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A Raedler

Publications and source records attributed to A Raedler.

At least 73 records · Page 4Linked to original sources
PubMed1988

Analysis of differentiation and transformation of cells by lectins.

During differentiation cells are known to change their biological behavior according to their genotype. This is thought to be accompanied by a modulation of cell surface determinants expressed on the outer cell membrane. Vice versa, cell surface molecules are suggested to mediate extracellular signals to the genome. Most of these molecules integrated in the cell membrane have been proven to be glycoconjugates. The carbohydrate moieties of these molecules can be detected by means of lectins that are characterized by their ability to react specifically with distinct terminal sugar sequences. Thus, lectins have been used as appropriate tools for studying the modulation of functionally important membrane-associated molecules during the differentiation of cells, in particular of B- and T-lymphocytes. Moreover, lectins have been proven to distinguish between differentiated cells and malignant cell clones, according to the hypothesis that transformed cells possess a glycoconjugate profile that corresponds to the stage of differentiation at which they are arrested. Since lectins, like monoclonal antibodies, make it possible to study functionally important molecules that are associated with differentiation and malignancy, they might be of value for diagnostic purposes and, moreover, for analyzing malignant transformation.

Cell Differentiation↗
PubMed1988

Phenotype and functional properties of Vicia villosa agglutinin (VVA) binding T cells in patients with Crohn's disease: detection of contrasuppressor activity in patients lacking extra-intestinal manifestations, abscesses and fistulas.

Patients with active Crohn's disease (CD) have significantly increased numbers of T cells binding the Vicia villosa agglutinin (VVA). In patients with CD these VVA+ T cells express either the CD4 or the CD8 determinants, while in normal controls the majority of VVA+ T cells are CD8+. VVA+ T cells are significantly decreased in number in the inflamed mucosa as compared to normal controls. However, in only a subgroup of the patients do the VVA+ T cells show contrasuppressor activity with respect to the IgA and total Ig secretion upon co-cultivation with autologous B cells. Regression analysis revealed that in all data presented, contrasuppression activity correlates significantly with the absence of extra-intestinal symptoms, abscesses and fistulas.

Adult↗
PubMed1987

CRF initiates biological actions within the brain that are observed in response to stress.

Corticotropin-releasing factor (CRF) is thought to be an endogenous mediator of adrenocorticotropic hormone release following stress. We examined if CRF initiates further biological actions that are observed in response to stressful events. Male beagle dogs (10-12 kg) were fitted with a chronic intracerebroventricular cannula, intra-arterial and intravenous catheters, as well as a gastric fistula. Synthetic human CRF was microinjected into the third cerebral ventricle in conscious animals. CRF (0.1-1.0 nmol/kg) significantly (P less than 0.01) increased plasma concentrations of epinephrine, norepinephrine, glucagon, and glucose and elevated mean arterial pressure and heart rate. Pretreatment of the animals with the ganglionic blocking agent chlorisondamine completely abolished the increases in plasma catecholamine and glucose concentrations as well as the elevations in blood pressure and heart rate. CRF significantly (P less than 0.01) inhibited gastric acid secretion, but not plasma gastrin concentrations stimulated by an 8% liquid peptone meal. The gastric inhibitory action of CRF was completely prevented by chlorisondamine and, in part, by naloxone and a vasopressin antagonist. In contrast, bilateral truncal vagotomy did not affect the gastric inhibitory action of CRF. The results of this study indicate that CRF acts within the central nervous system to increase plasma glucose and glucagon concentrations, mean arterial pressure, and heart rate by activation of the autonomic nervous system. CRF inhibits meal-stimulated gastric acid secretion by activation of the sympathetic nervous system and, in part, by opiate and vasopressin-dependent pathways and not by inhibition of gastrin release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

In vivo activated peripheral T cells in autoimmune disease.

Starting from the observation, if that in patients suffering from inflammatory bowel diseases elevated numbers of activated peripheral immunocytes can be detected in correlation to the activity of the disease, subpopulations of lymphocytes in immune-mediated disorders were analyzed for the expression of activation associated antigens. It was found that in patients with immunovasculitis, sarcoidosis, M. Behçet, multiple sclerosis, antibody-mediated hemophilia, SLE,--but not in those with scleroderma--, increased numbers of activated immunocytes could be detected during acute exacerbation, whereas, in remission, the population of activated immunocytes was in the upper normal range. Analyses of phenotypes revealed that the majority of activated immunocytes are T cells. However, a variable minority of cells bear B cell associated determinants. As is the case in total peripheral T cells, the T4 to T8 ratio was in a normal range. Only in Behçet disease and immunovasculitis was the ratio of activated T4 positive to activated T8 positive lymphocytes found to be decreased. In contrast to T cells in patients with inflammatory bowel disease, the majority of activated T cells in the autoimmune disorders under study does not express Fc alpha-receptors. In Behçet disease and immunovasculitis moreover, the incidence of activated Leu 7 positive (= natural killer) cells is low compared to T cells from patients with Crohn's disease or ulcerative colitis. These experiments lead to the conclusion that the assessment of activated immunocytes may serve as a parameter in the evaluation of the clinical activity of autoimmune diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1986

Developmental modulation of neuronal cell surface determinants.

Proceeding from the hypothesis that cellular differentiation processes are correlated with structural changes of the cell membrane, the expression of antigen and lectin receptors, as well as lectin-like molecules during migration and differentiation of pre- and perinatal neurons in the cerebral cortex, was analysed. It could be shown that a number of cell surface structures exist throughout the whole pre- and perinatal period, e.g. receptors for Robinia pseudoacacia lectin (RPL), pokeweed lectin (PWL) and concanavalin A (ConA) and the Ia and H-2-D/K antigens of the major histocompatibility complex (MHC). The expression of other cell surface structures, for example receptors for peanut and Limulus polyphemus lectin (LPL) and of Thy-1, is determined by the developmental stage; i.e. in the perinatal period higher amounts are found than in early prenatal stages. Binding sites for Phaseolus vulgaris lectin, PWL and anti-Thy-1.2 are not only demonstrated on perikaryal membranes, but additionally on diverse tangential or radial fibre structures. While on cells of the ventricular layer - the proliferating cell compartment - peanut lectin (PNL) receptors are observed in low density, LPL receptors in high density, in the migration zone, i.e. the intermediate layer, receptors are found predominantly for PNL and only few cells carry a significant number of LPL-binding sites. After the preneurons have migrated through the intermediate layer and the neighbouring cortical plate, remaining at the pia-near border of the latter, LPL receptors are again expressed on the cell surface of the now bipolar preneurons, while PNL receptors cannot be demonstrated any more. Experimental evidence is put forward indicating the possibility that this modulation of exposed carbohydrate residues on the cell surface might be mediated by a membrane-associated enzyme system on the same single molecule. For the investigation of neuronal cell interaction the ability of disintegrated suspended preneurons was used to reaggregate spontaneously in vitro and to build histiotypic cell formations within these reaggregates. It was found that this reaggregation of suspended neuronal single cells is dependent on the presence of ionized calcium, on the temperature, and on the conditions that influence the frequency of cell contacts. Furthermore, the structures expressed on the cell surface of preneurons during the pre- and perinatal period were investigated in regard to their influence on the reaggregation of these cells by means of a blockade by monoclonal antibodies or saccharides, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

The use of lectins to study normal differentiation and malignant transformation.

Lectins are polypeptides that specifically recognize carbohydrate residues of glycoproteins and glycolipids. They can be extracted from plants, invertebrates and vertebrates. The binding between lectins and carbohydrate moieties can be blocked by the inhibitory sugar for which the lectin is specific. In analogy to antibodies, lectins can be used to analyse cell surface determinants. Thus, differentiation of cells, in particular of immunocytes, has been studied and lectin receptors are now important markers for distinguishing different developmental stages of T-lymphocytes. In consequence, premature, but already committed, T-cells can be eliminated from human bone marrow by means of lectins prior to transplantation in order to avoid graft-versus-host reactions. Moreover, it has been shown that malignant cells can be distinguished from their non-malignant counterparts by the profile of lectin receptors on their surface. This had led to the use of lectin binding sites as tumour markers in lymphomas and carcinomas.

Animals↗
PubMed1985

Involvement of the immune system in the pathogenesis of Crohn's disease. Expression of the T9 antigen on peripheral immunocytes correlates with the severity of the disease.

Peripheral lymphocyte cells from patients suffering from Crohn's disease were analyzed for the expression of the "activation" antigens T9 and HLA-DR on their cell surface. It was found that high numbers of "activated" lymphocytes, the majority of which have proven to be T cells, could be detected in patients with active Crohn's disease, whereas in healthy controls and inactive disease only a small subfraction of lymphocytes was positive for these antigens. This difference was highly significant (p = 0.0001). Within the subpopulation of T9-positive cells the ratio between T4- and T8-positive cells is about 1.8 (compared with 2.0 in the total T-cell subset). All HLA-DR-positive, non-B and non-glass-adherent cells could be detected in the T9-positive cell fraction. The presence of T9 antigens was found to correlate with the grade of severity of the disease as assessed by a Crohn's disease activity index. The presence of high amounts of T cells exhibiting this antigen is not restricted to Crohn's disease but is thought to be of importance as a marker for the involvement of the immune system in other maladies as well. Nevertheless, the determination of T9 antigen is expected to provide objective data reflecting the severity of Crohn's disease.

Antibodies, Monoclonal↗
PubMed1985

Elevated numbers of peripheral T cells in inflammatory bowel diseases displaying T9 antigen and Fc alpha receptors.

Elevated numbers of peripheral T cells expressing the activation associated antigen T9 are found in patients with active Crohn's disease. Expression of T9 is found to be correlated to the activity of the disease. However the presence of activated peripheral T cells is not restricted to Crohn's disease, but could also be found in other maladies with a supposed involvement of the immune system, e.g. ulcerative colitis, sarcoidosis, connective tissue disease and after organ transplantation. Significant elevation of the number of activated T cells could not be detected in cases of viral or bacterial enteritis and coeliac disease. Analysing the subset of T9 positive T cells with regard to the expression of Fc alpha receptors, a significantly increased number of Fc alpha receptor positive cells, within the subset of T9 positive cells in the peripheral blood of patients with Crohn's disease and ulcerative colitis was found, which could not be demonstrated in the case of other diseases analysed in this study. Thus the T9+ Fc alpha receptor +T cell subset may be considered to be pathognomonic for inflammatory bowel diseases. Analysis of the regulatory properties of T9 positive cells, with regard to the immunoglobulin isotype secretion in a pokeweed mitogen stimulated autologeous B cell assay, suggests that peripheral T9 positive T cells are involved in the suppression of IgA synthesis or secretion.

Antigens↗
PubMed1985

Interaction between intestinal and peripheral blood mononuclear cells.

Effective methods are available to isolated immunocytes from human intestinal mucosa. Isolated mononuclear cells from the mucosa of patients with Crohn's disease and normal controls were classified according to ultrastructure and cell-surface profile by the use of a panel of monoclonal antibodies. In both compartments of the mucosa, i.e., the lamina propria and the epithelial layer, no differences were found between intestinal tissue from control patients and unaffected mucosa of patients with Crohn's disease. Inflamed mucosa was characterized by an accumulation of surface-Ig+ cells and, to a lesser degree, of monocytes and granulocytes. The predominant T cell phenotypes were a T4 cell in the lamina propria and a T8 cell in the epithelial layer. Most of the isolated immunocytes were found to be HLA/DR. Analysis of the functional properties of mucosa-associated T cells in a pokeweed-stimulated autologous B cell assay revealed that T cells originating from normal mucosa enhance the generation of IgA-producing B cells, whereas those from chronically inflamed mucosa do not. In contrast, peripheral T cells from patients with Crohn's disease favour expression of the IgA isotype, as compared with peripheral T cells from normal controls. Removal of Fc + T4 cells resulted in a significantly reduced number of IgA B cells. These findings point to an alteration of isotypic immunoregulation in Crohn's disease. It is postulated that a shift from IgA to IgG and IgM in the local immune response could result in antibody-dependent cytotoxicity for enterocytes.

Crohn Disease↗
PubMed1984

[Glycoconjugate cell surfaces as markers of differentiation and malignancy].

The composition of cell membrane-associated glycoproteins and glycolipids is changed during differentiation. Moreover, normal mature cells differ from transformed ones in regard to their glycoconjugate profile. These differences have been analyzed, by means of lectins, concerning intrathymic lymphocytes, T-lymphoma cell lines as well as epithelial carcinomas and tumor cell lines. It was found that lectins recognize molecular structures of the cell membrane which are characteristic of certain developmental stages of intrathymic T-lymphocyte differentiation and, moreover, "tumor"-associated determinants on T-lymphomas as well as on epithelial carcinoma cells.

Animals↗
PubMed1984

Lymphocytes express specific antigen-independent contact interaction sites upon activation.

Cell contact between lymphocytes can be observed in the form of clustering in autologous cultures of rat or mouse lymph node cells. Mutual binding takes place in the absence of adherent cells and is displayed by B cells as well as by T cells, with the exception of immature (Lyt 1,2+) T cells. Contact formation is related to activation of the lymphocytes since thymidine-incorporating cells as well as plaque-forming cells are concentrated in the cluster cell fraction and the formation of clusters is greatly increased by periodate stimulation. The interaction is selective with respect to cell type (cells of other tissue origin are not bound) and differentiation (only activated lymphocytes and some of several lymphoid cell lines are able to interact). The reaction is not genetically restricted, but takes place even between different (but related) species. Neither antigen nor MHC structures are involved in contact formation. Protease treatment abolishes the ability to form clusters, but one part of the interacting receptor/acceptor structures is apparently trypsin resistant. The interaction is dependent on the presence of magnesium, whereas calcium ions have no supporting effect. Involvement of the cytoskeleton is shown by a partial inhibition of the cluster formation by cytochalasin B and azide. No indication for a lectin nature of the binding structures could be found by carbohydrate inhibition studies. The relation of this interaction mechanism to other models of physical interaction in the immune system as well as its possible function for signal exchange and local recruitment of activated cells is discussed.

Animals↗
PubMed1984

Local proliferation of brain macrophages in central nervous system tissue cultures.

Mouse central nervous system tissue cultured for different lengths of time was analyzed for the proliferation of macrophages. These cells were identified and characterized by ultrastructural features, cell surface determinants and their ability to ingest latex particles and bacteria. Under the experimental conditions chosen brain macrophages were derived from perivascular cells which in short term cultures remained attached to blood vessels and later differentiated into brain macrophages with a typical ultrastructural appearance. Identical results were obtained when intravascular cells were largely removed by extensive saline perfusion before culturing. Macrophages assembled around stab wounds of the central nervous system or obtained from peritoneal lavage showed comparable cytological characteristics and cell membrane determinants.

Animals↗
PubMed1983

Lectin-defined cell surface glycoconjugates of pancreatic cancer cells and their nonmalignant counterparts.

Alterations of cell surface carbohydrates of human pancreatic cancer cells from long-term cultures (COLO 357, RPMI 7451, PC 103, PC 107) were assessed ultrastructurally by use of an array of lectin-enzyme conjugates, and compared with lectin-defined changes of glycoconjugates on human pancreatic tissue sections of normal and various pathological conditions. Ulex europeus and, to a lesser degree, Lotus tetragonolobus lectin binding indicate that L-fucose-containing glycoconjugates are expressed predominantly on pancreatic cancer cell surfaces, but not, or restricted to intracytoplasmic structures, on nonmalignant pancreas cells. A comparable binding pattern to pancreatic carcinoma cells is found for Phaseolus vulgaris lectin. This is in contrast to the results with soy bean lectin, the reactivity of which was not restricted to cancer cell surfaces, and with Helix pomatia lectin, which did not bind to pancreatic cancer cells at all, although the latter three lectins possess similar sugar specificities. Between the long-term-cultured malignant pancreas cells differences were observed concerning the binding of wheat germ and pokeweed lectin. Besides, qualitative assets of lectin-binding absorption analyses elaborated quantitative differences in the expression of lectin-defined glycoconjugates on pancreatic cancer cell surfaces.

Carbohydrates↗
PubMed1983

The intrathymic microenvironment: expression of lectin receptors and lectin-like molecules of differentiation antigens and MHC gene products.

The expression of MHC products, differentiation antigens and lectin receptors has been investigated in the various cell types populating different compartments of the thymus. The ultrastructural classification of suspended thymic epithelial cells was facilitated by using a technique that preserves cortical nursing cells or medullary epithelial cell clusters. A subset of peanut lectin positive lymphocytes could be distinguished by their ability to bind soybean lectin also. This subset corresponds to the large proliferating lymphocytes that populate the area between the thymic capsule and the cortex. Ia and H-2 D/K antigens could be detected on nearly all epithelial and lymphoid cells. Expression of H-2 antigens, however, is more pronounced on medullary epithelial cells. T-cell differentiation antigens such as Thy-1 and Lyt-1 could be demonstrated not only on lymphocytes, but, interestingly enough, on cortical epithelial cells as well. These latter cells, in addition, exhibit a cell membrane-bound lectin with a specificity for D-galactose which might well be the structure responsible for binding the galactosyl residues of the peanut lectin receptor of thymic lymphocytes. Binding sites for a large set of lectins could be demonstrated on both, thymic lymphocytes and epithelium. The intrathymic differentiation pathway of T-lineage cells is discussed with regard to those lymphocytic and epithelial cell surface structures considered to enable cellular interaction.

Animals↗
PubMed1982

The median ventricular formation. A distinct structure at the mesencephalic apex.

The prenatal ontogenesis of the median ventricular formation (MVF)--a cell group at the seam between both sides of the mesencephalic roof--was analyzed ultrastructurally, autoradiographically and for the expression of intracytoplasmatic structures, i.e. glial filament antigen. As compared with other regions of the mesencephalic roof it was found that from embryonal day 12 onwards DNA synthesis of ventricular cells in the dorsal midline is significantly reduced. This reduction is more pronounced at later developmental stages. On the other hand, the MVF gains drastically in width during ontogenesis. It was shown that this increase may be caused by an immigration of postmitotic neighbouring ventricular cells. The characteristic morphological feature of MVF cells is their extension from the ventricular lining to the pial basement membrane. Their dorsal processes are joined to a thin fibre bundle and predominantly display microtubules as well as filaments and glycogen within their electrolucent cytoplasm. They also contain intracellular structures that react with antibodies against glial filaments as revealed by an enzyme-coupled immunolabelling. The perikarya of MVF cells, on the other hand, are almost all situated at the same level within the ventral third of the mesencephalic roof, thus bulging concentrically at the lateral sides of the MVF. Characteristically, a subfraction of MVF cells exhibits vast amounts of rough ER. The nature and function of the MVF cells is discussed in the light of the concept of guidance of preneurons by radial glia (Sidman and Rakic 1973).

Animals↗