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J Robert

Publications and source records attributed to J Robert.

At least 343 records · Page 19Linked to original sources
PubMed1989

Iron-binding proteins and 67Ga accumulation by tumor cells.

Tumor cells incubated with 67Ga-citrate plus lactoferrin showed a lactoferrin concentration-dependent increase of 67Ga uptake while for transferrin the effect was an inhibition. A correlation was observed between the binding of 131I-labelled lactoferrin or 131I-labelled transferrin and the uptake of 67Ga by the cells. Saturation with iron did not change significantly the effects of the iron-binding proteins. Preincubation with lactoferrin, transferrin or ferric citrate increased 67Ga uptake. The formation of a ternary complex in which 67Ga mimics iron is discussed.

Animals↗
PubMed1989

[Comparative in vitro bacteriostatic and bactericidal effect of 5 macrolides: roxithromycin, erythromycin, oleandomycin, josamycin and spiramycin against 284 hospital bacterial strains].

The bacteriostatic and bactericidal activities of five macrolides (roxithromycin, erythromycin, troleandomycin, josamycin and spiramycin) were tested against 284 bacterial strains belonging to various species of Gram positive (staphylococci, streptococci, pneumococci, Listeria sp, Corynebacterium sp, Bacillus sp) and Gram negative bacteria (Neisseria sp, H. influenzae, P. multocida). The activity of these compounds on the whole strains showed near results: 71.8% of susceptible strains to erythromycin and spiramycin, 70% to josamycin, 67.6% to roxithromycin, 65.5% to troleandomycin. Resisting strains were MLSB resistant cocci Gram positive, H. influenzae and P. multocida strains. Species usually less studied (nongroupable streptococci, Corynebacterium sp, Bacillus sp) were very susceptible to macrolides with MICS equal or inferior to 1 mg/l for the two last genus. A bactericidal effect was observed for 38.8% of 72 tested strains (erythromycin), 36.1% (josamycin), 34.7% (spiramycin), 31.9% (roxithromycin), 20.8% (troleandomycin). Among various tested species, this bactericidal effect concerned especially group A streptococci, N. meningitidis and Corynebacterium (except D2 and JK species).

Cross Infection↗
PubMed1989

[Transplacental passage of doxorubicin].

The transplacental passage of doxorubicin, an anthracycline used for lymphoproliferative disorders and breast cancer, was studied by in vitro perfusion of term human placenta. Placentas from women with uncomplicated pregnancy were collected immediately after vaginal delivery and put into a 37 degree C thermostatically-controlled hood. A cotyledon was chosen and placed into the perfusion chamber; fetal and maternal compartments of the isolated lobe were thus perfused with separated "open" circuits. Perfusion of fetal surface of the placenta was started immediately at a flow rate of 6 ml/mn and then so was the perfusion of the intervillous space at a rate of 12 ml/mn. Perfusion medium used was Earle's solution. Antipyrine, to validate experience, and doxorubicin were added to the maternal perfusate. Samples were collected from arterial inflow and venous outflow respective of the maternal and fetal compartment and timed measurements of the fetal venous return were used to calculate flow rates. After a stability study of doxorubicin solutions under experimental conditions, the transplacental transfer of doxorubicin was then investigated for three doses: 3 mg/l, 30 mg/l and 150 mg/l. The global transfer value is low (2.96% +/- 0.75%) and doesn't seem dose-dependent. Adriamycinol, a plasma doxorubicin metabolite, has not been found even for the greatest concentration. The low transfer value can explain the rarity of fetal accidents in clinical reports.

Doxorubicin↗
PubMed1988

Alteration of ganglioside composition and metabolism in doxorubicin-resistant rat tumoral cells.

We have investigated the ganglioside levels, composition and metabolism in two lines of doxorubicin-resistant cells and in the corresponding wild strains, the C6 rat glioblastoma and the HTC rat hepatoma. The only ganglioside present was GM3, and its level was increased 2-fold in C6 resistant cells and decreased nearly 2-fold in HTC resistant cells. A decrease of cytidine 5'-monophospho-N-acetylneuraminic acid:galactosylglucosylceramide sialyltransferase activity was observed in both resistant lines as compared to sensitive ones, and could not, therefore, explain the increase in the GM3 level observed in the C6 resistant line. Alterations of acid neuraminidase activity were also observed; a 5-fold decrease was noticed in the C6 resistant line and could account for the increase in the GM3 level observed in these cells; in contrast, a 2-fold increase of acid neuraminidase activity was noticed in the HTC resistant cells: together, with reduced synthesis, it could explain the decrease in the GM3 level observed in these cells. No alterations of exogenous ganglioside transport was exhibited by the C6 resistant cells.

Animals↗
PubMed1988

Different cytotoxicity and metabolism of doxorubicin, daunorubicin, epirubicin, esorubicin and idarubicin in cultured human and rat hepatocytes.

Both cytotoxicity and metabolism of five anthracyclines, namely doxorubicin, daunorubicin, epirubicin, esorubicin and idarubicin, were investigated in primary cultures of both rat and human adult hepatocytes and, for comparison, in a rat liver epithelial cell line. Toxicity was assessed by morphological examination and measurement of lactate dehydrogenase leakage after 24 hr of treatment. The rank order of toxicity for both rat and human hepatocytes was esorubicin greater than doxorubicin = epirubicin greater than or equal to idarubicin greater than daunorubicin, and for rat epithelial cells: esorubicin greater than or equal to epirubicin greater than idarubicin = daunorubicin = doxorubicin. Human cells were around 2-fold less sensitive than rat hepatocytes to all anthracyclines. Anthracyclines and their metabolites were analyzed by HPLC. Differences in both the percentages and routes of metabolism were demonstrated between rat and human hepatocytes. The main metabolite was the 13-dihydro-derivative (-ol derivative) in both species from daunorubicin, idarubicin and esorubicin. Glucuronides of epirubicin and epirubicinol were found only in human hepatocytes. In addition, several unidentified metabolites were detected of esorubicin, idarubicin and daunorubicin in rat hepatocytes. In human hepatocytes, only one unknown metabolite from daunorubicin and doxorubicin was found to be formed by cells from a different donor. In spite of variations between individuals, human hepatocytes generally metabolized anthracyclines more actively than did rat hepatocytes. Rat liver epithelial cells were only able to convert daunorubicin and idarubicin, the two molecules which have the best affinity for the non-specific NADPH-dependent aldoketoreductase system. Three compounds (doxorubicin, epirubicin and esorubicin) were present in large amounts in the cells as the parent drug, another (idarubicin) as the 13-dihydro-derivative. This comparative study on cytotoxicity and metabolism of five anthracyclines in rat and human hepatocyte cultures emphasises species differences and the importance of this in vitro model system for further analysis of the metabolism and effect of anthracyclines.

Adolescent↗
PubMed1988

The reversal of doxorubicin resistance by verapamil is not due to an effect on calcium channels.

Using a model of doxorubicin-resistant rat glioblastoma cells, we have studied the relationship between the reversal of multi-drug resistance by verapamil and calcium fluxes into the cells. Although it is known to be a voltage-dependent calcium channel blocker, verapamil exerted no effect on calcium entry into the cells. In the absence of calcium in the medium, drug resistance was not affected and verapamil was still active. It was possible to modify calcium fluxes into the cells by using manganese ions (decreasing calcium uptake) or the calcium ionophore A23187 (increasing calcium uptake). These agents had only a marginal effect on the expression of drug resistance by the cells and did not prevent the action of verapamil on its reversal.

Animals↗
PubMed1988

Purification and characterization of cytoplasmic creatine kinase isozymes of Xenopus laevis.

The soluble creatine kinase isozymes CK-II, CK-III, and CK-IV from Xenopus laevis have been purified to apparent homogeneity and their subunits characterized by means of molecular weight, peptide pattern, and dissociation-reassociation experiments. CK-III and CK-IV are homodimeric isozymes whose subunits are distinct in both molecular weight (42,000 and 41,000, respectively) and Staphylococcus aureus V8 peptide pattern. In dissociation-reassociation experiments, those two subunits do form active heterodimeric isozymes with one another or with rabbit M-CK subunits. Hybrid CK-III/IV isozymes occur also during embryonic differentiation and in adult heart muscle, whereas most other adult tissues contain only homodimeric CK-III or CK-IV isozymes. The CK-II isozyme is a heterodimer composed of one CK-III subunit and another subunit specific to CK-II (Mr = 41,000). Neither in vivo nor in vitro does this subunit seem able to form homodimers or heterodimers with CK-IV and rabbit M-CK subunits. If we take into account the apparent association of CK-I isozyme with cellular organelles, these results corroborate earlier statements and suggest that the CK isozyme system of X. laevis is encoded by at least four differentially regulated genomic loci.

Animals↗
PubMed1988

Pharmacokinetics and metabolism of pirarubicin in advanced cancer patients.

We have studied the pharmacokinetics and metabolism of pirarubicin (4'-O-tetrahydropyranyldoxorubicin) in six patients included in an EORTC phase II study. Pirarubicin was injected as an i.v. bolus of 5 min on 3 consecutive days at a dose of 20 mg/m2 per day. Blood samples were collected at regular times after each injection. Urine was collected over 12 h periods for 3 days and then over 24 h periods. Pirarubicin and metabolites were extracted on Sep-pak cartridges, and analyzed by HPLC with fluorometric detection. Unchanged pirarubicin followed three similar plasma concentration curves, which could be fitted by a two-compartment model with successive half-lives of 22.0 min and 12.7 h. Total plasma clearance of the drug was 90 l/h/m2 and total volume of distribution 1380 l/m2. Doxorubicin was the main metabolite in plasma after an injection of pirarubicin; its concentration was lower than that of pirarubicin but progressively increased from day to day and exceeded the level of pirarubicin 8 h after the 3rd injection of the drug until the end of the blood sampling. Pirarubicinol and doxorubicinol were also metabolites of pirarubicin in plasma; pirarubicinol followed similar plasma concentration curves during the 3 days of treatment whereas doxorubicinol progressively increased from day to day. Total urinary excretion represented about 6% of the dose injected. The same metabolites as in plasma were found in urine. Whereas the total amount of pirarubicin and pirarubicinol was the same in urine during the 24 h after each injection, the amounts of doxorubicin and doxorubicinol excreted increased from day to day, so that doxorubicin became progressively the main compound in urine after the end of the treatment. The progressive accumulation of pirarubicin metabolites (doxorubicin and doxorubicinol) after the repetitive injections of pirarubicin are probably due to the protracted half-lives of these compounds as compared to that of pirarubicin.

Adult↗
PubMed1988

[Eczema and hyper-IgE. Effect of cephalosporins].

Atopic dermatitis is a disease in which staphylococcal cutaneous superinfection and immune disorders, especially hyper IgE, are closely related. Cephalosporins are very effective on exacerbations of superinfections; among them, Cefadroxil diminishes immunoglobulins E in vivo. In vitro, this antibiotic promotes from the macrophage the PgE2 synthesis to which the T suppression is classically sensitive. In DNP-OVA sensitized rats which produce anti DNP IgE, the secondary response is inhibited by Cefadroxil. From clinical to research experiments, the hypothesis is the effect of cephalosporins, and especially Cefadroxil, on IgE synthesis.

Animals↗
PubMed1988

Mechanisms of gallium-67 accumulation by tumors: role of cell membrane permeability.

The effects of citrate ion on in vitro and in vivo uptake of [67Ga]citrate by tumor cells have been studied. Carrier-free [67Ga]citrate seems to follow the physical diffusion of citrate ions into the cell, and the presence of carrier gallium inhibits that diffusion, reducing considerably its uptake. These results appear to support the hypothesis that increased permeability of tumor cells is the principal cause of [67Ga]citrate accumulation by tumors.

Animals↗
PubMed1988

On the role of transferrin in 67Ga uptake by tumor cells.

In vitro uptake of 67Ga-citrate and 59Fe-citrate by DS sarcoma cells in the presence of tumor-bearing animal blood plasma showed a dramatic inhibition of both 67Ga and 59Fe uptakes: about 1/10 of 67Ga and 1/50 of the 59Fe are taken up by the cells. Subcellular fractionation appears to indicate no specific binding to cell structures, and the difference of binding seems to be related to the transferrin chelation and transmembrane transport differences.

Animals↗
PubMed1988

Surgical treatment of hydatid disease of the liver: a survey of 69 patients.

Sixty-nine patients were operated on because of hydatid disease of the liver from 1960 to 1986. There were 32 male and 37 female patients, with a mean age of 38 years at operation (range, 13 to 76 years). Forty-two cysts were solitary, 20 multiple, and 7 bilateral; 45 were located in the left lobe. Radical surgical procedures were carried out in 45 patients and consisted of cystectomy in six, pericystectomy in 25, and hepatectomy in 14; a conservative approach was used in 11 (resection of prominent part, internal or external drainage). The remaining 13 patients underwent a combination of both techniques. There were no deaths. Postoperative morbidity was low and equally distributed whether surgery was radical or conservative. Local complications occurred in six patients (9%), and seven other patients (10%) had systemic disorders. Four patients required reoperation: two for hemostasis and two for persistent fistulae (one biliary and one bronchobiliary). Of the 42 patients available for follow-up (61%), four (9%) had recurrent disease. One had undergone a pericystectomy and three, conservative procedures, at the time of primary surgery. Our results support the view that excisional surgery is a safe and valid option for patients with hydatid liver disease.

Adolescent↗
PubMed1988

Modification of the ionic environment in the tumor cell by hyperthermia.

Tumor cells submitted to hyperthermia (45 degrees C) showed changes in the ionic composition: Increased calcium and decreased potassium concentrations. These changes are likely to affect vital functions of the cell. The observed decrease in ATP concentration supports the hypothesis that hyperthermia affects the ATP-dependent extrusion mechanism of the cell and, consequently, induces that ionic environment modification. Lactate production was also decreased by hyperthermia, a phenomenon that could be related to the fall in potassium concentration. The intracellular increase in Ca2-concentration during hyperthermia appears to support the earlier hypothesis on the role of Ca2+ in tumor inhibition by hyperthermia.

Animals↗
PubMed1988

In vivo changes of ionic composition of tumors treated by hyperthermia.

Experimental tumors submitted in vivo to hyperthermia, in the presence, or not, of lanthanum (La3+), have shown modifications in the concentration of extra- and intracellular cations. Sacrificed immediately after hyperthermia, only the group treated with La3+ presented ionic changes (lower magnesium and potassium). After 48 hours, in both cases calcium and sodium were increased while magnesium and potassium were decreased.

Animals↗