Genetik der koronaren Herzkrankheit und des Herzinfarkts

Because of their high prevalence, cases of coronary artery disease (CAD) and myocardial infarction (MI) are frequently found when asking for a patient’s family history. It is common knowledge that a positive familial history constitutes a risk factor for CAD in its own right, in addition to smoking, increased alcohol intake, diabetes, obesity, hypertension, and hyperlipidemia. Nevertheless, for correct risk assessment it is crucial to accurately distinguish between sporadic and true familial cases of CAD and MI. Familial disposition is present when at least one male first-grade relative under the age of 55 or one female first-grade relative under the age of 65 has/had been diagnosed with myocardial infarction or significant coronary artery disease. In the review presented here, we compile the relevant epidemiological and genetic studies that constitute the scientific basis of this risk assessment. Furthermore, a short overview of the state of the art of genetic CAD/MI research is given.     

Zahnanomalien in der Neuropädiatrie

Dental anomalies in children with neuropediatric disorders are easy to diagnose and can be essential in the diagnosis of different entities. They are present in well-known disorders as Incontinentia pigmenti, but also in rare diseases as in Kohlschütter-Tönz syndrome or the recently described ataxia, delayed dentition and hypomyelination. Anomalies of dental shape, enamel and in this case also teeth color, dental number and eruption are all encountered. Knowledge of these abnormalities is important for both clinical geneticist and child neurologist.     

Enhancement of citrus resistance to the Mediterranean fruit fly

Precolorbreak treatment of Marsh grapefruit and Shamouti and Valencia oranges with 20 or 50 ppm gibberellic acid (GA) reduced fruit susceptibility to laboratory infestation by Ceratitis capitata (Wiedemann). Treatment effects were dose-dependent and the benefits were most pronounced with the orange cultivars. The implications of these findings are discussed in relation to use of GA treatment for improved fruit fly control in citrus.

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Zusammenfassung In den hier beschriebenen Versuchen wurde untersucht, wie weit durch die Anwendung von Gibberilinsäure (GA) im Freiland die Resistenz von Pampelmuse (Marsh), sowie von Shamoutiund Valencia-Orangen gegenüber Befall durch die Mittelmeerfruchtfliege, Ceratitis capitata (Wiedemann) gesteigert werden kann.In den Jahren 1982/83 spritzten wir in Israel Bäume dieser drei Zitrusarten mit GA in den Konzentrationen von 5 ppm und 50 ppm zu zwei verschiedenen Zeitpunkten vor dem Farbumschlag der Früchte (September, Oktober). Die so behandelten Früchte wurden anschliessend während der Reifeperiode in verschiedenen Zeitpunkten adulten Mittelmeerfruchtfliegen für die Eiablage dargeboten. Diese Exposition wurde sowohl im Freiland mit Früchten am Baum sowie im Laboratorium mit gepflückten Früchten durchgeführt. Untersucht wurde einerseits die Anfälligkeit resp. Resistenz der Früchte bezüglich der Eiablage, andererseits die Entwicklung der Larven in den Früchten.Wir stellten fest, dass die Behandlung mit GA bei Pampelmuse in Abhängigkeit vom Zeitpunkt und Konzentration der Behandlung eine gewisse erhöhte Befallsresistenz bewirken konnte. Bezüglich der beiden geprüften Orangensorten konnten wegen ungünstigen Witterungsbedingungen während der Reifezeit keine schlüssigen Befunde erarbeitet werden.Im Winterhalbjahr 1983/84 wurden Bäume aller drei Zitrussorten vor dem Farbwechsel der Früchte mit 20 ppm und 50 ppm GA behandelt. Um den negativen Einfluss der Witterung in den Expositionsversuchen auszuschalten, wurden die Versuchsfrüchte den Fruchtfliegen während der Reifeperiode ausschliesslich im Laboratorium dargeboten. In dieser Versuchsperiode stellten wir auch bei Orangen eine erhöhte Widerstandsfähigkeit gegen Fruchtfliegenbefall fest, und zwar in erhöhtem Ausmass bei Valencia-Orangen. Gleichzeitig beobachteten wir eine stark verzögerte Entwicklung des Farbwechsels von grün auf orange als Folge der hohen GA-Konzentration.

     

Intercellular junctions in the uterine epithelium of Salamandra salamandra (L.) (Amphibia,Urodela)

Summary Intercellular junctions in the uterine epithelium of the ovoviviparous urodele Salamandra salamandra were studied in pregnant and non-pregnant females by freeze-fracture technique. Junctional complexes consist of zonulae occludentes (tight junctions) and numerous maculae adhaerentes (desmosomes); z. adhaerentes and nexuses (gap junctions) could not be identified. Tight junctions are of the flexible type exhibiting loosely interconnected fibrils. The fibrillary network appears stretched more often in pregnant females possibly due to the mechanical stress of pregnancy. The structure and occurrence of the junctions identified, especially that of the tight junctions, is discussed with regard to the functions of the uterus during pregnancy.Zusammenfassung Mit Hilfe der Gefrierbruchtechnik wurden im Uterus-epithel trächtiger und nichtträchtiger Feuersalamanderweibchen (Salamandra salamandra) Zonulae occludentes und Maculae adhaerentes, jedoch keine Z. adhaerentes sowie Nexus identifiziert. Die Z. occludentes sind flexibel. Ihr fibrilläres Netzwerk ist bei trächtigen Weibchen öfter gestreckt; das ist möglicherweise auf die stärkere Ausdehnung des Uterusgewebes während der Trächtigkeit zurückzuführen. Das Vorkommen der verschiedenen Kontakt-strukturen, namentlich das der Z. occludentes, wird im Hinblick auf die Funktionen des Uterus während der Trächtigkeit diskutiert.We are indebted to Mrs. K. Ott for excellent technical assistance and to Miss Dr. U. Beigel for linguistic help     

Weshalb hemmen Würmer Allergien? Parasiten als Immunologen

Parasitic worms survive within their immunocompetent hosts by modulating their immune system and by inhibiting inflammatory responses directed against the parasites. This immunomodulation has a spill over effect and also inhibits inflammatory responses originating from other causes. For this reason, persons who are infected with certain species of worms show a lower rate of allergic diseases as compared to persons who are free of parasites. In the same line, studies in mouse models revealed that many inflammatory diseases can be treated by worm infections. This effect is among others owing to specific proteins that are released by the worms. Such secreted immunomodulators, shaped by co‐evolution between parasites and their hosts, could become lead compounds for the development of new therapies against allergic and inflammatory diseases.     

Characterization of the lipid-carrier involved in the synthesis of enterobacterial common antigen (ECA) and identification of a novel phosphoglyceride in a mutant of Salmonella typhimurium defective in ECA synthesis

The polysaccharide chains of enterobacterial common antigen (ECA) consist of linear trisaccharide repeat units with the structure -->3)- alpha-d-Fuc4NAc-(1-->4)-beta-d-ManNAcA-(1--> 4)-alpha-d-GlcNAc-(1-->, where Fuc4NAc is 4-acetamido-4, 6-dideoxy-d-galactose, ManNAcA is N - acetyl-d- mannosaminuronic acid, and GlcNAc is N -acetyl-d-glucosamine. The major form of ECA (ECAPG) consists of polysaccharide chains that are believed to be covalently linked to diacylglycerol through phosphodiester linkage; the phospholipid moiety functions to anchor molecules in the outer membrane. The ECA trisaccharide repeat unit is assembled as a polyisoprenyl-linked intermediate which has been tentatively identified as Fuc4NAc-ManNAcA-GlcNAc- pyrophosphorylundecaprenol (lipid III). Subsequent chain-elongation presumably occurs by a block-polymerization mechanism. However, the identity of the polyisoprenoid carrier-lipid has not been established. Accordingly, the current studies were conducted in an effort to structurally characterize the polyisoprenyl lipid-carrier involved in ECA synthesis. Isolation and characterization of the lipid carrier was facilitated by the accumulation of a ManNAcA-GlcNAc- pyrophosphorylpolyisoprenyl lipid (lipid II) in mutants of Salmonella typhimurium defective in the synthesis of TDP-Fuc4NAc, the donor of Fuc4NAc residues for ECA synthesis. Analyses of lipid II preparations by fast atom bombardment tandem mass spectroscopy (FAB-MS/MS) resulted in the identification of the lipid-carrier as the 55-carbon polyisoprenyl alcohol, undecaprenol. These analyses also resulted in the identification of a novel glycolipid which copurified with lipid II. FAB-MS/MS analyses of this glycolipid revealed its structure to be 1,2-diacyl- sn -glycero-3-pryophosphoryl-GlcNAc-ManNAcA (DGP- disaccharide). An examination of purified ECAPGby phosphorus-31 nuclear magnetic resonance spectroscopy confirmed that the polysaccharide chains are linked to diacylglycerol through phosphodiester linkage. Thus, DGP-disaccharide does not appear to be an intermediate in ECAPGsynthesis. Nevertheless, although the available evidence clearly indicate that lipid II is a precursor of DGP-disaccharide, the function of this novel glycolipid is not yet known, and it may be an intermediate in the biosynthesis of a molecule other than ECAPG.      

Molekulare Karyotypisierung in der klinischen Diagnostik

The term “molecular karyotyping” refers to the genome-wide analysis of copy number variations using arrays that cover the genome with genomic markers with varying density. Currently the main application is the investigation of patients with otherwise unexplained mental retardation and multiple congenital anomalies. Studies of such patients who remained without etiological diagnosis after conventional karyotyping, subtelomeric screening, and targeted molecular–cytogenetic studies for well-known microdeletion syndromes revealed chromosomal microaberrations in about 10% of cases and allowed the delineation of several new microdeletion and microduplication syndromes. Nevertheless, because of the large number of copy number polymorphisms, interpretation of unique findings needs thorough consideration.