Association of the p85 regulatory subunit of phosphatidylinositol 3- kinase with an essential erythropoietin receptor subdomain

Using an active, HAI epitope-tagged form of the murine erythropoietin (EPO) receptor and via direct coimmunoprecipitation, the p85 regulatory subunit of phosphatidyl inositol-3 kinase (p85/PI3-K) is shown to associate with the EPO receptor in transfected FDC-P1 cell lines. Coimmunoprecipitation of p85 with epitope-tagged EPO receptors was observed initially in FDC-HER cells labeled metabolically with [32P]orthophosphate, and association of these factors was confirmed by Western analyses of receptor immunoprecipitates using p85 antiserum. Interestingly, this association occurred in the absence of ligand, and exposure of FDC-HER cells to EPO did not detectably affect levels of receptor-associated p85 or overall levels of p85 phosphorylation. However, EPO was observed to stimulated the rapid formation of phosphatidylinositol 32P-phosphate in FDC-HER and FDC-ER cells. Through baculovirus-mediated expression of epitope-tagged EPO receptor forms in SF9 cells, domains for p85 association were mapped. Analyses of receptor forms with cytosolic truncations and deletions delineated a candidate subdomain for p85 binding to an essential extended box-2 region (P329-E374; including a putative motif for SH2 binding, Y343LVL). These findings extend a mechanistic alignment between the EPO receptor and protein tyrosine kinase-encoding receptors that likewise activate PI3-K, and expand the importance of further defining pathways to PI3-K activation.     

217. Röntgenologische Funktionsuntersuchungen der total oder partiell ersetzten Speiseröhre

Zusammenfassung An dem Krankengut der Chirurgischen Universitätsklinik München der Jahre 1969–1970 von Patienten mit teilweisem oder vollständigem Speiseröhrenersatz durch Dünndarm oder Ileo-Colon wurde die Funktion der Interponate röntgenologisch untersucht. Die beste Funktion weist das isoperistaltische Dünndarminterponat auf. Bei erhaltenem terminalen Oesophagus wird trotz dessen Entspannung und trunculärer Vagotomie eine vollkommene Schlußfähigkeit der Cardia gefunden, eine spastische Komponente vermißt. Isoperistaltisch interponierter Dickdarm besaß in einem Fall kräftige Peristaltik, zeigte aber sonst lediglich segmentäre Kontraktionen mit passivem Kontrastmittelabtransport. Gastrocolischer und gastro-jejunaler Reflux wurden bei gut funktionierender Pyloroplastik nicht beobachtet.

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Functional X-ray examination of partial or complete oesophagus substitution

Summary In a series of patients (1969–1970) of the Chirurgische Universitätsklinik München, who underwent partial or complete oesophagus substitution by small bowel or ileo-colon, a radiological examination has been performed. The best functioning shows the isoperistaltic small bowel-substitute. In spite of relaxation and truncular vagotomy the part left-over of the terminal oesophagus shows no spasm at all, the cardia is functioning well. The isoperistaltic colonic substitute shows strong peristalsis in one case, in other cases there are only segmental contractions with passive contrast-medium transport. Gastro-colic and gastro-jejunal reflux were not seen.

     

Progesterone receptors in carcinomas of the upper aerodigestive tract

This study had three major goals: (1) to vigorously verify the presence of progesterone receptors in squamous cell carcinoma of the upper aerodigestive tract (HN-SCC). Antiprogesterone receptor monoclonal antibodies revealed a distinct band at approximately 120 kilodaltons in samples taken from two of four patients with HN-SCC. These results illustrate that progesterone receptor in HN-SCC has the same molecular weight as progesterone receptor in normal human uterus and human breast cancer. Steroid specificity and saturability results support the evidence that it is true progesterone receptors that are measured and not other receptors or sex steroid-binding globulins; (2) to confirm the biochemical function of progesterone receptors in HN-SCC by assessing the binding of progesterone receptor to acceptor sites on chromosomes in the nucleus; and (3) to establish the clinical significance of progesterone receptor measurement. Patients with positive assays were more likely to be free of disease a mean of 6 months after resection. We used logistic regression to account for site of primary disease, grade of tumor, and stage of disease. This logistic regression was significant with a p = 0.014. Patients with a binding index greater than 2 (19 of 73 patients) were 4.34 times more likely to be free of disease than patients with negative assays.