Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014118 (endocarditis)
 15,629 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Viridans streptococci are a heterogeneous group of gram-positive bacteria that are normal inhabitants of the mouth. These organisms are thought to contribute significantly to the etiology of infective endocarditis, although recently they have been implicated in serious infections in other settings. Another group of oral bacteria, gram-negative anaerobes, is associated with chronic dental infections, such as periodontal diseases or endodontic lesion formation. We evaluated the ability of the oral pathogens Streptococcus mutans and Porphyromonas endodontalis to induce a pathogenic response in vivo, with the goal of quantifying the inflammatory response in soft tissue by measuring leukocyte recruitment and hard tissues by measuring osteoclastogenesis. S. mutans induced a strong inflammatory response and was a potent inducer of osteoclast formation, while P. endodontalis was not. To further study the mechanisms by which P. endodontalis and S. mutans elicit significantly different levels of inflammatory responses in vivo, we tested the capacity of each to induce production of cytokines by mononuclear cells in vitro. S. mutans stimulated high levels of interleukin-12 (IL-12), gamma interferon (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha), all of which are associated with inflammation, enhanced monocyte function, and generation of a Th1 response. In contrast, P. endodontalis stimulated production of IL-10 but not of TNF-alpha, IL-12, or IFN-gamma. These results demonstrate that oral pathogens differ dramatically in their abilities to induce inflammatory and immunoregulatory cytokines. Moreover, there is a high degree of correlation between the cytokine profile induced by these bacteria in vitro and their pathogenic capacity in vivo.
 ...
PMID:Bacterium-dependent induction of cytokines in mononuclear cells and their pathologic consequences in vivo. 1022 64

Cardiovascular disease is on the rise. In India and other developing countries, rheumatic heart disease (RHD) continues to be a major public health problem and contributes to significant cardiac morbidity and mortality. RHD in the juvenile age group namely juvenile mitral stenosis is a variant which is unique to the Indian subcontinent. Severe valve deformities lead to high morbidity and mortality. Despite various measures no appreciable decline in prevalence of RHD has been documented. At autopsy, mitral valve was most commonly affected either alone or in combination with aortic and tricuspid valves. Both functional and organic involvement of tricuspid valve was documented. It has been convincingly demonstrated that molecular mimicry between Streptococcus pyogenes antigen and human proteins lead to autoimmune reactions both humoral and cell mediated causing RF/RHD. Heart tissues namely the valves, left atrial appendage (LAA) and myocardium reveal variable amounts of infiltration by lymphocytes. Significant endocarditis and valvulitis is observed in these cases. CD4+ T cells are most likely the ultimate effectors of chronic valve lesions in RHD. They can recognize Streptococcal M5 protein peptides and produce various inflammatory cytokines such as TNF-alpha, IFN-gamma, IL-10, IL-4 which could be responsible for progressive fibrotic valvular lesions. Cardiac myosin has been defined as a putative autoantigen recognized by autoantibodies of RF patients. Cross reactivity between cardiac myosin and group A beta hemolytic Streptococcal M protein has been adequately demonstrated. Cardiac myosin has been shown to produce myocarditis in rats and mice. Valvulitis/ endocarditis has been observed in excised LAA, cardiac valves and in hearts at autopsy from cases of RHD. The disease predominantly affects the valvular endocardium culminating in crippling valve deformities. Endocardial infiltrate and their migration into the valve substance has been elegantly demonstrated in rats and mice. Immune responses against cardiac myosin lead to valvular heart disease and infiltration of the heart by Streptococcal M protein reactive T lymphocytes. Mitral valves showed various degrees of calcification. An interesting observation is the nature of calcification in diseased/distorted valves in RHD. Recent studies indicate that calcification is not merely an inactive, "dystrophic" process but involves a regulated inflammatory process associated with expression of osteoblast markers and neoangiogenesis. Increased plasma osteopontin levels correlated with severity of mitral valve calcification. Further evidence of inflammation is supported by high levels of advanced oxidation protein products and high sensitive C-reactive protein in plasma detected in patients with RHD. Presence of inflammatory cells and increased expression of several cytokines in cases of "end stage" RHD reflects a possible subclinical, ongoing insult/injury to some unrecognized antigenic stimulus by beta hemolytic Streptococcal antigens that have sensitized/primed the various target tissues and which further culminate in permanent valve deformities.
 ...
PMID:Pathology and pathogenesis of rheumatic heart disease. 1830 30