Connective tissues of the periodontium: a summary of current work.
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Biomedical subjects
Publications and source records attributed to R C Page.
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Fibroblasts growth synthesis activities appear to be under exquisite control. This control is mediated in part by substances present in blood plasma or released by other cells. We have studied the role of peripheral blood mononuclear cells (PBM) activated with phytohemagglutinin-P (PHA) on DNA synthesis, proliferation, and the cell cycle of human diploid fibroblasts. Culture medium from activated but not from unactivated PBM cultures inhibited fibroblast DNA synthesis and growth in a dose-dependent manner. The activity, which was designated as lymphocyte factor (LF), was very potent; it inhibited 50% of the DNA synthesis and cell growth at a dilution of 1:160. It has a molecular weight between 50,000 and 100,000 daltons and it is destroyed by trypsin digestion or by heating at 80 degrees C for 30 minutes. The activity was not due to the presence of prostaglandin. Furthermore, using immunoprecipitation and affinity chromatography, it was shown conclusively to to be distinctly different from alpha lymphotoxin (alpha-LT). It was not cytotoxic, as shown by the 51chromium release technique. Using flow microfluorimetry it was shown that the activity regulates fibroblast growth by preventing quiescent cells in the G0 or G1 stage of the cell cycle from entering the S phase. Cells already in S at the time of exposure complete DNA synthesis but cannot divide, and they accumulate in G2. The activity also has marked effects on protein synthesis. Activated mononuclear cells may play a major role in regulating fibroblast growth and synthesis in normally healing wounds and in acute and chronic inflammatory processes.
Phenytoin (Dilantin) induces gingival overgrowth characterized by an accumulation of connective tissue The cell-to-matrix ratio in the mature lesion is normal, yet there must be more fibroblasts per oral cavity if there is excessive tissue mass. Using a mongrel cat model system, we studied the early, developing phenytoin-induced lesion by quantitating fibroblasts per unit of tissue in papilla biopsies collected over a 3-month period of daily drug administration. At 6 and 8 weeks, the number of fibroblasts per unit of tissue increased dramatically. By 3 months, as the lesions matured, the fibroblast-to-matrix ratio returned to normal. We suggest that the drug interacts with resident gingival fibroblasts, causes them to proliferate and thus induces a true, but transient, hypercellularity. Cell division then appears to slow or cease, and rapid production of connective tissue matrix ensues, returning the cell-to-matrix ratio to normal.
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The degree of responsiveness of lymphoid cells to activation by mitogens and antigens is commonly assessed in vitro by measuring radioactive DNA precursor incorporation. Several lines of evidence indicate that artifacts affect the results and that these measurements may not be an accurate reflection of cell activation. Cultures of blastogenically activated lymphocytes contain soluble, noncytotoxic factors that inhibit the incorporation of radioactive nucleosides into DNA by dividing cells without affecting their rate of DNA synthesis. Inhibitors were found in the serum component of the medium and in the bacterial homogenates used to activate the cells, and they were produced by the activated cells. Inhibitor activity in serum has properties expected of a nucleoside such as thymidine, including a molecular weight of less than 10(3). The inhibitor activity present in some bacterial homogenates and that produced by activated cells enzymically degrade labeled DNA precursors, thereby preventing their availability for incorporation. Other bacterial preparations contain DNA precursors, which compete with labeled nucleosides for incorporation, and additional low-molecular-weight inhibitor is produced when the preparations are incubated. Preparations of various bacteria differ greatly with regard to the potency of their inhibitor activity. In some cases incorporation of label in activated cultures is reduced to background levels. Inhibition by these substances leads to erroneous conclusions regarding the proliferative activity of cultured lymphocytes, since the amount of label incorporated does not accurately indicate the true rate of DNA synthesis of the cells.
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This study investigated the effects of marathon group counseling on the attitudes of imprisoned male illicit drug users. Residents selected randomly into a control and an experimental group responded to a semantic differential which included the following concepts: Kindness, Anger, Guilt, Reality, My Real Self, The Future, Drug Treatment Programs, Counselors, Counseling, and Group Counseling. The scores of the control and marathon group participants were compared on posttests by t-tests. The posttest scores of the marathon group participants were significantly higher than the scores of the control group participants on the following scales: Counselor (E), Group Counseling (E), and Drug Treatment Programs (P).
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In the gingiva and other connective tissues, alteration in the collagens is primarily responsible for their functional impairment during disease. To study the collagen alterations, we extracted diseased human gingival tissue with neutral and acidic solvents and then with pepsin. The pepsin extract was separated into proteins soluble in 2.5 and 1.5 M NaCl and proteins insoluble in 1.5 M NaCl. By the criteria of solubility behavior in NaCl solutions, elution from (carboxymethyl)cellulose (CM-cellulose) columns, sodium dodecyl sulfate (NaDodSO4)-polyacrylamide gel electrophoresis, CNBr peptide pattern, and amino acid composition, the collagens of acidic and neutral solvent extracts and 1.5 M soluble fraction of pepsin extract were characterized as type I collagen and the 1.5 M NaCl insoluble collagen as type III. The 2.5 M NaCl fraction contained alpha 2, A, and B chains. The alpha 1 chains resembled alpha 1[I] in amino acid composition, and, since alpha 2 chains were lacking, it appeared that these chains derived from type I trimer collagen. The A and B chains were purified from the 2.5 M NaCl fractions by salting out at acidic pH. The final (A plus B) chain fraction was resolved into two major and one minor protein peaks by phosphocellulose chromatography. The major peaks were characterized as A and B chains on the basis of amino acid composition and CNBr peptide patterns. The minor peak had electrophoretic mobility slightly less than B chains, and the amino acid composition was different. Analysis of the proportion of different collagen types extracted indicated that type III collagen, which is the second major fraction in other connective tissues, is only a minor constituent in the gingiva. More interestingly, A and B chains accounted for a greater proportion than type III. Unlike the fibroblast cultures, the type I trimer formed only a small proportion of collagens of diseased gingival tissue.