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Biomedical subjects

H Cain

Publications and source records attributed to H Cain.

At least 19 recordsLinked to original sources

Neural differentiation in the retina of the larval sea lamprey (Petromyzon marinus).

The peripheral retina of the sea lamprey develops in a 5-year-long process in which only certain neurons differentiate each year. The growth of cell layers, the differentiation of the neurons, and the morphology of their dendrites and axons were studied with normal, HRP, and Golgi preparations. Ganglion cells are differentiated in 3-year-old larvae, amacrine and horizontal cells in 4-year-old larvae, photoreceptor cells in stage I transformers, and bipolar cells in stage III transformers. Each new development is expressed as a radial gradient of differentiation. As a result of this protracted and stepped process, lamprey retinal neurons, particularly ganglion cells, differentiate in the absence of other cells to which they will ultimately be connected and may express their individual genetic programs more fully than in other vertebrate retinas. This could account for the unusual relationship of the ganglion cell, inner plexiform, and optic nerve layers and for the very high ratio of displaced to orthotopic ganglion cells.

Animals↗

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↗

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↗

Evidence for a cerebral cholinergic system and suggested pharmacological patterns of neural organization in the prostomium of the polychaete Nereis virens (SARS).

The histological visualization of choline acetyltransferase (CAT) and acetylcholinesterase (AChE) on frozen sections of prostomia of Nereis virens indicate a concentration of cholinergic activity in the anterior brain. Components are probably sensory epithelial cells with cholinergic axons entering the brain in cephalic nerves and efferent cholinergic axons to prostomial muscle leaving the brain in the same nerves. There are also subepidermal cholinergic cells that may be second order motor neurons serving epidermal mucous cells. The smaller, second lobe of the corpora pedunculata and its associated vertical fibre tract are CAT(+) and appear continuous, on each side of the cerebral ganglion, with a dorsal and ventral longitudinal bundle of AChE(+) fibers. This system tapers to nothing at the level of the posterior eyes. There is a small AChE(+) component to each optic nerve and AChE is present in the nuchal epithelium. These observations are discussed in relation to earlier studies on aminergic and neurosecretory activity in the same ganglion.

Acetylcholinesterase↗

Uptake of tritium-labelled biogenic amines by the prostomium of the polychaete Nereis virens (Sars) (Annelida).

The uptake of tritium-labelled 5-HT, noradrenaline, 5-hydroxytrytophan, DOPA and dopamine by the cerebral ganglion and prostomial nervous system of the polychaete Nereis virens has been examined using radioautography at the level of the light microscope. Pronounced uptake of (3)H-5HT occurred in the antennal, palpal, tegumentary and nuchal nerves as well as in ganglionic nuclei 13, 14, 15, 16, 17, 20, 24 and 25, the mid-brain neuropile, the neurosecretory neuropil and the infracerebral organ; (3)H-NA uptake was observed in small cells in the prostomial epidermis, and the infracerebral organ; (3)H-dopamine only in one of two common types of epidermal mucus cells. Prostomial muscles labelled generally with (3)H-NA and at specific sites with (3)H-5HT. These observations support the concept of an efferent serotonergic system originating in several cerebral ganglionic nuclei and serving prostomial muscle and epidermis. Evidence for an afferent adrenergic system is less substantial. The role of dopamine remains obscure.

5-Hydroxytryptophan↗

[Etiology and morphogenesis of the socalled bronchial arterioma (author's transl)].

Angiomatoid vascular convolusions may develop during the intrapulmonic course of the bronchial artery. The angiomatoid convolusions are arranged segmentally along the longitudinal axis of a bronchus. Histopathologic examinations of 26 cases reveal that the angiomatous lesions form from branches of the bronchial artery, arterial bronchopulmonic connections and their arteriovenous anastomoses, as well as from branches of the pulmonary artery and vein. Common morphologic findings include marked tortuosity with branching, variable lumens, stenosing intimal scars, thrombotic occlusions, pronounced longitudinal muscle bundles and focal necrosis of the vessel wall. Such vascular formations, usually confined to one lung segment, may arise from inborn malformations in this vascular area. Such cases are to be called angioma arteriovenosum racemosum (5 cases from our material). In 21 observations however they have developed secondarily following primary inflammatory, stenosing or deforming diseases of the bronchus, the peribronchial tissues and the surrounding lung tissues. In such cases the angiomatoid changes are the consequence of local stress on blood vessels, blood flow and blood presssure; they do not develop on the basis of a congenital bronchial or vascular dysplasia. We propose the term secondary angiomatoid vascular convolusions in a scarred, deformed bronchial wall or peribronchial tissue. Pulmonary hypertension does not accompany the angiomatoid lesion and their clinical significance lies in dangerous hemorrhages into the bronchial tree.

Adult↗

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↗

The bivalence of juxtaglomerular cells in the maturing rat kidney. A comparative study of secretory and contractile potential.

A comparative immunofluorescence and light microscopical study of the three cell types of the juxtaglomerular apparatus (pure muscle cells, pure granular cells and mixed cells) was performed on the growing and maturing kidney of the rat. Mixed cells, containing contractile protein and secretory granules, are detectable on the first postnatal day in about one third of the JGAs. From the third week, the number of bivalent cells increases, while the proportion of pure muscle or pure granular cells decreases. Morphological and functional maturation, achieved by 3 to 4 weeks, is associated with increasing numbers of bivalent cells and a shift in the main site of renin production from the inner to the outer cortical zone. The divergent internal structure of JGA cell types expresses the range of varied differentiation expressed by one cell line. Pure muscle or granular cells are at the extremes of the range and mixed cells take up an intermediate position.

Animals↗