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Affected Cells (affected + cell)
Selected AbstractsComparison of extent of tau pathology in patients with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), frontotemporal lobar degeneration with Pick bodies and early onset Alzheimer's diseaseNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 4 2006A.-M. Shiarli In order to gain insight into the pathogenesis of frontotemporal lobar degeneration (FTLD), the mean tau load in frontal cortex was compared in 34 patients with frontotemporal dementia linked to chromosome 17 (FTDP-17) with 12 different mutations in the tau gene (MAPT), 11 patients with sporadic FTLD with Pick bodies and 25 patients with early onset Alzheimer's disease (EOAD). Tau load was determined, as percentage of tissue occupied by stained product, by image analysis of immunohistochemically stained sections using the phospho-dependent antibodies AT8, AT100 and AT180. With AT8 and AT180 antibodies, the amount of tau was significantly (P < 0.001 in each instance) less than that in EOAD for both FTDP-17 (8.5% and 10.0% respectively) and sporadic FTLD with Pick bodies (16.1% and 10.0% respectively). With AT100, the amount of tau detected in FTDP-17 was 54% (P < 0.001) of that detected in EOAD, but no tau was detected in sporadic FTLD with Pick bodies using this particular antibody. The amount of insoluble tau deposited within the brain in FTDP-17 did not depend in any systematic way upon where the MAPT mutation was topographically located within the gene, or on the physiological or structural change generated by the mutation, regardless of which anti-tau antibody was used. Not only does the amount of tau deposited in the brain differ between the three disorders, but the pattern of phosphorylation of tau also varies according to disease. These findings raise important questions relating to the role of aggregated tau in neurodegeneration , whether this represents an adaptive response which promotes the survival of neurones, or whether it is a detrimental change that directly, or indirectly, brings about the demize of the affected cell. [source] Accumulation of multiple forms of lamin A with down-regulation of FACE-1 suppresses growth in senescent human cellsGENES TO CELLS, Issue 3 2007Ryo Ukekawa 5-Bromodeoxyuridine (BrdU) clearly induces a senescence-like phenomenon in every cell type. Proteome analysis revealed that lamin A and C were most highly increased in the nuclei of HeLa cells upon addition of BrdU. Immunoblot analysis also revealed marked accumulation of nuclear prelamin A. Consistently, farnesylated-proteins converting enzyme 1 (FACE-1) was markedly down-regulated in the same cells. Similar phenomena were also observed in normal human fibroblasts undergoing replicative senescence. Immunochemical analysis confirmed the above results. Lamin A is a major component of lamina and responsible for several genetic diseases. Thus, we ectopically expressed a wild-type, a mature type and a premature type of lamin in HeLa cells. All of these forms similarly inhibited colony formation and delayed cell cycle progression mainly through G2 phase. These results suggest that a change in the amount of lamin A, rather than appearance of its truncated form, is responsible for growth retardation in affected cells. [source] Fatal HHV6 infection in an immunocompromised patient presenting with skin involvementJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2010Anjela Galan Infection with human herpesvirus-6 (HHV6) has a broad distribution in the human population, with a seroprevalence approaching 100% worldwide. Primary infection takes place during childhood, after which the virus remains latent mostly in lymphocytes and monocytes at various sites. Immunosuppression can result in viral reactivation, associated with clinical sequelae and even death. We report a case of a disseminated HHV6 infection in a 53-year-old patient, who was immunocompromised after allogeneic bone marrow transplant treatment for acute lymphocytic leukemia. Initially, he presented with a macular eruption of the skin, followed by involvement of other sites. Histopathologic analysis of skin biopsies revealed superficial perivascular large atypical mononuclear cells with intranuclear and intracytoplasmic inclusions. Most affected cells labeled with antibodies to CD3 and CD43 as lymphocytes, and some labeled with CD68 as macrophages. Polymerase chain reaction (PCR) studies of the blood, skin, liver, colon, cerebrospinal fluid and brain were positive for HHV6 virus. Additionally, the serologic titers for HHV6 were high. Viral particles were also detected by electron microscopy (EM) in the colon. Although rare, HHV6 virus may be an important pathogen in immunocompromised patients, and may present initially in the skin. Awareness of this infection is critical to diagnosis in acute settings. Galan A, McNiff JM, Nam Choi J and Lazova R. Fatal HHV6 infection in an immunocompromised patient presenting with skin involvement. [source] New insight into the mechanism of hip prosthesis loosening: Effect of titanium debris size on osteoblast functionJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2004Daniel T. O'Connor Abstract The incidence of rheumatoid arthritis and osteoarthritis is on the rise due to our expanding elderly population. Total joint arthroplasty is the most successful, prevalent treatment modality for these and other degenerative hip conditions. Despite the wide array of prosthetic devices commercially available, hip prostheses share a common problem with a gradual and then accelerating loss of bone tissue and bone,implant interface integrity, followed by implant instability and loosening. Implant failure is largely the result of inevitable wear of the device and generation of wear debris. To provide information for the development of improved prosthetic wear characteristics, we examined the effects of size-separated titanium particles on bone forming cell populations. We demonstrate unequivocally that particle size is a critical factor in the function, proliferation, and viability of bone-forming osteoblasts in vitro. In addition, we have elucidated the time-dependent distribution of the phagocytosed particles within the osteoblast, indicating an accumulation of particles in the perinuclear area of the affected cells. The report finds that particle size is a critical factor in changes in the bone formation-related functions of osteoblasts exposed to simulate wear debris, and that 1.5,4 ,m titanium particles have the greatest effect on osteoblast proliferation and viability in vitro. The size of titanium particles generated through wear of a prosthetic device may be an important consideration in the development of superior implant technology. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Recent advances in rational gene transfer vector design based on poly(ethylene imine) and its derivativesTHE JOURNAL OF GENE MEDICINE, Issue 8 2005Michael Neu Abstract The continually increasing wealth of knowledge about the role of genes involved in acquired or hereditary diseases renders the delivery of regulatory genes or nucleic acids into affected cells a potentially promising strategy. Apart from viral vectors, non-viral gene delivery systems have recently received increasing interest, due to safety concerns associated with insertional mutagenesis of retro-viral vectors. Especially cationic polymers may be particularly attractive for the delivery of nucleic acids, since they allow a vast synthetic modification of their structure enabling the investigation of structure-function relationships. Successful clinical application of synthetic polycations for gene delivery will depend primarily on three factors, namely (1) an enhancement of the transfection efficiency, (2) a reduction in toxicity and (3) an ability of the vectors to overcome numerous biological barriers after systemic or local administration. Among the polycations presently used for gene delivery, poly(ethylene imine), PEI, takes a prominent position, due to its potential for endosomal escape. PEI as well as derivatives of PEI currently under investigation for DNA and RNA delivery will be discussed. This review focuses on structure-function relationships and the physicochemical aspects of polyplexes which influence basic characteristics, such as complex formation, stability or in vitro cytotoxicity, to provide a basis for their application under in vivo conditions. Rational design of optimized polycations is an objective for further research and may provide the basis for a successful cationic polymer-based gene delivery system in the future. Copyright © 2005 John Wiley & Sons, Ltd. [source] Wiskott,Aldrich syndrome protein and the cytoskeletal dynamics of dendritic cellsTHE JOURNAL OF PATHOLOGY, Issue 4 2004Yolanda Calle Abstract The regulated migration and spatial localization of dendritic cells in response to environmental signals are critical events during the initiation of physiological immune responses and maintenance of tolerance. Cells deficient in the Wiskott,Aldrich syndrome protein (WASP) have been used to demonstrate the importance of the dynamic remodelling of the actin-based cytoskeleton during the selective adhesion and migration of these cells. Unlike most cell types, macrophages, dendritic cells, and osteoclasts utilize a specialized adhesive array termed the podosome in order to migrate. Podosomes are composed of many of the same structural and regulatory proteins as seen in the more commonly found focal adhesion, but are unique in their requirement for WASP. Without WASP, podosomes cannot form and the affected cells are obliged to use focal adhesions for their migratory activities. Once activated by a series of upstream regulatory proteins, WASP acts as a scaffold for the binding of the potent actin nucleating protein complex known as Arp2/3. This article reviews the available evidence that suggests that failures in the regulation of the actin cytoskeleton may contribute significantly to the immunopathology of the Wiskott,Aldrich syndrome. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Dopamine D2 receptor knockout mice develop features of Parkinson disease,ANNALS OF NEUROLOGY, Issue 4 2009Rogan B. Tinsley PhD Objective This study questions whether increased dopamine (DA) turnover in nigral neurons leads to formation of Lewy bodies (LBs), the characteristic ,-synuclein,containing cytoplasmic inclusion of Parkinson disease (PD). Methods Mice with targeted deletion of the dopamine D2 receptor gene (D2R[,/,]) have higher striatal and nigral dopamine turnover and elevated oxidative stress. These mice were examined for evidence of histological, biochemical, and gene expression changes consistent with a synucleinopathy. Results LB-like cytoplasmic inclusions containing ,-synuclein and ubiquitin were present in substantia nigra pars compacta (SNpc) neurons of older D2R(,/,) mice, and were also occasionally seen in aged wild-type mice. These inclusions displaced the nucleus of affected cells and were eosinophilic. Diffuse cytosolic ,-synuclein immunoreactivity in SNpc neurons increased with age in both wild-type and D2R(,/,) mice, most likely because of redistribution of ,-synuclein from striatal terminals to SNpc cell bodies. Gene and protein expression studies indicated endoplasmic reticulum (ER) stress and changes in trafficking and autophagic pathways in D2R(,/,) SNpc. These changes were accompanied by a loss of DA terminals in the dorsal striatum, although there was no evidence of progressive cell death in the SNpc. Interpretation Increased sprouting and DA turnover, as observed in PD and D2R(,/,) mice, augments LB-like inclusions and axonal degeneration of dopaminergic neurons. These changes are associated with ER stress and autophagy. Ann Neurol 2009;66:472,484 [source] | |||||||||||||