Analiza efektywności techniki MLPA w inwazyjnej diagnostyce prenatalnej najczęstszych aneuploidii

Cel badania: Ustalenie efektywności metody MLPA (multiplex ligation dependent probe amplification) w prenatalnej diagnostyce najczęściej występujących aneuploidii (chromosomów 21, 18, 13, X oraz Y) oraz porównanie wyników uzyskanych tą metodą z wynikami rutynowych technik prążkowych. Materiał i metoda: Przeprowadzono badanie metodą MLPA z zastosowaniem zestawu sond SALSA MLPA P095 (MRC – Holland) na 195 próbkach DNA wyizolowanego z materiału pochodzącego z inwazyjnych badań prenatalnych wykonanych w Pracowni USG SPSK im. Prof. Orłowskiego od października 2008 r. do lipca 2012 r. u pacjentek o podwyższonym ryzyku aberracji chromosomowych u płodu oraz 5 próbkach materiału po poronieniu indukowanym. Jednocześnie prowadzono hodowle komórkowe i oceniano kariotyp klasyczną metodą cytogenetyczną. Wyniki: Kariotyp oznaczono w 192 badaniach prenatalnych (98,5%; 192/195). W 52 przypadkach (26,8%) stwierdzono nieprawidłowy kariotyp płodu – w większości proste aneuploidie chromosomów 13, 18, 21, X i Y (86,5%, 45/52). Wynik metodą MLPA udało się uzyskać w 180 próbkach DNA z materiału pobranego prenatalnie (92,3 180/195). Bezwzględna czułość i swoistość metody MLPA wyniosła 100%. W dziewięciu próbkach pobranych prenatalnie metodą MLPA nie zidentyfikowano aberracji wykrytych klasyczną metodą prążkową lub FISH. W żadnym z tych przypadków nie było możliwe uzyskanie rzeczywistego wyniku stosowanym zestawem sond. We wszystkich próbkach materiału po poronieniu udało się przeprowadzić reakcję MLPA. Wnioski: MLPA jest skuteczną metodą wykrywania najczęstszych aneuploidii w diagnostyce prenatalnej. Ze względu na małą ilość przeprowadzonych reakcji na materiale po poronieniu, ocena przydatności metody w tych przypadkach wymaga dalszych badań

VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses

VISTA suppresses T cell proliferation and cytokine production and can influence autoimmunity and antitumor responses in mice

Kinesiophobia in People with Multiple Sclerosis and Its Relationship with Physical Activity, Pain and Acceptance of Disease

Background and Objectives: Multiple sclerosis (MS) is the most common chronic demyelinating disease. Factors that reduce the occurrence of symptoms include physical activity (PA). However, the data indicate that PA levels among people with MS are lower than those of healthy peers. The cause may be kinesiophobia. The aim of the study was to determine the level of kinesiophobia among people with MS and its relationship with age, disease duration, functional status, PA, and degree of acceptance of the disease. Materials and Methods: Eighty people aged 35–69 were examined: 60 women (75%) and 20 men (25%). The Expanded Disability Status Scale (EDSS) was used to determine the level of disability (median: 3.50; min–max: 1–6). The research questionnaire consisted of a metric section, Visual Analogue Scale (VAS) for pain, Tampa Scale of Kinesiophobia (TSK), Acceptance of Illness Scale (AIS), and Modified Baecke Questionnaire for Older Adults for physical activity. Results: Of the respondents, 52.50% were characterized by a high level of kinesiophobia (>37 points). Correlation analysis: TSK and PA showed the following: r = −0.363 (p = 0.001). Regression explains kinesiophobia in 44% (R2 = 0.4364; p p p p Conclusions: The problem of kinesiophobia is significant in MS patients, and its predictors are the functional status of the patients, low degree of acceptance of the disease, and low level of physical activity. The age and duration of the disease do not determine the problem of fear of movement

Molecular mechanism and function of CD40/CD40L engagement in the immune system

During the generation of a successful adaptive immune response, multiple molecular signals are required. A primary signal is the binding of cognate antigen to an antigen receptor expressed by T and B lymphocytes. Multiple secondary signals involve the engagement of costimulatory molecules expressed by T and B lymphocytes with their respective ligands. Because of its essential role in immunity, one of the best characterized of the costimulatory molecules is the receptor CD40. This receptor, a member of the tumor necrosis factor receptor family, is expressed by B cells, professional antigen-presenting cells, as well as non-immune cells and tumors. CD40 binds its ligand CD40L, which is transiently expressed on T cells and other non-immune cells under inflammatory conditions. A wide spectrum of molecular and cellular processes is regulated by CD40 engagement including the initiation and progression of cellular and humoral adaptive immunity. In this review, we describe the downstream signaling pathways initiated by CD40 and overview how CD40 engagement or antagonism modulates humoral and cellular immunity. Lastly, we discuss the role of CD40 as a target in harnessing anti-tumor immunity. This review underscores the essential role CD40 plays in adaptive immunity

Isolation Related to the COVID-19 Pandemic in People Suffering from Parkinson’s Disease and Activity, Self-Assessment of Physical Fitness and the Level of Affective Disorders

Background: Staying at home for long periods and limiting various types of activities and social contacts due to the COVID-19 pandemic may have negative consequences for health. This is especially true for people suffering from chronic diseases, in whom an appropriate level of activity and social contacts delay the progress of the disease. This group includes people diagnosed with Parkinson’s disease—PD. Aim: It was decided to investigate the effect of COVID-19 isolation related to self-assessment of physical fitness, physical activity, and the level of anxiety and depression in people with PD. Methods: The study included 30 patients diagnosed with Parkinson’s disease. We compared the results of the pre-pandemic questionnaire and the telephone interview with the same questions—after the period of isolation due to COVID-19. The questionnaire included questions about physical activity and fitness self-assessment. The level of affective disorders was tested using HADS. Results: There was a statistically significant decrease in the physical activity of the respondents after isolation related to COVID-19 (p < 0.05). Self-assessment of physical fitness also decreased, but the differences were not statistically significant. In the post-isolation study, only 50% of the respondents had normative values for anxiety and only 40% for depression. The analysis showed that the level of physical activity—the independent variable, explains anxiety in 30% and depression in 27%. Conclusions: Pandemic isolation has significantly reduced physical activity in PD patients. There was a certain drop in the self-esteem of physical fitness in these people. Physical fitness is an important predictor of preventing the affective disorders of anxiety and depression. The effects of isolation due to COVID-19 require further research

Kinesiophobia in Stroke Patients, Multiple Sclerosis and Parkinson’s Disesase

Background: Stroke (S), multiple sclerosis (MS), Parkinson’s disease (PD) are chronic neurological diseases that are a challange for public health and represent a real social problem. Physical activity (PA) improves functional performance, reduces various symptoms in PD and MS, in stroke- reduced neurological impairment of patients and provides a chance for independence. One of the main obstacles in successful rehabilitation is patients’ movement passivity. The reason might be the psychological aspects, in particular fear of movement—kinesiophobia. Aim: To determine how many patients with S, MS, and PD suffer from kinsiophobia and what factors influence this process. Methods: Fifty patients after stroke, eighty one MS patients and sixty one PD patients were consecutively recruited from hospital and outpatients clinics. The sociodemographic data, self- assesment of fitness, Visual Analogue Scale (VAS) for pain, Tampa Scale of Kinesiophobia (TSK) and The Modified Baecke Questionnarie for Older Adults for physical activity were collected. A score >37 was considered to indicate a high level of kinesiophobia according to the TSK. Results: High level of kinesiophobia was shown in 66.67% of the subjects. TSK medians in particular illnesses were above the cut-off score and amounted: S—42.50 points; MS—38 points; PD—42.00 points. Regression showed 15% of fluctuation of variance (R2 = 0.1498; p < 0.0001), where regression factor showed: for mobility self-assessment: b = −0.2137 and for the age b = 0.0065. Conclusions: Kinesiophobia among the patients suffering from S, MS and PD concerns most of the subjects. Predictors of kinesiophobia are: limitations connected with functioning and age. The meaning of kinesiophobia in neurological disorders requires further research

Dendritic cells require the NF-kappaB2 pathway for cross-presentation of soluble antigens

NF-kappaB-inducing kinase (NIK) is responsible for activation of the non-canonical p100 processing pathway of NF-kappaB activation. This kinase has been shown to be critical for activation of this pathway after signaling through several TNF family members including CD40. The functional importance of this pathway in CD40 and TLR-induced dendritic cell (DC) differentiation was studied in vivo in the alymphoplasia (Aly) mouse. The Aly mouse expresses a mutant NIK molecule that prohibits the induction of the non-canonical pathway. We show that while MHC class II presentation and in vivo migration of Aly DCs is intact, these cells are unable to cross-prime CD8+ T cells to exogenous Ag. Gene expression array analysis of DCs matured in vivo indicates multiple defects in Ag processing pathways after maturation and provide a global view of the genes that are regulated by the NF-kappaB2 pathway in DCs. These experiments indicate a possible role for NIK in mediating cross-priming of soluble Ag. In addition, our findings explain the profound immune unresponsiveness of the Aly mouse

Mast cells impair the development of protective anti-tumor immunity

Mast cells have emerged as critical intermediaries in the regulation of peripheral tolerance. Their presence in many precancerous lesions and tumors is associated with a poor prognosis, suggesting mast cells may promote an immunosuppressive tumor microenvironment and impede the development of protective anti-tumor immunity. The studies presented herein investigate how mast cells influence tumor-specific T cell responses. Male MB49 tumor cells, expressing HY antigens, induce anti-tumor IFN-γ+ T cell responses in female mice. However, normal female mice cannot control progressive MB49 tumor growth. In contrast, mast cell-deficient c-Kit(Wsh) (W(sh)) female mice controlled tumor growth and exhibited enhanced survival. The role of mast cells in curtailing the development of protective immunity was shown by increased mortality in mast cell-reconstituted W(sh) mice with tumors. Confirmation of enhanced immunity in female W(sh) mice was provided by (1) higher frequency of tumor specific IFN-γ+ CD8+ T cells in tumor-draining lymph nodes compared with WT females and (2) significantly increased ratios of intratumoral CD4+ and CD8+ T effector cells relative to tumor cells in W(sh) mice compared to WT. These studies are the first to reveal that mast cells impair both regional adaptive immune responses and responses within the tumor microenvironment to diminish protective anti-tumor immunity

Tryptophan hydroxylase-1 regulates immune tolerance and inflammation

Nutrient deprivation based on the loss of essential amino acids by catabolic enzymes in the microenvironment is a critical means to control in ammatory responses and immune tolerance. Here we report the novel nding that Tph-1 (tryptophan hydroxylase-1), a synthase which catalyses the conversion of tryptophan to serotonin and exhausts tryptophan, is a potent regulator of immunity. In models of skin allograft tolerance, tumor growth, and experimental autoimmune encephalomyelitis, Tph-1 de ciency breaks allograft tolerance, induces tumor remission, and intensi es neuroin ammation, respectively. All of these effects of Tph-1 de ciency are independent of its downstream product serotonin. Because mast cells (MCs) appear to be the major source of Tph-1 and restoration of Tph-1 in the MC compartment in vivo compensates for the defect, these experiments introduce a fundamentally new mecha- nism of MC-mediated immune suppression that broadly impacts multiple arms of immunity