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J Robert

Publications and source records attributed to J Robert.

At least 325 records · Page 18Linked to original sources
PubMed1989

Comparative activity of anthracycline 13-dihydrometabolites against rat glioblastoma cells in culture.

We have studied the growth inhibition, DNA synthesis inhibition and cell incorporation of five 13-dihydrometabolites of anthracyclines in a model of doxorubicin-sensitive and -resistant rat C6 glioblastoma cells. These compounds were major metabolites for doxorubicin, epirubicin, daunorubicin, idarubicin and the new anthracycline 4'-deoxy-4'-iododoxorubicin and are known to be present in appreciable amounts in the plasma of patients treated with these drugs. We have shown that in vitro growth inhibition in sensitive cells was either much lower than that of the parent drug (doxorubicinol, epirubicinol, daunorubicinol), or similar to it (idarubicinol, 4'-iodoxorubicinol). In resistant cells, growth inhibition was about 100 times lower than in wild cells, and was always lower than that of the parent anthracycline. DNA synthesis inhibition occurred in sensitive cells for doses about 100 times higher than those required for growth inhibition, but in resistant cells, similar doses provided growth inhibition and DNA synthesis inhibition. Metabolite incorporation was always lower than that of the corresponding parent anthracycline; it was greatly reduced in resistant cells as compared to sensitive ones. The calculated intracellular concentrations obtained for the same growth inhibition are higher in resistant cells than in sensitive cells; in contrast, the calculated intracellular concentrations obtained for the same DNA synthesis inhibition are similar in resistant and sensitive cells, and similar for all the metabolites studied. These results suggest that the amount of drug incorporated is primarily responsible for DNA synthesis inhibition, which is directly correlated to growth inhibition in resistant cells, but not in sensitive cells.

Animals↗
PubMed1989

Enhancement of colloid uptake by tumor cell surface electrical charge modification.

Colloidal [51Cr]chromic phosphate uptake is considerably increased by preincubation of P388 ascites leukemia cells with poly(DL-lysine). The uptake increase is in direct relationship with the concentration and the degree of polymerization of poly(DL-lysine). The probable implication of cell surface electrical charge modification in these phenomena is discussed.

Animals↗
PubMed1989

Comparative cytotoxicity, DNA synthesis inhibition and drug incorporation of eight anthracyclines in a model of doxorubicin-sensitive and -resistant rat glioblastoma cells.

We have compared the growth inhibition, DNA synthesis inhibition and cell incorporation of eight anthracyclines in a model of doxorubicin-sensitive and -resistant rat C6 glioblastoma cells. The anthracyclines studied were both the reference molecules (daunorubicin, doxorubicin) and the new drugs recently introduced in clinical use or in trials (epirubicin, idarubicin, pirarubicin, esorubicin, rubidazone, 4'-deoxy-4'-iododoxorubicin). We have shown that the in vitro growth inhibition was correlated with the LD50. The new anthracyclines were more potent than the reference drugs in the sensitive cells and the resistance patterns revealed a reduced cross resistance of idarubicin, pirarubicin and 4'-deoxy-4'-iododoxorubicin towards the doxorubicin-resistant line. DNA synthesis inhibition occurred for much higher doses than growth inhibition in sensitive cells, but for similar doses in resistant cells. This suggests that different mechanisms could be involved in the mechanism of growth inhibition in sensitive and resistant cells. For similar exposures, reduction of drug incorporation was a general feature in the resistant line when compared to the sensitive one. However, no correlation was shown, for the various drugs, between the reduction of incorporation and the resistance factor. Moreover, the intracellular concentration required for growth inhibition is much higher in resistant cells than in sensitive cells, suggesting that increased drug efflux might not be the only mechanism to explain drug resistance.

Animals↗
PubMed1989

Assessment of the experimental model of transplanted C6 glioblastoma in Wistar rats.

Establishing in vivo glioblastoma models from cell lines requires a very strict methodology, in order to obtain reproducible tumors presenting all the characteristics of human spontaneous glioblastomas. In this respect, we have developed a model of glioblastoma in Wistar rats by stereotaxic intracerebral transplantation of a 10 microliters suspension of 6 x 10(6) C6 cells grown in vitro. The tumor take was very high in these conditions, only 1 rat over 30 had no tumor. The median survival time varied from 14 to 20 days. The growth curve of the tumor has revealed an exponential growth up to the 10th day after transplantation with a doubling time of 36 h. Histological examination of the tumors has shown several characteristic features of spontaneous glioblastomas, such as neovasculature, parenchymal invasion, nuclear pleiomorphism, and presence of hemorrhagic and necrotic areas. This C6 model is closer to the usual histological characteristics of spontaneous glioblastomas when using the Wistar rather than other strain, and it should be used in that way for preclinical therapeutic evaluation of new drugs or drug combinations in glioblastoma.

Animals↗
PubMed1989

Clinical and pharmacokinetic study of 96-h infusions of doxorubicin in advanced cancer patients.

A phase I and a pharmacokinetic study of 96-h infusions of doxorubicin were performed in order to evaluate the maximum tolerated dose with this schedule of administration. Seventeen patients suffering from a digestive carcinoma were included in the study and a total of 71 courses of treatment were performed. The starting dose was 15 mg/m2/day and was increased in 2.5 mg/m2/day increments. The main toxicities observed were neutropenia and mucositis, which became limiting from 22.5 mg/m2/day (90 mg/m2 over a 96-h period); this dose was therefore defined as the maximal tolerated dose. No objective response to treatment was observed. For further studies, the recommended dose should not exceed 20 mg/m2/day. A plasma plateau concentration of doxorubicin was reached within 24 h. Despite a constant infusion rate, the plasma concentration of doxorubicin showed transient variations in several patients. However, an average plasma concentration could be evaluated for 33 courses of treatment, and this was linearly related to the dose. Doxorubicinol was the only detected metabolite of doxorubicin and its plasma concentration progressively increased throughout infusion. A detailed pharmacokinetic study was performed in 13 courses of treatment. The mean plasma clearance of doxorubicin was 25.2 l/h/m2 and the mean terminal half-lives of doxorubicin and doxorubicinol were respectively 43.6 and 66.2 h. Urinary excretion of doxorubicin plus metabolite was regular from the 24th to the 96th hour of infusion; however, the proportion of doxorubicinol progressively increased in urine. The protracted half-life of this metabolite probably explains its accumulation during infusion.

Adult↗
PubMed1989

Acute pancreatitis and normoamylasemia. Not an uncommon combination.

A consecutive series of 352 attacks of acute pancreatitis (AP) was studied prospectively in 318 patients. AP was ascertained by contrast-enhanced CT scan in all but four cases in which diagnosis was made at operation or autopsy. Sixty-seven of these cases (19%) had normal serum amylase levels on admission (i.e., less than 160 IU/L, a limit that includes 99% of control values), a figure considerably higher than generally admitted. When compared to AP with elevated serum amylase, normoamylasemic pancreatitis was characterized by the following: (1) the prevalence of alcoholic etiology (58% vs. 33%, respectively, p less than 0.01), (2) a greater number of previous attacks in alcoholic pancreatitis (0.7 vs. 0.4, p less than 0.01); and (3) a longer duration of symptoms before admission (2.4 vs. 1.5 days, p less than 0.005). In contrast AP did not appear to differ significantly in terms of CT findings, Ranson's score, and clinical course, when comparing normo- and hyperamylasemic patients, although there was a tendency for normoamylasemic patients to follow milder courses. Serum lipase was measured in 65 of these normoamylasemic cases and was found to be elevated in 44 (68%), thus increasing diagnostic sensitivity from 81% when amylase alone is used to 94% for both enzymes. A peritoneal tab was obtained in 44 cases: amylase concentration in the first liter of dialysate was greater than 160 IU/L in 24 cases (55%), and lipase was greater than 250 U/L in 31 cases (70%). Twelve of these 44 cases had low peritoneal fluid and plasma concentrations for both enzymes. Thus little gain in diagnostic sensitivity was obtained when adding peritoneal values (96%) to serum determinations. AP is not invariably associated with elevated serum amylase. Multiple factors may contribute to the absence of hyperamylasemia on admission, including a return to normal enzyme levels before hospitalization or the inability of inflamed pancreases to produce amylase. Approximately two thirds of cases with normal amylasemia were properly identified by serum lipase determinations. AP does not appear to behave differently when serum amylase is normal or elevated, and should therefore be submitted to similar therapeutic regimens in both conditions.

Acute Disease↗
PubMed1989

Phosphorus nuclear magnetic resonance evidence of abnormal skeletal muscle metabolism in chronic alcoholics.

Pathophysiologic events leading to rhabdomyolysis in alcoholics are not clearly understood. We examined 18 alcoholic patients (10 with and 8 without a recent history of rhabdomyolysis) and 15 healthy non-alcoholic volunteers by phosphorus nuclear magnetic resonance spectroscopy of thenar eminence muscle. At rest, phosphocreatine, ATP, and pH levels were similar in patients and control subjects. During aerobic exercise, phosphocreatine utilization was greater, pH fell more slowly, and maximum acidosis was less in alcoholics with previous rhabdomyolysis than in control subjects. During ischemic exercise, both patient groups exhibited a significantly slower and smaller decrease in pH than did control subjects. These findings are consistent with impaired muscular glycolysis or glycogenolysis in both alcoholic groups. This metabolic myopathy may contribute to the onset of acute rhabdomyolsis.

Adult↗
PubMed1989

[In vitro effect of various antibiotics: beta lactams, aminoglycosides and fluoroquinolones alone and in combination against P. aeruginosa isolated from patients with mucoviscidosis].

The antibacterial activity of fluoroquinolones (ciprofloxacin and ofloxacin) combined with beta lactams (ceftazidime and imipenem) or aminoglycosides (tobramycin and amikacin) against 22 P. aeruginosa isolated from the sputum of patients with cystic fibrosis was determined by the checkerboard method and compared with the combination of beta lactams (with ticarcillin) with aminoglycosides. Synergistic association (defined as FIC index less than ou = 0.5) was founded for 23 to 41% of strains with beta lactams (except imipenem)/aminoglycosides, in 18% with ceftazidime/ciprofloxacin, in 13% with imipenem/ciprofloxacin, in 0 or 13% with quinolones/aminoglycosides. For a FIC index less than ou = 0.75, the values are highest with 82% for ciprofloxacin/ceftazidime and 50% for ofloxacin/ceftazidime. The CMI's achieved in these combinations may allowed concentrations near to sputum concentrations.

Aminoglycosides↗
PubMed1989

[Keratinocyte-fibroblast interactions: I. Production by the keratinocytes of soluble factors stimulating the proliferation of normal human skin fibroblasts].

Epidermal cells produce IL-1 and contra IL-1 which respectively stimulate and decrease fibroblast proliferation. In order to get better insight into the nature of keratinocyte-fibroblast interactions, we have analyzed the effect of soluble factors produced by unstimulated normal human keratinocytes and keratinocyte cell lines on the proliferation of normal human dermal fibroblasts. The results were compared to these obtained with human recombinant IL-1 and IL-2. We observed that: 1) normal keratinocytes (monolayers or stratified) released in the culture medium a factor stimulating fibroblast proliferation by 45 to 160%; 2) supernatants of unstimulated PAM 212 keratinocyte cell line also contained the stimulatory activity; 3) addition of IL-1 beta to the culture medium at concentration ranging from 0.1 to 1.000 U/ml induced a dose-dependent increase in fibroblast proliferation, whereas IL-2 was ineffective; 4) gel filtration analysis (ACA 54) of serum-free supernatant showed that the activity could be eluted from 3 peaks (Mw ranging from 10 to 20 kD). The present data show that unstimulated normal human keratinocytes produce soluble factor(s) (maybe related to IL-1) which stimulate human dermal fibroblast proliferation and which could be of major importance in the modulation of fibroblast metabolism, in vivo.

Adult↗
PubMed1989

[Respiratory sensitization to molds in children: myth or reality?].

The authors have made a systematic study by PRICK-test and RAST, sometimes followed by a rhino-manometric provocation, of the frequency of sensitization to the two moulds Alternaria and Cladosporium in 200 "all comers" children in a paediatric consultation. The frequency was low, only 10% for those consulting in the groups of asthma, rhinitis, pollinosis, repeated respiratory infections and syndromes of obstructed expiration taken together, and 13% for allergic asthma only. This sensitivity is rarely isolated, but is most often accompanied, or complicated by, other pneumoallergens, such as dust, mites, pollens and sometimes cockroaches. It imposes certain particular clinical traits on asthma (summer asthma or recurring asthma) and in others appears to be strongly influenced by the habitat. The skin tests seem to be very weak and RAST insufficient to be sure of real sensitization. Diagnosis, always difficult, is probably best done by a provocation test (preferably rhino-manometry) and this jumps over the bundle of clinical and biological arguments, as well as being, at least in our country, the most useful mimic of atmospheric moulds. The authors insist on the importance of the interrogation which should be concerned with the chronological and environmental circumstances and all respiratory infections that are suspected of having an allergic factor.

Adolescent↗
PubMed1989

Influence of various extracellular matrix components on the behavior of cultured chick embryo dermal cells.

Dermal cells isolated from the back of 7-day chick embryos were cultured on homogeneous two-dimensional substrates consisting of one or two extracellular matrix components (type I, III or IV collagen, fibronectin and several glycosaminoglycans: hyaluronate, chondroitin-4, chondroitin-6, dermatan or heparan sulfate). The effect of these substrates on cell behavior was compared with that of culture dish polystyrene. Three parameters of cell behavior were examined: cell proliferation and patterning, spreading (cell surface) and locomotion (velocity and directionality). Data were collected by sequential microphotography and analyzed by computer assisted morphometry. Types I and III collagen, hyaluronate and heparan sulfate had a slowing down effect on cell proliferation and patterning. The inhibitory effect of type I collagen was also detected in mixtures with glycosaminoglycans. The other components had no effect. While the smallest spreading was observed on fibronectin substrate, the largest was recorded on chondroitin-6 sulfate and heparan sulfate. The slowest velocity of locomotion was measured on fibronectin, types I and IV collagen and a mixture of type I collagen and chondroitin-6 sulfate. The fastest speed was recorded on chondroitin-4 sulfate. These effects are discussed in view of our knowledge of the role of the dermis in the development of skin and cutaneous appendages, and in the light of the morphogenetically related microheterogeneous distribution of collagens, fibronectin and various glycosaminoglycans in the developing skin.

Animals↗
PubMed1989

[Value of digital subtraction of left ventriculographies by the venous route. Comparison with balanced scintigraphy of the heart cavities].

The development of numerisation material in radiology currently permits to perform usual cardiovascular tests. The authors report a series of 48 patients who benefited from the determination by numerised left ventriculography, of their stroke volume (SV). In 37 cases, the peripheral venous route is used while in 11 cases the central venous route is used, in the pulmonary artery trunk. The SV values obtained with both methods (one advocated by the manufacture and another one developed by the authors), are correlated with the SV values obtained with the isotopic method, used as reference. The correlations are satisfactory, approximately 0.79 for all patients of the study, and markedly improve when the injection of the contrast material is performed in the pulmonary artery (approximately 0.95). The authors conclude that determination of the left ventricle SV by numerisation is an interesting technique in centers where there is no department of nuclear medicine, and is absolutely necessary to complement right catheterisation.

Female↗
PubMed1989

[Single-stage excision anastomosis of left colonic obstruction excision treated as an emergency].

The results of four different types of operation were compared retrospectively in terms of mortality, morbidity, duration of hospital stay. Eighty-eight consecutive patients suffering from left colonic obstruction underwent emergency surgery from December 1976 to January 1988. There were 36 male and 52 female patients, aged from 41 to 93 years (mean 71), 25% of them being 78 or older. Carcinoma was the most frequent lesion (75/88, 85%). 1) One-stage resection and anastomosis was carried out in 23 patients with only one temporary ileostomy; there were two fatalities (8.7%) and one clinical anastomotic leak (4%) treated conservatively with success; mean hospital stay was 21.5 days. 2) Thirty-six patients underwent a Hartmann procedure, with four fatalities (11%) and a mean hospital stay of 23.0 days; 17 of the surviving 32 (53%) later had the second stage procedure, with no fatality, one clinical leak (6%), and mean stay of 20.7 days. 3) Twenty-six patients had simple decompressing colostomies with nine fatalities (35%); eight of the surviving 17 (47%) had colectomy and colostomy closure during the same hospitalization, with one fatality (6%); mean hospital stay was 41.4 days. 4) Finally, subtotal colectomy imposed by caecal ischemia (twice) or a previous right colectomy (in one instance) was performed three times with no death. Since january 1986, resections and primary anastomoses have been performed 20 times for 26 consecutive obstructions (77%). Our overall results in terms of mortality, morbidity and duration of hospital stay appear to favor resection and primary anastomosis in the treatment of selected cases of left colonic obstruction.

Adult↗
PubMed1989

Production of fibronectin and collagen types I and III by chick embryo dermal cells cultured on extracellular matrix substrates.

Dermal cells isolated from the back skin of 7-day chick embryos were cultured on homogeneous two-dimensional substrates consisting of one or two extracellular matrix components (type I, III, or IV collagen, fibronectin and several glycosaminoglycans (GAGs): hyaluronate, chondroitin-4, chondroitin-6, dermatan and heparan sulfates). The effect of these substrates on the production of fibronectin, of types I, III and IV collagen by cells was compared with that of culture dish polystyrene. Using immunofluorescent labeling of cultured cells, it was observed that, on all substrates, in 1-day and 7-day cultures, 85 to 95% of cells contain type I collagen in the perinuclear cytoplasm; label was absent from cell processes. Type I collagen was also detected in extracellular fibers extending between neighboring cells. By contrast, on all substrates, only 5 to 20% of cells produced type III collagen. Otherwise distribution of type III collagen was similar to that of type I collagen. With anti-type IV collagen antibody no staining of either cell content or extracellular spaces was detected. Staining with anti-fibronectin antibody revealed two types of distribution patterns. On polystyrene and on all but type I collagen substrates, labeling revealed clusters of short thick strands and patches of fibronectin-rich material in extracellular spaces. On type I collagen substrate, however, immunostaining revealed a delicate network of regularly spaced parallel fibrils of fibronectin extending between and along cells. Using quantitative radioimmunoassay of the culture media, it was shown that, after 7 days of culture, cells secreted more type I than type III collagen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗