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Pathological Mechanisms (pathological + mechanism)
Selected AbstractsDifferences in grey and white matter atrophy in amnestic mild cognitive impairment and mild Alzheimer's diseaseEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2009M. L. F. Balthazar Background:, Grey matter (GM) atrophy has been demonstrated in amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD), but the role of white matter (WM) atrophy has not been well characterized. Despite these findings, the validity of aMCI concept as prodromal AD has been questioned. Methods:, We performed brain MRI with voxel-based morphometry analysis in 48 subjects, aiming to evaluate the patterns of GM and WM atrophy amongst mild AD, aMCI and age-matched normal controls. Results:, Amnestic mild cognitive impairment GM atrophy was similarly distributed but less intense than that of mild AD group, mainly in thalami and parahippocampal gyri. There were no difference between aMCI and controls concerning WM atrophy. In the mild AD group, we found WM atrophy in periventricular areas, corpus callosum and WM adjacent to associative cortices. Discussion:, We demonstrated that aMCI might be considered a valid concept to detect very early AD pathology, since we found a close proximity in the pattern of atrophy. Also, we showed the involvement of WM in mild AD, but not in aMCI, suggesting a combination of Wallerian degeneration and microvascular ischaemic disease as a plausible additional pathological mechanism for the discrimination between MCI and AD. [source] Cold-induced apoptosis of rat liver cells in University of Wisconsin solution: The central role of chelatable ironHEPATOLOGY, Issue 3 2002Uta Kerkweg Although University of Wisconsin (UW) solution aims at the prevention of cold-induced cell injury, it failed to protect against cold-induced apoptosis of hepatocytes and liver endothelial cells: when incubated in UW solution at 4°C for 24 hours and subsequently rewarmed at 37°C, 72% ± 8% of rat hepatocytes and 81% ± 5% of liver endothelial cells lost viability. In both cell types, the observed cell damage occurred under an apoptotic morphology; it appeared to be mediated by a rapid increase in the cellular chelatable iron pool by a factor ,2 (as determined in hepatocytes) and subsequent formation of reactive oxygen species (ROS). Consequently, this cell injury was decreased by iron chelators to 6 to 25% (hepatocytes) and 4% ± 2% (liver endothelial cells). Deferoxamine nearly completely inhibited the occurrence of apoptotic morphology in both cell types. In liver endothelial cells, cold-induced apoptosis occurring during rewarming after 24 hours of cold incubation in UW solution was far more pronounced than in cell culture medium (loss of viability: 81% ± 5% vs. 28% ± 13%), but viability could even be maintained for 2 weeks of cold incubation by use of deferoxamine. In conclusion, this pathological mechanism might be an explanation for the strong endothelial cell injury known to occur after cold preservation. With regard to the extent of this iron-mediated injury, addition of a suitable iron chelator to UW solution might markedly improve the outcome of liver preservation. [source] Single nucleotide polymorphisms and haplotype of MD-1 gene associated with high serum IgE phenotype with mite-sensitive allergy in Taiwanese childrenINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 6 2007J. Y. Wang Summary MD-1 (myeloid differentiation 1; also known as Ly86, lymphocyte antigen 86), interacting with RP105, plays an important role in Toll-like receptor 4 (TLR4) signalling pathway. It has been suggested to be involved in the pathological mechanism of inflammation and atopic diseases. The purpose of this study was to investigate the genetic association between single nucleotide polymorphisms (SNPs) of MD-1 promoter and coding region and mite-sensitive allergy in Taiwanese children. We conducted a case-control study on 237 controls and 281 allergic patients sensitive to Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f) by genotyping 35 SNPs in MD-1 gene region. In the promoter region we identified three SNPs, rs1334710, rs4959389, and rs977785 that are associated with mite-sensitive allergy in Taiwanese children. The P -values ranged from 0.0150 to 0.009. The haplotypes including promoter region were also associated with mite-sensitive allergy. Our results suggested that MD-1 could be a susceptible gene for mite-sensitive allergy in Taiwanese children. [source] Cerebral Embolism of Iodized Oil (Lipiodol) after Transcatheter Arterial Chemoembolization for Hepatocellular CarcinomaJOURNAL OF NEUROIMAGING, Issue 4 2009Joon-Tae Kim MD ABSTRACT Cerebral lipiodol embolism is a rare complication of transcatheter arterial chemoembolization (TACE). Its pathological mechanism remains ambiguous despite several investigations. In Case 1, a 67-year-old man with hepatocellular carcinoma (HCC) experienced neurological deficits soon after undergoing a fourth session of TACE. Computed tomography (CT) scan showed multiple hyperdense lesions along the gyrus of frontal lobes and in the subcortical white matter. Transcranial Doppler (TCD) and transesophageal echocardiogram performed during the intravenous injection of agitated saline documented the presence of a right-to-left shunt (RLS) by demonstrating microbubbles in the left middle cerebral artery and left atrium. In Case 2, a 63-year-old woman underwent a third TACE due to a large HCC. After the procedure, her mental status deteriorated. Brain CT showed multiple hyperdense lesions on the cerebral and cerebellar cortex. TCD with agitated saline showed multiple microembolic signals shortly after the injection of agitated saline. The risk of cerebral lipiodol embolism may increase with recurrence and progression of HCC in patients who have a pre-existing RLS in the heart or lung. A test for the detection of an RLS may be necessary to identify patients with a heightened risk of cerebral embolism when multiple TACE procedures are required. TACE for HCC can cause pulmonary embolism or infarction.1,2 However, cerebral lipiodol embolism is rare after TACE. There have been several reports of cerebral embolism after TACE, but their exact mechanism has not yet been fully elucidated. We report herein 2 patients who developed cerebral lipiodol embolism after undergoing multiple TACE procedures for remnant HCC through a pre-existing RLS. [source] Structural white matter abnormalities in patients with idiopathic dystoniaMOVEMENT DISORDERS, Issue 8 2007Leonardo Bonilha MD Abstract We investigated whether structural white matter abnormalities, in the form of disruption of axonal coherence and integrity as measured with diffusion tensor imaging (DTI), constitute an underlying pathological mechanism of idiopathic dystonia (ID), independent of genotype status. We studied seven subjects with ID: all had cervical dystonia as their main symptom (one patient also had spasmodic dysphonia and two patients had concurrent generalized dystonia, both DYT1-negative). We compared DTI MR images of patients with 10 controls, evaluating differences in mean diffusivity (MD) and fractional anisotropy (FA). ID was associated with increased FA values in the thalamus and adjacent white matter, and in the white matter underlying the middle frontal gyrus. ID was also associated with increase in MD in adjacent white matter to the pallidum and putamen bilaterally, left caudate, and in subcortical hemispheric regions, including the postcentral gyrus. Abnormal FA and MD in patients with ID indicate that abnormal axonal coherence and integrity contribute to the pathophysiology of dystonia. These findings suggest that ID is not only a functional disorder, but also associated with structural brain changes. Impaired connectivity and disrupted flow of information may contribute to the impairment of motor planning and regulation in dystonia. © 2006 Movement Disorder Society [source] Anaesthetics and postoperative cognitive dysfunction: a pathological mechanism mimicking Alzheimer's diseaseANAESTHESIA, Issue 4 2010V. Fodale Summary With longevity, postoperative cognitive decline in the elderly has emerged as a major health concern for which several factors have been implicated, one of the most recent being the role of anaesthetics. Interactions of anaesthetic agents and different targets have been studied at the molecular, cellular and structural anatomical levels. Recent in vitro nuclear magnetic resonance spectroscopy studies have shown that several anaesthetics act on the oligomerisation of amyloid , peptide. Uncontrolled production, oligomerisation and deposition of amyloid , peptide, with subsequent development of amyloid plaques, are fundamental steps in the generation of Alzheimer's disease. Amyloid , peptide is naturally present in the central nervous system, and is found at higher tissue concentrations in the elderly. We argue that administering certain general anaesthetics to elderly patients may worsen amyloid , peptide oligomerisation and deposition and thus increase the risk of developing postoperative cognitive dysfunction. The aim of this review is to highlight the clinical aspects of postoperative cognitive dysfunction and to find plausible links between possible anaesthetic effects and the molecular pathological mechanism of Alzheimer's disease. It is hoped that our hypothesis will stimulate further enquiry, especially triggering research into elucidating those anaesthetics that may be more suitable when cognitive dysfunction is a particular concern. [source] Actin mutations are one cause of congenital fibre type disproportionANNALS OF NEUROLOGY, Issue 5 2004Nigel G. Laing PhD We report three heterozygous missense mutations of the skeletal muscle alpha actin gene (ACTA1) in three unrelated cases of congenital fiber type disproportion (CFTD) from Japan and Australia. This represents the first genetic cause of CFTD to be identified and confirms that CFTD is genetically heterogeneous. The three mutations we have identified Leucine221Proline, Aspartate292Valine, and Proline332Serine are novel. They have not been found previously in any cases of nemaline, actin, intranuclear rod, or rod-core myopathy caused by mutations in ACTA1. It remains unclear why these mutations cause type 1 fiber hypotrophy but no nemaline bodies. The three mutations all lie on one face of the actin monomer on the surface swept by tropomyosin during muscle activity, which may suggest a common pathological mechanism. All three CFTD cases with ACTA1 mutations had severe congenital weakness and respiratory failure without ophthalmoplegia. There were no clinical features specific to CFTD cases with ACTA1 mutations, but the presence of normal eye movements in a severe CFTD patient may be an important clue for the presence of a mutation in ACTA1. Ann Neurol 2004 [source] "Click Peptides",Chemical Biology-Oriented Synthesis of Alzheimer's Disease-Related Amyloid , Peptide (A,) Analogues Based on the "O- Acyl Isopeptide Method"CHEMBIOCHEM, Issue 10 2006Youhei Sohma Abstract A clear understanding of the pathological mechanism of amyloid , peptide (A,) 1,42, a currently unexplained process, would be of great significance for the discovery of novel drug targets for Alzheimer's disease (AD) therapy. To date, though, the elucidation of these A,1,42 dynamic events has been a difficult issue because of uncontrolled polymerization, which also poses a significant obstacle in establishing experimental systems with which to clarify the pathological function of A,1,42. We have recently developed chemical biology-oriented pH- or phototriggered "click peptide" isoform precursors of A,1,42, based on the "O -acyl isopeptide method", in which a native amide bond at a hydroxyamino acid residue, such as Ser, is isomerized to an ester bond, the target peptide subsequently being generated by an O,N intramolecular acyl migration reaction. These click peptide precursors did not exhibit any self-assembling character under physiological conditions, thanks to the presence of the one single ester bond, and were able to undergo migration to give the target A,1,42 in a quick and easy, one-way (so-called "click")conversion reaction. The use of click peptides could be a useful strategy to investigate the biological functions of A,1,42 in AD through inducible activation of A,1,42 self-assembly. [source] The epidemiology of depression in diabetesEUROPEAN DIABETES NURSING, Issue 3 2008K Winkley BSc, PhD Lecturer in Diabetes, Psychology Abstract Depression is characterised by a period of low mood and loss of interest in everyday activities, and its prevalence in people with diabetes is thought to be twice as high as for those without the condition. Depression in diabetes is associated with a number of adverse outcomes such as increased morbidity, mortality and poor quality of life. As diabetes is increasingly common amongst the economically active, this has serious implications for health services and in the UK, the National Health Service (NHS) has recognised that depression in people with diabetes is a significant problem and recommends screening for depression in this group. Risk factors for depression in diabetes are almost identical to those in people without diabetes, but less is known about its course when people have diabetes, although the available evidence suggests it is more chronic. Research into the mechanisms by which depression is bad for people with diabetes suggests that biological, psychological and social factors play a part but the inter-relationships between these factors are likely to be complex and are not yet fully understood. Depression in people with diabetes can be treated successfully with pharmacological and psychological treatments at least in the short-term, but we do not yet know which treatments are successful in the long-term. Further research into the pathological mechanisms of depression and its treatment are needed if we are to continue to improve the health and lives of people with diabetes. Copyright © 2008 FEND [source] The current status of investigative dermatology IIEXPERIMENTAL DERMATOLOGY, Issue 10 2010Stephen I. Katz Abstract:, Major advances in skin biology and skin diseases are heralding new and more specific forms of treatment that are based on better characterization of pathological mechanisms involved in the individual diseases. The advances that we have seen are being made by dermatologists, skin biologists, and others who have come to appreciate the skin as an organ that is reflective of many important systemic mechanisms. In this commentary, I identify some of what I feel are the most important advances that will be the basis for many future studies. [source] The mechanisms of coronary restenosis: insights from experimental modelsINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 2 2000Gordon A.A. Ferns Since its introduction into clinical practice, more than 20 years ago, percutaneous transluminal coronary angioplasty (PTCA) has proven to be an effective, minimally invasive alternative to coronary artery bypass grafting (CABG). During this time there have been great improvements in the design of balloon catheters, operative procedures and adjuvant drug therapy, and this has resulted in low rates of primary failure and short-term complications. However, the potential benefits of angioplasty are diminished by the high rate of recurrent disease. Up to 40% of patients undergoing angioplasty develop clinically significant restenosis within a year of the procedure. Although the deployment of endovascular stents at the time of angioplasty improves the short-term outcome, ,in-stent' stenosis remains an enduring problem. In order to gain an insight into the mechanisms of restenosis, several experimental models of angioplasty have been developed. These have been used together with the tools provided by recent advances in molecular biology and catheter design to investigate restenosis in detail. It is now possible to deliver highly specific molecular antagonists, such as antisense gene sequences, to the site of injury. The knowledge provided by these studies may ultimately lead to novel forms of intervention. The present review is a synopsis of our current understanding of the pathological mechanisms of restenosis. [source] Cutaneous metastasis from a parotid myoepithelial carcinoma: a case report and review of the literatureJOURNAL OF CUTANEOUS PATHOLOGY, Issue 12 2008Deng-qi He Myoepithelial carcinoma of the parotid gland is a rare salivary gland tumour, and its distant cutaneous metastasis has not been reported to date. Here, we report a case of myoepithelial carcinoma of the left parotid gland, which had metastasised to the skin of the right thorax after parotidectomy and radiotherapy. Diagnosis of the primary and metastatic tumour was based on the clinical findings and was confirmed by immunohistochemistry. A literature review of the clinical features of the skin metastases of parotid malignancies and their related pathological mechanisms is included in this case study. It was noted that myoepithelial carcinoma of the parotid gland has the potential to develop distant skin metastasis, which may be indicative of widespread dissemination and poor prognosis. Attention should be paid to initial treatment of the primary tumour and to emerging cutaneous masses whose location is distant from the primary tumour during follow up. [source] Altered apolipoprotein E glycosylation is associated with A,(42) accumulation in an animal model of Niemann-Pick Type C diseaseJOURNAL OF NEUROCHEMISTRY, Issue 6 2010Ching-Ching Chua J. Neurochem. (2010) 112, 1619,1626. Abstract Neurodegeneration is the final cause of death in Niemann-Pick Type C (NPC) disease, a cholesterol-storage disorder. Accumulating evidence indicates that NPC may share common pathological mechanisms with Alzheimer's disease, including the link between aberrant cholesterol metabolism and amyloid-, (A,) deposition. Apolipoprotein E (apoE) is highly expressed in the brain and plays a pivotal role in cholesterol metabolism. ApoE can also modulate A, production and clearance, and it is a major genetic risk factor for Alzheimer's disease. Although apoE is glycosylated, the functional significance of this chemical alteration on A, catabolism is unclear. In this study using an NPC animal model, we detect specific changes in apoE glycosylation that correlate with increased A,(42) accumulation prior to the appearance of neurological abnormalities. This suggests that increased apoE expression could be a compensatory response to the increased A,(42) deposition in NPCnih mice. We also observe what appears to be a simplification of the glycosylation process on apoE during neurodegeneration. [source] Defective calcium homeostasis in the cerebellum in a mouse model of Niemann,Pick A diseaseJOURNAL OF NEUROCHEMISTRY, Issue 6 2005Luba Ginzburg Abstract We recently demonstrated that calcium homeostasis is altered in mouse models of two sphingolipid storage diseases, Gaucher and Sandhoff diseases, owing to modulation of the activities of a calcium-release channel (the ryanodine receptor) and of the sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA) respectively, by the accumulating sphingolipids. We now demonstrate that calcium homeostasis is also altered in a mouse model of Niemann,Pick A disease, the acid sphingomyelinase (A-SMase)-deficient mouse (ASM,/,), with reduced rates of calcium uptake via SERCA in the cerebellum of 6,7-month-old mice. However, the mechanism responsible for defective calcium homeostasis is completely different from that observed in the other two disease models. Thus, levels of SERCA expression are significantly reduced in the ASM,/, cerebellum by 6,7 months of age, immediately before death of the mice, as are levels of the inositol 1,4,5-triphosphate receptor (IP3R), the major calcium-release channel in the cerebellum. Systematic analyses of the time course of loss of SERCA and IP3R expression revealed that loss of the IP3R preceeded that of SERCA, with essentially no IP3R remaining by 4 months of age, whereas SERCA was still present even after 6 months. Expression of zebrin II (aldolase C), a protein found in about half of the Purkinje cells in the adult mouse cerebellum, was essentially unchanged during development. We discuss possible pathological mechanisms related to calcium dysfunction that may cause Purkinje cell degeneration, and as a result, the onset of neuropathology in Niemann,Pick A disease. [source] Is Gadolinium Enhancement Predictive of the Development of Brain Atrophy in Multiple Sclerosis?JOURNAL OF NEUROIMAGING, Issue 4 2002A Review of the Literature ABSTRACT Background and Purpose. Several studies have demonstrated that brain atrophy can be detected over relatively short intervals from the earliest stages of multiple sclerosis (MS). Reviewing the published data, the authors highlight some hypothetical pathological mechanisms proposed as determinants of brain atrophy. Methods. Using the terms multiple sclerosis, MRI (magnetic resonance imaging), and brain atrophy, 181 citations were identified. The authors considered only studies with prospective designs with natural-course MS patients and/or placebo-treated patients of therapeutic trials, in which patients under-went baseline and follow-up scans with a T1-weighted gadolinium diethylenetriamine penta-acetic acid sequence (0.1 mmol/kg body weight), and correlation analyses between Gd enhancement activity and brain atrophy progression. Results. Five hundred thirty-two patients of 5 natural history studies and 5 therapeutic trial studies participated in the review process. The main observation was that in patients with a relapsing-remitting (RR) disease course, there was a correlation between Gd enhancement activity and brain atrophy progression. This correlation was not influenced by any other demographic and clinical additional data considered in the review process. Conclusions. Examination of the pathological mechanisms pro-posed in the reviewed studies led the authors to believe that inflammation is only in part responsible for the development of brain atrophy. This conclusion may have an implication for the strategies of tissue protection advocated in the early stages of the RR course and strengthen recent evidence indicating that anti-inflammatory immunomodulatory agents and immunosuppressive treatments, which predominantly act against the inflammatory component of disease activity, may not have similar effects on progressive tissue loss, either in RR or progressive MS. [source] Understanding and Treating Patients With Alcoholic Cirrhosis: An UpdateALCOHOLISM, Issue 7 2009Giovanni Addolorato Alcoholic cirrhosis represents the terminal stage of alcoholic liver disease (ALD) and one of the main causes of death among alcohol abusers. The aim of this review was to provide an update on alcoholic cirrhosis, with an emphasis on recent findings. Increased alcohol consumption in developing countries is expected to increase cirrhosis mortality. There is a need, therefore, to develop new approaches to the prevention of ALD, including more attention to co-factors that may increase risk of ALD (i.e., obesity and diabetes, chronic HCV infection, and smoking). Furthermore, a better understanding of the pathological mechanisms on the basis of alcohol cirrhosis represents a cornerstone in order to develop new pharmacological treatments. Inflammatory and immune responses along with oxidative stress and alterations in adipokine secretion might contribute in different ways to the evolution of alcohol-induced fibrosis/cirrhosis. As of this date, patients with severe alcoholic hepatitis with a Maddrey Discriminant Factor (MDF) 32 should be offered pentoxifylline and/or corticosteroids unless contraindications exist. For ambulatory patients, S-adenosylmethionine (SAMe) may be considered in a motivated patient with nutritional support. Current studies do not support use of anti-tumor necrosis factor (TNF)-alpha antibody. Finally, achieving total alcohol abstinence should represent the main aim in the management of patients affected by any stage of cirrhosis. In the last decades, several drugs able to increase abstinence and prevent alcohol relapse have been evaluated and some of them have obtained approval for alcohol dependence. Patients with alcoholic cirrhosis; however, are usually excluded from such treatments. A recent study demonstrated the efficacy and safety of baclofen in inducing and maintaining alcohol abstinence in cirrhotic alcohol-dependent patients with cirrhosis. All together the information available suggests the need of a multimodal approach in the clinical management of these patients. [source] Limb-girdle muscular dystrophies , from genetics to molecular pathologyNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 2 2004S. H. Laval The limb-girdle muscular dystrophies are a diverse group of muscle-wasting disorders characteristically affecting the large muscles of the pelvic and shoulder girdles. Molecular genetic analyses have demonstrated causative mutations in the genes encoding a disparate collection of proteins involved in all aspects of muscle cell biology. Muscular dystrophy includes a spectrum of disorders caused by loss of the linkage between the extracellular matrix and the actin cytoskeleton. Within this are the forms of limb-girdle muscular dystrophy caused by deficiencies of the sarcoglycan complex and by aberrant glycosylation of ,-dystroglycan caused by mutations in the fukutin-related protein gene. However, other forms of this disease have distinct pathophysiological mechanisms. For example, deficiency of dysferlin disrupts sarcolemmal membrane repair, whilst loss of calpain-3 may exert its pathological influence either by perturbation of the I,B,/NF-,B pathway, or through calpain-dependent cytoskeletal remodelling. Caveolin-3 is implicated in numerous cell-signalling pathways and involved in the biogenesis of the T-tubule system. Alterations in the nuclear lamina caused by mutations in laminA/C, sarcomeric changes in titin, telethonin or myotilin at the Z-disc, and subtle changes in the extracellular matrix proteins laminin-,2 or collagen VI can all lead to a limb-girdle muscular dystrophy phenotype, although the specific pathological mechanisms remain obscure. Differential diagnosis of these disorders requires the careful application of a broad range of disciplines: clinical assessment, immunohistochemistry and immunoblotting using a panel of antibodies and extensive molecular genetic analyses. [source] Pharmacology and immunological actions of a herbal medicine ASHMITM on allergic asthmaPHYTOTHERAPY RESEARCH, Issue 7 2010Tengfei Zhang Abstract Allergic asthma is a chronic and progressive inflammatory disease for which there is no satisfactory treatment. Studies reported tolerability and efficacy of an anti-asthma herbal medicine intervention (ASHMI) for asthma patients, developed from traditional Chinese medicine. To investigate the pharmacological actions of ASHMI on early- and late-phase airway responses (EAR and LAR), Ovalbumin (OVA)-sensitized mice received 6 weeks of ASHMI treatment beginning 24,h following the first intratracheal OVA challenge. EAR were determined 30,min following the fourth challenge and LAR 48,h following the last challenge. ASHMI effects on cytokine secretion, murine tracheal ring contraction and human bronchial smooth muscle cell prostaglandin (PG) production were also determined. ASHMI abolished EAR, which was associated with significantly reduced histamine, leukotriene C4, and OVA-specific IgE levels, as well as LAR, which was associated with significantly reduced bronchoalveolar lavage fluid (BALF) eosinophils, decreased airway remodeling, and lower Th2 cytokine levels in BALF and splenocyte cultures. Furthermore, ASHMI inhibited contraction of murine tracheal rings and increased production of the potent smooth muscle relaxer PGI2. ASHMI abrogation of allergic airway responses is associated with broad effects on asthma pathological mechanisms. Copyright © 2009 John Wiley & Sons, Ltd. [source] Search for the tumor-related proteins of transition cell carcinoma in Taiwan by proteomic analysisPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 3 2006Kun-Hung Sheng Abstract To better understand the carcinogenesis of bladder cancer in Taiwan, we utilized the proteomic approach to search for potential biomarkers of transitional cell carcinoma,(TCC). Analysis by 2-DE and MS/MS indicated that seven proteins are down-regulated and three proteins up-regulated in grade III samples as compared with those of grade,II. Of these deregulated proteins, fatty acid binding proteins, annexin,V, heat-shock protein,27, and lactate dehydrogenase have been shown to be associated with bladder cancer. Our studies also found altered expression of a group of proteins that have not been documented previously in bladder cancer, including annexin,I, 15-hydroxyprostaglandin dehydrogenase, galectin-1, lysophospholipase and mitochondrial short-chain enoyl-coenzyme,A hydratase,1 precursor. These results illustrate a pattern of differential protein expression between low- and high-grade tumors and it may be utilized as the molecular fingerprinting of a subset of bladder cancers. In addition, the present study provides a valuable resource in the study of pathological mechanisms in cancers of urothelial origin. The immunohistochemical staining of grade,II and III TCC samples with antiserum to annexin,I protein was utilized to confirm that the annexin,I protein is up-regulated in grade,III TCC. [source] Proteomic profiling of animal models mimicking skeletal muscle disordersPROTEOMICS - CLINICAL APPLICATIONS, Issue 9 2007Philip Doran Abstract Over the last few decades of biomedical research, animal models of neuromuscular diseases have been widely used for determining pathological mechanisms and for testing new therapeutic strategies. With the emergence of high-throughput proteomics technology, the identification of novel protein factors involved in disease processes has been decisively improved. This review outlines the usefulness of the proteomic profiling of animal disease models for the discovery of new reliable biomarkers, for the optimization of diagnostic procedures and the development of new treatment options for skeletal muscle disorders. Since inbred animal strains show genetically much less interindividual differences as compared to human patients, considerably lower experimental repeats are capable of producing meaningful proteomic data. Thus, animal model proteomics can be conveniently employed for both studying basic mechanisms of molecular pathogenesis and the effects of drugs, genetic modifications or cell-based therapies on disease progression. Based on the results from comparative animal proteomics, a more informed decision on the design of clinical proteomics studies could be reached. Since no one animal model represents a perfect pathobiochemical replica of all of the symptoms seen in complex human disorders, the proteomic screening of novel animal models can also be employed for swift and enhanced protein biochemical phenotyping. [source] Translational Research: Animal Models of Obliterative Bronchiolitis after Lung TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009M. Sato Obliterative bronchiolitis (OB) or chronic graft dysfunction remains the major limitation to long-term success of lung transplantation. Investigation using animal models is a critical component of research to understand the underlying pathological mechanisms and to develop novel preventive and therapeutic strategies for OB. Multiple animal models of OB exist, including orthotopic lung transplantation in rodents and large animals, orthotopic tracheal transplantation and heterotopic transplantation of a trachea in variable sites such as subcutaneous, intraomental and intrapulmonary sites. The most important issue for researchers is not specifically which model is the best but which is the most appropriate model to test their scientific hypothesis. For example, while orthotopic lung transplantation best mimics the overall surgical procedure, a question regarding fibrotic processes of OB may be better answered using heterotopic tracheal transplant models because of their reliable reproducibility of allograft obliterative airway fibrosis. Animal models should be continuously refined, modified and sometimes combined to fit the particular research purpose. We review the available animal models, their modifications and possible applications to assist researchers in choosing the appropriate model for their intended research. [source] Relationship between atrophy and ,-amyloid deposition in Alzheimer diseaseANNALS OF NEUROLOGY, Issue 3 2010Gaël Chételat PhD Objective Elucidating the role of aggregated ,-amyloid in relation to gray matter atrophy is crucial to the understanding of the pathological mechanisms of Alzheimer disease and for the development of therapeutic trials. The present study aims to assess this relationship. Methods Brain magnetic resonance imaging and [11C]Pittsburgh compound B (PiB)-positron emission tomography scans were obtained from 94 healthy elderly subjects (49 with subjective cognitive impairment), 34 patients with mild cognitive impairment, and 35 patients with Alzheimer disease. The correlations between global and regional neocortical PiB retention and atrophy were analyzed in each clinical group. Results Global and regional atrophy were strongly related to ,-amyloid load in participants with subjective cognitive impairment but not in patients with mild cognitive impairment or Alzheimer disease. Global neocortical ,-amyloid deposition correlated to atrophy in a large brain network including the hippocampus, medial frontal and parietal areas, and lateral temporoparietal cortex, whereas regional ,-amyloid load was related to local atrophy in the areas of highest ,-amyloid load only, that is, medial orbitofrontal and anterior and posterior cingulate/precuneus areas. Interpretation There is a strong relationship between ,-amyloid deposition and atrophy very early in the disease process. As the disease progresses to mild cognitive impairment and Alzheimer disease clinical stages, pathological events other than, and probably downstream from, aggregated ,-amyloid deposition might be responsible for the ongoing atrophic process. These findings suggest that antiamyloid therapy should be administered very early in the disease evolution to minimize synaptic and neuronal loss. ANN NEUROL 2010;67:317,324 [source] | |||||||||||||||||||||||||||||||