Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031099 (periodontitis)
 12,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Connective tissue fibroblasts undergo cytopathic degenerative changes during certain long-term inflammatory diseases such as rheumatoid arthritis and periodontitis. The failure of inflamed tissues to repair properly may result from functional alterations of fibroblasts within the affected tissues. Numerous previous studies indicate that direct cytotoxicity by bacterial or other substances may be responsible for the cellular alterations observed in vivo. We have tested this hypothesis by exposing cultures of human diploid fibroblasts to homogenates of Actinomyces viscosus (a microorganism associated with periodontitis and capable of causing other chronic inflammatory diseases) and analyzing the effects on cell viability, morphology, and function. The cells bind and subsequently engulf relatively large quantities of the bacterial substances. These substances do not appear to be toxic to fibroblasts as determined by 51Cr release and microcytotoxicity assays, although there is a slight but significant decrease in protein synthesis (P less than 0.01) as measured by the incorporation of [14C]proline. However, collagen production was not altered, and the cytopathic alterations observed in diseased tissues in vivo did not occur in the exposed cells. These findings suggest that A. viscosus substances do not directly cause injury to connective tissue fibroblasts in periodontal disease but may, through cell-surface binding, mark these cells for subsequent immune-mediated damage.
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PMID:Morphological features and functional properties of human fibroblasts exposed to Actinomyces viscosus substances. 62 91

Phospholipase A2 (PLA2) is a proinflammatory enzyme in the synovial fluids of all--and sera of some--patients with rheumatoid arthritis. Due to the similarities in pathogenesis between rheumatoid arthritis and periodontitis, we sought to study the enzymatic properties of PLA2 in periodontal tissue. In this study, we demonstrated PLA2 activity in rat gingival tissue, about 80% of which was present in the cytosolic fraction. We characterized the cytosolic PLA2 enzyme with respect to substrate specificity, sensitivity to detergent, Ca2+ ion dependency and optimum pH. We found that phosphatidylethanolamine, rather than phosphatidylcholine, was the preferred substrate, the Ca2+ ion was essential for the expression of PLA2 activity, the enzyme was active over a broad pH range, with the optimum at pH 9.0, and sodium-deoxycholate inhibited the enzyme activity strongly in a concentration-dependent manner. These results are consistent with those which have been obtained with synovial fluid PLA2 and suggest that gingival PLA2 may be involved in the pathogenic processes of gingivitis and periodontitis.
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PMID:Phospholipase A2 in rat gingival tissue. 140 82

A group of cases is presented in which dramatic repair and regeneration of periodontal tissues lost as a result of periodontitis have occurred following systemic administration of tetracycline either alone or in combination with other forms of periodontal therapy. The nature and extent of regeneration demonstrated in these patients appears to be more dramatic than what has been shown previously when more conventional forms of periodontal therapy were utilized, even including bone grafting and guided tissue regeneration. The type of repair described has been shown in many instances to be long standing and is probably not totally related to the antibacterial characteristics of tetracycline. It is suggested that the ability of this drug to inhibit collagenolytic enzymes (collagenases) may have influenced the favorable clinical results achieved. The anti-collagenolytic properties of tetracycline are being considered with increasing frequency in the treatment of other systemic diseases characterized by collagen breakdown such as corneal ulcers, rheumatoid arthritis, diabetes, and dystrophic epidermolysis bullosa. Given the highly collagenous nature of the tissues of the periodontium, this report suggests that tetracycline could be of considerable value in the treatment of some types of periodontitis.
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PMID:Enhanced repair and regeneration of periodontal lesions in tetracycline-treated patients. Case reports. 164 89

This study investigated the occurrence of an autoantibody, IgM rheumatoid factor, that may result from the chronic inflammation noted in periodontal disease and rheumatoid arthritis. In order to detect IgM-RF, a biotin-avidin ELISA was developed. This assay was found to be sensitive and accurate by testing a rheumatoid arthritis population. The characteristics of this rheumatoid arthritis group were further determined, such that the total serum immunoglobulin concentrations were slightly elevated although within the normal range for IgM, IgG, and IgA; IgG antibody levels were elevated against oral microorganisms of the genus Capnocytophaga, while elevated IgM antibody levels were noted to Bacteroides species. In a population of 260 subjects of which 171 were periodontal disease patients, 16 of 171 (9.4%) were seropositive for IgM-RF, of which the predominant disease types were advanced destructive periodontitis and adult periodontitis. For comparison, a random population of seronegative periodontal disease patients was constructed that was matched for sex and approximate age to the seropositive group. The total immunoglobulin levels of the two groups were not significantly different and the means of both were slightly lower than the rheumatoid arthritis group. When the antibody profiles of the two periodontal disease populations were compared it became evident that the RF-positive group showed IgM and IgG antibody that was significantly elevated to Capnocytophaga species and F. nucleatum. Therefore, the chronic inflammation associated with periodontitis appears to increase significantly the formation of IgM-RF; however, there does appear to be a relationship between IgM-RF and elevated antibody to selected oral microorganisms.
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PMID:Rheumatoid factor (RF) distribution in periodontal disease. 189 Jan 63

Collagenases are known to be associated with tissue destruction in chronic inflammatory diseases such as periodontal diseases and rheumatoid arthritis. Collagenases are secreted by circulating inflammatory cells (polymorphonuclear leukocytes and monocytes), resident mesenchymal cells and epithelial cells in latent forms, which can be activated by proteases and compounds reacting with protein thiol groups. We have studied here the effects of oxygen-derived free radicals (ODFR) on latent human neutrophil collagenase. Also, in order to elucidate the cellular sources of collagenases, the ability of human gingival crevicular fluid (GCF) collagenases both from adult periodontitis (AP) and localized juvenile periodontitis (LJP) patients to degrade soluble interstitial collagen types I and II was studied. ODFR generated by the xanthine oxidase/hypoxanthine system in the presence of trace amounts of iron and EDTA activated latent neutrophil collagenase to an equal extent as the known activators phenylmercuric chloride and gold thioglucose. ODFR activation was inhibited by desferoxamine and mannitol as well as by superoxide dismutase and catalase. Clear differences in the susceptibility of collagen types I and II to AP and LJP GCF collagenases were observed. AP GCF collagenase degraded type I and II collagens at equal rates, resembling the substrate-specificity of human neutrophil collagenase. LJP GCF collagenase degraded type I collagen considerably faster than type II collagen, which was only negligibly degraded. This corresponds to the substrate specificity of fibroblast collagenase. Zymographic evaluation of gelatinolytic proteases showed the presence of 90 and 68 kD gelatinases in both AP and LJP GCF. Non-proteolytic means apparently provide a potent activation pathway of neutrophil collagenase in vivo and the hydroxyl radical was identified to be one of the potent activating oxidants.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Non-proteolytic activation of latent human neutrophil collagenase and its role in matrix destruction in periodontal diseases. 256 61

The relationship between human leukocyte antigens (HLA) determinants and periodontitis has been examined by several authors without showing any particular pattern. However, no study has investigated the HLA-D determinants, which are generally associated with immune disorders, and rapidly progressive periodontitis (RPP). The HLA profile of 10 RPP patients was compared with that of a healthy control population (n = 120). Although no significant difference was found for HLA-A, HLA-B, and HLA-C, HLA-DR4 of the HLA-D group was found in 80% of patients but only in 38.3% of controls. A high frequency of HLA-DR4 has been reported in rheumatoid arthritis (RA) patients. This finding may be significant in light of previous reports highlighting similarities between RA and periodontal disease.
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PMID:Human leukocyte antigen (HLA) DR4. Positive association with rapidly progressing periodontitis. 349 13

The effect of bradykinin and desArg9-bradykinin on bone was studied in cultures of calvarial bones taken from 6-7-day-old mice. Bradykinin, at and above a 3-nM concentration, caused a dose-dependent stimulation of bone mineral mobilization and matrix degradation. Bradykinin-stimulated resorption was inhibited by calcitonin, an increased concentration of phosphate in the culture medium, hydrocortisone, dexamethasone, indomethacin, meclofenamic acid, naproxen, and 5, 8, 11, 14-eicosatetraenoic acid. The results suggest that bradykinin stimulates osteoclast-mediated bone resorption by a process that is dependent on endogenous prostaglandin production. The stimulatory effect of bradykinin, but not of parathyroid hormone and prostaglandin E2, was potentiated by the angiotensin-converting enzyme inhibitor, BPP5a. Treatment with carboxypeptidase B did not affect the capacity of the peptide to stimulate 45Ca release. DesArg9-bradykinin (1 mumole/liter) stimulated 45Ca release to the same degree as did bradykinin. Bradykinin (3 microM) did not affect the degradation of cartilage proteoglycans, as assessed by the release of 35S-sulfate from prelabeled calf articular cartilage in organ culture. These findings suggest that generation of bradykinin in inflammatory lesions of rheumatoid arthritis and periodontitis may contribute to the bone resorptive process seen in the joints and alveolar bone; however, bradykinin does not directly activate chondrocytes into a catabolic state.
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PMID:Bradykinin, a new potential mediator of inflammation-induced bone resorption. Studies of the effects on mouse calvarial bones and articular cartilage in vitro. 359 36

One child and one adult with severe periodontitis were investigated for relevant systemic factors and predominant periodontal pocket bacteria. The child had a chronic neutropenia, the adult late yaws, a chronic iron deficiency and possibly rheumatoid arthritis. The predominant organisms in both pocket floras were gram-negative cocci showing occasional filament formation and resembling strains of Bacteroides asaccharolyticus and possibly Actinobacillus actinomycetemcomitans described by others. There were indications that the flora was determined by the host response rather than vice versa and that thorough systemic investigation may aid the efficient diagnosis and treatment of patients with severe periodontitis.
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PMID:Plaque-host imbalance in severe periodontitis. A discussion based on two cases. 657 40

A soluble extract from Actinobacillus actinomycetemcomitans (designated strain Y4) caused dose-dependent cytotoxic changes in PMN isolated from the gingival crevices (C-PMN) of normal adults. When the toxin was preincubated with sera from patients with juvenile periodontitis, there was a significant inhibition of toxic activity. In contrast a variety of other sera from normal subjects with healthy gingiva, and from patients with chronic gingivitis, chronic periodontitis, recurrent herpes labialis, rheumatoid arthritis, or ulcerative colitis enhanced the leukotoxic activity. The neutralization of toxin by serum from patients with juvenile periodontitis was probably due to specific antibodies. Since Actinobacillus actinomycetemcomitans organisms can be frequently identified in subgingival plaque from patients with juvenile periodontitis, the capacity of Y4 toxin to kill C-PMN may contribute to the pathogenesis of this disease.
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PMID:Leukotoxicity of an extract from Actinobacillus actinomycetemcomitans for human gingival polymorphonuclear leukocytes. 722 51

Inflammation-induced localized bone resorption in diseases such as marginal and apical periodontitis, rheumatoid arthritis, and osteomyelitis is due to activation and recruitment of osteoclasts by locally produced cytokines and inflammatory mediators. Thus several interleukins (1, 3, 4, 6, and 11), tumor necrosis factors (alpha, beta), colony-stimulating factors (M and GM), leukemia inhibitory factor, gamma-interferon, and transforming growth factor-beta have effects on bone resorption and bone formation in vivo and in vitro. The kallikrein-kinin system and the coagulation cascade are also activated in inflammation. We have found that peptides produced in the kallikrein-kinin system (bradykinin, kallidin) and thrombin, the end product in the coagulation cascade, can stimulate bone resorption in vitro. The stimulatory effect of bradykinin is linked both to B1 and B2 bradykinin receptors. Both kinins and thrombin stimulate prostaglandin biosynthesis in bone parallel with the bone resorptive effect. The stimulatory effect of bradykinin on bone resorption is completely lost when the prostaglandin response is abolished, whereas thrombin can stimulate bone resorption both via prostaglandin-dependent and independent mechanisms. In addition, bradykinin and thrombin act in concert with interleukin-1 to synergistically stimulate bone resorption and prostaglandin biosynthesis. We also have found that one of the acute-phase reactants, haptoglobin, can stimulate bone resorption in vitro, indicating the possibility of generalized bone loss in chronic inflammatory diseases. Moreover, haptoglobin synergistically potentiates bradykinin-induced and thrombin-induced prostanoid biosynthesis in osteoblasts. These observations indicate that the rate of bone resorption in inflammation-induced bone loss may not be due to a single factor but to the concerted action of several local or systemic factors.
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PMID:Regulation of bone metabolism by the kallikrein-kinin system, the coagulation cascade, and the acute-phase reactants. 752 72


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