Search results for "PATHOGENESIS"
showing 10 items of 761 documents
FRI0344 IL-9 and CD4+Il9+ T Lymphocytes Are over Expressed in the Synovium of Patients with Rheumatoid Arthritis, Elicited in Vitro by Citrullinated …
2014
Background Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by joint erosion and damage. Several cytokines and recruitment of auto-reactive lymphocytes (characterized by a marked shift toward the Th1 and Th17 phenotype) to inflamed tissue is a defined feature of the disease. In addition to Th1/Th17 and Th2 cells, another subset of effector T cells, identified by the potent production of IL-9 and named Th9 cells, has been recently demonstrated. IL-9 was found in particular to be increased before the clinical onset of the articular disease in RA patients, and associated with the presence of RA-related autoantibodies and circulating biomarkers of inflammation. The exact …
Cross-reactivity of a pathogenic autoantibody to a tumor antigen in GABA(A) receptor encephalitis
2021
Encephalitis associated with antibodies against the neuronal gamma-aminobutyric acid A receptor (GABA A -R) is a rare form of autoimmune encephalitis. The pathogenesis is still unknown but autoimmune mechanisms were surmised. Here we identified a strongly expanded B cell clone in the cerebrospinal fluid of a patient with GABA A -R encephalitis. We expressed the antibody produced by it and showed by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry that it recognizes the GABA A -R. Patch-clamp recordings revealed that it tones down inhibitory synaptic transmission and causes increased excitability of hippocampal CA1 pyramidal neurons. Thus, the antibody likely contributed to…
Importance of Propionibacterium acnes hemolytic activity in human intervertebral discs: A microbiological study
2018
Most patients with chronic lower back pain (CLBP) exhibit degenerative disc disease. Disc specimens obtained during initial therapeutic discectomies are often infected/colonized with Propionibacterium acnes, a Gram-positive commensal of the human skin. Although pain associated with infection is typically ascribed to the body's inflammatory response, the Gram-positive bacterium Staphylococcus aureus was recently observed to directly activate nociceptors by secreting pore-forming α-hemolysins that disrupt neuronal cell membranes. The hemolytic activity of P. acnes in cultured disc specimens obtained during routine therapeutic discectomies was assessed through incubation on sheep-blood agar. T…
Clostridium difficile Toxins Disrupt Epithelial Barrier Function by Altering Membrane Microdomain Localization of Tight Junction Proteins
2001
ABSTRACT The anaerobic bacterium Clostridium difficile is the etiologic agent of pseudomembranous colitis. C. difficile toxins TcdA and TcdB are UDP-glucosyltransferases that monoglucosylate and thereby inactivate the Rho family of GTPases (W. P. Ciesla, Jr., and D. A. Bobak, J. Biol. Chem. 273:16021–16026, 1998). We utilized purified reference toxins of C. difficile , TcdA-10463 (TcdA) and TcdB-10463 (TcdB), and a model intestinal epithelial cell line to characterize their influence on tight-junction (TJ) organization and hence to analyze the mechanisms by which they contribute to the enhanced paracellular permeability and disease pathophysiology of pseudomembranous colitis. The increase i…
Serum Dehydroepiandrosterone Sulfate and Risk for Type 2 Diabetes in Older Men and Women: The Pro.V.A Study
2016
Objective: A large body of clinical data suggests the importance of endogenous sex hormones in the pathogenesis of diabetes, but very little is known about the possible relationship between dehydroepiandrosterone sulfate (DHEAS) and diabetes, particularly in the elderly. We aimed, therefore, to examine whether high serum levels of DHEAS have any protective effects on the incidence of type 2 diabetes and to elucidate the possible role of gender in a cohort of older subjects. Methods: We followed 1258 community-dwelling subjects aged ≥65 years without type 2 diabetes who belonged to the Progetto Veneto Anziani (Pro.V.A.) for 4.4±1.2 years. DHEAS were measured at baseline and categorized into …
Evidence for a dysfunction and disease-promoting role of the circadian clock in the diabetic retina.
2021
Diabetic retinopathy is a major complication of chronic hyperglycemia and a leading cause of blindness in developed countries. In the present study the interaction between diabetes and retinal clocks was investigated in mice. It was seen that in the db/db mouse - a widely used animal model of diabetic retinopathy - clock function and circadian regulation of gene expression was disturbed in the retina. Remarkably, elimination of clock function by Bmal1-deficiency mitigates the progression of pathophysiology of the diabetic retina. Thus high-fat diet was seen to induce histopathology and molecular markers associated with diabetic retinopathy in wild type but not in Bmal1-deficient mice. The d…
Circulating immune complexes and platelet thromboxane synthesis in patients with insulin-dependent (type I) diabetes mellitus
1984
Platelets from diabetic subjects with circulating immune complexes (CIC) synthesized greater amounts of thromboxane than did platelets from CIC-negative patients or controls. In view of the known action of CIC on platelet function, a relationship between these two factors may be suggested in the initiation and progression of microangiopathy in diabetes.
The first comprehensive and quantitative analysis of human platelet protein composition allows the comparative analysis of structural and functional …
2012
AbstractAntiplatelet treatment is of fundamental importance in combatting functions/dysfunction of platelets in the pathogenesis of cardiovascular and inflammatory diseases. Dysfunction of anucleate platelets is likely to be completely attributable to alterations in posttranslational modifications and protein expression. We therefore examined the proteome of platelets highly purified from fresh blood donations, using elaborate protocols to ensure negligible contamination by leukocytes, erythrocytes, and plasma. Using quantitative mass spectrometry, we created the first comprehensive and quantitative human platelet proteome, comprising almost 4000 unique proteins, estimated copy numbers for …
Potential of Multidimensional, Large-scale Biodatabases to Elucidate Coagulation and Platelet Pathways as an Approach towards Precision Medicine in T…
2019
Cardiovascular and especially thrombotic diseases remain a major cause of morbidity and mortality worldwide. In past years, significant improvements in understanding disease processes, risk assessment, and prediction of clinical outcome in the field of thrombosis and haemostasis have been made by using large-scale biodatabases. These important research resources enable a comprehensive research approach by integrating clinical, environmental, genomic, and molecular information. Cutting edge, high throughput technologies open new data dimensions for clinical large-scale investigations. Joining multiple information levels from several pathophysiological pathways in contrast to a single marker …
Buerger`s Disease and Hyperhomocysteinemia: Is there a Relationship?
2009
Thromboangiitis obliterans, also known as Buerger's disease, is a cause of juvenile lower limb ischaemia. Buerger's disease is idiopathic and one of diagnostic criteria is the absence of atherosclerotic risk factors other than smok- ing. A possible involvement of thrombophilia has been investigated and the role of hyperhomocysteinemia is still matter of discussion. We describe 9 patients with Buerger's disease followed-up for the past 3 years. We found a significant in- crease in circulating homocysteine levels (mean: 31.6 in patients vs 8.2 μmol/L in control subjects). We also analyzed the C677T mutation of MTHFR; 5/9 Buerger's patients were heterozygotes and 4/9 homozygotes for the mutati…