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Disease Pathology (disease + pathology)
Kinds of Disease Pathology Selected AbstractsZoonotic Deep Cutaneous Filariasis,Three Pediatric Cases from Québec, CanadaPEDIATRIC DERMATOLOGY, Issue 2 2008Victor Kokta M.D. These rare cases were processed at our pediatric hospital within the last 6-year period. Patient age, travel information, lesional characteristics, systemic findings, serology, histopathology, treatment, and follow-up were gathered from the submitting specimen and the treating physicians. Species identification was performed by the Parasitic Disease Branch, Division of Infectious and Tropical Diseases Pathology, AFIP, Washington, DC. [source] Adult stem cell maintenance and tissue regeneration in the ageing context: the role for A-type lamins as intrinsic modulators of ageing in adult stem cells and their nichesJOURNAL OF ANATOMY, Issue 1 2008Vanja Pekovic Abstract Adult stem cells have been identified in most mammalian tissues of the adult body and are known to support the continuous repair and regeneration of tissues. A generalized decline in tissue regenerative responses associated with age is believed to result from a depletion and/or a loss of function of adult stem cells, which itself may be a driving cause of many age-related disease pathologies. Here we review the striking similarities between tissue phenotypes seen in many degenerative conditions associated with old age and those reported in age-related nuclear envelope disorders caused by mutations in the LMNA gene. The concept is beginning to emerge that nuclear filament proteins, A-type lamins, may act as signalling receptors in the nucleus required for receiving and/or transducing upstream cytosolic signals in a number of pathways central to adult stem cell maintenance as well as adaptive responses to stress. We propose that during ageing and in diseases caused by lamin A mutations, dysfunction of the A-type lamin stress-resistant signalling network in adult stem cells, their progenitors and/or stem cell niches leads to a loss of protection against growth-related stress. This in turn triggers an inappropriate activation or a complete failure of self-renewal pathways with the consequent initiation of stress-induced senescence. As such, A-type lamins should be regarded as intrinsic modulators of ageing within adult stem cells and their niches that are essential for survival to old age. [source] High-resolution magic angle spinning proton NMR analysis of human prostate tissue with slow spinning ratesMAGNETIC RESONANCE IN MEDICINE, Issue 3 2003Jennifer L. Taylor Abstract The development of high-resolution magic angle spinning (HR-MAS) NMR spectroscopy for intact tissue analysis and the correlations between the measured tissue metabolites and disease pathologies have inspired investigations of slow-spinning methodologies to maximize the protection of tissue pathology structures from HR-MAS centrifuging damage. Spinning sidebands produced by slow-rate spinning must be suppressed to prevent their complicating the spectral region of metabolites. Twenty-two human prostatectomy samples were analyzed on a 14.1T spectrometer, with HR-MAS spinning rates of 600 Hz, 700 Hz, and 3.0 kHz, a repetition time of 5 sec, and employing various rotor-synchronized suppression methods, including DANTE, WATERGATE, TOSS, and PASS pulse sequences. Among them, DANTE, as the simplest scheme, has shown the most potential in suppression of tissue water signals and spinning sidebands, as well as in quantifying metabolic concentrations. Magn Reson Med 50:627,632, 2003. © 2003 Wiley-Liss, Inc. [source] Translational medicine perspective in development of disease modifying therapies for Alzheimer's disease: biomarkers to buy down the riskDRUG DEVELOPMENT RESEARCH, Issue 2 2009Hong I. Wan Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of age-related dementia. Currently available pharmacologic therapies, including acetylcholinesterase (AChE) inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists, only treat symptoms and do not address the underlying neurodegeneration. In addition to potentially improve the accuracy of diagnosis, biomarkers serve important roles for the development of putative disease-modifying drugs for AD. In this article, we review the existing and emerging areas of biomarker research and development for AD. Biochemical biomarkers in cerebrospinal fluid have been used to provide a link to disease pathology and may provide important proof of concept data for several classes of emerging therapeutics. Imaging biomarkers including volumetric magnetic resonance imaging and positron emission tomography assessing either glucose utilization or radioligands binding to amyloid plaque are discussed. Appropriate uses of these biomarkers in the context of the development of disease-modifying therapies are discussed. Drug Dev Res 70, 2009. © 2009 Wiley-Liss, Inc. [source] Diagnostic difficulties in inflammatory bowel disease pathologyHISTOPATHOLOGY, Issue 2 2006R K Yantiss This review summarizes some of the common diagnostic problems encountered by pathologists when evaluating patients with chronic colitis and in whom inflammatory bowel disease (IBD) is either suspected or within the differential diagnosis. Both ulcerative colitis (UC) and Crohn's disease (CD) show characteristic, but non-specific, pathological features that may overlap and result in a diagnosis of ,indeterminate colitis' (IC). However, other reasons why pathologists may entertain a diagnosis of IC include failure to recognize or accept certain ,hardcore' histological features as indicative of CD, an attempt to classify cases of chronic colitis based on mucosal biopsy material or in the absence of adequate clinical and radiographic information, and the presence of other disease processes that mask, or mimic, IBD. In addition, some cases of UC may show unusual CD-like features, such as discontinuous or patchy disease, ileal inflammation, extracolonic inflammation, granulomatous inflammation in response to ruptured crypts, aphthous ulcers, or transmural inflammation. Furthermore, other forms of colitis, such as microscopic colitis, diverticulitis and diversion colitis may, on occasion, also show IBD-like changes. The clinical and pathological features that aid in the distinction between these entities, and others, are covered in detail in this review. [source] c-DNA Microarray to determine molecular events in neurodegeneration and neuroprotectionJOURNAL OF NEUROCHEMISTRY, Issue 2002M. B. H. Youdim Cell death in CNS involves complex processes, many of which have not been identified biochemically. At the present biochemical techniques cannot adequately establish these. However, the advent of cDNA microarray or microchips, in which the expression of thousands of genes can be measured at once to give a global assessment in disease pathology, its progress or animal models, has simplified this. We have employed this technique to study the mechanism of neurotoxicity of MPTP and 6-hydroxydoapmine induced in neuronally derived cells in culture, in the animal models of Parkinson's disease and neuroprotection initiated by monoamine oxidase B inhibitor, rasagiline; iron chelators, R-apomorphine and EGCG and other neuroprotective drugs. Our studies have clearly indicated that MPTP induced early gene expression, prior to cell death (first 24 h), are prerequirement for 51 late gene expression changes implicated at the time of neuronal death. The latter genes include those involved in iron metabolism, oxidative stress, inflammatory processes, glutaminergic excitotoxicity, nitric oxide, growth factors, transcription factors, cell cycle, intermediatory metabolism and other gene previously not identified. The expressions of many of the latter genes, also identified by in situ hybridization, are prevented when the animals are pretreated with the above neuroprotective drugs. These studies have clearly shown that neurodegeneratrion is a complex cascades of ,domino' effect. Thus a single neuroprotective drug treatment may not be adequate to prevent it, but, that a cocktail of drugs might. [source] Functional colonography of Min mice using dark lumen dynamic contrast-enhanced MRIMAGNETIC RESONANCE IN MEDICINE, Issue 3 2008C. Chad Quarles Abstract Dark lumen MRI colonography detects colonic polyps by minimization of the intestinal lumen signal intensity. Here we validate the use of perfluorinated oil as an intestinal-filling agent for dark lumen MRI studies in mice, enabling the physiological characterization of colonic polyps by dynamic contrast-enhanced MRI. In control and Min (multiple intestinal neoplasia) mice with and without pretreatment with oral dextran sodium sulfate (DSS), polyps as small as 0.94 mm diameter were consistently identified using standard 2D gradient echo imaging (voxel size, 0.23 × 0.16 × 0.5 mm). In serial studies, polyp growth rates were heterogeneous with an average ,5% increase in polyp volume per day. In DSS-treated control mice the colon wall contrast agent extravasation rate constant, Ktrans, and extravascular extracellular space volume fraction, ve, values were measured for the first time and found to be 0.10 ± 0.03 min,1 and 0.23 ± 0.09, respectively. In DSS-treated Min mice, polyp Ktrans values (0.09 ± 0.04 min,1) were similar to those in the colon wall but the ve values were substantially lower (0.16 ± 0.03), suggesting increased cellular density. The functional dark-lumen colonography approach described herein provides new opportunities for the noninvasive assessment of gastrointestinal disease pathology and treatment response in mouse models. Magn Reson Med 60:718,726, 2008. © 2008 Wiley-Liss, Inc. [source] Corticobasal syndrome with Alzheimer's disease pathologyMOVEMENT DISORDERS, Issue 1 2009Akiko Imamura MD [source] Reply: Corticobasal syndrome with Alzheimer's disease pathologyMOVEMENT DISORDERS, Issue 1 2009Pratap Chand DM [source] Cerebellar metabolic symmetry in essential tremor studied with 1H magnetic resonance spectroscopic imaging: Implications for disease pathologyMOVEMENT DISORDERS, Issue 6 2004Elan D. Louis MD Abstract The pathological basis for essential tremor (ET) is not known; however, metabolic changes in the cerebellum can be observed in positron emission tomography (PET) and 1H magnetic resonance spectroscopic imaging (MRSI) studies. Tremor is relatively symmetric in ET, suggesting that underlying metabolic changes could be also symmetric. The degree of metabolic asymmetry in the cerebellum, however, has not yet been studied in ET, and knowledge about distribution and laterality of metabolic changes might shed some light on basic disease mechanisms. We measured brain metabolism (N -acetylaspartate[NAA]/creatine [tCR]) to obtain an asymmetry index for cerebellar cortical metabolism ET patients compared with that in controls. This index, a percentage, was calculated as |(value right , value left)|/(value right + value left) × 100. Multislice 1H MRSI data were acquired for 20 patients and 11 controls. In ET patients, mean right and left cerebellar cortical NAA/tCR values were 1.61 ± 0.42 and 1.55 ± 0.38, respectively, compared with 1.81 ± 0.62 and 1.87 ± 0.49 in controls. The difference between right and left cerebellar cortical NAA/tCR was also calculated for each subject. In ET patients, the mean right-left difference was 0.14 ± 0.11, compared with 0.32 ± 0.27 in controls (P = 0.016). The mean cerebellar cortical asymmetry index was low in ET (8.8 ± 6.1%), one-half of that in controls (17.0 ± 13.7%, P = 0.027). These data suggest that pathological lesions in ET patients, which remain elusive, might be distributed similarly in each cerebellar cortex. Postmortem studies are needed to confirm these preliminary imaging results. © 2004 Movement Disorder Society [source] Distinct proteome features of plasma microparticlesPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 7 2005Ming Jin Abstract Plasma microparticles (MPs) are spherical cell membrane fragments derived from either apoptotic or activated cells. Characterized by a rich phospholipid moiety and many protein constituents, MPs normally circulate in the blood and contribute to numerous physiological processes. In disease states, MPs derived from the injured organ likely contain valuable markers for determining the site, type, and extent of disease pathology. However, the basic protein characteristics of plasma MPs have yet to be described. In this study, MPs from a pooled plasma sample derived from 16 healthy donors, all of group A blood type, were prepared by ultracentrifugation. Flow cytometry confirmed that a majority of these MPs are smaller than 1 µm. Factor Xa generation assay revealed the presence of tissue factor activity in these MPs, confirming MPs' role in initiating blood coagulation. The MP proteome was analyzed by two-dimensional (2-D) gel electrophoresis performed in triplicate, and compared with a 2-D gel of pooled whole plasma and blood platelets. Overall, plasma MPs displayed distinct protein features and a greater number of protein spots (1021,1055) than that detected in whole plasma (331,370). Protein spots expressed in high abundance in the MP proteome were then excised and submitted for protein identity determination. This process provided protein identification for 169 protein spots and reported their relative protein quantities within the MP proteome. These 169 protein spots represented 83 different proteins and their respective isoforms. Thirty of these proteins have never before been reported in previous proteome analyses of human plasma. These results provide unprecedented information on the MP proteome and create a basis for future studies to understand MP biology and pathophysiology. [source] Chemical and morphological alterations of spines within the hippocampus and entorhinal cortex precede the onset of Alzheimer's disease pathology in double knock-in miceTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 4 2007Chiye Aoki Abstract Mice with knock-in of two mutations that affect beta amyloid processing and levels (2xKI) exhibit impaired spatial memory by 9,12 months of age, together with synaptic plasticity dysfunction in the hippocampus. The goal of this study was to identify changes in the molecular and structural characteristics of synapses that precede and thus could exert constraints upon cellular mechanisms underlying synaptic plasticity. Drebrin A is one protein reported to modulate spine sizes and trafficking of proteins to and from excitatory synapses. Thus, we examined levels of drebrin A within postsynaptic spines in the hippocampus and entorhinal cortex. Our electron microscopic immunocytochemical analyses reveal that, by 6 months, the proportion of hippocampal spines containing drebrin A is reduced and this change is accompanied by an increase in the mean size of spines and decreased density of spines. In the entorhinal cortex of 2xKI brains, we detected no decrement in the proportion of spines labeled for drebrin A and no significant change in spine density at 6 months, but rather a highly significant reduction in the level of drebrin A immunoreactivity within each spine. These changes are unlike those observed for the somatosensory cortex of 2xKI mice, in which synapse density and drebrin A immunoreactivity levels remain unchanged at 6 months and older. These results indicate that brains of 2xKI mice, like those of humans, exhibit regional differences of vulnerability, with the hippocampus exhibiting the first signatures of structural changes that, in turn, may underlie the emergent inability to update spatial memory in later months. J. Comp. Neurol. 505:352,362, 2007. © 2007 Wiley-Liss, Inc. [source] Influence of lipopolysaccharide and interleukin-6 on RANKL and OPG expression and release in human periodontal ligament cellsAPMIS, Issue 10 2009ANNA C. KRAJEWSKI Recent research into periodontal disease pathology focuses on the role of receptor activator of nuclear factor-,B ligand (RANKL) and osteoprotegerin (OPG) in periodontal bone destruction processes. RANKL regulates the differentiation of osteoclast by binding to its specific receptor RANK, while OPG inhibits the differentiation of osteoclasts by binding RANKL and therefore preventing RANKL to bind RANK. The aim of the present study was to investigate the influence of Porphyromonas gingivalis lipopolysaccharide (LPS) and interleukin-6 (IL-6) on RANKL and OPG expression and release in periodontal ligament (PDL) cells. Human PDL cells were stimulated for 48 h with purified P. gingivalis LPS and IL-6. OPG and sRANKL release were assessed by using enzyme-linked immunosorbent assay technique. OPG and RANKL expression was quantitatively measured by using the real-time PCR technique. Whereas P. gingivalis LPS induced sRANKL release, expression was only slightly increased, IL-6 did not show an effect on RANKL expression or release. In conclusion the data demonstrate that stimulation of PDL cells with P. gingivalis LPS leads to an increased release of sRANKL, rather than increased RANKL expression. Through this action, P. gingivalis LPS may exert its biological effect on osteoclast formation and bone resorption. [source] Selective functional inhibition of JAK-3 is sufficient for efficacy in collagen-induced arthritis in miceARTHRITIS & RHEUMATISM, Issue 8 2010Tsung H. Lin Objective All ,-chain cytokines signal through JAK-3 and JAK-1 acting in tandem. We undertook this study to determine whether the JAK-3 selective inhibitor WYE-151650 would be sufficient to disrupt cytokine signaling and to ameliorate autoimmune disease pathology without inhibiting other pathways mediated by JAK-1, JAK-2, and Tyk-2. Methods JAK-3 kinase selective compounds were characterized by kinase assay and JAK-3,dependent (interleukin-2 [IL-2]) and ,independent (IL-6, granulocyte,macrophage colony-stimulating factor [GM-CSF]) cell-based assays measuring proliferation or STAT phosphorylation. In vivo, off-target signaling was measured by IL-22, and erythropoietin (EPO),mediated models, while on-target signaling was measured by IL-2,mediated signaling. Efficacy of JAK-3 inhibitors was determined using delayed-type hypersensitivity (DTH) and collagen-induced arthritis (CIA) models in mice. Results In vitro, WYE-151650 potently suppressed IL-2,induced STAT-5 phosphorylation and cell proliferation, while exhibiting 10,29-fold less activity against JAK-3,independent IL-6, or GM-CSF,induced STAT phosphorylation. Ex vivo, WYE-151650 suppressed IL-2,induced STAT phosphorylation, but not IL-6,induced STAT phosphorylation, as measured in whole blood. In vivo, WYE-151650 inhibited JAK-3,mediated IL-2,induced interferon-, production and decreased the natural killer cell population in mice, while not affecting IL-22,induced serum amyloid A production or EPO-induced reticulocytosis. WYE-151650 was efficacious in mouse DTH and CIA models. Conclusion In vitro, ex vivo, and in vivo assays demonstrate that WYE-151650 is efficacious in mouse CIA despite JAK-3 selectivity. These data question the need to broadly inhibit JAK-1,, JAK-2,, or Tyk-2,dependent cytokine pathways for efficacy. [source] Lack of association between an estrogen receptor 1 gene polymorphism and Parkinson's disease with dementiaACTA NEUROLOGICA SCANDINAVICA, Issue 3 2002K. M. Mattila Objective, To test for an association between an estrogen receptor 1 (ESR1) gene polymorphism and Parkinson's disease with dementia (PDD) in Finnish subjects. Subjects and methods, Forty-one clinically demented and pathologically confirmed PDD patients and 59 cognitively intact aged individuals with normal neuropathology were genotyped for the ESR1 PvuII polymorphism. Results, We found no significant differences in the genotype or allele frequencies when the PDD patients were compared with the controls. Nor were there any significant differences in these frequencies when the PDD patients with coexisting Alzheimer's disease pathology were compared with the control group. Conclusion, We failed to demonstrate an association between dementia-associated PD and the ESR1 PvuII polymorphism in Finnish subjects. [source] 2325: Dynamic retinal vessel analysis , how different parameters create the whole pictureACTA OPHTHALMOLOGICA, Issue 2010I LANZL Purpose Dynamic vessel analysis is usually associated with the observation of the reaction of retinal vessels to a defined stimulus. The data which is generated this way may be further analysed with respect to the dynamic unstimulated and stimulated vessel behaviour. Assessment of different parameters may highlight different aspects of the underlying disease. Methods Vessel diameters of retinal vessel segments were assessed by Dynamic Vessel Analyzer (DVA) in healthy volunteers of different age groups and patients with diabetes, glaucoma and systemic hypertension. Mathematical analysis of unstimulated vessels was used to describe vessel wall characteristics. Methods of signal analysis including Fourier Transformation, spectral filtration, auto- and cross correlation were applied to evaluate characteristic oscillations and pulse wave propagation along the vessel. Results Characteristic different vessel behaviour and vessel wall conformation are obtained by dynamic quantitative evaluations from the unstimulated vessels in physiologic aging and disease. Conclusion Dynamic vessel analysis includes information which may lead to further understanding of the vascular status and underlying disease pathology. It is also feasible to assess pulse wave velocities in retinal arterioles und thus clinically characterize the elasticity of the upstream vasculature in health and disease. [source] | |||||||||||||