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Biomedical subjects

M Jezequel-Cuer

Publications and source records attributed to M Jezequel-Cuer.

8 recordsLinked to original sources

[Hepatocellular carcinoma].

Hepatocellular carcinoma is a rapidly fatal tumor that usually becomes symptomatic only at a stage beyond the reach of currently available treatments. The only hope for a cure lies in early diagnosis. It follows that an effective screening strategy should be used in high-risk populations, including patients with cirrhosis due to any cause, patients with chronic hepatitis B or C, and asymptomatic carriers of the B virus genome (and probably the C virus genome). Screening currently relies on physical examination and on two investigations, ultrasound scanning and the alpha-fetoprotein (AFP) assay, whose sensitivity and specificity vary with tumor size. The optimal interval between evaluations seems to be four to six months, although large prospective studies confirming this are not yet available. Because the AFP assay lacks sensitivity and specificity in patients with small tumors, other serum markers are being evaluated. In parallel, hepatitis B immunization and alpha interferon therapy of chronic hepatitis C are expected to decrease the incidence of hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

Sequential study of serum glycoprotein fucosylation in acute hepatitis.

BACKGROUND: alpha-Fetoprotein is a useful diagnostic marker in hepatocellular carcinoma, during which its serum level increases and its glycan structure is hyperfucosylated. Normally-expressed glycoproteins (alpha 1-antitrypsin and transferrin) are also hyperfucosylated in hepatocellular carcinoma. alpha-fetoprotein serum levels are also increased in conditions associated with hepatic regeneration, such as acute hepatitis. We conducted a longitudinal study of the alpha 1-6 fucosylation pattern of serum alpha-fetoprotein in ten patients with acute hepatitis and compared it to that of transferrin and alpha 1-antitrypsin. METHODS: Protein levels were measured by using immunochemical assays. Crossed affinoimmunoelectrophoresis in the presence of Lens culinaris agglutinin was performed for each protein, and the fucosylation index, corresponding to the agglutinin reactive fraction, was determined. The results were compared to those in 25 healthy donors and five newborns. RESULTS: alpha-Fetoprotein was hyperfucosylated and remained stable throughout the course of the disease. In contrast, serum transferrin and alpha 1-antitrypsin gradually became hyperfucosylated during the course of acute hepatitis. The transferrin and alpha 1-antitrypsin fucosylation indexes correlated with each other, but not with the alpha-fetoprotein fucosylation index. No correlation was found between alpha-fetoprotein, alpha 1-antitrypsin and transferrin fucosylation indexes and the corresponding glycoprotein serum levels. CONCLUSIONS: Hyperfucosylation of alpha-fetoprotein is not specific to hepatocellular carcinoma. Increased alpha 1-6 fucosylation should not be considered solely as a tumour marker, but might also reflect cell proliferation. The study of alpha 1-6 hyperfucosylation process of normally-expressed glycoproteins awaits further investigation, to test its usefulness as a new marker of liver regeneration during the follow-up of acute hepatitis.

Acute Disease↗

[Determination of serum or plasma alpha-tocopherol by high performance liquid chromatography: optimization of operative models].

A previous multicentric study set up by the Société française de biologie clinique has emphasized the usefulness of a standardized procedure for the determination by high performance liquid chromatography of alpha-tocopherol in serum or plasma. In our study, we have tested every step of the different published procedures: internal standard adduct, lipoprotein denaturation and vitamin extraction. Reproducibility of results was improved by the use of tocol as an internal standard when compared to retinol or alpha-tocopherol acetates. Lipoprotein denaturation was more efficient with ethanol addition than with methanol and when the ethanol/water ratio was > or = 0.7. Use of n-hexane or n-heptane gave the same recovery of alpha-tocopherol. When organic solvent/water ratio was > or = 1, n-hexane enabled to efficiently extract, in a one-step procedure, the alpha-tocopherol from both normo and hyperlipidemic sera. Performances of the selected procedure were: detection limit: 0.5 microM--linear range: 750 microM--within run coefficient of variation: 2.03%--day to day: 4.76%. Finally, this pluricentric study allows us to propose an optimised procedure for the determination of alpha-tocopherol in serum or plasma.

Chromatography, High Pressure Liquid↗

[Recent aspects of liver biochemistry: from physiopathology to functional liver exploration].

The advent of liver transplantation and the availability of effective medical therapeutics have recently made possible treatments of chronic liver diseases. These improvements have evidenced new needs for evaluation of the treated patients. In this review, authors present new biochemical liver tests proposed for a better monitoring in the course of the disease, to assess the therapeutic response in clinical trials and to reduce the number of liver biopsies. The different aspects of this paper concern the evaluation of hepatic uptake and biliary elimination, cholestasis, jaundice, cellular injury, fibrosis and liver tumor.

Aspartate Aminotransferases↗

[Stability of alpha-tocopherol: pre-analytical conditions in its determination in blood samples].

Incomplete and controversial data exist concerning vitamin E or alpha-tocopherol stability in biological samples. Recent clinical interest in the protective function of alpha-tocopherol provided another reason for the setting-up of a multicenter study by the Sociéte Française de Biologie Clinique. Our purpose was to examine the effects on alpha-tocopherol stability, firstly, of collection and transportation of blood samples, and, secondly, of the temperature (-20 degrees C and -80 degrees C) and period of storage of serum or plasma. alpha-tocopherol was determined in serum or plasma by isocratic liquid chromatography with UV detection at 292 nm. Our results established that alpha-tocopherol was extremely stable in blood, serum or plasma over 8 hours without special handling conditions (light, temperature). Pools of serum or plasma were stable for at least 3 months at -20 degrees C and -80 degrees C. They are suitable for use in the quality control of alpha-tocopherol. On the other hand, in some samples, we observed great variability in the rate of alpha-tocopherol degradation. However, there was lesser degradation when these plasma samples were stored at -80 degrees C instead of -20 degrees C. We therefore do not advise storing serum or plasma for more than 1 month at -20 degrees C for more than 3 months at -80 degrees C. This latter temperature is recommended in epidemiological studies.

Adult↗

Oligosaccharide specificity of normal human hepatocyte alpha 1-3 fucosyltransferase.

A purified alpha 1-3 fucosyltransferase (alpha 1-3 FT) was recovered in the Golgi fraction of isolated hepatocytes from normal human liver tissue. The efficiency of purification was controlled by measurement of fucose transfer to asialotransferrin (for alpha 1-3 FT), to phenyl-beta-D-galactose (for alpha 1-2 FT) and to 2' fucosyl lactose (for alpha 1-3/4 FT). The initial hepatocyte isolation step got rid of 97% and 94% of alpha 1-2 and alpha 1-3/4 total liver FT, respectively. After Golgi enrichment (26-fold purification and a yield of 7.6%), alpha 1-3 FT extract expressed a specific activity of 2 pM/min per mg protein. When incubated in optimized conditions with type 1, 2 or 6 oligosaccharide acceptors (10 mM), hepatocellular alpha 1-3 FT efficiently transferred fucose to N-acetyllactosamine and its 3' sialylated derivative, but poorly to lactose. When incubated with neutral or sialylated biantennary N-glycans, the enzyme expressed the highest affinity (Km = 0.38 mM) for the 3'bisialylated derivative. This suggests that hepatocellular alpha 1-3 FT is involved in the synthesis of sialosyl Le(x) determinants on cirrhotic alpha 1AGP.

Carbohydrate Sequence↗

Variations in human liver fucosyltransferase activities in hepatobiliary diseases.

The hyperfucosylation of a number of glycoconjugates observed in liver diseases involves the action of several specific fucosyltransferases (F.T.) notably responsible for synthesizing histo-blood group antigens. We determined the activities of alpha 3, alpha 2 and alpha 3/4 F.T. in 35 liver biopsy samples from patients with fatty liver, alcoholic or post-hepatic liver cirrhosis, primary or secondary biliary cirrhosis, acute hepatitis or a normal liver. F.T. activities were measured by transfer of GDP [14C] fucose to asialotransferrin for alpha 3 F.T., to phenyl beta-D-galactoside for alpha 2 F.T. and to 2' fucosyllactose for alpha 3/4 F.T. The diseased liver extracts showed an early increase in non-Le gene-associated alpha 3 F.T. activity (p = 0.001), which was related to the number of steatosic hepatocytes and the degree of intralobular inflammatory infiltration. Overexpression of this alpha 3 F.T. provides an explanation for the strong expression of 3-fucosyl lactosamine structures described in several hepatobiliary diseases. alpha 2 F.T. levels were significantly elevated in the two groups of liver cirrhosis and acute hepatitis (p = 0.05), but not enough to consider alpha 2 F.T. as a sensitive feature of mesenchymal cell injury. All Lewis-positive biopsies displaying biliary alterations showed increased Le gene-encoded alpha 3/4 F.T. activity (p = 0.001), which was related to the intensity of neoductular proliferation. Elevated levels of alpha 3/4 F.T. may be a very early sign of biliary regeneration.

Bile Duct Diseases↗