Search PubMed⌕ Search

Biomedical subjects

P Anderson

Publications and source records attributed to P Anderson.

At least 55 records · Page 3Linked to original sources
PubMed2001

TIA-1 regulates the production of tumor necrosis factor alpha in macrophages, but not in lymphocytes.

OBJECTIVE: To determine whether TIA-1 differentially regulates the production of tumor necrosis factor a (TNFalphalpha) in macrophages and lymphocytes. METHODS: Peritoneal macrophages derived from wild-type and TIA-1-/- mice were cultured in the absence or presence of lipopolysaccharide (LPS) before comparison of the production of TNFalpha protein by intracellular flow cytometry and the secretion of TNFalpha protein by enzyme-linked immunosorbent assay. In parallel experiments, splenocytes were cultured in the absence or presence of concanavalin A (Con A), phorbol myristate acetate (PMA)/ionomycin, or anti-CD3/anti-CD28 before comparing the production of TNFalpha protein. Finally, the relative expression of TIA-1 protein in macrophages and splenocytes was compared using immunoblotting analysis. RESULTS: LPS-activated peritoneal macrophages derived from TIA-1-/- mice produced significantly more TNFalpha than macrophages from wild-type controls. In contrast, splenic lymphocytes (CD3+, CD4+, or CD8+) derived from wild-type and TIA-1-/- mice produced similar amounts of TNFalpha in response to Con A, PMA/ionomycin, or anti-CD3/anti-CD28. Lymphocytes and macrophages expressed similar amounts of TIA-1 protein, indicating that differential expression of TIA-1 cannot account for these results. CONCLUSION: TIA-1 is the target of a regulatory pathway that operates in activated macrophages, but not in activated lymphocytes. Developing drugs that target this pathway might prevent the pathologic overexpression of TNFalpha without subverting the T lymphocyte response to microbial pathogens.

Animals↗
PubMed2001

Porcine neural xenografts in rats and mice: donor tissue development and characteristics of rejection.

Embryonic ventral mesencephalic tissue from the pig is a potential alternative donor tissue for neural transplantation to Parkinson's disease patients. For stable graft survival, the host immune response has to be prevented. This study was performed in order to analyze the mechanisms and dynamics of neural xenograft rejection, as well as neurobiological properties of the donor tissue. Adult normal mice and rats, and cyclosporin A-treated rats, received intrastriatal transplants of dissociated embryonic ventral mesencephalic pig tissue that was 27 or 29 embryonic days of age (E27 and E29). The animals were perfused at 2, 4, 6, and 12 weeks after grafting and the brains were processed for immunohistochemistry of dopaminergic (tyrosine hydroxylase positive) neurons, CD4(+) and CD8(+) lymphocytes, natural killer cells, macrophages, microglia, and astrocytes. Thirty-five rats received daily injections of BrdU for 5 consecutive days at different time points after transplantation and were perfused at 6 weeks. These animals were analyzed for proliferation of cells in the donor tissue, both in healthy and in rejecting grafts. No tyrosine hydroxylase-positive cells proliferated after grafting. Our results demonstrated that E27 was superior to E29 donor tissue for neurobiological reasons. Cyclosporin A immunosuppression was protective only during the first weeks and failed to protect the grafts in a long-term perspective. Grafts in mice were invariably rejected between 2 and 4 weeks after transplantation, while occasional grafts in untreated rats survived up to 12 weeks without signs of an ongoing rejection process. CD8(+) lymphocytes and microglia cells are most likely important effector cells in the late, cyclosporin A-resistant rejection process.

Animals↗
PubMed2001

Monoclonal antibodies derived from BALB/c mice immunized with apoptotic Jurkat T cells recognize known autoantigens.

It has been postulated that post-translational modifications and relocalization of proteins during apoptosis may lead to presentation of these molecules to the immune system in such a way that normal mechanisms of tolerance are bypassed. In the present study, Jurkat cells were induced to undergo apoptosis by treatment with the chemotherapeutic agent Ara-C. BALB/c mice were then immunized with the apoptotic cells and hybridomas were generated. Using an indirect immunofluorescence assay, the monoclonal antibodies produced were screened by flow cytometry for those monoclonal antibodies demonstrating reactivity with permeabilized apoptotic Jurkat cells but not with non-permeabilized normal or apoptotic Jurkat cells. Of 281 monoclonal antibodies, 20 monoclonal antibodies with these properties were selected for further analysis. Using 32P- or 35S-metabolically labelled Jurkat cells, these selected monoclonal antibodies were screened for their ability to recognize autoantigens by immunoprecipitation and Western blotting. Well characterized autoimmune sera were then used to confirm the identity of autoantigens by immunoblotting. We demonstrate that immunization of normal mice with apoptotic Jurkat cells results in the formation of antibodies targeting multiple autoantigens or autoantigen complexes, including Ku, rRNPs, snRNPs and vimentin. These findings are consistent with the hypothesis that apoptosis can contribute to the development of autoimmunity.

Animals↗
PubMed2001

Brn-3a activates the expression of Bcl-x(L) and promotes neuronal survival in vivo as well as in vitro.

The determination of cell fate plays a critical role during the later stages of embryogenesis and the early postnatal period-a time during which approximately half of neurons born during neurogenesis undergo programmed cell death. It has previously been reported that the type IV POU domain transcription factor Brn-3a plays a role in the maturation and survival of sensory neuronal populations. Indeed we have shown that the long form of Brn-3a is capable of activating expression of the antiapoptotic Bcl-2 gene and enhancing neuronal survival in cultures of sensory neurons. In this study, we report the identification of another antiapoptotic family member, Bcl-x(L), as a target gene of Brn-3a in sensory neurons, providing a further mechanism by which Brn-3a determines sensory neuronal fate during development. Bcl-x(L) gene expression is activated by Brn-3a in sensory but not in sympathetic neurons and its expression is reduced by antisense inhibition of Brn-3a expression in sensory neurons. Most importantly, both Bcl-x(L) expression and neuronal survival are enhanced by the overexpression of Brn-3a in dorsal root ganglion in vivo in a model of sciatic nerve injury in the intact animal.

Animals↗
PubMed2001

Use of the radial forearm free tissue flap to treat persistent stricture after esophagogastrectomy.

BACKGROUND: Persistent stricturing or anastomotic leakage at the cervical esophagogastric anastomosis can be a troublesome complication of gastric pull-up procedures. When the stricture is the result of ischemia of the stomach, the strictures are long and often not responsive to dilatation and require large operations such as jejunal interposition or replacement with colonic pull-up. In this report we describe the use of a radial forearm flap to patch strictures. METHODS: The radial forearm flap is a fascia cutaneous flap taken from the forearm and based on the radial artery and its venae comitantes. The advantages of this flap are that it is thin and pliable, conforms easily, has excellent reliability due to the size of the feeding vessels, and has a relatively long pedicle. The vascular anastomosis can be made to several arteries and veins within the neck. The epithelial component can be made in sizes up to 10 by 20 cm. RESULTS: We have used the radial forearm flap to patch strictures in 6 patients with persistent complex strictures in the cervical region after esophagectomy. Results were excellent in 4 patients (able to eat liquids and solids without problems) and good in 1 patient (liquids okay, some problem with solids), and 1 patient died postoperatively. Follow-up is 4 months to 7 years. CONCLUSIONS: The radial forearm flap is an excellent option for handling persistent stricture after esophagogastrectomy. In many instances, this flap can be used in lieu of a jejunal interposition flap and obviates a laparotomy to harvest jejunum. The flap fits easily into the neck and conforms to the space.

Adult↗
PubMed2001

Community voices: views on the training of future doctors in Birmingham, UK.

The United Kingdom (UK) population is diverse with nearly 6% minority ethnic communities. Both patients and doctors experience difficulties when dealing with someone from a different ethnic group. Medical education has failed to keep pace with the changing needs of the diverse population. We report a project in which 12 established (religious/cultural and specific interest) community groups expressed their views on what future doctors should learn about serving diverse populations. Data were obtained by group discussion and through the media using a structured format. Fifteen themes emerged which were grouped under three broad themes: firstly, the identification by group members of their perception of the 'differences' in social and cultural beliefs and behaviours of their individual community; secondly, the identification of characteristics of a culturally sensitive doctor; and lastly, recommendations for changes in medical training. New teaching has been introduced to the medical curriculum that incorporates the themes raised by the communities and which reflects consciousness raising and communication issues.

Attitude to Health↗
PubMed2001

Plant odor analysis of apple: antennal response of codling moth females to apple volatiles during phenological development.

Volatile compounds were collected from apple branches (Malus domestica) at different developmental stages, and the antennal response of codling moth females (Cydia pomonella) to these compounds was recorded by electroantennography coupled to gas chromatography. Presence of a range of terpenoid compounds, many of which had antennal activity, was characteristic for volatile collections from branches with leaves, and from small green apples. Nine compounds from branches with leaves and green fruit consistently elicited an antennal response: methyl salicylate, (E)-beta-farnesene, beta-caryophyllene, 4,8-dimethyl-1,3(E),7-nonatriene, (Z)3-hexenol, (Z,E)-alpha-farnesene, linalool, germacrene D, and (E,E)-alpha-farnesene. The bouquet emitted from flowering branches contained in addition several benzenoid compounds which were not found after bloom. Small green apples, which are the main target of codling moth oviposition during the first seasonal flight period, released very few esters. In comparison, fully grown apples released a large number of esters, but fewer terpenoids. The study of apple volatiles eliciting an antennal response, together with a survey of the seasonal change in the release of these compounds, is the first step toward the identification of volatiles mediating host-finding and oviposition in codling moth females.

Animals↗
PubMed2001

Olfactory responses of Ips duplicatus from inner Mongolia, China to nonhost leaf and bark volatiles.

Leaf and bark volatiles from nonhost angiosperm trees were tested on Ips duplicatus by gas chromatographic-electroantennographic detection (GC-EAD) and by pheromone-baited traps in Sweden and Inner Mongolia, China, respectively. GC-EAD analysis of the headspace volatiles from fresh bark chips of Betula pubescens revealed trans-conophthorin, two green leaf volatiles (GLVs): 1-hexanol and (Z)-3-hexen-1-ol, and two C8 alcohols: 3-octanol and 1-octen-3-ol, that consistently elicited antennal responses by I. duplicatus. The identification of these EAD-active compounds was confirmed in further GC-EAD recordings with synthetic mixtures. Antennal responses were also found to synthetic (E)-2-hexen-1-ol and linalool, which have been identified from the leaves of nonhost birch and aspen species. No antennal responses of I. duplicatus were found to hexanal, (E)-2-hexenal, and (Z)-3-hexyl acetates. In field trapping experiments, blends of EAD-active green leaf alcohols or C8 alcohols, or transconophthorin alone resulted in significant reductions (27-60%) in the number of I. duplicatus captured compared with pheromone-baited traps. The unsuitable host compound, verbenone (Vn), also significantly reduced trap catches by up to 60% in both experiments. The strongest disruptive effect resulted from the addition of the combination of green leaf alcohols, C8 alcohols, and verbenone to the pheromone trap, which caused an 84% reduction in trap catch. The blend of two green leaf aldehydes plus the acetate increased the trap catches in 1998 and had no negative or positive effects in 1999. Our results suggest that these nonhost volatiles (NHVs) are important olfactory signals used by I. duplicatus in host selection. They may have great significance in developing semiochemical-based management programs for I. duplicatus by reducing or stopping attacks on suitable hosts.

Animals↗
PubMed2001

A quantitative study of the effect of pumicing and etching on the remineralisation of enamel opacities.

AIMS: The aim of this study was to investigate the effects of pumicing and acid etching on the remineralisation of enamel opacities using quantitative measurement methods. METHODS: Teeth with diffuse opacities were subjected to a treatment sequence of: (a) pumicing for 30-35 seconds (b) etch with 37.5% phosphoric acid for 2 minutes, (c) pumicing for 30-35 seconds and (d) etch for 1 minute, or served as controls. Both groups were then placed in a remineralising solution containing 1.5 mmol/L Ca2+ for 3 weeks. Mineral content changes were measured using contact microradiography and x-ray microtomography. In addition, the reflectivity of the opacities was monitored with infrared reflectance. RESULT: The treatment sequence removed 34 +/- 4 microns of the surface enamel but no mineral loss was observed in the subsurface layer. The treatment sequence enhanced the formation of a new remineralised surface layer with a mean thickness of 22 +/- 3 microns. This new surface layer was less reflective. CONCLUSION: Pumicing and acid etching can be used as a simple technique for the conservative treatment of enamel opacities.

Acid Etching, Dental↗
PubMed2001

Critical pH in resting and stimulated whole saliva in groups of children and adults.

OBJECTIVE: The concentrations of calcium and phosphate in saliva have significant influence on the protective mechanisms of dental hard tissues within the oral environment. A lower calcium concentration means: 1) a lower thermodynamic driving force for hydroxyapatite precipitation at normal oral pH; 2) a higher driving force for hydroxyapatite dissolution at low pH; 3) a lower critical pH. The aims of this study were to: 1. determine the calcium and phosphate concentrations 2. calculate the critical pH for enamel and 3. determine the driving forces for demineralization and remineralization in a group of children and adults. METHODS: In this comparative study, calcium and phosphate concentrations were measured in the resting and stimulated saliva of child and adult volunteers using a spectrophotometric system used in routine blood analysis. Salivary flow rates were also measured in each group. RESULTS: The calcium concentrations were lower in children than adults, but the phosphate concentrations were not significantly different. The critical pH was significantly higher for children than adults in both resting and stimulated saliva. Therefore, the thermodynamic driving forces for; (1) demineralisation at low oral pH, is greater, and (2) for remineralisation at normal oral pH, is lower, in children compared to adults. CONCLUSION: The results of this study show that from thermodynamic considerations alone, there is increased risk of demineralization in children compared with adults.

Adult↗
PubMed2001

Epidemiology and resource utilization for patients hospitalized for lower respiratory tract infection.

OBJECTIVES: To determine referral rates, patient characteristics, and resource utilization for patients admitted to hospital with community-acquired lower respiratory tract infections (LRTI). METHODS: Six hundred and thirteen patients, accounting for 704 LRTI episodes, were included in the study, if the referral diagnosis was LRTI and if both signs and symptoms on admission and patient management were consistent with this diagnosis. Patient records were abstracted to collect information on co-morbidities, patient demographics, resource utilization, episode outcome, pharmacy prescribing and diagnostic service utilization. RESULTS: Annual hospital admissions for LRTI ranged from 15 per 10 000 population in the age range 16-40 years to over 300 per 10 000 in the population aged >79 years, with a population average of 62.3 per 10 000. Less than 37% of admissions were for community-acquired pneumonia and the majority of episodes were in patients with pre-existing respiratory disease (41.2%). Marital status, gender, diabetic status, type of infection and number of days in hospital within the past year were all significantly associated with changes in mean length of stay. CONCLUSIONS: Hospital episodes of LRTI are seen predominantly in the over-60 age group, which account for almost 90% of bed day utilization, yet represent only 27% of the adult population. Referral of patients to hospital with LRTI represents a major resource implication for secondary health-care provision.

Adolescent↗
PubMed2001

Signal transduction in rheumatoid arthritis.

Extracellular signals are transduced intracellularly by multiple pathways, resulting in alterations in the transcription and translation of specific proteins. The end result of some of these signalling pathways is the production of proteins, including cytokines and matrix metalloproteinases, that are implicated in the pathogenesis of rheumatoid arthritis. This chapter includes a discussion of these signal transduction pathways, including tumour necrosis factor receptor signalling, interleukin-1, -4, and -6 receptor signalling, stress- and mitogen-activated protein kinase pathways, CD14 and Toll-like receptor signalling, and T cell signal transduction. The known effects of currently available rheumatoid arthritis (RA) therapeutics on these signalling pathways are also reviewed. In addition, potential future targets for therapeutic intervention in RA are discussed.

Arthritis, Rheumatoid↗
PubMed2001

Organisational change: a methodology to uncover the business idea.

A study was undertaken to identify the "Business Idea", as defined by van der Heijden (1996), in The Family Planning Association of WA Inc (FPWA) which is a Non-Government Organisation (NGO) in Perth, Western Australia. This organisation was chosen as, along with many other NGOs, it was undergoing major changes in its funding, role and required outcomes. A qualitative interpretivist single case study methodology employing grounded theory research principles and methods was used to study the Business Idea framework in this setting. Thirty-four members of FPWA's staff were interviewed and data was managed using NUD*IST4 and Decision Explorer data storage, data retrieval and graphical reproduction facilities. Results indicated that images of the Business Idea model within FPWA were largely consistent across all staff levels excepting members of the Board of Management. Changes within the organisation were impacting heavily on staff, who needed to be assisted over the transitional phase. Strong leadership and corporate direction were identified as essential if the FPWA was to balance the strongly held sense of social justice amongst its staff with a need for greater productivity efficiency and accountability across the organisation.

Commerce↗
PubMed2001

Assessment and development of organizational ability: the Rey Complex Figure Organizational Strategy Score (RCF-OSS).

The Rey Complex Figure Organizational Strategy Score (RCF-OSS) was devised for pediatric populations to cater for developmental variability. A sample consisting of 376 children aged between 7.0 and 13.11 years was recruited for the standardization of RCF-OSS. The interrater reliability (.85 to .92) and temporal stability (.79 to .94) of the RCF-OSS are acceptable. RCF-OSS correlated moderately with RCF accuracy, memory and organization, however it seems to be measuring an independent aspect of performance, possibly strategy. Moderate linear relationships were observed with executive function and memory measures. Considerable age-related variation in strategy formation was observed with significant maturity occurring between the ages of 7 years and 11 years. Surprisingly, older children used fragmented strategies more than the younger age groups. In conclusion, the RCF-OSS is a useful adjunct to traditional accuracy scoring procedures, and the normative data indicates that organizational skills may not consolidate until middle to late adolescence.

Adolescent↗
PubMed2001

A multi-laboratory evaluation of an enzyme-linked immunoassay quantitating human antibodies to Streptococcus pneumoniae polysaccharides.

An enzyme-linked immunoassay (EIA) is described and evaluated which quantitates human antibodies to serotype specific S. pneumoniae polysaccharide (PnPs) in human sera. Based on the observations previously described by Koskela (1), native PnPs are used as coating antigens and sera are absorbed with a soluble pneumococcal absorbant material containing C-polysaccharide (CPs) to ensure measurement of serotype specific anti-PnPs antibodies. The robustness of this method was evaluated by ten laboratories using the same reagents, protocol, and five human serum samples. Reproducible antibody values were obtained for IgM, IgG, and IgA antibodies to five different PnPs serotypes, 3, 6B, 14, 19F, and 23F. The overall mean percent coefficients of variation in this interlaboratory study for all five selotype specific anti-PnPs determinations with the five coded sera were 30% for IgG, 3/% for IgM, and 36% for IgA. This assay can be standardized for quantitation of serotype specific anti-PnPs antibodies, allowing comparison of antibody values in vaccine trials evaluating pneumococcal vaccines.

Enzyme-Linked Immunosorbent Assay↗
PubMed2001

Lenercept (p55 tumor necrosis factor receptor fusion protein) in severe sepsis and early septic shock: a randomized, double-blind, placebo-controlled, multicenter phase III trial with 1,342 patients.

OBJECTIVE: Phase III study to confirm a trend observed in a previous phase II study showing that a single dose of lenercept, human recombinant p55 tumor necrosis factor receptor-immunoglobulin G1 (TNFR55-IgG1) fusion protein, decreased mortality in patients with severe sepsis or early septic shock. DESIGN: Multicenter, double-blind, phase III, placebo-controlled, randomized study. SETTING: A total of 108 community and university-affiliated hospitals in the United States (60), Canada (6) and Europe (42). PATIENTS: A total of 1,342 patients were recruited who fulfilled the entry criteria within the 12-hr period preceding the study drug administration. INTERVENTION: After randomization, an intravenous dose of 0.125 mg/kg lenercept or placebo was given. The patient was monitored for up to 28 days, during which standard diagnostic, supportive, and therapeutic care was provided. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was 28-day all-cause mortality. Baseline characteristics were as follows: a total of 1,342 patients were randomized; 662 received lenercept and 680 received placebo. The mean age was 60.5 yrs (range, 17-96 yrs); 39% were female; 65% had medical admissions, 8% had scheduled surgical admissions, and 27% had unscheduled surgical admissions; 73% had severe sepsis without shock, and 27% had severe sepsis with early septic shock. Lenercept and placebo groups were similar at baseline with respect to demographic characteristics, simplified acute physiology score II-predicted mortality, profiles of clinical site of infection and microbiological documentation, number of dysfunctioning organs, and interleukin-6 (IL-6) plasma concentration. Lenercept pharmacokinetics were similar in severe sepsis and early septic shock patients. Tumor necrosis factor was bound in a stable manner to lenercept as reflected by the accumulation of total serum tumor necrosis factor alpha concentrations. There were 369 deaths, 177 on lenercept (27% mortality) and 192 on placebo (28% mortality). A one-sided Cochran-Armitage test, stratified by geographic region and baseline, predicted 28-day all-cause mortality (simplified acute physiology score II), gave a p value of .141 (one-sided). Lenercept treatment had no effect on incidence or resolution of organ dysfunctions. There was no evidence that lenercept was detrimental in the overall population. CONCLUSION: Lenercept had no significant effect on mortality in the study population.

APACHE↗
PubMed2001

Use of the Internet in pathology resident training and education.

The Internet has revolutionized the computer and communications world. It has grown to become a worldwide mechanism for information exchange without regard for geographic boundaries. The tremendous growth in this wealth of information poses several questions regarding the utility of this powerful tool in pathology practice and education. This article reviews the advantages and disadvantages of using the Internet in pathology resident education, in general, and how it has impacted the repertoire of educational opportunities at our own institution. The various Internet resources of educational value for pathology trainees are outlined. Basic Internet concepts are also elucidated.

Computer-Assisted Instruction↗