Abnormal lactate dehydrogenase isoenzyme pattern in serum of a patient with a testicular tumor.
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Adult↗
Biomedical subjects
G Favre
Publications and source records attributed to G Favre.
[Targeting of tumor cells by low density lipoproteins: principle and use of ellipticin derivatives].
Cells acquire cholesterol via de novo synthesis and high affinity receptor-mediated uptake of low-density lipoprotein (LDL). Some tumor tissues display increased receptor-mediated uptake of LDL as compared with the corresponding normal tissues. This increased LDL receptor activity is unexplained: a high cholesterol demand for cell growth or a mechanism directly linked to cell transformation. LDL has therefore been proposed as a potential carrier for chemotherapeutic agents. Various methods have been used to incorporate antineoplastic lipophilic drugs into LDL. The resultant drug-LDL complexes have been shown to be cytotoxic towards tumor cells in vitro, via the LDL receptor dependent pathway. However little is now on the in vivo fate of this complex. We described the incorporation of lipophilic derivatives of ellipticine into LDL by a fusion or facilitated transfer technique between drug containing microemulsions and LDL. The drug-LDL complex expressed similar metabolic activity, in vitro and in vivo, than native LDL. Initial experiments with melanoma B16 tumor-bearing mice suggest that LDL may be a potential drug carrier in the treatment of malignant diseases. The knowledge of the molecular mechanism of the expression of the LDL receptor in tumor cells and the ability to downregulate the LDL receptor in the normal tissues, will define the application field of this targeting approach.
Animals↗
A sensitive immunochemiluminescence assay for human serum amyloid A protein.
We describe an immunochemiluminescence assay for human plasma serum amyloid A protein (SAA) in which specific rabbit polyclonal antibodies against synthetic peptides are used. The detection of the antigen-antibody reaction at 425 nm is based on a brief emission of light by a luminophor component (signal) in response to chemical energy. The working range of the assay covers plasma SAA concentrations from 5 to 100 micrograms/L. The lower detection limit is 5 micrograms/L, the within- and between-assay CVs are less than 12%. Bilirubin, cholesterol and triglyceride in final concentrations of up to 220 mumol/L, 8.1 mmol/L and 2.68 mmol/L, respectively, do not interfere with the assay. Results were correlated with those obtained by the enzyme-linked immunosorbent assay using the same antibodies (r = 0.95; p less than 0.001; n = 50). This method is inexpensive, simple and easily automated.
Antibodies↗
Comparative study of the incorporation of ellipticine-esters into low density lipoprotein (LDL) and selective cell uptake of drug--LDL complex via the LDL receptor pathway in vitro.
Esters of elliptinium with stearic (ST-NME), palmitic (PAL-NME) or oleic (OL-NME) acids, a series of lipophilic derivatives of ellipticine, were synthetized, in order to evaluate their incorporation into Low Density Lipoprotein (LDL). Among the three derivatives, OL-NME shows the most potent incorporation (83 micrograms/mg protein LDL) compared to ST-NME (37 micrograms/mg protein LDL) and PAL-NME (58 micrograms/mg protein LDL). The size of OL-NME-LDL was determined by size distribution particles, showing their homogeneity compared to native LDL. When culture normal human fibroblasts were incubated with [125I]LDL incorporated drug, they bound to the LDL receptor with the same affinity as native LDL and were internalized and degraded intracellularly. The presence of excess native LDL inhibited the cellular uptake and degradation of [125I]drug-LDL. We have used [125I]acetyl-LDL as a probe for a binding site on macrophages that mediated the uptake and degradation of chemically altered or denatured LDL. Mouse peritoneal macrophages were shown to take up and degrade [125I]acetyl-LDL at rates that were greater than those for the uptake and degradation of native [125I]LDL and [125I]drug-LDL. The in vitro cytotoxic test on L1210 murine leukemic cells demonstrated that the complex was cytotoxic and was more effective than the free drug. This cytotoxic activity of the drug-LDL complex depends on the LDL high affinity receptor since the addition of native LDL reduces the killing power. In contrast, methylated LDL, which does not bind to the LDL receptor, has no effect on it. We conclude that it is possible to incorporate a large amount of cytotoxic drug into LDL without modifying their cellular metabolism via the high affinity LDL receptor pathway. It indicates also that the delivery of lipophilic drugs using LDL might provide distinct advantages over the use of synthetic carriers.
Alkaloids↗
[Statement: alkaline phosphatases. Genetic aspects. Identification and clinical interpretation].
The human alkaline phosphatases constitute a family of several isoenzyme forms. They are coded by 3 different structural genes. The authors find respectively the placental isoenzymes, the intestinal isoenzymes, and the isoenzymes coded by a gene called aspecific tissular. These last isoenzymes coming from the liver and the bone tissue have very similar structures leading to a very difficult differentiation and quantification. In this study, a summary is made of the main procedures at the disposal of biologist, which allows to have a differentiation of liver and bone fractions. The selected technique proposes the reactivity by affinity with a lectin. Owing to its excellent resolution, this method must contribute to a better follow-up of bone and liver metastasis and to the detection of intestinal isoenzymes, allowing the research of a possible link with different pathologies.
Alkaline Phosphatase↗
[Determination of cerebrospinal fluid proteins using the Cobas Fara centrifugal analyser. Adaptation of the turbidimetric technic to benzethonium chloride].
The authors have adapted a turbidimetric assay on centrifugal Cobas Fara analyser for cerebrospinal fluid proteins determinations. The later method is proposed by SFBC Protein Analysis Committee using benzethonium chloride as monoreagent. This adaptation is more sensitive than manual method. The linearity range is greater (0.08-1.85 g/l instead of 0.2-1.2 g/l). Sample assay and time of analysis were reduced by 90 p. cent.
Benzethonium↗
Proliferative effect of high density lipoprotein (HDL) and HDL fractions (HDL1,2, HDL3) on virus transformed lymphoblastoid cells.
The growth-promoting activities of plasma lipoproteins (LDL, HDL, HDL1,2, HDL3) and total HDL apolipoproteins on a virus transformed lymphoblastoid cell line in vitro, has been compared. When maintained in lipoprotein-deficient serum-supplemented medium, these cells do not proliferate optimally. The addition of either HDL, HDL1,2 or HDL3 induced optimal cell proliferation as compared to the result observed in fetal calf serum-supplemented medium. The HDL1,2 subfraction was found to be more potent than the HDL3 subfraction in supporting cell growth. Total HDL apolipoproteins were able to support significant cell proliferation. In contrast, LDL did not promote cell growth. In serum-free conditions and in the presence of transferrin, only HDL and HDL subfractions induced cell proliferation. These results suggest that HDL and HDL subfractions could initiate B lymphoblastoid cell growth and that total HDL apolipoproteins could support a part of cell proliferation.
B-Lymphocytes↗
Preparation of low density lipoprotein-9-methoxy-ellipticin complex and its cytotoxic effect against L1210 and P 388 leukemic cells in vitro.
Previous studies have suggested that low density lipoprotein (LDL) may be used as a drug targeting carrier for chemotherapeutic agents to neoplastic cells. In this study the cytotoxic agent 9-methoxy-ellipticin (MeOE) was incorporated into dimirystoyl phosphatidylcholine, cholesteryl oleate stabilized microemulsion and the latter fused with human LDL. Both agarose electrophoresis migration and the electron microscopic shape of the drug-LDL complexes were similar to those of native LDL. The in vitro cytotoxic tests on L1210 and P388 leukemic cells demonstrated that the complex was able to kill cells and was more effective than the free drug. This cytotoxic activity of the drug-LDL complex depends on the LDL high affinity receptor: the native LDL reduces the killing power. In contrast, methylated LDL, which does not bind to the LDL receptor, has no effect on it. On the other hand, heparin, which prevents binding on the cell surface receptors, partially reduced the cytotoxic activity of the drug-lipoprotein complex. These results suggest that it is possible to incorporate lipophilic cytotoxic drugs into LDL, using a technique of fusion with the microemulsion which contains the drug. This technique allows us to obtain a drug-LDL complex which is able to kill cells via the LDL receptor pathway.
Alkaloids↗
[Vectorization of antineoplastic drugs by low density lipoproteins: incorporation of acyl celiptium and metabolism of complexes in the cellular receptor of human fibroblasts].
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Alkaloids↗
Evidence for qualitative abnormalities in high-density lipoproteins from myeloma patients: the presence of amyloid A protein could explain HDL modifications.
HDL apolipoproteins (apo) from normal subjects and patients with multiple myeloma were studied by isoelectric focusing (IEF) and by two-dimensional gel electrophoresis. Qualitative abnormalities were detected in myeloma HDL apolipoproteins. We observed two new bands not previously described in this disease. As determined by IEF and two-dimensional gel electrophoresis, the relative molecular weight of these two proteins was 12,600, with pI = 6.04 and 6.36, respectively. They correspond to two isoforms of serum amyloid A protein (SAA), as confirmed by western blot assay against specific antiserum to SAA. The high sensitivity of this assay revealed also other SAA isoforms. Our data are consistent with the hypothesis that major apolipoproteins of normal HDL, apo A-I and apo A-II, could be displaced by SAA isoproteins in myeloma HDL. This could lead structural changes in HDL.
Aged↗
Quantitative abnormalities of lipoprotein particles in multiple myeloma.
Serum concentrations of total cholesterol and lipoprotein cholesterol, of apolipoproteins A I and A II and of apolipoprotein A I in lipoprotein particles (Lp A I and Lp A) were determined in 43 patients with multiple myeloma. There were striking alterations in the plasma levels of these analytes relative to normal subjects. We observed a decrease of cholesterol levels in LDL, HDL and HDL3 fractions, and of apolipoproteins A I and A II compared with normal subjects. The HDL2 cholesterol was increased. The decrease of apolipoprotein A II was more prominent than apolipoprotein A I. The decrease of apolipoprotein A I concerns only the A I (Lp A), while the A I (Lp A I) was increased. Most of these modifications were correlated with the monoclonal Ig levels.
Adult↗
Serum apolipoproteins A-I, A-II and B in hepatic metastases. Comparison with other liver diseases: hepatomas and cirrhosis.
Serum concentrations of lipids and apolipoprotein A-I, A-II and B were determined in patients with hepatic metastases of colorectal cancer, with primary liver cancer and with cirrhosis. In all three liver diseases, the HDL fraction and apolipoproteins A-I and A-II showed significantly low values, while apolipoprotein B was only increased in hepatic metastases. The decrease of apolipoprotein A-II levels was more prominent in cirrhosis, thereby enhancing the A-I/A-II ratio. This ratio is decreased in metastasis and normal in hepatomas. In patients with hepatic metastases a correlation was observed between alkaline phosphatase and apolipoprotein A-II (p less than 0.05), and between gamma-glutamyltransferase and the A-I/A-II ratio (p less than 0.05). The present work suggests that determination of apolipoproteins and lipids of the HDL fraction offers a new approach to the study of liver diseases.
Alkaline Phosphatase↗
[Determination of serum apolipoproteins A1 and B by immunoturbidimetry using the Cobas-Bio centrifugal analyzer. Influence of hyperlipemia].
The authors describe an immunoturbidimetric technique for the determination of the serum apolipoproteins A1 and B using a Cobas-Bio centrifugal analyser. This methods is sensitive and reproducible (CV less than 5%) and show a good correlation with electroimmunodiffusion which was taken as method of reference. It may be applied to serum stored at 4 degrees C or frozen at -20 degrees C. No light is transmitted in the case of either turbid hyperlipemic sera or sera extensively icteric or hemolyzed. The physiological values found in a large population of men and women of various ages are in agreement with those reported in the literature. The method described thus provides a suitable means of investigation adapted to large series for screening for coronary disease states.
Adult↗
Physico-chemical properties and evidence for electrophoretic variants of rat transcortin.
Isolation of rat plasma transcortin was carried out by affinity chromatography, as previously described for human. The protein was shown to be pure by PAGE and one single N-terminal amino acid was identified (Ser), which suggested that the protein molecule has a single polypeptide chain. This assumption is supported by SDS-PAGE. The amino acid composition was reported and compared with the one of human transcortin. The purified protein always migrated in PAGE (with or without SDS) as a double band; the faster component being more intense than the slower one. Whether transcortin was free or bound to corticosterone, the same aspect was observed. Molecular weight of these two variants were determined by SDS-PAGE as 65,900 and 75,800. Polymers only appeared after irreversible denaturation of the protein, as previously described for human transcortin. Various other physical parameters were determined: a sedimentation coefficient of 3.71 S +/- 0.18 was calculated by ultracentrifugation in sucrose gradient, association constants at 4 degrees C for corticosterone and cortisol (2.7 X 10(9) M-1 and 4.2 X 10(8) M-1, respectively).
Amino Acids↗
Reversible dissociation of cortisol-transcortin complex by sodium para-chloromercuribenzoate.
Mercurials are considered as sulphydryl group specific reagents and one of them, sodium para-chloromercuribenzoate (PCMB), is currently used for SH titration. It has been shown that cellular steroid receptors are reversibly inactivated by mercurials even when the binding site is occupied by the steroid (Coty, W.A. (1980) J. Biol. Chem. 255, 8035-8037). This is a striking difference with alkylating SH reagents such as iodoacetic acid or N-ethylmaleimide, since these reagents inactivate only steroid-free receptors. In order to explain this discrepancy, we tested, in the present study, the specificity of PCMB on a blood plasma steroid binding protein: human transcortin. This protein presents the advantage, over cellular receptors, of being well characterized and to be available in a pure state. The transcortin-cortisol complex was also reversibly inactivated by PCMB when the reaction was carried out at a high excess of reagent over protein; such conditions are those previously used with steroid receptors. The reversibility was obtained not only with a reducing agent (dithiothreitol) but also with EDTA, which suggests a poor stability of the protein mercurial bond and therefore a nonspecific action. The decrease of activity was the result of a loss of binding sites and Scatchard plot analysis did not reveal any detectable decrease of the affinity constant for cortisol. Transcortin possesses two SH groups per molecule, one of these being buried in native conformation. After blockage of the accessible SH group by aminoethylation, transcortin kept the same activity, but when this aminoethylated transcortin was incubated with PCMB a loss of activity was obtained, although the residual buried SH group was again titrable with Ellman's reagent. Therefore, we can conclude that the action of PCMB on proteins must be interpreted with precaution, since it can induce an inactivation that is SH-independent.
Chloromercuribenzoates↗
[Plasma lipoproteins and multiple myeloma. Variations of lipid constituents of HDL and apolipoproteins A1 and B].
Patients with myeloma disease showed in general very important abnormalities of circulating lipoproteins. Beside the presence of lipoprotein complexes with abnormal electrophoresis migration, we can observe either an hyperlipidemia associated with antilipoprotein auto-antibodies either, in contrary, an hypolipidemia. We studied 34 myeloma and one alpha heavy chain disease. In these subjects, all presenting clinical and biological myeloma tests but free of hepatic disease we evaluate after HDL separation their major lipid components: cholesterol and phospholipid. By electro immunodiffusion method we evaluate apolipoproteins A1 and B. We observe a decrease of Chol-HDL and PL-HDL in 51 p. cent of cases and a decrease of apo A1 in 80 p. cent of cases, this more marked in myeloma with gamma isotype. In contrary, apo B in all subjects studied remain normal. A correlation test with monoclonal immunoglobulin levels and its isotype is studied; the different parameters of monoclonal disease are discussed in relation with lipoprotein abnormalities.
Apolipoprotein A-I↗
[Anaphylactic shock: a severe emergency in allergology].
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Adult↗
Premenstrual syndrome and atopy: a double-blind clinical evaluation of treatment with a gamma-globulin/histamine complex.
The relationship between atopy and premenstrual syndrome was studied in 138 women, aged between 20 and 39-years' old, who had suffered from symptoms for at least 6 months. The results showed that there was a high incidence of a personal or familial history of allergy, immediate positive skin test reactions to conventional allergens, eosinophilia, low titre of histamine latex test and high levels of IgE in the premenstrual syndrome patients compared with the normal controls. A preliminary study in 40 patients showed that a course of treatment using a gamma-globulin/histamine complex by subcutaneous injection produced a satisfactory response in 70%. A follow-on double-blind, placebo-controlled study was carried out using the same drug in 42 out of 86 women. Very effective or effective symptomatic relief was significantly higher in the group receiving active treatment. The best results were obtained in patients who had high IgE levels.
Adult↗