Inhibition of leukotriene formation and IL-8 release by the PAF-receptor antagonist SM-12502

We analyzed the effect of the PAF receptor antagonist (+)-cis-3,5-dimethyl-2-(3-pyridyl) thiazolidin-4-one hydrochloride (SM-12502) on the release of leukotriene B₄ and IL-8 from human leukocytes. Peripheral blood from healthy donors was separated in two different fractions: polymorphonuclear leukocytes (PMN) and a lymphocyte, monocyte and basophil granulocyte cell fraction (LMB). After incubation of the cell population with different concentrations of SM-12502 the cells were subsequently stimulated with either the Ca ionophore A23187, the bacterial derived peptide fMLP, or with an activator of heterotrimetric G-proteins, the sodium fluoride (NaF, in the presence of Al³⁺). The PAF receptor antagonist led to a concentration and time dependent inhibition of LTB₄ formation and IL-8 release from PMN and LMB. Our data clearly indicate an inhibitory effect of the PAF receptor antagonist SM-12502 on the formation of mediators of the lipoxygenase pathway and on the release of IL-8.     

Calculation of macrocyclization equilibria for poly(ethylene terephthalate)

The cyclization equilibria constant K_x is evaluated for the formation of cyclic poly(ethylene terephthalate)s (PET) in the range of degree of polymerization 2 ≤ x ≤ 10 on the basis of an elaborated form of the Jacobson-Stockmayer theory. According to this theory, K_x = W( 0 )·2Γ₀(1)/(σ_cx N_A), where W( r ) is the probability density function for the chain vector r ; Γ₀(γ) is the probability distribution, when r = 0 of γ = cos Δθ; Δθ being the deviation of the bond angle formed by cyclization from its unconstrained value; σ_cx corresponds to the symmetry number of the ring; N_A is Avogadro's number. The evaluation of W( r ) is performed in different approximations. The required configurational averages for computing the density distribution W( r ) and the angular correlation factor Γ₀(1) are obtained by Monte Carlo techniques. The density W( 0 ) of chain vectors at r = 0 is overestimated by the Gaussian approximation. Values of W( 0 ) calculated in higher approximation lower K_x for x < 10. By taking into account the oriental correlation between terminal bonds of the x-meric acyclic sequence, K_x is lowered additionally by factors of ca. 2,2, 1,3 and 1,1 for x = 4, 5 and 6, respectively. Similar to other polymer chains treated so far, K_x is lowered for medium sized chain lengths by taking into account the deviation from Gaussian distribution and angular correlations of chain ends. This result is in contradiction to experimental data, which yield even higher K_x-values than expected by the classical Jacobson-Stockmayer theory for medium sized chain lengths. The inclusion of cis-ester residues into the all trans-ester PET chain only slightly reduces this discrepancy. Structural modifications of the PET chain during cyclization experiments are discussed as a rationale for the deviations from the present theory.     

Linkage analysis of anorexia and bulimia nervosa cohorts using selected behavioral phenotypes as quantitative traits or covariates.

To increase the likelihood of finding genetic variation conferring liability to eating disorders, we measured over 100 attributes thought to be related to liability to eating disorders on affected individuals from multiplex families and two cohorts: one recruited through a proband with anorexia nervosa (AN; AN cohort); the other recruited through a proband with bulimia nervosa (BN; BN cohort). By a multilayer decision process based on expert evaluation and statistical analysis, six traits were selected for linkage analysis (1): obsessionality (OBS), age at menarche (MENAR), and anxiety (ANX) for quantitative trait locus (QTL) linkage analysis; and lifetime minimum body mass index (BMI), concern over mistakes (CM), and food-related obsessions (OBF) for covariate-based linkage analysis. The BN cohort produced the largest linkage signals: for QTL linkage analysis, four suggestive signals: (for MENAR, at 10p13; for ANX, at 1q31.1, 4q35.2, and 8q13.1); for covariate-based linkage analyses, both significant and suggestive linkages (for BMI, one significant [4q21.1] and three suggestive [3p23, 10p13, 5p15.3]; for CM, two significant [16p13.3, 14q21.1] and three suggestive [4p15.33, 8q11.23, 10p11.21]; and for OBF, one significant [14q21.1] and five suggestive [4p16.1, 10p13.1, 8q11.23, 16p13.3, 18p11.31]). Results from the AN cohort were far less compelling: for QTL linkage analysis, two suggestive signals (for OBS at 6q21 and for ANX at 9p21.3); for covariate-based linkage analysis, five suggestive signals (for BMI at 4q13.1, for CM at 11p11.2 and 17q25.1, and for OBF at 17q25.1 and 15q26.2). Overlap between the two cohorts was minimal for substantial linkage signals.     

Observation of a nematic phase displayed by a polysiloxane with trinitrofluorenones as side groups

The synthesis and the results of the structural study of two copolysiloxanes with laterally fixed trinitrofluorenone (TNF) units is reported. The two copolysiloxanes having 2,4 ( 1a ) and 5,3 ( 1b ) dimethylsiloxane comonomer units per TNF side group differ significantly in their phase behaviour as evident from optical microscopy, differential scanning calorimetry and X-ray scattering: 1b shows a nematic mesophase whereas 1a is an amorphous material. The different phase behaviour is discussed in terms of microphase separation between the siloxane backbone and TNF side groups.     

Defective peroxisomal catabolism of branched fatty acyl coenzyme A in mice lacking the sterol carrier protein-2/sterol carrier protein-x gene function

Gene targeting in mice was used to investigate the unknown function of Scp2, encoding sterol carrier protein-2 (SCP2; a peroxisomal lipid carrier) and sterol carrier protein-x (SCPx; a fusion protein between SCP2 and a peroxisomal thiolase). Complete deficiency of SCP2 and SCPx was associated with marked alterations in gene expression, peroxisome proliferation, hypolipidemia, impaired body weight control, and neuropathy. Along with these abnormalities, catabolism of methyl-branched fatty acyl CoAs was impaired. The defect became evident from up to 10-fold accumulation of the tetramethyl-branched fatty acid phytanic acid in Scp2(−/−) mice. Further characterization supported that the gene disruption led to inefficient import of phytanoyl-CoA into peroxisomes and to defective thiolytic cleavage of 3-ketopristanoyl-CoA. These results corresponded to high-affinity binding of phytanoyl-CoA to the recombinant rat SCP2 protein, as well as high 3-ketopristanoyl-CoA thiolase activity of the recombinant rat SCPx protein.     

Investigation of poly(arylenevinylene)s, 40. Electrochemical studies on poly(p-phenylenevinylene)s

Differential pulse polarography (DPP) and cyclovoltammetry (CV) were conducted to study the redox behaviour of poly(p-phenylenevinylene) (PPV; E = 0,76 V; E = ?1,74 V) as well as of three insoluble PPV-derivatives and four soluble aryl-substituted PPV's. Oxidation studies of DP-PPV, DMOP-PPV and DPOP-PPV in comparison with two series of the oligomeric model compounds 1a–e and 2a–d lead to the conclusion that for DMOP-PPV (E = 0,98, 1,24,1,31 V) and DPOP-PPV (E = 1,10, 1,29, 1,44 V) three distinct oxidation stages exist, which are reversibly occupied and represent 1/2, 1 and 2 positive charges per repeating unit. In DP-PPV two oxidation stages representing 1/2 and 1 positive charges were found to be reversibly occupied (E = 1,17, 1,69 V), whereas at higher potentials irreversible dehydrocyclization occurred.     

Light controlled solubility change of polymers: Copolymers of N,N-dimethylacrylamide and 4-phenylazophenyl acrylate

Copolymers of N,N-dimethylacrylamide (DMA) and 4-phenylazophenyl acrylate (PAPA) have been prepared by free-radical copolymerization in dioxane (DMAP-x). The molecular weights of the copolymers show a strong decrease with increasing azobenzene content due to the retardation effect of the azobenzene group. An analogous decrease in molecular weight was found with a number of polymers of DMA which were polymerized in the presence of the non-polymerizable model 4-phenylazophenyl propionate (PAPP). We were able to induce a lower critical solution temperature (LCST) above a certain content of azobenzene moieties in the copolymers (DMAP-x) in contrast to the good water solubility of poly(DMA). Due to the reversible photoisomerization and the concomitant change in the dipole moment of the azobenzene moieties, the LCST depends not only on the content of azobenzene but also on the degree of isomerization. A difference in the LCST up to 20°C was found for dark adapted polymer solutions (0% Z-isomer) and polymer solutions in the photostationary state (ca. 85% Z-isomer). Within this temperature range the polymer can be precipitated by irradiation with light.     

δ-aminolevulinic acid dehydrase (porphobilinogen synthase) in two families with inherited enzyme deficiency

The inheritance of a deficient delta-aminolevulinic acid dehydrase (ALA-D; synonym: porphobilinogen synthase; EC 4.2.1.24) was studied in blood samples of two families over three generations. The propositus in each family was a young male acute hepatic porphyria patient with an almost complete ALA-D deficiency in the homozygous state (ALA-D activity less than 2% of controls). Heterozygotes are clinically non-affected (mean ALA-D 36% of controls). The mode of transmission could be traced by enzyme activity and electrophoretic polymorphism studies. Heterozygotes are detected by the demonstration of enzyme activity in the gel. The notation D was used for the gene expressing the defective enzyme. The "phenotype" D-1 was observed in six, the "phenotype" D-2 in three of all heterozygotes studied. These results are compatible with a single normal allele in heterozygotes responsible for enzyme activity. Quantitative assays and the segregation pattern in both families suggest a 3-allele-system for the inheritance of ALA-D deficiency.