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Biomedical subjects

B Kraus

Publications and source records attributed to B Kraus.

At least 55 records · Page 3Linked to original sources

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

Comparative 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.

Animals↗

Immunofluorescence microscopic demonstration of vimentin filaments in asteroid bodies of sarcoidosis. A comparison with electron microscopic findings.

Asteroid 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 preexistent 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.

Cytoskeleton↗

Formation of giant cells in vivo.

In vivo, the development of multinucleate giant cells in granulomas always proceeds in accordance with a given mode (simultaneous phagocytosis--fusion--unordered multinucleate giant cells--ordered multinucleate giant cells). This mode is both quantitatively and qualitatively modifiable, showing a dependence on the quantity, shape, size, and digestibility of the phagocytic material: on uncoated coverslips implanted i.p. in rats, only a few small syncytia develop, bit by bit, on coverslips coated with phagocytotic material, on the other hand, numerous very large, always initially unordered, multinucleate syncytia showing simultaneous aggregation around large phagocytic objects are seen. These can develop into ordered giant cells of the Langhans type, by re-distribution of the cytoplasmic contents, but only when most of the phagocytosed material has been digested. Actively phagocytosing mononuclear macrophages, which coalesce or have already fused to form syncytia frequently develop various types of junctions that probably have the same function in granulomas as in epithelia. Pentalaminar structures in multinucleate giant cells are frequently observed in close conjunction with residual phagocytic material and obviously represent outer cell-membranes that have coalesced during fusion and been incorporated into the cytoplasm. The clear zones surrounding such areas probably represent an element of the cytoskeleton.

Animals↗

Cellular aspects of granulomas.

We investigated granulomas of sarcoidosis and de Quervain's thyroiditis of man as well as experimental granulomas of the rat-peritoneum. Though differing in their cellular composition, they show common features in their organisation. A central zone consisting predominantly of epithelioid cells, epithelioid cell equivalents and macrophages without phagosomes in contact with lymphocytes. An outer zone mainly consisting of large macrophages, rich in phagosomes, dark epithelioid cells, necrotic elements and newly immigrated cells. The outer zone is considered to be a functional transitional area. Many of the newly immigrated monocytes are often binucleate, which we consider to be due to disturbances in the spindle cleavage of mitosis following injury. Ordered multinucleate giant cells (Langhans type) are centrally organised under the influence of centrioles and cytoskeleton. They have one phagocytic pole, one large pluricorpuscular cytocentre and a nuclear pole. The ordered internal structure of these lightly stained giant cells indicates their functional activity. In contrast we consider the darkly stained giant cells to be exhausted elements possibly progressing to coagulative necrosis. Intercellular contacts in granulomas e.g. between macrophages are seen as interdigitations of microvilli with the formation of desmosome-similar junctions. We suppose them to be in part for exchange of information and fixation. Epithelioid cells are characterised by their prominent secretory apparatus as well as by a large centrosphere with radially diverging numerous Golgi dictyosomes. Microtubules, together with microfilaments, are significantly involved in transporting secretory granules towards the periphery of the cell. Degranulation also occurs in co-operation with the various components of the cytoskeleton. Disintegration of the membranes of epithelioid cells leading to necrosis may result from massive degranulation. We suppose the various subtypes of epithelioid cells described by other authors to be various stages of the same but not different types of epithelioid cells.

Adult↗

The cytoskeleton in activated and in functionally disordered cells of the macrophage system.

In animal experiments, and for various granulomatous diseases of humans, components of the so-called cytoskeleton in cells of the macrophage system were investigated in the electron microscope and with the aid of indirect immunofluorescence microscopy using monospecific antibodies. In young monocytes and in non-activated or only slightly activated mononuclear phagocytes, predilection areas and characteristic patterns of arrangement were found: F-actin is observable, densely arranged, in particular, around the nucleus and below the cytomembrane; intermediate filaments of the vimentin type form a broad, intensely fluorescent wreath around the cell nucleus; microtubules radiate from the perinuclear centriole in all directions into the neighbouring cytoplasm, taking the form of a microaster. Modifications of this pattern of distribution begin in the pre-mitotic phase, and become highly evident in karyokinesis and cytokinesis. Increases in the cell function are associated with changes in the arrangement of the cytoskeleton of quite a different nature, in particular in the regions of the cytomembrane, the cytocentre, including the Golgi dictyosomes and neighbouring portions of the rough endoplasmic reticulum, at sites of endocytosis and exocytosis and polarization and orientation, and in conjunction with intracytoplasmic translocations after the fusion of macrophages to form multinucleate giant cells. We do not consider the findings described here to be a sort of more or less static compartimentalization phenomenon, but, rather, believe them to bear a causal relationship to the functional dynamism of highly activated and specially differentiated macrophages, epithelioid cell equivalents, epithelioid cells and giant cells. Moreover, they are suggestive of function-dependent, intimate interactions of the individual cytoskeletal components. The experimental, reversible disturbance by the use of colchicine leads in macrophages to a transient loss of structural and functional identity with drastic alterations of microtubules and vimentin filaments.

Adult↗

Centrioles, microtubules and microfilaments in activated mononuclear and multinucleate macrophages from rat peritoneum: electron-microscopic and immunofluorescence microscopic studies.

In male Wistar rats of the BD I strain, mononuclear macrophages and multinucleate giant cells obtained from the peritoneum 1 day to 5 weeks after implantation of coverslips coated with dermoid cyst sebum, were examined by light microscopy and immunofluorescence microscopy, using antibodies specific for actin and tubulin and also by scanning and transmission electron microscopy. In activated mononuclear macrophages, microtubules radiate from the centrioles, situated in the perinuclear area, into the cytoplasm and the major cell processes. Microfilaments form a dense meshwork beneath the plasmalemma. When mononuclear macrophages fuse to form multinucleate giant cells, the initially unordered ("Foreign body") syncytia still reveal the original distribution patterns of centrioles, microtubules and microfilaments similar to those seen in the individual cells. In the ordered (Langhans) multinucleate giant cell all centrioles are accumulated in a main pluricorpuscular central group. Centrioles are the initiating and organising centres in the formation of microtubules. From the centrioles microtubules extend into the entire cytoplasm of the syncytium as a uniformly organised, stellate, radial system. The centrosphere, which is characteristic for ordered multinucleate giant cells, seems free from microfilaments, which form a ring-shaped woven network encircling the nuclei. Depolymerisation and inhibition of microtubules upon exposure to colchicine, indicates that both the organisation of the cytoplasm and the cellular movements depend on the undisturbed coordination of centrioles, microtubules and microfilaments. This applies also to the fusion of mononuclear macrophages to form syncytia, the ordering processes within multinucleate giant cells, and the function of ordered giant cells.

Animals↗

Giant mitochondria in the human myocardium--morphogenesis and fate.

Electron-microscopical examination of myocardial biopsy material obtained from a 58-year-old man revealed giant mitochondria having a length of 30 micron. Such giant mitochondria (also called megamitochondria) evolve by fusion of the membranes of numerous large individual organelles. Initially they are polymorphous and of diverse shapes, but later they are seen to be arranged among and parallel with the filaments of the myocardial fibres, where they present a smooth, cigar-like appearance. Deposits of glycogen in the giant mitochondria result from the accidental inclusion of glycogen granules during fusion. The abundance of cristae, which often form dense stacks in the megamitochondria, is evidence for the genuine synthesis of new cristal material. The aetiological and exact pathogenetic mechanisms of the evolution of giant mitochondria in the myocardium, as also their function, remain unclear. Particularly large specimens are obviously inefficient and disturbing to the cell. They are degraded by autophagy.

Autophagy↗

Is there a carcinoma in situ of gastric mucosa?

Carcinoma in situ, a precancerous lesion in the strict sense, was first recognized in stratified squamous epithelia. It is characterized by markedly atypical cells replacing the autochthonous epithelial cells without stromal invasion, the basement membrane being well preserved. Notwithstanding gradual transitions between carcinoma in situ on the one hand and dysplasias and invasive cancer on the other hand, its histological separation from the latter is feasible in the uterine portio. Its recognition has decisive therapeutic and prognostic implications, particularly in view of the frequently observed latent period between purely superficial spread and early invasive growth. In contrast difficulties are encountered in applying the concept of Carcinoma in situ to mucosal lesions of the stomach, though an analogous replacement stage has to be postulated, because the gastric and cervical mucous membranes differ fundamentally in their structural characteristics. The epithelial cells of the surface, pits and tubular glands do exhibit progressive atypia during cancerization. However, the single-layered epithelium offers far less distinctive criteria than the stratified squamous epithelium. Newly formed glandular complexes cannot be accepted as evidence for in situ growth. The latent period between purely superficial replacement by atypical cells and invasion appears to be considerably shorter in the stomach than in the portio, probably because the mechanical resistance of the loosely textured gastric lamina propria is small. In addition, stromal invasion may originate from any one epithelial cell in the gastric mucosa, whilst it is just the basal layer from which invasively growing cells may emanate in the uterine portio. The occurrence of dysplasia in the mucosa of the stomach does not justify a gastrectomy, according to our current experience, there being no intervention in gastric surgery equivalent to that of conization.

Carcinoma in Situ↗

[Clinical and morphological findings and problems in malacoplakia of the urinary bladder (author's transl)].

Malacoplakia of the urinary bladder (observations on 4 female patients, average age 47 years, longest duration 8 years) is, under light microscopy, arranged in 4 layers. Zone 1 contains inflammatory granulation tissue. Zone 2 is composed of von Hansemann cells (macrophages). In zone 3, Michaelis-Gutmann bodies appear. Finally, the deepest zone 4 contains connective tissue, blood vessels, and lymphoplasmacellular infiltrates. By electron microscopy, the gradual formation of residual bodies from the remains of phagocytosed materials in the macrophages in these layers can be observed. Through loading with calcium and iron compounds, the residual bodies take on the characteristic appearance of Michaelis-Gutmann bodies. Etiologically, the origin of malacoplakia is probably involved with coliform bacteria, but apparently additional factors are required for the development of a disease process: e.g., disturbance of macrophage function. There are certain parallels between malacoplakia and Whipple's disease. With atypical localization outside the urinary bladder, differential diagnostic difficulties can arise in separating malacoplakia from inflammatory-granulomatous processes (granulomatous orchitis, xanthogranulomatous pyelonephritis). The prognosis of malacoplakia in the urinary bladder is good in all cases, but timely treatment of recurrence and constant supervision are indicated.

Adult↗

Asteroid bodies: derivatives of the cytosphere. An electron microscopic contribution to the pathology of the cytocentre.

An 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 A. 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, function 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.

Female↗

[Developmental anomalies of the liver and carcinoma of the liver in infants and children (author's transl)].

Several forms of intrahepatic developmental anomalies were found on histological examination in 40 children, among them several siblings and polyovular twins. These anomalies affect in principle all structural elements of the liver. In several cases--some of them complicated by cholangitis-there was cholangiofibrosis and cholangiodysplastic pseudo-cirrhosis. In addition, in six children there developed hepatocellular carcinoma between the ages of six months and twelve years. In the course of the development of hepatic carcinoma obligatory nodular for occur. They are made up of light, glycogen-loaded epithelial cells, which later are transformed into small atypical, basophilic cells. These dark cells have a high mitosis rate, have already escaped from the physiological regulation of proliferation. Presumably the various embryonic disorders of liver structure and carcinoma of the liver are based on the action of the same causative factor, which may be of chemical-toxic origin and transferred across the placenta.

Age Factors↗

[Studies on the surgical and chemotherapeutic management of oral cancer].

Of the 101 patients who have been treated with bleomycin since 1971 two groups were formed: Group I: Preoperative chemotherapy with 345 mg bleomycin, followed by radical operation. Group II: 200 mg bleomycin preoperatively, followed by radical operation and postoperative chemotherapy up to a total dose of 345 mg bleomycin. 1. Bleomycin- induced cellular alterations showed a dose-time relation. 2. The treatment plan for group II with 200 mg bleomycin preoperatively plus postoperative cytostatic therapy up to a total of 345 mg resulted in less recurrences and fewer distant metastases than the sole preoperative application of the full dose of 345 mg bleomycin. 3. In all cases, preoperative microscopic examination after administration of the full dose of 345 mg still showed tumor cells with possible growth potential.

Bleomycin↗