Studies on the thyroid in transgenic mice expressing the genes for human and bovine growth hormone

The thyroid glands of transgenic mice (TM) expressing the genes for human (h) and bovine (b) growth hormone (GH) were studied. The percentages of larger follicles in hGH TM of either sex were significantly greater than in the corresponding normal littermates, and follicles ranging up to 350 microns in diameter were present in male hGH TM. In contrast, thyroid follicles were only slightly enlarged in male bGH TM, and were unchanged in female bGH TM. The serum concentrations of T4 were significantly decreased in male bGH TM and not altered in the other groups. Serum concentrations of T3 were slightly, but significantly increased in female hGH TM and female bGH TM, but were unaffected in male TM of either type. Since the principal difference between these foreign GHs in rodents is the additional lactogenic activity of human GH, these results may indicate that the effects of prolactin can influence the development of the thyroid.     

2-Br-α-Ergokryptin: Beeinflussung von Fertilität und Laktation bei der Ratte

Summary The inhibitory actions of -ergocryptin on fertility and lactation in the rat are altered differentially in the 2-bromo derivative of this ergot alcaloid. It is therefore unlikely that the fertility inhibiting and the lactation inhibiting effects of 2-bromo--ergocryptin are governed by a single mechanism of action.     

APP dimer formation is initiated in the endoplasmic reticulum and differs between APP isoforms

The amyloid precursor protein (APP) is part of a larger gene family, which has been found to form homo- or heterotypic complexes with its homologues, whereby the exact molecular mechanism and origin of dimer formation remains elusive. In order to assess the cellular location of dimerization, we have generated a cell culture model system in CHO-K1 cells, stably expressing human APP, harboring dilysine-based organelle sorting motifs [KKAA-endoplasmic reticulum (ER); KKFF-Golgi], accomplishing retention within early secretory compartments. We show that APP exists as disulfide-bonded dimers upon ER retention after it was isolated from cells, and analyzed by SDS-polyacrylamide gel electrophoresis under non-reducing conditions. In contrast, strong denaturing and reducing conditions, or deletion of the E1 domain, resulted in the disappearance of those dimers. Thus we provide first evidence that a fraction of APP can associate via intermolecular disulfide bonds, likely generated between cysteines located in the extracellular E1 domain. We particularly visualize APP dimerization itself and identified the ER as subcellular compartment of its origin using biochemical or split GFP approaches. Interestingly, we also found that minor amounts of SDS-resistant APP dimers were located to the cell surface, revealing that once generated in the oxidative environment of the ER, dimers remained stably associated during transport. In addition, we show that APP isoforms encompassing the Kunitz-type protease inhibitor (KPI) domain exhibit a strongly reduced ability to form cis-directed dimers in the ER, whereas trans-mediated cell aggregation of Drosophila Schneider S2-cells was isoform independent. Thus, suggesting that steric properties of KPI-APP might be the cause for weaker cis-interaction in the ER, compared to APP695. Finally, we provide evidence that APP/APLP1 heterointeractions are likewise initiated in the ER.     

Insights from von Willebrand disease animal models

von Willebrand disease is a genetic bleeding disorder that arises from abnormalities in von Willebrand factor, an adhesive glycoprotein involved in both primary hemostasis and coagulation. It is the most common inherited bleeding disorder in humans, and over the years several animal species have also been described as suffering from this disease whether through a spontaneous mutation (pigs, dogs) or a genetically engineered one (mouse). These different animal models are extremely useful in exploring the characteristics of von Willebrand disease and in testing new treatments. This review provides an update of the various von Willebrand disease models and the contribution that these models can make to a better understanding of human von Willebrand disease.     

Antagonism of 2-Br-α-ergokryptine-methanesulfonate (CB 154) to certain endocrine actions of centrally active drugs

Zusammenfassung Bei Ratten mit drei verschiedenen Modellen pharmakologisch induzierter Pseudogravidität wird gezeigt, dass 2-Br--ergokryptin-methansulfonat (CB 154) auch die durch Pharmaka stimulierte Prolactinsekretion zu hemmen vermag.     

Untersuchungen über die β-adrenolytische Wirkung sowie den Einfluss auf Refraktärzeit und Kontraktilität von INPEA und MJ1999 am Meerschweinchenvorhof

Summary In isolated guinea-pig atria, the-adrenolytic isomerd(–)INPEA provoked a stronger prolongation of the refractory period (rp) than did the inactivel(+) isomer. The-adrenolytic drug MJ 1999 prolonged likewise the rp, although it caused no unspecific effect, i.e. an inhibition of contractile force. These observations lead to the conclusion that not only the unspecific local anaesthetic but also the specific-adrenolytic effect is of importance for the prolongation of rp.     

The natures of numbers in and around Bombelli’s L’algebra

The purpose of this article is to analyse the mathematical practices leading to Rafael Bombelli’s L’algebra (1572). The context for the analysis is the Italian algebra practiced by abbacus masters and Renaissance mathematicians of the fourteenth to sixteenth centuries. We will focus here on the semiotic aspects of algebraic practices and on the organisation of knowledge. Our purpose is to show how symbols that stand for underdetermined meanings combine with shifting principles of organisation to change the character of algebra.