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Biomedical subjects

C Price

Publications and source records attributed to C Price.

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

Isolation of a Schizosaccharomyces pombe gene which in high copy confers resistance to the nucleoside analogue 5-azacytidine.

Treatment of Schizosaccharomyces pombe with the C5 DNA methyltransferase (C5Mtase) inhibitor 5-azacytidine (5-azaC) has previously been shown to induce G2 checkpoint-dependent cell cycle arrest. S. pombe strains defective in both the checkpoint control pathways and in DNA repair processes are sensitive to 5-azaC. Here we describe the isolation of azr1+, as a multi-copy suppressor of the 5-azaC sensitivity of G2 checkpoint and DNA repair-deficient strains. azr1+ encodes a putative 25 kDa protein with limited homology to a Saccharomyces cerevisiae open reading frame of unknown function. The azr1+ gene is not essential and the null mutant shows no alteration in either DNA repair or checkpoint properties. We also report the sequence of the putative fission yeast cytidine deaminase gene, designated pcd1+, which lies immediately adjacent to azr1+ but which plays only a moderate role in suppression of 5-azaC sensitivity.

Amino Acid Sequence↗
PubMed1997

Genetic divergence among the group B coxsackieviruses.

As documented in the preceding discussion, the noncoding regions, and in particular the 5' NTR, of the CVB are tolerant of a substantial degree of nucleotide diversity while still being capable of fulfilling the life cycle requirements for these viruses. While diversity among the CVB is observed in the sequences encoding for the capsid proteins, it tends to involve predominantly those regions coding for amino acids located at the surface of the virus and not those responsible for the structural integrity of the mature virion, i.e., beta-barrels and alpha-helices. It is these capsid surface differences that define the six serotypes of the CVB and subdivide them antigenically into strains. Additionally, these proteins most likely play the major role in determining host and cellular tropism. The most conserved of the CVB proteins and, therefore those with the least diversity in their coding sequences, appear to be the nonstructural proteins. Perhaps, as speculated earlier, it is a conformational requirement imposed by the necessity to interact with host or viral substrates that maintains the high degree of amino acid identity of this group of viral proteins.

Amino Acid Sequence↗
PubMed1997

Characterisation of the Schizosaccharomyces pombe rad4/cut5 mutant phenotypes: dissection of DNA replication and G2 checkpoint control function.

Mutation of the essential Schizosaccharomyces pombe rad4/cut5 gene causes sensitivity to UV and ionising radiation at the permissive temperature whilst at the restrictive temperature cells fail to undergo DNA replication but still attempt mitosis owing to a defective S-phase checkpoint response. Many mutations in genes encoding DNA replication proteins also abolish checkpoint responses, possibly because the replication machinery is a pre-requisite for the generation of the signal. We demonstrate here that rad4/cut5 cells fail to arrest cell division when treated with the replication inhibitor hydroxyurea at the semi-permissive temperature 32 degrees C, but retain essentially normal replicative capacity. This demonstrates that the replication and checkpoint function of the rad4/cut5 gene product can be separated and that the Rad4 protein differs from other replication proteins in being directly involved in generating the S-phase checkpoint signal. Furthermore, we have investigated the checkpoint response or rad4/cut5-deficient cells to gamma-irradiation and UV-mimetic drugs. We find that, at the restrictive temperature, the rad4-/cut5- cells fail to delay mitosis in response to gamma-irradiation whilst retaining a normal checkpoint response to the UV-mimetic drug 4-nitroquinoline-1-oxide. The lack of the gamma-irradiation checkpoint is reminiscent of the deficiency associated with mutation of the human ATM locus, the causative deficiency of the heritable disorder ataxia telangiectasia. The implications of our results for the organisation of distinct checkpoint-response pathways in both fission yeast and mammalian cells are discussed. Moreover the data are consistent with a model in which the generation of the S-Phase checkpoint signal is DNA polymerase epsilon dependent.

4-Nitroquinoline-1-oxide↗
PubMed1997

Alcohol removal of the epithelium for excimer laser ablation: outcomes analysis.

PURPOSE: To determine whether removing the corneal epithelium by dilute alcohol is equal to other epithelial removal techniques. SETTING: The Bochner Eye Institute, Toronto, Ontario, Canada. METHODS: Epithelium was removed using 25% alcohol placed on a circular pledget; the alcohol remained on the cornea for 3 minutes. Irrigation was performed with cold balanced salt solution. The epithelium was then lifted with forceps and removed. Ninety-one eyes having photorefractive keratectomy for low myopia (less than 8.00 diopters) were treated; 41 eyes were followed between 4 and 10 months (mean 6 months). Complications such as haze and loss of best corrected visual acuity (BCVA) were recorded. RESULTS: All alcohol-treated eyes achieved a BCVA of 20/40 or better, 65.9% had 20/20 and 92.7%, 20/25 or better. There were no complications or adverse effects. CONCLUSIONS: Epithelial removal using 25% alcohol did not adversely affect the algorithms used with the VISX 20/20 excimer laser, indicating the technique is safe, predictable, and effective. There was no significant loss of BCVA, toxic effects, or stromal hydration.

Adult↗
PubMed1997

A comparison of a film-based and a direct digital dental radiographic system using a proximal caries model.

OBJECTIVES: To compare the diagnostic accuracy of a dental radiographic film (Ektaspeed Plus) with the Sens-A-Ray direct digital imaging system using a proximal caries model. To study the effects of a scattering medium and compare the interpretations of dentists with dental students. METHODS: We used 20 extracted premolar and molar teeth with 10 sound and 15 naturally carious surfaces, and prepared artificial cavities in the remaining 15 surfaces. Seven dentists and seven senior dental students reported the presence of lesions using a five point confidence scale. We analysed our data by Receiver Operating Characteristic (ROC) analysis and by obtaining sensitivities and specificities. RESULTS: ROC areas showed no significant differences in the diagnostic accuracy achieved by dentists and dental students or by the addition of 20 mm of water as a scattering medium. A paler set of exposures produced significantly poorer diagnostic accuracy, but a darker set gave insignificant differences. Highly significant differences were found between the ROC areas for film and Sens-A-Ray and natural caries and artificial cavities, but the magnitudes of the differences were small. Sensitivities and specificities showed greater differences between methods and identified inferior interpretation of sound surfaces by students. CONCLUSIONS: Film was superior to Sens-A-Ray in the interpretation of proximal caries. The effects of a scattering medium were insignificant or trivial. Students were less reliable than dentists in the interpretation of sound surfaces but performed equally well with respect to natural caries and artificial cavities.

Analysis of Variance↗
PubMed1997

The structural components of music perception. A functional anatomical study.

This work explores the cerebral structures involved in the appreciation of music. We studied six young healthy subjects (right handed, French, without musical talent), using a high resolution PET device (CTI 953B) and 15O-labelled water. In three tasks, we studied the effects of selective attention to pitch, timbre and rhythm; a final task studied semantic familiarity with tunes (considered as divided attention for pitch and rhythm). These four tasks were performed on the same material (a tape consisting of 30 randomly arranged sequences of notes). We selected a paradigm, without a reference task, to compare the activations produced by attention to different parameters of the same stimulus. We expected that the activations recorded during each task would differ according to the differences in cognitive operations. We found activations preferentially in the left hemisphere for familiarity, pitch tasks and rhythm, and in the right hemisphere for the timbre task. The familiarity task activated the left inferior frontal gyrus, Brodmann area (BA) 47, and superior temporal gyrus (in its anterior part, BA 22). These activations presumably represent lexico-semantic access to melodic representations. In the pitch task, activations were observed in the left cuneus/precuneus (BA 18/19). These results were unexpected and we interpret them as reflecting a visual mental imagery strategy employed to carry out this task. The rhythm task activated left inferior Broca's area (BA 44/6), with extention into the neighbouring insula, suggesting a role for this cerebral region in the processing of sequential sounds.

Adult↗
PubMed1997

The Read Thesaurus--creation and beyond.

The creation of the Read Thesaurus was a unique undertaking, involving over 2000 clinicians. This clinically-led, multidisciplinary enterprise posed many organisational and professional challenges. The process of term collection and integration and the problems encountered are described. A brief account is given of the large task of maintenance and refinement. This paper looks at the practical and cultural aspects and describes how problems were tackled by good organisation, clear guidelines and much goodwill.

Disease↗
PubMed1997

The Asian element in Australia: 1996.

"There has been much public debate about the size of the Asian-born and Asian ethnic-origin population in Australia (unmixed). By combining these two elements, it is estimated that the total unmixed Asian component of Australia's population is 8.16 percent."

Asia↗
PubMed1997

Semantic quality through semantic definition: refining the Read Codes through internal consistency.

Checks of internal consistency in controlled medical vocabularies facilitate their development and assist refinement of the underlying terminological model. Two simple checks of consistency between knowledge in the subtype hierarchy and that in semantic definitions of concepts are described. It is proposed that these checks are a helpful adjunct to, but not a replacement for, large-scale involvement of domain experts in construction of controlled vocabularies.

Classification↗
PubMed1997

Evaluating the terminology requirements to support multi-disciplinary diabetes care.

Diabetes mellitus is a multi-system disease requiring lifetime multi-disciplinary care, which has proven individual and economic benefits. The delivery of service involves co-operation and communication between patient, carer and health care professionals, and systematic auditing of processes and outcomes. Sustained improvement necessitates regular data acquisition, aggregation and analysis. The terminology requirements to support patient-centred records and identified datasets are examined, and differences in purpose and scope highlighted. The many stakeholders involved in diabetes care have their own sublanguages and terminology requirements which need harmonising around a common core. The problems and solutions of accommodating these needs are explored in relation to the Read Thesaurus.

Databases, Factual↗
PubMed1996

5-Azacytidine treatment of the fission yeast leads to cytotoxicity and cell cycle arrest.

A fission yeast gene which shares considerable sequence homology with cytosine-specific DNA methyltransferases has recently been identified. This discovery has led us to investigate the effects of the treatment of fission yeast with the nucleoside analogue 5-azacytidine (5-azaC). 5-AzaC is known to inhibit cytosine methylation as a result of the formation of stable covalent complexes between DNA (cytosine-5) methyltransferases (C5 Mtases) and 5-azaC containing DNA. Here we demonstrate that 5-azaC treatment of Schizosaccharomyces pombe leads to reversible cell cycle arrest at the G2/M transition. This reversible arrest is dependent on the cell cycle checkpoint mechanisms which act to prevent the onset of mitosis in the presence of either damaged or unreplicated DNA. Treatment of S. pombe cell division cycle and checkpoint mutants indicates that 5-azaC causes DNA damage and is likely to inhibit a late stage in DNA replication. The data show that viability in the presence of the drug requires both the DNA damage and the replication checkpoint pathways to be functional. 5-AzaC also elicits a transcriptional response which is associated with DNA damage and the inhibition of DNA replication in fission yeast, and this response is absent in cells carrying G2 checkpoint mutations. The implications of these observations for both the use of 5-azaC in cancer chemotherapy and the existence of cytosine methylation in fission yeast are discussed.

Azacitidine↗
PubMed1996

Functional anatomy of a common semantic system for words and pictures.

The relationship between the semantic processing of words and of pictures is a matter of debate among cognitive scientists. We studied the functional anatomy of such processing by using positron-emission tomography (PET). We contrasted activity during two semantic tasks (probing knowledge of associations between concepts, and knowledge of the visual attributes of these concepts) and a baseline task (discrimination of physical stimulus size), performed either with words or with pictures. Modality-specific activations unrelated to semantic processing occurred in the left inferior parietal lobule for words, and the right middle occipital gyrus for pictures. A semantic network common to both words and pictures extended from the left superior occipital gyrus through the middle and inferior temporal cortex to the inferior frontal gyrus. A picture-specific activation related to semantic tasks occurred in the left posterior inferior temporal sulcus, and word-specific activations related to semantic tasks were localized to the left superior temporal sulcus, left anterior middle temporal gyrus, and left inferior frontal sulcus. Thus semantic tasks activate a distributed semantic processing system shared by both words and pictures, with a few specific areas differentially active for either words or pictures.

Adult↗
PubMed1996

The genetics of the repair of 5-azacytidine-mediated DNA damage in the fission yeast Schizosaccharomyces pombe.

We have recently demonstrated that Schizosaccharomyces pombe cells treated with the nucleoside analogue 5-azacytidine (5-azaC) require previously characterised G2 checkpoint mechanisms for survival. Here we present a survey of known DNA repair mutations which defines those genes required for survival in the presence of 5-azaC. Using a combination of single-mutant and epistasis analyses we find that the excision, mismatch and recombinational repair pathways are all required in some degree for the repair of 5-azaC-mediated DNA damage. There are distinct differences in the epistatic interactions of several of the repair mutations with respect to 5-azaC-mediated DNA damage relative to UV-mediated DNA damage.

Adenosine Triphosphatases↗
PubMed1996

412-positive mesodermal cells and the gonadal mesoderm are separate from the fat-cell lineage.

The Drosophila retrotransposon, 412, is expressed in a cell-specific manner during embryogenesis. At stage 11, 412 transcripts are present in bilateral clusters of cells within the mesoderm. The posterior clusters of 412-positive cells become associated with the gonads at stage 13; however, the fate of the cells in the remaining clusters is unknown. We have tested by in situ hybridization to whole-mount embryos the possible identity of these cells with known precursor cell types present in bilateral clusters. We simultaneously located the 412-positive cells and the precursor cells to visceral muscle or the fat body. We have determined that the 412-positive cells do not correspond to these precursor cells and that the development of the visceral muscle or fat body does not affect the expression of 412 during embryogenesis.

Adipocytes↗
PubMed1996

rTP: a candidate telomere protein that is associated with DNA replication.

In this paper we describe the isolation and characterization of rTP, the replication Telomere Protein, formerly known as the telomere protein homolog. The rTP was initially identified because of its homology to the gene for the Oxytricha telomere-binding protein alpha-subunit. The protein encoded by the rTP gene has extensive amino acid sequence identity to the DNA-binding domain of the telomere-binding proteins from both Euplotes crassus and Oxytricha nova. We have now identified the protein encoded by the rTP gene and have shown that it differs from the telomere-binding protein in its abundance, solubility and intracellular location. To learn more about the function of rTP, we determined when during the Euplotes life cycle the gene is transcribed. The transcript was detectable only in nonstarved vegetative cells and during the final stages of macronuclear development. Since the peak transcript level coincided with the rounds of replication that take place toward the end of macronuclear development, it appeared that rTP might be involved in DNA replication. Immunolocalization experiments provided support for this hypothesis as antibodies to rTP specifically stain the replication bands. Replication bands are the sites of DNA replication in Euplotes macronuclei. Our results suggest that rTP may be a new telomere replication factor.

Amino Acid Sequence↗