University of Marburg

About: University of Marburg is a education organization based out in Marburg, Germany. It is known for research contribution in the topics: Population & Gene. The organization has 23195 authors who have published 42907 publications receiving 1506069 citations. The organization is also known as: Philipps University of Marburg & Philipps-Universität.

An Essential Role for Macrophage Migration Inhibitory Factor (MIF) in Angiogenesis and the Growth of a Murine Lymphoma

Abstract: Macrophage migration inhibitory factor (MIF) has been shown to counterregulate glucocorticoid action and to play an essential role in the activation of macrophages and T cells in vivo. MIF also may function as an autocrine growth factor in certain cell systems. We have explored the role of MIF in the growth of the 38C13 B cell lymphoma in C3H/HeN mice, a well-characterized syngeneic model for the study of solid tumor biology. Tumor-bearing mice were treated with a neutralizing anti-MIF monoclonal antibody and the tumor response assessed grossly and histologically. Tumor capillaries were enumerated by immunohistochemistry and analyzed for MIF expression. The effect of MIF on endothelial cell proliferation was studied in vitro, utilizing both specific antibody and antisense oligonucleotide constructs. The role of MIF in angiogenesis also was examined in a standard Matrigel model of new blood vessel formation in vivo. The administration of anti-MIF monoclonal antibodies to mice was found to reduce significantly the growth and the vascularization of the 38C13 B cell lymphoma. By immunohistochemistry, MIF was expressed predominantly within the tumor-associated neovasculature. Cultured microvascular endothelial cells, but not 38C13 B cells, produced MIF protein and required its activity for proliferation in vitro. Anti-MIF monoclonal antibody also was found to markedly inhibit the neovascularization response elicited by Matrigel implantation. These data significantly expand the role of MIF in host responses, and suggest a new target for the development of anti-neoplastic agents that inhibit tumor neovascularization.

Protease resistance and conformation of laminin.

Abstract: Laminin, obtained from a tumor basement membrane, was treated with neutral proteases (trypsin, chymotrypsin, elastase, subtilisin, Stuphylococcus aureus protease), which all produced similar fragment patterns upon prolonged digestion. The patterns were different from those obtained for fibronectin, which showed a much higher susceptibility to proteolysis by the same enzymes. Four large fragments could be purified which accounted together for more than half of the mass of laminin. They were found to differ in size, amino acid composition, spectral properties and antigenicity. The largest fragment 1 (Mr 260000-300000) was rich in half-cystine (120 residues/1000) and showed a circular dichroism spectrum indicating the absence of α helix and β structure. Fragment 3 (Mr= 50000) possessed beta; structure and was able to bind onto heparin-Sepharose. Fragments 2 (Mr= 50000) and 4 (Mr= 75000) were related structures and their relative yields depended on the protease used. They showed spectra similar to those of fragment 1. Electron microscopy revealed that fragment 1 consists of three rodlike elements (length 26 nm) connected to each other at one end. The other fragments appeared as globules (fragment 3), short rods (fragment 2) or globules connected to a short rod (fragment 4). Data obtained from limited proteolysis indicated that fragment 1 and 4 (or 2) are in close proximity to each other in the three short arms of laminin, which in its intact form has the shape of an asymmetric cross. The long arm appeared to be readily degraded by proteases. Circular dichroism studies of native laminin indicated about 55%, aperiodic structures, 15%β structure and 30%× helix. The α helix was readily destroyed by proteolysis and showed a sharp, reversible transition at 58° C. Stability of these structures was decreased by reduction of disulfide bonds or by increasing concentrations of guanidine. Heat denaturation rendered laminin susceptible to plasmin, which did not degrade the native protein. Cleavage occurred mainly within the 440000-Mrpolypeptide chain of laminin and was accompanied by a partial loss of the long arm.

Finite state machines for strings over infinite alphabets

Abstract: Motivated by formal models recently proposed in the context of XML, we study automata and logics on strings over infinite alphabets. These are conservative extensions of classical automata and logics defining the regular languages on finite alphabets. Specifically, we consider register and pebble automata, and extensions of first-order logic and monadic second-order logic. For each type of automaton we consider one-way and two-way variants, as well as deterministic, nondeterministic, and alternating control. We investigate the expressiveness and complexity of the automata and their connection to the logics, as well as standard decision problems. Some of our results answer open questions of Kaminski and Francez on register automata.