Profile identification of disease-associated humoral antigens using AMIDA, a novel proteomics-based technology

We describe AMIDA (autoantibody-mediated identification of antigens), a novel target identification technology based on the immunoprecipitation of disease-specific antigens by autologous serum antibodies followed by two-dimensional electrophoretic separation, and their identification via mass spectrometry. Twenty-seven potential carcinoma antigens were identified including proteins of hitherto unknown function. Validation of one of the identified antigens, cytokeratin 8, revealed its de novo expression in hyperplastic tissue, gradual overexpression with increasing malignancy, and ectopic localization on the cell surface. Furthermore, a strong prevalence of CK8-specific antibodies occurred in the serum of cancer patients already at early disease stages. In situ hybridization for one marker of unknown function, KIAA1273/TOB3, demonstrated its strong overexpression in head and neck carcinomas, thus making it a likely tumor antigen candidate. Eventually, AMIDA could foster significant improvements for the diagnosis and therapy of human diseases eliciting a humoral immune response, and allows for the rapid identification of new target molecules.Received 30 January 2004; received after revision 3 March 2004; accepted 8 March 2004     

Infection of cultured intestinal epithelial cells with severe acute respiratory syndrome coronavirus

To identify a model for the study of intestinal pathogenesis of severe acute respiratory syndrome (SARS) we tested the sensitivity of six human intestinal epithelial cell lines to infection with SARS coronavirus (SARS-CoV). In permissive cell lines, effects of SARS-CoV on cellular gene expression were analysed using high-density oligonucleotide arrays. Caco-2 and CL-14 cell lines were found to be highly permissive to SARS-CoV, due to the presence of angiotensin-converting enzyme 2 as a functional receptor. In both cell lines, SARS-CoV infection deregulated expression of cellular genes which may be important for the intestinal pathogenesis of SARS.Received 23 May 2004; received after revision 23 June 2004; accepted 25 June 2004     

Identifizierung von Psilocin

Summary Psilocin, a by-product of Psilocybin which is the active principle of hallucinogenic mushrooms, has been identified as 4-hydroxy-dimethyltryptamine.     

Time function of corticosteroid levels in the blood plasma of rats under the influence of 222Rn inhalation.

The time function of cortocosteroid level in plasma of rats under two different 222Rn concentrations was investigated. Both curves show a maximum after 8h. Whereas the higher activity of 222Rn produces a second maximum after 5 days, the lower activity reaches its second maximum not before 9 days. From both time functions, a two-step mechanism in the intracellular control can be concluded.     

β-Ergokryptine,a new alkaloid of the ergotoxine group

Zusammenfassung Es wird die Isolierung eines neuen Isomeren des Ergokryptins beschrieben, das sich von diesem nur durch den Ersatz des Leucin-Restes durch den Isoleucin-Rest im Peptidteil des Moleküls unterscheidet. Das neue Isomere soll als-Ergokryptin und das früher beschriebene Alkaloid als-Ergokryptin bezeichnet werden. Die beiden Isomeren, ebenso ihre Dihydro-Derivate, unterscheiden sich pharmakologisch nur ganz unwesentlich.

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Mitteilung über Mutterkornalkaloide (65. Mitteilung:H. Ott, A. Hofmann andA. J. Frey, J. Am. chem. Soc.88, 1251 (1966)).     

Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases

The receptor for advanced glycation end products (RAGE), a multi-ligand member of the immunoglobulin superfamily of cell surface molecules, interacts with distinct molecules implicated in homeostasis, development and inflammation, and certain diseases such as diabetes and Alzheimer's disease. Engagement of RAGE by a ligand triggers activation of key cell signalling pathways, such as p21ras, MAP kinases, NF-kappaB and cdc42/rac, thereby reprogramming cellular properties. RAGE is a central cell surface receptor for amphoterin, a polypeptide linked to outgrowth of cultured cortical neurons derived from developing brain. Indeed, the co-localization of RAGE and amphoterin at the leading edge of advancing neurites indicated their potential contribution to cellular migration, and in pathologies such as tumour invasion. Here we demonstrate that blockade of RAGE-amphoterin decreased growth and metastases of both implanted tumours and tumours developing spontaneously in susceptible mice. Inhibition of the RAGE-amphoterin interaction suppressed activation of p44/p42, p38 and SAP/JNK MAP kinases; molecular effector mechanisms importantly linked to tumour proliferation, invasion and expression of matrix metalloproteinases.