Brigitte Kraus

Immunofluorescence microscopic demonstration of vimentin filaments in asteroid bodies of sarcoidosis

SummaryAsteroid bodies in multinucleate giant cells from sarcoid granulomas were investigated by immunofluorescence and electron microscopy. The following points have been established :1.Asteroid bodies are made up of individual components of the so-called cytoskeleton, predominantly vimentin filaments. Microtubules are involved in smaller amounts in the formation of the asteroid bodies.2.They arise within the area of the cytosphere. The body of the asteroid includes the centrioles while the arms of the asteroid usually extend into the Golgi area and occasionally up to the cell nuclei.3.Asteroid bodies result from aggregation of the flexible filamentous and microtubular systems of the centrosphere. The processes of aggregation probably result from local fluid shifts and sol-gel transformations.4.The stellate form of the aggregations is determined by the pre-existent radial arrangement of the elements of the cytosphere.5.The prevailing specific environment of the underlying granulomatous disease, together with the internal characteristics of the structure and function of the giant cells, in particular in states of exhaustion may play a part in their development.

Vimentin filaments in peritoneal macrophages at various stages of differentiation and with altered function

SummaryComparative immunofluorescence microscopic, transmission and scanning electron microscopic investigations were carried out to study the arrangement and significance of vimentin filaments in monocytes, macrophages, epithelioid cell equivalents and multinucleate giant cells under various different functional conditions, and in the presence of functional disorders.Uncoated or sebum-coated coverslips were implanted in the peritoneal cavity of Wistar rats. Some of the animals received repeated i.p. injections of colchicine. Rats were killed at various times 1 to 14 days after initiation of the experiment. The number of macrophages, the degree of their activation, and the growth of cells on the coverslips was considerably greater on sebum-coated than on uncoated implants. Various characteristic vimentin distribution patterns were found dependent on the cell cycle, the form and volume of the cell, and on the degree of differentiation and maturity; they were also related to the type and intensity of cell function. These patterns were best developed in ordered multinucleate giant cells.Repeated administrations of colchicine resulted in a marked flattening of the cell body on the coverslips — which correlated with a considerable reduction in the number of vimentin filaments and of cytoplasmic processes — and also in the formation of circumscribed erect, tree-like protuberances. The “trunk” of these structures comprised closely bundled vimentin filaments, and the cell nucleus was located at its base. These morphologic changes, which were associated with a functional insufficiency, proved to be reversible.

Asteroid bodies: Derivatives of the cytosphere

SummaryAn electron microscopic study of asteroid bodies in granulomatous diseases of man, in particular in sarcoidosis and foreign body reactions, has led to the following conclusions.1.Asteroid cytoplasmic inclusions are composed of organic proteineous structures. The body and arms of the stars consist mainly of longitudinally orientated, partially helically wound, collagen free, microfilaments with a diameter of approximately 50 Å. Microtubules participate in their composition to a lesser degree. The filaments intertwine in various directions within the corpus of the stars.2.Deeply osmiophilic compact structures, considered to represent condensation forms of protein, are consistently present within the body of the stars. These structures are partially granular and partially ring-shaped; in the latter case, transverse sections of tubules are noted. Since it is disputed whether they constitute procentrioles or postcentrioles, they are best referred to as paracentrioles.3.The asteroid bodies are derivatives of the cytosphere, thus relating, in the broad sense, to the microfilamentous and microtubular apparatus of the cell.4.The asteroid bodies in multinucleated giant cells participate in the spatial compartmentalization of the cytoplasmic content and nuclei. The sphere, aided by the centrioles, induces the formation of the mitotic spindle and, in addition, functions as an organizing system of the cell.5.The light microscopical periastral clear zone does not correspond to a fluid space. Rather, it consists of closely packed accumulations of laminated and whorled myelin figures, which are derived from the degradation of lipoid substances.ZusammenfassungEigene elektronenmikroskopische Strukturanalysen von Asteroid-bodies in verschiedenen Granulomen des Menschen, besonders bei Morbus Boeck und Fremdkörper-Reaktionen, haben folgendes ergeben :1.Asteroide Zytoplasmainclusionen sind aus organischen Proteinstrukturen zusammengesetzt. Sternkörper und Sternarme bestehen hauptsächlich aus längsorientierten, z.T. spiralig gewundenen kollagenfreien Mikrofilamenten mit einem Durchmesser von ca. 50 Å. In geringerer Menge sind Mikrotubuli an ihrem Aufbau beteiligt. Im Corpus der Sterne durchflechten sich die Filamente in verschiedenen Richtungen.2.Im Stemcorpus finden sich regelmäßig kräftig osmiophile Verdichtungen, die wir für Kondensationsformen von Protein halten. Sie sind teils granulaartig, teils ringförmig und dann mit Tubulusquerschnitten versehen. Wir deuten diese Gebilde als Prozentriolen oder Postzentriolen und nennen sie daher Parazentriolen.3.Asteroide sind ein Derivat der Zytosphäre, sie gehören somit zum mikrofilamentären und mikrotubulären Apparat der Zelle im weiteren Sinne.4.Asteroid-bodies sind in mehrkernigen Riesenzellen an der räumlichen Gliederung des Zytoplasmainhaltes und der Kerne beteiligt. Die Sphäre bildet nicht nur mit Hilfe der Zentriolen die Teilungsspindel aus, sondern stellt grundsätzlich ein ordnendes System in der Zelle dar.5.Die lichtmikroskopische periastrale Aufhellung entspricht nicht einem Flüssigkeitsraum. Sie besteht vielmehr aus dichten Ansammlungen geschichteter, wirbeliger Myelinfiguren, die dem Abbau lipoider Substanzen entstammen.

Arterielle Hypertonie bei reninsezernierendem retroperitonealem Leiomyosarkom

A case report of an extrarenal retroperitoneal metastatic leiomyosarcoma with associated paraneoplastic renin production is presented. Due to the renin excess syndrome, accelerated hypertension was present combined with the signs of secondary hyperaldosteronism, hypokalemia, and alkalosis. In contrast to other publications of extrarenal malignoma with paraneoplastic renin activity, this case elucidates a histologically close relationship to epitheloid muscle cells of kidney vasa afferentia and derived benign tumors. The retroperitoneal tumor and its brain metastase were morphologically identical. In contrast to histological criteria only the primary tumor exhibited high renin activity, no activity could be detected in the metastase.SummaryA case report of an extrarenal retroperitoneal metastatic leiomyosarcoma with associated paraneoplastic renin production is presented. Due to the renin excess syndrome, accelerated hypertension was present combined with the signs of secondary hyperaldosteronism, hypokalemia, and alkalosis. In contrast to other publications of extrarenal malignoma with paraneoplastic renin activity, this case elucidates a histologically close relationship to epitheloid muscle cells of kidney vasa afferentia and derived benign tumors. The retroperitoneal tumor and its brain metastase were morphologically identical. In contrast to histological criteria only the primary tumor exhibited high renin acticity, no activity could be detected in the metastase.

Der juxtaglomeruläre Apparat der Niere bei maligner Hypertonie und terminaler Niereninsuffizienz

SummaryFour patients with malignant hypertension and terminal renal insufficiency were subjected to bilateral nephrectomy, since hypertension neither was to be controlled by diminishing of sodium and plasma volume in hemodialysis nor by antihypertensive medication. After nephrectomy the blood pressure significantly decreased.Micromorphological findings and juxtaglomerular granulation index show a strong hyperplasia, hypertrophy and hypergranulation of the vascular part of the juxtaglomerular apparatus. The abundant presence of cytoplasmic organelles which are responsible for secretion, and the appearance of granules in different stages of maturation represent a truede novo synthesis of secretion material. The release of secretion and its effect upon the vascular system can be concluded from the highly elevated blood pressure before nephrectomy and from its decrease after nephrectomy.The cause of increased production of renin in malignant hypertension is not clear. Intrarenal regulations certainly are disturbed by the strong morphological alterations of vessels and nephrons. They can be followed by a dissociation of intrarenal control mechanisms, possibly combined with an uninhibited production of renin. Extrarenal stimulations of humoral or nerval nature may play a primordial role in releasing malignant hypertension.ZusammenfassungVier Patienten mit maligner Hypertonie und terminaler Niereninsuffizienz wurden beidseitig nephrektomiert, da der Hochdruck weder durch Salz- und Volumenentzug bei chronischer Hämodialyse, noch medikamentös unter Kontrolle zu bringen war. Nach der Nephrektomie sank der Blutdruck rasch und signifikant und ließ sich nun auch durch Natrium- und Wasserentzug korrigieren.Die mikromorphologischen Befunde an den entfernten Nieren und die Bestimmung des juxtaglomerulären Granulationsindex ergaben eine starke Hyperplasie, Hypertrophie und Hypergranulierung der juxtaglomerulären Gefäßpole. Die reichliche Bereitstellung von Cytoplasmastrukturen, die der Sekretherstellung dienen, und das Auftreten verschiedener Reifungsstadien von Granula in den Zellen der Vasa afferentia sprechen für eine echt vermehrte Neubildung von Sekretmaterial. Die Freisetzung des Sekretes aus den Zellen und seine Wirkung am Gefäßsystem können aus dem stark erhöhten Blutdruck vor Nephrektomie und dem deutlichen Absinken der Werte nach Entfernung der Nieren geschlossen werden.Die Ursache der ungehemmten Produktion von Renin, das bei der malignen Hypertonie eine Schlüsselstellung einnimmt, ist nicht bekannt. Intrarenale Regulationen sind bei den schweren morphologischen Veränderungen der Gefäße und der nachgeschalteten Nephrone sicher gestört und können eine Loslösung der Reninproduktion aus dem Reglerkreis zur Folge haben. Möglicherweise spielen extrarenale Stimulationen humoraler oder nervaler Art in der Auslösung der malignen Hypertorie eine übergeordnete Rolle.