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Gastric M1 mucin and the MUC5AC gene show a similar oncofetal expression in the colon. Our aim was to determine whether M1 mucin is the product of the MUC5AC gene. A recombinant baculovirus encoding the C‐terminal portion of the MUC5AC gene as a fusion protein was isolated and the immunoreactivity of the recombinant mucin (rM) toward M1 antibodies studied. Chicken antibodies also were raised against purified rM. Besides its reactivity with L56/C, a serum recognizing the bacterially expressed MUC5AC gene product, rM was endowed with M1 immunoreactivity: (i) rM‐expressing cells were stained specifically with anti‐M1 serum and with the monoclonal antibody (MAb) 21M1, defining the M1‐f epitope; (ii) both L56/C and anti‐M1 antibodies recognized the same bands in immunoblots of rM‐containing cell extracts; (iii) the 21M1 antibody reacted with rM in an immunoradiometric assay. Among the 7 M1 epitopes, M1‐f was the only one encoded by the 3′ portion of the MUC5AC gene. It was the only epitope detected in a native mucin M1‐derived 170 kDa bromelain proteolytic fragment. Furthermore, the staining patterns of human tissues obtained with either anti‐rM chicken antibodies or anti‐M1 antibodies were identical. We conclude that M1 immunoreactivity is encoded at least in part by the MUC5AC gene. Int. J. Cancer 75:767–773, 1998.© 1998 Wiley‐Liss, Inc.

Platelets are critical for normal hemostasis. Their deregulation can lead to bleeding or to arterial thrombosis, a primary cause of heart attack and ischemic stroke. Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP1) is a 5-phosphatase capable of dephosphorylating the phosphatidylinositol 3,4,5-trisphosphate second messenger into phosphatidylinositol 3,4-bisphosphate. SHIP1 plays a critical role in regulating the level of these 2 lipids in platelets. Using SHIP1-deficient mice, we found that its loss affects platelet aggregation in response to several agonists with minor effects on fibrinogen binding and β 3 integrin tyrosine phosphorylation. Accordingly, SHIP1-null mice showed defects in arterial thrombus formation in response to a localized laser-induced injury. Moreover, these mice had a prolonged tail bleeding time. Upon stimulation, SHIP1-deficient platelets showed large membrane extensions, abnormalities in the open canalicular system, and a dramatic decrease in close cell-cell contacts. Interestingly, SHIP1 appeared to be required for platelet contractility, thrombus organization, and fibrin clot retraction. These data indicate that SHIP1 is an important element of the platelet signaling machinery to support normal hemostasis. To our knowledge, this is the first report unraveling an important function of SHIP1 in the activation of hematopoietic cells, in contrast to its well-documented role in the negative regulation of lymphocytes. IntroductionPlatelet activation is a highly regulated process and critical for mediating normal hemostasis. Vascular injury exposes subendothelial matrix proteins that allow platelet arrest and their subsequent spreading, activation, and secretion of soluble mediators. These soluble agonists recruit circulating platelets, allowing aggregation for the bleeding to stop. In pathological states, platelet activation can contribute to thrombosis and cerebrovascular and arterial occlusion and eventually to heart attacks and strokes. Several signaling mechanisms have been shown to contribute to platelet activation, including the phospholipase C (PLC)/Ca 2+ and the PI3K pathways. By generating phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P 3 ] and phosphatidylinositol 3,4-bisphosphate [PtdIns(3,4)P 2 ] second messengers, PI3K plays an important role in platelet activation and plug stability (1-3). Using a selective PI3K β inhibitor, Jackson et al. (3) recently suggested that this lipid kinase could be a potential target for antithrombotic therapy.It is now well established in several models that phosphoinositide phosphatases involved in the hydrolysis of PtdIns(3,4,5)P 3 and PtdIns(3,4)P 2 , such as the phosphatase and tensin homolog (PTEN), are essential for the negative regulation of PI3K pathways (4). PTEN is commonly deleted or inactivated in several cancers,

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a b s t r a c tVicia faba L. seeds were grown in a pot experiment on soil, mine tailings, and a mixture of both to mimic field situations in cultivated contaminated areas near mining sites. Metals in the substrates and their translocation in root, stem and leaf tissues were investigated, including morphological responses of plants growing on mine tailings. Metal concentration -and generally bioaccumulation -was in the order: roots > leaves > stems, except Pb and Cd. Translocation was most significant for Zn and Cd, but limited for Pb. Metal concentration in root and leaf was not proportional to that in the substrates, unexpectedly the minimum being observed in the mixed substrate whilst plant growth was retarded by 20% (38% on tailings). Calcium, pH, organic matter and phosphorus were the main influencing factors for metal translocation. The ultrastructure of V. faba L. cells changed a lot in the mine tailings group: root cell walls were thickened with electron dense Pb, Zn and C particles; in chloroplasts, the number of plastoglobuli increased, whereas the thylakoids were swollen and their number decreased in grana. Finally, needleshaped crystalline concretions made of Ca and P, with Zn content, were formed in the apoplast of the plants. The stratagems of V. faba L. undergoing high concentrations of toxic metals in carbonate substrate, suggest root cell wall thickening to decrease uptake of toxic metals, a possible control of metal transport from roots to leaves by synthesizing phytochelators-toxic metal complexes, and finally a control of exceeded Ca and metal concentration in leaves by crystal P formation as ultimate response to stress defense. The geochemical factors influencing metal availability, guaranty a reduction of metal content in plant growing on mixed tailing/soil substrate as far as carbon te are not completely dissolved.