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2. Experimental infection with the hookworm, Necator americanus, is associated with stable gut microbial diversity in human volunteers with relapsing multiple sclerosis

Author

Jenkins, TP, Pritchard, DI, Tanasescu, R, Telford, G, Papaiakovou, M, Scotti, R, Cortes, A, Constantinescu, CS, Cantacessi, C, Jenkins, TP, Pritchard, DI, Tanasescu, R, Telford, G, Papaiakovou, M, Scotti, R, Cortes, A, Constantinescu, CS, and Cantacessi, C

Abstract

BACKGROUND: Helminth-associated changes in gut microbiota composition have been hypothesised to contribute to the immune-suppressive properties of parasitic worms. Multiple sclerosis is an immune-mediated autoimmune disease of the central nervous system whose pathophysiology has been linked to imbalances in gut microbial communities. RESULTS: In the present study, we investigated, for the first time, qualitative and quantitative changes in the faecal bacterial composition of human volunteers with remitting multiple sclerosis (RMS) prior to and following experimental infection with the human hookworm, Necator americanus (N+), and following anthelmintic treatment, and compared the findings with data obtained from a cohort of RMS patients subjected to placebo treatment (PBO). Bacterial 16S rRNA high-throughput sequencing data revealed significantly decreased alpha diversity in the faecal microbiota of PBO compared to N+ subjects over the course of the trial; additionally, we observed significant differences in the abundances of several bacterial taxa with putative immune-modulatory functions between study cohorts. Parabacteroides were significantly expanded in the faecal microbiota of N+ individuals for which no clinical and/or radiological relapses were recorded at the end of the trial. CONCLUSIONS: Overall, our data lend support to the hypothesis of a contributory role of parasite-associated alterations in gut microbial composition to the immune-modulatory properties of hookworm parasites.

Published
2021

12. Fertilizer Banding Influence on Spatial and Temporal Distribution of Soil Inorganic Nitrogen in a Corn Field

Author

Zebarth, B. J., Younie, M. F., Paul, J. W., Hall, J. W., and Telford, G. A.

Subjects
Crops and nitrogen -- Research, Corn -- Research, Earth sciences
Abstract

Fertilizer N is commonly applied as a sidedress band application in corn (Zea mays L.) fields. The objectives of this study were to determine the implications of fertilizer band application on spatial and temporal variations in soil inorganic N and to evaluate different sampling strategies for their suitability in estimating the average soil inorganic N concentration of a field. Treatments were 0, 60, and 120 kg N [ha.sup.-1] in 1994, and 0, 120, and 240 kg N [ha.sup.-1] in 1995, replicated three times at each of two sites. Fertilizer was applied as a band of [NH.sub.4][NO.sub.3] 15 cm on each side of each corn row at the corn six-leaf stage. Soil samples taken at eight interrow locations 0, 5, 10, 15, 20, 25, 30, and 35 cm from the corn row and at depth increments of 0 to 15, 15 to 30, and 30 to 60 cm and on five sampling dates were analyzed for soil [NO.sub.3] and [NH.sub.4] concentrations. Random sampling and five systematic sampling strategies were evaluated with respect to bias in estimation of field soil [NO.sub.3] and [NH.sub.4] concentration for three depth increments, and with respect to the number of samples required to achieve a given precision and probability level combination for soil [NO.sub.3] concentration for the 0- to 15-cm depth. All systematic sampling strategies provided adequate estimates of the true soil inorganic N concentration as estimated based on uniform sampling across all interrow locations. There was no consistent benefit to using any one systematic strategy with respect to the number of cores required to obtain a given level of precision in soil [NO.sub.3] concentration at a given level of probability. Systematic sampling strategies were at least as good as, or superior to, random sampling, particularly after fertilizer band application and at high N rates. The apparent insensitivity of estimated field soil [NO.sub.3] concentration to sampling strategy was attributed to the relatively high mobility of [NO.sub.3] in soil and variation in placement of the fertilizer band relative to the corn row during side-dressing.

Published
1999

13. Invasive Pathogens in Plant Biosecurity. Case Study: Citrus Biosecurity

Author

Gordh, Gordon, McKirdy, Simon, Barkley, P., Schubert, T., Schutte, G. C., Godfrey, K., Hattingh, V., Telford, G., Beattie, G. A. C., Hoffman, K., Gordh, Gordon, McKirdy, Simon, Barkley, P., Schubert, T., Schutte, G. C., Godfrey, K., Hattingh, V., Telford, G., Beattie, G. A. C., and Hoffman, K.

Published
2014

15. Analysis of the production planning and inventory control system used by NADEP, North Island for the repair of the T-64 series engine

Author

Trietsch, Dan, Greer, Willis R., Naval Postgraduate School (U.S.), Boyer, Telford G., Trietsch, Dan, Greer, Willis R., Naval Postgraduate School (U.S.), and Boyer, Telford G.

Abstract

This thesis is an analysis of the current production planning and inventory control system used by NADEP, North Island for the repair of the T-64 series engine. The system is described and analyzed for its effect on repair time and work-in-process inventory. Recommendations are made to improve repair time and reduce work-in-process inventory levels. A simulation and queueing theory are used to compare the queue of awaiting maintenance engines under the current system versus the queue when a specified monthly repair rate is maintained. Keywords: Production planning, Queueing theory. (jes), http://archive.org/details/analysisofproduc1094522895, Lieutenant, United States Navy, Approved for public release; distribution is unlimited.

Published
2012

16. Reduced helminth burden increases allergen skin sensitization but not clinical allergy: a randomized, double-blind, placebo-controlled trial in Vietnam

Author

Flohr, C, Tuyen, LN, Quinnell, RJ, Lewis, S, Minh, TT, Campbell, J, Simmons, C, Telford, G, Brown, A, Hien, TT, Farrar, J, Williams, H, Pritchard, DI, Britton, J, Flohr, C, Tuyen, LN, Quinnell, RJ, Lewis, S, Minh, TT, Campbell, J, Simmons, C, Telford, G, Brown, A, Hien, TT, Farrar, J, Williams, H, Pritchard, DI, and Britton, J

Abstract

BACKGROUND: Observational evidence suggests that infection with helminths protects against allergic disease and allergen skin sensitization. It is postulated that such effects are mediated by helminth-induced cytokine responses, in particular IL-10. OBJECTIVE: We tested this hypothesis in a rural area of central Vietnam where hookworm infection is endemic. METHODS: One thousand five hundred and sixty-six schoolchildren aged 6-17 were randomly allocated to receive either anti-helminthic therapy or a placebo at 0, 3, 6, and 9 months. We compared changes in the prevalence of exercise-induced bronchoconstriction, allergen skin sensitization, flexural eczema on skin examination, questionnaire-reported allergic disease (wheeze and rhinitis symptoms), and immunological parameters (hookworm-induced IFN-gamma, IL-5, IL-10) between 0 and 12 months. RESULTS: One thousand four hundred and eighty-seven children (95% of these randomized) completed the study. The most common helminth infections were hookworm (65%) and Ascaris lumbricoides (7%). There was no effect of the therapy on the primary outcome, exercise-induced bronchoconstriction (within-participant mean percent fall in peak flow from baseline after anti-helminthic treatment 2.25 (SD 7.3) vs. placebo 2.19 (SD 7.8, P=0.9), or on the prevalence of questionnaire-reported wheeze [adjusted odds ratio (OR)=1.16, 95% confidence interval (CI) 0.35-3.82, P=0.8] and rhinitis (adjusted OR=1.39, 0.89-2.15, P=0.1), or flexural dermatitis on skin examination (adjusted OR=1.15, 0.39-3.45, P=0.8). However, anti-helminthic therapy was associated with a significantly higher allergen skin sensitization risk (adjusted OR=1.31, 1.02-1.67, P=0.03). This effect was particularly strong for children infected with A. lumbricoides at baseline (adjusted OR=4.90, 1.48-16.19, P=0.009). Allergen skin sensitization was inversely related to hookworm-specific IL-10 at baseline (adjusted OR=0.76, 0.59-0.99, P=0.04). No cytokine tested, including IL-10, cha

Published
2010

19. Reduced helminth burden increases allergen skin sensitization but not clinical allergy: a randomized, double‐blind, placebo‐controlled trial in Vietnam

Author

Flohr, C., primary, Tuyen, L. N., additional, Quinnell, R. J., additional, Lewis, S., additional, Minh, T. T., additional, Campbell, J., additional, Simmons, C., additional, Telford, G., additional, Brown, A., additional, Hien, T. T., additional, Farrar, J., additional, Williams, H., additional, Pritchard, D. I., additional, and Britton, J., additional

Published
2009
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30. Total antioxidant capacity of colon in patients with chronic ulcerative colitis.

Author

Koch, Timothy, Yuan, L.-X., Stryker, Steven, Ratliff, Priscilla, Telford, Gordon, Opara, Emmanuel, Koch, T R, Stryker, S J, Ratliff, P, Telford, G L, and Opara, E C

Subjects
ANTIOXIDANTS, CHRONIC diseases, COLON (Anatomy), COMPARATIVE studies, INTESTINAL mucosa, RESEARCH methodology, MEDICAL cooperation, PEROXIDES, RESEARCH, ULCERATIVE colitis, EVALUATION research, IN vitro studies
Abstract

It has been proposed that oxidative stress is involved in the pathophysiology of ulcerative colitis. We have reported the depletion of the nonenzymatic antioxidant, glutathione, in colon from active and inactive ulcerative colitis. The colon contains several biochemically linked antioxidant systems. We hypothesized that diminished total antioxidant capacity in active ulcerative colitis would be associated with increased colonic lipid peroxidation. This study was designed to determine total antioxidant capacity and lipid hydroperoxide levels using colon obtained at surgery from controls (N = 16; 4 females, 12 males; mean age 70 years), and active and inactive ulcerative colitis (N = 15; 3 females, 12 males; mean age 39). Total antioxidant capacity of control colon was higher in muscularis externa compared to the mucosal-submucosal layer (P < 0.05). There were no differences in colonic total antioxidant capacity or lipid hydroperoxide levels comparing control colon to inactive and active ulcerative colitis. The results did not support depletion of tissue total antioxidant capacity by free radicals. Depletion of glutathione in ulcerative colitis may be a specific disorder rather than a secondary defect attributable to global oxidative stress. Nonspecific antioxidant supplements appear unlikely to be beneficial in the treatment of ulcerative colitis. [ABSTRACT FROM AUTHOR]

Published
2000
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31. Suppression of autoimmune disease in NZB/W F1 mice by treatment with the novel immunomodulator BTS 63155.

Author

Appleby, P., Telford, G., and Naylor, G. B.

Subjects
*AUTOIMMUNE diseases, *IMMUNOLOGICAL adjuvants, *CYCLOSPORINE, *LUPUS nephritis, *DRUGS, *SYSTEMIC lupus erythematosus
Abstract

Autoimmune disease in NZB/W F1 mice was treated from 23 weeks of age with the novel immunomodulator BTS 63155 and, for comparative purposes, the established immunosuppressive agent cyclosporin A. Both drugs significantly improved survival compared with untreated controls. Lupus nephritis was also significantly reduced in the drug-treated groups, and this was related to reduced glomerular deposition of IgG. Autoantibody (ANA) levels were lowered by treatment with cyclosporin A, but not by BTS 63155. This latter finding may indicate a different mode of action for the two drugs. In a long term study, neither drug effected a complete cure, as autoimmune disease recurred on withdrawal of drug treatment. [ABSTRACT FROM AUTHOR]

Published
1993
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33. Synthetic Analogues of the Bacterial Signal (Quorum Sensing) Molecule N-(3-Oxododecanoyl)-<SCP>l</SCP>-homoserine Lactone as Immune Modulators

Author

Chhabra, S. R., Harty, C., Hooi, D. S. W., Daykin, M., Williams, P., Telford, G., Pritchard, D. I., and Bycroft, B. W.

Abstract

Comparative immune modulatory activity for a range of synthetic analogues of a Pseudomonas aeruginosa signal molecule, N-(3-oxododecanoyl)-l-homoserine lactone (3O, C12-HSL), is described. Twenty-four single or combination systematic alterations of the structural components of 3O, C12-HSL were introduced as described. Given the already defined immunological profile of the parent compound, 3O, C12-HSL, these compounds were assayed for their ability to inhibit murine and human leucocyte proliferation and TNF-α secretion by lipopolysaccharide (LPS) stimulated human leucocytes in order to provide an initial structure−activity profile. From IC50 values obtained with a murine splenocyte proliferation assay, it is apparent that acylated l-homoserine lactones with an 11−13 C side chain containing either a 3-oxo or a 3-hydroxy group are optimal structures for immune suppressive activity. These derivatives of 3O, C12-HSL with monounsaturation and/or a terminal nonpolar substituent on the side chain were also potent immune suppressive agents. However, structures lacking the homoserine lactone ring, structures lacking the l-configuration at the chiral center, and those with polar substituents were essentially devoid of activity. The ability of compounds selected from the optimal activity range to modulate mitogen-driven human peripheral blood mononuclear cell proliferation and LPS-induced TNF-α secretion indicates the suitability of these compounds for further investigation in relation to their molecular mechanisms of action in TNF-α driven immunological diseases, particularly autoimmune diseases such as psoriasis, rheumatoid arthritis, and type 1 (autoimmune) diabetes.

Published
2003

37. The Pseudomonas aeruginosa quorum-sensing signal molecule N-(3-oxododecanoyl)-L-homoserine lactone has immunomodulatory activity.

Author

Telford, G, Wheeler, D, Williams, P, Tomkins, P T, Appleby, P, Sewell, H, Stewart, G S, Bycroft, B W, and Pritchard, D I

Abstract

Diverse gram-negative bacterial cells communicate with each other by using diffusible N-acyl homoserine lactone (AHL) signal molecules to coordinate gene expression with cell population density. Accumulation of AHLs above a threshold concentration renders the population "quorate," and the appropriate target gene is activated. In pathogenic bacteria, such as Pseudomonas aeruginosa, AHL-mediated quorum sensing is involved in the regulation of multiple virulence determinants. We therefore sought to determine whether the immune system is capable of responding to these bacterial signal molecules. Consequently the immunomodulatory properties of the AHLs N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL) and N-(3-oxohexanoyl)-L-homoserine lactone (OHHL) were evaluated in murine and human leukocyte immunoassays in vitro. OdDHL, but not OHHL, inhibited lymphocyte proliferation and tumor necrosis factor alpha production by lipopolysaccharide-stimulated macrophages. Furthermore, OdDHL simultaneously and potently down-regulated the production of IL-12, a Th-1-supportive cytokine. At high concentrations (>7 x 10(-5) M) OdDHL inhibited antibody production by keyhole limpet hemocyanin-stimulated spleen cells, but at lower concentrations (<7 x 10(-5) M), antibody production was stimulated, apparently by increasing the proportion of the immunoglobulin G1 (IgG1) isotype. OdDHL also promoted IgE production by interleukin-4-stimulated human peripheral blood mononuclear cells. These data indicate that OdDHL may influence the Th-1-Th-2 balance in the infected host and suggest that, in addition to regulating the expression of virulence determinants, OdDHL may contribute to the pathogenesis of P. aeruginosa infections by functioning as a virulence determinant per se.

Published
1998

40. Analysis of the production planning and inventory control system used by NADEP, North Island for the repair of the T-64 series engine

Author

Boyer, Telford G., Trietsch, Dan, Greer, Willis R., and Naval Postgraduate School (U.S.)

Subjects
NADEP, Queueing Theory, Production Planning, Management
Abstract

This thesis is an analysis of the current production planning and inventory control system used by NADEP, North Island for the repair of the T-64 series engine. The system is described and analyzed for its effect on repair time and work-in-process inventory. Recommendations are made to improve repair time and reduce work-in-process inventory levels. A simulation and queueing theory are used to compare the queue of awaiting maintenance engines under the current system versus the queue when a specified monthly repair rate is maintained. Keywords: Production planning, Queueing theory. (jes) http://archive.org/details/analysisofproduc1094522895 Lieutenant, United States Navy Approved for public release; distribution is unlimited.

Published
1988

41. Analysis of the Production Planning and Inventory Control System used by NADEP (Naval Aviation Depot)

Author

NAVAL POSTGRADUATE SCHOOL MONTEREY CA, Boyer, II, Telford G., NAVAL POSTGRADUATE SCHOOL MONTEREY CA, and Boyer, II, Telford G.

Abstract

This thesis is an analysis of the current production planning and inventory control system used by NADEP, North Island for the repair of the T-64 series engine. The system is described and analyzed for its effect on repair time and work-in-process inventory. Recommendations are made to improve repair time and reduce work-in-process inventory levels. A simulation and queueing theory are used to compare the queue of awaiting maintenance engines under the current system versus the queue when a specified monthly repair rate is maintained. Keywords: Production planning, Queueing theory.

Published
1988

42. Analysis of the production planning and inventory control system used by NADEP, North Island for the repair of the T-64 series engine

Author

Trietsch, Dan, Greer, Willis R., Naval Postgraduate School (U.S.), Boyer, Telford G., Trietsch, Dan, Greer, Willis R., Naval Postgraduate School (U.S.), and Boyer, Telford G.

Abstract

This thesis is an analysis of the current production planning and inventory control system used by NADEP, North Island for the repair of the T-64 series engine. The system is described and analyzed for its effect on repair time and work-in-process inventory. Recommendations are made to improve repair time and reduce work-in-process inventory levels. A simulation and queueing theory are used to compare the queue of awaiting maintenance engines under the current system versus the queue when a specified monthly repair rate is maintained. Keywords: Production planning, Queueing theory. (jes)

Published
1988

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