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Biomedical subjects

L Armstrong

Publications and source records attributed to L Armstrong.

At least 73 records · Page 4Linked to original sources
PubMed1991

Cytoskeletal reorganizations in human umbilical vein endothelial cells as a result of cytokine exposure.

Treatment of HUVECs in culture with several cytokines and phorbol esters caused reorganizations of the actin and microtubule networks, as well as a redistribution of focal contract proteins. However, expression of the cytoskeletal proteins which link cells, via integrins, to the substrate, was not significantly affected. Indirect immunofluorescence microscopy of endothelial cells after treatment with interleukin-1 alpha and beta, gamma-interferon, tumor necrosis factor (TNF), phorbol 12-myristate 13-acetate, and phorbol 12,13-dibutyrate allowed us to observe reductions in the areas of cell-cell contact, redistribution of the stress fiber network, and concomitant changes in focal contacts. Microtubule arrays in TNF-treated cells became bundled. Phorbol esters induced formation of microtubule organizing centers not seen in resting or TNF-treated HUVECs. Talin was distributed along stress fibers and not exclusively in focal contacts. Vitronectin receptor was observed in focal contacts, occasionally at cell-cell contacts, and in vesicular structures close to the lumenal surface, after both types of treatment. Although these morphological changes were easily observed by indirect immunofluorescence, no quantitative differences in specific cytoskeletal proteins were detected by immunoblots and [35S]cysteine metabolic labeling experiments.

Cell Adhesion Molecules↗
PubMed1991

UV-microbeam irradiations of the mitotic spindle: spindle forces and structural analysis of lesions.

Mitotic PtK1 spindles were UV irradiated (285 nm) during metaphase and anaphase between the chromosomes and the pole. The irradiation, a rectangle measuring 1.4 x 5 microns parallel to the metaphase plate, severed between 90 and 100% of spindle microtubules (MTs) in the irradiated region. Changes in organization of MTs in the irradiated region were analyzed by EM serial section analysis coupled with 3-D computer reconstruction. Metaphase cells irradiated 2 to 4 microns below the spindle pole (imaged by polarization optics) lost birefringence in the irradiated region. Peripheral spindle fibers, previously curved to focus on the pole, immediately splayed outwards when severed. We demonstrate via serial section analysis that following irradiation the lesion was devoid of MTs. Within 30 s to 1 min, recovery in live cells commenced as the severed spindle pole moved toward the metaphase plate closing the lesion. This movement was concomitant with the recovery of spindle birefringence and some of the severed fibers becoming refocused at the pole. Ultrastructurally we confirmed that this movement coincided with bridging of the lesion by MTs presumably growing from the pole. The non-irradiated half spindle also lost some birefringence and shortened until it resembled the recovered half spindle. Anaphase cells similarly irradiated did not show recovery of birefringence, and the pole remained disconnected from the remaining mitotic apparatus. Reconstructions of spindle structure confirmed that there were no MTs in the lesion which bridged the severed spindle pole with the remaining mitotic apparatus. These results suggest the existence of chromosome-to-pole spindle forces are dependent upon the existence of a MT continuum, and to a lesser extent to the loss of MT initiation capacity of the centrosome at the metaphase/anaphase transition.

Anaphase↗
PubMed1990

Bone scans after total knee arthroplasty in asymptomatic patients. Cemented versus cementless.

The natural history of bone scans after total knee arthroplasty (TKA) was studied in 26 patients with 28 cemented TKAs and 29 patients with 31 cementless TKAs. The bone scans were examined at specified postoperative intervals. Radionuclide activity of the femoral, tibial, and patellar regions was measured. Six patients who developed pain postoperatively were excluded. Bone scans immediately postoperative and at three months demonstrated increased uptake, which gradually decreased to baseline levels at ten to 12 months. Radioisotope uptake was comparable in the cemented and cementless groups, but was highly variable in individual patients and in each of the follow-up periods. A single postoperative bone scan cannot differentiate component loosening from early bone remodeling. Sequential bone scans, as a supplement to the clinical examination and conventional radiography, may prove useful in the diagnosis of TKA failure.

Aged↗
PubMed1989

Selective reduction of anaphase B in quinacrine-treated PtK1 cells.

Quinacrine, an acridine derivative which competitively binds to ATP binding sites, has previously been shown to cause the reorganization of metaphase spindle microtubules (MTs) due to changes in interactions of non-kinetochore microtubules (nkMTs) of opposite polarity (Armstrong and Snyder: Cell Motil. Cytoskeleton 7:10-19, 1987). In the study presented here, mitotic PtK1 cells were treated in early anaphase with concentrations of quinacrine ranging from 2 to 12 microM to determine energy requirements for chromosome motion. The rate and extent of chromosome-to-pole movements (anaphase A) were not affected by these quinacrine treatments. The extent of anaphase B (kinetochore-kinetochore separation) was reduced with increasing concentrations of quinacrine. Five micromolar quinacrine reduced the extent of kinetochore-kinetochore separation by 20%, and addition of 12 microM quinacrine reduced the kinetochore-kinetochore separation by 40%. To determine the role of nkMTs in anaphase spindle elongation, quinacrine-treated metaphase cells were treated with hyperosmotic sucrose concentrations, and spindle elongation was measured (Snyder et al.: Eur J. Cell Biol. 39:373-379, 1985). Metaphase cells treated with 2-10 microM concentrations of quinacrine for 2-5 min reduced spindle lengths by 10-50% prior to 0.5 M sucrose treatment for 5 min. This treatment showed a significant reduction in the ability of sucrose to induce spindle elongation in cells pretreated with quinacrine. As spindle length and birefringence was reduced by quinacrine treatment, sucrose-induced elongation was concomitantly diminished. These data suggest that quinacrine-sensitive linkages are necessary for anaphase B motions. Reduction in these linkages and/or MT length in the nkMT continuum may reduce the ability of the nkMTs to hold compression at metaphase. This form of energy is thought to drive a significant proportion of normal anaphase B in PtK1 cells and sucrose-induced metaphase spindle elongation.

Anaphase↗
PubMed1987

Quinacrine-induced changes in mitotic PtK1 spindle microtubule organization.

Quinacrine, an acridine derivative which competitively binds to ATP binding sites, has been used to study the role of ATP requiring molecules in microtubule organization in mitotic PtK1 cells. Brief treatments of metaphase cells with concentrations of quinacrine ranging from 2 to 10 microM decreased spindle length and birefringence in a concentration-dependent manner. With either increasing quinacrine concentrations or duration of treatment, metaphase cells demonstrated a specific reorganization of spindle microtubules. Both polarization and electron microscopy showed a substantial loss of non-kinetochore spindle microtubules with an increase in astral microtubules: this was particularly evident in the region adjacent to the spindle domain. Addition of millimolar concentrations of dinitrophenol to quinacrine-containing medium did not potentiate the response of metaphase cells to quinacrine treatment. Time-lapse video analysis demonstrated that the astral microtubules are the result of reorganization of spindle microtubules. These data suggest that functional ATP binding sites are required to maintain stable interactions between microtubules and that these interactions are responsible for maintaining the bowed configuration of non-kinetochore spindle microtubules which are under compression at metaphase.

Adenosine Triphosphate↗
PubMed1986

In vitro and in vivo cytotoxicity of T cells cloned from rejecting allografts.

Epa-1 is a tissue-restricted, non-major histocompatibility (MHC) antigen that may be responsible for the extreme sensitivity of skin to allograft rejection and graft-versus-host disease (GVHD), especially with MHC-compatible donors and recipients. To confirm that Epa-1 serves as a target in allograft rejection and GVHD, we isolated Epa-1-specific cytotoxic T lymphocyte (CTL) clones completely in vivo from sponge-matrix allografts and from lymph nodes draining rejecting skin allografts. These clones induced GVHD-like skin lesions in antigen-specific, MHC-restricted fashion following intradermal inoculation into appropriate hosts. The in vivo-derived clones are conventional CTL since they are IL-2-dependent and express the Thy-1.2+, Lyt-1-, Lyt-2+, L3T4- phenotype. The results of this study also are pertinent to the controversy over which T-cell subset actually mediates allograft immunity, since the intragraft isolation and subsequent cloning of conventional CTL that induce necrotizing skin lesions are direct evidence that CTL are the proximal mediators of allograft rejection.

Animals↗
PubMed1985

Reduction of aspirin-induced fecal blood loss with low-dose misoprostol tablets in man.

Misoprostol (SC-29333), a synthetic prostaglandin E1 methyl ester analog, was given simultaneously with acetylsalicylic acid in a double-blind, placebo-controlled randomized prospective study of 32 healthy human male subjects. Fecal blood loss was measured for eight days using the 51Cr-labeled red blood cell technique. Aspirin (650 mg qid) and misoprostol (25 micrograms qid) or placebo were given during days 3, 4, and 5. There was a significant (P less than 0.05) increase in median blood loss (modified Friedman test) from 0.81 to 6.05 ml/day in the aspirin with placebo group (N = 16). Median blood loss was increased (from 0.75 to 3.75 ml/day) in the aspirin with misoprostol group (N = 16), but this was significantly less (Mann-Whitney U test, P less than 0.01) than the placebo group. Mean serum salicylate concentrations in the placebo and misoprostol groups were similar (7.8 and 6.8 micrograms/ml, respectively). There were no significant changes in laboratory values in any of the subjects studied, nor were any major side-effects encountered. This study demonstrates that oral misoprostol reduces aspirin-induced gastrointestinal bleeding even when administered simultaneously and at a dose level below its threshold for significant acid inhibition. This indicates a potential role for misoprostol in the prevention of gastric mucosal damage in selected patients.

Adult↗
PubMed1983

Osteogenesis after bone and bone marrow transplantation. Studies of cellular behaviour using combined myelo-osseous grafts in the subscorbutic guinea pig.

In order to study factors influencing osteogenesis after bone and bone marrow transplantation, we have caused guinea pigs to become scorbutic, and looked at the cell morphology at sites of bone formation. We had previously studied normal guinea pigs and found that autologous marrow in intermuscular implants was associated with bone production by the ninth day, regardless of the type of stored allogeneic bone transplanted with it. In subscorbutic guinea pigs, using identical implants, bone did not appear within the first 13 days, and the cell population around the implants was different. These experiments support the dominant role of bone marrow cells in osteogenesis and cast further doubt on the primary role of devitalised bone as an inducer of bone formation. Interference with cell function by deprivation of a single essential molecule, Vitamin C, produces great change in the ability of cells to synthesise bone, or pre-osseous matrix.

Animals↗