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Biomedical subjects

F Giraud

Publications and source records attributed to F Giraud.

At least 91 records · Page 5Linked to original sources
PubMed1988

Stimulation of polyphosphoinositide turnover upon activation of protein kinases in human erythrocytes.

Activation of protein kinase C in erythrocytes by 4-beta-phorbol 12-myristate 13-acetate (PMA) resulted in a parallel stimulation (time course and dose response) of the phosphorylation of both membrane proteins (heterodimers of 107 kDa and 97 kDa, protein 4.1 and 4.9, respectively) and of phosphatidylinositol 4-phosphate (PIP) and, to a lesser extent, of phosphatidylinositol 4,5-bisphosphate (PIP2). Evidence that the effect on lipid was mediated by protein kinase C activation and not by a direct action of PMA was provided by (1) the lack of effect of a phorbol ester that did not activate protein kinase C or of PMA addition on isolated membranes from control erythrocytes, (2) the reversal of the effect in the presence of protein kinase C inhibitors (alpha-cobrotoxin, H-7 (1-(5-isoquinolinesulfonyl)-2-methylpiperazine) or trifluoperazine). PMA treatment did not change the specific activity of ATP or the content of PIP2, but increased the content of PIP and decreased that of PI, indicating that the phosphorylation or dephosphorylation reactions linking PI and PIP were the target for the action of PMA. PMA treatment had no effect on the Ca2+-dependent PIP/PIP2 phospholipase C activity measured in isolated membranes. Mezerein, another protein kinase activator, had similar effects on both protein and lipid phosphorylation, when added with alpha-cobrotoxin. Activation of protein kinase A by cAMP also produced increases in phosphorylation, although quantitatively different from those induced by protein kinase C, in proteins and PIP. Simultaneous addition of PMA and cAMP at maximal doses resulted in only a partially additive effect on PIP labelling. These results show that inositol lipid turnover can be modulated by a protein kinase C and protein kinase A-dependent process involving the phosphorylation of a common protein. This could be PI kinase or PIP phosphatase or another protein regulating the activity of these enzymes.

Adenosine Triphosphate↗
PubMed1988

The acrocallosal syndrome.

The acrocallosal syndrome is characterized by peculiar facies, polydactyly of the hands and/or feet, and agenesis of the corpus callosum. Two unrelated 4-month-old boys with consanguineous parents are reported. Both exhibited the main features of the syndrome, but neither of them had partial reduplication of halluces. Consequently, pre-axial polydactyly of the feet is not considered to be a constant feature of the acrocallosal syndrome. The similarity of the acrocallosal syndrome to Greig syndrome is discussed, but it appears unlikely that the two syndromes are identical. Consanguinity in both cases is a strong argument in favour of a recessive mode of inheritance.

Agenesis of Corpus Callosum↗
PubMed1988

Achondroplasia in sibs of normal parents.

A new case of recurrent achondroplasia in sibs of normal parents is reported. Two sisters and a half sister were affected. Various mechanisms can be postulated to account for unexpected recurrence of achondroplasia in the same sibship. Germinal mosaicism and unstable premutation are discussed here.

Achondroplasia↗
PubMed1988

[Balanced chromosome rearrangements with abnormal phenotype].

27 cases in which apparent balanced chromosomal rearrangements (reciprocal and translocations and pericentric inversions) are associated with phenotypic abnormalities are reported and compared with the previous published cases. Almost all patients display mental retardation and a non specific dysmorphism. Genetic counseling is different whether the abnormality is inherited or de novo. When an unexpected structural rearrangements is found in fetal cells, the attitude depends on the results of the parent's chromosomal study.

Chromosome Aberrations↗
PubMed1987

Stimulation of the 23-Kd protein cAMP dependent phosphorylation by inositol 1,4,5 trisphosphate in human platelet membrane vesicles.

The effect of inositol 1,4,5 trisphosphate (IP3) has been investigated on the cAMP-induced phosphorylation of the 23-Kd protein involved in platelet calcium fluxes by isolated membrane vesicles. The studies were conducted using the catalytic subunit of the cAMP-dependent protein kinase (C. Sub.). A dose-dependent stimulation of the 23 Kd protein phosphorylation induced by C. Sub. was initiated by IP3 with a half-maximal effect of 0.5 microM. The maximal effect was observed after 1-2 min. The effect was detected in the absence of Ca2+ and in the presence of phosphatase inhibitors. These results can suggest that the 23 Kd is an associated protein to the IP3 receptor in human platelets.

Blood Platelets↗
PubMed1987

Possible role of a cAMP-dependent phosphorylation in the calcium release mediated by inositol 1,4,5-trisphosphate in human platelet membrane vesicles.

The addition of inositol 1,4,5-trisphosphate (IP3) to a 45Ca-preloaded human platelet membrane fraction (dense tubular system) induced a transient release of Ca2+. When the vesicle fraction was loaded with 45Ca2+ to isotopic equilibrium in the presence of the catalytic subunit of the cAMP-dependent protein kinase, the level of Ca2+ uptake was increased and the subsequent IP3-induced Ca2+ release was enhanced. The stimulation was observed regardless of the IP3 concentration used, and was maximal with an enzyme concentration of 5 micrograms/ml. The addition of the protein kinase inhibitor prevented the stimulatory effect of the catalytic subunit on IP3-induced calcium release, and also abolished the calcium release detected in the absence of added enzyme. It is concluded that a cAMP-dependent protein phosphorylation may be involved in the regulation of the IP3-induced Ca2+ release in human platelets.

Blood Platelets↗
PubMed1987

Relationship between cAMP and Ca2+ fluxes in human platelet membranes.

The effect of cAMP (which involved a 23 kDa protein phosphorylation) has been studied on the Ca2+ uptake and Ca2+ release from a human platelet membrane vesicle fraction. It was tested in the presence of the catalytic subunit of the cAMP-dependent protein kinase (C Sub). The addition of C Sub increased the steady state level of the Ca2+ uptake into the membrane vesicles. The effect was enhanced when tested in the absence of Ca2+ precipitating agent. The response was proportional to the dose of C Sub. Moreover, the effect varied with the Ca2+ concentration. The effect of C Sub has been tested on the inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release. A phosphorylated state of the 23 kDa protein appeared to be necessary. Indeed, a phosphorylation inhibition prevented the IP3 effect and the addition of C Sub increased the percentage of released Ca2+ (without modification of the time course). However, the C Sub dose-dependent response was not linear. The effect of cAMP on the two functions (Ca2+ uptake and Ca2+ release) appears to be different. Therefore, these results led us to suggest a more complex role of cAMP in the regulation of platelet Ca2+ concentration.

Blood Platelets↗
PubMed1987

[Social diffusion of genetic counseling in the Provence Alpes-Côte d'Azur region].

Accessibility to medical care in general, and to new techniques in particular, is unequal as much from a social as a geographical standpoint. We have reconstituted the geographical distribution network for genetic consultation at Marseilles for consultees having benefitted from genetic counselling in 1983 (984 files). For the region (except the Alpes Maritimes) the incidence rate for this consultation was 13.6 per 10,000 women of child bearing age. A parallel study of doctors participating in the recruitment of these patients objectifies the essential role of obstetricians, gynaecologists as well as general practitioners and shows different directions for training and data for the medical profession liable to contribute to better prevention of handicaps of genetic origin.

Female↗
PubMed1987

Ca2+ permeability and cytosolic Ca2+ concentration are not impaired in beta-thalassemic and hemoglobin C erythrocytes.

Total calcium content, determined by atomic absorption spectroscopy, Ca2+ influx, and cytosolic free Ca2+ concentration ( [Ca]i), estimated by a method involving the incorporation of a Ca2+ chelator (Quin 2), were measured in erythrocytes from beta-thalassemic (beta-thal) and hemoglobin C (CC) patients. Elevation of the total calcium content was observed in the cells from all patients, particularly in CC and splenectomized beta-thal. However, [Ca]i was within the normal range (approximately 25 nmol/L) in all the pathologic cells. Ca2+ influx in CC cells and in cells from nonsplenectomized beta-thal patients was also within the same range as that observed in control erythrocytes. In cells from splenectomized beta-thal patients, the kinetic of 45Ca influx was biphasic, indicating the existence of two pools of exchangeable Ca2+. Density fractionation of the cells from one splenectomized beta-thal patient showed that the rapid pool corresponded to the lightest cell fraction, which was also found to have the highest calcium content. The dense cells exhibited a normal Ca2+ influx as well as a smaller increase in total calcium content. It is suggested that, as in sickle cell anemia, the excess of Ca2+ in beta-thal cells is not free in the cytoplasm but trapped within endocytic vacuoles, especially in a population of abnormal cells that are normally removed by the spleen. In CC patients, who have a functional spleen, a different mechanism could be responsible for the calcium retention. In conclusion, the present results demonstrate that in these two cases of hemolytic anemia associated with high calcium content, Ca2+ permeability and the the level of cytosolic Ca2+ are normal.

Adenosine Triphosphate↗
PubMed1986

Cholesterol depletion affects the Ca2+ influx but not the Ca2+ pump in human erythrocytes.

Control and cholesterol-depleted human erythrocytes were loaded with permeant Ca2+ chelators (Benz2-AM or Quin2-AM) in order to increase their exchangeable Ca2+ pool and to measure both Ca2+ fluxes and [Ca]i (free cytoplasmic calcium concentration). The fluxes were independent of the concentration and of the nature of the intracellular chelator. The ATP content was not decreased by more than 50% under our experimental conditions. Cholesterol depletion (up to 28%) induced a decrease in both Ca2+ fluxes and [Ca]i which was proportional to the extent of the depletion. It is shown that cholesterol depletion primarily altered the properties of the system responsible for Ca2+ entry causing a diminution of the [Ca]i. This, in turn, induced a diminution of the activity of the Ca2+ pump without affecting the properties of this pump.

Adenosine Triphosphate↗
PubMed1986

Phosphoinositide reorganization in human erythrocyte membrane upon cholesterol depletion.

The effect of cholesterol depletion on the activity of phosphatidylinositol/phosphatidylinositol 4-phosphate and diacylglycerol kinases and polyphosphoinositide phosphodiesterase has been studied in isolated membranes of human normal and cholesterol-depleted erythrocytes. Polyphosphoinositide synthesis (phosphatidylinositol/phosphatidylinositol 4-phosphate kinase activities) were found to depend on the permeability and sidedness characteristics of the membrane vesicles, which could limit the accessibility of ATP for the enzymes. When measured under proper conditions, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate synthesis were decreased in cholesterol-depleted membranes as compared with control membranes. The same level of synthesis could be obtained in both membranes by the addition of phosphatidylinositol (and Triton X-100) or of phosphatidylinositol 4-phosphate. Phosphatidic acid synthesis (diacylglycerol kinase activity) was also decreased in cholesterol-depleted membranes as compared with control membranes when measured in the presence of Ca2+. Addition of diolein (and Triton X-100) caused a large increase in phosphatidic acid synthesis which reached approximately the same level in both membranes. This showed that the apparent inhibition of polyphosphoinositide and phosphatidic acid synthesis was not due to a loss or to an inactivation of the kinases. Ca2+-activated polyphosphoinositide phosphodiesterase promoted the hydrolysis of 65-70% of the polyphosphoinositides in control and of only 45-55% in cholesterol-depleted membranes without changing the Ca2+ concentration for half-maximum hydrolysis (1 microM). Upon addition of sodium oleate, the extent of polyphosphoinositide hydrolysis became identical in both membranes, indicating again that there was no loss nor inactivation of the polyphosphoinositide phosphodiesterase in the cholesterol-depleted membranes. Since the concentration of the polyphosphoinositides was not changed by cholesterol depletion [Giraud, M'Zali, Chailley & Mazet (1984) Biochim. Biophys. Acta 778, 191-200], the reduction in both their synthesis and degradation observed here could be attributed to a reorganization of the phosphoinositides in membrane domains where they were not accessible to the kinases and phosphodiesterase. The reduction in phosphatidic acid synthesis was likely caused by a reduction in the total amount of the substrate diacylglycerol in cholesterol-depleted membranes as already shown [Giraud, M'Zali, Chailley & Mazet (1984) Biochim. Biophys. Acta 778, 191-200].

Calcium↗
PubMed1986

Inositol trisphosphate-induced Ca2+ release from rat parotid subcellular fractions.

Inositol trisphosphate (IP3) has been shown to induce a release of sequestered calcium in a large (7,000-48,000 g) microsomal fraction isolated from rat parotid gland. This effect was also observed after the calcium uptake had been stopped by EGTA and thus was not the result of an inhibition of the active calcium transport. IP3-induced Ca2+ release was also demonstrated in a more purified microsomal fraction (16,000-48,000 g) apparently free of mitochondria, and in a fraction enriched in rough endoplasmic reticulum markers. These results support the hypothesis that IP3 may be a second messenger for intracellular calcium mobilization during stimulation of the parotid gland by calcium mobilising agonists.

Animals↗
PubMed1986

[Massive digestive hemorrhage caused by aorto-esophageal fistula].

A very rare diagnosis before a terminal hemorrhagic accident, aorto-esophageal fistula (FAO) is almost always fatal. Three cases of this exceptional lesion are reported. The first patient died within a few minutes of admission from a cataclysmic hematemesis. This 52 year old man had a recurring adenocarcinoma of the cardia that had been treated by laser. A "premonitory hematemesis" of bright red blood had occurred eight hours before admission. In the two other cases the problem arose with an "open abdomen" in exsanguinated patients operated upon as emergencies for massive hematemesis. In both cases, an intra-esophageal balloon catheter and controlled hypotension allowed performance of a left thoracotomy and aortic clamping. One patient had a cancer of middle third of esophagus that had perforated into the descending aorta. A resection-graft of the aortic isthmus and a retrosternal gastric esophagoplasty was successfully carried out at the time of exploration. The other patient had an FAO in the aortic isthmus region probably due to a foreign body. Operation involved an esophagectomy with cervical esophagotomy and gastrotomy combined with a resection-graft of aortic isthmus using a Dacron prosthesis. This patient died on the 21st postoperative day from rupture of the brachiocephalic trunk over a tracheotomy tube. In both of these patients a "premonitory hematemesis" with dysphagia had preceded the severe hemorrhagic accident. Successful treatment is rarely obtained with such lesions, since difficulties in ensuring rapid hemostasis in exsanguinated patients operated upon usually without diagnosis and for massive hemorrhage only, are associated with the risks of aortic repair surgery in a hemorrhagic field and with a mediastinum infected from the esophageal wound.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

[Dissemination of genetic counseling and prenatal diagnosis: impact of the physicians' knowledge].

This article presents a survey carried out among 2,549 doctors (general practitioners, pediatricians, obstetricians and gynecologists) practicing in two south of France "departements" (administrative subdivisions): Bouches-du-Rhône and Hautes-Alpes. The influence of socio-demographic and professional characteristics on knowledge of prenatal diagnosis indicators is studied here for each specialty. While knowledge among general practitioners is apparently a product of their formal education, among gynecologists and obstetricians the most important factor seems to be professional experience. In France, the GP is a central figure in referrals for genetic counselling and prenatal diagnosis, hence the importance of improving his training and possibilities of continuing education.

Adult↗
PubMed1985

The measurement in vivo of the rate of unesterified cholesterol exchange between rat plasma and erythrocytes.

In order to investigate the rate of unesterified cholesterol exchange between plasma and erythrocytes in vivo, cholesterol labelling in rats was achieved in one of the following ways: intravenous injection of cholesterol-labelled erythrocytes, subcutaneous injection of labelled acetate, feeding of labelled cholesterol. The specific activity of the unesterified cholesterol was measured at intervals up to 24 h and a kinetic analysis of the data was performed. It assumes that both the cholesterol in the erythrocytes and the unesterified cholesterol in the plasma were homogeneous pools. The rate constants obtained for the movements of unesterified cholesterol from erythrocytes to plasma and from plasma to erythrocytes were not significantly different in the three labelling conditions (mean values: 0.26 and 1.5 h-1, respectively).

Animals↗
PubMed1985

Inositol 1,4,5-triphosphate microinjection triggers activation, but not meiotic maturation in amphibian and starfish oocytes.

Inositol 3,4,5-triphosphate (InsP3) brought about cortical granule exocytosis and elevation of a fertilization membrane, due to a rapid increase of free calcium in cytoplasm, when injected into oocytes of the amphibian Xenopus laevis arrested at second meiotic metaphase. The same result was observed when injection was performed into oocytes of the starfish Marthasterias glacialis arrested either at the first meiotic prophase or after completion of meiosis. Although meiotic maturation was induced in both animals by specific hormones which have been previously shown to release Ca2+ within cytoplasm, InsP3 microinjection into prophase-arrested oocytes did not release them from prophase block.

Adenine↗