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Biomedical subjects

S Whelan

Publications and source records attributed to S Whelan.

At least 19 recordsLinked to original sources

Statistics on cancer in China: cancer registration in 2002.

The objective of this study was to determine how many population-based cancer registries exist in China, what methods are being used, and the statistical data that are available from them, and to identify future needs with respect to technical support. A two-stage survey was conducted in 2002 at provincial and cancer registry level. Based on the questionnaire used in these two stages, the basic distribution and descriptive information on population-based cancer registry practices in China are addressed. There are 48 cancer registries in China, covering 73 million people (5.7% of the total population of China in 2000). The oldest three registries are LinZhou, ShangHai and QiDong. There are marked variations in practice between registries, with respect to data collection, data management and coding. Differences are also found in administrative aspects and sources of financial support. In conclusion, this first national survey of Chinese cancer registry practice provides a benchmark against which development and standardization can be evaluated in the future. The survey suggests that lack of qualified personnel, insufficient funding support and lack of stability of the population are major problems in carrying out registration work in China. It also indicates several ways in which registry practice, and hence availability and quality of incidence and survival data can be improved.

Benchmarking↗

Human glioma PKC-iota and PKC-betaII phosphorylate cyclin-dependent kinase activating kinase during the cell cycle.

Cell cycle phase transition is regulated in part by the trimeric enzyme, cyclin-dependent kinase activating kinase (CAK) which phosphorylates and activates cyclin-dependent kinases (cdks). Protein kinase C (PKC) inhibitors prevent cell cycle phase transition, suggesting a fundamental role for PKCs in cell cycle regulation. We report that in glioma cells, CAK (cdk7) is constitutively associated with PKC-iota. In vitro phosphorylation, co-immunoprecipitation, and analysis of phosphorylated proteins by autoradiography indicate that CAK (cdk7) is a substrate for PKC-iota and PKC-betaII hyperphosphorylation. These results establish a role for PKC-iota and PKC-betaII in the activation of CAK during the glioma cell cycle.

Cell Cycle↗

Molecular phylogenetics: state-of-the-art methods for looking into the past.

As the amount of molecular sequence data in the public domain grows, so does the range of biological topics that it influences through evolutionary considerations. In recent years, a number of developments have enabled molecular phylogenetic methodology to keep pace. Likelihood-based inferential techniques, although controversial in the past, lie at the heart of these new methods and are producing the promised advances in the understanding of sequence evolution. They allow both a wide variety of phylogenetic inferences from sequence data and robust statistical assessment of all results. It cannot remain acceptable to use outdated data analysis techniques when superior alternatives exist. Here, we discuss the most important and exciting methods currently available to the molecular phylogeneticist.

Animals↗

A general empirical model of protein evolution derived from multiple protein families using a maximum-likelihood approach.

Phylogenetic inference from amino acid sequence data uses mainly empirical models of amino acid replacement and is therefore dependent on those models. Two of the more widely used models, the Dayhoff and JTT models, are estimated using similar methods that can utilize large numbers of sequences from many unrelated protein families but are somewhat unsatisfactory because they rely on assumptions that may lead to systematic error and discard a large amount of the information within the sequences. The alternative method of maximum-likelihood estimation may utilize the information in the sequence data more efficiently and suffers from no systematic error, but it has previously been applicable to relatively few sequences related by a single phylogenetic tree. Here, we combine the best attributes of these two methods using an approximate maximum-likelihood method. We implemented this approach to estimate a new model of amino acid replacement from a database of globular protein sequences comprising 3,905 amino acid sequences split into 182 protein families. While the new model has an overall structure similar to those of other commonly used models, there are significant differences. The new model outperforms the Dayhoff and JTT models with respect to maximum-likelihood values for a large majority of the protein families in our database. This suggests that it provides a better overall fit to the evolutionary process in globular proteins and may lead to more accurate phylogenetic tree estimates. Potentially, this matrix, and the methods used to generate it, may also be useful in other areas of research, such as biological sequence database searching, sequence alignment, and protein structure prediction, for which an accurate description of amino acid replacement is required.

Algorithms↗

Quantitative histological analysis of amyloid deposition in Alzheimer's double transgenic mouse brain.

The development of transgenic mice has created new opportunities for the generation of animal models of human neurodegenerative diseases where previously there was no animal counterpart. The first successful transgenic mouse model of Alzheimer's disease expressed increased levels of mutant human amyloid precursor protein, exhibiting neuritic-type amyloid deposits and behavioral deficits at six to nine months of age. More recently, it was shown that transgenic mice expressing both mutant human amyloid precursor protein and presenilin 1 exhibit neuritic-type amyloid deposits and behavioral deficits in as little as 12 weeks. This accelerated Alzheimer phenotype greatly reduces the time necessary to conduct preclinical drug trials, as well as animal housing costs. The purpose of this study was to quantify the deposition of amyloid in five regions of the cortex and two regions of the hippocampus of transgenic mice expressing amyloid precursor protein (K670N, M671L) and presenilin 1 (M146L) mutations at various ages, using quantitative methods of confocal laser scanning microscopy and image analysis. Amyloid burden, expressed as the percentage area occupied by thioflavin S-positive amyloid deposits, increased an average of 179-fold from 12 to 54 weeks of age (0.02+/-0.01% to 3.57+/-0.29%, mean+/-S.E.M., respectively) in five regions of the cortex and two of the hippocampus. This was a function of increases in both deposit number and size. This transgenic mouse provides an ideal animal model for evaluating the efficacy of potential therapeutic agents aimed at reducing amyloid deposition, such as inhibitors of amyloid fibril formation or secretase inhibitors.

Alzheimer Disease↗

Evaluation of an electric bed frame and pressure-reducing mattresses.

Pressure ulcers remain a challenge to all healthcare professionals. With the trend towards caring for ill patients in the community there is a need to ensure that equipment used to prevent pressure ulcers in these patients is effective. It is not always appropriate to simply use equipment designed for hospital. This article describes the evaluation of an electric bed frame and three mattresses specifically designed for patients in the community, in either their own homes or nursing home/residential care. The location of this research can reduce the number of participants recruited. In order to compensate for this, three different methods of evaluation were employed - clinical, laboratory and anecdotal - which have produced results relevant to both purchasers and users of the system tested.

Aged↗

Evidence for mitochondrial DNA recombination in a human population of island Melanesia.

Mitochondrial DNA (mtDNA) analysis has proved useful in studies of recent human evolution and the genetic affinities of human groups of different geographical regions. As part of an extensive survey of mtDNA diversity in present-day Pacific populations, we obtained sequence information of the hypervariable mtDNA control region of 452 individuals from various localities in the western Pacific. The mtDNA types fell into three major groups which reflect the settlement history of the area. Interestingly, we detected an extremely rare point mutation at high frequency in the small island of Nguna in the Melanesian archipelago of Vanuatu. Phylogenetic analysis of the mtDNA data indicated that the mutation was present in individuals of separate mtDNA lineages. We propose that the multiple occurrence of a rare mutation event in one isolated locality is highly improbable, and that recombination between different mtDNA types is a more likely explanation for our observation. If correct, this conclusion has important implications for the use of mtDNA in phylogenetic and evolutionary studies.

Biological Evolution↗

Cancer in Gabon, 1984-1993: a pathology registry based relative frequency study.

A pathology based cancer registry was established in 1977 in the pathology department of the faculty of health sciences of the University of Omar Bongo in Librevile, Gabon, which is the only pathology service catering to the needs of the population of approximately 1 million of Gabon. Analysis of the histologically diagnosed cancers during 1984 through 1993 revealed 1,367 male and 1,235 female cases. The leading sites in males were: skin (11.0%), liver (8.9%), non-Hodgkin's lymphoma (8.7%), prostate (7.8%), lung (6.9%), mouth (4.9%) and tongue (4.7%). The predominant sites in females were: uterine cervix (26.3%), breast (13.9%), non-Hodgkin's lymphoma (7.1%), skin (5.1%), liver (3.9%) and ovary (3.3%). Considering the little information available on cancer patterns in Africa, even relative frequency data for different periods from different sources are of considerable interest. We propose to establish population based cancer registration in Libreville (pop 400,000) where 40% of the national population lives, in the near future, which should provide reliable information on the cancer burden and patterns in Gabon.

Adolescent↗

Extent of terminal complementarity modulates the balance between transcription and replication of vesicular stomatitis virus RNA.

We compared the template properties of a subgenomic RNA that contained the authentic 5' and 3' ends of the vesicular stomatitis virus genome with those of RNAs in which the wild-type termini were engineered to extend their complementarity from 8 to 51 nucleotides as seen in defective interfering RNAs. The RNA with authentic 5' and 3' ends directed abundant transcription but low replication. In contrast, RNAs with complementary termini derived from either end of the genome replicated well but transcribed poorly or not at all. These results have implications for understanding the mechanisms of RNA replication and transcription; they explain the replicative dominance of defective interfering RNAs and demonstrate that the extent of terminal complementarity rather than its exact sequence is a major determinant of whether the template predominantly directs transcription or replication.

Base Sequence↗

Survey of employers' policies on HIV and AIDS in North Nottinghamshire.

To ascertain the extent to which local employers in North Nottinghamshire currently have policies for dealing with AIDS/HIV in the workplace, and the areas covered by any such policies, a survey of 148 companies was carried out. Eighty-six companies returned completed questionnaires (58 per cent). Of these, 17 reported that they had policies. These were more likely to be local outlets of national or regional companies. Companies with policies had larger workforces than those without (p < 0.0001). It is concluded that few companies have AIDS/HIV policies, despite the potential benefits to themselves and employees. Departments of public health should encourage companies to adopt such policies.

Acquired Immunodeficiency Syndrome↗