Showing papers by "Université catholique de Louvain published in 1972"

Chemotherapy through lysosomes with a DNA-daunorubicin complex.

Abstract: WHEN a drug can pass freely across cell membranes, it becomes distributed throughout the body fluids whichever its route of administration and invades all cells by diffusion at comparable rates. But if it is firmly associated with a non-permeant, pino-cytizable and digestible carrier, it will tend to remain confined within a smaller fluid space determined by its route of administration, its excretion will be slow and its intracellular penetration will be restricted to the endocytic route (Fig. 1). Free drug will then appear first within lysosomes, following digestion of the carrier. From the lysosomes it will diffuse into the other parts of the cells and eventually into the extracellular fluids. The intracellular concentration of the drug thus becomes dependent on the pinocytic activity of the cells and on the digestive potential of their lysosomes and must exceed the extracellular concentration in the most active cells. Obviously, this model requires the complex to be stable in the body fluids and to dissociate inside lysosomes. The drug itself must be resistant to lysosomal inactivation.

The release of collagenase as an inactive proenzyme by bone explants in culture

Abstract: 1. A latent collagenase, activated only by limited proteolysis, was found in culture media of mouse bone explants. It could be activated by trypsin or, less efficiently, by chymo-trypsin. Skin explants also released latent collagenase. 2. Bone collagenase attacks native collagen at about neutral pH when it is in solution, in reconstituted fibrils or in insoluble fibres, producing two fragments representing 75 and 25% of the molecule. It requires calcium and is inhibited by EDTA, cysteine or serum. 3. Latent collagenase is not activated by trypsin-activated collagenase but by a distinct unidentified thermolabile agent present in a latent trypsin-activatable state in the culture media, or by purified liver lysosomes between pH5.5 and pH7.4. Trypsin activation decreases the molecular weight of latent collagenase from 105000 to 84000 as determined by gel filtration. 5. The latency of collagenase is unlikely to be due to an enzyme–inhibitor complex. Although some culture media contain a collagenase inhibitor, its presence is not constant and its molecular weight (at least 120000) is not compatible with the decrease in molecular weight accompanying activation; also combinations of collagenase with inhibitor are not reactivated by trypsin. Moreover, the latency remains after gel filtration, or treatment by high dilution, exposure to pH values between 2.5 and 10, or high ionic strength, urea or detergent. 6. It is proposed that latent collagenase represents an inactive precursor of the enzyme, a `procollagenase9, and that the extracellular activity of collagenase is controlled by another protease that activates procollagenase by a limited proteolysis of its molecule.

Electron and hole transport in bismuth

Abstract: Measurements of the low field galvanomagnetic tensor components of bismuth from 77 to 300K are reported. The eight magnetoresistivity coefficients /b A//sub ij/ are found to vary as /b T//sup -2 / up to nearly 120 K, then as /b T//sup -3.9/ from 120 to 300 K. The electronic parameters are computed. The values of the electron ellipsoid tilt angle lie between 6 degrees 40' and 8 degrees 30' and the carrier density varies from 4.55*10/sup 17/ to 24.5*10/sup 17/ cm/sup -3/ at 77 K and 300 K respectively. All mobilities except mu /sub 2/ vary as /b T/ /sup -2/ in the lowest temperature range.

Transplantable immunoglobulin-secreting tumours in rats. I. General features of LOU-Ws1 strain rat immunocytomas and their monoclonal proteins.

Abstract: This article describes a peculiar tumour which originates in the ileocoecal lymph node of the LOU/Ws1 strain rat. The tumour cells usually have the appearance of very poorly differentiated lymphoid cells showing a tendency to develop ribosome-studded ergastoplasmic membranes. In about 60% of the cases, such tumours synthesize monoclonal immunoglobulins of the IgG or IgA class, or Bence-Jones proteins. These tumours are readily transplantable in isologous hosts or their F hybrids. The great majority of the transplanted growths retain their capacity for immunoglobulin production during many successive passages in vivo. A scrutiny of older and more recent literature has revealed several descriptions of rat tumours having the same macroscopic and microscopic features as the tumours described here, except for the immunoglobulin-secreting properties which were never tested in the earlier studies. It is proposed to call this tumour the rat ileocoecal immunocytoma. TUMEURS TRANSPLANTABLES SUR LES RATS ET SECRETANT DES IMMUNOGLOBULINES. I. CARACTERISTIQUES GENERALES DES IMMUNOCYTOMES DES RATS LOUiWsl ET DE LEURS PROTEINES MONOCLONALES Cct article dikrit une tumeur particulikre qui se ddveloppe a partir du ganglion ile'o-coccal de /a souche de rat LOU1 Wsl. Les cellules tumorales ont ge'niralement une apparence lympholde. EIles sont trks peu dife'rencie'es et ont tendance a ddvelopper des membranes ergastoplasmiques parseme'es de ribosomes. Dans environ 60% des cas, ces tumeurs synthe'tisent des immunoglobulines morioclonales de type IgC ou IgA, ou des protiines de Bence- Jones. Ces tumeurs sont transplantables sur des rats de mme souche ou sur leurs hybrides de premikre gdne'ration. La capacite' de synthe'tiser des immunoglobulines est conservke par la majorite' des tumeurs au cours des passages successi' in vivo. L'examen de la litte'rature a permis de retrouver plusieurs descriptions de tumeurs rat ayant des caractdristiques macroscopiques et microscopiques identiques a celles des tumeurs du rat LOU, mise a part la propriiti de synthitiser des immunoglobulines qui n'a jamais d t k recherchhe dans les dtudes prhckdentes. II est propos; de nommer cette tumeur: I'immunocytome ildo-coecal du rat.

Rodent and Human Acid α‐Glucosidase

Abstract: The lysosomal acid α-glucosidase has been purified more than 10000-fold from rat and mice liver and from human placenta. The kinetic properties of the human enzyme are similar to those previously described for the rodent enzyme, with the main exception of the absence of inhibition by an excess of maltose. Antibodies were obtained by injection of the pure rat liver, mouse liver or human placental α-glucosidase to rabbits. The property of the enzyme of hydrolysing glycogen or to catalyse transglucosylation from maltose to glycogen could be nearly completely inhibited by the antibodies whereas the hydrolysis of small molecular substrates was much less inhibited. Within the same species, the same amount of enzyme was inhibited by a given amount of antibodies, whatever the tissue used as a source of enzyme. A partial cross-reactivity was observed from species to species. The presence of an immunologically reacting protein in tissues from patients with type-II-glycogenosis could not be demonstrated either by double-diffusion test or by antibodies consumption. Similar negative results were also obtained with normal human liver in which acid α-glucosidase has been inactivated at alkaline pH.

A Computer On-Line Marketing Mix Model

Abstract: This approach to developing and implementing a dynamic, competitive marketing mix model for a major oil company combines econometric methods, simulation techniques, and subjective judgments Regression coefficients provide estimates of the response functions of the different inputs

The anomalous infra-red absorption of alkali metals and collective oscillations in small metal particles

Abstract: It is shown that the resonance like absorption peaks, which were discovered by Mayer for bulk samples of Na and K, and which could not be explained in terms of the bulk properties of the metal, are actually due to a surface roughness effect. The ellipsometric method leads, indeed, to a systematic error when the metal surface is covered by a dense distribution of small metal particles. The apparent optical constants depend on the optical constants of the bulk metal and on the effective optical constants of the thin granular film. Resonance absorption is particularly strong, when it occurs in the spectral region where the absorption of the bulk metal is very small, as it happened to be for these alkali metals.

Motor cortex vestibular responses in the chloralosed cat.

Abstract: Controlled electrical stimulation of an ampullar nerve in the inner ear was used to demonstrate vestibular projections to the motor cortex of cats anaesthetized with chloralose. Macroelectrode recordings from the cortical surface in the somatomotor region, around the cruciate sulcus, show two kinds of vestibular evoked responses: the latency, shape and distribution of these potentials indicate a different origin for each type, as do also the results of experiments investigating somato-vestibular interactions. A study of the somatic and vestibular inputs to individual pericruciate neurons, and of their possible output into the pyramidal tract, revealed that 1. the vestibular afferents (reaching 40% of the population studied) are principally distributed among the somatic neurons receiving their input from several limbs, and 2. some of the cortical cells receiving vestibular afferents contribute axons to the pyramidal tract. Results are discussed with respect to the possible functional significance of such a vestibular input to the motor area for the adequate performance of movements.

The uptake of cardiac glycosides in relation to their actions in isolated cardiac muscle

Abstract: 1. The uptake of (3)H-digitoxin, (3)H-ouabain and (3)H-dihydro-ouabain by isolated guinea-pig atria has been studied and compared with the inhibition of the sodium pump and with the inotropic effect.2. Analysis of the curve relating the uptake of digitoxin and ouabain at equilibrium to the bath concentration enabled a non-saturable and a saturable binding site to be distinguished.3. The uptake of inactive doses of dihydro-ouabain was only by a non-saturable mechanism.4. The uptake of labelled digitoxin and ouabain was reduced in the presence of another glycoside. The amount of bound glycoside was nearly equivalent to the estimated non-saturable uptake.5. The uptake was reduced at 4 degrees C to the clearance of the non-saturable site.6. ED50 of digitoxin and of ouabain for inhibition of the sodium pump were measured and compared to the ED50 for inotropic effect and to the concentrations producing a half-saturation of the saturable binding site.7. It is concluded that binding to the saturable site may be responsible for the cardiac actions of the glycosides.

Study on the mechanism of lysosome labilization by inorganic mercury in vitro.

Abstract: This investigation demonstrates that the labilization of rat liver lysosomes by Hg2+in vitro is the result of a complex series of events. The initial rapid binding of Hg2+ on lysosomal membranes is followed by an autocatalytic breakdown of lysosomes by the lysosomal hydrolytic enzymes. This secondary action is dependent on the concentration of Hg2+ which decreases the hydrolytic activity of the lysosomal enzymes. Furthermore an Hg2+ exchange reaction between solubilized lysosomal proteins, which have bound Hg2+, and lysosome membranes can induce lysosome labilization.

Mössbauer spectroscopy study of iron-carbon austenite and virgin martensite

Abstract: In agreement with B. E. C. thermodynamic results, it is found by Mossbauer spectroscopy that high carbon iron-carbon austenite is an ideal solid solution of the carbon atoms distributed in the octahedral interstitial sites. On the other hand Mossbauer spectra for unaged martensite have been reinterpreted on the basis of Lysak’s hypothesis that half of the carbon atoms occupy tetrahedral rather than octahedral interstitial sites.

Comparative study of 3 H-thymidine labelling of the dermal infiltrate of skin allergic and irritant patch test reactions in man.

Abstract: Summary.— The 3H-Thymidine (3HT) nuclear labelling index of “round” cells of the dermal infiltrate in allergic and irritant patch test reactions in man has been compared. The skin of 15 positive allergic patch test reactions (to different allergens) and of 15 positive irritant reactions (5 to croton oil, 5 to potassium hydroxide and 5 to white spirit) was biopsied 48 hours after the application of the chemical. Thin slices of each specimen were incubated for 60 min in the presence of 3HT. then fixed and prepared for light microscopy radioautography. Two thousand “round” cells of the infiltrate were counted in each specimen. The mean values of the 3HT labelling indices (±S.E.) were 2·91±0·18%, in the allergic group and 0·58 ± 0·06% in the irritant group. The difference between the 2 means was highly significant (P 0.05). All the labelled cells were mononucleated. This method could be useful to differentiate clinically dubious allergic and irritant reactions.

The conversion of (4- 3 H)fructose and of (4- 3 H)glucose to liver glycogen in the mouse. An investigation of the glyceraldehyde crossroads.

Abstract: [4-3H,6-14C]Fructose or [4-3H,6-14C]glucose were injected into mice and the recovery of the two isotopes in liver glycogen was measured. As a mean, the 3H/14C ratio in glycogen was 36.6 and 51.8% of that in the injected fructose and glucose, respectively. From the comparison of these two ratios, the loss of tritium proper to fructose metabolism was equal to 29.2%. In the same experiments, the C-6 to C-1 randomization proper to fructose metabolism was, as a mean, equal to 27.4%. These findings are in agreement with the hypothesis that the glyceraldehyde formed in the liver upon aldolic splitting of fructose 1-phosphate is metabolized by phosphorylation into glyceraldehyde 3-phosphate under the action of triokinase. The oxidation of d-glyceraldehyde into d-glycerate would have resulted in a complete loss of tritium in glycogen. Furthermore, the 3H/14C ratio in d-glyceraldehyde formed from fructose was the same as in the precursor despite the fact that the aldehyde dehydrogenase discriminates against [1-3H]glyceraldehyde. Our results therefore preclude any important participation of the glycerate pathway in the metabolism of fructose. In the isolated rat diaphragm, the loss of tritium relative to 14C was of the order of 20%, for both glucose and fructose, confirming that, in muscle these two sugars are converted to glycogen by the same pathway. When incubated in vitro with a liver preparation deprived of glucose 6-phosphatase, doubly labelled UDPG lost no 3H relative to 14C. Doubly labelled hexose 6-phosphates underwent a rapid loss of tritium in the same conditions, and this loss was cancelled by fructose diphosphate. It appears probable that the tritium loss is due to an interconversion of hexosephosphates with pentosephosphates, the hydrogen exchange occurring at the level of the pentosephaosphate 3-epimerase. In agreement with an exchange of hydrogen at the level of hexose 6-phosphates in the liver, it was observed that the decay of [4-3H]glucose in the blood is faster than that of [U14C]glucose.

Effects of Aldosterone on RNA and Protein Synthesis in the Toad Bladder

Abstract: The hypothesis of a stimulatory effect of aldosterone on RNA, and consequently protein synthesis has been investigated. The influence of this hormone on the incorporation of precursors into RNA and protein was examined in the toad urinary bladder through which sodium transport is stimulated by aldosterone in vitro. Aldosterone increases total nuclear RNA synthesis and also uridine uptake. Particular fractions of this RNA characterized by density gradient centrifugation might be specifically influenced. No effect of aldosterone on cytoplasmic RNA turn-over rate or on mRNA synthesis could be demonstrated. Examination of the pattern of protein synthesis at the polysome level, of ribosome processing, and of protein turn-over rate also failed to disclose any definite influence of aldosterone on these parameters. The proposal that the effect of aldosterone on sodium transport is mediated by its action on transcription and translation in target tissues remains therefore founded on indirect evidence to date.