TY - JOUR A1 - Lohse, M. J. A1 - Maurer, K. A1 - Klotz, Karl-Norbert A1 - Schwabe, U. T1 - Synergistic effects of calcium-mobilizing agents and adenosine on histamine release from rat peritoneal mast cells N2 - 1 Adenosine and its metabolically stable analogue N.etbyl-carboxamidoadenosine (NECA) enhance histamine release from rat peritoneal mast cells when tbese are stimulated by calciummobilizing agents. NECA and adenosine shift the concentration-response curve of tbe calcium ionophore A23187 to lower concentrations. 2 The potencies of NECA or adenosinein enhancing A23187-induced histamine release are dependent on the Ievel of stimulated release in tbe absence of adenosine analogues. At high Ievels of release their potencies are up to 20 times higher than at low Ievels. Consequently, averaged concentration-response curves of adenosine and NECA for enhancing bistamine release are shallow. 3 The adenosine transport blocker S-(p-nitrobenzyl)-6-thioinosine (NBTI) has no effect by itself at low Ievels of stimulated histamine release, but abolishes the enhancing effect of adenosine. At high Ievels of release, however, NBTI alone enhances the release of histamine. 4 lt is concluded that adenosine and calcium reciprocally enhance the sensitivity of the secretory processes to the effects of the other agent. The Ievels of intracellular adenosine obtained by trapping adenosine inside stimulated mast cells are sufficient to enhance histamine release substantially, suggesting that this effect may play a physiological and pathophysiological role. KW - Toxikologie Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60346 ER - TY - JOUR A1 - Klotz, Karl-Norbert A1 - Lohse, M. J. A1 - Schwabe, U. A1 - Cristalli, G. A1 - Vittori, S. A1 - Grifantini, M. T1 - 2-Chloro-N\(^6\)-[\(^3\)H]cyclopentyladenosine ([\(^3\)H]CCPA) - a high affinity agonist radioligand for A\(_1\) adenosine receptors N2 - The tritiated analogue of 2-chloro-N6-cyclopentyladenosine (CCPA), an adenosine derivative with subnanomolar affinity and a 10000-fold selectivity for A1 adenosine receptors, has been examined as a new agonist radioligand. [3H]CCP A was prepared with a specifi.c radioactivity of 1.58 TBqjmmol ( 43 Ci/mmol) and bound in a reversible manner to A1 receptors from rat brain membranes with a high affinity K0 -value of 0.2 nmol/1. In the presence of GTP a K0 -value of 13 nmol/1 was determined for the low affinity state for agonist binding. Competition of several adenosine receptor agonists and antagonists for [3H]CCPA binding to rat brain membranes confrrmed binding to an A1 receptor. Solubilized A1 receptors bound [3H]CCPA with similar affinity for the high affinity state. At solubilized receptors a reduced association rate was observed in the presence of MgC12, as has been shown for the agonist [ 3H]N6-phenylisopropyladenosine ([3H]PIA). [3H]CCPA was also used for detection of A1 receptors in rat cardio myocyte membranes, a tissue with a very low receptor density. A K0 -value of 0.4 nmol/1 and a Bmax-value of 16 fmol/ mg protein was determined in these membranes. In human platelet membranes no specific binding of [3H]CCPA was measured at concentrations up to 400 nmoljl, indicating that A2 receptors did not bind [3H]CCPA. Based on the subnanomolar affinity and the high selectivity for A1 receptors [ 3H]CCPA proved to be a useful agonist radioligand for characterization of A 1 adenosine receptors also in tissues with very low receptor density. KW - Toxikologie KW - Adenosine receptors KW - Radioligauds KW - agonists Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60328 ER - TY - JOUR A1 - Tawfik-Schlieper, H. A1 - Klotz, Karl-Norbert A1 - Kreye, V. A. W. A1 - Schwabe, U. T1 - Characterization of the K\(^+\)-channel-coupled adenosine receptor in guinea pig atria N2 - In the present work we studied the pharmacological profile of adenosine receptors in guinea pig atria by investigating the effect of different adenosine analogues on 86Rb + -efflux from isolated left atria and on binding of the antagonist radioligand 8-cyclopentyl-1 ,3-[\(^3\)H]dipropylxanthine ([\(^3\)H]DPCPX) to atrial membrane preparations. The rate of \8^{86}\)Rb\(^+\) -effiux was increased twofold by the maximally effective concentrations of adenosine receptor agonists. The EC50-values for 2-chloro-N\(^6\)-cyclopentyladenosine (CCPA), R-N\(^6\)-phenylisopropyladenosine (R-PIA), 5'-Nethylcarboxamidoadenosine (NECA), and S-N\(^6\)-phenylisopropyladenosine (S-PIA) were 0.10, 0.14, 0.24 and 12.9 \(\mu\)M, respectively. DPCPX shifted the R-PIA concentration-response curve to the right in a concentration-dependent manner with a K\(_B\)-value of 8.1 nM, indicating competitive antagonism. [\(^3\)H]DPCPX showed a saturable binding to atrial membranes with a Bmax·value of 227 fmol/mg protein and a K\(_D\)-value of 1.3 nM. Competition experiments showed a similar potency for the three agonists CCPA, R-PIA and NECA. S-PIA is 200 times less potent than R-PIA. Our results suggest that the K\(^+\) channel-coupled adenosine receptor in guinea pig atria is of an A\(_1\) subtype. KW - Toxikologie KW - A1 Adenosine receptors KW - K + -channels KW - Atria KW - Radioligand binding - 86Rb + -efflux Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60333 ER - TY - JOUR A1 - Moll, Heidrun A1 - Scollay, Roland T1 - L3T4+ T cells promoting susceptibility to murine cutaneous leishmaniasis express the surface marker Ly-24 (Pgp-1) N2 - No abstract available KW - Biologie Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61275 ER - TY - JOUR A1 - Moll, Heidrun A1 - Mitchell, Graham F. A1 - McConville, Malcom J. A1 - Handman, Emanuela T1 - Evidence for T cell recognition in mice of a purified lipophosphoglycan from Leishmania major N2 - We have previously reported that a Leishmania major lipophosphoglycan (LPG), given with killed Corynebacterium parvum as an adjuvant, can vaccinate mice against cutaneous leishmaniasis. In order to analyze whetber T cells are able to recognize this important parasite antigen, we have studied both humoral and cellular immune responses to L. major LPG that bad been isolated from promastigotes by sequential solvent extraction and bydrophobic chromatography. The data sbow that immunization of mice with highly purified LPG induced an increase in frequency of L. major-reactive T cells and the production of immunoglobulin G antibodies to LPG. Furthermore, genetically resistant mice infected with L. major were able to develop a specific delayed-type hypersensitivity response in the ear to L. major LPG. These findings strongly suggest that T cells can recognize and respond to glycolipid antigens, in this case a bost-protective Leishmania LPG, even though such antigens appear not to be potent T-cell stimulators in mice. KW - Biologie Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61288 ER - TY - JOUR A1 - Heinsen, Helmut A1 - Heinsen, Y. L. A1 - Beckmann, H. A1 - Gallyas, F. A1 - Haas, S. A1 - Scharff, G. T1 - Laminar neuropathology in Alzheimer's disease by a modified Gallyas impregnation N2 - No abstract available KW - Medizin KW - Alzheimer-Krankheit Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59933 ER - TY - JOUR A1 - Ernsberger, Uwe A1 - Sendtner, Michael A1 - Rohrer, Hermann T1 - Proliferation and differentiation of embryonic chick sympathetic neurons: Effects of ciliary neurotropic factor. N2 - At early developmental stages (embryonic day 7, E7), chick paravertebral sympathetic ganglia contain a cell population that divides in culture while expressing various neuronal properties. In an attempt to identify factors that control neuronal proliferation, we found that ciliary neurotrophic factor (CNTF) specifically inhibits the proliferation of those cells expressing neuronal markers. In addition, CNTF affects the differentiation of sympathetic ganglion cells by inducing the expression of vasoactive intestinal peptide immunoreactivity (VIP-IR). After 1 day in culture, tyrosine hydroxylase immunoreactivity (TH-I R) was expressed by about 86% of the cells whereas VIP-IR was virtually absent. In the presence of CNTF, 50%-60% of the cells expressed VIP-IR after 4 days in culture; however, none of the cells expressed VIP-IR in the absence of CNTF. These results, and the demonstration of cells that express both VIP and TH-IR, indicate that VIP is induced in cells that initially express tyrosine hydroxylase. The findings suggest a potential role for CNTF as a factor affecting the proliferation and differentiation of developing sympathetic neurons. Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-31721 ER - TY - JOUR A1 - Borasio, Gian Domenico A1 - John, Jacob A1 - Wittinghofer, Alfred A1 - Barde, Yves-Alain A1 - Sendtner, Michael A1 - Heumann, Rolf T1 - ras p21 protein promotes survival and fiber outgrowth of cultured embryonic neurons N2 - Although evidence obtained with the PC12 cell line has suggested a role for the ras oncogene proteins in the signal transduction of nerve growth factor-mediated fiber outgrowth, little is known about the signal transduction mechanisms involved in the neuronal response to neurotrophic factors in nontransformed cells. We report here that the oncogene protein T24-ras, when introduced into the cytoplasm of freshly dissociated chick embryonic neurons, promotes the in vitro survival and neurite outgrowth of nerve growth factor-responsive dorsal rootganglion neurons, brain-derived neurotrophic factor-responsive nodose ganglion neurons, and ciliary neuronotrophic factor-responsive ciliary ganglion neurons. The proto-oncogene product c-Ha-ras also promotes neuronal survival, albeit less strongly. No effect could be observed with truncated counterparts of T24-ras and c-Ha-ras lacking the 23 C-terminal amino acids including the membrane-an-choring, palmityl-accepting cysteine. These results sug-gest a generalized involvement of ras or ras-like proteins in the intracellular signal transduction pathway for neurotrophic factors. Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-32621 ER - TY - JOUR A1 - Solbach, W. A1 - Bogdan, C. A1 - Moll, Heidrun A1 - Lohoff, M. A1 - Röllinghoff, M. T1 - Parasitäre Evasionsmechanismen: Beispiel Leishmanien T1 - Mechanisms of Parasite Evasion: Leishmania as an Example N2 - Leishmanien besitzen eine Vielzahl von Mechanismen, die humorale und zelluläre Immunabwehr effektiv zu unterlaufen. Diese hängen eng mit der Expression von hauptsächlich zwei Glykokonjugaten auf der Parasitenoberfläche zusammen, dem gp63 und dem Lipophosphoglykan. Die Parasiten sind einerseits schlechte Aktivatoren des alternativen Komplementweges und umgehen damit ihre eigene extrazelluläre Lyse. Oberflächengebundene Komplementfaktoren fördern andererseits die Aufnahme der Leishmanien durch Makrophagen. Solange diese nicht durch T-Zellen aktiviert sind, dienen sie den Parasiten als "Refugium". Dies gilt insbesondere, als Leishmanien in der Lage sind, 1. den "oxidative burst" zu hemmen; 2. toxische Sauerstoffmetaboliten zu entgiften; 3. abbauende lysosomale Enzyme zu hemmen und 4. das saure Milieu in den Lysosomen für ihren eigenen Metabolismus auszunutzen. Schließlich unterlaufen Leishmanien die zelluläre Immunabwehr des Wirts, indem sie die Aktivierung von T-Lymphozyten hemmen und die Expansion von T-Zell-Sub-populationen bewirken, die für ihr eigenes Überleben nützlich sind. N2 - Leishmania display a variety of mechanisms for effective evasion of the humoral and cellular immune responses of the host which are strongly associ-ated with the expression of two major surface glycoconjugates, gp63 and lipophosphoglycan. The parasites are poor activators of the alternative com-plement pathway thus avoiding their own extracellular lysis. Complement bound on the surface of promastigotes promotes the uptake of leishmania by macrophages which function as »safe targets« as long as they are not acti-vated by T lymphocytes. This is due to the fact that intracellular parasites are able to 1. decrease the oxidative burst; 2. scavenge toxic oxygen metabolites; 3. inhibit degradative lysosomal enzymes; 4. exploit the acidic milieu of lysosomes for their own metabolism. Finally, leishmania have been shown to evade the host's cellular immune response by down-regulating T cell-activat-ing processes and by initiating the expansion of T cell subpopulations which promote their own survival. KW - Leishmanien KW - Immunsystem KW - Evasionsmechanismen KW - Makrophagen KW - T-Zellen KW - leishmania KW - immune System KW - evasion mechanisms KW - macrophages KW - T cells Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-30920 ER - TY - JOUR A1 - Tiu, W. U. A1 - Davern, K. M. A1 - Garcia, E. G. A1 - Moll, Heidrun A1 - Mitchell, Graham F. T1 - Monoclonal antibodies reacting with Schistosoma japonicum eggs and their target epitopes N2 - Ten monoclonal antibodies (McAbs) raised to Schistosoma japonicum eggs could be assigned using several serological and immunochemical techniques to 3 groups. The McAbs, termed A, B and C-McAbs, apparently recognize carbohydrate epitopes that can be located on the same antigen molecule. The antibodies, generally of IgM isotype, are idiotypically related. They are distinct from another IgM McAb (Group D-McAb) the carbohydrate target epitope of which can also be associated with the epitopes of A. B and C-McAbs. The McAbs produce large vacuolated bleb reactions in the circumoval precipitin test (COPT) and target epitopes have different representations in various life cycle stages such as immature and mature eggs, male and female worms (including S. mansoni). Antigens affinity purified on columns containing A, B, C and D-McAbs stimulate proliferation of T cells from egg-sensitized mice and elicit DTH reactions in such mice. This raises the possibility that the target antigens of these carbohydrate-reactive monoclonal antibodies are immunopathologic and involved in egg-induced granuloma formation. KW - Schistosoma japonicum; Egg antigen; Carbohydrate epitope; Circumoval precipitin test; Immunoassay Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-30916 ER -