Biomedical subjects
Publications and source records attributed to R C Page.
Radiographic, gross, and histologic evidence is provided to demonstrate the development of caries and periodontal disease over a 5-year period in an unerupted tooth. The authors speculate on the pathogenesis of these disease processes.
Type I trimer is a collagen species, which is synthesized by many cell types under abnormal conditions or when derived from pathologically altered tissues, and by embryonic cell types. In order to investigate the susceptibility of type I trimer to mammalian collagenases, renatured type I trimer and type I collagens were incubated with human fibroblast and neutrophil enzymes and enzyme degradation was followed by viscometry and by polyacrylamide gel electrophoresis. A comparison of reaction rates determined by viscometry revealed that the type I trimer was degraded at less than one-fifth the rate of type I collagen by both enzymes. The human fibroblast collagenase had Km values of 8.4 +/- 1.6 and 6.3 +/- 0.7 microM for the type I trimer and type I collagens, respectively. These values were not significantly different. However the type I trimer had a kcat value of 10.6 +/- 2.0/hour which was only one fifth of 51.2 +/- 5.5/hour obtained for the type I collagen. From these results we conclude that the type I trimer collagen is a poor substrate for the skin and PMN collagenases relative to type I.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Extensive clinical, laboratory and microbiological studies were performed on members of a family with an unusually high prevalence of early-onset severe periodontitis. Clinical observations included intraoral photographs and assessment of inflammation, plaque, probing depths and bone loss. Pocket bacteria were sampled, cultivated and identified. Immunological studies included assessment in vitro of neutrophil (PMN) and monocyte (MN) chemotaxis, assessment of PMN phagocytosis and other functions using the iodination assay, measurement of serum opsonic and chemoattractant activities and determination of levels of serum antibodies specific to various putative periodontal pathogens. The proband, a 19-year-old white woman, had rapidly progressive periodontitis (RP). Of her six siblings available for study, all had juvenile periodontitis (JP), and both parents had been edentulous since early adulthood. Early edentulism and recurrent infections, especially otitis media, were prevalent in the forebearers, especially on the maternal side. Two married sisters of the proband had young male children with recurrent infections. Abnormalities in leukocyte chemotaxis were found in the proband, in two of her siblings and in both parents. The pocket flora was predominantly Gram-negative, anaerobic rods with a high prevalence of Bacteroides species, and serum antibodies specific to Bacteroides species were detected in the sera of five of the seven patients studied. Actinobacillus actinomycetemcomitans was not found in any of the pockets studied, nor were antibodies specific to any of the three known serotypes of this bacterium detected in the serum of any of the patients. There was a relatively good correlation between the bacterial species isolated from the periodontal pockets and the antibodies found in the serum. PMN iodination and serum opsonic activity were normal in all of the patients. Thus not all JP patients have detectable Actinobacillus species in their periodontal pockets, nor do all have antibody detectable with the techniques we used specific to these bacteria in their serum. In contrast, JP patients may have Bacteroides species in their periodontal pockets and antibody specific to Bacteroides species in their serum. Although abnormal leukocyte chemotaxis is generally common in RP and JP patients, in this family the correlation between this defect and the presence of these diseases was poor.
Explore the source record for details and available documents.
The biosynthesis of type V collagen and its regulation were studied using diploid human gingival fibroblasts. Cells were metabolically labeled with radioactive amino acids and labeled proteins were subjected to limited pepsin digestion, DEAE-cellulose chromatography at 15 degrees C, and polyacrylamide gel electrophoresis. Proteins eluted from DEAE-cellulose columns by 0.25 M NaCl contained a collagen species which was resistant to mammalian collagenase and had alpha chains with hydroxylysine/lysine ratios and CNBr peptide patterns similar to alpha 1(V) and alpha 2(V). Procollagen(V) fractions obtained by DEAE-cellulose chromatography and immunoprecipitates of type V collagen antibody contained polypeptides with Mr = 239,000, 219,000, 198,000, 174,000, 157,000, and 132,000. By comparing the CNBr peptide maps of these proteins with those of standard alpha 1(V) and alpha 2(V) chains, the first three polypeptides were shown to be related to alpha 1(V) and the others to alpha 2(V). It was concluded that the gingival fibroblasts synthesize type V collagen, that the pro alpha 1(V) and the pro alpha 2(V) chains have Mr = 239,000 and 174,000, respectively, and that the alpha 1(V) and alpha 2(V) chains laid in the form of fibrils have Mr = 198,000 and 132,000, respectively. A detectable amount of type V collagen was synthesized only at high cell density, and it was associated with the cell layer. The amount and proportion of type V synthesized were increased when the cells were labeled in the presence of serum, and the increase was accompanied by a decrease in type III. This effect was dependent on serum concentration. Serum obtained from platelet-poor plasma failed to elicit this effect, and it was restored by the addition of platelet-derived growth factor. Platelet-derived growth factor was effective in medium with and without platelet-poor serum. Thus, it appears that platelet-derived growth factor may be an important regulatory factor in the synthesis of types V and III collagens.
Biochemical alterations in the connective tissue matrix are a common feature of many diseases, and they account in major part for their functional impairment. Such alterations are especially important in acute and chronic inflammatory diseases where they may take the form of degradation of matrix components or their excessive accumulation leading to fibrosis. Although a wealth of morphologic information is available, very little is known about these changes at the biochemical level. Using human gingival tissue as a model, we have carried out studies aimed at assessing the effects of chronic inflammation on the collagen isotypes comprising the connective tissue matrix. Tissue obtained from patients undergoing surgical treatment for periodontitis was separated on the basis of clinical features into healthy and inflamed portions. After confirming the inflammatory status of each specimen histologically, each set of tissue pairs was extracted at 4 degrees C in 0.5 M acetic acid containing 1 mg/ml of pepsin, and the extracted collagens were fractionated with NaCl. Alpha chains were separated by polyacrylamide slab gel electrophoresis, and methods devised for their quantitation. The results showed that the proportions of type I and III collagens present in normal and inflamed tissues did not differ significantly. In contrast, the type V collagen, which accounted for 0.1 to 1.3% of the total collagens present in normal tissue, was increased by 2- to 9-fold in the chronically inflamed tissue. Because of the unique binding and connecting role type V collagen is thought to play, this alteration may have major pathologic and functional significance.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Regeneration of a fibrous attachment to tooth roots previously exposed to periodontal pockets requires interaction between the root surface and fibroblasts. Experiments were designed to assess whether or not fibroblasts will attach, grow and synthesize normally on tooth roots and determine the efficacy of various treatments of diseased root surfaces on these activities. Extracted teeth were collected, washed and stored frozen until used. The roots were sectioned and the surface area determined. All roots were thoroughly planed to remove most of the cementum and some were then treated with fibronectin or citric acid. Each root was placed in a Linbro well and a suspension of fibroblasts in Dulbecco Vogt medium with 10% fetal calf serum added. After cell attachment, each root was transferred to a fresh well and incubated. Some roots were examined by scanning electron microscopy. Attachment and growth were assessed by harvesting and counting cells after various incubation times. The pattern of protein synthesis was determined by preparing fluorographs from cultures pulse labeled with radioactive S35-methionine. Cells attach and grow on planed root surfaces. The number that attach to normal and diseased roots is greatly enhanced by pretreatment with fibronectin or citric acid. By day three, the cells become confluent at approximately 20,000/cm2. The pattern of proteins produced is comparable to that seen in cultures maintained in petri dishes. After root planing, cells attach, grow and synthesize equally well on diseased and normal roots.
We report radiographic, clinical, historical, and laboratory observations on seven patients selected to illustrate the features and characteristics of rapidly progressive periodontitis, with the aim of establishing this disease as a distinct clinical entity. This form of periodontitis is seen most commonly in young adults in their twenties, but it can occur in postpubertal individuals up to approximately 35 years of age. During the active phase, the gingival tissues are extremely inflamed and there is hemorrhage, proliferation of the marginal gingiva, and exudation. Destruction is very rapid, with loss of much of the alveolar bone occurring within a few weeks or months. This phase may be accompanied by general malaise, weight loss, and depression, although these symptoms are not seen in all patients. The disease may progress, without remission, to tooth loss, or alternatively, it may subside and become quiescent with or without therapy. The quiescent phase is characterized by the presence of clinically normal gingiva that may be tightly adapted to the roots of teeth with very advanced bone loss and deep periodontal pockets. The quiescent phase may be permanent, it may persist for an indefinite period, or the disease activity may return. Most patients with rapidly progressive periodontitis have serum antibodies specific for various species of Bacteroides, Actinobacillus, or both, and manifest defects in either neutrophil or monocyte chemotaxis. Affected patients generally respond favorably to treatment by scaling and open or closed curettage, especially when accompanied by standard doses of antibiotics for conventional time periods. A small minority of patients do not respond to any treatment, including antibiotics, and the disease progresses inexorably to tooth loss even in the presence of aggressive periodontal therapy and maintenance. At the present time it is not possible to distinguish prior to treatment which individuals will respond to therapy and which will not.
Explore the source record for details and available documents.
Studies were designed to assess factors other than pathologic status of the cell donor which affect the blastogenic responsiveness in vitro of peripheral blood mononuclear cells (PBMs) from normal donors and patients with periodontitis. Cultures were established and activated using phytohemagglutinin-P (PHA) or homogenates of Actinomyces viscosus (AVIS), a gram-positive plaque microorganism, and Fusobacterium nucleatum (FUSO), a gram-negative plaque microorganism. Activation was assessed by measuring the incorporation of labeled precursor into DNA. The effects of incubation time, vessel shape, cell concentration, prostaglandin E2 and indomethacin on blastogenic responsiveness were studied. Blastogenic responsiveness became maximal after 5 to 8 days' activation with the bacterial substances, and after 3 days' activation with PHA. Radioactivity incorporated by cultures in microtest wells with flat, round and conical bottoms was 5.9, 7.8 and 10.6 X 10(3) cpm, respectively. Cultures of cells from all of the patients and normal subjects were activated by PHA, AVIS and FUSO, and cell concentration was a major determinant of the magnitude of the blastogenic response. Responsiveness of cultures from all patients and control subjects activated with AVIS and FUSO was inhibited significantly by prostaglandin E-2 (PGE2) at a concentration of 10 microM. Inhibition was generally 50% or greater. Indomethacin, an inhibitor of prostaglandin production, at a concentration of 0.5 micrograms/ml significantly enhanced responsiveness of AVIS- and FUSO-activated cultures from control donors and patients, indicating that prostaglandins are produced endogenously, and that they affect cell responsiveness. The effect of PGE2 and indomethacin on PHA-activated cultures was more variable and, where present, of a lesser magnitude than that observed for cultures activated with bacterial homogenates. In most cultures the effects were not statistically significant. Our data show that in studies of lymphocyte activation, the incubation time, culture-vessel shape, cell concentration and presence of endogenous inhibitors need to be taken into account.
The therapeutic community is a widely used method for treating people with difficulties in their interpersonal relationships. The process by which the residents of this type of treatment center grow personally and interpersonally is described. Methods for assessing the manner in which the residents of therapeutic communities change are also discussed.
The interaction of the purified C1q component of human C with synchronized, quiescent human gingival fibroblasts was investigated, and the presence of a specific binding site was demonstrated. Quantitative binding studies with radioiodinated C1q showed that binding was specific, saturable, and reversible upon addition of unlabeled C1q or by increasing the salt concentration. Scatchard plot analysis of the data yielded an affinity constant of 2 X 10(7) M-1 for all cell strains examined. The capacity for C1q binding varied among the eight cell strains examined. The number of binding sites per cell ranged from 2.6 to 17.7 X 10(6) with an average of 8.4 X 10(6). The receptor was insensitive to trypsin digestion, and it bound the collagen-like portion of the C1q molecule. Specific immunofluorescence staining showed that virtually all the viable cultured fibroblasts were able to bind added C1q. Flow cytometric analysis demonstrated a spectrum of fluorescence intensity among the cell strains, and there was a positive correlation between fluorescence intensity and the number of binding sites detected by using radiolabeled C1q.