Endoreduplication in conjunction with tumor progression in an aneuploid laryngeal squamous cell carcinoma

We report the case of a 58-year-old man who presented with a squamous cell carcinoma pT1a G2 of the left vocal cord. Six months after histologically verified complete resection, the patient experienced an endolaryngeal and extralaryngeal local recurrence pT4 pN2b G2. We applied DNA flow cytometry (FCM) and comparative genomic hybridization (CGH) on both primary and recurrent tumor. The primary tumor and the endolaryngeal compartment of the relapse was an aneuploid cell clone with a FCM DNA index of 1.42 and 1.44, respectively. The extralaryngeal compartment showed a shift featuring a DNA index of 2.78. In the primary tumor and in both compartments of the recurrence there was an identical pattern of complex chromosomal imbalances as detected in CGH (CGH karyotype: rev ish enh [8q24.2-q24.3, 10q26.1-q26.3, 11q24-q25, 12q24.2-q23.33,X], dim [4q, 13q14.3-q31], amp[1p36.1-p36.2]). Hence, the recurrence was not associated with further gains and losses of chromosomal material. However, in the anterior part of the recurrence, the aneuploid tumor cell genome had completely doubled, obviously due to endoreduplication. Immunohistochemical analysis of several cell-cycle regulators revealed altered expression of checkpoint proteins, pointing to a complex disturbance in cell-cycle regulation.     

Beitrag zur Methodik der Bestimmung des „Leicht Abspaltbaren“ Eisens im Serum und Einige Klinische Ergebnisse

Zusammenfassung Es wird in Kürze der Stand des Untersuchungsverfahrens bei der Erforschung des leicht abspaltbaren Eisens im Serum besprochen, sowie die ungeklärte und schwierige Lage der klinischen Bearbeitung dieses Gebietes im allgemeinen dargelegt. Es folgt eine Schilderung der bei der eigenen Arbeit verwandten Barkanschen Methode und der mit ihr gemachten Erfahrungen.Aus der Darstellung der Ergebnisse und den Tabellen am Schluß, die einen Überblick über Untersuchungsweise und klinische Befunde der verschiedenen Untersucher bieten sollen, geht ein widerspruchsvolles Bild hervor, aus dem auch auf die Schwierigkeit und teilweise Unzuverlässigkeit der Methoden geschlossen werden darf. Die hohe Fehlergrenze, die ich mit der Barkanschen Methode hatte, zeigt dasselbe.Im übrigen darf man wohl aus den Zusammenstellungen folgern, daß zwischen dem Serumeisen und dem Blutfarbstoff kein unmittelbarer Zusammenhang besteht, ein Schluß, zu dem sowohl Kliniker, wie Chemiker auch im einzelnen schon gekommen sind, der jedoch nicht unwidersprochen ist.Herrn Prof.Schottmüller danke ich für die Überlassung des erforderlichen Materials an seiner Klinik, Herrn Prof.Schumm für die freundliche Überlassung eines Arbeitsplatzes und seine liebenswürdige Unterstützung meiner Arbeit, sowie Fräulein Dr.Mertens und den Herren Dr.Budelmann und Dr.Dohmen für ihre freundliche Hilfsbereitschaft.     

Depth scanning for a conformal ion beam treatment of deep seated tumours

Only target-conformal treatment allows one to exploit the advantages of ion beams (the increased dose and high biological efficiency at the end of the particle range) to a maximum extent. Up to now, target-conformal treatments such as spot scanning or intensity-controlled raster scanning have used fast magnetic lateral deflection in one or two directions perpendicular to the beam axis and a slow range variation in the longitudinal axis by active or passive energy variation. The present paper describes a new method for conformal irradiation with a fast intensity-controlled longitudinal scan in the beam direction, called 'depth scanning'. Its advantages and disadvantages will be discussed. First experimental results from depth scanning will be presented.     

Synectin/syndecan-4 regulate coronary arteriolar growth during development.

Syndecan-4 and its cytoplasmic binding partner, synectin, are known to play a role in FGF-2 signaling and vascular growth. To determine their roles in coronary artery/arteriolar formation and growth, we compared syndecan-4 and synectin null mice with their wild-type counterparts. Image analysis of arterioles visualized by smooth muscle alpha-actin immunostaining revealed that synectin (-/-) mice had lower arteriolar length and volume densities than wild-type mice. As shown by electron microscopic analysis, arterioles from the two did not differ in morphology, including their endothelial cell junctions, and the organization and distribution of smooth muscle. Using micro-computer tomography, we found that the size and branching patterns of coronary arteries (diameters > 50 microm) were similar for the two groups, a finding that indicates that the growth of arteries is not influenced by a loss of synectin. Syndecan-4 null male mice also had lower arteriolar length densities than their gender wild-type controls. However, female syndecan-4 null mice were characterized by higher arteriolar length and volume densities than their gender-matched wild-type controls. Thus, we conclude that both synectin and syndecan-4 play a role in arteriolar development, a finding that is consistent with previous evidence that FGF-2 plays a role in coronary arterial growth. Moreover, our data reveal that gender influences the arteriolar growth response to syndecan-4 but not to synectin.     

Plasma lipids and lipoproteins and essential hypertension

In recent years there have been many studies demonstrating a correlation between increased arterial blood pressure and altered lipid profiles, and there has been an especially positive correlation between high cholesterol levels and blood pressure. There are differences between the various reports that are important. In our study the lipid distribution in 105 hypertensive patients with mild or moderate arterial hypertension according to WHO criteria without clinically or ultrasonographically apparent atherosclerosis was compared to the lipid distribution in 65 age-matched healthy persons. On the epidemiological level a significant, positive association was found between LDL serum levels (P 0.001), Apo B serum levels (P 0.001), serum triglyceride levels (P 0.05) and VLDL serum levels (P 0.01) and arterial hypertension. However, in contrast to recent reports, no significant difference was found between total serum cholesterol levels in normotensives and hypertensives, and there was no difference in HDL serum levels. No evidence could be found for a significant increase in lipoprotein (a) serum levels in hypertensives.Abbreviations LDL low density lipoprotein - VLDL very low density lipoprotein - HDL high density lipoprotein - Apo B 100 apolipoprotein B 100 - Apo A I apolipoprotein A I Correspondence to: H. Vetter     

Lamina propria plasma cells in inflammatory bowel disease: intracellular detection of immunoglobulins using flow cytometry

This is the first application of flow cytometry for the detection of lamina propria plasma cells and their intracellular immunoglobulins in patients with inflammatory bowel disease compared to healthy controls. The study has been focused on the distribution of IgA, IgG, IgM and the four IgG subclasses. Plasma cells were detected as high CD38 positive cells. For fixation and permeabilisation a single step reagent, Ortho Permeafix®, was used.

By flow cytometry, in patients with inflammatory bowel disease compared to healthy controls, a higher percentage of IgG⁺ cells can be observed, in Crohn's disease also a higher percentage of IgM⁺ cells. Regarding the IgG subclass distribution, patients with Crohn's disease show an increase in IgG2⁺ cells, patients with ulcerative colitis an increase in IgG1⁺ and IgG3⁺ cells. These results do agree with and expand the results of earlier immunohistochemical and functional studies, which are favoured today. For the determination of lymphocyte subset proportions and the detection of intracellular antigens, flow cytometry provides a useful alternative to well-established immunohistochemical methods. By analysing a larger number of cells, this method is more reproducible and less prone to interobserver variations than immunohistochemistry, which needs the pre-selection of a mucosal area, the microscopic scoring of a limited number of cells and the circumvention of high background staining. The optimized flow cytometric protocol used in this study might be a promising tool for further investigations of various purposes.     

Bestimmung der enteralen Resorption hoher Calciumdosen mittels stabiler Isotope

Zusammenfassung Bei 8 gesunden Versuchspersonen (Durchschnittsalter 25,6 Jahre) wurde nach oraler Applikation von 500 mg und 1000 mg Calcium die Calcium-Resorption bestimmt. Hierzu wurde ein Doppelisotopenverfahren mit angereicherten stabilen Calciumisotopen verwendet, das, da im Gegensatz zu Radiotracermethoden jegliche Strahlenbelastung vermieden wird, uneingeschränkt anwendbar ist. Die oral verabreichten Calciumsalze wurden mit⁴⁸Ca, das intravenös injizierte CaCl₂ mit⁴⁶Ca markiert. Die Bestimmung der beiden Isotope in Serum- und Urinproben erfolgte mit Hilfe der Neutronenaktivierungsanalyse. Für die Resorptionsquote wurde, unabhängig von der Calcium-Dosis, ein Wert von 30% gefunden. Aus dem⁴⁶Ca-Gehalt im Serum wurde für das in 24 h ausgetauschte Körper-Calcium ein mittlerer Wert von 6,4±1,0 g Calcium oder 98,8±15,4 mg Ca/kg Körpergewicht berechnet.