Association of a new c-Cbl related protein with the very first stages of apoptosis induction

in Cancer Detection and Prevention (2002), 26(2), 93-104

This study investigates the involvement of the c-cbl proto-oncogene during the first stages of the apoptotic process. We have already shown that a c-Cbl aptotosis-related protein of 90 kDa (CARP 90) is ... [more ▼]

This study investigates the involvement of the c-cbl proto-oncogene during the first stages of the apoptotic process. We have already shown that a c-Cbl aptotosis-related protein of 90 kDa (CARP 90) is detected very rapidly in the cytoplasm as well as in the nucleus of murine thymocytes after hydrocortisone (HC) treatment. We report here that this protein appeared as well after in vivo treatment of mice by gamma-irradiation or injection of anti-CD3 monoclonal antibody, two potent thymic apoptosis inductors, providing a close relationship between the occurrence of apoptosis and the appearance of CARP 90. We showed that CARP 90 and p120(cbl) share numerous epitopes strikingly suggesting that CARP 90 is coded by c-cbl. In addition, KO mice do not sustain CARP 90 appearance. We finally showed that CARP 90 contains N- and C-terminal end epitopes of p120(cbl) which suggests that CARP 90 is an alternative spliced form of c-cbl. This protein was also observed under gamma-irradiation in tissues of different origin, which enlarges the physiological significance of this phenomenon. The very rapid CARP 90 appearance under apoptotic conditions in the nucleus of cells originating in different tissues makes this protein if not a possible new actor of the apoptotic process, at least an interesting marker of this process. (C) 2002 International Society for Preventive Oncology. Published by Elsevier Science Ltd. All rights reserved. [less ▲]

Association of acute leukemia and autoimmune polyendocrine syndrome in two kindreds.

in Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K (2003), 17(9), 1912-1914

The association of astrocytoma and pituitary adenoma in a patient with alcaptonuria.

in Journal of the Neurological Sciences (1992), 108(1), 32-34

A female patient with a juvenile pilocytic astrocytoma and a pituitary adenoma is described. The patient also has alcaptonuria, a rare inborn error of metabolism with autosomal recessive mode of ... [more ▼]

A female patient with a juvenile pilocytic astrocytoma and a pituitary adenoma is described. The patient also has alcaptonuria, a rare inborn error of metabolism with autosomal recessive mode of inheritance. The association of these three disorders has never been reported previously. The possible existence of a common genetic factor in the development of both tumors and alcaptonuria is discussed. [less ▲]

Association of fibroblastoid features with the invasive phenotype in human bronchial cancer cell lines

in Clinical & Experimental Metastasis (1998), 16(2), 105-12

The acquisition of a metastatic phenotype by epithelial cells implicates a series of changes altering their differentiation, their overall behavior and morphology. In the present study, we have examined ... [more ▼]

The acquisition of a metastatic phenotype by epithelial cells implicates a series of changes altering their differentiation, their overall behavior and morphology. In the present study, we have examined the relationships between the cellular morphology, E-cadherin expression, matrix metalloproteinases expression and in vitro invasive properties in two human bronchial immortalized cell lines. The (16HBE14o-) cell line which did not show any invasive abilities in the Boyden chamber assay displayed a typical epithelial morphology in monolayer, expressed high levels of E-cadherin and synthesized neither MMP-2 and MT1-MMP nor vimentin. In contrast, the BZR cell line which was highly invasive displayed a more elongated phenotype in monolayer, did not produce E-cadherin but expressed vimentin, MMP-2 and MT1-MMP. Our data therefore suggest that the metastatic progression of broncho-pulmonary cancer cells results in a cellular dedifferentiation and the gain of some mesenchymal attributes (loss of E-cadherin and expression of vimentin) associated with enhanced degradative properties (expression of metalloproteinases) [less ▲]

Association of milk traits with SSCP polymorphisms at the growth hormone gene in the serrana goat

in Small Ruminant Research (2003), 50

The five exons and the 5' and 3'-untranslated regions (5'-UTR and 3'-UTR) of the oGH gene were screened for mutations using PCR-single strand conformation polymorphism (PCR-SSCP) procedures in 523 Serra ... [more ▼]

The five exons and the 5' and 3'-untranslated regions (5'-UTR and 3'-UTR) of the oGH gene were screened for mutations using PCR-single strand conformation polymorphism (PCR-SSCP) procedures in 523 Serra da Estrela ewes and were found to be highly polymorphic. The region extending across and between the GH2-N and GH2-Z copies was sequenced allowing the design of primers for the specific PCR amplification of each copy. These were cloned and sequenced in 20 animals representative of all SSCP patterns. The corresponding genotypes were established for each copy following nucleotide sequencing of SSCP alleles. Twenty-four polymorphic sites were found at the GH2-N (or GH1) and fourteen at the GH2-Z copies. Eight amino acid substitutions were predicted at the GH2-N and six at the GH2-Z copies. Milk yield adjusted to 150 lactation days was analysed for the genotype of each oGH gene copy taken separately or together (associated genotypes) by restricted maximum likelihood (REML) through a univariate best linear unbiased prediction (BLUP) animal model with repeated measures. Significant associations between genotypes and milk yield were observed. Within GH2-N genotypes there was a milk yield differential of 21.4+/-0.2 l/150 d between the most (N7) and the least (N5) productive ones. Within GH2-Z genotypes there was a differential of 21.6+/-0.2 l/150 d between the most (Z8) and the least (Z1) productive ones. The effect of associated GH2-N and GH2-Z genotypes revealed a differential of 39.6+/-0.3 l/150 d between the most (N1+Z7) and the least (N3+Z2) productive associated genotypes. The results show that GH2-N and GH2-Z genotypes significantly affect milk yield in Serra da Estrela ewes. Moreover, the apparent joint effect of GH2-N and GH2-Z genotype could improve milk yield in 25% as compared with the mean milk production of the analysed population. [less ▲]

Association Of Synthetic Peptide-Fragments Of Human Apolipoprotein-A-I With Phospholipids

in Journal of Lipid Research (1995), 36(8), 1686-96

The sequences of the plasma apolipoproteins have a high degree of internal homology as they contain several 22-mer internal repeats. These amphipathic helical repeats are considered as the structural and ... [more ▼]

The sequences of the plasma apolipoproteins have a high degree of internal homology as they contain several 22-mer internal repeats. These amphipathic helical repeats are considered as the structural and functional units of this class of proteins. We proposed that the 22-mer repeats of the plasma apolipoproteins consist of 17-mer helical segments separated by extended beta-strands comprising five amino acid residues with a proline in the center of this segment. These beta-strand segments help reverse the orientation of the consecutive helices of apoA-I, A-IV, and E in a discoidal apolipoprotein-phospholipid complex. In order to support this hypothesis, we synthesized apoA-I fragments consisting of, respectively, one putative helix (residues 166-183), one helix plus a beta-strand (residues 161-183), and a pair of helices separated by a beta-strand (residues 145-183). The structural and lipid-binding properties of these peptides were investigated by turbidity, fluorescence, binding studies with unilamellar phospholipid vesicles, electron microscopy, and circular dichroism measurements. Our data show that one single putative helical segment or one helical segment plus one extended beta-strand do not form stable complexes with phospholipids. The addition of a second adjacent helix has no influence on the lipid affinity of the apoA-I 145-183 peptide compared to the shorter segments but substantially improves the stability of the complexes. The helical content of the peptide increases upon lipid association as observed with apoA-I. The complexes generated with the apoA-I 145-183 peptide appear as discoidal particles by negative staining electron microscopy, with heterogeneous sizes ranging between 250 and 450 A. The relative orientation of the peptide and the phospholipid is the same as in a DMPC/apoA-I complex as the helices are oriented parallel to the acyl chains of the phospholipid. However, the stability of these complexes is significantly lower than that of the corresponding DMPC/apoA-I complexes. The transition temperature, fluidity, and cooperativity of the phospholipid bilayer are only weakly affected by the association with the apoA-I 145-183 peptide. These data suggest that a pair of helical peptides linked through a beta-strand associates more tightly with lipids and can form discoidal lipid-peptide complexes, than a single helix. A comparison with the properties of native apoA-I suggests, however, that the cooperativity between pairs of helices in native apoA-I further contributes to strengthen the lipid-protein association. [less ▲]

Association of the adaptor TANK with the IκB kinase (IKK) regulator NEMO connects IKK complexes with IKKε and TBK1 kinases

in Journal of Biological Chemistry (2002), 277(40), 37029-37036

Canonical activation of NF-kappaB is mediated via phosphorylation of the inhibitory IkappaB proteins by the IkappaB kinase complex (IKK). IKK is composed of a heterodimer of the catalytic IKKalpha and ... [more ▼]

Canonical activation of NF-kappaB is mediated via phosphorylation of the inhibitory IkappaB proteins by the IkappaB kinase complex (IKK). IKK is composed of a heterodimer of the catalytic IKKalpha and IKKbeta subunits and a presumed regulatory protein termed NEMO (NF-kappaB essential modulator) or IKKgamma. NEMO/IKKgamma is indispensable for activation of the IKKs in response to many signals, but its mechanism of action remains unclear. Here we identify TANK (TRAF family member-associated NF-kappaB activator) as a NEMO/IKKgamma-interacting protein via yeast two-hybrid analyses. This interaction is confirmed in mammalian cells, and the domains required are mapped. TANK was previously shown to assist NF-kappaB activation in a complex with TANK-binding kinase 1 (TBK1) or IKKepsilon, two kinases distantly related to IKKalpha/beta, but the underlying mechanisms remained unknown. Here we show that TBK1 and IKKepsilon synergize with TANK to promote interaction with the IKKs. The TANK binding domain within NEMO/IKKgamma is required for proper functioning of this IKK subunit. These results indicate that TANK can synergize with IKKepsilon or TBK1 to link them to IKK complexes, where the two kinases may modulate aspects of NF-kappaB activation. [less ▲]

Association of Tibolone and Fluoride Displays a Pronounced Effect on Bone Mineral Density in Postmenopausal Osteoporotic Women

in Gynecological Endocrinology : The Official Journal of the International Society of Gynecological Endocrinology (1999), 13(5), 361-8

A double-blind, placebo-controlled, randomized, prospective two-center study was carried out to assess the effects of tibolone + fluoride versus placebo + fluoride therapy on trabecular and cortical bone ... [more ▼]

A double-blind, placebo-controlled, randomized, prospective two-center study was carried out to assess the effects of tibolone + fluoride versus placebo + fluoride therapy on trabecular and cortical bone in postmenopausal osteoporotic women. Ninety-four subjects (mean age 61.1 years, postmenopausal 13.5 years on average) with low bone mineral density (BMD) at baseline were randomized to 2.5 mg of tibolone (Org OD 14, Livial) plus 26.4 mg of fluoride (Fluocalcic) or placebo plus 26.4 mg of fluoride daily over 2 years; 55 (58.5%) subjects completed the study, the main reason for discontinuation being untoward gastrointestinal effects. BMD at the lumbar spine was measured by both dual photon absorptiometry (DPA) and dual-energy X-ray absorptiometry (DXA), and at the hip by DXA at 6-month intervals. Baseline values (DXA, g/cm2) for tibolone + fluoride and placebo + fluoride groups were 0.733 and 0.744 for the lumbar spine, and 0.761 and 0.788 for the hip. Change from baseline and percentage change from baseline were calculated for the intent-to-treat and completers groups. An analysis of variance (ANOVA) model or Wilcoxon test was used for statistical evaluation. There was a mean increase in BMD at the lumbar spine measured by DPA of 25.3% and 12.3% in tibolone + fluoride and placebo + fluoride groups, respectively (p = 0.01); with DXA, respective changes were 32.6% and 14.0% (p = 0.013). Data on BMD at the hip showed mean increases of 7.9% and 2.6% for the tibolone + fluoride and placebo + fluoride groups, respectively. We conclude that combined tibolone + fluoride treatment induces a highly significant increase in BMD at the lumbar spine without simultaneous loss of the cortical bone allowing for a meaningful reduction of the fluoride dose when given in combination with tibolone. [less ▲]

Association of two single-isomer anionic CDs in NACE for the chiral and achiral separation of fenbendazole, its sulphoxide and sulphone metabolites: Application to their determination after in vitro metabolism

Poster (2010, March)

L'associationnisme régional italien en Belgique : point final de l'immigritude?

in Van Der Wee, H.; Dumoulin, M. (Eds.) Hommes, cultures et capitaux dans les relations italo-belges aux XIXe et XXe siècles (1993)