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Biomedical subjects

F Gauthier

Publications and source records attributed to F Gauthier.

At least 163 records · Page 9Linked to original sources
PubMed1988

Purification of the cystatin C-like inhibitors from urine of nephropathic rats.

Two cysteine proteinase inhibitors of the cystatin C type have been purified from urine of sodium chromate-treated rats. Both strongly inhibit papain as well as rat liver cathepsin L (Ki less than 10(-11) M) whereas rat liver cathepsins B and H are inhibited to a lesser extent. They differ by their apparent molecular mass of 17 kDa and 22 kDa and by their isoelectric point greater than or equal to 9.5 and 7.7 respectively. These two molecules share complete immunochemical identity and are precipitated by antibodies directed against human cystatin C but not by anti rat thiostatin and anti rat H-kininogen antibodies. They are also found in large amounts in seminal vesicles where they represent most of the cysteine proteinase inhibitory capacity.

Animals↗
PubMed1988

Possible relationship between the restricted biological function of rat T kininogen (thiostatin) and its behaviour as an acute phase reactant.

Studies on biological properties of rat T kininogen have shown that the role of this peculiar kininogen so far specific to the rat probably differs significantly from that of other low molecular mass kininogens. In particular the kinin precursor function has been either lost or considerably reduced as a result of structural modifications during evolution. The calpain inhibiting function demonstrated for other low and high molecular mass kininogens has also probably disappeared from T kininogen, and since T genes do not allow the synthesis of high molecular mass kininogens [Kitagawa et al. (1987) J. Biol. Chem. 262, 2190-2198], the procoagulant function devoted to the light chain of high molecular mass kininogen has also been lost by T genes products. The only remaining function of rat T kininogen would be therefore that of a lysosomal cysteine proteinase inhibitor which is expressed either by the native molecule or by proteolytic products which appear to be more easily released than vasoactive peptides. Such a specialization for a given function could be related to the behaviour of T kininogen as an acute phase reactant, the dramatic changes in concentration of which could at the same time serve certain functions and be damageable for others.

Acute-Phase Reaction↗
PubMed1987

Biosynthesis and regulation of rat alpha 1-inhibitor3, a negative acute-phase reactant of the macroglobulin family.

The biosynthesis of rat alpha 1-inhibitor3, a negative acute-phase reactant specifically found in rodents, was studied in vitro in a cell-free translation system from rabbit reticulocytes, in rat hepatocyte primary cultures and in vivo by immunocytochemistry using normal and turpentine-injected rats. By sucrose-gradient centrifugation and subsequent translation of the fractionated RNA in vitro it was found that the mRNA coding for alpha 1-inhibitor3 exhibited a size of about 28S. For the alpha 1-inhibitor3 translated in vitro an apparent Mr of 155,000 was determined. A continuous decrease in the level of alpha 1-inhibitor3 in serum during experimental inflammation induced by turpentine injection was demonstrated by means of quantitative 'rocket' immunoelectrophoresis. This result agrees with the observation by immunocytochemistry of a drastic decrease in alpha 1-inhibitor3 levels in hepatocytes 24 h after turpentine injection. At that time alpha 1-inhibitor3 is mainly located in the Golgi apparatus, whereas it is also present in the membranes of the rough and smooth endoplasmic reticulum when normal liver is used. All hepatocytes, but no other hepatic cells, contain alpha 1-inhibitor3. When hepatocyte primary cultures were labelled with [35S]methionine and alpha 1-inhibitor3 was immunoprecipitated from the hepatocyte medium and the supernatant of homogenized cells, two different forms of alpha 1-inhibitor3 were found. The intracellular form of alpha 1-inhibitor3, with an apparent Mr of 173,000, is characterized by oligosaccharide side chains of the high-mannose type. The form of alpha 1-inhibitor3 in the medium exhibited an Mr of 186,000 and carried carbohydrate side chains of the complex type. After labelling hepatocytes with radioactive sugars, [3H]mannose was found in both forms of alpha 1-inhibitor3, whereas [3H]fucose and [3H]galactose were incorporated only into the form found in the medium. In the presence of tunicamycin an unglycosylated alpha 1-inhibitor3 with an apparent Mr of 154,000 was found in cells and in the medium. In a pulse-chase experiment it was shown that inhibition of glycosylation by tunicamycin resulted in a marked delay of secretion of alpha 1-inhibitor3. Thus the oligosaccharide side chains of alpha 1-inhibitor3 play an important role during its transport into the medium.

Acute-Phase Proteins↗
PubMed1987

Identification and sequencing of cDNA clones for the rodent negative acute-phase protein alpha 1-inhibitor 3.

Rat alpha 1-inhibitor 3 clones were isolated by immunological screening of a lambda gt11 cDNA library prepared from rat liver poly(A)-rich RNA. The recombinant cDNA clones were identified by the absence of their immunoprecipitable products following hybrid-arrested in vitro translation. The size of the cognate poly(A)-rich RNA was estimated to be roughly 5000 residues. Approximately 16 h after induction of inflammation the amount of alpha 1-inhibitor 3 poly(A)-rich RNA decreases as shown by dot-blot hybridization and Northern analyses. The response of this negative acute-phase plasma protein to inflammation may therefore be considered to be at the pretranslational level. The characterized DNA constitutes an open reading frame of 225 amino acids followed by a canonical eucaryotic polyadenylation signal and a poly(A) tail. Sequence microheterogeneity, particularly in the 3'-flanking region was observed. An amino acid homology of 70% for alpha 1-inhibitor 3 with human and rodent alpha 2-macroglobulin emphasizes the evolutionary relationship of the macroglobulins.

Acute-Phase Proteins↗
PubMed1987

Bilio-pancreatic common channel in children. Clinical, biological and radiological findings in 12 children.

Twelve patients (11 girls and 1 boy) with dilated bile ducts and anomalous junction between the common bile duct and pancreatic duct are reported. All patients underwent preoperative opacification of the bile ducts either by transhepatic cholangiography or percutaneous cholecystography. Abdominal pain and jaundice were the main clinical symptoms. Reflux of pancreatic enzymes in the bile duct was proven by measuring amylase and lipase activity in the biliary system after IV injection of 1 IU/kg of cholecystokinin. All patients were operated upon. Bile ducts size returned to normal in all patients who are clinical well with a follow-up from 1 to 6 years.

Adolescent↗
PubMed1987

Second operation for repair of biliary atresia.

In our experience with biliary atresia, there are few cases amenable to reoperation for recurrent jaundice. All authors would agree that specific conditions such as complete bile flow recovery from the first operation followed by early recurrence should be an unquestionable case for revision of the anastomosis, inasmuch as no biologic signs of ongoing cholangitis can be traced. The same decision would apply to the problem of bile leakage after hepatoportocholecystostomy. In other cases, however, one should be aware that these reoperations expose the child to ascitis, poor healing of the abdominal wound, liver failure, and also bring with the decision to reoperate undue hopes to the parents of the child. Moreover, if the child should be a future candidate for liver transplantation, it may be wiser to avoid useless laparotomies and abdominal dissections that are known to complicate the task of hepatectomy.

Biliary Atresia↗
PubMed1987

[Management of uropathies diagnosed prenatally. Discussion based on a series of 53 cases].

From 1982 to 1986, 53 newborns (26 boys and 27 girls) were referred to the authors for the management of a congenital anomaly of the urinary tract, following a prenatal ultrasonographic diagnosis. The postnatal diagnosis was hydronephrosis in 27 children (10/27 bilateral cases), unilateral multicystic dysplasia in 11, ureteral duplication in 6, primary megaureter or orthotopic ureterocele in 5 (1/5 bilateral case) and posterior urethral valves in 4. An early urinary tract infection was noticed in 5 cases only and 2 boys with urethral valves had an altered renal function at birth. Eight children with a mild lesion were not operated. A radical procedure was performed in 15 cases: excision of a multicystic kidney (10 cases) or heminephrectomy of an upper non-functioning pyelon (5 cases: 3 with heterotopic ureterocele and 2 with ectopic ureter). Thirty children were submitted to a corrective procedure: electrocoagulation of urethral valves (4 cases), ureteroneocystostomy (6 cases) or pyeloplasty (19 unilateral and 1 bilateral procedure). Except in a case of pyeloplasty the result of the reconstructive surgery was considered as good or satisfactory from a radiological point of view, with a mean follow-up of 1.5 year. The essential point of discussion is the evaluation of the factors which must be taken in account to plan an early reconstructive surgical treatment. The main factor, I.e. the natural history of these congenital anomalies remains at yet difficult to predict in a great number of cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1987

[Congenital dilatation of the common bile duct].

During a period of 18 years, 41 cases of congenital dilatation of the common bile duct in young patients (11 of them were less than 12 months of age) were treated at Bicetre Hospital. A retrospective analysis of these cases underline the following points. A close etiopathogenic relation exists between the presence of a common hepatico-pancreatic duct and a congenital dilatation of the common bile duct (in this study, 16 cases demonstrated the anomaly out of 20 cases for which the common bile duct could be analysed). Early surgical treatment must be undertaken before occurrence of liver complications (6 patients have cirrhosis when first treated, 4 of them were children less than 12 months of age). Abdominal echotomography (100% of preoperative diagnosis) and transparietal cholangiogram are the best investigations for providing pictures of hepatico-pancreatic abnormalities and collecting bile samples for bacteriological and chemical study. The treatment of congenital dilatation of common bile duct by cyst excision and Roux en Y hepaticojejunostomy has good long term results. After 20 cases of complete cyst excision, 6 of them were children under 12 months, and 17 cases or partial cyst excision respecting the cyst fundus when they were intraduodenal and retropancreatic in position (4 were children under 2 months) we have noted that 83% of these children had a good outcome with a mean follow up of 7 years. Complications include hepatico-jejunal stenosis at the anastomosis site in 2 patients, for which they were reoperated and cholangitis with hepatico-jejunal anastomosis in 6 cases. There were 3 deaths in children under 12 months who already developed hepatic cirrhosis and episodes of severe cholangitis when preoperative diagnosis was first proved. In conclusion, the future life of the majority of these children is expected to be uneventful inasmuch that bile stasis has been corrected, with resolution of inflammatory lesions which are known to expose to secondary malignancies of the biliary tract.

Adolescent↗
PubMed1986

Relationship between the cysteine-proteinase-inhibitory function of rat T kininogen and the release of immunoreactive kinin upon trypsin treatment.

The potential kininogenic function of rat T kininogen has been studied in parallel with the cysteine-proteinase-inhibitory function also carried by this molecule. Proteolytic cleavage of the molecule was observed upon incubation with catalytic amounts of trypsin. These conditions do not permit any significant release of immunoreactive kinin and do not modify the total papain-inhibiting capacity of T kininogen. As trypsin concentration increases in the reaction mixture, immunoreactive kinin is liberated and the total papain-inhibiting capacity decreases accordingly, as indicated by titration studies. This decrease, however, does not exceed 50% of the initial value even at a trypsin concentration as high as 75 microM, indicating that only one of the two inhibitory sites has been inactivated. The remaining inhibitory fragment corresponds to a peptide of apparent Mr 24 000, which binds papain at least as well as native T kininogen. T kininogen, therefore, appears as a potent proteinase inhibitor and/or a proteinase inhibitor precursor, whereas its kininogenic function remains questionable since no specific kininogenase able to release T kinin or another kinin under physiologically compatible conditions has been found so far.

Animals↗
PubMed1986

Hepatoblastoma and hepatocarcinoma in children: analysis of a series of 29 cases.

Twenty-nine cases of liver malignancies, 26 hepatoblastomas (HB) and 3 hepatocarcinomas (HC), were treated in a 13-year period. All children were submitted to operation but four had nonresectable tumors, even after chemotherapy. Surgery in the 25 cases consisted of right lobectomy in 14, a left lobectomy in 9, and a tumorectomy in 2; a secondary operation had to be performed in 5 cases, either because of histologic doubt on the cut section of the presumed normal parenchyma, or for local recurrence. Preoperative chemotherapy, instituted on a routine basis since 1982, did appear to facilitate surgery in otherwise inoperable tumors. The benefits of preoperative embolization, done for three children, were minimal. Ten children died, one in the immediate postoperative period, eight others from the disease, and one from a complication of chemotherapy. Follow-up for the 18 surviving children, all recurrence and metastasis-free, with normal alphafetoprotein (AFP) is less than 2 years for four and from 2 to 11 years for 14. One teen-age girl, with a fibrolamellar carcinoma has just recently been reoperated because of recurrence three years later. In spite of the fact that 6 out of 7 children operated without adjunctive treatment are cured, a systematic course of preoperative chemotherapy has been prescribed in the more recent cases. Follow-up for these is yet too short.

Adolescent↗
PubMed1986

[Common channel for bile and pancreatic ducts. Presentation of 12 cases and discussion].

Between 1978 and 1985, 11 girls and one boy underwent an elective operation for a congenital choledochal dilatation associated with an anomalous biliopancreatic junction. In 10 out of these 12 cases the children suffered several episodes of abdominal pain, and the diagnosis was missed since a jaundice appeared. The ultrasonographic examination demonstrated in all cases a dilatation of both extra- and intrahepatic bile ducts. The preoperative diagnosis was always established by the mean of a transhepatic cholangiography (8 cases) or a percutaneous cholecystography (4 cases), which showed in every case a dilated choledochus, and a common biliopancreatic channel, 15 to 35 mm long. A high amylase level was found in the bile in 10/10 cases when it was measured. A cholecystokinin test was performed in 4 cases, resulting in each case in a considerable increase of amylase and lipase levels in bile. All children were treated by excision of the dilated choledochus and gallbladder, followed by an hepaticojejunostomy with a Roux en Y loop. The follow-up is 6 months to 5 years for 9 children: 8 are cured, and on girl, who had a major dilatation of the left intrahepatic bile ducts, suffered from episodic abdominal pain and an episode od cholangitis 6 years after the operation. The role of such a common channel in the pathogeny of congenital choledochal cysts, acute pancreatitis in children, and biliary carcinomas in young adults is discussed according to the literatures of the last 10 years.

Adolescent↗
PubMed1986

[Portal hypertension in children. Therapeutic approach in cases of failure of a portosystemic shunt].

88 porto systemic shunts were performed between 1977-1985; 14 failures were observed. These failures occurred in ten children with extra-hepatic portal obstruction and in four with intra-hepatic obstruction. The treatment of these failures was different in these two groups: 7 reoperations in the extra-hepatic obstruction, none in the intra-hepatic. That reoperation is often not suitable in the intrahepatic obstruction because of the hepatic failure. The use of sclerotherapy or the beta receptor blocking agents is discussed in this group.

Adolescent↗
PubMed1985

Rat plasma alpha 1-inhibitor3: a member of the alpha-macroglobulin family.

The overall mechanism of interaction with proteinases of alpha 1-inhibitor3, a plasma proteinase inhibitor so far specific to the rat, has been shown to be closely similar to that described for alpha-macroglobulins. This mechanism includes: (i) the cleavage of at least one susceptible peptidic bond which leads to structural changes in the molecule. (ii) The cleavage of a putative thiol ester bond in another site of the molecule which permits the covalent linkage of the enzyme. Moreover, fragmentation of alpha 1-inhibitor3 upon heating as observed for alpha-macroglobulin quarter subunits has been demonstrated. The question is raised of the presence of such a molecule in rat plasma in addition to two alpha-macroglobulin species, all of these proteinase inhibitors being antigenically unrelated.

Acute-Phase Proteins↗
PubMed1985

Fluorescence methods for localizing proteinases and proteinase inhibitors in skeletal muscle.

Proteinases and proteinase inhibitors have become suspect in a wide variety of muscle wasting conditions that might be treatable if knowledge of the cellular locale and function of these molecules were known. Fluorescent probes have been useful in the localization of proteinases in muscle samples from human and animal specimens. These include the histochemical localization of proteinases based on the specific fluorescence of hydrolysis product derivatives, but this approach has been limited to the lysosomal proteinases because of the acidic requirements of the trapping reaction of the primary reaction product. Immunohistochemical techniques do not have the same restrictions and a number of lysosomal and nonlysosomal proteinases have been identified in muscle by this means. Unfortunately, they do not yield any information as to the activity of the enzymes. This is an important consideration since the extracellular environment contains a number of proteinase inhibitors, some of which may be internalized by the cell.

Animals↗