Study of microfilaments network during volume regulation process of cultured PC 12 cells.
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Biomedical subjects
Publications and source records attributed to R Gilles.
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The action of the macromolecular inducer glycoprotein on sexual reproduction in the green alga Volvox carteri can be modified by altering the external (intraspheroidal) cAMP concentration. Direct proof for the presence of cAMP in the spheroids is given. Protein binding assay and HPLC-fluorimetric analysis independently demonstrate the existence of cAMP in the matrix, cells, and culture medium. Its concentration is higher in sexual cultures, pointing to a transmitting function in sex induction. The presence in the matrix of other members of a protein phosphorylation system suggests an induction-specific signal cascade in this plant.
This study deals with the effects of hyper- and hypo-osmotic media on the ultrastructure of four different types of cells and tissues: rat pheochromocytoma cells of line PC12, mouse Ehrlich ascites tumor cells, rat kidney cortex and intestine. Application of hyper-osmotic conditions induces in the nuclear compartment of the tested cell types a condensation of chromatin, a ruffling of the nuclear envelope with loosening of condensed chromatin from the lamina, and an apparent loss of nucleolar fibrillar component which disappears in a background of diffuse granular material. In hypo-osmotic media, there is a marked decondensation of chromatin and a fragmentation of the granular material of the nucleolus. As far as the cytoplasmic compartment is concerned, the electron density of the cytosol is markedly increasing when going from hypo- to hyper-osmotic conditions and there is no vacuolization in hypo-osmotic media. In kidney cortex slices, application of hypo-osmotic shocks further results in a marked reduction of the extracellular space delimited by the infoldings of the tubular cells plasma membranes. These modifications are discussed in relation to the volume regulation process and the changes in ion concentration that occur in cells submitted to anisosmotic media.
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Rabbit kidney cortex slices behave as osmometers when withstanding either hyperosmotic shocks or hypo-osmotic shocks of amplitude up to P1/P2 = 1.25. For hypo-osmotic shocks of amplitude larger or equal to P1/P2 = 1.5 a volume regulation process occurs. Na+ is the main osmotic effector implicated in volume control.
The volume regulation process at work in rabbit kidney cortex slices submitted to hypo-osmotic media show both a swelling limitation and a volume readjustment phase. Swelling limitation is Na+ dependent and is blocked by ouabain 10(-3) M. There is, however, no need to implicate the activity of a ouabain sensitive Na+ /K+ pump in this process.
Rabbit kidney cortex slices behave an osmometers when withstanding hyperosmotic or hyposmotic shocks of amplitude up to pi 1/pi 2 = 1.25. For hyposmotic shocks of amplitude larger than or equal to pi 1/pi 2 = 1.50, the maximum swelling achieved is less than what can be expected on the basis of the van't Hoff relation, thereby indicating that a volume regulation process is taking place. Volume regulation in kidney slices can be dissociated into two distinct phases. The first one, of swelling limitation, is very rapid and keeps maximum cell volume at values lower than expected when the tissue is considered as an osmometer. This phase is followed by a slow volume readjustment process during which volume progressively decreases towards control values. The major intracellular osmotic effector loss during both swelling limitation and volume readjustment is Na+. The overall volume regulation process is insensitive to furosemide, vanadate, and bumetanide. Swelling limitation is blocked by addition of ouabain. Contrary to what has been believed previously, there is, however, no need to implicate control of the activity of a ouabain-sensitive, Na+/K+ pump in the Na-dependent volume regulation mechanism.
Radiotherapy is an effective tool in the treatment of thoracic cancers. However, radiotherapy also carries a risk of severe cardiac complications. The cancers most commonly concerned are Hodgkin's and non-Hodgkin's lymphomas (90 per cent of cases), breast cancers, especially on the left side (4 per cent) and bronchogenic cancers (2 per cent). Ionizing radiation can damage the three layers of the heart and the coronary arteries. Pericardial involvement is the most frequent, occurring in 10 to 12 per cent of cases. It generally occurs 6 to 18 months after the radiotherapy and may present either acutely (35 per cent of cases) or chronically (65 per cent of cases). It is often latent, only detected on X-rays or on ultrasound. Constrictive forms can occur, which require pericardiectomy. Myocardial fibrosis, which is anatomically common, may present as disturbances of repolarization, arrhythmia or disturbances of conduction, or even cardiac failure. Rarely, radiation damage of the coronary arteries can cause angina or myocardial infarction. These cases can benefit from coronary artery by-pass grafts. All of these lesions have a common anatomical denominator:fibrosis, which develops progressively following the radiotherapy. It has now been demonstrated that the incidence of cardiac radiation lesions can be reduced by homogeneous distribution of the dose of radiation administered to the mediastinum, by treating each side alternately, by fractionating the radiation and staggering the sessions and by reducing the cardiac mass which is irradiated.
Electrical breakdown of cell membranes is interpreted in terms of an electro-mechanical model. It postulates for certain finite membrane areas that the actual membrane thickness depends on the voltage across the membrane and the applied pressure. The magnitude of the membrane compression depends both on the dielectric constant and the compressive, elastic modulus transverse to the membrane plane. The theory predicts the existence of a critical absolute hydrostatic pressure at which the intrinsic membrane potential is sufficiently high to induce "mechanical" breakdown of the membrane. The theoretically expected value for the critical pressure depends on the assumption made both for the pressure-dependence of the elastic modulus of the membrane and of the intrinsic membrane potential. It is shown that the critical pressure is expected at about 65 M Pa. The prediction of a critical pressure could be verified by subjecting human erythrocytes to high pressures (up to 100 M Pa) in a hyperbaric chamber. The net potassium efflux in dependence on pressure was used as an criterion for breakdown. Whereas the potassium net efflux was linearly dependent on pressure up to 60 M Pa, a significant increase in potassium permeability was observed towards higher pressure in agreement with the theory. The increase in the net potassium efflux above 60 M Pa was reversible, as indicated by measurements in which the same erythrocyte sample was subjected to several consecutive pressure pulses. Temperature changes in the erythrocyte suspension during compression and decompression were so small (less than 2 degrees C) that they could not account for the observed effects.
Above a hydrostatic pressure of about 600 b a pronounced reversible increase in the net K+-efflux from human erythrocytes is observed. The effect is explained in terms of an electro-mechanical compression of the membrane, resulting in a reversible breakdown of the membrane.
Pericarditis is the commonest cardiac manifestation of rhumatoid arthritis. It is often clinically latent but it may evolve to constriction or less often to tamponade. The case presented is of a 60 year-old woman with a 5 year history of seropositive nodular rhumatoid arthritis in whom bilateral pleural effusions and constrictive pericarditis were observed after sudden termination of corticotherapy. She was treated successfully by pericardectomy. This complication is far from being exceptional (55 cases already reported). It justifies a systematic search for pericarditis in rhumatoid arthritis, especially by echocardiography.
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1. The effects of high hydrostatic pressures have been studied on the ATPases extracted from tissues implicated in iono- and osmoregulation of a frog and various teleostean fishes. Pressure affects enzyme activity in the same qualitative way, whatever the tissue and the species considered. 2. The Mg2+ ATPase activity is maximally enhanced at 250 kg/cm2. A slight inhibition is observed at higher pressures up to 1000 kg/cm2. 3. The (Na+ + K+)ATPase is little affected by low pressures but strongly inhibited at 500 kg/cm2 and more. 4. The results are discussed in terms of pressure effects on the recently described protein-lipid interaction linked to ATPase activity.
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The cardiac complications of radiotherapy have been reviewed in the light of 46 case histories collected from 16 treatment centres in France. They are usually found after radiotherapy for Hodgkin's disease and carcinoma of the breast. Although histologically there may be diffuse fibrosis involving the endocardium, myocardium and pericardium, it is pericarditis which is the usual clinical feature. It often occurs late, and takes many forms. The dry constrictive fibrous type of pericarditis is the most severe because of the amount of myocardial fibrosis usually associated with it. It is rare for there to be clinical features of myocardial fibrosis, and if present they are variable: isolated disorders of repolarisation or of conduction, or true cardiomyopathies. Lesions of the coronary arteries are exceptionally rare after radiotherapy, and involve fibrosis of the intima or atherosclerosis.
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The flavonoid O-(beta-hydroxyethyl)-rutoside appears to have a slight inhibitory action upon the oxidative metabolism and lactate production of culured human varicose saphenous veins. The possibility that exogenous glucose would be utilized in other metabolic pathways is discussed.