Cancer patients show large individual variation in their response to chemotherapeutic agents. Gemcitabine (dFdC) and AraC, two cytidine analogues, have shown significant activity against a variety of tumors. We previously used expression data from a lymphoblastoid cell line-based model system to identify genes that might be important for the two drug cytotoxicity. In the present study, we used ...

4 -Thio-D-arabinofuranosyl cytosine (TaraC) is in phase I development for treatment of cancer. In human equilibrative nucleoside transporter (hENT) 1-containing CEM cells, initial rates of uptake (10 M; picomoles per microliter of cell water per second) of [H]TaraC and [H]1-D-arabinofuranosyl cytosine (araC) were low (0.007 003 and 0.034 0.003, respectively) compared with that of [H]uridine (0....

Olfactory bulb (OB) interneurons are continuously renewed throughout an animal's lifespan. Despite extensive investigation of this phenomenon, little is known about bulbar circuitry functioning and olfactory performances under conditions of ablated arrival of new neurons into the adult OB. To address this issue we performed morphological, electrophysiological, and behavioral analysis in mice wi...

Mutations in the interdomain linker of the gene for the AraC regulatory protein of Escherichia coli that severely interfere with the protein's ability either to repress or to activate transcription have been found. These mutations have relatively small effects on the dimerization domain's ability to bind arabinose or to dimerize the protein or on the DNA-binding domain's affinity for a single D...

contained a chromosome 7 abnormality (also mostly monosomy 7). Four of 11 patients with complex karyotype including aberrations of chromosome 7 showed cytogenetic responses (Figure 1; Table 1) compared with 2 responders of 9 patients with complex karyotype not containing a chromosome 7 abnormality. This high response rate in patients with chromosome 7 abnormalities is in stark contrast to the n...

RAS mutations are frequently found among acute myeloid leukemia patients (AML), generating a constitutively active signaling protein changing cellular proliferation, differentiation and apoptosis. We have previously shown that treatment of AML patients with high-dose cytarabine is preferentially beneficial for those harboring oncogenic RAS. On the basis of a murine AML cell culture model, we as...

We have isolated mutations in AraC protein that specifically block either induction or repression at the ara pBAD promoter. These hemiplegic mutations identify amino acid residues that, correspondingly, are involved only in the induction or only in the repression activities of the protein. Residues key only for induction are 13, 15, and 18, which are located in the N-terminal arm of AraC, and r...

We studied the formation of open complexes of RNA polymerase and promoter DNA as activated by the AraC protein at the Escherichia coli araBAD promoter pBAD and by the cyclic AMP receptor protein at the galKTE promoter P1. The DNA migration retardation assay was demonstrated to be suitable for the detection and quantitation of open complexes by the correspondence in the properties of open comple...

AraC protein, a transcriptional regulator of the L-arabinose operon in Escherichia coli, is dimeric. Each monomer consists of a domain for DNA binding plus transcription activation and a domain for dimerization plus arabinose binding. These are connected to one another by a linker region of at least 5 amino acids. Here we have addressed the question of whether any of the amino acids in the link...

The dimeric AraC protein of Escherichia coli binds specifically to DNA sequences upstream of promoters whose transcription is regulated by arabinose. Here we show with affinity measurements, DNase footprinting, dimethyl sulfate premethylation interference and dimethyl sulfate footprinting studies that AraC protein can recognize paired half-sites in direct repeat orientation or inverted repeat o...