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)

Enzyme activity in whole saliva of trypsin-like protease, elastase-like protease, general protease, and three glycosidases was measured by colorimetric assays, using synthetic substrates. A study group of 24 adults with advanced periodontitis was compared to a control group of 25 subjects with healthy periodontium. Clinical parameters and levels of enzyme activity were assessed at baseline, after non-surgical periodontal therapy (at 8 months), following the maintenance phase or periodontal surgery (at 15 months), and after the maintenance phase with or without systemic chemotherapy (at 20 months). The mean values of the proteolytic enzymatic activity and the activity of two glycosidases in whole saliva were significantly higher in the study group than in the control group at baseline. After the initial treatment phase at 8 months, all three proteases were reduced significantly, but the glycosidases were still high. After all treatment phases at 20 months, the activity of both the proteases and glycosidases approximated the values of the healthy group. In the saliva samples collected prior to treatment and following non-surgical periodontal therapy, the activity of salivary elastase correlated significantly with the number of deep gingival pockets (PD > or = 6 mm) and with either gingival index (GI) or the percentage of bleeding sites (BOP%). The enzyme activity in whole saliva appears to reflect the status of periodontal health. Salivary elastase shows good potential to serve as a novel adjunct to detect destructive periodontal inflammation and to follow periodontal healing after treatment.
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PMID:The effect of treatment on the activity of salivary proteases and glycosidases in adults with advanced periodontitis. 848 92

A total of 259 Gram-negative Porphyromonas-like rods isolated from subgingival plaque samples of 16 family-owned dogs with naturally occurring periodontitis were characterized phenotypically by biochemical reactions, metabolic end products and enzymatic activities (API-ZYMTM, RoscoTM). Four distinct groups were found. Group A isolates (63) were asaccharolytic, lipase negative, trypsin positive and produced phenylacetic acid (PAA) from peptone-yeast extract glucose broth. Unlike P. gingivalis strains they were catalase positive. Group B isolates (42) differed from those of group A by a positive lipase reaction and from those of group D by failing to ferment sugars. Group C isolates (88) were asaccharolytic and did not produce PAA. They were alpha-fucosidase, N-acetyl-beta-glucosaminidase (beta-NAG) and trypsin negative, resembling P. endodontalis, but unlike human isolates, they were catalase positive. Subgroup C.1 isolates (6) differed from those of parent group C by producing minor amounts of PAA, and subgroup C.2 isolates (12) were beta-NAG positive. Group D isolates (46) were weakly fermentative, lipase, catalase and trypsin positive, and produced PAA. They resembled the B (P.) salivosus type strain which, in our hands, fermented weakly glucose, lactose and mannose. Two isolates could not be assigned to any of the previous groups.
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PMID:Porphyromonas-like gram-negative rods in naturally occurring periodontitis in dogs. 851 57

The anaerobic bacterium Porphyromonas gingivalis has been implicated as a primary causative agent in adult periodontitis. Several proteinases are produced by this bacterium, and it is suggested that they contribute to virulence and to local tissue injury resulting from infection by P. gingivalis. Cysteine proteinases with specificities to cleave either Arg-X or Lys-X peptide bonds (i.e., gingipains) have been characterized as predominant enzymes associated with vesicles shed from the surface of this bacterium. It has recently been demonstrated that these proteinases are capable of degrading the blood complement component C5, resulting in the generation of biologically active C5a. By using an affinity-purified rabbit antibody raised against residues 9 to 29 of the C5a receptor (C5aR; CD88), we demonstrate that noncysteinyl proteinases associated with vesicles obtained from P. gingivalis cleave the C5aR on human neutrophils. Proteolytic attack of the C5aR by enzymes from the P. gingivalis vesicles was inhibited by TPCK (tolylsullonyl phenylalanyl chloromethyl ketone), PMSF (phenylmethylsulfonyl fluoride), and dichloroisocoumarin, suggesting that serine proteinases are primarily responsible for this degradative activity. The purified vesicle proteinase Lys-gingipain but not Arg-gingipain also cleaved the N-terminal region of the C5aR on the human neutrophils. Lys-gingipain activity was essentially resistant to these inhibitors but was inhibited by TLCK (Nalpha-p-tosyl-L-lysine chloromethyl ketone) and iodoacetamide. A synthetic peptide that mimics the N-terminal region of C5aR (residues 9 to 29; PDYGHY DDKDTLDLNTPVDKT) was readily cleaved by chymotrypsin but not by trypsin, despite the presence of two potential trypsin (i.e., lysyl-X) cleavage sites. The specific sites of cleavage in the C5aR 9-29 peptide were determined by mass spectroscopy for both chymotrypsin and Lys-gingipain digests. This analysis demonstrated that the C5aR peptide is susceptible to cleavage at both potential Lys-gingipain sites (i.e., between residues 17 and 18 [K-D] and 28 and 29 [K-T]) and at two chymotrypsin sites (between residues 14 and 15 [Y-D] and 20 and 21 [L-D]), respectively. These studies suggest that P. gingivalis contains at least two enzymes capable of cleaving the C5aR, Lys-gingipain and a second nontryptic serine proteinase that is distinct from either Arg- or Lys-gingipain.
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PMID:Proteolytic inactivation of the leukocyte C5a receptor by proteinases derived from Porphyromonas gingivalis. 867 97

Gingival crevicular fluid (GCF) contains several different proteinase activities and the study sought to clarify their sources. Gingival tissue and GCF were collected from chronic periodontitis patients. Gel-filtration chromatography of crude tissue extracts yielded cathepsin B and tryptase fractions sensitive to cysteine and serine proteinase inhibitors, respectively. Cell sonicates of suspected periodontal pathogens were prepared from broth cultures of reference strains. Of these, Porphyromonas gingivalis showed much the strongest activity and this had an effector response consistent with the metal-dependent cysteine proteinase described by others. Banding patterns in GCF, tissue and bacterial samples were compared on substrate-impregnated overlay membranes applied to isoelectric focusing gels. On Z-Val-Lys-Lys-Arg-AFC overlays, GCF had bands corresponding to tissue cathepsin B and the enzyme from P. gingivalis, though a contribution from Treponema denticola could not be ruled out. Use of D-Val-Leu-Arg-AFC overlays showed GCF activity similar to tissue tryptase. In GCF there were additional bands that did not correspond to any tissue or bacterial samples and on Z-Ala-Ala-Lys-AFC overlays these closely resembled activity in parotid saliva. The results confirmed that GCF contains tissue cathepsin B and tryptase, while the apparent presence of enzymes from P. gingivalis and possibly T. denticola is consistent with previous reports linking activity to these organisms. The saliva bands demonstrated that contamination of GCF may occur despite rigorous collection procedures.
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PMID:A comparison of cysteine and serine proteinases in human gingival crevicular fluid with tissue, saliva and bacterial enzymes by analytical isoelectric focusing. 880 1

In our previous study, we reported that only 13 of 46 adult patients with advanced periodontitis responded well to initial non-surgical periodontal therapy. In the present follow-up study, the remaining 33 patients were randomly treated further using either modified Widman flap surgery or systemic metronidazole. The patients responding unsatisfactorily to this 2nd treatment phase, received supplementary systemic chemotherapy or surgery, respectively. By using this study design, we determined which baseline clinical variables and/or laboratory findings predicted the treatment outcome in these study patients. Clinical variables included the assessment of bleeding, suppuration, probing pocket depth, furcation lesions, relative attachment level and radiographic infrabony defects. Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were cultured from subgingival plaque samples. The specific IgG and IgA antibody levels against 5 serotypes of A. actinomycetemcomitans were determined in serum and saliva. Elastase-like, trypsin-like and general protease activities were assessed from saliva. The bivariate statistical analyses showed that the most pronounced difference between the patients responding well to initial non-surgical therapy (group MC, n = 13), to either supplementary surgery or chemotherapy (group FT1, n = 11), or those responding to the complex therapy (group FT2, n = 17), was the prior extent of periodontal destruction expressed as the proportion of > or = 6 mm deep periodontal pockets. When multiple linear regression was used to investigate the influence of clinical and laboratory findings on the variation of treatment response between the 3 groups, the most significant explanatory factor was the simultaneous presence of subgingival A. actinomycetemcomitans and multiple deep periodontal pockets. None of the immunological or biochemical variables used had any further influence in the model. Pretreatment microbiological examination, especially for the detection of A. actinomycetemcomitans, seems to be a valuable laboratory screening method for identifying complex treatment need in adult patients with advanced periodontitis. However, the evaluation of the extent and pattern of periodontal breakdown remains crucial for choosing the treatment strategy including surgery and/or chemotherapy in A. actinomycetemcomitans-infected adult periodontitis patients.
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PMID:Value of some laboratory and clinical measurements in the treatment plan for advanced periodontitis. 881 78

The anaerobic bacteria P. gingivalis has been implicated as a primary causative agent in adult periodontitis. Several proteinases are produced by this bacteria and it is suggested that they contribute to virulence and to local tissue injury resulting from infection by P. gingivalis. Collagenases and cysteine proteinases (i.e., the gingipains) have been characterized as the predominant vesicular enzymes produced by this bacterium. It has been shown that an arginine-specific cysteine proteinase from P. gingivalis, called gingipain-1 or Arg-gingipain, can selectively cleave complement components C3 and C5. In the case of C5, cleavage by Arg-gingipain results in the generation of C5a, a potent chemotactic factor for PMNs. Since these bacterial proteinases are capable of generating pro-inflammatory factors at sites of infection, we examined the possibility that gingipains or other proteinases from this bacterium might attack or destroy cell surface proteins, such as receptor molecules. Using an affinity-purified rabbit antibody raised against residues 9-29 of the C5a receptor (i.e., C5aR; CD88), the signal transmitting element for the pro-inflammatory mediator C5a, we demonstrated that the mixture of proteinases in P. gingivalis vesicles cleaves the C5a receptor on human neutrophils. This vesicular proteinase activity did not require cysteine activation which indicates that proteinases other than the gingipains may be responsible for cleavage of the C5aR molecule. in addition, the purified Lys-gingipain, but not Arg-gingipain, also cleaved C5aR on the human neutrophils. The N-terminal region of CaR (residues 9-29, PDYGHYDDKDTLDLNTPVDKT) was readily cleaved by chymotrypsin, but not by trypsin, despite the presence of potential trypsin (i.e., lysyl-X) cleavage sites. The specific sites of C5aR 9-29 peptide cleavage were determined by mass spectroscopy for both chymotrypsin and Lys-gingipain. These studies suggest that the proteolytic activity in the bacterial vesicles that is responsible for cleaving C5aR is primarily a non-tryptic proteinase, distance from either Arg- or Lys-gingipain. Consequently, there appear to be additional proteinase(s) in the vesicles that attacks the cell surface molecule C5aR which are not the same (i.e., Arg- and Lys-gingipain) as were shown to generate pro-inflammatory activity from complement components C3 and C5. Evidence that the proteinases which attack the inflammatory precursor molecules (i.e., C3 and C5) exhibit different specificities than those that attack receptors to these bioactive complement products makes a particularly interesting story of how this bacteria avoids major host defense mechanisms. It is well known that generation of pro-inflammatory factors such as C3a and C5a at extra-vascular sites can promote edema, leukocyte recruitment and cellular activation responses that could lead to the release of toxic oxygen products and to phagocytosis of the bacteria. Destruction of receptors to these cellular activating factors generated by bacterial proteinases may eliminate the ability of these (i.e., complement-derived) and other mediators to carry out their anti-bacterial actions and thereby limit the host's defense mechanisms in responses to the infecting bacteria. The concept of anti-bacterial responses (i.e., oxygen radical generation and phagocytosis) being effectively eliminated at the injury site, by bacterial proteinases acting at the cellular receptor level, has not been studied in detail. In this case, the situation is particularly unusual because, once the bacterial gingipains generate potent plasma-derived inflammatory factors that can enhance edema and deliver essential nutrients to the bactgeria, other bacterial proteinases may destsroy their cellular receptors. These receptors transmit the signal activation mechanisms in the infiltrating cells that elicit bacterial killing.(ABSTRACT TRUNCATED)
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PMID:Cleavage of the human C5A receptor by proteinases derived from Porphyromonas gingivalis: cleavage of leukocyte C5a receptor. 886 Oct 6

The immunodominant antigens of Porphyromonas gingivalis 381 whole cells that reacted with sera from high-responder patients were examined in this study. Whole cells, phenol-water extracted lipopolysaccharide, and fimbriae from P. gingivalis 381 were analyzed using sera from 14 patients with adult periodontitis, rapidly progressive periodontitis or juvenile periodontitis as well as from two healthy subjects. Western blot analysis and enzyme-linked immunosorbent assay (ELISA) were performed. On Western blots, among many prominent protein bands, a smear was observed which was removed after adsorption of the sera with P. gingivalis phenol-water extracted lipopolysaccharide. Two major protein bands of 43 kDa and 41 kDa were found to be prominent even at very high dilutions of sera, the latter of which showed the same molecular weight as the fimbrilin band. These two bands were resistant to treatment by papain and trypsin. ELISA titers remained high after adsorption of the sera with P. gingivalis phenol-water extracted lipopolysaccharide. The results of this study suggest that the 43-kDa and the fimbrilin (41 kDa) proteins may play an important role as immunodominant antigens of P. gingivalis 381.
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PMID:Characterization of the immunodominant antigens of Porphyromonas gingivalis 381 in high-responder patients. 900 75

Porphyromonas gingivalis contains exceedingly high concentrations of cysteine proteinases with trypsin-like activity which have been implicated as virulence factors in adult-onset periodontitis. These enzymes, referred to as gingipains, cleave protein and peptide substrates after arginine (gingipain R) and lysine residues (gingipain K), and it has been found that neither is easily inhibited by host proteinase inhibitors. Examination of the properties of each proteinase clearly indicates a role(s) for both in the dysregulation of a number of normally tightly controlled pathways. The effects of such uncontrolled proteolysis are the development of edema (kallikrein/kinin pathway activation by gingipain R), neutrophil infiltration (complement pathway activation by gingipain R), and bleeding (degradation of fibrinogen by gingipain K). Since three of the major hallmarks of periodontitis involve increased crevicular flow, neutrophil accumulation at infected sites and bleeding on probing, it seems likely that both P. gingivalis-derived proteinases are important virulence factors in the development of periodontal disease.
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PMID:Porphyromonas gingivalis proteinases as virulence factors in the development of periodontitis. 908 21

As a diagnostic test, "Periocheck" can detect the N-carbobenzoxyglycyl-glycy-arginyl peptidase that is produced by Treponema denticola, Porphyromonas gingivalis, and Bacteroides forsythus. The aim of this study was to clarify the relationship between peptidase activity and attachment loss. After Phase 1 and surgical therapy, a total of 111 sites from 47 adult periodontitis patients were divided into four groups according to peptidase activity (trypsin unit, TU): A, < 0.1 TU; B, 0.1-0.2 TU; C and D > or = 0.2 TU. All sites in groups A, B, and C were untreated, whereas both subgingival 3% hydrogen peroxide irrigation and 2% minocycline application were undertaken every 45 days throughout the experiment in group D. All subjects were recalled at 3-month intervals. Peptidase activity and clinical assessments were measured for the 18-month period. Significant attachment loss associated with high values of the peptidase activity was found through the experimental period in groups B and C. In contrast, no obvious change of attachment loss was found in groups A and D following low peptidase activity at 6, 12, and 18 months. The mean attachment loss throughout the 18-month period was 0.22 mm in group A, 1.04 mm in group B, 1.53 mm in group C, and -0.35 mm in group D. Probing depth and percentages of bleeding on probing significantly increased in group C, whereas they decreased in group D. This peptidase test displayed a 77.8% sensitivity and 68.6% specificity regarding the detection of > or = 1 mm attachment loss with a cut-off value of 0.1 TU. Multiple linear regression analysis showed a close relationship between peptidase activity and predictable attachment loss within a 12-month period. These findings suggest that this peptidase test is useful in identifying the risk sites for predictable attachment loss.
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PMID:Relationship between peptidase activity from Treponema denticola, Porphyromonas gingivalis, and Bacteroides forsythus and attachment loss. 911 69

Counts of cultivable Porphyromonas gingivalis, assays of microbial proteases and the concentration in gingival crevicular fluid of proteoglycan metabolites were investigated at periodontitis and gingivitis sites in 16 patients with chronic adult periodontitis before and after treatment. Two periodontitis sites and two gingivitis sites were selected from each patient on the basis of a clinical examination. Gingival crevicular fluid from each site was analysed for the concentrations of the glycosaminoglycans chondroitin-4-sulphate and hyaluronan and subgingival plaque samples were analysed for cultivable P. gingivalis and microbial trypsin-like proteases assayed by benzoyl-DL-arginine-naphthylamide (BANA) hydrolysis. Significantly higher concentrations (p = 0.007) of chondroitin-4-sulphate were found at periodontitis than gingivitis sites but there was no significant difference in hyaluronan (p = 0.36) between these sites. Although the majority of periodontal sites were P. gingivalis-negative (23/32), there were significantly higher concentrations of chondroitin-4-sulphate (p = 0.05) and hyaluronan (p = 0.04) at the P. gingivalis-positive, compared to negative, periodontitis sites. At BANA-positive periodontitis sites there were also higher concentrations of chondroitin-4-sulphate (p = 0.0015) and hyaluronan (p = 0.0001) than at BANA-positive gingivitis sites. There was a significant decrease in concentrations of chondroitin-4-sulphate and hyaluronan at periodontitis sites after treatment. This study lends support to the hypothesis that P. gingivalis may be actively involved in the destruction of connective tissue components at culture-positive sites but shows that elevated concentrations of connective tissue breakdown products may occur in gingival crevicular fluid from periodontal sites where this organism is absent.
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PMID:The relationship between microbial factors and gingival crevicular fluid glycosaminoglycans in human adult periodontitis. 913 20


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