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Y Cayre

Publications and source records attributed to Y Cayre.

At least 19 recordsLinked to original sources
PubMed2001

Determination of myeloid antigen expression on childhood acute lymphoblastic leukaemia cells: discrepancies using different monoclonal antibody clones.

Prospective clinical studies including large numbers of patients have led to the conclusion that co-expression of myeloid antigens in childhood acute lymphoblastic leukaemia (My+ ALL) does not have prognostic significance. However, reports of the frequency of My+ ALL in children vary widely across laboratories using different mAb clones and staining and analysing procedures. Taking two commonly accepted thresholds of positivity for myeloid antigens (20 and 30%), we analysed the immunoreactivity of the most widely employed mAb clones against CD13 (SJ1D1, L138 and My7) and CD33 (My9, P67.6 and D3HL60) and compared the proportions of My+ ALL detected by these clones in childhood ALL. The correlation between myeloid antigen expression and the presence of the t(12;21) translocation was analysed concomitantly in the same samples. The percentage of ALL cases positive for myeloid markers varied significantly depending on the mAb clone and the positive threshold. Among patients with B-ALL, the proportion of CD13+ ALL was significantly lower using SJ1D1 than using L138 or My7, while the proportion of CD33+ ALL was significantly higher for My9 than for P67.6 or D3HL60. Analysis of the co-expression of CD13 and CD33 on B-ALL cells using combinations of mAb clones showed that this frequency was either underestimated by the SJ1D1/D3HL60 or overestimated by the L138/P67.6 and My7/My9 combinations. A correlation between CD13/CD33 positivity and the t(12;21) translocation was uniformly observed in B-ALL patients for a positive threshold of 30%, whereas SJ1D1/D3HL60 detected no correlation between t(12;21) and CD13/CD33 positivity when the threshold was lowered to 20%. These data show that the mAb clones commonly used to detect the CD13 and CD33 surface antigens have variable immunoreactivity against childhood ALL cells, which may partly explain the conflicting reports concerning the prognostic significance of myeloid antigen expression in paediatric ALL and its association with different translocations. The present findings may also be of clinical importance for therapeutic choices.

Antibodies, Monoclonal↗
PubMed2001

Determination of myeloid antigen expression on childhood acute lymphoblastic leukaemia cells: discrepancies using different monoclonal antibody clones.

Prospective clinical studies including large numbers of patients have led to the conclusion that co-expression of myeloid antigens in childhood acute lymphoblastic leukaemia (My+ ALL) does not have prognostic significance. However, reports of the frequency of My+ ALL in children vary widely across laboratories using different mAb clones and staining and analysing procedures. Taking two commonly accepted thresholds of positivity for myeloid antigens (20 and 30%), we analysed the immunoreactivity of the most widely employed mAb clones against CD13 (SJ1D1, L138 and My7) and CD33 (My9, P67.6 and D3HL60) and compared the proportions of My+ ALL detected by these clones in childhood ALL. The correlation between myeloid antigen expression and the presence of the t(12;21) translocation was analysed concomitantly in the same samples. The percentage of ALL cases positive for myeloid markers varied significantly depending on the mAb clone and the positive threshold. Among patients with B-ALL, the proportion of CD13+ ALL was significantly lower using SJ1D1 than using L138 or My7, while the proportion of CD33+ ALL was significantly higher for My9 than for P67.6 or D3HL60. Analysis of the co-expression of CD13 and CD33 on B-ALL cells using combinations of mAb clones showed that this frequency was either underestimated by the SJ1D1/D3HL60 or overestimated by the L138/P67.6 and My7/My9 combinations. A correlation between CD13/CD33 positivity and the t(12;21) translocation was uniformly observed in B-ALL patients for a positive threshold of 30%, whereas SJ1D1/D3HL60 detected no correlation between t(12;21) and CD13/CD33 positivity when the threshold was lowered to 20%. These data show that the mAb clones commonly used to detect the CD13 and CD33 surface antigens have variable immunoreactivity against childhood ALL cells, which may partly explain the conflicting reports concerning the prognostic significance of myeloid antigen expression in paediatric ALL and its association with different translocations. The present findings may also be of clinical importance for therapeutic choices.

Antibodies, Monoclonal↗
PubMed1999

The oncogenic TEL/PDGFR beta fusion protein induces cell death through JNK/SAPK pathway.

The TEL/PDGFR beta (T/P) fusion protein isolated from patients bearing a t(5;12) translocation is transforming when expressed in haematopoietic cells. To examine the signal transduction events activated by this protein, we measured the effect of T/P on activation of the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) in mouse bone marrow-derived Ba/F3 cells. Significant increase in the activity of JNK/SAPK1 was observed in transient transfection as well as in Ba/F3 cells stably expressing T/P. This activation was abrogated when the T/P-expressing cells were treated with a specific inhibitor of the PDGFR beta tyrosine kinase, indicating that the activity of the PDGFR beta part of the fusion protein was involved in JNK/SAPK activation. Expression of a dominant negative mutant of mitogen-activated protein kinase kinase 4 (MKK4), a direct activator of JNK/SAPK, prevented T/P-induced JNK/SAPK activation. In addition, inhibition of phosphoinositide-3 OH kinase (PI-3 kinase), a promoting survival factor, potentiated the effect of T/P on JNK/SAPK activation. Interestingly, expression of T/P was shown to initiate an apoptotic response that was enhanced by treatment of cells with the PI-3 kinase inhibitor LY294002, suggesting that T/P mediated cell death through activation of JNK/SAPK signalling pathway. Consistent with this hypothesis, expression of the dominant negative mutant of MKK4 decreased T/P-mediated apoptosis, while a dominant-negative mutant of PI-3 kinase enhances cell death. These findings indicate that activation of JNK/SAPK by T/P is related to apoptosis rather than cell proliferation and transformation.

Animals↗
PubMed1999

Genomic organization and chromosomal localization of mouse proteinase 3 (Myeloblastin).

Proteinase 3 (PR3), is a matrix-degrading serine proteinase expressed in different hematopoietic cell lineages. The PR3 protein appears to regulate the myeloid differentiation and was found to be the autoantigen associated with Wegener granulomatosis. We have isolated and characterized the gene for mouse PR3 (mPR3) and determined its chromosomal location. The gene has been localized to Chromosome (Chr) 10. Comparison of mouse PR3 genomic structure with that of its human counterpart indicates that: 1) the mPR3 gene spans 7 kb organized in 5 exons and 4 introns, 2) the codons of His-Asp-Ser of the catalytic site are conserved and spread out over different exons, similar to the human gene, and 3) the gene product encodes a pre-proform of the protein. Knowledge of the structure and chromosomal location of the mPR3 gene may help better the understanding of the temporal and cell-specific expression of mouse PR3.

Amino Acid Sequence↗
PubMed1989

Glucocorticoid regulation of hepatic 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene expression.

The effect of adrenalectomy and triamcinolone treatment on mRNA encoding rat hepatic 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase was studied. Adrenalectomy decreased both the kinase and the bisphosphatase activities of the bifunctional enzyme to about 30% of the values in livers of normal rats. Triamcinolone treatment restored both activities to normal by 24 h. These changes were caused by alterations in the concentration of the enzyme as determined by immunoblotting and by an assay that measures phosphoenzyme formation. Messenger RNA for liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase was markedly decreased by adrenalectomy and was increased 15-fold by triamcinolone administration for 8 h. The rate of transcription of the bifunctional enzyme gene, measured in rat liver nuclei, was also decreased in adrenalectomy, and triamcinolone treatment increased this rate 5-fold within 8 h. Similarly, liver nuclear precursors of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase mRNA were decreased by adrenalectomy to 25% of the level in nuclei from normal rats. Triamcinolone treatment restored heterogeneous values by 2 h, while treatment for 30 h increased it 12-fold over the adrenalectomized levels. It was concluded that glucocorticoids regulate the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, at least in part, by modulating the transcription rate of the gene.

Adrenalectomy↗
PubMed1988

Immunochemical evidence that three protein kinase C isozymes increase in abundance during HL-60 differentiation induced by dimethyl sulfoxide and retinoic acid.

Activity of the Ca2+/phospholipid-dependent protein kinase C has been shown to increase during differentiation of the human promyelocytic leukemia cell line HL-60 by dimethyl sulfoxide and retinoic acid (Zylber-Katz, E., and Glazer, R. I. (1985) Cancer Res. 45, 5159-5164). Antipeptide antibodies were prepared that specifically recognize the alpha, beta, and gamma isozymes of protein kinase C in rat brain cytosol and HL-60 cell extracts. The three isozymes do not share a common tissue distribution pattern. The gamma enzyme is abundant in brain but a relatively minor component in HL-60 cells; the opposite is true for the alpha enzyme. All three isozymes increase at least 2-fold in abundance in HL-60 cells exposed to 1.2% dimethyl sulfoxide for 48 h. The increase in abundance of the alpha and beta isoforms reaches 7- and 5-fold, respectively, by 96 h without further increase in the abundance of the gamma isozyme. Similarly, all three isozymes increase at least 1.5-fold in abundance after 48 h and 3-fold after 96 h with 1 microM retinoic acid. No further increase in the abundance of any of the isozymes is seen between 96 and 144 h of incubation with retinoic acid. The increase in protein kinase C activity is not limited to the cytosolic forms of the enzyme; a parallel increase in membrane-associated protein kinase C is also observed during differentiation. Approximately 10% of total protein kinase C activity is membrane-associated in both control and differentiating cells. These studies provide the first immunochemical evidence that all three protein kinase C isozymes increase during HL-60 cell differentiation, and they suggest that the increase in the isozyme levels may be coordinately regulated.

Amino Acid Sequence↗
PubMed1988

1,25-Dihydroxyvitamin D3 transcriptionally regulates tumour necrosis factor mRNA during HL-60 cell differentiation.

We investigated TNF-alpha gene expression in HL-60 cells under the influence of 1,25(OH)2D3. Our results show that TNF-alpha gene expression is transcriptionally activated by 1,25(OH)2D3. Despite the increase of TNF-alpha mRNA, very little TNF protein is found in either supernatants or cell lysates of HL-60 cells cultured in the presence of the vitamin. Therefore 1,25(OH)2D3 is regulating the transcription of the TNF-alpha gene in HL-60 cells without affecting translation. Our data suggest that an additional signal is necessary under physiological conditions to control post-transcriptionally TNF-alpha protein synthesis and secretion.

Calcitriol↗
PubMed1987

Model for intermediate steps in monocytic differentiation: c-myc, c-fms, and ferritin as markers.

A mature hematopoietic cell represents the end product of a stepwise differentiation process. As a model system for studying differentiation, the human promyelocytic leukemia cell line HL-60 undergoes terminal monocytic/macrophagic differentiation following exposure to either phorbol 12-myristate 13-acetate or 1,25-dihydroxyvitamin D3. We have derived and analyzed a variant HL-60 cell line, 1F10, that permits the study of several intermediate steps in the myeloid differentiation process. These intermediate steps are documented by cell cycle data and phenotype analysis as well as markers such as c-myc, c-fms, and both subunits of ferritin.

Antibodies, Monoclonal↗
PubMed1984

Structural study of hemoglobin Hazebrouck, beta 38(C4)Thr----Pro. A new abnormal hemoglobin with instability and low oxygen affinity.

A new beta-variant has been detected and structurally defined in a French male, with a life-long history of hemolytic anemia. This variant is moderately unstable and has a low oxygen affinity. The abnormal hemoglobin was not detected by standard electrophoretic procedures. It moved slightly slower than Hb A during isoelectric focusing (IEF). Two minor fractions were also seen; the first migrated just cathodal to Hb F, as did partially oxidized Hb A or hemichrome derivatives of some unstable hemoglobins; the second in the position of free alpha-chains. The abnormal beta-chain was readily separated from both beta A- and alpha A-chains by acid-urea-Triton globin chain electrophoresis. Structural study was conducted simultaneously by fingerprinting and high-performance liquid chromatography (HPLC) of tryptic peptides. A new mutation beta 38(C4)Thr----Pro was found, which was named Hb Hazebrouck.

Adult↗
PubMed1983

Structure and expression of the mouse beta 2-microglobulin gene isolated from somatic and non-expressing teratocarcinoma cells.

Mouse teratocarcinoma cells express neither H-2 heavy chains nor beta 2-microglobulin (beta 2-m). We have constructed two genomic libraries, one from PCC4-aza-RI embryonal carcinoma cells and the other from their adult syngenic counterpart 129/Sv liver cells (H-2bc). The libraries were screened with a full length mouse beta 2-m cDNA probe which we isolated and sequenced. Two cosmid clones carrying the entire beta 2-m gene were isolated, one from each library. There was no detectable difference in structure between the two genes. Furthermore, both were shown to be active and to restore beta 2-m synthesis upon transfer into mutant cells deficient in beta 2-m. Irreversible DNA alterations in or around the beta 2-m gene are thus unlikely to account for the lack of beta 2-m gene expression in embryonal teratocarcinoma cells.

Animals↗
PubMed1981

Expression of an antigen receptor on T cells does not require recombination at the immunoglobulin JH-C mu locus.

Considerable evidence has accumulated suggesting that the antigen receptor(s) on T cells is coded for by genes for the variable (V) region of the immunoglobulin heavy (H) chains. In B cells, a complete gene for the immunoglobulin VH region is formed by somatic recombination of VH and joining region heavy chain (JH) gene segments [through an intermediate diversity(D) region gene segment]. In an attempt to determine whether a complete immunoglobulin VH region is expressed on T cells that bear an antigen receptor, we analyzed the restriction map of the JH-C mu locus in genomic DNA from two cloned murine cytotoxic T-lymphocyte (CTL) lines specific for the x-ray-induced leukemia RL male 1. We found no rearrangement of the JH C mu locus in the CTL lines, indicating that the T-cell antigen receptor(s) in these CTLs is not coded for by a complete immunoglobulin VH gene formed by joining of VH, (DH), and JH genes. In addition, we determined that C mu genes on both chromosomes were present and that there was no rearrangement of the C alpha, C kappa, or lambda chain genes in these CTL cells.

Animals↗
PubMed1981

Isolation of a subset of thymocytes inducible for terminal transferase biosynthesis.

A new technique using direct binding of nucleated hematopoietic cells to PNA-coated rabbit red blood cell monolayers was used to separate PNA + and PNA - cells from murine thymus. The rigorously purified PNA - thymocyte population was found to lack TdT and to be low in TL. Incubation of the negative fraction with TP 5 resulted in the synthesis of TdT in a large number of cells in the fraction, and the appearance of TL on the surface of about 20% of the cells. Isolation of this inducible population has led us to propose a new class of cells in intrathymic T cell development.

Agglutinins↗