Showing papers by "University of Duisburg-Essen published in 1993"

A gene for the mouse pink-eyed dilution locus and for human type II oculocutaneous albinism

Abstract: THE mouse pink-eyed dilution (p) locus on chromosome 7 is associated with defects of skin, eye and coat pigmentation1. Mutations at p cause a reduction of eumelanin (black-brown) pigment and altered morphology of black pigment granules (eumelano-somes), but have little effect on pheomelanin (yellow-red) pigment2. We show here that the human complementary DNA DN10, linked to thep locus in mice3–5, identifies the human homologue (P) of the mouse pgene, and appears to encode an integral membrane transporter protein. The expression pattern of this gene in various p mutant mice correlates with the pigmentation phenotype; moreover, an abnormally sized messenger RNA is detected in one mutant,pun, which reverts to the normal size in pun revertants. The human P gene corresponds to the D15S12locus within the chromosome segment 15qll–ql3, which is typically deleted in patients with Prader–Willi and Angelman syndrome (see ref. 5 for review). These disorders are phenotypically distinct, depending on the parent of origin of the deleted chromosome5–7, but both syndromes are often associated with hypopigmentation of the skin, hair and eyes (see ref. 8 for review), and deletion of theP gene may be responsible for this hypopigmentation. In addition, we report a mutation in both copies of the human P gene in one case of tyrosinase-positive (type II) oculocutaneous albinism, recently linked to 15qll–ql3 (ref. 9).

Ifosfamide plus doxorubicin in previously untreated patients with advanced soft-tissue sarcoma.

Abstract: The objective of this phase II trial was to assess the therapeutic activity and toxicity of doxorubicin plus ifosfamide in previously untreated patients with advanced soft-tissue sarcoma. Treatment consisted of an intravenous bolus injection of doxorubicin at a dose of 50 mg/m 2 followed by a 24-h infusion of ifosfamide at 5 g/m 2 plus mesna, with therapy being repeated every 3 weeks until disease progression or unacceptable toxicity occurred. Of the 203 patients entered, 175 were evaluable for response. The overall response rate was 35% (95% confidence interval, 28%-42%), with 9% of patients achieving complete responses and 26% showing partial responses

Molecular characteristics of HGF-SF and its role in cell motility and invasion.

Abstract: Scatter factor (SF), a secretory protein of fibroblasts, dissociates and increases the motility of epithelial cells and may be involved in cell migration processes during embryogenesis and tumor progression. Hepatocyte growth factor (HGF) is a potent mitogen for hepatocytes and other cells, and is thought to play a role in liver regeneration. We have presented structural and functional evidence that human SF and human HGF are identical proteins encoded by a single gene, since (i) no differences could be found by protein sequencing, by cDNA analysis, or by immunological comparison, and (ii) SF acts as a hepatocyte growth factor--i.e., stimulates DNA synthesis of primary hepatocytes and is a morphogen of kidney epithelial cells--whereas HGF exhibits SF activity--i.e., dissociates and induces invasiveness of various epithelial cells. Furthermore, there exists only one gene for human HGF-SF which is located on chromosome 7, bands q11.2-21 (Weidner et al., Proc. Natl. Acad. Sci. USA 88, 7001-7005, 1991). HGF-SF has been found to be the ligand of the c-met receptor tyrosine kinase (Naldini et al., EMBO J. 10, 2867-2878, 1991b). We have recently used transient expression of naturally occurring and in vitro mutagenized cDNAs of HGF-SF in order to delineate the protein domains necessary for biological activity and c-met receptor activation. (i) A single-chain HGF-SF resulting from the destruction of the protease cleavage site between heavy and light chain (Arg494 to Gln) was largely inactive, indicating that proteolytic cleavage is essential for acquisition of the biologically active conformation. (ii) A HGF-SF 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 met receptor, stimulated its tyrosine phosphorylation, and induced dissociation of epithelial cells but not mitogenesis. These data indicate that a functional domain in the N-terminal region and/or the first two kringle domains of HGF-SF is sufficient for binding to and activation of the met receptor (Hartmann et al., Proc. Natl. Acad. Sci. USA, in press).

Immunoaffinity purification and gas chromatography—mass spectrometric quantification of 3-alkyladenines in urine: metabolism studies and basal excretion levels in man

Abstract: Immunoaffinity gels were prepared by coupling monoclonal antibody (Mab) EM-6-47 to protein A-Sepharose, and were used to make small columns retaining 3-alkyladenines (3-alkAde) of diverse structure. An analytical procedure for determination of 3-methyladenine (3-MeAde), 3-ethyladenine (3-EtAde), 3-(2-hydroxyethyl)adenine (3-HOEtAde) and 3-benzyladenine (3-BzAde) was developed. Deuterated internal standards (d3-3-MeAde, d5-3-EtAde, d4-3-HOEtAde and d7-3-BzAde) were synthesized and added to urine samples prior to immunoaffinity purification. 3-alkAde were separated and quantitated as tert-butyl-dimethylsilyl (TBDMS) derivatives by capillary gas chromatography-low resolution mass spectrometry (GC-MS). Detection limits for 3-MeAde, 3-EtAde and 3-HOEtAde were 0.2 pmol/ml urine and for 3-BzAde, 1 pmol/ml urine. Studies in two volunteers showed that 3-MeAde and 3-HOEtAde were excreted almost quantitatively (> 90%) within 24 h, that 3-EtAde was less well excreted (67-74%) and that 3-BzAde was poorly excreted (21-25%). Studies on basal levels of 3-alkAde urinary excretion in three volunteers showed that 3-MeAde was > 90% derived from the diet as the preformed product. 3-HOEtAde was present at approximately 10 nmol/day and was reduced to approximately 1 nmol/day when the diet was standardized suggesting that it is also dietary in origin. 3-BzAde was not detected in human urine. 3-EtAde was not only excreted at low levels (< 1 nmol/day) but was also only very slightly affected by diet. This general and sensitive method will be useful in biomonitoring studies in subjects exposed to alkylating agents of diverse structure.

Clonal cytogenetic evolution in a squamous cell carcinoma of the skin from a xeroderma pigmentosum patient

Abstract: Cytogenetic changes in epithelial neoplasms are often complex, making it difficult to determine which are the primary abnormalities and which are secondary. In this report, we describe clonal evolution in a cytogenetically simple, but clinically aggressive squamous cell cancer of the skin from a patient with xeroderma pigmentosum. Chromosome preparations were analyzed from a direct harvest, three independent primary harvests, and passaged cell lines. Three closely related tumor subclones were identified in the primary cultures, and all three proliferated in vitro. Monosomy 4 and a chromosome 9 rearrangement were present in all three subclones and monosomy 21 was present in two subclones. An i(9p) and an i(9q) were derived from the same chromosome 9, and there was concurrent loss of the homologous chromosome 9. In addition, each subclone was characterized by a further specific evolutionary change: t(5;7) (q11.2;p22) in subclone 1, der (11)t(10;11) (q21;p14) in subclone 2, and der (14)t(13;14) (q14;q32) in subclone 3. All three subclones were represented by hypodiploid and hypotetraploid metaphases. Loss of chromosomes from hypotetraploid cells and an 11q+ were the only other changes found in this tumor. The early genetic events in the evolution of this squamous cell cancer, monosomy 4, i(9p), i(9q), and monosomy 21, represent loss of chromosome regions that are commonly lost in other squamous cell carcinomas of the head and neck region. Taken together, these observations indicate that genes on these chromosomal regions are probably important and possibly sufficient for the development of squamous cell carcinoma.

Schwann cell lineage-specific neu (erbB-2) gene expression in the developing rat nervous system.

Abstract: Initiation of oncogenesis in the immature peripheral nervous system (PNS) of rats by the DNA-reactive carcinogen N-ethyl-N-nitrosourea (EtNU) involves a specific T:A -� A:T transversion mutation at nucleotide 2012 of the neu (erbB-2) receptor tyrosine kinase gene in cells of the Schwann cell lineage. Although this mutation is invariably detected in the resulting malignant schwannomas, it is not found in EtNUinduced tumors of the central nervous system (CNS). We have evaluated expression of the neu gene in the PNS and CNS as a function of developmental stage. Cellular levels of neu mRNA and gp185� were analyzed in the trigeminal and sciatic nerve and in brain, using a quantitative reverse transcriptionpolymerase chain reaction, in situ hybridization, immunocytochemistry, and fluorescence-activated cell sorting. In the PNS, expression of the neu gene is restricted to cells of the Schwann cell lineage and markedly exceeds expression in the CNS from prenatal day 20 onward. In trigeminal Schwann cells, neu

High-temperature kinetics of Si atom oxidation by NO based on Si, N, and O atom measurements

Abstract: In the present investigation the well-known high-temperature thermal decomposition of silane was used as Si atom source. Its oxidation by NO was studied behind reflected shock waves in SiH 4 /NO/Ar systems by applying the atomic resonance absorption spectroscopy (ARAS) technique for detecting Si, N, and O atoms. Initial mixtures of 0.5-10 ppm SiH 4 and 75-300 ppm NO in Ar were used to perform experiments in the temperature range 1660 K≤T≤3360 K at pressures 0.4 bar≤p≤1.5 bar

ARAS measurements on the thermal decomposition of silane

Abstract: In the present investigation the thermal dissociation of silane was measured behind reflected shock waves using the Atomic Resonance Absorption Spectroscopy (ARAS) for detecting Si, H, and O atoms. The experiments were performed at temperatures 1250 K ≤ T ≤ 2115 K and pressures between 0.7 and 1.5 bar. Initial mixtures of 0.15 to 5 ppm SiH4 diluted in Ar and 5 ppm SiH4 with 500 ppm O2 diluted in Ar were studied. The H atom measurements show formation rates, which are much less than the respective rates for Si atom formation. This indicates that the H atoms were formed by secondary reactions and are not primary dissociation products of silane or silylene. A reaction mechanism suitable to describe all measured H atom concentration profiles is given in this paper. Si atoms also measured during the silane thermal decomposition were found to be useful to understand the kinetics of this process. From the Si concentration profiles together with computer simulations rate coefficients for the reactions SiH4 + M ⇋ SiH2 + H2 + M (1) SiH2 + M ⇋ Si2 + H2 + M (2) were derived, which can be summarized by the following Arrhenis expressions: k1 = 9.9×1015exp(−24000 K/T) cm3mol−1 s−1 k2 = 9.1×1013exp(−15100 K/T) cm3mol−1 s−1. In the case of the SiH4/O2/Ar mixtures no detectable Si atom concentrations were found, while the observed O atom formation rates were identical to that of Si atoms in mixtures without O2 under comparable reaction conditions. This means that Si originating from the thermal decomposition of silane is directly converted into O by reaction with O2, i.e. O is in this system a measure of Si.

Ein Nickel-Anthracen-Komplex, der in einem Kristall η3- und η4-koordiniert vorliegt†

Abstract: Two isomeric nickel-anthracene complexes of I, i.e., h3- and h4-coordination, are characterized by x-ray crystallog. and the crystal data is compared to other known similar structures.

Influence of NaCl Supplementation on Vasopressin Secretion and Water Excretion in Premature Infants

Abstract: The study was carried out to assess the possible involvement of excess AVP and free water retention in the development of late hyponatremia by comparing the postnatal course of plasma AVP and urinary

Glassy and domain states in random dipolar systems

Abstract: The importance of quenched dipolar and quadrupolar fields in disordered dipolar systems with effective ferroelectric interaction is reviewed. Stable or metastable domain states appear e.g. in K1 - xLixTaO3 (x = 0.063), KTa1 - xNbxO3 (x = 0.017) and PbMg1/3Nb2/3O3. Occasionally, unsmearing of the ferroelectric phase transition is possible by application of an electric field. Spontaneous relaxation towards quadrupolar long-range order is observed in KTa1 - xNbxO3, x = 0.017. In the low-x limit both ferroelectricity and random-field interactions become irrelevant in comparison with the random and frustrated interactions. They give rise to an Ising-type dipole glass transition in K1 - xLixTaO3, x = 0.011.

Umlagerungsreaktionen von Metallodiphosphapropenen des Typs (η5‐C5Me5)(CO)2FeP(SiMe3) — P = C(R)(SiMe3) (R = SiMe3, Ph)

Abstract: Rearrangements of the Metallodiphosphapropenes (η5-C5Me5)(CO)2FeP(SiMe3 — P = C(R)(SiMe3) (R = SiMe3, Ph) Heating of a methylcyclohexane solution of (η5-C5Me5)-(CO)2FeP(SiMe3) — P = C(SiMe3)2 (1a) gives rise to the insertion of the P = C moiety into the CH bond of a ring methyl group with formation of the chelate complex η5-ηC5Me4CH2P-[CH(SiMe3)2]P(SiMe3)Fe(CO)2 (2) which is converted into the pentacarbonylchromium derivative [5-C5Me4CH2P[CH-(SiMe3)2]P(SiMe3)[Cr(CO)5]Fe(CO)2] (3). In contrast, a similar treatment of (5-C5Me5)(CO)2FeP(SiMe3) — P = C(Ph)(SiMe3) (1 b) furnishes the diphosphirane (5-C5Me5)(CO)2FeP — C(Ph)-SiMe3) — P (SiMe3) (5). By chromatography of its (CO)5Cr adduct 6, the P — Si bond is hydrolyzed to give the (diphosphirane)-chromium complex [(5-C5Me5)(CO)2FeP-C(Ph)(SiMe3)P(H)]-Cr(CO)5 (8). The molecular structures of 3 and 8 are determined by single-crystal X-ray analysis.

On the Hodge Structure of Projective Hypersurfaces in Toric Varieties

Abstract: This paper generalizes classical results of Griffiths, Dolgachev and Steenbrink on the cohomology of hypersurfaces in weighted projective spaces. Given a $d$-dimensional projective simplicial toric variety $P$ and an ample hypersurface $X$ defined by an polynomial $f$ in the homogeneous coordinate ring $S$ of $P$ (as defined in an earlier paper of the first author), we show that the graded pieces of the Hodge filtration on $H^d(P - X)$ are naturally isomorphic to certain graded pieces of $S/J(f)$, where $J(f)$ is the Jacobian ideal of $f$. We then discuss how this relates to the primitive cohomology of $X$. Also, if $T$ is the torus contained in $X$, then the intersection of $X$ and $T$ is an affine hypersurface in $T$, and we show how recent results of the second author can be stated using various ideals in the ring $S$. To prove our results, we must give a careful description (in terms of $S$) of $d$-forms and $(d-1)$-forms on the toric variety $P$. For completeness, we also provide a proof of the Bott-Steenbrink-Danilov vanishing theorem for simplicial toric varieties. Other topics considered in the paper include quasi-smooth hypersurfaces and $V$-submanifolds, the structure of the complement of $U$ when $P$ is represented as the quotient of an open subset $U$ of affine space, a generalization of the Euler exact sequence on projective space, and the relation between graded pieces of $R/J(f)$ and the moduli of ample hypersurfaces in $P$.

Constant intravenous pentoxifylline infusions in allogeneic marrow transplant recipients: results of a dose escalation study.

Abstract: An uncontrolled open prospective dose escalation study of daily constant-rate 24-h i.v. pentoxifylline (PTX) infusions was performed in 24 consecutive adult patients with hematologic malignancies undergoing allogeneic BMT. The objective of this study was to determine the maximum tolerable dose and to evaluate steady-state plasma concentrations of PTX and its major active 5-hydroxylated metabolite (MI) with this application route. On each of three dose levels of PTX (10, 15 and 20 mg/kg/day), eight patients were enrolled in this study. The prominent dose-dependent and dose-limiting adverse effect attributable to PTX infusions was moderate to severe nausea and vomiting which occurred on the 15 mg/kg and 20 mg/kg dose levels. In addition, one patient on each of the higher doses developed central nervous system toxicity which manifested as acute obtundation and myoclonias. Monitoring of steady-state plasma concentrations revealed that metabolite MI contributed 70-80% to both active compounds with a dose-dependent increase of parent drug and metabolite MI concentrations. In patients pretreated by high-dose busulfan and cyclophosphamide (CY), steady-state plasma concentrations of metabolite MI were significantly increased on all dose levels over those of patients who received total body irradiation and CY as a preparative regimen. Furthermore, impairment of excretory liver function led to significant accumulation of parent drug and metabolite MI. In conclusion, constant i.v. PTX infusions in allogeneic marrow transplant recipients are limited by dose-dependent nausea and vomiting with an estimated maximum tolerable dose in the range of 10 mg/kg/day.(ABSTRACT TRUNCATED AT 250 WORDS)

Rearrangements of Free Radicals, XIII[1]. Thermal and Photochemical Rearrangements of Cyclic C8H9 Radicals in Adamantane Matrix

Abstract: The ESR spectra observed after X-irradiation of bicyclo-[5.1.0]octa-2,5-diene (homotropylidene) (12) in a [D16]adamantane matrix at 210 K have been identified to be mainly due to the cyclooctatrienyl radical (8), formed by thermal ring opening of the initial bicyclo[5.1.0]octa-2,5-diene-4-yl (homotropylidenyl) radical (7). The same spectrum has also been observed in X-irradiation of bromocyclooctatriene and a mixture of bromocyclooctatriene and 7-bromobicyclo[4.2.0]cycloocta-2,4-diene in a [D16]adamantane matrix. In all cases, UV irradiation of the matrix caused an irreversible transformation of radical 8 (and probably 7) into the bicyclo[3.3.0]octa-2,6-diene-4-yl radical (17). Tricyclo[3.3.0.02,4]oct-6-en-7-yl radical (19), generated by X-irradiation of tricyclo[3.3.0.02,4]oct-2-ene (20) in adamantane, is thermally stable up to 370 K, but also undergoes a facile rearrangement to the radical 17 on UV irradiation. This process is reasonably explained to occur stepwise via radicals 7 and 8. The postulated reaction paths and the spectral assignments are supported by semiempirical (AM1, PM3), abinitio (UHF/3-21G*), and molecular mechanics (MM2ERW) calculations, which are in accord with the finding that 8 is energetically more stable than 7. The quantum mechanical calculations predict that a degenerate sigmatropic circumambulation of the cyclopropane ring in radical 7 should favorably compete with its ring opening.

ARAS measurements on the S(1D) formation in shock heated COS/Ar mixtures

Abstract: The formation of electronically excited S(1D) atoms was studied during the thermal decomposition of carbonyl sulfide behind reflected shock waves by using atomic resonance absorption spectroscopy (ARAS). The experiments were performed in highly diluted mixtures of Ar with relative concentrations of COS between 8 to 100 ppm in the temperature range 2130 K≤T≤3020 K at pressures of about 1.2 bar. The measured rate of the linear S(1D) increases divided by the initial reactants was found to obey the Arrhenius law: . Assuming a fast thermalisation between the (3P) and (1D) states of S atoms this result is in agreement with previous measurements of the S(3P) formation during the thermal decomposition of COS reported recently [1].

Anomalous electron diffusion in irradiated thin gold films

Abstract: We report on topographical and electrical properties of an evaporated (as-prepared) thin gold film before and after irradiation with 200 keV Ar+ ions TEM-investigations reveal for the as-prepared film voids and channels of small size, and a pronounced percolative structure with large scale inhomogeneities after irradiation Magnetoresistance measurements carried out before and after irradiation yield the temperature dependence of the phase coherence lengthLψ, when analysing the experimental data within current theories for 2-dimensional (2d) weak localization The results can be explained by normal electron diffusion if-for the as-prepared film-Lψ is larger than the size of structural inhomogeneities, and-for the irradiated film-by anomalous electron diffusion ifLψ becomes smaller The analysis ofLψ(T) for the irradiated film yields critical exponents for 2d-percolation, in good agreement with predictions of percolation theory

High‐Temperature Kinetics of Si Atom Oxidation by NO Based on Si, N, and O Atom Measurements.

Abstract: In the present investigation the well-known high-temperature thermal decomposition of silane was used as Si atom source. Its oxidation by NO was studied behind reflected shock waves in SiH 4 /NO/Ar systems by applying the atomic resonance absorption spectroscopy (ARAS) technique for detecting Si, N, and O atoms. Initial mixtures of 0.5-10 ppm SiH 4 and 75-300 ppm NO in Ar were used to perform experiments in the temperature range 1660 K≤T≤3360 K at pressures 0.4 bar≤p≤1.5 bar