Comparative genomic hybridization (CGH) discloses chromosomal and subchromosomal copy number changes in Merkel cell carcinomas

We analyzed three Merkel cell carcinomas (MCC), applying comparative genomic hybridization (CGH) with DNA from paraffin-embedded and cultured tumor material as the probes. By this method, numerous changes in chromosome copy numbers were observed in each tumor investigated. Recurrent gains of chromosomes 1, 6, 18q and 20 were detected in two tumors. A third tumor showed complex chromosomal copy number changes, including gain of chromosome 8 and 9. These gains, as well as gain of chromosome 1 in the first two tumors, were confirmed by fluorescence in situ hybridization to paraffin tissue sections. Our results support the view that important genes for MCC development may be located on chromosomes 1, 6, 18q and 20.     

Acute therapy of ischemic cerebral infarct

The ischaemic cerebral attack is a disease prevailingly of older age. Its prognosis is distinguished by a mortality rate as high as ever. From 1975 to 1985, 520 patients with ischaemic cerebral attack have been treated in hospital, with specific acute therapy changing from the so-called vasodilator therapy via osmotherapy into haemodilution therapy with lowmolecular dextrane. Since during vasodilator therapy any early mobilisation nor continuous physiotherapy were carried out and the patients prevailingly died of bronchopneumonia, the significantly lower mortality rate under osmotherapy and haemodilution therapy cannot be attributed to the specific drug therapy. In all probability it is a result of the improvement of care and of the active early mobilisation of the patients.     

Rolle der Winkelstabilität bei der intramedullären Stabilisierung

Zusammenfassung Winkelstabile Plattenfixateur-interne-Systeme haben in den letzten 20 Jahren zunehmend an Bedeutung gewonnen. Die aus der Winkelstabilität resultierende flächenhafte Krafteinleitung und gleichmäßigere Kraftverteilung führen zu einer besseren Knochenbruchheilung insbesondere im metaphysischen Bereich und bei Osteoporose. Bei Marknagelsystemen ist die Winkelstabilität bislang nur partiell verwirklicht. Der vorgestellte winkelstabile Tibiamarknagel realisiert an jedem einzelnen Bolzen eine Winkelstabilität mit dem einliegenden intramedullären Kraftträger. Von Februar 2002–August 2004 wurden 21 Patienten mit ihm behandelt. In 13 Fällen wurden Frakturen stabilisiert, 6 Patienten hatten Fehlstellungen, 2 Patienten Pseudarthrosen. Zum Nachuntersuchungszeitpunkt waren alle Behandlungen abgeschlossen. Postoperative Komplikationen traten nicht auf. In allen Fällen wurde eine vollständige Durchbauung erreicht. In 6 Fällen fand sich radiologisch eine verzögerte Knochenbruchheilung. Die ersten klinischen Erfahrungen mit dem winkelstabilen Tibiamarknagel zeigen, dass dieser aufgrund der höheren Primärstabilität insbesondere im metaphysären Knochenbereich mit kurzen Fragmenten sowie bei Osteoporose Vorteile gegenüber anderen nichtwinkelstabilen oder nur partiell winkelstabilen Marknagelsystemen erbringt. Die verzögerten Knochenbruchheilungen bedürfen weiterer klinischer und biomechanischer Untersuchungen.     

Rationale for clinical trials of opiate antagonists in treating patients with personality disorders and self-injurious behavior

A subgroup of patients with personality disorders from the DSM-III-R (American Psychiatric Association 1987) "flamboyant" cluster is characterized by repetitive self-injurious behavior (SIB) apparently not motivated by suicidal intent. After describing the clinical and demographic characteristics of these patients, the clinical and preclinical evidence suggesting the involvement of endogenous opiate systems in this behavior is reviewed. Patients with personality disorders and SIB have been found to have elevated levels of plasma beta-endorphin. However, the available evidence is not sufficient to show whether this is a cause of or a consequence of SIB. Behavioral stereotypies resulting in self-injury in animals and SIB in mentally retarded patients have been shown to be abolished by opiate antagonist administration in a significant proportion of both groups. The available evidence suggests that clinical trials of oral opiate antagonist drugs should be undertaken because of the promise such drugs have in the treatment of this sometimes life-threatening disorder.     

Serotoninbestimmungen an Thrombocyten und an Fraktionen von Thrombocyten

Zusammenfassung Aus Suspensionen zerstörter Thrombocyten des Menschen wurden reine Fraktionen von Hyalomer und Granulomer hergestellt. Von den Fraktionen wurde jeweils ein Teil für die elektronenmikroskopische Untersuchung, ein anderer Teil für die Bestimmung des Serotonins verwandt. Durch die elektronenmikroskopische Untersuchung jeder einzelnen Fraktion wurde die Reinheit der Fraktionen überprüft. Die Bestimmung des Serotoningehaltes erfolgte am isolierten Rattenmagen. In Kontrollversuchen wurde ferner der Serotoningehalt intakter Thrombocyten bestimmt.Intakte Thrombocyten besitzen im Mittel einen Serotonin-Gehalt von 52 ng/10⁸ Thrombocyten. In den Fraktionierungsversuchen fanden wir 95% des Serotonins in den Hyalomer-Fraktionen und nur 5% des Serotonins in den Granulomer-Fraktionen. In vivo findet sich also der hohe Serotoningehalt fast ausschließlich im Hyalomer der Thrombocyten.

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Summary Pure fractions of hyalomer and granulomer were prepared from suspensions of destroyed human thrombocytes. One portion of the fractions was used for the electron microscopic studies, and the other part for the determination of serotonin (5-hydroxytryptamine). The electron microscopic investigation allowed to check the purity of each single fraction. On the isolated rat stomach the determination of the concentration of serotonin was performed. In control preparations we studied the serotonin concentration of intact thrombocytes. These thrombocytes have a mean serotonin concentration of 52 ng/10⁸ platelets. In fractioning experiments we found 95% of the serotonin in the hyalomer fractions and only 5% of the serotonin in the granulomer fractions. In vivo therefore, the high concentration of the serotonin is found almost exclusively in the hyalomer of the thrombocytes.

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Die Ergebniss wurden vor der Medizinischen Gesellschaft Düsseldorf am 23. 1. 1963 mitgeteilt. Herrn Prof. Dr.Meessen danken wir für die Anregung und Förderung der Arbeit, Herrn Prof. Dr.Greeff für die Hilfe bei den Serotoninbestimmungen.     

Activity and cross-reactivity of antibodies induced in mice by immunization with a group B meningococcal conjugate

The capsular polysaccharide of group B Neisseria meningitidis is composed of a linear homopolymer of alpha(2-8) N-acetyl neuraminic acid or polysialic acid (PSA) that is also carried by isoforms of the mammalian neural cell adhesion molecule (NCAM), which is especially expressed on brain cells during development. Here we analyzed the ability of antibodies induced by the candidate vaccine N-propionyl polysaccharide tetanus toxoid conjugate to recognize PSA-NCAM. We hyperimmunized mice to produce a pool of antisera and a series of immunoglobulin G monoclonal antibodies and evaluated their self-reactivity profile by using a battery of tests (immunoprecipitation, immunoblotting, and immunofluorescence detection on live cells and human tissue sections) chosen for their sensitivity and specificity to detect PSA-NCAM in various environments. We also searched for the effects of the vaccine-induced antibodies in two functional assays involving cell lysis or cell migration. Although they were highly bactericidal, all the antibodies tested showed very low or no recognition of PSA-NCAM, in contrast to PSA-specific monoclonal antibodies used as controls. Different patterns of cross-reactions were revealed by the tests used, likely due to affinity and specificity differences among the populations of induced antibodies. Furthermore, neither cell lysis nor perturbation of migration was observed in the presence of the tested antibodies. Importantly, we showed that whereas enzymatic removal of PSA groups from the surfaces of live cells perturbed their migration, blocking them with PSA-specific antibodies was not functionally detrimental. Taken together, our data indicated that this candidate vaccine induced antibodies that could not demonstrate an immunopathologic effect.     

Genetic study of oxygen resistance and melanization in Cryptococcus neoformans.

Genetic analysis of oxygen-sensitive mutants of Cryptococcus neoformans revealed two loci (oxy1 and oxy2) linking hyperoxia sensitivity to production of melanin, a known virulence factor. Hyperoxia-sensitive strain 562 (oxy1 oxy2) is albino and avirulent. oxy2-defective strains lacking the oxy1 defect are melanin deficient but show normal hyperoxia resistance. Mutants defective at three additional mapped melanin loci fail to show hyperoxia sensitivity in the oxy1 background. Revertants of strain 562, which regain the ability to synthesize melanin by mutation at suppressor sites unlinked to oxy2, retain the oxygen sensitivity conferred by their oxy1 and oxy2 defects. These data identify the melanin gene oxy2 as unique in its association of hyperoxia resistance and melanization.