413 research outputs found
A uniform questionnaire for use in case control studies of multiple sclerosis
No full textMembers of the Oslo International Think-Tank on MS Epidemiology have requested questionnaire for established research groups and received 16 questionnaires and clinical databases from around the world. The goal was to to produce a uniform questionnaire for use in etiological research on MS
Human a-mannosidase produced in transgenic tobacco plants is processed in human a-mannosidosis cell lines
No full textDeficiency in human lysosomal α-mannosidase (MAN2B1) results in α-mannosidosis, a lysosomal storage disorder; patients present a wide range of neurological, immunological, and skeletal symptoms caused by a multisystemic accumulation of mannose-containing oligosaccharides. Here, we describe the expression of recombinant MAN2B1 both transiently in Nicotiana benthamiana leaves and in the leaves and seeds of stably transformed N. tabacum plants. After purification from tobacco leaves, the recombinant enzyme was found to be N-glycosylated and localized in vacuolar compartments. In the fresh leaves of tobacco transformants, MAN2B1 was measured at 10200units/kg, and the purified enzyme from these leaves had a specific activity of 32-45U/mg. Furthermore, tobacco-produced MAN2B1 was biochemically similar to the enzyme purified from human tissues, and it was internalized and processed by α-mannosidosis fibroblast cells. These results strongly indicate that plants can be considered a promising expression system for the production of recombinant MAN2B1 for use in enzyme replacement therap
REDUCED DURATION OF BREASTFEEDING IS ASSOCIATED WITH A HIGHER RISK OF MS IN BOTH ITALIAN AND NORWEGIAN ADULT MALES: THE ENVIMS STUDY
No full textBackground: Longer duration of breastfeeding is associated
with a reduced risk of allergic and immune-mediated diseases
including multiple sclerosis (MS). With a large multinational casecontrol
study, we investigated the association between breastfeeding
and MS risk in two distinct populations.
Methods: A questionnaire (EnvIMS-Q) eliciting information
on feeding practices during the first year of life was administered
to individuals with MS and frequency age and sex-matched controls
from Italy and Norway. Two exposure categories were created:
breastfeeding for at least 4 months (reference), no
breastfeeding/breastfeeding for 3 months or less (reduced exposure).
Logistic regression with odds ratio (ORs) and 95% confidence
intervals (95% CIs), adjusting for covariates was used to
assess the association.
Results: 547 cases and 1039 controls in Italy, and 737 cases and
1335 controls in Norway were included. A significant association
of MS with ‘reduced exposure’ to breastfeeding was found in Italy
(ORadj = 1.37 (1.09, 1.73)), but not in Norway (ORadj = 1.13
(0.91, 1.40)). For both countries significant associations were
observed in men (ORItaly 2.33 (1.50, 3.65), ORNorway 2.11 (1.30,
3.44)).
Conclusion: Shorter duration of breastfeed was associated with
an increased risk of MS in men in Italy and in Norway.
Acknowledgements: FISM (2007/R/14, 2008/R/19), Regione
Autonoma Sardegna, Assessorato Igiene/Sanità, Italy
Epidemiologic study of etiological factors in multiple sclerosis. Guidelines for future analytical research.
No full textReview of analytical studies on multiple sclerosi
Timing of use of cod liver oil, a vitamin D source, and multiple sclerosis risk: The EnvIMS study
No full textBackground: Low vitamin D levels have been associated with an increased risk of multiple sclerosis
(MS), although it remains unknown whether this relationship varies by age.
Objective: The objective of this paper is to investigate the association between vitamin D3 supplementation through cod liver oil at different postnatal ages and MS risk.
Methods: In the Norwegian component of the multinational case-control study Environmental Factors In
Multiple Sclerosis (EnvIMS), a total of 953 MS patients with maximum disease duration of 10 years and
1717 controls reported their cod liver oil use from childhood to adulthood.
Results: Self-reported supplement use at ages 13–18 was associated with a reduced risk of MS (OR 0.67,
95% CI 0.52–0.86), whereas supplementation during childhood was not found to alter MS risk (OR 1.01,
95% CI 0.81–1.26), each compared to non-use during the respective period. An inverse association was
found between MS risk and the dose of cod liver oil during adolescence, suggesting a dose-response relationship (p trend = 0.001) with the strongest effect for an estimated vitamin D3 intake of 600–800 IU/d
(OR 0.46, 95% CI 0.31–0.70).
Conclusions: These findings not only support the hypothesis relating to low vitamin D as a risk factor for
MS, but further point to adolescence as an important susceptibility period for adult-onset M
A Questionnaire for multinational case–control studies of environmental risk factors in multiple sclerosis (EnvIMS-Q)
No full textObjectives: The increasing incidence of multiple sclerosis (MS) worldwide, especially in women, points to the crucial role of environmental and lifestyle risk factors in determining the disease occurrence. An international multicentre case–control study of Environmental Risk Factors In Multiple Sclerosis (EnvIMS) has been launched in Norway, Sweden, Italy, Serbia and Canada, aimed to examine MS environmental risk factors in a large study population and disclose reciprocal interactions. To ensure equivalent methodology in detecting age-related past exposures in individuals with and without MS across the study sites, a new questionnaire (EnvIMS-Q) is presented.
Materials and methods: EnvIMS-Q builds on previously developed guidelines for epidemiological studies in MS and is a 6-page self-administered postal questionnaire. Participants are de-identified through the use of a numerical code. Its content is identical for cases and controls including ‘core’ and population-specific questions as proxies for vitamin D exposure (sun exposure, dietary habits and supplementation), childhood infections (including infectious mononucleosis) and cigarette smoking. Information on possible confounders or effect modifiers is also obtained. EnvIMS-Q was initially drafted in English and subsequently translated into Italian, Serbian, Norwegian, Swedish and French-Canadian. EnvIMS-Q has been tested for acceptability, feasibility and reliability.
Results and Conclusions: EnvIMS-Q has shown cross-cultural feasibility, acceptability and reliability in both patients with MS and healthy subjects from all sites. EnvIMS-Q is an efficient tool to ensure proper assessment of age-specific exposure to environmental factors in large multinational population-based case–control studies of MS risk factors
Evidence of early childhood as the susceptibility period in multiple sclerosis: space-time cluster analysis in a Sardinian population
No full textThe authors analyzed the natural history of multiple sclerosis (MS) before onset to identify the period of susceptibility
and exogenous factors that might play a role in causing the disease. Space-time cluster analysis was
performed among northern Sardinians, a genetically stable Italian population that showed an increasing risk of MS
between 1965 and 1999. Residence changes from birth to clinical onset were recorded for all MS patients with
clinical onset between 1965 and 1999 in the province of Sassari. Closeness in space and time was defined as living
in the same municipality and differing in year of birth by 1, 2, or 5 years. Analyses were performed for the period
from birth to age 25 years or MS onset and in demographic and clinical subgroups. Clustering was substantial in
early childhood. Clustering was most marked in the most recent cases, among women, and among patients with
early age at onset, a relapsing-remitting course, and in the eastern subarea. No clustering was found when
closeness in time was defined as a fixed number of years before onset, which argues against a fixed latency
period. Early childhood seemed to be a period of increased susceptibility to MS. This evidence and the increasing
incidence of MS in northern Sardinia are compatible with a change in environmental exposure
Does low socioeconomic status in early life protect against multiple sclerosis? A multinational, case-control study
No full textBackground and purpose: The findings from existing research on the association between socioeconomic status (SES) and multiple sclerosis (MS) are inconsistent. Most previous studies are limited to one country and do not adequately adjust for other risk factors for the disease. Methods: The association between SES and MS was examined using data from the multinational Environmental Risk Factors in Multiple Sclerosis (EnvIMS) case-control study, comprising 2144 cases and 3859 controls from Norway, Canada and Italy. Multiple logistic regression was used to estimate the odds ratios and 95% confidence intervals for the association between early life SES, measured by parental educational level, and MS. Analyses were adjusted for age, sex, sunlight exposure, history of infectious mononucleosis, smoking, obesity and family size. Results: Relative to those whose parents had primary school education or below, the adjusted odds ratio (95% confidence interval) for MS amongst individuals with university-educated parents, and the P value for trend across education levels, were 1.45 (1.03-2.05) in Canada (P for trend 0.030), 1.09 (0.85-1.39) in Norway (P for trend 0.395) and 0.65 (0.39-1.07) in Italy (P for trend 0.158). Conclusion: There is no consistent association between parental SES and MS risk in Norway, Canada and Italy, with a protective effect of low SES only found in Canada
Risk of cancer after lung transplantation for COPD
No full textMagnus Ekström,1 Gerdt C Riise,2 Hanan A Tanash3 1Department of Clinical Sciences, Division of Respiratory Medicine & Allergology, Lund University, Lund, Sweden; 2Department of Respiratory Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden; 3Department of Respiratory Medicine, Skåne University Hospital, Lund University, Malmö, Sweden Background: The risk of cancer is increased and affects survival after lung transplantation (LTx), but has not been well characterized in COPD. We aimed to evaluate the incidence and prognosis of cancer following LTx for COPD.Methods: A prospective, population-based study of patients undergoing LTx for end-stage COPD at the two transplantation centers in Sweden between 1990-2013, with follow-up for incident cancer and death, using national registers. The excess risk of cancer was calculated as standardized incidence ratios compared with the general population matched for age, sex, and calendar year. Risk factors for cancer were analyzed using Fine-Gray regression, and survival after cancer diagnosis with Kaplan–Meier.Results: In total, 331 patients (mean age 55.4 years; 64% women; 97% former smokers) were included. At a median follow-up of 2.8 years, 35% of patients had developed cancer and the risk was increased more than 10-fold ([95% CI] 8.1-11.8). The highest excess risks were for non-Hodgkin lymphoma (20.8-66.7), skin cancer (20.3-35.2), lung (11.7-31.2), liver (3.6-51.6), and colorectal cancer (6.1-19.5). Median survival was longer for skin cancer (8 years; 95% CI, 3-15) compared with non-skin cancer (4 years; 95% CI, 2.8-4.8; p<0.001).Conclusion: The cancer risk is markedly increased after LTx for COPD. It could not be predicted by the factors evaluated, but contributed significantly to a negative prognosis. Keywords: cancer, COPD, lung transplantation, severe alpha-1-antitrypsin deficiency, survival 
T Cell Responses and Regulation and the Impact of In Vitro IL-10 and TGF-beta Modulation During Treatment of Active Tuberculosis
No full textMycobacterium tuberculosis (Mtb) is particularly challenging for the immune system being an intracellular pathogen, and a variety of T cell subpopulations are activated by the host defence mechanism. In this study, we investigated T cell responses and regulation in active TB patients with drug-sensitive Mtb (N = 18) during 24 weeks of efficient anti-TB therapy. T cell activation, differentiation, regulatory T cell (Treg) subsets, Mtb-induced T cell proliferation and in vitro IL10 and TGF-beta modulation were analysed by flow cytometry at baseline and after 8 and 24 weeks of therapy, while soluble cytokines in culture supernatants were analysed by a 9-plex Luminex assay. Successful treatment resulted in significantly reduced co-expression of HLA-DR/CD38 and PD-1/CD38 on both CD4(+) and CD8(+) T cells, while the fraction of CD4+ CD25 high CD127 low Tregs (P = 0.017) and CD4(+) CD25(high) CD127(low) CD147(+) Tregs (P = 0.029) showed significant transient increase at week 8. In vitro blockade of IL-10/TGF-beta upon Mtb antigen stimulation significantly lowered the fraction of ESAT-6-specific CD4(+) CD25(high) CD127(low) Tregs at baseline (P = 0.047), while T cell proliferation and cytokine production were unaffected. Phenotypical and Mtb-specific T cell signatures may serve as markers of effective therapy, while the IL-10/ TGF-beta pathway could be a target for early inhibition to facilitate Mtb clearance. However, larger clinical studies are needed for verification before concluding
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