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Biomedical subjects

P Fournier

Publications and source records attributed to P Fournier.

At least 91 records · Page 5Linked to original sources

[A new cause of torsades de pointes: combination of terfenadine and troleandomycin].

The authors report a case of wave-burst arrhythmia which occurred during combined treatment with terfenadine and troleandomycin. After the treatment had been stopped and the QT interval returned to normal, terfenadine treatment was reintroduced with no major change in repolarization. However, as soon as troleandomycin was associated, there was a significant and progressive prolongation of QT. Normal repolarization was restored again with troleandomycin alone. These findings suggest drug interaction between terfenadine and troleandomycin. Although it is not possible to carry out serum assays of terfenadine, one possible physiopathological hypothesis would be an overdose of terfenadine. Terfenadine undergoes hepatic oxidative metabolism involving the cytochrome P450 pathway and troleandomycin inhibits cytochrome P450. In the literature, a case has already been described of wave-burst arrhythmia related to terfenadine overdose when associated with a cytochrome P450 inhibitor.

Aged↗

[Evaluation of a new cardiotonic agent on human isolated atrium].

The action of a phosphodiesterase inhibitor, RGW 29 38, was analysed experimentally. A preliminary study with guinea pig isolated heart, using Langhendorf's method, revealed a cardiotonic effect, though less than with isoprenaline and dobutamine, with which it was compared. The inotropic action of the compound was then studied using human isolated atrium. The model is described. It consisted of measurement by a strain gauge of the contractions obtained in a stimulated atrial fragment obtained during a surgical procedure. The following parameters were analysed, expressed as percentage increase in relation to baseline conditions: maximum tension developed, positive dP/dt and negative dP/dt. The effect of RGW (n = 6) was compared with that of isoprenaline (n = 7). RGW caused an increase in maximum tension of 195% +/- 91%, in positive dp/dt of 110% +/- 72% and in negative dp/dt of 168 +/- 54%. This increase was, however, less than that seen in the isoprenaline group. Thus RGW had a definite positive inotropic effect on guinea pig isolated heart and human isolated atrium, though less than that of the catecholamines with which it was compared. Isolated human atrium appears to be a useful study model, in particular for analysis of the inotropic action of drugs.

Animals↗

Expression of a chimaeric heat-shock-inducible Agrobacterium 6b oncogene in Nicotiana rustica.

The T-6b gene of Agrobacterium tumefaciens strain Tm4 induces tumours on Nicotiana rustica by an as yet unknown mechanism. These tumours cannot be regenerated into normal plants. To study the effect of the T-6b gene product on normal plant cells, the T-6b gene was placed under control of the Drosophila melanogaster hsp70 heat-shock promoter and introduced into N. rustica. Progeny of an hsp70-T-6b transformant developed into normal plants. The inducibility of the hsp70-T-6b construct was shown by northern analysis and by heat-shock-dependent growth alterations on the level of whole seedlings. Upon wounding at normal temperature conditions hsp70-T-6b plants formed small tumours on leaves and stems. Grafts between transformed plants and normal plants led to a wound callus which remained limited to transformed tissues, indicating that the T-6b gene product does not diffuse. Protoplasts of hsp70-T-6b plants divided in the same way as control protoplasts under standard culture conditions. However, when protoplast cultures were started in the absence of hormones, normal cells rapidly lost their sensitivity towards hormones, whereas hsp70-T-6b cells remained sensitive for a significantly longer period. Thus, the T-6b gene product alters hormone sensitivity during the initial phases of protoplast culture.

Base Sequence↗

Cloning of the mating-type gene MATA of the yeast Yarrowia lipolytica.

The mating type gene MATA of the dimorphic yeast Yarrowia lipolytica was cloned. The strategy used was based on the presumed function of this gene in the induction of sporulation. A diploid strain homozygous for the mating type B was transformed with an integrative gene bank from an A wild-type strain. A sporulating transformant was isolated, which contained a plasmid with an 11.6 kb insert. This sequence was rescued from the chromosomal DNA of the transformant and deletion mapping was performed to localize the MAT insert. The MAT gene conferred both sporulating and non-mating phenotypes on a B/B diploid. A LEU2 sequence targeted to this locus segregated like a mating type-linked gene. The A strain did not contain silent copies of the MAT gene.

Chromosome Deletion↗

Intestinal transfer of manganese: resemblance to and competition with calcium.

The effect of calcium, phosphate and the sugars lactose and sorbitol on the intestinal absorption of manganese were studied in adult male rats. Gastric gavage showed that lactose (100 mM or 200 mM) increased the hepatic retention of 54Mn, while phosphate decreased it. In situ ileal loop studies indicated that Mn absorption was normally complete in 30 min. Sorbitol had no effect on uptake during this period, but extended Mn absorption from 30 min to 120 min. Low concentrations of Mn (10 microM) did not alter the enhancing effect of lactose on calcium transport (10 mM), but the enhancing effect of lactose on Mn transport was blocked by this high calcium concentration. Intestinal alkaline phosphatase activity was rapidly stimulated by Mn. These similarities plus the competition between cations, especially calcium, suggest that a common mechanism exists in their intestinal transport.

Alkaline Phosphatase↗

Anthropometric status, serum prealbumin level and immune response to measles vaccination in Mali children.

Protein energy malnutrition (PEM) is known to depress cell-mediated immunity. Its effect on humoral immunity is less clear-cut. The purpose of the study was to assess seroconversion following measles vaccination according to child nutritional status as assessed by anthropometry and serum thyroxine-binding prealbumin (TBPA). Prior to vaccination, 200 Malian children aged 8-22 months (mode: 9 months) and free of infection were weighed and measured. A venous blood sample was drawn for determination of serum TBPA by radial immunodiffusion and of measles specific immunoglobulins (Ig) by Enzyme-linked Immuno-Sorbent Assay (ELISA). IgG and IgM were again assayed 6 weeks post-vaccination after excluding pre-immune subjects. Seroconversion took place in 91 per cent of the children (95 per cent confidence interval: 86-96 per cent). Based on the NCHS standards, 30 per cent of the children were wasted (weight-for-height less than -2.0 SD) and 18 per cent were stunted (height-for-age less than -2.0 SD). Low serum TBPA (less than 10 mg/dl) was found in 38 per cent of them. TBPA was significantly correlated with weight-for-height and weight-for-age (P less than 0.001), but not with height-for-age. Seroconversion was not significantly related to age, anthropometric indices or TBPA. This study using sensitive methods for the assessment of protein status and of the immune response confirms that children should be vaccinated against measles irrespective of their nutritional status, and PEM was not shown to impair their antibody response.

Anthropometry↗

Mistreatment of the aged in the home environment in northern France: a year survey (1990).

As the percentage of the population which is aged increases in the developed countries, public health problems arise from the limited autonomy and physical or mental infirmity of the elderly. Cohabitation arrangements, often used to permit the elderly to stay at home, can give rise to conflict and the mistreatment of the aged. We analysed questionnaires distributed in 1990 to 25 home nursing units and two hospitals in a part of the northern region of France. Fifty-five observations of mistreatment were collected, 22 from hospital and 33 from home-based inquiries. The types of mistreatment and the characteristics of the victims and perpetrators are detailed and discussed. Penal and legal aspects of mistreatment of the aged in France are discussed.

Aged↗

Modulation of ileal calcium transport by phosphate-exchanging compounds.

Calcium transport in the ileal-ligated loop was studied in the adult rat in the presence of either phosphate alone or phosphate-binding compounds, namely either hydroxylated or aminated substances. Sorbitol or creatine (50 mM) added to a 10-mM CaCl2 solution, which was instilled into ileal loop, markedly enhanced calcium transport, as determined by 45Ca radioactivity appearing in plasma and from 45Ca radioactivity disappearing from the loop. The presence of both compounds maintained Ca soluble in an instilled solution at a constant concentration, whereas with a control solution the Ca concentration progressively decreased towards zero after an incubation period of 60 min. Phosphate, which was either simultaneously added with sorbitol or creatine or which was present as sorbitol or creatine phosphate, led to an equally marked decrease in calcium transport. Calcium transfer was even more reduced when phosphate alone was present with calcium in the ileal loop, in the absence of sorbitol. Similar to the above phosphate-binding compounds, adenosine and its constitutive component, ribose, increased calcium transfer, whereas adenine, the other constitutive component of adenosine, was ineffective. Guanosine was twice more active than adenosine in stimulating ileal calcium transport. Interestingly, the structure of guanosine allows the binding of two phosphates, with one binding site being on the ribose and the other on the guanine base moiety. Thus guanosine is capable of binding a greater amount of phosphate than the two other aminated compounds examined, namely adenosine and alanine, when transphosphorylation from ATP is studied with intestinal microvilli preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

[Thrombi of the right heart. Value of thrombolytic therapy in mobile thrombi].

Seven patients with mobile right heart thrombi, 4 floating and 3 pediculated, were recensed between 1985 and 1990. Two patients were admitted for congestive cardiac failure (Group I) and 5 patients for pulmonary embolism (Group II). Both patients in Group I were treated with heparin without complications. In one case, the size of the thrombus decreased in 10 days whereas, in the second case, it disappeared within 8 days. In Group II, the first patient underwent successful thrombectomy. The other four patients were given thrombolytic therapy (UK = 2, rt-PA = 2) associated with appropriate doses of heparin. In the two patients given UK (3M units the first day followed by 1.2 M units per day for 4 days) the thrombus disappeared in the first 48 hours of treatment. One patient had a recurrent pulmonary embolism after 2 hours' treatment; both patients had a fall in haemoglobin of 3 cg/ml at the second day. The second patient died at the 5th day. In the two patients treated by rt-PA (100 mg/7 hours) the thrombus disappeared within 4 hours of starting therapy. One patient had a probable recurrent pulmonary embolism. Both patients had a fall in haemoglobin of 3 cg/ml at the 2nd day of treatment. Right heart thrombi are rare (168 cases in the literature of which 111 were mobile). The prognosis seems to be related to echocardiographic appearances: mortality of mural thrombi is about 4% compared with 50% in mobile thrombi. Very mobile "worm-like" masses are therapeutic emergencies because of the risk of embolism (about 68%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Metabolic effects of phosphate receptors stimulating the ileal transport of calcium].

Several compounds, either metabolizable such as sorbitol and creatine or unmetabolizable such as L-xylose or ethyl-ethanolamine, increase ileal calcium transport, similarly to the well documented effect of lactose. These compounds increase the duration time but not the rate of calcium transport. They have no specific effect on intestinal calcium absorption but they prolong the presence of soluble calcium in the ileal loop, thus allowing the calcium absorption. This stimulating effect of these compounds on mineral absorption is associated with an increase of ileal mucosal ATP content.

Animals↗

Scarcity of ars sequences isolated in a morphogenesis mutant of the yeast Yarrowia lipolytica.

Previous attempts is isolate autonomously replicating sequences (ars) from the dimorphic yeast Yarrowia lipolytica have been unsuccessful. We isolated a Fil- mutant unable to produce hyphae and growing only in a yeast form to facilitate ars isolation. This mutant was transformed with a Y. lipolytica DNA bank and several unstable clones were obtained. Extrachromosomal plasmids were evidenced in yeast, recovered in Escherichia coli and characterized by restriction mapping. They were able to retransform Fil- and Fil+ yeast strains at high frequency and transformants displayed a slightly unstable phenotype. The detailed analysis of the plasmids showed that only two different ars sequences had been isolated, each of them corresponding to a unique sequence in the Y. lipolytica genome. We concluded that functional ars sequences that can be cloned on plasmids are rare in this yeast.

Base Sequence↗

Effect of some alkaline phosphatase inhibitors on intestinal calcium transfer.

1. There is a good correlation between the capacity of sugars to stimulate calcium transfer and their capacity to be phosphorylated by the intestinal alkaline phosphate with a part of the phosphate liberated from an ester phosphate. 2. On the sugar dependent and sugar independent calcium transfer, inhibitors of this enzyme act differently. 3. Phosphate, a competitive inhibitor suppresses both transfers. 4. Only the dependent sugar transfer was suppressed with phloridzin acting competitively at the sugar site, or with EDTA which could react close to the active site. 5. L-phenylalanine and phenobarbital, not competitive inhibitors does not act on either type of calcium transfer, the sugar dependent or the sugar independent.

Alkaline Phosphatase↗

Use of ars18 based vectors to increase protein production in Yarrowia lipolytica.

The isolation of ars sequence from the yeast Yarrowia lipolytica has recently been reported (Fournier et al., 1991). Vectors containing ars18 have been used to increase homologous and heterologous protein production. Examples presented are the Yarrowia lipolytica alkaline extracellular protease (AEP), the porcine alpha 1-interferon and the bovine prochymosin. A 2- to 6-fold increase in the corresponding protein production was observed and in several cases it was established that it corresponded to the copy number of plasmid in the cell.

Animals↗

Effects of iron depletion and sub-inhibitory concentrations of antibodies on siderophore production by Staphylococcus aureus.

The effect of various sub-MICs of oxacillin and amikacin, alone or in combination, on siderophore production by Staphylococcus aureus growing under iron-depleted conditions was evaluated. Siderophore production varied greatly from strain to strain, ranging from 3.0 to 383.4 microM of Desferal equivalents. Siderophore production by some S. aureus strains was reduced significantly (P less than 0.001) under some sets of conditions. However, siderophore excretion in cultures with amikacin was sometimes equal to or greater than control cultures. Thus, at some sub-MICs, the bacteria tested were able to increase siderophore production under metabolic stress. This phenomenon may be a secondary effect of the antibiotics upon intermediary metabolism as a consequence of inhibition of peptidoglycan or protein synthesis. Alternatively the antibiotics may decrease the cellular association of siderophore molecules.

Amikacin↗

[Evaluation of an automated system in bacteriology. Application to bacteriological susceptibility tests].

Susceptibility tests have been compared between a new automated system and the reference method by agar diffusion. The COBAS-Micro apparatus for bacterial susceptibility tests is intended for rapid determinations with, normally, an incubation time of 5 h at 37 degrees C. Its is compatible with strains requiring greater than 18 h incubation. With this technique a large range of antibacterial substances (greater than 60) can be studied, in groups of fifteen. With the help of a computerized soft-ware, one growth-index:EPR (End Point Ratio) is calculated, in comparison with a standard, for each antibacterial agent tested and expressed in three categories: SIR. The findings are optimized according to the limits prescribed by the NCCLS. The reference method, by agar-diffusion, is as described by the Comité de l'Antibiogramme de la Société Française de Microbiologie (CA-SFM). A total of 1,048 strains were tested by the two techniques: 518 Gram negative rods, 530 Gram positive cocci, with four common antibiotics. The percentages of agreement between the two groups were: 96% full agreement and minor discrepancy, 4% major and very major discrepancy. This automated system seems to be perfectly suitable for susceptibility testing in a routine laboratory, especially with strains isolated from ambulatory patients.

Anti-Bacterial Agents↗