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Pathogenetic Aspects (pathogenetic + aspect)
Selected AbstractsNeurofibromatosis type 1 is a disorder of dysplasia: The importance of distinguishing features, consequences, and complications,BIRTH DEFECTS RESEARCH, Issue 1 2010Vincent Michael Riccardi BACKGROUND: The disorder neurofibromatosis type 1 (NF1) is caused by mutations in the NF1 gene, which influences the availability of activated Ras and the latter's control of cellular proliferation. Emphasis on this aspect of NF1 has focused attention on the tumor suppression function of NF1 and thereby displaced attention from the gene's role in initial normal tissue formation, maintenance, and repair. METHODS: Clinical and neuroimaging data systematically compiled over more than 30 years are analyzed to document the involvement of multiple organs and tissues, often with an embryonic origin. In addition, recent literature based on selective knockout mouse experiments is cited to corroborate embryonic dysplasia as an element of NF1 pathogenesis. RESULTS: Tissue dysplasia, both ab initio and as part of tissue maintenance and wound healing, is a key clinical and pathogenetic aspect of NF1 and thereby provides a rationale for differentiating the elements of NF1 into features, consequences, and complications. CONCLUSIONS: NF1 is a histogenesis control gene that also has properties that overlap with those of a tumor suppressor gene. Both its neoplastic and dysplastic manifestations become more amenable to understanding and treatment if they are differentiated at three levels,specifically, features, consequences and complications. Birth Defects Research (Part A), 2010. © 2009 Wiley-Liss, Inc. [source] A clinical perspective of rheumatoid arthritisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2009Hans Ulrich Scherer Abstract In recent years, factors potentially involved in pathogenesis of rheumatoid arthritis have mostly been identified by studying well-defined patient cohorts. Characterization of antibodies from sera of affected patients, family-based heritability studies, genome-wide association scans, the analysis of environmental factors and data from clinical trials have contributed largely to a thorough reassembly of our perception of rheumatoid arthritis. Modified animal models are now crucial to obtain experimental evidence for suggested pathogenetic pathways based on these observations and are currently being developed and explored. Some of the novel pathogenetic aspects, however, already influence decision making in the clinic. [source] Candidate genes for panic disorder: insight from human and mouse genetic studiesGENES, BRAIN AND BEHAVIOR, Issue 2007M. Gratacòs Panic disorder is a major cause of medical attention with substantial social and health service cost. Based on pharmacological studies, research on its etiopathogenesis has been focused on the possible dysfunction of specific neurotransmitter systems. However, recent work has related the genes involved in development, synaptic plasticity and synaptic remodeling to anxiety disorders. This implies that learning processes and changes in perception, interpretation and behavioral responses to environmental stimuli are essential for development of complex anxiety responses secondary to the building of specific brain neural circuits and to adult plasticity. The focus of this review is on progress achieved in identifying genes that confer increased risk for panic disorder through genetic epidemiology and the use of genetically modified mouse models. The integration of human and animal studies targeting behavioral, systems-level, cellular and molecular levels will most probably help identify new molecules with potential impact on the pathogenetic aspects of the disease. [source] Developmental and benign movement disorders in childhood,MOVEMENT DISORDERS, Issue 10 2010Cecilia Bonnet MD Abstract Developmental and benign movement disorders are a group of movement disorders with onset in the neonatal period, infancy, or childhood. They are characterized by the absence of associated neurological manifestations and by their favorable outcome, although developmental abnormalities can be occasionally observed. Knowledge of the clinical, neurophysiological, and pathogenetic aspects of these disorders is poor. Based on a comprehensive review of the literature and our practical experience, this article summarizes current knowledge in this area. We pay special attention to the recognition and management of these movement disorders in children. © 2010 Movement Disorder Society [source] Pathogenesis of equine herpesvirus-1 infection in the mouse modelAPMIS, Issue 1 2009GEORG GOSZTONYI Equine herpesvirus-1 (EHV-1) is a major equine pathogen causing respiratory diseases, abortions and severe neurological disorders. The basis of neurological disturbances is, as in other organs, infection of endothelial cells, followed by vasculitis, thrombosis and ischaemic damage of the parenchyma. Here, a murine model was used to explore the mechanism of entry to, and spread within the brain, the cell affinity of the agent and the modulating role of the immune defence, which are all factors governing the pathogenesis of the neurological disease. Because controversial views exist about these mechanisms, we undertook a neuropathological study with intranasally infected adult mice. EHV-1 entered the brain through the olfactory neuroepithelium and along the olfactory nerves, and spread transsynaptically in rostro-caudal direction, using olfactory and limbic neuronal networks. Exclusively neurons were infected. The cellular immune reaction exerted a restraining effect on virus dissemination. Following nasal infection, the olfactory route was the major pathway for virus entry and dissemination, involvement of the trigeminal nerve in virus spread seems much less probable. In the adult mouse brain EHV-1 behaves as a typical neurotropic agent, using, similarly to other herpesviruses, the neuronal networks for dissemination. Vasculitis, the predominant type of lesion in natural infection, and endothelial cell positivity for EHV-1 were detectable only in the lung. Thus, this agent exhibits in the mouse a dual affinity: it is neurotropic in the brain, and endotheliotropic in visceral organs. Consideration of pathogenetic aspects of equine and experimental murine EHV-1 infections also helps a better understanding of human herpetic brain disease. [source] | |||||||||||||