Showing papers by "University of Duisburg-Essen published in 1992"

A functional domain in the heavy chain of scatter factor/hepatocyte growth factor binds the c-Met receptor and induces cell dissociation but not mitogenesis.

Abstract: We recently found that scatter factor (SF), a cell motility factor with a multimodular structure, is identical to hepatocyte growth factor (HGF), a potent mitogen of various cell types. SF/HGF is the ligand of the c-Met receptor tyrosine kinase. Here we used transient expression of naturally occurring and in vitro mutagenized cDNAs of SF/HGF to delineate the protein domains necessary for biological activity and binding to the c-Met receptor. (i) A single-chain SF/HGF resulting from the destruction of the protease cleavage site between heavy and light chain (Arg-494--> Gln) was largely inactive, indicating that proteolytic cleavage is essential for acquisition of the biologically active conformation. (ii) A SF/HGF splice variant encoding a protein with a 5-amino acid deletion in the first kringle domain was as highly active as the wild-type molecule. (iii) The separately expressed light chain (with serine protease homology) was inactive in all assays tested. (iv) The separate heavy chain as well as a naturally occurring splice variant consisting of the N terminus and the first two kringle domains bound the c-Met receptor, stimulated tyrosine auto-phosphorylation, and induced scattering of epithelial cells but not mitogenesis. These data indicate that a functional domain in the N terminus/first two kringle regions of SF/HGF is sufficient for binding to the Met receptor and that this leads to the activation of the downstream signal cascade involved in the motility response. However, the complete SF/HGF protein seems to be required for mitogenic activity.

Metaphase and interphase cytogenetics with Alu-PCR-amplified yeast artificial chromosome clones containing the BCR gene and the protooncogenes c-raf-1, c-fms, and c-erbB-2.

Abstract: A human yeast artificial chromosome (YAC) library was screened by polymerase chain reaction with oligonucleotide primers defined for DNA sequences of the BCR gene and the protooncogenes c- raf-1 , c- fms , and c- erB-2 . Alu-PCR-generated human DNA sequences were obtained from the respective YAC clones and used for fluorescence in situ hybridization experiments under suppression conditions. After chromosomal in situ suppression hybridization to GTG-banded human prometaphase chromosomes, seven of nine initially isolated YAC clones yielded strong signals exclusively in the chromosome bands containing the respective genes. Two clones yielded additional signals on other chromosomes and were excluded from further tests. The band-specific YACs were successfully applied to visualize specific structural chromosome aberrations in peripheral blood cells from patients with myelodysplasia exhibiting del(5)(q13q34), chronic myeloid leukemia and acute lymphocytic leukemia with t(9;22)(q34;q11), acute promyelocytic leukemia (M3) with t(15;17)(q22;q21), and in a cell line established from a proband with the constitutional translocation t(3;8)(p14.2;q24). In addition to the analysis of metaphase spreads, we demonstrate the particular usefulness of these YAC clones in combination with whole chromosome painting to analyze specific chromosome aberrations directly in the interphase nucleus.

Neuropeptide Y (NPY) receptors in HEL cells: comparison of binding and functional parameters for full and partial agonists and a non-peptide antagonist.

Abstract: 1 We have compared the binding and Ca2+ mobilizing properties of various full agonists, partial agonists and a non-peptide antagonist at the neuropeptide Y (NPY) receptor of human erythroleukemia (HEL) cells. 2 [125I]-NPY binding to intact HEL cells was rapid, saturable, of high affinity and with a specificity typical for the Y1-like subtype: NPY, peptide YY (PYY) and [Pro34]-NPY competed for [125I]-NPY binding with high affinity whereas NPY13–36 and NPY18–36 had only low affinity. 3 NPY, PYY and [Pro34]-NPY potently increased intracellular Ca2+ in HEL cells and had equal efficacy. NPY13–36, vasoactive intestinal peptide (VIP) and pancreatic polypeptide (PP) increased intracellular Ca2+ only poorly. 4 Whereas VIP and PP did not significantly affect NPY-stimulated Ca2+ mobilization, NPY13–36 inhibited NPY-stimulated Ca2+ increases and shifted the NPY concentration-response curve to the right without altering its maximal effect. 5 The agonist (pEC50) potencies of the various peptides corresponded well with the affinities of these compounds in the binding assay (pKi), whereas the antagonist potencies (pKb) of the peptide partial agonists and the pA2 value of the non-peptide NPY antagonist (He 90481), calculated from functional data, were lower than the respective affinities determined in the binding studies. 6 A plot of the fractional Ca2+ response vs the fractional receptor occupancy did not reveal any nonlinear receptor-effector coupling for NPY or [Pro34]-NPY; a small receptor reserve might exist for PYY. 7 We conclude that the binding and functional properties of HEL cell NPY receptors are very similar. NPY, PYY and [Pro34]NPY are full agonists at these receptors, whereas NPY13–36 is a partial agonist.

Premature chromosome condensation reveals DNA-PK independent pathways of chromosome break repair.

Abstract: Cells of higher eukaryotes process double strand breaks (DSBs) in their genome using a non-homologous end joining apparatus that utilizes DNA-PK and other well characterized factors (D-NHEJ). Cells with defects in D-NHEJ, repair the majority of DSBs using a slow-repair pathway which is independent of genes of the RAD52 epistasis group and functions as a backup (B-NHEJ). Recent studies implicate DNA ligase III, PARP-1 and histone H1 in this pathway of NHEJ. The present study investigates the operation of B-NHEJ in the repair of interphase chromosome breaks visualized in irradiated G0 human lymphocytes by premature chromosome condensation (PCC). Chromosome breaks are effectively repaired in human lymphocytes, but repair is significantly compromised after treatment with wortmannin, a DNA-PK inhibitor. Despite slower kinetics, cells exposed to wortmannin rejoin the majority of IR induced chromosome breaks suggesting that B-NHEJ is also functional at the chromosome level. Complementation of D-NHEJ defect in wortmannin-treated lymphocytes by newly made DNA-PK is only possible under conditions of nuclear envelope break down and premature chromosome condensation, suggesting that in interphase cells the shunting of chromosome breaks from D-NHEJ to B-NHEJ is irreversible. The understanding of chromosomal aberration formation allows mechanistic explanations for the carcinogenic potential of D-NHEJ defects.

Equilibrium triangulations of the complex projective plane

Abstract: Starting with the well-known 7-vertex triangulation of the ordinary torus, we construct a 10-vertex triangulation of ℂP2 which fits the equilibrium decomposition of ℂP2 in the simplest possible way. By suitable positioning of the vertices, the full automorphism group of order 42 is realized by a discrete group of isometries in the Fubini-Study metric. A slight subdivision leads to an elementary proof of the theorem of Kuiper-Massey which says that ℂP2 modulo conjugation is PL homeomorphic to the standard 4-sphere. The branch locus of this identification is a 7-vertex triangulation ℝP27of the real projective plane. We also determine all tight simplicial embeddings of ℂP210and ℝP27.

Scaling behavior in disordered sandpile automata

Abstract: We study numerically the scaling behavior of disordered sandpile automata with preferred direc­ tion on a two-dimensional square lattice. We consider two types of bulk defects that modify locally the dynamic rule: (i) a random distribution of holes, through which sand grains may leave the sys­ tem, and (ii) several models with a random distribution of critical heights. We find that at large time and length scales the self-organized critical behavior, proved exactly in the pure model, is lost for any finite concentration of defects both in the model of random holes and in those models of random critical heights in which the dynamic rule violates the height conservation law. In the case of the ran­ dom critical height model with the height-conserving dynamics, we find that self-organized criticality holds for the entire range of concentrations of defects, and it belongs to the same universality class as the pure model. In the case of random holes we analyze the scaling properties of the probability distributions P(T,p, L) and D(s,p, L) of avalanches of duration larger than T and size larger than s, respectively, at lattices with linear size L and concentration of defect sites p. We find that in general the following scaling forms apply: P(T) = T-ap(T/x,T/L) and D(s) = sT 1J(s/m,s/L"), where x == x(p) and m == m(p) are the characteristic duration (length) and the characteristic size (mass) of avalanches for a given concentration of defects. The power-law behavior of the distributions still persists for length scales T <: x(p) and mass scales s <: m(p). The characteristic length x(p) and mass m(p) are finite for small concentrations of defects and diverge at p -+ 0 according to the power law x(p) '" p-I-I" and m(p) '" p-I-'m, with the numerically determined values of the exponents close to /l-x = 1 and /l-m = 1.5. The finite-size of the lattice may affect the measured probability distributions if for a given concentration of defects the characteristic length x(p) exceeds the lattice size L. A finite-size scaling analysis for the mass distribution yields the exponent v = 1.5, while the duration of the avalanches scales linearly with the size. We also determine the exponent D = 1.5 that connects the mass and the duration of avalanches.

The spin texture in Fe/Tb multilayers

Abstract: Fe/Tb multilayers (ML) have been prepared in UHV. The layer thickness for Fe was varied from 10 to 80 A with Tb-layer thicknesses of 3.5, 7, 14 and 26 A. Different substrate temperatures Ts between Ts=130 K and RT have been used. The magnetic spin texture was studied by57Fe-Mossbauer spectroscopy from T=4.2 K to 670 K. The ferrimagnetic coupling between Fe and Tb moments was observed by Mossbauer studies in external fields up to 5 T.

Variability of dynamic compliance measurements in spontaneously breathing and ventilated newborn infants.

Abstract: We studied reproducibility and variability of dynamic pulmonary compliance (Cdyn) by making measurements with the esophageal balloon at multiple locations within the esophagus, in both spontaneously breathing and mechanically ventilated newborn infants. Reliable measurements could be obtained over a range similar to that reported for measurements with a liquid-filled catheter. In spontaneously breathing infants Cdyn was found to be highly variable. This variability was unrealated to catheter position but was associated with concomitant changes in pulmonary resistance. Probably because of the high variability, the correlation of Cdyn with a measurement of respiratory system compliance (Crs) was rather poor (r = 0.63). Cdyn measured in mechanically ventilated infants was significantly less variable and compared favorably to Crs (r = 0.86), but its accuracy could not be adequately assessed since the comparison of esophageal and airway occlusion pressure was not feasible in all infants. In addition, significant differences in Cdyn were found between spontaneous and ventilated breaths during mechanical ventilation. Further studies in both ventilated and spontaneously breathing infants are needed to assess the variability of Cdyn over extended time periods. Pediatr pulmonol.1992; 12:73–80.

NPY and carbachol raise Ca2+ in SK-N-MC cells by three different mechanisms. Evidence for inositol phosphate-independent Ca2+ mobilization by NPY.

Abstract: We have compared the mechanism of NPY-and carbachol-stimulated Ca2+ increases in SK-N-MC cells. NPY stimulated Ca2+ mobilization via a pertussis toxin-sensitive mechanism. Carbachol stimulated Ca2+ mobilization and influx via pertussis toxin-insensitive and -sensitive mechanisms, respectively. Carbachol but not NPY stimulated inositol phosphate accumulation by a pertussis toxin-insensitive mechanism. We conclude that carbachol promotes Ca2+ influx via a pertussis toxin-sensitive G protein and Ca2+ mobilization via a pertussis toxin-insensitive G-protein coupling to inositol phosphate generation; NPY stimulates Ca2+ mobilization via a pertussis toxin-sensitive G protein without apparent involvement of inositol phosphates.

Cardinal interpolation with differences of tempered functions

Abstract: In this paper, we investigate the existence and uniqueness of cardinal interpolants associated with functions arising from the k th order iterated discrete Laplacian ▿ k applied to certain radial basis functions. In particular, we concentrate on determining, for a given radial function Φ, which functions ▿ k Φ give rise to cardinal interpolation operators which are both bounded and invertible l 2 ( Z 3 ). In addition to solving the cardinal interpolation problem (CIP) associated with such functions ▿ k Φ , our approach provides a unified framework and simpler proofs for the CIP associated with polyharmonic splines and Hardy multiquadrics.

Low-output syndrome after heart surgery: is a monotherapy with phosphodiesterase-III inhibitors feasible? A comparative study of amrinone and enoximone.

Abstract: In order to determine whether the primary use of a phosphodiesterase-III (PDE) inhibitor as monotherapy for severe cardiac low-output states (LOS) is in fact practicable, we investigated the haemodynamic effects of amrinone and enoximone in a prospective randomized study. After elective CABG, AVR, or MVR, patients with cardiac LOS were given amrinone (n = 10) or enoximone (n = 9). Following bolus saturation (1.0-2.0 mg/kg [XA = 1.4] or 0.5-1 mg/kg [XE = 0.9] in total), a dose of 5-10 microgram/kg/min was given by infusion. The standard monitoring program included discontinuous haemodynamic measurements (Swan-Ganz) over a maximum time period of 48 hours, arterial and venous blood-gas analyses, and clinical chemistry. The preoperative clinical and haemodynamic status of the enoximone (E) group (55% CABG patients; MPAP 27 +/- 2.5 mmHg, PCWP 20 +/- 2.9 mmHg, PVR 201 +/- 35 dyn.s.cm-5) was considerably worse than that of the amrinone (A) group (70% CABG patients; MPAP 23 +/- 2.3 mmHg, PCWP 16 +/- 3.5 mmHg, PVR 153 +/- 28 dyn.s.cm-5). Both PDE inhibitor preparations led to a significant increase in cardiac index (from 1.9 +/- 0.1 to 2.5 +/- 0.12 L/min/m2 (A) and from 1.98 +/- 0.1 to 2.6 +/- 0.18 L/min/m2 (E) within 30 minutes, accompanied by a simultaneous decrease in filling pressures and vascular resistances. For up to 2 hours, 3/10 (A) and 2/9 (E) patients required additional positive inotropic support with adrenaline. There were no significant differences between the two groups at any time.(ABSTRACT TRUNCATED AT 250 WORDS)

Structural Analysis of Gold Clusters Using Exafs

Abstract: Three gold clusters, Au 55 (PPh 3 ) 12 Cl 6 , Au 55 {PPh 2 (C 6 H 4 SO 3 Na)} 12 Cl 6 and Au 11 {PPh 2 (p-ClC 6 H 4 )} 7 I 3 (which we shall denote Au 55 , Au 55 , and Au 11 for convenience) have been studied using EXAFS. Average near-neighbour bond lengths are contracted from the bulk by approximately 0.15A (±0.02A) for Au 55 , and 0.22A (± 0.02A) for Au 11 . Ligand contributions have been successfully modelled in the fitting. Debye-Waller factors for samples at room temperature and at 80K are compared to ascertain the relative degrees of thermal and static disorder present in the systems. Results clearly indicate that static structural disorder predominates over thermally induced vibrational disorder.

Tightness, torsion, and tubes

Abstract: We give examples of spaces with 3-torsion in the homology admitting Z3-tight polyhedral immersions into euclidean space. Polyhedral tubes are used to construct embedded hypersurfaces of this kind.