Mosaic hexasomy 21.

Cases in which there are more than three copies of a sex chromosome, and rarely of an autosome, have been reported, but to our knowledge hexasomy has never been described except in tissue undergoing neoplastic change. This report describes a female infant with multiple malformations in whom we found a mosaic hexasomy 21. This was first detected in amniotic fluid cells and subsequently in skin fibroblasts.     

Gemfibrozil absorption and elimination in kidney and liver disease

Summary The disposition of the lipid-lowering drug gemfibrozil was studied in patients with either renal (n= 8) or hepatic disease (n= 8) and compared to those of healthy volunteers (n= 6). Gemfibrozil was determined in plasma and urine by means of a HPLC method. Urine was also analyzed for gemfibrozil conjugates.Following oral administration of 900 mg gemfibrozil, maximal plasma levels of the parent drug were 46.1±15.8 g/ml, attained after 2.2±1.1 h. In chronic renal failure and in liver cirrhosis the plasma concentrations of gemfibrozil did not significantly differ from that of controls except in those patients who were comedicated with antacids. These patients had significantly lower C_max and AUC values. The elimination half-life of the drug was 1.5 h in controls, 2.4 h in renal failure, and 2.1 h in liver disease. In healthy volunteers, only 0.02 to 0.15% of the given dose was recovered in the urine as parent gemfibrozil, while conjugates made up 7–14%. In patients with renal failure also, only traces of parent gemfibrozil could be detected, and conjugates accounted for 0.5–9.8%. In those with liver disease, however, about 0.1–0.2% were recovered in urine as parent gemfibrozil and up to 50% as conjugates. Strikingly, the amount of excreted conjugates in the urine was positively correlated to the direct bilirubin plasma concentration. It can be concluded that the elimination of gemfibrozil is not significantly influenced by renal failure. However, comedication with antacids markedly reduced plasma disposition of the drug. Patients with severe liver disease excreted more conjugated gemfibrozil via the kidney than did healthy controls. Thus, transfer across the canalicular cell membrane to the bile duct, rather than drug metabolization, is primarily disturbed in liver disease. Gemfibrozil accumulation is unlikely to occur in either kidney or liver disease.Abbreviations Cl_r creatinine clearance (ml/min) - HPLC high pressure liquid chromatography - C_max maximal plasma concentration (g/ml) - t_max time (h) after which C_max is attained - k_e elimination rate constant (h^–1) - t_1/2 elimination half-life (h) - A_e amount of drug excreted into the urine (% of given dose) - MRT mean residence time (h) - AUMC area under the first moment curve (g h²/ml) - AUC area under the plasma level time curve (g·h/ml) - ANOVA analysis of variance The paper is gratefully dedicated to G.W. Löhr     

Synthèse et caractérisation de copolymères coordinés par des sels métalliques

The anionic block copolymerisation of isoprene and 2-vinylpyridine (2VP) followed by a coordination with iron (III) chloride, leads to thermoreversibly crosslinked copolymers. These copolymers are character+ed by a low polydispersity (M?_w/M?_w≈1,1) between the coordination nodules of poly(2-vinylpyridine). The study of the swelling ratio at the equilibrium in benzene shows that such a polymeric network does not reach the equilibrium state expected from the thermodynamic analysis of the system. The presence of 2VP in the copolymer induces a screening effect which prevents the solvent diffusion through the polyisoprene network.     

Polymethacrylic acid derivatives, 2. Spectroscopic study of the compact conformation to coil transition

The compact → coil conformational transition of hydrophilic-hydrophobic copolymers derived from poly(methacrylic acid) was studied by UV Spectroscopy. Two copolymers were used in this study: a Poly(N-methacryloylalanine-co-N-phenylmethacrylamide) (P50) and a poly(methacrylic acid-co-benzyl methacrylate) (S25). Both samples exhibit hypochromism in the absorption band of the aromatic chromophore when they are under the compact conformation: 7% and 30% hypochromism for P50 and S25, respectively. This difference is explained by differences in the hydrophobic side chain-side chain interactions between the aromatic residues. Increasing the temperature was found to increase strongly the hypochromism of S25 and to have little effect on P50.     

Differential expression of FIZZ1 and Ym1 in alternatively versus classically activated macrophages

Alternatively activated macrophages (aaMphi) display molecular and biological characteristics that differ from those of classically activated macrophages (caMphi). Recently, we described an experimental model of murine trypanosomosis in which the early stage of infection of mice with a Trypanosoma brucei brucei variant is characterized by the development of caMphi, whereas in the late and chronic stages of infection, aaMphi develop. In the present study, we used suppression subtractive hybridization (SSH) to identify genes that are expressed differentially in aaMphi versus caMphi elicited during infection with this T. b. brucei variant. We show that FIZZ1 and Ym1 are induced strongly in in vivo- and in vitro-elicited aaMphi as compared with caMphi. Furthermore, we demonstrate that the in vivo induction of FIZZ1 and Ym1 in macrophages depends on IL-4 and that in vitro, IFN-gamma antagonizes the effect of IL-4 on the expression of FIZZ1 and Ym1. Collectively, these results open perspectives for new insights into the functional properties of aaMphi and establish FIZZ1 and Ym1 as markers for aaMphi.     

Restriction fragment pattern analysis of genomes from French isolates of suis herpes virus 1 (Aujeszky's disease virus)

Summary Purified DNA from 45 isolates of suis herpes virus 1 (SHV1) collected between 1980 and 1987 from clinical outbreaks of Aujeszky's disease on French farms was compared by restriction fragment pattern (RFP) analysis. The BamHI generated RFPs were found to be distinguishable, confirming RFP analysis as a potential epidemiological tool. The RFP could be assigned to two established major electrophoretic types and different subtypes. The RFP analysis indicated that the majority of outbreaks were caused by ADV with a central European genome type. The heterogeneity of RFPs among PRV isolates recovered from the central nervous system, lung, and foetus was not restricted specifically to one clinical entity. Variations in the virulence of the 45 isolates studied in mice, chicks, or piglets were unrelated to the RFP subtypes. One unusual RFP has been described for one strain of low virulence.