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David Martin

Publications and source records attributed to David Martin.

At least 91 records · Page 5Linked to original sources
PubMed2003

BioSPICE: access to the most current computational tools for biologists.

The goal of the BioSPICE program is to create a framework that provides biologists access to the most current computational tools. At the program midpoint, the BioSPICE member community has produced a software system that comprises contributions from approximately 20 participating laboratories integrated under the BioSPICE Dashboard and a methodology for continued software integration. These contributed software modules are the BioSPICE Dashboard, a graphical environment that combines Open Agent Architecture and NetBeans software technologies in a coherent, biologist-friendly user interface. The current Dashboard permits data sources, models, simulation engines, and output displays provided by different investigators and running on different machines to work together across a distributed, heterogeneous network. Among several other features, the Dashboard enables users to create graphical workflows by configuring and connecting available BioSPICE components. Anticipated future enhancements to BioSPICE include a notebook capability that will permit researchers to browse and compile data to support model building, a biological model repository, and tools to support the development, control, and data reduction of wet-lab experiments. In addition to the BioSPICE software products, a project website supports information exchange and community building.

Computational Biology↗
PubMed2003

Genome-wide identification of in vivo Drosophila Engrailed-binding DNA fragments and related target genes.

Chromatin immunoprecipitation after UV crosslinking of DNA/protein interactions was used to construct a library enriched in genomic sequences that bind to the Engrailed transcription factor in Drosophila embryos. Sequencing of the clones led to the identification of 203 Engrailed-binding fragments localized in intergenic or intronic regions. Genes lying near these fragments, which are considered as potential Engrailed target genes, are involved in different developmental pathways, such as anteroposterior patterning, muscle development, tracheal pathfinding or axon guidance. We validated this approach by in vitro and in vivo tests performed on a subset of Engrailed potential targets involved in these various pathways. Finally, we present strong evidence showing that an immunoprecipitated genomic DNA fragment corresponds to a promoter region involved in the direct regulation of frizzled2 expression by engrailed in vivo.

Animals↗
PubMed2003

In vitro studies with the calcimimetic, cinacalcet HCl, on normal human adult osteoblastic and osteoclastic cells.

This study examined whether the calcium-sensing receptor (CaR) is expressed in normal adult human osteoblastic and osteoclastic cells in culture, and whether the calcimimetic, cinacalcet HCl (AMG 073), potentiates the effects of calcium (via CaR, or some other receptor/mechanism). When mouse or human osteoblastic cells were treated with higher concentrations of calcium (6.6 or 8.6 mM in alpha-MEM/10% FBS) than present in control cultures (1.6 mM), the previously well-documented increase in cell number was demonstrated. Cinacalcet HCl affected cell proliferation of CHO cells transfected with CaR, dose dependently, but had no effect on human or mouse osteoblastic cell proliferation in calcium-containing medium (1.6 or 8.6 mM). To test cinacalcet HCl and calcium on osteoclastic cells, peripheral blood mononuclear cells were cultured in medium containing RANK ligand and M-CSF, supplemented with calcium, and/or cinacalcet HCl. Tartrate-resistant acid phosphatase-positive multinucleated osteoclastic cells on plastic or bone were then counted at 11 and 21 days, respectively. Calcium (greater than 6.0 mM) inhibited osteoclast formation, but cinacalcet HCl (30-1000 nM) had no effect on osteoclastic formation or resorption in the presence of calcium (1.6 or 6.1 mM). RT-PCR did not detect CaR in human, rat, or mouse primary osteoblastic cells and cell lines or osteoclastic cells. In conclusion, these studies indicate that the calcium-induced increase in osteoblastic cell number, and the decrease in formation/function of osteoclastic cells, involves a mechanism or receptor other than CaR. In addition, the calcimimetic agent did not potentiate the effects of calcium on normal adult human bone cells in vitro.

Animals↗
PubMed2002

Future of the BVA.

Explore the source record for details and available documents.

Age Distribution↗
PubMed2002

Leptin transport across the blood-brain barrier of the Koletsky rat is not mediated by a product of the leptin receptor gene.

Obesity in humans is thought to be caused by a resistance to leptin. Currently, the evidence suggests that this resistance is caused by an impaired transport of leptin across the blood-brain barrier (BBB). It has been assumed that the short form of the leptin receptor, which is a splice variant of the gene which produces all known leptin receptors, is the leptin transporter, but evidence for this is mixed. The Koletsky rat model should provide a clear answer as to whether transport is dependent on leptin receptors as it does not express any functional receptors. The transport of intravenous leptin across the BBB of the Koletsky rat has been found to be greatly reduced, but evidence for a residual of transport makes it unclear whether the transporter is essentially absent or simply saturated by the high levels of leptin in the serum. Here we used the brain perfusion method to negate the influence of serum levels. We found that, whereas no transport of intravenous leptin occurred in the obese Koletsky, the rate of transport was no different from controls when brain perfusion was used. Leptin was transported completely across the BBB, was saturable, and had the same distribution among brain regions as previously found in normal weight mice (highest transport into the hippocampus and hypothalamus, lowest in the frontal cortex). We conclude that a leptin transporter and possibly its gene have yet to be identified and that the short form likely plays a role in the modulation of transport activity.

Animals↗
PubMed2002

Autologous intervertebral disc cell implantation: a model using Psammomys obesus, the sand rat.

STUDY DESIGN: Work presented here used a small animal model to illustrate the feasibility of autologous disc cell implantation. OBJECTIVES: To develop a small animal model for autologous disc cell implantation. SUMMARY OF THE BACKGROUND DATA: The use of autologous disc cells in the potential treatment of disc degeneration offers attractive possibilities for novel therapies. Results are presented on the use of the sand rat (Psammomys obesus), a small rodent that spontaneously develops disc degeneration during aging, in experimental studies in which cells were harvested from a lumbar intervertebral disc, expanded in monolayer tissue culture, labeled with agents that allow subsequent immunolocalization of these cells, and implanted in a second disc site of the donor animal. METHODS: Tissue culture, disc surgery, histology, and immunocytochemistry were used. Cells were either engrafted in a bioresorbable carrier tested for cell compatibility or injected into the recipient disc. Results were assessed with radiographic examination of the implantation site and with histology and immunocytochemistry. CONCLUSION: Data from 15 animals were obtained with engraftment resident in the animal for up to 33 weeks. Immunocytologic identification of engrafted cells showed that they integrated into the disc and were surrounded by normal matrix at time points up to 8 months postengraftment. Engrafted cells exhibited either a spindle-shaped morphology in the annulus or a rounded chondrocyte-like morphology in the nucleus. Although technically challenging, the authors' experience showed that autologous disc cell implantation can be successful and that the sand rat is a valuable model for autologous disc cell studies.

Animals↗
PubMed2002

The effectiveness of breath-holding to stabilize lung and pancreas tumors during radiosurgery.

PURPOSE: To evaluate the effect of breath-holding on the short-term reproducibility and long-term variability of tumor position during image-guided radiosurgery. METHOD: Thirteen patients have undergone single-fraction radiosurgery treatments during which the tumor was repeatedly imaged radiographically to observe its position. The imaging data were used to monitor the efficacy of breath-holding and to periodically readjust the alignment of the treatment beam with the tumor. These measurements have allowed the effects of breathing, heartbeat, patient movement, and instrumental uncertainties to be separately identified in the record of tumor position. RESULTS: During inspiration breath-holding, the lung tumor position was reproducible to within 1 mm, on average, in the direction of maximum displacement during regular breathing, and to within 1.8 mm in three dimensions overall. The pancreas tumor position in three dimensions was reproducible to within 2.5 mm on average. Some patients showed a slow, steady drift of tumor position during the extended sequence of breath-holds, which was compensated by periodic retargeting of the treatment beam. CONCLUSION: Breath-holding can allow the reduction of tumor motion dosimetry margins to 2 mm or less for lung cancer treatments, provided that the treatment system can detect and adapt to long-term variations in the mean tumor position during a lengthy treatment fraction.

Humans↗
PubMed2002

Glial cell line-derived neurotrophic factor modulates kindling and activation-induced sprouting in hippocampus of adult rats.

Kindling, a phenomenon in which repeated electrical stimulation of certain forebrain structures leads to an increase in the evoked epileptogenic response, is widely used to investigate the mechanisms of epilepsy. Kindling also results in sprouting of the dentate gyrus mossy fiber pathway and triggers astrocyte hypertrophy and increased volume of the hilus of the dentate gyrus. Our previous studies showed that infusion of the neurotrophin nerve growth factor accelerated the behavioral progression of amygdala kindling and affected kindling-induced structural changes in the brain, whereas intrahilar infusion of another neurotrophin, brain-derived neurotrophic factor, delayed amygdala kindling-induced seizure development and reduced the growth in afterdischarge duration, but had little effect on kindling-induced structural changes. In this paper, we report the effects of infusion of glial cell line-derived neurotrophic factor, a neurotrophic factor of the TGF-beta superfamily having similar central nervous system neuronal targets as brain-derived neurotrophic factor. We show that continuous intraventricular infusion of glial cell line-derived neurotrophic factor inhibits the behavioral progression of perforant path kindling-induced seizures without affecting afterdischarge duration. In addition, we demonstrate that intraventricular administration of glial cell line-derived neurotrophic factor prevents kindling-induced increases in hilar area and blocks mossy fiber sprouting in the CA3 region of the hippocampus. Glial cell line-derived neurotrophic factor did not have a statistically significant effect on the mossy fiber density in the inner molecular layer. Our results raise the possibility that glial cell line-derived neurotrophic factor plays a role in kindling and activation-induced neural growth via mechanisms distinct from those of the neurotrophins.

Age Factors↗
PubMed2002

Molecular biology of mosquito vitellogenesis: from basic studies to genetic engineering of antipathogen immunity.

Elucidation of molecular mechanisms underlying stage- and tissue-specific expression of genes activated by a blood meal is of great importance for current efforts directed towards utilizing molecular genetics to develop novel strategies of mosquito and pathogen control. Regulatory regions of such genes can be used to express anti-pathogen effector molecules in engineered vectors in a precise temporal and spatial manner, designed to maximally affect a pathogen. The fat body is a particularly important target for engineering anti-pathogen properties because in insects, it is a potent secretory tissue releasing its products to the hemolymph, an environment or a crossroad for most pathogens. Recently, we have provided proof of this concept by engineering stable transformant lines of Aedes aegypti mosquito, in which the regulatory region A. aegypti vitellogenin (Vg) gene activates high-level fat body-specific expression of a potent anti-bacterial factor, defensin, in response to a blood meal. Further study of the Vg gene utilizing Drosophila and Aedes transformation identified cis-regulatory sites responsible for state- and fat body-specific activation of this gene via a blood-meal-triggered cascade. These analyses revealed three regulatory regions in the 2.1-kb upstream portion of the Vg gene. The proximal region, containing binding sites to EcR/USP, GATA, C/EBP and HNF3/fkh, is required for the correct tissue- and stage-specific expression at a low level. The median region, carrying sites for early ecdysone response factors E74 and E75, is responsible for a stage-specific hormonal enhancement of the Vg expression. Finally, the distal GATA-rich region is necessary for extremely high expression levels characteristic to the Vg gene. Furthermore, our study showed that several transcription factors involved in controlling the Vg gene expression, are themselves targets of the blood meal-mediated regulatory cascade, thus greatly amplifying the effect of this cascade on the Vg gene. This research serves as the foundation for the future design of mosquito-specific expression cassettes with predicted stage- and tissue specificity at the desired levels of transgene expression.

Aedes↗
PubMed2002

YfcX enables medium-chain-length poly(3-hydroxyalkanoate) formation from fatty acids in recombinant Escherichia coli fadB strains.

Expression of Escherichia coli open reading frame yfcX is shown to be required for medium-chain-length polyhydroxyalkanoate (PHA(MCL)) formation from fatty acids in an E. coli fadB mutant. The open reading frame encodes a protein, YfcX, with significant similarity to the large subunit of multifunctional beta-oxidation enzymes. E. coli fadB strains modified to contain an inactivated copy of yfcX and to express a medium-chain-length synthase are unable to form PHA(MCL)s when grown in the presence of fatty acids. Plasmid-based expression of yfcX in the FadB(-) YfcX(-) PhaC(+) strain restores polymer formation. YfcX is shown to be a multifunctional enzyme that minimally encodes hydratase and dehydrogenase activities. The gene encoding YfcX is located downstream from yfcY, a gene encoding thiolase activity. Results of insertional inactivation studies and enzyme activity analyses suggest a role for yfcX in PHA monomer unit formation in recombinant E. coli fadB mutant strains. Further studies are required to determine the natural role of YfcX in the metabolism of E. coli.

Escherichia coli↗
PubMed2002

Mental impairment in the West Midlands: 10 years on.

In 1989, a survey was undertaken to describe the learning disabled population, originating from the West Midlands, classified as mentally impaired or severely mentally impaired under the Mental Health Act 1983. The results obtained were then used to help guide future service development within the region. Given the marked changes in service provision over the subsequent decade, the study was repeated in 1998-1999, looking at the same population on 1st December 1997 (prior to the Bournewood Ruling). Attempts were made to identify all people residing within the West Midlands region, or originating from it, and classified as mentally impaired or severely mentally impaired under the Mental Health Act (1983). This was achieved by contacting medical records departments, learning disability consultants and Health Authorities. The same data set as the original study was then collected from case notes to allow comparison. The current study however, collected extra information, relating to diagnosis, treatment and outcome. Ninety-three people were identified for the study. Over the 10 years, there has been approximately a 100% increase in the numbers of people detained under these categories of the Mental Health Act (1983). There has been a marked increase in the use of the private sector, as well as out-of-region placements. Sexual offending seemed a common reason for detention. The authors attempt to explain this phenomenon. They also highlight the need for future developments and greater systematic data collection.

Adolescent↗
PubMed2002

Diabetes mellitus in the First Nations population of British Columbia, Canada. Part 3. Prevalence of diagnosed cases.

OBJECTIVES: To describe the prevalence of diabetes mellitus in the on-reserve Status Indian population of British Columbia based on a survey conducted in 1997 and to compare these rates with previous surveys carried out in 1987, 1992 and 1995. STUDY DESIGN: Survey questionnaires were distributed to health centres, health stations and nursing stations providing health services to the 198 First Nations reserves in British Columbia. RESULTS: Data were received from 82 of 198 First Nations communities (41%) representing 24,407 (45%) of the on-reserve population of the province (53,893). A total of 636 cases of diabetes were identified. Seventy-seven percent of cases were age 35 plus. The overall prevalence in 1997 was 2.6% for all ages combined, more than doubled from 1.2% in 1987. First Nation's men and women 35 and older when compared to the general population by indirect age-standardization experienced a higher prevalence ratio-males 1.27, 95% CI 1.22, 1.40 and females 2.53, 95% CI: 2.77, 2.58. Among those with diabetes for > 20 years, 62.5% used insulin compared to 13% who had the disease < five years (622/636 reporting). Diabetic complications were reported in 48% of individuals. Diagnosed gestational diabetes was 28/1000 live births. CONCLUSIONS: General preventive initiatives must continue including Screening, nutrition and fitness education, and improved diabetic management directed at reduction in complications.

British Columbia↗
PubMed2002

Geography for the 2001 Census in England and Wales.

This article provides an overview of 2001 Census geography systems in England and Wales, concentrating primarily on the creation of output geography. It is important to note that there are significant differences between the systems being implemented in England and Wales and those which apply to Northern Ireland and Scotland. The Northern Ireland system is broadly similar to that described here, whereas the entire data infrastructure and output area design process in Scotland are different.

Censuses↗
PubMedDate not supplied

Long-term outcome after haploidentical stem cell transplantation in children.

We present an update of our results with transplantation of highly purified stem cells from one to three loci mismatched parental donors. Sixty-three pediatric patients with acute lymphoblastic leukemias (n = 32), acute myeloid, chronic myeloid and myelomonocytic leukemias (n = 13), myelodysplastic syndromes (n = 4), lymphomas (n = 4), and various nonmalignant diseases (n = 10) underwent transplantation. Mobilized peripheral-blood stem cells were selected with either anti-CD34- or anti-CD133-coated microbeads. Patients received a median of 19.5 x 10(6) purified cells and <25,000 CD3+ T lymphocytes per kilogram, with no regular posttransplant pharmacological immunosuppression. Engraftment occurred in 98% of patients (primary sustained engraftment, 83%; engraftment after reconditioning/stem cell boosts, 15%). Moreover, all survivors but one had a stable three-lineage engraftment with a median follow up of 4.1 years (range 0.6-8 years). Primary acute graft-versus-host disease (GvHD) grade II was seen in only 7% of patients. No severe primary acute GvHD grades III-IV occurred. Thirteen percent of the patients developed transient chronic GvHD. Probability of disease-free survival (DFS) at 3 years was 60% for patients with nonmalignant diseases and 48% for patients with acute lymphatic leukemia (ALL)/non-Hodgkin lymphoma (NHL) in complete remission (CR)1-3. None of the ALL/NHL patients with active disease survived. Children with acute and chronic myeloid leukemias had a poorer outcome (3-year DFS = 18%), whereas two of four patients with myelodysplastic syndrome (MDS) are alive. Relapse probability of the whole group was not significantly increased when compared to a historical control group. The incidence of lethal viral infections was 18% between 1995 and 2002 and has since been reduced to 8% by the introduction of new therapeutic strategies. In summary, the use of stem cells from haploidentical parental donors should be strongly considered in all children who need transplantation but lack an identical donor.

Adolescent↗
PubMedDate not supplied

Results of a pilot intervention trial to improve antiretroviral adherence among HIV-positive patients.

A small pilot trial of a multicomponent (behavioral strategies, simplified patient information, and social support) and multidisciplinary (cognitive-behavioral therapy and nursing) medication adherence intervention was conducted for HIV-infected adults prescribed antiretrovirals. Patients (N = 33) were randomly assigned to the intervention condition or standard care. Compared to the control group, patients in the intervention condition had significantly higher self-efficacy to communicate with clinic staff (p = .04) and to continue treatment (p = .04), were significantly more likely to be using behavioral and cognitive strategies (p = .01 and p = .04), reported significantly higher life satisfaction (p = .03), reported significantly increased feelings of social support (p = .04), and showed a trend toward an increase in taking their medications on schedule (p = .06). The intervention, however, did not appear to affect health-related anxiety or to significantly improve adherence to dose. Implications for future intervention planning are discussed.

Adaptation, Psychological↗
PubMedDate not supplied

How to use non-verbal signs in assessments of suicide risk.

Many tools routinely used by health professionals to assess suicide risk rely heavily upon verbal information received from patients during the course of an interview, despite the majority of interpersonal communication in the health care setting being of a non-verbal nature. A verbal statement of suicidal intent may be of little value as the person may be performing according to interviewer expectations and interview context. To facilitate more accurate and meaningful suicide risk assessment and effective clinical judgement, the non-verbal components of patient behaviour must be addressed and more specifically measured.

Humans↗