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Medical Sciences	75%

Selected Abstracts

Identification of genetic aberrations on chromosome 22 outside the NF2 locus in schwannomatosis and neurofibromatosis type 2,

HUMAN MUTATION, Issue 6 2005
Patrick G. Buckley
Abstract Schwannomatosis is characterized by multiple peripheral and cranial nerve schwannomas that occur in the absence of bilateral 8th cranial nerve schwannomas. The latter is the main diagnostic criterion of neurofibromatosis type 2 (NF2), which is a related but distinct disorder. The genetic factors underlying the differences between schwannomatosis and NF2 are poorly understood, although available evidence implicates chromosome 22 as the primary location of the gene(s) of interest. To investigate this, we comprehensively profiled the DNA copy number in samples from sporadic and familial schwannomatosis, NF2, and a large cohort of normal controls. Using a tiling-path chromosome 22 genomic array, we identified two candidate regions of copy number variation, which were further characterized by a PCR-based array with higher resolution. The latter approach allows the detection of minute alterations in total genomic DNA, with as little as 1.5,kb per measurement point of nonredundant sequence on the array. In DNA derived from peripheral blood from a schwannomatosis patient and a sporadic schwannoma sample, we detected rearrangements of the immunoglobulin lambda (IGL) locus, which is unlikely to be due to a B-cell specific somatic recombination of IGL. Analysis of normal controls indicated that these IGL rearrangements were restricted to schwannomatosis/schwannoma samples. In the second candidate region spanning GSTT1 and CABIN1 genes, we observed a frequent copy number polymorphism at the GSTT1 locus. We further describe missense mutations in the CABIN1 gene that are specific to samples from schwannomatosis and NF2 and make this gene a plausible candidate for contributing to the pathogenesis of these disorders. Hum Mutat 26(6), 540,549, 2005. © 2005 Wiley-Liss, Inc. [source]

VEGF in 105 pheochromocytomas: enhanced expression correlates with malignant outcome

APMIS, Issue 4 2003
KAISA SALMENKIVI
Pheochromocytomas are rare sympathoadrenal tumors that are highly vascular. Their malignancy is extremely difficult to estimate on the basis of histopathological features. Vascular endothelial growth factor (VEGF) is one of the most important angiogenic factors involved in both tumor growth and metastasis. In our search for new prognostic markers, we investigated the expression of VEGF in normal adrenal gland, in 105 primary pheochromocytomas, and in 6 metastases by using immunohistochemistry and Northern blot analysis. We also calculated the microvessel density of these tumors by staining the endothelial cells with monoclonal CD34 antibody. VEGF messenger ribonucleic acid was found in all pheochromocytomas studied. Immunohistochemically, VEGF was not found in normal adrenal medullary cells. Interestingly, all malignant pheochromocytomas (n=8), regardless of their primary location, had strong or moderate VEGF immunoreactivity, while most benign adrenal pheochromocytomas (26 of 37, 70.3%) were either negative or only weakly positive. The staining was heterogenous in extraadrenal pheochromocytomas as well as in a group of tumors that had histologically suspicious features but had not metastasized, here called borderline tumors (n=29). The microvessel density varied greatly in all of the tumor groups, and no statistical difference was found between these groups. Here we report moderate to strong VEGF expression in malignant pheochromocytomas, and negative or weak expression in benign adrenal pheochromocytomas. Normal medullary cells are immunohistochemically negative. Thus, low VEGF expression in pheochromocytomas favors a benign diagnosis. [source]

The analysis of immunophenotype of gastrin-producing tumors of the pancreas and gastrointestinal tract

CANCER, Issue 9 2003
Larissa Gurevich M.D., Ph.D.
Abstract BACKGROUND Gastrinomas are located more frequently in the pancreas, which normally has no cells that can produce gastrin. They have a more aggressive course than other pancreatic endocrine tumors and extrapancreatic gastrinomas associated with multiple endocrine neoplasia Type 1 syndrome. The current study analyzed immunophenotypes of gastrinomas and compared them with other pancreatic endocrine tumors. METHODS Twenty-one formalin-fixed, paraffin-embedded specimens (15-tumors in the pancreas, 1 in the duodenum, 1 in the stomach, 1 in the liver, and 3 of unknown primary location) accompanied by Zollinger,Ellison syndrome and 17 other pancreatic endocrine tumor specimens were investigated. They were stained immunohistochemically for gastrin, chromogranin A, synaptophysin, insulin, glucagon, somatostatin, pancreatic polypeptide, calcitonin, serotonin, chorionic gonadotropin, adrenocorticotropic hormone, carcinoembryonic antigen, epithelial membrane antigen, and cytokeratin 19. RESULTS Gastrinomas coexpressed neuroendocrine and exocrine markers, including chromogranin A, synaptophysin, carcinoembryonic antigen, cytokeratin 19, and epithelial membrane antigen. Carcinoembryonic antigen was found in all 17 gastrinomas (100%), cytokeratin 19 was found in 15 of 17 (88.2%) gastrinomas, and epithelial membrane antigen was found in 16 of 18 (88.9 %) gastrinomas. Cytokeratin 19, epithelial membrane antigen, and carcinoembryonic antigen were not found to be present in the pancreatic endocrine tumors, but chromogranin A and synaptophysin were. Chorionic gonadotropin was found in 16 gastrinomas (100%), but only in 2 of 17 other pancreatic endocrine tumors (11.8 %). CONCLUSIONS Pancreatic gastrinomas were characterized by the coexpression of neuroendocrine markers, exocrine markers, and chorionic gonadotropin. Therefore, pancreatic gastrinomas made a special intermediate group of tumors, which phenotypically combined features of neuroendocrine and exocrine neoplasms. These findings suggested that sporadic pancreatic gastrinomas and other pancreatic endocrine tumors are different phenotypically and are possibly of different origin. Cancer 2003. © 2003 American Cancer Society. [source]

Experimental evaluation of the JenaClip transcatheter aortic valve,

CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, Issue 3 2009
Alexander Lauten
Abstract Objective: Transcatheter techniques of aortic valve replacement are a treatment option for valvular heart disease in high-risk surgical candidates. We evaluated a self-expanding valve system with a novel mechanism of fixation in an experimental setting in an acute animal model and ex vivo in aortic root specimens. Method: A self-expanding nitinol stent containing a pericardial tissue valve was implanted in a transapical approach in 15 sheeps. The valve was introduced under fluoroscopic guidance through a 22F sheath by means of a specially designed delivery catheter. Deployment was performed on the beating heart without cardiopulmonary bypass or rapid ventricular pacing and facilitated by positioning feelers anchoring the device to the native aortic cusps. To investigate release and anchoring of the device during retrograde implantation, the stent was also implanted in aortic root specimens obtained from an autopsy series. Results: In animal experiments, stent deployment was primarily successful in 12 (80%) animals. Positioning feelers facilitated implantation by confirming the correct implantation plane of the stent and anchoring to the native aortic cusps. If primary location was not satisfactory the stent was retracted into the catheter and repositioned. After successful implantation no significant changes of hemodynamics were observed. Two animals (13%) developed ventricular fibrillation early in this experimental series due to displacement of one positioning element into a coronary ostium, major regurgitation was observed in two animals. Ex vivo evaluation of the device in aortic root specimens proved feasibility of stent release and leaflet fixation; ex vivo implantation was successful in all cases. Conclusion: .In this study, we demonstrate feasibility of a leaflet-fixation device in nondiseased aortic valves. The JenaClip provides an effective concept of fixation with positioning feelers that allows exact positioning without outflow obstruction and anchoring the valve to the native leaflets. Further studies are necessary to investigate this concept in diseased aortic valves. © 2009 Wiley-Liss, Inc. [source]