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Biomedical subjects

M Fosse

Publications and source records attributed to M Fosse.

16 recordsLinked to original sources

Sleep, learning, and dreams: off-line memory reprocessing.

Converging evidence and new research methodologies from across the neurosciences permit the neuroscientific study of the role of sleep in off-line memory reprocessing, as well as the nature and function of dreaming. Evidence supports a role for sleep in the consolidation of an array of learning and memory tasks. In addition, new methodologies allow the experimental manipulation of dream content at sleep onset, permitting an objective and scientific study of this dream formation and a renewed search for the possible functions of dreaming and the biological processes subserving it.

Animals↗

Vanadate inhibition of hepatocytic autophagy. Calcium-modulated and osmolality-modulated antagonism by asparagine.

The phosphate analogue vanadate, at 10 mM, strongly (approximately 90%) inhibited the autophagic sequestration of endogenous lactate dehydrogenase in isolated rat hepatocytes. The effect of vanadate was markedly (approximately 80%) antagonized by asparagine (20 mM), and to a lesser extent by glutamine, glycine, and alanine. The antagonism was only observed in the presence of Ca2+ when an isotonic standard incubation medium was used, but by increasing the medium osmolality this Ca2+ requirement could be eliminated. Asparagine induced a cell swelling (17% at 20 mM) that might account for at least part of its vanadate antagonism, since hypotonic cell swelling by itself stimulated autophagy (with a maximal effect at approximately 200 mosM). Conversely, hypertonic media inhibited autophagy and were additive to vanadate. In a strongly hypotonic medium (less than 200 mosM), both asparagine and vanadate were inhibitory. However, since vanadate alone had no effect on cell volume, the vanadate-asparagine antagonism could not be exerted exclusively at the level of cell volume regulation. An additional mechanism might be a partial deamination of asparagine, generating ammonia, which was found to oppose the vanadate inhibition of autophagy while having no effect on cell volume. Other metabolizable amino acids, like alanine and glycine, were moderately vanadate-antagonistic while failing to induce cell swelling. These results are compatible with a vanadate-antagonistic effect of asparagine mediated partly through an unknown mechanism (possibly pH change) by its deamination product, ammonia, partly through cell swelling and a secondary Ca2+ influx that could compensate for a vanadate-induced depletion of intracellular calcium stores.

Adenosine Triphosphate↗

Dependence of hepatocytic autophagy on intracellularly sequestered calcium.

Autophagic sequestration of endogenous lactate dehydrogenase or electroinjected [3H]raffinose in isolated rat hepatocytes was strongly suppressed by the Ca2+ chelator EGTA, unless the cells had previously been electroloaded in the presence of high concentrations of Ca2+ (1.2 mM). The extracellular Ca2+ chelator bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA) and the intracellular Ca2+ chelator BAPTA/tetra(acetoxymethyl)-ester (BAPTA/AM) both inhibited autophagy to the same extent as did EGTA. Inhibitors of Ca(2+)-activated protein kinases (KN-62, H-7, W-7) had little or no effect on autophagy, indicating that the Ca2+ requirement of autophagy was not mediated by such kinases. Agents that elevate cytosolic Ca2+ by releasing Ca2+ from intracellular stores, like thapsigargin, 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ) and the ionophores A23187 and ionomycin, inhibited autophagy strongly, implicating depletion of sequestered rather than of cytosolic intracellular Ca2+ as a common mechanism of inhibition. Lysosomal (propylamine-sensitive) protein degradation, known to be largely autophagy-dependent, was inhibited by thapsigargin and tBuBHQ. Thapsigargin had no effect on cellular ATP levels, but all agents tested (thapsigargin, tBuBHQ, ionophores) inhibited protein synthesis. Our results suggest that autophagy, like protein synthesis, is dependent on the presence of Ca2+ in some intracellular storage compartment.

Animals↗

The effect of anthralin (dithranol) on mitochondria.

The short-term effect of topical application of anthralin (dithranol) on normal human skin was investigated by electron microscopy. Mitochondria appeared markedly damaged. By contrast other cellular structures, particularly the nuclear and cytoplasmic membranes were unchanged. In vitro experiments were therefore performed on isolated rat liver mitochondria and it was shown that anthralin acts as an uncoupler of oxidative phosphorylation. These results suggest that anthralin can inhibit the adenosine triphosphate supply in epidermal cells. This loss of energy supply in keratinocytes could explain, at least in part, the therapeutic efficiency of anthralin in psoriasis.

Animals↗

Psoriasis: a defect in the regulation of epidermal proteases, as shown by serial biopsies after cantharidin application.

The possible role of epidermal serine proteases in the genesis of psoriatic lesions was investigated by sequential biopsies of the epidermal damage induced by topical cantharidin. In the skin of normal subjects, epidermal damage was followed by the transient appearance of proteolytic activity in the upper epidermis accompanied by temporary hyperacanthosis and perivascular inflammatory cells in the superficial dermis. In the uninvolved skin of five patients with psoriasis this proteolysis persisted longer, for more than 7 days. Thereafter, in three of the patients, the proteolysis abated, and this was followed by disappearance of the hyperacanthosis and the dermal infiltrate; in the other two psoriatics the proteolysis and hyperacanthosis increased, and a typical Koebner phenomenon ensued. Migration of neutrophils into the epidermis occurred as a later event. Thus the abnormal persistence of proteolytic activity in the upper epidermis after cantharidin application distinguishes the normal from the psoriatic skin injury response and might initiate the psoriatic lesion.

Cantharidin↗

Endogenous peroxidases in normal human dermis: a marker of fibroblast differentiation.

Incubation of unfixed and unfrozen slices of normal human skin allows visualization of a peroxidase activity associated with the perinuclear envelope and with the endoplasmic reticulum of resident dermal macrophages, dermal mastocytes, and also of some dermal fibroblasts. No peroxidase activity can be detected in fibroblasts cultivated in monolayer, while 80% of fibroblasts in an "in vitro" collagen lattice, called a dermal equivalent, express a peroxidase activity in the perinuclear envelope and the endoplasmic reticulum. Hence expression of this peroxidase activity in normal human skin fibroblasts serves as a marker of fibroblast differentiation and seems to depend on an interaction to fibroblast with the elements of a three-dimensional matrix.

Adult↗

Diaminobenzidine cytochemistry in unfixed human epidermis: a marker for epidermal differentiation and for mitochondria.

Intubation of unfixed and unfrozen slices of skin in diaminobenzidine allows visualization of a peroxidatic activity in perinuclear envelope of suprabasal keratinocytes undergoing orthokeratotic differentiation. Basal keratinocytes and melanocytes are always negative. This enzyme is absent in mucous and parakeratotic (psoriatic) differentiation. Mitochondria are also strongly stained by this technique and it was shown that the number of epidermal mitochondria is greatly increased in psoriatic lesions.

3,3'-Diaminobenzidine↗

A cytochemical marker for epidermal differentiation, Langerhans cells, skin resident macrophages and mitochondria.

Incubation of unfixed and unfrozen slices of skin in diaminobenzidine allows visualization of peroxidatic activity in the perinuclear envelope and endoplasmic reticulum of normal human Langerhans cells. A similar peroxidatic activity is observed in supra-basal keratinocytes undergoing orthokeratotic differentiation. Basal keratinocytes and melanocytes are always negative. This enzyme is absent in mucous and parakeratotic (psoriatic) differentiation. A peroxidatic activity was also found in the endoplasmic reticulum of normal resident skin macrophages. Mitochondria are also strongly stained by this technique and it was shown that the number of epidermal mitochondria is greatly increased in psoriatic lesions.

Cell Differentiation↗

Cellular events leading to blister formation in bullous pemphigoid.

Cellular events occurring in eight patients with bullous pemphigoid were studied by light and electron microscopy. Sections (0.5 micrometer) of large surface area, overlapping blisters and surrounding skin, were examined and correlated ultrastructural studies were performed on selected areas. The peroxidase contained in granules of neutrophils, eosinophils and young macrophages was visualized by incubation with diaminobenzidine and hydrogen peroxide. This cytochemical reaction was used as a marker to study the release of granule enzymes from these inflammatory cells. The release of such enzymes from eosinophils and occasionally from macrophages on the epidermal basement membrane (more precisely in the lamina lucida) was demonstrated in the skin surrounding the blisters in four patients. The release of these enzymes was also observed in the floor of the blisters in all eight patients. It is well known that these granules contain several proteolytic enzymes. These observations are therefore consistent with the proposal that proteolytic enzymes of eosinophils play a pathogenic role during the initial stages of blister formation in bullous pemphigoid.

Blister↗

A simple method for correlating observations on skin at the light and electron microscopic levels.

A method is described which allows the embedding of 6 mm cutaneous punch biopsies for subsequent light and electron microscopic examination. Sections of 20 mm2 cut at 0.5-I micrometer are stained for light microscopy. The subtle tinctorial affinities, which approach those achieved on haematological smears, and the preservation of cellular detail frequently make subsequent ultrastructural examination unnecessary. However, when required, a special technique for trimming and resectioning the tissue blocks allows a good correlation between light and electron microscopic observations.

Azure Stains↗

Endogenous peroxidases: a morphological and functional marker to study inflammatory skin diseases.

The visualization of peroxidase positive lysosomes by diaminobenzidine plus H2O2 allowed easy identification of neutrophils, eosinophils, monocytes and young tissue macrophages in 0.2 micrometer to 0.5 micrometer skin plastic sections of large surface area. Evaluation of the lysosomal functions of these phagocytic cells was greatly improved by the possibility of correlating observations on the same cell at light and electron microscopic levels.

3,3'-Diaminobenzidine↗