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Biomedical subjects

D Birnbaum

Publications and source records attributed to D Birnbaum.

At least 235 records · Page 13Linked to original sources
PubMed1991

Murine Flt3, a gene encoding a novel tyrosine kinase receptor of the PDGFR/CSF1R family.

Receptor-type tyrosine kinases presenting an extracellular region with five immunoglobulin-like domains, and strongly related by sequence similarities in the intracellular region, constitute a family of receptors involved in development and function of various cell lineages. We have isolated and characterized the mouse Flt3 gene, encoding the sixth member of this family. The Flt3 gene possesses an open reading frame of 3000 nucleotides, and therefore appears to code for a protein of 1000 amino acids. The deduced structure of the FLT3 protein presents all the characteristics of a receptor-type kinase of this family. The gene is expressed in placenta, in various adult tissues including gonads and brain, and in hematopoietic cells. The Flt3 transcript is 3.7 kb long, except in the testis, where two shorter post-meiotic transcripts are detected. These results suggest a role for this novel receptor and its yet unidentified ligand in placenta, gonads and hematopoietic and nervous systems.

Amino Acid Sequence↗
PubMed1991

Production and functional characterization of human recombinant FGF-6 protein.

The fibroblast growth factor (FGF) gene family to date comprises seven members and has been implicated in a wide range of physiological and biological processes, including angiogenesis, morphogenesis, and tumorigenesis. The FGFs are mitogens for a broad range of cells of various embryological origins and can act as differentiation factors. The FGFs can bind to tyrosine kinase and non-tyrosine kinase transmembrane receptors; the physiological basis for this is still unknown. In order to study more thoroughly the activities of FGF-6, we have constructed a bacterial expression vector by inserting FGF-6 complementary DNA sequences into the T7 RNA polymerase-based pET3a vector. The resulting construct is able to drive the expression of a high amount of FGF-6 protein in Escherichia coli, which can be solubilized and purified through heparin-Sepharose chromatography and high salt elution. The purified FGF-6 protein displays a strong mitogenic activity on BALB/c 3T3 cells and is able to morphologically transform these cells. By contrast, adult bovine aortic endothelial cells, which normally require the presence of FGF-2 for their growth, show only a limited mitogenic response that is highly dependent on heparin concentration.

3T3 Cells↗
PubMed1991

BEK and FLG, two receptors to members of the FGF family, are amplified in subsets of human breast cancers.

Tumor DNA samples from 387 breast carcinomas have been investigated for amplification of BEK and FLG genes, both of which have been shown to code for cell surface receptors to FGFs. BEK and FLG were found amplified in 11.5 and 12.7% of breast tumors respectively. Statistical analysis, performed on the subset of 297 primary cancers without presurgical therapy, showed for BEK a trend of preferential amplification in patients above 50 years (P = 0.055), whereas amplification of FLG could significantly be correlated with nodal involvement (P = 0.032) and seemed prevalent in steroid hormones receptor positive tumors. Since the same tumors were previously analysed for the amplification of MYC, ERBB2 and HST/INT2/BCL1 possible associations with BEK and FLG amplifications were looked for. BEK was found significantly correlated with MYC and FLG with HST/INT2/BLC1. The amplification of these two FGF receptor genes may therefore represent additional steps in the molecular phenotyping of breast cancer.

Age Factors↗
PubMed1991

Putative structure of the FGF6 gene product and role of the signal peptide.

The human FGF6 gene is an oncogene related by sequence similarities to the fibroblast growth factor (FGF) gene family, which encodes mitogenic peptides implicated in various physiological processes including angiogenesis, morphogenesis, tissue regeneration and survival and oncogenesis. Nucleotide sequence analysis of the FGF6 gene and of cDNA clones revealed an open reading frame able to code for a protein of 208 residues. The FGF6 protein shares 32-70% residues with the other members of the family within the C-terminal two-thirds of the molecule. In vitro, three in-frame ATG codons are able to initiate the translation of three peptides of 175, 198 and 208 residues. These three peptides differ at their amino termini with respect to the relative position of a hydrophobic leader peptide, which extends from residues 16 to 40, and is therefore absent from the shorter (175 amino acids) form. In-vitro analysis indicates that this signal peptide is able to drive the FGF6 protein through the endoplasmic reticulum, where it becomes glycosylated. The presence of this signal peptide sequence appears essential for the in vivo transforming capacity of the FGF6 gene.

Amino Acid Sequence↗
PubMed1991

Fibroblast growth factor gene expression in AIDS-Kaposi's sarcoma detected by in situ hybridization.

Biopsy samples from five acquired immune deficiency syndrome (AIDS)-Kaposi's sarcomas and one non-AIDS-associated Kaposi's sarcoma were assayed by in situ RNA hybridization onto paraformaldehyde-fixed, paraffin-embedded skin sections for the presence of two fibroblast growth factor gene transcripts, FGFB and FGF5. FGF5 gene expression was detected in the characteristic Kaposi's sarcoma spindle-shaped cells in the five samples from human immunodeficiency-positive (HIV+) patients. FGFB transcripts were detected in Kaposi's sarcoma cells as well as in epidermis of HIV- and HIV+ patients. These results complement the observations about growth factor gene expression done on Kaposi's sarcoma-derived cell lines, which thus appear to be representative of what happens in vivo. Furthermore, they demonstrate a contrasting expression pattern of FGF5 and FGFB genes, both involved in the growth factor pathogenic cascade leading to Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Restriction and complexity of Mcf2 proto-oncogene expression.

MCF2/DBL is an X-linked proto-oncogene encoding a protein with a yet undetermined function. It can be activated in vitro by loss of 5' sequences in NIH3T3 bioassays; in vivo, deletion of the gene has been found in some hemophilia B patients. PCR analysis of its expression in mouse tissues shows a restriction to the gonads and tissues of neuroectodermal origin. It also identifies an exon encoding 42 amino acids that is alternatively spliced in murine, but not human testis.

Amino Acid Sequence↗
PubMed1990

Inhibition of alpha-aminoadipate-semialdehyde dehydrogenase from Trichosporon adeninovorans by lysine and lysine analogues.

The alpha-aminoadipate-semialdehyde dehydrogenase (EC 1.2.1.31) of Trichosporon adeninovorans, an enzyme of lysine biosynthesis, was partially purified, some properties of the enzyme were studied and a novel regulatory pattern was found. The Km values of the enzyme were estimated to be 0.78 mM for alpha-aminoadipate, 1.0 mM for ATP, 0.23 mM for NADPH and 0.77 mM for MgCl2. It is demonstrated that the enzyme can be regulated by lysine and lysine analogues. L-Lysine (Ki of 0.09 mM), S-(beta-aminoethyl)-L-cysteine (Ki of 0.007 mM) and delta-hydroxylysine (Ki of 1.65 mM) inhibited the enzyme activity. The inhibition was competitive with respect to alpha-aminoadipate and non-competitive with respect to both ATP and NADPH.

Aldehyde Oxidoreductases↗
PubMed1990

The 11q13 amplicon of a mammary carcinoma cell line.

Fifteen to 20% of breast carcinomas show amplification of genes located at 11q13. The HST/FGFK and INT2 fibroblast growth factor (FGF)-related genes and the BCL1 locus are usually present in the amplification units. We have investigated the structure and chromosomal location of the 11q13 amplicon of the MDA-MB-134 mammary carcinoma cell line by using in situ chromosomal and pulsed field gel hybridizations. The results indicate that a limited number of amplification units are involved in the constitution of an extended chromosomal region located on 11q. These units do not show any important rearrangement over rather large distances around the HST/INT2 and BCL1 loci.

Blotting, Northern↗
PubMed1990

Occurrence of the general control of amino acid biosynthesis in yeasts.

The response of three amino acid biosynthetic enzymes, threonine dehydratase, tyrosine aminotransferase and saccharopine dehydrogenase, to conditions of histidine, tryptophan or lysine limitation was investigated in 15 yeast species. The activities of all these enzymes increased about two- to fourfold as a result of action of the general control of amino acid biosynthesis in Brettanomyces anomalus, Candida maltosa, Hansenula polymorpha, Rhodosporidium toruloides, Saccharomyces cerevisiae and Yarrowia lipolytica. No evidence for the existence of the general control was found in Candida brumptii, Candida utilis, Hansenula anomala, Hansenula henricii, Kluyveromyces marxianus, Pichia guilliermondii, Saccharomycopsis capsularis, Trichosporon adeninovorans and Trigonopsis variabilis.

Amino Acids↗
PubMed1990

Mapping of the glucoamylase gene of Trichosporon adeninovorans by mitotic haploidization using hybrids from protoplast fusions.

In two strains of Trichosporon adeninovorans genes of unknown location were assigned to linkage groups. Diploid strains were produced by protoplast fusion and partially haploidized by growth on benomyl causing mitotic haploidization. We show that both strains synthesize an extracellular glucoamylase with different properties. These differences could be used to map the corresponding gene in the segregants. We could map the glucoamylase gene from one of these yeast strains on linkage group II, one of the three linkage groups identified so far.

Chromosome Mapping↗
PubMed1990

Corneal endothelial permeability after anterior chamber silicone oil.

One of six silicone oils, differing in both viscosity and manufacture, was infused into the anterior chambers of rabbit eyes. Polydimethylsiloxane oil, 5000 cps, caused an increased corneal endothelial permeability to inulin and dextran at 24, 96, and 168 hours after placement into the eye. Intraocular pressures were slightly elevated in the experimental eyes, compared with contralateral controls, at 24 and 144 hours after infusion. The effects of five other oils on corneal endothelial permeability were examined 168 hours after infusion. All oils increased permeability and caused thinning of endothelial cells, together with the appearance of a retrocorneal membrane, except Dow Corning Medical Fluid 360. The results indicated that contact of most silicone oils with corneal endothelium rapidly induces physiologic and morphologic changes.

Animals↗
PubMed1990

Adoption of guidelines for Universal Precautions and Body Substance Isolation in Canadian acute-care hospitals.

The impact of recently recommended hospital infection control guidelines on Canadian acute-care hospitals is unknown. A confidential cross-sectional mailed survey of all acute-care Canadian hospitals was conducted to determine rates of receipt and adoption of published guidelines for Universal Precautions (UP) or Body Substance Isolation (BSI), rationale for adoption and knowledge of costs and benefits. Five hundred and seventy-nine of 943 sites (61%) responded (exceeding 80% in urban centers); 94% among hospitals with at least 300 beds and 57% among those under 300 beds. Seventy-four percent of responders claimed adoption of UP (65%) or BSI (9%), staff protection being their primary motivation. Adoption of either UP or BSI was associated with size (p less than .001), increasing progressively from 45% in the smallest group (less than 25 beds) to 84% in the largest (greater than or equal to 500 beds). Many hospitals introduced modifications and some substituted names other than UP or BSI in adopting a new strategy. In practice, UP and BSI now mean different things in different hospitals, and the distinction between them has become blurred. Furthermore, only 5% claiming adoption of a new strategy adopted all of the fundamental policies expected under UP or BSI. Receipt of guidelines was also correlated with size: one-third of hospitals under 200 beds had not received key publications defining UP and BSI. Only 19% claiming adoption of a new strategy indicated knowledge of cost implications. These results suggest a need for closer collaboration among hospitals and government agencies in developing uniform infection control policies, and for systematic evaluation of the cost and effectiveness of new strategies.

Body Fluids↗
PubMed1990

Localization of the mouse Mcf-2 (Dbl) protooncogene within a conserved linkage group on the mouse X chromosome.

A mouse cDNA probe homologous to the human MCF2 transforming sequence has been identified and partially cloned, and is used here to localize the gene on the mouse X chromosome. The human gene has been physically mapped to within 60 kb of the gene for coagulation factor IX, within a large conserved linkage group between the mouse and human genomes which extends from HPRT to G6PD on the X chromosomes of both mammalian species. In situ hybridization of the mouse Mcf-2 probe onto mouse metaphase chromosomes indicates that this gene lies in the same region of the X chromosome as Cf-9, the mouse gene for coagulation factor IX. Moreover, segregation of species-specific genomic DNA polymorphisms for Mcf-2 and Cf-9 in a total of 203 individuals derived from two large interspecific mouse backcross populations (which are also segregating for 17 other X-linked molecular markers) demonstrates that the mouse genes are separated by only 0.5 +/- 0.5 cM. Despite this short distance we were able to order Mcf-2 and Cf-9 relative to one another and other genes in this region. The mouse gene order Hprt-Cf-9-Mcf-2-G6pd predicts a similar ordering of genes on the human X chromosome, a gene order which has only recently been demonstrated by physical mapping. Thus, the map location and linkage relationships of the Mcf-2 gene are similar in man and mouse, and this unique protooncogenic locus is part of a conserved linkage group on the mammalian X chromosome.

Animals↗