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Biomedical subjects

D Birnbaum

Publications and source records attributed to D Birnbaum.

At least 217 records · Page 12Linked to original sources

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↗

Regulation of chorismate mutase activity of various yeast species by aromatic amino acids.

The regulatory properties of chorismate mutase, its cellular localization and isoenzyme pattern were investigated in 23 yeast species. All yeasts contained only a single form of the enzyme, which is localized exclusively in the cytosol. The enzyme activity from all sources was activated 3-(Rhodotorula aurantiaca) to 185-fold (Candida maltosa) by tryptophan. The tryptophan concentration, which was necessary to obtain half maximum velocity was determined to be between 2 (Pichia guilliermondii) and 95 microM (Yarrowia lipolytica). Ten yeast species possessed an enzyme that was inhibited by both phenylalanine and tyrosine. The chorismate mutase from four strains was inhibited only by tyrosine and the enzyme from two species was inhibited by phenylalanine alone. The enzyme inhibition by phenylalanine and tyrosine was completely reversed by tryptophan. Six enzyme sources were not inhibited and the Y. lipolytica chorismate mutase was slightly activated by both amino acids.

Amino Acids↗

Isolation and chromosomal localization of a novel FMS-like tyrosine kinase gene.

We have isolated and sequenced part of a new gene of the tyrosine kinase family. This gene, called FLT3, has strong sequence similarities with members of a group of genes encoding growth factor receptors: FMS, KIT, and PDGFR. We have localized the human FLT3 gene to chromosome 13, band q12, and its mouse homolog to chromosome 5, region G.

Amino Acid Sequence↗

D11S146 and BCL1 are physically linked but can be discriminated by their amplification status in human breast cancer.

Band q13 of chromosome 11 is frequently altered in a number of human cancers. We have undertaken physical mapping in this region, starting with D11S146, an anonymous 11q13 DNA fragment. This probe has been used by others as a landmark to locate MEN1, a locus of predisposition to multiple endocrine neoplasia. Long-range restriction mapping locates D11S146 within approximately 400 kb of the BCL1 translocation breakpoint involved in certain B-cell malignancies. BCL1 and two proto-oncogenes, INT2 and HST, were previously found to be coamplified in approximately 1/5 breast carcinomas. Although close to BCL1, D11S146 is present in less than 3/4 of these amplification units and delimits their centromeric boundary. Therefore, we propose that D11S146 defines two genetic regions. The centromeric region--PYGM/D11S146--contains MEN1. The telomeric one includes the D11S146/BCL1/INT2/HST area and is relevant to DNA amplification in carcinomas and to B-cell translocations.

Breast Neoplasms↗

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Cross Infection↗

Influence of ischaemic cardioplegic arrest on the haemodynamic efficacy of the PDE-III inhibitor, enoximone.

The haemodynamic support from an enoximone infusion (2 x bolus 0.5 mg.kg-1, infusion 0.5 micrograms.kg-1min-1) in the early postischaemic phase is modified by a transient diminution of the drug's positive inotropic and vasodilatory effect (1 to 4 h). Forty-five min after weaning off cardiopulmonary bypass (CPB) the initial increase in cardiac index (CI) induced by enoximone (+26 +/- 8%) faded and was no longer discernible in the control group. A significant increase in CI was observed again 4-6 h after cardioplegic arrest (ultimate steady state values greater than 10 h; CI +0.71.min-1 x m-2; +21%). This pharmacodynamic fading occurred in the presence of constant plasma concentrations of enoximone (442 +/- 31 ng.ml-1) and elevated high plasma norepinephrine (926 +/- 70 pg.ml-1). Two independent processes might be responsible for the ischaemia-induced complex time dependency of the pharmacodynamic effect: (1) sensitization of the adrenergic receptor pathway and/or activation of sarcolemmal Ca-influx, rapidly reversed during reperfusion, and (2) impaired sarcoplasmic reticulum responses, which are slowly repaired after weaning off CPB.

Cardiac Output↗

Occurrence of a novel yeast enzyme, L-lysine epsilon-dehydrogenase, which catalyses the first step of lysine catabolism in Candida albicans.

The yeast Candida albicans is able to utilize L-lysine as the sole nitrogen and carbon source accompanied by intracellular accumulation of alpha-aminoadipate-delta-semialdehyde. A novel yeast amino acid dehydrogenase catalysing the oxidative deamination of the epsilon-group of L-lysine was found in this yeast. The enzyme, L-lysine epsilon-dehydrogenase, is strongly induced in cells grown on L-lysine as the sole nitrogen source. The enzyme is specific for both L-lysine and NADP+. The Km values were determined to be 0.87 mM for L-lysine and 0.071 mM for NADP+. An apparent Mr of 87,000 was estimated by gel filtration. The enzyme has maximum activity at pH 9.5 and a temperature optimum of 32 degrees C under our assay conditions.

Amino Acid Oxidoreductases↗