Identification of ‘cystic fibrosis protein’ as a complex of two calcium-binding proteins present in human cells of myeloid origin

Cystic fibrosis protein is a serum protein characterized by a pI close to 8.4 and present with a higher concentration in serum and plasma of cystic fibrosis carriers than in controls. This protein was found immunologically indistinguishable from the cystic fibrosis antigen isolated from granulocytes and presenting a sequence analogous to that of MRP-8, a calcium-binding protein expressed in the myeloid cell lineage. Using antibodies directed against MRP-8 and its closely associated calcium-binding protein, MRP-14, we demonstrate here that cystic fibrosis protein purified from serum is a complex of the two proteins MRP-8 and MRP-14.     

Vitamin E up-regulates arachidonic acid release and phospholipase A2 in megakaryocytes

The alteration in calcium transport in the liver nuclei of rats orally administered carbon tetrachloride (CCl4) was investigated. Rats received a single oral administration of CCl₄(5, 10, and 25%, 1.0ml/100 g body weight), and 5, 24 and 48 h later the animals were sacrificed. The administration of CCl₄ (25%) caused a remarkable elevetion of calcium content in the liver tissues and the nuclei of rats. Liver nuclear Ca2+-ATPase activity was markedly decreased by CCl₄ (25%) administration. The presence of dibutyryl cyclic AMP(10^-4 and 10^-3 M) or inositol 1,4,5-trisphosphate (10^-6 and 10^-5 M) in the enzyme reaction mixture caused a significant decrease in Ca²⁺-ATPase activity in the liver nuclei obtained from normal rat, while the enzyme activity was significantly increased by calmodulin (1.0 and 2.0 g/ml). These signaling factor's effects were completely impaired in the liver nuclei obtained from CCl₄ (25%)-administered rats. DNA fragmentation in the liver nuclei obtained from CCl₄ -administered rats was significantly decreased by the presence of EGTA (2 mM) in the reaction mixture, suggesting that the endogenous calcium activates nuclear DNA fragmentation. The present study demonstrates that calcium transport system in the liver nuclei is impaired by liver injury with CCl₄ administration in rats.     

Diagnostic and prognostic value of antibodies against chimeric fibrin/filaggrin citrullinated synthetic peptides in rheumatoid arthritis

Introduction

Evidence suggests that citrullinated fibrin(ogen) may be a potential in vivo target of anticitrullinated protein/peptide antibodies (ACPA) in rheumatoid arthritis (RA). We compared the diagnostic yield of three enzyme-linked immunosorbent assay (ELISA) tests by using chimeric fibrin/filaggrin citrullinated synthetic peptides (CFFCP1, CFFCP2, CFFCP3) with a commercial CCP2-based test in RA and analyzed their prognostic values in early RA.

Methods

Samples from 307 blood donors and patients with RA (322), psoriatic arthritis (133), systemic lupus erythematosus (119), and hepatitis C infection (84) were assayed by using CFFCP- and CCP2-based tests. Autoantibodies also were analyzed at baseline and during a 2-year follow-up in 98 early RA patients to determine their prognostic value.

Results

With cutoffs giving 98% specificity for RA versus blood donors, the sensitivity was 72.1% for CFFCP1, 78.0% for CFFCP2, 71.4% for CFFCP3, and 73.9% for CCP2, with positive predictive values greater than 97% in all cases. CFFCP sensitivity in RA increased to 80.4% without losing specificity when positivity was considered as any positive anti-CFFCP status. Specificity of the three CFFCP tests versus other rheumatic populations was high (> 90%) and similar to those for the CCP2. In early RA, CFFCP1 best identified patients with a poor radiographic outcome. Radiographic progression was faster in the small subgroup of CCP2-negative and CFFCP1-positive patients than in those negative for both autoantibodies. CFFCP antibodies decreased after 1 year, but without any correlation with changes in disease activity.

Conclusions

CFFCP-based assays are highly sensitive and specific for RA. Early RA patients with anti-CFFCP1 antibodies, including CCP2-negative patients, show greater radiographic progression.     

EphB receptors trigger Akt activation and suppress Fas receptor-induced apoptosis in malignant T lymphocytes

Treatment of hematopoietic malignancies often requires allogeneic bone marrow transplantation, and the subsequent graft-versus-leukemia response is crucial for the elimination of malignant cells. Cytotoxic T lymphocytes and NK cells responsible for the immunoelimination express Fas ligand and strongly rely on the induction of Fas receptor-mediated apoptosis for their action. Although cancer cells are removed successfully by graft-versus-leukemia reactions in myeloid malignancies, their efficiency is low in T cell leukemias. This may be partially because of the ability of malignant T cells to escape apoptosis. Our work shows that Eph family receptor EphB3 is consistently expressed by malignant T lymphocytes, most frequently in combination with EphB6, and that stimulation with their common ligands, ephrin-B1 and ephrin-B2, strongly suppresses Fas-induced apoptosis in these cells. This effect is associated with Akt activation and with the inhibition of the Fas receptor-initiated caspase proteolytic cascade. Akt proved to be crucial for the prosurvival response, because inhibition of Akt, but not of other molecules central to T cell biology, including Src kinases, MEK1 and MEK2, blocked the antiapoptotic effect. Overall, this demonstrates a new role for EphB receptors in the protection of malignant T cells from Fas-induced apoptosis through Akt engagement and prevention of caspase activation. Because Fas-triggered apoptosis is actively involved in the graft-versus-leukemia response and cytotoxic T cells express ephrin-Bs, our observations suggest that EphB receptors are likely to support immunoevasivenes of T cell malignancies and may represent promising targets for therapies, aiming to enhance immunoelimination of cancerous T cells.     

Les genres Costa et Paleocosta (Ostracodes) du paléogène aquitain: Les structures de populations,témoins des paléoenvironnements. Description de Paleocosta aquitanica nov. sp.

Costa tricostata (Reuss) and Paleocosta aquitanicanov. sp. are polymorph species of the Paleogene Aquitaine. In this study, their constituent forms are both described and illustrated. These are particularly ornamented and show Mesogene affinites; their geographical distribution area is limited within the Aquitaine Basin and Bay of Biscaye.In bathyal environments, the spatial distribution of the Costa, reveals three domains characterized by an increase of faunal density and polymorphism and a morpho- functional adaptation through the strengthening of the shell architecture. We attribute these changes to the effects of an adaptative strategy of the populations within an environment of increasing dynamic activity either near drainage channels and/or accumulation zones of terrigenous material continentally-derived, or within highly intensive upwelling zones.In less shallow environments and/or more close tooceanic influences, the Costa and Paleocosta populations flourish but lose their polymorphism. They announce the ecologic limit of the species.     

Agrobacterium tumefaciens T-DNA gene 6b stimulates rol-induced root formation, permits growth at high auxin concentrations and increases root size

Summary All Agrobacterium tumefaciens strains studied up to now transfer an active 6b gene to plant cells. However, the role of this gene in natural tumour induction is unknown. Various effects of 6b on plant cell growth have been described, but the precise mechanism by which 6b causes these effects has not been elucidated. Earlier experiments indicated that the 6b gene might increase auxin sensitivity as do the A. rhizogenes rol genes. The 6b gene from Tm4 (T-6b) was therefore compared with the rolB and rolABC genes. Although T-6b was unable to induce root formation, it strongly interfered with root induction and root elongation. In rolABC/T-6b coinfection experiments on carrots, T-6b-transformed cells stimulated root outgrowth of rolABC-transformed cells, indicating that the biologically active T-6b product is diffusible. Carrot rolABC roots containing the T6b gene rapidly developed into unorganized calli. Nicotiana rustica roots with rolABC and T-6b continued their development, but became very large. Fragments of such roots formed callus at -naphthaleneacetic acid concentrations which inhibited growth of rolABC and normal root fragments, suggesting that the role of 6b genes in natural tumour induction may be to reduce the inhibitory effects of high auxin levels and to keep cells in an undifferentiated state.