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Biomedical subjects

S A Swanson

Publications and source records attributed to S A Swanson.

At least 19 recordsLinked to original sources
PubMed1991

Effect of sodium butyrate on metallothionein induction and cadmium cytotoxicity in ROS 17/2.8 cells.

ROS 17/2.8 cells, a cloned rat osteosarcoma cell line, are exceptionally sensitive to the cytotoxic effects of cadmium. This sensitivity is associated with the inability of this metal to induce the synthesis of metallothionein, a transition metal-binding protein, which detoxifies this metal by its sequestration. Sodium butyrate induces the synthesis of metallothionein in these cells in a concentration-dependent manner. Treatment with this agent also significantly increases the resistance of these cells to the cytotoxic effects of cadmium and the protective effect of butyrate is reversed upon its removal from culture medium. Butyrate treatment did not significantly alter the accumulation of cadmium by these cells. Hence, the increased synthesis of metallothionein in butyrate-treated cells is not due to increased cellular uptake of cadmium. Inhibition of DNA synthesis due to butyrate was not a sufficient condition to alter metallothionein synthesis or to protect against Cd-induced cytotoxicity. Equivalent inhibition of DNA synthesis with hydroxyurea failed to increase metallothionein synthesis in cadmium-treated cells. These results indicate that modulation of metallothionein gene expression in this cell line is the critical factor in determining cellular sensitivity to the cytotoxic effects of cadmium.

Animals↗
PubMed1991

Polyethylene wear from retrieved acetabular cups.

Laboratory wear testing of ultra high molecular weight polyethylene from 12 Charnley acetabular cups, removed after periods of up to 17.5 years showed that the large patient-to-patient variations in clinical penetration rate cannot be explained by batch-to-batch variation in the wear resistance of the material. Nor was there any evidence of a time-dependent degradation in wear resistance of the material.

Acetabulum↗
PubMed1990

Effect of 5-azacytidine on metallothionein inducibility and sensitivity to lethality of cadmium in rat osteosarcoma (ROS 17/2.8) cells.

ROS 17/2.8 cells, a cloned rat osteoblastic osteosarcoma cell line, were found to be extremely sensitive to the lethal effects of cadmium and to synthesize little, if any, metallothionein in response to cadmium exposure. Culture of cells for 24 h in the presence of 1 microM 5-azacytidine, a cytidine analog, increased the inducibility of metallothionein by cadmium and significantly reduced (P less than 0.001) cytotoxicity. Anion exchange chromatographic analysis of cadmium binding to low molecular mass cytotoxicity. Anion exchange chromatographic analysis of cadmium binding to low molecular mass cytosolic proteins showed that cells treated with cadmium and 5-azacytidine expressed at least 2 isoforms of metallothionein. One isoform of metallothionein with a low affinity for cadmium was constitutively expressed by these cells. The association of poor inducibility of metallothionein by cadmium with extreme sensitivity of cells to cadmium emphasizes the role of this protein in the cellular response to this toxic metal. The modulation of metallothionein inducibility and sensitivity to cadmium by 5-azacytidine treatment suggest that metallothionein gene structure and regulation are altered in ROS 17/2.8 cells.

Animals↗
PubMed1990

Toxicity of cadmium to rat osteosarcoma cells (ROS 17/2.8): protective effect of 1 alpha,25-dihydroxyvitamin D3.

Inadequate vitamin D intake is an important cofactor in clinical and experimental bone disease induced by chronic cadmium exposure. The interaction was investigated by culture of rat osteoblastic osteosarcoma cells (ROS 17/2.8) in a serum-free medium with equimolar concentrations of cadmium chloride and 1 alpha,25-(OH)2 vitamin D3. After addition of cadmium alone to culture medium, the unstimulated secretion of osteocalcin and cellular alkaline phosphatase activity were inhibited at 10 pM, and of DNA synthesis and proline incorporation into collagen at 500 nM. In the presence of equimolar amounts of cadmium and 1 alpha,25-(OH)2 vitamin D3, all four responses paralleled those of 1 alpha,25-(OH)2 vitamin D3 alone up to the inhibitory concentration of 500 nM cadmium. Neither 10 nM 1 alpha,25-(OH)2 vitamin D3 nor 1 microM cadmium induced synthesis of metallothionein in these cells indicating that the protective effect of D3 was not related to the induction of a metallothionein-like protein in ROS 17/2.8 cells. In the presence or absence of D3, cadmium inhibited osteoblastic function at concentrations below the whole-organ concentration of cadmium in bone as reported in experimental and clinical cadmium-induced osteotoxicity. The extreme sensitivity of ROS 17/2.8 cells to cadmium may relate to the absence of metallothionein synthesis.

Animals↗
PubMed1990

Lead inhibits the basal and stimulated responses of a rat osteoblast-like cell line ROS 17/2.8 to 1 alpha,25-dihydroxyvitamin D3 and IGF-I.

Low-level exposure to lead impairs longitudinal growth in children and in experimental animals. The proposed mechanisms include decreased osteocalcin secretion in response to 1 alpha,25-(OH)2 vitamin D3 and decreased response to insulin-like growth factor-I. The interaction of lead, 1 alpha,25-(OH)2 vitamin D3, and insulin-like growth factor-I was investigated in an osteoblast-like cell line from rat osteosarcoma, ROS 17/2.8. Cells were cultured 24 hr in a serum-free medium with lead, 1 alpha,25-(OH)2 vitamin D3, and insulin-like growth factor-I. 1 alpha,25-(OH)2 vitamin D3 (10 nM) evoked a 4-5 X increase in osteocalcin secretion and a 100% increase in cellular alkaline phosphatase activity but no increase in DNA/cell layer. Insulin-like growth factor-I (92.5 ng/ml) evoked a 100% increase of osteocalcin secretion and a 20% increase in cellular DNA contents but no change in cellular alkaline phosphatase activity. Basal and stimulated cellular osteocalcin secretion, cellular alkaline phosphatase activity, and DNA contents were significantly inhibited by addition of 1-10 microM lead. The data are consistent with a toxic effect of lead on osteoblastic function and the cellular responses to 1 alpha,25-(OH)2 vitamin D3 and insulin-like growth factor-I. This interaction may be relevant to impaired childhood growth at low levels of lead exposure.

Alkaline Phosphatase↗
PubMed1990

DNA content of juvenile granulosa tumors determined by flow cytometry.

Juvenile granulosa tumors (JGT) often exhibit worrisome morphologic features, yet usually behave in a benign fashion. Thirteen JGT were examined by flow cytometric analysis of paraffin material to determine if DNA content and cell kinetics are related to prognosis. The patients ranged in age from stillborn to 16 years. Unilateral salpingoophorectomy was the most common therapy. Eleven patients with follow-up were free of disease. Marked nuclear atypia was evident in three cases, and high mitotic counts were observed in six, but only marked atypia correlated with DNA content. Flow cytometry revealed that 46% of the JGT had abnormal DNA content and increased average growth fraction. The neoplasms with the highest DNA indices were found predominantly in postmenarchal girls. JGT may exhibit abnormal DNA content, nuclear atypia, and numerous mitoses, yet behave benignly. DNA flow cytometric studies of higher stage JGT are warranted.

Adolescent↗
PubMed1990

Proliferation markers Ki-67 and p105 in soft-tissue lesions. Correlation with DNA flow cytometric characteristics.

Frozen tissue immunoreactivity with Ki-67, a monoclonal antibody that recognizes a nuclear antigen in nonresting or proliferating cells, was compared to DNA flow cytometry results (from fresh tissue) in a diverse group of 60 soft-tissue lesions. Both DNA index and Ki-67 score were independently reported to be associated with grade and prognosis in sarcomas, but no direct comparison of these two variables was made. It was attempted to measure proliferative activity in fixed paraffin-embedded tissues immunohistochemically in a subset of lesions using an antibody to another nuclear proliferation antigen, p105. Lesions were given a grade according to lesion category (reactive, 1; benign, 2; low-grade malignant, 3; and high-grade malignant, 4). Ki-67 reactivity correlated relatively well with this grading system (r = 0.59); benign lesions usually exhibited a low Ki-67 score and malignant lesions usually but not always exhibited a high score. For example, some malignant fibrous histiocytomas contained only rare positive cells. Some disparity between Ki-67 score and grade and within histologic types indicates some independence from these features, a fact that may be important when correlation with prognosis is performed. However Ki-67 did not correlate well with flow data such as percentage S phase (r = 0.30), percentage S + G2M phases (r = 0.37), or DNA index (r = 0.39). This probably is due to the fact that Ki-67 also marks cells in the G1 phase, whereas these are excluded in flow data analyses. Anti-p105 highlighted almost all nuclei in all cases tested, including fibromatosis, and did not correlate with Ki-67 score, histologic grade or DNA flow cytometric data. Results with p105 could not be favorably affected by titration experiments. It is reasonable to conclude that the Ki-67 score is a variable related to but independent of histologic grade, histologic type, and DNA flow values. Whether it is prognostically important in human sarcomas, as has been suggested, awaits further clinicopathologic study.

Antigens, Surface↗
PubMed1989

Analysis of lymphoepithelioma and lymphoepithelioma-like carcinomas for Epstein-Barr viral genomes by in situ hybridization.

Lymphoepithelioma of the nasopharynx has a strong association with Epstein-Barr virus (EBV). To test the hypothesis that lymphoepithelioma-like carcinomas occurring at other sites are also associated with EBV virus, we used in situ hybridization to analyze 20 cases of lymphoepithelioma and histologically similar lesions and five basaloid squamous cell carcinomas for evidence of EBV genomes. EBV genomes were demonstrated in six of six lymphoepitheliomas of the nasopharynx but in none of five basaloid squamous cell carcinoma. Only one of 14 lymphoepithelioma-like carcinomas was found to contain EBV genomes. The single positive lymphoepithelioma-like carcinoma occurred in the lung of an Asian patient, suggesting that ethnic or geographic influences may be important in determining whether EBV is associated with these nonnasopharyngeal neoplasms. Despite their histologic similarity, most lymphoepithelioma-like carcinomas probably have a different pathogenesis from nasopharyngeal lymphoepithelioma.

Adult↗
PubMed1988

Ectopic midline spinal ganglion in diastematomyelia: a study of its connections.

The connections of an ectopic midline spinal ganglion associated with an asymptomatic sacral diastematomyelia were studied. The ganglion was intercalated in the ventral root of one hemicord and sent its efferents to the dorsal root of the other hemicord. The afferents joined the anterior root to form a midline intradural spinal nerve in the cauda equina. Islands of ectopic glia were present in both roots and the spinal nerve. Both the midline position of the ganglion and the glial heterotopias can be tentatively explained by the failure of incorporation of the dorsal cell wedge ("Zwischenstrang") into the divided neural tube.

Choristoma↗
PubMed1988

Lymphoepithelioma-like carcinoma of the skin.

Carcinomas histologically resembling nasopharyngeal lymphoepithelioma have been identified in the salivary gland, thymus, tonsil, and uterine cervix. Five patients with similar tumors primary in the skin are described. The patients ranged in age from 50 to 81 yr. Four neoplasms were situated on the head, and one was located on the shoulder. Microscopically, they were concentrated in the mid- and deep dermis and lacked connections with epidermis. The pattern was of multiple nodules, smaller irregular islands, and cords. The uniform tumor cells had moderate amounts of lightly eosinophilic cytoplasm and vesicular nuclei with one or two prominent nucleoli. A lymphoid infiltrate was intimately associated with each neoplasm and obscured the malignant epithelium in one. Neither squamous nor glandular differentiation was present, but all tumors exhibited intracytoplasmic mucin. Immunohistochemistry was positive for cytokeratin (5 of 5; diffuse) and epithelial membrane antigen (4 of 5; 3 diffuse, 1 focal). Focal reactivity was also noted for carcinoembryonic antigen (1 of 5), neuron-specific enolase (1 of 5), and vimentin (1 of 5). S100 protein, leukocyte common antigen, Factor VIII-related antigen, prostate-specific antigen (males), Leu M1, and salivary amylase reactivity were absent. One patient developed local recurrence and metastases after 39 mo and was dead of disease at 57 mo. The remaining four were free of disease after 46, 27, 25, and 6 mo of follow-up. The diagnosis of lymphoepithelioma-like carcinoma of the skin is based on microscopic findings and exclusion of occult malignancy. The tumor can be confused with a lymphoid infiltrate and is differentiated from Merkel cell carcinoma primarily on cytologic grounds. The neoplasm may be of adnexal origin.

Aged↗
PubMed1979

Constraints and fixation for implanted joint replacements.

Observations made on both cemented and uncemented joint prostheses after about two years of use show a layer of fibrous tissue next to the bone. The fibrous layer smooths over surface features up to 1mm in size, and must be assumed to be weak in tension and shear. Prosthesis-bone interfaces should therefore be designed to transmit all forces acting on the prosthesis as compressive stresses. The forces acting across prostheses are controlled by the constraints exerted by the articulating surfaces; if the useful ligaments present are allowed to do their job of transmitting tension, the articulating surfaces can be designed to transmit only such forces and moments as can safely be transmitted across the prosthesis-bone interfaces.

Bone and Bones↗
PubMed1978

Loosening of the femoral component in surface replacement of the knee.

The incidence of loosening of the femoral component of the ICLH knee has been found to be lower than that of the tibial component. This is thought to be due to the fact that the compressive strength of the distal femur has been found to be greater than that of the proximal tibia. It has further been shown that the strength of even the femur can be so reduced by the osteoporosis accompanying Rheumatoid Arthritis that it becomes insufficient for adequate prosthetic fixation.

Bone Cements↗
PubMed1978

Mechanical tests on the tibial components of non-hinged knee prostheses.

Cadaveric knees replaced with the Geomedic, ICLH, Marmor and Total Condylar prostheses were tested in axial compression, in rotation and in hyperextension in order to observe the strength of fixation of the tibial components. In axial compression the strengths at failure varied widely, both with any one prosthesis and between prostheses. This is attributed largely to the strength of the cancellous bone of the tibia, which was measured in each case and also varied widely. Three natural knees failed at loads of 7300, 7600 and 8300 newtons respectively, whereas the strengths of replaced knees ranged from 3000 to 15750 newtons. At least one example of each design failed at less than 7300 newtons, suggesting little or no reserve of strength. The strength of fixation was greater when the tibial prosthesis was large enough to rest on the whole cross-section of the tibia. In rotation the three prostheses embodying rollers in troughs were stiffer than the Marmor which had a nearly flat tibial-bearing surface. The presence or absence of the cruciate ligaments had a negligible effect on torsional stiffness. In hyperextension, knees replaced with the ICLH, Marmor and Total Condylar prostheses failed by rupture of the posterior capsule at moments of about 60 newton-metres, compared with about 100 for natural knees. With the Marmor prosthesis the anterior cruciate ligament was avulsed at about 20 newton-metres compared with about 75 in natural knees, suggesting that in this respect the retention of the cruciate ligaments contributes little. None of the four knees tested after inserting a Geomedic prosthesis showed strengths as high as those replaced with the other three designs.

Humans↗