Hans Bankl

Increase and Redistribution of Cardiac Mast Cells in Auricular Thrombosis Possible Role of kit Ligand

BACKGROUND The atrial appendage is a predilection site for thrombus formation. Mast cells (MC) are a rich source of mediators that may be involved in the regulation of thrombus formation. We examined number, distribution, and phenotype of MC in thrombosed versus unaffected auricles to elucidate their possible role in auricular thrombosis (AUTHR). METHODS AND RESULTS Sections of atrial appendages (AUTHR, n = 14; controls (CO), n = 13) were analyzed for MC by Giemsa, toluidine blue, and berberine sulfate stains and by immunohistochemistry. Cardiac MC expressed CD antigens corresponding to the classic MC phenotype as well as tryptase, chymase, and heparin. Thrombosis was associated with a twofold increase in the number of MC in the total appendage (CO, 3.1 +/- 1.0 versus AUTHR, 6.4 +/- 1.1 MC/mm2, P < .01). Moreover, in AUTHR, a redistribution of MC to the upper endocardium was observed (AUTHR, 5.3 +/- 1.4 versus CO, 0.07 +/- 0.15 MC/mm2, P < .01). Mast cell growth factor (MGF) was expressed in the endothelium and subendothelial space of thrombosed appendages but not in the normal endocardium. Overexpression of MGF was accompanied by a weak or absent expression of the MGF receptor c-kit on redistributed MC in AUTHR. Patients with unilateral atrial appendage thrombosis did not exhibit a MC increase or redistribution in the unaffected contralateral appendage. No augmentation of other inflammatory cells was observed. Stimulation of isolated cardiac MC with MGF resulted in mediator release. CONCLUSIONS This study provides evidence that AUTHR is associated with MC increase and redistribution and MGF overexpression. The role of redistributed MC and their mediators in the pathophysiology of atrial thrombosis requires further investigation.

Characterization of Human Prostate Mast Cells and Their Increase in Periprostatic Vein Thrombosis

Recent data suggest that mast cells (MCs) and their products are involved in the pathophysiology of thrombosis. In the present study, we analyzed the number, distribution, and phenotype of prostate MCs and periprostatic MCs in patients with unilateral periprostatic vein thrombosis (PVT) by immunohistochemical analysis and electron microscopy. MCs reacted with monoclonal antibodies to tryptase, chymase, and c-kit/CD117 and stained positively for tissue-type plasminogen activator (tPA) and urokinase receptor (uPAR/CD87) but did not express detectable urokinase (uPA) or plasminogen activator inhibitors (PAI-1, PAI-2). We found an increase in the mean +/- SEM number of MCs in PVT compared with control (PVT, 14.36 +/- 1.57 vs control, 5.23 +/- 0.57/mm2). The majority of MCs accumulated in the adventitia of thrombosed veins and showed a decrease in chymase expression. As MCs increase in number in PVT and express a profibrinolytic phenotype, we hypothesize that MC-derived molecules have a role in endogenous fibrinolysis.

Mast cells are augmented in deep vein thrombosis and express a profibrinolytic phenotype

A number of recent data suggest that mast cells (MC) and their products are involved in the pathophysiology of thrombosis. In the current study, we have evaluated the number, distribution, and phenotype of MC in patients with deep vein thrombosis of the lower limb (DVT) (n = 15). Contralateral nonthrombosed limb veins served as control (CO). MC were examined by Giemsa staining and by immunohistochemistry using antibodies against tryptase, chymase, tissue-type plasminogen activator (tPA), urokinase (uPA), urokinase receptor (uPAR), and plasminogen activator inhibitors (PAI-1, PAI-2). We found an increase in the number of tryptase-positive MC in DVT compared with CO (DVT: 9.1+/-1.0 v CO: 4.7+/-0.6 MC/mm2, P < .05). Most of these MC appeared to accumulate in the adventitia of the thrombosed veins, in vicinity of the vasa vasorum. In both DVT and CO, MC reacted with monoclonal antibodies to c-kit, tryptase, and chymase. MC also stained positive for tPA and urokinase receptor, but did not express detectable PAI-1 or PAI-2. As compared with CO, a decreased proportion of MC in DVT was found to stain positive for chymase and tPA. Together, our results show that MC increase in number in DVT and express a profibrinolytic phenotype. We hypothesize that MC and MC-derived profibrinolytic molecules play a role in the pathophysiology of DVT.

Expression of fibrinolytic antigens in redistributed cardiac mast cells in auricular thrombosis

Recent data suggest that auricular thrombosis is associated with an increase and accumulation of mast cells (MC) in the subendothelial region of the upper endocardium. However, the molecular basis and the functional role of MC in this process are not known. In the current study, expression of fibrinolytic and antifibrinolytic antigens in human cardiac MC was analyzed by immunohistochemistry. MC were found to react with antibodies against tissue-type plasminogen activator (tPA) and urokinase receptor (uPAR/CD87), but not with antibodies against urokinase (uPA) or plasminogen activator inhibitors (PAI-1, PAI-2). Significant changes were observed when the phenotype of accumulated MC in the upper endocardium in patients with auricular thrombosis was compared with the phenotype of myocardial MC in the same patients or with MC in normal hearts. These redistributed MC stained less intensely with antibodies against tPA and chymase but retained their staining for tryptase and uPAR. Together, these data indicate that cardiac MC are a source of fibrinolytic antigens and that accumulation of MC in auricular thrombosis is associated with phenotypic changes of MC and loss of cellular tPA. It is hypothesized that MC and their products may play a role in endogenous fibrinolysis in auricular thrombosis.

Der Tod und seine Feststellung

Seit Epikur konnten die Philosophen uns mit solchen Aussagen beruhigen. Heute „erleben“ und „uberleben“ manche Organe durch maschinelle Unterstutzung den Tod des Individuums. Ein dissoziierter Todesbegriff hat sich etabliert. Auch wenn der Tod kein Inhalt unseres Lebens mehr ist, so handelt es sich doch um einen integralen Bestandteil unseres diesseitigen Denkens. Wie wir dem Tod gegenuber eingestellt sind, ob tabuisierend-verdrangend, angstlich oder gefast, ob wir ihn philosophisch, theologisch oder rein biologisch betrachten, die Auseinandersetzung mit der unwiderruflichen Tatsache des „Sterben-mussens“und des „Tot-seins“, ist fur jeden Menschen von fundamentaler Bedeutung.

Anleitung zur Befunderhebung an einzelnen Organen

Voraussetzung einer exakten Befunderhebung ist das genauebeschreibende Registrieren morphologischer Tatsachen. Erst aufgrund des objektiven Sachverhaltes der gestaltlichen Organveranderungen ist es moglich, eine Diagnose zu stellen.

Das Obduktionsprotokoll und die klinisch-pathologische Konferenz

Von jeder Obduktion ist ein schriftlicher Befundbericht zu verfassen. Dieser besteht in der Regel aus 3 bzw. 4 Komponenten: 1. Obduktionsanweisung, moglichst mit beigelegten Auszugen aus der klinischen Krankengeschichte. 2. Pathologisch-anatomische Beschreibung, d.h. der morphologische Befundbericht. 3. Pathologisch-anatomische Diagnosen. 4. Eventuell histologische Beschreibungen und mikroskopische Diagnosen.

Situs der Brustorgane und Mediastinum

Verziehung zur Seite der Veranderung bei schrumpfender Pleuraschwarte, Accretio cordis, chronisch-schwieliger Mediastinoperikarditis und atelektatischem Lungenkollaps

Situs der Bauchorgane

Unmittelbar nach Eroffnung des Abdomens und Freilegung der Bauchorgane ist auf Befunde und Veranderungen zu achten, die durch weitere Manipulation entstellt und fehlinterpretiert werden konnten.

Grundsätzliches zur Arbeit im Seziersaal

Um ein guter Prosektor zu sein mus der Obduzent uber technische Geschicklichkeit verfugen, grundsatzliche Kenntnisse in der normalen und pathologischen Anatomie besitzen, stets uber die Fortschritte auf dem gesamten Gebiet der Medizin orientiert sein, immer volle Objektivitat bewahren und es verstehen, die erhobenen Befunde miteinander rasch und richtig zu kombinieren.