversation is short and ends from Leichhardt’s point of view without results. Unfortunately this is going to be the only meeting between the two scientists even though the two Prussians have more in common than their passion for the natural sciences. Way too seldomly have biographical analogy and geographical productivity of the two men been compared. Résumé En juillet 1841 une rencontre entre deux hommes a lieu, qui au premier abord semble sans importance, mais qui des années plus tard est considéré comme un événement historique majeur. Dans son bureau parisien, le naturaliste Alexandre de Humboldt, alors âgé de 71 ans, reçoit le jeune Prussien Ludwig Leichhardt. Le jeune scientifique en devenir

  5. Herstellung und Charakterisierung einer rekombinanten, sequenzspezifischen Protease zur Generierung bioaktiver Peptide

    OpenAIRE

    2009-01-01

    Ziel der vorliegenden Arbeit war es, eine sequenzspezifische, mikrobielle Protease herzustellen, biochemisch zu charakterisieren und mittels dieses Enzyms aus Lebensmittelprotein hydrolytisch bioaktive Peptide zu generieren. Um die Serin-Protease PRT1 aus Xanthomonas campestris pv. campestris bezüglich ihrer Substratspezifität zu untersuchen, wurde dieser Stamm im Schüttelkolben kultiviert. Nach Dialyse des Kulturüberstandes und Zugabe von 1,10-Phenantrolin zur Inaktivierung der Metalloprotea...

  6. Acylation of Therapeutic Peptides

    DEFF Research Database (Denmark)

    Trier, Sofie; Henriksen, Jonas Rosager; Jensen, Simon Bjerregaard

    peptides are similar in size and structure, but oppositely charged at physiological pH. Both peptides were acylated with linear acyl chains of systematically increasing length, where sCT was furthermore acylated at two different positions on the peptide backbone. For GLP-2, we found that increasing acyl...... stems from a synergy between the positive peptide charge and membrane-active acyl moiety, supported by its pH-dependency, whereby the effect increased with decreasing pH and concomitant charge increase. The extent of permeation enhancing effect was highly dependent on acylation chain length and position...

  7. Topical peptides as cosmeceuticals

    Directory of Open Access Journals (Sweden)

    Varadraj Vasant Pai

    2017-01-01

    Full Text Available Peptides are known to have diverse biological roles, most prominently as signaling/regulatory molecules in a broad variety of physiological processes including defense, immunity, stress, growth, homeostasis and reproduction. These aspects have been used in the field of dermatology and cosmetology to produce short, stable and synthetic peptides for extracellular matrix synthesis, pigmentation, innate immunity and inflammation. The evolution of peptides over the century, which started with the discovery of penicillin, has now extended to their usage as cosmeceuticals in recent years. Cosmeceutical peptides may act as signal modulators of the extracellular matrix component, as structural peptides, carrier peptides and neurotransmitter function modulators. Transdermal delivery of peptides can be made more effective by penetration enhancers, chemical modification or encapsulation of peptides. The advantages of using peptides as cosmeceuticals include their involvement in many physiological functions of the skin, their selectivity, their lack of immunogenicity and absence of premarket regulatory requirements for their use. However, there are disadvantages: clinical evidence for efficacy is often weak, absorption may be poor due to low lipophilicity, high molecular weight and binding to other ingredients, and prices can be quite high.

  8. Neurochirurgische Therapie von atypischen neuropathischen Gesichtsschmerzen und Clusterkopfschmerz mit Darstellung von Kernaspekten neurochirurgischer Schmerztherapie

    Directory of Open Access Journals (Sweden)

    Eisner W

    2016-01-01

    Full Text Available Die primäre Behandlung von Schmerzen jeglicher Art erfolgt pharmakologisch, physikalisch-medizinisch oder verhaltenstherapeutisch. Wenn diese konservativen Therapiemaßnahmen versagen, geraten Therapeuten und Patienten schnell in große Not; Alternativmethoden werden herangezogen. Solange geholfen wird und eine Schmerzerleichterung erkennbar ist, ist nichts dagegen einzuwenden. Versagen auch diese Methoden, sucht der Patient erneut Spezialisten auf, denen die schwere Aufgabe zukommt, dem Patienten weitere therapeutische Möglichkeiten zu ermöglichen oder ihn seinem Schicksal zu überlassen.br Die vorliegende Arbeit über atypische Gesichtsschmerzen möchte über neurochirurgische Behandlungsmöglichkeiten informieren. Die Komplexität dieser Erkrankungen benötigt die Interdisziplinarität von Neurologen, Schmerztherapeuten sowie Psychologen und nicht Beisätze wie „Vorsicht, Chirurgen, die schneiden überall rein und dann erst …“.

  9. Charakterisierung von Mutanten im Lösungsmittelstoffwechsel von Clostridium acetobutylicum

    OpenAIRE

    Hönicke, Daniel

    2015-01-01

    Im Rahmen dieser Arbeit wurden insgesamt neun durch ClosTron-basierte Mutagenese erhaltene Insertionsmutanten von C. acetobutylicum ATCC 824 einer umfangreichen Charakterisierung unterzogen. Für alle im Batch-Fermentationsmaßstab und/oder in kontinuierlicher Kultur fermentierten Stämme erfolgte eine globale Analyse des Transkriptoms unter Verwendung der DNA-Microarray-Technologie. Für eine Analyse des Acetat- und Aceton-Stoffwechsels wurden Stämme mit einer inaktivierten Phosphotransacetyl...

  10. Update: SPECT in der Diagnostik von Parkinson-Syndromen

    Directory of Open Access Journals (Sweden)

    Pirker W

    2015-01-01

    Full Text Available Die Diagnose des Morbus Parkinson fußt primär auf Anamnese und klinischer Untersuchung. Die Abgrenzung von milden Bewegungsstörungen bei ansonsten gesunden älteren Personen, von medikamenteninduzierten und vaskulären Parkinson-Syndromen sowie von Tremor-Syndromen kann jedoch schwierig sein. Die Differenzierung zwischen M. Parkinson und atypischen Parkinson-Erkrankungen wie der Multisystematrophie (MSA und der progressiven supranukleären Paralyse (PSP ist im Frühstadium häufig unmöglich und kann auch in fortgeschrittenen Stadien Probleme bereiten. Die SPECT-Untersuchung mit Dopamin-Transporter- (DAT- Liganden wie 123I-FP-CIT erlaubt mit wenigen Ausnahmen bereits im Frühstadium eine Dokumentation der dopaminergen Degeneration beim M. Parkinson und atypischen Parkinson- Erkrankungen und damit meist eine Abgrenzung von nichtdegenerativen Parkinson- und Tremor-Syndromen. Sie kann die einzelnen degenerativen Parkinson-Syndrome jedoch nicht voneinander unterscheiden. Die Untersuchung postsynaptischer Dopamin- D2-Rezeptoren mit der 123I-IBZM-SPECT kann zur Differenzierung von M. Parkinson und MSA bzw. PSP beitragen. Neueren Untersuchungen zufolge dürften die Untersuchung des zerebralen Glukosemetabolismus mittels 18F-FDG-PET sowie moderne MRT-basierte Methoden in dieser Fragestellung jedoch eine höhere Sensitivität und Spezifität haben. Während Medikamente die diagnostische Aussagekraft von DAT-SPECT-Untersuchungen selten beeinflussen, kann das Ergebnis der IBZM-SPECT sowohl durch dopaminerge Substanzen als auch durch Dopaminantagonisten stark verfälscht werden. Die richtige Interpretation von SPECT-Daten setzt darüber hinaus die Kenntnis der individuellen strukturellen bildgebenden Befunde voraus. Eine MRT- oder CCTUntersuchung sollte zum Ausschluss von läsionellen Parkinson-Syndromen und zur Dokumentation von Kopathologien immer Bestandteil der Parkinson-Abklärung sein.

  11. Informationssuchverhalten als Grundlage für die Gestaltung von Veranstaltungen zum Erwerb von Informationskompetenz

    Directory of Open Access Journals (Sweden)

    Martin Wollschläger-Tigges

    2015-09-01

    Full Text Available Für die Gestaltung bibliothekarischer Veranstaltungen zum Erwerb von Informationskompetenz stellen die bisherigen Ergebnisse und Befunde der Forschung zum Informationssuchverhalten eine wertvolle Grundlage dar, indem bestimmte und v.a. typische Verhaltensmuster, Routinen und Präferenzen im Umgang mit Informationsressourcen und Informationen in konzeptionelle und inhaltliche Anpassungen von IK- Veranstaltungen eingebracht und eingesetzt werden. Das Informationssuchverhalten untersucht sowohl individuelle als auch kollektive Informationsprozesse und Faktoren, die diese maßgeblich beeinflussen. Hierzu werden der gesamte Informationsprozess oder einzelne Abschnitte untersucht, die den Information Need, Seeking und Using (INSU-Prozess bilden. Die Befunde der einzelnen INSU-Prozesses-Einheiten zeigen, dass Faktoren wie Informationsbedarf, Informationsart und -form sowie die Einbindung in übergeordnete Arbeitsprozesse wesentlichen Einfluss auf das Informationssuchverhalten haben. Des Weiteren konnte die ISB-Forschung eine Klassifizierung von Benutzergruppen entwickeln und z.B. Fast Surfers, Broad Scanners und Deep Divers charakterisieren bzw. auch das Bouncing oder Flicking Behavior beschreiben. Hinzu kommen mehrere Modelle, die Informationssuchverhalten und Informationsverhalten in bestimmten Situationen nachbilden und darstellen können.

  12. Valence bond and von Neumann entanglement entropy in Heisenberg ladders.

    Science.gov (United States)

    Kallin, Ann B; González, Iván; Hastings, Matthew B; Melko, Roger G

    2009-09-11

    We present a direct comparison of the recently proposed valence bond entanglement entropy and the von Neumann entanglement entropy on spin-1/2 Heisenberg systems using quantum Monte Carlo and density-matrix renormalization group simulations. For one-dimensional chains we show that the valence bond entropy can be either less or greater than the von Neumann entropy; hence, it cannot provide a bound on the latter. On ladder geometries, simulations with up to seven legs are sufficient to indicate that the von Neumann entropy in two dimensions obeys an area law, even though the valence bond entanglement entropy has a multiplicative logarithmic correction.

  13. A von Bertalanffy growth model with a seasonally varying coefficient

    Science.gov (United States)

    Cloern, James E.; Nichols, Frederic H.

    1978-01-01

    The von Bertalanffy model of body growth is inappropriate for organisms whose growth is restricted to a seasonal period because it assumes that growth rate is invariant with time. Incorporation of a time-varying coefficient significantly improves the capability of the von Bertalanffy equation to describe changing body size of both the bivalve mollusc Macoma balthicain San Francisco Bay and the flathead sole, Hippoglossoides elassodon, in Washington state. This simple modification of the von Bertalanffy model should offer improved predictions of body growth for a variety of other aquatic animals.

  14. Bioaktivitäten von Wertstoffen aus Saccharomyces Hefen

    OpenAIRE

    Jährig, Silke Christiane

    2007-01-01

    In der vorliegenden Arbeit wurden die antioxidative Aktivität sowie die immunmodulierende Kapazität von Zellwänden und Zellwandbestandteilen der Bierhefe Saccharomyces cerevisiae untersucht. Die Zellwände von Saccharomyces-Hefen bestehen aus (1→3),(1→6)-β-D-Glucan, Mannanen, Proteinen und Lipiden. Als potentieller Immunmodulator ist vor allem das (1→3),(1→6)-β-D-Glucan von Interesse. Vor kurzem konnte für dieses Glucan zusätzlich eine antioxidative Wirkung nachgewiesen werden [KOGAN et al., 2...

  15. Emotionales Erleben von Lehrkräften beim Unterrichten

    OpenAIRE

    Frenzel, Anne C.; Götz, Thomas

    2007-01-01

    Ziel dieser Studie war es, das Ausmaß an Variabilität des Erlebens von Freude, Angst und Ärger bei Lehrkräften zu ermitteln, das auf ihre Persönlichkeit, das Unterrichtsfach (hier: Mathematik vs. Physik) und die jeweils unterrichtete Klasse zurückzuführen ist. Zudem wurde der Einfluss von Person- und Kontextmerkmalen auf das emotionale Erleben beim Unterrichten untersucht. 59 Gymnasiallehrkräfte (9 weiblich) gaben anhand von einem Fragebogen sowie einem Tagebuch Auskunft über ihre Unterrichts...

  16. Über die Ethoxylierung von Octanol im Mikrostrukturreaktor

    OpenAIRE

    2015-01-01

    Die basisch katalysierte ringöffnende Polymerisation von Ethylenoxid mit Octanol (Ethoxylierung) wurde in einem kontinuierlich betriebenen Mikrostrukturreaktor untersucht. Es wurde die Kinetik dieser Reaktion unter intensivierten Bedingungen ermittelt. Die Reaktion wurde homogen in der Flüssigphase durchgeführt, bei Drücken bis 100 bar und Temperaturen im Bereich von 130 °C bis 240 °C. Für die Propagationsreaktion eine Aktivierungsenergie von 73 kJ/mol gefunden. Es wurde gezeigt, dass die Pro...

  17. Modernisation of ventilation systems; Modernisierung von Lueftungsanlagen

    Energy Technology Data Exchange (ETDEWEB)

    Richter, W. [Technische Univ. Dresden (Germany). Inst. fuer Thermodynamik und Technische Gebaeudeausruestung

    1997-12-31

    When redeveloping buildings it is common to use window constructions with air-tight rabbets which obviate the inflow of fresh air almost entirely. This leads to the well-known structural-physics and hygienic consequences. As an added effect, the distinctly enhanced thermal insulation results in changes in dynamic heat loss. The paper focuses on the issues of how to safeguard the inflow of fresh air, and the heating capacity of radiators. (MSK) [Deutsch] Da die bei Gebaeudesanierungen eingesetzten fugendichten Fensterkonstruktionen die Nachstroemmoeglichkeiten fuer die Zuluft fast ganz unterbinden, fuehrt das zu den bekannten bauphysikalischen und hygienischen Konsequenzen. Dazu kommen veraenderte dynamische Waermverlustverhaeltnisse aufgrund der deutlich verbesserten Waermedaemmung. Im Folgenden wird schwerpunktmaessig auf die Probleme Zuluftsicherung und Waermeleistung von Heizkoerpern eingegangen.

  18. Wirksame Alternativen zur Behandlung von klimakterischen Beschwerden

    Directory of Open Access Journals (Sweden)

    Stute P

    2011-01-01

    Full Text Available Vasomotorische Beschwerden (VMS werden von 75 % der postmenopausalen Frauen angegeben. Neben der konventionellen Hormontherapie stehen verschiedene Behandlungsmöglichkeiten aus dem Bereich der Alternativ- und Komplementärmedizin (CAM zur Verfügung. Soja Isoflavone und Traubensilberkerze können bei jüngeren peri- und frühen postmenopausalen Frauen mit leichten bis moderaten VMS hilfreich sein. Die Studienlage zur CMA ist jedoch insgesamt unzureichend. In Zukunft wäre es wünschenswert, nicht nur das Wirkungsvermögen, sondern auch die Effizienz einer Behandlung in randomisiert-kontrollierten Studien zu untersuchen. Hierfür bietet sich die ICF Klassifikation der WHO an.

  19. Hermann von Helmholtz and the empiricist vision.

    Science.gov (United States)

    Turner, R S

    1977-01-01

    The philosophical convictions of Hermann von Helmholtz and the empiricist psychology he developed have been extensively discussed in historical literature. This literature has not usually emphasized the tacti assumptions about human physiology that underlaid these convictions nor the way in which Helmholtz's epistemology served as a methodological directive in his research. Helmholtz assumed nerve transmission between sense organs and the mind to be a passive process. Distortion in stimulus patterns occurs physically in the sense organs, which can therefore be treated through mechanical analogies. Stimuli become converted to the perceptions of consciousness through mental processes that are essentially analogous to conscious, inductive inference and that are therefore susceptible, in principle, to introspective investigation. This view of mental function reflected Helmholtz's intellectual debt to German idealism, especially to the philosophical views of J.G. Fichte.

  20. Hepatische Effekte von Wachstumshormon auf den Glukosestoffwechsel

    Directory of Open Access Journals (Sweden)

    Rufinatscha K

    2015-01-01

    Full Text Available Untherapierter Wachstumshormonmangel im Erwachsenenalter (AGHD ist mit viszeraler Adipositas, Dyslipidämie, Insulinresistenz und Fettleber verbunden. Interessanterweise finden sich viele der AGHD-Merkmale auch bei Patienten mit metabolischem Syndrom. Die nichtalkoholische Fettlebererkrankung (NAFLD gilt als hepatische Manifestation des metabolischen Syndroms. In einigen Studien wurden bei Patienten mit NAFLD verminderte Konzentrationen von zirkulierendem IGF-1, dessen Synthese zu einem großen Teil durch Wachstumshormon (GH reguliert wird, beschrieben. Mäuse, welche eine hepatische Wachstumshormondefizienz aufweisen, zeigen zahlreiche phänotypische Charakteristika des metabolischen Syndroms, unter anderen auch eine Fettlebererkrankung. Dies legt einen Zusammenhang zwischen dem Wachstumshormon und der Entstehung einer NAFLD nahe. Ziel unserer Studie ist es, in einem Zellkulturmodell die Effekte des Wachstumshormons auf den intrazellulären Glukosestoffwechsel näher zu untersuchen. Im Detail sollen Auswirkungen einer verminderten Wachstumshormonrezeptorexpression auf den Insulinsignaltransduktionsweg, den Glykogengehalt und auf Schlüsselenzyme der Glukoneogenese untersucht werden. Präliminäre Daten zeigen, dass eine verminderte Wachstumshormonrezeptorexpression mit intrazellulären Veränderungen des hepatischen Glukosestoffwechsels verbunden ist. Die verminderte Insulinsensitivität könnte auf Alterationen im Insulinsignaltransduktionsweg und Änderungen der Glukoneogenese zurückzuführen sein. Diese präliminären Daten weisen darauf hin, dass Wachstumshormon einen direkten Einfluss auf den Glukosestoffwechsel in der Leber hat. Zudem legen sie nahe, dass Veränderungen im Wachstumshormonstoffwechsel einen wichtigen pathophysiologischen Mechanismus in der Entstehung der Fettlebererkrankung bei Patienten mit metabolischem Syndrom darstellen könnten. Der folgende Artikel soll einen kurzen Überblick über die Effekte von Wachstumshormon

  1. Insulin C-peptide test

    Science.gov (United States)

    C-peptide ... the test depends on the reason for the C-peptide measurement. Ask your health care provider if ... C-peptide is measured to tell the difference between insulin the body produces and insulin someone injects ...

  2. PNA Peptide chimerae

    DEFF Research Database (Denmark)

    Koch, T.; Næsby, M.; Wittung, P.;

    1995-01-01

    Radioactive labelling of PNA has been performed try linking a peptide segment to the PNA which is substrate for protein kinase A. The enzymatic phosphorylation proceeds in almost quantitative yields.......Radioactive labelling of PNA has been performed try linking a peptide segment to the PNA which is substrate for protein kinase A. The enzymatic phosphorylation proceeds in almost quantitative yields....

  3. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds known as peptide nucleic acids, bind complementary DNA and RNA strands, and generally do so more strongly than the corresponding DNA or RNA strands while exhibiting increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from...

  4. Avian host defense peptides

    NARCIS (Netherlands)

    Cuperus, Tryntsje; Coorens, M.; van Dijk, A.; Haagsman, H.P.

    2013-01-01

    Host defense peptides (HDPs) are important effector molecules of the innate immune system of vertebrates. These antimicrobial peptides are also present in invertebrates, plants and fungi. HDPs display broad-spectrum antimicrobial activities and fulfill an important role in the first line of defense

  5. Bacteriocin Inducer Peptides

    Science.gov (United States)

    Novel peptides produced by bacteriocin-producing bacteria stimulate the production of bacteriocins in vitro. The producer bacteria are cultured in the presence of a novel inducer bacteria and a peptide having a carboxy terminal sequence of VKGLT in order to achieve an increase in bacteriocin produc...

  6. APD: the Antimicrobial Peptide Database

    OpenAIRE

    Wang, Zhe; Wang, Guangshun

    2004-01-01

    An antimicrobial peptide database (APD) has been established based on an extensive literature search. It contains detailed information for 525 peptides (498 antibacterial, 155 antifungal, 28 antiviral and 18 antitumor). APD provides interactive interfaces for peptide query, prediction and design. It also provides statistical data for a select group of or all the peptides in the database. Peptide information can be searched using keywords such as peptide name, ID, length, net charge, hydrophob...

  7. Von Krahli Teater viis Helsingisse kaks menulavastust / Andres Laasik

    Index Scriptorium Estoniae

    Laasik, Andres, 1960-2016

    2003-01-01

    Von Krahli Teater esineb 29. nov. Helsingis "Baltic Circle" festivalil lavastustega "Luikede järv" ja "Taksojuhid". Tutvustatakse lühidalt ka paari olulisemat soome lavastust ("Puksiirabi" ja "Hamlet"), mis tulevad festivalil esitamisele

  8. CFD-Simulation von Mehrkomponentenadsorption in einem Festbett

    OpenAIRE

    2016-01-01

    von Clemens Gößnitzer Arbeit an der Bibliothek noch nicht eingelangt - Daten nicht geprueft Abweichender Titel nach Übersetzung der Verfasserin/des Verfassers Technische Universität Wien, Univ., Diplomarbeit, 2016

  9. Spurensuche einer Rezeptionsgeschichte Alexander von Humboldt und Johann Gottfried Herder

    National Research Council Canada - National Science Library

    Bernhard Hunger

    2009-01-01

    Article in German, Abstracts in English, German and Spanish.Alexander von Humboldt's work displays traces of Johann Gottfried Herder which are as multifaceted as the references to the latter are scarce...

  10. Von Krahli Teatri lavastus pääses tippfestivalile

    Index Scriptorium Estoniae

    1999-01-01

    Von Krahli Teatri uuendatud lavastus "Eesti mängud. Pulm" esietendub festivalil Theater Der Welt Berliinis. Peeter Jalaka multimeediaetendus Eesti ajaloost ja traditsioonidest osaleb ka suveteatrite festivalil Hamburgis, seejärel antakse kuus etendust Amsterdamis

  11. Magnus Georg von Paucker (1787-1855) / Eckhard Spring

    Index Scriptorium Estoniae

    Spring, Eckhard

    2013-01-01

    Eestis sündinud ja Tartu Ülikoolis õppinud silmapaistvast baltisaksa teadlasest ja tema lapselapsest Alexandrine Pauckerist. 23. novembril 2012 Jelgavas/Mitaus toimunud Magnus Georg von Pauckerile pühendatud teaduskonverentsist

  12. Von Krahli Teatri lavastus pääses tippfestivalile

    Index Scriptorium Estoniae

    1999-01-01

    Von Krahli Teatri uuendatud lavastus "Eesti mängud. Pulm" esietendub festivalil Theater Der Welt Berliinis. Peeter Jalaka multimeediaetendus Eesti ajaloost ja traditsioonidest osaleb ka suveteatrite festivalil Hamburgis, seejärel antakse kuus etendust Amsterdamis

  13. Nash y von Neumann: mundos posibles y juegos de lenguaje

    Directory of Open Access Journals (Sweden)

    Salazar , Boris

    2004-06-01

    Full Text Available Este ensayo emplea las nociones de juego de lenguaje y de equivalencia entre juegos para examinar la decisión de John Nash de no jugar el juego coalicional que propuso John von Neumann. El argumento central es que Nash concibió una clase de mundos posibles incompatible con la de von Neumann, y que en el origen de esa divergencia estarían sus distintas nociones de racionalidad.

  14. Kooperation mit der Industrie bei der Ausbildung von Softwareingenieuren

    OpenAIRE

    2010-01-01

    Vor allem in Regionen, in denen der Personalbedarf der Unternehmen nicht durch Absolventen gedeckt werden kann, sollte sich die Hochschulausbildung auch an den Anforderungen der Industrie orientieren. In diesem Beitrag werden diese Anforderungen für Softwareingenieure für den Standort Görlitz spezifiziert und es werden Kooperationsmöglichkeiten von Hochschule und lokalen Unternehmen aufgezeigt. Dabei wird auf die praxisorientierte Ausbildung, auf die Übernahme von Ausbildungsverantwortung dur...

  15. Hans von Hattingberg (1879-1944) Leben und Werk

    OpenAIRE

    Keifenheim, Katharina Eva

    2011-01-01

    Hans von Hattingberg, geboren am 18.11.1879 in Wien, wird heute vor allem mit dem Deutschen Institut für Psychologische Forschung und Psychotherapie („Göring-Institut“) in Verbindung gebracht, wo er sich mit der „Neuen Deutschen Seelenheilkunde“ und der Erarbeitung von „Thesen zur Neurosenlehre“ befasste. Interessanterweise war Hattingberg bis 1932 eher eine Randfigur in der Psychotherapeutenszene und galt vielen als unbelehrbarer Querulant. Viele seiner Arbeiten wurden nie veröffentlicht, u...

  16. Numerical Analysis Of Buckling Of Von Mises Planar Truss

    Directory of Open Access Journals (Sweden)

    Kalina Martin

    2015-12-01

    Full Text Available A computational algorithm of a discrete model of von Mises planar steel truss is presented. The structure deformation is evaluated by seeking the minimal potential energy. The critical force invented by mathematical solution was compared with solution by computer algorithm. Symmetric and asymmetric effects of initial shape of geometric imperfection of axis of struts are used in model. The shapes of buckling of von Mises planar truss of selected vertical displacement of top joint are shown.

  17. Wie vergleichbar sind Ergebnisse von Rechtschreib-und Lesetests?

    OpenAIRE

    Steinhauser, Susanne

    2006-01-01

    Eine umschriebene Lese-Rechtschreibstörung (ICD-10: F81) ist durch eine Diskrepanz zwischen den allgemeinen kognitiven Fähigkeiten eines Kindes und dessen Lese-Rechtschreibleistungen gekennzeichnet. Für die Diagnostik steht eine Vielzahl von Lese- und Rechtschreibtests zur Verfügung. In der Studie wurde untersucht, ob die Diagnosestellung von der Wahl des Testverfahrens abhängt. Es wurden Kinder mit mehreren Rechtschreib- und Lesetests untersucht. Die allgemeinen kognitiven Fähigkeiten wur...

  18. Modellbasierte Merkmalsplanung zur objektbezogenen laserscannerbasierten Navigation von Fahrzeugen

    OpenAIRE

    Stahn, Roland

    2010-01-01

    In dieser Dissertation wird ein neues System zur modellbasierten Merkmalsplanung für die objektbezogene laserscannerbasierte Navigation von Fahrzeugen vorgestellt. Die robuste Orientierung und Bewegung in natürlichen Umgebungen ist eine zentrale Problemstellung der mobilen Robotik. Die präzise Navigation relativ zu Objekten der Umgebung bildet ein Teilgebiet, welches speziell für die Realisierung von zukünftigen Assistenz- und Autonomiefunktionen bei Fahrzeugen, fahrerlosen Transportsystemen ...

  19. Untersuchungen zum enzymatisch-physikalischen Aufschluss von Apfeltrester

    OpenAIRE

    Schalow,Sebastian

    2009-01-01

    Apfeltrester fallen in großen Mengen als Reststoffe bei der industriellen Fruchtsaftproduktion an. Neben der Pektinherstellung können Apfeltrester u. a. für die Alkoholerzeugung genutzt werden. Im Gegensatz zur Produktion von technischem Alkohol werden bei der Trinkalkoholherstellung jedoch höhere Anforderungen an die chemische Zusammensetzung und die sensorischen Eigenschaften der erzeugten Destillate gestellt. Apfeltrester besitzen eine Trockensubstanz von ca. 25 %, die sich zum größten Tei...

  20. Geschlechterstereotype - Qualifikationsbarrieren von Frauen in der Fußballtrainerausbildung?

    OpenAIRE

    Weigelt-Schlesinger, Yvonne

    2007-01-01

    Eines der letzten fast vollständig männlichen dominierten Reservoirs des Sports ist der Trainerbereich. Vor dem Hintergrund dieser Einsicht setzt sich die Arbeit mit der Frage auseinander, weshalb Frauen erst gar keine Ausbildung zur Trainerin beginnen oder die begonnene Ausbildung wieder abbrechen. Dabei interessiert insbesondere die Bedeutung von Geschlechtsstereotypen bei der Ausgrenzung von Frauen aus oder der Benachteiligung während der Trainerausbildung. So fragt die Autorin danach,...

  1. Identifizierung und Charakterisierung eines Sdr-Proteins von Staphylococcus saprophyticus

    OpenAIRE

    Sakinç, Türkân

    2001-01-01

    Gegenstand der vorliegenden Arbeit war es, das Oberflächenprotein Ssp zu klonieren und zu charakterisieren. Stattdessen wurde ein neues Zellwand-assoziertes Protein, das SdrI, ein MSCRAMM, kloniert. Dies sollte zur Klärung der Uropathogenität von Staphylococcus saprophyticus weiterhelfen. Die Voraussetzungen zur Untersuchung der Funktion des SdrI Protein von Staphylococcus saprophyticus wurde durch die Konstruktion einer isogenen Mutante geschaffen. Die Bedeutung der SdrI-Protein ...

  2. Politische Bildung im Kontext von Regierung, Unterricht und Zucht

    Directory of Open Access Journals (Sweden)

    Thomas Rucker

    2014-02-01

    Full Text Available Johann Friedrich Herbart (1776-1841 gilt als der Begründer der wissenschaftlichen Pädagogik. In diesem Beitrag wird zu zeigen versucht, dass Herbart die Unterstützung politischer Bildung als eine Aufgabe von Regierung, Unterricht und Zucht bestimmt und in seinem Werk wichtige „Bausteine“ für eine Theorie der politischen Bildung unter den Bedingungen von Erziehung vorlegt hat. Nach Herbart ist das politische Selbst- und Weltverhältnis auf Sachverhalte bezogen, die nicht nur die Lebensführung einzelner Menschen, sondern die Lebensführung einer Mehrzahl von Menschen betreffen. Nicht das Zusammenleben von Menschen generell ist jedoch Orientierungsgesichtspunkt des politischen Selbst- und Weltverhältnisses, sondern nur das problematisch gewordene Zusammenleben. Politik ergibt sich nach Herbart aus einem Konflikt hinsichtlich der Frage, wie das Zusammenleben von Menschen geregelt sein sollte. Während die Regierung lediglich mittelbar einen Beitrag zur politischen Bildung leistet, indem sie die Voraussetzungen für Unterricht und Zucht bereitstellt, fungieren die beiden zuletzt genannten Formen von Erziehung als die eigentlichen Medien, in denen die politische Bildung im Sinne Herbarts ihren Ort hat.

  3. Prophylaxis escalation in severe von Willebrand disease: A prospective study from the von Willebrand Disease Prophylaxis Network

    NARCIS (Netherlands)

    T.C. Abshire (Thomas Calvin); J. Cox-Gill; C.L. Kempton; F.W.G. Leebeek (Frank); M. Carcao (M.); P. Kouides (P.); S. Donfield (S.); E. Berntorp

    2015-01-01

    textabstractBackground: Treatment of mucosal bleeding (epistaxis, gastrointestinal bleeding, and menorrhagia) and joint bleeding remains problematic in clinically severe von Willebrand disease (VWD). Patients are often unresponsive to treatment (e.g. desmopressin or antifibrinolytic therapy) and may

  4. Electronic Resource Management System. Vernetzung von Lizenzinformationen

    Directory of Open Access Journals (Sweden)

    Michaela Selbach

    2014-12-01

    Full Text Available In den letzten zehn Jahren spielen elektronische Ressourcen im Bereich der Erwerbung eine zunehmend wichtige Rolle: Eindeutig lässt sich hier ein Wandel in den Bibliotheken (fort vom reinen Printbestand zu immer größeren E-Only-Beständen feststellen. Die stetig wachsende Menge an E-Ressourcen und deren Heterogenität stellt Bibliotheken vor die Herausforderung, die E-Ressourcen effizient zu verwalten. Nicht nur Bibliotheken, sondern auch verhandlungsführende Institutionen von Konsortial- und Allianzlizenzen benötigen ein geeignetes Instrument zur Verwaltung von Lizenzinformationen, welches den komplexen Anforderungen moderner E-Ressourcen gerecht wird. Die Deutsche Forschungsgemeinschaft (DFG unterstützt ein Projekt des Hochschulbibliothekszentrums des Landes Nordrhein-Westfalen (hbz, der Universitätsbibliothek Freiburg, der Verbundzentrale des Gemeinsamen Bibliotheksverbundes (GBV und der Universitätsbibliothek Frankfurt, in dem ein bundesweit verfügbares Electronic Ressource Managementsystem (ERMS aufgebaut werden soll. Ein solches ERMS soll auf Basis einer zentralen Knowledge Base eine einheitliche Nutzung von Daten zur Lizenzverwaltung elektronischer Ressourcen auf lokaler, regionaler und nationaler Ebene ermöglichen. Statistische Auswertungen, Rechteverwaltung für alle angeschlossenen Bibliotheken, kooperative Datenpflege sowie ein über standardisierte Schnittstellen geführter Datenaustausch stehen bei der Erarbeitung der Anforderungen ebenso im Fokus wie die Entwicklung eines Daten- und Funktionsmodells. In the last few years the importance of electronic resources in library acquisitions has increased significantly. There has been a shift from mere print holdings to both e- and print combinations and even e-only subscriptions. This shift poses a double challenge for libraries: On the one hand they have to provide their e-resource collections to library users in an appealing way, on the other hand they have to manage these

  5. Descriptors for antimicrobial peptides

    DEFF Research Database (Denmark)

    Jenssen, Håvard

    2011-01-01

    Introduction: A frightening increase in the number of isolated multidrug resistant bacterial strains linked to the decline in novel antimicrobial drugs entering the market is a great cause for concern. Cationic antimicrobial peptides (AMPs) have lately been introduced as a potential new class...... examples of different peptide QSAR studies, this review highlights some of the missing links and illuminates some of the questions that would be interesting to challenge in a more systematic fashion. Expert opinion: Computer-aided peptide QSAR using molecular descriptors may provide the necessary edge...

  6. Entwicklung von molekularen Sonden für die sichere Identifizierung von Hefen der Gattungen Brettanomyces, Dekkera

    OpenAIRE

    Röder, Christoph

    2007-01-01

    Hefen der Gattungen Brettanomyces/Dekkera sind in der Produktion von fermentierten Getränken, insbesondere in der Bier-, Sekt- und Weinherstellung bekannt. Sie können als Schädlingshefen insbesondere durch die Bildung von charakteristischen Sekundärmetaboliten zu einer negativen geschmacklichen Veränderung des Getränks führen. Aufgrund ihres langsamen Wachstums werden diese Hefen bei Routineanalysen mit konventionellen Kultivierungsmethoden leicht übersehen. Ein schneller und eindeutiger N...

  7. Von Roll RCP method - first experiences; Von Roll RCP - Verfahren. Erste Erfahrungen

    Energy Technology Data Exchange (ETDEWEB)

    Capitaine, P.; Engweiler, J. [Roll Umwelttechnik AG, Zuerich (Switzerland)

    1998-09-01

    The RCP method was designed as a residue-optimised alternative to the thermally optimised grate firing of residual wastes. Its technical realisation and development to market maturity took no more than 5 years. In the first process stage the waste is converted to high-carbon pyrolysis charcoal and high-rank gas in the absence of oxygen. In the second stage these substances are oxidised by addition of oxygen. The resulting temperature causes the non-combustible constituents of the slag to melt. In a third, optional, stage this molten slag can be liberated of (heavy) metals to such an extent that it can subsequently be used directly as additive for grinding. Further exhaust gas treatment is facilitated by the use of a circulatory fluidised-bed secondary combustion chamber. Despite the reduced flue gas volume and resultant higher pollutant concentrations in the crude gas, overall emissions are lower than in conventional plants. [Deutsch] Das reststoffoptimierte RCP Verfahren ist als Alternative zur thermisch optimierten Rostverbrennung von Restabfaellen konzipiert. In nur fuenf Jahren wurde das Verfahren technisch umgesetzt und zur Marktreife entwickelt. In einer ersten Stufe des Verfahrens wird der Abfall unter Luftabschluss in einen kohlenstoffreichen Pyrolysekoks und eine heizwertreiches Gas umgesetzt. Im zweiten Schritt werden diese Stoffe unter Zugabe von Sauerstoff oxidiert. Dabei treten Temperaturen auf, bei denen die nichtbrennbaren Bestandteile der Schlacke schmelzen. Optional wird diese Schmelzschlacke in einem dritten Schritt derart von (Schwer-) Metallen befreit, dass sie anschliessend direkt als Zement-Zumahlstoff eingesetzt werden kann. Die Nutzung der zirkulierenden Wirbelschicht - Nachbrennkammer zur Abgasbehandlung vereinfacht die weitergehende Abgasbehandlung. Trotz verringertem Rauchgasvolumen und damit hoeheren Schadstoffkonzentrationen im Rohgas werden die Gesamtemissionen gegenueber konventionellen Anlagen verringert. (orig./SR)

  8. Nachhaltigkeit von E-Learning-Innovationen: Von der Pionierphase zur nachhaltigen Implementierung

    Directory of Open Access Journals (Sweden)

    Sabine Seufert

    2003-11-01

    Full Text Available In den letzten Jahren wurden an den meisten Hochschulen im In- und Ausland E-Learning-Projekte in die Wege geleitet. Nach den Projekt- und Impulsprogrammen folgen die Konsolidierungsphasen. Schon während der Projektphasen zeigen sich Problemgruppen, die darauf verweisen, dass E-Learning nicht «nur» eine Angelegenheit der Pädagogik und Didaktik ist. Der erste Teil des Aufsatzes benennt einzelne dieser Problemfelder. Der zweite Teil zeigt auf, dass E-Learning die Hochschulen als Ganzes betrifft, und unterbreitet ein Rahmenkonzept, in dem gezeigt wird, wie die benannten Probleme bei der Implementierung von E-Learning vermieden werden können.

  9. Diskriminierung in der 'longue durée' : von der Notwendigkeit der Kontextualisierung von Strukturproblemen

    OpenAIRE

    2006-01-01

    "Diskriminierung auf der Grundlage von Rasse, Ethnie, Geschlecht, Herkunft, körperlicher Verfassung oder Bildungsniveau ist ein Kennzeichen der westlichen Moderne. Das für moderne Nationalstaaten charakteristische Gewaltmonopol übte nicht nur eine Schutzfunktion in Bezug auf das Leben und Eigentum der Staatsbürger aus, sondern verfügte darüber hinaus über die Definitionsmacht, die Kriterien der Zugehörigkeit zur nationalen Gemeinschaft festlegte und dabei Gewalt gegenüber Nicht-Staatsbürgern ...

  10. Entstehungsbedingungen von Übergängen von der Schule in den Beruf aus qualitativer und quantitativer Perspektive

    Directory of Open Access Journals (Sweden)

    Nora Gaupp

    2013-03-01

    Full Text Available Methodenintegration wird in den Sozialwissenschaften mit dem Argument sich ergänzender Erkenntnismöglichkeiten häufig gefordert. Die vorliegende Analyse zu Übergangswegen von der Schule in Ausbildung und Arbeit von Jugendlichen mit Hauptschulbildung beruht auf Daten einer quantitativen Panelstudie und einer qualitativen Ergänzungsstudie. Aus quantitativer und qualitativer Perspektive wird jeweils ein Einzelfall betrachtet sowie im Rahmen einer Modellbildung eine Verallgemeinerung auf Aggregatebene vorgenommen. Über ein logistisches Regressionsmodell wird die Bedeutung von zentralen individuellen, sozialen und strukturellen Merkmalen wie Schulleistungen, beruflichen Plänen, individuellen Problembelastungen, Migrationshintergrund und Arbeitslosigkeit der Eltern sowie regionaler Arbeitsmarktsituation für den Verlauf von Übergangswegen (Direkteinstieg in Ausbildung, Umweg in Ausbildung über schulische oder berufsvorbereitende Zwischenschritte, fortgesetzter mehrjähriger Schulbesuch und prekäre Wege in Ausbildungslosigkeit untersucht. Über das qualitative Paradigma konnten vier für den Verlauf von Übergängen zentrale Dimensionen identifiziert werden: Agency, Motivation, kritische biografische Ereignisse und soziale Interaktionen. Der Schritt der Modellbildung integriert die vier Erfahrungsebenen und zeigt ihre Bedeutung für Übergänge von der Schule in den Beruf. Die Diskussion fragt nach Möglichkeiten und Grenzen der Erkenntnisentwicklung der beiden Forschungszugänge. URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs1302126

  11. Diversity-oriented peptide stapling

    DEFF Research Database (Denmark)

    Tran, Thu Phuong; Larsen, Christian Ørnbøl; Røndbjerg, Tobias

    2017-01-01

    as a powerful method for peptide stapling. However, to date CuAAC stapling has not provided a simple method for obtaining peptides that are easily diversified further. In the present study, we report a new diversity-oriented peptide stapling (DOPS) methodology based on CuAAC chemistry. Stapling of peptides...

  12. Anti-antimicrobial Peptides

    Science.gov (United States)

    Ryan, Lloyd; Lamarre, Baptiste; Diu, Ting; Ravi, Jascindra; Judge, Peter J.; Temple, Adam; Carr, Matthew; Cerasoli, Eleonora; Su, Bo; Jenkinson, Howard F.; Martyna, Glenn; Crain, Jason; Watts, Anthony; Ryadnov, Maxim G.

    2013-01-01

    Antimicrobial or host defense peptides are innate immune regulators found in all multicellular organisms. Many of them fold into membrane-bound α-helices and function by causing cell wall disruption in microorganisms. Herein we probe the possibility and functional implications of antimicrobial antagonism mediated by complementary coiled-coil interactions between antimicrobial peptides and de novo designed antagonists: anti-antimicrobial peptides. Using sequences from native helical families such as cathelicidins, cecropins, and magainins we demonstrate that designed antagonists can co-fold with antimicrobial peptides into functionally inert helical oligomers. The properties and function of the resulting assemblies were studied in solution, membrane environments, and in bacterial culture by a combination of chiroptical and solid-state NMR spectroscopies, microscopy, bioassays, and molecular dynamics simulations. The findings offer a molecular rationale for anti-antimicrobial responses with potential implications for antimicrobial resistance. PMID:23737519

  13. Tumor penetrating peptides

    Directory of Open Access Journals (Sweden)

    Tambet eTeesalu

    2013-08-01

    Full Text Available Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC, contains the integrin-binding RGD motif. RGD mediates tumor homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular zip code of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is

  14. Richard von Volkmann: surgeon and Renaissance man.

    Science.gov (United States)

    Willy, Christian; Schneider, Peter; Engelhardt, Michael; Hargens, Alan R; Mubarak, Scott J

    2008-02-01

    Richard von Volkmann (1830-1889), one of the most important surgeons of the 19(th) century, is regarded as one of the fathers of orthopaedic surgery. He was a contemporary of Langenbeck, Esmarch, Lister, Billroth, Kocher, and Trendelenburg. He was head of the Department of Surgery at the University of Halle, Germany (1867-1889). His popularity attracted doctors and patients from all over the world. He was the lead physician for the German military during two wars. From this experience, he compared the mortality of civilian and war injuries and investigated the general poor hygienic conditions in civilian hospitals. This led him to introduce the "antiseptic technique" to Germany that was developed by Lister. His powers of observation and creativity led him to findings and achievements that to this day bear his name: Volkmann's contracture and the Hueter-Volkmann law. Additionally, he was a gifted writer; he published not only scientific literature but also books of children's fairy tales and poems under the pen name of Richard Leander, assuring him a permanent place in the world of literature as well as orthopaedics.

  15. Geschichte der Natur bei Alexander von Humboldt

    Directory of Open Access Journals (Sweden)

    Christian Helmreich

    2009-05-01

    Full Text Available Article in German, Abstracts in English, German and French.This article analyses the importance of an historical view of nature in the works of Alexander von Humboldt. In several of his first writings, Humboldt seems to outline the importance of what one may call history of nature. But even before his famous American travel, his position changed and he became reluctant to accept the seriousness of historical enquiry in the area of natural sciences: if we want to reconstruct the past state of nature, we cannot rely on empirical proofs; and history of nature is therefore necessarily based on uncertain hypotheses. Humboldt kept his sceptical attitude in the first decades of the 19th century, despite the positive results of the palaeontological researches of his scientific colleagues. However, he gradually convinced himself of the scientific interest of historical investigations in the natural sciences. The Cosmos paradoxally displays two apparently conflicting points of view: in his methodological remarks, Humboldt maintains that precise accounts of the past state of nature are out of reach of human knowledge, yet elsewhere in the same Cosmos he gives broad and rather vivid descriptions of the eventful history of nature.

  16. Modellbasierte Steuerung, Regelung und Diagnose von Brennstoffzellenantrieben

    Science.gov (United States)

    Bußhardt, Joachim; Baaser, Bernhard; Formanski, Volker; Schäfer, Sascha; Sinsel, Stefan

    Steigende Bevölkerungszahlen und damit zunehmender Energiebedarf stellen eine große Herausforderung für Menschheit und Umwelt dar. Mit steigendem Wohlstand ist auch ein stärkeres Bedürfnis nach Mobilität und damit ein höherer Energieverbrauch verbunden. Die derzeitigen enormen Steigerungen des Bruttoinlandsproduktes in China und Indien - zwei Ländern, die zusammen mehr als ein Drittel der Weltbevölkerung stellen - lassen auch zukünftig ungebrochene Steigerungen des Weltenergieverbrauches erwarten. Dies gilt für alle Bereiche, besonders aber für den Verkehrssektor. Letzterer stellt mit seinem signifikanten Anteil am Energieverbrauch sowie den damit einhergehenden Emissionen und seinem hohen Wachstumspotenzial ein besonderes Handlungsfeld dar. Insbesondere wegen der in diesem Sektor zu erwartenden ansteigenden CO2-Emissionen stehen Effizienzverbesserungen und die Entwicklung alternativer Antriebe im Vordergrund. Dabei spielt die Brennstoffzelle als Fahrzeugantrieb eine entscheidende Rolle, da sie einen hohen Systemwirkungsgrad mit fehlenden CO2- und Schadstoffemissionen verbindet. Wegen der hohen Komplexität sind dabei moderne Steuerungs-, Regelungs- und Diagnoseverfahren von besonderer Bedeutung, auf die in diesem Beitrag näher eingegangen wird. Neben einigen grundlegenden Konzepten wird an Hand zweier Beispiele das Potenzial modellgestützter Methoden aufgezeigt.

  17. Zur Struktur und Funktion von Synonymen

    Directory of Open Access Journals (Sweden)

    Marina Zorman

    1998-12-01

    Full Text Available Der Artikel behandelt die Synonyme im Licht der funktionell-strukturellen Sprachtheorie Coserius. 1 Die Wahl der theoretischen Grundsätze wurde durch die Festellung diktiert, daß die bisherigen Erkenntnisse über die Synonymie widersprüchlich sind und daß auch schon über alle Feststellungen berechtigte Einsprüche erhoben wurden. Deshalb wird in dieser Arbeit auf der genannten theoretischen Grundlage, die verschiedene Gesichtspunkte des Problems verbindet, anstatt sie zu trennen (s. Punkt 2, ein Modell für die Analyse von Synonymen vorgestellt (3, das die klassischen Schwächen der Semantikforschung (zu geringe Menge tatsächlicher Daten, Subjektivität und Introspektion durch eine empirische Untersuchung in einem Textkorpus zu ersetzen versucht. In die Analyse sind drei Inhaltsebenen einbezogen (Bezeichnung, Bedeutung und Sinn und ihnen sind jeweils entsprechende Untersuchungsmethoden zugeordnet. Im Sinne des Modells wurden in der Arbeit Zorman 1997 zwei slowenische Synonympaare (kuverta - ovojnica und borba - boj analysiert, die als Beispiele reiner (und totaler Synonymie gelten können. Die Analyse wird aus Platzgründen an dieser Stelle nicht detailliert dargestellt,2 veranschaulicht werden nur ihre Tragweite und die Ergebnisse (4. Im letzten Teil (5 werden die Leistungen der vorgeschlagenen Methode bewertet und einige Annahmen dargestellt, die der weiteren Erforschung der Synonyme dienen könnten. Die objektive Behandlung der Synonymie unter unterschiedlichen Gesichtspunkten scheint einige Dogmen über Synonyme in Frage zu  stellen.

  18. Antimicrobial Peptides in Echinoderms

    OpenAIRE

    Li, C; Haug, T; K Stensvåg

    2010-01-01

    Antimicrobial peptides (AMPs) are important immune effector molecules for invertebrates, including echinoderms, which lack a vertebrate-type adaptive immune system. Here we summarize the knowledge of such peptides in echinoderms. Strongylocins are a novel family of cysteine-rich AMPs, recently identified in the sea urchins, Strongylocentrotus droebachiensis and S. purpuratus. Although these molecules present diverse amino acid sequences, they share an identical cysteine arrangement pattern, d...

  19. Immunotherapy with Allergen Peptides

    OpenAIRE

    Larché Mark

    2007-01-01

    Specific allergen immunotherapy (SIT) is disease-modifying and efficacious. However, the use of whole allergen preparations is associated with frequent allergic adverse events during treatment. Many novel approaches are being designed to reduce the allergenicity of immunotherapy preparations whilst maintaining immunogenicity. One approach is the use of short synthetic peptides which representing dominant T cell epitopes of the allergen. Short peptides exhibit markedly reduced capacity to cro...

  20. Eine Frau in der Kultur, die Kultur einer Frau: Caroline von Humboldt. A woman in the culture, the culture of a woman: Caroline von Humboldt

    Directory of Open Access Journals (Sweden)

    Elžbieta M. Kowalska

    2008-01-01

    Full Text Available The subject of this presentation is Wilhelm von Humboldt’s wife, Alexander von Humboldt’s sisterin-law, a close female friend of Lotte Schiller and of her sister, Caroline von Wolzogen, held in high regard by Goethe, admired by Schiller, the former Fräulein von Dacheröden from Erfurt, the future Caroline von Humboldt. She was the ancestress of one of the most respected and best German noble families, a mother of eight children, an intellectually gifted woman, in which the German ideals of femininity were fulfilled, who knew to lead the salons and to talk about arts and literature.

  1. [Determination of von Willebrand factor multimers in Mexican population].

    Science.gov (United States)

    Hernández-Zamora, Edgar; Zavala-Hernández, Cesar; Viveros-Sandoval, Martha Eva; Ochoa-Rico, Angeles; Martínez-Murillo, Carlos; Reyes-Maldonado, Elba

    2014-01-01

    Antecedentes: la enfermedad de von Willebrand es un padecimiento hereditario en el que la estructura, función y concentración del factor de von Willebrand están alteradas y, en consecuencia, también la interacción plaqueta-factor de von Willebrand-endotelio. En México no hay registros epidemiológicos de la enfermedad, sólo se han efectuado algunos estudios aislados desde el punto de vista clínico y hematológico. Material y métodos: estudio retrospectivo efectuado en 155 mexicanos mestizos, 75 de ellos con diagnóstico presuntivo de enfermedad de von Willebrand, 15 con sospecha de hemofilia A y 65 donadores sanos (testigos). Se realizaron pruebas: básicas de coagulación, especiales y de clasificación: análisis de la composición multimérica. Resultados: 15 pacientes se diagnosticaron con hemofilia A; de los 75 sujetos con sospecha de enfermedad de von Willebrand se diagnosticaron 50 de la manera siguiente: tipo 1 (62%), tipo 2 (22%) [subtipos: 2A (14%), 2B (2%) y 2N (6%)] y tipo 3 (16%). Conclusión: el análisis de los multímeros del factor de von Willebrand es un método que cumple con las características adecuadas para el diagnóstico de la enfermedad de von Willebrand, por lo que es necesario implementar esta metodología para su estudio y mejorar su diagnóstico específico.

  2. Locally Compact Quantum Groups. A von Neumann Algebra Approach

    Science.gov (United States)

    Van Daele, Alfons

    2014-08-01

    In this paper, we give an alternative approach to the theory of locally compact quantum groups, as developed by Kustermans and Vaes. We start with a von Neumann algebra and a comultiplication on this von Neumann algebra. We assume that there exist faithful left and right Haar weights. Then we develop the theory within this von Neumann algebra setting. In [Math. Scand. 92 (2003), 68-92] locally compact quantum groups are also studied in the von Neumann algebraic context. This approach is independent of the original C^*-algebraic approach in the sense that the earlier results are not used. However, this paper is not really independent because for many proofs, the reader is referred to the original paper where the C^*-version is developed. In this paper, we give a completely self-contained approach. Moreover, at various points, we do things differently. We have a different treatment of the antipode. It is similar to the original treatment in [Ann. Sci. & #201;cole Norm. Sup. (4) 33 (2000), 837-934]. But together with the fact that we work in the von Neumann algebra framework, it allows us to use an idea from [Rev. Roumaine Math. Pures Appl. 21 (1976), 1411-1449] to obtain the uniqueness of the Haar weights in an early stage. We take advantage of this fact when deriving the other main results in the theory. We also give a slightly different approach to duality. Finally, we collect, in a systematic way, several important formulas. In an appendix, we indicate very briefly how the C^*-approach and the von Neumann algebra approach eventually yield the same objects. The passage from the von Neumann algebra setting to the C^*-algebra setting is more or less standard. For the other direction, we use a new method. It is based on the observation that the Haar weights on the C^*-algebra extend to weights on the double dual with central support and that all these supports are the same. Of course, we get the von Neumann algebra by cutting down the double dual with this unique

  3. Natriuretic Peptides, Diagnostic and Prognostic Biomarkers

    NARCIS (Netherlands)

    J.H.W. Rutten (Joost)

    2010-01-01

    textabstractIn humans, the natriuretic peptide family consists of three different types of peptides: atrial natriuretic peptide (synonym: atrial natriuretic factor), B-type natriuretic peptide (synonym: brain natriuretic peptide) and C-natriuretic peptide.1 Atrial natriuretic peptide (ANP) was the f

  4. Entwicklungsperspektiven von Social Software und dem Web 2.0

    Science.gov (United States)

    Raabe, Alexander

    Der Artikel beschäftigt sich zunächst mit dem derzeitigen und zukünftigen Einsatz von Social Software in Unternehmen. Nach dem großen Erfolg von Social Software im Web beginnen viele Unternehmen eigene Social Software-Initiativen zu entwickeln. Der Artikel zeigt die derzeit wahrgenommenen Einsatzmöglichkeiten von Social Software im Unternehmen auf, erörtert Erfolgsfaktoren für die Einführung und präsentiert mögliche Wege für die Zukunft. Nach der Diskussion des Spezialfalles Social Software in Unternehmen werden anschließend die globalen Trends und Zukunftsperspektiven des Web 2.0 in ihren technischen, wirtschaftlichen und sozialen Dimensionen dargestellt. Wie aus den besprochenen Haupttrends hervorgeht, wird die Masse an digital im Web verfügbaren Informationen stetig weiterwachsen. So stellt sich die Frage, wie es in Zukunft möglich sein wird, die Qualität der Informationssuche und der Wissensgenerierung zu verbessern. Mit dem Einsatz von semantischen Technologien im Web wird hier eine revolutionäre Möglichkeit geboten, Informationen zu filtern und intelligente, gewissermaßen verstehende" Anwendungen zu entwerfen. Auf dem Weg zu einem intelligenten Web werden sich das Semantic Web und Social Software annähern: Anwendungen wie Semantic Wikis, Semantic Weblogs, lightweight Semantic Web-Sprachen wie Microformats oder auch kommerzielle Angebote wie Freebase von Metaweb werden die ersten Vorzeichen einer dritten Generation des Webs sein.

  5. Acquired von Willebrand syndrome: A rare disorder of heterogeneous etiology

    Directory of Open Access Journals (Sweden)

    P Kasatkar

    2013-01-01

    Full Text Available Context: Acquired von Willebrand syndrome (AVWS is a rare bleeding disorder that mimics the inherited form of von Willebrand disease (VWD in terms of laboratory findings and clinical presentation. Aims: To study the etiology of acquired VWD. Settings and Design: The patients referred from various hospitals in and out of Mumbai were included in the study. Materials and Methods: Six patients with AVWS diagnosed at this center over the last 10 years were analyzed against 171 patients with inherited VWD. The differential diagnosis of AVWS was made based on reduced levels of von Willebrand antigen and von Willebrand ristocetin cofactor, decrease in ristocetin induced platelet aggregation, absence of correction in mixing studies with no prior history of bleeding problems and a negative family history for bleeding disorders. Results: In three patients, the disease was associated with systematic lupus erythematosus, out of which one was also associated with Kikuchi lymphadenitis and second with autoimmune hemolytic anemia. Fourth case was associated with hypothyroidism and fifth was a case of dermatitis and vitiligo. The last patient was a case of hemophilia A with Burkitts lymphoma, who developed autoantibodies to von Willebrand factor. Except two patients, all other patients responded to immune suppressive therapy with corticosteroids, while the patient with hypothyroidism responded to oral thyroxine. Conclusion: AVWS is a rare condition and may often be missed or diagnosed as inherited disease associated with heterogeneous disease conditions.

  6. Natriuretic Peptides, Diagnostic and Prognostic Biomarkers

    OpenAIRE

    Rutten, Joost

    2010-01-01

    textabstractIn humans, the natriuretic peptide family consists of three different types of peptides: atrial natriuretic peptide (synonym: atrial natriuretic factor), B-type natriuretic peptide (synonym: brain natriuretic peptide) and C-natriuretic peptide.1 Atrial natriuretic peptide (ANP) was the fi rst natriuretic peptide to be discovered and in humans ANP is predominantly formed in the cardiomyocytes of the atria.2 B-type natriuretic peptide (BNP) was fi rst discovered in porcine brain hen...

  7. Electron transfer in peptides.

    Science.gov (United States)

    Shah, Afzal; Adhikari, Bimalendu; Martic, Sanela; Munir, Azeema; Shahzad, Suniya; Ahmad, Khurshid; Kraatz, Heinz-Bernhard

    2015-02-21

    In this review, we discuss the factors that influence electron transfer in peptides. We summarize experimental results from solution and surface studies and highlight the ongoing debate on the mechanistic aspects of this fundamental reaction. Here, we provide a balanced approach that remains unbiased and does not favor one mechanistic view over another. Support for a putative hopping mechanism in which an electron transfers in a stepwise manner is contrasted with experimental results that support electron tunneling or even some form of ballistic transfer or a pathway transfer for an electron between donor and acceptor sites. In some cases, experimental evidence suggests that a change in the electron transfer mechanism occurs as a result of donor-acceptor separation. However, this common understanding of the switch between tunneling and hopping as a function of chain length is not sufficient for explaining electron transfer in peptides. Apart from chain length, several other factors such as the extent of the secondary structure, backbone conformation, dipole orientation, the presence of special amino acids, hydrogen bonding, and the dynamic properties of a peptide also influence the rate and mode of electron transfer in peptides. Electron transfer plays a key role in physical, chemical and biological systems, so its control is a fundamental task in bioelectrochemical systems, the design of peptide based sensors and molecular junctions. Therefore, this topic is at the heart of a number of biological and technological processes and thus remains of vital interest.

  8. Proof of pipeline strength based on measurements of inspection pigs; Festigkeitsnachweis von Pipelines aufgrund der Messergebnisse von Pruefmolchen

    Energy Technology Data Exchange (ETDEWEB)

    De la Camp, H.J.; Feser, G.; Hofmann, A.; Wolf, B.; Schmidt, H. [TUeV Sueddeutschland Bau und Betrieb GmbH, Muenchen (Germany); Herforth, H.E.; Juengling, K.H.; Schmidt, W. [TUeV Anlagentechnik GmbH, Berlin-Schoeneberg (Germany). Unternehmensgruppe TUeV Rheinland/Berlin-Brandenburg

    2002-01-01

    The report is aimed at collecting and documenting the state of the art and the extensive know how of experts and pipeline operators with regard to judging the structural integrity of pipelines. In order to assess the actual mechanical strength of pipelines based on measurement results obtained by inspection pigs, guidance is given for future processing, which eventually can be used as a basis for an industry standard. A literature study of the commercially available types of inspection pigs describes and synoptically lists the respective pros and cons. In essence the report comprises besides check lists of operating data for the pipeline and the pig runs mainly the evaluation of defects and respective calculating procedures. Included are recommendations regarding maintenance planning, verification of defects as well as repetition of pig runs. (orig.) [German] Ziel des Berichtes ist die Erfassung und Dokumentation zum derzeitigen Stand der Technik und des vorhandenen umfangreichen Know-how von Sachverstaendigen und Pipelinebetreibern auf dem Gebiet der sicherheitstechnischen Beurteilung von Pipelines. Fuer den Festigkeitsnachweis von Pipelines aufgrund der Messergebnisse von Pruefmolchen wurde ein Leitfaden als Basis fuer die zukuenftige Vorgehensweise erstellt, der eventuell die Grundlage eines normativen Regelwerkes bilden kann. In einer Literaturstudie wurden die auf dem Markt befindlichen Pruefmolchtypen zusammenfassend beschrieben und ihre Vor- und Nachteile tabellarisch gegenuebergestellt und bewertet. Neben der Erstellung von Checklisten fuer notwendige Daten zum Betrieb der Pipeline und der Molchlaeufe bildet die Fehlerbewertung mit entsprechenden Berechnungsverfahren den Hauptteil dieses Berichtes. Hinweise zur Instandhaltungsplanung (Fehlerverifikation und Molchlaufwiederholung) werden gegeben. (orig.)

  9. Applikation von fermentierter Soja bei Krebspatienten zur Verminderung von Kachexie und Erhöhung der Apoptose - eine prospektive Pilotstudie

    Directory of Open Access Journals (Sweden)

    Jacob U

    2009-01-01

    Full Text Available Kachexie ist eine Begleiterkrankung von Krebs, Aids oder rheumatoider Arthritis. Andere Symptome dieser Erkrankungen sind Depression sowie chronische Erschöpfung. Für alle diese Begleiterkrankungen, die die Lebensqualität der schwererkrankten Patienten negativ beeinflussen, wird eine Erhöhung von Entzündungsmediatoren (z.B. IL-6 und TNF-α verantwortlich gemacht. Für Krebs wird eine Erniedrigung der Apoptose, ausgelöst durch eine Erhöhung von NFκB verantwortlich gemacht. Eine Gabe eines fermentierten Soja-Produktes, das in den USA seit 10 Jahren zur Verbesserung der Lebensqualität von Krebspatienten eingesetzt wird, wurde in einer prospektiven Studie untersucht: Für je 5 Patienten, die unter Prostata-, Ovar- oder Brustkrebs litten, konnte eine signifikante Verminderung von Kachexie, Stress und Depression festgestellt werden. Gleichzeitig konnte man für Prostata- und Ovarkrebs-Patienten eine Erhöhung der Genexpression apoptotischer Marker disseminierter Tumorzellen feststellen. Zusätzlich wurde eine starke Erhöhung der Genexpression des Tumorsuppressorgens p21 festgestellt. Auch wenn die prospektive Studie präliminär ist und die Anzahl der untersuchten Patienten zu klein, so widerspricht sie nicht unserer Annahme, dass es einen direkten Zusammenhang zwischen Krebs und Begleiterkrankungen, besonders der Kachexie, gibt.

  10. Asymptotic structure of free product von Neumann algebras

    Science.gov (United States)

    Houdayer, Cyril; Ueda, Yoshimichi

    2016-11-01

    Let $(M, \\varphi) = (M_1, \\varphi_1) \\ast (M_2, \\varphi_2)$ be the free product of any $\\sigma$-finite von Neumann algebras endowed with any faithful normal states. We show that whenever $Q \\subset M$ is a von Neumann subalgebra with separable predual such that both $Q$ and $Q \\cap M_1$ are the ranges of faithful normal conditional expectations and such that both the intersection $Q \\cap M_1$ and the central sequence algebra $Q' \\cap M^\\omega$ are diffuse (e.g. $Q$ is amenable), then $Q$ must sit inside $M_1$. This result generalizes the previous results of the first named author in [Ho14] and moreover completely settles the questions of maximal amenability and maximal property Gamma of the inclusion $M_1 \\subset M$ in arbitrary free product von Neumann algebras.

  11. Renaturierung von subalpinen und alpinen Ökosystemen

    Science.gov (United States)

    Krautzer, B.; Klug, Brigitte

    Die große Vielfalt an alpinen und subalpinen Ökosystemen auf waldfreien Standorten stellt besonders hohe Anforderungen an Planung und Durchführung von Renaturierungsmaßnahmen. Zunehmende Meereshöhe, starke Hangneigungen und extreme klimatische Verhältnisse im Gebirge bedingen zudem seit jeher natürliche Erosionsprozesse. Die zahllosen menschlichen Aktivitäten der letzten Jahrzehnte, gepaart mit unzureichenden Begrünungsmaßnahmen, erhöhen dieses Risiko noch um ein Vielfaches: Geländekorrekturen im Zuge von Skipistenbauten, Almrevitalisierungen, Forst- und Almwegebauten, Maßnahmen zur Verbesserung der touristischen Infrastruktur oder Wildbach- und Lawinenverbauungen. Nur durch Verwendung von hochwertigem, dem Standort angepasstem Pflanzen-oder Saatgutmaterial in Kombination mit der passenden Begrünungstechnik kann dieser Bedrohung dauerhaft entgegengewirkt werden. Dabei sind folgende limitierende Faktoren besonders zu beachten.

  12. Zur Relevanz von sozialer Ungleichheit im Kontext der Mediensozialisationsforschung

    Directory of Open Access Journals (Sweden)

    Ingrid Paus-Hasebrink

    2009-05-01

    Full Text Available Ziel des vorliegenden Beitrags ist es, deutlich zu machen, dass Mediensozialisations­forschung nicht ohne den Blick auf die Lebenswelt Heranwachsender auskommen kann; diese wird geprägt vom sozialen Milieu (einer Manifestation des je spezifischen Zusammenhangs von sozialer Lage und Lebensentwurf der agierenden Personen, in dessen Rahmen sich das Aufwachsen von Kindern und Jugendlichen vollzieht. Seine spezifischen Konstellationen, zu denen auch die Medienumgangsweisen gehören, müssen daher in die Forschung miteinbezogen werden. Um die Bedeutung, die Mediensymbolik im Alltag von Heranwachsenden einnimmt, im Kontext untersuchen zu können, erscheint eine integrative sowie interdisziplinäre Forschung notwendig. Als Beispiel dafür wird eine Panelstudie zur (Medien-Sozialisation bei sozial benachteiligten Kindern in Österreich in ihrer theoretischen und methodologischen Anlage vorgestellt.

  13. Flexibilitätsbasierte Gestaltung der logistischen Auftragsabwicklung – Anwendung am Beispiel von Produktionsdienstleistern

    OpenAIRE

    Teich, Enrico

    2014-01-01

    Zur Bewältigung von Belastungsschwankungen in der industriellen Produktion – der systematischen Regelung von Kapazitätsangebot und -bedarf – existieren Methoden in der logistischen Auftragsabwicklung, deren Anwendungserfolg von den im Produktionsbereich vorhandenen Kapazitäts- und Belastungsflexibilitätsmaß abhängig ist. Die Entwicklung geeigneter Verfahren zur Messung dieser Flexibilitätstypen als auch von Ansätzen zur Nutzung der Messwerte bei der Gestaltung der logistischen Auftragsabwickl...

  14. Handgeführter Endeffektor für die automatisierte Handhabung von textilen Zuschnitten

    OpenAIRE

    Braun, Georg; Buchheim, Andreas; Gerngroß, Tobias

    2013-01-01

    Ein typischer Herstellungsprozess von CFK-Bauteilen erfordert die präzise und wiederholbare Handhabung von trockenen, textilen Halbzeugen, was derzeit vorwiegend durch manuelle Prozesse erfolgt. Für die Automatisierung dieser Arbeitsschritte wurden am Zentrum für Leichtbauproduktionstechnologie in Augsburg zwei Generationen von Endeffektoren entwickelt. Anwendungsszenarien stellten die Ablage von Textilien für einfach und doppelt gekrümmte Bauteilgeometrien dar. Diese Arbeit be...

  15. Screening for von Willebrand disease: contribution of an automated assay for von Willebrand factor activity.

    Science.gov (United States)

    Lasne, D; Dey, C; Dautzenberg, M-D; Cherqaoui, Z; Monge, F; Aouba, A; Torchet, M-F; Geloen, D; Landais, P; Rothschild, C

    2012-05-01

    Measuring von Willebrand factor (VWF) activity is essential to the diagnosis of von Willebrand disease (VWD). The VWF activity is usually assessed based on measurement of the ristocetin cofactor (VWF:RCo). However, that test is technically challenging and has high intra- and inter-assay variabilities. The HemosIL VWF activity (VWF:AC) is a fully automated assay, recently proposed as a good alternative to VWF:RCo for VWD diagnosis. This study was undertaken to assess this new method. First, the analytical performance of VWF:AC on an automated coagulo-meter (ACLTop) was determined, and then this new method was compared with VWF:RCo and the platelet function analyzer (PFA100) for 160 patients referred for VWD screening. The VWF:AC achieved acceptable precision with within-run and between-run coefficients of variation ranging from 2.3% to 14.1%, and linearity from 10% to 100%. Despite some marked differences between VWF:AC and VWF:RCo for 10 plasmas tested, their agreement for VWD diagnosis was good. The VWF:AC had sensitivity similar to that of PFA100 (close to 100%), but better specificity (97.7% vs. 66% or 60%, depending on the cartridge used). The good analytical performance, and the sensitivity and specificity of VWF:AC to detect VWF deficiency renders it a suitable method for VWD screening. Our findings support VWF:AC use for the diagnostic work-up of VWD, paying close attention to concomitant clinical signs and bleeding score, as recommended for VWD. © 2011 Blackwell Publishing Ltd.

  16. Die Bundesstatistik als Anbieter und Nutzer von raumbezogenen Daten

    Directory of Open Access Journals (Sweden)

    R. Humbel

    Einige konkrete und potentielle Anwendungen der vorhandenen Daten sollen das Potential und die Breite der Fragestellungen, die damit angegangen werden können, illustrieren. Eine besondere Stellung dürfte in Zukunft aber auch die Satellitenfernerkundung erhalten, deren Daten und Auswertungen eine willkommene Ergänzung für die eher traditionellen GIS-Datensätze bilden werden. Ein erster Pilotversuch wurde vor wenigen Monaten im BFS gestartet, der zum Ziel hat, die Machbarkeit einer gesamtschweizerischen Unterscheidung von Laub-, Nadel- und Mischwald als Ergänzung der auf der Grundlage von konventionellen Luftbildern erhobenen Arealstatistik nachzuweisen.

  17. IT und Kommunikationstechnologien dominieren die Freizeit von Jugendlichen

    OpenAIRE

    Bohmann, Sandra; Schupp, Jürgen

    2016-01-01

    Jugendliche gestalten ihre Freizeit heute deutlich anders als noch vor fünfzehn Jahren. Die Nutzung von Informations- und Kommunikationstechnologien ist zur bedeutendsten Freizeitbeschäftigung für sie geworden. Auf repräsentativer statistischer Basis lässt sich anhand von Daten der Längsschnittstudie Sozio-oekonomisches Panel (SOEP) belegen, dass Internet- und PC-bezogene Freizeitbeschäftigungen heute für über 95 Prozent aller 17-Jährigen eine wichtige Rolle spielen, ungeachtet des Geschlecht...

  18. Comparison of automated von Willebrand factor activity assays

    DEFF Research Database (Denmark)

    Timm, Annette; Hillarp, Andreas; Philips, Malou

    2015-01-01

    activity/antigen ratios in samples classified as having VWD (activity classification power might interfere with the interpretation......INTRODUCTION: Von Willebrand Disease (VWD) is the most common inherited bleeding disorder. Measurement of von Willebrand factor (VWF) activity in plasma is often based on platelet agglutination stimulated by the ristocetin cofactor activity. Novel assays, based on latex beads with recombinant...... glycoprotein Ib instead of platelets, have recently been developed but it is unclear whether these can improve the diagnostic capability for VWD. AIM: To compare four automated VWF activity methods in a mixed population of patients referred for evaluation of bleeding tendency. METHODS: The analytical...

  19. Unterstützung von Lerngemeinschaften in verteilten intelligenten Lehrsystemen

    OpenAIRE

    Harrer, Andreas Georg

    2007-01-01

    Intelligente Lehrsysteme (ILS) ermöglichen einzelnen Lernern einen dem individuellen Kenntnisstand und Eigenschaften angepassten rechnergestützten Unterricht. Lernen in Gruppen bietet zusätzlich die Möglichkeit zur Einübung sozialer Fähigkeiten und zur flexiblen Gestaltung von Lernformen. Bisherige Ansätze von Gruppenlernsystemen stellen eine verteilte Lernumgebung zur Verfügung, durch die eine Zusammenarbeit räumlich oder zeitlich verteilter Studenten ermöglicht wird, ohne jedoch die charakt...

  20. Moyal's Characteristic Function, the Density Matrix and von Neumann's Idempotent

    OpenAIRE

    Hiley, Basil J.

    2014-01-01

    In the Wigner-Moyal approach to quantum mechanics, we show that Moyal's starting point, the characteristic function $M(\\tau,\\theta)=\\int \\psi^{*}(x)e^{i(\\tau {\\hat p}+\\theta{\\hat x})}\\psi(x)dx$, is essentially the primitive idempotent used by von Neumann in his classic paper "Die Eindeutigkeit der Schr\\"odingerschen Operatoren". This paper provides the original proof of the Stone-von Neumann equation. Thus the mathematical structure Moyal develops is simply a re-expression of what is at the h...