@article{KleenePfannerPfalleretal.1987,
author = {Kleene, R. and Pfanner, N. and Pfaller, R. and Link, T. A. and Sebald, Walter and Neupert, W. and Tropschug, M.},
title = {Mitochondrial porin of Neurospora crassa: cDNA cloning, in vitro expression and import into mitochondria},
url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62566},
year = {1987},
abstract = {No abstract available},
subject = {Biochemie},
language = {en}
}
@article{FlueggeFischerGrossetal.1989,
author = {Fl{\"u}gge, U. I. and Fischer, K. and Gross, A. and Sebald, Walter and Lottspeich, F. and Eckerskorn, C.},
title = {The triose phosphate-3-phosphoglycerate-phosphate translocator from spinach chloroplasts: nucleotide sequence of a full-length cDNA clone and import of the in vitro synthesized precursor protein into chloroplasts},
url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62559},
year = {1989},
abstract = {No abstract available},
subject = {Biochemie},
language = {en}
}
@article{WeigelMeyerSebald1989,
author = {Weigel, U. and Meyer, M. and Sebald, Walter},
title = {Mutant proteins of human interleukin 2. Renaturation yield, proliferative activity and receptor binding},
url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62543},
year = {1989},
abstract = {No abstract available},
subject = {Biochemie},
language = {en}
}
@article{MerzFliednerLehrnbecheretal.1990,
author = {Merz, H. and Fliedner, A. and Lehrnbecher, T. and Sebald, Walter and M{\"u}ller-Hermelink, H. K. and Feller, A. C.},
title = {Cytokine expression in B-cell non-Hodgkin lymphomas},
url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62539},
year = {1990},
abstract = {No abstract available},
subject = {Biochemie},
language = {en}
}
@article{TonyLehrnbecherMerzetal.1991,
author = {Tony, H. P. and Lehrnbecher, T. and Merz, H. and Sebald, Werner and Wilhelm, M.},
title = {Regulation of IL-4 responsiveness in lymphoma B cells},
url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62520},
year = {1991},
abstract = {The responsiveness to IL-4 with and without costimulation with anti-IgM antibodies or phorbolester was studied in 35 cases of low grade non-Hodgkin Iymphoma by analyzing enhancement of CD23 and HLA dass li expression. The predominant phenotype responds directly to IL-4. Separate differentiation states can be distinguished according to coordinate or differential upregulation of CD23 and HLA dass II molecules by IL-4 alone, and differences in responsiveness to anti-IgM antibodies. A particular subgroup of B-lymphoma cells defines a separate stage of B-eeil differentiation. They fail to express high affinity binding sites for IL-4 and accordingly do not respond to IL-4- mediated signals. Cross-linking membrane lgM receptors or direct activation of protein kinase C via phorbolester induces IL-4 receptor expression and subsequent IL-4 reactivity.},
subject = {Biochemie},
language = {en}
}
@article{PreiserSchmartzVanderLindenetal.1991,
author = {Preiser, J. C. and Schmartz, D. and Van der Linden, P. and Content, J. and Vanden Bussche, P. and Buurman, W. and Sebald, Werner and Dupont, E. and Pinsky, M. R. and Vincent, J. L.},
title = {Interleukin-6 administration has no acute hemodynamic or hematologic effect in the dog},
url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62511},
year = {1991},
abstract = {To investigate the possible hemodynamic efl'ects of interleukin-6 (IL-6), a single dose of 15 mcg/kg of recombinant IL-6 isolated from Escherichia coli was injected intravenously in six pentobarbital-anesthetized dogs. After 30 min, saline infusion was performed to maintain the - pulmonary artery balloon-occluded pressure at baseline Ievel. The animals were observed for up to 5 hours. No other hemodynamic alteration was observed than a gradual decline in cardiac output attributed to anesthesia. Hematologic variables, blood glucose, and total serum proteins were also constant. IL-6 levels were markedly elevated in the blood, bot no tumor necrosis factor activity was detected. Thus a primary role for IL-6 in the early cardiovascular alterations associated with septic shock seems unlikely.},
subject = {Biochemie},
language = {en}
}
@article{KruseLehrnbecherSebald1991,
author = {Kruse, N. and Lehrnbecher, T. and Sebald, Walter},
title = {Site-directed mutagenesis reveals the importance of disulfide bridges and aromatic residues for structure and proliferative activity of human interleukin-4},
url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62505},
year = {1991},
abstract = {Mutant proteins (muteins) of human lnterleukin-4 (llA) were constructed by means of in vitro mutagenesis. The muteins were expressed in E. co/1, submitted to a renaturation and purification protocol and analysed for biological activity. Exchange of the cysteines at either position 46 or 99 which form one of the three disulfide bridges resulted. in a nearly co•mplete loss · of biological actiyity and an unstable protein. The exchange of tyrosine 124 also inactivated the protein, while a mutation of tyrosine 56 left some residual activity. Exchange of the other four cysteines or of · the single tryptophane had smaller etTects.},
subject = {Biochemie},
language = {en}
}
@article{MerzFliednerOrschescheketal.1991,
author = {Merz, H. and Fliedner, A. and Orscheschek, K. and Binder, T. and Sebald, Walter and M{\"u}ller-Hermelink, H. K. and Feller, A. C.},
title = {Cytokine expression in T-cell lymphomas and Hodgkin's disease. Its possible implication in autocrine or paracrine production as a potential basis for neoplastic growth},
url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62483},
year = {1991},
abstract = {No abstract available},
subject = {Biochemie},
language = {en}
}
@article{DummerPosseckertNestleetal.1992,
author = {Dummer, R. and Posseckert, G. and Nestle, F. and Witzgall, R. and Burger, M. and Becker, J. C. and Sch{\"a}fer, E. and Wiede, J. and Sebald, Walter and Burg, G.},
title = {Soluble interleukin-2 receptors inhibit interleukin 2-dependent proliferation and cytotoxicity: explanation for diminished natural killer cell activity in cutaneous T-cell lymphomas in vivo?},
url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62473},
year = {1992},
abstract = {No abstract available},
subject = {Biochemie},
language = {en}
}
@article{LehrnbecherMerzSebaldetal.1991,
author = {Lehrnbecher, T. and Merz, H. and Sebald, Walter and Poot, M.},
title = {Interleukin 4 drives phytohemagglutinin-activated T cells through several cell cycles: no synergism between interleukin 2 and interleukin 4},
url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62491},
year = {1991},
abstract = {Cell kinetic studies of T cells stimulated with the interleukin 2 (11-2), D-4, or both lymphokines were performed with conventional [3H] thymidine incorporation and with the bivariate BrdU/Hoechst technique. 11-2 and 11-4 are able to drive phytohemagglutininactivated T cells through more than one cell cycle. Neither synergistic nor inhibitory efl'ect on T -cell proliferationwas seen for the stimulation with both 11-2 and 11-4 as compared with the effect ofll-2 alone. The quantitative data ofthe cell cycle distribution ofphytohemagglutininactivated T cells suggestthat the population ofll-4-responsive cells is at least an overlapping population, if not a real subset of the ·population of the 11-2-responsive cells.},
subject = {Biochemie},
language = {en}
}
@article{KruseTonySebald1992,
author = {Kruse, N. and Tony, H. P. and Sebald, Walter},
title = {Conversion of human interleukin-4 into a high affinity antagonist by a single amino acid replacement},
url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62469},
year = {1992},
abstract = {lnterleukin-4 (IL-4) represents a prototypic lymphokine (for a recent review see Paul, 1991). It promotes differentiation of B-cells and the proliferation of T- and B-cell, and other cell types of the lymphoid system. An antagonist of human IL-4 was discovered during the studies presented here after Tyr124 of the recombinant proteinbad been substituted by an aspartic acid residue. This IL-4 variant, Y124D, bound with high affinity to the IL-4 receptor (K\(_D\) = 310 pM), but retained no detectable proliferative activity for T -<:ells and inhibited IL-4-dependent T -cell proliferation competitively (K\(_i\) = 620 pM). The loss of efficacy in variant Y124D was estimated to be > 100-fold on the basis of a weak partial agonist activity for the very sensitive induction of CD23 positive B-cells. The subsitution of Tyr124 by either phenylalanine, histidine, asparagine, Iysine or glycine resulted in partial agonist variants with unaltered receptor binding atTmity and relatively small deficiencies in efficacy. These results demoostrate that high affinity binding and signal generation can be uncoupled efticiently in a Iigand of a receptor betonging to the recently identified hematopoietin receptor family. In addition we show for the first time, that a powerful antagonist acting on the IL-4 receptor system can be derived from the IL-4 protein.},
subject = {Biochemie},
language = {en}
}
@article{KruseShenArnoldetal.1993,
author = {Kruse, N. and Shen, B. J. and Arnold, S. and Tony, H. P. and M{\"u}ller, T. and Sebald, Walter},
title = {Two distinct functional sites of human interleukin 4 are identified by variants impaired in either receptor binding or receptor activation},
url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62451},
year = {1993},
abstract = {Interleukin 4 (IL-4) exerts a decisive role in the coord.ination of proteelive immune responses against parasites, particularly helminths. A disregulation of ll.r4 function is possibly involved in the genesis of allergic disease states. The search for important amino acid residues in human ll.r4 by mutational analysis of charged invariant amino acid positions identified two distinct functional sites in the 4-helix-bundle protein. Site 1 was marked by amino acid substitutions of the glutamic acid at position 9 in helix A and arginine at position 88 in helix C. Exchanges at both positions led to IL-4 variants deficient in binding to the extracellular domain of the ll.r4 receptor (IL-4ReJ. In parallel, up to 1000-fold increased concentrations of this type of variant were required to induce T -cell proliferation and B-eeil CD23 expression. Site 2 was marked by amino acid exchanges in helix D at positions 121, 124 and 125 (arginine, tyrosine and serine respectively in the wild-type).ß.A variants affected at site 2 exhibited partial agonist activity during T -cell proliferation; however, they still bound with high affinity to IL-4Rex. [The generation of an IL-4 antagonist by replacing tyrosine 124 with aspartic acid has been described before by Kruse et al. (1992) (EMBO }., 11, 3237-3244)]. These findings indicate that IL-4 functions by bind.ing IL-4Rex via site 1 which is constituted by residues on helices A and C. They further suggest that the association of a second, still undetined receptor protein with site 2 in helix D activates the receptor system and generates a transmembrane signal.},
subject = {Biochemie},
language = {en}
}
@article{MuellerDieckmannSebaldetal.1994,
author = {M{\"u}ller, T. and Dieckmann, T. and Sebald, Walter and Oschkinat, H.},
title = {Aspects of receptor binding and signalling of interleukin-4 investigated by site-directed mutagenesis and NMR spectroscopy},
url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62444},
year = {1994},
abstract = {Cytokines are hormones that carry information from ceJI to ceH. This information is read from their surface upon binding to transmembrane receptors and by the subsequent initiation of receptor oligomerization. An inftuence on this process through mutagenesis on the hormone surface is highly desirab)e for medical reasons. However, an understanding of hormone-receptor interactions requires insight into the structural changes introduced by the mutations. In this line structural studies on human TL-4 and the medically important IL-4 antagonists YI24D and Y124G are presented. The site a.round YI24 is an important epitope responsible for the a.bility of 11-4 t.o ca.use a signal in the target cells. It is shown that the local main-chain structure around residue 124 in the variants remains unchanged. A strategy is presented here which allows the study of these types of proteins and their variants by NMR which does not require carbon Iabeiied sa.mples.},
subject = {Biochemie},
language = {en}
}
@article{LehrnbecherPootOrschescheketal.1994,
author = {Lehrnbecher, T. and Poot, M. and Orscheschek, K. and Sebald, Walter and Feller, A. C. and Merz, H.},
title = {Interleukin 7 as interleukin 9 drives phytohemagglutinin-activated T cells through several cell cycles; no synergism between interleukin 7, interleukin 9 and interleukin 4},
url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62438},
year = {1994},
abstract = {The effects of the interlenkins IL-7 and IL-9 on cell cycle progression were investigated by conventional [3H]thymidine incorporation and by the bivariate BrdU/Hoechst technique. 8oth IL· 7 and IL-9 drive phytohemagglutinin-activated T cells through more than one cell cycle, but IL-7 wasmorepotent on cell cycle progression than IL-9. Neither synergistic nor inhibitory effects were seen between various combinations of the lymphokines IL-7, IL-9 and IL-4 compared to each lymphokine alone. When T cells are activated with phytohemagglutinin for 3 days, all or most IL-4 responsive cells respond to IL-7 as weil, whereas only a part of IL-7 responders are IL-4 responders. In contrast, when T cells are activated with phytohemagglutinin for 7 days, the quantitative data of the cell cycle distribution soggest that the population of IL-7 responders is at least an overlapping, if not a real subset of the population of the IL-4 responders.},
subject = {Biochemie},
language = {en}
}
@article{DemchukMuellerOschkinatetal.1994,
author = {Demchuk, E. and Mueller, T. and Oschkinat, H. and Sebald, Walter and Wade, R. C.},
title = {Receptor binding properties of four-helix-bundle growth factors deduced from electrostatic analysis},
url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62424},
year = {1994},
abstract = {Hormones of the hematopoietin class mediate signal transduction by binding to specific transmembrane receptors. Structural data show that the human growth hormone (hGH) forms a complex with a homodimeric receptor and that hGH is a member of a class of hematopoietins possessing an antiparallel 4-a-helix bundle fold. Mutagenesis experiments suggest that electrostatic interactions may have an important influence on hormonereceptor recognition. In order to examine the specificity of hormone-receptor complexation, an analysis was made of the electrostatic potentials of hGH, interleukin-2 (IL-2), interleukin-4 (IL-4), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and the hGH and IL-4 receptors. The binding surfaces of hGH and its receptor, and of IL-4 and its receptor, show complementary electrostatic potentials. The potentials of the hGH and its receptor display approximately 2-fold rotational symmetry because the receptor subunits are identical. In contrast, the potentials of GM-CSF and IL-2 Iack such symmetry, consistent with their known high affinity for hetero-oligomeric receptors. Analysis of the electrostatic potentials supports a recently proposed hetero-oligomeric model for a high-affinity IL-4 receptor and suggests a possible new receptor binding mode for G-CSF; it also provides valuable information for guiding structural and mutagenesis studies of signal-transducing proteins and their receptors.},
subject = {Biochemie},
language = {en}
}
@article{ReuschArnoldHeusseretal.1994,
author = {Reusch, P. and Arnold, S. and Heusser, C. and Wagner, K. and Weston, B. and Sebald, Walter},
title = {Neutralizing monoclonal antibodies define two different functional sites in human interleukin-4},
url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62418},
year = {1994},
abstract = {Human interleukin-4 (IL-4) is a small four-helix-bundle protein which is essential for organizing defense reactions against macroparasites, in particular helminths. Human IL-4 also appears to exert a pathophysiological role during various IgE-mediated allergic diseases. Seven different monoclonal antibodies neutralizing the activity of human IL-4 were studied in order to identify functionally important epitopes. A collection of 41 purified IL-4 variants was used to analyse how defined amino acid replacements affect binding affinity for each individual mAb. Specific amino acid positions could be assigned to four different epitopes. mAbs recognizing epitopes on helix A and/or C interfered with IL-4 receptor binding and thus inhibited IL-4 function. However, other mAbs also inhibiting IL-4 function recognized an epitope on helix D of IL-4 and did not inhibit IL-4 binding to the receptor protein. One mAb, recognizing N-terminal and C-terminal residues, partially competed for binding to the receptor. The results of these mAb epitope analyses confirm and extend previous data on the functional consequences of the amino acid replacements which showed that amino acid residues in helices A and C of IL-4 provide a binding site for the cloned IL-4 receptor and that a signalling site in helix D interacts with a further receptor protein.},
subject = {Biochemie},
language = {en}
}
@article{MuellerSebaldOschkinat1994,
author = {M{\"u}ller, T. and Sebald, Walter and Oschkinat, H.},
title = {Antagonist design through forced electrostatic mismatch},
url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62408},
year = {1994},
abstract = {No abstract available},
subject = {Biochemie},
language = {en}
}
@article{TonyShenReuschetal.1994,
author = {Tony, H. P. and Shen, B. J. and Reusch, P. and Sebald, Walter},
title = {Design of human interleukin-4 antagonists inhibiting interleukin-4-dependent and interleukin-13-dependent responses in T-cells and B-cells with high efficiency},
url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62394},
year = {1994},
abstract = {Human interleukin-4 possesses two distinct sites for receptor activation. A signaHing site, comprising residues near the C-terminus on helix D, determines the efficacy of interleukin-4 signal transduction without affecting the binding to the interleukin-4 receptor a subunit. A complete antagonist and a series of low-efficacy agonist variants of human interleukin-4 could be generated by introducing combinations of two or three negatively charged aspartic acid residues in this site at positions 121, 124, and 125. One of the double variants, designated [R121D,Y124D]interleukin-4, with replacements of b{\"o}th Arg121 and Tyr124 by aspartic acid residues was completely inactive in all analysed cellular responses. The loss of efficacy in [R121D,Y124D]interleukin-4 is estimated to be larger than 2000-fold. Variant [R121D,Y124D]interleukin-4 was also a perfect antagonist for inhibition of interleukin-13-dependent responses in B-cells and the TF-1 cellline with a K\(_i\) value of approximately 100 pM. In addition, inhibition of both interleukin-4-induced and interleuk.in-13- induced responses could be obtained by monoclonal antibody X2/45 raised against interleukin-4Rm the extracellular domain of the interleuk.in-4 receptor a subunit. These results indicate that efficient interleukin-4 antagonists can be designed on the basis of a sequential two-step activation model. In addition, the experiments indicate the functional participation of the interleukin-4 receptor a subunit in the interleukin-13 receptor system.},
subject = {Biochemie},
language = {en}
}
@article{KueblerReutherKirchneretal.1994,
author = {K{\"u}bler, N. and Reuther, J. and Kirchner, T. and Pfaff, M. and M{\"u}ller-Hermelink, H. K. and Albert, R. and Sebald, Walter},
title = {IgG monoclonal antibodies that inhibit osteoinductivity of human bone matrix-derived proteins (hBMP/NCP)},
url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62388},
year = {1994},
abstract = {Monoclonal hBMP/NCP (human bone morphogenetic protein anrl associaterl noncollagenous proteins) antiborlies of the lgG class were prorlucerl. In vitro, 12 of 19 hBMP/NCP antiborlies showerl functional inhibition of hBMP/ NCP-induced chondroneogenesis in a neonatal muscle tissue assay. Inducing factors were characterized by their inhibiting antibodies with immunoblotting. Several peptide factors seem to be involved in the cascade of inducerl chondro- and osteogenesis.},
subject = {Biochemie},
language = {en}
}
@article{GesslerBarnekow1984,
author = {Gessler, Manfred and Barnekow, Angelika},
title = {Differential expression of the cellular oncogenes c-src and c-yes in embryonal and adult chicken tissues},
url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-59289},
year = {1984},
abstract = {The cellular onc-genes c-src and c-yes are expressed very differently during chicken embryonic development. The c-src mRNA and its translational product are detectable at high levels in brain extracts of chicken embryos and adult chickens, whereas muscle extracts show an age-dependent decrease in the amounts of c-src-specific mRNA and pp60c-src kinase activity. In contrast, the Ievels of c-yes mRNA in brain, heart, and muscle are relatively low in early embryonic stages and increase later on to values comparable to those found for liver, while in adult animals the pattern of c-yes expression is similar to that of the c-src gene. From the close correlation between the Ievels of pp60c-src, its enzymatic activity, and its corresponding mRNA at a given stage of development and in given tissues, it appears that the expression of pp60c-src is primarily controlled at the level of transcription. It is suggested that because of the different patterns of expression, the two cellular oncogenes, c-src and c-yes, play different roles in cell proliferation during early embryonic stages as weil as in ensuing differentiation processes.},
subject = {Biochemie},
language = {en}
}