TY - JOUR A1 - Waelbroeck, M. A1 - Camus, J. A1 - Tastenoy, M. A1 - Lambrecht, G. A1 - Mutschler, E. A1 - Kropfgans, M. A1 - Sperlich, J. A1 - Wiesenberger, F. A1 - Tacke, R. A1 - Christophe, J. T1 - Thermodynamics of antagonist binding to rat muscarinic \(M_2\) receptors: antimuscarinics of the pridinol, sila-pridinol, diphenidol and sila-diphenidol type JF - British Journal of Pharmacology N2 - 1 We studied the effect of temperature on the binding to rat heart \(M_2\) muscarinic receptors of antagonists related to the carbon/silicon pairs pridinol/sila-pridinol and diphenidol/sila-diphenidol (including three germanium compounds) and six structurally related pairs of enantiomers [(R)- and (S)-procyclidine, (R)- and (S)-trihexyphenidyl, (R)- and (S)-tricyclamol, (R)- and (S)-trihexyphenidyl methiodide, (R)- and (S)-hexahydro-diphenidol and (R)- and (S)-hexbutinol]. Binding affinities were determined in competition experiments using \([^3H]\)-N-methyl-scopolamine chloride as radioligand. The reference drugs were scopolamine and N-methyl-scopolamine bromide. 2 The affinity of the antagonists either increased or decreased with temperature, van 't Hoff plots were linear in the 278–310°K temperature range. Binding of all antagonists was entropy driven. Enthalpy changes varied from large negative values (down to \(−29 kJ mol^{−1}\)) to large positive values (up to \(+ 30 kJ mol^{−1}\)). 3 (R)-configurated drugs had a 10 to 100 fold greater affinity for \(M_2\) receptors than the corresponding (S)-enantiomers. Enthalpy and entropy changes of the respective enantiomers were different but no consistent pattern was observed. 4 When silanols \((R_3SiOH)\) were compared to carbinols \((R_3COH)\), the affinity increase caused by C/Si exchange varied between 3 and 10 fold for achiral drugs but was negligible in the case of chiral drugs. Silanols induced more favourable enthalpy and less favourable entropy changes than the corresponding carbinols when binding. Organogermanium compounds \((R_4Ge)\) when compared to their silicon counterparts (R4Si) showed no significant difference in affinity as well as in enthalpy and entropy changes. 5 Exchange of a cyclohexyl by a phenyl moiety was associated with an increase or a decrease in drug affinity (depending on the absolute configuration in the case of chiral drugs) and generally also with a more favourable enthalpy change and a less favourable entropy change of drug binding. 6 Replacement of a pyrrolidino by a piperidino group and increasing the length of the alkylene chain bridging the amino group and the central carbon or silicon atom were associated with either an increase or a decrease of entropy and enthalpy changes of drug binding. However, there was no clear correlation between these structural variations and the thermodynamic effects. 7 Taken together, these results suggest that hydrogen bond-forming OH groups and, to a lesser extent, polarizable phenyl groups contribute significantly to the thermodynamics of interactions between these classes of muscarinic antagonists and \(M_2\) muscarinic receptors. KW - entropy KW - binding KW - M2 muscarinic receptors KW - thermodynamics KW - van 't Hoff plot KW - enthalpy Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128439 VL - 109 IS - 2 ER - TY - JOUR A1 - Müller, J. G. A1 - Krenn, V. A1 - Schindler, C. A1 - Czub, S. A1 - Stahl-Henning, C. A1 - Coulibaly, C. A1 - Hunsmann, G. A1 - Kneitz, C. A1 - Kerkau, T. A1 - Rethwilm, A. A1 - ter Meulen, V. A1 - Müller-Hermelink, H. K. T1 - Alterations of Thymus Cortical Epithelium and Interdigitating Dendritic Cells but No Increase of Thymocyte Cell Death in the Early Course of Simian Immunodeficiency Virus Infection JF - American Journal of Pathology N2 - The role of the thymus in the pathogenesis of simian acquired immunodeficiency syndrome was investigated in 18 juvenile rhesus monkeys (Macaca mulatta). The thymus was infected from the first week post-SIVmac inoculation, but the amount of virus-positive cells was very low « 1 in 1 04 T cells) as demonstrated by polymerase chain reaction and in situ hybridization. First morphological alteration was a narrowing of the cortex at 12 and 24 wpi. Morphometry revealed no increase of pyknotic T cells but a decrease of the proliferation rate andflow cytometry showed a reduction of the immature \(CD4^+/CD8^+\) double-positive T cells. Ultrastructural analysis revealed vacuolization, shrinkage, andfinally cytolysis of the cortical epithelial cells and the interdigitating dendritic cells. Immunofluorescence staining exhibited a widespread loss of cortical epithelial cells. This damage to the thymic microenvironment could explain the breakdown of the intrathymic T cell proliferation. It preceded fully developed simian acquired immunodeficiency syndrome and is therefore considered to play a major role in its pathogenesis. Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128250 VL - 143 IS - 3 ER - TY - JOUR A1 - Tafler, R. A1 - Herbert, M. K. A1 - Schmidt, R. F. A1 - Weis, K. H. T1 - Small reduction of capsaicin-induced neurogenic inflammation in human forearm skin by the glucocorticoid prednicarbate JF - Agents Actions N2 - No abstract available. Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127698 VL - 38 IS - Special Conference Issue ER - TY - JOUR A1 - Herbert, M. K. A1 - Tafler, R. A1 - Schmidt, R. F. A1 - Weis, K. H. T1 - Cyclooxygenase inhibitors acetylsalicylic acid and indomethacin do not affect capsaicin-induced neurogenic inflammation in human skin JF - Agents Actions N2 - Neurogenic inflammation is evoked by neuropeptides released from primary afferent terminals and, presumably, by other secondarily released inflammatory mediators. This study examines whether prostaglandins might participate in the development of neurogenic inflammation in humans and whether cyclooxygenase inhibitors have any anti-inflammatory effect on this type of inflammation. In healthy volunteers, neurogenic inflammation was elicited by epicutaneously applied capsaicin (1 %), after systemic pretreatment with acetylsalicylic acid, or topically applied indomethacin compared to pretreatment with saline or vehicle, respectively. The extent of neurogenic inflammation was quantified by planimetry of visible flare size and recording the increase of superficial cutaneous blood flow (SCBF) with a laser Doppler flowmeter. Capsaicin-induced flare sizes and outside SCBF (both representing neurogenically evoked inflammation) were unaffected by acetylsalicylic acid or indomethacin. Only the capsaicin-induced increase; of inside SCBF was attenuated by local pretreatment with indomethacin, reflecting the participation of prostaglandins in the inflammatory response of those areas which were in direct contact with capsaicin. Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127666 VL - 38 IS - Special Conference Issue ER - TY - JOUR A1 - Wilhelm, Gernot A1 - Zaccagnini, Carlo T1 - Tell Karrana 3, Tell Jikan, Tell Khirbet Salih N2 - No abstract available. KW - Tell Karrana KW - Tell Jikan KW - Tell Khirbet Salih Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-87646 ER - TY - JOUR A1 - Schneider, Wolfgang A1 - Näslund, Jan Carol T1 - The impact of early metalinguistic competencies and memory capacity on reading and spelling in elementary school: Results of the Munich Longitudinal Study on the Genesis of Individual Competencies (LOGIC) N2 - This paper reports on a longitudinal study dealing with the development of literacy in young children. A total of 163 children were first tested during their last year in kindergarten using a variety of tasks that tapped phonological processing, memory capacity, early literacy, and intelligence. Children's ward decoding, reading comprehension, and spelling skills were assessed in elementary school several years later. As a main result, all of the predictor domains had a significant impact on the acquisition of literacy in elementary school, although the contribution of each domain differed as a function of the criterion measure. An attempt to identify children-at-risk using a kindergarten screening test provided encouraging results. Nonetheless, it was shown that whereas group predictions of reading and spelling performance can be quite accurate, the individual prognosis of school problems is far from perfect. KW - Lese- und Schreibfähigkeit KW - Gedächtnisleistung KW - Phonologische Bewusstheit KW - Acquisition of literacy KW - Children-at-Risk KW - Memory capacity KW - Phonological awareness Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-87421 ER - TY - JOUR A1 - Schneider, Wolfgang T1 - Introduction: The early prediction of reading and spelling N2 - No abstract available. KW - Prognose KW - Schreiben KW - Lesen Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-87418 ER - TY - JOUR A1 - Schartl, Manfred A1 - Wittbrodt, J. A1 - Mäueler, W. A1 - Raulf, F. A1 - Adam, D. A1 - Hannig, G. A1 - Telling, A. A1 - Storch, F. A1 - Andexinger, S. A1 - Robertson, S. M. T1 - Oncogenes and melanoma formation in Xiphoporus (Teleostei: Poeciliidae) N2 - In Xiphophorus melanoma formation has been attributed by classical genetic findings to the overexpression of a cellular oncogene (Tu) due to elimination of the corresponding regulatory gene locus in hybrids. We have attempted to elucidate this phenomenon on the molecular biological level. Studies on the structure and expression of known proto-oncogenes revealed that several of these genes, especially the c-src gene of Xiphophorus, may act as effectors in establishing the neoplastic phenotype of the melanoma cells . However, these genes appear more to participate in secondary steps of tumorigenesis. Another gene, being termed Xmrk, which represents obviously a so far unknown proto-oncogene but with a cons iderably high similarity to the epidermal growth-factorreceptor gene, was mapped to the Tu-containing region of the chromosome. This gene shows features with respect to its structure and expression that seem to justify it to be regarded as a candidate for a gene involved in the primary processes leading to neoplastic transformation of pigment cells in Xiphophorus. KW - Schwertkärpfling KW - Onkogen KW - Melanom Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-87149 ER - TY - JOUR A1 - Macht, Michael A1 - Janke, Wilhelm T1 - Effects of short-term energy deprivation on stress reactions in humans N2 - No abstract available. KW - Stressreaktion Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-87093 ER - TY - JOUR A1 - Epe, Bernd A1 - Häring, Martin A1 - Ramaiah, Danaboyina A1 - Stopper, Helga A1 - Abou-Elzahab, Mohamed M. A1 - Adam, Waldemar A1 - Saha-Möller, Chantu R. T1 - DNA damage induced by furocoumarin hydroperoxides plus UV (360 nm) N2 - Wben irradiated at 360 nm, furocoumarins with a hydroperoxide group in a side chain effciently give rise to a type of DNA damage that can best be explained by a photoinduced generation of hydroxyl radicals from the excited pbotosensitizers. The observed DNA damage profiles, i.e. the ratios of single-strand breaks, sites of base loss (AP sites) and base modifications sensitive to fonnamidopyrimidine-DNA glycosylase (FPG protein) and endonuclease m, are similar to the DNA damage profile produced by hydroxyl radicals generated by lonizing radiation or by xanthine and xanthine oxidase in the presence of Fe(III)-EDTA. No such damage is observed with the corresponding furocoumarin alcohols or in the absence of near-UV radiation. The damage caused by the photo-excited hydroperoxides is not influenced by superoxide dismutase (SOD) or catalase or by D2O as solvent. The presence of t-butanol, however, reduces both the formation of single-strand breaks and of base odifications sensitive to FPG protein. The cytotoxicity caused by one of the hydroperoxides in L5178Y mome lymphoma cells is found to be dependent on the near-UV irradiation and to be much higher than that of the corresponding alcohol. Therefore the new type of photoinduced damage occurs inside cells. Intercalating photosensitizers with an attached hydroperoxide group might represent a novel and versatile class of DNA damaging agents, e.g. for phototherapy. KW - DNS-Schädigung Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86870 ER -