Suppression of immunization to tuberculosis and diphtheria by an extract of lymphoid tissue

Zusammenfassung Dank einer neuen Anwendung von Lymphknotenextrakten (statt Röntgenextrakten, Corticosteroiden, Antilymphozytenserum usw.) wird eine erhebliche Reduktion der immunologischen Reaktion erzielt, wenn die Tiere mit diesen Extrakten vorbehandelt und gleichzeitig mit Antigenen behandelt werden.

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This investigation was supported in part by U.S.P.H.S. Research Grant No. CA-02624 from National Cancer Institute; and in part by an institutional grant to Detroit Institute of Cancer Research from United Foundation of greater Detroit allocated through Michigan Cancer Foundation and the Detroit General Hospital Research Corporation, and Newaygo County Cancer Society.     

Identification of an emerin–β-catenin complex in the heart important for intercalated disc architecture and β-catenin localisation

How mutations in the protein emerin lead to the cardiomyopathy associated with X-linked Emery-Dreifuss muscular dystrophy (X-EDMD) is unclear. We identified emerin at the adherens junction of the intercalated disc, where it co-localised with the catenin family of proteins. Emerin bound to wild type β-catenin both in vivo and in vitro. Mutating the GSK3β phosphorylation sites on β-catenin abolished this binding. Wild type but not mutant forms of emerin associated with X-EDMD were able to reduce β-catenin protein levels. Cardiomyocytes from emerin-null mice hearts exhibited erroneous β-catenin distribution and intercalated disc architecture. Treatment of wild type cardiomyocytes with phenylephrine, which inactivates GSK3β, redistributed emerin and β-catenin. Emerin was identified as a direct target of GSK3β activity since exogenous expression of GSK3β reduced emerin levels at the nuclear envelope. We propose that perturbation to or total loss of the emerin–β-catenin complex compromises both intercalated disc function and β-catenin signalling in cardiomyocytes.     

Der Vitaminbedarf des amerikanischen ReismehlkäfersTribolium confusum Duval

Summary As previously reported the larvae ofTribolium confusum require two unknown factors obtainable from yeast apart from various vitamines of the B-group for normal growth. One of these possesses acidic properties. This factor could be fully replaced by a folic acid preparation of potency 4000 kindly placed at our disposal by Prof.R. J. Williams. This may be regarded as a possibility but not as a proof that folic acid is the reported factor.

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C. A. Grob dankt der Haco-Gesellschaft AG., Gümligen, für die Unterstützung dieser Arbeit.     

Uptake of3H-noradrenaline and3H-5-hydroxytryptamine in cultured rat brainstem

Zusammenfassung Die zelluläre Lokalisation der Aufnahme von³H-NA und³H-5HT in den Hirnstamm von Ratten wurde am Modell der Nervengewebskultur untersucht. Im Gegensatz zu den Aminosäure-Transmittern, welche in Neurone und Gliazellen aufgenommen werden, zeigen Monoamine nur eine Aufnahme in Zellkörper und Fortsätze von Neuronen, nicht jedoch in Gliazellen. Es besteht eine Korrelation zwischen den Ergebnissen von fluoreszenzmikroskopischen Versuchen und unseren autoradiographischen Untersuchungen.     

Über die Zytologie der Parthenogenese und der Geschlechtsbestimmung bei der GallmückeOligarces paradoxus Mein

Summary InOligarces paradoxus, the chromosomal behaviour was compared during pedogenetic development of and . The -egg undergoes a single non-reductional maturation division, the -egg shows two divisions which result in reduced nuclei. After maturation in the -egg, the number of chromosomes is restored by endomitosis. The nuclei of germ-line cells contain a high number of chromosomes (: 74\2-82; : at least 58) in both sexes. In somatic nuclei, the number is diminished by elimination to 10 in , to 5 in .     

Synchrone Replikation aller Chromosomen beiXenopus laevis

Summary Autoradiographics showed synchronous replication of all chromosomes inXenopus laevis.     

A histochemical study of immune destruction of the lymphopoietic system

Zusammenfassung Eine auffallende Zunahme von -Galactosidase kommt im lymphoetischen Säuger-Gewebe im Zusammenhang mit der immunologischen Auflösung dieses Systems vor. Die hernach auftretende Proliferation retikulärer Zellen steht im Zusammenhang mit der Regeneration dieses Organs. Diese Zellen enthalten eine reichliche Anzahl lysosomatischer Enzyme (z.B. -Galactosidase).

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This investigation was supported in part by Public Health Service Research Grants Nos. Ca 02624 and CA 02903 from the National Cancer Institute and in part by an institutional grant to the Detroit Institute of Cancer Research Division of the Michigan Cancer Foundation from the United Foundation of Greater Detroit, and Detroit General Hospital Research Corporation. Newaygo County Cancer Association. We wish to express our gratitude for stenographic assistance to Mrs.Connie Malucusky and MissPatricia Warzocha.     

PTC124 targets genetic disorders caused by nonsense mutations

Nonsense mutations promote premature translational termination and cause anywhere from 5-70% of the individual cases of most inherited diseases. Studies on nonsense-mediated cystic fibrosis have indicated that boosting specific protein synthesis from <1% to as little as 5% of normal levels may greatly reduce the severity or eliminate the principal manifestations of disease. To address the need for a drug capable of suppressing premature termination, we identified PTC124-a new chemical entity that selectively induces ribosomal readthrough of premature but not normal termination codons. PTC124 activity, optimized using nonsense-containing reporters, promoted dystrophin production in primary muscle cells from humans and mdx mice expressing dystrophin nonsense alleles, and rescued striated muscle function in mdx mice within 2-8 weeks of drug exposure. PTC124 was well tolerated in animals at plasma exposures substantially in excess of those required for nonsense suppression. The selectivity of PTC124 for premature termination codons, its well characterized activity profile, oral bioavailability and pharmacological properties indicate that this drug may have broad clinical potential for the treatment of a large group of genetic disorders with limited or no therapeutic options.