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D R Wilson

Publications and source records attributed to D R Wilson.

At least 19 recordsLinked to original sources
PubMed2003

Batch growth of Salmonella typhimurium LT2: stoichiometry and factors leading to cessation of growth.

Salmonella typhimurium LT2 was grown in batch culture (trypticase soy broth, with 0.3%(w/v) yeast extract, 1% (w/v) glucose and 0.5% (w/v/) NaCl, 20 degrees C) at a range of initial pH (4.4, 4.8, 5.0 and 7.0). The consumption of oxygen and glucose was found to be independent of initial pH, and stoichiometric with growth. Mean yield coefficients of 6.9 x 10(-15) and 15.5 x 10(-15) mol oxygen/cell were estimated. Calculation of the instantaneous state of carbon during the cultivation showed stoichiometric conversion of glucose into biomass, carbon dioxide and organic acids. The concentration of the undissociated form of the primary acidic product (acetic acid) was shown to be the factor limiting growth.

Acetic Acid↗
PubMed2003

Sublingual immunotherapy for allergic rhinitis.

BACKGROUND: Allergic rhinitis is a common condition which, at its most severe, can significantly impair quality of life despite optimal treatment with antihistamines and topical nasal corticosteroids. Allergen injection immunotherapy significantly reduces symptoms and medication requirements in allergic rhinitis but its use is limited by the possibility of severe systemic reactions. There has therefore been considerable interest in alternative routes for delivery of allergen immunotherapy, particularly the sublingual route. OBJECTIVES: To evaluate the efficacy of sublingual immunotherapy (SLIT), compared with placebo, for reductions in symptoms and medication requirements. SEARCH STRATEGY: The Cochrane Controlled Trials Register, MEDLINE (1966-2002), EMBASE (1974-2002) and Scisearch were searched, up to September 2002, using the terms (Rhin* OR hay fever) AND (immunotherap* OR desensiti*ation) AND (sublingual). SELECTION CRITERIA: All studies identified by the searches were assessed by the reviewers to identify randomised controlled trials involving participants with symptoms of allergic rhinitis and proven allergen sensitivity, treated with SLIT or corresponding placebo. DATA COLLECTION AND ANALYSIS: Data from identified studies were abstracted onto a standard extraction sheet and subsequently entered into RevMan 4.1. Analysis was performed by the method of Standardised Mean Differences (SMD) using a random effects model. P values <0.05 were considered statistically significant. Subgroup analyses were performed according to the type of allergen administered, the age of participants and the duration of treatment. MAIN RESULTS: Twenty two trials involving 979 patients were included. There were 6 trials of SLIT for House Dust Mite allergy, 5 for Grass Pollen, 5 for Parietaria, 2 for Olive and one each for, Ragweed, Cat, Tree and Cupressus. Four studies enrolled exclusively children. Seventeen studies administered the allergen by sublingual drops subsequently swallowed, 3 by drops subsequently spat out and 2 by sublingual tablets. Eight studies involved treatment for less than 6 months, 10 studies for 6-12 months and 4 studies for greater than 12 months. All included studies were double-blind placebo-controlled trials of parallel group design. Concealment of treatment allocation was considered adequate in all studies and the use of identical placebo preparations was almost universal. There was significant heterogeneity, most likely due to widely differing scoring systems between studies, for most comparisons. Overall there was a significant reduction in both symptoms (SMD -0.34, 95% confidence interval -0.69 to -0.15; p=0.002) and medication requirements (SMD -0.43 [-0.63, -0.23]; p=0.00003) following immunotherapy. Subgroup analyses failed to identify a disproportionate benefit of treatment according to the allergen administered. There was no significant reduction in symptoms and medication scores in those studies involving only children but total numbers of participants were small, casting doubt on the validity of the conclusion. Increasing duration of treatment does not clearly increase efficacy. The total dose of allergen administered may be important but insufficient data were available to analyse this factor. REVIEWER'S CONCLUSIONS: SLIT is a safe treatment which significantly reduces symptoms and medication requirements in allergic rhinitis. The size of this benefit compared to that of other available therapies, particularly injection immunotherapy, is not clear, having been assessed directly in very few studies. Further research is required concentrating on optimising allergen dosage and patient selection.

Administration, Sublingual↗
PubMed2003

Accuracy and repeatability of a pressure measurement system in the patellofemoral joint.

The objective of this study was to assess how accurately and repeatably the Iscan system measures force and pressure in the natural patellofemoral joint. These measurements must be made to test widely held assumptions about the relationships between mechanics, pain and cartilage degeneration. We assessed the system's accuracy by using test rigs in a materials testing machine to apply known forces and force distributions across the sensor. The root mean squared error in measuring resultant force (for five trials at each of seven load levels) was 6.5 +/- 4.4% (mean +/- standard deviation over all trials at all load levels), while the absolute error was -5.5 +/- 5.6%. For force distribution, the root mean squared error (for five trials at each of five force distributions) was 0.86 +/- 0.58%, while the absolute error was -0.22 +/- 1.03%. We assessed the repeatability of the system's measurements of patellofemoral contact force, pressure and force distribution in four cadaver specimens loaded in continuous and static flexion. Variability in measurement (standard deviation expressed as a percentage of the mean) was 9.1% for resultant force measurements and 3.0% for force distribution measurements for static loads, and 7.3% for resultant force and 2.2% for force distribution measurements for continuous flexion. Cementing the sensor to the cartilage lowered readings of resultant force by 31 +/- 32% (mean +/- standard deviation), area by 24 +/- 13% and mean pressure by 9 +/- 34% (relative to the uncemented sensor). Maximum pressure measurement, however, was 24 +/- 43% higher in the cemented sensor than in the uncemented sensor. The results suggest that the sensor measures force distribution more accurately and repeatably than absolute force. A limitation of our work, however, is that the sensor must be cemented to the patellar articular surface to make the force distribution measurements, and our results suggest that this process reduces the accuracy of force, pressure and area measurements. Our results suggest that the Iscan system's pressure measurement accuracy and repeatability are comparable to that of Fuji Prescale film, but its advantages are that it is thinner than most Fuji Prescale film, it measures contact area more accurately and that it makes continuous measurements of force, pressure and area.

Compressive Strength↗
PubMed2003

Salmonella enterica serovar Typhimurium and Listeria monocytogenes acid tolerance response induced by organic acids at 20 degrees C: optimization and modeling.

An acid tolerance response (ATR) has been demonstrated in Listeria monocytogenes and Salmonella enterica serovar Typhimurium in response to low pH poised (i.e., adapted) with acetic or lactic acids at 20 degrees C and modeled by using dynamic differential equations. The ATR was not immediate or prolonged, and optimization occurred after exposure of L. monocytogenes for 3 h at pH 5.5 poised with acetic acid and for 2 h at pH 5.5 poised with lactic acid and after exposure of S. enterica serovar Typhimurium for 2 h at pH 5.5 poised with acetic acid and for 3 h at pH 5.5 poised with lactic acid. An objective mechanistic analysis of the acid inactivation data yielded estimates of the duration of the shoulder (t(s)), the log-linear decline (k(max)), and the magnitude of a critical component (C). The magnitude of k(max) gave the best agreement with estimates of conditions for optimum ATR induction made from the raw data.

Acetic Acid↗
PubMed2001

Organic nitrogen in precipitation: real problem or sampling artefact?

Published observations of organic nitrogen (N) compounds in precipitation go back almost a century. Several different methods have been used to measure both the total and ionic concentrations of N. There is therefore some uncertainty as to whether reported "organic N" is real, or simply the result of uncertainties in chemical analyses or inadequate sampling methods. We found that the materials from which the collector was made (polypropylene, steel, or glass) had no significant effect on the composition of dissolved organic N (DON). The use of a biocide was found to be very important during sampling and storage of samples before analysis. We set up a network of seven collectors across the U.K., from the Cairngorms to Dorset, all operating to the same protocol, and including a biocide. Samples were analysed centrally, using proven methods. Over 6 months, organic N contributed about 20% to the total N in U.K. precipitation, but with a large variation across the country. This means that current estimates of wet deposited N to the U.K., which are based only on the ammonium and nitrate concentrations, are too small. Organic N is not an artefact, but a real problem that needs to be addressed.

Air Pollutants↗
PubMed2001

Tumor suppression and therapy sensitization of localized and metastatic breast cancer by adenovirus p53.

We have examined the effects of a replication-defective adenovirus encoding p53 (RPR/INGN 201 [Ad5CMV-p53]; Adp53), alone or in combination with the breast cancer therapeutic doxorubicin (Adriamycin), to suppress growth and induce apoptosis in breast cancer cells in vitro. We have also examined the in vivo effect of intratumoral administration of Adp53, alone or in combination with doxorubicin, to suppress the growth of established subcutaneous MDA-MB-435 breast cancer tumors. Finally, using the MDA-MB-435 orthotopic model of metastatic breast cancer, we have examined the effect of systemic administration of Adp53, alone or in combination with doxorubicin, to reduce the incidence of metastases. We find that whereas in vitro treatment of cells with Adp53 reduces [(3)H]thymidine incorporation by about 90% at 48 hr, cell viability at 6 days is reduced by only some 50% relative to controls. Although apoptosis is detectable in Adp53-treated cultures, these results suggest that a large fraction of Adp53-treated cells merely undergo reversible cell cycle arrest. Combined treatment with Adp53 and doxorubicin results in a greater than additive loss of viability in vitro and increased apoptosis. In vivo, locally administered Adp53 suppresses growth of established subcutaneous tumors in nude mice and suppression is enhanced by doxorubicin. In the metastatic breast cancer model, systemic administration of Adp53 plus doxorubicin leads to a significant reduction in the incidence of metastases relative to Adp53 or doxorubicin alone. Taken together, these data indicate an additive to synergistic effect of Adp53 and doxorubicin for the treatment of primary and metastatic breast cancer.

Adenoviridae↗
PubMed2001

Persistent IgE synthesis in the nasal mucosa of hay fever patients.

The location of IgE synthesis has been a longstanding controversy, with previous evidence favoring either the mucosa or lymphoid tissue in the region of allergen entry. The evidence for IgE synthesis in mucosal tissues has always been circumstantial. We have developed a novel explant culture system, using ELISA and radioactive amino acid incorporation, to measure de novo IgE protein synthesis in the nasal mucosa of hay fever patients. Surprisingly, IgE synthesis continues between seasons in the explants from grass pollen-sensitive patients and a higher proportion of this IgE compared to serum IgE is allergen specific. Persistent IgE synthesis may ensure the expression of immediate hypersensitivity in the mucosa and promote rapid amplification of the allergic response in the local lymphoid tissue on allergen provocation. Our work demonstrates definitively for the first time that the local mucosa is a site of ongoing IgE synthesis.

Adult↗
PubMed2001

Successful treatment of primary and disseminated human lung cancers by systemic delivery of tumor suppressor genes using an improved liposome vector.

Delivery of therapeutic genes to disseminated tumor sites has been a major challenge in the field of cancer gene therapy due to lack of an efficient vector delivery system. Among the various vectors currently available, liposomes have shown promise for the systemic delivery of genes to distant sites with minimal toxicity. In this report, we describe an improved extruded DOTAP:cholesterol (DOTAP:Chol) cationic liposome that efficiently delivers therapeutic tumor suppressor genes p53 and FHIT, which are frequently altered in lung cancer, to localized human primary lung cancers and to experimental disseminated metastases. Transgene expression was observed in 25% of tumor cells per tumor in primary tumors and 10% in disseminated tumors. When treated with DOTAP:Chol-p53 and -FHIT complex, significant suppression was observed in both primary (P < 0.02) and metastatic lung tumor growth (P < 0.007). Furthermore, repeated multiple treatments revealed a 2.5-fold increase in gene expression and increased therapeutic efficacy compared to single treatment. Finally, animal survival experiments revealed prolonged survival (median survival time: 76 days, P < 0.001 for H1299; and 96 days, P = 0.04 for A549) when treated with liposome-p53 DNA complex. Our findings may be of importance in the development of treatments for primary and disseminated human lung cancers.

Acid Anhydride Hydrolases↗
PubMed2001

Grass pollen immunotherapy inhibits seasonal increases in basophils and eosinophils in the nasal epithelium.

BACKGROUND: Symptoms of allergic rhinitis are accompanied by infiltration of the nasal mucosa with inflammatory cells, predominantly eosinophils and metachromatic cells (basophils and mast cells). Specific immunotherapy (IT) reduces mucosal eosinophilia and numbers of metachromatic cells in the epithelium. A specific marker distinguishing basophils from mast cells was recently developed. OBJECTIVES: The basophil-specific monoclonal antibody 2D7 was used to determine the influence of subcutaneous IT on numbers of nasal mucosal basophils compared with the effects of IT on neutrophils, eosinophils and mast cells. METHOD: During a randomized, placebo-controlled trial of grass pollen IT in 44 adults with severe summer hay fever, nasal biopsies were taken at baseline, out of the pollen season, and at the peak of the pollen season following 2 years treatment. Biopsies were processed for immunohistochemistry for basophils (2D7+), mast cells (AA1+), eosinophils (MBP+) and neutrophils (neutrophil elastase+). RESULTS: In placebo-treated (PL) patients there were significant seasonal increases in basophils (P < 0.01), mast cells (P < 0.05) and eosinophils (P = 0.002) in the nasal submucosa. In IT-treated patients significant increases in 2D7+ cells (P < 0.01) and eosinophils (P = 0.01) but not AA1+ cells (P = 0.9) were observed. These differences were significant between groups for eosinophils (P < 0.05). In the epithelium there were seasonal increases in AA1+ cells and eosinophils in both groups (PL: P < 0.01, IT: P < 0.05 for both). The between-group difference was significant for eosinophils (P = 0.05). Basophils were observed in the epithelium of six out of 17 in the placebo group and one out of 20 in the IT group (P = 0.03). Neutrophil numbers remained constant in both epithelium and submucosa. CONCLUSION: Successful grass pollen immunotherapy was associated with inhibition of seasonal increases in basophils and eosinophils, but not mast cells or neutrophils within the nasal epithelium. Immunotherapy may act, at least in part, by reducing seasonal recruitment of basophils and eosinophils into the epithelium.

Adult↗
PubMed2001

Mechanical testing of bioresorbable implants for use in metacarpal fracture fixation.

The purpose of this study was to evaluate the mechanical properties of a bioresorbable plate and screw system that was developed for the treatment of unstable metacarpal fractures and to compare the strength and stiffness of this system with those of conventional titanium plates and screws. Using a 4-point bending test, we measured the strength and stiffness of these implants over a 12-week period of in vitro degradation. Our data suggest that these implants provide stable bending strength and stiffness for 8 weeks and gradually lose their strength over a period of 12 weeks. Further research is necessary to determine whether this level of fixation is adequate to stabilize unstable metacarpal fractures.

Absorbable Implants↗
PubMed2001

Grass pollen immunotherapy for seasonal rhinitis and asthma: a randomized, controlled trial.

BACKGROUND: Grass pollen immunotherapy significantly reduces hay fever symptoms and medication requirements. Effects on seasonal asthma are less clear, and concerns over safety persist. OBJECTIVE: The goal of this study was to assess the effects of grass pollen immunotherapy on symptoms, bronchial hyperresponsiveness, and quality of life in seasonal rhinitis and asthma. METHODS: Forty-four patients with severe summer hay fever (of whom 36 reported seasonal chest symptoms and 28 had seasonal bronchial hyperresponsiveness) participated in a randomized, double-blind, placebo-controlled, parallel group study. After symptom monitoring for one summer, participants received injections of a depot grass pollen vaccine (n = 22) or matched placebo injections (n = 22) in a rapid updosing cluster regimen for 4 weeks, followed by monthly injections for 2 years. Outcome measures included hay fever symptoms and medication use, health-related quality of life, and measurements of nonspecific bronchial responsiveness. RESULTS: Significant reductions were observed in the immunotherapy group compared with the placebo group in hay fever symptoms (49%, 15%; P =.01), medication scores (80%, 18%; P =.007), and seasonal chest symptoms (90%, 11%; P <.05). Impairment of overall quality of life (mean score of 7 domains) during the pollen season was less in the immunotherapy group than in the placebo group (median difference [95% CI], 0.8 [0.18-1.5]; P =.02). During the pollen season there was no change in airway methacholine PC(20) (provocation concentration producing a 20% fall in FEV(1)) in the immunotherapy-treated group (P =.5), compared with an almost 3 doubling-dose decrease in the placebo-treated group (P =.01, between-group difference). There were no significant local or systemic side effects during the study. CONCLUSION: Grass pollen immunotherapy improves quality of life in seasonal allergic rhinitis and reduces seasonal asthma symptoms and bronchial hyperresponsiveness.

Adult↗
PubMed2001

Grass pollen immunotherapy: symptomatic improvement correlates with reductions in eosinophils and IL-5 mRNA expression in the nasal mucosa during the pollen season.

BACKGROUND: Tissue eosinophilia and infiltration by T(H)2-type T cells are characteristic features of allergic rhinitis both after allergen challenge and during natural allergen exposure. Specific immunotherapy inhibits allergen-induced nasal eosinophilia. OBJECTIVES: We sought to assess, in the context of a randomized trial, the relationships between symptomatic improvement after immunotherapy and eosinophil numbers and IL-5 expression in the nasal mucosa during the pollen season. METHODS: Nasal biopsy specimens were taken from 37 adults with severe summer hay fever at baseline (out of season) and at peak season after 2 years of treatment with a depot grass pollen extract or placebo. Biopsy specimens were processed for immunohistochemistry by using mAbs against eosinophils (EG2), T cells (CD3), and IL-2 receptor-positive cells (CD25), as well as for in situ hybridization by using a sulfur 35-labeled antisense riboprobe directed against IL-5. RESULTS: Immunotherapy significantly reduced symptoms (49%, P =.01) and medication requirements (80%, P =.007) compared with placebo. There was a 400% increase (P =.004) in eosinophils during the pollen season in placebo-treated patients, which was inhibited in the immunotherapy group (20% increase, P =.04 between groups). Seasonal increases were also observed for CD25(+) cells (P =.002), CD3(+) cells (P =.02), and IL-5 mRNA-expressing cells (P =.03) in the placebo group but not in the immunotherapy group. A significant correlation was observed between eosinophils and IL-5 expression (r = 0.5, P <.05). Both eosinophils (r = 0.6, P <.02) and IL-5 (r = 0.6, P <.02) correlated with symptoms after immunotherapy. CONCLUSION: Improvement in symptoms after grass pollen immunotherapy may result, at least in part, from inhibition of IL-5-dependent tissue eosinophilia during the pollen season.

Biopsy↗
PubMed2001

Adenovirus-mediated wild-type p53 gene expression radiosensitizes non-small cell lung cancer cells but not normal lung fibroblasts.

PURPOSE: We compared the ability of adenoviral-mediated wild-type p53 RPR/INGN201(Ad5/CMV/p53) to radiosensitize non-small cell lung carcinoma (NSCLC) and normal lung fibroblast cells. MATERIALS AND METHODS: NSCLC cell lines (A549 and H322) and human lung fibroblast cells (MRC-9 and CCD-16) were used in this study. Radiosensitivity was determined by clonogenic assay and tumor growth delay. Expression of p53, Bax, and p21WAF1 protein were evaluated by immunoblot. A FITC conjugate of annexin V was used for flow cytometric detection of apoptosis. RESULTS: Clonogenic and apoptotic assays indicated that Ad5/CMV/p53 enhanced the radiosensitivity of both NSCLC cell lines. On the other hand, the two normal human fibroblast cell lines appeared to be resistant to the cytotoxic effects of Ad5/CMV/p53 and were not radiosensitized compared to the NSCLC cells. According to immunoblot analysis, Bax expression was increased in the NSCLC cells treated with the combination therapy; Bax expression, however, was unchanged in normal cells. In in vivo studies, tumor growth suppression was enhanced by this combination strategy in xenograft tumors growing in nude mice compared to Ad5/CMV/p53 or radiation therapy when used alone. CONCLUSIONS: Our data indicate that therapy using Ad5/CMV/p53 and irradiation in combination is more effective than either treatment when used alone on NSCLC cells, is not limited to cells with defective endogenous p53, and does not enhance the radiosensitivity of normal cells.

Adenoviridae↗
PubMed2001

Torsades de pointes associated with high dose levomethadyl acetate (ORLAAM).

A patient undergoing management of heroin dependency with high dosages of the long-acting methadone derivative, levomethadyl acetate HCl (LAAM; ORLAAM) developed a prolonged QTc interval and polymorphic QRS complexes on EKG consistent with torsades de pointes (TdP). The patient was taking other drugs known to prolong the QTc interval (fluoxetine and IV cocaine), and those known to antagonize the activity of the P450 enzymes responsible for the metabolism of LAAM and its active metabolite (fluoxetine, cocaine and marijuana). No previous reports have appeared in the literature attributing this adverse event to LAAM therapy; however, five similar cases have been reported to the manufacturer. Animal studies indicate that LAAM and metabolites prolong the action potential duration of myocardial cells. We propose that predisposed patients on high doses of LAAM may be at risk for developing TdP. Patients being treated with LAAM should receive dosages consistent with guidelines and be evaluated for concomitant diseases, interacting drug therapies, and EKG abnormalities.

Adult↗
PubMed2000

Gender vs sex.

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Sex↗
PubMed2000

Adenovirus-mediated p16INK4a gene expression radiosensitizes non-small cell lung cancer cells in a p53-dependent manner.

We examined the influence of adenovirus-mediated wild-type p16INK4a (Ad/p16) expression on the radiation sensitivity of NSCLC cell lines, all of which lacked constitutive p16INK4a but each of which varied in p53 status: A549 (-p16INK4a/ +pRb/wt-p53), H322 (-p16INK4a/ +pRb/mt-p53), and H1299 (-p16INK4a/ +pRb/deleted-p53). The in vitro clonogenic survival results indicate that Ad/p16 enhanced the radiosensitivity of A549 but not H322 or H1299. Further analysis indicated that the apoptosis induced by combination therapy using Ad/p16 plus irradiation was dependent on the endogenous p53 status of the cancer cells. We performed Western blotting to analyse the p53 protein expression of A549 cells treated with either Ad/p16 or Ad/Luc. Endogenous p53 protein levels were higher in A549 cells transfected with Ad/p16 than in those transfected with Ad/Luc. Furthermore, when wt-p53 protein expression was restored in H1299 using Ad/ p53, Ad/p16 stabilized p53 protein expression and radiosensitized the cells. These results suggest that Ad/ p16-induced stabilization of p53 protein may play an important role in Ad/p16 mediated radiosensitization by enhancing or restoring apoptosis properties. Thus, Ad/ p16 plus radiation in combination may be a useful gene therapy strategy for tumors that have wt-p53 but nonfunctional p16INK4a.

Adenoviruses, Human↗