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Precise Mechanisms Underlying (precise + mechanism_underlying)
Selected AbstractsPathogenesis of medulloblastoma and current treatment outlookMEDICINAL RESEARCH REVIEWS, Issue 6 2007Jaroslaw Jozwiak Abstract Medulloblastoma is the most common malignant tumor of the cerebellum in children, with a tendency to metastasize via CSF pathway. Survival rate varies depending on several factors, but is rather favorable, with radiotherapy as the treatment of choice. Irradiation of the craniospinal axis results, however, in severe neuropsychological and psychosocial impairments pertaining to memory, attention, motor functioning, language, and visuospatial abilities. Precise mechanisms underlying the formation of medulloblastoma are still unclear, but implication of at least three signaling molecules is postulated: insulin-like growth factor-I, WNT, and Sonic hedgehog. Thanks to increasing knowledge on the cellular mechanisms contributing to tumor formation, it is possible to propose new therapies that could replace radiotherapy or allow decreasing irradiation doses. The current review presents recent developments in medulloblastoma pathophysiology research and proposed inhibitors that could constitute good candidates for further pharmacological research. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 6, 869,890, 2007 [source] Epineurial compartments and their role in intraneural ganglion cyst propagation: An experimental studyCLINICAL ANATOMY, Issue 7 2007Robert J. Spinner Abstract New patterns of intraneural ganglion cyst formation are emerging that have not previously been explained in current pathoanatomic terms. We believe there are three important elements underlying the appearance of these cysts: (a) an articular branch of the nerve that connects to a nearby synovial joint; (b) ejected synovial fluid following the path of least resistance along tissue planes; and (c) the additional effects of pressure and pressure fluxes. The dynamic nature of cyst formation has become clearly apparent to us in our clinical, operative and pathologic practice, but the precise mechanism underlying the process has not been critically studied. To test our hypothesis that a fibular (peroneal) or tibial intraneural cyst derived from the superior tibiofibular joint could ascend proximally into the sciatic nerve, expand within it and descend into terminal branches of this major nerve, we designed a series of simple, qualitative laboratory experiments in two cadavers (four specimens, six experiments). Injecting dye into the outer or "epifascicular" epineurium of the fibular and the tibial nerves we observed its ascent, cross over and descent patterns in three of three specimens as well as its cross over after an outer epineurial sciatic injection. In contrast, injecting dye into the inner or "interfascicular" epineurium led to its ascent within the tibial nerve and its division within the sciatic nerve in one specimen and lack of cross over in a sciatic nerve injection. Histologic cross-sections of the nerves at varying levels demonstrated a tract of disruption within the outer epineurium of the nerve injected and the nerve(s) into which the dye, after cross over, descended. Those specimens injected in the inner epineurium demonstrated dye within this tract but without disruption of or dye intrusion into the outer epineurium. In no case did the dye pass through the perineurial layers. Coupled with our observations in previous detailed studies, these anatomic findings provide proof of concept that sciatic cross over occurs due to the filling of its common epineurial sheath; furthermore, these findings, support the unifying articular theory, even in cases wherein patterns of intraneural ganglion cyst formation are unusual. Additional work is needed to be done to correlate these anatomic findings with magnetic resonance imaging and surgical pathology. Clin. Anat. 20:826,833, 2007. © 2007 Wiley-Liss, Inc. [source] Transcription factor HNF and hepatocyte differentiationHEPATOLOGY RESEARCH, Issue 10 2008Masahito Nagaki To know the precise mechanisms underlying the life or death and the regeneration or differentiation of cells would be relevant and useful for the development of a regenerative therapy for organ failure. Liver-specific gene expression is controlled primarily at a transcriptional level. Studies on the transcriptional regulatory elements of genes expressed in hepatocytes have identified several liver-enriched transcriptional factors, including hepatocyte nuclear factor (HNF)-1, HNF-3, HNF-4, HNF-6 and CCAAT/enhancer binding protein families, which are key components of the differentiation process for the fully functional liver. The transcriptional regulation by these HNFs, which form a hierarchical and cooperative network, is both essential for hepatocyte differentiation during mammalian liver development and also crucial for metabolic regulation and liver function. Among these liver-enriched transcription factors, HNF-4 is likely to act the furthest upstream as a master gene in transcriptional cascade and interacts with other liver-enriched transcriptional factors to stimulate hepatocyte-specific gene transcription. A link between the extracellular matrix, changes in cytoskeletal filament assembly and hepatocyte differentiation via HNF-4 has been shown to be involved in the transcriptional regulation of liver-specific gene expression. This review provides an overview of the roles of liver-enriched transcription factors in liver function. [source] Unravelling a histone code for malaria virulenceMOLECULAR MICROBIOLOGY, Issue 6 2007Christy A. Comeaux Summary Epigenetic phenomena have been shown to play a role in the regulated expression of virulence genes in several pathogenic organisms, including the var gene family in Plasmodium falciparum. A better understanding of how P. falciparum can both maintain a single active var gene locus through many erythrocytic cycles and also achieve successive switching to different loci in order to evade the host immune system is greatly needed. Disruption of this tightly co-ordinated expression system presents an opportunity for increased clearance of the parasites by the immune system and, in turn, reduced mortality and morbidity. In the current issue of Molecular Microbiology, Lopez-Rubio and colleagues investigate the correlation of specific post-translational histone modifications with different transcriptional states of a single var gene, var2csa. Quantitative chromatin immunoprecipitation is used to demonstrate that different histone methylation marks are enriched at the 5, flanking and coding regions of active, poised or silenced var genes. They identify an increase of H3K4me2 and H3K4me3 in the 5, flanking region of an active var locus and expand on an earlier finding that H3K9me3 is enriched in the coding regions of silenced var genes. The authors also present evidence that H3K4me2 bookmarks the active var gene locus during later developmental stages for expression in the subsequent asexual cycle, hinting at a potential mechanism for transcriptional ,memory'. The stage is now set for work generating a complete catalogue of all histone modifications associated with var gene regulation as well as functional studies striving to uncover the precise mechanisms underlying these observations. [source] | ||||||||||