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Biomedical subjects

S Fossum

Publications and source records attributed to S Fossum.

At least 73 records · Page 4Linked to original sources
PubMed1985

Effects of bromocriptine on cell cycle distribution and cell morphology in cultured rat pituitary adenoma cells.

The effects of bromocriptine, a dopamine (DA) agonist, on cell cycle distribution and cell morphology have been studied in a clonal strain of rat pituitary adenoma cells (GH3) which produce and secrete spontaneously both prolactin (Prl) and growth hormone (GH). DNA flow cytometry showed that bromocriptine caused a dose-dependent delay in cell cycle traverse concomitantly with a reduction in cellular growth rate. The lowest concentration of bromocriptine (5 X 10(-6) mol/l) significantly (P less than 0.05) increased the relative number of cells in the S phase and reduced the proportion of cells in the G1 phase. At higher concentrations (1 X 10(-5)-5 X 10(-5) mol/l) bromocriptine delayed cell cycle traverse through effects on cells in the S, G1 and G2 phases. These effects occurred already after 24 h of treatment. These results were supported by autoradiography of nuclear uptake of [3H]thymidine and by measurements of the number of cells arrested in metaphase after colcemide treatment (mitotic rate). Bromocriptine at 5 X 10(-5) mol/l altered profoundly GH3 cell structure inducing cell clustering and typical changes in mitochondrial and nuclear ultrastructures. Since Prl and GH production is a characteristic of cells in G1 phase, the inhibitory effect of the lowest antiproliferative concentration of bromocriptine (5 X 10(-6) mol/l) can only partly be explained by alterations in phase distribution. At the highest concentration of bromocriptine (5 X 10(-5) mol/l) hormone production and cell division are also inhibited due to general toxic effects as reflected by the ultrastructural changes.

Adenoma↗
PubMed1985

The rapid rejection of allogeneic lymphocytes by a non-adaptive, cell-mediated mechanism (NK activity).

The fate of allogeneic lymphocytes (AO or DA) transferred to non-immune PVG recipients was studied in the light of previous evidence (Heslop & McNeilage, 1983; Rolstad & Ford, 1983) that allogeneic lymphocytes can be rapidly destroyed in certain strain combinations of rats and mice by a mechanism that is distinct from either T-cell mediated immunity or an alloantibody response. AO lymphocytes injected into PVG recipients were discriminated from syngeneic lymphocytes within 15-30 min of i.v. injection, as testified by the excess release of 51Cr into the lymph plasma of the recipient. The following experiments were intended to distinguish between natural antibody and natural killer (NK) cells as the mechanism responsible for the allogeneic lymphocyte cytotoxicity (ALC) displayed by PVG rats. Nude rats treated from birth with anti-mu chain serum and shown to be lacking B and T lymphocytes, as well as being profoundly deficient in immunoglobulin, displayed more aggressive ALC than did control nude rats which, in turn, showed stronger ALC than did euthymic rats. Serum from PVG nude rats exerted no inhibitory or destructive effect on allogeneic lymphocytes in an antibody-dependent cellular cytotoxicity system, an assay of graft-versus-host activity, or when injected into 3-4-week-old PVG rats which had not yet developed ALC. Treatment of nude rats with anti-asialo GM 1 antiserum depressed ALC and NK activity in parallel, thus adding to a wide range of circumstances in which ALC and NK activity are closely correlated. In conclusion, ALC is implemented by a non-adaptive, cell-mediated mechanism independent of immunoglobulin, but the precise identity of the effector cell in the recipients' lymphatic tissues remains to be settled.

Animals↗
PubMed1984

Recovery of peripheral lymph cells from congenitally athymic nude rats.

Thoracic-duct cannulation of mesenteric lymphadenectomized (MLNx) congenitally athymic nude rats was studied as a method of obtaining peripheral lymph cells. A higher recovery of non-lymphoid cells (NLC) was obtained from nude than from euthmyic littermates. Both a higher percentage and a greater number of NLC were found in nude animals. Most of these cells resembled dendritic or veiled cells and were strongly positive for Ia antigens. This population could further be enriched by irradiation of the animal, but with a risk of cell damage. Splenectomy had no effect on early output of Ia+ NLC. A substantial population of lymphoid cells from MLNx nude rats expressed T-cell antigens defined by the monoclonal antibodies OX 19, OX 8 or W3/25. These cells were more radiosensitive than were mature T cells. In addition, a large population of cells in the peripheral lymph from nude rats did not display surface antigens recognized by monoclonal antibodies directed either against B cells or against T cells. This cell fraction increased after irradiation. These cells resembled small lymphocytes but had a more irregular nucleus and multiple large granules.

Animals↗
PubMed1984

Characterization of Ia+ non-lymphoid cells in peripheral lymph from congenitally athymic nude rats.

Non-lymphoid cells (NLC) were obtained by thoracic-duct cannulation of mesenteric lymphadenectomized (MLNx) congenitally athymic nude rats. The cells were similar to NLC collected directly from testicular lymph and from the thoracic duct of MLNx euthymic rats. Ia+ NLC were characterized by a highly irregular, veiled or dendritic surface. Otherwise the cells were heterogeneous with regard to ultrastructure, non-specific acid esterase activity, and surface antigens. Roughly a third of the cells had surface Thy-1 antigen. A negative correlation was found between the presence of Thy-1 and non-specific acid esterase activity. Compared with macrophages and granulocytes they showed limited phagocytosis of simple test substances. However, Ia+ NLC often contained lysosomes and some were occasionally observed in the act of phagocytosing and ingesting other cells, thus demonstrating phagocytic ability. Since Ia+ NLC were abundant in peripheral lymph but rare in central lymph, they must be held back by the draining lymph nodes. Their relationship to NLC within lymph nodes is discussed.

Animals↗
PubMed1984

Natural killer (NK) cell cytotoxicity in athymic (nude) rats.

The in vitro and in vivo natural killer (NK) cell activity of congenitally athymic, nude (ATH) rats and of normal, euthymic (EUTH) rats was compared. We found: a) a higher level of in vitro NK cell activity in blood, spleen and lymph nodes of ATH rats compared with their heterozygous littermates, b) in the spleen the number of NK lytic units per organ was not higher in ATH compared with EUTH whereas it was significantly higher in lymph nodes, c) a lack of age-dependence of in vitro NK cell activity tested in culture with heat inactivated fetal calf serum, d) a higher rate of in vivo elimination of target tumor cells in 4-week ATH rats compared with EUTH rats, e) an age-dependent decrease in the rate of in vivo target cell elimination in both groups, and finally, f) an age-dependent increase in the inhibitory effect of autologous serum on NK cell activity in vitro in both groups. These findings show that the blood and lymphoid organs of athymic rats contain a substantially higher proportion of NK cells, active both in vitro and in vivo against K562 tumor cells, than their euthymic littermates. In the spleen this increased proportion can be attributed to the lack of T cells, whereas in the ATH rat lymph nodes there is an absolute increase in NK cell activity, and that the decrease of cytotoxicity in vivo with age reflects the increasing inhibitory properties of autologous serum both in nude and in normal rats.

Animals↗
PubMed1983

The architecture of rat lymph nodes. I. Combined light and electron microscopy of lymph node cell types.

Non-lymphoid cells in rat lymph nodes are described as seen by combined light and electron microscopy of normal adult, congenitally athymic, germ-free, irradiated, or newborn rats. The cells are divided into stromal and non-stromal. The latter category consists of a variety of morphologically distinct cell types with characteristic distribution patterns. The presence of paracortical interdigitating cells in lymph nodes of germ-free rats, athymic rats, and newborn euthymic and athymic rats, refutes the ideas that interdigitating cells differentiate from macrophages under immune stimulation or T cell influences. Follicular dendritic cells are more clearly visualized and appear to be polynucleated after emptying the follicles of lymphoid cells by irradiation. Follicular dendritic cells and tingible body macrophages are found in conventionally raised euthymic and athymic rats, but not in germ-free rats. The interrelationships of these and other types of non-lymphoid cells are discussed.

Animals↗
PubMed1983

The migration of lymphocytes across specialized vascular endothelium VII. The migration of T and B lymphocytes from the blood of the athymic, nude rat.

The primary migration of lymphocytes from the blood was compared in nude rats and in euthymic rats. The flatter endothelium in the post-capillary venules (PCV) in the lymph nodes of nude rats was as efficient as the high endothelium of PCV in euthymic rats at capturing both T and B lymphocytes from the blood, although lymphocytes took a longer time to cross the PCV wall in nude recipients. The organ distribution of both lymphocytes and lymphoblasts ([125I]UdR-labelled cells) was broadly similar in nude and euthymic recipients. A second aim was to compare B and T lymphocytes with respect to the rate and sites at which they leave the blood after intravenous injection. As judged by sampling venous blood, B lymphocytes left the blood faster, but this was partly attributable to a larger intravascular pool of B lymphocytes in small blood vessels, especially in the lung. Thoracic duct lymphocytes from nude rats collected under standard conditions (16 h, O degrees C) entered the cervical lymph nodes very poorly, but when lymphocyte transfer was performed under more physiological conditions entry of B lymphocytes into lymph nodes was about half that of T lymphocytes. B lymphocytes did show a slight preference for entry into Peyer's patches compared with lymph nodes.

Animals↗
PubMed1983

The recirculation of T and B lymphocytes in the athymic, nude rat.

The recirculation of lymphocytes through the tissues and their return to the blood were compared in nude and euthymic rats. Three approaches were used: the organ distribution of 15Cr-labelled lymphocytes from nude or euthymic donors at 24 h after injection; the compartmental distribution of B and T lymphocytes as assessed by autoradiography of the spleen, lymph nodes, and Peyer's patches; and the tempo of recirculation from blood to thoracic duct lymph as estimated by counting timed fractions of lymph from a recipient of labelled lymphocytes. The following conclusions were drawn: (1) The distribution of lymphocytes between organs and within organs is very similar in nude and euthymic recipients. In particular, B lymphocytes proceed normally to the follicular areas in the absence of T cells. (2) The recirculation from blood to lymph is delayed in nude rats. (3) For equal numbers of B and T cells injected intravenously about half as many B cells as T cells enter mesenteric and cervical lymph nodes, but approximately equal numbers of B and T cells enter the spleen and Peyer's patches.

Animals↗
PubMed1981

The stimulus to host cell proliferation in graft-versus-host reactions.

Two experiments are described concerned with the mechanism of host cell activation in the rat popliteal lymph node (LN) undergoing a graft-versus-host (GVH) reaction. (1) Irradiated, F1 hybrid hosts (750 rad) mounted an impaired response to parental strain T cells. This was augmented by an intravenous injection of F1 hybrid lymphocytes but not by parental strain B lymphocytes syngeneic with the initiating T cells. When the donor T cells (footpad) and B lymphocytes (intravenous) were completely allogeneic the residual response of the irradiated F1 was completely inhibited. (2) The popliteal LN response in the semi-allogeneic situation of the type (A x C)F1 leads to (B x C)F1 was, if anything, weaker than in the allogeneic situation AA leads to BB. These results and other data are discussed in terms of a possible major histocompatibility complex (MHC) requirement for host cell activation. The sharing of an MHC haplotype between donor and host cells is unlikely to be a necessary or sufficient condition for host cell activation.

Animals↗
PubMed1980

The architecture of rat lymph nodes. II. Lymph node compartments.

Although lymph nodes are conventionally regarded as composed of superficial cortex, deep cortex, and medullary cords merge gradually into each other, the sinuses, the interstitium, and the germinal centres are separated by cellular borders that seem sufficiently complete to limit the rate of exchange of cells and molecules. Accordingly, the cellular composition shows distinct differences on either side of these borders. These compartments show further division into regions, the sinuses into superficial and deeply situated sinuses, the interstitium into superficial interstitium, follicles, paracortical nodules, and medullary interstitium, characterized by differences in densities of various cell types. Mechanisms behind the different distribution of cells within the different lymph node compartments and regions are discussed.

Animals↗
PubMed1980

The architecture of rat lymph nodes. III. The lymph nodes and lymph-borne cells of the congenitally athymic nude rat (rnu).

The lymph nodes (LN) of the congenitally athymic nude rat(rnu) were compared with the LN of non-nude littermates. The mesenteric and coeliac LN were smaller in the rnu rats, but the axillary and the cervical LN were larger. Germinal centres were found in the LN of nude rats. They were scarce and often very small, but some were of normal structure, especially in the cervical LN. The endothelium of post-capillary venules in the LN or normal rats, was seen. The paracortex was extremely depleted of lymphocytes but remained a distinct area occupied predominantly by pale interdigitating cells. In some LN the medullary sinuses were distended and the cords engorged with plasma cells. The predominant cells in thoracic duct lymph were immunoglobulin-positive B lymphocytes. The hourly output of these cells was the same as that in non-nude littermates. However, small numbers of thoracic duct cells were positive for the markers identified by the monoclonal antibodies W3/13 and W3/25, although in normal rats these are not expressed on small B lymphocytes.

Animals↗
PubMed1980

The architecture of rat lymph nodes. IV. Distribution of ferritin and colloidal carbon in the draining lymph nodes after foot-pad injection.

Rat popliteal and the iliac lymph nodes were examined after foot-pad injections of colloidal carbon and ferritin-tetramethylrhodamine isothiocyanate. Carbon rapidly entered medullary sinuses, but the entry of carbon into the interstitium was prohibited by avid phagocytosis, by sinus macrophages and by the lymphoendothelium, which apparently formed a barrier to diffusion. In contrast, little carbon was phagocytosed in subcapsular sinuses, from where the particles entered the underlying cortex through holes in the lymphoendothelium created by penetrating frilly cells. The distribution of ferritin was similar to that of carbon. Both carbon and ferritin localized poorly in follicles; however, preinjection of specific antibody caused enhanced follicular localization of ferritin. By electron microscopy clusters of ferritin molecules were found on the surface of dendritic cells. These cells showed different morphology from that of the interdigitating cells of the paracortex. The latter cells did not bind ferritin to their surface, even in the presence of specific antibody.

Animals↗
PubMed1978

Non-specific acid esterase activity in rat lymphocytes.

In a first night's collection of rat thoracic duct lymphocytes B- and T-cells were distinguished on cytocentrifuge smears by complementary markers: B-cells by rosette-formation with Staphylococcus aureus Strain Cowan 1 armed with rabbit antiserum to rat F(ab')2 and T-cells by high uptake of 3H-uridine demonstrated by autoradiography. On incubation of the cytocentrifuge smears for demonstration of alpha-naphthyl-acetate esterase (ANAE)-activity, most B-cells showed large, intense colour deposits often located in the uropod. T-cell ANAE-activity on the other hand was variable, possibly due to variations in experimental conditions. When present, the T-cell colour deposits were small, dot-like and of low intensity. ANAE-activity may then be used to differentiate between rat T- and B-cells, being a marker for the latter cell type. This is unexpected as others have reported that ANAE-activity is specific for T-cells in mouse and man. Studies with inhibitors indicate that the rat B-cell enzyme belongs to the acetylesterases.

Acetates↗
PubMed1977

Stereological and biochemical analysis of prolactin and growth hormone secreting rat pituitary cells in culture. Stereology combined with non-parametrical statistics.

The secretion of prolactin is increased by treatment of prolactin producing rat pituitary cells with the hypothalamic tripeptide thyroliberin. To investigate the underlying mechanisms we used three closely related rat pituitary tumor cell strains (GH1 2C1, GH3 and GH4C1), which synthesize and spontaneously secrete prolactin and/or growth hormone. Growth hormone and prolactin released into the culture medium over a period of 24 h were measured by radioimmunoassay. Initial rates of synthesis were measured by immunoprecipitation of intracellular growth hormone and prolactin after incubation of cell cultures with 3H-leucine. The observed increase in prolactin synthesis and release was correlated with morphological effects of thyroliberin treatment. The volume density of Golgi complexes and the volume and surface densities of rough endoplasmic reticulum were compared in untreated cells and thyroliberin treated cells. As normal distribution could not be assumed the non-parametric rank test of Wilcoxon was used whereby the densities calculated for each cell section were ranked. All three morphological parameters increased after thyroliberin treatment in cells secreting prolactin only (GH4C1), implying that the increase of prolactin secretion, at least in part, is due to increased prolactin synthesis.

Animals↗