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C Dean

Publications and source records attributed to C Dean.

At least 91 records · Page 5Linked to original sources
PubMed1997

A novel zinc finger protein is encoded by the Arabidopsis LSD1 gene and functions as a negative regulator of plant cell death.

Arabidopsis Isd1 mutants are hyperresponsive to cell death initiators and fail to limit the extent of cell death. Superoxide is a necessary and sufficient signal for cell death propagation. Thus, LSD1 monitors a superoxide-dependent signal and negatively regulates a plant cell death pathway. We isolated LSD1 via its map position. The predicted LSD1 protein contains three zinc finger domains, defined by CxxCxRxxLMYxxGASxVxCxxC. These domains are present in three additional Arabidopsis genes, suggesting that LSD1 defines a zinc finger protein subclass. LSD1 is constitutively expressed, consistent with the mutant phenotype. Alternate splicing gives rise to a low abundance mRNA encoding an extra five amino-terminal amino acids. We propose that LSD1 regulates transcription, via either repression of a prodeath pathway or activation of an antideath pathway, in response to signals emanating from cells undergoing pathogen-induced hypersensitive cell death.

Alternative Splicing↗
PubMed1997

Medical abortion with oral methotrexate and vaginal misoprostol.

OBJECTIVE: To evaluate the safety and efficacy of oral methotrexate and vaginal misoprostol for medical abortion. METHODS: A prospective multicenter trial involved 300 women up to 49 days' gestation seeking elective abortion. Subjects received methotrexate 50 mg orally followed 5-6 days later by misoprostol 800 micrograms vaginally. The misoprostol dose was repeated if abortion did not occur. RESULTS: Complete abortion occurred in 273 of 299 women (91.3%; 95% confidence interval [CI] 87.5, 94.2%); one woman was lost to follow-up. Abortion occurred within 8 days of the methotrexate in 233 women (77.9%; 95% CI 72.8, 82.5%); the remaining 13.4% of women who aborted did so after a delay of 23.5 +/- 9.8 days (median 23 days, range 10-45). Vaginal bleeding lasted an average of 15 and 11 days in immediate and delayed-success abortions, respectively. Complete abortion rates decreased linearly with increasing body surface area. After methotrexate and misoprostol administration, nausea was reported in 37% and 33%, vomiting in 11% and 18%, diarrhea in 12% and 18%, and subjective fever or chills in 15% and 31% of subjects, respectively. CONCLUSION: Oral methotrexate followed by vaginal misoprostol is effective for abortion and represents an acceptable alternative to intramuscular methotrexate in regimens for medical abortion.

Abortifacient Agents, Nonsteroidal↗
PubMed1997

Multiple repetitive DNA sequences in the paracentromeric regions of Arabidopsis thaliana L.

Nine repetitive DNA sequences, present in the haploid Arabidopsis thaliana genome in 7-300 copies, were hybridized in situ to metaphase and interphase chromosomes. Every sequence was detected on all five chromosome pairs, but was not evenly dispersed over the genome. Clusters of signals were found in particular regions of the centromeric heterochromatin, and each sequence showed a characteristic distribution pattern. Some sequences hybridized more strongly on different chromosomes, reflecting chromosome-specific amplification or the presence of homologous sequences. No hybridization signals could be detected on euchromatic regions. In situ hybridization on extended chromatin fibres showed that the pAL1 repeats are interrupted by another repetitive DNA sequence. A cosmid subclone (74A) contained a (GA)38 microsatellite motif, and hybridization with a (GA) oligonucleotide revealed that most of the hybridization sites of 74A correspond to the distribution of this microsatellite motif. The results show that the paracentromeric heterochromatin of A. thaliana chromosomes is composed not only of the tandemly arranged 180-bp repeat family pAL1/pAtMr, but also of some other repetitive sequences, thus giving a better understanding of the organization of sequences at the centromeres of A. thaliana.

Arabidopsis↗
PubMed1997

Description of 31 YAC contigs spanning the majority of Arabidopsis thaliana chromosome 5.

In order to generate a physical map of Arabidopsis thaliana chromosome 5, 142 molecular markers mapping chromosome 5 have been used in colony hybridization experiments with four Arabidopsis, ecotype Columbia, yeast artificial chromosome (YAC) libraries. This resulted in 634 YAC clones being anchored on chromosome 5. Southern blot analysis confirmed their positioning and provided data, which along with knowledge of the sizes of all the YAC clones, enabled the clones to be arranged into 31 contigs. Genetic mapping of markers located within 29 of these contigs on the Landsberg erecta/Columbia recombinant inbred lines allowed positioning of the contigs along the chromosome. A high proportion of the YAC clones were found to contain chimaeric inserts. The availability of this YAC contig map will accelerate chromosome-walking experiments, provide substrates for large-scale genomic sequencing projects and facilitate the mapping of new probes to this chromosome.

Arabidopsis↗
PubMed1997

Inefficient and incorrect processing of the Ac transposase transcript in iae1 and wild-type Arabidopsis thaliana.

As part of the analysis of the Arabidopsis mutant iae1-1 (increased Ac excision), quantitative studies of the Ac transposase transcript were conducted. The primary transcript of Ac contains three small introns (introns 1-3; mean size 89 bp) and one larger intron (intron 4; 387 bp). We analysed the splicing of intron 3 and intron 4 in wild-type Arabidopsis and the iae1-1 mutant. Our results demonstrate that the splicing of Ac introns 3 and 4 is inefficient (splicing efficiencies 57 and 30% respectively) compared with that of an intron of an endogenous Arabidopsis gene (PHYB intron 1; splicing efficiency 90%). The poor splicing efficiency of Ac intron 4 was found to correlate with aberrant processing. Steady state levels of total Ac transcript were higher in the iae1-1 mutant than wild-type, but the same aberrant processing occurred. The inefficient processing of Ac in Arabidopsis prompted us to construct an Ac element lacking introns (Ac::cDNA) in an attempt to increase transposition frequencies. Autonomous activity of the Ac::cDNA element was undetectable in Arabidopsis, despite its ability to transpose at high frequency in response to a strong transposase source (35S::transposase) in trans, and the demonstrable autonomy of the same element in tobacco. A number of smaller transcripts were detected in Arabidopsis lines containing Ac::cDNA or Ac. Analysis of these smaller transcripts revealed a high frequency of premature polyadenylation in exon 2 and splicing of cryptic introns.

Arabidopsis↗
PubMed1997

Comparative analysis of non-random DNA repair following Ac transposon excision in maize and Arabidopsis.

Ac/Ds transposable elements often leave short DNA rearrangements, or 'footprints,' at the sites where they excise. Previous studies at the maize waxy (wx) gene suggest that the DNA repair that forms transposon footprints is not random. Each excision site consistently displays a different, predominant repair product suggesting flanking DNA may influence footprint formation. We have expanded these studies to show that predominant end-joining products also form in association with Ac/Ds excision in Arabidopsis and that chromosomal location of the Ac-containing construct does not appear to influence this repair. The predominant repair product is identical in both maize and Arabidopsis for Ac elements with the same adjacent DNA sequences. However, a broader range of minor footprint types is observed in Arabidopsis, including footprints that are rare in maize, suggesting potential differences in the host proteins involved in either transposition, repair or both. The data also suggest that the sequences influencing footprint formation are within 39 bp 5' and 18 bp 3' of the transposon. These studies demonstrate that transgenic Ac/Ds-containing plants will be useful tools in dissecting plant DNA repair processes.

Arabidopsis↗
PubMed1997

Cardiovascular disease control efforts among local health departments in Missouri: four-year trends and policy implications.

Knowledge, attitudes, and activities in cardiovascular disease (CVD) control among local health departments in Missouri were surveyed in 1990 and in 1994, following four years of a community-based CVD risk-reduction project. Hypertension screening was rated as the most frequently performed CVD-related activity in 1990 and in 1994. Differences in mean scores between baseline and follow-up surveys showed no significant changes except for cholesterol screening. Respondents preferred individual patient education rather than community-wide approaches to risk reduction. Our findings highlight the need for more emphasis on coalition building and community-based programs for preventing and controlling CVD at the local health department level.

Cardiovascular Diseases↗
PubMed1997

The Arabidopsis downy mildew resistance gene RPP5 shares similarity to the toll and interleukin-1 receptors with N and L6.

Plant disease resistance genes operate at the earliest steps of pathogen perception. The Arabidopsis RPP5 gene specifying resistance to the downy mildew pathogen Peronospora parasitica was positionally cloned. It encodes a protein that possesses a putative nucleotide binding site and leucine-rich repeats, and its product exhibits striking structural similarity to the plant resistance gene products N and L6. Like N and L6, the RPP5 N-terminal domain resembles the cytoplasmic domains of the Drosophila Toll and mammalian interleukin-1 transmembrane receptors. In contrast to N and L6, which produce predicted truncated products by alternative splicing, RPP5 appears to express only a single transcript corresponding to the full-length protein. However, a truncated form structurally similar to those of N and L6 is encoded by one or more other members of the RPP5 gene family that are tightly clustered on chromosome 4. The organization of repeated units within the leucine-rich repeats encoded by the wild-type RPP5 gene and an RPP5 mutant allele provides molecular evidence for the heightened capacity of this domain to evolve novel configurations and potentially new disease resistance specificities.

Alleles↗
PubMed1997

Increased Ac excision (iae): Arabidopsis thaliana mutations affecting Ac transposition.

The maize transposable element Ac is highly active in the heterologous hosts tobacco and tomato, but shows very much reduced levels of activity in Arabidopsis. A mutagenesis experiment was undertaken with the aim of identifying Arabidopsis host factors responsible for the observed low levels of Ac activity. Seed from a line carrying a single copy of the Ac element inserted into the streptomycin phosphotransferase (SPT) reporter fusion, and which displayed typically low levels of Ac activity, were mutagenized using gamma rays. Nineteen mutants displaying high levels of somatic Ac activity, as judged by their highly variegated phenotypes, were isolated after screening the M2 generation on streptomycin-containing medium. The mutations fall into two complementation groups, iae1 and iae2, are unlinked to the SPT::Ac locus and segregate in a Mendelian fashion. The iae1 mutation is recessive and the iae2 mutation is semi-dominant. The iae1 and iae2 mutants show 550- and 70-fold increases, respectively, in the average number of Ac excision sectors per cotyledon. The IAE1 locus maps to chromosome 2, whereas the SPT::Ac reporter maps to chromosome 3. A molecular study of Ac activity in the iae1 mutant confirmed the very high levels of Ac excision predicted using the phenotypic assay, but revealed only low levels of Ac re-insertion. Analyses of germinal transposition in the iae1 mutant demonstrated an average germinal excision frequency of 3% and a frequency of independent Ac re-insertions following germinal excision of 22%. The iae mutants represents a possible means of improving the efficiency of Ac/Ds transposon tagging systems in Arabidopsis, and will enable the dissection of host involvement in Ac transposition and the mechanisms employed for controlling transposable element activity.

Arabidopsis↗
PubMed1997

Response of Schwann cells to mitogens in vitro is determined by pre-exposure to serum, time in vitro, and developmental age.

We compared the mitogenic response of Schwann cells freshly isolated from adult, neonatal, and embryonic nerves, and compared these cells with cells that had been cultured in serum for 5 days. DNA synthesis in response to growth factors was measured using bromodeoxyuridine and immunocytochemistry. Freshly isolated adult Schwann cells were unresponsive to growth factors with or without forskolin to elevate intracellular cAMP levels. After 5 days of culture in serum, or alternatively in defined medium containing fibroblast growth factor 2 plus forskolin, or neu-differentiation factor beta2, adult cells were responsive to mitogens, whereas cells cultured in defined medium alone remained unresponsive. Serum also increased expression of type 1 fibroblast growth factor receptor. Freshly isolated embryonic and neonatal Schwann cells in contrast responded to growth factors even in the absence of forskolin. This responsiveness changed with time in culture. Neonatal cells cultured for 5 days in defined medium in the presence or absence of serum no longer responded to FGF alone, but required forskolin for a mitogenic response. Thus, the response of freshly isolated cells to mitogens is developmentally regulated; extrinsic signals are required to render adult cells responsive to mitogens; and with time in culture, neonatal cells develop a requirement for cAMP elevation for mitogenic response.

Animals↗
PubMed1996

A novel repetitive sequence associated with the centromeric regions of Arabidopsis thaliana chromosomes.

The middle repetitive fraction of the Arabidopsis genome has been relatively poorly characterized. We describe here a novel repetitive sequence cloned in the plasmid mi167, and present in approximately 90 copies in the genome of Arabidopsis thaliana ecotype Columbia. Hybridization analysis to physically mapped YAC clones representing Arabidopsis chromosome 4 revealed four mi167-hybridizing loci, all clustered near the centromere. No other loci were detected on YAC clones covering chromosome 4. In situ hybridisation experiments to Arabidopsis chromosome spreads showed that mi167-hybridizing sequences are clustered at the centromeric heterochromatin of all five chromosomes; on two chromosomes the hybridization appeared to be localised on one arm. Additional mi167-hybridizing loci were detected, one of which was adjacent to a non-centromeric, heterochromatic region. This work supports the idea that the majority of middle repetitive DNA in the Arabidopsis genome is clustered. It also adds to our understanding of the organization of the centromere of Arabidopsis chromosome 4.

Arabidopsis↗
PubMed1996

Identification and distribution of seven classes of middle-repetitive DNA in the Arabidopsis thaliana genome.

In order to analyse further the genomic distribution of repetitive sequences in the Arabidopsis genome, we have identified and characterized seven novel repetitive sequences. Analysis of genomic representation, genomic location and DNA sequence divided the seven repeated sequences into two classes. The first was represented by three cosmid subclones (182A, 74A, 191A) carrying sequences that hybridised to up to 20 genomic fragments and showed sequence homology to the genes, Arabidopsis CCR2, Arabidopsis MYB and to various ATP-binding transport proteins. These multigene families mapped to various positions within the genome, as judged by hybridization to YAC clones constituting the Arabidopsis physical map. The second class was represented by four cosmid subclones (106B, 164A, 163A, 278A) that hybridised to between 20 and 300 genomic fragments. One of these, 106B, is a diverged, partial copy of the LTR of the Arabidopsis retrotransposon Athila. The other three sequences showed no homology to known genes or proteins. The distribution of these sequences on chromosome 4 was analysed and sequences hybridizing to 106B, 164A and 163A were found exclusively at the centromeric region of this chromosome. Their detailed arrangement at the centromeric region of chromosome 4, relative to other repeated sequence families and single copy sequences, was determined.

Arabidopsis↗
PubMed1996

A twin study examining the effect of parity on the prevalence of psychiatric disorder.

The study compares the prevalence of current and lifetime psychiatric illness in twin pairs where one twin is more parous than the other. The main finding was that parity did not affect the prevalence of psychiatric disorder. This adds confirmation to the study of Bebbington et al. (1991) that high prevalence rates in women with children is due to an effect of marriage rather than an effect of parity. There was a diagnostic difference between the twins with the less parous twin having significantly more cases of Research Diagnostic Criteria (RDC; Spitzer et al., 1978) major and minor depression and the more parous twin more cases of generalised anxiety disorder. The life events and difficulties in the previous 12 months were also established in the whole group and events and difficulties over the whole of the subjects life for the first 20 pairs. The total number of events in the previous 12 months was significantly higher in the more parous twin of the pair, these were child-related events and not associated with an increased likelihood of current psychiatric illness. There were no differences in the number of events and difficulties during the lifetime between the first 20 twin pairs.

Adult↗
PubMed1996

Monoclonal antibodies to the EGF receptor act as betacellulin antagonists.

Betacellulin (BTC), a recently discovered member of the EGF family that is produced by certain tumour cells, is thought to be involved in autocrine growth by activating the EGF receptor (EGFR). We have investigated whether monoclonal antibodies (mAbs) to the EGFR which act as EGF, TGF alpha and HB-EGF antagonists could also be effective as BTC antagonists by blocking its binding to the EGFR. We report that the binding of 125I-BTC to a range of tumour cells expressing the EGFR was inhibited by rat mAbs that bound to three distinct epitopes on the extracellular domain of the EGFR. We show that one of these mAbs (ICR62) also prevents activation of the EGFR by betacellulin as evidenced by reversal of the effects on the growth of human fibroblasts and the head and neck carcinoma cell line HN5 and by inhibition of receptor phosphorylation in HN5 cells. We conclude that mAbs such as ICR62 have potential for use as therapeutic agents by blocking betacellulin-induced growth of tumours which over-express the EGFR.

Animals↗
PubMed1996

Analysis of the occurrence and nature of repeated DNA in an 850 kb region of Arabidopsis thaliana chromosome 4.

The occurrence and nature of repeated DNA sequences has been analysed within an 850 kb YAC contig on Arabidopsis thaliana chromosome 4. Hybridization analysis with seven RFLP markers, six cosmid contigs, 29 YAC end probes and eight YAC clones showed that a least 585 kb of the 850 kb contained only low-copy sequences. One YAC end probe, EG15C8LE, hybridized to multiple genomic fragments and contained a sequence with predicted protein homology to cytochrome P450 monooxygenases. Another one, EG11B7RE, was found to be non-contiguous with the other YAC clones and contained a dispersed repetitive sequence associated with centromeric regions.

Arabidopsis↗
PubMed1996

Phase I trial and tumour localisation of the anti-EGFR monoclonal antibody ICR62 in head and neck or lung cancer.

The purpose of this study was to determine the effect of the first rat monoclonal antibody (MAb ICR62) to the epidermal growth factor receptor (EGFR) in a phase I clinical trial in patients with unresectable squamous cell carcinomas. This antibody effectively blocks the binding of EGF, transforming growth factor (TGF)-alpha and HB-EGF to the EGFR, inhibits the growth in vitro of tumour cell lines which overexpress the EGFR and eradicates such tumours when grown as xenografts in athymic mice. Eleven patients with squamous cell carcinoma of the head and neck and nine patients with squamous cell carcinoma of the lung, whose tumours expressed EGFR, were recruited. Groups of three patients were treated with 2.5 mg, 10 mg, 20 mg or 40 mg of ICR62 and a further eight patients received 100 mg. All patients were evaluated for toxicity using WHO criteria. Patients' sera were tested for the clearance of MAb ICR62 and the development of human anti-rat antibodies (HARA). No serious (WHO Grade III-IV) toxicity was observed in patients treated with up to 100 mg of antibody ICR62. Antibody ICR62 could be detected at 4 h and 24 h in the sera of patients treated with 40 mg or 100 mg of ICR62. Only 4/20 patients showed HARA responses (one at 20 mg, one at 40 mg and two at 100 mg doses) and of these only the former two were anti-idiotypic responses. In four patients receiving doses of ICR62 at 40 mg or greater, biopsies were obtained from metastatic lesions 24 h later and examined for the localisation of ICR62 using anti-rat antibody reagent. In these patients we showed the localisation of MAb ICR62 to the membranes of tumour cells; this appeared to be more prominent at the higher dose of 100 mg. On the basis of these data we conclude that MAb ICR62 can be administered safely to patients with squamous cell carcinomas and that it can localise efficiently to metastases even at relatively low doses.

Adult↗
PubMed1996

Arabidopsis mutants showing an altered response to vernalization.

Flowering in many plant species is accelerated by a long period of cold temperature, known as a vernalization period. This research investigates how this cold temperature signal is perceived by plant cells and the mechanism by which it influences the transition to flowering. Mutagenesis of the late-flowering, vernalization-responsive, Arabidopsis mutant, fca, has yielded five independent mutations (termed vrn mutations) conferring an altered vernalization response. Allelism tests showed that these mutations fall into at least three complementation groups defining three loci named VRN 1, 2 and 3. The vrn1 and vrn2 mutations did not affect the acclimation response as judged by expression of cold-induced transcripts and freezing tolerance assays. vrn1-1 affected the short-day vernalization response of Landsberg erecta and reduced the vernalization response of other late-flowering Arabidopsis mutants. The acceleration of flowering by GA3 was not affected by vrn1-1. The VRN 1 locus was mapped to chromosome 3.

Acclimatization↗