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Sample records for von hippel-lindau disease

  1. von Hippel-Lindau disease

    DEFF Research Database (Denmark)

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

    2013-01-01

    Endolymphatic sac tumours (ELSTs) of the inner ear occur in 16% of patients with the hereditary tumor syndrome von Hippel-Lindau disease (vHL). ELSTs of all sizes can cause irreversible hearing loss which can, however, be prevented through early diagnosis and treatment. We aim to emphasize the ch...

  2. Von Hippel-Lindau Disease

    Directory of Open Access Journals (Sweden)

    Hes Frederik J

    2005-11-01

    Full Text Available Abstract A germline mutation in the Von-Hippel Lindau (VHL gene predisposes carriers to development of abundantly vascularised tumours in the retina, cerebellum, spine, kidney, adrenal gland and pancreas. Most VHL patients die from the consequences of cerebellar haemangioblastoma or renal cell carcinoma. The VHL gene is a tumour suppressor gene and is involved in angiogenesis by regulation of the activity of hypoxia-inducible factor 1-α (HIF1-α. Clinical diagnosis of VHL can be confirmed by molecular genetic analysis of the VHL gene, which is informative in virtually all VHL families. A patient with (suspicion for VHL is an indication for genetic counselling and periodical examination.

  3. Compliance with periodic surveillance for Von-Hippel-Lindau disease.

    Science.gov (United States)

    Lammens, Chantal R M; Aaronson, Neil K; Hes, Frederik J; Links, Thera P; Zonnenberg, Bernard A; Lenders, Jacques W M; Majoor-Krakauer, Danielle; Van Os, Theo A M; Gomez-Garcia, Encarna B; de Herder, Wouter; van der Luijt, Rob B; van den Ouweland, Ans M W; Van Hest, Liselot P; Verhoef, Senno; Bleiker, Eveline M A

    2011-06-01

    To assess compliance with a periodic surveillance regimen for Von Hippel-Lindau disease. In this nationwide study, Von Hippel-Lindau disease mutation carriers and those at 50% risk were invited to complete a questionnaire assessing (compliance with) advice given for periodic surveillance. Medical record data on compliance with recommended radiologic surveillance examinations were also collected. Of the 84 (77%) participants, 78 indicated having received advice to undergo periodic surveillance. Of these, 71 reported being fully compliant with that advice. In 64% of the cases, this advice was only partially consistent with published guidelines. Based on medical record data, between one quarter and one third of individuals did not undergo surveillance as recommended in the guidelines for central nervous system lesions and one half for visceral lesions. Screening delay for central nervous system lesions was significantly higher in one hospital and in those cases where "the advice given" deviated from the guidelines. The majority of those with or at risk of Von Hippel-Lindau disease reported having received and being fully compliant with screening advice. However, in many cases, the advice given was only partially consistent with published guidelines, and screening delays were observed. Efforts should be undertaken to stimulate guideline-based surveillance advice and to minimize screening delay.

  4. 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...

  5. MR imaging of von Hippel-Lindau disease

    International Nuclear Information System (INIS)

    Sato, Y.; Waziri, M.H.; Smith, W.L.; Frey, E.E.; Franken, E.A.

    1986-01-01

    Sixteen patients with von Hippel-Lindau disease (VH-L) and 11 asymptomatic family members underwent a total of 29 central nervous system (CNS) and 23 body MR imaging evaluations during a 2-year study period. Nineteen CNS and spinal lesions and nine abdominal visceral lesions were identified on MR imaging and were confirmed at surgery or by other imaging modalities. MR imaging is superior to CT in the evaluation of intraocular vitreous abnormalities and cerebellar and spinal hemangioblastomas because of superior tissue characterization and lack of bone artifacts. MR imaging adequately demonstrated the abdominal visceral lesions. MR imaging is a sensitive and reliable imaging modality for the various lesions of VH-L

  6. 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.

  7. Molecular analysis of the von hippel-lindau disease gene.

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    Chernoff, A; Kasparcova, V; Linehan, W M; Stolle, C A

    2001-01-01

    Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that predisposes the affected individual to develop characteristic tumors. These include CNS hemangioblastoma, retinal angiomas, endolymphatic sac tumors, pancreatic cysts and tumors, epididymal cystadenomas, pheochromocytomas, renal cysts, and clear-cell renal carcinoma. The VHL gene was localized to 3p25 and then isolated by Latif et al. (1). The gene contains three exons with an open reading frame of 852 nucleotides, which encode a predicted protein of 284 amino acids. The VHL protein is believed to have several functions. It is involved in transcription regulation through its inhibition of elongation by binding to the B and C subunits of elongin. Mutations of VHL allow the B and C subunits to bind with the A subunit. This complex then overcomes "pausing" of RNA polymerase during mRNA transcription (2,3). Several studies suggest that the VHL protein is also involved in regulation of hypoxia-inducible transcripts, particularly vascular endothelial growth factor (VEGF), by altering mRNA stability (4,5). Therefore, VHL gene mutations permit the overexpression of VEGF under normoxic conditions, which leads to the angiogenesis believed to be required for tumor growth. The VHL-elongin BC complex (VBC) also binds two other proteins-CUL2 and Rbx1-in a complex that has structural similarity to other E3 ubiquitin ligase complexes (6). Such complexes mediate the degradation of cell-cycle regulatory proteins.

  8. Imaging appearances of von Hippel-Lindau disease

    International Nuclear Information System (INIS)

    Ma Xiaolong; Wang Jianhua; Lu Jianping; Wang Li; Liu Qi; Jiang Hui; Wei Wei

    2013-01-01

    Objective: To assess imaging appearances of von Hippel-Lindau disease (VHLD). Methods: The clinical and imaging data of ten patients who met VHLD gene diagnostic criteria were retrospectively analyzed. Seven underwent CT abdominal scan, three underwent MRI abdominal scan. All patients underwent MRI cranial scan. Eight patients were treated by surgery, and three of them underwent endoscopic ultrasound guided aspiration biopsy of pancreatic tumors. Results: All patients had multiple cysts of the pancreas, eight patients suffered multiple cysts of kidneys. Three patients suffered multiple islet cell tumors of pancreas: one was accompanied with pancreatic serous cystadenoma, another was accompanied with left adrenal pheochromocytoma. Three patients had bilateral renal cell carcinoma (one of them had the right kidney cut off), one patient had right renal cell carcinoma. Two patients suffered cerebellar hemangioblastomas, and one of them was accompanied with mutiple spinal hemangioblastomas and the left retinal hemangioblastoma. Two patients with multiple cysts of pancreas and kidneys had not been found any tumor. Conclusion: Multiple cysts of pancreas and kidney are highly suggestive of VHLD. At the same time, endocrine tumors of pancreas, serous cystadenoma of pancreas, adrenal pheochromocytoma, renal carcinomas, multiple hemangioblastomas of central nervous system and retinal hemangioblastoma can also occur in VHLD. (authors)

  9. Zr-89-Bevacizumab PET Visualizes Disease Manifestations in Patients with von Hippel-Lindau Disease

    NARCIS (Netherlands)

    Oosting, Sjoukje F.; van Asselt, Sophie J.; Brouwers, Adrienne H.; Bongaerts, Alfons H. H.; Steinberg, Julia D. J.; de Jong, Johan; Lub-de Hooge, Marjolijn N.; Horst-Schrivers, van der Anouk N. A.; Walenkamp, Annemiek M. E.; Hoving, Eelco W.; Sluiter, Wim J.; Zonnenberg, Bernard A.; de Vries, Elisabeth G. E.; Links, Thera P.

    2016-01-01

    Patients with von Hippel-Lindau disease (VHL) are at risk to develop multiple tumors. The growth of lesions is unpredictable, and regular surveillance is critical for early treatment to control local damage. Vascular endothelial growth factor A (VEGF-A) produced locally is supposed to play an

  10. 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

  11. Patient-specific factors influence somatic variation patterns in von Hippel?Lindau disease renal tumours

    OpenAIRE

    Fei, Suzanne S.; Mitchell, Asia D.; Heskett, Michael B.; Vocke, Cathy D.; Ricketts, Christopher J.; Peto, Myron; Wang, Nicholas J.; S?nmez, Kemal; Linehan, W. Marston; Spellman, Paul T.

    2016-01-01

    Cancer development is presumed to be an evolutionary process that is influenced by genetic background and environment. In laboratory animals, genetics and environment are variables that can largely be held constant. In humans, it is possible to compare independent tumours that have developed in the same patient, effectively constraining genetic and environmental variation and leaving only stochastic processes. Patients affected with von Hippel?Lindau disease are at risk of developing multiple...

  12. 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.

  13. Ga-68 Somatostatin Receptor PET/CT in von Hippel-Lindau Disease

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Jong-Ryool; Min, Jung-Joon [Chonnam National Univ. Hwasun Hospital, Hwasun (Korea, Republic of); Kulkarui, Harshad; Carreras, Cecilia; Schalch, Georg; Baum, Richard P. [Nuclear Medicine and Center for PET/CT, Zentralk Bad Berka, Bad Verka (Germany)

    2012-06-15

    Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome with a variety of benign and malignant tumors such as retinal and central nervous system hemangioblastomas, endolymphatic sac tumors, renalcysts and tumors, pancreatic cysts and tumors, pheochromo-cytomas, and epididymal cystadenomas. Cross-sectional mo-dalities (computed tomography and magnetic resonance imaging) as well as ultrasound play a major role in the initial evaluation and follow-up of the various manifestations of VHL disease. Ga-68-labeled somatostatin receptor analogs already have a significant role in the diagnosis, staging, and therapy management of neuroendocrine neoplasms and neural crest tumors. Herein, we report a case presenting a variety of malignancies in VHL and showing the usefulness of Ga-68 somatostatin receptor PET/CT as a one-stop-shop imaging modality in the management of VHL disease.

  14. Ga-68 Somatostatin Receptor PET/CT in von Hippel-Lindau Disease

    International Nuclear Information System (INIS)

    Oh, Jong-Ryool; Min, Jung-Joon; Kulkarui, Harshad; Carreras, Cecilia; Schalch, Georg; Baum, Richard P.

    2012-01-01

    Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome with a variety of benign and malignant tumors such as retinal and central nervous system hemangioblastomas, endolymphatic sac tumors, renalcysts and tumors, pancreatic cysts and tumors, pheochromo-cytomas, and epididymal cystadenomas. Cross-sectional mo-dalities (computed tomography and magnetic resonance imaging) as well as ultrasound play a major role in the initial evaluation and follow-up of the various manifestations of VHL disease. Ga-68-labeled somatostatin receptor analogs already have a significant role in the diagnosis, staging, and therapy management of neuroendocrine neoplasms and neural crest tumors. Herein, we report a case presenting a variety of malignancies in VHL and showing the usefulness of Ga-68 somatostatin receptor PET/CT as a one-stop-shop imaging modality in the management of VHL disease

  15. Von Hippel-Lindau disease (vHL)

    DEFF Research Database (Denmark)

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

    2013-01-01

    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....../MRI of the abdomen, e) annual plasma-metanephrine, plasma-normetanephrine, and plasma-chromogranin A tests, and f) annual hearing examination at a department of audiology. It is advised that one doctor takes on the responsibility of coordination of and referral to the many examinations, and the communication...

  16. 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. 

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

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    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.

  18. Clinical features and natural history of von Hippel-Lindau disease.

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    Maher, E R; Yates, J R; Harries, R; Benjamin, C; Harris, R; Moore, A T; Ferguson-Smith, M A

    1990-11-01

    The clinical features, age at onset and survival of 152 patients with von Hippel-Lindau disease were studied. Mean age at onset was 26.3 years and 97 per cent of patients had presented by aged 60 years. Retinal angioma was the first manifestation in 65 patients (43 per cent), followed by cerebellar haemangioblastoma (n = 60, 39 per cent) and renal cell carcinoma (n = 15, 10 per cent). Overall, 89 patients (59 per cent) developed a cerebellar haemangioblastoma, 89 (59 per cent) a retinal angioma, 43 (28 per cent) renal cell carcinoma, 20 (13 per cent) spinal haemangioblastoma and 11 (7 per cent) a phaeochromocytoma. Renal, pancreatic and epididymal cysts were frequent findings but their exact incidence was not accurately assessed. Mean age at diagnosis of renal cell carcinoma (44.0 +/- 10.9 years) was significantly older than that for cerebellar haemangioblastoma (29.0 +/- 10.0 years) and retinal angioma (25.4 +/- 12.7 years). The probability of a patient with von Hippel-Lindan disease developing a cerebellar haemangioblastoma, retinal angioma or renal cell carcinoma by age 60 years was 0.84, 0.7 and 0.69, respectively. A comprehensive screening protocol for affected patients and at-risk relatives is presented, based on detailed analysis of age at onset data for each of the major complications. Median actuarial survival was 49 years, with renal cell carcinoma the leading cause of death.

  19. Endolymphatic sac tumour in von Hippel-Lindau disease: management strategies.

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    Zanoletti, E; Girasoli, L; Borsetto, D; Opocher, G; Mazzoni, A; Martini, A

    2017-10-01

    Endolymphatic sac tumour (ELST) is infrequent, as emerges from small series reported in the literature. It is a slow-growing malignancy with local aggressiveness and a low risk of distant metastases. It is often misdiagnosed because of the late onset of symptoms and difficulty in obtaining a biopsy. Its frequency is higher in von Hippel-Lindau (VHL) disease (a genetic systemic syndrome involving multiple tumours), with a prevalence of around 25%. The diagnosis is based on radiology, with specific patterns on contrast-enhanced MRI and typical petrous bone erosion on bone CT scan. Our experience of ELST in the years between 2012-2015 concerns 7 cases, one of which was bilateral, in patients with VHL disease. Four of the 7 patients underwent 5 surgical procedures at our institution. Each case is described in detail, including clinical symptoms, and the intervals between symptom onset, diagnosis and therapy. Postoperative morbidity was low after early surgery on small tumours, whereas extensive surgery for large tumours was associated with loss of cranial nerve function (especially VII, IX, X). The critical sites coinciding with loss of neurological function were the fallopian canal, jugular foramen, petrous apex and intradural extension into the posterior cranial fossa. Early surgery on small ELST is advocated for patients with VHL disease, in whom screening enables a prompt diagnosis and consequently good prognosis. © Copyright by Società Italiana di Otorinolaringologia e Chirurgia Cervico-Facciale, Rome, Italy.

  20. Pancreatic involvement in Korean patients with von Hippel-Lindau disease

    International Nuclear Information System (INIS)

    Lee, Kwang-Hyuck; Lee, Jae-Seung; Kim, Bum-Jin; Lee, Jong-Kyun; Kim, Seong-Hyun; Kim, Seung-Hoon; Lee, Kyu-Taek

    2009-01-01

    The aim of this study was to describe pancreatic involvement in von Hippel-Lindau (VHL) disease and to document the changes that occur in pancreatic lesions. We retrospectively analyzed the medical records and CT scans of 18 VHL patients who were diagnosed between 1994 and 2007 at the Samsung Medical Center. The clinical history with a detailed family history, biochemical test results, and imaging studies of the pancreas, adrenal glands, and kidneys were reviewed. Genetic analysis was performed in 12 patients. The changes in pancreatic lesions, such as an increase in cystic lesions, calcifications, and dilatation of the pancreatic duct, were analyzed in patients who had CT scans at least 1 year apart. Pancreatic lesions existed in 89% (16/18) of the patients. All 16 patients had multiple cystic lesions. Two patients had co-existing neuroendocrine tumors (NET), and two patients had co-existing serous cystadenomas (SCA). At least one of three features of pancreatic lesions (cystic lesions, calcifications, and dilatation of the pancreatic duct) progressed in all nine patients who had CT scans 1 year apart. Pancreatic involvement in VHL disease was relatively common in Korean patients. The most common type of pancreatic involvement was a multiple cystic lesion. NET and SCA existed in approximately 10% of VHL patients with pancreatic involvement. Pancreatic lesions in VHL disease progressed, at least according to radiological images. (author)

  1. Preventive medicine for von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Krauss, Tobias; Ferrara, Alfonso Massimiliano; Links, Thera P; Wellner, Ulrich; Bancos, Irina; Kvachenyuk, Andrey; Villar Gómez de Las Heras, Karina; Yukina, Marina; Petrov, Roman; Bullivant, Garrett; von Duecker, Laura; Jadhav, Swati S; Ploeckinger, Ursula; Welin, Staffan; Schalin-Jantti, Camilla; Gimm, Oliver; Pfeifer, Marija; Ngeow, Joanne; Hasse-Lazar, Kornelia; Sanso, Gabriela; Qi, Xiao-Ping; Ugurlu, Umit; Diaz, Rene Eduardo; Wohllk, Nelson; Peczkowska, Mariola; Aberle, Jens; Lourenço, Delmar Muniz; Pereira, Maria Adelaide; Fragoso, Maria Candida Barisson Villares; Hoff, Ana O; Almeida, Madson Queiroz; Violante, Alice H D; Quidute, Ana R P; Zhang, Zheiwei; Recasens, Monica; Robles Diaz, Luis; Kunavisarut, Tada; Wannachalee, Taweesak; Sirinvaravong, Sirinart; Jonasch, Eric; Grozinsky-Glasberg, Simona; Fraenkel, Merav; Beltsevich, Dmitry; Egorov, Viacheslav I; Bausch, Dirk; Schott, Matthias; Tiling, Nikolaus; Pennelli, Gianmaria; Zschiedrich, Stefan; Därr, Roland; Ruf, Juri; Denecke, Timm; Link, Karl-Heinrich; Zovato, Stefania; von Dobschuetz, Ernst; Yaremchuk, Svetlana; Amthauer, Holger; Makay, Ozer; Patocs, Attila; Walz, Martin K; Huber, Tobias B; Seufert, Jochen; Hellman, Per; Kim, Raymond H; Kuchinskaya, Ekaterina; Schiavi, Francesca; Malinoc, Angelica; Reisch, Nicole; Jarzab, Barbara; Barontini, Marta; Januszewicz, Andrzej; Shah, Nalini; Young, William; Opocher, Giuseppe; Eng, Charis; Neumann, Hartmut P H; Bausch, Birke

    2018-05-10

    Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2,330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs <2.8cm vs ≥2.8 cm (94% vs 85% by 10 years; P=0.020; 80% vs 50% at 10 years; P=0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.

  2. Von Hippel-Lindau disease: an evaluation of natural history and functional disability.

    Science.gov (United States)

    Feletti, Alberto; Anglani, Mariagiulia; Scarpa, Bruno; Schiavi, Francesca; Boaretto, Francesca; Zovato, Stefania; Taschin, Elisa; Gardi, Mario; Zanoletti, Elisabetta; Piermarocchi, Stefano; Murgia, Alessandra; Pavesi, Giacomo; Opocher, Giuseppe

    2016-07-01

    Although many studies have been published about specific lesions characterizing von Hippel-Lindau(VHL) disease, none have dealt with the natural history of the whole disease and the consequent disabilities. We aim to define the comprehensive natural history of VHL disease and to describe the functional disabilities and their impact upon patients' quality of life, thereby tailoring the follow-up schedule accordingly. We performed a prospective analysis on 128 VHL-affected patients beginning in 1996. For each affected organ, we defined intervals between the first and subsequent VHL-related manifestations and compared them with current VHL surveillance protocols. We looked for any association of the number of involved organs with age, sex, type of VHL gene mutation, and functional domain mutation. Ultimately, we assessed the organ-specific disabilities caused by VHL disease. Hemangioblastomas show different patterns of progression depending on their location, whereas both renal cysts and carcinomas have similar progression rates. Surgery for pheochromocytoma and CNS hemangioblastoma is performed earlier than for pancreatic or renal cancer. The number of involved organs is associated with age but not with sex, type of VHL gene mutation, or functional domain mutation. A thorough analysis of functional disabilities showed that age is related to the first-appearing functional impairment, but it is not predictive of the final number of disabilities. Our study defines the disease progression and provides a comprehensive view of the syndrome over time. We analyzed for the first time the functional disability of VHL patients, assessing the progression for each function. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Systemic Sunitinib Malate Treatment for Advanced Juxtapapillary Retinal Hemangioblastomas Associated with von Hippel-Lindau Disease.

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    Knickelbein, Jared E; Jacobs-El, Naima; Wong, Wai T; Wiley, Henry E; Cukras, Catherine A; Meyerle, Catherine B; Chew, Emily Y

    2017-01-01

    To describe the clinical course of advanced juxtapapillary retinal capillary hemangioblastomas (RCH) associated with von Hippel-Lindau (VHL) disease treated with systemic sunitinib malate, an agent that inhibits both anti-vascular endothelial growth factor and anti-platelet-derived growth factor signaling. Observational case review. Three patients with advanced VHL-related juxtapapillary RCH treated with systemic sunitinib malate. Patient 1 was followed routinely every 4 months while on systemic sunitinib prescribed by her oncologist for metastatic pancreatic neuroendocrine and kidney tumors. Patients 2 and 3 were part of a prospective clinical trial evaluating the use of systemic sunitinib for ocular VHL lesions during a period of 9 months. Visual acuity, size of RCH, and degree of exudation were recorded at each visit. Optical coherence tomography (OCT) and fluorescein angiography were also obtained at some visits. Visual acuity, size of RCH, and degree of exudation. Three patients with advanced VHL-associated juxtapapillary RCH were treated with systemic sunitinib malate. While none of the patients lost vision during therapy, treatment with sunitinib malate did not improve visual acuity or reduce the size of RCH. Improvements in RCH-associated retinal edema were observed in two patients. All patients experienced multiple adverse effects, including thyroid toxicity, thrombocytopenia, nausea, fatigue, jaundice, and muscle aches. Two of the three patients had to discontinue treatment prematurely and the third required dose reduction. Systemic sunitinib malate may be useful in slowing progression of ocular disease from VHL-associated RCH. However, significant systemic adverse effects limited its use in this small series, and systemic sunitinib malate may not be safe for treatment of RCH when used at the doses described in this report. Further studies are required to determine if this medication used at lower doses with different treatment strategies, other

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Metastatic Renal Cell Carcinoma versus Pancreatic Neuroendocrine Tumor in von Hippel-Lindau Disease: Treatment with Interleukin-2

    Directory of Open Access Journals (Sweden)

    Christopher Williams

    2005-01-01

    Full Text Available Differentiating between clear cell neuroendocrine tumor (NET of the pancreas and renal cell carcinoma (RCC metastatic to the pancreas can be challenging in patients with von Hippel-Lindau disease (VHL. The clear cell features of both NET and RCC in VHL patients may lead to misdiagnosis, inaccurate staging, and alternative treatment. We present a patient in which this occurred. As clear cell NETs closely resembling metastatic RCC are distinctive neoplasms of VHL and metastatic RCC to the pancreas in the VHL population is rare, careful pathologic examination should be performed prior to subjecting patients to definitive surgical or medical therapies.

  6. Clinical Study on Patients with Renal-Cell Carcinoma Accompanied with Von Hippel Lindau Disease Treated with Radiofrequency Ablation

    OpenAIRE

    波越, 朋也; 島本, 力; 辛島, 尚; 亀井, 麻依子; 福原, 秀雄; 深田, 聡; 佐竹, 宏文; 蘆田, 真吾; 山崎, 一郎; 鎌田, 雅行; 井上, 啓史; 山西, 伴明; 小川, 恭弘; 伊藤, 悟志; 執印, 太郎

    2014-01-01

    We report 12 renal cell carcinomas in 6 patients with Von Hippel-Lindau (VHL) disease treated with radiofrequency ablation (RFA). The mean age of the patients was 46 (range 38-53) years (male : 4, female : 2). Computed tomography (CT)-guided transcutaneous RFA was performed under conscious sedation with local anesthetics. The mean size of the tumors was 2.4 (range 0.7-8.1) cm. Nine of the 12 tumors (75%) were locally well controlled. However, 3 tumors in 2 patients developed visceral metastas...

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  9. [Clinical study on patients with renal-cell carcinoma accompanied with Von Hippel-Lindau disease treated with radiofrequency ablation].

    Science.gov (United States)

    Nao, Tomoya; Shimamoto, Tsutomu; Karashima, Takashi; Kamei, Maiko; Fukuhara, Hideo; Fukata, Satoshi; Satake, Hirofumi; Ashida, Shingo; Yamasaki, Ichiro; Kamata, Masayuki; Inoue, Keiji; Yamanishi, Tomoaki; Ogawa, Yasuhiro; Ito, Satoshi; Shuin, Taro

    2014-09-01

    We report 12 renal cell carcinomas in 6 patients with Von Hippel-Lindau (VHL) disease treated with radiofrequency ablation (RFA). The mean age of the patients was 46 (range 38-53) years (male : 4, female : 2). Computed tomography (CT)-guided transcutaneous RFA was performed under conscious sedation with local anesthetics. The mean size of the tumors was 2.4 (range 0.7-8.1) cm. Nine of the 12 tumors (75%) were locally well controlled. However, 3 tumors in 2 patients developed visceral metastases after RFA. While minimal flank pain, nausea, perinephritic hematoma and lumbago were observed, there was no major complication during or after the procedure. The therapy with CT-guided transcutaneous RFA is efficient and minimal invasive for renal cell carcinoma in patients with VHL, leading to preservation of renal function.

  10. Cloning and characterization of a mouse gene with homology to the human von Hippel-Lindau disease tumor suppressor gene: implications for the potential organization of the human von Hippel-Lindau disease gene.

    Science.gov (United States)

    Gao, J; Naglich, J G; Laidlaw, J; Whaley, J M; Seizinger, B R; Kley, N

    1995-02-15

    The human von Hippel-Lindau disease (VHL) gene has recently been identified and, based on the nucleotide sequence of a partial cDNA clone, has been predicted to encode a novel protein with as yet unknown functions [F. Latif et al., Science (Washington DC), 260: 1317-1320, 1993]. The length of the encoded protein and the characteristics of the cellular expressed protein are as yet unclear. Here we report the cloning and characterization of a mouse gene (mVHLh1) that is widely expressed in different mouse tissues and shares high homology with the human VHL gene. It predicts a protein 181 residues long (and/or 162 amino acids, considering a potential alternative start codon), which across a core region of approximately 140 residues displays a high degree of sequence identity (98%) to the predicted human VHL protein. High stringency DNA and RNA hybridization experiments and protein expression analyses indicate that this gene is the most highly VHL-related mouse gene, suggesting that it represents the mouse VHL gene homologue rather than a related gene sharing a conserved functional domain. These findings provide new insights into the potential organization of the VHL gene and nature of its encoded protein.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Solid renal tumor severity in von Hippel Lindau disease is related to germline deletion length and location.

    Science.gov (United States)

    Maranchie, Jodi K; Afonso, Anoushka; Albert, Paul S; Kalyandrug, Sivaram; Phillips, John L; Zhou, Shubo; Peterson, James; Ghadimi, Bijan M; Hurley, Katheen; Riss, Joseph; Vasselli, James R; Ried, Thomas; Zbar, Berton; Choyke, Peter; Walther, McClellan M; Klausner, Richard D; Linehan, W Marston

    2004-01-01

    von Hippel Lindau disease (VHL) is an autosomal dominant familial cancer syndrome linked to alteration of the VHL tumor suppressor gene. Affected patients are predisposed to develop pheochromocytomas and cystic and solid tumors of the kidney, CNS, pancreas, retina, and epididymis. However, organ involvement varies considerably among families and has been shown to correlate with the underlying germline alteration. Clinically, we observed a paradoxically lower prevalence of renal cell carcinoma (RCC) in patients with complete germline deletion of VHL. To determine if a relationship existed between the type of VHL deletion and disease, we retrospectively evaluated 123 patients from 55 families with large germline VHL deletions, including 42 intragenic partial deletions and 13 complete VHL deletions, by history and radiographic imaging. Each individual and family was scored for cystic or solid involvement of CNS, pancreas, and kidney, and for pheochromocytoma. Germline deletions were mapped using a combination of fluorescent in situ hybridization (FISH) and quantitative Southern and Southern blot analysis. An age-adjusted comparison demonstrated a higher prevalence of RCC in patients with partial germline VHL deletions relative to complete deletions (48.9 vs. 22.6%, p=0.007). This striking phenotypic dichotomy was not seen for cystic renal lesions or for CNS (p=0.22), pancreas (p=0.72), or pheochromocytoma (p=0.34). Deletion mapping revealed that development of RCC had an even greater correlation with retention of HSPC300 (C3orf10), located within the 30-kb region of chromosome 3p, immediately telomeric to VHL (52.3 vs. 18.9%, p <0.001), suggesting the presence of a neighboring gene or genes critical to the development and maintenance of RCC. Careful correlation of genotypic data with objective phenotypic measures will provide further insight into the mechanisms of tumor formation. Copyright 2003 Wiley-Liss, Inc.

  14. von Hippel-Lindau development in children and adolescents

    DEFF Research Database (Denmark)

    Launbjerg, Karoline; Bache, Iben; Galanakis, Michael

    2017-01-01

    on expert opinions. We aimed to describe the course of vHL development in children and adolescents, focusing on age at first manifestation, manifestation frequencies, and types. The prevalence of vHL diagnosis as well as manifestations in childhood were evaluated based on 99 patients, who had started......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...... surveillance before 18 years: 37 Danish patients from the national vHL research database and 62 international patients reported in 15 articles. Overall, 70% (69 of 99) developed manifestations before 18 years (median age at first manifestation: 12 years (range: 6–17 years)). Thirty per cent (30 of 99) had...

  15. Pancreatic neuroendocrine tumor with complete replacement of the pancreas by serous cystic neoplasms in a patient with von Hippel-Lindau disease: a case report.

    Science.gov (United States)

    Maeda, Shimpei; Motoi, Fuyuhiko; Oana, Shuhei; Ariake, Kyohei; Mizuma, Masamichi; Morikawa, Takanori; Hayashi, Hiroki; Nakagawa, Kei; Kamei, Takashi; Naitoh, Takeshi; Unno, Michiaki

    2017-09-25

    von Hippel-Lindau disease is a dominantly inherited multi-system syndrome with neoplastic hallmarks. Pancreatic lesions associated with von Hippel-Lindau include serous cystic neoplasms, simple cysts, and neuroendocrine tumors. The combination of pancreatic neuroendocrine tumors and serous cystic neoplasms is relatively rare, and the surgical treatment of these lesions must consider both preservation of pancreatic function and oncological clearance. We report a patient with von Hippel-Lindau disease successfully treated with pancreas-sparing resection of a pancreatic neuroendocrine tumor where the pancreas had been completely replaced by serous cystic neoplasms, in which pancreatic function was preserved. A 39-year-old female with von Hippel-Lindau disease was referred to our institution for treatment of a pancreatic neuroendocrine tumor. Abdominal computed tomography demonstrated a well-enhanced mass, 4 cm in diameter in the tail of the pancreas, and two multilocular tumors with several calcifications, 5 cm in diameter, in the head of the pancreas. There was complete replacement of the pancreas by multiple cystic lesions with diameters ranging from 1 to 3 cm. Magnetic resonance cholangiopancreatography showed innumerable cystic lesions on the whole pancreas and no detectable main pancreatic duct. Endoscopic ultrasound-guided fine-needle aspiration of the mass in the pancreatic tail showed characteristic features of a neuroendocrine tumor. A diagnosis of pancreatic neuroendocrine tumor in the tail of the pancreas and mixed-type serous cystic neoplasms replacing the whole pancreas was made and she underwent distal pancreatectomy while avoiding total pancreatectomy. The stump of the pancreas was sutured as firm as possible using a fish-mouth closure. The patient made a good recovery and was discharged on postoperative day 9. She is currently alive and well with no symptoms of endocrine or exocrine pancreatic insufficiency 8 months after surgery. A pancreas

  16. Radiologic manifestations of Hippel-Lindau disease

    International Nuclear Information System (INIS)

    Ziemianski, A.; Pecold, K.; Sosnowski, P.; Paprzycki, W.; Juszkat, R.

    1994-01-01

    Examinations have been performed in 15 patients from 5 families. CT of abdomen as well as MR of eyeballs and of the subtentorial part of the central nervous system were performed. Three patients who exhibited changes in MR and 2 patients who showed changes in CT underwent additional examinations with contrast media. In MR the most frequently observed changes have been found in eyeballs, in cerebellum and spinal cord. In CT kidney changes and pancreas changes were most frequently observed. In 2 patients neither CT nor MR changes have been found. It is believed that appropriate diagnostic procedure in Hippel-Lindau disease should include MR examination of the central nervous system, and CT examination of abdomen. Both examinations should be performed with contrast enhancement. (author)

  17. Two-stage resection of a bilateral pheochromocytoma and pancreatic neuroendocrine tumor in a patient with von Hippel-Lindau disease: A case report

    Directory of Open Access Journals (Sweden)

    Yutaka Endo

    Full Text Available Introduction: von Hippel-Lindau disease (vHL disease is a hereditary disease in which tumors and cysts develop in many organs, in association with central nervous system hemangioblastomas, pheochromocytomas, and pancreatic tumors. We herein report a case of vHL disease (type 2A associated with bilateral pheochromocytomas, pancreatic neuroendocrine tumors (PNET, and cerebellar hemangioblastomas treated via pancreatectomy after adrenalectomy. Case presentation: A 51-year-old woman presented with a cerebellar tumor, bilateral hypernephroma, and pancreatic tumor detected during a medical checkup. 18F-fluorodeoxyglucose positron emission tomography–computed tomography revealed a bilateral adrenal gland tumor and a tumor in the head of the pancreas, while an abdominal computed tomography examination revealed a 30-mm tumor with strong enhancement in the head of the pancreas. Cranial magnetic resonance imaging showed a hemangioblastoma in the cerebellum. Therefore, a diagnosis of vHL disease (type 2A was made. Her family medical history included renal cell carcinoma in her father and bilateral adrenal pheochromocytoma and spinal hemangioblastoma in her brother. A detailed examination of endocrine function showed that the adrenal mass was capable of producing catecholamine. Treatment of the pheochromocytoma was prioritized, and therefore, laparoscopic left adrenalectomy and subtotal resection of the right adrenal gland were performed. Once the postoperative steroid levels were replenished, subtotal stomach-preserving pancreatoduodenectomy was performed for the PNET. After a good postoperative course, the patient was discharged in remission on the 11th day following surgery. Histopathological examination findings indicated NET G2 (MIB-1 index 10–15% pT3N0M0 Stage II A and microcystic serous cystadenoma throughout the resected specimen. The patient is scheduled to undergo treatment for the cerebellar hemangioblastoma. Conclusion: A two-staged resection

  18. A Review of Von Hippel-Lindau Syndrome

    Directory of Open Access Journals (Sweden)

    Neha Varshney

    2017-08-01

    Full Text Available Von Hippel-Lindau syndrome (VHL is a familial neoplastic condition seen in approximately 1 in 36,000 live births. It is caused by germline mutations of the tumor suppressor gene VHL, located on the short arm of chromosome 3. While the majority of the affected individuals have a positive family history, up to 20% of cases arise from de novo mutations. VHL syndrome is characterized by the presence of benign and malignant tumors affecting the central nervous system, kidneys, adrenals, pancreas, and reproductive organs. Common manifestations include hemangioblastomas of the brain, spinal cord, and retina; pheochromocytoma and paraganglioma; renal cell carcinoma; pancreatic cysts and neuroendocrine tumors; and endolymphatic sac tumors. Diagnosis of VHL is prompted by clinical suspicion and confirmed by molecular testing. Management of VHL patients is complex and multidisciplinary. Routine genetic testing and surveillance using various diagnostic techniques are used to help monitor disease progression and implement treatment options. Despite recent advances in clinical diagnosis and management, life expectancy for VHL patients remains low at 40–52 years. This article provides an overview of the major clinical, histological, and radiological findings, as well as treatment modalities.

  19. 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.

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

    International Nuclear Information System (INIS)

    Kim, Ok Hwa

    2015-01-01

    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.

  1. Clinicopathologic correlation of argon laser photocoagulation of retinal angiomas in a patient with von Hippel-Lindau disease followed for more than 20 years.

    Science.gov (United States)

    Rosa, R H; Goldberg, M F; Green, W R

    1996-01-01

    The authors review the histopathologic findings in the eyes of a patient with multiple retinal angiomas and von Hippel-Lindau disease, who underwent treatment with argon laser photocoagulation with follow-up of more than 20 years. The patient was studied ophthalmoscopically and by fluorescein angiography before and after argon laser photocoagulation of retinal angiomas. The eyes were obtained postmortem, and the central portion of the right eye, including the macula and optic nerve head, was sectioned serially for light microscopy. The pupil-optic nerve segment of the left eye was step-sectioned serially for light microscopy. Histopathologic study of the right eye disclosed mild cystoid macular edema and focal areas of exudation in the midperiphery possibly secondary to irradiation of the head. A 1.5 x 0.3-mm area of residual angioma was present in the nasal peripapillary retina. Superotemporally, four chorioretinal scars were present in one photocoagulated area. These scars were composed of dense fibrous tissue with vascularization and variable retinal pigment epithelium hyperplasia. Large, nonangiomatous vessels within each of the scars were continuous with other retinal vessels. Inferotemporally, two chorioretinal scars were present in one photocoagulated area. Histopathologically, these scars were similar to the superotemporal scars, except that no patent retinal vessels traversed the inferotemporal scars. Neovascularization of the retina was associated with one superotemporal and one inferotemporal scar. No residual angiomatous tissue was present in the supero- or inferotemporal areas. Histopathologic examination of the left eye disclosed extensive vitreous organization and periretinal fibrovascular proliferation, extensive gliosis of the retina, and a 4.5 x 2-mm schisis cavity filled with fibrinous exudate. Three angiomas with variable fibrosis were present in the left eye. Despite a poor clinical course in one eye treated with xenon arc photocoagulation

  2. Genotype and phenotype correlation in von Hippel-Lindau disease based on alteration of the HIF-α binding site in VHL protein.

    Science.gov (United States)

    Liu, Sheng-Jie; Wang, Jiang-Yi; Peng, Shuang-He; Li, Teng; Ning, Xiang-Hui; Hong, Bao-An; Liu, Jia-Yuan; Wu, Peng-Jie; Zhou, Bo-Wen; Zhou, Jing-Cheng; Qi, Nie-Nie; Peng, Xiang; Zhang, Jiu-Feng; Ma, Kai-Fang; Cai, Lin; Gong, Kan

    2018-03-29

    PurposeVon Hippel-Lindau (VHL) disease is a rare hereditary cancer syndrome that reduces life expectancy. We aimed to construct a more valuable genotype-phenotype correlation based on alterations in VHL protein (pVHL).MethodsVHL patients (n = 339) were recruited and grouped based on mutation types: HIF-α binding site missense (HM) mutations, non-HIF-α binding site missense (nHM) mutations, and truncating (TR) mutations. Age-related risks of VHL-associated tumors and patient survival were compared.ResultsMissense mutations conferred an increased risk of pheochromocytoma (HR = 1.854, p = 0.047) compared with truncating mutations. The risk of pheochromocytoma was lower in the HM group than in the nHM group (HR = 0.298, p = 0.003) but was similar between HM and TR groups (HR = 0.901, p = 0.810). Patients in the nHM group had a higher risk of pheochromocytoma (HR = 3.447, p counseling and pathogenesis studies.Genetics in Medicine advance online publication, 29 March 2018; doi:10.1038/gim.2017.261.

  3. [Genetic analysis of a family with Von Hippel-Lindau syndrome].

    Science.gov (United States)

    Lafuente-Sanchis, Aránzazu; Cuevas, José M; Alemany, Pilar; Cremades, Antonio; Zúñiga, Ángel

    Von Hippel-Lindau syndrome (VHL) is an autosomal dominant inherited disease associated with mutations in the VHL tumour suppressor gene located on chromosome 3p25. VHL is characterized by the development of multiple malignant and benign tumours in the central nervous system and internal organs, including liver, pancreas and the adrenal gland. More than 823 different mutations of the VHL gene have currently been identified. In the present study we describe the case of a family affected by VHL treated at the University Hospital of La Ribera and the results of the genetic analysis of three relatives, identifying the mutation R167G in exon 3 of VHL gene as the cause of VHL syndrome in this family. Copyright © 2016 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.

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

    International Nuclear Information System (INIS)

    Prasad, Vikas; Brenner, Winfried; Tiling, Nikolaus; Ploeckinger, Ursula; Denecke, Timm

    2016-01-01

    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, 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 68 Ga-DOTATOC PET/CT in screening of patients with vHLD. 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 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. 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 node metastasis. pNETs were

  5. 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

  6. Haemangioblastoma of a cervical sensory nerve root in Von Hippel-Lindau syndrome.

    Science.gov (United States)

    McEvoy, A W; Benjamin, E; Powell, M P

    2000-10-01

    Spinal haemangioblastomas are rare, accounting for only about 7% of all central nervous system cases. The case of a 40-year-old woman with a haemangioblastoma arising solely from a cervical sensory nerve root is presented. At operation via a cervical laminectomy, it was possible to resect the tumour en masse with the sensory ramus, by extending the laminectomy through the exit foramen for C6. Haemangioblastomas are commonly intramedullary, and have only been reported in this location on one previous occasion. The patient has Von Hippel-Lindau syndrome and a history of multiple solid tumours. The possible role of the Von Hippel-Lindau tumour suppressor gene in the pathogenesis of these neoplasms is discussed.

  7. Risk of new tumors in von Hippel-Lindau patients depends on age and genotype

    DEFF Research Database (Denmark)

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

    2016-01-01

    PURPOSE: The von Hippel-Lindau (vHL) phenotype is variable, which complicates genetic counseling and surveillance. We describe how the rate of new tumor development varies through the lifetimes of vHL patients and how it is influenced by age and genotype. METHODS: In a national cohort study, we i...... 02 April 2015Genetics in Medicine (2015); doi:10.1038/gim.2015.44....

  8. TLX controls angiogenesis through interaction with the von Hippel-Lindau protein

    OpenAIRE

    Zhao-jun Zeng; Erik Johansson; Amiko Hayashi; Pavithra L. Chavali; Nina Akrap; Takeshi Yoshida; Kimitoshi Kohno; Hiroto Izumi; Keiko Funa

    2012-01-01

    Summary TLX is known as the orphan nuclear receptor indispensable for maintaining neural stem cells in adult neurogenesis. We report here that neuroblastoma cell lines express high levels of TLX, which further increase in hypoxia to enhance the angiogenic capacity of these cells. The proangiogenetic activity of TLX appears to be induced by its direct binding to the von Hippel-Lindau protein (pVHL), which stabilizes TLX. In turn, TLX competes with hydroxylated hypoxia-inducible factor (HIF-α) ...

  9. Úskalí života s onemocněním Von Hippel - Lindau

    OpenAIRE

    ŠEREDOVÁ, Eva

    2014-01-01

    Morbus Von Hippel Lindau (VHL) is still an unkonwn term for many people. It refers to a genetic oncological desease affecting 1/39000 to 1/50000 persons. VHL is connected with a great deal of manifestation. It is a disease with a very unstable prognosis. Those diagnosed with VHL require medical care by a large number of specialists. However, an early detection may significantly improve the quality of patients´ life. The disease is manifestated by numerous negative side effects, which is the m...

  10. 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.

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

    OpenAIRE

    Minervini, Giovanni; Mazzotta, Gabriella M.; Masiero, Alessandro; Sartori, Elena; Corr?, 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 t...

  12. Negative regulation of hypoxia-inducible genes by the von Hippel-Lindau protein.

    OpenAIRE

    Iliopoulos, O; Levy, A P; Jiang, C; Kaelin, W G; Goldberg, M A

    1996-01-01

    Inactivation of the von Hippel-Lindau protein (pVHL) has been implicated in the pathogenesis of renal carcinomas and central nervous system hemangioblastomas. These are highly vascular tumors which overproduce angiogenic peptides such as vascular endothelial growth factor/vascular permeability factor (VEGF/VPF). Renal carcinoma cells lacking wild-type pVHL were found to produce mRNAs encoding VEGF/VPF, the glucose transporter GLUT1, and the platelet-derived growth factor B chain under both no...

  13. The von Hippel-Lindau tumor suppressor regulates programmed cell death 5-mediated degradation of Mdm2

    NARCIS (Netherlands)

    Essers, P B; Klasson, T D; Pereboom, T C; Mans, D A; Nicastro, M; Boldt, K; Giles, R H; MacInnes, A W

    2015-01-01

    Functional loss of the von Hippel-Lindau (VHL) tumor suppressor protein (pVHL), which is part of an E3-ubiquitin ligase complex, initiates most inherited and sporadic clear-cell renal cell carcinomas (ccRCC). Genetic inactivation of the TP53 gene in ccRCC is rare, suggesting that an alternate

  14. Beta-2-glycoprotein-1 and alpha-1-antitrypsin as urinary markers of renal cancer in von Hippel-Lindau patients.

    Science.gov (United States)

    Mandili, Giorgia; Notarpietro, Agata; Khadjavi, Amina; Allasia, Marco; Battaglia, Antonino; Lucatello, Barbara; Frea, Bruno; Turrini, Francesco; Novelli, Francesco; Giribaldi, Giuliana; Destefanis, Paolo

    2018-03-01

    Von Hippel-Lindau disease (VHLD) is a rare inherited neoplastic syndrome. Among all the VHLD-associated tumors, clear cell renal cell carcinoma (ccRCC) is the major cause of death. The aim of this paper is the discovery of new non-invasive biomarker for the monitoring of VHLD patients. We compared the urinary proteome of VHLD patients, ccRCC patients and healthy volunteers. Among all differentially expressed proteins, alpha-1-antitrypsin (A1AT) and APOH (beta-2-glycoprotein-1) are strongly over-abundant only in the urine of VHLD patients with a history of ccRCC. A1AT and APOH could be promising non-invasive biomarkers.

  15. 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

  16. TLX controls angiogenesis through interaction with the von Hippel-Lindau protein.

    Science.gov (United States)

    Zeng, Zhao-Jun; Johansson, Erik; Hayashi, Amiko; Chavali, Pavithra L; Akrap, Nina; Yoshida, Takeshi; Kohno, Kimitoshi; Izumi, Hiroto; Funa, Keiko

    2012-06-15

    TLX is known as the orphan nuclear receptor indispensable for maintaining neural stem cells in adult neurogenesis. We report here that neuroblastoma cell lines express high levels of TLX, which further increase in hypoxia to enhance the angiogenic capacity of these cells. The proangiogenetic activity of TLX appears to be induced by its direct binding to the von Hippel-Lindau protein (pVHL), which stabilizes TLX. In turn, TLX competes with hydroxylated hypoxia-inducible factor (HIF-α) for binding to pVHL, which contributes to the stabilization of HIF-2α in neuroblastoma during normoxia. Upon hypoxia, TLX increases in the nucleus where it binds in close proximity of the HIF-response element on the VEGF-promoter chromatin, and, together with HIF-2α, recruits RNA polymerase II to induce VEGF expression. Conversely, depletion of TLX by shRNA decreases the expression of HIF-2α and VEGF as well as the growth-promoting and colony-forming capacity of the neuroblastoma cell lines IMR-32 and SH-SY5Y. On the contrary, silencing HIF-2α will slightly increase TLX, suggesting that TLX acts to maintain a hypoxic environment when HIF-2α is decreasing. Our results demonstrate TLX to play a key role in controlling angiogenesis by regulating HIF-2α. TLX and pVHL might counterbalance each other in important fate decisions such as self-renewal and differentiation, as well as angiogenesis and anti-angiogenesis.

  17. TLX controls angiogenesis through interaction with the von Hippel-Lindau protein

    Directory of Open Access Journals (Sweden)

    Zhao-jun Zeng

    2012-04-01

    TLX is known as the orphan nuclear receptor indispensable for maintaining neural stem cells in adult neurogenesis. We report here that neuroblastoma cell lines express high levels of TLX, which further increase in hypoxia to enhance the angiogenic capacity of these cells. The proangiogenetic activity of TLX appears to be induced by its direct binding to the von Hippel-Lindau protein (pVHL, which stabilizes TLX. In turn, TLX competes with hydroxylated hypoxia-inducible factor (HIF-α for binding to pVHL, which contributes to the stabilization of HIF-2α in neuroblastoma during normoxia. Upon hypoxia, TLX increases in the nucleus where it binds in close proximity of the HIF-response element on the VEGF-promoter chromatin, and, together with HIF-2α, recruits RNA polymerase II to induce VEGF expression. Conversely, depletion of TLX by shRNA decreases the expression of HIF-2α and VEGF as well as the growth-promoting and colony-forming capacity of the neuroblastoma cell lines IMR-32 and SH-SY5Y. On the contrary, silencing HIF-2α will slightly increase TLX, suggesting that TLX acts to maintain a hypoxic environment when HIF-2α is decreasing. Our results demonstrate TLX to play a key role in controlling angiogenesis by regulating HIF-2α. TLX and pVHL might counterbalance each other in important fate decisions such as self-renewal and differentiation, as well as angiogenesis and anti-angiogenesis.

  18. Von Hippel-Lindau Syndrome: Diagnosis and Management of Hemangioblastoma and Pheochromocytoma

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    P. Vaganovs

    2013-01-01

    Full Text Available Introduction. Von Hippel-Lindau (VHL syndrome is a pathological condition that causes various clinical symptoms and is difficult to diagnose. The most common pathological lesions are hemangioblastomas of the central nervous system, retinal angiomas, renal clear cell carcinomas, and pheochromocytomas. Case Report. A 23-year-old female had a syncope episode in 2008. Magnetic resonance imaging (MRI revealed a right temporal hemangioblastoma, which was treated surgically. Genetic screening identified a VHL gene mutation, and computed tomography (CT revealed a left adrenal mass. Since it was unclear whether the mass was a pheochromocytoma, or another benign or malignant tumors, laparoscopic adrenalectomy was performed. A month after surgery, the patient complained of general fatigue, poor concentration, loss of appetite, and insomnia. After careful clinical investigation, the patient was referred to a psychiatrist due to suspected depression, which was confirmed. Conclusions. VHL genetic screening should be performed in cases of hemangioblastoma. In VHL syndrome cases, pheochromocytoma cannot always be diagnosed by biochemical catecholamine analyses; therefore, CT or MRI scanning of the abdomen must be performed. Due to the long treatment period, some patients may develop episodes of depression, which can simulate VHL syndrome.

  19. Functioning Mediastinal Paraganglioma Associated with a Germline Mutation of von Hippel-Lindau Gene

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    Thibault Bahougne

    2018-05-01

    Full Text Available We report the case of a 21-year old woman presenting with high blood pressure and raised normetanephrine levels. Indium-111-pentetreotide single photon-emission computed tomography with computed tomography (SPECT/CT and 2-deoxy-2-[fluorine-18]fluoro-d-glucose (FDG positron emission tomography/computed tomography (PET/CT imaging showing isolated tracer-uptake by a 2 cm tumor close to the costovertebral angle of the third thoracic vertebra. Thoracic surgery led to normalization of normetanephrine levels. Histological findings were consistent with the presence of a paraganglioma. Mutations in SDHA, SDHB, SDHC, SDHD, RET, SDHAF2, TMEM127, MAX, NF1, FH, MDH2, and EPAS1 were absent, but a heterozygous missense mutation, c.311G > T, was found in exon 1 of the von Hippel-Lindau gene, VHL, resulting in a glycine to valine substitution in the VHL protein at position 104, p.Gly104Val. This same mutation was found in both the mother and the 17-year old sister in whom a small retinal hemangioblastoma was also found. We diagnose an unusual functional mediastinal paraganglioma in this young patient with a germline VHL gene mutation, a mutation previously described as inducing polycythemia and/or pheochromocytoma but not paraganglioma or retinal hemangioblastoma.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Posterior fossa scintiangiography: documentation of genetic penetrance of von Hippel--Lindau syndrome in a clinically unaffected girl and her father

    International Nuclear Information System (INIS)

    Hattner, R.S.

    1975-01-01

    The syndrome of von Hippel and Lindau is a rare hereditary disorder constituted by retinal angiomata, posterior fossa and spinal cord hemangioblastomata, cystic and adenomatous dysplasia of major organs, and occasionally renal cell carcinomata. Although the syndrome is transmitted by an autosomal dominant gene, the penetrance is variable and affected persons may have any or all of the elements of the disease. The 16-year-old clinically normal daughter of a patient with the von Hippel--Lindau syndrome demonstrated a vascular posterior fossa lesion on /sup 99m/Tc-DTPA scintiangiography that failed detection in delayed images. Contrast arteriography corroborated the presence of a hemangioblastoma. Noninvasive demonstration of the genetic penetrance of this disorder offers its victims an opportunity for low morbidity early surgical cure of the associated brain lesions. (auth)

  3. Zebrafish mutants in the von Hippel-Lindau tumor suppressor display a hypoxic response and recapitulate key aspects of Chuvash polycythemia

    NARCIS (Netherlands)

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

    2009-01-01

    We have generated 2 zebrafish lines carrying inactivating germline mutations in the von Hippel-Lindau (VHL) tumor suppressor gene ortholog vhl. Mutant embryos display a general systemic hypoxic response, including the up-regulation of hypoxia-induced genes by 1 day after fertilization and a severe

  4. Fluorodeoxyglucose positron emission tomography-computed tomography scan in von Hippel-Lindau syndrome: a case report and review of literature

    International Nuclear Information System (INIS)

    Solav, Shrikant; Bhandari, Ritu

    2012-01-01

    Von Hippel-Lindau (VHL) syndrome is a hereditary autosomal dominant disorder caused by defective tumor suppression gene at 3p25-p26. The gene for VHL disease is found on chromosome 3, and is inherited in a dominant fashion. The VHL gene is a tumor suppressor gene. This means that its role in a normal cell is to stop the uncontrolled growth and proliferation. It is characterized by abnormal growth of blood vessels. It strikes the eyes, central nervous system, kidneys, endocrine glands, etc. It predisposes the patient to retinal angiomas, central nervous system hemangioblastoma, renal cell carcinoma (RCC), pheochromocytomas, islet cell tumor of the pancreas, endolymphatic sac tumors, renal, pancreatic, epididymal cysts. We present a case of familial VHL syndrome whose Fluorine 18-fluorodeoxyglucose positron emission tomography-computed tomography scan was truly positive for adrenal pheochromocytoma but was falsely negative for RCC. Review of literature related to this entity is made. (author)

  5. Constitutional von Hippel-Lindau (VHL) gene deletions detected in VHL families by fluorescence in situ hybridization.

    Science.gov (United States)

    Pack, S D; Zbar, B; Pak, E; Ault, D O; Humphrey, J S; Pham, T; Hurley, K; Weil, R J; Park, W S; Kuzmin, I; Stolle, C; Glenn, G; Liotta, L A; Lerman, M I; Klausner, R D; Linehan, W M; Zhuang, Z

    1999-11-01

    von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited cancer syndrome predisposing to a variety of tumor types that include retinal hemangioblastomas, hemangioblastomas of the central nervous system, renal cell carcinomas, pancreatic cysts and tumors, pheochromocytomas, endolymphatic sac tumors, and epididymal cystadenomas [W. M. Linehan et al., J. Am. Med. Assoc., 273: 564-570, 1995; E. A. Maher and W. G. Kaelin, Jr., Medicine (Baltimore), 76: 381-391, 1997; W. M. Linehan and R. D. Klausner, In: B. Vogelstein and K. Kinzler (eds.), The Genetic Basis of Human Cancer, pp. 455-473, McGraw-Hill, 1998]. The VHL gene was localized to chromosome 3p25-26 and cloned [F. Latif et al., Science (Washington DC), 260: 1317-1320, 1993]. Germline mutations in the VHL gene have been detected in the majority of VHL kindreds. The reported frequency of detection of VHL germline mutations has varied from 39 to 80% (J. M. Whaley et al., Am. J. Hum. Genet., 55: 1092-1102, 1994; Clinical Research Group for Japan, Hum. Mol. Genet., 4: 2233-2237, 1995; F. Chen et al., Hum. Mutat., 5: 66-75, 1995; E. R. Maher et al., J. Med. Genet., 33: 328-332, 1996; B. Zbar, Cancer Surv., 25: 219-232, 1995). Recently a quantitative Southern blotting procedure was found to improve this frequency (C. Stolle et al., Hum. Mutat., 12: 417-423, 1998). In the present study, we report the use of fluorescence in situ hybridization (FISH) as a method to detect and characterize VHL germline deletions. We reexamined a group of VHL patients shown previously by single-strand conformation and sequencing analysis not to harbor point mutations in the VHL locus. We found constitutional deletions in 29 of 30 VHL patients in this group using cosmid and P1 probes that cover the VHL locus. We then tested six phenotypically normal offspring from four of these VHL families: two were found to carry the deletion and the other four were deletion-free. In addition, germline mosaicism of the VHL gene was identified in

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

    OpenAIRE

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

    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-1?) 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...

  7. The allele frequency of two single nucleotide polymorphisms in the von Hippel-Lindau (VHL) tumor suppressor gene in the Taiwanese population.

    Science.gov (United States)

    Wang, Wen-Chung; Chen, Hui-Ju; Shu, Wei-Pang; Tsai, Yi-Chang; Lai, Yen-Chein

    2011-10-01

    The von Hippel-Lindau (VHL) tumor suppressor gene located on chromosome 3p25-26 is implicated in VHL disease. Two informative single nucleotide polymorphisms are at positions 19 and 1149 on the nucleotide sequence from Gene Bank NM_000551. In this study we examined the allele frequencies at these two loci in the Taiwanese population and compared the results to those from European ethnic populations. The allele frequency was examined in 616 healthy individuals including 301 university students and 315 neonates. Both A/G polymorphisms were investigated using restriction fragment length polymorphism analysis created by restriction enzymes, BsaJ I and Acc I. Among these subjects, the allele frequencies at 19 SNP and 1149 SNP for variant G were 0.130 and 0.133, respectively. And these results were significant differences from those of the Caucasian populations. In addition, 90% of the tested subjects had identical genotypes at these two loci suggesting the existence of nonrandom association of alleles. We found that the G allele frequency at these two loci in the Taiwanese population is much lower than that in people from Western countries. This phenomenon may be attributed to ethnic effects. Copyright © 2011. Published by Elsevier B.V.

  8. MicroRNAs Associated with Von Hippel-Lindau Pathway in Renal Cell Carcinoma: A Comprehensive Review.

    Science.gov (United States)

    Schanza, Lisa-Maria; Seles, Maximilian; Stotz, Michael; Fosselteder, Johannes; Hutterer, Georg C; Pichler, Martin; Stiegelbauer, Verena

    2017-11-22

    Renal cell carcinoma (RCC) are the most common renal neoplasia and can be divided into three main histologic subtypes, among which clear cell RCC is by far the most common form of kidney cancer. Despite substantial advances over the last decade in the understanding of RCC biology, surgical treatments, and targeted and immuno-therapies in the metastatic setting, the prognosis for advanced RCC patients remains poor. One of the major problems with RCC treatment strategies is inherent or acquired resistance towards therapeutic agents over time. The discovery of microRNAs (miRNAs), a class of small, non-coding, single-stranded RNAs that play a crucial role in post-transcriptional regulation, has added new dimensions to the development of novel diagnostic and treatment tools. Because of an association between Von Hippel-Lindau (VHL) genes with chromosomal loss in 3p25-26 and clear cell RCC, miRNAs have attracted considerable scientific interest over the last years. The loss of VHL function leads to constitutional activation of the hypoxia inducible factor (HIF) pathway and to consequent expression of numerous angiogenic and carcinogenic factors. Since miRNAs represent key players of carcinogenesis, tumor cell invasion, angiogenesis, as well as in development of metastases in RCC, they might serve as potential therapeutic targets. Several miRNAs are already known to be dysregulated in RCC and have been linked to biological processes involved in tumor angiogenesis and response to anti-cancer therapies. This review summarizes the role of different miRNAs in RCC angiogenesis and their association with the VHL gene, highlighting their potential role as novel drug targets.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Efficient generation of dopamine neuron-like cells from skin-derived precursors with a synthetic peptide derived from von Hippel-Lindau protein.

    Science.gov (United States)

    Kubo, Atsuhiko; Yoshida, Tetsuhiko; Kobayashi, Nahoko; Yokoyama, Takaakira; Mimura, Toshiro; Nishiguchi, Takao; Higashida, Tetsuhiro; Yamamoto, Isao; Kanno, Hiroshi

    2009-12-01

    Skin-derived precursors (SKPs) from mammalian dermis represent neural crest-related stem cells capable of differentiating into both neural and mesodermal progency. SKPs are of clinical interest because they serve as accessible autologous donor cells for neuronal repair for neuronal intractable diseases. However, little is known about the efficient generation of neurons from SKPs, and phenotypes of neurons generated from SKPs have been restricted. In addition, the neuronal repair using their generated neurons as donor cells has not been achieved. The von Hippel-Lindau protein (pVHL) is one of the proteins that play an important role during neuronal differentiation, and recently neuronal differentiation of neural progenitor cells by intracellular delivery of a synthetic VHL peptide derived from elongin BC-binding site has been demonstrated. In the present study, a synthetic VHL peptide derived from elongin BC-binding site was conjugated to the protein transduction domain (PTD) of HIV-TAT protein (TATVHL peptide) to facilitate entry into cells, and we demonstrate the efficient generation of cells with dopaminergic phenotype from SKPs with the intracellular delivery of TATVHL peptide, and characterized the generated cells. The TATVHL peptide-treated SKPs expressed neuronal marker proteins, particularly dopamine neuron markers, and also up-regulated mRNA levels of proneural basic helix-loop-helix factors. After the TATVHL peptide treatment, transplanted SKPs into Parkinson's disease (PD) model rats sufficiently differentiated into dopamine neuron-like cells in PD model rats, and partially but significantly corrected behavior of PD model rats. The generated dopamine neuron-like cells are expected to serve as donor cells for neuronal repair for PD.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Psychological impact of von Hippel-Lindau genetic screening in patients with a previous history of hemangioblastoma of the central nervous system.

    Science.gov (United States)

    Rochette, Claire; Baumstarck, Karine; Canoni-Zattara, Hélène; Abdullah, Ahmad Esmaeel; Figarella-Branger, Dominique; Pertuit, Morgane; Barlier, Anne; Castinetti, Frédéric; Pacak, Karel; Metellus, Philippe; Taïeb, David

    2018-05-15

    Von Hippel-Lindau (VHL) syndrome is a hereditary cancer syndrome characterized by a high risk of developing benign and malignant tumors, including central nervous system hemangioblastomas (CNS HBs). For an early diagnosis of VHL, before the occurrence of cancers (especially renal cell carcinoma), it is of huge importance to initiate VHL genetic testing in at-risk patients. The aim of the study was to assess the psychological impact of VHL genetic testing in patients previously diagnosed with a CNS HB. From 1999 until 2015, 55 patients underwent surgery for CNS HBs. Eleven patients were already screened for VHL mutations and 3 patients deceased before the start of the study. From the remaining 42 patients, 24 were accepted to be enrolled in the study. Assessment of psychological impact of VHL genetic testing was performed by measuring anxiety levels, mood disorders, quality of life, and psychological consequences of genetic screening. Twenty-one of the enrolled 24 patients underwent VHL genetic testing and 12 patients came back for the communication of positive genetic results. The baseline psychological status did not differ between these 2 groups. Patients who attended the visit of communication of genetic results had similar anxiety levels compared to those who had not. Furthermore, they also experienced an improvement in the level of anxiety and two QoL dimension scores compared to their baseline status. In summary, there is no evidence of a negative psychosocial impact of VHL genetic testing in patients with a previous history of CNS HB. We, therefore, recommend the recall of patients who have not been previously screened.

  13. Von Hippel-Lindau tumor suppressor gene loss in renal cell carcinoma promotes oncogenic epidermal growth factor receptor signaling via Akt-1 and MEK-1.

    Science.gov (United States)

    Lee, S Justin; Lattouf, Jean-Baptiste; Xanthopoulos, Julie; Linehan, W Marston; Bottaro, Donald P; Vasselli, James R

    2008-10-01

    Clear-cell renal cell carcinoma (RCC) is the most prevalent form of kidney cancer and is frequently associated with loss of von Hippel-Lindau (VHL) gene function, resulting in the aberrant transcriptional activation of genes that contribute to tumor growth and metastasis, including transforming growth factor-alpha (TGF-alpha), a ligand of the epidermal growth factor receptor (EGFR) tyrosine kinase. To determine the functional impact of EGFR activation on RCC, we suppressed critical components of this pathway: EGFR, Akt-1, and MEK-1. Stable transfection of RCC cells with plasmids bearing shRNA directed against each of these genes was used to individually suppress their expression. Transfectants were characterized for growth and invasiveness in vitro and tumorigenesis in vivo. RCC cell transfectants displayed significantly reduced growth rate and matrix invasion in vitro and RCC tumor xenograft growth rate in vivo. Analysis of tumor cells that emerged after extended periods in each model showed that significant EGFR suppression was sustained, whereas Akt-1 and MEK-1 knock-down cells had escaped shRNA suppression. EGFR, Akt-1, and MEK-1 are individually critical for RCC cell invasiveness in vitro and tumorigenicity in vivo, and even partial suppression of each can have a significant impact on tumor progression. The emergence of transfectants that had escaped Akt-1 and MEK-1 suppression during tumorigenicity experiments suggests that these effectors may each be more critical than EGFR for RCC tumorigenesis, consistent with results from clinical trials of EGFR inhibitors for RCC, where durable clinical responses have not been seen.

  14. Von Hippel-Lindau Tumor Suppressor Gene Loss in Renal Cell Carcinoma Promotes Oncogenic Epidermal Growth Factor Receptor Signaling via Akt-1 and MEK1

    Science.gov (United States)

    Lee, S. Justin; Lattouf, Jean-Baptiste; Xanthopoulos, Julie; Linehan, W. Marston; Bottaro, Donald P.; Vasselli, James R.

    2008-01-01

    Objectives Clear-cell renal cell carcinoma (RCC) is the most prevalent form of kidney cancer and is frequently associated with loss of von Hippel-Lindau (VHL) gene function, resulting in the aberrant transcriptional activation of genes that contribute to tumor growth and metastasis, including transforming growth factor-α (TGF-α), a ligand of the epidermal growth factor receptor (EGFR) tyrosine kinase. To determine the functional impact of EGFR activation on RCC, we suppressed critical components of this pathway: EGFR, Akt-1, and MEK-1. Methods Stable transfection of RCC cells with plasmids bearing shRNA directed against each of these genes was used to individually suppress their expression. Transfectants were characterized for growth and invasiveness in vitro and tumorigenesis in vivo. Results RCC cell transfectants displayed significantly reduced growth rate and matrix invasion in vitro and RCC tumor xenograft growth rate in vivo. Analysis of tumor cells that emerged after extended periods in each model showed that significant EGFR suppression was sustained, whereas Akt-1 and MEK-1 knockdown cells had escaped shRNA suppression. Conclusions EGFR, Akt-1, and MEK-1 are individually critical for RCC cell invasiveness in vitro and tumorigenicity in vivo, and even partial suppression of each can have a significant impact on tumor progression. The emergence of transfectants that had escaped Akt-1 and MEK-1 suppression during tumorigenicity experiments suggests that these effectors may each be more critical than EGFR for RCC tumorigenesis, consistent with results from clinical trials of EGFR inhibitors for RCC, where durable clinical responses have not been seen. PMID:18243508

  15. 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.

  16. The von Hippel-Lindau tumor suppressor gene inhibits hepatocyte growth factor/scatter factor-induced invasion and branching morphogenesis in renal carcinoma cells.

    Science.gov (United States)

    Koochekpour, S; Jeffers, M; Wang, P H; Gong, C; Taylor, G A; Roessler, L M; Stearman, R; Vasselli, J R; Stetler-Stevenson, W G; Kaelin, W G; Linehan, W M; Klausner, R D; Gnarra, J R; Vande Woude, G F

    1999-09-01

    Loss of function in the von Hippel-Lindau (VHL) tumor suppressor gene occurs in familial and most sporadic renal cell carcinomas (RCCs). VHL has been linked to the regulation of cell cycle cessation (G(0)) and to control of expression of various mRNAs such as for vascular endothelial growth factor. RCC cells express the Met receptor tyrosine kinase, and Met mediates invasion and branching morphogenesis in many cell types in response to hepatocyte growth factor/scatter factor (HGF/SF). We examined the HGF/SF responsiveness of RCC cells containing endogenous mutated (mut) forms of the VHL protein (VHL-negative RCC) with that of isogenic cells expressing exogenous wild-type (wt) VHL (VHL-positive RCC). We found that VHL-negative 786-0 and UOK-101 RCC cells were highly invasive through growth factor-reduced (GFR) Matrigel-coated filters and exhibited an extensive branching morphogenesis phenotype in response to HGF/SF in the three-dimensional (3D) GFR Matrigel cultures. In contrast, the phenotypes of A498 VHL-negative RCC cells were weaker, and isogenic RCC cells ectopically expressing wt VHL did not respond at all. We found that all VHL-negative RCC cells expressed reduced levels of tissue inhibitor of metalloproteinase 2 (TIMP-2) relative to the wt VHL-positive cells, implicating VHL in the regulation of this molecule. However, consistent with the more invasive phenotype of the 786-0 and UOK-101 VHL-negative RCC cells, the levels of TIMP-1 and TIMP-2 were reduced and levels of the matrix metalloproteinases 2 and 9 were elevated compared to the noninvasive VHL-positive RCC cells. Moreover, recombinant TIMPs completely blocked HGF/SF-mediated branching morphogenesis, while neutralizing antibodies to the TIMPs stimulated HGF/SF-mediated invasion in vitro. Thus, the loss of the VHL tumor suppressor gene is central to changes that control tissue invasiveness, and a more invasive phenotype requires additional genetic changes seen in some but not all RCC lines. These

  17. Renal Cell Carcinoma Programmed Death-ligand 1, a New Direct Target of Hypoxia-inducible Factor-2 Alpha, is Regulated by von Hippel-Lindau Gene Mutation Status.

    Science.gov (United States)

    Messai, Yosra; Gad, Sophie; Noman, Muhammad Zaeem; Le Teuff, Gwenael; Couve, Sophie; Janji, Bassam; Kammerer, Solenne Florence; Rioux-Leclerc, Nathalie; Hasmim, Meriem; Ferlicot, Sophie; Baud, Véronique; Mejean, Arnaud; Mole, David Robert; Richard, Stéphane; Eggermont, Alexander M M; Albiges, Laurence; Mami-Chouaib, Fathia; Escudier, Bernard; Chouaib, Salem

    2016-10-01

    Clear cell renal cell carcinomas (ccRCC) frequently display a loss of function of the von Hippel-Lindau (VHL) gene. To elucidate the putative relationship between VHL mutation status and immune checkpoint ligand programmed death-ligand 1 (PD-L1) expression. A series of 32 renal tumors composed of 11 VHL tumor-associated and 21 sporadic RCCs were used to evaluate PD-L1 expression levels after sequencing of the three exons and exon-intron junctions of the VHL gene. The 786-O, A498, and RCC4 cell lines were used to investigate the mechanisms of PD-L1 regulation. Fisher's exact test was used for VHL mutation and Kruskal-Wallis test for PD-L1 expression. If no covariate accounted for the association of VHL and PD-L1, then a Kruskal-Wallis test was used; otherwise Cochran-Mantel-Haenzsel test was used. We also used the Fligner-Policello test to compare two medians when the distributions had different dispersions. We demonstrated that tumors from ccRCC patients with VHL biallelic inactivation (ie, loss of function) display a significant increase in PD-L1 expression compared with ccRCC tumors carrying one VHL wild-type allele. Using the inducible VHL 786-O-derived cell lines with varying hypoxia-inducible factor-2 alpha (HIF-2α) stabilization levels, we showed that PD-L1 expression levels positively correlate with VHL mutation and HIF-2α expression. Targeting HIF-2α decreased PD-L1, while HIF-2α overexpression increased PD-L1 mRNA and protein levels in ccRCC cells. Interestingly, chromatin immunoprecipitation and luciferase assays revealed a direct binding of HIF-2α to a transcriptionally active hypoxia-response element in the human PD-L1 proximal promoter in 786-O cells. Our work provides the first evidence that VHL mutations positively correlate with PD-L1 expression in ccRCC and may influence the response to ccRCC anti-PD-L1/PD-1 immunotherapy. We investigated the relationship between von Hippel-Lindau mutations and programmed death-ligand 1 expression. We

  18. Von Hippel-Lindau Syndrome

    Science.gov (United States)

    ... starting. For more information, talk with an assisted reproduction specialist at a fertility clinic. How common is ... when a person has: Multiple hemangioblastomas of the brain, spinal cord, or eye, or 1 hemangioblastoma and ...

  19. The in vitro and in vivo effects of re-expressing methylated von Hippel-Lindau tumor suppressor gene in clear cell renal carcinoma with 5-aza-2'-deoxycytidine.

    Science.gov (United States)

    Alleman, Wade G; Tabios, Ray L; Chandramouli, Gadisetti V R; Aprelikova, Olga N; Torres-Cabala, Carlos; Mendoza, Arnulfo; Rogers, Craig; Rodgers, Craig; Sopko, Nikolai A; Linehan, W Marston; Vasselli, James R

    2004-10-15

    Clear cell renal carcinoma (ccRCC) is strongly associated with loss of the von Hippel-Lindau (VHL) tumor suppressor gene. The VHL gene is functionally lost through hypermethylation in up to 19% of sporadic ccRCC cases. We theorized that re-expressing VHL silenced by methylation in ccRCC cells, using a hypo-methylating agent, may be an approach to treatment in patients with this type of cancer. We test the ability of two hypo-methylating agents to re-express VHL in cell culture and in mice bearing human ccRCC and evaluate the effects of re-expressed VHL in these models. Real-time reverse transcription-PCR was used to evaluate the ability of zebularine and 5-aza-2'-deoxycytidine (5-aza-dCyd) to re-express VHL in four ccRCC cell lines with documented VHL gene silencing through hypermethylation. We evaluated if the VHL re-expressed after hypo-methylating agent treatment could recreate similar phenotypic changes in ccRCC cells observed when the VHL gene is re-expressed via transfection in cell culture and in a xenograft mouse model. Finally we evaluate global gene expression changes occurring in our cells, using microarray analysis. 5-Aza-dCyd was able to re-express VHL in our cell lines both in culture and in xenografted murine tumors. Well described phenotypic changes of VHL expression including decreased invasiveness into Matrigel, and decreased vascular endothelial growth factor and glucose transporter-1 expression were observed in the treated lines. VHL methylated ccRCC xenografted tumors were significantly reduced in size in mice treated with 5-aza-dCyd. Mice bearing nonmethylated but VHL-mutated tumors showed no tumor shrinkage with 5-aza-dCyd treatment. Hypo-methylating agents may be useful in the treatment of patients having ccRCC tumors consisting of cells with methylated VHL.

  20. Radiological diagnosis of visceral manifestations in Hippel-Lindau Syndrome

    International Nuclear Information System (INIS)

    Wittich, G.; Czembirek, H.; Fridrich, L.; Imhof, H.; Vienna Univ.

    1980-01-01

    The efficiency of radiological methods in the diagnosis of visceral manifestations of Hippel-Lindau Syndrome is discussed by means of a case report as well as by the results from studies of other authors. The importance of detecting small renal malignancies (often occurring bilaterally and multifocally in this disease) is stressed since benign (cystic, adenomatous, angiomatous) lesions of visceral organs are of minor clinical relevance. Pheochromocytomas, found in about 20% of cases, are primarily diagnosed clinically. The diagnostic goal of precise quantification of neoplastic renal tumors and of unequivocal differentiation between cystic and solid lesions appears to be achieved by the combination of computertomographic and pharmaco-angiographic techniques. A prerequisite for the alternative use of ultrasound is optimal imaging of all parts of renal parenchyma. (orig.) [de

  1. 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

    the international diagnostic criteria. We found an overall penetrance of 87% at age 60 years. When considering only vHL patients who have not attended surveillance, 20% will still be asymptomatic at age 60 years. This should be considered in the context of genetic counselling, especially when assessing the risk...... of vHL in asymptomatic adult first-degree relatives who are often not genetically tested.European Journal of Human Genetics advance online publication, 14 December 2016; doi:10.1038/ejhg.2016.173....

  2. Von Hippel-Lindau Disease: A Rare Familiar Multi-System Disorder and the Impact of the Clinical Nurse Specialist

    Science.gov (United States)

    1993-01-01

    hemodialysis has been reported by Fetner, Barilla , Scott, Ballard, and Peters (1976). They have proposed renal transplantation if their patient survives five...Urology, 18, 599-600. Feldstein, M., & Rait, D. (1992). Family assessment in an oncology setting. Cancer Nursing, 15(3), 161-172. Fetner, C., Barilla , D

  3. Polycystic kidney disease in a patient with achondroplasia ...

    African Journals Online (AJOL)

    Autosomal dominant polycystic kidney disease is a multisystem disease involving many organs. An association with other diseases such as tuberous sclerosis, von Hippel-Lindau disease and Marfan syndrome have been previously described. We describe a 35 year old female with achondroplasia who developed ...

  4. Epithelial hyperplasia in human polycystic kidney diseases. Its role in pathogenesis and risk of neoplasia.

    OpenAIRE

    Bernstein, J.; Evan, A. P.; Gardner, K. D.

    1987-01-01

    The importance of tubular epithelial hyperplasia in polycystic kidney diseases has become apparent during the last decade. Micropapillary hyperplasia occurs in autosomal dominant polycystic kidney disease, in localized cystic disease, and in acquired cystic disease. Neoplastic or severely dysplastic epithelial hyperplasia occurs in von Hippel-Lindau disease. A histopathologically distinctive epithelial hyperplasia occurs in tuberous sclerosis. In each of these conditions, epithelial hyperplas...

  5. Genetics Home Reference: von Hippel-Lindau syndrome

    Science.gov (United States)

    ... 17 [updated 2015 Aug 6]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): ...

  6. 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.

  7. 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...... is not due to concurrence of a naturally milder tumor development in women's fertile ages, as the rate of new tumor development increases for both men and women from 20 years of age, even more in men than in women....... of increasing lengths of 1, 3, and 5 years after conception. Furthermore, we compared age-related manifestation rates for women and men. RESULTS: From birth to the participants' current age, 581 manifestations were diagnosed; mean age was 37.5 years (range 2-64 years). Seventeen women had completed 30...

  8. 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 of t...

  9. [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.

  10. 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....

  11. The allele frequency of two single nucleotide polymorphisms in the von Hippel-Lindau (VHL tumor suppressor gene in the Taiwanese population

    Directory of Open Access Journals (Sweden)

    Wen-Chung Wang

    2011-10-01

    Conclusion: We found that the G allele frequency at these two loci in the Taiwanese population is much lower than that in people from Western countries. This phenomenon may be attributed to ethnic effects.

  12. Dissecting fragment-based lead discovery at the von Hippel-Lindau protein:hypoxia inducible factor 1α protein-protein interface.

    Science.gov (United States)

    Van Molle, Inge; Thomann, Andreas; Buckley, Dennis L; So, Ernest C; Lang, Steffen; Crews, Craig M; Ciulli, Alessio

    2012-10-26

    Fragment screening is widely used to identify attractive starting points for drug design. However, its potential and limitations to assess the tractability of often challenging protein:protein interfaces have been underexplored. Here, we address this question by means of a systematic deconstruction of lead-like inhibitors of the pVHL:HIF-1α interaction into their component fragments. Using biophysical techniques commonly employed for screening, we could only detect binding of fragments that violate the Rule of Three, are more complex than those typically screened against classical druggable targets, and occupy two adjacent binding subsites at the interface rather than just one. Analyses based on ligand and group lipophilicity efficiency of anchored fragments were applied to dissect the individual subsites and probe for binding hot spots. The implications of our findings for targeting protein interfaces by fragment-based approaches are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Renal cystic disease: A practical overview

    International Nuclear Information System (INIS)

    Hartman, D.S.

    1987-01-01

    Renal cystic disease includes a group of lesions with extremely diverse clinical, radiographic, and pathologic findings. The recent development of multiple imaging systems to study renal cystic disease has resulted in considerable interest in correlating the images obtained by different modalities with each other and with the underlying gross pathology. A thorough knowledge of the disturbed morphology and natural history of these diseases will lead to a better understanding of their appearance on radiologic imaging. This refresher course correlates disturbed morphology with appearances on diagnostic imaging, urography, US, angiography, CT, and MR imaging. The advantages and limitations of each imaging method are detailed. A practical classification emphasizing differential features is presented. The presentation is divided into two parts. In the first part typical and atypical cystic masses, including acquired cystic disease (from dialysis), Von Hippel-Lindau disease, and the cystic disease of tuberous sclerosis are discussed. In the second part, polycystic kidney disease (dominant and recessive), medullary cystic disease, medullary sponge kidney, multicycle-dysplastic kidney, renal sinus cysts (peripelvic), and pluricystic kidney disease are discussed

  14. 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.

  15. MicroRNAs in the pathogenesis of cystic kidney disease.

    Science.gov (United States)

    Phua, Yu Leng; Ho, Jacqueline

    2015-04-01

    Cystic kidney diseases are common renal disorders characterized by the formation of fluid-filled epithelial cysts in the kidneys. The progressive growth and expansion of the renal cysts replace existing renal tissue within the renal parenchyma, leading to reduced renal function. While several genes have been identified in association with inherited causes of cystic kidney disease, the molecular mechanisms that regulate these genes in the context of post-transcriptional regulation are still poorly understood. There is increasing evidence that microRNA (miRNA) dysregulation is associated with the pathogenesis of cystic kidney disease. In this review, recent studies that implicate dysregulation of miRNA expression in cystogenesis will be discussed. The relationship of specific miRNAs, such as the miR-17∼92 cluster and cystic kidney disease, miR-92a and von Hippel-Lindau syndrome, and alterations in LIN28-LET7 expression in Wilms tumor will be explored. At present, there are no specific treatments available for patients with cystic kidney disease. Understanding and identifying specific miRNAs involved in the pathogenesis of these disorders may have the potential to lead to the development of novel therapies and biomarkers.

  16. MANAGEMENT OF ENDOCRINE DISEASE: Outcome of adrenal sparing surgery in heritable pheochromocytoma.

    Science.gov (United States)

    Castinetti, F; Taieb, D; Henry, J F; Walz, M; Guerin, C; Brue, T; Conte-Devolx, B; Neumann, H P H; Sebag, F

    2016-01-01

    The management of hereditary pheochromocytoma has drastically evolved in the last 20 years. Bilateral pheochromocytoma does not increase mortality in MEN2 or von Hippel-Lindau (VHL) mutation carriers who are followed regularly, but these mutations induce major morbidities if total bilateral adrenalectomy is performed. Cortical sparing adrenal surgery may be proposed to avoid definitive adrenal insufficiency. The surgical goal is to leave sufficient cortical tissue to avoid glucocorticoid replacement therapy. This approach was achieved by the progressive experience of minimally invasive surgery via the transperitoneal or retroperitoneal route. Cortical sparing adrenal surgery exhibits management of all patients with MEN2 or VHL hereditary pheochromocytoma. Hereditary pheochromocytoma is a rare disease, and a randomized trial comparing cortical sparing vs classical adrenalectomy is probably not possible. This lack of data most likely explains why cortical sparing surgery has not been adopted in most expert centers that perform at least 20 procedures per year for the treatment of this disease. This review examined recent data to provide insight into the technique, its indications, and the results and subsequent follow-up in the management of patients with hereditary pheochromocytoma with a special emphasis on MEN2. © 2016 European Society of Endocrinology.

  17. Von Hippel–Lindau disease

    Directory of Open Access Journals (Sweden)

    Juhara Haron

    2017-04-01

    Full Text Available Von Hippel–Lindau (VHL disease is a rare autosomal dominantly inherited multisystem disorder characterised by the development of a variety of benign and malignant tumours. We report a case of VHL disease that was inherited by a daughter from her father, who both presented at a young age with progressive headache and were found to have a posterior fossa haemangioblastoma (HB on magnetic resonance imaging (MRI. Multiple benign pancreatic and renal cysts were also noted in both patients.

  18. Tailored imaging of islet cell tumors of the pancreas amidst increasing options

    NARCIS (Netherlands)

    Fiebrich, Helle-Brit; van Asselt, Sophie J.; Brouwers, Adrienne H.; van Dullemen, Hendrik M.; Pijl, Milan E. J.; Elsinga, Philip H.; Links, Thera P.; de Vries, Elisabeth G. E.

    Pancreatic islet cell tumors are neuroendocrine tumors, which can produce hormones and can arise as part of multiple endocrine neoplasia type 1 or von-Hippel-Lindau-disease, two genetically well-defined hereditary cancer syndromes. Currently, technical innovation improves conventional and specific

  19. Impact of upper gastrointestinal endoscopic ultrasound in children

    DEFF Research Database (Denmark)

    Bjerring, Ole Steen; Durup, Jesper; Qvist, Niels

    2008-01-01

    , 18 patients (12 boys, 6 girls; median age 12 years, range 0.5-15) underwent EUS. The indications were as follows: tumor (9), epigastric pain (3), recurrent pancreatitis (2), unexplained jaundice (2), hypoglycemia (1), and von Hippel-Lindau disease (1). We concluded that EUS had a significant impact...

  20. Papillary Cystadenoma: An Incidental Finding in Tubal Ligation

    Directory of Open Access Journals (Sweden)

    Tabitha Lynn Ward

    2018-01-01

    Full Text Available von Hippel-Lindau disease (vHLD is a rare autosomal dominant disorder with multiple benign and malignant tumors of different organs. We report a papillary cystadenoma of the mesosalpinx found in close association with an adenomatoid tumor discovered incidentally following tubal ligation in a patient with vHLD.

  1. 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.

  2. Genetics of Kidney Cancer (Renal Cell Cancer) (PDQ®)—Health Professional Version

    Science.gov (United States)

    Genetics of Kidney Cancer (Renal Cell) includes the hereditary cancer syndromes von Hippel-Lindau disease, hereditary leiomyomatosis and renal cell cancer, Birt-Hogg-Dubé syndrome, and hereditary papillary renal carcinoma. Get comprehensive information on these syndromes in this clinician summary.

  3. Von Willebrand disease protects against arterial thrombosis

    NARCIS (Netherlands)

    Sanders, Y.V.; Eikenboom, J.C.; De Wee, E.M.; Van Der Bom, J.G.; Cnossen, M.H.; Degenaar-Dujardin, M.E.; Fijnvandraat, K.; Kamphuisen, P.W.; Laros-Van Gorkum, B.A.; Meijer, K.; Mauser -Bunschoten, E.P.; Leebee k, F.W.

    Background and Aims: Von Willebrand disease (VWD) is caused by reduced levels of or dysfunctional von Willebrand factor (VWF) and is characterized by a bleeding tendency. It is well known that individuals with high VWF levels have a higher risk for arterial thrombosis. Although it has never been

  4. Progression of Epididymal Maldevelopment Into Hamartoma-like Neoplasia in VHL Disease

    Directory of Open Access Journals (Sweden)

    Gautam U. Mehta

    2008-10-01

    Full Text Available Inactivation of the von Hippel-Lindau (VHL gene and activation of the hypoxia-inducible factor (HIF in susceptible cells precedes formation of tumorlets and frank tumor in the epididymis of male VHL patients. We performed detailed histologic and molecular pathologic analysis of tumor-free epididymal tissues from VHL patients to obtain further insight into early epididymal tumorigenesis. Four epididymides from two VHL patients were serially sectioned to allow for three-dimensional visualization of morphologic changes. Areas of interest were genetically analyzed by tissue microdissection, immunohistochemistry for HIF and markers for mesonephric differentiation, and in situ hybridization for HIF downstream target vascular endothelial growth factor. Structural analysis of the epididymides revealed marked deviations from the regular anatomic structure resulting from impaired organogenesis. Selected efferent ductules were represented by disorganized mesonephric cells, and the maldeveloped mesonephric material was VHL-deficient by allelic deletion analysis. Furthermore, we observed maldeveloped mesonephric material near cystic structures, which were also VHL-deficient and were apparent derivatives of maldeveloped material. Finally, a subset of VHL-deficient cells was structurally integrated in regular efferent ductules; proliferation of intraductular VHL-deficient cells manifests itself as papillary growth into the ductular lumen. Furthermore, we clarify that that there is a pathogenetic continuum between microscopic tumorlets and formation of tumor. In multiple locations, three-dimensional reconstruction revealed papillary growth to extend deeply into ductular lumina, indicative of progression into early hamartoma-like neoplasia. We conclude epididymal tumorigenesis in VHL disease to occur in two distinct sequential steps: maldevelopment of VHL-deficient mesonephric cells, followed by neoplastic papillary proliferation.

  5. Pin1, a new player in the fate of HIF-1α degradation: an hypothetical mechanism inside vascular damage as Alzheimer’s disease risk factor.

    Directory of Open Access Journals (Sweden)

    Elena eLonati

    2014-01-01

    Full Text Available Aetiology of neurodegenerative mechanisms underlying Alzheimer's disease (AD are still under elucidation. The contribution of cerebrovascular deficiencies (such as cerebral ischemia/stroke has been strongly endorsed in recent years. Reduction of blood supply leading to hypoxic condition is known to activate cellular responses mainly controlled by hypoxia-inducible transcription factor-1 (HIF-1. Thus alterations of oxygen responsive HIF-1α subunit in the central nervous system may contribute to the cognitive decline, especially influencing mechanisms associated to APP (amyloid precursor protein amyloidogenic metabolism. Although HIF-1α protein level is known to be regulated by von Hippel-Lindau (VHL ubiquitin-proteasome system, it has been recently suggested that Gsk-3β (glycogen synthase kinase-3β promotes a VHL-independent HIF-1α degradation. Here we provide evidences that in rat primary hippocampal cell cultures, HIF-1α degradation might be mediated by a synergic action of Gsk-3β and Pin1 (peptidyl-prolyl cis/trans isomerase. In post-ischemic conditions, such as those mimicked with oxygen glucose deprivation (OGD, HIF-1α protein level increases remaining unexpectedly high for long time after normal condition restoration jointly with the increase of LDH (lactate dehydrogenase and BACE1 (β-secretase 1 protein expression (70% and 140% respectively. Interestingly the Pin1 activity decreases about 40%-60% and Pin1S16 inhibitory phosphorylation significantly increases, indicating that Pin1 binding to its substrate and enzymatic activity are reduced by treatment. Co-immunoprecipitation experiments demonstrate that HIF-1α/Pin1 in normoxia are associated, and that in presence of specific Pin1 and Gsk-3β inhibitors their interaction is reduced in parallel to an increase of HIF-1α protein level. Thus we suggest that in post-OGD neurons the high level of HIF-1α might be due to Pin1 binding ability and activity reduction which affects HIF-1

  6. The Molecular Genetics of von Willebrand Disease

    Directory of Open Access Journals (Sweden)

    Ergül Berber

    2012-12-01

    Full Text Available Quantitative and/or qualitative deficiency of von Willebrand factor (vWF is associated with the most common inherited bleeding disease von Willebrand disease (vWD. vWD is a complex disease with clinical and genetic heterogeneity. Incomplete penetrance and variable expression due to genetic and environmental factors contribute to its complexity. vWD also has a complex molecular pathogenesis. Some vWF gene mutations are associated with the affected vWF biosynthesis and multimerization, whereas others are associated with increased clearance and functional impairment. Moreover, in addition to a particular mutation, type O blood may result in the more severe phenotype. The present review aimed to provide a summary of the current literature on the molecular genetics of vWD.

  7. The molecular genetics of von Willebrand disease.

    Science.gov (United States)

    Berber, Ergül

    2012-12-01

    Quantitative and/or qualitative deficiency of von Willebrand factor (vWF) is associated with the most common inherited bleeding disease von Willebrand disease (vWD). vWD is a complex disease with clinical and genetic heterogeneity. Incomplete penetrance and variable expression due to genetic and environmental factors contribute to its complexity. vWD also has a complex molecular pathogenesis. Some vWF gene mutations are associated with the affected vWF biosynthesis and multimerization, whereas others are associated with increased clearance and functional impairment. Moreover, in addition to a particular mutation, type O blood may result in the more severe phenotype. The present review aimed to provide a summary of the current literature on the molecular genetics of vWD. None declared.

  8. von Willebrand Disease (For Parents)

    Science.gov (United States)

    [Skip to Content] for Parents Parents site Sitio para padres General Health Growth & Development Infections Diseases & Conditions Pregnancy & Baby Nutrition & Fitness Emotions & Behavior School & Family ...

  9. [Precocious puberty and von Recklinghausen's disease].

    Science.gov (United States)

    Barg, Ewa; Wikiera, Beata; Basiak, Aleksander; Głab, Ewa

    2006-01-01

    Von Recklinghausen's disease belongs to a group of neurocutaneous syndromes and is characterised by skin, nerve and bone abnormalities. We present a case of von Recklinghausen's disease and precocious puberty in 7-year-old boy. At the age of three café au lait spots on the skin and an incranial tumour situated near the optic chiasm--qualified as inoperable--were discovered. At the age of 7 first signs of precocious puberty appeared (pubic hair P3 and enlargement of the testes (15 ml) and penis). Laboratory measurements included: LH 7.5 mIU/ml, FSH 1.1 mIU/ml, testosterone 183 ng/ml, assessment of bone age: 9 years. The response to LHRH stimulation was characteristic for true precocious puberty (LH 15.9 mIU/ml and FSH 1.5 mIU/ml after 30 minutes). The MRI of the brain showed a tumour of the suprasellar region with compression of pituitary stalk. True precocious puberty was diagnosed. Treatment with Diphereline was introduced. At present the boy is 9 years old and has been treated with Diphereline for 16 months. The volume of the testicles has decreased to 7 ml and loss of pubic hair was noted. The MRI does not show any progression in tumour growth. The authors would like to underline the need of close observation of children with von Reclinghausen disease with regard to possibility of uncovering true precocious puberty which is critical for rapid diagnosis and introduction of correct treatment.

  10. Translational Medicine Advances in von Willebrand Disease

    Science.gov (United States)

    Lillicrap, David

    2014-01-01

    Following the recognition of von Willebrand disease (VWD) in 1926 and the cloning of the gene for von Willebrand factor (VWF) in 1985, significant advances have been made in our fundamental knowledge of both the disease and the protein. Some of this new knowledge has also begun to impact the clinical management of VWD. First, the progressive increase in our understanding of the molecular genetic basis of VWD has resulted in rational applications of molecular testing to complement the current range of phenotypic tests for VWD. These molecular genetic strategies are most effectively directed at the prenatal diagnosis of type 3 VWD and confirmatory testing for types 2B and 2N disease. In contrast, the use of molecular testing to clarify the diagnosis of type 1 VWD is of marginal benefit, at best. In terms of VWD therapies, a new recombinant VWF concentrate has recently completed successful clinical trials and is now awaiting more widespread application. There have even been some pre-clinical successes with VWF gene transfer although the clinical rationale for this therapeutic strategy needs careful consideration. Much more remains to be learnt about the biology of VWF and further translational advances for the enhancement of VWD care will inevitably be realized. PMID:23809112

  11. The value of CT-scanning in supratentorial haemangioblastomas

    International Nuclear Information System (INIS)

    Pinto, J.A.; Pereira, J.R.; Guimaraes, A.; Veiga-Pires, J.A.

    1987-01-01

    The authors describe a case of supratentorial haemangioblastoma, presenting with epileptic fits, without association with polyoythemia, or Von Hippel-Lindau syndrome, which, if present, would have given a clinical clue as to the nature of the lesion. (orig.)

  12. 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

  13. 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

    íodo perioperatorio. CONTENIDO: Se definieron las características de la enfermedad de von Willebrand en cuanto a las fisiopatologías, la clasificación, al diagnóstico laboratorial, al tratamiento actual y a los cuidados con el manejo del paciente en el período perioperatorio. CONCLUSIONES: La enfermedad de von Willebrand es el disturbio hemorrágico hereditario más común, sin embargo ella está subdiagnosticada por la complejidad de la propia enfermedad. La correcta clasificación del paciente, el uso apropiado de la desmopresina y la transfusión del factor de von Willebrand son medidas fundamentales para la realización del procedimiento anestésico exitoso.BACKGROUND AND OBJECTIVES: von Willebrand's disease is secondary to a mutation on chromosome 12, and is characterized by a qualitative and quantitative deficiency of the von Willebrand's factor. The diversity of the mutations is responsible for several different clinical manifestations, enabling the classification of several types and subtypes. The coagulopathy is manifested basically through a platelet dysfunction associated with a reduction in the serum levels of factor VIII. The objective of this review was to present the perioperative care of patients with von Willebrand's disease. CONTENTS: The physiopathology, classification, laboratorial diagnosis, and current treatment of von Willebrand's disease, as well as the perioperative management of these patients are discussed. CONCLUSIONS: von Willebrand's disease is the most common hereditary coagulopathy, but it is underdiagnosed due to the complexity of the disease itself. The right classification, proper use of desmopressin, and transfusion of von Willebrand's factor are fundamental for a successful anesthesia.

  14. Coats' disease, Turner syndrome, and von Willebrand disease in a patient with Wildtype Norrie disease pseudoglioma.

    Science.gov (United States)

    Desai, Rajen U; Saffra, Norman A; Krishna, Rati P; Rosenberg, Steven E

    2011-01-01

    The authors describe a girl diagnosed as having Coats' disease, Turner syndrome (45X karyotype), and type 1 von Willebrand disease. She tested negative for the Norrie disease pseudoglioma (NDP) gene located on the X-chromosome, which has been suspected of contributing to Coats' disease. Copyright 2010, SLACK Incorporated.

  15. Von Willebrand's Disease in Two Families of Doberman Pinschers

    OpenAIRE

    Johnstone, I. B.; Crane, S.

    1981-01-01

    The history, clinical symptoms and laboratory results in two families of Doberman pinschers with von Willebrand's disease are described. The affected animals illustrate the rather nonspecific bleeding problems that may be encountered in mild and moderate forms of this disease. In both families a bleeding diathesis was suspected when one member of the family underwent surgery with serious postoperative bleeding complications. These cases illustrate the importance of a thorough presurgical hist...

  16. Neuro image in neuroectodermal disorders. Part III: angiomatous and melanotic syndromes

    International Nuclear Information System (INIS)

    Marti-Bonmati, L.; Menor, F.; Poyatos, C.; Cortina, H.; Esteban, M.J.; Vilar, J.

    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. Blocking protein quality control to counter hereditary cancers

    DEFF Research Database (Denmark)

    Kampmeyer, Caroline; Nielsen, Sofie V.; Clausen, Lene

    2017-01-01

    cancer susceptibility syndromes, such as Lynch syndrome and von Hippel-Lindau disease, are caused by missense mutations in tumor suppressor genes, and in some cases, the resulting amino acid substitutions in the encoded proteins cause the cellular PQC system to target them for degradation, although...... by stabilizing with chemical chaperones, or by targeting molecular chaperones or the ubiquitin-proteasome system, may thus avert or delay the disease onset. Here, we review the potential of targeting the PQC system in hereditary cancer susceptibility syndromes....

  18. DEEP VEIN THROMBOSIS IN PATIENT WITH VON WILLEBRAND DISEASE

    Directory of Open Access Journals (Sweden)

    V. A. Elykomov

    2016-01-01

    Full Text Available Objective: to identify the possible factors of thrombogenic risk and ways of its prevention in patients with von Willebrand disease.Case description. Patient X., 42 years old, who suffers from von Willebrand disease type 3 with 5-years of age. Asked on reception to the traumatologist in the polyclinic of the Regional Hospital with pain in the left hip joint. Recommended planned operative treatment in the Altai Regional Clinical Hospital. Preoperative preparation included the infusion of concentrate of von Willebrand factor and coagulation factor VIII. Operation – cement total arthroplasty of the left hip joint. In the postoperative period analgesic treatment, elastic compression of the lower extremities, iron supplements, also conducted infusion of concentrate of von Willebrand factor and coagulation factor VIII for 20 days and thromboprophylactic with dabigatran. On the 3rd day after the operation the patient revealed deep vein thrombosis of the femoral segment (floating clot.Results. The patient was operated for emergency indications in the Department of endovascular surgery – installation of venous cava filter “Volan”. Dabigatran is cancelled, appointed clexane for 3 months. In our clinical example the patient lacked risk factors of pulmonary embolism as obesity, age, smoking, prolonged immobilization, estrogen therapy. Overdose of factor VIII were not observed – the level of factor did not exceed 135 % on transfusions. At the same time, the patient was found polymorphisms in the genes ITGA2, FGB, MTHFR, MTR – heterozygote, MTRR – mutant homozygote, which may indicate the genetic factors of thrombogenic risk. Also a significant risk factor was massive surgical intervention (total hip replacement. Despite preventive measures (elastic compression, thromboprophylactic dabigatran, early activation we cannot to avoid thrombotic complications.Conclusion. This article presents a case demonstrating a thrombotic complication in patients

  19. Sporadic Endolymphatic Sac Tumor-A Very Rare Cause of Hearing Loss, Tinnitus, and Dizziness

    DEFF Research Database (Denmark)

    Schnack, Didde Trærup; Kiss, Katalin; Hansen, Søren

    2017-01-01

    Sporadic endolymphatic sac tumor is a very rare neoplasm. It is low malignant, locally destructive and expansive, but non-metastasizing. The tumor is very rare in the sporadic form, but more often associated with Von Hippel-Lindau disease. A 65-year old man with left sided tinnitus and hearing loss......-operative freeze-microscopy showed inflammation tissue, whereas subsequent microscopy showed papillary-cystic endolymphatic sac tumor. Endolymphatic sac tumor is a rare neoplasm. The tumor may present with asymmetrically sensory neural hearing loss with or without tinnitus, dizziness and facial nerve paresis...

  20. Papillary cystadenoma of the epididymis.

    Science.gov (United States)

    Kallie, N R; Fisher, G F; Harker, J R

    1983-03-01

    The case of a 30-year-old man with papillary cystadenoma of the epididymis is presented. This extremely rare lesion is often associated with von Hippel-Lindau disease, although in this case there were no such signs or symptoms. The gross and microscopic features of this lesion and theories of its origin are reviewed. The constant microscopic features are: efferent duct ectasia with papillary formation, a lining of cuboidal epithelium, often with clear vacuolated cytoplasm, and a stroma of hyalinized fibrous tissue infiltrated by inflammatory cells.

  1. Genetics Home Reference: von Willebrand disease

    Science.gov (United States)

    ... mildest and most common of the three types, accounting for 75 percent of affected individuals. Type 3 ... diseases that affect bone marrow or immune cell function. This rare form of the condition is characterized ...

  2. Von Willebrand's disease in the German shepherd dog : clinical communication

    Directory of Open Access Journals (Sweden)

    R.G. Lobetti

    2000-07-01

    Full Text Available Two litters of Germanshepherd dogs were evaluated for a haemorrhagic tendency that was characterised by excessive bleeding from the umbilicus at birth, haemorrhage and haematoma formation at vaccination, excessive bruising, and lameness due to haemarthrosis. Platelet counts, clotting times and Von Willebrand's factor (VWF assays were assessed in all dogs. Factor VIII determination was performed in 1 puppy and its parents. Based on the clotting times and VWF assay, 6 puppies (4 male and 2 female showed type I Von Willebrand's disease (VWD, 5 (4 male and 1 female possible type II VWD, and 4 were unaffected. One puppy with possible type II VWD had very low factor VIII activity; its sire had a normal factor activity, whereas the dam was in the low-normal range. This article reports type I and possible type II VWD in 2 related litters of German shepherd dogs, the latter being rare in German shepherd dogs.

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

    Science.gov (United States)

    Echahdi, Hanae; El Hasbaoui, Brahim; El Khorassani, Mohamed; Agadr, Aomar; Khattab, Mohamed

    2017-01-01

    Von Willebrand Disease (VWD) is the most common human inherited bleeding disorder due to a defect of Von Willebrand Factor (VWF), which a glycoprotein crucial for platelet adhesion to the subendothelium after vascular injury. VWD include quantitative defects of VWF, either partial (type 1 with VWF levels < 50 IU/dL) or virtually total (type 3 with undetectable VWF levels) and also qualitative defects of VWF (type 2 variants with discrepant antigenic and functional VWF levels). The most bleeding forms of VWD usually do not concern type 1 patients with the mildest VWF defects (VWF levels between 30 and 50IU/dL). Von willebrand factor is a complex multimeric protein with two functions: it forms a bridge between the platelets and areas of vascular damage and it binds to and stabilizes factor VIII, which is necessary for the clotting cascade. By taking a clinical history of bleeding (mucocutaneous bleeding symptoms suggestive of a primary haemostatic disorder, a quantitative or qualitative abnormality of VWF is possible) it is important to think about VWD and to make the appropriate diagnosis. If the VWD is suspected diagnostic tests should include an activated partial thromboplastin time, bleeding time, factor VIII: C Ristocetin cofactor and vWF antigen. Additional testing of ristocetin induced plattlet adhesion (RIPA) the multimeric structure and collagen binding test and genanalysis allow diagnosing the different types of von. Willebrand Disease. The treatment of choice in mild forms is the synthetic agent desmopressin. In patients with severe type 1, type 2B, 2N and type 3 or in people who do not response to desmopressin, the appropriate treatment is a factor VIII concentrate that is rich of VWF. We report a case of infant in 27-month-old boy who had been referred due to haemorrhagic shock. His birth histories, his familie's social history and developmental milestones were unremarkable. He was born at full term with no antenatal or perinatal complications. Prior to

  4. Diagnosis and management of von Willebrand disease: guidelines for primary care.

    Science.gov (United States)

    Yawn, Barbara; Nichols, William L; Rick, Margaret E

    2009-12-01

    Von Willebrand disease is an inherited condition characterized by deficiency of von Willebrand factor, which is essential in hemostasis. The National Heart, Lung, and Blood Institute has released new evidence-based guidelines for the diagnosis and management of the disease. There are three major subtypes of von Willebrand disease, classified as partial quantitative deficiency (low levels) of von Willebrand factor (type 1), qualitative deficiency (type 2), or virtually complete deficiency (type 3). Diagnosis is usually made by reviewing the patient's personal and family history of bleeding and by clinical evaluation for more common reasons for bleeding, supplemented with laboratory tests. Assessment may be used to determine bleeding risk before surgery and other invasive procedures, and to diagnose reasons for unexplained hemorrhaging. Von Willebrand factor levels of 30 IU per dL or lower are required for the definite diagnosis of inherited von Willebrand disease. Persons with levels of 30 to 50 IU per dL may not have the disease, but may need agents to increase von Willebrand factor levels during invasive procedures or childbirth. Treatment is tailored to the subtype of the disease: increasing plasma concentration of von Willebrand factor by releasing endogenous stores with desmopressin or replacing nonexistent or ineffective von Willebrand factor by using human plasma-derived, viral-inactivated concentrates; treatment is often combined with hemostatic agents that have mechanisms other than increasing von Willebrand factor. Regular prophylaxis is seldom required, and treatment is initiated before planned invasive procedures or in response to bleeding.

  5. [Papillary cystadenoma of the epididymis. 2 case reports].

    Science.gov (United States)

    Raimoldi, A; Berti, G L; Canclini, L; Giola, V; Leidi, G L; Maccaroni, A; Sironi, M; Veneroni, L; Bacchioni, A M; Assi, A

    1997-12-01

    Tumors of the epididymis are very rare. They are benign tumors in 75 per cent of the cases. Papillary cystadenoma represents 4-9 per cent of epididymal benign tumors. Often associated with the syndrome of von Hippel Lindau and infertility, histologically it can be confused with metastatic renal cell carcinoma. We report two cases of papillary cystadenoma located in the head of the right epididymis, with no concomitance with the syndrome of von Hippel Lindau, cured by the removal of the neoplastic nodule. There was no recidivation, in confirmation of the neoplastic benignity.

  6. Nordic Haemophilia Council's practical guidelines on diagnosis and management of von Willebrand disease

    DEFF Research Database (Denmark)

    Lassila, Riitta; Holme, Pål André; Landorph, Andrea

    2011-01-01

    Von Willebrand disease (VWD) is the most common inherited bleeding disorder characterized by spontaneous or tissue injury-related, mostly mucocutaneous, bleeding events. VWD affects both males and females and is caused by quantitative or qualitative deficiency of Von Willebrand factor. The diagno......Von Willebrand disease (VWD) is the most common inherited bleeding disorder characterized by spontaneous or tissue injury-related, mostly mucocutaneous, bleeding events. VWD affects both males and females and is caused by quantitative or qualitative deficiency of Von Willebrand factor...... subtyping may also be problematic. This article summarizes the guidelines of the Nordic Haemophilia Council (NHC), which are intended to serve as a practical tool and provide the standards for diagnosing and treating VWD patients. The complete Nordic Guidelines on VWD are available at the NHC Web site (http://nordhemophilia.org)....

  7. Changes in bleeding patterns in von Willebrand disease after institution of long-term replacement therapy : results from the von Willebrand Disease Prophylaxis Network

    NARCIS (Netherlands)

    Holm, Elena; Abshire, Thomas C; Bowen, Joel; Álvarez, M Teresa; Bolton-Maggs, Paula; Carcao, Manuel; Federici, Augusto B; Gill, Joan Cox; Halimeh, Susan; Kempton, Christine; Key, Nigel S; Kouides, Peter; Lail, Alice; Landorph, Andrea; Leebeek, Frank; Makris, Michael; Mannucci, Pier; Mauser-Bunschoten, Eveline P; Nugent, Diane; Valentino, Leonard A; Winikoff, Rochelle; Berntorp, Erik

    Clinically, the leading symptom in von Willebrand disease (VWD) is bleeding, chiefly of mucosal type, for example, epistaxis, gingival, or gastrointestinal bleeding, and menorrhagia. In severe forms of VWD with secondary deficiency of factor VIII, spontaneous joint bleeding, resembling that observed

  8. X-ray diagnostics of thorax diseases; Roentgendiagnostik von Thoraxerkrankungen. Von der Deskription zur Diagnose

    Energy Technology Data Exchange (ETDEWEB)

    Kulke, H.M. [Wuerzburg Univ. (Germany). Universitaetsklinikum

    2013-11-01

    The book on X-ray diagnostics of thorax diseases covers the following issues: diagnostic procedures, inflammatory thorax diseases, malign thorax diseases, heart and large blood vessels, hear insufficiency, pulmonary congestion, pulmonary edema, interstitial pulmonary diseases, intensive care and traumatology.

  9. Evaluation of von Willebrand factor during pregnancy, lactation and oestrous cycle in bitches affected and unaffected by von Willebrand disease.

    Science.gov (United States)

    Mattoso, C R S; Takahira, R K; Beier, S L; Araujo, J P; Corrente, J E

    2013-06-01

    Plasmatic concentrations of von Willebrand Factor (vWF) increase during pregnancy in humans and dogs; however the mechanism of such increase is still not well defined. The aims of this study were: (i) to evaluate changes in vWF concentration during pregnancy and during the subsequent oestrous cycle in bitches affected and unaffected by von Willebrand Disease (vWD); (ii) to correlate the vWF levels and cortisol levels in both groups. Seven vWD affected (GI) and nine unaffected (GII) bitches were used. The animals were assessed during pregnancy, parturition, lactation and non-gestational oestrous cycle in 11 moments (Pregnancy 1, Pregnancy 2, Parturition, Lactation 1, Lactation 2, Lactation 3, Anestrus, Proestrus, Oestrus, Diestrus 1, and Diestrus 2). The following tests were performed; measurement of von Willebrand factor antigen (vWF:Ag), albumin and cortisol. In both groups, vWF concentration remained stable during the non-gestational oestrous cycle, but increased during pregnancy, with the highest value observed at parturition. Increases of 70% and 124% in vWF were seen in GI and GII, respectively, compared to anestrus. No correlation was found between vWF and cortisol. Values of vWF:Ag changed during pregnancy, with a peak at parturition, both in vWD affected and unaffected animals. Values of vWF were not altered in the different phases of the oestrous cycle following pregnancy in both groups. Evaluation of vWF during pregnancy can cause false negative results for vWD, but assessment can be performed at any point in the oestrous cycle of non-pregnant bitches. © 2012 Blackwell Verlag GmbH.

  10. Phenotypic correction of von Willebrand disease type 3 blood-derived endothelial cells with lentiviral vectors expressing von Willebrand factor

    Science.gov (United States)

    De Meyer, Simon F.; Vanhoorelbeke, Karen; Chuah, Marinee K.; Pareyn, Inge; Gillijns, Veerle; Hebbel, Robert P.; Collen, Désiré; Deckmyn, Hans; VandenDriessche, Thierry

    2006-01-01

    Von Willebrand disease (VWD) is an inherited bleeding disorder, caused by quantitative (type 1 and 3) or qualitative (type 2) defects in von Willebrand factor (VWF). Gene therapy is an appealing strategy for treatment of VWD because it is caused by a single gene defect and because VWF is secreted into the circulation, obviating the need for targeting specific organs or tissues. However, development of gene therapy for VWD has been hampered by the considerable length of the VWF cDNA (8.4 kb [kilobase]) and the inherent complexity of the VWF protein that requires extensive posttranslational processing. In this study, a gene-based approach for VWD was developed using lentiviral transduction of blood-outgrowth endothelial cells (BOECs) to express functional VWF. A lentiviral vector encoding complete human VWF was used to transduce BOECs isolated from type 3 VWD dogs resulting in high-transduction efficiencies (95.6% ± 2.2%). Transduced VWD BOECs efficiently expressed functional vector-encoded VWF (4.6 ± 0.4 U/24 hour per 106 cells), with normal binding to GPIbα and collagen and synthesis of a broad range of multimers resulting in phenotypic correction of these cells. These results indicate for the first time that gene therapy of type 3 VWD is feasible and that BOECs are attractive target cells for this purpose. PMID:16478886

  11. Multiple schwannomas of cauda equine in the absence of von Recklinghausen's disease

    International Nuclear Information System (INIS)

    Kayaoglu, Cetin R.; Sengul, G.; Aydin, Ismail H.

    2007-01-01

    Multiple schwannomas in the absence of neurofibromatosis is rarely reported in the literature. We present a 56-year-old female with a history of severe leg and back pain on the left side for one year. Magnetic resonance imaging revealed 4 schwannomas located in the cauda equine in the absence of von Recklinghausen's disease. (author)

  12. [Familial astrocytoma associated with von Recklinghausen's disease: report of two cases].

    Science.gov (United States)

    Ito, Y; Oki, S; Mikami, T; Ogasawara, H; Kawamoto, Y; Sato, H; Yamaguchi, S; Hayashi, Y; Shindo, H

    1997-03-01

    Two cases of astrocytoma associated with von Recklinghausen's disease (neurofibromatosis type; NF-1) were reported. The first case wes a 60-year-old man who had been diagnosed as von Recklinghausen's disease on the basis of skin findings. Magnetic resonance imaging (MRI) showed a tumor in the left temporal lobe. Partial removal was performed with neuronavigator, and because of the existence of Rosenthal fiber the histological diagnosis was pilocytic astrocytoma. Radiation therapy was performed. The second case was a 6-year-old boy suffering from headache and left hemiparesis including his face. MRI showed a tumor with a cyst in the right thalamus and obstructive hydrocephalus. Initially CT-guided stereotactic biopsy was performed, and the histological diagnosis, on the basis of increased cellularity, pleomorphism and nuclear atypia without necrosis or vascular proliferation, was anaplastic astrocytoma. Radiation and chemo-immuno therapy were carried out after V-P shunt. It is well known that von Recklinghausen's disease (NF-1) is often associated with optic glioma (5-36%). In the literature, the glioma seldom occurs in other parts of the brain, supratentorial glioma especially is rare. Only two familial cases of supratentorial glioma associated with von Recklinghausen's disease have been reported. The prognosis of supratentorial glioma associated with NF-1 was poor in these reports. In this paper, the diagnostic and therapeutic problems are discussed.

  13. A systematic review of the effects of hemophilia and von Willebrand disease on arterial trombosis

    NARCIS (Netherlands)

    Biere-Rafi, Sara; Zwiers, M.; Peters, Marjolein; Van Der Meer, Jan; Rosendaal, Frits R; Buller, Harry R; Kamphuisen, Pieter W

    Background: Patients with hemophilia and von Willebrand disease (VWD) may be protected against arterial thrombosis, through a hy-pocoagulable state or atherosclerosis. We performed a systematic review to assess the association between these clotting disorders, arterial thrombosis and the prevalence

  14. Von-Willebrand Disease Presenting as Intractable Epistaxis after Nasal Polypectomy

    Directory of Open Access Journals (Sweden)

    Jeong Jin Park

    2014-01-01

    Full Text Available Von-Willebrand disease (VWD is one of the platelet dysfunction disorders that results from a deficiency of Von-Willebrand factor, which is essential for hemostasis. VWD patients typically have normal laboratory results on screening for bleeding disorders. To suspect and diagnose VWD, a careful review of past medical history and laboratory tests is critical. A 59-year-old male patient presented with intractable nasal bleeding after nasal polypectomy. The bleeding was controlled by platelet transfusion, and he was later diagnosed with VWD.

  15. Pseudo (Platelet-type von Willebrand disease in pregnancy: a case report

    Directory of Open Access Journals (Sweden)

    Grover Neetu

    2013-01-01

    Full Text Available Abstract Background Pseudo (platelet-type-von Willebrand disease is a rare autosomal dominant bleeding disorder caused by an abnormal function of the glycoprotein lb protein; the receptor for von Willebrand factor. This leads to an increased removal of VWF multimers from the circulation as well as platelets and this results in a bleeding diathesis. Worldwide, less than 50 patients are reported with platelet type von Willebrand disease (PT-VWD. Case presentation We describe the management of platelet type von Willebrand disease in pregnancy of a 26 year old Caucasian primigravida. The initial diagnosis was made earlier following a significant haemorrhage post tonsillectomy several years prior to pregnancy. The patient was managed under a multidisciplinary team which included obstetricians, haematologists, anaesthetists and neonatologists. Care plans were made for the ante- natal, intra-partum and post-partum periods in partnership with the patient. The patient’s platelet count levels dropped significantly during the antenatal period. This necessitated the active exclusion of other causes of thrombocytopenia in pregnancy. A vaginal delivery was desired and plans were made for induction of labour at 38 weeks of gestation with platelet cover in view of the progressive fall of the platelet count. The patient however went into spontaneous labour on the day of induction. She was transfused two units of platelets before delivery. She had an unassisted vaginal delivery of a healthy baby. The successful antenatal counselling has encouraged the diagnosis of the same condition in her mother and sister. We found this to be a particularly interesting case as well as challenging to manage due to its rarity. Psuedo von Willebrand disease in pregnancy can be confused with a number of other differential diagnoses, such as gestational thrombocutopenia, idiopathatic thrombocytopenia, thrombotic thrombocytopenic purpura and pre-eclampsia; all need consideration

  16. A study of the effect of ethamsylate (Dicynene) on the bleeding time, von Willebrand factor level and fibrinolysis in patients with von Willebrand's disease.

    Science.gov (United States)

    Hutton, R A; Hales, M; Kernoff, P B

    1988-12-22

    Nine patients with clinically moderate or severe Type I von Willebrand's disease were treated for 2 weeks with ethamsylate (2 g/day in four equal doses) and with a matched placebo in a randomised double-blind trial. Template bleeding time, von Willebrand factor activity (ristocetin co-factor) and antigen, euglobulin lysis time and type I tissue plasminogen activator inhibitor were determined before and at the end of each treatment period. None of these parameters showed any significant change attributable to ethamsylate. Thus, despite the fact that five patients thought subjectively that their bleeding symptoms improved during ethamsylate treatment compared to only one while on placebo, we obtained no evidence that the drug was of benefit to patients with von Willebrand's disease.

  17. Dynamics of von Willebrand factor reactivity in sickle cell disease during vaso-occlusive crisis and steady state

    NARCIS (Netherlands)

    Sins, J. W. R.; Schimmel, M.; Luken, B. M.; Nur, E.; Zeerleder, S. S.; van Tuijn, C. F. J.; Brandjes, D. P. M.; Kopatz, W. F.; Urbanus, R. T.; Meijers, J. C. M.; Biemond, B. J.; Fijnvandraat, K.

    2017-01-01

    Background: Endothelial activation plays a central role in the pathophysiology of vaso-occlusion in sickle cell disease (SCD), facilitating adhesive interactions with circulating blood cells. Upon activation, various adhesive molecules are expressed, including von Willebrand factor (VWF). Increased

  18. 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.

  19. BIlateral juxtapapillary retinal capillary haemangioma: Usefulness of aflibercept in the management of its complications.

    Science.gov (United States)

    Campos Polo, R; Rubio Sánchez, C; García Guisado, D M; Díaz Luque, M J

    2017-10-01

    A 45 year-old man with a history of adrenal phaeochromocytoma presented with a subretinal juxtapapillary haemorrhage on his left eye and a small asymptomatic vascular tumour in the contralateral eye. With the mentioned findings, the patient was diagnosed with bilateral retinal capillary haemangioma in the context of a von Hippel Lindau disease. Intravitreal aflibercept was prescribed, with a good outcome of the disease. Many treatments have been proposed for the management of juxtapapillary retinal capillary haemangioma with variable results. Intravitreal aflibercept can be a useful treatment with a good safety profile. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Frequency of von willebrand disease in patients of heavy menstrual bleeding

    International Nuclear Information System (INIS)

    Anjum, N.; Shaheen, Z.; Altaf, C.

    2016-01-01

    Objective: To determine the frequency of Von Willebrand disease (vWD) in patients of heavy menstrual bleeding (HMB). Study Design: Hospital based cross sectional study. Place and Duration of Study: Study was conducted at the Gynecology and Obstetrics department, Military Hospital, Rawalpindi in collaboration with Haematology Department of Armed Forces Institute of Pathology (AFIP) Rawalpindi, from Jul to Dec 2015. Material and Methods: Women presenting with HMB were enrolled in the study after informed consent. HMB was defined as cyclical bleeding at normal intervals but patient is using more than 5 pads per day or increase in duration 8/28 or more for at least last 06 months. Venous blood samples were taken and screened for the hemoglobin level (Hb), platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT) and Von Willebrand antigen (vWF:Ag) in addition to bleeding time (BT) at the Armed Forces Institute of Pathology (AFIP). The demographic details (age, age at menarche), clinical features (menstrual history, quantity of bleeding) and laboratory findings were recorded on the study proforma. Results: A total of 200 patients were enrolled in this study with mean age of 32.3 +- 8.5 years. Mean flow of menstrual blood was 9.8 +- 2.5 pads / day. Mean Hb percent was 8.1 +- 1.4 g/dl. Twenty nine (14.5 percent) patients were having low level of vWF:Ag. Conclusion: There is high frequency of von Willebrand disease among females presenting with heavy menstrual bleeding in our set up. Therefore all patients with heavy menstrual bleeding except those with obvious causes like multiple fibroid should be screened for von Willebrand disease. (author)

  1. 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.)

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

    International Nuclear Information System (INIS)

    Hermier, M.; Cotton, F.; Froment, J.C.; Saint-Pierre, G.; Jouvet, A.; Ongolo-Zogo, P.; Fischer, G.

    2002-01-01

    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.)

  3. Microcystic adenoma of the pancreas associated with non-functioning islet cell tumor: a case report

    International Nuclear Information System (INIS)

    Kong, Keun Young; Lee, Dong Ho; Ko, Young Tae; Kim, Youn Wha

    1997-01-01

    Among cystic tumors arising in the pancreas, microcystic adenoma is relatively uncommon;it is usually benign, and is comprised of cysts that vary in size from microscopic to 2 cm in diameter. It has recently been reported to be associated with other pancreatic tumors with malignant potential; in particular, microcystic adenoma with coexistent islet cell tumor has been reported in von Hippel-Lindau disease. We report a case of microcystic adenoma of the pancreas associated with coexistent surgically-proven islet cell tumor. On spiral CT, the islet cell tumor was seen as a highly enhanced inhomogeneous solid mass in the pancreatic head, and microcystic adenoma as numerous small cysts throughout the pancreas.=20

  4. Familial Investigations of Childhood Cancer Predisposition

    Science.gov (United States)

    2018-01-03

    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 Leukemia; 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

  5. Differential effects of the loss of intrachain- versus interchain-disulfide bonds in the cystine-knot domain of von Willebrand factor on the clinical phenotype of von Willebrand disease

    NARCIS (Netherlands)

    Tjernberg, Pernilla; Vos, Hans L.; Spaargaren-van Riel, Caroline C.; Luken, Brenda M.; Voorberg, Jan; Bertina, Rogier M.; Eikenboom, Jeroen C. J.

    2006-01-01

    Von Willebrand factor (VWF) contains a large number of cysteine residues, which all form disulfide bonds. Mutations of cysteines located in the cystine-knot (CK) domain of VWF have been identified in both qualitative type 2A (IID) and quantitative type 3 von Willebrand disease (VWD). Our objective

  6. Joint assessment in von Willebrand disease : Validation of the Haemophilia Joint Health score and Haemophilia Activities List

    NARCIS (Netherlands)

    van Galen, Karin P. M.; Timmer, Merel A.; de Kleijn, Piet; Fischer, Kathelijn; Foppen, Wouter; Schutgens, Roger E. G.; Eikenboom, Jeroen; Meijer, Karina; Cnossen, Marjon H.; Fijnvandraat, Karin; van der Bom, Johanna G.; Laros-van Gorkom, Britta A. P.; Leebeek, Frank W. G.; Mauser-Bunschoten, Eveline P.

    Assessment of clinical outcome after joint bleeding is essential to identify joint damage and optimise treatment, to prevent disability. However, disease-specific tools to assess the musculoskeletal status in patients with von Willebrand disease (VWD) are lacking. We aimed to determine validity and

  7. Percutaneous coronary intervention and the management of acute coronary syndromes in patients with von Willebrand disease.

    Science.gov (United States)

    Rathore, Sulaiman; Deleon, Dexter; Akram, Hafsa; Sane, David; Ball, Timothy

    2013-04-01

    Von Willebrand disease (vWD) results from quantitative or qualitative deficiency of von Willebrand factor (vWF). The occurrence of myocardial infarction is very rare in patients with vWD. A few case reports of acute coronary syndrome (ACS) in vWD patients are present in the literature, but no definite management recommendations are available for such patients. We report a case of successful percutaneous coronary intervention (PCI) with bare-metal stent (BMS) implantation in a 46-year-old woman with type 1 vWD and history of coronary artery disease (CAD). She received periprocedural dual-antiplatelet therapy for 2 weeks and then continued aspirin without any bleeding complications. The optimal management of patients with vWD and ACS is complex and presents a therapeutic challenge. We propose that dual-antiplatelet therapy can be used safely in most vWD patients presenting with ACS as most of them are type 1 vWD. PCI with BMS can be done safely. Long-term management of these patients requires a systemic approach including hematological consultation, ascertaining vWF levels, as well as patient education and close outpatient follow-up.

  8. Diagnosis and management of von Willebrand disease: a developing country perspective.

    Science.gov (United States)

    Nair, Sukesh Chandran; Viswabandya, Auro; Srivastava, Alok

    2011-07-01

    Special challenges exist in the management of patients with von Willebrand disease (VWD) because of limitations in diagnostic facilities and therapeutic options. However, even within these limitations, it is possible to establish comprehensive services for this condition. Our data show that among 202 patients with VWD, 107 were type 3, 62 were type 1, and the others different categories of type 2. Basic tests such as bleeding time and activated partial thromboplastin time with factor (F)VIII coagulant are able to diagnose most of those with severe disease. We have been able to adapt the specific tests such as von Willebrand factor (VWF) ristocetin cofactor and VWF antigen from the tedious batched manual methods to cost-effective automated methods on advanced coagulometers. Discriminatory tests such as VWF collagen binding, VWF:FVIIIB, ristocetin-induced platelet agglutination (RIPA) are done in batches. Therapeutic options and for the treatment of bleeding include desmopressin, cryoprecipitate, and intermediate purity VWF-containing clotting factor concentrates. Tranexamic acid is also widely used as well as hormonal therapy for menorrhagia. We have also shown that modest doses of intermediate purity FVIII (Koate DVI; Talecris Biotherapeutics, Raleigh, NC, USA) at 35 IU/kg preoperatively and 10 to 20 IU/kg after that are sufficient for surgical hemostasis in these patients. © Thieme Medical Publishers.

  9. Characterization of a novel mutation in the von Willebrand factor propeptide in a distinct subtype of recessive von Willebrand disease

    DEFF Research Database (Denmark)

    Lanke, Elsa; Kristoffersson, Ann-Charlotte; Philips, Malou

    2008-01-01

    von Willebrand factor (VWF) is a plasma protein that consists of a series of multimers of which the high-molecular-weight VWF multimers are the most potent in platelet adhesion and aggregation. The propeptide of the VWF (VWFpp) is known to be essential in the process of multimer assembly. Genetic...... mutation in the VWFpp abolishes multimerization of VWF. The mutation probably disrupts the normal configuration of the VWFpp, which is essential for correct orientation of the protomers and ultimately multimerization. The mutant amino acid is located in a region that is highly conserved across several...

  10. Congenital hepatic fibrosis associated with von Recklinghausen's disease Fibrosis hepática congénita asociada a enfermedad de von Recklinghausen

    Directory of Open Access Journals (Sweden)

    O. A. Jorge

    2006-09-01

    Full Text Available Congenital hepatic fibrosis is characterized by a ductal plate malformation with duct-like structures and fibrosis. It manifests clinically with portal hypertension and may be associated with multiple congenital defects. We present the case of a 16-year-old male with splenomegaly, leukopenia and thrombocytopenia, esophageal varices, and a histopathological diagnosis of congenital hepatic fibrosis. He exhibits "café au lait' spots and "Lisch' nodules, with a diagnosis of von Recklinghausen's disease. Congenital hepatic fibrosis belongs to the so-called fibropolycystic diseases, in which there is a disordered interaction between cells and the extracellular matrix. Von Recklinghausen's disease affects tissues derived from the neural crest and its diagnosis is based on clinical criteria. It is associated with multiple diseases. We describe its association with congenital hepatic fibrosis for the first time.La fibrosis hepática congénita se origina como consecuencia de una malformación de la placa ductal con estructuras tipo ductales acompañadas de fibrosis. Se manifiesta con hipertensión portal y puede asociarse a múltiples defectos congénitos. Presentamos un varón de 16 años con esplenomegalia, leuco- y plaquetopenia, varices esofágicas y diagnóstico histopatológico de fibrosis hepática congénita. La exploración física mostraba la existencia de manchas de "café con leche' y nódulos de "Lisch' con diagnóstico de enfermedad de von Recklinghausen. La fibrosis hepática congénita forma parte de las enfermedades fibropoliquísticas donde existiría una alteración en la interacción entre las células y la matriz extracelular. La enfermedad de von Recklinghausen afecta a los tejidos derivados de la cresta neural y su diagnóstico se basa en criterios clínicos. Se asocia a múltiples patologías. Presentamos por primera vez su asociación con fibrosis hepática congénita.

  11. Towards personalised therapy for von Willebrand disease: a future role for recombinant products.

    Science.gov (United States)

    Favaloro, Emmanuel J

    2016-05-01

    von Willebrand disease (VWD) is reportedly the most common bleeding disorder and is caused by deficiencies and/or defects in the adhesive plasma protein von Willebrand factor (VWF). Functionally, normal VWF prevents bleeding by promoting both primary and secondary haemostasis. In respect to primary haemostasis, VWF binds to both platelets and sub-endothelial matrix components, especially collagen, to anchor platelets to damaged vascular tissue and promote thrombus formation. VWF also stabilises and protects factor VIII in the circulation, delivering FVIII to the site of injury, which then facilitates secondary haemostasis and fibrin formation/thrombus stabilisation. As a result of this, patients with VWD suffer a bleeding diathesis reflective of a primary defect caused by defective/deficient VWF, which in some patients is compounded by a reduction in FVIII. Management of VWD, therefore, chiefly entails replacement of VWF, and sometimes also FVIII, to protect against bleeding. The current report principally focuses on the future potential for "personalised" management of VWD, given the emerging options in recombinant therapies. Recombinant VWF has been developed and is undergoing clinical trials, and this promising therapy may soon change the way in which VWD is managed. In particular, we can envisage a personalised treatment approach using recombinant VWF, with or without recombinant FVIII, depending on the type of VWD, the extent of deficiencies, and the period and duration of treatment.

  12. Dynamics of von Willebrand factor reactivity in sickle cell disease during vaso-occlusive crisis and steady state

    NARCIS (Netherlands)

    Sins, J. W.R.; Schimmel, Marein; Luken, Brenda M.; Nur, Erfan; Zeerleder, S.; van Tuijn, Charlotte F. J.; Brandjes, Dees P. M.; Kopatz, W. F.; Urbanus, R. T.; Meijers, Joost C. M.; Biemond, B. J.; Fijnvandraat, K.

    2017-01-01

    Essentials The role of von Willebrand Factor (VWF) in the pathophysiology of sickle cell disease is unclear. We assessed markers of VWF during admission for vaso-occlusive crisis (VOC) and steady state. VWF reactivity was higher during VOC and was associated with inflammation and neutrophil

  13. Bleeding spectrum in children with moderate or severe von Willebrand disease: Relevance of pediatric-specific bleeding

    NARCIS (Netherlands)

    Sanders, Yvonne V.; Fijnvandraat, Karin; Boender, Johan; Mauser-Bunschoten, Evelien P.; van der Bom, Johanna G.; de Meris, Joke; Smiers, Frans J.; Granzen, Bernd; Brons, Paul; Tamminga, Rienk Y. J.; Cnossen, Marjon H.; Leebeek, Frank W. G.

    2015-01-01

    The bleeding phenotype of children with von Willebrand disease (VWD) needs to be characterized in detail to facilitate diagnosis during childhood and aid in the planning and assessment of treatment strategies. The objective was to evaluate the occurrence, type, and severity of bleeding in a large

  14. Clinical and laboratory diagnosis of von Willebrand disease: A synopsis of the 2008 NHLBI/NIH guidelines

    Science.gov (United States)

    Nichols, William L.; Rick, Margaret E.; Ortel, Thomas L.; Montgomery, Robert R.; Sadler, J. Evan; Yawn, Barbara P.; James, Andra H.; Hultin, Mae B.; Manco-Johnson, Marilyn J.; Weinstein, Mark

    2017-01-01

    Von Willebrand factor (VWF) mediates blood platelet adhesion and accumulation at sites of blood vessel injury, and also carries coagulation factor VIII (FVIII) that is important for generating procoagulant activity. Von Willebrand disease (VWD), the most common inherited bleeding disorder, affects males and females, and reflects deficiency or defects of VWF that may also cause decreased FVIII. It may also occur less commonly as an acquired disorder (acquired von Willebrand syndrome). This article briefly summarizes selected features of the March 2008 evidence-based clinical and laboratory diagnostic recommendations from the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel for assessment for VWD or other bleeding disorders or risks. Management of VWD is also addressed in the NHLBI guidelines, but is not summarized here. The VWD guidelines are available at the NHLBI Web site (http://www.nhlbi.nih.gov/guidelines/vwd). PMID:19415721

  15. Technological advances in diagnostic testing for von Willebrand disease: new approaches and challenges.

    Science.gov (United States)

    Hayward, C P M; Moffat, K A; Graf, L

    2014-06-01

    Diagnostic tests for von Willebrand disease (VWD) are important for the assessment of VWD, which is a commonly encountered bleeding disorder worldwide. Technical innovations have been applied to improve the precision and lower limit of detection of von Willebrand factor (VWF) assays, including the ristocetin cofactor activity assay (VWF:RCo) that uses the antibiotic ristocetin to induce plasma VWF binding to glycoprotein (GP) IbIXV on target platelets. VWF-collagen-binding assays, depending on the type of collagen used, can improve the detection of forms of VWD with high molecular weight VWF multimer loss, although the best method is debatable. A number of innovations have been applied to VWF:RCo (which is commonly performed on an aggregometer), including replacing the target platelets with immobilized GPIbα, and quantification by an enzyme-linked immunosorbent assay (ELISA), immunoturbidimetric, or chemiluminescent end-point. Some common polymorphisms in the VWF gene that do not cause bleeding are associated with falsely low VWF activity by ristocetin-dependent methods. To overcome the need for ristocetin, some new VWF activity assays use gain-of-function GPIbα mutants that bind VWF without the need for ristocetin, with an improved precision and lower limit of detection than measuring VWF:RCo by aggregometry. ELISA of VWF binding to mutated GPIbα shows promise as a method to identify gain-of-function defects from type 2B VWD. The performance characteristics of many new VWF activity assays suggest that the detection of VWD, and monitoring of VWD therapy, by clinical laboratories could be improved through adopting newer generation VWF assays. © 2014 John Wiley & Sons Ltd.

  16. From Wilhelm von Humboldt to Hitler-are prominent people more prone to have Parkinson's disease?

    Science.gov (United States)

    Horowski; Horowski; Calne; Calne

    2000-10-01

    We describe Parkinsonism in prominent people, where Wilhelm von Humboldt and Adolf Hitler provide just two spectacular, opposing examples. In both of them, there is little if any evidence that the disease did influence their life ambitions, methods of achieving them or cognitive function in general. Thus, Hitler's Parkinsonism should remain a 'footnote' to history, and historians should acknowledge that in his last years, his trembling, his curbed posture, his slow walking, mask-like face and low voice did not indicate remorse, fear or depression as a consequence of his crimes, but were mere expressions of his disease which, until the end, had no impact on his intellectual skills and methods. The apparently higher incidence of Parkinsonism in prominent people may be just due to their higher visibility, or a consequence of disease-related personality traits (e.g. ambition, perfectionism, rigidity) which may contribute to becoming, e.g., a prominent authoritarian person. Perhaps even some early behaviour pattern (such as repressed emotions or acting in public-which could even increase the risk of some infection) contributes to a greater vulnerability for developing Parkinsonism. Further studying other prominent cases might lead us to better understanding of risk factors and the expression of early Parkinsonism.

  17. Von Willebrand Factor as a Novel Player in Valvular Heart Disease: From Bench to Valve Replacement.

    Science.gov (United States)

    Gragnano, Felice; Crisci, Mario; Bigazzi, Maurizio Cappelli; Bianchi, Renatomaria; Sperlongano, Simona; Natale, Francesco; Fimiani, Fabio; Concilio, Claudia; Cesaro, Arturo; Pariggiano, Ivana; Diana, Vincenzo; Limongelli, Giuseppe; Cirillo, Plinio; Russo, Mariagiovanna; Golia, Enrica; Calabrò, Paolo

    2018-02-01

    von Willebrand Factor (vWF) is a well-known mediator of hemostasis and vascular inflammation. Its dynamic modulation in the bloodstream, according to hemodynamic conditions, makes it an appealing biomarker in patients with valvular heart disease (VHD). Recent studies highlight the close connection between vWF and VHD, with possible implications in the pathogenesis of VHD, promoting valve aging and calcification or favoring the development of infective endocarditis. Moreover, vWF has been recently proposed as a new diagnostic and prognostic tool in patients with valve stenosis or regurgitation, showing a strict correlation with severity of valve disease, outcome, and bleeding (Heyde syndrome). A novel role for vWF is also emerging in patients undergoing percutaneous or surgical valve repair/replacement to select and stratify patients, evaluate periprocedural bleeding risk, and detect procedural complications. We also report our single-center experience, suggesting, for the first time, possible clinical implications for vWF in percutaneous mitral valve repair (MitraClip). This review summarizes recent advances in the role of vWF in VHD with an updated overview going from bench to operating room.

  18. Implication de la mucine membranaire MUC1 dans la progression tumorale rénale et identification de nouvelles cibles thérapeutiques

    OpenAIRE

    Bouillez , Audrey

    2014-01-01

    Renal cell carcinoma corresponds to 5% of all adult malignancies and originates from renal tubules. The main histologic subtype is represented by clear renal cell carcinoma. Ninety percent of cRCC present a biallelic inactivation of the von Hippel Lindau (VHL) tumor suppressor gene resulting in constitutive activation of hypoxia signaling pathway via the Hypoxia Inducible Factor (HIF) -1 transcription factor that contributes to the physiology of tumours. cRCC is typically highly resistant to ...

  19. Increased active von Willebrand factor during disease development in the aging diabetic patient population.

    Science.gov (United States)

    Chen, Shuang Feng; Xia, Zuo Li; Han, Ji Ju; Wang, Yi Ting; Wang, Ji Yue; Pan, Shao Dong; Wu, Ya Ping; Zhang, Bin; Li, Guang Yao; Du, Jing Wei; Gao, Hen Qiang; de Groot, Philip G; de Laat, Bas; Hollestelle, Martine J

    2013-02-01

    Type 2 diabetes is known to cause endothelial activation resulting in the secretion of von Willebrand factor (VWF). We have shown that levels of VWF in a glycoprotein Ib-binding conformation are increased in specific clinical settings. The aim of the current study is to investigate whether active VWF levels increase during aging and the development of diabetes within the population of patients suffering from type 2 diabetes. Patients and controls were divided into two groups based on age: older and younger than 60 years of age. VWF antigen, VWF propeptide, VWF activation factor and total active VWF were measured. Patients older than 60 years of age had increased levels of total active VWF, VWF activation factor and VWF propeptide compared to younger patients and controls. All measured VWF parameters were associated with age in diabetic patients. Total active VWF and VWF propeptide correlated with the period of being diagnosed with diabetes. Regression analyses showed that especially the VWF activation factor was strongly associated with diabetes in patients older than 60 years of age. In conclusion, we found that the conformation of VWF could be involved in the disease process of diabetes and that the VWF in a glycoprotein Ib-binding conformation could play a role as risk marker during the development of diabetes in combination with an increase in age. Our study shows that the active quality of VWF was more important than the quantity.

  20. Von recklinghausens disease: a series of four cases with variable expression.

    Science.gov (United States)

    Arun, K P; Thomas Joseph, P; Jaishankar, H P; Abhinethra, M S

    2015-03-01

    Though neurofibromatosis type I (NFI) is a fairly common condition, it has a variable expressivity and penetrance. Here we present a series of cases with striking differences in the presentation especially in the oral cavity. NFI, also known as von Recklinghausen's neurofibromatosis, is an autosomal dominantly inherited neurogenetic disorder affecting 1:3000 newborn (Bongiorno et al., Oral Dis 12:125-129, 2006). About 50 % of NFI patients have no family history of the disease. There is no prevalence for gender or race in NFI. Expressivity in NFI is tremendously variable, but subtle phenotypic patterns may exist within subgroups of affected patients. Furthermore, 50 % of cases are sporadic and arise from germ cell mutation (Bongiorno et al., Oral Dis 12:125-129, 2006). The precise constellation of findings in any one individual is extremely variable, both within a family and between different families (Batsakis, Tumors of the head and neck: clinical and pathological considerations, 2nd edn. Williams and Wilkins, Baltimore, pp 313-333, 1979). Only 4-7 % of patients affected by neurofibromatosis exhibit oral manifestations (Güneri et al., Turk J Pediatr 48(2):155-158, 2006).

  1. A case of von Willebrand disease discovered during treatment of a sacral pressure ulcer.

    Science.gov (United States)

    Murakami, Masahiro; Fukaya, Sumiko; Furuya, Masaichi; Hyakusoku, Hiko

    2010-12-01

    A sacral pressure ulcer developed in a patient hospitalized for cerebral infarction. Each time necrotic tissue was debrided from the ulcer, pressure hemostasis was necessary to stop the bleeding. As treatment continued, the pressure required to stop the bleeding caused the ulcer to worsen, leading to a downward spiral in the patient's condition. While trying to determine the cause of this problem, we discovered that the patient had von Willebrand disease. Medication controlled the bleeding, and the pressure ulcer began to heal at the same time. It was clear to us that conservative treatment would lead to a complete cure but that the healing process would take a long time and require continued administration of an expensive drug. We decided, therefore, to close the wound with a fasciocutaneous flap so that the patient could be quickly transferred to a rehabilitation hospital. About 1 month after surgery, epithelialization was complete, we were able to discontinue medication, and the patient was discharged. This experience demonstrates the importance of determining the cause of any deviation from the normal course of healing in pressure ulcers. It also indicates that the use of fasciocutaneous flaps, which involve little intraoperative bleeding in short surgeries, is appropriate in cases like this one.

  2. Successful Ultrasound-Guided Femoral Nerve Blockade and Catheterization in a Patient with Von Willebrand Disease

    Directory of Open Access Journals (Sweden)

    Youmna E. DiStefano

    2015-01-01

    Full Text Available Peripheral nerve blockade (PNB is superior to neuraxial anesthesia and/or opioid therapy for perioperative analgesia in total knee replacement (TKR. Evidence on the safety of PNB in patients with coagulopathy is lacking. We describe the first documented account of continuous femoral PNB for perioperative analgesia in a patient with Von Willebrand Disease (vWD. Given her history of opioid tolerance and after an informative discussion, a continuous femoral PNB was planned for in this 34-year-old female undergoing TKR. A Humate-P intravenous infusion was started and the patient was positioned supinely. Using sterile technique with ultrasound guidance, a Contiplex 18 Gauge Tuohy needle was advanced in plane through the fascia iliaca towards the femoral nerve. A nerve catheter was threaded through the needle and secured without complications. Postoperatively, a levobupivacaine femoral catheter infusion was maintained, and twice daily Humate-P intravenous infusions were administered for 48 hours; enoxaparin thromboprophylaxis was initiated thereafter. The patient was discharged uneventfully on postoperative day 4. Given documentation of delayed, unheralded bleeding from PNB in coagulopathic patients, we recommend individualized PNB in vWD patients. Multidisciplinary team involvement is required to guide factor supplementation and thromboprophylaxis, as is close follow-up to elicit signs of bleeding throughout the delayed postoperative period.

  3. Generation and validation of the Condensed MCMDM-1VWD Bleeding Questionnaire for von Willebrand disease.

    Science.gov (United States)

    Bowman, M; Mundell, G; Grabell, J; Hopman, W M; Rapson, D; Lillicrap, D; James, P

    2008-12-01

    Given the challenges involved in obtaining accurate bleeding histories, attempts at standardization have occurred and the value of quantifying hemorrhagic symptoms has been recognized. An extensive validated bleeding questionnaire (MCMDM-1VWD) was condensed by eliminating all details that did not directly affect the bleeding score (BS) and the correlation between the two versions was tested. Additionally, the diagnostic utility of the condensed version was prospectively tested. Data on 259 individuals who were administered the questionnaire are presented here; 217 being prospectively investigated for von Willebrand disease (VWD) (group 1) and 42 previously known to have type 1, 2 or 3 VWD (group 2). Of the 217 prospectively investigated, 35 had positive BS (> or =4) and 182 had negative scores. Seven individuals (all with positive BS) had laboratory results consistent with type 1 VWD. This results in a sensitivity of 100% and a specificity of 87%. The positive predictive value is 0.20 and the negative predictive value is 1. The correlation between the full MCMDM-1VWD and condensed versions is excellent (Spearman's 0.97, P type 2 > type 1 VWD (anova P < 0.001). There is a strong inverse relationship between VWF:Ag level and BS (Spearman's -0.411, P < 0.001). The Condensed MCMDM-1VWD Bleeding Questionnaire is an efficient, effective tool in the evaluation of patients for VWD.

  4. Hemophilia and von Willebrand's disease: 1. Diagnosis, comprehensive care and assessment. Association of Hemophilia Clinic Directors of Canada.

    Science.gov (United States)

    1995-07-01

    To present current strategies for the assessment and comprehensive care of patients with hemophilia and von Willebrand's disease. Hospital care, home care, single-provider care and multidisciplinary care. Morbidity and quality of life associated with bleeding and treatment. Relevant clinical studies and reports published from 1974 to 1994 were examined. A search was conducted of own reprint files, MEDLINE, citations in the articles reviewed and references provided by colleagues. In the MEDLINE search the following terms were used singly or in combination: "hemophilia," "von Willebrand's disease," "Factor VIII," "Factor IX," "von Willebrand factor," "diagnosis," "management," "home care," "comprehensive care," "inhibitor," "AIDS," "hepatitis," "life expectancy," "complications," "practice guidelines," "consensus statement" and "controlled trial." The in-depth review included only articles written in English from North America and Europe that were relevant to human disease and to a predetermined outline. The availability of treatment products in Canada was also considered. Minimizing morbidity and maximizing functional status and quality of life were given a high value. The optimal use of treatment procedures and home care offers patients the advantages of minimized disability, improved survival and financial benefit. It is also cost effective. Potential harm, including the risk of hepatitis B, hepatitis C and HIV infection, has now been minimized through viral inactivation of plasma-derived coagulation-factor concentrates and through the use of recombinant clotting factor concentrates and other non-plasma-derived hemostatic agents. Patients with hemophilia and severe von Willebrand's disease should be followed in comprehensive care centres that offer expertise in the diagnosis, assessment and management of bleeding and complications and that can meet the educational and counselling needs of patients, family members and health care providers. Eligible patients should

  5. Colour atlas on forest disease. Diagnosis of tree diseases. Farbatlas Waldschaeden. Diagnose von Baumkrankheiten

    Energy Technology Data Exchange (ETDEWEB)

    Hartmann, G.; Winter, K.; Nienhaus, F.; Butin, H.

    1988-01-01

    The 'Colour Atlas on Forest Disease' facilitates the diagnosis of syndromes due to different causes in 16 genera or species of forest trees. It contains a selection of more than 200 important, frequent, or conspicuous disease phenomena. These include: in a ratio of 8 percent partly novel, complex diseases due to causes not entirely elucidated, 35 percent known forms of damage of abiotic origin (extreme weather conditions, nutrient deficiency, classical damage due to environmental pollution and de-icing salt, damage through herbicides), and 57 percent diseases and harm of biotic origin (fungal infections, infestation with insect pest, bacterial, mycoplasmal, rickettsia-type and viral diseases, other damage). 418 colour photographs show characteristic features of tree diseases and provide clues to causes and possible alternative diseases liable to be mixed up with the actual one. The selection decided on is restricted to symptoms visible externally in the area of the crowns as far as they are distinguishable in the field. (orig./MG) With 418 colour photographs.

  6. Plasmatic ADAMTS-13 metalloprotease and von Willebrand factor in children with cyanotic congenital heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Soares, R.P.S. [Fundação Pró-Sangue Hemocentro de São Paulo, São Paulo, SP (Brazil); Bydlowski, S.P.; Nascimento, N.M. [Laboratório de Investigação Médica-31, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Thomaz, A.M.; Bastos, E.N.M.; Lopes, A.A. [Faculdade de Medicina, Instituto do Coração, Universidade de São Paulo, São Paulo, SP (Brazil)

    2013-04-05

    Changes in plasma von Willebrand factor concentration (VWF:Ag) and ADAMTS-13 activity (the metalloprotease that cleaves VWF physiologically) have been reported in several cardiovascular disorders with prognostic implications. We therefore determined the level of these proteins in the plasma of children with cyanotic congenital heart disease (CCHD) undergoing surgical treatment. Forty-eight children were enrolled (age 0.83 to 7.58 years). Measurements were performed at baseline and 48 h after surgery. ELISA, collagen-binding assays and Western blotting were used to estimate antigenic and biological activities, and proteolysis of VWF multimers. Preoperatively, VWF:Ag and ADAMTS-13 activity were decreased (65 and 71% of normal levels considered as 113 (105-129) U/dL and 91 ± 24% respectively, P < 0.003) and correlated (r = 0.39, P = 0.0064). High molecular weight VWF multimers were not related, suggesting an interaction of VWF with cell membranes, followed by proteolytic cleavage. A low preoperative ADAMTS-13 activity, a longer activated partial thromboplastin time and the need for cardiopulmonary bypass correlated with postoperative bleeding (P < 0.05). Postoperatively, ADAMTS-13 activity increased but less extensively than VWF:Ag (respectively, 2.23 and 2.83 times baseline, P < 0.0001), resulting in an increased VWF:Ag/ADAMTS-13 activity ratio (1.20 to 1.54, respectively, pre- and postoperative median values, P = 0.0029). ADAMTS-13 consumption was further confirmed by decreased ADAMTS-13 antigenic concentration (0.91 ± 0.30 to 0.70 ± 0.25 µg/mL, P < 0.0001) and persistent proteolysis of VWF multimers. We conclude that, in pediatric CCHD, changes in circulating ADAMTS-13 suggest enzyme consumption, associated with abnormal structure and function of VWF.

  7. Fluid-phase immunoradiometric assay for the detection of qualitative abnormalities of factor VIII/von Willebrand factor in variants of von Willebrand's disease

    International Nuclear Information System (INIS)

    Girma, J.P.; Ardaillou, N.; Meyer, D.; Lavergne, J.M.; Larrieu, M.J.

    1979-01-01

    Antigenic reactivity of F.VIII/WF in variants of von Willebrand's disease (vWd) was studied with both fluid-phase and solid-phase immunoradiometric assays. Two different (rabbit and goat) 125 I-labeled specific antibodies against purified F.VIII/WF were used in both their divalent (lgG) and their monovalent (Fab fragment) forms. Dose-response curves obtained by reacting a constant amount of antibody with serial dilutions of plasmas from normal or homozygous vWd demonstrated the specificity of the test. The accuracy was significantly higher with 125 I-Fab fragments of goat anti-F.VIII/WF antiserum than intact goat lgG or rabbit lgG or Fab fragments. The significant decrease of the slope of the dose-response curves obtained with plasma from variants of vWd has been interpreted as due to the presence of abnormal F.VIII/WF molecules with decreased antigenic reactivity. A similar anomaly was found in cryosupernatant prepared from normal plasma, paralleling similarities demonstrated between variants of vWd and cryosupernatant. Results of experiments performed by reacting constant plasma dilutions from control or variants of vWd and varying concentrations of anti-F.VIII/WF Fab fragments (rabbit or goat) confirmed the decreased antigenic reactivity of variant F.VIII/WF

  8. An essay on Wilhelm von Humboldt and the shaking palsy: first comprehensive description of Parkinson's disease by a patient.

    Science.gov (United States)

    Horowski, R; Horowski, L; Vogel, S; Poewe, W; Kielhorn, F W

    1995-03-01

    James Parkinson first described what is now known as Parkinson's disease in his essay in 1817 on the shaking palsy, but the disease became well-known to neurologists only in the second half of the 19th century. In his letters from 1828 until his death in 1835, Wilhelm von Humboldt, a well-known German academic reformer, humanist scholar, and statesman, precisely described the manifestations of this disease. These included resting tremor and especially problems in writing, called by him "a special clumsiness" that he attributed to a disturbance in executing rapid complex movements. In addition to lucidly describing akinesia, he was also the first to describe micrographia. He furthermore noticed his typical parkinsonian posture and, in all probability, his rigidity as "internal tremor not visible by others which causes a distortion of the continuity of my movements." He insisted, however, that he was suffering not from a disease but just from accelerated aging related to the death of his wife. His description of the disease is more complete than the observations and definition by James Parkinson; his attitude toward his disease illustrates why it was not readily accepted as a disease in itself but might have been considered an extreme variant of aging instead.

  9. A 12.3-kb Duplication Within the VWF Gene in Pigs Affected by Von Willebrand Disease Type 3

    Directory of Open Access Journals (Sweden)

    Stefanie Lehner

    2018-02-01

    Full Text Available Von Willebrand Disease (VWD type 3 is a serious and sometimes fatal hereditary bleeding disorder. In pigs, the disease has been known for decades, and affected animals are used as models for the human disease. Due to the recessive mode of inheritance of VWD type 3, severe bleeding is typically seen in homozygous individuals. We sequenced the complete porcine VWF (Von Willebrand Factor complementary DNA (cDNA and detected a tandem duplication of exons 17 and 18, causing a frameshift and a premature termination codon (p.Val814LeufsTer3 in the affected pig. Subsequent next generation sequencing on genomic DNA proved the existence of a 12.3-kb tandem duplication associated with VWD. This duplication putatively originates from porcine Short Interspersed Nuclear Elements (SINEs located within VWF introns 16 and 18 with high identity. The premature termination truncates the VWF open reading frame by a large part, resulting in an almost entire loss of the mature peptide. It is therefore supposed to account for the severe VWD type 3. Our results further indicate the presence of strong, nonsense-mediated decay in VWF messenger RNA (mRNA containing the duplication, which was supported by the almost complete absence of the complete VWF protein in immunohistochemistry analysis of the VWD-affected pig. In the past, differentiation of wild-type and heterozygous pigs in this VWD colony had to rely on clinical examinations and additional laboratory methods. The present study provides the basis to distinguish both genotypes by performing a rapid and simple genetic analysis.

  10. Dogs with hearth diseases causing turbulent high-velocity blood flow have changes in patelet function and von Willebrand factor multimer distribution

    DEFF Research Database (Denmark)

    Tarnow, Inge; Kristensen, Annemarie Thuri; Olsen, Lisbeth Høier

    2005-01-01

    The purpose of this prospective study was to investigate platelet function using in vitro tests based on both high and low shear rates and von Willebrand factor (vWf) multimeric composition in dogs with cardiac disease and turbulent high-velocity blood flow. Client-owned asymptomatic, untreated d...

  11. [Emergent Caesarean Section in a Patient with a Mediastinal Tumor and Von Recklinghausen Disease: A Case Report].

    Science.gov (United States)

    Owada, Mayuko; Inomata, Shinichi; Danmura, Masato; Yamada, Kumiko; Tanaka, Makoto

    2016-06-01

    It is rare to encounter a pregnant patient with a mediastinal tumor, and if the tumor size increases as the pregnancy progresses, this increase can cause complications such as airway constriction and vascular occlusion. We report a case of a pregnant patient diagnosed with von Recklinghausen disease at the age of seven and diagnosed with a mediastinal tumors just after her present admission. The impending suffocation progressed and fetal heart rate decreased during her hospitalization. Her trachea was intubated and she was moved to an operating room for an emergent cesarean section under general anesthesia. With this rapid response, we could rescue both patient and infant. If the size of mediastinal tumor increases as pregnancy progresses, the tumor will cause suffocation by airway compression from the outside, in addition to specific airway edema on the inward side. The present case demonstrates that appropriate desisoins must be made for airway manegement and initiation of surgery.

  12. An immunoradiometric assay for procoagulant factor VIII antigen: results in haemophilia, von Willebrand's disease and fetal plasma and serum

    International Nuclear Information System (INIS)

    Peake, I.R.; Bloom, A.L.; Giddings, J.C.; Ludlam, C.A.

    1979-01-01

    An immunoradiometric assay (IRMA) has been developed based on the inhibitor which arose in a polytransfused severe haemophiliac. The two-site IRMA measured antigens closely associated with the procoagulant parts of the factor VIII complex, which are termed FVIIIC antigens or FVIIICAG. FVIIICAG was present in normal plasma and also, at a slightly lower concentration, in normal serum. In 37 patients with haemophilia A, 36 had FVIIICAG levels of less than 10% of the normal plasma pool. In patients with von Willebrand's disease the levels of FVIIIC and FVIIICAG were in good agreement, both before and after treatment with cryoprecipitate or DDAVP. FVIIICAG was relatively stable in plasma at 37 0 C and could also be detected in cord and fetal serum. The assay is of potential value for detecting reduced levels of factor VIII, for carrier detection and for the prenatal diagnosis of haemophilia. (author)

  13. Platelet-type von Willebrand Disease: Diagnostic Challenges. Flaws and Pitfalls Experienced in the THROMKID Quality Project.

    Science.gov (United States)

    Maurer, M; Mesters, R; Schneppenheim, R; Knoefler, R; Streif, W

    2015-05-01

    Primary haemostasis defects comprise von Willebrand disease (VWD) and platelet disorders (PD). Although presenting with mild to moderate bleeding tendency in most cases, severe bleeding and blood loss may occur unexpectedly in trauma and surgery. Diagnosis of VWD and PD often remains difficult owing to the wide spectrum of clinical and laboratory manifestations. Platelet-type von Willebrand disease (PT-VWD) is frequently misdiagnosed as type 2B VWD. Discrimination between type 2B VWD and PT-VWD is crucial as treatment differs. A literature review revealed difficulties in diagnostic work-up and choice of optimal treatment of PT-VWD. Guidelines favour the therapeutic use of platelet concentrates. A telephone survey of diagnostic practice with regard to type 2B VWD/PT-VWD was conducted. The prevalence and incidence of type 2B and PT-VWD remained unclear, but PT-VWD may be underestimated. An international study estimated that PT-VWD constitutes up to 15% of the total number of patients diagnosed with type 2B VWD. Our survey confirmed difficulties with diagnosis and showed that some centres did not exclude PT-VWD in type 2B patients. Some authors emphasize that genetic testing is the gold standard for diagnosis, but functional testing allows immediate diagnosis. Due to the important therapeutic implications we suggest that type 2B VWD be confirmed by genetic testing and that in case of a negative result PT-VWD should be excluded. PT-VWD should be excluded in all suspected cases of type 2B. PT-VWD should be treated with platelet concentrates. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Molecular and clinical profile of von Willebrand disease in Spain (PCM-EVW-ES): comprehensive genetic analysis by next-generation sequencing of 480 patients.

    Science.gov (United States)

    Borràs, Nina; Batlle, Javier; Pérez-Rodríguez, Almudena; López-Fernández, María Fernanda; Rodríguez-Trillo, Ángela; Lourés, Esther; Cid, Ana Rosa; Bonanad, Santiago; Cabrera, Noelia; Moret, Andrés; Parra, Rafael; Mingot-Castellano, María Eva; Balda, Ignacia; Altisent, Carme; Pérez-Montes, Rocío; Fisac, Rosa María; Iruín, Gemma; Herrero, Sonia; Soto, Inmaculada; de Rueda, Beatriz; Jiménez-Yuste, Víctor; Alonso, Nieves; Vilariño, Dolores; Arija, Olga; Campos, Rosa; Paloma, María José; Bermejo, Nuria; Berrueco, Rubén; Mateo, José; Arribalzaga, Karmele; Marco, Pascual; Palomo, Ángeles; Sarmiento, Lizheidy; Iñigo, Belén; Nieto, María Del Mar; Vidal, Rosa; Martínez, María Paz; Aguinaco, Reyes; César, Jesús María; Ferreiro, María; García-Frade, Javier; Rodríguez-Huerta, Ana María; Cuesta, Jorge; Rodríguez-González, Ramón; García-Candel, Faustino; Cornudella, Rosa; Aguilar, Carlos; Vidal, Francisco; Corrales, Irene

    2017-12-01

    Molecular diagnosis of patients with von Willebrand disease is pending in most populations due to the complexity and high cost of conventional molecular analyses. The need for molecular and clinical characterization of von Willebrand disease in Spain prompted the creation of a multicenter project (PCM-EVW-ES) that resulted in the largest prospective cohort study of patients with all types of von Willebrand disease. Molecular analysis of relevant regions of the VWF , including intronic and promoter regions, was achieved in the 556 individuals recruited via the development of a simple, innovative, relatively low-cost protocol based on microfluidic technology and next-generation sequencing. A total of 704 variants (237 different) were identified along VWF , 155 of which had not been previously recorded in the international mutation database. The potential pathogenic effect of these variants was assessed by in silico analysis. Furthermore, four short tandem repeats were analyzed in order to evaluate the ancestral origin of recurrent mutations. The outcome of genetic analysis allowed for the reclassification of 110 patients, identification of 37 asymptomatic carriers (important for genetic counseling) and re-inclusion of 43 patients previously excluded by phenotyping results. In total, 480 patients were definitively diagnosed. Candidate mutations were identified in all patients except 13 type 1 von Willebrand disease, yielding a high genotype-phenotype correlation. Our data reinforce the capital importance and usefulness of genetics in von Willebrand disease diagnostics. The progressive implementation of molecular study as the first-line test for routine diagnosis of this condition will lead to increasingly more personalized and effective care for this patient population. Copyright© 2017 Ferrata Storti Foundation.

  15. Gene Discovery in Prostate Cancer: Functional Identification and Isolation of PAC-1, a Novel Tumor Suppressor Gene Within Chromosome 10p

    Science.gov (United States)

    1999-09-01

    I.. Zbar. B.. androle for the VHL gene in the development of hyperplasia in a number Lerman. I. I. Identification of the son Hippel-Lindau disease...of heterozy- gosity of chromosome 3p markers in small-cell lung cancer. Nature (Lond.). 329: eleguns produced hyperplasia in all tissues (26...central fibrovascular core lined by cuboidal tumor cells. Tumor weights were determined (Fig. 2d). At the end of 47 days after cells were

  16. Epidemiologic features of von Willebrand's disease in Doberman pinschers, Scottish terriers, and Shetland sheepdogs: 260 cases (1984-1988)

    Science.gov (United States)

    Brooks, M; Dodds, W J; Raymond, S L

    1992-04-15

    During a study period from 1985 through 1988, plasma von Willebrand's factor antigen (vWF:Ag) concentration was measured as a marker for prevalence of the von Willebrand's disease (vWD) trait in Doberman Pinschers (doberman, n = 5,554), Scottish Terriers (scottie, n = 1,363), and Shetland Sheepdogs (sheltie, n = 4,279). Significant increase in prevalence of the trait was seen in scotties and shelties during this period. In 1988, 73% of dobermans, 30% of scotties, and 28% of shelties tested had abnormal vWF:Ag concentration (less than 50% vWF:Ag). We found significant differences between breeds with respect to age and vWF:Ag concentration of clinically affected dogs at time of diagnosis. The affected dobermans were older (doberman mean age, 4.6 years; scottie mean age, 1.7 years; sheltie mean age, 1.9 years) and had higher concentration of plasma vWF:Ag (doberman mean vWF:Ag, 15%; scottie mean vWF:Ag, 0%; sheltie mean vWF:Ag, 8%). Bleeding in affected dogs of all 3 breeds was observed predominantly from mucosal surfaces and from cutaneous sites of surgery or trauma. The most common site of mucosal bleeding in scotties and shelties was oral or nasal cavity, and in dobermans was the urogenital tract. Differences in clinical manifestations of vWD in purebred dogs may reflect heterogeneous defects within the vWF gene, causing a variety of abnormalities in production, structure, and function of vWF protein. Analogous to vWD in human beings, acquired deficiencies of vWF may also contribute to the clinical variability of vWD in dogs.

  17. 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)

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

    Directory of Open Access Journals (Sweden)

    Kathryn E Hacker

    Full Text Available 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.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.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.

  19. Global warming and spread of infectious diseases; Globale Erwaermung und Ausbreitung von Infektionskrankheiten

    Energy Technology Data Exchange (ETDEWEB)

    Ebert, B.; Fleischer, B. [Bernhard-Nocht-Institut fuer Tropenmedizin (BNI), Hamburg (Germany)

    2005-01-15

    At the end of the twentieth century, tropical infectious diseases increased despite earlier successes of eradication campaigns. As a global warming of 1.4-5.8 C is anticipated to occur by 2100, mainly the vector-borne tropical diseases that are particularly sensitive to climate are expected to spread. Although biological reasons seemingly support this hypothesis, ecological and socio-economic factors have in the past proven to be stronger driving forces for the spread of infectious diseases than climate. (orig.)

  20. Nuclear medicine in hip disease of adults. Nuklearmedizinische Diagnostik von Hueftgelenkserkrankungen im Erwachsenenalter

    Energy Technology Data Exchange (ETDEWEB)

    Sciuk, S; Schober, O [Muenster Univ. (Germany, F.R.). Klinik und Poliklinik fuer Nuklearmedizin

    1989-10-01

    Skeletal scintigraphy has a high sensitivity but low specificity in early detection and follow up of hip diseases. Unexplained hip pain or indistinct X-rays may be the reason for scintigraphic examination. On the other hand, there is a wide range of clinical indications for nuclear medicine examination, such as metastatic and primary malignant disease, tumor-like lesions, inflammatory, infectious, degenerative and avascular diseases, and posttraumatic and postoperative changes. White blood cell scintigraphy is highly sensitive and highly specific in the detection of infectious disease of the hip. In the vast majority of cases, physiologic or postoperative granulocytic accumulation can be differentiated from infectious accumulation, which requires therapy. (orig.).

  1. 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.

  2. Science.gov (United States)

    Zanoletti, E.; Borsetto, D.; Opocher, G.; Mazzoni, A.; Martini, A.

    2017-01-01

    SUMMARY Endolymphatic sac tumour (ELST) is infrequent, as emerges from small series reported in the literature. It is a slow-growing malignancy with local aggressiveness and a low risk of distant metastases. It is often misdiagnosed because of the late onset of symptoms and difficulty in obtaining a biopsy. Its frequency is higher in von Hippel-Lindau (VHL) disease (a genetic systemic syndrome involving multiple tumours), with a prevalence of around 25%. The diagnosis is based on radiology, with specific patterns on contrast-enhanced MRI and typical petrous bone erosion on bone CT scan. Our experience of ELST in the years between 2012-2015 concerns 7 cases, one of which was bilateral, in patients with VHL disease. Four of the 7 patients underwent 5 surgical procedures at our institution. Each case is described in detail, including clinical symptoms, and the intervals between symptom onset, diagnosis and therapy. Postoperative morbidity was low after early surgery on small tumours, whereas extensive surgery for large tumours was associated with loss of cranial nerve function (especially VII, IX, X). The critical sites coinciding with loss of neurological function were the fallopian canal, jugular foramen, petrous apex and intradural extension into the posterior cranial fossa. Early surgery on small ELST is advocated for patients with VHL disease, in whom screening enables a prompt diagnosis and consequently good prognosis. PMID:29165437

  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. Genetic predisposition to kidney cancer.

    Science.gov (United States)

    Schmidt, Laura S; Linehan, W Marston

    2016-10-01

    Kidney cancer is not a single disease but is made up of a number of different types of cancer classified by histology that are disparate in presentation, clinical course, and genetic basis. Studies of families with inherited renal cell carcinoma (RCC) have provided the basis for our understanding of the causative genes and altered metabolic pathways in renal cancer with different histologies. Von Hippel-Lindau disease was the first renal cancer disorder with a defined genetic basis. Over the next two decades, the genes responsible for a number of other inherited renal cancer syndromes including hereditary papillary renal carcinoma, Birt-Hogg-Dube´syndrome, hereditary leiomyomatosis and renal cell carcinoma, and succinate dehydrogenase-associated renal cancer were identified. Recently, renal cell carcinoma has been confirmed as part of the clinical phenotype in individuals from families with BAP1-associated tumor predisposition syndrome and MiTF-associated cancer syndrome. Here we summarize the clinical characteristics of and causative genes for these and other inherited RCC syndromes, the pathways that are dysregulated when the inherited genes are mutated, and recommended clinical management of patients with these inherited renal cancer syndromes. Published by Elsevier Inc.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Papillary cystadenoma of the epididymis in a 12-year-old survivor of stage IV neuroblastoma

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    Nnenaya Agochukwu

    2018-04-01

    Full Text Available Papillary cystadenoma of the epididymis (PCE is the second most common benign neoplasm of the epididymis [1]. It is very uncommon and has never been reported in a prepubertal male. It may occur sporadically, but more often occurs in association with von Hippel- Lindau (VHL disease [2]. There have been over 60 reports of patients with such tumors, with the youngest patient being 16 years old.We present the case of a 12- year old male with a history of stage IV neuroblastoma. He presented with a left paratesticular mass that was discovered on routine follow up physical exam with his pediatric oncologist. He was asymptomatic at the time of presentation with no signs or symptoms of hypoandrogenism. A computed tomography scan of the abdomen and pelvis was negative for lymphadenopathy and additional disease sites. Given the patient's history of stage IV neuroblastoma, there was suspicion of yolk sac tumor or metastases; he underwent an open radical left orchiectomy. Frozen section was consistent with yolk sac tumor, however final pathology revealed normal testicle with PCE.To date, this patient is the youngest reported patient with this diagnosis; furthermore papillary cystadenoma of the epididymis has never been reported in a patient with neuroblastoma. Keywords: Papillary cystadenoma, Epididymis, Prepubertal male, Neuroblastoma

  7. 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.

  8. Identification and Characterization of Novel Variations in Platelet G-Protein Coupled Receptor (GPCR Genes in Patients Historically Diagnosed with Type 1 von Willebrand Disease.

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    Jacqueline Stockley

    Full Text Available The clinical expression of type 1 von Willebrand disease may be modified by co-inheritance of other mild bleeding diatheses. We previously showed that mutations in the platelet P2Y12 ADP receptor gene (P2RY12 could contribute to the bleeding phenotype in patients with type 1 von Willebrand disease. Here we investigated whether variations in platelet G protein-coupled receptor genes other than P2RY12 also contributed to the bleeding phenotype. Platelet G protein-coupled receptor genes P2RY1, F2R, F2RL3, TBXA2R and PTGIR were sequenced in 146 index cases with type 1 von Willebrand disease and the potential effects of identified single nucleotide variations were assessed using in silico methods and heterologous expression analysis. Seven heterozygous single nucleotide variations were identified in 8 index cases. Two single nucleotide variations were detected in F2R; a novel c.-67G>C transversion which reduced F2R transcriptional activity and a rare c.1063C>T transition predicting a p.L355F substitution which did not interfere with PAR1 expression or signalling. Two synonymous single nucleotide variations were identified in F2RL3 (c.402C>G, p.A134 =; c.1029 G>C p.V343 =, both of which introduced less commonly used codons and were predicted to be deleterious, though neither of them affected PAR4 receptor expression. A third single nucleotide variation in F2RL3 (c.65 C>A; p.T22N was co-inherited with a synonymous single nucleotide variation in TBXA2R (c.6680 C>T, p.S218 =. Expression and signalling of the p.T22N PAR4 variant was similar to wild-type, while the TBXA2R variation introduced a cryptic splice site that was predicted to cause premature termination of protein translation. The enrichment of single nucleotide variations in G protein-coupled receptor genes among type 1 von Willebrand disease patients supports the view of type 1 von Willebrand disease as a polygenic disorder.

  9. Identification and Characterization of Novel Variations in Platelet G-Protein Coupled Receptor (GPCR) Genes in Patients Historically Diagnosed with Type 1 von Willebrand Disease.

    Science.gov (United States)

    Stockley, Jacqueline; Nisar, Shaista P; Leo, Vincenzo C; Sabi, Essa; Cunningham, Margaret R; Eikenboom, Jeroen C; Lethagen, Stefan; Schneppenheim, Reinhard; Goodeve, Anne C; Watson, Steve P; Mundell, Stuart J; Daly, Martina E

    2015-01-01

    The clinical expression of type 1 von Willebrand disease may be modified by co-inheritance of other mild bleeding diatheses. We previously showed that mutations in the platelet P2Y12 ADP receptor gene (P2RY12) could contribute to the bleeding phenotype in patients with type 1 von Willebrand disease. Here we investigated whether variations in platelet G protein-coupled receptor genes other than P2RY12 also contributed to the bleeding phenotype. Platelet G protein-coupled receptor genes P2RY1, F2R, F2RL3, TBXA2R and PTGIR were sequenced in 146 index cases with type 1 von Willebrand disease and the potential effects of identified single nucleotide variations were assessed using in silico methods and heterologous expression analysis. Seven heterozygous single nucleotide variations were identified in 8 index cases. Two single nucleotide variations were detected in F2R; a novel c.-67G>C transversion which reduced F2R transcriptional activity and a rare c.1063C>T transition predicting a p.L355F substitution which did not interfere with PAR1 expression or signalling. Two synonymous single nucleotide variations were identified in F2RL3 (c.402C>G, p.A134 =; c.1029 G>C p.V343 =), both of which introduced less commonly used codons and were predicted to be deleterious, though neither of them affected PAR4 receptor expression. A third single nucleotide variation in F2RL3 (c.65 C>A; p.T22N) was co-inherited with a synonymous single nucleotide variation in TBXA2R (c.6680 C>T, p.S218 =). Expression and signalling of the p.T22N PAR4 variant was similar to wild-type, while the TBXA2R variation introduced a cryptic splice site that was predicted to cause premature termination of protein translation. The enrichment of single nucleotide variations in G protein-coupled receptor genes among type 1 von Willebrand disease patients supports the view of type 1 von Willebrand disease as a polygenic disorder.

  10. 3 tesla magnetic resonance imaging in children and adults with congenital heart disease; 3-Tesla-Magnetresonanztomographie zur Untersuchung von Kindern und Erwachsenen mit angeborenen Herzfehlern

    Energy Technology Data Exchange (ETDEWEB)

    Voges, I.; Hart, C.; Kramer, H.H.; Rickers, C. [Universitaetsklinikum Schleswig-Holstein, Klinik fuer angeborene Herzfehler und Kinderkardiologie, Kiel (Germany); Jerosch-Herold, M. [Harvard Medical School, Department of Radiology, Brigham and Women' s Hospital, Boston (United States); Helle, M. [Universitaetsklinikum Schleswig-Holstein, Institut fuer Neuroradiologie, Kiel (Germany)

    2010-09-15

    Cardiovascular magnetic resonance imaging (CMR) has become a routinely used imaging modality for congenital heart disease. A CMR examination allows the assessment of thoracic anatomy, global and regional cardiac function, blood flow in the great vessels and myocardial viability and perfusion. In the clinical routine cardiovascular MRI is mostly performed at field strengths of 1.5 Tesla (T). Recently, magnetic resonance systems operating at a field strengths of 3 T became clinically available and can also be used for cardiovascular MRI. The main advantage of CMR at 3 T is the gain in the signal-to-noise ratio resulting in improved image quality and/or allowing higher acquisition speed. Several further differences compared to MRI systems with lower field strengths have to be considered for practical applications. This article describes the impact of CMR at 3 T in patients with congenital heart disease by meanings of methodical considerations and case studies. (orig.) [German] Die kardiovaskulaere Magnetresonanztomographie (MRT) hat sich zu einer etablierten bildgebenden Methode zur Untersuchung von Patienten mit angeborenen Herzfehlern entwickelt. Sie erlaubt in einer einzigen Untersuchung die exakte Beurteilung von Anatomie, globaler und regionaler Funktion, Blutfluessen sowie der myokardialen Perfusion und Vitalitaet. In der klinischen Routine erfolgen die Untersuchungen zumeist bei einer Feldstaerke von 1,5 Tesla (T), mittlerweile gibt es jedoch Geraete und Bildgebungstechniken, die die kardiovaskulaere MRT auch bei 3 T ermoeglichen. Der wesentliche Vorteil der MRT bei 3 T ist das hoehere Signal-zu-Rausch-Verhaeltnis, das sowohl zu einer Verbesserung der Bildqualitaet als auch zu einer Verkuerzung der Untersuchungszeit genutzt werden kann. Darueber hinaus bestehen verschiedene andere Unterschiede gegenueber Systemen mit niedriger Feldstaerke, die im praktischen Einsatz beachtet werden muessen. Dieser Artikel beschreibt die Erfahrungen der 3-T-MRT fuer die

  11. Radiofrequency ablation of renal cell carcinoma under CT guidance. Present and Future status

    International Nuclear Information System (INIS)

    Nasu, Yasutomo; Kobayashi, Yasuyuki; Uematsu, Katsutoshi; Saika, Takashi; Kumon, Hiromi; Gohara, Hideo; Mimura, Hidefumi; Kanazawa, Susumu

    2011-01-01

    At Okayama University, radiofrequency ablation (RFA) of renal cell carcinoma was performed in May 2002 as the initial case in Japan. In 2004, it was regarded as an advanced medical technique by the Japanese authority. Since then, RFA has been actively performed for renal cell carcinoma not only at the primary site but also at the metastatic site, including the lung and bone. The clinical outcome has been compatible with other institutes and no serious adverse events have occurred. From the view paint of fusing technical innovation with medical safety, this treatment is a potent therapeutic option for renal cell carcinoma. In the era of laparoscopic surgery, RFA is indicated for cases with von Hippel-Lindau disease (VHL), recurrence after partial nephrectomy, a single kidney and intolerance to general anesthesia, due to its technical advantage in that RFA can be repeated. In this review, the current clinical outcome is reported and future prospects are discussed as to whether it can be the safest and most concrete treatment for renal cell carcinoma in the 21 st century. (author)

  12. Short-Spindled Cell Haemangioblastoma with CD34 Expression: New Histopathological Variant or Just a Stochastic Cytological Singularity?

    Directory of Open Access Journals (Sweden)

    Miguel Fdo. Salazar

    2016-01-01

    Full Text Available Haemangioblastomas are neoplasms of uncertain histogenesis with cellular and reticular variants advocated in current lore. Herein we describe an intriguing cerebellar specimen with unusual traits including spindle cell morphology and CD34 positivity. A thirty-nine-year old man had an infratentorial tumour discovered incidentally and resected three times. In all the instances, histopathological diagnosis was haemangioblastoma; nonetheless, he had neither physical stigmata nor family history of von Hippel-Lindau disease. By histology, the lesion was composed of areas of conventional stromal cells admixed with territories populated by short-spindled cells packed in lobules, sometimes giving the appearance of gomitoli. Immunoperoxidase-coupled reactions confirmed the expression of inhibin A, neuron-specific enolase (NSE, PS100, and CD57 but also revealed focal immunolabeling for CD34, CD99, and FXIIIa. This case highlights the potential phenotypical diversity that can be found within these neoplasms. Rather than uncertain histogenesis, it may in fact reflect multiple lines of differentiation—histomimesis—prone to adopt unusual morpho- and immunophenotypes in a subset of haemangioblastomas.

  13. 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.

  14. mTOR inhibitors in the treatment of advanced renal cell carcinoma

    International Nuclear Information System (INIS)

    Barilla, R.; Sycova-Mila, Z.

    2009-01-01

    Renal Cell Carcinoma (RCC) accounts for approximately 4 % of all malignancies. Much is known about the pathogenesis of RCC because of studies examining its close relationship with dysfunction of the Von Hippel-Lindau gene (VHL) and hypoxia inducible factor (HIF). Mammalian target of rapamycin (mTOR) regulates nutritional needs, cell growth, and angiogenesisi in cells by down regulating or up regulating a variety of proteins including HIF. Until 2005, only a single agent high dose interleukin 2 was approved by Food and Drug Administration (FDA) for treatment of advanced renal cell carcinoma. More recently thanks to better knowledge in the field of molecular biology new treatment options appeared. Sunitinib and bevacizumab are currently considered to be treatment of first choice for patients in good and intermediate prognostic group and sorafenib is preferred second line treatment in the same patient population pretreated with cytokines after disease progression. Temsirolimus and everolimus, rapamycin analouges, have recently been tested in III trials in first and second line treatment in patients with advanced metastatic clear cell renal cell carcinoma. (author)

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Disorders of brain development and phakomatosis

    International Nuclear Information System (INIS)

    Merhemis, Z.

    2006-01-01

    Full text: Disorders of brain development and phakomatosis are resulting from disturbed embryonic-foetal development One third of all major embryological anomalies involve CNS, and over 2000 different anomalies have been described. Anomalies of the brain often cause foetal and neonatal death, and mental and physical retardation in pediatric group. The majority of disorders of brain development and phakomatosis are idiopathic, and most of them are not hereditary or familial. Ultrasonography plays the important role in screening foetal and neonatal brain, but after closure of fontanels it is difficult to find the acoustic window. CT has limited contrast resolution, and disadvantage exposing infant to ionizing radiation. It is helpful to demonstrate the presence of calcifications. MR imaging has proved to be a diagnostic tool of major importance in children with disorders of brain development and phakomatosis. The excellent grey/white matter differentiation and multiplanar imaging capabilities of MR allow a systematic analysis of the brain. Disorders occurring in the first 4 weeks of gestation: Disorders of neural tube closure; Chiari malformation; Cephaloceles; Dermoid/Epidermoid. Disorders occurring between 5 and 10 weeks of gestation: Holoprosencephaly; Septo-optic dysplasia; Diencephalic cyst; Dandy Walker complex; Mega cistern magna. Disorders occurring between 2 and 5 months of gestation: Disorders of sulcation and cellular migration; Lissencephaly; Pachigyria; Schizencephaly; Heterotopias; Megaencephaly; Polymicrogyria; Porencephaly; Arachnoid cyst. Corpus callosum anomalies. Phakomatosis: Neurocutaneous Syndromes Neurofibromatosis Type 1 and 2; Tuberous Sclerosis; von Hippel-Lindau disease; Studge-Weber sy; Osler-Weber- Rendu sy

  18. 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.

  19. Metastatic phaeochromocytoma with a long-term response after iodine-131 metaiodobenzylguanidine therapy

    International Nuclear Information System (INIS)

    Pujol, P.; Bringer, J.; Faurous, P.; Jaffiol, C.

    1995-01-01

    Iodine-131 metaiodobenzylguanidine ([ 131 I] MIBG), a radiopharmaceutical agent, is used for treating malignant phaeochromocytoma. [ 131 I]MIBG therapy results in a hormone response rate of approximately 50%, but generally it yields only a partial or no tumour response. We present a case of a 46-year-old woman with a familial history of von Hippel-Lindau disease, who was treated with [ 131 I]MIBG for a metastatic phaeochromocytoma involving the lungs, liver and bones. The patient received a cumulative dose of 33.3 GBq (900 mCi) and a complete hormone response was observed, as evaluated on the basis of catecholamine and metanephrine levels. Conventional radiography, computerized tomography and [ 131 I]MIBG scintigraphy indicated that a near-complete tumour regression was achieved, with no evidence of relapse during a 4-year follow-up period. This case thus demonstrates that treatment with [ 131 I]MIBG may lead to a dramatic tumour response in malignant phaeochromocytoma presenting both soft tissue and bone metastases. (orig.)

  20. LOSS OF JAK2 REGULATION VIA VHL-SOCS1 E3 UBIQUITIN HETEROCOMPLEX UNDERLIES CHUVASH POLYCYTHEMIA

    Science.gov (United States)

    Russell, Ryan C.; Sufan, Roxana I.; Zhou, Bing; Heir, Pardeep; Bunda, Severa; Sybingco, Stephanie S.; Greer, Samantha N.; Roche, Olga; Heathcote, Samuel A.; Chow, Vinca W.K.; Boba, Lukasz M.; Richmond, Terri D.; Hickey, Michele M.; Barber, Dwayne L.; Cheresh, David A.; Simon, M. Celeste; Irwin, Meredith S.; Kim, William Y.; Ohh, Michael

    2011-01-01

    SUMMARY Chuvash polycythemia (CP) is a rare congenital form of polycythemia caused by homozygous R200W and H191D mutations in the von Hippel-Lindau (VHL) gene whose gene product is the principal negative regulator of hypoxia-inducible factor. However, the molecular mechanisms underlying some of the hallmark features of CP such as hypersensitivity to erythropoietin are unclear. Here, we show that VHL directly binds suppressor of cytokine signalling 1 (SOCS1) to form a heterodimeric E3 ligase that targets phosphorylated (p)JAK2 for ubiquitin-mediated destruction. In contrast, CP-associated VHL mutants have altered affinity for SOCS1 and fail to engage and degrade pJAK2. Systemic administration of a highly selective JAK2 inhibitor, TG101209, reverses the disease phenotype in vhlR200W/R200W knock-in mice, a model that faithfully recapitulates human CP. These results reveal VHL as a SOCS1-cooperative negative regulator of JAK2 and provide compelling biochemical and preclinical evidence for JAK2- targeted therapy in CP patients. PMID:21685897

  1. Premalignant Lesions in the Kidney

    Directory of Open Access Journals (Sweden)

    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.

  2. Diseases of the peritoneum and mesenterium; Erkrankungen von Peritoneum und Mesenterium

    Energy Technology Data Exchange (ETDEWEB)

    Ba-Ssalamah, A.; Uffmann, M.; Bastati, N.; Schima, W. [Medizinische Universitaet Wien, Universitaetsklinik fuer Radiodiagnostik, Wien (Austria)

    2009-07-15

    Peritoneal diseases can be seen in the different imaging modalities either as fluid collections or solid tumors along the ligaments, mesenteries, and spaces of the peritoneal cavity. The broad spectrum of different abnormalities includes inflammatory, infectious, traumatic, and neoplastic diseases. In this article, a large variety of peritoneal abnormalities such as ascites, peritonitis, intraperitoneal hemorrhage, and both primary and secondary peritoneal tumors are discussed. The different imaging modalities, characteristic radiological features, and typical pathways of anatomic spread are explained. (orig.) [German] Peritoneale Erkrankungen koennen sich in den verschiedenen Bildgebungsmodalitaeten entweder als Gas-/Fluessigkeitsansammlung oder als weichteildichte Gewebevermehrung entlang der verschiedenen Ligamente und Mesenterien der Peritonealhoehle manifestieren. Dieses breite Spektrum der pathologischen Veraenderungen beinhaltet entzuendliche, infektioese, neoplastische und verschiedenste Erkrankungen anderer Genese. In vorliegendem Artikel wird ein grosses Spektrum dieser Pathologien wie Aszites, Peritonitis, intraabdominelle Blutung und verschiedene primaere und sekundaere peritoneale Tumoren vorgestellt. Des Weiteren wird der Einsatz der verschiedenen radiologischen Untersuchungsmodalitaeten, v. a. der Computertomographie (CT) als wichtigster Untersuchungsmethode, erlaeutert. Die charakteristischen Bildgebungsmerkmale und die typischen anatomischen Ausbreitungswege werden erklaert. (orig.)

  3. Elevated levels of plasma von Willebrand factor and the risk of macro- and microvascular disease in type 2 diabetic patients with microalbuminuria

    DEFF Research Database (Denmark)

    Gaede, P; Vedel, P; Parving, H H

    2001-01-01

    BACKGROUND: The purpose of this study was to examine the concept suggesting that microalbuminuria in combination with high levels of plasma von Willebrand factor is a stronger predictor for cardiovascular disease and microvascular complications than microalbuminuria alone in type 2 diabetic...... patients. METHODS: One hundred and sixty patients with type 2 diabetes mellitus and persistent microalbuminuria were followed for an average of 3.8 (SD 0.3) years. 70% of the patients were treated with angiotensin converting enzyme (ACE)-inhibitors. Patients in this subanalysis were divided into two groups...... nephropathy or progression in diabetic retinopathy than microalbuminuria alone in patients with type 2 diabetes and persistent microalbuminuria....

  4. 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.

  5. pVHL's kryptonite: E2-EPF UCP.

    Science.gov (United States)

    Ohh, Michael

    2006-08-01

    E2-EPF ubiquitin carrier protein (UCP) is a member of an E2 family of enzymes that catalyzes the ligation of ubiquitin to proteins targeted for destruction by the proteasome. UCP is overexpressed in common human cancers, suggesting its involvement in oncogenesis, but a physiologic target of UCP has not been identified. In a recent report published in Nature Medicine, Jung et al. identified von Hippel-Lindau (VHL) tumor suppressor protein, which targets the alpha subunit of hypoxia-inducible factor (HIF) for ubiquitin-mediated destruction, as a bona fide substrate of UCP and demonstrated a potential pVHL-HIF pathway-dependent role for UCP in cancer development.

  6. Cesariana em paciente com doença de von Willebrand associada à infecção pelo HIV: relato de caso Cesárea en paciente con enfermedad de von Willebrand asociada a la infección por el HIV: relato de caso Anesthesia for cesarean section in patient with von Willebrand's disease and HIV infection: case report

    Directory of Open Access Journals (Sweden)

    Vanessa Rezende Balle

    2004-12-01

    Willebrand y HIV positiva sometida a cesárea. RELATO DEL CASO: Paciente de 24 años, portadora de anemia microcítica, enfermedad de von Willebrand y HIV, llegó a la emergencia obstétrica en inicio de trabajo de alumbramiento. No realizó prenatal. Fue indicada cesárea a fin de disminuir los riesgos de transmisión vertical en paciente con carga vírica de HIV desconocida. Presentaba hematomas por el cuerpo e historia de hematoma de pared abdominal en cesárea anterior. Los tests de coagulación estaban un poco alterados. Después de infusión de concentrado de factor VIII fue realizada anestesia general. Madre y recién nacido presentaron evolución satisfactoria. CONCLUSIONES: La evaluación de manifestaciones clínicas en pacientes con coagulopatia es fundamental en la decisión del tipo de anestesia que será indicada para cada paciente. La evaluación debe ser individualizada, considerando los riesgos y beneficios de la técnica escogida. En estas pacientes, se debe siempre restringir al máximo la indicación de interrupción de la gestación por vía alta, optándose siempre por los métodos menos invasivos. La terapia con concentrado de factor VIII es actualmente la mejor opción de tratamiento, corrigiendo la deficiencia específica y dismunuyendo los riesgos de transmisión vírica.BACKGROUND AND OBJECTIVES: Von Willebrand's disease is the most common hereditary coagulation disorder in young women. The incidence of HIV infection among women has been progressively increasing, and vertical transmission may account for 25% of cases. This report aimed at describing the case of an HIV-positive patient with von Willebrand's disease scheduled for cesarean section. CASE REPORT: Female HIV-positive patient, 24 years old, with microcytic anemia and von Willebrand's disease, admitted to the emergency room in early labor. She had no pre-natal care. Cesarean section was indicated to lower vertical transmission risks since HIV viral count was unknown. Patient had hematomas

  7. von Willebrand Disease

    Science.gov (United States)

    ... results from a physical exam and tests. Medical History Your doctor will likely ask questions about your ... a medical center that specializes in high-risk obstetrics and has a hematologist on staff for prenatal ...

  8. Von Gierke disease

    Science.gov (United States)

    ... sugar test Genetic testing Lactic acid blood test Triglyceride level Uric acid blood test If a person ... 45. Kishnani PS, Chen Y-T. Defects in metabolism of carbohydrates. In: Kliegman RM, Stanton BF, St. ...

  9. 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...

  10. 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...

  11. Paciente portadora de doença de von Willebrand submetida a cirurgia da valva mitral: uma estratégia para o controle da coagulopatia Patient with von Willebrand disease undergoing mitral valve repair: a strategy for the control of the coagulopathy

    Directory of Open Access Journals (Sweden)

    Ally Nader Roquetti Saroute

    2007-01-01

    Full Text Available Relatamos o caso de uma mulher de 60 anos portadora da doença de von Willebrand tipo I, submetida a cirurgia da valva mitral. A paciente necessitou de cuidados especiais em razão da coagulopatia e foi necessária a utilização de concentrado de fator VIII (VIIIf e fator de von Willebrand (vWf antes, durante e depois da cirurgia. Não houve complicações durante e após a cirurgia. Nove meses depois, a paciente encontra-se assintomática. A correção para valores adequados de VIIIf e vWf permitiu a realização da cirurgia com segurança.We report a case of a 60 year-old woman with von Willebrand disease type I that was submitted to a mitral valve repair. The patient needed special care due coagulopathy and needed VIII factor (VIIIf and von Willebrand factor (vWf, before, during and after surgery. There was no complication during or after surgery. Patient is asymptomatic nine months postoperatively. The correction of VIIIf and vWf allowed the realization of a safety surgery.

  12. Effect of outdoor and indoor air pollution on lung function, bronchial hyperresponsiveness and risk of pulmonary disease of adults; Langzeitevaluation von Umwelteinfluessen auf Lungenfunktion, bronchiale Hyperreagibilitaet und Krankheitsrisiko von Erwachsenen

    Energy Technology Data Exchange (ETDEWEB)

    Eltschka, R [Freiburg Univ. (Germany). Zentrum Innere Medizin

    1992-10-01

    The effect of outdoor exposure to SO{sub 2}, NO{sub 2}, particulate pollutants, ozone and pollen on pulmonary function and respiratory discomfort was studied over a period of 1 1/2 yr in 133 no smoking adults at the city of Freiburg. Concentration of indoor and outdoor pollutants were measured. Between January and December 1989 we found in comparison with other large towns low levels of SO{sub 2}, NO{sub 2} and particulate combustion products. The evaluation of individual exposure to air pollutants with lung function measurements shows that participants with essential hyperreactivity demonstrate a significant decrease of the FEV1/IVC - ratio with a threshold value of about 30 {mu}g/m{sup 3} NO{sub 2}. The analyses of the longitudinal study shows a significant correlation between daily peakflow measurements and ozone levels in patients with symptomatic asthma bronchiale and chronic obstructive pulmonary disease. For pollen, SO{sub 2}, NO{sub 2} and anorganic particulate pollutants we did not find any significant effects on peak expiratory flow measurements. (orig./MG) [Deutsch] Der Einfluss von Aussenluftschadstoffen (SO{sub 2}, NO{sub 2}, Staub und Ozon) auf die Lunge wurde in Freiburg in Form einer 1 1/2-jaehrigen Longitudinalstudie bei 133 nicht rauchenden Erwachsenen untersucht. Waehrend des Beobachtungszeitraumes 10/88 - 4/90 erfolgte die Messung der Aussen- und Innenluftschadstoffe. Die Messungen des DW und der LFU zeigen fuer den Zeitraum Januar-Dezember 1989 im Vergleich zu anderen Grossstaedten niedrige Schwefeldioxid-, Stickoxid- und Staubkonzentrationen. Die Querschnittsuntersuchung mit Anamnesefragebogen, Bodyplethysmographie und inhalativem Provokationstest zeigt bei Teilnehmern mit essentieller Hyperreagibilitaet eine signifikante Abnahme des gemessenen und adjustierten Tiffeneau-Index durch NO{sub 2} mit einem Schwellenwert bei 30 {mu}g/m{sup 3}. Die multivariate Analyse der Longitudinalstudie zeigt bei Patienten mit symptomatischem Asthma und

  13. Elevated levels of von Willebrand factor and high mobility group box 1 (HMGB1) are associated with disease severity and clinical outcome of scrub typhus.

    Science.gov (United States)

    Chen, Hongliu; Ning, Zong; Qiu, Ying; Liao, Yuanli; Chang, Haihua; Ai, Yuanyuan; Wei, Yinghua; Deng, Yiming; Shen, Ying

    2017-08-01

    This study aimed to investigate whether von Willebrand factor (vWF) and high mobility group box 1 (HMGB1) are associated with the severity and clinical outcome of scrub typhus and to seek novel biomarkers for surveillance and prediction of the prognosis of this infection. Serum concentrations of vWF and HMGB1 were measured twice by ELISA for scrub typhus patients (n=103), once prior to doxycycline therapy and then on day 7 of doxycycline therapy; concentrations were measured once for healthy controls (n=32). Among the total 103 patients enrolled, 38 had disease complicated by multiple organ dysfunction syndrome (MODS). Serum concentrations of vWF and HMGB1 were significantly higher in all the patients than in the healthy controls, both prior to doxycycline treatment and on day 7 of doxycycline treatment (pscrub typhus (area under the curve (AUC)=0.864, p=0.001, and AUC=0.862, p=0.001, respectively). Elevated levels of vWF and HMGB1 are associated with the severity and clinical outcome of scrub typhus. These represent possible new biomarkers for use in the assessment and prognostic prediction of this infection. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  14. Identification and characterization of a novel P2Y 12 variant in a patient diagnosed with type 1 von Willebrand disease in the European MCMDM-1VWD study.

    Science.gov (United States)

    Daly, Martina E; Dawood, Ban B; Lester, William A; Peake, Ian R; Rodeghiero, Francesco; Goodeve, Anne C; Makris, Michael; Wilde, Jonathan T; Mumford, Andrew D; Watson, Stephen P; Mundell, Stuart J

    2009-04-23

    We investigated whether defects in the P2Y(12) ADP receptor gene (P2RY12) contribute to the bleeding tendency in 92 index cases enrolled in the European MCMDM-1VWD study. A heterozygous mutation, predicting a lysine to glutamate (K174E) substitution in P2Y(12), was identified in one case with mild type 1 von Willebrand disease (VWD) and a VWF defect. Platelets from the index case and relatives carrying the K174E defect changed shape in response to ADP, but showed reduced and reversible aggregation in response to 10 muM ADP, unlike the maximal, sustained aggregation observed in controls. The reduced response was associated with an approximate 50% reduction in binding of [(3)H]2MeS-ADP to P2Y(12), whereas binding to the P2Y(1) receptor was normal. A hemagglutinin-tagged K174E P2Y(12) variant showed surface expression in CHO cells, markedly reduced binding to [(3)H]2MeS-ADP, and minimal ADP-mediated inhibition of forskolin-induced adenylyl cyclase activity. Our results provide further evidence for locus heterogeneity in type 1 VWD.

  15. Disorders of the pediatric pancreas: imaging features

    International Nuclear Information System (INIS)

    Nijs, Els; Callahan, Michael J.; Taylor, George A.

    2005-01-01

    The purpose of this manuscript is to provide an overview of the normal development of the pancreas as well as pancreatic pathology in children. Diagnostic imaging plays a major role in the evaluation of the pancreas in infants and children. Familiarity with the range of normal appearance and the diseases that commonly affect this gland is important for the accurate and timely diagnosis of pancreatic disorders in the pediatric population. Normal embryology is discussed, as are the most common congenital anomalies that occur as a result of aberrant development during embryology. These include pancreas divisum, annular pancreas, agenesis of the dorsal pancreatic anlagen and ectopic pancreatic tissue. Syndromes that can manifest pancreatic pathology include: Beckwith Wiedemann syndrome, von Hippel-Lindau disease and autosomal dominant polycystic kidney disease. Children and adults with cystic fibrosis and Shwachman-Diamond syndrome frequently present with pancreatic insufficiency. Trauma is the most common cause of pancreatitis in children. In younger children, unexplained pancreatic injury must always alert the radiologist to potential child abuse. Pancreatic pseudocysts are a complication of trauma, but can also be seen in the setting of acute or chronic pancreatitis from other causes. Primary pancreatic neoplasms are rare in children and are divided into exocrine tumors such as pancreatoblastoma and adenocarcinoma and into endocrine or islet cell tumors. Islet cell tumors are classified as functioning (insulinoma, gastrinoma, VIPoma and glucagonoma) and nonfunctioning tumors. Solid-cystic papillary tumor is probably the most common pancreatic tumor in Asian children. Although quite rare, secondary tumors of the pancreas can be associated with certain primary malignancies. (orig.)

  16. Disorders of the pediatric pancreas: imaging features

    Energy Technology Data Exchange (ETDEWEB)

    Nijs, Els [University Hospital Gasthuisberg, Department of Radiology, Leuven (Belgium); Callahan, Michael J.; Taylor, George A. [Boston Children' s Hospital, Department of Radiology, Boston, MA (United States)

    2005-04-01

    The purpose of this manuscript is to provide an overview of the normal development of the pancreas as well as pancreatic pathology in children. Diagnostic imaging plays a major role in the evaluation of the pancreas in infants and children. Familiarity with the range of normal appearance and the diseases that commonly affect this gland is important for the accurate and timely diagnosis of pancreatic disorders in the pediatric population. Normal embryology is discussed, as are the most common congenital anomalies that occur as a result of aberrant development during embryology. These include pancreas divisum, annular pancreas, agenesis of the dorsal pancreatic anlagen and ectopic pancreatic tissue. Syndromes that can manifest pancreatic pathology include: Beckwith Wiedemann syndrome, von Hippel-Lindau disease and autosomal dominant polycystic kidney disease. Children and adults with cystic fibrosis and Shwachman-Diamond syndrome frequently present with pancreatic insufficiency. Trauma is the most common cause of pancreatitis in children. In younger children, unexplained pancreatic injury must always alert the radiologist to potential child abuse. Pancreatic pseudocysts are a complication of trauma, but can also be seen in the setting of acute or chronic pancreatitis from other causes. Primary pancreatic neoplasms are rare in children and are divided into exocrine tumors such as pancreatoblastoma and adenocarcinoma and into endocrine or islet cell tumors. Islet cell tumors are classified as functioning (insulinoma, gastrinoma, VIPoma and glucagonoma) and nonfunctioning tumors. Solid-cystic papillary tumor is probably the most common pancreatic tumor in Asian children. Although quite rare, secondary tumors of the pancreas can be associated with certain primary malignancies. (orig.)

  17. The value of "liver windows" settings in the detection of small renal cell carcinomas on unenhanced computed tomography.

    Science.gov (United States)

    Sahi, Kamal; Jackson, Stuart; Wiebe, Edward; Armstrong, Gavin; Winters, Sean; Moore, Ronald; Low, Gavin

    2014-02-01

    To assess if "liver window" settings improve the conspicuity of small renal cell carcinomas (RCC). Patients were analysed from our institution's pathology-confirmed RCC database that included the following: (1) stage T1a RCCs, (2) an unenhanced computed tomography (CT) abdomen performed ≤ 6 months before histologic diagnosis, and (3) age ≥ 17 years. Patients with multiple tumours, prior nephrectomy, von Hippel-Lindau disease, and polycystic kidney disease were excluded. The unenhanced CT was analysed, and the tumour locations were confirmed by using corresponding contrast-enhanced CT or magnetic resonance imaging studies. Representative single-slice axial, coronal, and sagittal unenhanced CT images were acquired in "soft tissue windows" (width, 400 Hounsfield unit (HU); level, 40 HU) and liver windows (width, 150 HU; level, 88 HU). In addition, single-slice axial, coronal, and sagittal unenhanced CT images of nontumourous renal tissue (obtained from the same cases) were acquired in soft tissue windows and liver windows. These data sets were randomized, unpaired, and were presented independently to 3 blinded radiologists for analysis. The presence or absence of suspicious findings for tumour was scored on a 5-point confidence scale. Eighty-three of 415 patients met the study criteria. Receiver operating characteristics (ROC) analysis, t test analysis, and kappa analysis were used. ROC analysis showed statistically superior diagnostic performance for liver windows compared with soft tissue windows (area under the curve of 0.923 vs 0.879; P = .0002). Kappa statistics showed "good" vs "moderate" agreement between readers for liver windows compared with soft tissue windows. Use of liver windows settings improves the detection of small RCCs on the unenhanced CT. Copyright © 2014 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

  18. Metastatic renal cell carcinoma management

    Directory of Open Access Journals (Sweden)

    Flavio L. Heldwein

    2009-06-01

    Full Text Available PURPOSE: To assess the current treatment of metastatic renal cell carcinoma, focusing on medical treatment options. MATERIAL AND METHODS: The most important recent publications have been selected after a literature search employing PubMed using the search terms: advanced and metastatic renal cell carcinoma, anti-angiogenesis drugs and systemic therapy; also significant meeting abstracts were consulted. RESULTS: Progress in understanding the molecular basis of renal cell carcinoma, especially related to genetics and angiogenesis, has been achieved mainly through of the study of von Hippel-Lindau disease. A great variety of active agents have been developed and tested in metastatic renal cell carcinoma (mRCC patients. New specific molecular therapies in metastatic disease are discussed. Sunitinib, Sorafenib and Bevacizumab increase the progression-free survival when compared to therapy with cytokines. Temsirolimus increases overall survival in high-risk patients. Growth factors and regulatory enzymes, such as carbonic anhydrase IX may be targets for future therapies. CONCLUSIONS: A broader knowledge of clear cell carcinoma molecular biology has permitted the beginning of a new era in mRCC therapy. Benefits of these novel agents in terms of progression-free and overall survival have been observed in patients with mRCC, and, in many cases, have become the standard of care. Sunitinib is now considered the new reference first-line treatment for mRCC. Despite all the progress in recent years, complete responses are still very rare. Currently, many important issues regarding the use of these agents in the management of metastatic renal cancer still need to be properly addressed.

  19. Novel insights into the polycythemia-paraganglioma-somatostatinoma syndrome.

    Science.gov (United States)

    Därr, Roland; Nambuba, Joan; Del Rivero, Jaydira; Janssen, Ingo; Merino, Maria; Todorovic, Milena; Balint, Bela; Jochmanova, Ivana; Prchal, Josef T; Lechan, Ronald M; Tischler, Arthur S; Popovic, Vera; Miljic, Dragana; Adams, Karen T; Prall, F Ryan; Ling, Alexander; Golomb, Meredith R; Ferguson, Michael; Nilubol, Naris; Chen, Clara C; Chew, Emily; Taïeb, David; Stratakis, Constantine A; Fojo, Tito; Yang, Chunzhang; Kebebew, Electron; Zhuang, Zhengping; Pacak, Karel

    2016-12-01

    Worldwide, the syndromes of paraganglioma (PGL), somatostatinoma (SOM) and early childhood polycythemia are described in only a few patients with somatic mutations in the hypoxia-inducible factor 2 alpha (HIF2A). This study provides detailed information about the clinical aspects and course of 7 patients with this syndrome and brings into perspective these experiences with the pertinent literature. Six females and one male presented at a median age of 28 years (range 11-46). Two were found to have HIF2A somatic mosaicism. No relatives were affected. All patients were diagnosed with polycythemia before age 8 and before PGL/SOM developed. PGLs were found at a median age of 17 years (range 8-38) and SOMs at 29 years (range 22-38). PGLs were multiple, recurrent and metastatic in 100, 100 and 29% of all cases, and SOMs in 40, 40 and 60%, respectively. All PGLs were primarily norepinephrine-producing. All patients had abnormal ophthalmologic findings and those with SOMs had gallbladder disease. Computed tomography (CT) and magnetic resonance imaging revealed cystic lesions at multiple sites and hemangiomas in 4 patients (57%), previously thought to be pathognomonic for von Hippel-Lindau disease. The most accurate radiopharmaceutical to detect PGL appeared to be [ 18 F]-fluorodihydroxyphenylalanine ([ 18 F]-FDOPA). Therefore, [ 18 F]-FDOPA PET/CT, not [ 68 Ga]-(DOTA)-[Tyr3]-octreotate ([ 68 Ga]-DOTATATE) PET/CT is recommended for tumor localization and aftercare in this syndrome. The long-term prognosis of the syndrome is unknown. However, to date no deaths occurred after 6 years follow-up. Physicians should be aware of this unique syndrome and its diagnostic and therapeutic challenges. © 2016 Society for Endocrinology.

  20. Proteomic changes in renal cancer and co-ordinate demonstration of both the glycolytic and mitochondrial aspects of the Warburg effect.

    Science.gov (United States)

    Unwin, Richard D; Craven, Rachel A; Harnden, Patricia; Hanrahan, Sarah; Totty, Nick; Knowles, Margaret; Eardley, Ian; Selby, Peter J; Banks, Rosamonde E

    2003-08-01

    Renal cell carcinoma (RCC) is the tenth most common cancer although the incidence is increasing. The main clinical problems stem from the relatively late presentation of many patients due to the often asymptomatic nature of the illness, and the relative insensitivity of metastatic disease to conventional chemotherapy and radiotherapy. Despite increasing knowledge of some of the genetic changes underlying sporadic renal cancer such as those involving the Von Hippel Lindau (VHL) gene, many of the underlying pathophysiological changes are ill-defined and there remains a need for the identification of disease markers for use in diagnosis and prognosis or as potential therapeutic targets. This study has used a proteomic approach, based on two-dimensional gel electrophoresis and mass spectrometry, to compare the protein profiles of conventional RCC tissue with patient-matched normal kidney cortex. Sequencing of 32 protein spots with significantly increased expression in RCC samples (>/= 4/6 patients) and 41 proteins whose levels decreased (6/6 patients) confirmed several previously known RCC-associated changes such as increases in Mn-superoxide dismutase, lactate dehydrogenase-A, aldolase A and C, pyruvate kinase M2, and thymidine phosphorylase. Additionally, several previously unknown changes were identified, including increased expression of three members of the annexin family and increased levels of the actin depolymerisation factor cofilin. The Warburg effect was also demonstrated with the identification of increases in proteins involved in the majority of steps in the glycolytic pathway and decreases in the gluconeogenic reactions, together with a parallel decrease in several mitochondrial enzymes. A number of the alterations seen were further confirmed in additional samples by immunohistochemistry, Western blotting, and laser capture microdissection.

  1. Stereotactic radiosurgery for hemangioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Yoshimasa; Kobayashi, Tatsuya; Yamada, Yasushi; Kida, Yoshihisa; Iwakoshi, Takayasu; Yoshimoto, Masayuki [Komaki City Hospital, Aichi (Japan). Gamma Knife Center

    2001-12-01

    We evaluated the treatment results of Gamma Knife radiosurgery for intracranial hemanigioblastoma of von Hippel-Lindau syndrome or sporadic disease. Stereotactic radiosurgery was performed in 20 patients with 35 hemangioblastomas over a 9-year interval. The mean age of the patients was 48.5 years (range, 18-79 years). The volume of the tumors varied from 0.03 to 19 ml (mean, 3.0 ml), and the mean tumor margin dose was 17.8 Gy (range, 14-24 Gy). Clinical and neuroimaging follow-up was obtained 6 to 58 months (mean 26.2 months) after radiosurgery. Thirty-one (89%) of 35 tumors were controlled locally. Two tumors (6%) disappeared and 11 (31%) decreased in size during follow-up period. Eighteen (52%) remained unchanged in size. Three out of four enlarged tumors were resected surgically after radiosurgery. Another tumor was resected surgically to improve the patient's symptoms of nausea and vomiting caused by persistent perifocal edema in spite of reduced tumor volume. Only one patient, who had a tumor in the 4th ventricle arising from the brainstem, died 12 months after radiosurgery. Although the treated tumor remained stable in size, he developed aspiration pneumonia due to brainstem dysfunction caused by perifocal edema. All tumors less than 1 cm in diameter did not progress during follow-up period. For small hemangioblastomas, radiosurgery is a safe and effective option to control disease. If a large tumor is treated by radiosurgery, careful observation of the patient's neurological condition is necessary. (author)

  2. Von Reckling-hausen disease associated to thyroid carcinoma and malignant schwannoma of the chest wall. A case

    International Nuclear Information System (INIS)

    Diaz P, J.; Tantalean, E.; Guzman, R.; Pomatanta P, J.; Grados M, J.; Vilela, C.

    1999-01-01

    The multiple neurofibromatosis is an autosomal dominant hereditary disease associated to malignant schwannoma in about 3% of the cases and very rarely to others cancers. The study provides information on the case of a 32 year-old woman who suffers from this disease and presented two synchronous cancers: a papillary carcinoma of thyroid and a malignant schwannoma of the chest wall. The thyroid tumour was managed with hemithyroidectomy, hormonotherapy and radiotherapy, and the lesion of the thoracic wall was treated with local radical resection application of Marlex mesh and rotation of a musculocutaneous flap of the dorsal muscle. A review of the literature on the clinical aspects of this association and the surgical techniques employed to cover the defect of the chest wall is presented. (authors)

  3. Computed tomography for imaging of pediatric congenital heart disease; Die Computertomographie bei der Bildgebung von Kindern mit kongenitalen Herzvitien

    Energy Technology Data Exchange (ETDEWEB)

    Glaser-Gallion, N.; Stinn, B.; Wildermuth, S.; Leschka, S. [Kantonsspital St.Gallen, Universitaet Zuerich, Institut fuer Radiologie, St. Gallen (Switzerland); Alkadhi, H. [Universitaetsspital Zuerich, Institut fuer Diagnostisch und Interventionelle Radiologie, Zuerich (Switzerland); Lell, M. [Universitaetsklinikum Erlangen, Institut fuer Radiologie, Erlangen (Germany); Goo, H.W. [University of Ulsan, College of Medicine, Asan Medical Center, Department of Radiology, Seoul (Korea, Republic of); Paul, J.F. [Marie Lannelongue Hospital, Radiology Unit, Plessis Robinson (France)

    2011-01-15

    Congenital heart diseases are the most common congenital abnormalities of development. In general, echocardiography and cardiac catheter angiography are considered the gold standard for the evaluation of congenital heart disease. Cardiac magnetic resonance imaging has become an important supplementary imaging modality because of its ability to provide an accurate morphological and functional evaluation. The role of cardiac computed tomography in the imaging of patients with congenital heart disease is becoming increasingly more important due to the development of low radiation dose protocols and improvements in the spatial and temporal resolution. In the preoperative depiction and follow-up after surgical repair of congenital heart diseases, cardiac computed tomography provides detailed information of the heart, the venous and arterial pulmonary circulation as well as systemic arteries. This article reviews the technical aspects of cardiac CT and the modification of examination protocols according to the expected pathology and patient age. The potentials and limitations of the various radiation dose reduction strategies are outlined. (orig.) [German] Kongenitale Herzfehler sind die haeufigsten kongenitalen Fehlbildungen. Echokardiographie und Katheterangiographie gelten allgemein als Goldstandard zur Abklaerung angeborener Herzerkrankungen. Die Magnetresonanztomographie ist aufgrund ihrer Faehigkeit, Herzvitien morphologisch und funktionell zu charakterisieren, als ein wichtiges ergaenzendes Verfahren anzusehen. Durch mehr und mehr dosissparende Untersuchungsprotokolle der neuesten Geraetegenerationen und eine gleichzeitig bessere zeitliche und raeumliche Aufloesung findet die Computertomographie zunehmend Eingang in die Abklaerung kongenitaler Herzfehler. In der praeoperativen Planung und der postoperativen Kontrolle erlaubt sie eine uebersichtliche Darstellung komplexer Fehlbildung nicht nur des Herzens, sondern auch der pulmonalvenoesen und -arteriellen

  4. Surgical resection of medulla oblongata hemangioblastomas: outcome and complications.

    Science.gov (United States)

    Giammattei, Lorenzo; Messerer, Mahmoud; Aghakhani, Nozar; David, Philippe; Herbrecht, Anne; Richard, Stéphane; Parker, Fabrice

    2016-07-01

    The purpose of this study was to analyze the surgical outcome and complications of a single-center series of medulla oblongata (MO) hemangioblastomas. We retrospectively reviewed the medical charts of all medulla oblongata hemangioblastomas operated on at our institution between 1996 and 2015. All patients had a pre- and postoperative MRI and a minimum follow-up of 6 months. Patients were scored according to the Karnofsky Performance Scale (KPS) and McCormick Scale at the moment of admission, discharge and the last follow-up. Thirty-one surgical procedures were performed on 27 patients (16 females and 11 males). The mean age was 33 years, and 93 % of patients had von Hippel Lindau (VHL) disease. Three patients experienced very complicated postoperative courses, with one case ending in the death of the patient. Two patients required tracheostomy. According to McCormick's classification, 7 (23 %) of the 31 operations resulted in aggravation and 23 (74 %) in no change. Considering the seven patients with aggravation at discharge, four patients (60 %) returned to their preoperative status, one (14 %) improved but remained below his preoperative McCormick grade and two (29 %) did not improve. At last follow-up, KPS was ameliorated in 53 %, stable in 40 % and worsened in 7 % of cases. Surgery of medulla oblongata hemangioblastomas is a challenging procedure characterized by an acceptable morbidity. Transient morbidity is not negligible even if the long-term outcome is in most cases favorable. A compromised neurological condition seems to be the best predictor of unfavorable outcome.

  5. Cerebellar hemangioblastomas: A study of the immunoprofile of neoplastic stromal component

    Directory of Open Access Journals (Sweden)

    Tasić Desanka

    2004-01-01

    Full Text Available Background. Central nervous system hemangioblastomas (HBs are uncommon highly vascularized tumors that are predominantly found in the cerebellum. They occur sporadically or in association with von Hippel-Lindau (VHL disease. HBs are of unknown histogenesis, and the origin of stromal cells is still a subject of debate. The aim of this study was to investigate the immunoprofile of neoplastic stromal component, and to determine whether the profile of the expression of immunomarkers used can contribute to the elucidation of the histogenesis of HBs. Methods. A series of eight cerebellar HBs were histochemically examined for the detection of mast cells and immunohistochemically for the expression of factor VIII-related antigen (FVIII-RAg, CD34, vimentin, factor XIIIa (FXIIIa, S-100 protein, glial fibrillary acidic protein (GFAP, neuron-specific enolase (NSE neurofilaments (NF, synaptophysin, chromogranin, and somatostatin. Results. Mast cells were present in all hemangioblastomas, and were particularly abundant in one tumor. Immunohistochemically, intense reactivity for vimentin and NSE in the stromal cells was constantly seen. Immunoreactivity with S-100 protein and FXIIIa was variable, but generally many HBs stromal cells were negative for these markers. However, stromal cells were uniformly negative for FVIII-RAg in all HBs investigated. They were negative for CD34 GFAP, NF, synaptophysin, chromogranin, as well as somatostatin. GFAP-positivity of the occasional stromal type cells, located only peripherally, was interpreted as "pseudopositivity". Conclusion. The immunoprofile of neoplastic stromal component in this study suggested a possible origin from undifferentiated multipotential mesenchymal cells. High expression of NSE (glycolytic and hypoxia-inducible enzyme in the HBs stromal cells might be related to the loss of the VHL protein function.

  6. MRI finding of hemangioblastomas

    International Nuclear Information System (INIS)

    Park, Seung Cheol; Oh, Min Cheol; Chung, Hwan Hoon; Seol, Hye Young; Lee, Nam Joon; Kim, Jung Hyuk

    1994-01-01

    The purpose of this study is to evaluate the findings of magnetic resonance imaging (MRI) of posterior fossa hemanangioblastoma and usefulness of contrast enhancement with Gd-DTPA. Seven patients with posterior fossa hemangioblastoma were studied with both pre- and post-enhanced MRI. The MR images were reviewed regarding the location, size, signal intensities of cysts and mural nodules, and their contrast enhancement pattern. Five tumors were located in cerebellar hemisphere, one in vermis, and one in posterior part of medulla. One patient with von Hippel-Lindau disease had a medullary hemangioblastoma with multiple pancreatic cysts. In 6 cases, the major portion of the tumor was cysts and had small mulkal nodules. The solid portion was relatively lange in one cases, cemprising half of the tumor cysts were oval shaped and their sized were 3-6.7 cm in diameter. In five cases(71%), septations were noted within the cysts. Cysts were isointense or slightly hyperintense on T1-weighted image and hyperintense on T2- weighted image compared with cerebrospinal fluid. Mural nodules were oval or rounded radiotherapy had better prognosis than those treated with radiotherapy alwas 0.5-2.5 cm in diameter. Mural nodules were isointense to gray matter. They were detected in five cases on T1-weighted images and one case on T2-weighted images. In two cases, vascular signal void area was noted in mural nodules. On contrast-enhanced T1-weighted images, all mural nodules were intensely enhanced. MRI provide to be a good diagnostic method to detect and characterize posterior fossa hemangioblastoma. The most common finding is Cystic posterior fossa lesion with enhancing mural nodule. Contrast enhancement is essential for specific diagnosis

  7. 6-Mercaptopurine, an activator of Nur77, enhances transcriptional activity of HIF-1alpha resulting in new vessel formation.

    Science.gov (United States)

    Yoo, Y-G; Na, T-Y; Yang, W-K; Kim, H-J; Lee, I-K; Kong, G; Chung, J-H; Lee, M-O

    2007-05-31

    Hypoxia-inducible factor-1alpha (HIF-1alpha) plays a central role in oxygen homeostasis. Previously, we reported that the orphan nuclear receptor Nur77 functions in stabilizing HIF-1alpha. Here, we demonstrate that 6-mercaptopurine (6-MP), an activator of the NR4A family members, enhances transcriptional activity of HIF-1. 6-MP enhanced the protein-level of HIF-1alpha as well as vascular endothelial growth factor (VEGF) in a dose- and time-dependent manner. The induction of HIF-1alpha was abolished by the transfection of either a dominant-negative Nur77 mutant or si-Nur77, indicating a critical role of Nur77 in the 6-MP action. The HIF-1alpha protein level remained up to 60 min in the presence of 6-MP when de novo protein synthesis was blocked by cycloheximide, suggesting that 6-MP induces stabilization of the HIF-1alpha protein. The fact that 6-MP decreased the association of HIF-1alpha with von Hippel-Lindau protein and the acetylation of HIF-1alpha, may explain how 6-MP induced stability of HIF-1alpha. Further, 6-MP induced the transactivation function of HIF-1alpha by recruiting co-activator cyclic-AMP-response-element-binding protein. Finally, 6-MP enhanced the expression of HIF-1alpha and VEGF, and the formation of capillary tubes in human umbilical vascular endothelial cells. Together, our results provide a new insight for 6-MP action in the stabilization of HIF-1alpha and imply a potential application of 6-MP in hypoxia-associated human vascular diseases.

  8. Disease specific stress of tumor patients at the beginning of radiotherapy. Effect on psychosocial support requirement; Krankheitsspezifische Belastungen von Tumorpatienten zu Beginn einer Strahlentherapie. Auswirkungen auf den psychosozialen Betreuungsbedarf

    Energy Technology Data Exchange (ETDEWEB)

    Sehlen, S.; Hollenhorst, H.; Schymura, B.; Firsching, M.; Duehmke, E. [Ludwig-Maximilians-Univ., Muenchen (Germany). Klinik und Poliklinik fuer Strahlentherapie und Radioonkologie; Aydemir, U. [Inst. fuer Biometrie und Epidemiologie, Klinikum Grosshadern, Ludwig-Maximilians-Univ., Muenchen (Germany); Herschbach, P. [Technische Univ. Muenchen (Germany). Inst. und Poliklinik fuer Psychosomatische Medizin, Psychotherapie und medizinische Psychologie

    2001-10-01

    Purpose: Radiotherapy brings a tumor patient into a special life situation in which different variables play a role of often unknown importance. The goal of this study was to investigate disease specific stress of tumor patients at the beginning of radiotherapy with established psychodiagnostic questionnaires and to evaluate the effect on psychosocial support requirement in order to reduce stress and to improve quality of life and compliance during radiotherapeutical treatment. Patients and Methods: 732 patients were screened, of whom 446 (60.9%) fulfilled the criteria for inclusion (refusals 21.0%, low Karnofsky performance status 6.6%, management problems 3.4%, language barriers 3.0%, cognitive restrictions 2.6%, death 2.5%). Disease specific aspects of stress in the questionnaire (Fragebogen zur Belastung von Krebspatienten, FBK), life situation (LS) and self-defined care requirements (BB) were self-rated by patients with different tumor types before radiotherapy. Medical and sociodemographic data were also documented. We investigated 446 patients (262 male, 184 female; median age 60.0 years) with different diagnoses. Results: Stress was observed mainly due to reduction of efficiency, anxiety and pain on the subscales. Women had a significant higher stress on subscales of pain (p=0.016) and anxiety (p=0.009), patients younger than 45 years in the subscale information (p=0.002) and patients older than 45 and younger than 60 years in the subscale anxiety (p=0.002) and the total score (p=0.003). Patients with mamma carcinoma had the highest stress. The maximum percentages of patients under high stress were found for the subscales of efficiency (43%) and anxiety (40%). The support requirement was characterized by the need of more medical information and dialogue with the doctor. We saw a significant correlation of high stress and high care requirement. Conclusions: Psychosocial support should be founded on psychosocial stress diagnostic and self-defined care

  9. Radiation therapy of benign diseases: patterns of care study in Germany; Strahlentherapie von gutartigen Erkrankungen: eine Bestandsaufnahme fuer Deutschland

    Energy Technology Data Exchange (ETDEWEB)

    Seegenschmiedt, M.H. [Alfried Krupp Krankenhaus Essen (Germany). Klinik fuer Radioonkologie, Strahlentherapie und Nuklearmedizin; Katalinic, A. [Erlangen-Nuernberg Univ., Erlangen (Germany). Inst. fuer Medizinische Statistik und Dokumentation; Makoski, H.B. [Staedtische Kliniken Duisburg (Germany). Strahlenklinik; Haase, W. [St. Vincentius Krankenhaus Karlsruhe (Germany). Klinik fuer Radioonkologie und Strahlentherapie; Gademann, G. [Magdeburg Univ. (Germany). Klinik fuer Strahlentherapie; Hassenstein, E. [Krankenhaus Nordwest, Frankfurt am Main (Germany). Radioonkologische Klinik

    1999-11-01

    A questionnaire was mailed in 3 years (1994, 1995, 1996) to all radiation facilities in Germany, which assessed equipment, indications, number of patients and treatment concepts. A total of 134 (88%) institutions returned all requested data: 22 in East and 112 in West Germany; 30 in university and 104 in community/private hospitals. The average data of each institution and of all institutions were analyzed for frequencies and ratios between different regions and institutions. A mean of 2 (range 1 to 7) megavoltage (Linac/Cobalt 60) and 1.4 (range 0 to 4) orthovoltage units were available per institution; 32 (24%) institutions had no orthovoltage equipment. A mean of 20,082 patients were treated per year: 456 (2%) for inflammatory diseases (221 hidradenitis, 78 nail bed infection, 23 parotitis, 134 not specified), 12,600 (63%) for degenerative diseases (2,711 peritendinitis humeroscapularis, 1,555 epicondylitis humeri, 1,382 heel spur, 2,434 degenerative osteoarthritis, 4,518 not specified), 927 (5%) for hypertrophic diseases (146 Dupuytren's contracture, 382 keloids, 155 Peyronie's disease, 244 not specified), 1,210 (6%) for functional disorders (853 Graves' orbitopathy, 357 not specified), and 4,889 (24%) for other disorders (e.g. 3,680 heterotopic ossification prophylaxis). In univariate analysis, there were significant geographical (West vs East Germany) differences in the use of radiotherapy for inflammatory and degenerative disorders and institutional differences (university vs community/private hospitals) in the use of radiotherapy for hypertrophic and functional disorders (p<0.05). The prescribed dose concepts were mostly in the low dose range (<10 Gy), but varied widely and inconsistently within geographic regions and institution types. (orig./MG) [German] 1994, 1995 und 1996 wurde an alle strahlentherapeutischen Institutionen in Deutschland ein Fragebogen verschickt, mit dem technische Ausstattung, Indikationsspektrum, Patientenzahl und

  10. 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.

  11. 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....

  12. The von Meyenburg complex; Der von Meyenburg Komplex

    Energy Technology Data Exchange (ETDEWEB)

    Schwab, S.A.; Bautz, W.; Uder, M.; Kuefner, M.A. [Erlangen-Nuernberg Univ., Erlangen (Germany). Inst. fuer Radiologie

    2008-07-01

    The von Meyenburg complex (VMC) describes bile duct hamartomas and presents a rare, benign incidental finding in liver imaging. We report on a 61-year-old man, who was referred for a follow up study 14 years after remission of Hodgkin's disease. Computed tomography (CT) revealed multiple hypodense lesions throughout the liver, primary suggesting recurrent Hodgkin's disease. Previous CT-examinations, which were obtained at a later date, showed those lesions in identical distribution and morphology over the years, leading to diagnosis of multiple bile duct hamartomas (VMC). Making imaging-based diagnosis of VMC including ultrasound, CT and magnetic resonance imaging is a challenging task for the radiologist. Based on literature research findings, the impact of different modalities in the diagnostic work-up of VMC is discussed. (orig.)

  13. Effects of long-term exposure to raod traffic imissions on the pathogenesis of diseases of the skin and respiratory tract in children; Auswirkungen langfristiger Expositionen gegenueber Strassenverkehrsimissionen auf die Entwicklung von Haut- und Atemwegserkrankungen bei Kindern

    Energy Technology Data Exchange (ETDEWEB)

    Ising, H. [Umweltbundesamt, Berlin (Germany); Lange-Asschenfeldt, H. [Bundesministerium fuer Gesundheit, Berlin (Germany); Lieber, G.F.; Weinhold, H.; Eilts, M.

    2002-10-01

    The pathogenesis of allergies can be stimulated by adjuvant effects, i.e. air pollutants such as NO{sub x} and particles from diesel engines and also noise - the latter especially during the night. During sleep, noise signals that are associated with danger (e.g. noise from lorries) can potentially trigger stress reactions even if the noise level is low. Higher cortisol levels in the first half of the night seem to have an important role in this. In a blind interview study, the combined effects of chronic exposure to traffic-related air pollution and noise upon the risk of allergic skin and respiratory diseases in children were studied. All children between 5 and 12 years of age who had consulted one of two of the participating pediatricians were included in the study. The paediatricians' diagnoses for 400 children were analysed together with their parents' answers to questions on the density of road traffic in the streets where they live and several confounding factors. Multiple regression analyses revealed relative risks of asthma, chronic bronchitis and neurodermitis that rose significantly with increasingly heavy traffic. A comparison with corresponding results reported in the literature for air pollution alone showed that traffic noise during the night might have an enhancing (adjuvant) effect in the pathogenesis of these diseases. (orig.) [German] Die Entstehung von Allergien kann durch adjuvante Effekte - z.B. Immissionen aus dem Verkehrsbereich - gefoerdert werden. Zu solchen Immissionen zaehlen gas- und partikelfoermige Schadstoffe wie Stickoxide und Dieselruss sowie Laerm, insbesondere in der Nacht. Waehrend des Schlafs koennen Geraeusche, die mit Gefahren assoziiert sind (z.B. Lkw-Geraeusche) auch bei niedrigen Pegeln Stressreaktionen ausloesen. Kortisolerhoehungen in der ersten Haelfte der Nacht scheinen dabei eine wichtige Rolle zu spielen. In einer 'einfach-blind' durchgefuehrten Befragungsstudie wurden langzeitige Auswirkungen

  14. Inflammatory bowel diseases (IBD) - critical discussion of etiology, pathogenesis, diagnostics, and therapy; Chronisch entzuendliche Darmerkrankungen - Kritische Diskussion von Aetiologie, Pathogenese, Diagnostik und Therapie

    Energy Technology Data Exchange (ETDEWEB)

    Ochsenkuehn, T.; Sackmann, M.; Goeke, B. [Medizinische Klinik II, Klinikum der Universitaet Muenchen-Grosshadern (Germany)

    2003-01-01

    Aims Crohn's disease and ulcerative colitis are the most frequent inflammatory bowel diseases (IBD) with a prevalence of approximately one out of 500.Cytokine research opened new and potent treatment options and thus stimulated clinical and basic research.However, the IBD still remain a challenge for patients and physicians,demanding close cooperation between gastroenterologists,radiologists and surgeons.The basic understanding of IBD,which is necessary for efficient diagnostic and therapeutic concepts is reviewed. Based upon recent publications and our clinical experience we discuss aspects of etiology,pathogenesis,diagnostics,and therapy of Crohn's disease and ulcerative colitis. A genetically influenced, exaggerated and sustained immune response against the own gut flora seems to be one of the most important factors in the pathogenesis of IBD.Not less important are environmental influences.For instance, cigarette smoking had been judged to have some negative influence on the natural course of Crohn's disease.Now,however, recent studies show that smoking is even a significant independent risk factor in the pathogenesis of IBD. Since IBD and especially Crohn's disease can effect the whole body, detailed analysis of inflammatory organ involvement is necessary before therapy.For instance, the MRIenteroclysis technique adds a necessary diagnostic tool for the exploration of those parts of the small bowel that cannot been reached by routine endoscopy like the upper ileum and the lower jejunum. In terms of therapy, a change of paradigms can be observed: patients will no longer be treated only when symptoms arise, but will early be integrated into a therapeutic concept, which is determined by site and extent of the disease and adapted to the abilities and needs of the patient.Furthermore,immunosuppressive agents like azathioprine and 6-mercaptopurine will establish as central concept in the medical treatment of IBD.Discussion IBD-therapy should

  15. 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

  16. Schmetterlinge von Madeira

    NARCIS (Netherlands)

    Martin, K.

    1941-01-01

    Wer auf einer ozeanischen Insel Schmetterlinge sammeln will, darf seine Erwartungen nicht zu hoch spannen; aber dennoch waren meine Frau und ich sehr enttäuscht, als uns auf einer Reise nach Madeira von einer dort angesessenen, gebildeten Dame gesagt wurde, sie habe auf der Insel niemals einen

  17. Biologischer Anbau von Strauchbeeren

    OpenAIRE

    Schmid, Andi

    2004-01-01

    Das Merkblatt enthält auf Österreich angepasste, praxisnahe Informationen zur Produktion von hochwertigen Strauchbeeren wie Himbeeren, Brombeeren, Johannisbeeren, Stachelbeeren und Heidelbeeren. Weiterhin: übersichtliche Hinweise zur Planung, Standortwahl, Sortenauswahl, Bodenvorbereitung und Pflanzung, Bewässerung, Nährstoffversorgung, Witterungsschutz, Beikrautregulierung, Ernte und Lagerung. (Diese Publikation enthält spezifische Informationen für Österreich)

  18. 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.

  19. The homozygous VHL(D126N) missense mutation is associated with dramatically elevated erythropoietin levels, consequent polycythemia, and early onset severe pulmonary hypertension.

    Science.gov (United States)

    Sarangi, Susmita; Lanikova, Lucie; Kapralova, Katarina; Acharya, Suchitra; Swierczek, Sabina; Lipton, Jeffrey M; Wolfe, Lawrence; Prchal, Josef T

    2014-11-01

    von Hippel-Lindau (VHL) protein is the principal negative regulator of hypoxia sensing mediated by transcription factors. Mutations in exon 3 of the VHL gene lead to Chuvash (VHL(R200W)) and Croatian (VHL(H191D)) polycythemias. Here, we describe an infant of Bangladesh ethnicity with a novel homozygous VHL(D126N) mutation with congenital polycythemia and dramatically elevated erythropoietin (EPO) levels, who developed severe fatal pulmonary hypertension. In contrast to Chuvash polycythemia, erythroid progenitors (BFU-Es) did not reveal a marked EPO hypersensitivity. Further, NF-E2 and RUNX1 transcripts that correlate with BFU-Es EPO hypersensitivity in polycythemic mutations were not elevated. © 2014 Wiley Periodicals, Inc.

  20. Noticias de la ciencia

    Directory of Open Access Journals (Sweden)

    Oscar F. Ramos M.

    1993-07-01

    Full Text Available El uso de anti-inflamatorios no esteroides en el tratamiento de la enfermedad de Alzheimer / Cataclismos del futuro / Diseño molecular de nuevas drogas para el tratamiento del cáncer de colón, páncreas y pulmón / Mecanismos de acción de los anestésicos / El gene que causa "el niño de la burbuja" / Identificación del gen de la neurofibromatosis tipo II / El gen de la homosexualidad / El nuevo gen tumoral supresor : el gen de la enfermedad de von Hippel-Lindau / Diagnóstico cósmico.

  1. The histone demethylases JMJD1A and JMJD2B are transcriptional targets of hypoxia-inducible factor HIF

    DEFF Research Database (Denmark)

    Beyer, Sophie; Kristensen, Malene Maag; Jensen, Kim Steen

    2008-01-01

    of these modifications is exerted by histone methyltransferases and the recently discovered histone demethylases. Here we show that the hypoxia-inducible factor HIF-1a binds to specific recognition sites in the genes encoding the jumonji family histone demethylases JMJD1A and JMJD2B and induces their expression....... Accordingly, hypoxic cells express elevated levels of JMJD1A and JMJD2B mRNA and protein. Furthermore, we find increased expression of JMJD1A and JMJD2B in renal cancer cells that have lost the von Hippel Lindau tumor suppressor protein VHL and therefore display a deregulated expression of HIF. Studies...... on ectopically expressed JMJD1A and JMJD2B indicate that both proteins retain their histone lysine demethylase activity in hypoxia and thereby might impact the hypoxic gene expression program....

  2. Manganese (II) induces chemical hypoxia by inhibiting HIF-prolyl hydroxylase: Implication in manganese-induced pulmonary inflammation

    International Nuclear Information System (INIS)

    Han, Jeongoh; Lee, Jong-Suk; Choi, Daekyu; Lee, Youna; Hong, Sungchae; Choi, Jungyun; Han, Songyi; Ko, Yujin; Kim, Jung-Ae; Mi Kim, Young; Jung, Yunjin

    2009-01-01

    Manganese (II), a transition metal, causes pulmonary inflammation upon environmental or occupational inhalation in excess. We investigated a potential molecular mechanism underlying manganese-induced pulmonary inflammation. Manganese (II) delayed HIF-1α protein disappearance, which occurred by inhibiting HIF-prolyl hydroxylase (HPH), the key enzyme for HIF-1α hydroxylation and subsequent von Hippel-Lindau(VHL)-dependent HIF-1α degradation. HPH inhibition by manganese (II) was neutralized significantly by elevated dose of iron. Consistent with this, the induction of cellular HIF-1α protein by manganese (II) was abolished by pretreatment with iron. Manganese (II) induced the HIF-1 target gene involved in pulmonary inflammation, vascular endothelial growth factor (VEGF), in lung carcinoma cell lines. The induction of VEGF was dependent on HIF-1. Manganese-induced VEGF promoted tube formation of HUVEC. Taken together, these data suggest that HIF-1 may be a potential mediator of manganese-induced pulmonary inflammation

  3. The contribution of VHL substrate binding and HIF1-alpha to the phenotype of VHL loss in renal cell carcinoma.

    Science.gov (United States)

    Maranchie, Jodi K; Vasselli, James R; Riss, Joseph; Bonifacino, Juan S; Linehan, W Marston; Klausner, Richard D

    2002-04-01

    Clear-cell renal carcinoma is associated with inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene. VHL is the substrate recognition subunit of an E3 ligase, known to target the alpha subunits of the HIF heterodimeric transcription factor for ubiquitin-mediated degradation under normoxic conditions. We demonstrate that competitive inhibition of the VHL substrate recognition site with a peptide derived from the oxygen degradation domain of HIF1alpha recapitulates the tumorigenic phenotype of VHL-deficient tumor cells. These studies prove that VHL substrate recognition is essential to the tumor suppressor function of VHL. We further demonstrate that normoxic stabilization of HIF1alpha alone, while capable of mimicking some aspects of VHL loss, is not sufficient to reproduce tumorigenesis, indicating that it is not the critical oncogenic substrate of VHL.

  4. Volumetric MRI for evaluation of regional pattern and progression of neocortical degeneration in Alzheimer's disease; MR-Volumetrie zur Darstellung von Verteilung und zeitlicher Abfolge neokortikaler Degeneration bei Morbus Alzheimer

    Energy Technology Data Exchange (ETDEWEB)

    Leinsinger, G. [Institut fuer Klinische Radiologie, Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Muenchen (Germany); Institut fuer Klinische Radiologie, LMU Muenchen, Ziemssenstrasse 1, 80336, Muenchen (Germany); Teipel, S.; Pruessner, J.; Hampel, H. [Klinik fuer Psychiatrie, Ludwig-Maximilians-Universitaet Muenchen, Muenchen (Germany); Wismueller, A.; Born, C.; Meindl, T.; Flatz, W.; Schoenberg, S.; Reiser, M. [Institut fuer Klinische Radiologie, Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Muenchen (Germany)

    2003-07-01

    Volumetric analysis of the corpus callosum and hippocampus using MRI in Alzheimer's disease (AD) to evaluate the regional pattern and progression of neocortical neurodegeneration. In subsequent studies we investigated patients with AD and healthy controls. Volumetry was based on MRI-data from a sagittal 3D T1w-gradient echo sequence. The corpus callosum (CC) was measured in a midsagittal slice, and subdivided into 5 subregions. Volumetry of the hippocampus/amygdala-formation (HAF) was performed by segmentation in coronary reoriented slices. In AD patients we found a significant atrophy in the rostrum und splenium of CC. The atrophy was correlated with the severity of dementia, but no correlation was found with the load of white matter lesions. In comparison with {sup 18}FDG-PET, we found a significant correlation of regional CC-atrophy with the regional decline of cortical glucose metabolism. A ROC-analysis demonstrated no significant differences in the diagostic accuracy of HAF volumetry and regional CC volumetry of the splenium (region C5) even in mild stages of dementia. Regional atrophy of CC can be used as a marker of neocortical degeneration even in early stages of dementia in AD. (orig.) [German] Volumetrische Analyse des Corpus callosum und Hippokampus mittels MRT bei der Alzheimer-Erkrankung (AD), mit dem Ziel die regionale Verteilung und Progression der neokortikalen relativ zur allokortikalen Neurodegeneration zu erfassen. In mehreren Studienabschnitten wurden Patienten mit AD und gesunde Kontrollen untersucht. Als Grundlage fuer die Volumetrie diente eine sagittale 3D-T1w-Gradientenechosequenz. Die Vermessung des Corpus callosum (CC) erfolgte in der mittsagittalen Schicht, wobei 5 Subregionen definiert wurden. Die Volumetrie des Hippokampus-Amygdala-Komplexes (HAK) wurde durch Segmentierung an koronar reorientierten Schichten durchgefuehrt. Bei Patienten mit AD fand sich eine signifikante Atrophie in Rostrum und Splenium des CC. Dabei zeigte sich

  5. 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

    2017-02-21

    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.

  6. 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.

  7. Functional characterisation of the type 1 von Willebrand disease candidate VWF gene variants: p.M771I, p.L881R and p.P1413L.

    Science.gov (United States)

    Berber, Ergul; Ozbil, Mehmet; Brown, Christine; Baslar, Zafer; Caglayan, S Hande; Lillicrap, David

    2017-10-01

    Abnormalities in the biosynthetic pathway or increased clearance of plasma von Willebrand factor (VWF) are likely to contribute to decreased plasma VWF levels in inherited type 1 von Willebrand disease (VWD). Recent studies demonstrated that 65% of type 1 VWD patients have candidate VWF mutations, the majority of which are missense variants. The purpose of this study was to explore the effects of three VWF missense mutations (p.M771I, p.L881R and p.P1413L) located in different functional domains of VWF, reported as candidate mutations in type 1 VWD patients in the course of the MCMDM-1VWD study. The focus of these studies was on the intracellular biosynthetic processing and localisation of VWF in a heterologous cell system. Molecular dynamic simulation for p.M771I and p.P1413L was also performed to analyse the conformational effects of the changes. As determined by immunofluorescence antibody staining and confocal microscopy of HEK293 cells, the intracellular localisation of recombinant VWF with the p.M771I variation was impaired. Transient transfection studies and phorbol myristate acetate stimulation in COS-7 cells revealed significant intracellular retention. In addition, major loss of VWF multimers was observed for only the p.M771I mutation. Molecular dynamic simulations on p.M771I mutant VWF revealed distinct structural rearrangements including a large deviation in the E' domain, and significant loss of β-sheet secondary structure. The pathogenic effects of candidate VWF gene mutations were explored in this study. In vitro expression studies in heterologous cell systems revealed impaired secretion of VWF and a dominant negative effect on the processing of the wild-type protein for only the p.M771I mutation and none of the mutations affected the regulated secretion.

  8. Diagnostics for diseases of the gallbladder and biliary tract from the viewpoint of the internist and surgeon. Demands made on radiological diagnostics; Diagnostik von Erkrankungen der Gallenblase und - Wege aus Sicht des Internisten und Chirurgen. Anforderungen an die radiologische Diagnostik

    Energy Technology Data Exchange (ETDEWEB)

    Reimann, F.M. [Krankenhaus Salem, Heidelberg (Germany); Friess, H. [Krankenhaus Salem, Heidelberg (Germany); Universitaetsklinikum Heidelberg (Germany). Abteilung fuer Allgemein-, Viszeral- und Unfallchirurgie

    2005-11-01

    Jaundice and colic pain of the right upper quadrant are the main symptoms of biliary diseases. Gallstone-related diseases often lead to hospital admission. The evaluation of a patient with biliary symptoms requires a combination of history taking, physical examination, laboratory analysis, and imaging modalities. A high-quality magnetic resonance imaging (MRI) or computed tomography (CT) scan is usually sufficient to evaluate a patient with painless jaundice. Ultrasonography is helpful as an initial screening test to guide the diagnostic work-up. Invasive methods (e.g., ERCP) are mainly used for palliation of patients with incurable disease. (orig.) [German] Erkrankungen der Gallenwege manifestieren sich mit den beiden Kardinalsymptomen Ikterus und kolikartigen rechtsseitigen Oberbauchschmerzen. Die durch Gallensteine verursachten Beschwerden und Erkrankungen zaehlen zu den haeufigsten gastroenterologischen Krankheitsbildern, die eine Klinikaufnahme erfordern. Die Abklaerung eines Patienten mit biliaeren Symptomen erfolgt durch eine Kombination von Anamnese, Medikamentenanamnese, koerperlicher Untersuchung, Laboranalysen und bildgebenden Verfahren. Bei Patienten mit malignen Tumoren im Bereich der ableitenden Gallenwege reichen in vielen Faellen Computertomographie (CT) oder Magnetresonanztomographie (MRT) zur Abklaerung des schmerzlosen Ikterus aus, um Therapieentscheidungen fuer den Patienten zu faellen. Der Ultraschall ist fuer die Planung der weiteren Diagnostik oft entscheidend. Der Stellenwert invasiver Methoden, wie z. B. der endoskopischen retrograden Cholangio-Pankreatikographie (ERCP), liegt vornehmlich in der Intervention, insbesondere zur Palliation bei Patienten, deren Erkrankung nicht mehr heilbar ist. (orig.)

  9. Juvenile osteoarthritis as consequence of enchondral injuries.. Frostbite, Kashin-Beck disease, rat bites and other causes; Kindliche Arthrosen als Folge enchondraler Schaedigungen. Am Beispiel von Erfrierungen, der Kashin-Beck-Erkrankung, Rattenbissen und anderen Ursachen

    Energy Technology Data Exchange (ETDEWEB)

    Oestreich, A.E. [Children' s Hospital Medical Center, Cincinnati, OH (United States)

    2000-12-01

    Purpose. To review the similarities of the radiographic changes in frostbite, the Asian disease of Kashin-Beck, and long term growth damage from injury such as rate bite. Materials and Methods. Radiographs and literature from subjects with these diagnoses were analyzed for the common features and differences. Included was an infant with hand changes 8 months after unwitnessed rat bites. Results. Each condition revealed findings consistent with the hypothesis of localized damage to sites of enchondral ossification, including at acrophyses - the growth plates that are not between epiphysis and metaphysis, but instead lie at the margins of growth centers, including carpal and tarsal bones, and the non-epiphyseal ends of small tubular bones. Discussion. The patterns observed support a final common pathway of damage in frostbite due to cold injury, Kashin-Beck disease (endemic in China) of unknown etiology, and damage from toxines associated, for example, with rat bite. In frostbite, the distribution is acral because of the site of exposure, while the distribution in Kashin-Beck is more diffuse and often less contiguous. In each condition, arthrotic sequelae may be expected in the natural course of follow-up. MRI may play a role in acute diagnosis that might modify the course of each disease. (orig.) [German] Ziel dieser Arbeit ist es, die radiologische Gleichartigkeit enchondraler Wachstumsschaedigungen im Rahmen von Erfrierungen, der asiatischen Kashin-Beck-Erkrankung und (Ratten-)Bissverletzungen darzustellen. Alle 3 Krankheitsbilder zeigen Veraenderungen, die mit einer lokalen Schaedigung enchondraler Ossifikationszonen in Verbindung zu bringen sind. Zu diesen Ossifikationszonen zaehlen auch die sog. 'Akrophysen'. Das sind Wachstumszonen, die nicht zwischen Epi- und Metaphyse liegen, sondern am Rande der Wachstumszentren bzw. in den nichtepiphysialen Enden der kleinen Roehrenknochen. Das radiologisch aehnliche Erscheinungsbild deutet darauf hin, dass

  10. Von der Vielfalt einer Institution

    OpenAIRE

    Kabaum, Marcel; Buck, Marc Fabian

    2013-01-01

    Von der Vielfalt von Universitäten bzw. higher education institutions (HEIs) zu sprechen heißt, sich dem Dickicht an Komplexität zu stellen, das sich zwischen ihren Ideen und Realitäten ausbreitet. Der Text führt in den Sammelband "Ideen und Realitäten von Universitäten" ein und hebt die verschiedenen disziplinären Sichtweisen sowie die internationale Breite - Deutschland, Südamerika, USA, Afghanistan und China - der Beiträge hervor. (DIPF/Orig.)

  11. 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.

  12. 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.

  13. Degenerative diseases of the spine. Rare and often unrecognized causes of pain syndromes; Degenerative Erkrankungen der Wirbelsaeule. Seltene und oft verkannte Ursachen von Schmerzsyndromen

    Energy Technology Data Exchange (ETDEWEB)

    Baur-Melnyk, A.; Triantafyllou, M.; Reiser, M. [Klinikum Grosshadern der Ludwig-Maximilians-Universitaet, Institut fuer Klinische Radiologie, Muenchen (Germany); Birkenmaier, C. [Klinikum Grosshadern der Ludwig-Maximilians-Universitaet Muenchen, Orthopaedische Klinik und Poliklinik (Germany)

    2006-06-15

    The aim of this article is to describe rare and often unrecognized causes of spinal pain syndromes. Intervertebral disc degeneration frequently appears in early adulthood and can have a symptomatic or asymptomatic course. This article discusses incidence, pathophysiology, imaging, and pain symptomatology involved in the origin of back pain. Anulus tears are often found in asymptomatic individuals but could be implicated in lumbar pain symptomatology in correlation with the provocative discography. Transient disorders can lead to pseudarthrosis of the iliac bone and to degeneration or to a reactive hypermobility with intervertebral disc degeneration in the level above. Modic type 1 erosive osteochondrosis is characterized by bone marrow edema near the hyaline cartilage end plate, which mostly elicits severe pain and results in serious limitations in everyday activities. The most important differential diagnosis is spondylodiscitis. Schmorl's nodes can exhibit considerable surrounding bone marrow edema that can be mistaken for metastases. A combination of MRI and CT should be employed for the diagnostic work-up of fatigue fracture of the interarticular portion, which is often overlooked due to its location. Synovial cysts of the facet joints can lead to radicular symptoms. Insufficiency fracture of the sacrum is frequently mistaken for metastasis due to intense scintigraphic enhancement and its signal behavior in MRI. CT provides instructive information. Differential diagnosis should include less common causes such as anulus tears, transient disorders, activated Schmorl's nodes, synovial cysts of the facet joints, fatigue fractures of the interarticular portion of the spine and the sacrum and distinguish from metastases in particular. (orig.) [German] Darstellung seltener und oft verkannter Ursachen von Wirbelsaeulenschmerzsyndromen. Eine Bandscheibendegeneration tritt haeufig im fruehen Erwachsenenalter auf und kann symptomatisch oder asymptomatisch

  14. Richard von Volkmann

    Science.gov (United States)

    Willy, Christian; Schneider, Peter; Engelhardt, Michael; Hargens, Alan R.

    2008-01-01

    Richard von Volkmann (1830–1889), one of the most important surgeons of the 19th 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. PMID:18196438

  15. Aggregation und Management von Metadaten im Kontext von Europeana

    Directory of Open Access Journals (Sweden)

    Gerda Koch

    2017-09-01

    Full Text Available Mit dem In-Beziehung-Setzen und Verlinken von Daten im Internet wird der Weg zur Umsetzung des semantischen Webs geebnet. Erst die semantische Verbindung von heterogenen Datenbeständen ermöglicht übergreifende Suchvorgänge und späteres „Machine Learning“. Im Artikel werden die Aktivitäten der Europäischen Digitalen Bibliothek im Bereich des Metadatenmanagements und der semantischen Verlinkung von Daten skizziert. Dabei wird einerseits ein kurzer Überblick zu aktuellen Forschungsschwerpunkten und Umsetzungsstrategien gegeben, und darüber hinaus werden einzelne Projekte und maßgeschneiderte Serviceangebote für naturhistorische Daten, regionale Kultureinrichtungen und Audiosammlungen beschrieben.

  16. Essential role for SphK1/S1P signaling to regulate hypoxia-inducible factor 2α expression and activity in cancer.

    Science.gov (United States)

    Bouquerel, P; Gstalder, C; Müller, D; Laurent, J; Brizuela, L; Sabbadini, R A; Malavaud, B; Pyronnet, S; Martineau, Y; Ader, I; Cuvillier, O

    2016-03-14

    The sphingosine kinase-1/sphingosine 1-phosphate (SphK1/S1P) signaling pathway has been reported to modulate the expression of the canonical transcription factor hypoxia-inducible HIF-1α in multiple cell lineages. HIF-2α is also frequently overexpressed in solid tumors but its role has been mostly studied in clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, where HIF-2α has been established as a driver of a more aggressive disease. In this study, the role of SphK1/S1P signaling with regard to HIF-2α was investigated in various cancer cell models including ccRCC cells. Under hypoxic conditions or in ccRCC lacking a functional von Hippel-Lindau (VHL) gene and expressing high levels of HIF-2α, SphK1 activity controls HIF-2α expression and transcriptional activity through a phospholipase D (PLD)-driven mechanism. SphK1 silencing promotes a VHL-independent HIF-2α loss of expression and activity and reduces cell proliferation in ccRCC. Importantly, downregulation of SphK1 is associated with impaired Akt and mTOR signaling in ccRCC. Taking advantage of a monoclonal antibody neutralizing extracellular S1P, we show that inhibition of S1P extracellular signaling blocks HIF-2α accumulation in ccRCC cell lines, an effect mimicked when the S1P transporter Spns2 or the S1P receptor 1 (S1P1) is silenced. Here, we report the first evidence that the SphK1/S1P signaling pathway regulates the transcription factor hypoxia-inducible HIF-2α in diverse cancer cell lineages notably ccRCC, where HIF-2α has been established as a driver of a more aggressive disease. These findings demonstrate that SphK1/S1P signaling may act as a canonical regulator of HIF-2α expression in ccRCC, giving support to its inhibition as a therapeutic strategy that could contribute to reduce HIF-2 activity in ccRCC.

  17. John von Neumann selected letters

    CERN Document Server

    2005-01-01

    John von Neuman was perhaps the most influential mathematician of the twentieth century, especially if his broad influence outside mathematics is included. Not only did he contribute to almost all branches of mathematics and created new fields, but he also changed post-World War II history with his work on the design of computers and with being a sought-after technical advisor to many figures in the U.S. military-political establishment in the 1940s and 1950s. The present volume is the first substantial collection of (previously mainly unpublished) letters written by von Neumann to colleagues, friends, government officials, and others. The letters give us a glimpse of the thinking of John von Neumann about mathematics, physics, computer science, science management, education, consulting, politics, and war. Readers of quite diverse backgrounds will find much of interest in this fascinating first-hand look at one of the towering figures of twentieth century science.

  18. Automatisierung von HiL Tests

    OpenAIRE

    Asbach, Lennart; Ebrecht, Lars

    2010-01-01

    Automatisierung von HiL Tests. Darstellung und Bewertung einer praktischen Umsetzung. Das Poster zeigt die Motivation, die Durchführung, einen aktuellen Stand und einen Ausblick der Testautomatisierung im Bahnlabor RailSiTe. Als Beispiel dient der Konformitätstest von ETCS-Onboard Zugrechnern, um die Einführung von ETCS zu unterstützen.

  19. Prevention, screening and therapy of thyroid diseases and their cost-effectiveness; Praevention, Screening und Therapie gutartiger Schilddruesenerkrankungen unter dem Aspekt von Kosten und Nutzen

    Energy Technology Data Exchange (ETDEWEB)

    Dietlein, M.; Moka, D.; Schmidt, M.; Theissen, P.; Schicha, H. [Koeln Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin

    2003-10-01

    Cost-effectivness analyses focused on benign thyroid diseases are under-represented in the literature. The calculation of costs per additionally gained life year is difficult: The benefit of prevention is shifted into the distant future. The influence of an untreated subclinical thyroid disease on life expectancy can only be demonstrated by a long-term follow-up and by epidemiological databases. Iodine supplementation and programs for the prevention of tobacco smoking (primary prevention) are very cost-effective. Smoking increases the risk both of multinodular goiter and of Graves' disease. Screening programs (secondary prevention) are discussed for the laboratory parameters thyrotropin (TSH), calcium and calcitonin. TSH testing seems to be very cost-effective for epidemiological considerations in a certain lifespan (newborn, pregnancy, postpartal), older persons, hospitalisation due to acute diseases and in persons with previously elevated TPO-antibodies for TSH-values >2 mU/l, but dedicated cost-effectiveness analyses are lacking. On the other hand, the cost-effectiveness of a routine TSH testing beyond the age of 35 years has been shown by a high-quality decision analysis. Therapeutic strategies (tertiary prevention) aim at the avoidance of complications (atrial fibrillation, myocardial infarction, death for cardiac reasons) and of iatrogenic complications. Examples of a tertiary prevention are: firstly the definitive therapy of Graves' disease in patients who have on increased risk of relapse after antithyroid drugs (ATD), secondly the radioiodine therapy for subclinical hyperthyroidism and the radioiodine therapy of large goiters in older patients or in patients suffering from a relevant comorbidity. Cost-effectiveness analyses for different therapeutic strategies of Graves' disease were published using a lifelong time-horizon. The ablative radioiodine dose-regime is cost-effective as a fist line therapy if the risk of relapse after ATD exceeds

  20. Imaging technique and current status of valvular heart disease using cardiac MRI; Untersuchungstechniken und Stellenwert der MRT bei der Diagnostik von Herzklappenerkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Lotz, J.; Sohns, J.M. [Universitaetsmedizin Goettingen, Georg-August-Universitaet, Institut fuer Diagnostische und Interventionelle Radiologie, Goettingen (Germany)

    2013-10-15

    The main indications for cardiac magnetic resonance imaging (MRI) in the evaluation of valvular heart disease are pathologies of the aortic and pulmonary valve. For mitral and tricuspid valve pathologies MRI is not the first line modality as these are usually well visualized by echocardiography. The advantages of MRI in valvular heart disease are a high reliability in the evaluation of ventricular volumes and function as well as the assessment of the perivalvular arterial or atrial structures. This reliability and the limitless access to any imaging plane partially compensates for the lower temporal and spatial resolution in comparison to echocardiography. In patients with congenital heart disease, cardiac MRI is established as a valuable diagnostic tool in daily clinical management, especially for the evaluation of pulmonary valve defects. Nevertheless, echocardiography remains the first-line diagnostic imaging tool for the foreseeable future. (orig.) [German] Die Untersuchung der Herzklappen in der MRT umfasst derzeit v. a. die Aorten- und Pulmonalisklappe. Pathologien der atrioventrikulaeren Klappen bilden demgegenueber nur selten die zentrale Fragestellung einer kardialen MRT-Untersuchung, da diese normalerweise einer echokardiographischen Untersuchung gut zugaenglich sind. Die Staerke der MRT ist die hohe Zuverlaessigkeit, mit der neben der Klappenmorphologie und -funktion die Funktionsparameter des jeweiligen Ventrikels und die Morphologie der nachgeschalteten Arterien bestimmt werden koennen. Dadurch kann die MRT die prinzipielle Schwaeche in der Orts- und Zeitaufloesung gegenueber der Echokardiographie teilweise kompensieren. Bei Patienten mit kongenitalen Herzvitien ist die MRT-basierte Klappendiagnostik fester Bestandteil des klinischen Managements. Das gilt besonders fuer die Evaluation der Pulmonalisklappe. Die Echokardiographie bleibt absehbar die Modalitaet der ersten Wahl fuer die Klappendiagnostik am Herzen. (orig.)

  1. 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

  2. Surgical management of medulla oblongata hemangioblastomas in one institution: an analysis of 62 cases.

    Science.gov (United States)

    Liu, Xuesong; Zhang, Yuekang; Hui, Xuhui; You, Chao; Yuan, Fang; Chen, Wenjing; Zhang, Si

    2015-01-01

    patients (29.5%), 80 in 24 patients (39.3%) and 40 to 70 in 5 patients (8.2%). Seventeen cases were associated with von Hippel-Lindau (VHL) disease. In all the cases, tumor recurrence was observed during follow-up in only 2 patients. This study suggests that safe and effective surgical management of medulla oblongata hemangioblastomas can be achieved for most patients, even without preoperative embolization. With the assistance of intraoperative MEP and SEP, mistaken cutting of the vessels that feed the brainstem can be avoided. With improved microsurgical techniques, intraoperative neurophysiological monitoring and a better understanding of the vascular pattern of tumors, total and en bloc microsurgical removal can be performed with low mortality and favorable prognosis of neurological function.

  3. Increased hypoxia-inducible factor-1α in striated muscle of tumor-bearing mice.

    Science.gov (United States)

    Devine, Raymond D; Bicer, Sabahattin; Reiser, Peter J; Wold, Loren E

    2017-06-01

    Cancer cachexia is a progressive wasting disease resulting in significant effects on the quality of life and high mortality. Most studies on cancer cachexia have focused on skeletal muscle; however, the heart is now recognized as a major site of cachexia-related effects. To elucidate possible mechanisms, a proteomic study was performed on the left ventricles of colon-26 (C26) adenocarcinoma tumor-bearing mice. The results revealed several changes in proteins involved in metabolism. An integrated pathway analysis of the results revealed a common mediator in hypoxia-inducible factor-1α (HIF-1α). Work by other laboratories has shown that extensive metabolic restructuring in the C26 mouse model causes changes in gene expression that may be affected directly by HIF-1α, such as glucose metabolic genes. M-mode echocardiography showed progressive decline in heart function by day 19 , exhibited by significantly decreased ejection fraction and fractional shortening, along with posterior wall thickness. Using Western blot analysis, we confirmed that HIF-1α is significantly upregulated in the heart, whereas there were no changes in its regulatory proteins, prolyl hydroxylase domain-containing protein 2 (PHD2) and von Hippel-Lindau protein (VHL). PHD2 requires both oxygen and iron as cofactors for the hydroxylation of HIF-1α, marking it for ubiquination via VHL and subsequent destruction by the proteasome complex. We examined venous blood gas values in the tumor-bearing mice and found significantly lower oxygen concentration compared with control animals in the third week after tumor inoculation. We also examined select skeletal muscles to determine whether they are similarly affected. In the diaphragm, extensor digitorum longus, and soleus, we found significantly increased HIF-1α in tumor-bearing mice, indicating a hypoxic response, not only in the heart, but also in skeletal muscle. These results indicate that HIF-1α may contribute, in part, to the metabolic changes

  4. MicroRNA-214 Reduces Insulin-like Growth Factor-1 (IGF-1) Receptor Expression and Downstream mTORC1 Signaling in Renal Carcinoma Cells*

    Science.gov (United States)

    Das, Falguni; Dey, Nirmalya; Bera, Amit; Kasinath, Balakuntalam S.; Ghosh-Choudhury, Nandini; Choudhury, Goutam Ghosh

    2016-01-01

    Elevated IGF-1/insulin-like growth factor-1 receptor (IGF-1R) autocrine/paracrine signaling in patients with renal cell carcinoma is associated with poor prognosis of the disease independent of their von Hippel-Lindau (VHL) status. Increased expression of IGF-1R in renal cancer cells correlates with their potency of tumor development and progression. The mechanism by which expression of IGF-1R is increased in renal carcinoma is not known. We report that VHL-deficient and VHL-positive renal cancer cells possess significantly decreased levels of mature, pre-, and pri-miR-214 than normal proximal tubular epithelial cells. We identified an miR-214 recognition element in the 3′UTR of IGF-1R mRNA and confirmed its responsiveness to miR-214. Overexpression of miR-214 decreased the IGF-1R protein levels, resulting in the inhibition of Akt kinase activity in both types of renal cancer cells. IGF-1 provoked phosphorylation and inactivation of PRAS40 in an Akt-dependent manner, leading to the activation of mTORC1 signal transduction to increase phosphorylation of S6 kinase and 4EBP-1. Phosphorylation-deficient mutants of PRAS40 and 4EBP-1 significantly inhibited IGF-1R-driven proliferation of renal cancer cells. Expression of miR-214 suppressed IGF-1R-induced phosphorylation of PRAS40, S6 kinase, and 4EBP-1, indicating inhibition of mTORC1 activity. Finally, miR-214 significantly blocked IGF-1R-forced renal cancer cell proliferation, which was reversed by expression of 3′UTR-less IGF-1R and constitutively active mTORC1. Together, our results identify a reciprocal regulation of IGF-1R levels and miR-214 expression in renal cancer cells independent of VHL status. Our data provide evidence for a novel mechanism for IGF-1R-driven renal cancer cell proliferation involving miR-214 and mTORC1. PMID:27226530

  5. Radiosurgery for hemangioblastoma: results of a multiinstitutional experience

    International Nuclear Information System (INIS)

    Patrice, Stephen J.; Sneed, Penny K.; Flickinger, John C.; Shrieve, Dennis C.; Pollock, Bruce E.; Alexander, Eben; Larson, David A.; Kondziolka, Douglas S.; Gutin, Philip H.; Wara, William M.; McDermott, Michael W.; Lunsford, L. Dade; Loeffler, Jay S.

    1996-01-01

    treat multiple lesions in a single treatment session, which is particularly important for patients with Von Hippel-Lindau Syndrome; and that (c) better control rates are associated with higher doses and smaller tumor volumes

  6. Incidence and Prognosis of Spinal Hemangioblastoma: A Surveillance Epidemiology and End Results Study.

    Science.gov (United States)

    Westwick, Harrison J; Giguère, Jean-François; Shamji, Mohammed F

    2016-01-01

    Intradural spinal hemangioblastoma are infrequent, vascular, pathologically benign tumors occurring either sporadically or in association with von Hippel-Lindau disease along the neural axis. Described in fewer than 1,000 cases, literature is variable with respect to epidemiological factors associated with spinal hemangioblastoma and their treatment. The objective of this study was to evaluate the epidemiology of intradural spinal hemangioblastoma with the Surveillance, Epidemiology and End Results (SEER) database while also presenting an illustrative case. The SEER database was queried for cases of spinal hemangioblastoma between 2000 and 2010 with the use of SEER*Stat software. Incidence was evaluated as a function of age, sex and race. Survival was evaluated with the Cox proportionate hazards ratio using IBM SPSS software evaluating age, sex, location, treatment modality, pathology and number of primaries (p = 0.05). Descriptive statistics of the same factors were also calculated. The case of a 43-year-old patient with a surgical upper cervical intramedullary hemangioblastoma is also presented. In the data set between 2000 and 2010, there were 133 cases with an age-adjusted incidence of 0.014 (0.012-0.017) per 100,000 to the standard USA population. Hemangioblastoma was the tenth most common intradural spinal tumor type representing 2.1% (133 of 6,156) of all spinal tumors. There was no difference in incidence between men and women with an female:male rate ratio of 1.05 (0.73-1.50) with p = 0.86. The average age of patients was 48.0 (45.2-50.9) years, and a lower incidence was noted in patients incidence amongst the different races. Treatment included surgical resection in 106 (79.7%) cases, radiation with surgery in 7 (5.3%) cases, and radiation alone was used in only 1 (0.8%) case, and no treatment was performed in 17 (12.8%) cases. Mortality was noted in 12 (9%) cases, and median survival of 27.5 months (range 1-66 months) over the 10-year period. Mortality

  7. Analyse der pharmazeutischen Versorgungssituation von Patienten mit Psoriasis-Arthritis auf Basis von Routinedaten der Gesetzlichen Krankenversicherung.

    Science.gov (United States)

    Sondermann, Wiebke; Ventzke, Julia; Matusiewicz, David; Körber, Andreas

    2018-03-01

    Die Psoriasis-Arthritis (PsA) gehört zu den chronisch entzündlichen Gelenkerkrankungen. Trotz zahlreicher versorgungswissenschaftlicher Studien in Deutschland liegen zur pharmazeutischen Versorgungssituation von PsA-Patienten bisher kaum aktuelle Ergebnisse vor. Mit Hilfe einer systematischen Literaturrecherche sowie anhand von Routinedaten der Allgemeinen Ortskrankenkasse (AOK) Rheinland/Hamburg wird ein aktueller Überblick über die pharmazeutische Versorgung von PsA-Patienten in Deutschland gegeben. Selektiert wurden Versicherte aus dem ambulanten und stationären Bereich, die im 1. und 2. Quartal des Jahres 2014 die gesicherte Abrechnungsdiagnose Psoriasis-Arthritis L40.5+ aufwiesen. Anschließend wurden auf Basis dieser "vorab definierten" Kohorte die Arzneimitteldaten für 5 Jahre (01.01.2010-31.12.2014) abgerufen. Es konnten insgesamt n  =  3205 Versicherte (45 % männlich, 55 % weiblich) der AOK Rheinland/Hamburg mit einer gesicherten PsA-Diagnose selektiert werden. Das Durchschnittsalter betrug 58,9 Jahre. 53,7 % der PsA-Patienten wurden mit systemischen PsA-relevanten Arzneimitteln versorgt. Nichtsteroidale Antirheumatika (NSAR) wurden am häufigsten verordnet, gefolgt von systemischen Glucocorticoiden. Von den selektierten PsA-Patienten, die eine Systemtherapie erhielten, wurden 72,1 % mittels einer Disease-modifying-antirheumatic-Drug (DMARD)-Monotherapie behandelt, gefolgt von der Kombinationstherapie aus DMARDs und Biologika (20,9 %). Die pharmakologische Therapie der PsA muss eine Gewährleistung zwischen adäquater Versorgung der PsA mit Verhinderung der Krankheitsprogression und ökonomischer Verantwortung darstellen. © 2018 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  8. Properties of von Neumann entropy

    Indian Academy of Sciences (India)

    disentangled) as seen by moving observers, is used to investigate the properties of von Neumann entropy, as a measure of spin–momentum entanglement. To do so, we partition the total Hilbert space into momentum and spin subspaces so that the ...

  9. [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

  10. 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.

  11. Microfinance als Geflecht von Anreizproblemen

    OpenAIRE

    Schmidt, Reinhard H.; Tschach, Ingo E.

    2001-01-01

    Während sich die Entwicklungsfinanzierung in Theorie und Praxis generell mit dem Finanzwesen in Entwicklungs- und Transformationsländern befasst, steht im Teilgebiet der Microfinance die Frage im Vordergrund, wie in diesen Ländern der Zugang ärmerer Bevölkerungsgruppen und speziell von Klein- und Kleinstunternehmer(innen), Kleinbauern und sonstigen wirtschaftlich Selbständigen aus eher niedrigen sozialen Schichten zu Kredit und anderen Finanzdiensleistungen verbessert werden kann. Obwohl es e...

  12. 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...

  13. Entwicklung und Anwendung von Methoden zur Bestimmung von Selen-Spezies in human-biologischem Material

    OpenAIRE

    Jäger, Thomas

    2014-01-01

    Selen ist essentieller Bestandteil von mehr als 25 physiologisch wichtigen menschlichen Enzymen. Der tägliche Bedarf wird überwiegend in Form von organischen Selenverbindungen wie Selenmethionin oder Selenocystein aus der Nahrung aufgenommen. Weitere Expositionswege sind die Einnahme von Nahrungsergänzungsmitteln zur Selensupplementation sowie die inhalative oder dermale Aufnahme von in erster Linie anorganischen Selenverbindungen oder elementarem Selen an Arbeitsplätzen der Selen-verarbeiten...

  14. Die filmstilistische Darstellung von Klaras Gehbehinderung im Kinderfilm "Heidi"

    Directory of Open Access Journals (Sweden)

    Maria Ohrfandl

    2016-09-01

    Full Text Available Dieser Beitrag soll die Forschungslücke zur Darstellung von Behinderungen speziell im Kinderfilm im deutschsprachigen Raum füllen. Auf Basis einer neoformalistisch orientierten Filmanalyse nach Bordwell und Thompson (2008, wird anhand von drei Filmsequenzen eine mögliche Lesart des Kinderfilms "Heidi" (Marcus 2005 entwickelt, um die filmstilistische Darstellung der Gehbehinderung des Mädchens Klara zu untersuchen. Die Ergebnisse werden mit theoretischen Überlegungen zur Problematik der Begriffsbestimmung von Körperbehinderung sowie zur Mobilität und Selbstbestimmung von Menschen mit Körperbehinderungen in Bezug gesetzt. Dabei zeigt sich im Wesentlichen, dass im Kinderfilm "Heidi" (Marcus 2005 Klaras Gehbehinderung als 'heilbare Krankheit' und der Rollstuhl als Einschränkung von Mobilität begriffen wird. Außerdem unterliegt Klara aufgrund ihrer Körperbehinderung überwiegend der Fremdbestimmung von Erwachsenen. Zur Klärung wahrscheinlicher filmischer Bildungspotenziale werden die Ergebnisse schließlich anhand der von Jörissen und Marotzki (2009 entwickelten Orientierungsdimensionen "Wissens-, Handlungs-, Grenz- und Biographiebezug" diskutiert. This article aims to bridge a knowledge gap by showing ways of representing disabilities in the German children film genre. Using Bordwell and Thomson's (2008 neoformalistically orientated film analysis approach, the movie "Heidi" (Marcus 2005 is analysed. Bordwell and Thompson's (2008 method is applied to three sequences of "Heidi" in order to present an interpretation and to discuss the representation of Clara's walking impediment. The results are then associated with theoretical considerations regarding the mobility and self-determination of people with disabilities and problematic definitions of the term 'physical disability'. It is shown that characters in the children's film "Heidi" (Marcus 2005 regard Clara's walking impediment as a 'curable disease' and the wheelchair as a limitation

  15. 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.

  16. Wohnquartiersbeschreibung: ein Instrument zur Regionalisierung von Nachbarschaften

    OpenAIRE

    Hoffmeyer-Zlotnik, Jürgen H. P.

    2001-01-01

    'Ausgehend von der Annahme, daß soziale Differenzierung sich in räumlicher Differenzierung niederschlägt, bietet eine Beschreibung der Struktur des näheren Wohnumfeldes die Möglichkeit, das Wohnquartier als Handlungsraum und Sozialisationsinstanz zur Interpretation von Umfragedaten zu nutzen. Das vorliegende Instrumentarium erlaubt es, das Wohnquartier unabhängig von Zensusdaten über Merkmale, die in der eigenen Umfrage erhoben werden, zu charakterisieren.' (Autorenreferat) 'The general hy...

  17. Acquired Von Willebrand’s Syndrome in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Sara Taveras Alam

    2014-01-01

    Full Text Available Acquired von Willebrand syndrome (AVWS is an uncommon, underdiagnosed, and heterogeneous disease which is increasingly recognized as a cause of bleeding diatheses. Systemic lupus erythematosus (SLE is an infrequent cause of AVWS. Herein, we report a case of AVWS diagnosed during the initial presentation of SLE in a previously healthy young man with no family history of bleeding diathesis who presented with worsening epistaxis, gastrointestinal bleeding, and anasarca. He was found to have severe anemia and prolonged activated partial thromboplastin time (aPTT with severely decreased levels of von Willebrand factor (VWF measurements in addition to markedly decreased factor VIII levels. Further evaluation revealed nephrotic syndrome and interstitial lung disease due to SLE. He initially received combination therapy with intravenous immunoglobulin (IVIG and von Willebrand factor/factor VIII concentrates without significant improvement. Treatment with steroids, cyclophosphamide, and rituximab was followed by clinical improvement evidenced by cessation of bleeding. The short follow-up did not allow us to definitely prove the therapeutic effect of immunosuppressive treatment on AVWS in SLE patients. This case adds to the literature supporting the relationship between AVWS and SLE and highlights the importance of combination therapy in the treatment of severe AVWS as well as the role of IVIG, cyclophosphamide, and rituximab in AVWS associated with SLE.

  18. Fibrolipoma en un paciente con la enfermedad de Von Recklinghausen

    Directory of Open Access Journals (Sweden)

    Orlando L Rodríguez Calzadilla

    2000-08-01

    Full Text Available Se presenta el caso de un paciente, con antecedente de padecer de la enfermedad de Von Recklinghausen, el cual fue valorado y su conducta terapéutica fue diferida, por sospechar la presencia de un tumor neurofibromatoso. El paciente se remitió a la consulta externa de nuestro servicio y una vez concluido sus estudios, se realizó su tratamiento quirúrgco. El paciente no presentó complicaciones transoperatorias y posoperatorias; su estadía fue de 3 días. Anatomía patológica informó la presencia de un fibrolipoma (neoplasia mesodérmica. El control a los 3 años de operado mostró un paciente asintomático y sin recidiva local. En la literatura médica revisada no se informaron otros casos similares de pacientes con la presencia de un fibrolipoma en la enfermedad de Von Recklinghausen.The case of a patient who suffers from Von Recklinghausen´s disease is reported. The patient was evaluated and his therapeutic conduct was deferred because the presence of a neurofibromatous tumor was suspected. The patient was referred to the outpatient department of our service and once the studies were concluded, he underwent surgical treatment. The patient had no transoperative or postoperative complications. He stayed in hospital only 3 days. The Department of Pathological Anatomy reported the presence of a fibrolipoma (mesodermic neoplasia. 3 years later the patient proved to be asymptomatic and without local relapse. Similar cases of patients with a fibrolipoma in Von Recklinghausen´s disease are not reported in the reviewed medical literature.

  19. Research, design and education, Von Humboldt revisited

    NARCIS (Netherlands)

    Bax, M.F.T.; Doevendans, C.H.; Trum, H.M.G.J.; Langenhuizen, Anja; Ouwerkerk, Marieke van; Rosemann, Jurgen

    2001-01-01

    This paper is a result of reflection on the interrelation design-research-cultivation, and on the interpretation of Von Humboldt's maxim: 'Einheit von Forschung und Lehre', which governed the academic world in the past two centuries. It is argued that 'Forschung' should be interpreted as 'Research

  20. Diffusion von Leerstelleninseln auf Cu(111)

    NARCIS (Netherlands)

    Verheij, Laurens K.; Schlößer, Dietmar; Rosenfeld, Georg

    1998-01-01

    Die zufällige Bewegung von Leerstelleninseln wurde bisher vorwiegend in einem Bild beschrieben, das von der Diffusion einzelner Atome ausgeht. In diesem Bild kann man Inseldiffusion durch die Einstein-Beziehung für Brownsche Bewegung ((Δ r)2 = 4 D Δ t) beschreiben. Für die Diffusionskonstante D wird

  1. Measurement of thyrotropin receptor antibodies (TRAK) with a second generation assay in patients with Graves' disease; Die Bestimmung von Thyreotropin-Rezeptor-Antikoerpern (TRAK) mit einem Assay der zweiten Generation bei Patienten mit Morbus Basedow

    Energy Technology Data Exchange (ETDEWEB)

    Zoephel, K.; Wunderlich, G.; Franke, W.G. [Klinik und Poliklinik fuer Nuklearmedizin, Technische Univ. Dresden (Germany); Koch, R. [Inst. fuer Medizinische Informatik und Biometrie, Technische Univ. Dresden (Germany)

    2000-06-01

    Aim: The detection of TSH-receptor-antibodies (TRAb) in patients (pts) with Graves' disease (GD) is routinely used in nuclear medicine laboratories. It is performed by commercial, porcine radioreceptorassays (RRA) measuring TSH binding inhibitory activity. A second generation assay using the human, recombinant TSH-receptor was developed during the last years. The manufacturer composed this new assay as a coated tube RRA (CT RRA) and claimed a higher sensitivity for GD. Methods: TRAb was measured in 207 pts with various thyroid disorders and 205 healthy controls using the new coated tube RRA (Fa. B.R.A.H.M.S. Diagnostica GmbH, Berlin, Germany) as well as a conventional RRA (Fa. Medipan Diagnostica GmbH, Selchow, Germany): 60 pts suffering from GD showing a relapse after anti-thyroid drug treatment and before radioiodine therapy, 109 pts with disseminated autonomia (DA) and 38 pts suffering from Hashimoto's thyroiditis. A ROC-analysis was performed to find the optimal decision threshold level for positivity. Results: We found 42/60 TRAb-positive pts with GD in the established RRA (threshold 6 U/L) and 52/60 in the CT RRA, respectively. The sensitivity increased from 70% (RRA) to 86,7% (CT RRA). The CT RRA found 2 false positives (one Hashimoto's and one healthy control) and the RRA detected 3 Hashimoto's and 2 healthy controls as false positive. Conclusion: The increased sensitivity of CT RRA for GD provides an advantage compared to conventional RRA, especially in GD-patients relapsing afte antithyroid drug treatment. Functional sensitivity and Interassayvariation of CT RRA are very precisely compared to conventional RRA. Handling of the new assay is also improved. (orig.) [German] Ziel: Die Bestimmung der TSH-Rezeptorantikoerper (TRAK) bei Patienten mit Morbus Basedow ist fester Bestandteil der nuklearmedizinischen In-vitro-Diagnostik. Seit kurzem ist die Bestimmung mit einem TRAK-Assay moeglich, bei dem im Gegensatz zu den herkoemmlichen

  2. 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

  3. 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

  4. Eine Analyse des Zusammenhangs zwischen dem Konsum von Alkopops und dem Problemverhalten von Jugendlichen

    OpenAIRE

    Metzner, Cornelia Beate Isabel

    2007-01-01

    Zielsetzung: In dieser Arbeit wird untersucht, ob bei Jugendlichen ein Zusammenhang zwischen dem Konsum von Alkopops einerseits und dem sonstigen Alkoholtrinkverhalten, dem Konsum von Zigaretten und illegalen Drogen sowie weiteren Risikoverhaltensweisen andererseits besteht, ferner ob sich Unterschiede im Verhalten von Jungen und Mädchen ergeben. Theoretischer und empirischer Hintergrund: �Alkopops�, d. h. Mischgetränke diverser Hersteller aus Likör bzw. Schnaps und Limonade sowie wein- ...

  5. Analytik von Minorlipiden: Ferulasäureester von Phytosterolen (gamma-Oryzanol) in Reis

    OpenAIRE

    Miller, Andreas

    2005-01-01

    Ferulasäureestern von Phytosterolen (γ-Oryzanol) werden antioxidative und cholesterinsenkende Eigenschaften zugeschrieben. Bisher beschriebene Methoden zur Analytik von γ-Oryzanol in Reis erforderten eine aufwendige Aufreinigung des Probenextrakts. In dieser Arbeit wurde basierend auf der on-line LC-GC eine Methode entwickelt, die die simultane Bestimmung von γ-Oryzanol-Gehalt und Sterylferulat-Verteilung ohne Aufreinigung des Probenextrakts erlaubt. Mit Hilfe der Technik wurden die natürlich...

  6. Redoxspeziation von endlagerrelevanten Elementen mit Hilfe von Trennmethoden gekoppelt an ein Massenspektrometer mit induktiv gekoppeltem Plasma

    OpenAIRE

    Graser, Carl-Heinrich

    2015-01-01

    Im Rahmen dieser Arbeit wurden Redoxspeziationsanalysen von Eisen, Neptunium und Plutonium per CE-SF-ICP-MS durchgeführt. Durch Optimierung der Trennparameter konnten Trennungen der Pu Oxidationsstufen III bis VI und Trennungen der Np Oxidationsstufen IV bis VI binnen 15 Minuten mit einer Nachweisgrenze von 10-12 M durchgeführt werden. Die Trennung der Fe Oxidationsstufen II und III gelang in weniger als 5 Minuten mit einer Nachweisgrenze von 5-10-8 M.

  7. THE DIGITAL VON FAHRENHEID PYRAMID

    Directory of Open Access Journals (Sweden)

    M. Bura

    2017-08-01

    Full Text Available 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.

  8. Die Wirkung von Desacetylcefotaxin, einem Metaboliten von Cefotaxim, in vitro und auf die experimentelle Infektion mit Escherichia coli

    OpenAIRE

    Wirbelauer, J.; Hof, H.; Hacker, Jörg

    2009-01-01

    Die MHK-Werte von Desacetylcefotaxim gegen verschiedene, z. T. ampicillinresistente Stämme von Escherichia coH, die mit Hilfe einer Agardilutionsmethode erhoben wurden, waren höher als die von Cefotaxim und Ceftriaxon, jedoch niedriger als die von Cefoxitin. In einem Modell der systemischen Infektion der Maus mit einem plasmidtragenden, betalactamaseproduzierenden Stamm von E. coli führte die Therapie mit Desacetylcefotaxim zu einer starken Reduktion der Keime pro Leber. Im Vergleich zur Ther...

  9. VON WISPR Family Processors: Volume 1

    National Research Council Canada - National Science Library

    Wagstaff, Ronald

    1997-01-01

    ...) and the background noise they are embedded in. Processors utilizing those fluctuations such as the von WISPR Family Processors discussed herein, are methods or algorithms that preferentially attenuate the fluctuating signals and noise...

  10. Von Onlineplattformen und mittelalterlichen Märkten

    Directory of Open Access Journals (Sweden)

    Claudius Gräbner

    2017-12-01

    Full Text Available Mit der zunehmenden Digitalisierung und Vernetzung ökonomischer Systeme haben plattformbasierte Interaktionsbeziehungen stark an Bedeutung gewonnen. Hier werden zwei oder mehr Nutzungsgruppen durch eine dritte Seite, die Plattform, zusammengebracht. Die Interaktion wird in solchen zweiseitigen Märkten von den Plattformbetreibern kontrolliert. Kreditkartensysteme, Softwaremärkte oder werbefinanzierte Online-Communities stellen typische Beispiele dar. Da die Analyse von zweiseitigen Märkten mit Gleichgewichtsmodellen aufgrund der algebraischen Struktur des Problems in der Regel nicht praktikabel ist, präsentieren wir im vorliegenden Beitrag ein agentenbasiertes Modell, welches in einem kürzlich erschienenen Artikel ausführlicher diskutiert wird. Anhand von illustrativen Beispielen verdeutlichen wir die Implikationen eines agentenbasierten Ansatzes für die Innovationsökonomik im Allgemeinen und das Studium von Technologieentwicklung im Besonderen.

  11. Johann Friedrich Wilhelm Adolf von Baeyer

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 6. Johann Friedrich Wilhelm Adolf von Baeyer: A Pioneer of Synthetic Organic Chemistry. Gopalpur Nagendrappa. General Article Volume 19 Issue 6 June 2014 pp 489-522 ...

  12. 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.

  13. 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!

  14. The classification problem for von Neumann factors

    DEFF Research Database (Denmark)

    Sasyk, R.; Törnquist, Asger Dag

    2009-01-01

    We prove that it is not possible to classify separable von Neumann factors of types II, II or III, 0 ≤ λ ≤ 1, up to isomorphism by a Borel measurable assignment of "countable structures" as invariants. In particular the isomorphism relation of type II factors is not smooth. We also prove...... that the isomorphism relation for von Neumann II factors is analytic, but is not Borel....

  15. 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

  16. Bedeutung von Umwelt- und Organismusfaktoren bei Autoaggressionen

    OpenAIRE

    Rohmann, Ulrich H.; Elbing, Ulrich; Hartmann, Hellmut

    1988-01-01

    In der vorliegenden Arbeit werden übergeordnete Hypothesen zu autoaggressiven Verhaltensweisen formuliert, wobei prozeßhafte Abläufe von umweltbezogenen und organischen Variablen angenommen werden. Eine solche dynamische Beziehung hat ihre Bedeutung sowohl für verursachende als auch aufrechterhaltende Faktoren. In einer Querschnittuntersuchung lassen sich Korrelationen von Tageszeit- und Tätigkeitscharakteristiken (umweltbezogene Variablen) zur Autoaggressionshäufigkeit und Pulsfrequenz (Orga...

  17. An ELISA for the quantitation of von Willebrand Factor

    DEFF Research Database (Denmark)

    Vinholt, Pernille Just; Overgaard, Martin; Diederichsen, Axel Cosmus Pyndt

    2013-01-01

    for measurement of von Willebrand factor-osteoprotegerin complex (VWF:OPG) in human plasma. Furthermore, the significance of VWF:OPG complex as a marker of cardiovascular disease (CVD) was evaluated. PATIENTS/METHODS: A sandwich ELISA for quantification of VWF:OPG was developed using a polyclonal rabbit anti...... with and without documented coronary calcification (total n=118). RESULTS AND CONCLUSIONS: The assay detected VWF:OPG complexes in human plasma, while no significant signal was observed when testing solutions containing VWF or recombinant OPG alone. Importantly, the ELISA assay was able to detect in vitro formed...

  18. Visualisierung von typisierten Links in Linked Data

    Directory of Open Access Journals (Sweden)

    Georg Neubauer

    2017-09-01

    Full Text Available Das Themengebiet der Arbeit behandelt Visualisierungen von typisierten Links in Linked Data. Die wissenschaftlichen Gebiete, die im Allgemeinen den Inhalt des Beitrags abgrenzen, sind das Semantic Web, das Web of Data und Informationsvisualisierung. Das Semantic Web, das von Tim Berners Lee 2001 erfunden wurde, stellt eine Erweiterung zum World Wide Web (Web 2.0 dar. Aktuelle Forschungen beziehen sich auf die Verknüpfbarkeit von Informationen im World Wide Web. Um es zu ermöglichen, solche Verbindungen wahrnehmen und verarbeiten zu können sind Visualisierungen die wichtigsten Anforderungen als Hauptteil der Datenverarbeitung. Im Zusammenhang mit dem Sematic Web werden Repräsentationen von zuhammenhängenden Informationen anhand von Graphen gehandhabt. Der Grund des Entstehens dieser Arbeit ist in erster Linie die Beschreibung der Gestaltung von Linked Data-Visualisierungskonzepten, deren Prinzipien im Rahmen einer theoretischen Annäherung eingeführt werden. Anhand des Kontexts führt eine schrittweise Erweiterung der Informationen mit dem Ziel, praktische Richtlinien anzubieten, zur Vernetzung dieser ausgearbeiteten Gestaltungsrichtlinien. Indem die Entwürfe zweier alternativer Visualisierungen einer standardisierten Webapplikation beschrieben werden, die Linked Data als Netzwerk visualisiert, konnte ein Test durchgeführt werden, der deren Kompatibilität zum Inhalt hatte. Der praktische Teil behandelt daher die Designphase, die Resultate, und zukünftige Anforderungen des Projektes, die durch die Testung ausgearbeitet wurden.

  19. ˝FLUMINENSIA˝ VON FRAN KURELAC

    Directory of Open Access Journals (Sweden)

    Leopoldina Veronika Banaš

    1990-01-01

    Full Text Available Das Buch "Fluminensia" (1862 von Fran Kurelac enthält die für die Schulfestlichkeiten geschriebenen Reden, Gelegenheitsgedichte - Ehrengedichte den bedeutenden und verdienstvollen Zeitgenossen gewidmet: dem Bischof von Senj und Modrus" Mirko Ožegović, Bartol Zmajic von Bakar, dem kroatischen Ban Josip Jelačić u.a. Danach folgen Aufrufe ("Proglasi" aus stürmischem 1848, gerichtet auf die Granzlandbewohner, Deutscher, ungarische Kroaten, Rumänen und Slawonier. Die Aufrufe wurden von Kurelac im Namen der Banalregierung beschrieben. Am Ende des Buches steht eine sprachwissenschaftliche Abhandlung über die ubstantivbiegung. Die für die Schulfestlichkeiten geschreibenen Reden sind wissenschaftliche Inhalte, essaystisch-didaktisch gestalltet, mit der Meldung über die Bedeutung der Wisenschaft, über die Bedeutung und Rolle der Sprache und des Buches für den Fortschritt des Volkes. Der Verfasser widmete dieses Buch seinen ehemaligen Schülern. "Fluminensia" nimmt eine wichtige Stelle in literarischer und sprachwissenschaftlicher Schöpfung auf dem Gebiet von Rijeka und Kroatien im 19. Jahrhundert ein.

  20. Privatiserung von Geschichte. Probleme einer differenzierten Aufarbeitung

    Directory of Open Access Journals (Sweden)

    Birthe Kundrus

    2000-11-01

    Full Text Available Ausgangspunkt der Untersuchung von Vera Neumann ist die These, daß im Krieg Erlebtes und Erlittenes in den Wiederaufbau- und Wirtschaftswunderjahren Westdeutschlands einem Thematisierungstabu unterlegen sei. Anhand von 50 Interviews, die in den 80er Jahren im Rahmen des von Lutz Niethammer geleiteten Projekts „Lebensgeschichte und Sozialgeschichte im Ruhrgebiet 1930–1960“ (LUSIR entstanden sind und die sie jetzt anhand der Tonbandprotokolle und Abschriften ein zweites Mal auswertet, möchte die Historikerin diese Verschüttungen aufspüren. Im Anschluß an Niethammers These der „Privatisierung von Geschichte“ will sie zeigen, daß seelische und körperliche Kriegsfolgen wie Deprivations- und Überlastungsgefühle, der Verlust von Angehörigen und Kriegsbeschädigungen „privatisiert“, d.h. an die Familien übertragen wurden. Dort seien dann in erster Linie die weiblichen Familienmitglieder mit der Versorgungs- und Pflegearbeit konfrontiert worden. An vier Fallbeispiele schließt sich eine detaillierte Auswertung des gesamten Interviewmaterials an. Diesen Teilen folgt ein Abschnitt zur staatlichen Kriegsopferversorgung in der frühen Bundesrepublik.

  1. A new von Mises probabilistic formula for quartet invariants

    International Nuclear Information System (INIS)

    Giacovazzo, C.; Camalli, M.; Spagna, R.

    1989-01-01

    Von Mises formulas for quartet invariants, even is useful in most cases of practical interest, suffer from some systematic errors. A new von Mises formula is suggested with better theoretical features. (orig.)

  2. 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.

  3. IAS 25, Bilanzierung von Finanzinvestitionen (Accounting for Investments)

    OpenAIRE

    Steiner, Manfred

    1997-01-01

    IAS 25, Bilanzierung von Finanzinvestitionen (Accounting for Investments). - In: Rechnungslegung nach International Accounting Standards (IAS) / hrsg. von Jörg Baetge ... - Stuttgart : Schäffer-Poeschel, 1997. - S. 923-953

  4. Borel reductibility and classification of von neumann algebras

    DEFF Research Database (Denmark)

    Sasyk, R.; Törnquist, Asger Dag

    2009-01-01

    We announce some new results regarding the classification problem for separable von Neumann algebras. Our results are obtained by applying the notion of Borel reducibility and Hjorth's theory of turbulence to the isomorphism relation for separable von Neumann algebras....

  5. Medien und Berufsvorstellungen von Kindern: eine experimentelle Studie zum Einfluss von Kinderbüchern auf das Berufsspektrum von Kindergartenkindern

    OpenAIRE

    Brüggemann, Tim; Gehrau, Volker; Handrup, Jutta

    2015-01-01

    "Der Beitrag thematisiert zunächst den Stand der beruflichen Orientierung von Jugendlichen sowie die pädagogischen Bemühungen beim Übergang Schule-Beruf, insbesondere im Hinblick auf eine Erweiterung des häufig engen Spektrums von Berufen, die bei der Berufswahl berücksichtig werden. Dabei richten sich die Bestrebungen, diesem Problem entgegenzuwirken, bislang vor allem auf Jugendliche. Anschließend wird anhand vorliegender Ergebnisse aus der Medienforschung diskutiert, in welcher Weise Masse...

  6. 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.

  7. Von Willebrand protein binds to extracellular matrices independently of collagen.

    OpenAIRE

    Wagner, D D; Urban-Pickering, M; Marder, V J

    1984-01-01

    Von Willebrand protein is present in the extracellular matrix of endothelial cells where it codistributes with fibronectin and types IV and V collagen. Bacterial collagenase digestion of endothelial cells removed fibrillar collagen, but the pattern of fibronectin and of von Willebrand protein remained undisturbed. Exogenous von Willebrand protein bound to matrices of different cells, whether rich or poor in collagen. von Willebrand protein also decorated the matrix of cells grown in the prese...

  8. Von Willebrand factor regulation of blood vessel formation.

    Science.gov (United States)

    Randi, Anna M; Smith, Koval E; Castaman, Giancarlo

    2018-06-04

    Several important physiological processes, from permeability to inflammation to haemostasis, take place at the vessel wall and are regulated by endothelial cells (EC). Thus, proteins that have been identified as regulators of one process are increasingly found to be involved in other vascular functions. Such is the case for Von Willebrand Factor (VWF), a large glycoprotein best known for its critical role in haemostasis. In vitro and in vivo studies have shown that lack of VWF causes enhanced vascularisation, both constitutively and following ischemia. This evidence is supported by studies on blood outgrowth endothelial cells (BOEC) from patients with lack of VWF synthesis (type 3 von Willebrand disease [VWD]). The molecular pathways are likely to involve VWF binding partners, such as integrin αvβ3, and components of Weibel Palade bodies (WPB), such as Angiopoietin-2 and Galectin-3, whose storage is regulated by VWF; these converge on the master regulator of angiogenesis and endothelial homeostasis, vascular endothelial growth factor (VEGF) signalling. Recent studies suggest that the roles of VWF may be tissue-specific. The ability of VWF to regulate angiogenesis has clinical implications for a subset of VWD patients with severe, intractable gastrointestinal bleeding due to vascular malformations. In this article, we review the evidence showing that VWF is involved in blood vessel formation, discuss the role of VWF high molecular weight multimers in regulating angiogenesis, and the value of studies on BOEC in developing a precision medicine approach to validate novel treatments for angiodysplasia in congenital VWD and acquired von Willebrand syndrome. Copyright © 2018 American Society of Hematology.

  9. [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)

  10. 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)

  11. 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

    1997-12-31

    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)

  12. Spectral theory and quotients in Von Neumann algebras | West ...

    African Journals Online (AJOL)

    In this note we consider to what extent the functional calculus and the spectral theory in von Neumann algebras are preserved by the taking of quotients relative to two-sided ideals of the von Neumann algebra. Keywords:von Neumann algebra, functional calculus, spectral theory, quotient algebras. Quaestiones ...

  13. Der Einfluss von sozialer Ungleichheit und kulturellen Unterschieden auf die Wahrnehmung von finanziellen und Arbeitsplatzrisiken: Überlegungen zur Risikogesellschaft

    OpenAIRE

    Abbott, David; Quilgars, Deborah; Jones, Anwen

    2006-01-01

    Der vorliegende Artikel beruht auf Daten einer Studie, die sich mit der Frage beschäftigt, wie verschiedene soziale und kulturelle Gruppen die Risiken von Einkommens- und Arbeitsplatzverlust wahrnehmen und darauf reagieren. Autoren wie LASH, DOUGLAS und LUPTON betonten die Bedeutung von Gruppenzugehörigkeit und sozialen Kategorien für die Strukturierung der Reaktionsweisen auf verschiedene Risikoarten. Sie sprechen daher lieber von Risikokulturen als von der Risikogesellschaft. Trotzdem erken...

  14. Bewertung von Fahrzeuggeräuschen

    Science.gov (United States)

    Genuit, Klaus; Schulte-Fortkamp, Brigitte; Fiebig, André; Haverkamp, Michael

    Bei der Wahrnehmung und Beurteilung eines Automobils sind unzählige Merkmale und Eigenschaften von Bedeutung. Dabei können Merkmale objektiv-technisch beschrieben werden, wie Angaben zur Motorisierung, Höchstgeschwindigkeit, Drehmoment, zulässige Zuladung, Verbrauch usw. Daneben sind weitere Eigenschaften von Bedeutung, die sich einer einfachen objektiv-technischen Beschreibung entziehen. Hier sind Begriffe zu nennen, wie Sicherheit, allgemeine Qualitätsanmutung, Design, Ergonomie, Komfort, Haptik, Fahrdynamik, Zuverlässigkeit, die deutlich schwieriger objektiv erfassbar und beschreibbar sind (Abb. 4.1).

  15. Asymptotic analysis of a von Koch beam

    International Nuclear Information System (INIS)

    Carpinteri, Alberto; Pugno, Nicola; Sapora, Alberto

    2009-01-01

    Fractal geometry is used in diverse research areas, being an useful tool in describing the mechanical behaviour of natural and man-made structures. In this paper, the structural behaviour of a von Koch cantilever beam is analyzed in the small deformations regime. Analytical recursive formulae for the strain energy scaling are derived, which have been found in good agreement with numerical simulations. Energy considerations suggest a peculiar scaling for the beam rigidity in order to prevent compliance divergence. The results are then extended to evaluate the stiffness matrix of a von Koch beam.

  16. 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.

  17. 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...

  18. Evaluation von Bildungssoftware im Spannungsfeld von Objektivität und praktischer Anwendung

    Directory of Open Access Journals (Sweden)

    Cornelia Biffi

    2002-05-01

    Full Text Available Das Angebot an Bildungs- bzw. Lernsoftware umfasst eine breite Palette von sehr unterschiedlichen Produkten. Eigentliche Unterrichtssoftware, die speziell für den Unterricht hergestellt und auf Lehrmittel und Curriculum abgestimmt ist, gibt es kaum. Im Projekt «Lernsoftware Evaluation» des Pestalozzianums Zürich ermitteln Lehrpersonen die Qualität von Bildungssoftware, indem sie diese im Unterricht einsetzen und anhand eines Kriterienrasters beurteilen. Eine Analyse der in der Evaluation generierten Daten belegt die Problematik des Anspruchs einer objektiven Qualitätsbeurteilung. Es werden die Probleme bei der Anwendung von Kriterienraster und Beurteilungsmodus aufgezeigt und ermittelt, worin die subjektiven Qualitätsmassstäbe der Evaluierenden begründet sind. Diese Ausführungen sind Teil eines Forschungsprojekts für die Weiterentwicklung einer theoretisch fundierten, aber dennoch praxisnahen Evaluation von Bildungssoftware.

  19. 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.

  20. Erzeugung gleichverteilter Stichproben von Lozenge-Teilungen mittels Kopplung von Markovketten

    OpenAIRE

    Keller, Peter

    2011-01-01

    Aus dem Inhalt: 1 Einleitung 2 Eigenschaften der Lozengeteilungen 3 Coupling From The Past (CFTP) 4 Simulation von uniform verteilten Lozengeteilungen 5 Programmlisting und Diskussion der Implementierung 6 Ausblick A Anhang

  1. 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.

  2. von Willebrand factor, Jedi knight of the bloodstream.

    Science.gov (United States)

    Springer, Timothy A

    2014-08-28

    When blood vessels are cut, the forces in the bloodstream increase and change character. The dark side of these forces causes hemorrhage and death. However, von Willebrand factor (VWF), with help from our circulatory system and platelets, harnesses the same forces to form a hemostatic plug. Force and VWF function are so closely intertwined that, like members of the Jedi Order in the movie Star Wars who learn to use "the Force" to do good, VWF may be considered the Jedi knight of the bloodstream. The long length of VWF enables responsiveness to flow. The shape of VWF is predicted to alter from irregularly coiled to extended thread-like in the transition from shear to elongational flow at sites of hemostasis and thrombosis. Elongational force propagated through the length of VWF in its thread-like shape exposes its monomers for multimeric binding to platelets and subendothelium and likely also increases affinity of the A1 domain for platelets. Specialized domains concatenate and compact VWF during biosynthesis. A2 domain unfolding by hydrodynamic force enables postsecretion regulation of VWF length. Mutations in VWF in von Willebrand disease contribute to and are illuminated by VWF biology. I attempt to integrate classic studies on the physiology of hemostatic plug formation into modern molecular understanding, and point out what remains to be learned. © 2014 by The American Society of Hematology.

  3. Untersuchungen zur Entwicklung von Satellitengalaxien

    Science.gov (United States)

    Seidel, Björn

    2002-01-01

    Gleichgewichtsmodelle ein- und zweikomponentiger Satellitengalaxien werden erzeugt und die Gezeiteneinwirkungen der als starres äußeres Potential angenommenen Milchstraße auf sie betrachtet. Eine erste Reihe von Simulationen mit anfänglich kugelsymmetrischen einkomponentigen Satelliten zeigt, daß sich nach elliptischer Deformation ein Balken und Schweife ungleicher Länge ausbilden, deren Aussehen sich periodisch ändert. Mithilfe von Vergleichssimulationen wurden folgende Phänomene am Satelliten entdeckt: (1) Hochdichtebereiche in den Schweifen, (2) Niedrigdichtebereiche um den Kern bzw. Balken und (3) ein oft verdeckter Balken. Analysiert wird das Erscheinungsbild in Zeitabhängigkeit. Die Teilchen gehen dem Kern über den Balken verloren und bewegen sich entlang gewisser stets gleich aussehender charakteristischer Strukturen in die Schweife. Nach einer Herleitung allgemeiner Größen des mehrkomponentigen Kingprofils werden drei stabile Standardmodelle zweikomponentiger Satellitengalaxien mit Massenverhältnis 1:10 (baryonische zu dunkle Materie) und unterschiedlicher Verteilung der dunklen und sichtbaren Materie gefunden. Ohne die Allgemeinheit der Ergebnisse zu beeinträchtigen, wurde dabei die Große Magellanische Wolke als Grundlage der Modelle genommen. Nach geeigneter Wahl der Bahn, zu der der Gezeitenradius des verwendeten dreikomponentigen Milchstraßenpotentials sowohl analytisch als auch numerisch berechnet wird, werden Simulationen der Modelle analysiert. Hauptaugenmerk ist das unterschiedliche Verhalten der Komponenten. Hauptergebnisse: (1) Es ist möglich, große Anteile dunkler, jedoch nur geringe sichtbarer Materie abzulösen. Dunkle und sichtbare Materie können unterschiedliche morphologische Strukturen bilden. (2) Je nach Konzentration der Komponenten ist die Eigengravitation der Teilchen mehr oder weniger für das Aussehen bestimmend. (3) Die Kernauflösung des Satelliten findet im Perigalaktikum (PG), sein Zerfall aber erst im

  4. A note on derivations of Murray–von Neumann algebras

    Science.gov (United States)

    Kadison, Richard V.; Liu, Zhe

    2014-01-01

    A Murray–von Neumann algebra is the algebra of operators affiliated with a finite von Neumann algebra. In this article, we first present a brief introduction to the theory of derivations of operator algebras from both the physical and mathematical points of view. We then describe our recent work on derivations of Murray–von Neumann algebras. We show that the “extended derivations” of a Murray–von Neumann algebra, those that map the associated finite von Neumann algebra into itself, are inner. In particular, we prove that the only derivation that maps a Murray–von Neumann algebra associated with a factor of type II1 into that factor is 0. Those results are extensions of Singer’s seminal result answering a question of Kaplansky, as applied to von Neumann algebras: The algebra may be noncommutative and may even contain unbounded elements. PMID:24469831

  5. A note on derivations of Murray-von Neumann algebras.

    Science.gov (United States)

    Kadison, Richard V; Liu, Zhe

    2014-02-11

    A Murray-von Neumann algebra is the algebra of operators affiliated with a finite von Neumann algebra. In this article, we first present a brief introduction to the theory of derivations of operator algebras from both the physical and mathematical points of view. We then describe our recent work on derivations of Murray-von Neumann algebras. We show that the "extended derivations" of a Murray-von Neumann algebra, those that map the associated finite von Neumann algebra into itself, are inner. In particular, we prove that the only derivation that maps a Murray-von Neumann algebra associated with a factor of type II1 into that factor is 0. Those results are extensions of Singer's seminal result answering a question of Kaplansky, as applied to von Neumann algebras: The algebra may be noncommutative and may even contain unbounded elements.

  6. 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)

  7. Alexander von Humboldt and Coenraad Jacob Temminck

    NARCIS (Netherlands)

    Raat, A.J.P.

    1976-01-01

    INTRODUCTION In the archives of the Rijksmuseum van Natuurlijke Historie in Leiden there is a map with three letters written by Alexander von Humboldt (17691859) to the first director of the Museum, Coenraad Jacob Temminck (1778-1858). The map, the hard cover of John Gould's "Synopsis of the birds

  8. Differential functional von Foerster equations with renewal

    Directory of Open Access Journals (Sweden)

    H.Leszczyński

    2008-06-01

    Full Text Available Natural iterative methods converge to the exact solution of a differential-functional von Foerster-type equation which describes a single population dependent on its past time and state densities as well as on its total size. On the lateral boundary we impose a renewal condition.

  9. Wege zur Entdeckung von Communities in Folksonomies

    OpenAIRE

    Jäschke, Robert; Hotho, Andreas; Schmitz, Christoph; Stumme, Gerd

    2006-01-01

    Ein wichtiger Baustein des neu entdeckten World Wide Web - des "Web 2.0" - stellen Folksonomies dar. In diesen Systemen können Benutzer gemeinsam Ressourcen verwalten und mit Schlagwörtern versehen. Die dadurch entstehenden begrifflichen Strukturen stellen ein interessantes Forschungsfeld dar. Dieser Artikel untersucht Ansätze und Wege zur Entdeckung und Strukturierung von Nutzergruppen ("Communities") in Folksonomies.

  10. Hans von Engel and the ICPIG Conference

    International Nuclear Information System (INIS)

    Franklin, R.

    2000-01-01

    The history of the, organized by Hans von Engel, International Conference on Phenomena in Ionized Gases is presented: Oxford (1953), Delft (1955), Venice (1957), Uppsala (1959), Munich (1961), Oxford (1971) and Berlin (1977). Some organizational aspects, financial support and remarkable events like international prizes in field of plasma physics are given

  11. Guido von Pirquet: Austrian pioneer of astronautics

    Science.gov (United States)

    Sykora, F.

    1977-01-01

    The works of Guido von Pirquet, Austrian pioneer of rocketry, were assessed. Major emphasis was given to Pirquet's calculation of the route to Venus which in fact was followed by the first Russian rocket to Venus. Of interest also is Pirquet's valuable construction of a space station and his analysis of interstellar space flight.

  12. 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,

  13. 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

  14. 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

  15. 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)

  16. Von der lernenden Region zur "Smart Region“

    OpenAIRE

    Poschwatta, Wolfgang

    2004-01-01

    Von der lernenden Region zur "Smart Region“ / M. Hilpert, W. Poschwatta. - In: Nabizadeh-Araghi, Nima : Auf dem Weg zur "Smart Region" : regionale Entwicklung am Beispiel der Pistazienproduktion im Iran. - Augsburg : Müllerdruck, 2004. - S. 5-9. - (Terra facta ; 2)

  17. Disease: H00152 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ed by mutation in the ABC transporter gene and characterized by elevated plasma levels of plant sterols due ...dhop T, von Bergmann K ... TITLE ... Sitosterolemia--a rare disease. Are elevated plant sterols an additional

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Suppression of mitochondrial respiration with auraptene inhibits the progression of renal cell carcinoma: involvement of HIF-1α degradation.

    Science.gov (United States)

    Jang, Yunseon; Han, Jeongsu; Kim, Soo Jeong; Kim, Jungim; Lee, Min Joung; Jeong, Soyeon; Ryu, Min Jeong; Seo, Kang-Sik; Choi, Song-Yi; Shong, Minho; Lim, Kyu; Heo, Jun Young; Kweon, Gi Ryang

    2015-11-10

    Renal cell carcinoma (RCC) progression resulting from the uncontrolled migration and enhanced angiogenesis is an obstacle to effective therapeutic intervention. Tumor metabolism has distinctive feature called Warburg effect, which enhances the aerobic glycolysis rapidly supplying the energy for migration of tumor. To manipulate this metabolic change characteristic of aggressive tumors, we utilized the citrus extract, auraptene, known as a mitochondrial inhibitor, testing its anticancer effects against the RCC4 cell line. We found that auraptene impaired RCC4 cell motility through reduction of mitochondrial respiration and glycolytic pathway-related genes. It also strongly disrupted VEGF-induced angiogenesis in vitro and in vivo. Hypoxia-inducible factor 1a (HIF-1a), a key regulator of cancer metabolism, migration and angiogenesis that is stably expressed in RCCs by virtue of a genetic mutation in the von Hippel-Lindau (VHL) tumor-suppressor protein, was impeded by auraptene, which blocked HIF-1a translation initiation without causing cytotoxicity. We suggest that blockade HIF-1a and reforming energy metabolism with auraptene is an effective approach for suspension RCC progression.

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

    International Nuclear Information System (INIS)

    Choi, Jieun; Koh, Eunjin; Lee, Yu Shin; Lee, Hyun-Woo; Kang, Hyeok Gu; Yoon, Young Eun; Han, Woong Kyu; Choi, Kyung Hwa; Kim, Kyung-Sup

    2016-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Molecular basis for the regulation of hypoxia-inducible factor-1α levels by 2-deoxy-D-ribose.

    Science.gov (United States)

    Ikeda, Ryuji; Tabata, Sho; Tajitsu, Yusuke; Nishizawa, Yukihiko; Minami, Kentaro; Furukawa, Tatsuhiko; Yamamoto, Masatatsu; Shinsato, Yoshinari; Akiyama, Shin-Ichi; Yamada, Katsushi; Takeda, Yasuo

    2013-09-01

    The angiogenic factor, platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP), stimulates the chemotaxis of endothelial cells and confers resistance to apoptosis induced by hypoxia. 2-Deoxy-D-ribose, a degradation product of thymidine generated by TP enzymatic activity, inhibits the upregulation of hypoxia-inducible factor (HIF) 1α, BNIP3 and caspase-3 induced by hypoxia. In the present study, we investigated the molecular basis for the suppressive effect of 2-deoxy-D-ribose on the upregulation of HIF-1α. 2-Deoxy-D-ribose enhanced the interaction of HIF-1α and the von Hippel-Lindau (VHL) protein under hypoxic conditions. It did not affect the expression of HIF-1α, prolyl hydroxylase (PHD)1/2/3 and VHL mRNA under normoxic or hypoxic conditions, but enhanced the interaction of HIF-1α and PHD2 under hypoxic conditions. 2-Deoxy-D-ribose also increased the amount of hydroxy-HIF-1α in the presence of the proteasome inhibitor MG-132. The expression levels of TP are elevated in many types of malignant solid tumors and, thus, 2-deoxy-D-ribose generated by TP in these tumors may play an important role in tumor progression by preventing hypoxia-induced apoptosis.

  3. Cinnamic aldehyde suppresses hypoxia-induced angiogenesis via inhibition of hypoxia-inducible factor-1α expression during tumor progression.

    Science.gov (United States)

    Bae, Woom-Yee; Choi, Jae-Sun; Kim, Ja-Eun; Jeong, Joo-Won

    2015-11-01

    During tumor progression, hypoxia-inducible factor 1 (HIF-1) plays a critical role in tumor angiogenesis and tumor growth by regulating the transcription of several genes in response to a hypoxic environment and changes in growth factors. This study was designed to investigate the effects of cinnamic aldehyde (CA) on tumor growth and angiogenesis and the mechanisms underlying CA's anti-angiogenic activities. We found that CA administration inhibits tumor growth and blocks tumor angiogenesis in BALB/c mice. In addition, CA treatment decreased HIF-1α protein expression and vascular endothelial growth factor (VEGF) expression in mouse tumors and Renca cells exposed to hypoxia in vitro. Interestingly, CA treatment did not affect the stability of von Hippel-Lindau protein (pVHL)-associated HIF-1α and CA attenuated the activation of mammalian target of rapamycin (mTOR) pathway. Collectively, these findings strongly indicate that the anti-angiogenic activity of CA is, at least in part, regulated by the mTOR pathway-mediated suppression of HIF-1α protein expression and these findings suggest that CA may be a potential drug for human cancer therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Hif1a inactivation rescues photoreceptor degeneration induced by a chronic hypoxia-like stress.

    Science.gov (United States)

    Barben, Maya; Ail, Divya; Storti, Federica; Klee, Katrin; Schori, Christian; Samardzija, Marijana; Michalakis, Stylianos; Biel, Martin; Meneau, Isabelle; Blaser, Frank; Barthelmes, Daniel; Grimm, Christian

    2018-04-17

    Reduced choroidal blood flow and tissue changes in the ageing human eye impair oxygen delivery to photoreceptors and the retinal pigment epithelium. As a consequence, mild but chronic hypoxia may develop and disturb cell metabolism, function and ultimately survival, potentially contributing to retinal pathologies such as age-related macular degeneration (AMD). Here, we show that several hypoxia-inducible genes were expressed at higher levels in the aged human retina suggesting increased activity of hypoxia-inducible transcription factors (HIFs) during the physiological ageing process. To model chronically elevated HIF activity and investigate ensuing consequences for photoreceptors, we generated mice lacking von Hippel Lindau (VHL) protein in rods. This activated HIF transcription factors and led to a slowly progressing retinal degeneration in the ageing mouse retina. Importantly, this process depended mainly on HIF1 with only a minor contribution of HIF2. A gene therapy approach using AAV-mediated RNA interference through an anti-Hif1a shRNA significantly mitigated the degeneration suggesting a potential intervention strategy that may be applicable to human patients.

  5. VHL-dependent regulation of a β-dystroglycan glycoform and glycogene expression in renal cancer.

    Science.gov (United States)

    Aggelis, Vassilis; Craven, Rachel A; Peng, Jianhe; Harnden, Patricia; Schaffer, Lana; Hernandez, Gilberto E; Head, Steven R; Maher, Eamonn R; Tonge, Robert; Selby, Peter J; Banks, Rosamonde E

    2013-11-01

    Identification of novel biomarkers and targets in renal cell carcinoma (RCC) remains a priority and one cellular compartment that is a rich potential source of such molecules is the plasma membrane. A shotgun proteomic analysis of cell surface proteins enriched by cell surface biotinylation and avidin affinity chromatography was explored using the UMRC2- renal cancer cell line, which lacks von Hippel-Lindau (VHL) tumour suppressor gene function, to determine whether proteins of interest could be detected. Of the 814 proteins identified ~22% were plasma membrane or membrane-associated, including several with known associations with cancer. This included β-dystroglycan, the transmembrane subunit of the DAG1 gene product. VHL-dependent changes in the form of β-dystroglycan were detected in UMRC2-/+VHL transfectants. Deglycosylation experiments showed that this was due to differential sialylation. Analysis of normal kidney cortex and conventional RCC tissues showed that a similar change also occurred in vivo. Investigation of the expression of genes involved in glycosylation in UMRC2-/+VHL cells using a focussed microarray highlighted a number of enzymes involved in sialylation; upregulation of bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) was validated in UMRC2- cells compared with their +VHL counterparts and also found in conventional RCC tissue. These results implicate VHL in the regulation of glycosylation and raise interesting questions regarding the extent and importance of such changes in RCC.

  6. The cytosolic chaperonin CCT/TRiC and cancer cell proliferation.

    Directory of Open Access Journals (Sweden)

    Chafika Boudiaf-Benmammar

    Full Text Available The molecular chaperone CCT/TRiC plays a central role in maintaining cellular proteostasis as it mediates the folding of the major cytoskeletal proteins tubulins and actins. CCT/TRiC is also involved in the oncoprotein cyclin E, the Von Hippel-Lindau tumour suppressor protein, cyclin B and p21(ras folding which strongly suggests that it is involved in cell proliferation and tumor genesis. To assess the involvement of CCT/TRiC in tumor genesis, we quantified its expression levels and activity in 18 cancer, one non-cancer human cell lines and a non-cancer human liver. We show that the expression levels of CCT/TRiC in cancer cell lines are higher than that in normal cells. However, CCT/TRiC activity does not always correlate with its expression levels. We therefore documented the expression levels of CCT/TRiC modulators and partners PhLP3, Hop/P60, prefoldin and Hsc/Hsp70. Our analysis reveals a functional interplay between molecular chaperones that might account for a precise modulation of CCT/TRiC activity in cell proliferation through changes in the cellular levels of prefoldin and/or Hsc/p70 and CCT/TRiC client protein availability. Our observation and approaches bring novel insights in the role of CCT/TRiC-mediated protein folding machinery in cancer cell development.

  7. Novel homozygous VHL mutation in exon 2 is associated with congenital polycythemia but not with cancer.

    Science.gov (United States)

    Lanikova, Lucie; Lorenzo, Felipe; Yang, Chunzhang; Vankayalapati, Hari; Drachtman, Richard; Divoky, Vladimir; Prchal, Josef T

    2013-05-09

    Germline von Hippel-Lindau (VHL) gene mutations underlie dominantly inherited familial VHL tumor syndrome comprising a predisposition for renal cell carcinoma, pheochromocytoma/paraganglioma, cerebral hemangioblastoma, and endolymphatic sac tumors. However, recessively inherited congenital polycythemia, exemplified by Chuvash polycythemia, has been associated with 2 separate 3' VHL gene mutations in exon 3. It was proposed that different positions of loss-of-function VHL mutations are associated with VHL syndrome cancer predisposition and only C-terminal domain-encoding VHL mutations would cause polycythemia. However, now we describe a new homozygous VHL exon 2 mutation of the VHL gene:(c.413C>T):P138L, which is associated in the affected homozygote with congenital polycythemia but not in her, or her-heterozygous relatives, with cancer or other VHL syndrome tumors. We show that VHL(P138L) has perturbed interaction with hypoxia-inducible transcription factor (HIF)1α. Further, VHL(P138L) protein has decreased stability in vitro. Similarly to what was reported in Chuvash polycythemia and some other instances of HIFs upregulation, VHL(P138L) erythroid progenitors are hypersensitive to erythropoietin. Interestingly, the level of RUNX1/AML1 and NF-E2 transcripts that are specifically upregulated in acquired polycythemia vera were also upregulated in VHL(P138L) granulocytes.

  8. 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.

  9. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia

    Science.gov (United States)

    Metallo, Christian M.; Gameiro, Paulo A.; Bell, Eric L.; Mattaini, Katherine R.; Yang, Juanjuan; Hiller, Karsten; Jewell, Christopher M.; Johnson, Zachary R.; Irvine, Darrell J.; Guarente, Leonard; Kelleher, Joanne K.; Vander Heiden, Matthew G.; Iliopoulos, Othon; Stephanopoulos, Gregory

    2013-01-01

    Acetyl coenzyme A (AcCoA) is the central biosynthetic precursor for fatty acid synthesis and protein acetylation. In the conventional view of mammalian cell metabolism, AcCoA is primarily generated from glucose-derived pyruvate through the citrate shuttle and adenosine triphosphate citrate lyase (ACL) in the cytosol1-3. However, proliferating cells that exhibit aerobic glycolysis and those exposed to hypoxia convert glucose to lactate at near stoichiometric levels, directing glucose carbon away from the tricarboxylic acid cycle (TCA) and fatty acid synthesis4. Although glutamine is consumed at levels exceeding that required for nitrogen biosynthesis5, the regulation and utilization of glutamine metabolism in hypoxic cells is not well understood. Here we show that human cells employ reductive metabolism of alpha-ketoglutarate (αKG) to synthesize AcCoA for lipid synthesis. This isocitrate dehydrogenase 1 (IDH1) dependent pathway is active in most cell lines under normal culture conditions, but cells grown under hypoxia rely almost exclusively on the reductive carboxylation of glutamine-derived αKG for de novo lipogenesis. Furthermore, renal cell lines deficient in the von Hippel-Lindau (VHL) tumor suppressor protein preferentially utilize reductive glutamine metabolism for lipid biosynthesis even at normal oxygen levels. These results identify a critical role for oxygen in regulating carbon utilization in order to produce AcCoA and support lipid synthesis in mammalian cells. PMID:22101433

  10. Functional significance of erythropoietin in renal cell carcinoma

    International Nuclear Information System (INIS)

    Morais, Christudas; Johnson, David W; Vesey, David A; Gobe, Glenda C

    2013-01-01

    One of the molecules regulated by the transcription factor, hypoxia inducible factor (HIF), is the hypoxia-responsive hematopoietic factor, erythropoietin (EPO). This may have relevance to the development of renal cell carcinoma (RCC), where mutations of the von Hippel-Lindau (VHL) gene are major risk factors for the development of familial and sporadic RCC. VHL mutations up-regulate and stabilize HIF, which in turn activates many downstream molecules, including EPO, that are known to promote angiogenesis, drug resistance, proliferation and progression of solid tumours. HIFs typically respond to hypoxic cellular environment. While the hypoxic microenvironment plays a critical role in the development and progression of tumours in general, it is of special significance in the case of RCC because of the link between VHL, HIF and EPO. EPO and its receptor, EPOR, are expressed in many cancers, including RCC. This limits the use of recombinant human EPO (rhEPO) to treat anaemia in cancer patients, because the rhEPO may be stimulatory to the cancer. EPO may also stimulate epithelial-mesenchymal transition (EMT) in RCC, and pathological EMT has a key role in cancer progression. In this mini review, we summarize the current knowledge of the role of EPO in RCC. The available data, either for or against the use of EPO in RCC patients, are equivocal and insufficient to draw a definitive conclusion

  11. E2-EPF UCP targets pVHL for degradation and associates with tumor growth and metastasis.

    Science.gov (United States)

    Jung, Cho-Rok; Hwang, Kyung-Sun; Yoo, Jinsang; Cho, Won-Kyung; Kim, Jin-Man; Kim, Woo Ho; Im, Dong-Soo

    2006-07-01

    The von Hippel-Lindau tumor suppressor, pVHL, forms part of an E3 ubiquitin ligase complex that targets specific substrates for degradation, including hypoxia-inducible factor-1alpha (HIF-1alpha), which is involved in tumor progression and angiogenesis. It remains unclear, however, how pVHL is destabilized. Here we show that E2-EPF ubiquitin carrier protein (UCP) associates with and targets pVHL for ubiquitin-mediated proteolysis in cells, thereby stabilizing HIF-1alpha. UCP is detected coincidently with HIF-1alpha in human primary liver, colon and breast tumors, and metastatic cholangiocarcinoma and colon cancer cells. UCP level correlates inversely with pVHL level in most tumor cell lines. In vitro and in vivo, forced expression of UCP boosts tumor-cell proliferation, invasion and metastasis through effects on the pVHL-HIF pathway. Our results suggest that UCP helps stabilize HIF-1alpha and may be a new molecular target for therapeutic intervention in human cancers.

  12. Deregulation of E2-EPF ubiquitin carrier protein in papillary renal cell carcinoma.

    Science.gov (United States)

    Roos, Frederik C; Evans, Andrew J; Brenner, Walburgis; Wondergem, Bill; Klomp, Jeffery; Heir, Pardeep; Roche, Olga; Thomas, Christian; Schimmel, Heiko; Furge, Kyle A; Teh, Bin T; Thüroff, Joachim W; Hampel, Christian; Ohh, Michael

    2011-02-01

    Molecular pathways associated with pathogenesis of sporadic papillary renal cell carcinoma (PRCC), the second most common form of kidney cancer, are poorly understood. We analyzed primary tumor specimens from 35 PRCC patients treated by nephrectomy via gene expression analysis and tissue microarrays constructed from an additional 57 paraffin-embedded PRCC samples via immunohistochemistry. Gene products were validated and further studied by Western blot analyses using primary PRCC tumor samples and established renal cell carcinoma cell lines, and potential associations with pathologic variables and survival in 27 patients with follow-up information were determined. We show that the expression of E2-EPF ubiquitin carrier protein, which targets the principal negative regulator of hypoxia-inducible factor (HIF), von Hippel-Lindau protein, for proteasome-dependent degradation, is markedly elevated in the majority of PRCC tumors exhibiting increased HIF1α expression, and is associated with poor prognosis. In addition, we identified multiple hypoxia-responsive elements within the E2-EPF promoter, and for the first time we demonstrated that E2-EPF is a hypoxia-inducible gene directly regulated via HIF1. These findings reveal deregulation of the oxygen-sensing pathway impinging on the positive feedback mechanism of HIF1-mediated regulation of E2-EPF in PRCC. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  13. Unconventional functions of mitotic kinases in kidney tumourigenesis

    Directory of Open Access Journals (Sweden)

    Pauline eHascoet

    2015-10-01

    Full Text Available Human tumours exhibit a variety of genetic alterations, including point mutations, translocations, gene amplifications and deletions, as well as aneuploid chromosome numbers. For carcinomas, aneuploidy is associated with poor patient outcome for a large variety of tumour types, including breast, colon and renal cell carcinoma. The Renal cell cancer (RCC is a heterogeneous carcinoma consisting of different histologic types. The clear renal cell carcinoma (ccRCC is the most common subtype and represents 85 % of the RCC. Central to the biology of the ccRCC is the loss of function of the Von Hippel Lindau gene but is also associated with genetic instability that could be caused by abrogation of the cell cycle mitotic spindle checkpoint and may involve the Aurora kinases, which regulate centrosome maturation. Aneuploidy can also result from the loss of cell-cell adhesion and apical-basal cell polarity that also may be regulated by the mitotic kinases (Plk1, CK2, DLCK1 and Aurora kinases. In this review, we describe the non mitotic unconventional functions of these kinases in renal tumourigenesis.

  14. Low sensitivity of glucagon provocative testing for diagnosis of pheochromocytoma.

    Science.gov (United States)

    Lenders, Jacques W M; Pacak, Karel; Huynh, Thanh-Truc; Sharabi, Yehonatan; Mannelli, Massimo; Bratslavsky, Gennady; Goldstein, David S; Bornstein, Stefan R; Eisenhofer, Graeme

    2010-01-01

    Pheochromocytomas can usually be confirmed or excluded using currently available biochemical tests of catecholamine excess. Follow-up tests are, nevertheless, often required to distinguish false-positive from true-positive results. The glucagon stimulation test represents one such test; its diagnostic utility is, however, unclear. The aim of the study was to determine the diagnostic power of the glucagon test to exclude or confirm pheochromocytoma. Glucagon stimulation tests were carried out at three specialist referral centers in 64 patients with pheochromocytoma, 38 patients in whom the tumor was excluded, and in a reference group of 36 healthy volunteers. Plasma concentrations of norepinephrine and epinephrine were measured before and after glucagon administration. Several absolute and relative test criteria were used for calculating diagnostic sensitivity and specificity. Expression of the glucagon receptor was examined in pheochromocytoma tumor tissue from a subset of patients. Larger than 3-fold increases in plasma norepinephrine after glucagon strongly predicted the presence of a pheochromocytoma (100% specificity and positive predictive value). However, irrespective of the various criteria examined, glucagon-provoked increases in plasma catecholamines revealed the presence of the tumor in less than 50% of affected patients. Diagnostic sensitivity was particularly low in patients with pheochromocytomas due to von Hippel-Lindau syndrome. Tumors from these patients showed no significant expression of the glucagon receptor. The glucagon stimulation test offers insufficient diagnostic sensitivity for reliable exclusion or confirmation of pheochromocytoma. Because of this and the risk of hypertensive complications, the test should be abandoned in routine clinical practice.

  15. A Human Long Non-Coding RNA ALT1 Controls the Cell Cycle of Vascular Endothelial Cells Via ACE2 and Cyclin D1 Pathway

    Directory of Open Access Journals (Sweden)

    Wen Li

    2017-10-01

    Full Text Available Background/Aims: ALT1 is a novel long non-coding RNA derived from the alternatively spliced transcript of the deleted in lymphocytic leukemia 2 (DLEU2. To date, ALT1 biological roles in human vascular endothelial cells have not been reported. Methods: ALT1 was knocked down by siRNAs. Cell proliferation was analyzed by cck-8. The existence and sequence of human ALT1 were identified by 3’ rapid amplification of cDNA ends. The interaction between lncRNA and proteins was analyzed by RNA-Protein pull down assay, RNA immunoprecipitation, and mass spectrometry analysis. Results: ALT1 was expressed in human umbilical vein endothelial cells (HUVECs. The expression of ALT1 was significantly downregulated in contact-inhibited HUVECs and in hypoxia-induced, growth-arrested HUVECs. Knocking down of ALT1 inhibited the proliferation of HUVECs by G0/G1 cell cycle arrest. We observed that angiotensin converting enzyme Ⅱ(ACE2 was a direct target gene of ALT1. Knocking-down of ALT1 or its target gene ACE2 could efficiently decrease the expression of cyclin D1 via the enhanced ubiquitination and degradation, in which HIF-1α and protein von Hippel-Lindau (pVHL might be involved. Conclusion: The results suggested the human long non-coding RNA ALT1 is a novel regulator for cell cycle of HUVECs via ACE2 and cyclin D1 pathway.

  16. Acute Vhl gene inactivation induces cardiac HIF-dependent erythropoietin gene expression.

    Directory of Open Access Journals (Sweden)

    Marta Miró-Murillo

    Full Text Available Von Hippel Lindau (Vhl gene inactivation results in embryonic lethality. The consequences of its inactivation in adult mice, and of the ensuing activation of the hypoxia-inducible factors (HIFs, have been explored mainly in a tissue-specific manner. This mid-gestation lethality can be also circumvented by using a floxed Vhl allele in combination with an ubiquitous tamoxifen-inducible recombinase Cre-ER(T2. Here, we characterize a widespread reduction in Vhl gene expression in Vhl(floxed-UBC-Cre-ER(T2 adult mice after dietary tamoxifen administration, a convenient route of administration that has yet to be fully characterized for global gene inactivation. Vhl gene inactivation rapidly resulted in a marked splenomegaly and skin erythema, accompanied by renal and hepatic induction of the erythropoietin (Epo gene, indicative of the in vivo activation of the oxygen sensing HIF pathway. We show that acute Vhl gene inactivation also induced Epo gene expression in the heart, revealing cardiac tissue to be an extra-renal source of EPO. Indeed, primary cardiomyocytes and HL-1 cardiac cells both induce Epo gene expression when exposed to low O(2 tension in a HIF-dependent manner. Thus, as well as demonstrating the potential of dietary tamoxifen administration for gene inactivation studies in UBC-Cre-ER(T2 mouse lines, this data provides evidence of a cardiac oxygen-sensing VHL/HIF/EPO pathway in adult mice.

  17. Lack of a Functional VHL Gene Product Sensitizes Renal Cell Carcinoma Cells to the Apoptotic Effects of the Protein Synthesis Inhibitor Verrucarin A

    Directory of Open Access Journals (Sweden)

    Girma M. Woldemichael

    2012-08-01

    Full Text Available Verrucarin A (VA is a small molecule derived from the fungal plant pathogen Myrothecium verrucaria and was identified as a selective inhibitor of clear cell renal cell carcinoma (CCRCC cell proliferation in a high-throughput screen of a library of naturally occurring small molecules. CCRCC arises as a result of loss-of-function mutations in the von Hippel-Lindau (VHL gene. Here we show that VA inhibits protein translation initiation culminating in apoptosis through the extrinsic signaling pathway. Reintroduction of the VHL gene in CCRCC cells afforded resistance to VA's apoptotic effects. This resistance is mediated in part by the formation of stress granules that entrap signaling molecules that initiate the apoptotic signaling cascade. The VHL gene product was found to be a component of stress granules that develop as result of VA treatment. These findings reveal an important role for the VHL gene product in cytotoxic stress response and have important implications for the rational development of VA-related compounds in chemotherapeutic targeting of CCRCC.

  18. Lack of a functional VHL gene product sensitizes renal cell carcinoma cells to the apoptotic effects of the protein synthesis inhibitor verrucarin A.

    Science.gov (United States)

    Woldemichael, Girma M; Turbyville, Thomas J; Vasselli, James R; Linehan, W Marston; McMahon, James B

    2012-08-01

    Verrucarin A (VA) is a small molecule derived from the fungal plant pathogen Myrothecium verrucaria and was identified as a selective inhibitor of clear cell renal cell carcinoma (CCRCC) cell proliferation in a high-throughput screen of a library of naturally occurring small molecules. CCRCC arises as a result of loss-of-function mutations in the von Hippel-Lindau (VHL) gene. Here we show that VA inhibits protein translation initiation culminating in apoptosis through the extrinsic signaling pathway. Reintroduction of the VHL gene in CCRCC cells afforded resistance to VA's apoptotic effects. This resistance is mediated in part by the formation of stress granules that entrap signaling molecules that initiate the apoptotic signaling cascade. The VHL gene product was found to be a component of stress granules that develop as result of VA treatment. These findings reveal an important role for the VHL gene product in cytotoxic stress response and have important implications for the rational development of VA-related compounds in chemotherapeutic targeting of CCRCC.

  19. VHL-mediated hypoxia regulation of cyclin D1 in renal carcinoma cells.

    Science.gov (United States)

    Bindra, Ranjit S; Vasselli, James R; Stearman, Robert; Linehan, W Marston; Klausner, Richard D

    2002-06-01

    Renal cell carcinoma is associated with mutation of the von Hippel-Lindau (VHL) tumor suppressor gene. Cell lines derived from these tumors cannot exit the cell cycle when deprived of growth factors, and the ability to exit the cell cycle can be restored by the reintroduction of wild-type protein VHL (pVHL). Here, we report that cyclin D1 is overexpressed and remains inappropriately high in during contact inhibition in pVHL-deficient cell lines. In addition, hypoxia increased the expression of cyclin D1 specifically in pVHL-negative cell lines into which pVHL expression was restored. Hypoxic-induction of cyclin D1 was not observed in other pVHL-positive cell lines. This suggests a model whereby in some kidney cell types, pVHL may regulate a proliferative response to hypoxia, whereas the loss of pVHL leads to constitutively elevated cyclin D1 and abnormal proliferation under normal growth conditions.

  20. Lack of a Functional VHL Gene Product Sensitizes Renal Cell Carcinoma Cells to the Apoptotic Effects of the Protein Synthesis Inhibitor Verrucarin A12

    Science.gov (United States)

    Woldemichael, Girma M; Turbyville, Thomas J; Vasselli, James R; Linehan, W Marston; McMahon, James B

    2012-01-01

    Verrucarin A (VA) is a small molecule derived from the fungal plant pathogen Myrothecium verrucaria and was identified as a selective inhibitor of clear cell renal cell carcinoma (CCRCC) cell proliferation in a high-throughput screen of a library of naturally occurring small molecules. CCRCC arises as a result of loss-of-function mutations in the von Hippel-Lindau (VHL) gene. Here we show that VA inhibits protein translation initiation culminating in apoptosis through the extrinsic signaling pathway. Reintroduction of the VHL gene in CCRCC cells afforded resistance to VA's apoptotic effects. This resistance is mediated in part by the formation of stress granules that entrap signaling molecules that initiate the apoptotic signaling cascade. The VHL gene product was found to be a component of stress granules that develop as result of VA treatment. These findings reveal an important role for the VHL gene product in cytotoxic stress response and have important implications for the rational development of VA-related compounds in chemotherapeutic targeting of CCRCC. PMID:22952429

  1. Development of a cell-based reporter assay for screening of inhibitors of hypoxia-inducible factor 2-induced gene expression.

    Science.gov (United States)

    Woldemichael, Girma M; Vasselli, James R; Gardella, Roberta S; McKee, Tawnya C; Linehan, W Marston; McMahon, James B

    2006-09-01

    Reporter cell lines have been developed for the identification of inhibitors of gene expression enhanced by hypoxia-inducible factor 2, which has been implicated as a transcription factor involved in the tumorigenesis of clear cell renal carcinoma. Stably transformed reporter clones of the human renal clear cell carcinoma cell line 786-O were generated by transfection or retroviral infection. Luciferase reporter expression in the vectors used was driven by either the natural human vascular endothelial growth factor (VEGF) promoter-enhancer or by the VEGF and the human endothelial nitric oxide synthase enhancers modulating minimal human cytomegalovirus promoter. Utility of the generated reporter cell lines was validated by introducing the von Hippel-Lindau protein complex and testing for reporter inducibility by hypoxia. The dynamic range in reporter activity under hypoxic stress was found to be at least 30- to 40-fold, with a signal-to-noise ratio of 60:1. Properties of the cell lines such as tolerance to up to 3% DMSO, signal stability with multiple in vitro passages, and utility in both 96- and 384-well plate formats indicated their suitability for use in a high-throughput screen. In addition, the potential use of these reporter lines in the evaluation of high-throughput screening hits in vivo in various mice models has been demonstrated.

  2. An Elongin-Cullin-SOCS Box Complex Regulates Stress-Induced Serotonergic Neuromodulation

    Directory of Open Access Journals (Sweden)

    Xicotencatl Gracida

    2017-12-01

    Full Text Available Neuromodulatory cells transduce environmental information into long-lasting behavioral responses. However, the mechanisms governing how neuronal cells influence behavioral plasticity are difficult to characterize. Here, we adapted the translating ribosome affinity purification (TRAP approach in C. elegans to profile ribosome-associated mRNAs from three major tissues and the neuromodulatory dopaminergic and serotonergic cells. We identified elc-2, an Elongin C ortholog, specifically expressed in stress-sensing amphid neuron dual ciliated sensory ending (ADF serotonergic sensory neurons, and we found that it plays a role in mediating a long-lasting change in serotonin-dependent feeding behavior induced by heat stress. We demonstrate that ELC-2 and the von Hippel-Lindau protein VHL-1, components of an Elongin-Cullin-SOCS box (ECS E3 ubiquitin ligase, modulate this behavior after experiencing stress. Also, heat stress induces a transient redistribution of ELC-2, becoming more nuclearly enriched. Together, our results demonstrate dynamic regulation of an E3 ligase and a role for an ECS complex in neuromodulation and control of lasting behavioral states.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. [Homocysteine and von Willebrand factor in chronic alcoholism].

    Science.gov (United States)

    Koriakin, A M; Epifantseva, N N; Dadyka, I V; Gorbatovskiĭ, Ia A

    2010-04-01

    The levels of homocysteine (HC) and von Willebrand factor (VWF) as cardiovascular risk factors were studied in patients with Stage II chronic alcoholism. Forty-one men with Stage II chronic alcoholism without clinical signs of somatic and infectious diseases were examined. Their median age was 37 (range 32-40) years; the alcoholization period was 12 (range 8-17) years. Plasma HC and VWF (amount and activity) levels were determined. In 63.4% of chronic alcoholic patients, HC levels was twice as high as in the controls; in 80.6%, both the content and activity of VWF were increased. There was no correlation between the levels of HC and VWF. Vascular endothelial damage concurrent with hyperhomocysteinemia increases a cardiovascular risk in patients with Stage II chronic alcoholism.

  5. Morbidity and mortality of aggressive resection in patients with advanced neuroendocrine tumors.

    Science.gov (United States)

    Norton, Jeffrey A; Kivlen, Maryann; Li, Michelle; Schneider, Darren; Chuter, Timothy; Jensen, Robert T

    2003-08-01

    There is considerable controversy about the treatment of patients with malignant advanced neuroendocrine tumors of the pancreas and duodenum. Aggressive surgery remains a potentially efficacious antitumor therapy but is rarely performed because of its possible morbidity and mortality. Aggressive resection of advanced neuroendocrine tumors can be performed with acceptable morbidity and mortality rates and may lead to extended survival. The medical records of patients with advanced neuroendocrine tumors who underwent surgery between 1997 and 2002 by a single surgeon at the University of California, San Francisco, were reviewed in an institutional review board-approved protocol. Surgical procedure, pathologic characteristics, complications, mortality rates, and disease-free and overall survival rates were recorded. Disease-free survival was defined as no tumor identified on radiological imaging studies and no detectable abnormal hormone levels. Proportions were compared statistically using the Fisher exact test. Kaplan-Meier curves were used to estimate survival rates. Twenty patients were identified (11 men and 9 women). Of these, 10 (50%) had gastrinoma, 1 had insulinoma, and the remainder had nonfunctional tumors; 2 had multiple endocrine neoplasia type 1, and 1 had von Hippel-Lindau disease. The mean age was 55 years (range, 34-72 years). In 10 patients (50%), tumors were thought to be unresectable according to radiological imaging studies because of multiple bilobar liver metastases (n = 6), superior mesenteric vein invasion (n = 3), and extensive nodal metastases (n = 1). Tumors were completely removed in 15 patients (75%). Surgical procedures included 8 proximal pancreatectomies (pancreatoduodenectomy or whipple procedure), 3 total pancreatectomies, 9 distal pancreatectomies, and 3 tumor enucleations from the pancreatic head. Superior mesenteric vein reconstruction was done in 3 patients. Liver resections were done in 6 patients, and an extended periaortic node

  6. 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.

  7. von Neumann's hypothesis concerning coherent states

    International Nuclear Information System (INIS)

    Zak, J

    2003-01-01

    An orthonormal basis of modified coherent states is constructed. Each member of the basis is an infinite sum of coherent states on a von Neumann lattice. A single state is assigned to each unit cell of area h (Planck constant) in the phase plane. The uncertainties of the coordinate x and the square of the momentum p 2 for these states are shown to be similar to those for the usual coherent states. Expansions in the newly established set are discussed and it is shown that any function in the kq-representation can be written as a sum of two fixed kq-functions. Approximate commuting operators for x and p 2 are defined on a lattice in phase plane according to von Neumann's prescription. (leeter to the editor)

  8. Theodor von Grotthuss’ Contribution to Electrochemistry

    International Nuclear Information System (INIS)

    Pauliukaite, Rasa; Juodkazytė, Jurga; Ramanauskas, Rimantas

    2017-01-01

    Freiherr Christian Johann Dietrich Theodor von Grotthuss (1785-1822) lived and worked in Lithuania. Inspired by Volta's pile he proposed the first theory of water electrolysis, which was published in 1805 in Rome. Michael Faraday acknowledged T. Grotthuss for this theory in his further investigations of electrolysis processes. Having studied in Germany and France Grotthuss brought science to province by establishing his laboratory in Gedučiai village in his mother's real estate. Lithuanian scientists are proud that life of Theodor von Grotthuss was related to this country. Many events to remember this prominent scientist are organised in Vilnius and other places. His works and example provided a good basis for further development of electrochemical science in Lithuania. Grotthuss insights into the mechanism of proton transport still are of great relevance to such areas of modern science as membrane biochemistry, energy conversion and storage.

  9. Inattentional blindness and the von Restorff effect.

    Science.gov (United States)

    Schmidt, Stephen R; Schmidt, Constance R

    2015-02-01

    Sometimes we fail to notice distinctive or unusual items (inattentional blindness), while other times we remember distinctive items more than expected items (the von Restorff effect). A three-factor framework is presented and tested in two experiments in an attempt to reconcile these seemingly contradictory phenomena. Memory for different types of unexpected stimuli was tested after an easy or difficult Stroop color-naming task. Highly arousing taboo words were well remembered even when the difficult Stroop task limited attentional resources. However, a conceptual isolation effect was only observed when the nature of the category change was highlighted by the Stroop task, the Stroop task was easy, and/or the isolated targets enjoyed a retrieval advantage relative to comparison targets. As proposed in the three-factor framework, the arousing qualities of the stimuli, the attentional demands of the primary task, and the relevance of isolated features at encoding and retrieval combine to produce inattentional blindness and the von Restorff effect.

  10. Radiosurgery for hemangioblastoma: results of a multi-institutional experience

    Energy Technology Data Exchange (ETDEWEB)

    Patrice, Stephen J; Sneed, Penny K; Flickinger, John C; Alexander, Eben; Larson, David A; Shrieve, Dennis C; Pollock, Bruce E; Kondziolka, Douglas S; Gutin, Philip H; Wara, William M; McDermott, Michael W; Lunsford, L Dade; Loeffler, Jay S

    1995-07-01

    Purpose/Objective: Hemangioblastoma is a primary solid or cystic vascular tumor of the central nervous system that occurs most frequently in the cerebellum, brain stem and spinal cord. Between June 1988 and June 1994, 38 hemangioblastomas were treated with stereotactic radiosurgery (SR) at 3 active SR centers in order to evaluate the efficacy and potential toxicity of this therapeutic modality as an adjuvant or alternative treatment to surgical resection. Materials and Methods: SR was performed using either a 201-cobalt source Gamma Knife unit or a dedicated SR linear accelerator. Of the 18 primary tumors treated, 16 had no prior history of surgical resection and were treated definitively with SR and 2 primary lesions were subtotally resected and subsequently treated with SR. Twenty lesions were treated with SR after prior surgical failure (17 tumors) or failure after prior surgery and conventional radiotherapy (3 tumors). Eight patients were treated with SR for multifocal disease (total, 24 known tumors). SR tumor volumes measured 0.05 to 12 cc (median, 0.97 cc). Minimum tumor doses ranged from 12 to 20 Gy (median, 15.5 Gy). Results: Median follow-up from the time of SR was 24.5 months (range, 6 to 77 months). The 2-year actuarial overall survival was 88% +/- 15% (95% confidence interval). To date, 4 of the 22 patients in the study have died. Of these 4 patients, 2 who received SR for salvage of surgical failure died of progressive intracranial tumor, 1 died of metastatic breast carcinoma, and 1 died of renal failure as a result of systemic complications of von Hippel-Lindau Syndrome (VHL). Three-year actuarial freedom from progression was 86% +/- 12% (95% confidence interval). Thirty-one of the 36 evaluable tumors (86%) were controlled locally. None of the 18 primary tumors that were treated with SR as definitive therapy have failed to date. All 5 lesions that ultimately failed to be controlled by SR were recurrent tumors that had been treated with SR for salvage

  11. Verbesserung der Symmetrie von Hirnaufnahmen entlang der Sagittalebene

    Science.gov (United States)

    Ens, Konstantin; Wenzel, Fabian; Fischer, Bernd

    Die lokale Symmetrie von Hirnscans entlang der Sagittalebene zu ermitteln und zu modizifieren, ist für eine Reihe neurologischer Anwendungen interessant. Beispielsweise kann der voxelweise Vergleich von rechter und linker Hirnhälfte nur dann Aufschluss über die Lokalisierung von Läsionen geben, wenn durch Transformation ein Hirnscan eine möglichst hohe Symmetrie aufweist. Ein weiteres Anwendungsgebiet ist die Visualisierung von medialen Hirnschnitten, für die die Trennfläche beider Hirnhälfte möglichst eben sein sollte. Diese Arbeit stellt die Entwicklung eines Verfahrens vor, mit dessen Hilfe die Symmetrie von Hirnaufnahmen entlang der Sagittalebene verbessert werden kann. Dies geschieht unter Verwendung von aktiven Konturen, die mit Hilfe einer neuartigen Kostenfunktion gesteuert werden. Experimente am Ende der Arbeit mit strukturellen Kernspinaufnahmen demonstrieren die Leistungsfähigkeit des Verfahrens.

  12. Rohlin flows on Von Neumann algebras

    CERN Document Server

    Masuda, Toshihiko

    2016-01-01

    The authors will classify Rohlin flows on von Neumann algebras up to strong cocycle conjugacy. This result provides alternative approaches to some preceding results such as Kawahigashi's classification of flows on the injective type II_1 factor, the classification of injective type III factors due to Connes, Krieger and Haagerup and the non-fullness of type III_0 factors. Several concrete examples are also studied.

  13. Marktorientierte Vertriebs-Reorganisation von Energieversorgungsunternehmen

    OpenAIRE

    Beutin, Nikolas; Scholl, Michael; Fürst, Andreas

    2003-01-01

    Seit der Liberalisierung des Energiemarktes im Jahre 1998 sehen sich Energieversorgungsunternehmen (EVUs) einer veränderten Markt- und Wettbewerbssituation gegenüber. Neben Risiken, wie dem Eintritt von Wettbewerbern in das vormals geschützte Gebiet, eröffnete sich ihnen hierdurch aber auch die Chance, außerhalb des eigenen Netzbereiches neue Kunden zu gewinnen. Um sowohl dem Margenverfall als auch der direkten Vergleichbarkeit mit ...

  14. 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.

  15. Visuelle Analyse von E-mail-Verkehr

    OpenAIRE

    Mansmann, Florian

    2003-01-01

    Diese Arbeit beschreibt Methoden zur visuellen geographischen Analyse von E-mail Verkehr.Aus dem Header einer E-mail können Hostadressen und IP-Adressen herausgefiltert werden. Anhand einer Datenbank werden diesen Host- und IP-Adressen geographische Koordinaten zugeordnet.Durch eine Visualisierung werden in übersichtlicher Art und Weise mehrere tausend E-mail Routen dargestellt. Zusätzlich dazu wurden interktive Manipulationsmöglichkeiten vorgestellt, welche eine visuelle Exploration der Date...

  16. Zur Kenntnis von Gnetum neglectum Bl

    NARCIS (Netherlands)

    Markgraf, F.

    1960-01-01

    Gnetum neglectum war nicht nur, wie der Name andeutet, bis zu Blumes Zeit übersehen worden, sondern es wurde von Späteren wiederum verkannt, wie ich in Bull. J. B. Buitenzorg 3. Ser. 10 (1930) 474 näher ausgeführt habe. Die echte Art taucht verhältnismässig selten in den Herbarien auf. Sie ist eine

  17. 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.

  18. 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.

  19. Gespiegelte Planeten – Die Anordnung der Pyramiden von Gizeh

    OpenAIRE

    Jelitto, Hans

    2000-01-01

    Antike Bauwerke wurden wiederholt auf astronomische Zusammenhänge hin untersucht, so z. B. ihre Ausrichtung in Bezug auf die Bewegung von Sonne oder Sternen. Vor diesem Hintergrund wurden für die Pyramiden von Gizeh drei ungewöhnliche Gleichungen entdeckt, die die Pyramidengrößen mit einer Genauigkeit von ca. 0,1 % festlegen. Gleichzeitig legen diese drei Gleichungen nahe, die drei Pyramiden in der Reihenfolge Mykerinos-, Chefren- und Cheopspyramide den inneren drei Planeten unseres Sonnensys...

  20. 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

  1. Arbeitszeiten von Professorinnen und Professoren in Deutschland 2016

    OpenAIRE

    Weihs, Claus; Hernández Rodríguez, Tanja; Doeckel, Maximilian; Marty, Christoph; Wormer, Holger

    2018-01-01

    In dieser Studie werden belastbare Prognoseintervalle der wöchentlichen Gesamtarbeitszeit von Universitätsprofessorinnen und -professoren aus Daten einer Umfrage aus dem Jahre 2016 und a-priori Informationen aus früheren Studien bestimmt. Neben der Gesamtarbeitszeit werden auch Teilarbeitszeiten zum Beispiel für Lehre und Forschung ermittelt. Die Ergebnisse von frequentistischer und Bayesianischer Analyse werden verglichen. Aus den gültigen Fragebögen von aktiven Vollzeit arbeitenden Universi...

  2. [Heredity in renal and prostatic neoplasia].

    Science.gov (United States)

    Prayer Galetti, T; D'Arrigo, L; De Zorzi, L; Patarnello, T

    1997-09-01

    There is an ever growing report of data supporting the evidence that accumulated genetic changes underlie the development of neoplasia. The paradigma of this multistep process is colon cancer were cancer onset is associated, over decades, with at least seven genetic events. The number of genetic alterations increases moving from adenomatous lesions to colon cancer and, although the genetic alterations occur according to a preferred sequence, the total accumulation of changes rather than their sequential order is responsible of tumor biological behavior. It is noteworthy that, at least for this neoplasia, carcinogenesis appears to arise as a result of the mutational activation of oncogenes coupled with the mutational inactivation of tumor suppressor genes. In some cases mutant suppressor genes appear to exert a phenotypic effect even when present in the heterozygous state thus been non "recessive" at the cellular level. The general features of this model may apply also to renal cell cancer (RCC) and prostate cancer (CaP). Extensive literature exists on the cytogenetic and molecular findings in RCC. Only 2% of RCC are familiar, but molecular genetic studies of these cancers have provided important informations on RCC pathogenesis. As with other cancers, familiar RCC is characterized by an early age of onset and frequent multicentricity. A pathological classification useful in studying these patients subdivide renal cancers in papillary (pRCC) and non papillary (RCC) neoplasms. The most common cause of inherited RCC is the Von Hippel Lindau disease (VHL) a dominantly inherited multisystem disorder characterized by retinal and cerebellar hemangioblastomas, pheochromocytomas, pancreatic cysts and RCC. Over 70% of these patients will develop an RCC by their sixth decade. In 1993 the isolation of the tumor suppressor gene in VHL disease at the level of chromosome 3p25-p26 have lead to a better understanding of RCC. Most missense mutations are associated with high risk of

  3. Untersuchungen zur Farbreaktion von Amilorid, Chlorhexidin und Proguanil mit Hypobromit

    OpenAIRE

    Huth, Silke

    2004-01-01

    Bei der Reaktion von Amiloridhydrochlorid (1· HCl) mit Brom in alkalischer Lösung wird ein gelbbraunes Dehydrierungsprodukt erhalten, daß als 3-(3-Amino-1,2,4-oxadiazol-5-yl)-5-chlor-2,6-pyrazindiamin (6) identifiziert werden konnte. Durch Vergleich von Massen- und NMR-Spektren der Verbindung 6 mit Spektren von 1· HCl und Referenzsubstanzen I-III konnte auf die verbindung 6 geschlossen werden. Die Struktur wurde durch eine Röntgenstrukturanalyse abgesichert. Erhitzen von Amiloridhydrochlorid ...

  4. Chancen und Gefahren von Global-Marketing-Konzepten

    OpenAIRE

    Berndt, Ulrike

    1990-01-01

    Chancen und Gefahren von Global-Marketing-Konzepten. - Augsburg : Förderges. Marketing, 1990. - 57, XII S. - Zugl: Augsburg, Univ., Diplomarb. - (Arbeitspapiere zur Schriftenreihe Schwerpunkt Marketing ; 29)

  5. A bicategorical approach to Morita equivalence for von Neumann algebras

    International Nuclear Information System (INIS)

    Brouwer, R. M.

    2003-01-01

    We relate Morita equivalence for von Neumann algebras to the ''Connes fusion'' tensor product between correspondences. In the purely algebraic setting, it is well known that rings are Morita equivalent if they are equivalent objects in a bicategory whose 1-cells are bimodules. We present a similar result for von Neumann algebras. We show that von Neumann algebras form a bicategory, having Connes's correspondences as 1-morphisms, and (bounded) intertwiners as 2-morphisms. Further, we prove that two von Neumann algebras are Morita equivalent iff they are equivalent objects in the bicategory. The proofs make extensive use of the Tomita-Takesaki modular theory

  6. Radioimmunoassay of serum myoglobin and its signifance for diagnosis and therapy of musculoskeletal diseases. Der radioimmunologische Myoglobinnachweis im Serum und seine Bedeutung bei der Diagnostik und Therapie von Skelettmuskelerkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Kiessling, W.R.

    1982-01-01

    A commercial test kit for radioimmunologic proof of myoglobin in serum was tested with regard to its specificty, sensitivity, precision, reproducibility, recovery and use in the diagnosis and therapy of musculoskeletal diseases. In the serum of 164 healthy control persons (age: 2-79 years) the individual myoglobin concentrations ranged from 4 to 60 ng/ml. Among 300 patients with muscular diseases extreme myoglobinaemia in acute rhabdomyolysis, polymyositis and dermatomyositis and different progressive muscular dystrophies could be detected. Slightly increased myoglobin concentrations could be proved in a number of patient with amyotrophic lateral sklerosis, neural muscular atrophy and in all cases of spinal muscular atrophy of the Kugelberg-Welander type. Confirmed DMD patients exhibited in about 80% of the cases hypermyoglobinaemia, and about 11% of 43 possible DMD patients showed an increase in myoglobin. Taking acute rhabdomyolysis and myositis as an example, it was found that myoglobin correlates well with the clinical course of these diseases and permits safe inferences as to the efficiency of the therapy chosen.

  7. Der Einfluß der Ablauforganisation auf die Effizienz von Entscheidungen: Eine empirische Untersuchung am Beispiel von Bilanzanalysen

    OpenAIRE

    Gemünden, Hans Georg

    1987-01-01

    Der vorliegende Beitrag widmet sich einem in der Organisationstheorie stark vernachlässigten Problem: der Ablauforganisation von Entscheidungen. Am Beispiel von Bilanzanalysen wird empirisch geprüft, in welcher Weise eine Gliederung des Prozesses nach Verrichtungen oder Objekten die Qualität der Analyse beeinflußt. Hierzu wird ein validiertes Konzept zur Messung der Qualität von Bilanzanalysen entwickelt. Es wird gezeigt, wie man mittels prozeßbegleitender experimenteller Organisationsforschu...

  8. Beeinflussung der Wirkung von Ernährungsinformation durch Framing: Analyse am Beispiel von Folsäure

    OpenAIRE

    Lensch, Kathrin; Hartmann, Monika; Simons, Johannes

    2011-01-01

    Die Bereitstellung und verbrauchergerechte Aufbereitung von Informationen stellt eine Möglichkeit dar, Konsumenten darin zu unterstützen, Gesundheitsaspekte vermehrt in das Kauf- und Essverhalten zu integrieren. In der Verhaltensökonomik gelten Framing-Effekte als wichtige Bestimmungsfaktoren für die Wahrnehmung von Informationen. Im Rahmen des vorliegenden Beitrags werden Framing-Effekte am Beispiel von Ernährungsinformationen über Folsäure mit Hilfe eines Experiments untersucht. Die Ergebni...

  9. 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.

  10. Stage-dependent prognostic impact of molecular signatures in clear cell renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Weber T

    2014-05-01

    Full Text Available Thomas Weber,1,2 Matthias Meinhardt,3 Stefan Zastrow,1 Andreas Wienke,4 Kati Erdmann,1 Jörg Hofmann,1 Susanne Fuessel,1 Manfred P Wirth11Department of Urology, Technische Universität Dresden, Dresden, Germany; 2Department of Oncology and Hematology, Martin-Luther-University Halle-Wittenberg, Halle (Saale, Germany; 3Institute of Pathology, Technische Universität Dresden, Dresden, Germany; 4Institute of Medical Epidemiology, Biostatistics, and Informatics, Martin-Luther-University Halle-Wittenberg, Halle (Saale, GermanyPurpose: To enhance prognostic information of protein biomarkers for clear cell renal cell carcinomas (ccRCCs, we analyzed them within prognostic groups of ccRCC harboring different tumor characteristics of this clinically and molecularly heterogeneous tumor entity.Methods: Tissue microarrays from 145 patients with primary ccRCC were immunohistochemically analyzed for VHL (von Hippel-Lindau tumor suppressor, Ki67 (marker of proliferation 1, p53 (tumor protein p53, p21 (cyclin-dependent kinase inhibitor 1A, survivin (baculoviral IAP repeat containing 5, and UEA-1 (ulex europaeus agglutinin I to assess microvessel-density.Results: When analyzing all patients, nuclear staining of Ki67 (hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.04–1.12 and nuclear survivin (nS; HR 1.04, 95% CI 1.01–1.08 were significantly associated with disease-specific survival (DSS. In the cohort of patients with advanced localized or metastasized ccRCC, high staining of Ki67, p53 and nS predicted shorter DSS (Ki67: HR 1.07, 95% CI 1.02–1.11; p53: HR 1.05, 95% CI 1.01–1.09; nS: HR 1.08, 95% CI 1.02–1.14. In organ-confined ccRCC, patients with high p21-staining had a longer DSS (HR 0.96, 95% CI 0.92–0.99. In a multivariate model with stepwise backward elimination, tumor size and p21-staining showed a significant association with DSS in patients with "organ-confined" ccRCCs. The p21-staining increased the concordance index of tumor size from

  11. Modified diagnosis of cardiovascular diseases: Application and comparison of diagnostic techniques in clinical medicine, radiology, ultrasonography and nuclear medicine. Final report. Einsatz und Vergleich klinischer, roentgenologischer, sonographischer und nuklearmedizinischer Methoden zur abgestuften Diagnostik von Herzkrankheiten. Schlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Adam, W.; Boettcher, D.; Christl, H.; Baew-Christow, T.; Holper, H.; Meindl, S.; Meyer, U.; Pfannenstiel, P.

    1985-01-01

    The main point of interest of the project is the question whether ultrasonography, myocardial scintiscanning, and radionuclide angiocardiography can replace the invasive techniques of cardiovascular diagnosis, and thus save costs at that. The results show that the above non-invasive techniques are indispensable in case of a diagnosis for cardiosurgery, almost sufficient in case of valvular heart disease, and sufficient in all cases of cardiomyopathy. Optimally planned application of the non-invasive methods could save about DM 7.3 millions a year in the FRG. (TRV).

  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. 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

  14. 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

  15. Polychaeten aus den Zoologischen Museen von Leiden und Amsterdam I

    NARCIS (Netherlands)

    Augener, H.

    1933-01-01

    In der vorliegenden Arbeit ist die Untersuchung eines sehr umfangreichen Polychaeten-Materials niedergelegt, das mir von Herrn Prof. Dr. E. D. van Oort in Leiden und Herrn Prof. Dr. L. F. de Beaufort in Amsterdam zur Bearbeitung übergeben wurde. Von diesem Material ist der dem Museum in Leiden

  16. [Hans Jakob Christoffel von Grimmelshausen. Saksa Simplicissimuse seiklused] / Meelis Friedenthal

    Index Scriptorium Estoniae

    Friedenthal, Meelis, 1973-

    2011-01-01

    Tutvustus: Grimmelshausen, Hans Jakob Christoffel von. Saksa Simplicissimuse seiklused, teisisõnu: ühe veidra vagabundi elulugu, kel Melchior Sternfels von Fuchshaim nimeks, et kus ja mis moel ta siia ilma sündis ning mida siin nägi, õppis, oma nahal tunda sai ja kannatas, nagu sellestki, miks ta siinsest ilmast vabatahtlikult loobub. [Tallinn] : Pegasus, c2010

  17. Von Neumann algebras as complemented subspaces of B(H)

    DEFF Research Database (Denmark)

    Christensen, Erik; Wang, Liguang

    2014-01-01

    Let M be a von Neumann algebra of type II1 which is also a complemented subspace of B( H). We establish an algebraic criterion, which ensures that M is an injective von Neumann algebra. As a corollary we show that if M is a complemented factor of type II1 on a Hilbert space H, then M is injective...

  18. An accurate von Neumann's law for three-dimensional foams

    NARCIS (Netherlands)

    Hilgenfeldt, Sascha; Kraynik, Andrew M.; Koehler, Stephan A.; Stone, Howard A.

    2001-01-01

    The diffusive coarsening of 2D soap froths is governed by von Neumann's law. A statistical version of this law for dry 3D foams has long been conjectured. A new derivation, based on a theorem by Minkowski, yields an explicit analytical von Neumann's law in 3D which is in very good agreement with

  19. 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.

  20. 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)

  1. Unlawfulness of environmental zones; Rechtswidrigkeit von Umweltzonen

    Energy Technology Data Exchange (ETDEWEB)

    Balbach, Jan

    2016-07-01

    The author examines the new findings on the effectiveness of the environmental zones and, in this context, questions their legitimacy. In addition, the efforts of the European and German legislators are analyzed in order to reduce the particulate matter pollution. In addition, legal protection against the exceeding of limits for particulate matter is critically appreciated. [German] Der Autor beleuchtet die neuen Erkenntnisse zur Wirksamkeit der Umweltzonen und hinterfragt vor diesem Hintergrund deren Rechtmaessigkeit. Darueber hinaus werden die Bemuehungen des europaeischen und deutschen Gesetzgebers analysiert, um die Feinstaubbelastung zu senken. Zudem wird der Rechtsschutz gegen die Ueberschreitung von Feinstaubgrenzwerten kritisch gewuerdigt.

  2. A Metabiography of Alexander von Humboldt

    Directory of Open Access Journals (Sweden)

    Nicolaas A. Rupke

    2006-04-01

    Full Text Available Article in English.The author's recently published monograph on Alexander von Humboldt describes the multiple images of this great cultural icon. The book is a metabiographical study that shows how from the middle of the nineteenth century to the present day Humboldt has served as a nucleus of crystallisation for a variety of successive socio-political ideologies, each producing its own distinctive representation of him. The historiographical implications of this biographical diversity are profound and support current attempts to understand historical scholarship in terms of memory cultures.

  3. Die Biopsie von Knochen- und Weichteiltumoren

    OpenAIRE

    Fuchs, B

    2008-01-01

    Technisch stellt die Biopsie von Knochen- und Weichteiltumoren einen simplen Akt dar, intellektuell aber ist die Planung einer Biopsie höchst anspruchsvoll. Zu häufig werden heutzutage immer noch Biopsien unsachgemäss durchgeführt, so dass die Behandlung - im besten Fall - erschwert wird. Eine unsachgemäss durchgeführte Biopsie führt häufig zu negativen funktionellen Konsequenzen für den Patienten, im schlimmsten Fall kann es die Prognose direkt beeinträchtigen. Aus diesem Grund soll...

  4. Die Altäre von Selinunt

    OpenAIRE

    Voigts, Clemens

    2014-01-01

    In der Dissertation wurden die Altäre von Selinunt, einer griechischen Kolonie auf Sizilien, mit den Methoden der Bauforschung untersucht. Die neun behandelten Brandopferaltäre sind monumentale Quaderbauten, die bis zu 20 m Länge erreichen. Sie stammen aus der Blütezeit Selinunts, dem 6. und 5. Jh. v. Chr. Die Bauten waren bereits im 19. und 20. Jh. freigelegt worden und wurden nun in Bauaufnahmen dokumentiert, zeichnerisch rekonstruiert und zeitlich eingeordnet. Dabei ließ sich an ihnen eine...

  5. Alexander von Humboldt’s footnotes

    OpenAIRE

    Werner, Anja

    2015-01-01

    Alexander von Humboldts Fußnoten waren ihrer Zeit weit voraus, obwohl sie kaum den heutigen akademischen Standards entsprechen. Dieser Artikel untersucht die Fußnoten in Humboldts Essai politique sur l‘île de Cuba (1826). Zwar ist es nicht immer leicht, die manchmal recht geheimnisvollen Verweise zu entschlüsseln, dennoch lohnt sich der Versuch: Humboldts Fußnoten geben nicht nur Auskunft über seine umfassenden Netzwerke des Wissens. Sie verweisen auch auf Auseinandersetzungen verschiedener G...

  6. [Carl Adolph von Basedow--150th anniversary of his death].

    Science.gov (United States)

    Meng, Wieland

    2004-05-01

    Carl Adolph von Basedow was the son of an aristocratic family and was born 1799 in Dessau. He was the grandson of the famous pedagogue Johann Bernhard Basedow. He studied medicine at the university of Halle and spent two years in the surgical service of Paris hospitals--the Charité and the Hôtel Dieu. In 1822, he settled in Merseburg as a physician. He was soon acclaimed as a genial and skilled helper in all branches of medical practice. He performed his own post-mortem examinations and published findings on a number of different diseases. His famous contribution in the thyroid field appeared in 1840 entitled "Exophthalmos due to hypertrophy of the cellular tissue in the orbit". Exophthalmos, goiter and palpitation of the heart have become known as the Merseburg Triad. In 1848, he published the autopsy findings on a patient who died from "exophthalmic cachexia". In Germany and some other countries, the disease was named as Morbus Basedow since 1858. In 1854 he pricked in his finger in the postmortem room when examining a patient who had died of typhus and he succumbed to septicemia at the early age of fifty-five. The date of his death was April 11, 1854. On April 14, he was laid in the Sixtus Cemetery in Merseburg. Basedow postulated that a wrong mixing of the blood manifested in cell tissue congestion and glandular vegetation cause the manifestations of disease. If we abstract our modern knowledge and accept circulating antibodies and disturbance of the immune balance as a dyscrasia as well as the proliferation of lymphocytic clones and local cellulary infiltration in terms of immune thyroiditis and autoimmune orbitopathy as cell tissue congestion and glandular vegetations, then doubt arise whether we have indeed made much progress in the last 150 years. At least, respect for the genius of the general physician Carl Adolph von Basedow is becoming greater. We may all hope that in the contributions and the discussions, we shall learn where we stand at the end of

  7. Techniques for quantification of liver fat in risk stratification of diabetics; Techniken zur Leberfettquantifizierung bei der Risikostratifikation von Diabetikern

    Energy Technology Data Exchange (ETDEWEB)

    Kuehn, J.P.; Spoerl, M.C.; Mahlke, C.; Hegenscheid, K. [Universitaetsmedizin Greifswald, Abteilung Experimentelle Radiologie, Institut fuer Diagnostische Radiologie und Neuroradiologie, Greifswald (Germany)

    2015-04-01

    Fatty liver disease plays an important role in the development of type 2 diabetes. Accurate techniques for detection and quantification of liver fat are essential for clinical diagnostics. Chemical shift-encoded magnetic resonance imaging (MRI) is a simple approach to quantify liver fat content. Liver fat quantification using chemical shift-encoded MRI is influenced by several bias factors, such as T2* decay, T1 recovery and the multispectral complexity of fat. The confounder corrected proton density fat fraction is a simple approach to quantify liver fat with comparable results independent of the software and hardware used. The proton density fat fraction is an accurate biomarker for assessment of liver fat. An accurate and reproducible quantification of liver fat using chemical shift-encoded MRI requires a calculation of the proton density fat fraction. (orig.) [German] Die Fettleber scheint einen unmittelbaren Einfluss auf die Pathophysiologie des Diabetes mellitus Typ 2 zu besitzen. Zur Detektion und Quantifizierung des Leberfetts werden in der klinischen Diagnostik akkurate Verfahren gebraucht. Ein einfaches Verfahren ist die Chemical-shift-kodierte Magnetresonanztomographie (MRT). Eine suffiziente Quantifizierung von Leberfett mithilfe der Chemical-shift-kodierten MRT erfordert eine Beruecksichtigung von Stoervariablen, wie den T2*-Zerfall, den T1-Wiederaufbau und die multispektrale Komplexitaet von Fett. Eine Korrektur aller Stoervariablen wird als Proton-density-Fettfraktion bezeichnet. Diese liefert unabhaengig von der verwendeten Einstellung und Hardware reproduzierbare Ergebnisse. Die korrigierte Proton-density-Fettfraktion ist ein akkurater Biomarker zur Quantifizierung von Leberfett. Die akkurate und reproduzierbare Quantifizierung von Leberfett in der MRT erfordert eine Berechnung der Proton-density-Fettfraktion. (orig.)

  8. [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

  9. 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...

  10. 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

  11. 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.)

  12. 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.

  13. 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

  14. CD31-Expression am Primärtumor und Nachweis hämatogen disseminierter Tumorzellen im Knochenmark von Brustkrebspatientinnen

    OpenAIRE

    Eisenmann, Petra

    2005-01-01

    Der Nachweis von disseminierten Tumorzellen im Knochenmark von Patientinnen mit primärem Mammakarzinom ist ein wichtiger prognostischer Parameter. In der vorliegenden Arbeit wurde der Nachweis von CD31 am Primärtumor Mammakarzinom mit dem Auftreten von Mikrometastasen im Knochenmark korreliert. Ferner wurde die prognostische Bedeutung von disseminierten Tumorzellen im Knochenmark und die prognostische Bedeutung von CD31 evaluiert. Bei 50 Patientinnen des Gesamtkollektivs von 195 (25,6%) wu...

  15. Radiofrequency ablation of liver metastases; Radiofrequenzablation von Lebermetastasen

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, P.L.; Clasen, S.; Schmidt, D.; Wiskirchen, J.; Tepe, G.; Claussen, C.D. [Abt. fuer Radiologische Diagnostik, Eberhard-Karls-Univ. Tuebingen (Germany); Boss, A. [Abt. fuer Radiologische Diagnostik, Eberhard-Karls-Univ. Tuebingen (Germany); Sektion fuer Experimentelle Radiologie der Abt. fuer Radiologische Diagnostik, Eberhard-Karls-Univ. Tuebingen (Germany); Gouttefangeas, C. [Abt. Immunologie des Inst. fuer Zellbiologie, Eberhard-Karls-Univ. Tuebingen (Germany); Burkart, C. [Zentrum fuer gastroenterologische Onkologie der Medizinischen Klinik, Eberhard-Karls-Univ. Tuebingen (Germany)

    2004-04-01

    The liver is the second only to lymph nodes as the most common site of metastatic disease irrespective of the primary tumor. Up to 50% of all patients with malignant diseases will develop liver metastases with a significant morbidity and mortality. Although the surgical resection leads to an improvement of the survival time, only approximately 20% of the patients are eligible for surgical intervention. Radiofrequency (RF) ablation represents one of the most important alternatives as well as complementary methods for the therapy of liver metastases. RF ablation can lead in a selected patient group to a palliation or to an increased life expectancy. RF ablation appears either safer (vs. cryotherapy) or easier (vs. laser) or more effective (percutaneous ethanol instillation [PEI]), transarterial chemoembolisation [TACE] in comparison with other minimal invasive procedures. RF ablation can be performed percutaneously, laparoscopically or intraoperatively and may be combined with chemotherapy as well as with surgical resection. Permanent technical improvements of RF systems, a better understanding of the underlying electrophysiological principles and an interdisciplinary approach will lead to a prognosis improvement in patients with liver metastases. (orig.) [German] Die Leber ist unabhaengig vom Primaertumor nach den Lymphknoten die zweithaeufigste Lokalisation von Metastasen. Bis zu 50% aller Patienten mit malignen Erkrankungen werden im Verlauf ihrer Erkrankung Lebermetastasen entwickeln, die mit einer signifikanten Morbiditaet und Mortalitaet verbunden sind. Obwohl die chirurgische Resektion zu einer verlaengerten Ueberlebenszeit fuehrt, sind nur ca. 20% der Patienten fuer einen chirurgischen Eingriff geeignet. Die Radiofrequenz-(RF-)Ablation stellt derzeit eine der effektivsten Alternativen und komplementaeren Methoden bei der Therapie von Lebermetastasen dar. In einem selektierten Patientengut fuehrt die RF-Ablation ueber den palliativen Einsatz hinaus zu einer

  16. Clarifying the link between von Neumann and thermodynamic entropies

    Science.gov (United States)

    Deville, Alain; Deville, Yannick

    2013-01-01

    The state of a quantum system being described by a density operator ρ, quantum statistical mechanics calls the quantity - kTr( ρln ρ), introduced by von Neumann, its von Neumann or statistical entropy. A 1999 Shenker's paper initiated a debate about its link with the entropy of phenomenological thermodynamics. Referring to Gibbs's and von Neumann's founding texts, we replace von Neumann's 1932 contribution in its historical context, after Gibbs's 1902 treatise and before the creation of the information entropy concept, which places boundaries into the debate. Reexamining von Neumann's reasoning, we stress that the part of his reasoning implied in the debate mainly uses thermodynamics, not quantum mechanics, and identify two implicit postulates. We thoroughly examine Shenker's and ensuing papers, insisting upon the presence of open thermodynamical subsystems, imposing us the use of the chemical potential concept. We briefly mention Landau's approach to the quantum entropy. On the whole, it is shown that von Neumann's viewpoint is right, and why Shenker's claim that von Neumann entropy "is not the quantum-mechanical correlate of thermodynamic entropy" can't be retained.

  17. Die Rolle von RANK-Ligand und Osteoprotegerin bei Osteoporose

    Directory of Open Access Journals (Sweden)

    Hofbauer LC

    2004-01-01

    Full Text Available Receptor activator of nuclear factor (NF- κB ligand (RANKL, sein zellulärer Rezeptor RANK und der Decoy-Rezeptor Osteoprotegerin (OPG stellen ein essentielles Zytokinsystem für die Zellbiologie von Osteoklasten dar. Verschiedene Untersuchungen belegen die Bedeutung von Störungen des OPG/RANKL/RANK-Systems bei der Pathogenese metabolischer Knochenerkrankungen. In dieser Arbeit werden die wichtigsten Störungen des OPG/RANKL/RANK-Systems bei verschiedenen Osteoporoseformen dargestellt. Östrogenrezeptor- (ER- Agonisten wie 17 β-Östradiol, Raloxifen und Genistein stimulieren die osteoblastäre Produktion von OPG durch Aktivierung von ER- α in vitro, während Lymphozyten von Patientinnen mit Östrogenmangel RANKL überexprimieren. Die parenterale Gabe von OPG vermag den mit Östrogenmangel assoziierten Knochenverlust im Tiermodell und in einer kleineren klinischen Studie zu verhindern. Glukokortikoide und Immunsuppressiva steigern gleichzeitig die RANKL-Expression und hemmen die OPG-Produktion in osteoblastären Zellen in vitro. Glukokortikoide sind auch in vivo imstande, die OPG-Serumspiegel deutlich zu reduzieren. Dagegen hemmen biomechanische Reize in vitro die RANKL-Produktion und steigern die OPG-Produktion. Ein Fehlen dieser biomechanischen Reize bei längerer Immobilisierung kann daher den RANKL/OPG-Quotienten steigern, während die tierexperimentelle Immobilisierungs-Osteoporose durch die parenterale Gabe von OPG gemildert werden kann.

  18. Das Geschäftsmodell von Retail Banken im Wandel der Digitalisierung

    OpenAIRE

    Messikommer, Cédric

    2016-01-01

    Der Prozess der Digitalisierung führt in unterschiedlichen Branchen zu tiefgreifenden Veränderungen. Dazu gehört auch der Finanzsektor, dessen Umfeld von erodierenden Margen und Tiefstzinsen geprägt ist. Die Digitalisierung hat weitreichende Auswirkungen auf die Geschäftsmodelle von Banken und speziell von Retail Banken. Deren Basisdienstleistungen werden zunehmend von neuen Mitbewerbern mit modernster Internet-Technologie angeboten. Damit sind wesentliche Teile der Wertschöpfungskette von Re...

  19. Strukturbasierte Entwicklung von Assaysystemen und Charakterisierung von orthosterischen und allosterischen Kinaseinhibitoren

    OpenAIRE

    Klüter, Sabine

    2010-01-01

    Die Proteinkinasen stellen eine wichtige Enzymklasse für die Regulation der Signaltransduktion dar. Sie steuern diese diffizil regulierten, intrazellulären Signalkaskaden durch Übertragung der ?-Phosphatgruppe von ATP auf andere Proteine. Fehlregulationen dieser komplexen Stoffwechselwege können Krankheiten wie Krebs, Diabetes oder Autoimunkrankheiten verursachen. Somit gehören die Kinasen in den letzten Jahren zu den wichtigsten Zielproteinen der Pharmaindustrie. Die klassi...

  20. Der Effekt von Akupunktur in der Prävention von Prüfungsangst

    OpenAIRE

    Krüger, Peter

    2017-01-01

    Prüfungsangst ist ein weit verbreitetes gesellschaftliches Phänomen, das bisher in nur wenigen wissenschaftlichen Ansätzen untersucht wurde. Die Zahl der Studenten, die Gehirn - Doping zur Leistungssteigerung und zur Minimierung von Prüfungsangst nutzen, steigt stetig an. In bisherigen Studien wurde Akupunktur an Herz 7 als vielversprechende Behandlungsalternative dargestellt. Basierend auf diesen Ergebnissen, wurde in dieser Arbeit untersucht, ob eine Einzelpunktakupunktur an Herz 7 die ...

  1. [Albert Reder Ritter von Schellmann (1826-1904)].

    Science.gov (United States)

    Schmidt, G; Holubar, K

    1990-01-01

    Albert Reder von Schellmann (1826-1904) was an important syphilidologist of the Vienna Medical School in the second half of the nineteenth century. He went in for the dualistic concept of the origin of syphilis and ulcer caused by soft chancre. In 1870 - Reder became head of a third dermato-syphilidologic department in the "Josephinum" in Vienna, where military surgeons got their medical education. At the same time the two full professorships of dermatosyphilidology in the Vienna General Hospital were held by Ferdinand von Hebra (1816-1880) and Carl Ludwig Sigmund von Ilanor (1810-1883).

  2. Speziation von Gadolinium-MRT-Kontrastmitteln in Umweltmatrizes

    OpenAIRE

    Lindner, Uwe

    2017-01-01

    Gd-Kontrastmittel werden in der Medizin für die Magnetresonanztomographie (MRT) benötigt, um einen besseren Bildkontrast zu erzielen. Nach der Anwendung gelangen diese Arzneimittel über das Abwasser in die Klärwerke und von dort in die jeweiligen anliegenden Oberflächengewässer. Somit wird es notwendig, den Verbleib der Gd-MRT-Kontrastmittel in der Umwelt zu verfolgen und aufzuklären. In dieser Arbeit werden für die Analyse von Umweltproben Methoden zur Speziesanalytik von Gd-Kontrastmitteln ...

  3. 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.

  4. Of von Willebrand factor and platelets.

    Science.gov (United States)

    Bryckaert, Marijke; Rosa, Jean-Philippe; Denis, Cécile V; Lenting, Peter J

    2015-01-01

    Hemostasis and pathological thrombus formation are dynamic processes that require multiple adhesive receptor-ligand interactions, with blood platelets at the heart of such events. Many studies have contributed to shed light on the importance of von Willebrand factor (VWF) interaction with its platelet receptors, glycoprotein (GP) Ib-IX-V and αIIbβ3 integrin, in promoting primary platelet adhesion and aggregation following vessel injury. This review will recapitulate our current knowledge on the subject from the rheological aspect to the spatio-temporal development of thrombus formation. We will also discuss the signaling events generated by VWF/GPIb-IX-V interaction, leading to platelet activation. Additionally, we will review the growing body of evidence gathered from the recent development of pathological mouse models suggesting that VWF binding to GPIb-IX-V is a promising target in arterial and venous pathological thrombosis. Finally, the pathological aspects of VWF and its impact on platelets will be addressed.

  5. Ex-ante Evaluation von Investitionsalternativen

    Directory of Open Access Journals (Sweden)

    Matthias Müller

    2017-12-01

    Full Text Available Der Beitrag zeigt, wie mit Hilfe der Methode der agentenbasierten Modellierung und Simulation (ABMS ein Beitrag zur ex-ante Policy-Beratung geleistet werden kann. Anhand eines exemplarischen Anwendungsfalls, der VISIBLE Simulationsumgebung („Virtual Simulation Lab for the Analysis of Investments in Learning and Education“, diskutieren wir die Konsequenzen unterschiedlicher Kooperationsförderinstrumente für Wissensdiffusionsprozesse in Netzwerken am Beispiel der Region Heilbronn-Franken. Die Simulationsergebnisse zeigen, dass die strukturelle Konfiguration eines regionalen Innovationssystems eine zentrale Bedeutung für die Gestaltung von Kooperationsfördermaßnahmen hat und dass Interventionen, die darauf abzielen, Wissenstransfer zwischen den Akteuren anzuregen, genau die entgegengesetzten Wirkungen entfalten können.

  6. Budke, Alexandra; Kanwischer, Detlef; Pott, Andreas (Hg.), Internetgeographien : Beobachtungen zum Verhältnis von Internet, Raum und Gesellschaft / [rezensiert von] Helmut Klüter

    OpenAIRE

    Klüter, Helmut

    2009-01-01

    Rezensiertes Werk: Internetgeographien : Beobachtungen zum Verhältnis von Internet, Raum und Gesellschaft / hrsg. von Alexandra Budke ... - Stuttgart : Steiner, 2004. - 192 S. : Ill., graph. Darst., Kt. - (Erdkundliches Wissen ; 136) ISBN 3-515-08506-8

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

    African Journals Online (AJOL)

    By taking a clinical history of bleeding (mucocutaneous bleeding symptoms suggestive of a primary haemostatic disorder, a quantitative or qualitative abnormality of VWF is possible) it is important to think about VWD and to make the appropriate diagnosis. If the VWD is suspected diagnostic tests should include an activated ...

  8. Patient with von Willebrand Disease for Gynaecologic Surgery - Perianaesthetic Concerns

    Directory of Open Access Journals (Sweden)

    Rakesh Garg

    2008-01-01

    Patients with vWD do not carry an increased operative risk during elective procedures if appropriate prophylac-tic and corrective therapy is administered. Although the administration of cryoprecipitate and other blood products has traditionally been the cornerstone of treatment for vWD, the recent development of desmopressin(DDAVP for clinical use may provide an effective alternative to replacement therapy with blood products. Further laparaoscopic procedures, taking care during ryle′s tube and foley′s catheter insertion, in such patients are the safer alternative for all kind of gynecologic surgeries.

  9. Entwicklung der Reglementierung von 10 MEM-Berufen im Kontext von Bildungsreformen und dem Wandel in der Arbeitswelt: Eine Kurzstudie im Auftrag von LIBS: Eine Kurzstudie im Auftrag von LIBS Industrielle Berufslehren Schweiz, Baden

    OpenAIRE

    Egg, Maria Esther; Renold, Ursula

    2015-01-01

    Im Auftrag der LIBS Industrielle Berufslehren Schweiz, hat die KOF die Entwicklung von 10 MEM1-Berufsbildern seit dem ersten Berufsbildungsgesetz dargestellt und diese eingebettet in eine kurze Zusammenfassung der wichtigsten Etappenschritte des Schweizer Berufsbildungssystems.

  10. 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

  11. Warum das Controlling den systematischen Einsatz von Simulationen vorantreiben sollte

    DEFF Research Database (Denmark)

    Spitzner, Jan; Schneider, Melanie L.

    2017-01-01

    Simulationen werden in der Unternehmenssteuerung heutzutage noch nicht systematisch eingesetzt. Dass sich jedoch die existierenden Hemmnisse durchaus überwinden lassen, legen die Antworten von Studienteilnehmern nahe, die Simulationen häufig einsetzen. Dabei kann Controlling eine Vorreiterrolle e...

  12. Pharmakobotanische Untersuchungen von Lavendelsorten auf dem Plattensee- Plateau

    Directory of Open Access Journals (Sweden)

    Tóth, Frida

    2014-09-01

    Full Text Available Auf dem Hof Dörgicsei Levendula Major GmbH wurden 9 Lavendelsorten (6 Sorten von Lavandula angustifolia und 3 Sorten von Lavandula x intermedia untersucht. Neben den morphologischen und Wachstumseigenschaften wurden auch Frisch- und Trockengewichte bewertet. Quantitative und qualitative Untersuchungen von den Blüten- und Ätherischöldrogen wurden auch durchgeführt. Die statistische Analyse zeigte signifikant höhere Erträge bei den Sorten L. angustifolia ’Essence Purple’ und L. x intermedia ’Edelweiss’. Gehalt und Zusammensetzung von ätherischem Öl war eindeutig bei der Sorte L. angustifolia ’Ellagance Purple’ am günstigsten.

  13. Pure Jauch-Piron states on von Neumann algebras

    International Nuclear Information System (INIS)

    Hamhalter, J.

    1993-01-01

    We study Jauch-Piron states and two-valued measures on von Neumann algebra. We prove as the main result that, under some set-theoretical assumption, a pure state of a von Neumann algebra A not containing a central abelian portion is Jauch-Piron if and only if it is σ-additive. Moreover, we show that this result holds for type I factor indenpendently on the set-theoretical axiomatics. As a consequence we obtain a lucid characterization of pure Jauch-Piron states on von Neumann algebras acting on a Hilbert space with real-nonmeasurable dimension (this can be viewed as a generalization of the paper). We also characterize the von Neumann algebras whose logic of projections is Jauch-Piron. Finally, we prove that every two-valued measure on the projection logic of A, where A contains no type I 2 central portion, has to be concentrated at an abelian direct summand of A. (orig.)

  14. Von Krahli Teater toob Eestisse erakordse auhinna / Tiit Tuumalu

    Index Scriptorium Estoniae

    Tuumalu, Tiit, 1971-

    2004-01-01

    Bessie-auhinna puhul, millega New Yorgis pärjati Von Krahli Teatri lavastust "Luikede järv." Mõjukuselt on seda võrreldud Broadway teatriauhinna Tonyga. Lisatud lühiandmed P. Jalaka ja S. Pepeljajevi kohta

  15. Frobenius theory for positive maps of von Neumann algebras

    International Nuclear Information System (INIS)

    Albeverio, S.; Hoegh-Krohn, R.

    1978-01-01

    Frobenius theory about the cyclic structure of eigenvalues of irreducible non negative matrices is extended to the case of positive linear maps of von Neumann algebras. Semigroups of such maps and ergodic properties are also considered. (orig.) [de

  16. Optimized sampling of hydroperoxides and investigations of the water vapour dependence of hydroperoxide formation during ozonolysis of alkenes; Optimierung der Probenahme von Hydroperoxiden und Untersuchungen zur Wasserdampfabhaengigkeit der Bildung von Hydroperoxiden bei der Ozonolyse von Alkenen

    Energy Technology Data Exchange (ETDEWEB)

    Becker, K.H.; Plagens, H.

    1997-06-01

    There are several sampling methods for hydroperoxides none of which is particularly reliable. The authors therefore tested three new methods in order to optimize hydroperoxide sampling and, using the optimized sampling procedure, to investigate the water vapour dependence of hydroperoxide formation during ozonolysis of alkenes. (orig.) [Deutsch] Fuer die Probenahme von Hydroperoxiden existieren verschiedene Verfahren, von denen bisher keines als besonders zuverlaessig angesehen werden konnte. Daher wurden in dieser Arbeit drei Verfahren getestet, um die Probenahme von Hydroperoxiden zu optimieren und mit dem entsprechenden Verfahren die Wasserdampfabhaengigkeit der Bildung von Hydroperoxiden bei der Ozonolyse von Alkenen zu untersuchen. (orig.)

  17. 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.

  18. Analytische und Effektor-Studien von N-Acyl-Ethanolaminphosphaten

    OpenAIRE

    Ates, Ebru

    2011-01-01

    Bei N-Acyl-Ethanolaminphosphaten handelt es sich um eine bislang wenig untersuchte Klasse polarer Substanzen, deren Erforschung aufgrund ihrer strukturellen Analogie zu apolaren, physiologisch wirksamen N-Acyl-Ethanolaminen von Interesse ist. Zu bear-beiten waren analytische Fragestellungen, die auch synthetische Aufgaben beinhalteten, wie Methodenentwicklung und Versuche zur Erfassung von N-Acyl-Ethanolamin-phosphaten in ausgewählten Lebensmitteln sowie strukturelle Studien zur „Bioaktivität...

  19. Spurenstoffuntersuchungen zur Bildung und Ausbreitung von Wassermassen im subpolaren Nordatlantik

    OpenAIRE

    Hildebrandt, Hauke

    2001-01-01

    In der vorliegenden Arbeit wurde ein umfangreicher Spurenstoffdatensatz aus dem subpolaren Nordatlantik erstellt und ausgewertet, der Tritium-, Helium- und Neon- sowie O-18-Messungen umfaßt. Das Hauptaugenmerk galt dabei der Bildung und Ausbreitung der tiefen Wassermassen und deren Variabilität auf Zeitskalen von einigen Jahren. Anhand von Tracermittelwerten, die mit Hilfe eines optimierten Interpolationsverfahrens gewonnen wurden, konnte gezeigt werden, daß die konvektive Neubildung de...

  20. 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.

  1. Von Neumann's impossibility proof: Mathematics in the service of rhetorics

    Science.gov (United States)

    Dieks, Dennis

    2017-11-01

    According to what has become a standard history of quantum mechanics, in 1932 von Neumann persuaded the physics community that hidden variables are impossible as a matter of principle, after which leading proponents of the Copenhagen interpretation put the situation to good use by arguing that the completeness of quantum mechanics was undeniable. This state of affairs lasted, so the story continues, until Bell in 1966 exposed von Neumann's proof as obviously wrong. The realization that von Neumann's proof was fallacious then rehabilitated hidden variables and made serious foundational research possible again. It is often added in recent accounts that von Neumann's error had been spotted almost immediately by Grete Hermann, but that her discovery was of no effect due to the dominant Copenhagen Zeitgeist. We shall attempt to tell a story that is more historically accurate and less ideologically charged. Most importantly, von Neumann never claimed to have shown the impossibility of hidden variables tout court, but argued that hidden-variable theories must possess a structure that deviates fundamentally from that of quantum mechanics. Both Hermann and Bell appear to have missed this point; moreover, both raised unjustified technical objections to the proof. Von Neumann's argument was basically that hidden-variables schemes must violate the ;quantum principle; that physical quantities are to be represented by operators in a Hilbert space. As a consequence, hidden-variables schemes, though possible in principle, necessarily exhibit a certain kind of contextuality. As we shall illustrate, early reactions to Bohm's theory are in agreement with this account. Leading physicists pointed out that Bohm's theory has the strange feature that pre-existing particle properties do not generally reveal themselves in measurements, in accordance with von Neumann's result. They did not conclude that the ;impossible was done; and that von Neumann had been shown wrong.

  2. Räumliche Aspekte von Transformationsproblemen aus systemtheoretischer Perspektive

    OpenAIRE

    Klüter, Helmut

    2000-01-01

    Der mit dem Topos "Transformation von Wirtschafts- und Gesellschaftssystemen" axiomatisch angenommene Unvereinbarkeit sozialistischer und marktwirtschaftlicher Strukturen ist aus raumwissenschaftlicher Sicht nicht nachvollziehbar. Zum einen gibt es in Wirtschaftsgeographie und Infrastrukturtheorie eine ganze Reihe von Gemeinsamkeiten und Berührungspunkten, die man für den konstruktiven Systemumbau nutzen kann. Zum andern benötigt der Umbau selbst eine räumliche Infrastruktur. Und zum dritten ...

  3. Integration von 3D-Kamerasystemen am Gabelstapler

    OpenAIRE

    Kleinert, Steffen; Overmeyer, Ludger

    2013-01-01

    Dieser Beitrag beschreibt die Integration von laufzeitmessenden 3D Kamerasystemen in die Gabelzinkenspitzen eines Flurförderzeugs. Mit Hilfe der integrierten Kameras und deren ausgewerteter Aufnahmen wurde ein Assistenzsystem für die Handhabung von Ladungsträgern realisiert, das dem Fahrer des Flurförderzeugs Verfahrempfehlungen für die Optimierung der Relativposition zwischen Gabelzinken und Ladungsträger bzw. Lagerplatz ausgibt. Neben der Vorstellung der verwendeten Kamera-Hardware und der ...

  4. Die Darstellung von guten und schlechten Beziehungen in Kinderzeichnungen

    OpenAIRE

    Gramel, Sabine

    2005-01-01

    Nach welchen Kriterien sich Bilder, auf denen Kinder eine positive Beziehung darstellen, von Bildern unterscheiden, auf denen negative Beziehungen dargestellt sind, wurde an einer Stichprobe von 45 Kindern zwischen 4;6 und 11;6 Jahren untersucht. Die Kinder fertigten jeweils ein positives und ein negatives Beziehungsbild an. Es zeigte sich, dass die Kinder in beiden Beziehungskategorien zum großen Teil Gleichaltrige darstellten. Sie benannten für ihre Bilder Kriterien, anhand derer man die po...

  5. Zur Dialektik von Soft Skills und fachlicher Kompetenz

    OpenAIRE

    Jendrowiak, Hans-Werner

    2010-01-01

    [Der Autor stellt folgende Thesen zur Dialektik von Soft Skills und fachlicher Bildung auf:] 1. Soft Skills sind normale Bildungskategorien und Teil einer Allgemeinen Bildung. […] 2. Soft Skills sind als personalgebundene Kriterien auch immer schon Gegenstand bildungstheoretischer Debatten. […] 3. Soft Skills ist eine trendorientierte Bezeichnung für Bildung. […] 4. Soft Skills sind Ausdruck von Vorstellungen, Ideen und Theorien (Schulkultur, Unternehmenskultur, Unternehmensphilosophie). 5. S...

  6. 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.

  7. Interdisciplinary approach to the management of childhood ependymomas; Die interdisziplinaere Therapie von Ependymomen im Kindesalter

    Energy Technology Data Exchange (ETDEWEB)

    Timmermann, B.; Kortmann, R.D.; Bamberg, M. [Abt. Strahlentherapie der Univ. Tuebingen (Germany); Kuehl, J. [Kinderklinik der Univ. Wuerzburg (Germany); Willich, N. [Abt. Strahlentherapie der Univ. Muenster (Germany)

    2002-09-01

    Material and Method: Based on historical reports, the recent literature, present guidelines, and ongoing trials an overview is provided for the management of ependymomas in childhood. Results: Local tumor control is the most important aim. Recurrences occur predominantly at the primary tumor region. The main instrument is surgery to effect maximal tumor resection. The addition of radiotherapy could improve survival significantly from 10% to 50%. Regarding the volume of irradiation there is confidence today that local fields are sufficient for all non-disseminated ependymomas. Local dose escalation has been introduced using hyperfractionated schedules. In recent studies this has been shown to increase local control up to 70%. Regarding chemotherapy in ependymomas trials have shown limited efficacy to date. For metastatic disease standard treatment has shown to be insufficient and high dose chemotherapy regimens to increase survival are in study. In younger children radiotherapy should be delayed using early chemotherapy. With preirradiation chemotherapy survival rates of 63.3% for children under age of 3 were achieved. (orig.) [German] Material und Methode: Auf der Grundlage der historischen Entwicklung, aktueller Literatur, geltender Leitlinien und laufender Studien wird ein Ueberblick ueber das Management von Ependymomen gegeben. Ergebnisse: Die lokale Tumorkontrolle ist von ausschlaggebender prognostischer Bedeutung; nur wenige Rezidive treten ausserhalb des Primaertumorgebietes auf. Daher dominiert eine moeglichst komplette Resektion das Therapiekonzept. Bei intrakraniellen Tumoren hat die postoperative Strahlentherapie die Ueberlebenschance deutlich verbessern koennen von ehemals 10 auf ueber 50%. Bei der Zielvolumendefinition hat bei nicht metastasierten Ependymomen unabhaengig von Histologie oder Tumorsitz die ausschliessliche Behandlung der Tumorregion aehnliche Erfolge gezeigt wie eine Liquorraumbehandlung. Mit lokaler Dosiseskalation durch

  8. The impact of statin therapy on plasma levels of von Willebrand factor antigen. Systematic review and meta-analysis of randomised placebo-controlled trials

    NARCIS (Netherlands)

    Sahebkar, Amirhossein; Serban, Corina; Ursoniu, Sorin; Mikhailidis, Dimitri P.; Undas, Anetta; Lip, Gregory Y. H.; Bittner, Vera; Ray, Kausik; Watts, Gerald F.; Hovingh, G. Kees; Rysz, Jacek; Kastelein, John J. P.; Banach, Maciej

    2016-01-01

    Increased plasma levels of von Willebrand factor antigen (vWF:Ag) are associated with high risk of coronary artery disease. The effect of statin therapy on vWF:Ag levels remains uncertain. Therefore the aim of this meta-analysis was to evaluate the effect of statin therapy on vWF:Ag Levels. A

  9. Entwicklung von Extraktions- und Absorptionssystemen auf Basis ionischer Flüssigkeiten für die Entschwefelung von Kohlenwasserstoffen

    OpenAIRE

    Kuhlmann, Esther

    2008-01-01

    Da die Anforderungen an den Schwefelgehalt der fossilen Brennstoffe - nicht zuletzt durch gesetzliche Richtlinien bezüglich der Schadstoffemissionen - im Laufe der Zeit ständig gestiegen sind, sind effektive Entschwefelungsverfahren für fossile Brennstoffe von hohem Interesse. Die derzeitige Entschwefelungstechnologie basiert auf dem HDS-Verfahren, alternative Verfahren sind aber wünschenswert, insbesondere wenn Anwendungen einen Schwefelgehalt von weit unter 10 ppm erforderlich machen. Daher...

  10. 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

  11. Noninfectious differential diagnoses of pneumonia; Nichtinfektioese Differenzialdiagnosen von Pneumonien

    Energy Technology Data Exchange (ETDEWEB)

    Wielandner, A.; Toelly, A. [Medizinische Universitaet Wien, Universitaetsklinik fuer Radiologie und Nuklearmedizin, Wien (Austria); Agarwal, P. [Medizinische Universitaet Freiburg, Universitaetsklinik fuer Radiologie, Freiburg (Germany); Bardach, C. [Krankenhaus Hietzing, Abteilung fuer Radiologie, Wien (Austria)

    2017-01-15

    In patients with a clinical suspicion of pneumonia, typical clinical and laboratory features along with the detection of infiltrates on chest X-ray are as a rule considered diagnostic and therapy is immediately initiated; however, studies have shown that in up to 5% of patients with an initial suspicion of pneumonia, another noninfectious pulmonary disease was the underlying cause. Early recognition and differentiation of diseases mimicking pneumonia are prerequisites for an adequate therapy. The aim of this review is to present the important noninfectious differential diagnoses of pneumonia and to provide the reader with tools for a systematic diagnostic approach. A literature search was carried out. As alterations in the lungs often result in similar imaging appearances and a differentiation between transudates, exsudates, blood and cells is not feasible by chest X-ray or CT, a systematic approach is essential to make an appropriate diagnosis. Hence, consideration of the temporal course, predominant pattern, distribution of findings, additional findings and clinical presentation are indispensable. (orig.) [German] Bei der Verdachtsdiagnose Pneumonie sind die Kombination aus typischer Klinik, Labor und der Nachweis einer Verdichtung in der Roentgenthoraxaufnahme in der Regel diagnostisch und es wird umgehend mit der Therapie begonnen. Studien haben jedoch gezeigt, dass bei bis zu 5 % der Patienten mit Erstverdacht auf Pneumonie eine andere (pulmonale) Erkrankung zugrunde liegt. Ein fruehzeitiges Erkennen und eine Differenzierung von Erkrankungen, die eine Pneumonie vortaeuschen, sind fuer die weitere Behandlung essenziell. Uebersicht ueber wesentliche nichtinfektioese Differenzialdiagnosen der Pneumonie. Es wurde eine Literaturrecherche durchgefuehrt. Da krankhafte Lungenveraenderungen oft aehnliche Bilder hervorrufen und anhand der Roentgenthoraxaufnahme oder der CT-Untersuchung nicht zwischen Blut, Transsudat, Exsudat und Zellen differenziert werden kann, ist

  12. J-GLOBAL MeSH Dictionary: von Willebrand病 [MeCab user dictionary for science technology term[Archive

    Lifescience Database Archive (English)

    Full Text Available MeCab user dictionary for science technology term von Willebrand病 名詞 一般 * * * * von Willebrand...病 ... MeSH D014842 200906053707829497 C LS51 UNKNOWN_2 von Willebrand 病

  13. 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)

  14. Einfluss von Informationskompetenz-Veranstaltungen auf die Qualität von Masterarbeiten

    Directory of Open Access Journals (Sweden)

    Gary Seitz

    2016-02-01

    Full Text Available Am Geographischen Institut der Universität Zürich haben die Studierenden, welche als erster Jahrgang die IK-Veranstaltung als Pflichtmodul absolvierten, ihre Masterarbeit abgeschlossen. Mit einer quantitativen Auswertung wird untersucht, ob sich die Qualität der Quellen in den Masterarbeiten verbessert hat. Dazu werden die Literaturverzeichnisse einer bibliometrischen Analyse unterzogen. Anschliessend werden die erhaltenen Werte mit denjenigen verglichen, welche von Arbeiten ohne IK-Schulung erhoben wurden. Diese Methodik könnte ein Werkzeug darstellen, um Informationskompetenz-Veranstaltungen bezüglich ihrer Relevanz für wissenschaftliches Arbeiten evaluieren zu können.

  15. "Die Toten reiten schnelle." Literarische Zitate in Briefen von und an Alexander von Humboldt

    Directory of Open Access Journals (Sweden)

    Ingo Schwarz

    2007-04-01

    Full Text Available Article in GermanAbstract in English and GermanAlexander von Humboldt and his correspondents liked to enrich or embellish their letters with quotations from classic works of ancient literature as well as from recent poems, plays, or novels. This paper tries to show that references to literature were very often used in order to express thoughts and feelings more clearly not so much for impressing the recipients of letters with high education. In educated circles a good knowledge of ancient and modern works of literature was a standard requirement, which often allowed the letter writers to use quotations in a playful manner.

  16. 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.

  17. 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.

  18. Hypercontractivity in group Von Neumann algebras

    CERN Document Server

    Junge, Marius; Parcet, Javier

    2017-01-01

    In this paper, the authors provide a combinatorial/numerical method to establish new hypercontractivity estimates in group von Neumann algebras. They illustrate their method with free groups, triangular groups and finite cyclic groups, for which they obtain optimal time hypercontractive L_2 \\to L_q inequalities with respect to the Markov process given by the word length and with q an even integer. Interpolation and differentiation also yield general L_p \\to L_q hypercontrativity for 1 < p \\le q < \\infty via logarithmic Sobolev inequalities. The authors' method admits further applications to other discrete groups without small loops as far as the numerical part-which varies from one group to another-is implemented and tested on a computer. The authors also develop another combinatorial method which does not rely on computational estimates and provides (non-optimal) L_p \\to L_q hypercontractive inequalities for a larger class of groups/lengths, including any finitely generated group equipped with a condit...

  19. Magnetic resonance imaging in the evaluation of pneumonia; Nachweis von pneumonischen Infiltraten mit der MRT

    Energy Technology Data Exchange (ETDEWEB)

    Eibel, R.; Herzog, P.; Dietrich, O.; Reiser, M.; Schoenberg, S.O. [Ludwig-Maximilians-Universitaet Muenchen (Germany). Institut fuer Klinische Radiologie; Rieger, C.; Ostermann, H. [Ludwig-Maximilians-Universitaet Muenchen (Germany). Abteilung fuer Haematologie/Onkologie, Klinikum Grosshadern

    2006-04-15

    Magnetic resonance imaging (MRI) of the lung is challenging because of substantial drawbacks. However, lung pathologies that are associated with increased attenuation values in CT enhance visualization in MRI: proton density is increased and tissue-air interfaces, resulting in susceptibility artifacts, are reduced in pneumonia, pneumonitis, edema, and carcinoma. On the other hand, many lung diseases result in shortness of breath, so that patients cannot hold their breath for long periods. Therefore, fast imaging techniques are required which should also allow for high spatial resolution so that small lesions can be detected. Calcifications and air pockets within lesions are not readily recognized with MRI. Thin section CT is standard for the diagnosis of pneumonia. With parallel imaging techniques, MRI examination of the lungs can be performed with short periods of breath holding, which allow for sub-centimeter resolution in the z-axis. Especially for follow-up examinations in immunocompromised patients and, in some instances, for the staging of malignant diseases (malignant pleural mesothelioma, lung cancer, respectively), MRI is very promising and may contribute to a decrease in the radiation exposure of the patients. (orig.) [German] Die MRT des Lungenparenchyms ist wegen des extrem niedrigen Protonengehalts des Lungengewebes und den starken Grenzflaechen zwischen Luft und Parenchym prinzipiell sehr problematisch. Allerdings liegt bei pathologischen Lungengewebeveraenderungen eine andere Situation vor, da infolge von Oedem, Entzuendung bzw. Tumorwachstum der Protonengehalt erhoeht und die Grenzflaechen reduziert sind. Viele Erkrankungen der Lunge fuehren dazu, dass der Patient den Atem nicht lange anzuhalten vermag. Daher sind MRT-Pulssequenzen erforderlich, die eine Datenakquisition in wenigen Sekunden gestatten. Aus technischer Sicht werden die vom CT bekannten Submillimeterschichten vielleicht nie realisierbar sein, sodass sicher auch in Zukunft kleine

  20. Ecobalance of natural gas vehicles; Oekobilanz von Erdgasfahrzeugen

    Energy Technology Data Exchange (ETDEWEB)

    Nigge, K.M. [Simon, Kucher und Partners Strategy und Marketing Consultants GmbH, Bonn (Germany)

    2000-07-01

    The impacts on human health and the natural environment of using natural gas, Diesel and petrol as fuels for city buses and passenger cars are compared in a Life Cycle Assessment. In addition to the burning of the fuels in the engines, this assessment also comprises the upstream processes of the fuel supply chain. Despite the increased energy demand of the vehicles, natural gas is associated with the lowest impacts overall for both city buses and passenger cars. The health impacts that can be avoided through the use of natural gas instead of Diesel or petrol thereby differ only weakly between the use of the vehicles in cities of various sizes within Germany. From the perspective of environmental protection, the market introduction of natural gas vehicles therefore does not need remain limited to large cities within agglomerated regions. (orig.) [German] Die Auswirkungen der Verwendung von Erdgas, Diesel und Benzin als Kraftstoffe fuer Stadtbusse und Pkw auf die menschliche Gesundheit und die natuerliche Umwelt werden in einer Oekobilanz verglichen. Diese umfasst neben der motorischen Verbrennung der Kraftstoffe auch die vorgelagerten Prozessketten der Kraftstoffbereitstellung. Sowohl fuer Stadtbusse als auch fuer Pkw schneidet Erdgas trotz eines energetischen Mehrbedarfes der Fahrzeuge insgesamt am guenstigsten ab. Die durch den Einsatz von Erdgas anstelle von Diesel oder Benzin vermeidbaren Gesundheitsschaeden unterscheiden sich dabei zwischen einem Einsatz der Fahrzeuge in Staedten verschiedener Groesse innerhalb von Deutschland nur wenig. Die Markteinfuehrung von Erdgasfahrzeugen muss also aus Sicht des Umweltschutzes nicht auf grosse Staedte in Ballungsgebieten beschraenkt bleiben. (orig.)

  1. DISEASES

    DEFF Research Database (Denmark)

    Pletscher-Frankild, Sune; Pallejà, Albert; Tsafou, Kalliopi

    2015-01-01

    Text mining is a flexible technology that can be applied to numerous different tasks in biology and medicine. We present a system for extracting disease-gene associations from biomedical abstracts. The system consists of a highly efficient dictionary-based tagger for named entity recognition...... of human genes and diseases, which we combine with a scoring scheme that takes into account co-occurrences both within and between sentences. We show that this approach is able to extract half of all manually curated associations with a false positive rate of only 0.16%. Nonetheless, text mining should...... not stand alone, but be combined with other types of evidence. For this reason, we have developed the DISEASES resource, which integrates the results from text mining with manually curated disease-gene associations, cancer mutation data, and genome-wide association studies from existing databases...

  2. 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.)

  3. Ein „neuer" javanischer Fundort von Phrynoglossus laevis laevis ( Gthr.)

    NARCIS (Netherlands)

    Brongersma, L.D.

    1935-01-01

    In der herpetologischen Sammlung, die dem Rijksmuseum van Natuurlijke Historie, Leiden, vor etwa hundert Jahre von Boie und Macklot übersandt wurde, befanden sich zwei Exemplare von Phrynoglossus laevis laevis (Gthr.). Diese Stücke wurden von Van Kampen (1923, p. 232 Fussnote: Oxyglossus laevis) in

  4. Neuro- und Gliotoxizität von Wolframcarbid-basierten Nanopartikeln in vitro

    OpenAIRE

    Bastian, Susanne

    2011-01-01

    Die Anzahl neurodegenerativer Erkrankungen nimmt in unserer Gesellschaft stetig zu. Obwohl inzwischen eine Reihe genetischer Ursachen identifiziert worden sind, wird auch der Einfluss von Umweltfaktoren bei der Pathogenese dieser Erkrankungen zunehmend in Betracht gezogen. Der Beitrag von ultrafeinen Partikeln aus Industrie und Umwelt auf neurodegenerative Erkrankungen steht daher zunehmend im Fokus der Forschung. Die Translokation von ultrafeinen Partikeln bzw. Nanopartikeln ins Gehirn ist b...

  5. Muuga / Mary von Grünewaldt ; tõlk. Mati Sirkel

    Index Scriptorium Estoniae

    Grünewaldt, Mary von

    2004-01-01

    Leo Zoegelt ostetud Muuga mõisahoone korrastamisest ja uue hoone ehitamisest C. T. von Neffi kunstikogu paigutamise tarbeks. Tütre mälestused. Tõlgitud raamatust: Skizzen und Bilder aus dem Leben Carl Timoleon von Neff / Mary von Grünewaldt. Darmstadt, 1887

  6. Die grossen Physiker und ihre Entdeckungen von den fallenden Körpern zu den Quarks

    CERN Document Server

    Segrè, Emilio

    1998-01-01

    Von Galileo Galilei bis zu Richard Feynman und Murray Gell-Mann - von den fallenden Körpern zu den Quarks: Der Physiknobelpreisträger Emilio Segre hat seine ganz persönliche Geschichte der Physik geschrieben. Er erzählt von den großen Gestalten und deren wichtigen Entdeckungen mit großer Anschaulichkeit und Lebendigkeit.

  7. Vergleich verschiedener Methoden zur Haftkraftmessung von Dentinadhäsiven

    OpenAIRE

    Schwertner, Katharina

    2010-01-01

    Zur Bestimmung der Haftkraft von Adhäsiven stehen verschiedene Methoden zur Verfügung. Ziel dieser Studie war es, vier gebräuchliche in vitro Haftkraftmessmethoden (Tensile Bond Strength Test, Shear Bond Strength Test, Microtensile Bond Strength Test, Push-out Bond Strength Test) an drei unterschiedlichen Adhäsivsystemen (Syntac, Clearfil SE Bond, Adper Scotchbond Multi Purpose) zu testen und die Ergebnisse zu vergleichen. Die Haftkräfte sind abhängig von der verwendeten Messmethode. Viele Pa...

  8. The smooth entropy formalism for von Neumann algebras

    International Nuclear Information System (INIS)

    Berta, Mario; Furrer, Fabian; Scholz, Volkher B.

    2016-01-01

    We discuss information-theoretic concepts on infinite-dimensional quantum systems. In particular, we lift the smooth entropy formalism as introduced by Renner and collaborators for finite-dimensional systems to von Neumann algebras. For the smooth conditional min- and max-entropy, we recover similar characterizing properties and information-theoretic operational interpretations as in the finite-dimensional case. We generalize the entropic uncertainty relation with quantum side information of Tomamichel and Renner and discuss applications to quantum cryptography. In particular, we prove the possibility to perform privacy amplification and classical data compression with quantum side information modeled by a von Neumann algebra

  9. Dr. Space the life of Wernher von Braun

    CERN Document Server

    Ward, Bob

    2013-01-01

    Written by veteran aerospace journalist Bob Ward, who spent years investigating his subject, this biography presents a revealing but even-handed portrait of the father of modern rocketry. As he chronicles Wernher von Braun's life, Ward explodes many myths and misconceptions about the controversial genius who was a hero to some, a villain to others. The picture of von Braun that emerges is of a brilliant scientist with limitless curiosity and a drive to achieve his goals at almost any price from, developing the world's first ballistic missile used against the Allies in World War II to help

  10. 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.

  11. The smooth entropy formalism for von Neumann algebras

    Energy Technology Data Exchange (ETDEWEB)

    Berta, Mario, E-mail: berta@caltech.edu [Institute for Quantum Information and Matter, California Institute of Technology, Pasadena, California 91125 (United States); Furrer, Fabian, E-mail: furrer@eve.phys.s.u-tokyo.ac.jp [Department of Physics, Graduate School of Science, University of Tokyo, Tokyo, Japan and Institute for Theoretical Physics, Leibniz University Hanover, Hanover (Germany); Scholz, Volkher B., E-mail: scholz@phys.ethz.ch [Institute for Theoretical Physics, ETH Zurich, Zurich (Switzerland)

    2016-01-15

    We discuss information-theoretic concepts on infinite-dimensional quantum systems. In particular, we lift the smooth entropy formalism as introduced by Renner and collaborators for finite-dimensional systems to von Neumann algebras. For the smooth conditional min- and max-entropy, we recover similar characterizing properties and information-theoretic operational interpretations as in the finite-dimensional case. We generalize the entropic uncertainty relation with quantum side information of Tomamichel and Renner and discuss applications to quantum cryptography. In particular, we prove the possibility to perform privacy amplification and classical data compression with quantum side information modeled by a von Neumann algebra.

  12. Kodierung von Metadaten digitaler Briefeditionen in TEI-XML

    OpenAIRE

    Dumont, Stefan

    2017-01-01

    Folien zu einem Vortrag im Rahmen des Digital-Humanities-Kolloquium an der BBAW am 7.7.2017. Der Vortrag erläutert, ausgehend von editionswissenschaftlichen Entwicklungen der 1980er und 1990er Jahre, wie die "Kopfdaten" eines Briefes nach den Richtlinien der Text Encoding Initiative (TEI) kodiert werden können. Insbesondere wird auf das TEI-Element correspDesc eingegangen und die Kodierung anhand eines Beispiels veranschaulicht. Darüber hinaus wird der Mehrwert von Briefmetadaten sowohl für d...

  13. Regulation of plasma von Willebrand factor [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Karl C Desch

    2018-01-01

    Full Text Available Von Willebrand factor (VWF is a multimeric plasma glycoprotein that plays a central role in the initiation of blood coagulation. Through interactions between its specific functional domains, the vascular wall, coagulation factor VIII, and platelet receptors, VWF maintains hemostasis by binding to platelets and delivering factor VIII to the sites of vascular injury. In the healthy human population, plasma VWF levels vary widely. The important role of VWF is illustrated by individuals at the extremes of the normal distribution of plasma VWF concentrations where individuals with low VWF levels are more likely to present with mucocutaneous bleeding. Conversely, people with high VWF levels are at higher risk for venous thromboembolic disease, stroke, and coronary artery disease. This report will summarize recent advances in our understanding of environmental influences and the genetic control of VWF plasma variation in healthy and symptomatic populations and will also highlight the unanswered questions that are currently driving this field of study.

  14. Entwicklung von Antikörper-Mikroarray : von Biophysik der Mikrospot-Reaktion bis zur Hochdurchsatzanalyse der Proteine

    OpenAIRE

    Kusnezow, Wlad

    2007-01-01

    Obwohl Protein-Mikroarrays ursprünglich aus dem gut entwickelten und fest etablierten DNA-Pendant entstanden sind, repräsentierte jedoch die Umstellung der Mikroarray-Technik von der DNA- auf die Proteinanalyse aufgrund der enormen physikalisch-chemischen Variabilität der Proteine, deren relativ niedrigen Stabilität und der komplexen Mikrospot-Kinetik eine große technologische Herausforderung. Deshalb setzt das Vorhaben, die Technik der Antikörper–Mikroarrays von ihrem konzeptuellen Zustand a...

  15. Automatische Ableitung und Anwendung von Regeln für die Rekonstruktion von Fassaden aus heterogenen Sensordaten

    OpenAIRE

    Becker, Susanne

    2011-01-01

    3D-Stadtmodelle finden seit einigen Jahren in immer stärkerem Maß und in den verschiedensten Bereichen Verwendung. Sie bilden unter anderem die Grundlage bei Stadtplanungen, für virtuelle Stadtrundgänge oder für die Berechnung von Simulationen. Internetdiensten wie Google Earth oder Microsoft Bing Maps ist es zu verdanken, dass 3D-Darstellungen von Gebäuden mittlerweile auch für eine breite Öffentlichkeit allgegenwärtig sind. Die erhöhte Nachfrage nach 3D-Gebäudemodellen verlangt nach effizie...

  16. Von-Neumann and Beyond: Memristor Architectures

    KAUST Repository

    Naous, Rawan

    2017-05-01

    An extensive reliance on technology, an abundance of data, and increasing processing requirements have imposed severe challenges on computing and data processing. Moreover, the roadmap for scaling electronic components faces physical and reliability limits that hinder the utilization of the transistors in conventional systems and promotes the need for faster, energy-efficient, and compact nano-devices. This work thus capitalizes on emerging non-volatile memory technologies, particularly the memristor for steering novel design directives. Moreover, aside from the conventional deterministic operation, a temporal variability is encountered in the devices functioning. This inherent stochasticity is addressed as an enabler for endorsing the stochastic electronics field of study. We tackle this approach of design by proposing and verifying a statistical approach to modelling the stochastic memristors behaviour. This mode of operation allows for innovative computing designs within the approximate computing and beyond Von-Neumann domains. In the context of approximate computing, sacrificing functional accuracy for the sake of energy savings is proposed based on inherently stochastic electronic components. We introduce mathematical formulation and probabilistic analysis for Boolean logic operators and correspondingly incorporate them into arithmetic blocks. Gate- and system-level accuracy of operation is presented to convey configurability and the different effects that the unreliability of the underlying memristive components has on the intermediary and overall output. An image compression application is presented to reflect the efficiency attained along with the impact on the output caused by the relative precision quantification. In contrast, in neuromorphic structures the memristors variability is mapped onto abstract models of the noisy and unreliable brain components. In one approach, we propose using the stochastic memristor as an inherent source of variability in

  17. Der Zusammenhang von Partnermarktopportunitäten aus dem Freundeskreis und der Stabilität von Paarbeziehungen : Eine Analyse mit den Daten des Partnermarktsurvey

    OpenAIRE

    Häring, Armando

    2014-01-01

    "Der Beitrag analysiert den Zusammenhang zwischen Partnermarktoportunitäten aus dem Freundeskreis und der Stabilität von Paarbeziehungen. Unter Verwendung des theoretischen Konzepts der Theorie der Interaktionsgelegenheiten sowie von Annahmen der Austauschtheorie und der Familienökonomie, werden mögliche Zusammenhänge zwischen gemeinsamen Freundeskreisen mit dem Partner, Partnermarktgelegenheiten aus dem Freundeskreis (sex ratio) und der Stabilität von Paarbeziehungen diskutiert. Der Beitrag ...

  18. Characterization of Zebrafish von Willebrand Factor Reveals Conservation of Domain Structure, Multimerization, and Intracellular Storage

    Directory of Open Access Journals (Sweden)

    Arunima Ghosh

    2012-01-01

    Full Text Available von Willebrand disease (VWD is the most common inherited human bleeding disorder and is caused by quantitative or qualitative defects in von Willebrand factor (VWF. VWF is a secreted glycoprotein that circulates as large multimers. While reduced VWF is associated with bleeding, elevations in overall level or multimer size are implicated in thrombosis. The zebrafish is a powerful genetic model in which the hemostatic system is well conserved with mammals. The ability of this organism to generate thousands of offspring and its optical transparency make it unique and complementary to mammalian models of hemostasis. Previously, partial clones of zebrafish vwf have been identified, and some functional conservation has been demonstrated. In this paper we clone the complete zebrafish vwf cDNA and show that there is conservation of domain structure. Recombinant zebrafish Vwf forms large multimers and pseudo-Weibel-Palade bodies (WPBs in cell culture. Larval expression is in the pharyngeal arches, yolk sac, and intestinal epithelium. These results provide a foundation for continued study of zebrafish Vwf that may further our understanding of the mechanisms of VWD.

  19. Von Kármán between Aachen and Pasadena

    Science.gov (United States)

    Krause, Egon; Kalkmann, Ulrich

    2013-05-01

    In the Introduction the reader is referred back to the academic ceremonials held after Theodore von Kármán's death in Aachen in May 1963. His work as the first director of the Aerodynamisches Institut (Institute of Aerodynamics) of the RWTH Aachen University of Technology from 1913 on and his initiative to re-establish international cooperation after World War I, resulting in the International Union of Theoretical and Applied Mechanics (IUTAM), are commented on. The following chapter describes von Kármán's relation to his former teacher Ludwig Prandtl. Some of von Kármán's scientific contributions during his time in Aachen are briefly reviewed. Thereafter, his first contacts to the California Institute of Technology are covered. Finally, the scientific and political circumstances, which led to von Kármán's decision to leave Germany in the early thirties, are elucidated in some detail. The English translation of the titles of the Aachen papers is given in Appendix I.

  20. Wernher von Braun: Reflections on His Contributions to Space Exploration

    Science.gov (United States)

    Goldman, Arthur E.

    2012-01-01

    In 1950, Dr. Wernher von Braun and approximately 100 of his team members came to Huntsville, Alabama, to begin work with the Army on what would later become America's historic space program. He would later serve as the first director of the Marshall Space Flight Center and led the development of the Saturn V launch vehicle that launched seven crewed American mission to the moon, as well as America s first space station, Skylab. Von Braun is best known for his team s technical achievements. He realized his dream of exploring outer space by helping place humans on the moon. His engineering and managerial talent during the Apollo era had contributed to a technological revolution. He was by all accounts a good engineer, but he was only one among many. What set Von Braun apart were his charisma, his vision, and his leadership skills. He inspired loyalty and dedication in the people around him. He understood the importance of communicating his vision to his team, to political and business leaders and the public. Today, the Marshall Center continues his vision by pursuing engineering and scientific projects that will continue to open space to exploration. This presentation will discuss Von Braun's impact on Huntsville, the Marshall Center, the nation and the world and look at his contributions in context of where world space exploration is today.

  1. Nonlinear von Neumann equations for quantum dissipative systems

    International Nuclear Information System (INIS)

    Messer, J.; Baumgartner, B.

    1978-01-01

    For pure states nonlinear Schroedinger equations, the so-called Schroedinger-Langevin equations are well-known to model quantum dissipative systems of the Langevin type. For mixtures it is shown that these wave equations do not extend to master equations, but to corresponding nonlinear von Neumann equations. Solutions for the damped harmonic oscillator are discussed. (Auth.)

  2. Nonlinear von Neumann equations for quantum dissipative systems

    International Nuclear Information System (INIS)

    Messer, J.; Baumgartner, B.

    For pure states nonlinear Schroedinger equations, the so-called Schroedinger-Langevin equations are well-known to model quantum dissipative systems of the Langevin type. For mixtures it is shown that these wave equations do not extend to master equations, but to corresponding nonlinear von Neumann equations. Solutions for the damped harmonic oscillator are discussed. (Author)

  3. Dr. von Braun With a Model of a Launch Vehicle

    Science.gov (United States)

    1950-01-01

    Dr. von Braun stands beside a model of the upper stage (Earth-returnable stage) of the three-stage launch vehicle built for the series of the motion picture productions of space flight produced by Walt Disney in the mid-1950's.

  4. Ernst von Glasersfeld's Radical Constructivism and Truth as Disclosure

    Science.gov (United States)

    Joldersma, Clarence W.

    2011-01-01

    In this essay Clarence Joldersma explores radical constructivism through the work of its most well-known advocate, Ernst von Glasersfeld, who combines a sophisticated philosophical discussion of knowledge and truth with educational practices. Joldersma uses Joseph Rouse's work in philosophy of science to criticize the antirealism inherent in…

  5. Eritrea : Von der Befreiung zur Unterdrückung

    NARCIS (Netherlands)

    van Reisen, Mirjam; Buck, K.D.

    2015-01-01

    Über das heutige Eritrea ist nur wenig bekannt. Als das kleine Land am Horn von Afrika 1993 die Unabhängigkeit erlangte, waren nicht nur im Land selbst die Hoffnungen groß, dass nach dem dreißig Jahre dauernden Befreiungskampf gegen Äthiopien eine bessere und friedliche Zukunft für alle beginnen

  6. Sakslased tulevad! Ärevad ajad Tallinnas Von Krahli Teatris

    Index Scriptorium Estoniae

    2001-01-01

    Von Krahli Teater ja Showcase Beat Le Mot valmistuvad oma esimeseks koostööprojektiks - lavastuseks "Pirates", kus osalevad mõlema teatri näitlejad ja tehnikud. Ühisprojekti toetavad Goethe Instituut, Hamburgi Linnavalitsus ja Eesti Kultuurkapital

  7. Professor Oberth and Dr. von Braun at ARS Banquet

    Science.gov (United States)

    1961-01-01

    Dr. Wernher von Braun holds the coveted Hermarn Oberth award presented to him by Professor Oberth during the banquet hosted by the Alabama Section of the American Rocket Society (ARS), on October 19, 1961. The Oberth award was given for outstanding technical contributions to the field of astronautics or for the promotion and advancement of astronautical sciences.

  8. Semiparametric Bernstein–von Mises for the error standard deviation

    NARCIS (Netherlands)

    Jonge, de R.; Zanten, van J.H.

    2013-01-01

    We study Bayes procedures for nonparametric regression problems with Gaussian errors, giving conditions under which a Bernstein–von Mises result holds for the marginal posterior distribution of the error standard deviation. We apply our general results to show that a single Bayes procedure using a

  9. Semiparametric Bernstein-von Mises for the error standard deviation

    NARCIS (Netherlands)

    de Jonge, R.; van Zanten, H.

    2013-01-01

    We study Bayes procedures for nonparametric regression problems with Gaussian errors, giving conditions under which a Bernstein-von Mises result holds for the marginal posterior distribution of the error standard deviation. We apply our general results to show that a single Bayes procedure using a

  10. De identiteit van Portulaca advena Reichg. & Von Poellnitz

    NARCIS (Netherlands)

    Geesink, R.

    1969-01-01

    Portulaca advena Reichg. & Von Poellnitz (1939), based on adventive specimens collected near Erp, prov. N.-Brabant, Netherlands, and afterwards cultivated in a garden at Nijmegen, appears to be identical with the South American P. papulosa Schldl. (1853). The adventive species of Portulaca found in

  11. Alexander von Humboldt's invention of the natural landscape

    NARCIS (Netherlands)

    Kwa, C.

    2005-01-01

    Landscape took on a new meaning through the new science of plant geography of Alexander von Humboldt (1769-1857). In the seventeenth and eighteenth centuries, "landscape" was foremost a painterly genre. Slowly, painted landscapes came to bear on natural surroundings, but by 1800 it was still not

  12. KK -theory and spectral flow in von Neumann algebras

    DEFF Research Database (Denmark)

    Kaad, Jens; Nest, Ryszard; Rennie, Adam

    2012-01-01

    We present a definition of spectral flow for any norm closed ideal J in any von Neumann algebra N. Given a path of selfadjoint operators in N which are invertible in N/J, the spectral flow produces a class in Ko (J). Given a semifinite spectral triple (A, H, D) relative to (N, t) with A separable...

  13. Enfermedad de Von Gierke: Reporte de tres casos

    Directory of Open Access Journals (Sweden)

    E. Espinosa

    2001-07-01

    Full Text Available La enfermedad de Von Gierke es un defecto en la glucosa 6 fosfatasa, degrada el glucógeno en el hígado, riñón e intestino. Asociada con hipoglicemia, acidosis láctica e hiperuricemia.

  14. A von Neumann type inequality for certain domains in Cn

    Czech Academy of Sciences Publication Activity Database

    Ambrozie, Calin-Grigore; Timotin, D.

    2002-01-01

    Roč. 131, č. 3 (2002), s. 859-869 ISSN 0002-9939 R&D Projects: GA ČR GA201/03/0041 Institutional research plan: CEZ:AV0Z1019905 Keywords : von Neumann inequality * multioperators * Nevanlinna-Pick problem Subject RIV: BA - General Mathematics Impact factor: 0.334, year: 2002

  15. Characterizing ξ-Lie Multiplicative Isomorphisms on Von Neumann Algebras

    Directory of Open Access Journals (Sweden)

    Yamin Song

    2014-01-01

    Full Text Available Let ℳ and be von Neumann algebras without central summands of type I1. Assume that ξ∈ℂ with ξ≠1. In this paper, all maps Φ:ℳ→ satisfying ΦAB-ξBA=ΦAΦB-ξΦBΦ(A are characterized.

  16. A bicategorical approach to Morita equivalence for Von Neumann algebras

    NARCIS (Netherlands)

    R.M. Brouwer (Rachel)

    2003-01-01

    textabstractWe relate Morita equivalence for von Neumann algebras to the ``Connes fusion'' tensor product between correspondences. In the purely algebraic setting, it is well known that rings are Morita equivalent if and only if they are equivalent objects in a bicategory whose 1-cells are

  17. A paradox of rationality à la von Neumann-Morgenstern

    NARCIS (Netherlands)

    Ismail, M.S.

    2015-01-01

    We show that there are games and decision situations in which it is not possible for the decision maker to be rational a la von Neumann-Morgenstern in both situations simultaneously, which is the source of the paradox presented in this note. We provide an assumption which is the necessary and

  18. Extensions of von Neumann's method for generating random variables

    International Nuclear Information System (INIS)

    Monahan, J.F.

    1979-01-01

    Von Neumann's method of generating random variables with the exponential distribution and Forsythe's method for obtaining distributions with densities of the form e/sup -G//sup( x/) are generalized to apply to certain power series representations. The flexibility of the power series methods is illustrated by algorithms for the Cauchy and geometric distributions

  19. Computed tomography of von Meyenburg complex simulating micro-abscesses

    International Nuclear Information System (INIS)

    Sada, P.N.; Ramakrishna, B.

    1994-01-01

    A case is presented of a bile duct hamartoma in a 44 year old man being evaluated for abdominal pain. The computed tomography (CT) findings suggested micro-abscesses in the liver and a CT guided tru-cut biopsy showed von Meyenburg complex. 9 refs., 3 figs

  20. Ueber die arten und den Skelettbau von Culcita

    NARCIS (Netherlands)

    Hartlaub, Clemens

    1892-01-01

    Das Genus Culcita Agass. zählt durch die merkwürdige Form und die ansehnliche Grösse seiner Arten zu den interessantesten Asteriden, und gut conservirte Exemplare davon gehören zu den Zierden unsrer Museen. Um so bedauerlicher erschien es mir, als ich vor einiger Zeit den Versuch machte die von