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F Gauthier

Publications and source records attributed to F Gauthier.

At least 145 records · Page 8Linked to original sources
PubMed1990

Current French system of post-marketing drug surveillance.

The French system of drug surveillance is characterized by several original features: thirty regional centres are selected to cover all of France to collect, analyze and enter the adverse drug events in the national data bank. The system is based on a bank of well documented files submitted to a decision of imputation; the report of severe events by prescribers is mandatory; cases are collected either by spontaneous reporting (routine) or by direct request (intensive validation study); the system is being involved in studies of epidemiological type as carried out by the national system of health or a few societies of medicine as well as by the centres themselves in cooperative works on defined populations.

Drug-Related Side Effects and Adverse Reactions↗
PubMed1989

The cDNA structure and expression analysis of the genes for the cysteine proteinase inhibitor cystatin C and for beta 2-microglobulin in rat brain.

Tissue patterns of gene expression were analyzed by measuring mRNA levels and incorporation of radioactive amino acids for cystatin C and beta 2-microglobulin, the two extracellular proteins in the brain with the highest ratio of concentration in cerebrospinal fluid over that in blood plasma. The primary structure of rat cystatin C mRNA from choroid plexus was determined by nucleotide sequencing of cloned cDNA and the tissue patterns of gene expression were analysed by RNA blot analysis and in situ hybridization. Cystatin C was found to be composed of 120 amino acids and to contain a potential site for N-linked glycosylation. The tissue with the highest cystatin C mRNA level was the choroid plexus of the brain. Cystatin C mRNA was also detected in lower levels in other areas of the brain, testis, epididymis, seminal vesicles, prostate, ovary, submandibular gland, and, in trace amounts, in liver. Choroid plexus pieces in culture secreted radioactive cystatin C when incubated with radioactive leucine. Rat beta 2-microglobulin cDNA was cloned and identified by nucleotide sequencing and comparison of the obtained sequence with that of mouse and human beta 2-microglobulin cDNA. Tissue levels of beta 2-microglobulin mRNA in the rat were measured by hybridization to rat beta 2-microglobulin cDNA. The highest levels of beta 2-microglobulin mRNA were observed in liver and choroid plexus. Other parts of the brain and testis contained lower levels of beta 2-microglobulin mRNA.

Amino Acid Sequence↗
PubMed1989

[Rapid liver perfusion in multiple organ procurement in children. For liver transplantation].

We report our experience of the rapid liver flush technique in multiple organ harvesting from donor children. Between January 1988 and May 1989, out of 33 liver transplantations in 30 children, 24 were performed using livers obtained from children. The donors' mean age was 75 months. In every case several organs were removed (24 kidneys, 9 heart-lung blocks, 9 hearts, 1 pancreas). The mean duration of the procedure was 153 minutes. Supernumerary hepatic vessels (6 left and 2 right hepatic arteries) were left intact. Twenty-two hepatic grafts were classified as functional. Two grafts classified as non-functional were responsible for 2 deaths in this series. The rapid liver flush technique seems to be satisfactory in donor children when the following characteristics are taken into account: tendency to haemodynamic instability, small caliber of the vessels and fragility of tissues.

Adolescent↗
PubMed1989

High-molecular-mass proteinases in rabbit reticulocytes: the multicatalytic proteinase is an ATP-independent enzyme and ATP-activated proteolysis is in part associated with a cysteine proteinase complexed to alpha 1-macroglobulin.

We have investigated the proteolytic degradation of [14C]methylcasein and 125I-labeled bovine serum albumin at pH 7.8 and 37 degrees C by lysates of rabbit reticulocytes purified from rabbit blood by two different procedures. (I) Lysates obtained from reticulocytes after removal of plasma and buffy coat as well as after washing of cells, degraded casein and albumin, and released from the two substrates 1.3%/h and 0.4%/h, respectively, of acid-soluble radioactivity. The activity towards both substrates was stimulated about 4-fold by ATP/Mg2+. Chromatography of whole blood on a column of cellulose prior to washing and lysis of cells had profound but differential effects on these activities in that stimulation of casein-degradation by ATP/Mg2+ was almost completely lost, whereas degradation of albumin, albeit at a low rate, was measurable in the presence of ATP/Mg2+ only. (II) Degradation of casein by these lysates is largely inhibited by a monospecific antibody against rabbit multicatalytic proteinase, whereas digestion of albumin is not affected by the antibody, either in the presence or absence of ATP/Mg2+. The latter activity is partially inhibited by a specific antibody against rabbit alpha 1-macroglobulin. (III) The immunoreactive amount of multicatalytic proteinase is about 1.2 micrograms per mg of lysate protein and almost identical in the two lysates. In contrast, the immunologically detectable levels of alpha 1-macroglobulin vary and are much lower in reticulocyte-lysates following chromatography on cellulose than in lysates from washed reticulocytes. (IV) Caseinolytic activity of multicatalytic proteinase, purified from rabbit reticulocyte lysate, is not activated by ATP/Mg2+ and the enzyme is proteolytically inactive towards albumin. On the other hand, a complex consisting of the proteinase inhibitor alpha 1-macroglobulin and the cysteine proteinase, cathepsin B, does degrade both substrates at pH 7.8, in an ATP/Mg2+-activated fashion. From these results it is concluded that the multicatalytic proteinase is an ATP-independent enzyme and a cellular constituent of rabbit reticulocytes whereas the activity stimulated by ATP/Mg2+ appears to be associated, at least in part, with a cysteine proteinase complexed to alpha 1-macroglobulin.

Adenosine Triphosphate↗
PubMed1989

Limited proteolysis of T-kininogen (thiostatin). Release of comparable fragments by different endopeptidases.

Limited proteolysis of T-kininogen by heterologous and homologous endopeptidases (bovine trypsin, human leukocyte elastase, rat submaxillary gland endopeptidase k, and rat mast cell chymase) produced similar fragmentation. Amino-terminal sequence analysis of whole T-kininogen lysates and purified proteolytic fragments identified four susceptible regions which contained all the preferential cleavage sites for these proteinases. Two of these susceptible regions were close to the junction between heavy chain cystatin-like domains, the third was in the kinin-containing region, and the fourth was close to the carboxyl terminus of the T-kininogen light chain. There was only one primary site for each proteinase in the kinin-containing region, which explains why catalytic amounts of these proteinases did not release immunoreactive kinin from this kininogen. However, preferential cleavage of T-kininogen close to the junction between cystatin-like domains released fragments which, provided they included cystatin-like domains 2 and/or 3, strongly inhibited papain and cathepsin L. The fragments were inhibitory even when parts of the amino-terminal ends of the domains were lacking. The highly conserved glycyl residue, thought to be involved in the inhibitory reactive site of cystatin-like inhibitors, was not required in purified domain 3 for inhibition of cathepsin L.

Amino Acid Sequence↗
PubMed1989

Radiological treatment of common bile duct lithiasis in infancy.

The authors report a series of 10 infants aged from 20 days to 11 months, presenting with CBD lithiasis, explored and cured by radiological procedure. US showed BD dilatation in 9 cases, sludge in the GB in 5 and in the CBD in 2. Histological findings of cholangitis were present in 4 infants. PTC was performed by GB puncture in 6 and BD puncture in 4. There was evidence of a filling defect in CBD but no anatomical anomaly. Blackish concretions were removed through a side-holes catheter or pushed in the duodenum by washing with saline. An external drainage was left a few days to allow control cholangiogram. Three infants underwent subsequent surgery but no residual lithiasis was found. No recurrence has occurred with a follow-up ranging from 10 months to 7 years. Mechanisms of this entity are discussed.

Diagnosis, Differential↗
PubMed1989

H-type shunt with an autologous venous graft for treatment of portal hypertension in children.

From 1981 to 1987, 86 children aged 16 months to 16 years underwent a portosystemic shunt procedure using an autologous venous graft (internal jugular vein in 80 cases). Fifty-five mesocaval, 20 splenorenal, 4 portacaval, and 7 makeshift shunts were constructed. The indication for shunting was an extrahepatic portal obstruction in 59 cases, intrahepatic portal obstruction in 23 cases (including 6 cases of congenital hepatic fibrosis), and Budd-Chiari syndrome in 4 cases. One patient of the latter group died early from intractable ascites with a nonfunctioning shunt, and a second child died 2 months after operation from unknown reasons with a patent shunt. With a follow-up over 1 year for 58 of the 84 survivors, 78 successes and 6 failures were recorded according to the clinical outcome and the findings of ultrasonic and endoscopic examinations. Three of the six children with a failed shunt have been submitted to a second successful H-type shunt operation. No case of encephalopathy was recorded in this series. Thus, with an approximate success rate of 95%, the H-type shunt with a venous graft should be recommended for treatment of portal hypertension of extrahepatic origin, especially in young children.

Adolescent↗
PubMed1988

Two rat homologues of human cystatin C.

Two immunochemically related forms of cystatin C-like inhibitors which differ in their Mr app and isoelectric point have been found both in urine and seminal vesicles of rats. Amino-terminal sequences of these two cystatins are identical within the same fluid and exhibit a high degree of homology with that of human cystatin C. However, cystatins C purified from urine lack eight residues at their amino-terminal end when compared to those of seminal vesicles. The occurrence of two cystatin C-like components in rat fluids has been found to be due to the presence of a glycosylated form reported here as cystatin Cg which specifically binds concanavalin A and is susceptible to endo-beta-N-acetylglucosaminidase treatment.

Amino Acid Sequence↗
PubMed1988

Cysteine-proteinase-inhibiting function of T kininogen and of its proteolytic fragments.

Previous attempts to liberate T kinin from T kininogen [Moreau et al. (1986) Eur. J. Biochem. 159, 341-346; Gutman et al. (1988) Eur. J. Biochem. 171, 577-582] have shown that complete fragmentation of the precursor molecule into inhibitory peptides was achieved before any vasoactive peptide was released, suggesting a possible physiological significance for this phenomenon. In this study, cysteine-proteinase-inhibiting properties of rat T kininogen and of its proteolytic fragments issuing from trypsin and submaxillary gland endopeptidase k hydrolysis, have been investigated using rat lysosomal cathepsins B, H and L, papain and bovine calpains I and II. All three lysosomal cathepsins were inhibited by T kininogen but tighter interactions were observed with cathepsin L and papain. Though higher Ki values were obtained for cathepsins B and H, rate constants for association were found to have high and almost similar values (in the 10(6) M-1 s-1 range) whatever the enzyme used. Proteolytic fragments also inhibited cathepsin L and papain very strongly and even better than the entire molecule for some of them, but no significant inhibition of cathepsins B and H was observed. Bovine calpains were not inhibited by T kininogen nor by its proteolytic fragments. From the results of this kinetic analysis, which indicates that both the association and the dissociation of lysosomal cysteine proteinases with T kininogen may occur rapidly, an hypothesis has been put forward on the possible in vivo functioning of T kininogen as a proteinase inhibitor.

Amino Acid Sequence↗
PubMed1988

T-kinin release from T-kininogen by rat-submaxillary-gland endopeptidase K.

Submaxillary gland extracts have been fractionated to characterize the enzyme responsible for the T-kininogenase activity previously reported in this tissue [Damas, J. & Adam, A. (1985) Mol. Physiol 8, 307-316] and to know whether this activity could be of physiological relevance, since no enzyme reacting in catalytic amounts has been described so far to be able to release a vasoactive peptide from T-kininogen. The purified enzyme, provisionally called endopeptidase K, has an apparent Mr of 27,000 when not reduced prior to analysis but 21,000 after reduction and an acidic pI of 4.3 +/- 0.1. Antigenically, it is not related to tissue kallikrein. Upon incubation with purified T-kininogen it may induce a complete liberation of T-kinin from the precursor provided it is added in stoichiometric amounts. However, in parallel with the liberation of immunoreactive kinin, a proteolysis of T-kininogen is observed which is not restricted to the site of insertion of T-kinin as would be expected using a specific kininogenase. In agreement with these results, no change of the mean blood pressure was observed upon injection of endopeptidase K into the circulation of normal rats even if the amount of injected enzyme was up to ten times that required for tissue kallikrein to induce a significant fall in blood pressure. However, in spite of the large proteolysis induced by incubation with stoichiometric amounts of endopeptidase K, the total papain inhibiting capacity of T-kininogen as well as the value of the apparent inhibition constant, Ki, with this proteinase remained unchanged. Proteolytic fragments which retain cysteine-proteinase-inhibiting activity may therefore be released from T-kininogen by endopeptidase K more easily than immunoreactive kinin, thus emphasizing a prominent function of proteinase inhibitor or of proteinase inhibitor precursor for this molecule.

Amino Acids↗
PubMed1988

Value of serum transthyretin measurements in the assessment of marginal protein-energy malnutrition in rats.

The influence of a wide range of protein and/or energy intakes on the serum level of rat transthyretin was studied. Young and adult rats were fed ad libitum diets containing 18, 9, 6, 4 and 0.5% protein (wt/wt) or were fed a control diet in restricted amounts. The transthyretin level was lower in young rats and was normal or slightly higher in adult rats fed low protein diets than in those fed the 18% protein diet. It was decreased with decreasing energy intake in all energy-restricted rats. Moderate energy restriction in rats fed equivalent amounts of protein also lowered the transthyretin level. Rats with similar body weights and similar protein intakes showed marked differences in serum transthyretin level, depending on the amount of energy consumed. Serum transthyretin changes were discussed in relation to the level of transthyretin in cerebrospinal fluid and to the serum concentration of albumin, transferrin and thyroid hormones. The results show that serum transthyretin is more closely related to the protein and energy intakes than to the protein and energy content of the diet. Our results indicate that serum transthyretin measurement is a reliable marker in the detection of early moderate and severe protein-energy restriction.

Animals↗
PubMed1988

[Surgery of hepatoblastoma and hepatocarcinoma in children in the era of preoperative chemotherapy. Current progress and limitations].

Twenty seven children aged 1 to 15 years were admitted from 1981 to 1987 for the investigation and/or the surgical treatment of a primary liver malignancy (25 hepatoblastomas and 2 hepatocellular carcinomas). All were submitted to preoperative multidrug chemotherapy. One child died from circulatory failure early after the diagnosis and two children considered to be non operable died also. A macroscopically satisfactory resection could be achieved in 24/27 cases. Sixteen out of these 24 children are alive and disease free, 11 of them with a follow-up over 2 years. Two of these 16 survivors underwent a second operation for resection of a local recurrence. Four children died after a massive unresectable hepatic relapse, two after a second relapse and a one after the onset of pulmonary metastases during her chemotherapeutic postoperative course. One further child is at yet in a critical situation because of a late small secondary hepatic relapse. Two factors contributed to improvement of survival an cure rates during the past ten years: 1. Routine preoperative chemotherapy, which may help in controlling the disease and greatly facilitates surgery by shrinking of massive tumors. 2. Better surgical management and especially the total hepatic vascular exclusion, used in 13 cases of this series. Three situations still have a poor outlook: 1. Hepatocellular carcinoma 2. Hepatoblastoma with a low response to chemotherapy 3. Multifocal tumors and those involving the main hepatic vessels. The feasibility of a liver transplantation in some selected cases is discussed.

Adolescent↗