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Biomedical subjects

D Muller

Publications and source records attributed to D Muller.

228 records · Page 13Linked to original sources
PubMed1976

Developmental aspects of xenobiotic transformation.

In most laboratory animals monooxygenases are apparently absent or barely detectable in fetal organs until just before birth. In this contribution hepatic cytochrome P-450-dependent reactions in the rat are considered only. The results are interpreted on basis of the reaction scheme of Estabrook. To avoid methodological pitfalls the basic kinetics for all reactions investigated have been investigated with liver preparations from newborn and adult rats. The low monooxygenase activity of rat liver during the perinatal period can be observed even under optimal conditions for the in vitro enzyme assay. There are different developmental patterns for various reactions O-demethylation of codeine, phenazone-hydroxylation, first and second steps on N-demethylation of amidopyrine, N-demethylation of ethylmorphine. There are marked differences not only in Vmax but also in the postnatal development of Km and the inductibility by phenobarbital. Thus the existence of a different cytochrome P-450 is evident also by this approach. The low monooxygenase activity of rat liver during the perinatal period is not due to a lack of NADPH or NADH, to an age-dependent NADPH cytochrome P-450 reductase activity or to an age-dependent NADH-cytochrome P-450 reduction. Moreover this low activity is not due to an insufficient mitochondria-endoplasmic reticulum interaction. It is accompanied by low delta Amax after addition of a typical type I substrate (hexobarbital) and by a small amount of metyrapone-binding centers: it can be explained by a smaller percentage of active cytochrome P-450 in comparison to adult rat liver.

Aminopyrine↗
PubMedDate not supplied

Affinity of human anti-factor VIII antibodies for functional polystyrene supports.

Human anti-factor VIII antibodies (anti-FVIII) neutralize Factor VIII (FVIII) procoagulant activity. These antibodies appear in about 5-15 per cent of severely affected patients with haemophilia A treated with FVIII concentrates (Mannucci, 1993). In order to obtain non-thrombogenic materials able to interact specifically with anti-FVIII, amino acids residues that mimic part of the FVIII molecule recognized by anti-FVIII have been grafted. Several cross-linked polystyrenes were functionalized with sulphonate and tyrosine sulphamide groups or tyrosine derivatives sulphamide groups such as methyl ester tyrosine, or the peptides aspartic acid methyl amide tyrosine, tyrosine aspatic acid methyl amide or aspartic acid aspatic acid methyl amide tyrosine. The in vitro removal of anti-FVIII from haemophilic A plasma was performed on different supports. These polymers exhibit strong and selective affinity for the anti-FVIII. The amount of adsorbed anti-FVIII varies with the composition of the polymer and a maximum is achieved for 15-35 per cent of amino acid sulphamide groups. The influence of different chemical groups on the surface of the polymeric solid supports on the adsorption of anti-FVIII was also studied.

Autoantibodies↗
PubMedDate not supplied

Modulation of human breast cancer cell adhesion by estrogens and antiestrogens.

In order to study the effect of estrogens and antiestrogens on the adhesive properties of human breast cancer cells, the attachment on endothelial cells (EC), on subendothelial extracellular matrix (ECM) and on ECM components (collagen I and IV, laminin, fibronectin) of estrogen-dependent (MCF-7, ZR75-1) and estrogen-independent (BT-20) breast cancer cell lines was investigated. The cells were grown under conditions of controlled exposure to estrogen [17 beta-estradiol (E2)] and/or antiestrogens [tamoxifen (Tam) or 4-hydroxytamoxifen (OH-Tam)]. Treatment by E2 enhanced the ability of ZR75-1 cells to adhere to the various substrates, which contrasts with the observed absence of effects with the BT-20 cells. Similarly, Tam or OH-Tam induced a reduction of the adhesion of ZR75-1 tumor cell, but not of BT-20 cells. This effect was reversed by competing concentrations of E2. The effects on MCF-7 cell adhesion were similar to those described for ZR75-1 cells, but could not be reproducibly observed. Adhesion assays carried out with ZR75-1 cells grown in the absence or presence of phenol red, a pH indicator which behaves as a weak estrogen, led to a similar pattern of cell attachment. Conditioned media harvested from E2- or Tam-treated ZR75-1 cells failed to induce any effect on adhesion of other ZR75-1 cells grown in E2-deprived medium, suggesting that secretory activities are not required for the control of cell adhesiveness. The results suggest that estrogens and antiestrogens can control the adhesive behavior of breast tumor cells through their hormone responsive structures possibly by regulating expression of cell adhesion proteins and/or their cell surface receptors.

Breast Neoplasms↗
PubMedDate not supplied

Hippocampal long-term potentiation and neural cell adhesion molecules L1 and NCAM.

Synaptic membranes express cell adhesion molecules. Here we investigate the role of the neural cell adhesion molecules L1 and NCAM in hippocampal long-term potentiation (LTP), a sustained-use-dependent increase in synaptic efficacy that has been implicated in learning and memory. L1 and NCAM mediate cell interactions during neural development and are strongly expressed in the hippocampus. They cooperate to strengthen L1-dependent cell adhesion and are coupled to second messenger pathways. We show that LTP in CA1 neurons of rat hippocampal slices was reduced by application of various L1 and NCAM antibodies, recombinant L1 fragments, and upon dissociation of the L1/NCAM complex through oligomannosidic carbohydrates and NCAM peptides. Neither the activation of NMDA (N-methyl-D-aspartate) receptors nor the maintenance of LTP was affected. These results suggest that L1 and NCAM modulate the development or the stabilization of LTP.

Animals↗
PubMedDate not supplied

Niosomes as carriers of radiopaque contrast agents for X-ray imaging.

Non-ionic surfactant vesicles (niosomes) are considered as carriers of iobitridol, a diagnostic agent used for X-ray imaging. The niosomes, with a diameter between 150 and 175 nm, are prepared using the film-hydration method followed by sonication. These vesicles were obtained with appropriate mixtures of D-alpha tocopheryl polyethylene glycol 1000 succinate, polyoxyethylene glycol 4000 stearate, sorbitan monostearate, cholesterol and dicetylphosphate. Methods allowing the increase of the rate of encapsulation and the stability of the vesicles were carried out. In addition to the study of the formulation of the vesicles, the physico-chemical and morphological properties of the vesicles have been studied.

Cholesterol↗
PubMedDate not supplied

Prevalence of IgE rheumatoid factor (IgE RF) in mixed cryoglobulinemia and rheumatoid arthritis.

IgE RF was measured by ELISA assay using aggregated IgG as a solid phase immunosorbent and alkaline phosphatase-conjugated Fc epsilon-specific monoclonal and polyclonal antibodies as indicators. The presence of IgE RF was defined in this assay as binding of the conjugate greater than 2.33 SD above the mean for control sera (N = 27). Total IgE was elevated in 25% (13/52) of sera of patients with seropositive Rheumatoid Arthritis (RA), yet was normal in the sera of 17/19 Mixed Cryoglobulinemia (MC) patients. IgE RF was present in 33% (21/63; p less than 0.05) RA sera, and none of sera from 19 MC patients tested. It did not correlate with IgM RF titer or total IgE, and was not detected in separated IgM and IgG fractions of 7 purified mixed cryoglobulins from patients with MC. These findings suggest that IgE RF may not be an important pathogenic factor in the clinical manifestations of MC. Its potential significance in RA is discussed.

Arthritis, Rheumatoid↗