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51.
Assessing the survival of transgenic plant DNA in the human gastrointestinal tract 总被引:14,自引:0,他引:14
Netherwood T Martín-Orúe SM O'Donnell AG Gockling S Graham J Mathers JC Gilbert HJ 《Nature biotechnology》2004,22(2):204-209
The inclusion of genetically modified (GM) plants in the human diet has raised concerns about the possible transfer of transgenes from GM plants to intestinal microflora and enterocytes. The persistence in the human gut of DNA from dietary GM plants is unknown. Here we study the survival of the transgene epsps from GM soya in the small intestine of human ileostomists (i.e., individuals in which the terminal ileum is resected and digesta are diverted from the body via a stoma to a colostomy bag). The amount of transgene that survived passage through the small bowel varied among individuals, with a maximum of 3.7% recovered at the stoma of one individual. The transgene did not survive passage through the intact gastrointestinal tract of human subjects fed GM soya. Three of seven ileostomists showed evidence of low-frequency gene transfer from GM soya to the microflora of the small bowel before their involvement in these experiments. As this low level of epsps in the intestinal microflora did not increase after consumption of the meal containing GM soya, we conclude that gene transfer did not occur during the feeding experiment. 相似文献
52.
Goedkoop AY Kraan MC Picavet DI de Rie MA Teunissen MB Bos JD Tak PP 《Arthritis research & therapy》2004,6(4):R326-R334
Psoriasis and psoriatic arthritis are inflammatory diseases that respond well to anti-tumour necrosis factor-α therapy. To
evaluate the effects of anti-tumour necrosis factor-α treatment on expression of adhesion molecules and angiogenesis in psoriatic
lesional skin and synovial tissue, we performed a prospective single-centre study with infliximab therapy combined with stable
methotrexate therapy. Eleven patients with both active psoriasis and psoriatic arthritis received infusions of infliximab
(3 mg/kg) at baseline, and at weeks 2, 6, 14 and 22 in an open-label study. In addition, patients continued to receive stable
methotrexate therapy in dosages ranging from 5 to 20 mg/week. Clinical assessments, including Psoriasis Area and Severity
Index (PASI) and Disease Activity Score (DAS), were performed at baseline and every 2 weeks afterward. In addition, skin biopsies
from a target psoriatic plaque and synovial tissue biopsies from a target joint were taken before treatment and at week 4.
Immunohistochemical analysis was performed to detect the number of blood vessels, the expression of adhesion molecules and
the presence of vascular growth factors. Stained sections were evaluated by digital image analysis. At week 16, the mean PASI
was reduced from 12.3 ± 2.4 at baseline to 1.8 ± 0.4 (P ≤ 0.02). The mean DAS was reduced from 6.0 ± 0.5 to 3.6 ± 0.6 (P ≤ 0.02). We found some fluctuations in DAS response as compared with the change in PASI, with the latter exhibiting a steady
decrease over time. After 4 weeks the cell infiltrate was reduced in both skin and synovium. There was a significant reduction
in the number of blood vessels in dermis and synovium at week 4. A significant reduction in the expression of αvβ3 integrin, a marker of neovascularization, was also found in both skin and synovium at week 4. In addition, a significant
reduction in the expression of adhesion molecules was observed in both skin and synovium at week 4. We also observed a trend
toward reduced expression of vascular endothelial growth factor in both skin and synovium. In conclusion, low-dose infliximab
treatment leads to decreased neoangiogenesis and deactivation of the endothelium, resulting in decreased cell infiltration
and clinical improvement in psoriasis and psoriatic arthritis. 相似文献
53.
J Mathers 《BMJ (Clinical research ed.)》1980,280(6218):941-942
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55.
Gillum LA Gouveia C Dorsey ER Pletcher M Mathers CD McCulloch CE Johnston SC 《PloS one》2011,6(2):e16837
Background
An analysis of NIH funding in 1996 found that the strongest predictor of funding, disability-adjusted life-years (DALYs), explained only 39% of the variance in funding. In 1998, Congress requested that the Institute of Medicine (IOM) evaluate priority-setting criteria for NIH funding; the IOM recommended greater consideration of disease burden. We examined whether the association between current burden and funding has changed since that time.Methods
We analyzed public data on 2006 NIH funding for 29 common conditions. Measures of US disease burden in 2004 were obtained from the World Health Organization''s Global Burden of Disease study and national databases. We assessed the relationship between disease burden and NIH funding dollars in univariate and multivariable log-linear models that evaluated all measures of disease burden. Sensitivity analyses examined associations with future US burden, current and future measures of world disease burden, and a newly standardized NIH accounting method.Results
In univariate and multivariable analyses, disease-specific NIH funding levels increased with burden of disease measured in DALYs (p = 0.001), which accounted for 33% of funding level variation. No other factor predicted funding in multivariable models. Conditions receiving the most funding greater than expected based on disease burden were AIDS ($2474 M), diabetes mellitus ($390 M), and perinatal conditions ($297 M). Depression ($719 M), injuries ($691 M), and chronic obstructive pulmonary disease ($613 M) were the most underfunded. Results were similar using estimates of future US burden, current and future world disease burden, and alternate NIH accounting methods.Conclusions
Current levels of NIH disease-specific research funding correlate modestly with US disease burden, and correlation has not improved in the last decade. 相似文献56.
Background and aims
Legume species in the fynbos vegetation of the Cape Floristic Region, that fix N2 in soils with low P, may have evolved for enhanced acquisition and efficient use of P. It was hypothesized that N2-fixing and combined-N supplied (N-supplied) A. linearis, P. calyptrata and C. genistoides are adapted to low P and would be relatively unresponsive to increased P of 100 μM.Methods
18 legume species were evaluated for their nodulation response to low P availability. The N X P interaction was then examined in A. linearis, P. calyptrata and C. genistoides reliant on either N2-fixation or 300 μM N (NH4NO3), and receiving 0.1, 1.0, 10 and 100 μM P (NaH2PO4).Results
In the species selection experiment, A. linearis, P. calyptrata and C. genistoides, with the greatest nodule fresh weight (FW) and nodule FW to root FW ratio, were the most prolific nodulating species. In the N X P experiment, with low P supply, the biomass of N2-fixing P. calyptrata and C. genistoides was consistently greater than that of N-supplied plants. In contrast, with high P supply of 100 μM P, all N-supplied plants accumulated more biomass than the corresponding N2-fixing plants. High P-use efficiency, poor down-regulation of P uptake and P storage was evident in A. linearis and P. calyptrata.Conclusion
The growth response to P and the significant N X P interactions indicate that N2-fixing and N-supplied plants were not adapted to low P, but rather colimited by both N and P. 相似文献57.
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