Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The conduction system of the heart was carefully examined at necropsy in two cases of rheumatoid arthritis and one of ankylosing spondylitis. All three patients had cardiac electrical instability and two fo the three died suddenly. The electrophysiological abnormalities of the three patients included paroxysmal atrial fibrillation in the first case, sustained atrial fibrillation with complete heart block and escape atrioventricular (A-V) junctional rhythm in the second case, and progressively increasing heart block eventually became complete in the third case. The sinus node exhibited extensive focal degeneration with and without associated inflammation in all three hearts, but the sinus node artery was not remarkably abnormal in any of these. All three hearts had important focal degenerative disease in the A-V node and His bundle, and in each of these there was marked narrowing of the local nutrient arteries, amounting to virtual occlusion in two hearts. The probable relationship of these postmortem histological findings to the electrocardiographic disturbances in each patient is discussed. Abnormalities in the cardiac conduction system of the hearts of these three patients are compared to ones previously reported for disseminated lupus erythematosus, polyarteritis nodosa, and scleroderma heart disease.
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PMID:De subitaneis mortibus. XXIII. Rheumatoid arthritis and ankylosing spondylitis. 83 14

Using a specific substrate, no leucocyte elastase activity could be detected in 55 synovial fluids, including 29 from patients with rheumatoid arthritis (RA). However, a high percentage of samples contained phagocytic inclusions of elastase, alpha 1-proteinase inhibitor (alpha 1-PI) and alpha 2-macroglobulin (alpha 2-MG) in both the polymorphonuclear (PMN) and mononuclear phagocytes. Immunofluorescence and indirect peroxidase-antiperoxidase staining of articular cartilage (ACA) from 52% of 21 patients with RA and one with juvenile RA (JRA) showed presence of elastase in the superficial layer of microscopically intact but proteoglycan depleted pannus-free ACA. In histologically altered pannus-free RA-ACA superficial elastase deposits were found in 24% of the cases. Adjacent ACA sections contained IgG, C3, alpha 1-PI and rarely alpha 2-MG. RA-ACA below or surrounded by pannus showed close contact with intact and decaying PMN in 62% and 48% of the cases, respectively. ACA specimens from patients with degenerative disease and systemic lupus were negative. These findings strongly suggest that PMN leucocyte elastase is operative in the degradation of RA-ACA and JRA-ACA, and that this activity is largely dependent upon the presence of entrapped immune complexes in such cartilage.
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PMID:Degradation in vivo of articular cartilage in rheumatoid arthritis by leucocyte elastase from polymorphonuclear leucocytes. 705 Dec 54

Chemokines and their receptors are essential in the recruitment and positioning of lymphocytes. To address the question of B cell migration into the inflamed synovial tissue of patients with rheumatoid arthritis (RA), peripheral blood naive B cells, memory B cells and plasma cells were analyzed for cell surface expression of the chemokine receptors CXCR3, CXCR4, CXCR5, CCR5, CCR6, CCR7 and CCR9. For comparison, B cells in the peripheral blood of patients with the autoimmune disease systemic lupus erythematosus (SLE) or with the degenerative disease osteoarthritis (OA) were analyzed. Expression levels of chemokine receptors were measured by flow cytometry and were compared between the different patient groups and healthy individuals. The analysis of chemokine receptor expression showed that the majority of peripheral blood B cells is positive for CXCR3, CXCR4, CXCR5, CCR6 and CCR7. Whereas a small fraction of B cells were positive for CCR5, practically no expression of CCR9 was found. In comparison with healthy individuals, in patients with RA a significant fraction of B cells showed a decreased expression of CXCR5 and CCR6 and increased levels of CXCR3. The downregulation of CXCR5 correlated with an upregulation of CXCR3. In patients with SLE, significant changes in CXCR5 expression were seen. The functionality of the chemokine receptors CXCR3 and CXCR4 was demonstrated by transmigration assays with the chemokines CXCL10 and CXCL12, respectively. Our results suggest that chronic inflammation leads to modulation of chemokine receptor expression on peripheral blood B cells. However, differences between patients with RA and patients with SLE point toward a disease-specific regulation of receptor expression. These differences may influence the migrational behavior of B cells.
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PMID:Differential expression of chemokine receptors on peripheral blood B cells from patients with rheumatoid arthritis and systemic lupus erythematosus. 1620 16

Major recent advances in the field of chromatin remodeling have dramatically changed our understanding of the ways in which genes are regulated. Epigenetic regulators such as histone deacetylases (HDACs) and histone acetyltransferases (HATs) are increasingly being implicated as direct or indirect components in the regulation of expression of neuronal, immune and other tissue specific genes. HDACs and HATs have been shown to play important roles in cell growth, cell cycle control, development, differentiation and survival. Mutations in genes that encode HDAC-binding proteins cause neurological disorders, such as MeCP2 mutations in Rett's syndrome. Mutations of CBP, a gene with HAT function, cause the mental retardation-associated Rubinstein-Taybi syndrome. Recently, HDAC inhibitors have been found to ameliorate progression of the spinal muscular atrophy (SMA) motor neuron disease and the Huntington disease mouse models. The neuroprotective role of HDAC inhibitors seems to extend to other diseases that share mechanisms of oxidative stress, inflammation and neuronal cell apoptosis. HDAC inhibitors also have widespread modulatory effects on gene expression within the immune system and have been used successfully in the lupus and rheumatoid arthritis autoimmune disease models. Recently, we demonstrated the efficacy of the HDAC inhibitor Trichostatin A in ameliorating disease in the multiple sclerosis (MS) animal model, experimental autoimmune encephalomyelitis (EAE). In this review we describe the current literature surrounding these inhibitors and propose a rationale for harnessing both their neuroprotective and anti-inflammatory effects to treat MS, an autoimmune, demyelinating and degenerative disease of the human central nervous system (CNS).
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PMID:Rationale for the use of histone deacetylase inhibitors as a dual therapeutic modality in multiple sclerosis. 1799 7

Osteoarthritis (OA) is a widespread degenerative disease of skeletal joints and is often associated with senescence in vertebrates. OA commonly results from excessive or abnormal mechanical loading of weight-bearing joints ('wear-and-tear'), arising from heavy long-term use or specific injuries; yet, in the absence of injury, the aetiology of OA remains obscure. We show that poor nutritional conditions experienced by moose (Alces alces) early in life are linked to greater prevalence of OA during senescence as well as reduced life expectancy. Moreover, we also found a negative relationship between kill rate by wolves (Canis lupus) and prevalence of OA, suggesting a potential connection between senescence of prey and the population ecology of predator-prey systems. This association between OA and early malnutrition also provides a basis for explaining the observation in anthropology that OA became more prevalent in native Americans as their diet become poorer - the result of relying more on corn and agriculture and less on hunting and gathering.
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PMID:Ecology of arthritis. 2061 43