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Biomedical subjects

B Steffensen

Publications and source records attributed to B Steffensen.

36 records · Page 2Linked to original sources

Immunohistological localization of cell adhesion proteins and integrins in the periodontium.

The distribution of the cell adhesion proteins vitronectin, fibronectin, tenascin, and laminin as well as several integrin subunits, alpha 2, alpha 5, and alpha v, was studied in primate periodontal tissues. Full baboon mandibular sections were analyzed by immunohistochemical methods in order to localize the molecules studied in both soft and hard tissues. Vitronectin was associated with the connective tissue of the marginal gingiva, the periodontal ligament, as well as the endosteum and periosteum. A notable finding was the particularly high staining intensity of vitronectin in the periodontal ligament. Fibronectin was widely distributed in the periodontal connective tissue and was also localized to the pericellular matrix of osteocytes and blood vascular elements. Epithelial basement membranes stained positively for both fibronectin and tenascin. These proteins were also expressed in the periosteal and endosteal connective tissues and the periodontal ligament. The staining intensity for tenascin was higher in zones along the cementum and bone surfaces. Laminin was, characteristically, limited to basement membranes of epithelium and endothelium. The distribution of fibronectin, tenascin, and laminin is related to previous findings in other species. The localization of the several integrin alpha-subunits is also described in full baboon mandibular sections. The vitronectin receptor (alpha v) had a uniquely strong expression in osteoclasts of the alveolar bone and was found, at lesser intensity, on periodontal ligament fibroblasts. The fibronectin receptor alpha subunit, alpha 5, was also observed on osteoclasts, and, in addition, was widely distributed on fibroblasts, cementoblasts, and osteoblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolar Process↗

Quantitative assay for morphogenesis indicates the role of extracellular matrix components and G proteins.

A quantitative assay for morphogenesis is described that involves counting the organizing centers (swirling patterns) formed by many cultured fibroblasts. Organizing centers, which are found in vivo, represent one of the smallest units of morphogenesis. We show that macroscopically visible organizing centers form by the merger of smaller organizing centers. Parallel orientation of cells on plastic substrata requires cell-cell contact, but organizing centers can develop without cell-cell contact on collagen gels. On collagen gels, the orientation of collagen fibers determines the orientation of cells with respect to one another. Although organizing centers resemble fingerprints, we have shown that a stochastic process determines the spatial orientation of organizing centers. Treatment of transformed cell lines with agents that increase cAMP levels or alter the activity of guanine nucleotide binding proteins resulted in the generation of organizing centers. Cholesterol precursors involved in protein isoprenylation were found to be potent reverse-transformation agents that could alter the two-dimensional morphogenesis of cells. The simple assay described should permit the analysis of morphogenesis at the molecular and cellular levels.

Animals↗

The alternative splicing of fibronectin pre-mRNA is altered during aging and in response to growth factors.

The reverse transcription-polymerase chain reaction was used to examine alternative splicing at each of the three fibronectin exons known to undergo alternative splicing, i.e. extra domain A (ED-A), extra domain B (ED-B), and type III connecting sequence (IIICS). Ratios of fibronectin mRNAs with or without a given exon were determined in several rat tissues and human cell lines during aging in vivo and cellular senescence in vitro. We demonstrate that statistically significant shifts in the alternative splicing of fibronectin occur during aging in vivo and in vitro. Since all three alternatively spliced exons are spliced out at a higher frequency in aging tissues and cells, the fibronectin protein produced by old cells should be slightly smaller than that obtained from young cells. The reverse transcription-polymerase chain reaction demonstrates tissue-specific patterns of alternative splicing in several tissues. Whereas fibronectin mRNAs from adult rat tissues were found to range from 0 to 25% ED-A+ and from 0 to 10% ED-B+, fibronectin mRNAs from cultured cell lines were found to be approximately 50-60% ED-A+ and 15-25% ED-B+. We observed similarity in splicing of fibronectin RNA by the different cultured cell lines obtained from many tissues and attribute this observation to the effect of growth factors. We demonstrate that serum deprivation; placement of cells into primary culture; and growth factors such as transforming growth factor beta 1, retinoic acid, and 1,25-dihydroxyvitamin D3 can all change the alternative splicing of fibronectin pre-mRNA in the ED-A, ED-B, and type III connecting sequence exons. Possible mechanisms for the regulation of the alternative splicing of fibronectin RNA by growth factors are discussed.

Aging↗

IL-1 beta and prostaglandins regulate integrin mRNA expression.

The purpose of this study was to examine the effects of IL-1 beta on integrin expression in MG-63 human osteosarcoma cells. Human recombinant IL-1 beta (rIL-1 beta) produced significant increases in both alpha 2- and alpha 5-subunit mRNA levels, as well as a smaller increase in alpha v-subunit mRNA. In contrast, IL-1 beta decreased alpha 4-subunit mRNA levels by approximately 30% relative to untreated controls. These findings suggest that human IL-1 beta differentially regulates expression of integrins. When cultures were treated with both IL-1 beta and the cyclooxygenase inhibitor, indomethacin, the expression of alpha 2-, alpha 5-, and alpha v-subunit mRNA levels were dramatically increased relative to untreated controls; co-treatment with 0.5 mM prostaglandin E2 (PGE2) partially reversed this effect. Indomethacin alone did not affect integrin mRNA levels. Treatment with IL-1 beta or IL-1 beta + indomethacin also induced significant changes in MG-63 morphology (i.e., increased cell elongation) and increased the ability of cells to contract collagen gels. PGE2 reversed the above effects on cell morphology and gel contraction. These findings indicate that (a) IL-1 beta differentially regulates the expression of integrins and (b) that PGE2, which is induced by IL-1 beta, may provide a negative feedback loop which counteracts the stimulatory effect of IL-1 beta on integrin gene expression. It is suggested that products of inflammation may affect cell behavior by differentially regulating the expression of various integrins.

Actins↗

Effect of region-of-interest in computerized densitometric analysis of radiographs.

The region-of-interest (ROI) in computer-assisted densitometric image analysis (CADIA) is defined by its size and location. This study evaluated the effects of these variables on two quantitative parameters, the change in density and the area with change in density. Pairs of radiographs for these analyses were obtained from sites with "no change" or "known loss" in Cynomolgus monkeys during a study of ligature-induced periodontitis. The size and location of the ROI had clear effects on the two CADIA parameters. To reduce these effects, a corrective procedure hypothesizing a linear relationship between the ROI size and the area with change in density was tested. While this procedure was sufficient to correct for ROI size-dependent differences among "no change" images, it was not effective in images with "known loss". In such images, additional adjustments by increasing threshold levels for the registered change in density were found to reduce but not to eliminate differences between ROIs of different size and location. When densitometric radiographic analysis is used for quantitative comparison of different sites, it is primarily recommended to select ROIs of similar size and location. Application of corrective procedures should follow only after careful evaluation of their effects on sensitivity and specificity.

Alveolar Bone Loss↗

Effects of immunization with Porphyromonas gingivalis and Prevotella intermedia on progression of ligature-induced periodontitis in the nonhuman primate Macaca fascicularis.

The nonhuman primate (Nhp) has proven to be a useful model of human periodontitis. This study describes the immunological characteristics of this model and the ability of active immunization to interfere with ecological changes in the microbiota and its associated disease symptoms. Nhps were parenterally immunized with whole-cell antigens of Porphyromonas gingivalis and Prevotella intermedia. The immunization elicited an approximate 2-log increase in serum immunoglobulin G (IgG), IgM, and IgA isotype antibody that was highly specific for these immunogens. Postimmunization and postligation, there was minimal change in the levels of specific antibody. P. gingivalis immunization significantly inhibited the emergence of this species during disease progression. In contrast, induction of anti-P. intermedia antibody had a minimal effect on this species within the subgingival plaque. Plaque indices showed few changes that could be attributed to active immunization. Both bleeding on probing and loss of attachment were higher in ligated sites of immunized animals than in the placebo-treated group. A significant increase in bone density loss was observed in the ligated teeth from immunized versus control animals. These findings indicate that active immunization of Nhps can elicit a substantial systemic immune response; however, while this response may effect the emergence of an individual microorganism, it appears that other ecological considerations are critical in disease progression. It is also possible that the induction of a broad-based immune response to multiple bacterial antigens can result in increased disease, potentially associated with hypersensitivity reactions to the bacteria in the subgingival plaque.

Animals↗

Correction of density changes caused by methodological errors in CADIA.

Quantitative evaluation of radiographic changes by computer-assisted densitometric image analysis (CADIA) requires exact knowledge about method errors. In the present study, density change errors were determined from pairs of films with "no change". From this distribution of error values, a series of threshold values for correction of changes due to method errors was selected. The threshold values were then applied to results from analysis of densitometric changes in sites with "known loss" or "no change" of the alveolar bone among films from cynomolgus monkeys. The density errors formed non-normal distributions with no difference in magnitudes between the absolute values expressing density decreases and density increases in the same areas. Calculation of sensitivity, specificity, type 1 and type 2 errors showed that these variables were clearly influenced by selection of different threshold values for correction of the density change errors. It is therefore recommended that threshold values be determined for each analytical system initially as well as following any equipment or computer program modification. Before selecting the threshold value for a specific radiographic analysis, the desired level of sensitivity and specificity should be evaluated.

Absorptiometry, Photon↗

The prognosis of tunnel preparations in treatment of class III furcations. A follow-up study.

The present study evaluated the long-term prognosis of tunnel preparations performed in a large number of teeth with advanced periodontal furcation defects. One hundred seven (107) patients, in which 156 teeth had been treated by tunnel preparations, were recalled for an evaluation, which was based on a questionnaire, a clinical examination, and radiographs; 102 patients attended (149 teeth = 95%). The mean observation time per tooth was 37.5 months (range 10 to 107 months). The results showed that 10 teeth (6.7%) had been extracted and 7 teeth (4.7%) hemisected. The indication for 12 of these extractions or hemisections was root caries. Among the remaining 132 teeth, 23 (15.4%) showed initial or established caries. There was no relationship between caries development and length of the observation time. Thus, approximately 75% of the teeth were still caries-free and in function. The findings demonstrated that tunnel preparations have a considerably better prognosis than previously reported and should be considered a valid treatment alternative.

Adult↗

Relationship between the radiographic periodontal defect angle and healing after treatment.

This study radiographically evaluated the correlation between the changes in alveolar bone level occurring in bony defects after periodontal therapy and the corresponding pretreatment defect angles. The defect angle was defined by the bony defect surface and the root surface. The changes were determined from identically exposed and processed radiographs obtained just prior to surgery and 15 to 18 months later. The defect angle was clearly correlated to the radiographic changes in alveolar bone level. Most defects with an angle less than 45 degree showed a gain of bone while defects with the largest defect angles showed a loss. In addition, defects on root surfaces without furcations showed better healing than defects associated with furcations.

Alveolar Process↗

Clinical effects of electromagnetic stimulation as an adjunct to periodontal therapy.

The clinical effects of electromagnetic stimulation (EMS) on periodontal soft tissues and alveolar bone level were studied among 23 patients. The sides of the arch to receive EMS were randomly selected and exposed for a period of eight weeks following periodontal surgery. The contralateral control sides received surgery only. The electromagnetic signal was a multiple pulse signal with 21 asymmetrical quasirectangular pulses per burst and a burst frequency of 16.9 Hz. The peak magnetic field strength reached 0.46 Gauss. Changes from baseline in clinical attachment level, probing depth, and radiographic alveolar bone level were assessed at six, 12, and 18 months postsurgically. A greater gain of clinical attachment level following EMS was observed only for pockets with initial depth of 1 to 3 mm. There were no consistent differences between test (EMS) and control sides in the change of clinical attachment level or probing depth for pockets deeper than 4 mm. Radiographically, the test sides demonstrated statistically significant gain of alveolar bone level compared with the control sides at six months following surgery. Hereafter, the rates of change were similar in the stimulated and unstimulated sides, and the total gain of alveolar bone level remained greater in the test side throughout the observation period. Within the limitations of this study, it was concluded that electromagnetic stimulation does not promote gains in clinical attachment or alveolar bone level to the extent that it can be recommended as an adjunct to conventional periodontal therapy.

Adult↗

Repair of periodontal angular bony defects evaluated by one- and two-dimensional radiographic analysis.

The healing of eighteen angular periodontal bony defects was evaluated radiographically 1 year after treatment. The pretreatment and posttreatment radiographs were exposed and processed in such a way that identical images were obtained. There was no correlation between one- and two-dimensional expressions of healing in such defects, and relative area changes were consistently larger than relative linear changes of the same defects. The area gain of bone was strongly correlated to the following morphologic variables: length of bone surface, original defect area, and height of the defect.

Alveolar Process↗

Relief from pain localized to the lower back in early labour. A double blind trial of ketocaine, a new, highly effective, local, cutaneous analgesic (A 2358, Ane-Pad), and placebo.

Pain localized to the lower back in the first stage of labour in 47 primiparous women was treated by epicutaneous application of ketocaine or placebo compresses. Twenty-three patients were treated with ketocaine compresses (Ane-Ped), and 24 patients with compresses soaked with isotonic saline. The pain relieving effect was almost the same in both treatment groups. Pain localized to the lower back was reduced in about 50% of the patients after one hour's application of ketocaine or placebo compresses. Supplementary analgesics had to be administered in about 60% of the patients in each group. No maternal or foetal systemic side effects related to the treatment were registered. Local erythema on the application area was only reported in the ketocaine group. The frequency of feeling of warmth during the application of compresses of ketocaine were high compared to the placebo group, 78% and 29% respectively.

Adult↗