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Biomedical subjects

David Pritchard

Publications and source records attributed to David Pritchard.

8 recordsLinked to original sources
PubMed2006

Poor sanitation and helminth infection protect against skin sensitization in Vietnamese children: A cross-sectional study.

BACKGROUND: Geohelminth infection and poor hygiene may be protective against allergic sensitization. OBJECTIVE: To determine whether current helminth infection is associated with a reduced prevalence of allergen skin test sensitization in a Southeast Asian population of children with a high prevalence of hookworm infection. METHODS: A total of 1742 Vietnamese schoolchildren were invited to take part in a cross-sectional survey. Allergen skin sensitization to house dust mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae) and American cockroach (Periplaneta americana) were measured and stool samples for qualitative and quantitative geohelminth estimation collected. RESULTS: A total of 1601 children age 6 to 18 participated. Sensitization to dust mites was present in 14.4% and to cockroach in 27.6% of children. In a mutually adjusted model, the risk of sensitization to dust mites was reduced in those with higher hookworm burden (adjusted odds ratio [OR] for 350+ vs no eggs per gram, 0.61; 95% CI, 0.39-0.96) and with Ascaris infection (adjusted OR, 0.28; 0.10-0.78), and increased in those using flush toilets (adjusted OR for flush toilet vs none/bush/pit, 2.51; 1.00-6.28). In contrast, sensitization to cockroach was not independently related to geohelminth infection but was increased in those regularly drinking piped or well water rather than from a stream (adjusted OR, 1.33; 1.02-1.75). CONCLUSION: Geohelminth infection, sanitation, and water supply influence the risk of allergic sensitization in Vietnamese children. This is consistent with a protective effect against allergy by geohelminth or other gastrointestinal infection. CLINICAL IMPLICATIONS: If the inverse relationship between geohelminth infection, poor sanitation, and allergic sensitization proves to be causal, drugs derived from parasite products may help to alleviate clinical allergic disease.

Adolescent↗
PubMed2006

Asthma and current intestinal parasite infection: systematic review and meta-analysis.

RATIONALE: Epidemiologic studies suggest that intestinal parasite infections may protect against asthma. OBJECTIVES: A systematic review and meta-analysis of epidemiologic studies to determine whether total or species-specific current parasite infection is associated with a reduced risk of asthma or wheeze. METHODS: We searched MEDLINE, EMBASE, and CINAHL (up to January 2006); reviews; and reference lists from publications, with no language restrictions. We included studies that reported asthma or wheeze as an outcome measure and ascertained parasite infection by fecal examination. We estimated pooled odds ratios (OR) and 95% confidence intervals (CI) using data extracted from published papers, or where available, original data provided by authors, using random effect models. MEASUREMENTS AND MAIN RESULTS: Thirty-three studies met the inclusion criteria. Infection with any parasite was associated with a small, nonsignificant increase in asthma risk (OR, 1.24; 95% CI, 0.98-1.57; 29 studies). In species-specific analysis, Ascaris lumbricoides was associated with significantly increased odds of asthma (OR, 1.34; 95% CI, 1.05-1.71; 20 studies), while hookworm infection was associated with a significantly strong reduction (OR, 0.50; 95% CI, 0.28-0.90; 9 studies) that was directly and significantly related to infection intensity (p < 0.001; OR for highest tertile of infection, 0.34; 95% CI, 0.19-0.62). Other species had no significant effects on asthma. Infection effects on wheeze were derived from smaller numbers, but revealed a broadly similar pattern of results. CONCLUSIONS: Parasite infections do not in general protect against asthma, but infection with hookworm may reduce the risk of this disease.

Adult↗
PubMed2006

Specific types of activated Factor XII increase following thrombolytic therapy with tenecteplase.

BACKGROUND: Activated Factor XII (XIIa) is believed to participate in a number of pathophysiological processes including inflammation, thrombosis and fibrinolysis. Increasing XIIa levels following thrombolytic therapy have previously been reported. In contrast to other thrombolytics, tenecteplase (TNK-tpa) does not show paradoxical thrombin activation, indicating a lower procoagulant effect of this fibrin-selective thrombolytic agent. Recent research has demonstrated that in-vivo XIIa exists in a number of different types, and the aim of this study was to investigate plasma variations of different types of XIIa following thrombolytic treatment with TNK-tpa. METHODS: Citrated blood samples were obtained from 34 patients admitted with acute ST-elevation myocardial infarction (STEMI) treated with TNK-tpa. Samples were taken immediately prior to treatment, 30-90 min after and 4 days post-treatment. XIIa measurements were performed using 2 ELISA assays designed to preferentially measure different types of XIIa; XIIaA and XIIaR. Both assays utilised a monoclonal antibody 2/215, which is highly specific for XIIa, as the solid phase capture antibody. The assay for XIIaA used a conjugate based on a polyclonal antibody against the entire XIIa molecule, whilst the assay for XIIaR incorporated a reagent to release otherwise unavailable XIIa and used a conjugate based on a monoclonal antibody against beta-XIIa. RESULTS: Changes in plasma XIIaA concentration as a result of therapy were more evident than changes in XIIaR concentration. XIIaA showed a significant increase from 67.1 (49.0-84.4) pM to 97.8 (75.5-133.1) pM [median and 25 and 75% percentiles] in the 30-90 min sample (P < 0.001), returning to pre-intervention levels 61.5 (47.5-81.0) pM by day 4. In contrast, no significant change in XIIaR concentration was observed following thrombolytic therapy with TNK-tpa. CONCLUSION: In patients admitted with STEMI, thrombolytic therapy with TNK-tpa resulted in a significant short-lasting increase in specific types of XIIa (namely XIIaA), whereas other types of XIIa (XIIaR) were largely unaffected by this intervention.

Aged↗
PubMed2006

Dose-ranging study for trials of therapeutic infection with Necator americanus in humans.

Epidemiological studies suggest that a hookworm infection producing 50 eggs/gram of feces may protect against asthma. We conducted a dose-ranging study to identify the dose of hookworm larvae necessary to achieve 50 eggs/gram of feces for therapeutic trials of asthma. Ten healthy subjects without asthma or airway hyperresponsiveness to inhaled methacholine received 10, 25, 50, or 100 Necator americanus larvae administered double blind to an area of skin on the arm. Subjects were seen weekly for 12 weeks and were then treated with mebendazole. Skin itching at the entry site and gastrointestinal symptoms were common at higher doses. Lung function did not change. Levels of blood eosinophils and IgE increased transiently, and levels of IgG increased progressively. All doses resulted in at least 50 eggs/gram of feces in the eight subjects who completed the study. Infection with 10 N. americanus larvae is well tolerated, elicits a modest host eosinophil response, and is potentially suitable for use in preliminary clinical therapeutic trials.

Adult↗
PubMed2004

Bacterial N-acylhomoserine lactone-induced apoptosis in breast carcinoma cells correlated with down-modulation of STAT3.

Cell growth is promoted by mitogens and survival factors, which activate intracellular signalling pathways to control cell cycle progression and cellular integrity. Proliferation signals are transmitted through Ras and Rho family small G-proteins coupled to mitogen-activated protein kinase (MAPK) cascades, while survival signals are propagated by lipid-dependent kinases such as phosphatidylinositide 3-kinases (PI3Ks) and protein kinase B (Akt/PKB). Recently, signal transducer and activator of transcription (STAT) proteins were identified as positive regulators of proliferation in a variety of cell types. Persistent activation of these pathways is associated with tumour cell growth, whereas their inhibition can halt proliferation and precipitate apoptotic cell death. The human pathogen Pseudomonas aeruginosa uses quorum-sensing signal molecules (QSSMs) to regulate virulence gene expression. QSSMs also suppress host immune responses although the mechanism of suppression is unknown. Here, we demonstrate that the QSSM N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL) from P. aeruginosa blocks proliferation and induces apoptosis in human BC cell lines. Analyses of signalling events reveal that OdDHL has little or no effect on MAPK cascades, partially inhibits the Akt/PKB pathway and ablates STAT3 activity. Pharmacological inhibition of each pathway independently indicates that STAT3 activity is critical for BC cell proliferation and survival, while a constitutively active STAT3 confers resistance to OdDHL. These results support the notion of OdDHL as a bioactive molecule in eukaryotic systems and a paradigm for a novel class of antiproliferative compounds.

4-Butyrolactone↗
PubMed2003

Molecular phenotype of spontaneously arising 4N (G2-tetraploid) intermediates of neoplastic progression in Barrett's esophagus.

Elevated 4N (G(2)-tetraploid) cell populations are unstable intermediates in the development of many human cancers. However, 4N cell populations are intermixed with larger diploid fractions in vivo, limiting investigation of these key intermediates of neoplastic progression. Therefore, to study elevated 4N cell populations in human neoplasia, we used flow cytometry to purify populations of spontaneously arising TP53(wt) and TP53(mut) 4N cells from cell strains derived from premalignant Barrett's esophagus biopsies. Using oligonucleotide arrays, we identified 625 genes differentially expressed in at least one replicate 2N/4N comparison in each strain and in hTERT-immortalized cultures of the TP53(mut) strains. Strikingly, when hierarchically clustered, these data contained a large node of 124 genes that were up-regulated in 4N TP53(mut) cells in the absence of condensed chromosomes. Most of these genes function in G(2)-M to mediate processes such as chromosome condensation and segregation. These results describe the molecular phenotype of dysregulated G(2)-M functions and cell cycle checkpoints in a key intermediate of human neoplastic progression.

Barrett Esophagus↗