CID755673 enhances mitogenic signaling by phorbol esters, bombesin and EGF through a protein kinase D-independent pathway.

Recently, CID755673 was reported to act as a highly selective inhibitor of protein kinase D (PKD). In the course of experiments using CID755673, we noticed that it exerted unexpected stimulatory effects on [(3)H]thymidine incorporation and cell cycle progression in Swiss 3T3 cells stimulated by bombesin, a Gq-coupled receptor agonist, phorbol 12,13-dibutyrate (PDBu), a biologically active tumor promoting phorbol ester and epidermal growth factor (EGF). These stimulatory effects could be dissociated from the inhibitory effect of CID755673 on PKD activity, since enhancement of DNA synthesis was still evident in cells with severely down-regulated PKD1 after transfection of siRNA targeting PKD1. A major point raised by our study is that CID755673 can not be considered a specific inhibitor of PKD and it should be used with great caution in experiments attempting to elucidate the role of PKD family members in cellular regulation, particularly cell cycle progression from G(1)/G(o) to S phase.

Detection of early abnormalities in gastric function in first-degree relatives of patients with pernicious anemia.

BACKGROUND: Pernicious anemia (PA), as many other autoimmune disorders, has a trend to appear in other members of the family of the affected patients. Although this fact has been recognized since some decades ago, less is known about the frequency with which the abnormalities detected in the patients appear also in their relatives, the correlations that exist among these abnormalities and to what extent these markers of the disease relate to serum cobalamin concentration. SUBJECTS AND RESULTS: For these reasons we studied the values of some markers of PA in a group of 79 first-degree relatives and we detected that the most frequent abnormalities are a decrease in serum pepsinogen I (22.7% of cases), an increase in serum gastrin (16.5% of cases) and in parietal cell antibody at a titer >or=40 (23.4% of cases). From a functional point of view, a decrease in hydrogen excretion in a magnesium breath test, indicative of achlorhydria, is also frequent (29.1%). The fall in cobalamin concentration runs in parallel with these abnormalities. The concentration of this vitamin was below normal levels in as much as 15.2% of cases. CONCLUSION: These findings emphasize the need for searching for the presence of occult or latent PA in relatives of patients with this diagnosis, not only to prevent the development of anemia but also to avoid other undesirable consequences of cobalamin deficiency.