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Biomedical subjects

John Powell

Publications and source records attributed to John Powell.

46 records · Page 3Linked to original sources
PubMed2003

The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma.

We used gene expression profiling to establish a molecular diagnosis of mantle cell lymphoma (MCL), to elucidate its pathogenesis, and to predict the length of survival of these patients. An MCL gene expression signature defined a large subset of MCLs that expressed cyclin D1 and a novel subset that lacked cyclin D1 expression. A precise measurement of tumor cell proliferation, provided by the expression of proliferation signature genes, identified patient subsets that differed by more than 5 years in median survival. Differences in cyclin D1 mRNA abundance synergized with INK4a/ARF locus deletions to dictate tumor proliferation rate and survival. We propose a quantitative model of the aberrant cell cycle regulation in MCL that provides a rationale for the design of cell cycle inhibitor therapy in this malignancy.

ADP-Ribosylation Factors↗
PubMed2002

The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma.

BACKGROUND: The survival of patients with diffuse large-B-cell lymphoma after chemotherapy is influenced by molecular features of the tumors. We used the gene-expression profiles of these lymphomas to develop a molecular predictor of survival. METHODS: Biopsy samples of diffuse large-B-cell lymphoma from 240 patients were examined for gene expression with the use of DNA microarrays and analyzed for genomic abnormalities. Subgroups with distinctive gene-expression profiles were defined on the basis of hierarchical clustering. A molecular predictor of risk was constructed with the use of genes with expression patterns that were associated with survival in a preliminary group of 160 patients and was then tested in a validation group of 80 patients. The accuracy of this predictor was compared with that of the international prognostic index. RESULTS: Three gene-expression subgroups--germinal-center B-cell-like, activated B-cell-like, and type 3 diffuse large-B-cell lymphoma--were identified. Two common oncogenic events in diffuse large-B-cell lymphoma, bcl-2 translocation and c-rel amplification, were detected only in the germinal-center B-cell-like subgroup. Patients in this subgroup had the highest five-year survival rate. To identify other molecular determinants of outcome, we searched for individual genes with expression patterns that correlated with survival in the preliminary group of patients. Most of these genes fell within four gene-expression signatures characteristic of germinal-center B cells, proliferating cells, reactive stromal and immune cells in the lymph node, or major-histocompatibility-complex class II complex. We used 17 genes to construct a predictor of overall survival after chemotherapy. This gene-based predictor and the international prognostic index were independent prognostic indicators. CONCLUSIONS: DNA microarrays can be used to formulate a molecular predictor of survival after chemotherapy for diffuse large-B-cell lymphoma.

Antibiotics, Antineoplastic↗
PubMed2002

Gene expression profile of human bone marrow stromal cells: high-throughput expressed sequence tag sequencing analysis.

Human bone marrow stromal cells (HBMSC) are pluripotent cells with the potential to differentiate into osteoblasts, chondrocytes, myelosupportive stroma, and marrow adipocytes. We used high-throughput DNA sequencing analysis to generate 4258 single-pass sequencing reactions (known as expressed sequence tags, or ESTs) obtained from the 5' (97) and 3' (4161) ends of human cDNA clones from a HBMSC cDNA library. Our goal was to obtain tag sequences from the maximum number of possible genes and to deposit them in the publicly accessible database for ESTs (dbEST of the National Center for Biotechnology Information). Comparisons of our EST sequencing data with nonredundant human mRNA and protein databases showed that the ESTs represent 1860 gene clusters. The EST sequencing data analysis showed 60 novel genes found only in this cDNA library after BLAST analysis against 3.0 million ESTs in NCBI's dbEST database. The BLAST search also showed the identified ESTs that have close homology to known genes, which suggests that these may be newly recognized members of known gene families. The gene expression profile of this cell type is revealed by analyzing both the frequency with which a message is encountered and the functional categorization of expressed sequences. Comparing an EST sequence with the human genomic sequence database enables assignment of an EST to a specific chromosomal region (a process called digital gene localization) and often enables immediate partial determination of intron/exon boundaries within the genomic structure. It is expected that high-throughput EST sequencing and data mining analysis will greatly promote our understanding of gene expression in these cells and of growth and development of the skeleton.

Bone Marrow Cells↗
PubMed2002

Genetics, molecular biology, neuropathology and phenotype of frontal lobe dementia: a case history.

BACKGROUND: Mutations in tau have been found in a group of related disorders including the frontal lobe dementias. AIMS: To describe the clinical features and molecular pathology changes in a single case of a patient with frontal lobe dementia. METHOD: A case report was compiled from neuropathological reports and genomic and gene expression analyses. RESULTS: A case with a splice-site mutation resulting in a typical frontotemporal clinical and neuropathological phenotype was found. Gene expression analysis suggests differential expression of isoforms of tau in regions in the brain. CONCLUSIONS; Frontotemporal dementia can result from gene mutations that alter splicing and expression of tau.

Dementia↗
PubMed2002

Systematic review of outreach clinics in primary care in the UK.

OBJECTIVES: To determine the benefits of holding specialist outreach clinics in primary care settings by means of a systematic literature review of UK studies. METHODS: Systematic searches of electronic databases, hand searches of journals, and contact with experts. Application of inclusion criteria. Study findings summarised. RESULTS: Fifteen studies met the inclusion criteria. Surveys of general practitioners (GPs), specialists and patients identified the perceived advantages of outreach clinics of improving GP-specialist communication and improving patients' experience and access. Reported disadvantages concerned administrative costs, accommodation costs and inefficient use of specialists' time. Comparative studies showed that more patients expressed a preference for outreach clinics than for hospital-based clinics, and measures of patients' satisfaction and convenience generally were higher for outreach clinics. Studies did not show any consistent difference in health outcome between outreach and hospital-based clinics. Outreach clinics had higher direct costs to the health system than hospital-based clinics. CONCLUSIONS: Health care purchasers and providers must decide whether the advantages in terms of patients' experience of outreach clinics are worth the additional costs. They also need to consider issues of equity, which have not been addressed in research to date.

Ambulatory Care Facilities↗
PubMedDate not supplied

Empirical studies assessing the quality of health information for consumers on the world wide web: a systematic review.

CONTEXT: The quality of consumer health information on the World Wide Web is an important issue for medicine, but to date no systematic and comprehensive synthesis of the methods and evidence has been performed. OBJECTIVES: To establish a methodological framework on how quality on the Web is evaluated in practice, to determine the heterogeneity of the results and conclusions, and to compare the methodological rigor of these studies, to determine to what extent the conclusions depend on the methodology used, and to suggest future directions for research. DATA SOURCES: We searched MEDLINE and PREMEDLINE (1966 through September 2001), Science Citation Index (1997 through September 2001), Social Sciences Citation Index (1997 through September 2001), Arts and Humanities Citation Index (1997 through September 2001), LISA (1969 through July 2001), CINAHL (1982 through July 2001), PsychINFO (1988 through September 2001), EMBASE (1988 through June 2001), and SIGLE (1980 through June 2001). We also conducted hand searches, general Internet searches, and a personal bibliographic database search. STUDY SELECTION: We included published and unpublished empirical studies in any language in which investigators searched the Web systematically for specific health information, evaluated the quality of Web sites or pages, and reported quantitative results. We screened 7830 citations and retrieved 170 potentially eligible full articles. A total of 79 distinct studies met the inclusion criteria, evaluating 5941 health Web sites and 1329 Web pages, and reporting 408 evaluation results for 86 different quality criteria. DATA EXTRACTION: Two reviewers independently extracted study characteristics, medical domains, search strategies used, methods and criteria of quality assessment, results (percentage of sites or pages rated as inadequate pertaining to a quality criterion), and quality and rigor of study methods and reporting. DATA SYNTHESIS: Most frequently used quality criteria used include accuracy, completeness, readability, design, disclosures, and references provided. Fifty-five studies (70%) concluded that quality is a problem on the Web, 17 (22%) remained neutral, and 7 studies (9%) came to a positive conclusion. Positive studies scored significantly lower in search (P =.02) and evaluation (P =.04) methods. CONCLUSIONS: Due to differences in study methods and rigor, quality criteria, study population, and topic chosen, study results and conclusions on health-related Web sites vary widely. Operational definitions of quality criteria are needed.

Evaluation Studies as Topic↗
PubMedDate not supplied

ACE genotype and cognitive decline in an African-Caribbean population.

The insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme (ACE) gene is believed to influence risk of cerebrovascular disease. However, associations with cognitive outcomes remain controversial. As far as we are aware, all studies to date have been carried out in white American or European populations. African-Caribbean populations have high prevalence rates of hypertension, diabetes and cerebrovascular disease but risk factors for cognitive outcomes remain under-researched. In a UK community sample of 148 African-Caribbean people aged 55-75 years, we investigated the association between ACE genotype and cognitive decline over 3 years using a battery of repeated tests. No direct association was found between ACE genotype and decline. However, the association between increased age and cognitive decline was significantly stronger in people with the ACE DD genotype (odds ratio 3.6 per 5-year increase, 95% CI: 1.9-6.7) compared to those with ID/II genotype (odds ratio 0.7, 95% CI 0.4-1.2). This interaction was particularly strong for decline in verbal memory and was not apparently mediated by vascular risk factors measured at baseline.

Africa↗
PubMedDate not supplied

Intertrochanteric osteotomy using a dynamic hip screw for femoral neck nonunion.

The dynamic hip screw, which is routinely used for intertrochanteric hip fractures, also provides a technically simple means of fixation for intertrochanteric valgus osteotomies in the treatment of femoral neck nonunions. Eight patients underwent intertrochanteric valgus osteotomy for femoral neck nonunion using a dynamic hip screw for fixation. One patient died 4 months postoperatively of causes unrelated to the procedure. The remaining 7 patients were followed for an average of 24 months postoperatively. The nonunion healed in all 7 cases. The average angle of the fracture plane decreased from 68 degrees to 41 degrees. All the hip fractures were classified as Pauwels type III preoperatively and Pauwels type II postoperatively. The average Harris Hip Score increased from 24 to 73. On radiographic review, no cases of osteonecrosis were identified postoperatively.

Bone Screws↗