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Biomedical subjects

J Robert

Publications and source records attributed to J Robert.

At least 415 records · Page 23Linked to original sources

Cellular pharmacokinetics of doxorubicin in cultured mouse sarcoma cells originating from autochthonous tumors.

We have studied the cellular pharmacology of doxorubicin in a line of mouse sarcoma cells isolated from a dimethylbenzanthracene-induced autochthonous tumor. We have studied the cytotoxicity of the drugs as a function of the exposure dose and of the exposure time to the drug. Cytotoxicity was evaluated as the inhibition of the incorporation of [3H-methyl]-thymidine in the cellular nucleic acids. Intracellular drug concentrations were measured by spectrofluorometry. We have shown that the intracellular drug concentration was a linear function of the extracellular drug concentration up to 5 micrograms/ml; the cytotoxicity was an exponential function of the exposure dose up to 1 micrograms/ml, but it was not an exponential function of the exposure time: the cytotoxicity may therefore be very different for similar total drug exposures. Incubation with a low dose for a long time did not provide a cytotoxicity as high as that obtained with a high dose for a short period of time. These results emphasize the role of the peak concentration of doxorubicin for its maximal action in the target cell.

9,10-Dimethyl-1,2-benzanthracene↗

Prl, TSH, FSH, beta-hCG and oestriol responses to repetitive (triple) LRH/TRH administration in the third trimester of human pregnancy.

The effects of repetitive administration of 50 micrograms of LRH and 100 micrograms of TRH in a single bolus at 0, 90 and 180 min on Prl, TSH, FSH, beta-hCG and oestriol were tested in 11 healthy pregnant women in their third trimester of pregnancy. Basal hormonal levels were in agreement with previous reports. The Prl and TSH peaks after each injection of LRH/TRH were similar for each hormone. No significant changes in serum FSH, beta-hCG and oestriol were detected after repetitive administration of LRH/TRH. Thus, the responsiveness of lactotroph and thyrotroph cells to pulsatile stimulation with LRH/TRH is not altered during the last trimester of pregnancy, and FSH, beta-hCG and oestriol levels remain constant during the period of sampling.

Chorionic Gonadotropin↗

[Comparative in vitro activity of 5 beta-lactams (cefoperazone, cefsulodin, ceftazidime, azthreonam, N-formimidoyl-thienamycin) on 90 strains of Pseudomonas aeruginosa with various levels of resistance to ticarcillin].

Five beta-lactams with anti-pseudomonal activity were tested against P. aeruginosa strains resistant to various concentrations of ticarcillin (from 256 to 8192 mg/l). MIC geometric means found for the totality of strains were as follows: 1.52 mg/l for ceftazidime; 1.80 mg/l for N-f-thienamycin; 4.79 mg/l for azthreonam; 17.3 mg/l for cefsulodin; 50.9 mg/l for cefoperazone. Activities of ceftazidime, N-f-thienamycin and azthreonam were not related to the level of ticarcillin resistance. Cefoperazone and, to a lesser degree, cefsulodin showed cross resistance with ticarcillin: these drugs were not active when ticarcillin MICs reached 512 mg/l and 4 096 mg/l respectively.

Anti-Bacterial Agents↗

[Influence of the inoculum effect on the MIC and MBC of 5 beta-lactams against Pseudomonas aeruginosa].

MICs and MBCs of five beta-lactams , i.e. ticarcillin, azlocillin, piperacillin, cefsulodin and ceftazidime for 20 strains of Pseudomonas aeruginosa were studied with inocula ranging from 10(3) to 10(9) CFU/ml. Each antibiotic exhibited an inoculum effect at 10(5)-10(7) CFU/ml. However, ticarcillin had smaller MIC and MBC increments than the four other drugs, making it more suitable in certain cases.

Anti-Bacterial Agents↗

Leg arteritis exploration by quantitative muscle scintigraphy with 201Tl.

Detection and localization of peripheral arterial disease was evaluated by an intravenous injection of 201Tl at peak exercise in 18 subjects and at rest in 6 patients. Images of the skull (S), thighs (T), knees (K), calves (C) and feet (F) were obtained at rest or after exercise and stored in a computer. Intraleg (T/K, T/C, T/F), and left to right interleg (TL/TR,...) count ratios were calculated. In addition, all patients were submitted to routine functional tests (walk perimeter, serial local arterial blood pressure measurement, Strandness test, venous occlusion plethysmography). Correlations between functional tests and the intra and interleg ratios were calculated. After exercise, there is a medium correlation between the tissular blood flow under hyperemia at the calf level and the T/C and C/K ratios. At the calf level a good correlation is obtained for CL/CR and the flux under hyperemia (r = 0.81, P 0.001). A ratio between the counting rates of limb segments after exercise and those of skull was established. The ratios T/S and C/S compared with the systolic pressure index of the most affected limb after a Strandness test give a correlation of 0.72 (P 0.02) for the thigh and of 0.86 (P 0.001) for the calf. For hyperemic flux, the correlation are 0.58 (P 0.005) with T/S and 0.75 (P 0.001) with C/S. In order to find the best quantitative scintigraphic index of the arterial illness, we compared the different ratio values with the distance walked. For T/S we found a relationship very close to a linear one and for C/S a less significant exponential one. Thus, quantitative scintigraphy using 201Tl appears as an accurate method to measure local muscular perfusion deficit in the cases of lower limb arterial disease.

Arteritis↗

Tumor uptake of high and low molecular weight fractions from 67Ga-citrate labelled blood plasma.

Blood plasma from tumor-bearing rats was incubated with 67Ga-citrate, and two fractions of high molecular weight (proteins) and low molecular weight were isolated by dialysis and by gel-filtration chromatography. Both fractions showed a different in vivo uptake by DS-sarcoma-bearing animals, the high molecular weight fraction being accumulated to a lesser extent. Compared to 67Ga-citrate the low molecular weight fraction showed a different uptake which for most tissues was significatively higher. This behavior suggests the presence of 67Ga in chemical forms other than citrate in the low molecular weight fraction. The lower uptake of the blood protein fraction is discussed.

Animals↗

Study of competitive binding of gallium and iron by tumor cells.

The influence of iron and gallium carriers on the in vitro and in vivo uptake of 67Ga and 59Fe by tumor cells has been studied. The results appear to indicate that ferritin might be involved in most of the systemic accumulation of 67Ga but that the mechanism of tumor uptake might be different.

Animals↗

[Digital dynamic telethermography: an aid in the study of vascular reactivity to cold].

Vascular reactivity to cold has been studied on 22 patients by means of digital dynamic thermography. Using an interface the thermographic images are digitized in real time and stocked in the computer. After the cooling (two minutes in water at 10 degrees C) the warming-up is followed by sequential thermographic images. Profiles of thermic evolution are represented for 12 regions of interest (at the level of each finger and two for the back of the hands). Four types of thermic profiles are observed: Type 0: all fingers and back of hands have the same basal temperature. After cooling the warming-up is immediate, synchronic for all fingers and goes on more or less rapidly. Type I: at the basal state all fingers have identical temperature. After cooling, the warming-up starts after a latency period of several minutes, which is identical for all fingers. After it the warming-up is fast and synchronic with a thermic "overshot" phenomenon at the end of the examination. Only the thumbs are warmed-up without a latency period. Type II: a latency period similar that of type I is observed but the following warming-up takes place with variable speeds for each considered finger. Type III: at the basal state the fingers are colder than the back of the hand. Spontaneously, some fingers are warmed only by the influence of the hand vertical position. After cooling, the warming-up takes place with variable speeds and after variable latency periods which are a characteristic of each finger.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Vessels↗

[Myocardial infarction before the age of 35. Clinical and coronarographic aspects].

Myocardial infarction under the age of 35 is no longer a rarity. A series of 22 patients exhibited all the usual epidemiological, clinical and angiographic features of the disease: risk factors, predominantly excessive smoking associated with dyslipoproteinaemia in 50% of the cases; onset during exercise in one quarter of the cases, more frequently than in elderly people; and absence of significant lesions at angiography in one third of the cases. Angiography of the coronary arteries, performed in the early stages of infarction in 5 patients, demonstrated the presence of several factors in the pathogenesis of arterial occlusion in young people, i.e. thrombosis in almost every case, arterial spasm in 10% of the patients and atheromatous plaques with little or no stenosis in one half.

Adult↗

Incorporation and metabolism of exogenous fatty acids by cultured normal and tumoral glial cells.

We have investigated the transformation of exogenous radioactive free fatty acids by cultured glial cells and their incorporation into complex lipids. The cells were either tumor lines (C6 and NN) or primary cultures from newborn rat hemispheres. The tumor lines could undergo morphological differentiation with dibutyryl cyclic AMP or bromodeoxyuridine. The fatty acid precursors used were palmitic, stearic, oleic, linoleic and linolenic acids. Tumor cells presented a higher incorporation of the precursors in the cell lipid acyl groups than did normal cells. Tumor cells desaturated and/or elongated palmitic, stearic and oleic acid to a higher extent than did normal cells. In contrast, tumor cells transformed linoleic and linolenic acids to their polyunsaturated derivatives to a lower extent than did normal cells. In differentiated tumor cells, these patterns of metabolism were shifted toward the patterns of normal cells. Tumor cells did not exhibit delta 4-desaturase activity, but such activity was restored in the C6 line upon dibutyryl cyclic AMP-induced differentiation. Transformation of linoleic and linolenic acid is likely to proceed through initial delta 6 desaturation. Phospholipids were preferentially labelled with the radioactive fatty acids, and only a little radioactivity was found in the neutral lipid fraction, mainly in diacylglycerols. Each fatty acid precursor label was incorporated in individual phospholipids to a proportion which reflected the typical acyl group composition of glycerophospholipids; we observed high levels of incorporation of palmitic acid and its derivatives into choline glycerophospholipids, and high levels of incorporation of linolenic acid and its derivatives into ethanolamine glycerophospholipids. This pattern was more marked in tumor cells than in normal cells, and the differentiation of tumor cells partially restored the normal pattern, mainly in bromodeoxyuridine-treated NN cells. Both types of differentiation of glial cell lines can be useful as models for the understanding of membrane physiology in normal and tumor cells.

Animals↗

Frequency dependence of water proton longitudinal NMR relaxation times in mouse tissues around the freezing transition.

Water proton longitudinal NMR relaxation times were measured in various tissues of healthy and tumor-bearing mice. Measurements were performed as a function of the Larmor frequency nu in the range 6-90 MHz, and at two temperatures (theta + and theta -) bracketing the 'freezing transition', at which the major part of the water signal disappears. At both temperatures, 1/T1 behaves according to: 1/T1 = A/square root nu + B A and B are obtained at theta + and theta -, and yield the proportion of bound water, which is convincingly identified with non-freezable water. The proportions found lie around 6% for tumors and 12% for other tissues. Discrimination between tissues via T1 is demonstrated to be essentially due to the bound water proportion. Bound water on the one hand and free water on the other hand behave similarly in all tissues including tumors. The activation energy for free water is found to be identical to that of pure water, although relaxation times are markedly different. It is noticed that determining the bound water proportion by signal intensity measurements at theta + and theta - is less reliable than by the T1 method.

Animals↗

Early-phase pharmacokinetics of doxorubicin in non-Hodgkin lymphoma patients. Dose-dependent and time-dependent pharmacokinetic parameters.

The early-phase (20 min) pharmacokinetics of doxorubicin was studied in 18 patients suffering from non-Hodgkin lymphoma and receiving various schedules and/or dosages of the drug. This pharmacokinetics was time-dependent in most patients over a 2-week interval: repeating similar doses in patients leads to a decrease of the drug exposure due to a decrease of the half-life and/or to a decrease of the extrapolation to 0 time (intercept parameter). The pharmacokinetics was generally time-independent within a 6-h interval in most patients. During this time interval, the kinetics was not linear: increasing the dose by large proportions does not lead to a proportional increase of drug exposure. This time- and dose-dependence of doxorubicin pharmacokinetics makes it very difficult to monitor the treatments according to the individual pharmacokinetic patterns of patients.

Adolescent↗

67Ga and 59Fe uptake by tumor cells treated with hyperthermia or hyperthermia plus lanthanum.

The uptake of 67Ga-citrate and 59Fe-citrate by tumor cells treated with hyperthermia or with hyperthermia plus lanthanum has been studied. The comparison of these results with ion flux determinations (42K) appears to indicate that hyperthermia alone or combined with lanthanum modifies the ionic permeability of the plasma membrane. This phenomenon seems to be responsible for the increased accumulation of 67Ga and 59Fe.

Animals↗

[Hyperthermia caused by ultrasonics: trials of mathematical modelling].

We describe preliminary results concerning the mathematical modelling of the hyperthermia induced by an ultrasound transducer. The developed method should allow to predict in advance the local temperatures in every clinical case, as well as to conceive and optimize more complex ultrasound generators.

Hyperthermia, Induced↗

On the mechanisms of 67Ga and 59Fe uptake by tumors.

The uptake of 67Ga-citrate and 59Fe-citrate in the presence or absence of gallium and iron carriers, was studied on DS-sarcoma-bearing rats. Differences of uptake pattern were observed with both radionuclides. The tumor uptake of 67Ga is greatly affected by both carriers while 59Fe uptake is independent of the presence of carriers. The role of isotopic dilution, ionic competition, and the probable presence of high and low affinity binding sites in this phenomenon are discussed.

Animals↗