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Biomedical subjects

J Robert

Publications and source records attributed to J Robert.

At least 307 records · Page 17Linked to original sources

Improvement of radioactive colloid binding by tumor cells.

Treatment of P388 leukemia cells with poly-DL-lysine (Poly-lys) considerably increases the binding of colloidal chromic phosphate (32P). This augmentation of the number of particles that are bound is in direct relationship with Poly-lys concentration, and very significantly with its degree of polymerization. Treatment with Poly-lys molecular weight 77,000 shows a 100% increase of binding with 200 micrograms and of 50% with 100 micrograms. Poly-lys M.W. 8,000 presents no significant increase, and for the other molecular weights the binding is intermediate.

Adsorption↗

[Phosphorus NMR spectroscopy. Its value in the diagnosis of metabolic myopathies. A case of Mac Ardle's disease].

Phosphorus nuclear magnetic resonance spectroscopy is a non-invasive method used to study muscle bioenergetics in vivo. A new case of Mc Ardle's disease (myophosphorylase deficiency) is reported here. In a context of metabolic myopathy this method can provide a diagnosis of glycogenosis. The spectra obtained at exercise and during recovery determine the degree of enzyme deficiency with satisfactory precision.

Adult↗

Clinical cancer progression in urinary bladder tumors evaluated by multiparameter flow cytometry with monoclonal antibodies. Laval University Urology Group.

Multiparameter flow cytometry studies were performed on clinical samples of human bladder tumors to simultaneously analyse DNA content and the expression of surface glycoproteins defined by monoclonal antibodies T16, Om5, T43, and T138. The results of tests performed on 80 samples of bladder irrigations and tumors from 68 patients were correlated with clinical findings at the time of sampling and with disease outcome prospectively (mean follow-up 2 years). Measuring the level of the panurothelial antigen T16 provided more precision in DNA analysis and served as an internal standard to measure the relative expression of the other cell surface antigens studied. The panel of monoclonal antibodies improved the analytical capacity to study the heterogeneity of antigenic phenotypes within individual samples. Aneuploidy frequently correlated with high stage cancers and with a high rate of clinical cancer progression defined as metastasis or death by cancer. However ploidy was not an entirely reliable prognostic indicator since a significant proportion of Ta and T1 nonprogressing tumors were aneuploid, while in 6/20 cases of cancer progression, the samples were near diploid. Contrary to Om5, T43 and T138 antigens were expressed significantly more often on aneuploid samples, although they appear to provide additional information. T138 was positive on 17/18 samples from patients with high stage cancers of which five were near diploid. It was also positive on 4/5 samples from patients with Ta and T1 tumors in whom disease progressed to metastasis and death. Overall, the expression of T138 antigen was a better single indicator of clinical cancer progression than was ploidy. Further stratification was obtained with combined results of DNA and T138 antigen studies. Within the near diploid group, the incidence of bladder cancer death was 0/26 for T138 negative and 5/13 (38%) for T138-positive patients (P less than 0.01). In the aneuploid group incidence of bladder cancer death was 2/10 (20%) for T138-negative and 12/19 (63%) for T138-positive patients (P less than 0.05). These results suggest that simultaneous flow cytometry measurements of DNA and surface antigens may better assess the prognostic behavior of human bladder tumors.

Antibodies, Monoclonal↗

Metabolism of epirubicin to glucuronides: relationship to the pharmacodynamics of the drug.

In pharmacokinetic studies of epirubicin, we observed that its main metabolite, epirubicin glucuronide, presented a marked interpatient variation. It was even possible to separate the patients into two groups: those with a high epirubicin glucuronide:epirubicin plasma ratio and those with a low ratio, with few patients in between. We retrospectively analyzed the clinical files of 48 patients who had been subjected to a pharmacokinetic study of epirubicin. We observed that those with a low epirubicin glucuronide:epirubicin ratio had significantly lower plasma levels of fibrinogen and alpha 2-globulins, suggesting that a reduced glucuronidation of epirubicin could be associated with hepatocellular insufficiency. These patients also had significantly lower percentages of change in granulocytes after therapy and responded better to the course of treatment studied. We cannot presently propose a hypothesis to explain these observations.

Epirubicin↗

Improved subtraction technique in intravenous digital left ventriculography: comparison with radionuclide studies.

Adequate processing of left ventricular angiograms depends on the visualisation of all segments of the ventricular wall. At the same time, subtraction of different images can enhance different heart segments but commercially available methods do not allow simultaneous viewing of several images masked by different processes. Using our software, for each studied frame, a four quadrant display permits the simultaneous visualisation of a mask mode image, a diastolic-systolic difference image, an image obtained by subtraction of a frame at the same cycle time and a composite mask subtracted image. The composite mask image is obtained by weighting three images according to videodensitometric measurements by reference to previously acquired data. This method facilitates contour delineation and computation of the ejection fraction by area-length method. Correlation with radionuclide estimates of left ventricular ejection fraction is higher (n = 60, r = 0.90, SEE = 8%) than using the classical mask mode display (n = 60, r = 0.82, SEE = 11%). In a subgroup of 30 patients the contrast medium was injected in an antecubital vein and the correlation coefficient remained satisfactory (n = 30, r = 0.89, SEE = 7%) when compared with the classical subtraction technique (n = 30, r = 0.70, SEE = 12%). We therefore conclude that the composite mask method gives comparatively similar values for left ventricular ejection fraction to those acquired by radionuclide angiography.

Angiography, Digital Subtraction↗

Effects of iron-binding proteins on in vitro uptake of 67Ga-citrate by tumor cells.

A comparative study of carrier-free 67Ga-citrate uptake by Ehrlich ascites tumor cells in the presence of lactoferrin, transferrin and ferritin has demonstrated that lactoferrin considerably increases the uptake of 67Ga, and that this increase seems to be determined by its iron-load. The other iron-binding proteins assayed have a null or negative effect. Their behavior in the presence of sodium citrate supports the concept of lactoferrin-binding by the cells as responsible for the uptake. The different behavior of 67Ga-citrate iron-binding protein complexes appears to support this hypothesis.

Animals↗

Cellular pharmacology of 4'-iodo-4'-deoxydoxorubicin.

We have studied the growth inhibition, DNA synthesis inhibition and cell incorporation of the new anthracycline 4'-iodo-4'-deoxydoxorubicin (4'-iododoxorubicin) and of its 13-dihydroderivative in a model of doxorubicin-sensitive and -resistant rat C6 glioblastoma cells; results were compared to those obtained with doxorubicin and doxorubicinol in the same model. 4'-Iododoxorubicin was 7.5 times more potent than doxorubicin on the wild cell line and 45 times on the doxorubicin-resistant line, indicating that cross-resistance was only partial between the two drugs. Whereas doxorubicinol presented only a very faint cytotoxic activity, 4'-iododoxorubicinol retained the same activity as the parent drug against sensitive cells and a lower activity against resistant cells. DNA synthesis inhibition occurred for much higher doses than growth inhibition in the sensitive cells, but for similar doses in resistant cells. In both cell lines, 4'-iododoxorubicin and its metabolite were incorporated to a higher extent than doxorubicin and doxorubicinol respectively. Incorporation of metabolites was always lower than that of their parent compound. We have studied the metabolism of doxorubicin and 4'-iododoxorubicin by sensitive and resistant cells; only traces (less than 5%) of metabolites were identified in the cells as well as in the culture medium. A new cell line was selected for resistance in the presence of low amounts of 4'-iododoxorubicin. It presented a 6-fold resistance to 4'-iododoxorubicin and an 85-fold resistance to doxorubicin. Doxorubicin incorporation was markedly reduced in this cell line while 4'-iododoxorubicin was incorporated to the same extent as in the sensitive line. Measurements of drug efflux were performed in the three cell lines. No significant difference was exhibited between the efflux of doxorubicin and that of 4'-iododoxorubicin in each cell line; these effluxes were very rapid in the doxorubicin-selected resistant line, slow in the wild line and intermediate in the 4'-iododoxorubicin-selected line.

Animals↗

Skeletal muscle metabolism in the leg during exercise in patients with congestive heart failure.

1. Using 31P nuclear magnetic resonance, it has previously been demonstrated that patients with congestive heart failure exhibit a greater than normal phosphocreatine (PCr) depletion in the working skeletal muscles of the arm. We have studied the importance of the work necessary to reach a similar PCr depletion ([PCr]/([PCr] + [Pi]) = 0.5) in calf muscle. Our results show significantly lower values for patients with congestive heart failure in both aerobic and ischaemic conditions (respectively: 0.009 +/- 0.007 vs 0.026 +/- 0.013 W/kg body weight, P less than 0.01; 0.29 +/- 0.16 vs 0.90 +/- 0.25 J/kg body weight, P less than 0.01). 2. This original model of skeletal muscle exercise facilitates a comparison of PCr recovery rate due to a similarity in the PCr depletion and intracellular pH in the two series at the start of recovery. However, the PCr recovery rate is similar after both normoxic and ischaemic exercise, i.e. respective percentages of PCr increase in the first 25 s recovery spectrum were: (a) aerobic exercise, congestive heart failure 133 +/- 18%, control series 138 +/- 18%; (b) ischaemic exercise, congestive heart failure 114 +/- 13%, control series 118 +/- 12%. The absence of a difference in PCr recovery rate and the greater PCr depletion by ischaemic work in patients with congestive heart failure suggest modifications that cannot be explained by a reduced blood flow to the muscle. 3. When comparing the two series, intracellular pH evolved similarly in normoxia and ischaemia during both work and recovery. Thus, no increase in anaerobic glycolytic activity appears when equivalent PCr depletion has occurred.

Adult↗

Intra-abdominal palpation of a nasogastric tube in the stomach does not assure appropriate placement.

Improperly placed nasogastric (NG) tubes have been associated with considerable morbidity. The only reliable indicator of correct NG tube placement appears to be the aspiration of gastric contents. We have reported a case of major morbidity from an improperly placed NG tube that perforated the cervical esophagus, dissected the mediastinum, and terminated in the omental bursa. No gastric aspirate was obtained by suctioning of the tube, but correct placement was presumed based upon the surgeon's direct intraoperative palpation of the tip of the tube. Failure to aspirate gastric contents should alert the practitioner to the possibility of improper NG tube placement.

Abdomen↗

Developmental expression of the creatine kinase isozyme system of Xenopus: maternally derived CK-IV isoform persists far beyond the degradation of its maternal mRNA and into the zygotic expression period.

The differential expression of the multilocus CK isozyme system throughout development of the two Xenopus species X. laevis and X. borealis was investigated. A cDNA containing the nearly complete coding sequence of the CK-IV subunit of X. laevis was isolated and sequenced. Early development of X. laevis proceeds with a stock of maternally derived CK-IV/IV isozyme. While the mRNA declines rapidly after fertilization and disappears before neurulation, maternal CK-IV/IV isozyme is active far beyond the onset of zygotic expression and is still detectable when tadpoles start feeding. Zygotic expression of CK-IV begins after neurulation, at stage 22/24, and seems to start simultaneously with that of another gene, CK-III. Modulation in the expression of these two genes and the appearance of two other isoforms, the CK-I and CK-II/III isozymes, take place during development in a tissue-specific manner. During metamorphosis, the CK phenotypes of eyes and skeletal musculature undergo additional changes. The final adult pattern only appears several weeks after metamorphosis. The presumed orthologous CK isozymes of X. borealis show a developmental profile similar to that of X. laevis, except that CK-II/II is equally present in oocytes and during early development, in addition to CK-IV/IV isozyme. These results show that the expression of each of the four CK genes of Xenopus is under differential developmental control.

Amino Acid Sequence↗

Development of mechanisms of protection against oxidative stress in doxorubicin-resistant rat tumoral cells in culture.

We have compared some mechanisms involved in the defense against doxorubicin-induced free radical damage in rat hepatoma and glioblastoma cell lines and their doxorubicin-resistant variants presenting an overexpression of the multidrug resistance gene. Immediate in vivo production of malondialdehyde was minor and was not different in sensitive and resistant cells. Alpha-tocopherol was undetectable in all cell lines. Glutathione levels were not different in sensitive and resistant cells and these levels did not vary upon doxorubicin treatment. Resistant cells exhibited either a 50% decrease (hepatoma) or a 25% increase (glioblastoma) of glutathione-S-transferase activity. Glutathione reductase presented no important change upon acquisition of resistance. In contrast, selenium-dependent glutathione peroxidase activity was consistently 2-6-fold increased in the resistant cells, which suggests a magnification of protection mechanisms against hydroxyle radical formation from H2O2 in resistant cells. Depletion of glutathione levels by buthionine sulfoximine sensitized hepatoma resistant cells to doxorubicin, but had no effect on doxorubicin cytotoxicity to glioblastoma cells.

Animals↗

Pharmacokinetics of idarubicin after oral administration in elderly leukemic patients.

We have studied the plasma pharmacokinetics of idarubicin (4-demethoxy daunorubicin) in 11 elderly patients suffering from acute myeloblastic leukemia receiving orally 30 mg/m2 per day for 3 consecutive days. Idarubicin culminated in plasma 4 hr after administration and followed three similar time courses after the three administrations. Idarubicinol (13-dihydro-4-demethoxy daunorubicin) was the only fluorescent metabolite in plasma and no aglycone could be detected; idarubicinol concentration was always higher than that of unchanged idarubicin. Due to its protracted half-life (64 hr in this study), this metabolite progressively accumulated and the ratio of the areas under the curve (0-24) idarubicinol/idarubicin increased from day to day. By comparison to results obtained after i.v. administration of the drug in another study, the bioavailability of idarubicin alone can be estimated to about 21%, whereas the bioavailability of the sum idarubicin + idarubicinol is about 41%.

Administration, Oral↗

[Perforated tubular duplication of the sigmoid colon in adults].

Intestinal duplications are rare malformations and a diagnostic challenge. The case presented herein relates to a perforated tubular duplication of the sigmoid colon in a 23-year-old man with intermittent abdominal pain during 3 months and a bout of peritonitis which resolved spontaneously. This case is unusual since duplications generally spare adults, are seldom found in the colon, and do not perforate. The only cases of duplication which can be suspected preoperatively belong to the communicating type or those containing ectopic gastric mucosa. The intraoperative finding in this case of a malformative mesenteric cyst reminds us that duplications can be found in association with other intestinal, vertebral, or genitourinary tract malformations. In conclusion, intestinal duplications should be resected even when they are asymptomatic, as occasional cancerous transformation associated with a poor prognosis have been reported.

Abscess↗

Ruptured aneurysm of the omentum. Case report.

A 61-year-old man was operated on for a ruptured aneurysm located on the free margin of the omentum. Such patients should have preoperative arteriography as the source of the haemorrhage can be difficult to find at operation.

Aneurysm↗