Factors underlying Dutch farmers' intentions to adapt their agronomic management to reduce Fusarium species infection in wheat.

Infection of wheat by Fusarium species can lead to Fusarium Head Blight (FHB) and mycotoxin contamination, thereby reducing food quality and food safety, and leading to economic losses. Agronomic management through the implementation of various pre-harvest measures can reduce the probability of Fusarium spp. infection in the wheat field. To design interventions that could stimulate wheat farmers to (further) improve their agronomic management to reduce FHB, it is key to understand farmers' behaviour towards adapting their management. The aim of this paper was to understand the intention, underlying behavioural constructs, and beliefs of Dutch wheat farmers to adapt their agronomic management to reduce FHB and mycotoxin contamination in wheat, applying the Theory of Planned Behaviour (TPB). Data were collected from 100 Dutch wheat farmers via a questionnaire. The standard TPB analysis was extended with an assessment of the robustness of the belief results to account for the statistical validity of the analysis on TPB beliefs (i.e. to address the so-called expectancy-value muddle). Forty-six percent of the farmers had a positive intention to change their management in the next 5 years. The two behavioural constructs significantly related to this intention were attitude and social norm, whereas association with the perceived behavioural control construct was insignificant indicating that farmers did not perceive any barriers to change their behaviour. Relevant attitudinal beliefs indicated specific attributes of wheat, namely yield, quality and safety (lower mycotoxin contamination). This indicates that strengthening these beliefs-by demonstrating that a change in management will result in a higher yield and quality and lower mycotoxin levels-will result in a stronger attitude and, subsequently, a higher intention to change management. Interventions to strengthen these beliefs should preferably go by the most important referents for social norms, which were the buyers and the farmer cooperatives in this study.

Selective expansion of merocytic dendritic cells and CD8DCs confers anti-tumour effect of Fms-like tyrosine kinase 3-ligand treatment in vivo.

Vaccination with autologous cancer cells aims to enhance adaptive immune responses to tumour-associated antigens. The incorporation of Fms-like tyrosine kinase 3-ligand (FLT3L) treatment to the vaccination scheme has been shown previously to increase the immunogenicity of cancer vaccines, thereby enhancing their therapeutic potential. While evidence has been provided that FLT3L confers its effect through the increase of absolute dendritic cell (DC) numbers, it is currently unknown which DC populations are responsive to FLT3L and which effect FLT3L treatment has on DC functions. Here we show that the beneficial effects of FLT3L treatment resulted predominantly from a marked increase of two specific DC populations, the CD8 DCs and the recently identified merocytic DC (mcDC). These two DC populations (cross)-present cell-associated antigens to T cells in a natural killer (NK)-independent fashion. FLT3L treatment augmented the absolute numbers of these DCs, but did not change their activation status nor their capacity to prime antigen-specific T cells. While both DC populations effectively primed CD8(+) T cell responses to cell-associated antigens, only mcDC were capable to prime CD4(+) T cells to cell-associated antigens. Consequentially, the transfer of tumour vaccine-pulsed mcDC, but not of CD8 DCs, protected mice from subsequent tumour challenge in a vaccination model and resulted in eradication of established tumours in a therapeutic approach. These results show that the beneficial effect of FLT3L is associated with the induction of mcDC and suggests that selective targeting to mcDC or instilling mcDC 'characteristics' into conventional DC populations could significantly enhance the efficacy of tumour vaccines.

Cross-priming is under control of the relB gene.

Cross-priming is an important mechanism of intercell transfer of antigenic material leading to the specific activation of cytotoxic T lymphocytes. Dendritic cells (DCs) are considered the central antigen-presenting cell in cross-priming. Here we decided to probe the role of the relB gene, a regulator of DC differentiation, in the in vivo cross-priming of a model tumour antigen, TAP(-/-) murine embryo cells (MEC), expressing human adenovirus type 5 early region 1. To this end, we used relB(-/-) mutant mice to generate bone marrow (BM) chimeras as these possess few residual DC but are capable of initiating CD4+ and CD8+ T-cell responses in vivo. Our results show that relB(-/-) BM chimeras are unable to cross-prime CD8+ T cells, suggesting that the relB gene regulates cross-priming.

The efficacy of immunotherapy in an experimental murine model of allergic asthma is related to the strength and site of T cell activation during immunotherapy.

In the present study, the relation between the efficacy of immunotherapy, and the strength and site of T cell activation during immunotherapy was evaluated. We used a model of allergic asthma in which OVA-sensitized and OVA-challenged mice display increased airway hyperresponsiveness, airway inflammation, and Th2 cytokine production by OVA-specific T cells. In this model, different immunotherapy strategies, including different routes of administration, or treatment with entire OVA or the immunodominant T cell epitope OVA(323-339), or treatment with a peptide analogue of OVA(323-339) with altered T cell activation capacity were studied. To gain more insight in how immunotherapy affects allergen-specific T cells, the site of Ag-specific T cell activation and the magnitude of the T cell response induced during different immunotherapy strategies were determined using an adoptive transfer model. Our data suggest that amelioration of airway hyperresponsiveness and inflammation is associated with the induction of a strong, synchronized, and systemic T cell response, resulting in a decreased OVA-specific Th2 response. In contrast, deterioration of the disease after immunotherapy is associated with the induction of a weak nonsynchronized T cell response, resulting in the enhancement of the OVA-specific Th2 response after challenge.

Modulation of Th2 responses by peptide analogues in a murine model of allergic asthma: amelioration or deterioration of the disease process depends on the Th1 or Th2 skewing characteristics of the therapeutic peptide.

Allergen-specific CD4+ Th2 cells play an important role in the immunological processes of allergic asthma. Previously we have shown that, by using the immunodominant epitope OVA323-339, peptide immunotherapy in a murine model of OVA induced allergic asthma, stimulated OVA-specific Th2 cells, and deteriorated airway hyperresponsiveness and eosinophilia. In the present study, we defined four modulatory peptide analogues of OVA323-339 with comparable MHC class II binding affinity. These peptide analogues were used for immunotherapy by s.c. injection in OVA-sensitized mice before OVA challenge. Compared with vehicle-treated mice, treatment with the Th2-skewing wild-type peptide and a Th2-skewing partial agonistic peptide (335N-A) dramatically increased airway eosinophilia upon OVA challenge. In contrast, treatment with a Th1-skewing peptide analogue (336E-A) resulted in a significant decrease in airway eosinophilia and OVA-specific IL-4 and IL-5 production. Our data show for the first time that a Th1-skewing peptide analogue of a dominant allergen epitope can modulate allergen-specific Th2 effector cells in an allergic response in vivo. Furthermore, these data suggest that the use of Th1-skewing peptides instead of wild-type peptide may improve peptide immunotherapy and may contribute to the development of a successful and safe immunotherapy for allergic patients.

Opposite effects of immunotherapy with ovalbumin and the immunodominant T-cell epitope on airway eosinophilia and hyperresponsiveness in a murine model of allergic asthma.

In the present study, we investigated immunotherapy using an entire protein or an immunodominant epitope in a murine model of allergic asthma. Immunotherapy was performed in ovalbumin (OVA)-sensitized mice before OVA challenge. Mice were treated subcutaneously with OVA, the immunodominant epitope OVA323-339, or vehicle. In vehicle-treated animals, repeated OVA challenge induced increased serum levels of OVA-specific immunoglobulin (Ig)G1, IgE, airway eosinophilia, and hyperresponsiveness, compared with saline-challenged animals. In addition, interleukin (IL)-4 and IL-5 production upon OVA restimulation of lung-draining lymph node cells in vitro were significantly increased in OVA-challenged animals. Immunotherapy using OVA significantly reduced airway eosinophilia and hyperresponsiveness. This finding was accompanied by significantly reduced OVA-specific IL-4 and IL-5 production. Further, OVA immunotherapy induced increased serum levels of OVA-specific IgG1, whereas OVA-specific IgG2a and IgE levels were not affected. In contrast to OVA immunotherapy, immunotherapy with OVA323-339 aggravated airway eosinophilia and hyperresponsiveness. OVA-specific IgG1, IgG2a, and IgE serum levels, and in vitro IL-4 and IL-5 production, were not affected. Thus, immunotherapy with protein resulted in beneficial effects on airway eosinophilia and hyperresponsiveness, which coincided with a local reduced T-helper 2 (Th2) response. In contrast, peptide immunotherapy aggravated airway hyperresponsiveness and eosinophilia, indicating a local enhanced Th2 response.

Regular physical activity and changes in risk factors for coronary heart disease: a nine months prospective study.

This study reports the non-acute effects of a long-term training programme of increasing intensity on some cardiovascular risk factors and the interrelation between these risk factors. Twenty sedentary men and 14 sedentary women were trained 3 to 4 times a week for nine months. After 36 weeks all individuals ran a half marathon run. The Wmax, weight, body mass index, systolic and diastolic blood pressure were recorded. The concentrations of fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor, triacylglycerols, total cholesterol, LDL cholesterol, HDL cholesterol and lipoprotein(a) were measured. The training programme induced a median increase in Wmax of 12% in the male group (from 226 to 251.5 Watt) and of 18% in the female group (from 160 to 188.5 Watt). These increases inn Wmax did not correlate with any other property under investigation in this study. Blood pressure was not altered, but body weight and body mass index were significantly decreased in the male group (from 74.6 to 72.2 kg and from 23.1 to 22.0 kg/m2, respectively) at the end of the training programme and decreased non-significantly in the female group (from 63.0 to 60.7 kg and from 21.6 to 21.5 kg/m2, respectively). In the male group total cholesterol, low density lipoprotein cholesterol and triacylglycerols decreased significantly under the influence of the training sessions. Furthermore, in both groups, a great decrease in plasma plasminogen activator inhibitor concentrations was noticed: in men from 22.5.10(3) AU/l to 4.5.10(3) AU/l and in women from 18.7 x 10(3) AU/l to 5.1 x 10(3) AU/l. However, the changes in the lipid and fibrinolytic quantities were not correlated with each other. Initial total cholesterol, LDL cholesterol and triacylglycerol levels correlated significantly with systolic blood pressure, while diastolic pressure was correlated to tissue plasminogen activator. Since tissue plasminogen activator also was significantly related to triacylglycerols, a trias existed between primary risk factors like blood pressure, lipid levels and fibrinolysis. In contrast, the changes in these properties under the influence of physical training were not interrelated. Median serum lipoprotein(a) concentrations were significantly increased in both men and women five days before the half marathon run: from 32 mg/l to 39 mg/l in men, and from 65 mg/l to 125.5 mg/l in women. Concomitantly, median fibrinogen concentrations were significantly elevated in men (from 2.32 g/l to 3.10 g/l) and non-significantly in women (from 2.62 g/l to 2.93 g/l), although no correlation existed between the changes in these properties. In conclusion, the nine months exercise programme increased the aerobic fitness in both men and women as indicated by the Wmax increase. This improvement coincided but was not correlated with beneficial changes in several anthropometric, lipid and fibrinolytic properties. Improvement in the risk factors under investigation was more pronounced in men than in women. The changes in lipid and haemostasis properties did not correlate with each other. The increases in lipoprotein(a) and fibrinogen concentrations, both atherogenic indices, could actually present a normal physiological response to the physical strain of exercise training of increasing workload.

Long-term physical exercise and lipoprotein(a) levels in a previously sedentary male and female population.

We investigated the effect of long-term physical exercise on serum lipoprotein(a) levels. 21 sedentary men and 15 sedentary women were trained three to four times a week with increasing intensity during 9 months. After 24 weeks all subjects ran a 15 km race and after 36 weeks a half marathon run (21 km). Blood samples were drawn before the training programme, 5 days before both races and 5 days after the half marathon run. Median (interquartile range) pre-training values in the male group were 32 (11-63) mg/L and in the female group 65 (23-199) mg/L. After 24 weeks of training, serum lipoprotein(a) concentrations had risen significantly in both male and female groups. Moreover, after 36 weeks of training, in preparation for the half marathon competition, median serum lipoprotein(a) rose almost twofold in both groups and was still elevated 5 days later. This study demonstrates that an exercise programme which includes running of increasing distances significantly increases serum lipoprotein(a) concentration.

Effects of long-term exercise of moderate intensity on anthropometric values and serum lipids and lipoproteins.

The influence of endurance training on serum lipids and lipoproteins was investigated in 20 sedentary males and 14 sedentary females. The total group was trained 3 to 4 times a week for 9 months. After 24 weeks all subjects ran a 15 km-race and after 36 weeks a half-marathon (21 km) race. Anthropometric values were determined before and after the training programme. Blood samples were drawn before the start of the training programme and, in order to avoid the measurement of acute effects, 5 days before both races. In the male group, median body weight and body mass were significantly decreased (p < 0.01) after nine months of training, while in the female group body weight and body mass index remained essentially unchanged. Percentage body fat, measured by skinfold thickness was significantly decreased in both groups at the end of the training programme. During the training period, median serum total cholesterol, low density lipid cholesterol and triacylglycerol concentrations decreased significantly (p < 0.01) in the male group, while in the female population the median serum lipid- and lipoprotein concentrations did not differ from pre-training values. The changes in serum lipids or lipoproteins did not correlate significantly with changes in body weight, body mass index or percentage body fat. Stepwise multiple regression showed that these changes were mostly dependent on initial concentrations in serum. Finally, no significant increase in median high density lipid cholesterol was observed in either the male or female group.(ABSTRACT TRUNCATED AT 250 WORDS)

Body mass, body composition and sleeping metabolic rate before, during and after endurance training.

Metabolic rate, more specifically resting metabolic rate (RMR) or sleeping metabolic rate (SMR), of an adult subject is usually expressed as a function of the fat-free mass (FFM). Chronic exercise is thought to increase FFM and thus to increase RMR and SMR. We determined body mass (BM), body composition, and SMR before, during, and after an endurance training programme without interfering with energy intake. The subjects were 11 women and 12 men, aged 37 (SD 3) years and body mass index 22.3 (SD 1.5) kg.m-2. The endurance training prepared subjects to run a half marathon competition after 44 weeks. The SMR was measured overnight in a respiration chamber. Body composition was measured by hydrostatic weighing. Measurements were performed at 0, 8, 20, 40, and 90 weeks after the start of the training. The BM had decreased from a mean value of 66.6 (SD 6.9) to 65.6 (SD 6.7) kg (P < 0.01), fat mass (FM) had decreased from 17.1 (SD 3.9) to 13.5 (SD 3.6) kg (P < 0.001), and FFM had increased from 49.5 (SD 7.3) to 52.2 (SD 7.6) kg (P < 0.001) at 40 weeks. Mean SMR before and after 40 weeks training was 6.5 (SD 0.7) and 6.2 (SD 0.6) MJ.day-1 (P < 0.05). The decrease in SMR was related to the decrease in BM (r = 0.62, P = 0.001). At 90 weeks, when most subjects had not trained for nearly a year, BM and SMR were not significantly different from the initial value while FM and FFM had not changed since week 40 of training.(ABSTRACT TRUNCATED AT 250 WORDS)

Prolonged physical conditioning and blood platelet release markers: a longitudinal study.

To study the long-term non-acute effect of endurance physical exercise on blood platelet activation, 20 sedentary males and 14 sedentary females were trained 3 to 4 times a week for 9 months. After 24 weeks all subjects ran a 15-km race; and after 36 weeks a half-marathon (21 km) race. Blood samples were drawn before the training programme and 5 days after both races. Median (interquartile range) platelet factor 4 and beta-thromboglobulin pretraining values for the total group were 9 (5-35) and 69 (40-495) IU/ml, respectively. During the course of the training programme, plasma platelet factor 4 concentrations rose steadily and significantly in both the male and female group (p < 0.05), together with a non-significant rise in plasma beta-thromboglobulin. At the end of the training procedure, 5 days after the half-marathon run, median (interquartile range) plasma factor 4 and beta-thromboglobulin concentrations for the total group were 150 (62-198) and 156 (84-288) IU/ml, respectively. No difference existed in median platelet factor 4 and beta-thromboglobulin concentrations of the male and female population before or during the training programme. In summary, the results of this study demonstrate that prolonged physical conditioning of increasing intensity is mainly associated with an elevation of the platelet protein platelet factor 4.

Circulating soluble tumor necrosis factor receptors, interleukin-2 receptors, tumor necrosis factor alpha, and interleukin-6 levels in rheumatoid arthritis. Longitudinal evaluation during methotrexate and azathioprine therapy.

OBJECTIVE: To assess whether circulating concentrations of soluble tumor necrosis factor receptors (sTNFR; p55 and p75), soluble interleukin-2 receptors (sIL-2R), tumor necrosis factor alpha (TNF alpha), and interleukin-6 (IL-6) reflect clinical response and whether changes are dependent on the drug used in rheumatoid arthritis (RA) patients taking methotrexate (MTX) or azathioprine (AZA). METHODS: These cytokines and soluble receptors were assessed in 20 control subjects and serially for up to 48 weeks in 61 RA patients, by bioassay (IL-6) and immunoassays (sTNFR, sIL-2R, TNF alpha, and IL-6). RESULTS: Concentrations of p55 and p75, sIL-2R, and TNF alpha (but not IL-6) were significantly higher in RA patients than in controls. Significant decreases in sIL-2R and p55 concentrations were associated with clinical improvement and were observed in patients treated with MTX, but not AZA. Both treatments induced decreases in IL-6 concentrations, but circulating AZA (or its metabolites) appears to interfere with the measurement of IL-6 bioactivity. TNF alpha and p75 levels did not show significant changes. CONCLUSION: Measurement of circulating sIL-2R, p55, and IL-6 may be useful in the evaluation of RA disease activity and response to therapy. Interference by circulating levels of drugs must be ruled out when bioassays are used to evaluate cytokine levels.

Long-term effect of physical activity on energy balance and body composition.

We studied the effect of an increase in physical activity on energy balance and body composition without interfering with energy intake (EI). Sixteen women and sixteen men, aged 28-41 years, body mass index 19.4-26.4 kg/m2, not participating in any sport before the start of the experiment, prepared to run a half-marathon competition after 44 weeks. Measurements of body composition, EI and energy expenditure (EE) were performed before (0 weeks), and 8, 20, and 40 weeks after the start of training. Body composition was measured with hydrodensitometry and isotope dilution, and EI with a 7 d dietary record. EE was measured overnight in a respiration chamber (sleeping metabolic rate (SMR)) and in a number of subjects over 2-week intervals with doubly-labelled water (average daily metabolic rate (ADMR)). ADMR showed an average increase of 30% in both sexes from the start of training onwards while SMR tended to decrease. EI showed a tendency to drop from week 20 to week 40 in the men and a tendency to increase from week 20 to week 40 in the women. Body mass (BM) did not change in both sexes until the observation at 40 weeks when the median value of the change in men was -1.0 kg (P < 0.01; Wilcoxon signed-rank) while the corresponding change of -0.9 kg in the women was not statistically significant. Body composition changes were most pronounced in men as well. Based on changes in BM, body volume and total body water, men lost 3.8 kg fat mass (FM) (P < 0.001; Wilcoxon signed-rank) and gained 1.6 kg protein mass (P < 0.01; Wilcoxon signed-rank) while the corresponding changes in women were 2.0 kg (P < 0.05; Wilcoxon signed-rank) and 1.2 kg (P < 0.05; Wilcoxon signed-rank). In men the loss of FM was positively correlated with the initial percentage body fat (Pearson r 0.92, P < 0.001). In conclusion, body fat can be reduced by physical activity although women tend to compensate for the increased EE with an increased EI, resulting in a smaller effect on BM and FM compared with men.

Removal of interleukin-1 beta and tumor necrosis factor from human plasma by in vitro dialysis with polyacrylonitrile membranes.

We studied the suitability of in vitro dialysis with polyacrylonitrile (PAN) membranes to remove small amounts of interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF) from plasma to be used as diluent for the standards in radioimmunoassays (RIA). Incubation of PAN membrane fragments with radiolabeled IL-1 beta or TNF yielded a significant binding of both cytokines to the membrane (percentage of membrane-bound cytokine after incubation in saline or plasma was 14-17% and 23-46%, respectively). Dialysis of plasma (containing radiolabeled cytokine) against plasma (initially devoid of cytokine) resulted in a binding percentage of IL-1 beta and TNF to the PAN membranes of 44 and 28%, respectively. When plasma was dialyzed against saline the percentage of membrane-bound IL-1 beta and TNF was 63 and 37%, respectively. After dialysis of plasma against either plasma or saline the percentage IL-1 beta recovered from the dialysate was approximately 16% in contrast with 1-2% TNF. The results confirm the capacity of in vitro dialysis with PAN membranes to remove IL-1 beta and to a lesser extent TNF from plasma. Removal is most marked in the first minutes of dialysis (suggesting saturation of the membrane) and less effective for TNF due to its low diffusion across the membrane.