Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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