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.     

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.     

Allergoprints in Horse Allergic Children

In order to determine the allergenic activity of five purified horse allergens, 22 children allergic to horses according to history, skin test, and leukocyte histamine release were evaluated. Washed leukocytes from all patients were tested for allergen-induced histamine release utilizing four epidermal horse allergens (Ags 6, 9, 11 , and 15) and horse serum albumin. Crossed radioimmunoelectrophoresis was carried out with a standardized horse dander extract and serum from each patient.
The results showed considerable variation in the individual allergoprints. Ag 11 had the highest mean allergenic activity. Sensitivity to horse serum albumin was demonstrated three times. Our data show that the amount of serum IgE antibodies bound by horse allergens correlates significantly with the capacity of the allergens to induce histamine release from washed leukocytes.     

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.     

Polymer diffusion in mixtures of polystyrene and polymethylstyrene studied by forced rayleigh scattering and photon correlation spectroscopy

Tracer diffusion coefficients D^* of both components were measured in mixtures of polystyrene (PS) and polymethylstyrene (PMS), a random copolymer from 60 wt.-% of m-methylstyrene and 40 wt.-% of p-methylstyrene. The results are interpreted in terms of the free-volume theory which yields master curves even for “asymmetric” mixtures of oligomer and polymer chains, if D^* is drawn versus the distance from the glass transition temperature, T–T_g. Whereas D^* was measured by the forced Rayleigh scattering technique, we also studied photon correlation spectroscopy in these mixtures and observed “slow modes” with decay constants that correspond to diffusion coefficients 2–3 decades smaller than the interdiffusion coefficient.     

13-cis retinoic acid inhibits development and progression of chronic allograft nephropathy

Chronic allograft nephropathy is characterized by chronic inflammation and fibrosis. Because retinoids exhibit anti-proliferative, anti-inflammatory, and anti-fibrotic functions, the effects of low and high doses of 13-cis-retinoic acid (13cRA) were studied in a chronic Fisher344-->Lewis transplantation model. In 13cRA animals, independent of dose (2 or 20 mg/kg body weight/day) and start (0 or 14 days after transplantation) of 13cRA administration, serum creatinine was significantly lower and chronic rejection damage was dramatically reduced, including subendothelial fibrosis of preglomerular vessels and chronic tubulointerstitial damage. The number of infiltrating mononuclear cells and their proliferative activity were significantly diminished. The mRNA expression of chemokines (MCP-1/CCL2, MIP-1alpha/CCL3, IP-10/CXCL10, RANTES/CCL5) and proteins associated with fibrosis (plasminogen activator inhibitor-1, transforming growth factor-beta1, and collagens I and III) were strikingly lower in treated allografts. In vitro, activated peritoneal macrophages of 13cRA-treated rats showed a pronounced decrease in protein secretion of inflammatory cytokines (eg, tumor necrosis factor-alpha, interleukin-6). The suppression of the proinflammatory chemokine RANTES/CCL5 x 13cRA in fibroblasts could be mapped to a promoter module comprising IRF-1 and nuclear factor-kappaB binding elements, but direct binding of retinoid receptors to promoter elements could be excluded. In summary, 13cRA acted as a potent immunosuppressive and anti-fibrotic agent able to prevent and inhibit progression of chronic allograft nephropathy.     

Über die Grenzbedingungen von Zelleben und spezifischer Zellfunktion am isolierten Muskel

Zusammenfassung 1. Es werden an quergestreiften Muskeln (Zwerchfell, Herzvorhof von Warmblütern, Froschherz) unter den Bedingungen von Substratund Sauerstoffmangel Funktion und histologischer Zustand verglichen.2. Drosselung der Energiezufuhr führt in jedem Falle zu negativer Inotropie und diastolischem Stillstand. Dies führt zu dem zwingenden Schluß, daß die Kontraktion und nicht die Erschlaffung den energieverbrauchenden Teil des Kontraktionsvorganges darstellt.3. Gleichzeitiger Glucose- und Sauerstoffmangel führt erst mit dem Erlöschen der Glykogenolyse zur Kontraktur, die nach völligem Glykogenschwund irreversibel wird (Totenstarre).4. Die Totenstarre wird als Modellkontraktion abgelehnt.5. Aus den untersuchten Mangelbedingungen läßt sich eine Reihenfolge der Energieausnützung für den quergestreiften Muskel ableiten, wobei wesentliche Unterschiede zwischen Warmblüter und Kaltblüter bestehen.Mit 7 Textabbildungen