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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

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

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

Mucopolysaccharidosis III A (Sanfilippo disease type A). Histochemical, electron microscopical and biochemical findings.

This is a report of two brothers iwth mucopolysaccharidosis. The 8- and 10-year-old boys presented the characteristic clinical symptoms of the syndrome in their entirety. Both had a highly increased excretion of heparan sulfate in urine. The elder boy died and was autopsied and diagnosed as having Sanfilippo disease Typ A by a drastic reduction of heparan sulfate sulfamidase activity in organ extracts. Histochemically, highly water-soluble, sulfate acid mucopolysaccharides were demonstrated in liver, spleen, and cerebrum of the deceased child. Chemical analyses revealed a 12-fold increase of sulfated mucopolysaccharide in the patients liver and a 4.5-fold increase in the cerebrum when compared with normal controls. The sulfated polysaccharide consisted mainly of heparan sulfate, which was of low molecular size, heterogeneous in charge, and rich in its sulfamino hexose content. In addition, the gangliocytes of cerebrum and cerebellum had accumulated glycolipids. Electron microscopically the storage cells were overloaded with lysosomal residual bodies. The mitral valve was also involved in the storage process, which is a rare manifestation of the Sanfilippo syndrome. Acid mucopolysaccharides were deposited intracellularly as well as extracellularly in the mitral valve tissue. Polarisation microscopically there was found a change from normally positive to negative birefringence in the connective tissue ground substance of the mitral valve when containing stored mucopolysaccharides.

Autopsy

The juxtaglomerular apparatus in malignant hypertension of man.

Investigation of the behaviour of the renal juxtaglomerular apparatus in 19 patients with malignant hypertension has shown that in kidneys fixed immediately after operation the juxtaglomerular granulation index is twice as high as in autopsy kidneys. The formation of renin by the epitheloid cells begins with the appearance of osmiophilic substances in the region of the endoplasmic reticulum. The first stages of granule formation are small rhomboid particles in the Golgi cisternes, which aggregate to form bigger round or polymorphic granules in the Golgi area. In pathological conditions the substances synthesized may be set free and become active locally as a result of fibrinoid necrosis of the vascular wall. The rate of production is increased firstly by forcing the production of active agents in the preexistent epitheloid cells, secondly by transformation of the so-called bivalent cells and finally, by cell division. In accelerated hypertension the production of renin also takes place in nephrons whose glomeruli, tubules and macula densa, are damaged. There is a correlation between blood pressure elevation and the juxtaglomerular granulation index.

Adult

Increase of mitosis in the tubular epithelium following intrarenal doses of various kidney homogenates and hemogenate fractions in the rat.

Earlier investigations about the consequences of experimental kidney ischemia raised the question, if there exists a substance in the renal tissue which is liberated by cell death or during regeneration of cells and which might stimulate mitosis of other cells. Therefore in recent experiments we directly injected into the left kidney parenchyma of receiver animals, homogenates, or their separated fractions from infarcted or regenerated kidneys of adult donors and from kidneys of juvenile donors. These are the results" 1. A small dose of kidney homogenate already produces a clear increase of mitoses in the tubular epithelium of the renal cortex 17-19 h after injection in the adult recipient of the same breed. The increase of proliferation is of short-duration, kidney-specific, and not to reproduce in different controls. 2. The mitogenetic effect of a unilateral intrarenal dose of kidney homogenate does not favor a special area. Without a recognizable principle of cellular selection it occurs everywhere in the kidney parenchyma. It must be understood as a "simple increase" of normal growth. The proliferation stimulus is humorally transmitted to the untouched contralateral kidney. Yet the mitotic acitivty is significantly higher in the left than in the right kidney. 3. The experiments demonstrate a much better efficiency of the sediment, especially of the mitochondrial and microsomal fraction, than of the supernatant. 4. Our results indicate that in the complicated regulation system of cell growth there must be taken into account different factors and signalizing ways for induction and termination of mitosis.

Animals

[Mitochondrial changes in the tubular epithelium of wistar-rats with spontaneous nephropathy (author's transl)].

The proximal tubular epithelium of Wistar-rats with a spontaneous glomerulopathy is greatly strained by the consecutive massive tubular storage of proteins in aging animals and by the progression of the disease. Together with the onset of increased tubular insufficiency the mitochondria show remarkable changes. These changes occur mainly in the epithelial cells containing many pigmented residual bodies. Besides changes of the mitochondrial arrangement of the cytoplasm most frequently megamitochondria can be seen. Matrix and cristae may contain multiple inclusions, the nature of which is not clear. The changes in the mitochondria are regarded as the expression of adaptation to an altered situation of energy.

Age Factors