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Biomedical subjects

E Luther

Publications and source records attributed to E Luther.

At least 19 recordsLinked to original sources

Cell cycle and hormonal control of nuclear-cytoplasmic localization of the serum- and glucocorticoid-inducible protein kinase, Sgk, in mammary tumor cells. A novel convergence point of anti-proliferative and proliferative cell signaling pathways.

The serum- and glucocorticoid-inducible kinase (sgk) is a novel serine/threonine protein kinase that is transcriptionally regulated in rat mammary tumor cells by serum under proliferative conditions or by glucocorticoids that induce a G1 cell cycle arrest. Our results establish that the subcellular distribution of Sgk is under stringent cell cycle and hormonal control. Sgk is localized to the perinuclear or cytoplasmic compartment as a 50-kDa hypophosphorylated protein in cells arrested in G1 by treatment with the synthetic glucocorticoid dexamethasone. In serum-stimulated cells, Sgk was transiently hyperphosphorylated and resided in the nucleus. Laser scanning cytometry, which monitors Sgk localization and DNA content in individual mammary tumor cells of an asynchronously growing population, revealed that Sgk actively shuttles between the nucleus (in S and G2/M) and the cytoplasm (in G1) in synchrony with the cell cycle. In cells synchronously released from the G1/S boundary, Sgk localized to the nucleus during progression through S phase. The forced retention of exogenous Sgk in either the cytoplasmic compartment, using a wild type sgk gene, or the nucleus, using a nuclear localization signal-containing sgk gene (NLS-Sgk), suppressed the growth and DNA synthesis of serum-stimulated cells. Thus, our study implicates the nuclear-cytoplasmic shuttling of sgk as a requirement for cell cycle progression and represents a novel convergence point of anti-proliferative and proliferative signaling in mammary tumor cells.

Animals

Hazmat havoc.

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Accidents, Occupational

Characterization of murine intercellular adhesion molecule-2.

Rat mAbs were raised against murine intercellular adhesion molecule-2 (ICAM-2). Immune precipitation and purification reveal that the murine ICAM-2 glycoprotein is 55 kDa and is similar in size to human ICAM-2. ICAM-2 is expressed on a variety of leukocyte cell lines, including T and B lymphoma, mastocytoma, and macrophage lines. ICAM-2 is well expressed on endothelioma cell lines, and in contrast to ICAM-1, expression is not increased by inflammatory cytokines. One of the mAb to ICAM-2 partially or completely inhibits binding of cells expressing LFA-1 to purified ICAM-2, and binding of cells expressing ICAM-2 to purified LFA-1. The findings in the mouse are congruent with those in the human, suggesting functional conservation of ICAM-2 across species.

Animals

Resolution of mitotic cells using laser scanning cytometry.

A microscope-based laser scanning cytometer (LSCM) has been developed that automatically measures multiple wavelength fluorescence and light scattering of cells on a microscope slide and generates lists of cytochemical and morphological features for each of thousands of cells in a typical sample. For a sample stained with a DNA stain, among the features generated are the value (DNA content), peak (chromatin condensation), and area (nuclear size), as well as the location of the cell on the slide. When combined with each other, these features give detailed resolution of the mammalian cell cycle, including the separation of mitotic from interphase cells. This is demonstrated under a variety of conditions, including cells that were fixed while in suspension and then adhered to a microscope slide, cytocentrifuge preparations, adherent cells fixed in situ on a microscope slide, on viable adherent cells, and on pathological tissue material. Galleries are shown of images of cells that were identified by the instrument as belonging to specific stages of the cell cycle, based on their biochemical staining, and were automatically relocated for viewing. The images are either epifluorescence images of the cells stained with the DNA fluorochrome or brightfield images of cells from slides that were restained with chromatic dyes.

Animals

Monocyte chemoattractant protein 1 acts as a T-lymphocyte chemoattractant.

We have utilized a transendothelial lymphocyte chemotaxis assay to identify and purify a lymphocyte chemoattractant in supernatants of mitogen-stimulated peripheral blood mononuclear cells. Amino acid sequence analysis revealed identity with monocyte chemoattractant protein 1 (MCP-1), a chemoattractant previously thought to be specific for monocytes. Recombinant MCP-1 is chemoattractive for purified T lymphocytes and for CD3+ lymphocytes in peripheral blood lymphocyte preparations. The T-cell response to MCP-1 is dose-dependent and chemotactic, rather than chemokinetic. Phenotyping of chemoattracted T lymphocytes shows they are an activated memory subset. The response to MCP-1 by T lymphocytes can be duplicated in the absence of an endothelial monolayer and the majority of T-lymphocyte chemotactic activity in mitogen-stimulated peripheral blood mononuclear cell supernatants can be neutralized by antibody to MCP-1. Thus, MCP-1 is the major lymphocyte chemoattractant secreted by mitogen-stimulated peripheral blood mononuclear cells and is capable of acting as a potent T-lymphocyte, as well as monocyte, chemoattractant. This may help explain why monocytes and T lymphocytes of the memory subset are always found together at sites of antigen-induced inflammation.

Amino Acid Sequence

Medical ethics in the German Democratic Republic.

Medical ethics has been developing in the German Democratic Republic (GDR) since the 1970's on the basis of the traditional ethics of physicians and the socio-economic fundamentals of our socialist state. Medical care provided in the framework of Marxist-Leninist medical ethics is based on rationality and humanity.

Attitude to Death

Circulating monoclonal B lymphocytes in non-Hodgkin's lymphoma.

Using a sensitive flow cytometric method ("kappa-lambda analysis"), we have found monoclonal B lymphocytes in the blood of 71 of 91 patients with non-Hodgkin's lymphoma. The presence of the B lymphocytes was independent of the histologic subclassification of the patient's disease. When we performed simultaneous analysis of the surface light-chain type in tumor tissue obtained by biopsy, the apparent light-chain type of the blood monoclonal cells corresponded with that of the tumor in 21 of 23 patients (P = 0.03). There was no correlation of the presence of these cells in the blood with morphologic evidence of bone-marrow involvement by lymphoma, but there was a strong correlation with clinical staging. Studies performed during prolonged clinical remission showed that whereas 16 of 25 patients with nodular non-Hodgkin's lymphoma had persistence of monoclonal lymphocytes, none of the 14 patients with diffuse histiocytic lymphoma in remission had these findings (P less than 0.005). Our analysis for B-cell clonal excess demonstrates the persistence of circulating monoclonal lymphocytes during complete remission in patients with forms of lymphoma that have a high probability of relapse, but we did not find these cells in patients in remission from categories of lymphoma in which prolonged remission is associated with cure. It is possible that the circulating monoclonal lymphocytes in patients with lymphoma are malignant cells, and their disappearance or persistence after remission may have prognostic importance.

B-Lymphocytes

Control of adrenocorticotrophin secretion by catecholamines in the pregnant and foetal sheep.

The effect of adrenaline on the maternal and foetal plasma ACTH concentration of twelve pregnant sheep with chronically implanted vascular catheters has been studied. Adrenaline infused into the jugular vein of the ewe or foetus produced carotid arterial adrenaline concentrations of 1-9 ng/ml. The foetal plasma ACTH was 253 +/- 73 pg/ml and it showed a fivefold increase during adrenaline infusion; the ACTH concentration achieved was proportional to the plasma adrenaline. In the ewe plasma ACTH was 99 +/- 23 pg/ml. During adrenaline infusion to the ewe this rose by an amount dependent on the adrenaline concentration achieved and there was also a rise in foetal plasma ACTH but no consistent change in foetal plasma adrenaline. There was no reproducible change in plasma corticosteroid concentration during adrenaline infusion into the foetus but a rise in maternal plasma corticosteroid concentration during infusion into the ewes. Because the adrenaline concentrations achieved during the infusions were within the physiological range, the results indicate that circulating catecholamines may directly or indirectly influence the concentration of ACTH in the circulation. Also, physiological rises in plasma catecholamines in pregnant animals may stimulate the release of ACTH from the foetal pituitary.

Adrenocorticotropic Hormone

The clearance of ACTH from the plasma of adult and fetal sheep.

The disappearance of 125-I-ACTH from the circulation of 4 pregnant and fetal sheep has been followed after a single injection to the ewe or fetus. The mean metabolic clearance rate for the fetus and the ewe was 55 and 34 ml/min/kg respectively, giving a half-life in each case of about 1 min. The higher fetal than maternal arterial plasma ACTH concentration has been ascribed to a higher rate of secretion rather than a reduced rate of clearance compared with the ewe. There was no evidence of placental transfer of immunologically reactive ACTH.

Adrenocorticotropic Hormone