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Biomedical subjects

C A McCulloch

Publications and source records attributed to C A McCulloch.

At least 163 records · Page 9Linked to original sources
PubMed1988

Neoplastic transformation of osteogenic cells: quantitative morphometric analysis of an in vitro model for osteosarcoma.

Previously we have reported the development of a model in vitro system for the study of osteosarcoma. In this system, when chick periosteal explants are infected with Fujinami sarcoma virus (FSV), osteosarcoma-like tissue is formed. In the present study, a series of histopathologic parameters of neoplastic transformation and osteogenesis were quantitated, at a single cell level, by computer-assisted morphometry. Most significantly, it was found that compared to uninfected (control) cultures, in the FSV-infected (experimental) cultures, the bone to osteoid ratio per unit area was decreased due to a relative decrease in the area of bone and an increase in the area of osteoid. The cellularity of the FSV-infected tissues was significantly increased due to an increase in the number of unlabeled and [3H]thymidine-labeled cells, while the proportion of alkaline phosphatase (AP) positive cells decreased. Double-label immunohistochemistry (with anti-P140gag-fps) and histochemistry for AP activity was performed, to demonstrate production of the oncogene-encoded protein, and osteoblastic differentiation respectively. In an in vitro transformation assay, single cells derived from control, uninfected cultures did not grow, while those derived from FSV-infected cultures formed colonies in semisolid medium. Some of these colonies demonstrated AP staining. Taken together these data show that in this in vitro system (i) neoplastic transformation of osteogenic cells does occur, (ii) changes in osteoid and bone production are related to neoplastic transformation, and (iii) osteosarcoma-like changes can be quantitated at the individual cell level.

Animals↗
PubMed1987

Paravascular cells in endosteal spaces of alveolar bone contribute to periodontal ligament cell populations.

Endosteal spaces of alveolar bone communicate with the periodontal ligament and may contribute to its cell populations. We examined cell proliferation and migration in endosteal spaces and in the periodontal ligament contiguous with these spaces. Radioautographs of mouse mandibular molar were prepared from animals pulse-injected with 3H-Tdr and sacrificed in groups of 22 mice each at 1 h, 1, 3, and 7 d after labeling. Cell counts, labeling indices, grain counts, and progenitor cell ratios were determined. The data indicate that endosteal spaces are enriched with 3H-Tdr-labeled progenitor cells whose progeny rapidly migrate out of the compartment. The periodontal ligament contiguous with the endosteal spaces exhibited 5 times as many labeled cells as other sites in this tissue. Thickened areas of cementum were coincident with the openings of endosteal spaces in over 64% of observations. The data are consistent with the hypothesis that cells migrate from endosteal spaces into the periodontal ligament and there express the phenotype for osteoblasts or cementoblasts.

Alveolar Process↗
PubMed1987

Gingival attachment level measurements with an automated periodontal probe.

The accurate and reproducible measurement of gingival attachment level is essential for studying the progression of periodontitis in human populations. An automated periodontal probe has been developed which measures gingival attachment level using the occlusal or incisal surface of the tooth as a fixed landmark and which transfers data directly to a computer. The probing force is adjustable and is regulated by changing the air pressure. A mercury level switch maintains uniform probe angulation during measurements. The reproducibility of measurements obtained with the automated periodontal probe was examined by making duplicate gingival attachment level measurements at 784 sites in 9 patients 1 week apart and comparing the difference between the paired values. A probing force of 0.30 N was used. There was no significant difference in the frequency distributions of measurement differences between either maxillary versus mandibular teeth or anterior versus posterior teeth. The data demonstrate that this device can be used to measure gingival attachment level without the need for stents or estimation of the level of the cementoenamel junction and that reproducible data can be obtained and automatically stored in a computer for subsequent analysis.

Adult↗
PubMed1986

Dexamethasone induces proliferation and terminal differentiation of osteogenic cells in tissue culture.

Dexamethasone is an important regulator of cellular proliferation and differentiation, but paradoxical effects have been noted in a variety of culture systems. The purpose of this study was to determine whether dexamethasone induces proliferation and differentiation of osteogenic precursor cells. Periosteal explants from embryonic chicks were grown in culture for 3 or 4 days, treated continuously with dexamethasone or ethanol vehicle, and then either pulse-labeled with 3H-thymidine at 3 days or labeled for 24 hr between day 3 and day 4. Histochemical and autoradiographic procedures were used to assess the proliferation and differentiation of osteogenic cells. At 3 days, the area of bone, the percentage of alkaline phosphatase-positive cells, the percentage of 3H-thymidine-labeled cells, and the percentage of cells labeled with both markers were significantly higher in dexamethasone-treated cultures. Between day 3 and day 4 no significant changes in these parameters were observed in the dexamethasone-treated cultures. In comparison, control cultures exhibited significant increases in the percentage of 3H-thymidine-labeled cells after 24 hr of continuous labeling. The data show that dexamethasone induces a burst of proliferation in a cohort of cells that undergo differentiation. Once these cells have divided, further proliferation within the culture is limited. Finally, it is apparent that the timing of experiments may be critical in determining whether dexamethasone will inhibit or stimulate proliferation.

Alkaline Phosphatase↗
PubMed1986

Simultaneous autoradiographic and histochemical analysis of bone formed in vitro.

The simultaneous histochemical demonstration of alkaline phosphatase activity and autoradiographic demonstration of [3H]-thymidine uptake is valuable for study of bone cell kinetics in vivo or in vitro. By use of this technique, it has been possible to detect changes induced by a single dose of dexamethasone (10(-7) M) in the time course of alkaline phosphatase activity, the number of alkaline phosphatase-positive cells, and [3H]-thymidine labeling in bone formed in vitro.

Alkaline Phosphatase↗
PubMed1985

Progenitor cell populations in the periodontal ligament of mice.

Stem cells in a variety of renewal tissues exhibit a slow rate of cell proliferation (Potten et al., 1979). The periodontal ligament of mouse molars was examined for the presence of slowly cycling progenitor cells to provide evidence for the existence of stem cells in this tissue. A pulse injection of 3H-thymidine was administered and mice were sacrificed between 1 hour and 14 days after injection. Analysis of radioautographs using percentage of labeled cells and grain counts demonstrated that a population of label-retaining cells within 10 micron of blood vessels traversed the cell cycle more slowly than proliferating cells located greater than 10 micron from blood vessels. These data suggest that there is a slowly dividing population of progenitor cells in paravascular sites in mouse molar periodontal ligament which may be stem cells.

Animals↗
PubMed1983

Cell density and cell generation in the periodontal ligament of mice.

The number of cell nuclei per mm2 and the volume density of cell nuclei and blood vessels in the periodontal ligament at different levels of the mesial root of the first mandibular molar of the adult mouse and in different areas of the ligament at each level have been examined in the light microscope. Significantly higher numbers of cell nuclei per mm2 were observed adjacent to bone, cementum, and blood vessels than in the avascular body of the ligament at all levels and on all aspects of the root. This distribution of number of cell nuclei per mm2 was constant over 4 1/2 months of aging and a doubling of body weight. The volume density of cell nuclei was significantly higher in cells adjacent to bone and cementum and in gingival connective tissue than in both the vicinity of blood vessels and the body of the ligament. The blood vessels, which were present predominantly in the bone-related half of the ligament, were absent from the zone immediately adjacent to cementum. The labeling indexes of periodontal ligament cells were determined from autoradiographs of the mesial root of the first mandibular molar of the mouse after pulse-labeling with 3H-Tdr. Labeling indexes were highest in zones adjacent to blood vessels, and the labeling index was significantly higher in the middle of the ligament than in zones adjacent to bone and cementum, and consequently was inversely related to cell density.

Animals↗
PubMed1983

A hospital planning response to the "geriatric imperative".

The emerging geriatric patient population, a situation for which few hospitals are adequately prepared, is examined within the context of the "geriatric imperative." Reductions in morbidity and increases in the elderly population and the chronic diseases and disabilities associated with aging are causing hospitals to reexamine their orientation to short-term episodic care to adapt to the needs of a more elderly patient population. A geriatric care planning framework is presented to assist hospitals with this process.

Aged↗
PubMedDate not supplied

Regulation of cell volume and intracellular pH in hyposmotically swollen rat osteosarcoma cells.

The maintenance of cell volume involves transduction of a volume-sensing signal into effectors of volume-regulatory transporters. After exposure to anisotonic conditions, cells undergo compensatory volume changes that are mediated by active transport and passive movement of ions and solutes. Intracellular pH (pHi) homeostasis may be compromised during these processes. We have studied pHi and some of the signal transduction mechanisms involved in the regulatory volume decrease (RVD) that occurs after exposure to hypoosmolar conditions in rat osteosarcoma cells, ROS 17/2.8. Cells were loaded with BCECF; pHi and cell volume were estimated by dual excitation ratio fluorimetry. Swelling of cells in 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffered hypotonic medium induced a rapid cell swelling followed by an incomplete RVD of approximately 30% in suspended (i.e., round) cells and approximately 60% in attached (i.e., spread) cells that was independent of subpassage number. RVD was inhibited by ouabain, valinomycin, and high external [K+], all of which should reduce the cell membrane electrochemical gradient for K+. Inhibition of RVD was induced also by decreasing intracellular [Ca2+] with BAPTA-AM and by depletion of Cl-, indicating the role of calcium-regulated K+ and Cl- efflux during RVD. Depolymerization of actin filaments by cytochalasin D prolonged the RVD three-fold and nonspecific activation of GTP-binding proteins up-regulated RVD. In attached cells the hypoosmolar-induced swelling caused a large reduction in pHi (approximately 0.7 units), which was sustained as long as cells were in hypoosmotic medium. The reduction of pHi induced by cell swelling was inhibited by Na(+)-free extracellular medium, ouabain, the tyrosine kinase inhibitor genistein, and to a lesser extent by Cl(-)-free medium. However, amiloride failed to inhibit the hypoosmolar-induced reduction of pHi. Collectively these data indicate that RVD of ROS 17/2.8 cells in HEPES-buffered medium is dependent on conductive efflux of K+ and Cl- that is regulated by cell shape, actin, and GTP-binding proteins. The sustained inhibition of pHi homeostasis induced by cell swelling may reflect the existence of cell volume sensing mechanisms that operate through tyrosine kinases to regulate pHi.

Actins↗