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Biomedical subjects

D Birnbaum

Publications and source records attributed to D Birnbaum.

At least 19 recordsLinked to original sources
PubMed1992

Expression of the FMS/KIT-like gene FLT3 in human acute leukemias of the myeloid and lymphoid lineages.

FLT3, a receptor belonging to the FMS/KIT family and localized to 13q12, could play a role in the biology of early hematopoietic progenitor cells. Because FMS and KIT are expressed in both normal progenitors and myeloid leukemias, we looked for FLT3 expression in fresh human leukemic cells using Northern blot analysis. High levels of FLT3 expression were detected in 92% of the cases of acute myeloid leukemia (AML) tested, ranging from the M1 to the M5 stages of differentiation assessed in the French-American-British classification. Immature (MO) AML cells, biphenotypic leukemias, and AML with megakaryocytic differentiation (M7 subtype) also expressed the FLT3 transcript. FLT3 was also expressed at high levels in acute lymphoid leukemias of T and B origins. Finally, it was not expressed in chronic myeloid leukemias in chronic phase, whereas it was expressed in most blast crisis samples. This pattern of expression of FLT3 contrasts with the expression of FMS and KIT restricted to myeloid leukemias, and suggests that the FLT3 product could play a role in the expansion of the leukemic blasts of both the myeloid and lymphoid lineages.

B-Lymphocytes↗
PubMed1992

Submicrometer intracellular chemical optical fiber sensors.

A thousandfold miniaturization of immobilized optical fiber sensors, a millionfold or more sample reduction, and at least a hundredfold shorter response time, all simultaneously, were achieved by combining nanofabricated optical fiber tips with near-field photopolymerization. Specifically, pH optical fiber sensors were prepared with internal calibration, making use of the differences in both fluorescence and absorption of the acidic and basic dye species. The submicrometer sensors have excellent detection limits, as well as photostability, reversibility, and millisecond response times. Successful applications include intracellular and intraembryonic measurements. Potential applications include spatially and temporally resolved chemical analysis and kinetics inside single biological cells and their substructures.

Aluminum↗
PubMed1992

Fusion and amplification of two originally non-syntenic chromosomal regions in a mammary carcinoma cell line.

The FLG/FGFRI gene, encoding a receptor for members of the FGF family, is located at 8p11.2-p12. It is amplified, overexpressed, and not grossly rearranged in the MDA-MB-134 breast carcinoma cell line, whereas other genes from the pericentromeric 8p region are not amplified. The FGF4/HSTFI gene, located at 11q13, is also amplified with a substantial portion of the 11q13 region, but is not overexpressed in MDA-MB-134 cells. In this cell line, amplified sequences constitute a large homogeneously staining region (HSR) which is part of a marker chromosome containing chromosome 8 and chromosome 11 sequences. Using probes for the FGF4/HSTFI and the FLG/FGFRI genes in fluorescence chromosomal in situ hybridization, we show that the HSR contains de novo fused and amplified 11q13 and 8p11-p12 sequences associated in a complex structure containing approximately the same number of FGF4 and FGFRI genes. The significance of this genetic abnormality for MDA-MB-134 cells, and for breast carcinogenesis in general, is unknown, but may underlie a particular type of oncogene activation.

Breast Neoplasms↗
PubMed1992

Fibroblast growth factor receptor-4 shows novel features in genomic structure, ligand binding and signal transduction.

Fibroblast growth factor (FGF) receptor (FGFR) gene family consists of at least four receptor tyrosine kinases that transduce signals important in a variety of developmental and physiological processes related to cell growth and differentiation. Here we have characterized the binding of different FGFs to FGFR-4. Our results establish an FGF binding profile for FGFR-4 with aFGF having the highest affinity, followed by K-FGF/hst-1 and bFGF. In addition, FGF-6 was found to bind to FGFR-4 in ligand competition experiments. Interestingly, the FGFR-4 gene was found to encode only the prototype receptor in a region where both FGFR-1 and FGFR-2 show alternative splicing leading to differences in their ligand binding specificities and to secreted forms of these receptors. Ligands binding to FGFR-4 induced receptor autophosphorylation and phosphorylation of a set of cellular polypeptides, which differed from those phosphorylated in FGFR-1-expressing cells. Specifically, the FGFR-1-expressing cells showed a considerably more extensive tyrosine phosphorylation of PLC-gamma than the FGFR-4-expressing cells. Structural and functional specificity within the FGFR family exemplified by FGFR-4 may help to explain how FGFs perform their diverse functions.

Alternative Splicing↗
PubMed1992

New gene in the homologous human 11q13-q14 and mouse 7F chromosomal regions.

Alterations in the chromosomal region 11q13-11q14 are involved in several pathologies in which most of the key genes remain to be identified. In an effort to isolate as many candidates as possible, we are cloning genes from this region. We report here the mapping of a new sequence from 11q13.5-11q14. This sequence, designated D11S833E, putatively encodes a new gene, provisionally named GARP. We cloned its homologous sequence in the mouse and located it on Chromosome (Chr) 7, region F. The human and mouse genes belong to a conserved group of synteny. This, together with the similar conservation of the FGF and TYR genes, indicates that the human 11q13-q14 and mouse 7E-7F regions share homology.

Animals↗
PubMed1992

Isolation and sequence of the murine Fgf6 cDNA.

We have studied the structure of the murine Fgf6 gene encoding a fibroblast growth factor with the purpose of looking for putative regulatory sequences in the 5' and 3' non-coding regions. The Fgf6 cDNA contains a very long 3' untranslated portion of 4015 nucleotides.

Animals↗
PubMed1992

Chromosomal localization of FLT4, a novel receptor-type tyrosine kinase gene.

A new human gene encoding a putative receptor-type tyrosine kinase (RTK) was isolated by screening a placenta cDNA library with a mouse Flt3 probe. The deduced amino acid sequence of the intracellular region of the molecule showed that it was strongly related to the FLT1 and KDR/FLK1 gene products and to a lesser degree to members of the class III RTKs: FMS/CSF1R, PDGFRA/B, KIT, and FLT3. The gene was named FLT4. Cosmid clones of the mouse Flt4 gene were isolated. The human gene was localized to bands q34-q35 of chromosome 5, i.e., slightly telomeric to the CSF1R/PDGRFB tandem of genes, and the mouse homolog to chromosome 11, region A5-B1.

Amino Acid Sequence↗
PubMed1992

Localization of 11q13 loci with respect to regional chromosomal breakpoints.

We have employed two strategies to map 13 markers located at 11q13. First, we used pulsed-field gel electrophoresis of DNA fragments obtained with methylation-sensitive restriction enzymes. The markers used in this study were scattered over 8.4 Mb and, for most of them, could not be linked one to another. A second mapping strategy employed hybridization to either DNA of somatic hybrids containing various parts of the long arm of chromosome 11 or metaphase chromosomes of a B-cell line containing the t(11;14)(q13;q32) translocation. We were able to sort out the centromeric from the telomeric probes with respect to translocation breakpoints taken as reference chromosomal landmarks by this approach. BCL1, which corresponds to the region where the t(11;14)(q13;q32) translocation breakpoints are clustered, appears as a boundary between two areas of human/mouse homology present in conserved syntenic regions on mouse chromosomes 7 and 19.

Animals↗
PubMed1992

Localization of the 5' end of the MCF2 oncogene to human chromosome 15q15----q23.

Oncogenic activation of the MCF.2 cell line-derived transforming sequence gene (MCF2) occurs through substitution of part of its 5' coding region by unrelated nonsyntenic sequences. Analysis of the MCF2 oncogene locus revealed complex recombination events involving four discontinuous human DNA segments. The upstream replacing sequence, named URS, represents the farthest 5' portion of the locus. The URS sequence maps to the D15S93 locus on human chromosome 15q15----q23.

Base Sequence↗
PubMed1992

DNA amplification at 11q13.5-q14 in human breast cancer.

Band q13 of chromosome 11 is frequently amplified in human breast cancers, but the gene(s) responsible for the emergence of this amplicon remain(s) elusive as yet. As a tribute to the complexity of the amplification events involving 11q13 sequences in human breast cancer, we have now studied a more telomeric region at 11q13.5-q14 defined by a new transcription unit, D11S833E. We have observed that amplicons present in cell lines and primary tumors amplified for both BCL1 and D11S833E could be interrupted between these two loci. Such discontinuities were demonstrated by using a probe for the KRN1 gene, which we have localized between the BCL1/FGF4 region and D11S833E. In fact, KRN1 was not present in 4 out of 10 amplicons bearing both BCL1 and D11S833E. Furthermore, we have observed tumors in which D11S833E could be amplified in the absence of amplification of other known markers of 11q13. Therefore, D11S833E defines a new and independent amplification unit in this region.

Breast Neoplasms↗