216 research outputs found

    Reconsidering Res Judicata: A Comparative Perspective

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    We aimed to prospectively investigate the paternal antigen-induced cytokine secretion by peripheral blood mononuclear cells (PBMCs) in response to hormone treatment in women undergoing in vitro fertilisation (IVF) and to examine the predictive value of the cytokine secretion profile in the outcome of IVF treatment, in a pilot study. Twenty-five women were included and IVF treatment was successful for six and unsuccessful for 19 women. Blood samples were collected before IVF treatment, on four occasions during IVF and four weeks after embryo transfer. The numbers of Th1-, Th2- and Th17-associated cytokine-secreting cells and cytokine levels in cell supernatants were analysed by enzyme-linked immunospot-forming (ELISpot), enzyme-linked immune-sorbent (ELISA) or Luminex assay. None of the cytokines (IFN-γ, IL-4, IL-5, IL-10, IL-12, IL-13, IL-17, TNF and GM-CSF) had any predictive value regarding IVF outcome. The majority of the cytokines reached their peak levels at ovum pick-up, suggesting an enhancing influence of the hormonal stimulation. Pregnancy was associated with a high number of IL-4-, IL-5- and IL-13-secreting cells four weeks after ET. In conclusion, the results do not support our hypothesis of a more pronounced peripheral Th1 and Th17 deviation towards paternal antigens in infertile women with an unsuccessful IVF outcome, although this is based on a small number of observations. A larger study is required to confirm this conclusion. Higher numbers of Th2-associated cytokine-secreting cells in pregnant women four weeks after ET do corroborate the hypothesis of a Th2 deviation during pregnancy

    Clinical, diagnostic and immunological characteristics of patients with possible neuroborreliosis without intrathecal Ig-synthesis against Borrelia antigen in the cerebrospinal fluid

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    The diagnosis of neuroborreliosis is not always straightforward. Intrathecal immunoglobulin (Ig) synthesis against Borrelia antigen may not be detected, at least early in the disease course. Also other neurological and infectious diagnoses have to be considered. We have studied patients with clinical possible neuroborreliosis without intrathecal Ig synthesis against Borrelia antigen in the cerebrospinal fluid (CSF) (n=17). Diagnosis was based on typical clinical history and at least one of the following findings; mononuclear leucocytosis in the CSF (n=4); typical erythema migrans >5 cm in diameter in relation to debut of symptoms (n=8); prompt clinical response to antibiotic teratment (n=14). Also other possible diagnoses had to be excluded. Seventeen patients first investigated because of suspected neuroborreliosis but later confirmed with other diagnoses were used as controls. All patients had a lumbar puncture. Borrelia specific IFN-γ and IL-4 secretion was investigated in peripheral blood (PBL) and CSF with an ELISPOT assay. Polymerase chain reaction (PCR) was used to reveal any Borrelia antigen in the CSF. Six of 17 patients with possible neuroborreliosis showed high IFN-γ secretion in peripheral blood, otherwise we found no statistically significant differences between the groups. PCR did not reveal any Borrelia antigen in CSF. The diagnosis and treatment of possible but not confirmed neuroborreliosis is a clinical challenge. The clinical response to treatment may be the best option in these cases

    Indications of Th1 and Th17 responses in cerebrospinal fluid from patients with Lyme neuroborreliosis: a large retrospective study

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    <p>Abstract</p> <p>Background</p> <p>Previous studies indicate that successful resolution of Lyme neuroborreliosis (NB) is associated with a strong T helper (Th) 1-type cytokine response in the cerebrospinal fluid (CSF) followed by a down-regulating Th2 response, whereas the role of the recently discovered Th17 cytokine response is unknown.</p> <p>Methods</p> <p>To investigate the relative contribution of different Th associated cytokine/chemokine responses, we used a multiple bead array to measure the levels of CXCL10 (Th1 marker), CCL22 (Th2 marker), IL-17 (Th17 marker) and CXCL8 (general inflammation marker), in serum and in CSF from untreated patients with confirmed NB (n = 133), and non-NB patients (n = 96), and related the findings to clinical data. Samples from patients with possible early NB (n = 15) and possible late NB (n = 19) were also analysed, as well as samples from an additional control group with orthopaedic patients (n = 17), where CSF was obtained at spinal anaesthesia.</p> <p>Results</p> <p>The most prominent differences across groups were found in the CSF. IL-17 was elevated in CSF in 49% of the patients with confirmed NB, but was not detectable in the other groups. Patients with confirmed NB and possible early NB had significantly higher CSF levels of CXCL10, CCL22 and CXCL8 compared to both the non-NB group and the control group (p < 0.0001 for all comparisons). Patients in the early NB group, showing a short duration of symptoms, had lower CCL22 levels in CSF than did the confirmed NB group (p < 0.0001). Furthermore, patients within the confirmed NB group showing a duration of symptoms <2 weeks, tended to have lower CCL22 levels in CSF than did those with longer symptom duration (p = 0.023). Cytokine/chemokine levels were not correlated with clinical parameters or to levels of anti-<it>Borrelia</it>-antibodies.</p> <p>Conclusion</p> <p>Our results support the notion that early NB is dominated by a Th1-type response, eventually accompanied by a Th2 response. Interestingly, IL-17 was increased exclusively in CSF from patients with confirmed NB, suggesting a hitherto unknown role for Th17 in NB. However, for conclusive evidence, future prospective studies are needed.</p

    Reinstating Vacated Findings in Employment Discrimination Class Actions: Reconciling General Telephone Co. v. Falcon With Hill v. Western Electric Co.

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    Type 2 T-helper cell (Th2)-skewed immunity is associated with successful pregnancy and the ability to easily direct immune responses to a Th2-polarised profile may be an evolutionary benefit. The Th2-like immunity associated with allergic disease might generate favourable effects for the maintenance of pregnancy, but could also promote development of Th2-like immune responses and allergic disease in the offspring. The aim of this study was to explore, by using IgE as a stable proxy for Th2, the Th1/Th2 balance in allergic and non-allergic women by measuring allergen-specific and total IgE antibody levels in plasma during pregnancy and after delivery. Specific and total IgE antibody levels were determined by ImmunoCAP technology at five occasions during pregnancy (gestational weeks 10-12, 15-16, 25, 35 and 39), as well as at 2 and 12 months after delivery. Thirty-six women without and 20 women with allergic symptoms were included, of whom 13 were sensitised with allergic symptoms and 30 were non-sensitised without allergic symptoms. The levels of total IgE, but not allergen-specific IgE, were increased during early pregnancy when compared to 12 months after delivery in the sensitised women with allergic symptoms, but not in the non-sensitised women without allergic symptoms (pandlt;0.01). This increase in total IgE levels during early pregnancy only in the sensitised women with allergic symptoms indicates that allergy is associated with an enhanced Th2 deviation during pregnancy.Original Publication: Martina Sandberg, Anne Frykman, Yvonne Jonsson, Marie Persson, Jan Ernerudh, Göran Berg, Leif Matthiesen, Christina Ekerfelt and Maria Jenmalm, Total and allergen-specific IgE levels during and after pregnancy in relation to maternal allergy, 2009, JOURNAL OF REPRODUCTIVE IMMUNOLOGY, (81), 1, 82-88. http://dx.doi.org/10.1016/j.jri.2009.04.003 Copyright: Elsevier Science B.V., Amsterdam. http://www.elsevier.com/</p

    Даследаванне рэкламы фестывальнага турызму

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    Материалы XII Междунар. науч. конф. студентов, магистрантов, аспирантов и молодых ученых, Гомель, 16–17 мая 2019 г

    Marginal-Zone B-Cells Are Main Producers of IgM in Humans, and Are Reduced in Patients With Autoimmune Vasculitis

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    In mice, B1 and marginal zone (MZ) B-cells play an important role in prevention of autoimmunity through production of regulatory cytokines and natural antibodies. There is limited knowledge about the human counterparts of these cells. We therefore investigated functions of MZ-like B-cells and the frequency of circulating MZ-like and B1-like B-cells in healthy controls (HC), as well as in patients with autoimmune vasculitis to learn more about the role of these cells in autoimmune disease. After stimulation with CpG oligodeoxynucleotides (ODN) of class B in vitro, MZ-like B-cells were the main producers of IgM whereas switched memory B-cells primarily produced IgG and IgA. TNF and IL-10 were produced by both MZ-like and switched memory B-cells. Neither antibody nor TNF/IL-10 production by the B-cell subsets differed between patients and HC. Patients with autoimmune vasculitis, irrespective of disease activity, had lower percentage and absolute numbers of circulating MZ-like B-cells, and lower absolute numbers of B1-like B-cells. The percentage of B1-like B-cells was reduced during active disease. These findings remained significant when the analysis was confined to active treatment-naïve patients (disease onset).Our results suggest that human innate-like B-cells might have a physiological role in prevention of autoimmunity

    Testing of the functional mathematical model of analysis of mechanisms of linkage of universal energy tools and general purpose tractor

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    Представлено формализованное описание проверки функциональной математической модели процесса перевода в транспортное положение косилки-плющилки прицепной КПП-4,2, агрегатируемой с универсальным энергетическим средством УЭС-2-280А и трактором общего назначения БЕЛАРУС 2022. Расчет выходных параметров механизмов навески УЭС-2-280А и БЕЛАРУС 2022 выполнен с помощью различных аналитических выражений. Идентичность сравниваемых результатов расчета выходных параметров механизмов навески УЭС-2-280А и БЕЛАРУС 2022 позволяет сделать вывод о правильности разработанной функциональной математической модели механизма навески, эффективной для мобильных энергетических средств.The article presents a formalized description of the checking of the functional mathematical model of the process of transferring to transport position of pull-type mower conditioners PTMC-4,2, aggregated with universal power tool UPT-2-280А and general-purpose tractor BELARUS 2022. Calculation of the output parameters of linkage mechanisms UPT-2-280А and BELARUS 2022 is performed using various analytical expressions. The identity of the compared results of calculating the output parameters of the linkage mechanisms UPT-2-280А and BELARUS 2022 allows to make a conclusion about the correctness of the developed functional mathematical model of the linkage mechanism, effective for mobile power equipment

    Integrated genomic and prospective clinical studies show the importance of modular pleiotropy for disease susceptibility, diagnosis and treatment

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    Background: Translational research typically aims to identify and functionally validate individual, disease-specific genes. However, reaching this aim is complicated by the involvement of thousands of genes in common diseases, and that many of those genes are pleiotropic, that is, shared by several diseases. Methods: We integrated genomic meta-analyses with prospective clinical studies to systematically investigate the pathogenic, diagnostic and therapeutic roles of pleiotropic genes. In a novel approach, we first used pathway analysis of all published genome-wide association studies (GWAS) to find a cell type common to many diseases. Results: The analysis showed over-representation of the T helper cell differentiation pathway, which is expressed in T cells. This led us to focus on expression profiling of CD4(+) T cells from highly diverse inflammatory and malignant diseases. We found that pleiotropic genes were highly interconnected and formed a pleiotropic module, which was enriched for inflammatory, metabolic and proliferative pathways. The general relevance of this module was supported by highly significant enrichment of genetic variants identified by all GWAS and cancer studies, as well as known diagnostic and therapeutic targets. Prospective clinical studies of multiple sclerosis and allergy showed the importance of both pleiotropic and disease specific modules for clinical stratification. Conclusions: In summary, this translational genomics study identified a pleiotropic module, which has key pathogenic, diagnostic and therapeutic roles
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