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C Dean

Publications and source records attributed to C Dean.

At least 55 records · Page 3Linked to original sources
PubMed1999

Bdp, a new member of a family of DNA-binding proteins, associates with the retinoblastoma gene product.

We have cloned a gene, BDP, encoding a protein with homology to the retinoblastoma-binding proteins Rbp1 and Rbp2. It also has homology to DNA-binding proteins such as Bright, a B-cell-specific trans-activator, and the Drosophila melanogaster dead ringer gene product. Like MyoD, Bdp binds to the COOH-terminal region of pRb through its conserved region and to hypophosphorylated pRb. It also binds to the MAR of the immunoglobulin heavy-chain locus. Thus Bdp may contribute to the transcriptional regulation of genes involved in differentiation and tissue-specific expression.

Amino Acid Sequence↗
PubMed1999

Modulation of sympathetic nerve activity by microinjection of the 5-HT1A receptor agonist 8-OH-DPAT into the rostroventrolateral medulla.

In the present study, renal sympathetic nerve activity was recorded simultaneously with sympathetic nerve activity to skeletal muscle vasculature to determine if the sympatho-inhibition evoked by microinjection of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)teralin (8-OH-DPAT) into the rostroventrolateral medulla (RVLM) was uniform or regional. Three patterns of sympatho-inhibition were observed in these sympathetic outflows and the type of response depended upon location of microinjection within the subretrofacial nucleus (SRF). Inhibition of renal nerve activity only was elicited by microinjections at rostral sites at the caudal pole of the facial nucleus. In contrast, inhibition of muscle sympathetic nerve activity was evoked from more caudal injections at the rostral pole of the inferior olives. Microinjection in the area between these two regions produced inhibition of both sympathetic outflows. This study demonstrates that differential inhibition of regional sympathetic outflows can be elicited by microinjection of the 5-HT1A receptor agonist 8-OH-DPAT into the RVLM. These data suggests that this modulation is due to differences in anatomical arrangement of the medullary neurons rather than differences in neuron sensitivity to the serotonergic agonist.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1999

Presence of glutamate receptor subtypes on barosensitive neurons in the nucleus tractus solitarius of the dog.

Afferent baroreceptor information is transmitted to the nucleus tractus solitarius (NTS) in the dorsal medulla where glutamate is thought to be the primary neurotransmitter. However, the subtypes of glutamate receptors involved in the baroreflex remain to be established. The present study compared the distribution of immunohistochemically labeled ionotropic receptor subtypes to the distribution of physiologically stimulated barosensitive neurons in the NTS of the dog and also identified ionotropic receptor subtypes located on barosensitive neurons. Both NMDA and non-NMDA receptors were located in barosensitive areas and on barosensitive neurons, suggesting that both may be involved in the baroreflex.

Animals↗
PubMed1999

Sitting balance I: trunk-arm coordination and the contribution of the lower limbs during self-paced reaching in sitting.

The effects of reach distance and type of task on the functional relationship between the trunk, upper limb segments and the lower limbs during self-paced reaching in sitting were examined. Two-dimensional kinematic, kinetic and electromyography (EMG) data were collected as six healthy subjects reached forward under three distance (60, 100, 140% arm's length) and two task (reaching to press a switch, reaching to grasp a glass) conditions. The results demonstrate that type of task affected primarily the temporal aspects of coordination, with the grasp task taking consistently longer than the press task. In contrast, reach distance affected both the spatio-temporal aspects of coordination between the trunk and arm segments and the active contribution of the lower limbs. As reach distance increased, the magnitude of trunk and upper-arm segmental motion increased, whereas forearm segmental motion decreased. However, at each reach distance the path of the hand was relatively straight and there was remarkable consistency in the relationship between trunk and arm segments both within and between subjects suggesting that despite the presence of redundant degrees of freedom, the individual uses a parsimonious coordinative pattern. The vertical ground reaction force (GRF) and EMG data demonstrated that the lower limbs actively contributed to support the body mass when the object was located at 140% arm's length.

Adult↗
PubMed1999

The arabinose kinase, ARA1, gene of Arabidopsis is a novel member of the galactose kinase gene family.

The arabinose-sensitive ara1-1 mutant of Arabidopsis is deficient in arabinose kinase activity. A candidate for the ARA1 gene. ISA1, has been previously identified through the Arabidopsis genome sequencing initiative. Here we demonstrate that (1) the ARA1 gene coincides with ISA1 in a positional cloning strategy; (2) there are mutations in the ISA1 gene in both the ara1-1 mutant and an intragenic suppressor mutant; and (3) the ara1-1 and suppressor mutant phenotypes can be complemented by the expression of the ISA1 cDNA in transgenic plants. Together these observations confirm that ISA1 is the ARA1 gene. ARA1 is a member of the galactose kinase family of genes and represents a new substrate specificity among this and other families of sugar kinases. A second gene with similarities to members of the galactose kinase gene family has been identified in the EST database. A 1.8 kb cDNA contained an open reading-frame predicted to encode a 496 amino acid polypeptide. The GAL1 cDNA was expressed in a galK mutant of Escherichia coli and in vitro assays of extracts of the strain expressing GAL1 confirmed that the cDNA encodes a galactose kinase activity. Both GAL1 and ARA1 cross-hybridise at low stringency to other sequences suggesting the presence of additional members of the galactose kinase gene family.

Amino Acid Sequence↗
PubMed1999

Genome-wide mapping with biallelic markers in Arabidopsis thaliana.

Single-nucleotide polymorphisms, as well as small insertions and deletions (here referred to collectively as simple nucleotide polymorphisms, or SNPs), comprise the largest set of sequence variants in most organisms. Positional cloning based on SNPs may accelerate the identification of human disease traits and a range of biologically informative mutations. The recent application of high-density oligonucleotide arrays to allele identification has made it feasible to genotype thousands of biallelic SNPs in a single experiment. It has yet to be established, however, whether SNP detection using oligonucleotide arrays can be used to accelerate the mapping of traits in diploid genomes. The cruciferous weed Arabidopsis thaliana is an attractive model system for the construction and use of biallelic SNP maps. Although important biological processes ranging from fertilization and cell fate determination to disease resistance have been modelled in A. thaliana, identifying mutations in this organism has been impeded by the lack of a high-density genetic map consisting of easily genotyped DNA markers. We report here the construction of a biallelic genetic map in A. thaliana with a resolution of 3.5 cM and its use in mapping Eds16, a gene involved in the defence response to the fungal pathogen Erysiphe orontii. Mapping of this trait involved the high-throughput generation of meiotic maps of F2 individuals using high-density oligonucleotide probe array-based genotyping. We developed a software package called InterMap and used it to automatically delimit Eds16 to a 7-cM interval on chromosome 1. These results are the first demonstration of biallelic mapping in diploid genomes and establish means for generalizing SNP-based maps to virtually any genetic organism.

Arabidopsis↗
PubMed1999

Genetic interactions of the Arabidopsis flowering time gene FCA, with genes regulating floral initiation.

The genes controlling the timing of the transition from vegetative to reproductive growth are likely candidates for regulators of genes initiating floral development. We have investigated the interaction of one particular gene controlling flowering time, FCA, with the meristem identity-genes TERMINAL FLOWER 1 (TFL1), APETALA 1 (AP1) and LEAFY (LFY) and the floral repression gene EMBRYONIC FLOWER 1 (EMF1). Double mutant combinations were generated and the phenotypes characterized. The influence of strong and intermediate fca mutant alleles on the phenotype conferred by a 35S-LFY transgene was also analysed. The results support a model where FCA function promotes flowering in multiple pathways, one leading to activation of LFY and AP1, and another acting in parallel with LFY and AP1. Only the latter pathway is predicted to be non-functional in the intermediate fca-4 allele. The results are also consistent with AP1 and TFL1 negatively regulating FCA function. Combination of Columbia fca and emf1 mutant alleles confirmed that FCA is required for the early flowering of emf1. EMF1 and FCA are therefore likely to operate in different floral pathways.

Alleles↗
PubMed1999

The distinctive roles of five different ARC genes in the chloroplast division process in Arabidopsis.

ARC (accumulation and replication of chloroplasts) genes control different aspects of the chloroplast division process in higher plants. In order to establish the hierarchy of the ARC genes in the chloroplast division process and to provide evidence for their specific roles, double mutants were constructed between arc11, arc6, arc5, arc3 and arc1 in all combinations and phenotypically analysed. arc11 is a new nuclear recessive mutant with 29 chloroplasts compared with 120 in wild type. All the phenotypes of the double mutants are unambiguous. ARC1 down-regulates proplastid division but is on a separate pathway from ARC3, ARC5, ARC6 and ARC11. ARC6 initiates both proplastid and chloroplast division. ARC3 controls the rate of chloroplast expansion and ARC11 the central positioning of the final division plane in chloroplast division. ARC5 facilitates separation of the two daughter chloroplasts. ARC5 maps to chromosome 3 and ARC11 and ARC6 map approximately 60 cM apart on chromosome 5.

Arabidopsis↗
PubMed1999

The DIF1 gene of Arabidopsis is required for meiotic chromosome segregation and belongs to the REC8/RAD21 cohesin gene family.

Cohesins are a group of conserved proteins responsible for cohesion between replicated sister chromatids during mitosis and meiosis and which are implicated in double-strand break repair and meiotic recombination. We describe here the identification and characterisation of an Arabidopsis gene - DETERMINATE, INFERTILE1 (DIF1), which is a homolog of the Schizosaccharomyces pombe REC8/RAD21 cohesin genes, and is essential for meiotic chromosome segregation. Five independent alleles of the DIF1 gene were isolated by transposon mutagenesis, and the mutants show complete male and female sterility. Pollen mother cells (PMCs) of dif1 mutants show multiple meiotic defects which are represented by univalent chromosomes and chromosome fragmentation at metaphase I, and acentric fragments and chromatin bridges in meiosis I and II. Consequently, chromosome segregation is strongly affected, resulting in meiotic products of uneven size, shape and of variable ploidy. The similarities in phenotype, and the sequence homology between DIF1 and the REC8/RAD21 cohesins suggests that cohesin function is largely conserved between eukaryotes and highlights the essential role cohesins play in plant meiosis.

Alleles↗
PubMed1999

Dose-Response Study of Vigabatrin as add-on therapy in patients with uncontrolled complex partial seizures.

PURPOSE: This placebo-controlled, randomized, double-blind, multicenter study examined the efficacy and safety of three daily doses of vigabatrin (VGB; 1, 3, or 6 g) as add-on therapy in 174 patients with previously uncontrolled complex partial seizures with or without secondary generalization. METHODS: A 12-week pretreatment assessment period was followed by drug therapy with a 6-week titration period and a 12-week maintenance phase. RESULTS: VGB doses of 3 and 6 g/day reduced median monthly frequency of seizures by 4.3 and 4.5 seizures, respectively, compared with 0.2 seizures for placebo (p = 0.0001). The percentages of patients classified as therapeutic successes (> or =50% reduction in seizure frequency) were 7% for placebo and 24, 51, and 54% for patients taking daily VGB doses of 1, 3, and 6 g, respectively; the comparison with placebo was significant for all treatment groups. The linear trend for dose response was highly significant (p< or =0.0001) for both median monthly seizure frequency and therapeutic success. Vigabatrin was well tolerated, causing no clinically significant changes in laboratory parameters, brain magnetic resonance imaging, evoked potentials, cognitive function, or psychosocial tests. Fatigue, drowsiness, and dizziness were the most common treatment-related adverse events in all treatment groups. Dropouts due to adverse events were higher in the 6-g/day group. CONCLUSIONS: VGB was significantly more effective than placebo as add-on therapy in reducing seizure frequency. VGB at 3 and 6 g/day produced the best efficacy: however, adverse events may limit the use of the 6-g/day dose in some patients.

Adult↗
PubMed1999

When to switch to flowering.

At a certain stage in their life cycle, plants switch from vegetative to reproductive development. This transition is regulated by multiple developmental and environmental cues. These ensure that the plant switches to flowering at a time when sufficient internal resources have been accumulated and the environmental conditions are favorable. The use of a molecular genetic approach in Arabidopsis has resulted in the identification and cloning of many of the genes involved in regulating floral transition. The current view on the molecular function of these genes, their division into different genetic pathways, and how the pathways interact in a complex regulatory network are summarized.

Genes, Plant↗
PubMed1999

An anatomic atlas of the medulla oblongata of the adult goat.

An anatomic atlas of the goat brain stem was developed for use in studies that analyze medullary neuronal groups, and factors that influence variability in the location of neuronal groups were determined. The medullas of 31 adult goats (weight, 17-88 kg) were fixed, harvested, frozen, serially sectioned, stained with 0.5% neutral red, and examined with a light microscope. Obex, the point at which the central canal opens into the fourth ventricle, was taken as the zero reference point from which the rostrocaudal and mediolateral coordinates of medullary neuronal groups were determined, whereas dorsoventral coordinates were calculated from the medullary surface. Histological variations with goat body weight were quantified, and linear regression analysis provided adjustment factors for weight in all three dimensions. Similar analysis of percentage of shrinkage on fixation and processing provided adjustment factors for precise coordinates of medullary neuronal groups. For accurate location of neuronal groups, body weight and histological procedure should be taken into account. The present study provided adjustment factors for body weight and standard histological processing to locate most major medullary neuronal groups in the adult goat.

Animals↗
PubMed1999

Prognostic role of cyclin D1 in lung cancer. Relationship to proliferating cell nuclear antigen.

We developed an immunohistochemical assay specific for cyclin D1 and suitable for formalin-fixed and paraffin-embedded sections, to evaluate cyclin D1 expression in a group of 135 surgically resected lung-cancer patients for the purpose of investigating the prognostic role of this protein in lung cancer. In addition, we compared cyclin D1 expression with the expression of proliferating cell nuclear antigen (PCNA), considered to be a reliable index of the proliferation rate. We found cyclin D1 expressed in more than 60% of the neoplastic cells in 26.5% of our specimens. A total of 24.5% of the specimens showed cyclin D1 expression in a percentage of cells ranging from 30 to 60%; 36.7% of the specimens expressed cyclin D1 in less than 30% of the cells; and 12.2% of the specimens expressed cyclin D1 in less than 1% of the evaluated cells. Western blot analyses confirmed the specificity of this assay by correlating statistically in a highly significant fashion with the immunohistochemical results (P = 0.0003). Furthermore, we found a direct relationship between cyclin D1 and PCNA immunodetection (P = 0.0004), which correlated cyclin D1 overexpression with a higher tumor proliferation rate. When we analyzed our data statistically, cyclin D1 expression was found to be a negative prognostic marker (P < 0.00005) whose expression correlates with a shorter patient survival time.

Adenocarcinoma↗
PubMed1999

Gait in stroke: assessment and rehabilitation.

This article discusses the assessment and treatment of gait disorders after stroke. After consideration of the effects (of the disturbed motor control resulting from stroke) on the gait movements and the expected rate of recovery of walking capacity, different methods of assessment are considered. Emphasis is placed on selecting the appropriate measurement tool according to the individual's level of function. Also, the need to measure walking performance under different environmental constraints and the importance of instrument responsiveness to change over the range of walking disabilities are discussed. Task-related training with the opportunity for large amounts of practice is recommended to improve walking performance after stroke.

Environment↗
PubMed1998

Modulation of arterial baroreflexes by antisense oligodeoxynucleotides to NMDAR1 receptors in the nucleus tractus solitarius.

An antisense oligodeoxynucleotide which specifically blocked the production of the glutamate receptor subtype NMDAR1 was administered to the nucleus tractus solitarius (NTS) in order to examine the role of this receptor in baroreflex control of heart rate. Baseline blood pressure and heart rate were unchanged by NTS treatment with the antisense oligodeoxynucleotide to the NMDAR1 receptor subunit. However, the reflex bradycardia evoked in response to the hypertension induced by bolus administration of phenylephrine was significantly attenuated following bilateral NTS antisense oligodeoxynucleotide treatment. Administration of the corresponding mismatched antisense oligodeoxynucleotide did not significantly alter the reflex bradycardia. These data indicate that NMDAR1 receptors are involved in neurotransmission in the baroreflex arc at the level of the NTS. The specificity of antisense oligodeoxynucleotides may prove to be a useful technique to analyze the role of receptor subtypes mediating neurotransmission in central pathways.

Animals↗
PubMed1998

Arabidopsis thaliana: a model plant for genome analysis.

Arabidopsis thaliana is a small plant in the mustard family that has become the model system of choice for research in plant biology. Significant advances in understanding plant growth and development have been made by focusing on the molecular genetics of this simple angiosperm. The 120-megabase genome of Arabidopsis is organized into five chromosomes and contains an estimated 20,000 genes. More than 30 megabases of annotated genomic sequence has already been deposited in GenBank by a consortium of laboratories in Europe, Japan, and the United States. The entire genome is scheduled to be sequenced by the end of the year 2000. Reaching this milestone should enhance the value of Arabidopsis as a model for plant biology and the analysis of complex organisms in general.

Arabidopsis↗