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Biomedical subjects

L C Andersson

Publications and source records attributed to L C Andersson.

At least 163 records · Page 9Linked to original sources
PubMed1984

The nuclear 3,5,3'-triiodothyronine receptor in human leukaemic cell lines.

The 3,5,3'-triiodothyronine (T3) receptor has been studied in a series of continuously growing human leukaemic cell lines. High concentrations of receptor were found in the erythroblastoid cell line K-562. T3 was bound to the nuclei of these cells with an association constant of 3.4 X 10(9) M-1, and capacity 104 fmol/100 micrograms DNA, or 8700 molecules/nucleus. This capacity is comparable to that of rat liver or growth hormone producing cells (GH cells) in culture, and suggests that the K-562 cell line could be a useful model for the study of T3 action on erythroid differentiation.

Cell Division↗
PubMed1983

Binding of progestins to the glucocorticoid receptor. Correlation to their glucocorticoid-like effects on in vitro functions of human mononuclear leukocytes.

A number of physiological and synthetic progestins were tested for their ability to compete with [3H]dexamethasone for the binding to the glucocorticoid receptor of human mononuclear leukocytes and their ability to elicit glucocorticoid-like effects on the same cells. As compared to the reference compound dexamethasone (relative receptor binding affinity defined as 100%), two potent synthetic progestins with a pregnane-type structure, megestrol acetate and medroxyprogesterone acetate, were found to display a considerable binding affinity towards the receptor (46 and 42%, respectively). The relative binding affinity of the naturally occurring ligand, cortisol, to the receptor was clearly lower (25%). The effective binding of medroxyprogesterone acetate to the glucocorticoid receptor was confirmed by direct binding studies utilizing a tritiated derivative of this steroid. No evidence for the existence of a specific progesterone receptor in human mononuclear leukocytes was obtained as judged by the results of competition experiments where a progesterone receptor-specific ligand [3H]Org 2058 was used. Medroxyprogesterone acetate and megestrol acetate also induced glucocorticoid-like effects on the lymphocyte functions. These included inhibition of the proliferative responses to the T-cell mitogens concanavalin A and phytohaemagglutinin and an enhanced accumulation of immunoglobulin secreting cells in pokeweed mitogen-stimulated cultures. The progestin effect appears to be mediated through a radiosensitive (suppressor) subpopulation of T lymphocytes. In contrast, the synthetic progestins related structurally to 19-nortestosterone, norethisterone and d-norgestrel, were virtually devoid of binding affinity towards the glucocorticoid receptor nor did they measurably influence the in vitro lymphocyte functions. These studies demonstrate that certain progestins in common clinical use probably possess inherent glucocorticoid activity and suggest that side effects attributable to this character (e.g. suppression of the pituitary-adrenal axis) might be expected when these compounds are used in pharmacological doses.

DNA Replication↗
PubMed1983

Protein A radio-assay of H-Y antigen on human leukocytes using mouse and rat antisera and monoclonal antibodies.

The presence of H-Y antigen on human leukocytes was investigated using a protein A radio-assay. H-Y antigen could be demonstrated on male cells using either conventional H-Y antisera produced in mice and rats, or monoclonal H-Y antibodies. With mouse antiserum and IgG-type monoclonal antibody the reaction was male-specific using a single antibody. The reaction obtained with rat antiserum was enhanced by the application of a second antibody (rabbit anti-mouse IgG). This technique provides a rapid, simple, objective, and semiquantitative method for the determination of cellular H-Y antigen, the results being expressed as radioactivity bound to the test cells and thus being independent of human observation. It requires only 10-20 ml of blood and small quantities of antiserum or antibody.

Animals↗
PubMed1983

Erythroid blast crisis in chronic myelogenous leukemia.

Blood or bone marrow specimens from 22 patients with chronic myelogenous leukemia in blast crisis were studied for the surface expression of glycophorin-A, a marker for early erythroid differentiation. The leukemic blasts were stained with rabbit anti-glycophorin-A antiserum. The glycophorin-A molecules detected by the rabbit antiserum were identified by polyacrylamide slab gel electrophoresis of the immunoprecipitates from the membrane lysates of surface-labeled blasts. Blasts expressing surface glycophorin-A were found in 9 of the 22 patients. In 4 patients, almost all blasts were glycophorin-A positive, and in 5 patients, less than half of the blast population expressed glycophorin-A. The present study shows that when glycophorin-A is used as a marker for erythroid blasts, involvement of the erythroid lineage during blast crisis of chronic myelogenous leukemia seems to occur more frequently than previously recognized.

Adolescent↗
PubMed1982

Glucocorticoid receptors in hairy-cell leukemia.

Glucocorticoid receptors were measured from leukemic cells of five patients with hairy-cell leukemia as well as a cell line (JOK-1) derived from one of the patients studied and grown in continuous culture in vitro. Receptor analyses were accomplished using a whole-cell binding assay with [3H]dexamethasone as the ligand. Glucocorticoid receptor sites in the leukemic hairy cells ranged from 5,710 to 11,400 sites/cell, and the mean dissociation constant (KD) between the receptor sites and [3H]dexamethasone was 0.67 +/- 0.03 X 10(-8) M. The glucocorticoid receptor nature of the binding activity was verified by demonstration of an appropriate order of competing ability for a selected group of ligands. The cell line JOK-1 contained 9830 receptor sites/cell with a KD of 0.78 X 10(-8) M. The in vitro growth pattern of this cell line was characterized by an almost complete insensitivity to glucocorticoids. We conclude that the postulated general presence of glucocorticoid receptors in various types of normal and malignant leukocytes extends to hairy-cell leukemia, a disease often characterized by resistance to antileukemic drugs, including corticosteroids. The sole presence of the glucocorticoid receptor thus does not seem to signify steroid responsiveness.

Binding, Competitive↗
PubMed1982

Role of sialic acid in the mobility of membrane proteins containing O-linked oligosaccharides on polyacrylamide gel electrophoresis in sodium dodecyl sulfate.

The major sialoglycoprotein of the human red-cell membrane, glycophorin A, contains 15 O-glycosidically linked oligosaccharides and one N-glycosidic oligosaccharide. The protein shows a decreased mobility on polyacrylamide gel electrophoresis in sodium dodecyl sulfate after neuraminidase treatment of the non-denatured protein. The molecular mechanism behind this phenomenon has been elucidated. Neuraminidase treatment of glycophorin A in intact cells or after solubilization in buffers containing Triton X-100 resulted in conversion of the predominant tetrasaccharide N-acetylneuraminosyl alpha 2-3galactosyl beta 1-3(N-acetylneuraminosyl alpha 2-6)-N-acetylgalactosamine to the trisaccharide galactosyl beta 1-3(N-acetylneuraminosyl alpha 2-6)-N-acetylgalactosamine and the disaccharide galactosyl beta 1-3-N-acetylgalactosamine. After denaturation with sodium dodecyl sulfate, Vibrio cholerae neuraminidase also liberated the N-acetylgalactosamine-bound sialic acids. Such treatment resulted in increased electrophoretic mobility. The results show that distal sialic acids linked to galactose are readily available to neuraminidase, and that their negative charge gives an increased electrophoretic mobility in polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. In contrast, most of the N-acetylgalactosamine-linked sialic acids of glycophorin A are not liberated by neuraminidase without denaturation of the substrate. Like sialic acids of complex-type oligosaccharides the decreased electrophoretic mobility caused by them is exclusively due to their mass while no significant contribution by the charge was seen.

Chemical Phenomena↗
PubMed1982

Glutamine requirements for purine metabolism in leukemic lymphoblasts.

The two pathways of purine metabolism that include glutamine-dependent reactions, purine synthesis de novo and guanine nucleotide synthesis, were studied in cultured lymphoblasts derived from patients with T cell (JM), B cell (BALL) or null cell (NALL) acute lymphoblastic leukemia (ALL). When glutamine was omitted from the incubation medium, purine synthesis de novo, measured by the incorporation of 14C-formate into purine compounds, was depressed to barely measurable rates in BALL and NALL cells, but proceeded at moderate though reduced rates in JM cells, when compared to synthesis in the presence of 2 mM glutamine. Similarly, the incorporation of 14C-hypoxanthine into guanine nucleotides was arrested at the glutamine-requiring XMP-aminase reaction in the BALL and NALL lines but not in the JM line, when exogenous glutamine was absent. The data suggest that glutamine deprivation, whether by omission from the culture medium in vitro or by glutaminase treatment in vivo, will have more profound biochemical consequences in B and null cell-derived ALL than in T All.

B-Lymphocytes↗
PubMed1982

Reduced level of cellular glucocorticoid receptors in patients with anorexia nervosa.

Specific glucocorticoid receptors were measured in circulating mononuclear leukocytes from 12 patients with anorexia nervosa and 21 healthy control subjects. Cells from patients were found to contain a significantly (p less than 0.01) lower level of glucocorticoid receptor (3830 +/- 210 sites/cell, mean +/- SE) than those from controls (4930 +/- 250 sites/cell). A partial glucocorticoid receptor defect may well explain the abnormal cortisol metabolism and glucocorticoid resistance commonly found in patients with anorexia nervosa.

Adolescent↗
PubMed1982

Acute erythroleukaemia with L3 morphology and the 14q+ chromosome.

L3 morphology according to the FAB classification and the 14q+ chromosome are usually ascribed to the Burkitt type of leukaemia or lymphoma with a B or pre-B cell phenotype. We report here a case of adult acute leukaemia with Burkitt morphology and the 14q+, which did not express lymphoid markers. Instead, the leukaemia was shown to be an acute erythroleukaemia. The erythrocyte marker glycophorin A was present on the surface of the leukemic blasts as shown by immunofluorescence and immunoprecipitation from membrane lysates of surface labeled cells with antiglycophorin A antiserum. Spectrin and fetal hemoglobin appeared after cultivation of the blasts in the presence of sodium butyrate. The present case shows that a short term cultivation is sometimes useful for further characterization of the commitment of acute leukaemias.

Acute Disease↗
PubMed1982

Expression of histoincompatibility antigens during spermatogenesis in the rat.

The expression of the AgB-SB and -LD (Ia-like) antigens on spermatogenic cells has been investigated by using a protein A-containing Staphylococcus Cowan I rosetting assay. The results show that the Ia-like antigens are present on all spermatogenic cells although the relative expression seems to decrease slightly concomitant with the differentiation. The AgB-SD antigens are detected on spermatogenia, leptotene, and zygotene spermatocytes but not on later developmental stages.

Animals↗
PubMed1981

Sex hormone regulation of in vitro immune response. Estradiol enhances human B cell maturation via inhibition of suppressor T cells in pokeweed mitogen-stimulated cultures.

The effects of the main male and female sex hormones, testosterones and estradiol, in pokeweed mitogen (PWM)-stimulated cultures of human blood lymphocytes were studied. We found that the addition of physiological concentrations of estradiol (780-2,600 pmol/liter) to PWM cultures significantly increased the accumulation of immunoglobulin M-containing and -secreting cells detected by immunofluorescence and/or by the reversed protein-A plaque assay. The dose range of estradiol that induced enhanced B cell maturation did not affect the proliferative response. Estradiol displayed the same effect in vitro on lymphocytes from both men and women. Fractionation of lymphocyte subpopulations before culturing revealed that estradiol does not display a direct mitogenic or stimulatory effect of B cells. Instead, estradiol inhibits the suppressive activity of a radio-sensitive (1,000 rad) subset of T lymphocytes bearing Fc-receptors for immunoglobulin G. Nontoxic concentrations fo testosterone did not influence the in vitro B cell maturation. These observations provide a cellular basis for the differences in the immunoreactivities of males and females. The estradiol-induced inhibiton of suppressor T cells might be important for the pathogenesis of various autoimmune disorders.

B-Lymphocytes↗
PubMed1981

Radioimmunoassay for H-Y antigen.

A sensitive direct radioimmunoassay for the detection of H-Y antigen on human blood mononuclear leukocytes is described. The cells were incubated with antisera obtained by immunization of inbred female rats or mice with male cells and tissues. The bound antibodies were detected by 125I-labeled protein A. Results are expressed as cpm bound to the cells.

Antigen-Antibody Complex↗