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Biomedical subjects

G Moulton

Publications and source records attributed to G Moulton.

At least 19 recordsLinked to original sources

PRINTS and its automatic supplement, prePRINTS.

The PRINTS database houses a collection of protein fingerprints. These may be used to assign uncharacterised sequences to known families and hence to infer tentative functions. The September 2002 release (version 36.0) includes 1800 fingerprints, encoding approximately 11 000 motifs, covering a range of globular and membrane proteins, modular polypeptides and so on. In addition to its continued steady growth, we report here the development of an automatic supplement, prePRINTS, designed to increase the coverage of the resource and reduce some of the manual burdens inherent in its maintenance. The databases are accessible for interrogation and searching at http://www.bioinf.man.ac.uk/dbbrowser/PRINTS/.

Amino Acid Motifs↗

Phylogenomic analysis and evolution of the potassium channel gene family.

Potassium channels govern the permeability of cells to potassium ions, thereby controlling the membrane potential. In metazoa, potassium channels are encoded by a large, diverse gene family. Previous analyses of this gene family have focused on its diversity in mammals. Here we have pursued a more comprehensive study in Caenorhabditis elegans, Drosophila melanogaster, and mammalian genomes. The investigation revealed 164 potassium channel encoding genes in C. elegans, D. melanogaster, and mammals, classified into seven conserved families, which we applied to phylogenetic analysis. The trees are discussed in relation to the assignment of orthologous relationships between genes and vertebrate genome duplication.

Animals↗

PRINTS and PRINTS-S shed light on protein ancestry.

The PRINTS database houses a collection of protein fingerprints. These may be used to make family and tentative functional assignments for uncharacterised sequences. The September 2001 release (version 32.0) includes 1600 fingerprints, encoding approximately 10 000 motifs, covering a range of globular and membrane proteins, modular polypeptides and so on. In addition to its continued steady growth, we report here its use as a source of annotation in the InterPro resource, and the use of its relational cousin, PRINTS-S, to model relationships between families, including those beyond the reach of conventional sequence analysis approaches. The database is accessible for BLAST, fingerprint and text searches at http://www.bioinf.man.ac.uk/dbbrowser/PRINTS/.

Amino Acid Motifs↗

Setting standards in the evaluation of community-based health promotion programmes--a unifying approach.

Community-based health promotion often emphasizes elements of empowerment, participation, multidisciplinary collaboration, capacity building, equity and sustainable development. Such an emphasis may be viewed as being in opposition to equally powerful notions of evidence-based decision making and accountability, and with funders' and government decision-makers' preoccupation with measuring outcomes. These tensions may be fuelled when community practitioners and lay participants feel evaluations are imposed upon them in a manner that fails to appreciate the uniqueness of their community, its programme, and practitioners' skills and experience. This paper attempts to provide an approach that depicts evaluation as being mutually beneficial to both funders/government and practitioners. First, a values stance for health promotion, termed a 'salutogenic' orientation, is proposed as a foundation for the evaluation of community-based health promotion. Secondly, we discuss possible objects of interest, the first component of an evaluation. We then discuss the spirit of the times and its implications for community-based health promotion. Finally, we address the key question of setting standards. A typology of standards is presented. Arbitrary, experiential and utility standards are based on perceived needs and priorities of practitioners, lay participants or professional decision-makers. Historical, scientific and normative standards are driven by empirical, objective data. Propriety and feasibility standards are those wherein the primary concern is for consideration of resources, policies, legislation and administrative factors. The 'model' standards approach is presented as an exemplar of a combined approach that incorporates elements of each of the other standards. We argue that the 'optimal' standard for community-based health promotion depends on the setting and the circumstances. There is no 'magic bullet', 'one-size-fits-all' or 'best' standard. Further, we argue that standards should be set from an inclusive, salutogenic orientation. This approach offers a means of creating a situation in which policy-makers and funders are more supportive of evaluation designs that fit with community realities, and community stakeholders are more capable and consistent in rigorously evaluating community-based health promotion programmes and policies.

Canada↗

Comparative proliferative and histopathologic changes in rat lungs after inhalation of chrysotile or crocidolite asbestos.

Patterns of cell proliferation in lung and pleura and development of histopathologic lesions were studied in lungs from Fischer 344 rats after inhalation exposure to chrysotile or crocidolite asbestos at average airborne concentrations of approximately 8 mg/m3 air for 5 and 20 days and after 20 days of exposure followed by an additional 20 days in room air (20 + 20 days). To assess cell proliferation rats were injected with 5-bromo-2'-deoxyuridine (BrdU) at various time points after initiation of exposure to asbestos. Image analysis was used to quantitate the effects of chrysotile and crocidolite on BrdU labeling indices in the following lung compartments: (1) interstitium, (2) alveolar duct region, (3) bronchial epithelium, and (4) visceral mesothelium. With the exception of mesothelium, which exhibited significant increases in BrdU incorporation in rats exposed to crocidolite at 20 + 20 days, asbestos-induced elevations in BrdU uptake in other compartments were transient with labeling comparable to sham controls at later time points. Histopathology of rat lungs revealed fibrotic lesions of a greater extent and severity at 20 days in rats exposed to crocidolite, but fibrosis occurred in both asbestos-exposed groups after an additional 20 days in clean air (20 + 20). Quantification of fiber burden in rat lung after inhalation of comparable airborne concentrations of either fiber type demonstrated that inhalation of crocidolite asbestos led to a higher fiber retention when compared to chrysotile asbestos. Our results indicate that chrysotile and crocidolite asbestos induce different patterns of cell proliferation in lung and pleural cells. The protracted increases in BrdU labeling of mesothelial cells by crocidolite may reflect increased retention of fibers and/or inherent differences between types of asbestos.

Administration, Inhalation↗

Modulation of cytokine expression by CD4+ T cells during coxsackievirus B3 infections of BALB/c mice initiated by cells expressing the gamma delta + T-cell receptor.

Two variants of coxsackievirus B3 have been used to investigate the pathogenesis of myocarditis in BALB/c mice. H3 virus induces moderate myocarditis and H310A1 virus induces minimal myocarditis, although both viruses infect and replicate in the heart. Cells expressing the gamma delta+ T-cell receptor composed 5 to 13% of the lymphocytes infiltrating the hearts of H3 virus-infected mice and belonged to either the CD4- CD8+ gamma delta+- or CD4- CD8- gamma delta+-cell population. Giving 5,000 gamma delta+ cells isolated from the hearts of H3 virus-infected mice to H310A1 virus-infected recipients restored myocarditis susceptibility in the recipient animals and shifted the pattern of cytokine production in the virus-immune CD4+-cell population from being predominantly interleukin-4 producing to being predominantly gamma interferon producing in the H310A1 virus-infected mice. Apoptosis was evident in the infiltrating lymphocyte population in the myocardia of H3 virus-infected mice by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling assay and in splenic lymphocytes by DNA fragmentation in agarose gel electrophoresis and was confined to the CD4+ population. No apoptosis was observed in H310A1 virus-infected mice, but apoptosis was induced subsequent to gamma delta +-T-cell transfer. These results are consistent with the hypothesis that gamma delta+ T cells may help modulate cytokine responses during virus infections in vivo and that apoptosis might be involved in this modulation.

Animals↗

Functional cerebral imaging in the evaluation and radiotherapeutic treatment planning of patients with malignant glioma.

PURPOSE: Functional magnetic resonance imaging (MRI) and positron emission tomography are relatively new modalities of great potential value in the evaluation, treatment, and subsequent follow-up care of patients with malignant glioma. We report our experience with the incorporation of functional imaging data into radiation therapy three-dimensional (3-D) treatment planning. METHODS AND MATERIALS: Over a 24-month period, a total of 37 positron emission tomography and 29 functional MRI studies have been conducted on eight consecutive patients prior to, during, and following the completion of radiation therapy. Functional imaging was conducted prior to radiation therapy treatment planning and at approximate 3-month follow-up time intervals. RESULTS: In two patients, functional imaging provided additional information over conventional imaging modalities and resulted in subsequent modification of conventional radiation therapy treatment planning. CONCLUSION: Although it is premature to make definitive statements regarding the use of these new imaging parameters in the prognostic setting, functional imaging may likely prove to be a useful adjunct in the initial evaluation, radiation treatment planning, and follow-up care of patients with malignant glioma.

Adult↗

Proton therapy at Harvard.

Fractionated precision high-dose proton radiotherapy has been carried out at the Harvard Cyclotron Laboratory (HCL) since 1973, in a collaborative effort with the Radiation Medicine Department of Massachusetts General Hospital (MGH) and the Retina Service of the Massachusetts Eye and Ear Infirmary (MEEI). This paper will discuss proton treatment in general, treatment planning procedures, and results to date in major patient categories. 846 patients have been treated with fractionated proton therapy at the Harvard Cyclotron, with normal tissue and tumor responses consistent with an RBE of 1.1 for the proton beam. Proton beam therapy is the treatment of choice for patients with uveal melanomas, and chordomas and chondrosarcomas involving the skull base and cervical spine. Improved dose distribution possible with protons have allowed greater doses than are given conventionally to be delivered to patients with prostatic carcinoma, head and neck malignancies, ano-rectal cancers, and retroperitoneal tumors. Doses employed have been usually 10 to 20% greater than normally would be delivered in our department to such tumors. Generally, local control rates have been good.

Animals↗