Chromosomal in situ suppression hybridization of human gonosomes and autosomes and its use in clinical cytogenetics

DNA libraries from sorted human gonosomes were used selectively to stain the X and Y chromosomes in normal and aberrant cultured human cells by chromosomal in situ suppression (CISS-) hybridization. The entire X chromosome was stained in metaphase spreads. Interphase chromosome domains of both the active and inactive X were clearly delineated. CISS-hybridization of the Y chromosome resulted in the specific decoration of the euchromatic part (Ypter-q11), whereas the heterochromatic part (Yq12) remained unlabeled. The stained part of the Y chromosome formed a compact domain in interphase nuclei. This approach was applied to amniotic fluid cells containing a ring chromosome of unknown origin (47,XY; +r). The ring chromosome was not stained by library probes from the gonosomes, thereby suggesting its autosomal origin. The sensitivity of CISS-hybridization was demonstrated by the detection of small translocations and fragments in human lymphocyte metaphase spreads after irradiation with 60Co-gamma-rays. Lymphocyte cultures from two XX-males were investigated by CISS-hybridization with Y-library probes. In both cases, metaphase spreads demonstrated a translocation of Yp-material to the short arm of an X chromosome. The translocated Y-material could also be demonstrated directly in interphase nuclei. CISS-hybridization of autosomes 7 and 13 was used for prenatal diagnosis in a case with a known balanced translocation t(7;13) in the father. The same translocation was observed in amniotic fluid cells from the fetus. Specific staining of the chromosomes involved in such translocations will be particularly important, in the future, in cases that cannot be solved reliably by conventional chromosome banding alone

Radiative processes in external gravitational fields

Kinematically forbidden processes may be allowed in the presence of external gravitational fields. These ca be taken into account by introducing generalized particle momenta. The corresponding transition probabilities can then be calculated to all orders in the metric deviation from the field-free expressions by simply replacing the particle momenta with their generalized counterparts. The procedure applies to particles of any spin and to any gravitational fields. transition probabilities, emission power, and spectra are, to leading order, linear in the metric deviation. It is also shown how a small dissipation term in the particle wave equations can trigger a strong backreaction that introduces resonances in the radiative process and deeply affects the resulting gravitational background.Comment: 5 pages, 1 figur

EFEMP1 binds the EGF receptor and activates MAPK and Akt pathways in pancreatic carcinoma cells

The EGF-related protein EFEMP1 (EGF-containing fibulin-like extracellular matrix protein 1) has been shown to promote tumor growth in human adenocarcinoma. To understand the mechanism of this action, the signal transduction activated upon treatment with this protein has been investigated. We show that EFEMP1 binds EGF receptor (EGFR) in a competitive manner relative to epidermal growth factor (EGF), implicating that EFEMP1 and EGF share the same or adjacent binding sites on the EGFR. Treatment of pancreatic carcinoma cells with purified EFEMP1 activates autophosphorylation of EGFR at the positions Tyr-992 and Tyr-1068, but not at the position Tyr-1048. This signal is further transduced to phosphorylation of Akt at position Thr-308 and p44/p42 MAPK (mitogen-activated protein kinase) at positions Thr-202 and Tyr-204. These downstream phosphorylation events can be inhibited by treatment with the EGFR kinase inhibitor PD 153035. The observed signal transduction upon treatment with EFEMP1 can contribute to the enhancement of tumor growth shown in pancreatic carcinoma cells overexpressing EFEMP1

Double in situ hybridization in combination with digital image analysis: A new approach to study interphase chromosome topography

Double in situ hybridization with mercurated and biotinylated chromosome specific DNA probes in combination with digital image analysis provides a new approach to compare the distribution of homologous and nonhomologous chromosome targets within individual interphase nuclei. Here we have used two DNA probes representing tandemly repeated sequences specific for the constitutive heterochromatin of the human chromosomes 1 and 15, respectively, and studied the relative arrangements of these chromosome targets in interphase nuclei of human lymphocytes, amniotic fluid cells, and fibroblasts, cultivated in vitro. We have developed a 2D-image analysis approach which allows the rapid evaluation of large numbers of interphase nuclei. Models to test for a random versus nonrandom distribution of chromosome segments are discussed taking into account the three-dimensional origin of the evaluated 2D-distribution. In all three human diploid cell types the measurements of target-target and target-center distances in the 2D-nuclear image revealed that the labeled segments of the two chromosomes 15 were distributed both significantly closer to each other and closer to the center of the nuclear image than the labeled chromosome 1 segments. This result can be explained by the association of nucleolus organizer regions on the short arm of chromosome 15 with nucleoli located more centrally in these nuclei and does not provide evidence for a homologous association per se. In contrast, evaluation of the interphase positioning of the two chromosome 1 segments fits the random expectation in amniotic fluid and fibroblast cells, while in experiments using lymphocytes a slight excess of larger distances between these homologous targets was occasionally observed. 2D-distances between the labeled chromosome 1 and 15 segments showed a large variability in their relative positioning. In conclusion our data do not support the idea of a strict and permanent association of these homologous and nonhomologous targets in the cell types studied so far

Mittlere und untere Vorgesetzte in der Industrie: Opfer der "schlanken Produktion"?

"Der Beitrag untersucht die Folgen der gegenwärtigen Bemühungen um Bürokratie- und Hierarchieabbau im Management für die Situation mittlerer und unterer Vorgesetzter. Bezugnehmend auf die Resultate von zehn Fallstudien über mittlere und große Unternehmen aus der Metall und Elektroindustrie wird die These vertreten, daß die Auswirkungen der Dezentralisierungspolitik auf die Arbeitssituation und die beruflichen Entwicklungsmöglichkeiten mittlerer und unterer Vorgesetzter sehr viel weiter reichen als die früheren Ansätze zur Rationalisierung des Managements. Die Einschätzung einer 'Erosion' des bürokratischen Karrieretypus wird in einem modifizierten Sinn bestätigt." (Autorenreferat, IAB-Doku

Reorganisation des Managements: Mythos und Realität des "Intrapreneurs"

"Die Reorganisation von Unternehmen nach dem Modell der „marktgesteuerten Dezentralisation“ und des „internen Unternehmertums“ bewirkt weitreichende Veränderungen der Rollen und des Status von Führungskräften. Die referierte Studie zeigt das beträchtliche Ausmaß, in dem Verantwortlichkeiten und Entscheidungsbefugnisse auch auf die unteren und mittleren Führungsebenen ausgeweitet werden. Für eine relevante Minderheit sind die Reorganisationen aber auch mit der Verschärfung des Kompetenz-Verantwortung-Dilemmas verbunden. Darüber hinaus beeinträchtigt die Reorganisation auch für diejenigen, die zunächst als „Gewinner“ dastehen, die bisherige Sicherheit des Arbeitsplatzes und der beruflichen Entwicklungsmöglichkeiten. Das neue Leitbild des Intrapreneurs wird deshalb bei weitem nicht so positiv aufgenommen, wie das in der Beraterliteratur propagierte euphorische Bild suggeriert, vielmehr dominiert Verunsicherung." (Autorenreferat)"The reorganization of companies following the model of ‘market driven decentralization’ and ‘intrapreneurship’ has far-reaching effects on roles and status of managers. The empirical study presented here, confirms the considerable shift of responsibilities and competencies to the middle and lower levels of management. However, a significant minority of managers is facing an increasing competenceresponsibility dilemma. Moreover, the reorganization is reducing the previous job security and career opportunities even for those who might at first glance be considered as ‘winners’. The new model of the ‘intrapreneur’ encounters a much less positive response than the euphoric picture propagated by the consulting literature might suggest. Instead feelings of insecurity prevail." (author's abstract