Showing papers by "University of Duisburg-Essen published in 1991"

Early mutation of the neu (erbB-2) gene during ethylnitrosourea-induced oncogenesis in the rat Schwann cell lineage

Abstract: The development of malignant tumors of the peripheral nervous system (schwannomas) within a defined intracranial section of the rat trigeminal nerve ("trigeminal box") was used as a model to identify genetic alterations typically associated with the process of cell-lineage-specific oncogenesis induced by exposure to N-ethyl-N-nitrosourea on postnatal day 1. All 47 trigeminal schwannomas (and 12 extracranial neurinomas) investigated carried a T.A----A.T transversion mutation at nucleotide 2012 of the neu (erbB-2) gene sequence encoding the transmembrane domain of pg185neu. This mutation was absent in all 18 tumors in the brain and spinal cord (central nervous system) isolated from the same animals. Identical observations were made in cell lines derived from N-ethyl-N-nitrosourea-induced rat schwannomas vs. brain tumors. By asymmetric PCR and mutant-specific Mnl I restriction fragment length analyses, cells carrying the mutant neu allele became detectable and could be localized within the trigeminal box as early as 7 days after the carcinogen pulse. The proliferation rate of the mutant cells strongly exceeded that of the wild-type cells up to the time of maturation of the trigeminal nerve around postnatal day 30 and thereafter to a lesser extent until the appearance of schwannomas. A specific mutation of the neu gene thus represents a very early, probably the first, step in the malignant conversion of immature rat Schwann cells exposed to N-ethyl-N-nitrosourea in vivo and is diagnostic for a subset of proliferative cells at high risk of progressing toward the expression of fully malignant phenotypes. Loss of heterozygosity for the mutant neu allele is a candidate event for a critical second step in the process.

Nigericin enhances mafosfamide cytotoxicity at low extracellular pH.

Abstract: The cytotoxicity of many alkylating anticancer drugs is increased at reduced intracellular pH (pHi). The therapeutic index of such agents could therefore be improved by lowering pHi in the target cells prior to their application. We have previously demonstrated that the formation of lactic acid can be selectively enhanced in malignant tissues via glucose-mediated stimulation of tumor cell glycolysis. However, the resulting reduction in pHi is partly compensated by the extrusion of H+ equivalents into the extracellular space, with pHi remaining closer to the physiological value than extracellular pH (pHe). For full exploitation of the proton-mediated increase in the cytotoxicity of alkylating agents, pHi should therefore be equilibrated with pHe in lactic acid-producing cells. In the present study we investigated the question as to whether nigericin, an H+/K+ antiporter enabling the entry into cells of H+ ions at low pHe, can be used to enhance the cytotoxic effect of mafosfamide (MAFO; a precursor of “activated” cyclophosphamide) on cultured M1R rat mammary carcinoma cells. At pHe 7.4, the cytotoxic effect of combined treatment with MAFO and nigericin was not superior to treatment with MAFO alone. At acidic pHe, however, MAFO cytotoxicity was potentiated by nigericin as indicated by the colony-forming capacity of M1R cells. For example, at pHe 6.2 (corresponding to the approximate mean “aggregated pH” in actively glycolyzing tumors), the colonyforming fraction of cells treated with a combination of MAFO and nigericin was 3×10−5 that of controls, as compared with a value of 5×10−2 found for cells exposed to MAFO alone. These results suggest that agents counteracting cellular mechanisms that control pHi may be candidate compounds for investigations aimed at the enhancement of alkylating drug cytotoxicity following glucosemediated pH reduction in malignant tumors in vivo.

Etoposide, folinic acid, and 5-fluorouracil in carboplatin-pretreated patients with advanced gastric cancer

Abstract: A group of 20 patients with gastric cancer, refractory to or with no change after two or three cycles of carboplatin were treated with etoposide/folinic acid/5-fluorouracil (ELF). An objective remission rate of 45% (9/20), a median remission duration of 8 months and a median survival time of 11 months were achieved. Toxicities were mild to moderate only. These results are comparable to those being achieved with ELF in previously untreated gastric cancer patients and confirm its efficacy and good tolerability.

Darstellung von (Perfluoralkyl)halogeno‐1,3‐diselenetanen aus entsprechenden Selenocarbonylfluoriden und Umsetzungen mit Bortrichlorid sowie Arsenpentafluorid1)

Abstract: Preparation of (Perfluoroalkyl)halogeno-1,3-diselenetanes from the Corresponding Selenocarbonyl Fluorides and Reactions with Boron Trichloride or Arsenic Pentafluoride1) Reactions of Hg(SeRt)2 (Rt = C2F5, C3F7, CF3) with (C2H5)2 All or All3 in octamethylcyclotetrasiloxane produce the unstable perfluoroalkaneselenocarbonyl fluorides 1 [R1 = CF3 (1 a), C2F5 (1 b), CF3Se (1 c)]. These compounds are very reactive and polymerize to rubberlike products. On heating the polymers decompose almost quantitatively to the monomers or dimers. In CFCl3 solution 1 dimerizes at 20°C in sunlight to the corresponding cis/trans-1,3-diselenetanes 2. The structure of 2 b is determined by single crystal X-ray diffraction. Different selenocarbonyl derivatives add to unsymmetrically substituted 1,3-diselenetanes 3. 1 a and 1 b react with cyclopentadiene to form the [4 + 2] cycloaddition products 4a and 4c. Halogen exchange reactions take place between 2a — d and BCl3. The cis-isomers react much faster than the trans-isomers to give a mixture of cis-, trans-forms of 5. When 2c,d is treated with BCl3 it is possible to isolate and characterize the pure trans-isomer 2d, which is separated by preparative gas chromatography from 5c,d. Fluorine abstraction with formation of 1,3-diselenetan-2-ylium ions (6a — f) are accomplished by reactions of 2 or 3 with AsF5 in SO2.

Microdissection of chromosome band 11 p 15.5: Characterization of probes mapping distal to the HBBC locus

Abstract: Both cytogenetic and molecular genetic analyses of the 11 p 155 subband suggest it may contain loci important in the genesis of a wide variety of tumors such as rhabdomyosarcomas and Wilms' tumors as well as the congenital tumors associated with the Beckwith-Wiedemann syndrome As a first step in further defining the involvement of this chromosomal region in these various maladies, a library was constructed from the specific microdissection of chromosomal fragments representing 11p 155-pter Of 98 microclones analyzed, 31 identified single copy human DNA sequences, 21 of which mapped to 11 p 155 while 10 mapped proximal to the HBBC locus Five of the 11 p 155-positioned microprobes detected restriction fragment length polymorphisms at their homologous genomic loci for various enzymes These microprobes are now being utilized in several ways in order to address the underlying basis of the Beckwith-Wiedemann syndrome and its associated tumors

Level statistics of a noncompact integrable billiard

Abstract: A noncompact, nonintegrable billiard of importance in cosmology---the infinite equilateral triangle on a space of constant negative curvature---gives rise to a natural noncompact integrable approximation, which is studied here quantum mechanically. The Weyl formula for the averaged spectral staircase contains a nonstandard logarithmic term due to the noncompactness of the billiard. For two symmetry classes we determine numerically the spectral staircase, the level-spacing distribution p(s), and the averaged ${\mathrm{\ensuremath{\Delta}}}_{3}$ statistic, and compare with analytical expressions that follow from Poisson statistics and semiclassical theory. The Poissonian result for the correlation function of ${\mathrm{\ensuremath{\Delta}}}_{3}$ is derived in closed form and also compared with the data.

Potential-shape effects in SPLEED from ferromagnets

Abstract: A fully relativistic theory of spin-polarized low-energy electron diffraction (SPLEED) from ferromagnets, which allows for non-spherical effective potentials and magnetic fields, is applied to the Fe (1 1 0) surface. Non-muffin-tin corrections turn out to produce some noticeable spectral changes. However, they do not affect a peak in the exchange scattering asymmetry, which is very sensitive to the assumed magnetic moment of the topmost layer. This peak is, however, significantly enhanced if one replaces the conventional form of the spherical magnetic field in the surface layer by a form close to that obtained in a slab ground state calculation. This implies a modification of a previous SPLEED analysis such that the magnetization of the topmost layer of Fe (1 1 0) is enhanced only by about 30 to 35% relative to the bulk.

[Zygomycoses: clinical aspects and pathology in 10 patients].

Abstract: Deep fungal infections caused by zygomycetes (so-called mucormycoses) are rare. Whereas in the past rhinocerebral mycosis dominated, today a wide range of clinical manifestations must be expected, especially pulmonary infections and invasion of vessel walls with systemic infarction. On the basis of 10 cases of Mucoraceae mycosis and a review of the literature, the predisposing conditions, clinical symptoms and pathologic-anatomic findings are described. Our observations include 7 patients with leukemia and 2 adults and one newborn without malignant neoplasia. Except for the patient with rhinocerebral mycosis, the diagnosis was not established during the patients' lifetime. 3 patients received systemic antimycotic therapy. Our observations suggest that infarctions of internal organs in immunocompromised patients should direct suspicion towards angio-related mycoses, not only of aspergillosis, but also of zygomycosis.

Combining SETL/E with Linda ∗

Abstract: SETL/E is a procedural prototyping language based on the theory of finite sets. The coordination language Linda provides a distributed shared memory model, called tuple space, together with some atomic operations on this shared data space. Process communication and synchronization in Linda is also called generative communication, because tuples are added to, removed from and read from tuple space concurrently. Synchronization is done implicitly. In this paper a proposal will be presented for enhancing the basic Linda model with multiple tuple spaces, additional nondeterminism and the facility for changing tuples in tuple space to combine set-oriented programming with generative communication: SETL/E-Linda.

Fully Relativistic Layer-KKR Green Function Theory and Its Application to Spin-Polarized Photoemission

Abstract: A fully relativistic layer-KKR formalism is developed for calculating the single-particle Green function in atomic layers parallel to crystalline surfaces of magnetic and nonmagnetic materials. Its application to spin-polarized photoemission is also discussed.

High-dose 1,2,4-triglycidylurazol given in regimens preparatory to bone marrow transplantation. A preclinical pharmacology study.

Abstract: To elucidate its potential role in the framework of bone marrow transplantation, we studied the toxicologic and pharmacologic properties of high doses of the triepoxide derivate 1,2,4-triglycidylurazol (TGU) in a preclinical dog model. Dose-dependent and dose-limiting gastrointestinal toxicity occurred in a dose range between 40 and 75 mg/kg, with the lethal dose for 50% of animals (LD50) being estimated at 60 mg/kg. Severe and life-threatening hematologic toxicity developed at all dose levels examined but was generally reversible. The combination of TGU and total-body irradiation produced synergistic gastrointestinal toxicity, necessitating reductions of the TGU dose by 50% as compared with the single-agent dose. In contrast, the combination of TGU and high-dose busulfan resulted in no apparent nonhematologic synergistic toxicities. The immunosuppressive properties of TGU given in this combination enabled sustained histocompatible allogeneic marrow engraftment in three of four animals. The pharmacokinetics of TGU were not influenced by prior total-body irradiation or high-dose busulfan. We conclude that the myelotoxic, pharmacologic and immunosuppressive properties of high-dose TGU observed in this preclinical model seem to render the drug particularly suitable for use in regimens preparatory to bone marrow transplantation.

Linear birefringence studies of incommensurate systems: I. NaNO2

Abstract: The temperature dependence of the linear birefringences Δn b and Δn c of NaNO2 is measured in the temperature range 295 ≤ T ≤ 450 K. Discontinuities are found at the hysteretic lock-in transition into the ferroelectric state at T − c = 436.8 K and T + c = 437.1 K, respectively. Bending points characterize the onset of the incommensurate phase below T i = 438.6 K. Critical t 1-α and |t|β behavior is found above and below T i , respectively, where t = T/T i - 1. α = -0.02 ± 0.01 and β = 0.82 ± 0.02 are in accordance with the 3d XY-model. Anomalies of Δn c and of the low-frequency complex dielectric permittivity occur on heating around T + c . They are ascribed to the formation of domains in the ferroelectric regime, which subsequently give rise to a chaotic incommensurate phase.

MAGNETIZATION AND PERPENDICULAR ANISOTROPY IN Pt/Co MULTILAYER FILM

Abstract: By means of a coupling of spin and obital moment under action of crystal electrical field, we deduced the theoretical expression of the interface energy Ks supporting the perpendicular anisotropy for one monolayer Co/19APt multilayer. As compared with the experimental value, Ks=-0.25erg/cm2, the permission combination of obital quantum number L and the ratio of the charge number ZPt/ZCo, carried by Pt and Co atoms respectively, is given for fitting the experimental Ks value.