WorldWideScience

Sample records for autoimmune diseases of the nervous system

  1. Neuromyelitis optica (NMO) - an autoimmune disease of the central nervous system (CNS)

    DEFF Research Database (Denmark)

    Asgari, N; Owens, T; Frøkiaer, J

    2010-01-01

    Asgari N, Owens T, Frøkiaer J, Stenager E, Lillevang ST, Kyvik KO. Neuromyelitis optica (NMO) - an autoimmune disease of the central nervous system (CNS).
Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2010.01416.x.
© 2010 John Wiley & Sons A/S. In the past 10 years, neuromyelitis optica (NMO) has...... or by intrathecal administration to naive mice. NMO may be characterized as a channelopathy of the central nervous system with autoimmune characteristics....

  2. Autoimmune Neurology of the Central Nervous System.

    Science.gov (United States)

    Tobin, W Oliver; Pittock, Sean J

    2017-06-01

    This article reviews the rapidly evolving spectrum of autoimmune neurologic disorders with a focus on those that involve the central nervous system, providing an understanding of how to approach the diagnostic workup of patients presenting with central nervous system symptoms or signs that could be immune mediated, either paraneoplastic or idiopathic, to guide therapeutic decision making. The past decade has seen a dramatic increase in the discovery of novel neural antibodies and their targets. Many commercial laboratories can now test for these antibodies, which serve as diagnostic markers of diverse neurologic disorders that occur on an autoimmune basis. Some are highly specific for certain cancer types, and the neural antibody profiles may help direct the physician's cancer search. The diagnosis of an autoimmune neurologic disorder is aided by the detection of an objective neurologic deficit (usually subacute in onset with a fluctuating course), the presence of a neural autoantibody, and improvement in the neurologic status after a course of immunotherapy. Neural autoantibodies should raise concern for a paraneoplastic etiology and may inform a targeted oncologic evaluation (eg, N-methyl-D-aspartate [NMDA] receptor antibodies are associated with teratoma, antineuronal nuclear antibody type 1 [ANNA-1, or anti-Hu] are associated with small cell lung cancer). MRI, EEG, functional imaging, videotaped evaluations, and neuropsychological evaluations provide objective evidence of neurologic dysfunction by which the success of immunotherapy may be measured. Most treatment information emanates from retrospective case series and expert opinion. Nonetheless, early intervention may allow reversal of deficits in many patients and prevention of future disability.

  3. Expanding Role of T Cells in Human Autoimmune Diseases of the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Deepti Pilli

    2017-06-01

    Full Text Available It is being increasingly recognized that a dysregulation of the immune system plays a vital role in neurological disorders and shapes the treatment of the disease. Aberrant T cell responses, in particular, are key in driving autoimmunity and have been traditionally associated with multiple sclerosis. Yet, it is evident that there are other neurological diseases in which autoreactive T cells have an active role in pathogenesis. In this review, we report on the recent progress in profiling and assessing the functionality of autoreactive T cells in central nervous system (CNS autoimmune disorders that are currently postulated to be primarily T cell driven. We also explore the autoreactive T cell response in a recently emerging group of syndromes characterized by autoantibodies against neuronal cell-surface proteins. Common methodology implemented in T cell biology is further considered as it is an important determinant in their detection and characterization. An improved understanding of the contribution of autoreactive T cells expands our knowledge of the autoimmune response in CNS disorders and can offer novel methods of therapeutic intervention.

  4. Neuromyelitis optica (NMO)--an autoimmune disease of the central nervous system (CNS).

    Science.gov (United States)

    Asgari, N; Owens, T; Frøkiaer, J; Stenager, E; Lillevang, S T; Kyvik, K O

    2011-06-01

    In the past 10 years, neuromyelitis optica (NMO) has evolved from Devic's categorical clinical description into a broader disease spectrum. Serum IgG antibodies have been identified in NMO patients with the water channel aquaporin-4 (AQP4) as their main target antigen. AQP4 antibodies/NMO-IgG have been shown to be a highly specific and moderately sensitive serum biomarker for NMO. The immunopathology of NMO lesions supports that anti-AQP4 antibodies/NMO-IgG are involved in the pathogenesis of NMO. In vitro studies have demonstrated that human NMO-IgG induce necrosis and impair glutamate transport in astrocytes. Certain ethnic groups, notably of Asian and African origin, seem to be more susceptible to NMO than others. The genetic background for these putative differences is not known, a weak human leucocyte antigen association has been identified. AQP4 gene variants could represent a genetic susceptibility factor for different clinical phenotypes within the NMO spectrum. Experimental models have been described including a double-transgenic myelin-specific B- and T-cell mouse. NMO-like disease has been induced with passive transfer of human anti-AQP4 antibodies to the plasma of mice with pre-established experimental autoimmune encephalomyelitis or by intrathecal administration to naive mice. NMO may be characterized as a channelopathy of the central nervous system with autoimmune characteristics. © 2010 John Wiley & Sons A/S.

  5. Peptide-based approaches to treat asthma, arthritis, other autoimmune diseases and pathologies of the central nervous system

    OpenAIRE

    Hauff, K.; Zamzow, C.; Law, W. J.; De Melo, J.; Kennedy, K.; Los, Marek Jan

    2005-01-01

    In this review we focus on peptide- and peptidomimetic-based approaches that target autoimmune diseases and some pathologies of the central nervous system. Special attention is given to asthma, allergic rhinitis, osteoarthritis, and Alzheimer's disease, but other related pathologies are also reviewed, although to a lesser degree. Among others, drugs like Diacerhein and its active form Rhein, Pralnacasan, Anakinra (Kineret), Omalizumab, an antibody "BION-1", directed against the common beta-ch...

  6. Proinflammatory bacterial peptidoglycan as a cofactor for the development of central nervous system autoimmune disease

    NARCIS (Netherlands)

    L. Visser (Lizette); J.D. Laman (Jon); H.J. de Heer; L.A. Boven (Leonie); M. van Meurs (Marjan); M.J. Melief (Marie-José); U. Zahringer; J. van Strijp; B.N.M. Lambrecht (Bart); E.E.S. Nieuwenhuis (Edward); D.A.J. van Riel (Debby)

    2005-01-01

    textabstractUpon stimulation by microbial products through TLR, dendritic cells (DC) acquire the capacity to prime naive T cells and to initiate a proinflammatory immune response. Recently, we have shown that APC within the CNS of multiple sclerosis (MS) patients contain peptidoglycan (PGN), a major

  7. Phenotype of Antigen Unexperienced TH Cells in the Inflamed Central Nervous System in Experimental Autoimmune Encephalomyelitis.

    Science.gov (United States)

    Franck, Sophia; Paterka, Magdalena; Birkenstock, Jerome; Zipp, Frauke; Siffrin, Volker; Witsch, Esther

    2017-06-01

    Multiple sclerosis is a chronic, disseminated inflammation of the central nervous system which is thought to be driven by autoimmune T cells. Genetic association studies in multiple sclerosis and a large number of studies in the animal model of the disease support a role for effector/memory T helper cells. However, the mechanisms underlying relapses, remission and chronic progression in multiple sclerosis or the animal model experimental autoimmune encephalomyelitis, are not clear. In particular, there is only scarce information on the role of central nervous system-invading naive T helper cells in these processes. By applying two-photon laser scanning microscopy we could show in vivo that antigen unexperienced T helper cells migrated into the deep parenchyma of the inflamed central nervous system in experimental autoimmune encephalomyelitis, independent of their antigen specificity. Using flow cytometric analyses of central nervous system-derived lymphocytes we found that only antigen-specific, formerly naive T helper cells became activated during inflammation of the central nervous system encountering their corresponding antigen.

  8. Serum Neuroinflammatory Disease-Induced Central Nervous System Proteins Predict Clinical Onset of Experimental Autoimmune Encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Itay Raphael

    2017-07-01

    Full Text Available There is an urgent need in multiple sclerosis (MS patients to develop biomarkers and laboratory tests to improve early diagnosis, predict clinical relapses, and optimize treatment responses. In healthy individuals, the transport of proteins across the blood–brain barrier (BBB is tightly regulated, whereas, in MS, central nervous system (CNS inflammation results in damage to neuronal tissues, disruption of BBB integrity, and potential release of neuroinflammatory disease-induced CNS proteins (NDICPs into CSF and serum. Therefore, changes in serum NDICP abundance could serve as biomarkers of MS. Here, we sought to determine if changes in serum NDICPs are detectable prior to clinical onset of experimental autoimmune encephalomyelitis (EAE and, therefore, enable prediction of disease onset. Importantly, we show in longitudinal serum specimens from individual mice with EAE that pre-onset expression waves of synapsin-2, glutamine synthetase, enolase-2, and synaptotagmin-1 enable the prediction of clinical disease with high sensitivity and specificity. Moreover, we observed differences in serum NDICPs between active and passive immunization in EAE, suggesting hitherto not appreciated differences for disease induction mechanisms. Our studies provide the first evidence for enabling the prediction of clinical disease using serum NDICPs. The results provide proof-of-concept for the development of high-confidence serum NDICP expression waves and protein biomarker candidates for MS.

  9. [Parasitic diseases of the central nervous system].

    Science.gov (United States)

    Schmutzhard, E

    2010-02-01

    Central nervous system infections and infestations by protozoa and helminths constitute a problem of increasing importance throughout all of central European and northern/western countries. This is partially due to the globalisation of our society, tourists and business people being more frequently exposed to parasitic infection/infestation in tropical countries than in moderate climate countries. On top of that, migrants may import chronic infestations and infections with parasitic pathogens, eventually also--sometimes exclusively--involving the nervous system. Knowledge of epidemiology, initial clinical signs and symptoms, diagnostic procedures as well as specific chemotherapeutic therapies and adjunctive therapeutic strategies is of utmost important in all of these infections and infestations of the nervous systems, be it by protozoa or helminths. This review lists, mainly in the form of tables, all possible infections and infestations of the nervous systems by protozoa and by helminths. Besides differentiating parasitic diseases of the nervous system seen in migrants, tourists etc., it is very important to have in mind that disease-related (e.g. HIV) or iatrogenic immunosuppression has led to the increased occurrence of a wide variety of parasitic infections and infestations of the nervous system (e. g. babesiosis, Chagas disease, Strongyloides stercoralis infestation, toxoplasmosis, etc.).

  10. Monogenic autoimmune diseases of the endocrine system.

    Science.gov (United States)

    Johnson, Matthew B; Hattersley, Andrew T; Flanagan, Sarah E

    2016-10-01

    The most common endocrine diseases, type 1 diabetes, hyperthyroidism, and hypothyroidism, are the result of autoimmunity. Clustering of autoimmune endocrinopathies can result from polygenic predisposition, or more rarely, may present as part of a wider syndrome due to a mutation within one of seven genes. These monogenic autoimmune diseases show highly variable phenotypes both within and between families with the same mutations. The average age of onset of the monogenic forms of autoimmune endocrine disease is younger than that of the common polygenic forms, and this feature combined with the manifestation of other autoimmune diseases, specific hallmark features, or both, can inform clinicians as to the relevance of genetic testing. A genetic diagnosis can guide medical management, give an insight into prognosis, inform families of recurrence risk, and facilitate prenatal diagnoses. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Deletion of the Mineralocorticoid Receptor in Myeloid Cells Attenuates Central Nervous System Autoimmunity

    Directory of Open Access Journals (Sweden)

    Elena Montes-Cobos

    2017-10-01

    Full Text Available Myeloid cells play an important role in the pathogenesis of multiple sclerosis (MS and its animal model experimental autoimmune encephalomyelitis (EAE. Monocytes, macrophages, and microglia can adopt two distinct phenotypes, with M1-polarized cells being more related to inflammation and autoimmunity while M2-polarized cells contribute to tissue repair and anti-inflammatory processes. Here, we show that deletion of the mineralocorticoid receptor (MR in bone marrow-derived macrophages and peritoneal macrophages caused their polarization toward the M2 phenotype with its distinct gene expression, altered phagocytic and migratory properties, and dampened NO production. After induction of EAE, mice that are selectively devoid of the MR in their myeloid cells (MRlysM mice showed diminished clinical symptoms and ameliorated histological hallmarks of neuroinflammation. T cells in peripheral lymphoid organs of these mice produced less pro-inflammatory cytokines while their proliferation and the abundance of regulatory T cells were unaltered. The numbers of inflammatory monocytes and reactive microglia in the central nervous system (CNS in MRlysM mice were significantly lower and they adopted an M2-polarized phenotype based on their gene expression profile, presumably explaining the ameliorated neuroinflammation. Our results indicate that the MR in myeloid cells plays a critical role for CNS autoimmunity, providing a rational to interfere with diseases such as MS by pharmacologically targeting this receptor.

  12. Time course and cellular localization of interleukin-10 mRNA and protein expression in autoimmune inflammation of the rat central nervous system.

    OpenAIRE

    Jander, S.; Pohl, J.; D'Urso, D.; Gillen, C.; Stoll, G.

    1998-01-01

    Experimental autoimmune encephalomyelitis of the Lewis rat is a T-cell-mediated autoimmune disease of the central nervous system characterized by a self-limiting monophasic course. In this study, we analyzed the expression of the anti-inflammatory cytokine interleukin (IL)-10 at the mRNA and protein level in experimental autoimmune encephalomyelitis actively induced with the encephalitogenic 68-86 peptide of guinea pig myelin basic protein. Semiquantitative reverse transcriptase-polymerase ch...

  13. In vivo imaging in autoimmune diseases in the central nervous system.

    Science.gov (United States)

    Kawakami, Naoto

    2016-07-01

    Intravital imaging is becoming more popular and is being used to visualize cellular motility and functions. In contrast to in vitro analysis, which resembles in vivo analysis, intravital imaging can be used to observe and analyze cells directly in vivo. In this review, I will summarize recent imaging studies of autoreactive T cell infiltration into the central nervous system (CNS) and provide technical background. During their in vivo journey, autoreactive T cells interact with many different cells. At first, autoreactive T cells interact with endothelial cells in the airways of the lung or with splenocytes, where they acquire a migratory phenotype to infiltrate into the CNS. After arriving at the CNS, they interact with endothelial cells of the leptomeningeal vessels or the choroid plexus before passing through the blood-brain barrier. CNS-infiltrating T cells become activated by recognizing endogenous autoantigens presented by local antigen-presenting cells (APCs). This activation was visualized in vivo by using protein-based sensors. One such sensor detects changes in intracellular calcium concentration as an early marker of T cell activation. Another sensor detects translocation of Nuclear factor of activated T-cells (NFAT) from cytosol to nucleus as a definitive sign of T cell activation. Importantly, intravital imaging is not just used to visualize cellular behavior. Together with precise analysis, intravital imaging deepens our knowledge of cellular functions in living organs and also provides a platform for developing therapeutic treatments. Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  14. Constitutive expression of a costimulatory ligand on antigen-presenting cells in the nervous system drives demyelinating disease

    DEFF Research Database (Denmark)

    Zehntner, Simone P; Brisebois, Marcel; Tran, Elise

    2003-01-01

    that transgenic mice constitutively expressing the costimulatory ligand B7.2/CD86 on microglia in the central nervous system (CNS) and on related cells in the proximal peripheral nervous tissue spontaneously develop autoimmune demyelinating disease. Disease-affected nervous tissue in transgenic mice showed...... recipients but not into non-transgenic recipients. These data provide evidence that B7/CD28 interactions within the nervous tissue are critical determinants of disease development. Our findings have important implications for understanding the etiology of nervous system autoimmune diseases such as multiple...

  15. Increased severity of experimental autoimmune encephalomyelitis, chronic macrophage/microglial reactivity, and demyelination in transgenic mice producing tumor necrosis factor-alpha in the central nervous system

    DEFF Research Database (Denmark)

    Taupin, V; Renno, T; Bourbonnière, L

    1997-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is an inflammatory cytokine implicated in a number of autoimmune diseases. Apoptotic cell death is induced by TNF-alpha in vitro, and has been suggested as one cause of autoimmune pathology, including autoimmune demyelinating diseases where oligodendrocytes...... are a target of immune attack. TNF-alpha also regulates macrophage activity which could contribute to autoimmune inflammation. We have expressed TNF-alpha at disease-equivalent levels in the central nervous system of transgenic mice, using a myelin basic protein (MBP) promoter. These mice were normal...... and showed no spontaneous pathology, but they developed experimental autoimmune encephalomyelitis (EAE) with greater severity than nontransgenic controls when immunized with MBP in adjuvant. Unlike nontransgenic controls, EAE then progressed to a nonabating demyelinating disease. Macrophage...

  16. Diazepam treatment reduces inflammatory cells and mediators in the central nervous system of rats with experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Fernández Hurst, Nicolás; Zanetti, Samanta R; Báez, Natalia S; Bibolini, Mario J; Bouzat, Cecilia; Roth, German A

    2017-12-15

    Benzodiazepines are psychoactive drugs and some of them also affect immune cells. We here characterized the inflammatory and infiltrating immune cells in the central nervous system (CNS) during the acute phase of experimental autoimmune encephalomyelitis (EAE) in animals treated with Diazepam. Also, we evaluated the expression of Translocator Protein (18kDa) (TSPO), which is a biomarker of neuroinflammatory diseases. The results indicate that Diazepam exerts protective effects on EAE development, decreasing the incidence of the disease and reducing the number of inflammatory cells in CNS, with a concomitant decrease of TSPO levels in brain tissue and CNS inflammatory CD11b + cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. From cannabis to endocannabinoids in multiple sclerosis: a paradigm of central nervous system autoimmune diseases.

    Science.gov (United States)

    Malfitano, Anna Maria; Matarese, Giuseppe; Bifulco, Maurizio

    2005-12-01

    An increasing body of evidence suggests that cannabinoids have beneficial effects on the symptoms of multiple sclerosis, including spasticity and pain. Endogenous molecules with cannabinoid-like activity, such as the "endocannabinoids", have been shown to mimic the anti-inflammatory properties of cannabinoids through the cannabinoid receptors. Several studies suggest that cannabinoids and endocannabinoids may have a key role in the pathogenesis and therapy of multiple sclerosis. Indeed, they can down regulate the production of pathogenic T helper 1-associated cytokines enhancing the production of T helper 2-associated protective cytokines. A shift towards T helper 2 has been associated with therapeutic benefit in multiple sclerosis. In addition, cannabinoids exert a neuromodulatory effect on neurotransmitters and hormones involved in the neurodegenerative phase of the disease. In vivo studies using mice with experimental allergic encephalomyelitis, an animal model of multiple sclerosis, suggest that the increase of the circulating levels of endocannabinoids might have a therapeutic effect, and that agonists of endocannabinoids with low psychoactive effects could open new strategies for the treatment of multiple sclerosis.

  18. Paraneoplastic and non-paraneoplastic autoimmunity to neurons in the central nervous system

    OpenAIRE

    Melzer, Nico; Meuth, Sven G.; Wiendl, Heinz

    2012-01-01

    Autoimmune central nervous system (CNS) inflammation occurs both in a paraneoplastic and non-paraneoplastic context. In a widening spectrum of clinical disorders, the underlying adaptive (auto) immune response targets neurons with a divergent role for cellular and humoral disease mechanisms: (1) in encephalitis associated with antibodies to intracellular neuronal antigens, neuronal antigen-specific CD8+ T cells seemingly account for irreversible progressive neuronal cell death and neurologica...

  19. Unimpaired Autoreactive T-Cell Traffic Within the Central Nervous System During Tumor Necrosis Factor Receptor-Mediated inhibition of Experimental Autoimmune Encephalomyelitis

    Science.gov (United States)

    Korner, Heinrich; Goodsall, Anna L.; Lemckert, Frances A.; Scallon, Bernard J.; Ghrayeb, John; Ford, Andrew L.; Sedgwick, Jonathon D.

    1995-11-01

    The critical role of tumor necrosis factor (TNF) as a mediator in autoimmune inflammatory processes is evident from in vivo studies with TNF-blocking agents. However, the mechanisms by which TNF, and possibly also its homologue lymphotoxin α, contributes to development of pathology in rheumatoid arthritis and Crohn disease and in animal models like experimental autoimmune encephalomyelitis is unclear. Possibilities include regulation of vascular adhesion molecules enabling leukocyte movement into tissues or direct cytokine-mediated effector functions such as mediation of tissue damage. Here we show that administration of a TNF receptor (55 kDa)-IgG fusion protein prevented clinical signs of actively induced experimental autoimmune encephalomyelitis. Significantly, the total number of CD4^+ T lymphocytes isolated from the central nervous system of clinically healthy treated versus diseased control animals was comparable. By using a CD45 congenic model of passively transferred experimental autoimmune encephalomyelitis to enable tracking of myelin basic protein-specific effector T lymphocytes, prevention of clinical signs of disease was again demonstrated in treated animals but without quantitative or qualitative impediment to the movement of autoreactive T lymphocytes to and within the central nervous system. Thus, despite the uninterrupted movement of specific T lymphocytes into the target tissue, subsequent disease development was blocked. This provides compelling evidence for a direct effector role of TNF/lymphotoxin α in autoimmune tissue damage.

  20. A rare association of localized scleroderma type morphea, vitiligo, autoimmune hypothyroidism, pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis. Case report.

    Science.gov (United States)

    Bonilla-Abadía, Fabio; Muñoz-Buitrón, Evelyn; Ochoa, Carlos D; Carrascal, Edwin; Cañas, Carlos A

    2012-12-20

    The localized scleroderma (LS) known as morphea, presents a variety of clinical manifestations that can include systemic involvement. Current classification schemes divide morphea into categories based solely on cutaneous morphology, without reference to systemic disease or autoimmune phenomena. This classification is likely incomplete. Autoimmune phenomena such as vitiligo and Hashimoto thyroiditis associated with LS have been reported in some cases suggesting an autoimmune basis. To our knowledge this is the first case of a morphea forming part of a multiple autoimmune syndrome (MAS) and presenting simultaneously with autoimmune thrombocytopenic purpura and central nervous system vasculitis. We report an uncommon case of a white 53 year old female patient with LS as part of a multiple autoimmune syndrome associated with pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis presenting a favorable response with thrombopoietin receptor agonists, pulses of methylprednisolone and cyclophosphamide. Is likely that LS have an autoimmune origin and in this case becomes part of MAS, which consist on the presence of three or more well-defined autoimmune diseases in a single patient.

  1. A rare association of localized scleroderma type morphea, vitiligo, autoimmune hypothyroidism, pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis. Case report

    Directory of Open Access Journals (Sweden)

    Bonilla-Abadía Fabio

    2012-12-01

    Full Text Available Abstract Background The localized scleroderma (LS known as morphea, presents a variety of clinical manifestations that can include systemic involvement. Current classification schemes divide morphea into categories based solely on cutaneous morphology, without reference to systemic disease or autoimmune phenomena. This classification is likely incomplete. Autoimmune phenomena such as vitiligo and Hashimoto thyroiditis associated with LS have been reported in some cases suggesting an autoimmune basis. To our knowledge this is the first case of a morphea forming part of a multiple autoimmune syndrome (MAS and presenting simultaneously with autoimmune thrombocytopenic purpura and central nervous system vasculitis. Case presentation We report an uncommon case of a white 53 year old female patient with LS as part of a multiple autoimmune syndrome associated with pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis presenting a favorable response with thrombopoietin receptor agonists, pulses of methylprednisolone and cyclophosphamide. Conclusion Is likely that LS have an autoimmune origin and in this case becomes part of MAS, which consist on the presence of three or more well-defined autoimmune diseases in a single patient.

  2. Chagas' disease and the involvement of the autonomic nervous system.

    Science.gov (United States)

    da Cunha, Ademir Batista

    2003-06-01

    Chagas' disease is a major endemic disease in Latin America and a great cause for concern due to its high incidence: it afflicts 16 to 18 million individuals and places over 90 million people at risk of infection. At present, five mechanisms can be proposed to explain the pathogenesis of chronic Chagas cardiopathy: 1. direct lesion of the tissue by Trypanosoma cruzi; 2. dysfunction of the autonomic nervous system (neurogenic concept); 3. microvascular disease; 4. immunologic reaction; 5. alterations in the extracellular matrix. The neurogenic concept is the most attractive explanation for the pathogenesis of chronic Chagas cardiopathy through the involvement of the autonomic nervous system, an issue that has been prominent ever since Chagas first initiated research in the field. Köberle, in his pioneering studies on the role of the autonomic nervous system in Chagas patients in the 1950s, adopted the technique of neuron counts, whereby he registered a reduction in parasympathetic nerve cells, and thus considered Chagas cardiopathy a "parasympathetic reduction" with predominance of the sympathetic. In the 1960s, systematic studies on autonomic function, organized by Professor Dalmo Amorim, were initiated in the School of Medicine in Ribeirão Preto. Several aspects of cardiac autonomic control were later described independently by teams in Brazil (Ribeirão Preto and Brasília), Argentina (Cordoba) and Venezuela (Mérida). In general, the studies performed in Ribeirăo Preto by Amorim and Marin Neto and in Brasília by Junqueira Jr. reflected the functional involvement of the parasympathetic system, while the studies performed in Córdoba were linked with the view of cardiovascular sympathetic dysfunction. In Brazil, the involvement of the sympathetic system, with relation to the functional aspect of sympathetic denervation, is well characterized by Marin Neto through the assessment of heart rate using the tilt test in both Chagas and control groups. Further

  3. Cytokine production in the central nervous system of Lewis rats with experimental autoimmune encephalomyelitis: dynamics of mRNA expression for interleukin-10, interleukin-12, cytolysin, tumor necrosis factor alpha and tumor necrosis factor beta

    DEFF Research Database (Denmark)

    Issazadeh-Navikas, Shohreh; Ljungdahl, A; Höjeberg, B

    1995-01-01

    The kinetics of mRNA expression in the central nervous system (CNS) for a series of putatively disease-promoting and disease-limiting cytokines during the course of experimental autoimmune encephalomyelitis (EAE) in Lewis rats were studied. Cytokine mRNA-expressing cells were detected in cryosect......The kinetics of mRNA expression in the central nervous system (CNS) for a series of putatively disease-promoting and disease-limiting cytokines during the course of experimental autoimmune encephalomyelitis (EAE) in Lewis rats were studied. Cytokine mRNA-expressing cells were detected...

  4. Involvement of the autonomic nervous system in Chagas heart disease

    Directory of Open Access Journals (Sweden)

    Edison Reis Lopes

    1983-12-01

    Full Text Available The autonomic nervous system and especially the intracardiac autonomic nervous system is involved in Chagas' disease. Ganglionitis and periganglionitis were noted in three groups ofpatients dying with Chagas'disease: 1 Those in heart failure; 2 Those dying a sudden, non violent death and; 3 Those dying as a consequence ofaccidents or homicide. Hearts in the threegroups also revealed myocarditis and scattered involvement of intramyocardial ganglion cells as well as lesions of myelinic and unmyelinic fibers ascribable to Chagas'disease. In mice with experimentally induced Chagas' disease weobserved more intensive neuronal lesions of the cardiac ganglia in the acute phase of infection. Perhaps neuronal loss has a role in the pathogenesis of Chagas cardiomyopathy. However based on our own experience and on other data from the literature we conclude that the loss of neurones is not the main factor responsible for the manifestations exhibited by chronic chagasic patients. On the other hand the neuronal lesions may have played a role in the sudden death ofone group of patients with Chagas'disease but is difficult to explain the group of patients who did not die sudderly but instead progressed to cardiac failure.

  5. Aluminum in the central nervous system (CNS): toxicity in humans and animals, vaccine adjuvants, and autoimmunity.

    Science.gov (United States)

    Shaw, C A; Tomljenovic, L

    2013-07-01

    We have examined the neurotoxicity of aluminum in humans and animals under various conditions, following different routes of administration, and provide an overview of the various associated disease states. The literature demonstrates clearly negative impacts of aluminum on the nervous system across the age span. In adults, aluminum exposure can lead to apparently age-related neurological deficits resembling Alzheimer's and has been linked to this disease and to the Guamanian variant, ALS-PDC. Similar outcomes have been found in animal models. In addition, injection of aluminum adjuvants in an attempt to model Gulf War syndrome and associated neurological deficits leads to an ALS phenotype in young male mice. In young children, a highly significant correlation exists between the number of pediatric aluminum-adjuvanted vaccines administered and the rate of autism spectrum disorders. Many of the features of aluminum-induced neurotoxicity may arise, in part, from autoimmune reactions, as part of the ASIA syndrome.

  6. Imaging in the infectious diseases of the central nervous system

    International Nuclear Information System (INIS)

    Brunet, F.; Gandon, Y.; Heautot, J.F.; Montagne, C.; Michelet, C.; Carsin, M.

    1989-01-01

    The basic signs of the major bacterial, viral, parasitic or mycotic infections of the central nervous system with CT and MRI are described. The problems arising from the presence of the HIV virus are emphasized and the attitude required according to the findings of imaging, is defined [fr

  7. Pathological differences in acute inflammatory demyelinating diseases of the central nervous system.

    Science.gov (United States)

    Wegner, C

    2005-04-01

    This article reviews the different pathological and immunological features of MS, acute variants of MS and acute disseminated encephalomyelitis (ADEM). T-cell-mediated inflammatory reactions are involved in all acute inflammatory diseases of the central nervous system, but the diseases discussed also exhibit distinct immunopathological features. The perivascular infiltrate of T-cells and macrophages seen in ADEM resembles the pathological pattern found in experimental autoimmune encephalomyelitis. In addition, there is evidence that humoral mechanisms play a crucial role in some acute MS lesions, Devics syndrome and Marburgs syndrome. Analysis of acute MS lesions shows many different structural and immunological features, indicating that different mechanisms may be involved in lesion formation. Distinct subtypes of acute lesions exhibit either similarities with T-cell-mediated autoimmune encephalomyelitis or signs of primary oligodendrocyte damage.

  8. Chronic experimental autoimmune encephalomyelitis in the guinea pig. Presence of anti-M2 antibodies in central nervous system tissue and the possible role of M2 autoantigen in the induction of the disease.

    Science.gov (United States)

    Lebar, R; Baudrimont, M; Vincent, C

    1989-04-01

    Experimental autoimmune encephalomyelitis (EAE) can be transferred adoptively with T cells sensitized to the basic protein of myelin (BP). However, in the guinea pig, the chronic form of EAE has not been found to be inducible with BP alone, nor has it been adoptively transferred. An antibody response to the central nervous system (CNS) myelin autoantigens was looked for in serum and target CNS tissue in S13 guinea pigs with isologous CNS tissue-induced chronic EAE. Antibody activity was estimated by an immunoenzymatic technique and by autoradiography, using immunoprecipitated and electrophoresed relevant radiolabelled antigens. In serum, IgG antibody response to BP and M2 reached its maximum level 30 to 40 d after immunization and then declined progressively until it became undetectable. On the other hand, while anti-BP antibodies were seldom detected in CNS tissue acid extract, anti-M2 IgG antibodies were always present in CNS tissue of chronic EAE animals, and the amount of these antibodies were related to the severity of symptoms and lesions. No antibody response to proteolipid or to galactocerebroside was detected in serum or CNS tissue. BP-immunized controls showed no chronic EAE and no response to M2 in their serum or CNS tissue. Inasmuch as M2 has been shown to be a glycoprotein of CNS myelin, and anti-M2 antibodies to have a demyelinating property, the latter would be responsible for CNS tissue demyelination in chronic EAE. A shared role of BP and M2 in the induction of chronic EAE in the guinea pig is suggested.

  9. Senescence of the adaptive immune system in health and aging-associated autoimmune disease

    NARCIS (Netherlands)

    van der Geest, Kornelis Stephan Mario

    2015-01-01

    Aging of the immune system may contribute to the development of aging-associated autoimmune diseases, such as giant cell arteritis, polymyalgia rheumatica and rheumatoid arthritis. The aim of this thesis was to identify aging-dependent changes of the adaptive immune system that promote autoimmunity

  10. Microtubules in health and degenerative disease of the nervous system.

    Science.gov (United States)

    Matamoros, Andrew J; Baas, Peter W

    2016-09-01

    Microtubules are essential for the development and maintenance of axons and dendrites throughout the life of the neuron, and are vulnerable to degradation and disorganization in a variety of neurodegenerative diseases. Microtubules, polymers of tubulin heterodimers, are intrinsically polar structures with a plus end favored for assembly and disassembly and a minus end less favored for these dynamics. In the axon, microtubules are nearly uniformly oriented with plus ends out, whereas in dendrites, microtubules have mixed orientations. Microtubules in developing neurons typically have a stable domain toward the minus end and a labile domain toward the plus end. This domain structure becomes more complex during neuronal maturation when especially stable patches of polyaminated tubulin become more prominent within the microtubule. Microtubules are the substrates for molecular motor proteins that transport cargoes toward the plus or minus end of the microtubule, with motor-driven forces also responsible for organizing microtubules into their distinctive polarity patterns in axons and dendrites. A vast array of microtubule-regulatory proteins impart direct and indirect changes upon the microtubule arrays of the neuron, and these include microtubule-severing proteins as well as proteins responsible for the stability properties of the microtubules. During neurodegenerative diseases, microtubule mass is commonly diminished, and the potential exists for corruption of the microtubule polarity patterns and microtubule-mediated transport. These ill effects may be a primary causative factor in the disease or may be secondary effects, but regardless, therapeutics capable of correcting these microtubule abnormalities have great potential to improve the status of the degenerating nervous system. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. SJL mice infected with Acanthamoeba castellanii develop central nervous system autoimmunity through the generation of cross-reactive T cells for myelin antigens.

    Directory of Open Access Journals (Sweden)

    Chandirasegaran Massilamany

    Full Text Available We recently reported that Acanthamoeba castellanii (ACA, an opportunistic pathogen of the central nervous system (CNS possesses mimicry epitopes for proteolipid protein (PLP 139-151 and myelin basic protein 89-101, and that the epitopes induce experimental autoimmune encephalomyelitis (EAE in SJL mice reminiscent of the diseases induced with their corresponding cognate peptides. We now demonstrate that mice infected with ACA also show the generation of cross-reactive T cells, predominantly for PLP 139-151, as evaluated by T cell proliferation and IAs/dextramer staining. We verified that PLP 139-151-sensitized lymphocytes generated in infected mice contained a high proportion of T helper 1 cytokine-producing cells, and they can transfer disease to naïve animals. Likewise, the animals first primed with suboptimal dose of PLP 139-151 and later infected with ACA, developed EAE, suggesting that ACA infection can trigger CNS autoimmunity in the presence of preexisting repertoire of autoreactive T cells. Taken together, the data provide novel insights into the pathogenesis of Acanthamoeba infections, and the potential role of infectious agents with mimicry epitopes to self-antigens in the pathogenesis of CNS diseases such as multiple sclerosis.

  12. Idiopathic inflammatory-demyelinating diseases of the central nervous system

    Energy Technology Data Exchange (ETDEWEB)

    Rovira Canellas, A. [Vall d' Hebron University Hospital, Magnetic Resonance Unit (I.D.I.), Department of Radiology, Barcelona (Spain); Rovira Gols, A. [Parc Tauli University Institute - UAB, UDIAT, Diagnostic Centre, Sabadell (Spain); Rio Izquierdo, J.; Tintore Subirana, M.; Montalban Gairin, X. [Vall d' Hebron University Hospital, Neuroimmunology Unit, Department of Neurology, Barcelona (Spain)

    2007-05-15

    Idiopathic inflammatory-demyelinating diseases (IIDDs) include a broad spectrum of central nervous system disorders that can usually be differentiated on the basis of clinical, imaging, laboratory and pathological findings. However, there can be a considerable overlap between at least some of these disorders, leading to misdiagnoses or diagnostic uncertainty. The relapsing-remitting and secondary progressive forms of multiple sclerosis (MS) are the most common IIDDs. Other MS phenotypes include those with a progressive course from onset (primary progressive and progressive relapsing) or with a benign course continuing for years after onset (benign MS). Uncommon forms of IIDDs can be classified clinically into: (1) fulminant or acute IIDDs, such as the Marburg variant of MS, Balo's concentric sclerosis, Schilder's disease, and acute disseminated encephalomyelitis; (2) monosymptomatic IIDDs, such as those involving the spinal cord (transverse myelitis), optic nerve (optic neuritis) or brainstem and cerebellum; and (3) IIDDs with a restricted topographical distribution, including Devic's neuromyelitis optica, recurrent optic neuritis and relapsing transverse myelitis. Other forms of IIDD, which are classified clinically and radiologically as pseudotumoral, can have different forms of presentation and clinical courses. Although some of these uncommon IIDDs are variants of MS, others probably correspond to different entities. MR imaging of the brain and spine is the imaging technique of choice for diagnosing these disorders, and together with the clinical and laboratory findings can accurately classify them. Precise classification of these disorders may have relevant prognostic and treatment implications, and might be helpful in distinguishing them from tumoral or infectious lesions, avoiding unnecessary aggressive diagnostic or therapeutic procedures. (orig.)

  13. Idiopathic inflammatory-demyelinating diseases of the central nervous system

    International Nuclear Information System (INIS)

    Rovira Canellas, A.; Rovira Gols, A.; Rio Izquierdo, J.; Tintore Subirana, M.; Montalban Gairin, X.

    2007-01-01

    Idiopathic inflammatory-demyelinating diseases (IIDDs) include a broad spectrum of central nervous system disorders that can usually be differentiated on the basis of clinical, imaging, laboratory and pathological findings. However, there can be a considerable overlap between at least some of these disorders, leading to misdiagnoses or diagnostic uncertainty. The relapsing-remitting and secondary progressive forms of multiple sclerosis (MS) are the most common IIDDs. Other MS phenotypes include those with a progressive course from onset (primary progressive and progressive relapsing) or with a benign course continuing for years after onset (benign MS). Uncommon forms of IIDDs can be classified clinically into: (1) fulminant or acute IIDDs, such as the Marburg variant of MS, Balo's concentric sclerosis, Schilder's disease, and acute disseminated encephalomyelitis; (2) monosymptomatic IIDDs, such as those involving the spinal cord (transverse myelitis), optic nerve (optic neuritis) or brainstem and cerebellum; and (3) IIDDs with a restricted topographical distribution, including Devic's neuromyelitis optica, recurrent optic neuritis and relapsing transverse myelitis. Other forms of IIDD, which are classified clinically and radiologically as pseudotumoral, can have different forms of presentation and clinical courses. Although some of these uncommon IIDDs are variants of MS, others probably correspond to different entities. MR imaging of the brain and spine is the imaging technique of choice for diagnosing these disorders, and together with the clinical and laboratory findings can accurately classify them. Precise classification of these disorders may have relevant prognostic and treatment implications, and might be helpful in distinguishing them from tumoral or infectious lesions, avoiding unnecessary aggressive diagnostic or therapeutic procedures. (orig.)

  14. Atypical presentation of CLIPPERS syndrome: a new entity in the differential diagnosis of central nervous system rheumatologic diseases.

    Science.gov (United States)

    Gul, Maryam; Chaudhry, Ammar A; Chaudhry, Abbas A; Sheikh, Mubashir A; Carsons, Steven

    2015-04-01

    Numerous autoimmune diseases can affect the central nervous system (CNS), and variable clinical presentations confound the differential diagnosis. The challenging task of properly characterizing various CNS autoimmune diseases enables patients to be rapidly triaged and appropriately treated. In this review article, we aim to explore different CNS manifestations of rheumatologic diseases with emphasis on the utility of imaging and cerebrospinal fluid findings. We review the classic physical examination findings, characteristic imaging features, cerebrospinal fluid results, and serum biomarkers. In addition, we also present a unique case of newly described autoimmune entity CLIPPERS syndrome. Our case is unique in that this is the first case which demonstrates involvement of the supratentorial perivascular spaces in addition to the classic infratentorial involvement as initially described by Pittock et al (Brain. 2010;133:2626-2634).

  15. Exacerbation of experimental autoimmune encephalomyelitis in prion protein (PrPc-null mice: evidence for a critical role of the central nervous system

    Directory of Open Access Journals (Sweden)

    Gourdain Pauline

    2012-01-01

    Full Text Available Abstract Background The cellular prion protein (PrPc is a host-encoded glycoprotein whose transconformation into PrP scrapie (PrPSc initiates prion diseases. The role of PrPc in health is still obscure, but many candidate functions have been attributed to the protein, both in the immune and the nervous systems. Recent data show that experimental autoimmune encephalomyelitis (EAE is worsened in mice lacking PrPc. Disease exacerbation has been attributed to T cells that would differentiate into more aggressive effectors when deprived of PrPc. However, alternative interpretations such as reduced resistance of neurons to autoimmune insult and exacerbated gliosis leading to neuronal deficits were not considered. Method To better discriminate the contribution of immune cells versus neural cells, reciprocal bone marrow chimeras with differential expression of PrPc in the lymphoid or in the central nervous system (CNS were generated. Mice were subsequently challenged with MOG35-55 peptide and clinical disease as well as histopathology were compared in both groups. Furthermore, to test directly the T cell hypothesis, we compared the encephalitogenicity of adoptively transferred PrPc-deficient versus PrPc-sufficient, anti-MOG T cells. Results First, EAE exacerbation in PrPc-deficient mice was confirmed. Irradiation exacerbated EAE in all the chimeras and controls, but disease was more severe in mice with a PrPc-deleted CNS and a normal immune system than in the reciprocal construction. Moreover, there was no indication that anti-MOG responses were different in PrPc-sufficient and PrPc-deficient mice. Paradoxically, PrPc-deficient anti-MOG 2D2 T cells were less pathogenic than PrPc-expressing 2D2 T cells. Conclusions In view of the present data, it can be concluded that the origin of EAE exacerbation in PrPc-ablated mice resides in the absence of the prion protein in the CNS. Furthermore, the absence of PrPc on both neural and immune cells does not

  16. Pulmonary aspergillosis and central nervous system hemorrhage as complications of autoimmune hemolytic anemia treated with corticosteroids.

    Science.gov (United States)

    Cleri, Dennis J; Moser, Robert L; Villota, Francisco J; Wang, Yue; Husain, Syed A; Nadeem, Shahzinah; Anjari, Tarek; Sajed, Mohammad

    2003-06-01

    Warm, active antibody adult autoimmune hemolytic anemia is the most common form of hemolytic anemia not related to drug therapy. Mortality in adult autoimmune hemolytic anemia is related to the inability to successfully treat patients' underlying disease, or the infectious complications of splenectomy and prolonged steroid therapy. Predisposing factors for invasive aspergillosis are neutropenia and steroid therapy. We present a fatal case of aspergillosis complicating a nonneutropenic case of warm active antibody adult autoimmune hemolytic anemia treated with prolonged steroid therapy.

  17. Overview of the Autonomic Nervous System

    Science.gov (United States)

    ... be reversible or progressive. Anatomy of the autonomic nervous system The autonomic nervous system is the part of ... organs they connect with. Function of the autonomic nervous system The autonomic nervous system controls internal body processes ...

  18. Elevated interferon gamma expression in the central nervous system of tumour necrosis factor receptor 1-deficient mice with experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Wheeler, Rachel D; Zehntner, Simone P; Kelly, Lisa M

    2006-01-01

    Inflammation in the central nervous system (CNS) can be studied in experimental autoimmune encephalomyelitis (EAE). The proinflammatory cytokines interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF) are implicated in EAE pathogenesis. Signals through the type 1 TNF receptor (TNFR1...

  19. A rare association of localized scleroderma type morphea, vitiligo, autoimmune hypothyroidism, pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis. Case report.

    OpenAIRE

    Bonilla Abadía, Fabio; Muñoz Buitrón, Evelyn; Ochoa, Carlos D.; Carrascal, Edwin; Cañas Dávila, Carlos Alberto

    2012-01-01

    The localized scleroderma (LS) known as morphea, presents a variety of clinical manifestations that can include systemic involvement. Current classification schemes divide morphea into categories based solely on cutaneous morphology, without reference to systemic disease or autoimmune phenomena. This classification is likely incomplete. Autoimmune phenomena such as vitiligo and Hashimoto thyroiditis associated with LS have been reported in some cases suggesting an autoimmune basis. To our kno...

  20. Effects of the Autonomic Nervous System, Central Nervous System ...

    African Journals Online (AJOL)

    The gastrointestinal tract is chiefly involved in the digestion of ingested food, facilitation of absorption process and expulsion of the undigested food material through motility process. Motility is influenced by neurohormonal system which is associated with the enteric nervous system , autonomic nervous system and the ...

  1. The nervous systems of cnidarians

    DEFF Research Database (Denmark)

    Grimmelikhuijzen, C J; Westfall, J A

    1995-01-01

    Cnidarians have simple nervous systems and it was probably within this group or a closely-related ancestor that nervous systems first evolved. The basic plan of the cnidarian nervous system is that of a nerve net which, at some locations, has condensed to form nerve plexuses, or circular...... specialized neurons that we find in higher animals today. The primitive nervous system of cnidarians is strongly peptidergic: from a single sea anemone species Anthopleura elegantissima, we have now isolated 16 different novel neuropeptides. These peptides are biologically active and cause inhibitions...... that the peptides are located in neuronal dense-cored vesicles associated with both synaptic and non-synaptic release sites. All these data indicate that evolutionarily "old" nervous systems use peptides as transmitters. We have also investigated the biosynthesis of the cnidarian neuropeptides. These neuropeptides...

  2. Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans

    NARCIS (Netherlands)

    Kox, M.; Eijk, L.T.G.J. van; Zwaag, J.; Wildenberg, J. van den; Sweep, F.C.; Hoeven, J.G. van der; Pickkers, P.

    2014-01-01

    Excessive or persistent proinflammatory cytokine production plays a central role in autoimmune diseases. Acute activation of the sympathetic nervous system attenuates the innate immune response. However, both the autonomic nervous system and innate immune system are regarded as systems that cannot

  3. Differential expression of neurotrophic factors and inflammatory cytokines by myelin basic protein-specific and other recruited T cells infiltrating the central nervous system during experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Muhallab, S; Lundberg, C; Gielen, A W; Lidman, O; Svenningsson, A; Piehl, F; Olsson, T

    2002-03-01

    Recent evidence suggests that autoimmune reactions in the central nervous system (CNS) not only have detrimental consequences but can also be neuroprotective, and that this effect is mediated by the expression of neuronal growth factors by infiltrating leucocytes. Here we dissect these two phenomena in guinea pig myelin basic protein peptide (gpMBP 63-88)-induced experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. Real-time TaqMan polymerase chain reaction (PCR) was used to measure mRNA for the nerve growth factors, brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-3. As reference, the well-known proinflammatory mediator molecules interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha were quantified. In whole lumbar cord tissue, both the nerve growth factors and the proinflammatory cytokines, IFN-gamma and TNF-alpha, displayed similar expression patterns, peaking at the height of the disease. Among the infiltrating inflammatory cells isolated and sorted from the CNS, alphabeta+/T-cell receptor (TCR)BV8S2+, but not alphabeta+/TCRBV8S2-, recognized the encephalitogenic MBP peptide. Interestingly, these two populations displayed contrasting expression patterns of nerve growth factors and proinflammatory cytokines with higher inflammatory cytokine mRNA levels in alphabeta+/TCRBV8S2+ cells at all time intervals, whereas the levels of BDNF and NT3 were higher in alphabeta+/TCRBV8S2- cells. We conclude that a potentially important neuroprotective facet of CNS inflammation dominantly prevails within other non-MBP peptide-specific lymphoid cells and that there are independent regulatory mechanisms for neurotrophin and inflammatory cytokine expression during EAE.

  4. The new era of autoimmune disease research

    OpenAIRE

    Koike, Takao

    2011-01-01

    Recent genome-wide association studies have advanced our understanding of genetic factors that underlie systemic lupus erythematosus (SLE), a multifactorial autoimmune disease characterized by various clinical manifestations. SLE also has an environmental component, which can trigger or exacerbate the disease. Despite extensive efforts aimed at elucidating the cellular and biological abnormalities that arise in the immune system of patients with SLE, its pathology remains unclear. Lee and col...

  5. The Diagnostic Value of Brain Scanning in the Diseases of the Central Nervous System

    International Nuclear Information System (INIS)

    Kim, Kwang Won; Lee, Myung Chul; Koh, Chang Soon; Lee, Mun Ho; Chang, Kee Hyun; Han, Man Chung; Choi, Kil Su; Son, Hyo Chung; Cho, Byung Kyu

    1974-01-01

    The purpose of this study is to evaluate the diagnostic value of the brain scanning and compare the diagnostic accuracy between the scan and carotid angiography. 109 cases which are proved by specific method to each disease, are analyzed to evaluate the diagnostic value of the brain scanning. The 70 cases among the proven 109 case are performed both the scanning and the arteriography and analyzed to compare the accuracy between the scanning and the arteriography. The results are as follows; 1) The diagnostic accuracy of the brain scanning in the diseases of the central nervous system is 64.2%. 2) The diagnostic accuracy of the brain scanning in the brain tumor is 88%, especially brain abscess, glioma, glioblastoma multiforme, meningioma and metastic tumor show high positive rate. 3) The diagnostic accuracy in the disease of the brain vessels is 54%. The comparison of the diagnostic value between the scanning and the arteriography is as follows;1) The diagnostic value in all diseases of the central nervous system is nearly equal. 2) The diagnostic accuracy in the intracranial tumor is slightly higher in the brain scanning (90. 9%) than in the arteriography (81.8%). 3) The diagnostic accuracy in the disease of the brain vessel is higher in the arteriography (77.3%) than in the scanning (54.5%). 5) The diagnostic value when combining the scanning and the arteriography, is 83% in the all central nervous system-lesions, 97% in the cranial tumor and 81.8% in the disease of the central nervous system-vessel. The brain scanning is simple and safe procedure, and moreover has excellent diagnostic value in the diagnosis of the central nervous system lesion.

  6. In Vivo Quantification of Inflammation in Experimental Autoimmune Encephalomyelitis Rats Using Fluorine-19 Magnetic Resonance Imaging Reveals Immune Cell Recruitment outside the Nervous System.

    Directory of Open Access Journals (Sweden)

    Jia Zhong

    Full Text Available Progress in identifying new therapies for multiple sclerosis (MS can be accelerated by using imaging biomarkers of disease progression or abatement in model systems. In this study, we evaluate the ability to noninvasively image and quantitate disease pathology using emerging "hot-spot" 19F MRI methods in an experimental autoimmune encephalomyelitis (EAE rat, a model of MS. Rats with clinical symptoms of EAE were compared to control rats without EAE, as well as to EAE rats that received daily prophylactic treatments with cyclophosphamide. Perfluorocarbon (PFC nanoemulsion was injected intravenously, which labels predominately monocytes and macrophages in situ. Analysis of the spin-density weighted 19F MRI data enabled quantification of the apparent macrophage burden in the central nervous system and other tissues. The in vivo MRI results were confirmed by extremely high-resolution 19F/1H magnetic resonance microscopy in excised tissue samples and histopathologic analyses. Additionally, 19F nuclear magnetic resonance spectroscopy of intact tissue samples was used to assay the PFC biodistribution in EAE and control rats. In vivo hot-spot 19F signals were detected predominantly in the EAE spinal cord, consistent with the presence of inflammatory infiltrates. Surprising, prominent 19F hot-spots were observed in bone-marrow cavities adjacent to spinal cord lesions; these were not observed in control animals. Quantitative evaluation of cohorts receiving cyclophosphamide treatment displayed significant reduction in 19F signal within the spinal cord and bone marrow of EAE rats. Overall, 19F MRI can be used to quantitatively monitored EAE disease burden, discover unexpected sites of inflammatory activity, and may serve as a sensitive biomarker for the discovery and preclinical assessment of novel MS therapeutic interventions.

  7. [Autoimmune diseases of the thyroid gland].

    Science.gov (United States)

    Allelein, S; Feldkamp, J; Schott, M

    2017-01-01

    Autoimmune diseases of the thyroid gland are considered to be the most frequent cause of thyroid gland disorders. Autoimmune thyroid diseases consist of two subgroups: autoimmune thyroiditis (AIT) and Graves' disease. The AIT is the most common human autoimmune disease. Infiltration of the thyroid gland with cytotoxic T‑cells can lead to an initial thyrotoxicosis und during the course to hypothyroidism due to destruction of the thyroid gland. Substitution with Levothyroxine is indicated for manifest hypothyroidism and subclinical hypothyroidism with increased thyroid antibodies with the intention of normalizing the serum thyroid stimulating hormone (TSH). Graves' disease is characterized by the appearance of stimulating TSH receptor antibodies leading to hyperthyroidism. Endocrine ophthalmopathy may also occur. Ablative therapy with radioiodine therapy or thyroidectomy is administered to patients with Graves' disease without remission after at least 1 year of antithyroid drug therapy.

  8. Development of central nervous system autoimmunity is impaired in the absence of Wiskott-Aldrich syndrome protein.

    Directory of Open Access Journals (Sweden)

    Marita Bosticardo

    Full Text Available Wiskott-Aldrich Syndrome protein (WASP is a key regulator of the actin cytoskeleton in hematopoietic cells. Defective expression of WASP leads to multiple abnormalities in different hematopoietic cells. Despite severe impairment of T cell function, WAS patients exhibit a high prevalence of autoimmune disorders. We attempted to induce EAE, an animal model of organ-specific autoimmunity affecting the CNS that mimics human MS, in Was(-/- mice. We describe here that Was(-/- mice are markedly resistant against EAE, showing lower incidence and milder score, reduced CNS inflammation and demyelination as compared to WT mice. Microglia was only poorly activated in Was(-/- mice. Antigen-induced T-cell proliferation, Th-1 and -17 cytokine production and integrin-dependent adhesion were increased in Was(-/- mice. However, adoptive transfer of MOG-activated T cells from Was(-/- mice in WT mice failed to induce EAE. Was(-/- mice were resistant against EAE also when induced by adoptive transfer of MOG-activated T cells from WT mice. Was(+/- heterozygous mice developed an intermediate clinical phenotype between WT and Was(-/- mice, and they displayed a mixed population of WASP-positive and -negative T cells in the periphery but not in their CNS parenchyma, where the large majority of inflammatory cells expressed WASP. In conclusion, in absence of WASP, T-cell responses against a CNS autoantigen are increased, but the ability of autoreactive T cells to induce CNS autoimmunity is impaired, most probably because of an inefficient T-cell transmigration into the CNS and defective CNS resident microglial function.

  9. Progress of radionuclide diagnostic methods in central nervous system diseases

    International Nuclear Information System (INIS)

    Badmaev, K.N.; Zen'kovich, S.G.

    1982-01-01

    A summarry on modern radionuclide diagnosis achivements of central nervous system diseases is presented. Most optimal tumorotropic preparations and compounds in the view of decreasing irradiation does and optimazing image are given

  10. The role of the autoimmunity laboratory in autoimmune diseases

    Directory of Open Access Journals (Sweden)

    SS Hasson

    2012-04-01

    Full Text Available Laboratory testing is of great value when evaluating a patient with a suspected autoimmune disease. The results can confirm a diagnosis, estimate disease severity, aid in assessing prognosis and are useful to follow disease activity. Components of the laboratory exam include complete blood count with differential, comprehensive metabolic panel, inflammatory markers, autoantibodies, and flow cytometry. Currently, autoimmunity laboratories are very vibrant owing to the constant and increasing availability of new tests, mainly due to the detection of new autoantibodies. The main characteristic that differentiates the autoimmunity laboratory from other laboratories is the use of immunoassays such as enzyme-linked immunosorbent assay (ELISA, as basic techniques which determines antibodies (autoantibodies and not antigens. For this reason, immunoassay techniques must employ antigens as reagents. However, over the last few years, a significant trend at autoimmunity laboratories has been the gradual replacement of immunofluorescence microscopy by immunoassay. Nowadays the revolution of new technology has taken place significantly, for examples; recombinant DNA technology has allowed the production of large quantities of antigens for autoantibody analysis. Flow cytometry for the analysis of microsphere-based immunoassays allows the simultaneous measurement of several autoantibodies. In the same way, autoantigen microarrays provide a practical means to analyse biological fluids in the search for a high number of autoantibodies. We are now at the beginning of an era of multiplexed analysis, with a high capacity of autoantibody specificities. The future tendency in this field will include immunoassays with greater analytical sensitivity, specificity, simultaneous multiplexed capability, the use of protein microarrays, and the use of other technologies such as microfluidics.

  11. Hydatid disease of the Central Nervous System: imaging characteristics and general features

    International Nuclear Information System (INIS)

    Abbassioun, K.; Amirjamshidi, A.; Sabouri Deylamie, M.

    2003-01-01

    Background: Hydatid disease primarily affects the liver and typically demonstrates characteristic imaging findings. Secondary involvement due to hematogenous dissemination may be seen in almost any locations, e.g., lung, kidney, spleen, bone and central nervous system. Objectives: To review the different aspects of hydatidosis of the central nervous system briefly and discuss the pathognomonic features and rare varieties of radiological findings useful in preoperative diagnosis of the disease in the human central nervous system. Materials and Methods: In a retrospective study, the records of almost 100 cases of central nervous system hydatidosis were analyzed . The available images were reviewed by independent observers, either a radiologist or a neurosurgeon, and reported separately. Results: In skull x-ray films, nonspecific changes denoted increased intracranial pressure, skull asymmetry and curvilinear calcification in rare instances. Computed tomography and magnetic resonance imaging demonstrated the round or oval, well-defined cystic mass with an attenuation or signal intensity similar to that of cerebrospinal fluid, with no associated perifocal edema, and no contrast enhancement as the pathognomonic findings of brain hydatidosis. Similar findings were detected in hydatid cysts involving the orbit, spinal column and spinal cord with some variations. Such findings as mild perifocal edema, non homogenous contrast enhancement, non-uniform shapes, calcification and multiplicity or septations have been the atypical radiological findings. Conclusion: In endemic areas, familiarity with typical and atypical radiological manifestations of hydatid disease of the central nervous system, will be helpful in making prompt and correct preoperative diagnosis leading to a better surgical outcome

  12. Induction of endogenous Type I interferon within the central nervous system plays a protective role in experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Khorooshi, Reza; Mørch, Marlene Thorsen; Holm, Thomas

    2015-01-01

    The Type I interferons (IFN), beta (IFN-β) and the alpha family (IFN-α), act through a common receptor and have anti-inflammatory effects. IFN-β is used to treat multiple sclerosis (MS) and is effective against experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Mice with EAE...

  13. Systemic Autoimmune, Rheumatic Diseases and Coinciding Psoriasis: Data from a Large Single-Centre Registry and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Anna Bazsó

    2015-01-01

    Full Text Available Psoriasis is a systemic immune-inflammatory disease characterized by chronic or recurrent skin symptoms, psoriatic arthritis, enthesopathy, and uveitis. Psoriasis has recently been published to appear with various autoimmune disorders, but the coexistence has been systematically reviewed by only few studies until now. In the present study, charts and electronic database of 4344 patients with various systemic autoimmune disorders, under regular medical control at our department, were reviewed retrospectively searching for association with psoriasis. Hereby, we demonstrate 25 psoriatic patients coinciding with various systemic autoimmune diseases. The coexistence of psoriasis and autoimmune diseases resulted in the worsening of the clinical outcome of the autoimmune diseases as indicated by higher frequency and dosages of glucocorticoid use, need for biologicals, and other comorbidities. These results suggest common environmental and genetic background as well as therapeutic possibilities in the future.

  14. Evaluation of a radiolabelled peripheral benzodiazepine receptor ligand in the central nervous system inflammation of experimental autoimmune encephalomyelitis: a possible probe for imaging multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Mattner, F.; Katsifis, A.; Ballantyne, P. [ANSTO, Radiopharmaceuticals Division, Lucas Heights (Australia); Staykova, M.; Willenborg, D.O. [Australian National University Medical School, The Canberra Hospital, Neurosciences Research Unit, Woden, Canberra (Australia)

    2005-04-01

    Peripheral benzodiazepine receptors (PBRs) are upregulated on macrophages and activated microglia, and radioligands for the PBRs can be used to detect in vivo neuroinflammatory changes in a variety of neurological insults, including multiple sclerosis. Substituted 2-phenyl imidazopyridine-3-acetamides with high affinity and selectivity for PBRs have been prepared that are suitable for radiolabelling with a number of positron emission tomography and single-photon emission computed tomography (SPECT) isotopes. In this investigation, the newly developed high-affinity PBR ligand 6-chloro-2-(4'-iodophenyl)-3-(N,N-diethyl)imidazo[1,2-a]pyridine-3-acetamide, or CLINDE, was radiolabelled with{sup 123}I and its biodistribution in the central nervous system (CNS) of rats with experimental autoimmune encephalomyelitis (EAE) evaluated. EAE was induced in male Lewis rats by injection of an emulsion of myelin basic protein and incomplete Freund's adjuvant containing Mycobacterium butyricum. Biodistribution studies with{sup 123}I-CLINDE were undertaken on EAE rats exhibiting different clinical disease severity and compared with results in controls. Disease severity was confirmed by histopathology in the spinal cord of rats. The relationship between inflammatory lesions and PBR ligand binding was investigated using ex vivo autoradiography and immunohistochemistry on rats with various clinical scores. {sup 123}I-CLINDE uptake was enhanced in the CNS of all rats exhibiting EAE when compared to controls. Binding reflected the ascending nature of EAE inflammation, with lumbar/sacral cord > thoracic cord > cervical cord > medulla. The amount of ligand binding also reflected the clinical severity of disease. Ex vivo autoradiography and immunohistochemistry revealed a good spatial correspondence between radioligand signal and foci of inflammation and in particular ED-1{sup +} cells representing macrophages and microglia. These results demonstrate the ability of {sup 123}I

  15. What Are the Parts of the Nervous System?

    Science.gov (United States)

    ... Email Print What are the parts of the nervous system? The nervous system consists of two main parts: the central nervous system and the peripheral nervous system: The central nervous system is made up of the brain and ...

  16. Individual features of autoimmune disoders in patients with arterial hypotension in structure of neurologic symptom complexes of organic lesion of the central nervous system

    Directory of Open Access Journals (Sweden)

    Елена Константиновна Зинченко

    2015-09-01

    Full Text Available This work deals with the special features of formation of individual clinical phenotype with an evident humoral sensitizing in patients with arterial hypotension in structure of neurologic symptom complexes of organic lesion of the central nervous system in accordance with the features of disorders of immune resistance and changes of the hormonal background.Materials and methods. There was carried out an examination of 201 patients: 89 with vegetative dysfunction, 50 in remote period of the closed craniocerebral trauma and 64 with cerebral arachnoiditis on the background of the chronic nidi of infection.45 examined persons with physiological arterial hypotension formed a control group. There were carried out clinical and neurological examinations, monitoring of arterial pressure, definition of the state of the primary, secondary immunity and hormonal background.Results. The main pathogenetic mechanisms in individual clinical phenotype with an evident humoral sensitizing that were formed on the background of the chronic infection are more connected with the humoral link of immunity (the high concentration of circulating immune complexes of the small values of molecular weight and peptides of the mean molecular weight, the growth of IgM content and form autoimmune disorders. This category can be related to the patients with irreversible functional states that complicates prescription of therapeutic measures.Conclusions. For patients with an evident humoral sensitizing it is reasonable to use desensitizing preparations, enterosorbents, plasmapheresis in the complex treatment. At persistent viral infection the use of specific antiviral immunoglobulins of IgG is recommended

  17. Autoimmune diseases — connecting risk alleles with molecular traits of the immune system

    Science.gov (United States)

    Gutierrez-Arcelus, Maria; Rich, Stephen S.; Raychaudhuri, Soumya

    2016-01-01

    Genome-wide strategies have driven the discovery of more than 300 susceptibility loci for autoimmune diseases. However, for almost all loci, understanding of the mechanisms leading to autoimmunity remains limited, and most variants that are likely to be causal are in non-coding regions of the genome. A critical next step will be to identify the in vivo and ex vivo immunophenotypes that are affected by risk variants. To do this, key cell types and cell states that are implicated in autoimmune diseases will need to be defined. Functional genomic annotations from these cell types and states can then be used to resolve candidate genes and causal variants. Together with longitudinal studies, this approach may yield pivotal insights into how autoimmunity is triggered. PMID:26907721

  18. When do the symptoms of autonomic nervous system malfunction appear in patients with Parkinson's disease?

    Science.gov (United States)

    De Luka, Silvio R; Svetel, Marina; Pekmezović, Tatjana; Milovanović, Branislav; Kostić, Vladimir S

    2014-04-01

    Dysautonomia appears in almost all patients with Parkinson's disease (PD) in a certain stage of their condition. The aim of our study was to detect the development and type of autonomic disorders, find out the factors affecting their manifestation by analyzing the potential association with demographic variables related to clinical presentation, as well as the symptoms of the disease in a PD patient cohort. The patients with PD treated at the Clinic of Neurology in Belgrade during a 2-year period, divided into 3 groups were studied: 25 de novo patients, 25 patients already treated and had no long-term levodopa therapy-related complications and 22 patients treated with levodopa who manifested levodopa-induced motor complications. Simultaneously, 35 healthy control subjects, matched by age and sex, were also analyzed. Autonomic nervous system malfunction was defined by Ewing diagnostic criteria. The tests, indicators of sympathetic and parasympathetic nervous systems, were significantly different in the PD patients as compared with the controls, suggesting the failure of both systems. However, it was shown, in the selected groups of patients, that the malfunction of both systems was present in two treated groups of PD patients, while de novo group manifested only sympathetic dysfunction. For this reason, the complete autonomic neuropathy was diagnosed only in the treated PD patients, while de novo patients were defined as those with the isolated sympathetic dysfunction. The patients with the complete autonomic neuropathy differed from the subjects without such neuropathy in higher cumulative and motor unified Parkinson's disease rating score (UPDRS) (p nervous system disturbances among PD patients from the near onset of disease, with a predominant sympathetic nervous system involvement. The patients who developed complete autonomic neuropathy (both sympathetic and parasympathetic) were individuals with considerable level of functional failure, more severe clinical

  19. CD1-dependent regulation of chronic central nervous system inflammation in experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Teige, Anna; Teige, Ingrid; Lavasani, Shahram

    2004-01-01

    The existence of T cells restricted for the MHC I-like molecule CD1 is well established, but the function of these cells is still obscure; one implication is that CD1-dependent T cells regulate autoimmunity. In this study, we investigate their role in experimental autoimmune encephalomyelitis (EA...

  20. Interferon gamma, interleukin 4 and transforming growth factor beta in experimental autoimmune encephalomyelitis in Lewis rats: dynamics of cellular mRNA expression in the central nervous system and lymphoid cells

    DEFF Research Database (Denmark)

    Issazadeh-Navikas, Shohreh; Mustafa, M; Ljungdahl, A

    1995-01-01

    to limit central nervous system (CNS) inflammation. In lymphoid organs, primed MBP 63-88 reactive T cells showed an interesting time-dependent evolution of their cytokine production in vitro. Thus, early after immunization there was a conspicuous MBP 63-88-induced production of both IFN-gamma and IL-4......-beta) both in sections of spinal cords and the antigen-induced expression of these cytokines by lymphoid cells after stimulation with a dominant encephalitogenic peptide of MBP (MBP 63-88) during the course of actively induced experimental autoimmune encephalomyelitis (EAE) in Lewis rats. In spinal cords...... autoimmunity systemically....

  1. SLEEP DISORDERS IN CHILDREN WITH DISEASES OF THE NERVOUS SYSTEM, ENT PATHOLOGY AND ALLERGY

    Directory of Open Access Journals (Sweden)

    E. A. Abashidze

    2012-01-01

    Full Text Available The purpose of this study was to assess the nature of the sleep changes in children with various pathologies. The study included 103 children with diseases of the nervous system, ENT disorders and allergic diseases. Polysomnography was carried out to all children — the synchronous recording of various physiological parameters during sleep. The vast majority of patients in the studied groups had changed microstructure of sleep in comparison with the healthy children (control group. Disorders of breathing during sleep were manifested in the form of episodes of apnea/hypopnea. These changes were associated with the severity of somatic pathology.  

  2. Role of Helicobacter pylori infection in autoimmune systemic rheumatic diseases.

    Science.gov (United States)

    Radić, Mislav

    2014-09-28

    The relationship between infection and autoimmunity has been increasingly defined over the last 20 years. The systemic rheumatic diseases are characterized by dysregulation of the immune system resulting in a loss of tolerance to self-antigen. The exact etiology for the majority of these diseases is unknown; however, a complex combination of host and environmental factors are believed to play a pivotal role. Helicobacter pylori (H. pylori) is one of the most widely studied infectious agents proposed as agents triggering autoimmune response. The persistent presence of H. pylori in the gastric mucosa results in chronic immune system activation with ongoing cytokine signaling, infiltration of gastric mucosa by neutrophils, macrophages, lymphocytes, as well as production of antibodies and effector T-cells. Various mechanisms have been proposed in an attempt to explain the extra-intestinal manifestations of H. pylori infections. These include: molecular mimicry, endothelial cell damage, superantigens and microchimerism. I performed a systematic literature review using the keywords "rheumatoid arthritis", "Sjögren's syndrome", "systemic sclerosis", "systemic lupus erythematosus", "Helicobacter pylori" and "pathogenesis". A systematic literature search was carried out in MEDLINE; EMBASE; Cochrane Library and ACR/EULAR meeting abstracts. In systemic rheumatic diseases H. pylori infection prevalence alone should not be expected to provide sufficient evidence for or against a pathologic role in the disease. In this article I review studies examining the potential involvement of H. pylori infection in autoimmune systemic rheumatic diseases. Further studies of the immunological response to H. pylori and its role in the pathogenesis of systemic rheumatic diseases are warranted.

  3. AUTOIMMUNE DISEASE DURING PREGNANCY AND THE MICROCHIMERISM LEGACY OF PREGNANCY

    Science.gov (United States)

    Adams Waldorf, Kristina M.; Nelson, J. Lee

    2009-01-01

    Pregnancy has both short-term effects and long-term consequences. For women who have an autoimmune disease and subsequently become pregnant, pregnancy can induce amelioration of the mother’s disease, such as in rheumatoid arthritis, while exacerbating or having no effect on other autoimmune diseases like systemic lupus erythematosus. That pregnancy also leaves a long-term legacy has recently become apparent by the discovery that bi-directional cell trafficking results in persistence of fetal cells in the mother and of maternal cells in her offspring for decades after birth. The long-term persistence of a small number of cells (or DNA) from a genetically disparate individual is referred to as microchimerism. While microchimerism is common in healthy individuals and is likely to have health benefits, microchimerism has been implicated in some autoimmune diseases such as systemic sclerosis. In this paper, we will first discuss short-term effects of pregnancy on women with autoimmune disease. Pregnancy-associated changes will be reviewed for selected autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus and autoimmune thyroid disease. The pregnancy-induced amelioration of rheumatoid arthritis presents a window of opportunity for insights into both immunological mechanisms of fetal-maternal tolerance and pathogenic mechanisms in autoimmunity. A mechanistic hypothesis for the pregnancy-induced amelioration of rheumatoid arthritis will be described. We will then discuss the legacy of maternal-fetal cell transfer from the perspective of autoimmune diseases. Fetal and maternal microchimerism will be reviewed with a focus on systemic sclerosis (scleroderma), autoimmune thyroid disease, neonatal lupus and type I diabetes mellitus. PMID:18716941

  4. Overview of the Autonomic Nervous System

    Science.gov (United States)

    ... process. Autonomic disorders may be reversible or progressive. Anatomy of the autonomic nervous system The autonomic nervous ... with acetylcholine and placed on the legs and forearm. Then, the volume of sweat is measured to ...

  5. Inflammatory Bowel Disease and the Risk of Autoimmune Diseases.

    Science.gov (United States)

    Wilson, J Claire; Furlano, Raoul I; Jick, Susan S; Meier, Christoph R

    2016-02-01

    An increased risk of autoimmune disease has been reported in patients with inflammatory bowel disease [IBD]. Using data from the Clinical Practice Research Datalink [CPRD], this study set out to further examine this relationship. Patients with a first-time IBD diagnosis were randomly matched to an equal-sized IBD-free comparison group. Incidence rates for new-onset autoimmune diseases were estimated. A nested case-control analysis comprising IBD patients was conducted, using conditional logistic regression to assess whether IBD severity, duration, or treatment influences the risk of developing autoimmune diseases. During follow-up, 1069 IBD and 585 IBD-free patients developed an incident autoimmune disease. An increased incidence of autoimmune disease was observed in IBD patients (incidence rate [IR] 9.65, 95% confidence interval [CI] 9.09-10.24) compared with the non-IBD comparison group [IR 5.22, 95% CI 4.82-5.66]. In IBD patients, increased disease severity was associated with an increased risk of autoimmune disease development (odds ratio [OR] 1.62, 95% CI 1.28-2.05). Current antibiotic use was also associated with an increased risk [adjusted OR 1.72, 95% CI 1.07-2.78]. A reduced risk of incident autoimmune diseases was observed for current long-term users of aminosalicylates [adjusted OR 0.72, 95% CI 0.57-0.91]. Individuals with IBD had an increased risk of developing an autoimmune disease. Increased disease severity and current antibiotic use were associated with an increased relative risk of developing additional autoimmune diseases in IBD patients. Long-term current aminosalicylate use was associated with a reduced risk. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  6. Cerebrospinal fluid analysis in infectious diseases of the nervous system: when to ask, what to ask, what to expect

    Directory of Open Access Journals (Sweden)

    Luis dos Ramos Machado

    2013-09-01

    Full Text Available Cerebrospinal fluid (CSF analysis very frequently makes the difference to the diagnosis, not only in relation to infections but also in other diseases of the nervous system such as inflammatory, demyelinating, neoplastic and degenerative diseases. The authors review some practical and important features of CSF analysis in infectious diseases of the nervous system, with regard to acute bacterial meningitis, herpetic meningoencephalitis, neurotuberculosis, neurocryptococcosis, neurocysticercosis and neurosyphilis.

  7. Neutron activation analysis of the central nervous system tissues in neurological diseases

    Energy Technology Data Exchange (ETDEWEB)

    Yasui, Masayuki; Ota, Kiichiro [Wakayama Medical Coll. (Japan); Sasajima, Kazuhisa

    1994-07-01

    As the diseases due to excessive metals in living bodies and the metals of their causes, Minamata disease due to Hg, itai-itai disease due to Cd, dialysis brain disease due to Al, hemochromatosis due to Fe, Wilson disease due to Cu and so on have been known. Also as the neural diseases, in which the possibility that metals take part in them is presumed, there are amyotrophic lateral sclerosis, Alzheimer disease, Parkinson disease, Parkinsonism dementia and so on. In order to know the causes of the diseases due to excessive metals in living bodies and neurological diseases, the authors have measured Cu, Ca, Al, Mn, Zn and Fe in central nervous system tissues by activation analysis nondestructive method. The cases investigated were 4 cases of hepatocerebral diseases, 6 cases of ALS, 4 cases of Parkinson disease, 4 cases of Parkinsonism dementia, 4 cases of multiple sclerosis and 5 cases without CNS disease for the control. The method of measurement is described. The results for respective diseases are reported. Cu and Fe are in the relation of mirror images, and Cu formed Cu-superoxide dismutase (SOD) similarly to Zn and Mn as SOD carrier metals, and protects living bodies and CNS from oxidative stress. (K.I.).

  8. The accuracy of administrative data diagnoses of systemic autoimmune rheumatic diseases.

    Science.gov (United States)

    Bernatsky, Sasha; Linehan, Tina; Hanly, John G

    2011-08-01

    To examine the validity of case definitions for systemic autoimmune rheumatic diseases [SARD; systemic lupus erythematosus (SLE), systemic sclerosis (SSc), myositis, Sjögren's syndrome, vasculitis, and polymyalgia rheumatica] based on administrative data, compared to rheumatology records. A list of rheumatic disease diagnoses was generated from population-based administrative billing and hospitalization databases. Subjects who had been seen by an arthritis center rheumatologist were identified, and the medical records reviewed. We found that 844 Nova Scotia residents had a diagnosis of one of the rheumatic diseases of interest, based on administrative data, and had had ≥ 1 rheumatology assessment at a provincial arthritis center. Charts were available on 824 subjects, some of whom had been identified in the administrative database with > 1 diagnosis. Thus a total of 1136 diagnoses were available for verification against clinical records. Of the 824 subjects, 680 (83%) had their administrative database diagnoses confirmed on chart review. The majority of subjects who were "false-positive" for a given rheumatic disease on administrative data had a true diagnosis of a similar rheumatic disease. Most sensitivity estimates for specific administrative data-based case definitions were > 90%, although for SSc, the sensitivity was 80.5%. The specificity estimates were also > 90%, except for SLE, where the specificity was 72.5%. Although health administrative data may be a valid resource, there are potential problems regarding the specificity and sensitivity of case definitions, which should be kept in mind for future studies.

  9. Glial fibrillary acidic protein (GFAP) and the astrocyte intermediate filament system in diseases of the central nervous system

    NARCIS (Netherlands)

    Hol, Elly M; Pekny, Milos

    Glial fibrillary acidic protein (GFAP) is the hallmark intermediate filament (IF; also known as nanofilament) protein in astrocytes, a main type of glial cells in the central nervous system (CNS). Astrocytes have a range of control and homeostatic functions in health and disease. Astrocytes assume a

  10. Glial fibrillary acidic protein (GFAP) and the astrocyte intermediate filament system in diseases of the central nervous system

    NARCIS (Netherlands)

    Hol, E.M.; Pekny, M.

    2015-01-01

    Glial fibrillary acidic protein (GFAP) is the hallmark intermediate filament (IF; also known as nanofilament) protein in astrocytes, a main type of glial cells in the central nervous system (CNS). Astrocytes have a range of control and homeostatic functions in health and disease. Astrocytes assume a

  11. Understanding Autoimmune Diseases

    Science.gov (United States)

    ... What are they? Points To Remember About Autoimmune Diseases Autoimmune diseases refer to problems with the immune system, ... Infectious Diseases Website: https://www.niaid.nih.gov/diseases-conditions/autoimmune-diseases American Autoimmune Related Diseases Association Website: https:// ...

  12. [The pathological TDP-43 protein expression in the central nervous system of motor neuron disease].

    Science.gov (United States)

    Zhu, Mingwei; Liu, Jia; Wang, Luning; Gui, Qiuping

    2015-01-01

    To understand pathological TDP-43 features in the central nervous systems of patients with clinically and autopsy confirmed motor neuron disease (MND). The clinical and histopathological features of 4 cases with MND confirmed by autopsy were summarized; anti-ubiquitin (Ub) and anti-TDP-43 immunohistochemical staining were carried out on tissue of brains and spinal cords from 4 cases with MND and 3 control cases without history of neurological disorders. These 4 cases presented with typical clinical and histologic features of MND. Ub-positive inclusions were observed in brain and spinal cord from 3 cases with the Ub-positive inclusions of skein- round- and lewy body- like structures. Strong TDP-43 pathological staining in brain and spinal cord was identified in 2 cases with MND presented as neuronal and glial cytoplasmic inclusions with various shapes. The TDP-43 positive inclusions were widely distributed in the motor cortex of brain and the anterior horn of spinal cord. TDP-43 weak staining in the spinal cord tissue was observed in 1 case with MND. No Ub- and TDP-43 positive inclusions were found in 3 control cases. There is widespread pathological TDP-43 expression in the central nervous system of MND. TDP-43 positive inclusions in MND have relatively high specificity. It is worth further study on their formation mechanism.

  13. Naive CD8 T-Cells Initiate Spontaneous Autoimmunity to a Sequestered Model Antigen of the Central Nervous System

    Science.gov (United States)

    Na, Shin-Young; Cao, Yi; Toben, Catherine; Nitschke, Lars; Stadelmann, Christine; Gold, Ralf; Schimpl, Anneliese; Hunig, Thomas

    2008-01-01

    In multiple sclerosis, CD8 T-cells are thought play a key pathogenetic role, but mechanistic evidence from rodent models is limited. Here, we have tested the encephalitogenic potential of CD8 T-cells specific for the model antigen ovalbumin (OVA) sequestered in oligodendrocytes as a cytosolic molecule. We show that in these "ODC-OVA" mice, the…

  14. Sympathetic nervous system overactivity and its role in the development of cardiovascular disease.

    Science.gov (United States)

    Malpas, Simon C

    2010-04-01

    This review examines how the sympathetic nervous system plays a major role in the regulation of cardiovascular function over multiple time scales. This is achieved through differential regulation of sympathetic outflow to a variety of organs. This differential control is a product of the topographical organization of the central nervous system and a myriad of afferent inputs. Together this organization produces sympathetic responses tailored to match stimuli. The long-term control of sympathetic nerve activity (SNA) is an area of considerable interest and involves a variety of mediators acting in a quite distinct fashion. These mediators include arterial baroreflexes, angiotensin II, blood volume and osmolarity, and a host of humoral factors. A key feature of many cardiovascular diseases is increased SNA. However, rather than there being a generalized increase in SNA, it is organ specific, in particular to the heart and kidneys. These increases in regional SNA are associated with increased mortality. Understanding the regulation of organ-specific SNA is likely to offer new targets for drug therapy. There is a need for the research community to develop better animal models and technologies that reflect the disease progression seen in humans. A particular focus is required on models in which SNA is chronically elevated.

  15. Comparative assessment of the prevalence of periodontal disease in subjects with and without systemic autoimmune diseases: A case-control study.

    Science.gov (United States)

    Ramesh Kumar, S G; Aswath Narayanan, M B; Jayanthi, D

    2016-01-01

    Immune mechanism shares a common pathway both for systemic autoimmune diseases and periodontal diseases. Scientific exploration of literature revealed limited studies on the association between systemic autoimmune diseases and periodontal diseases in India. The aim of the study is to find whether the presence of systemic autoimmune diseases in an individual is a risk factor for the development of periodontal disease. This was a hospital-based case-control study. A sample of 253 patients with systemic autoimmune diseases, attending the Rheumatology Department of Government General Hospital, Chennai-3, and 262 patients without systemic autoimmune diseases, attending the outpatient department of the Tamil Nadu Government Dental College and Hospital, Chennai-3, constituted the case and control groups, respectively. Age, gender, and oral hygiene status matching was done. Oral hygiene status was assessed using oral hygiene index (OHI) and periodontal status was assessed using community periodontal index (CPI) and loss of attachment (LOA) index. Statistical analysis was done using SPSS version 15 (SPSS Inc, 2006, Chicago). Results showed 99.2% and 73.9% prevalence of gingivitis and periodontitis, respectively, in the case group as compared to 85.5% and 14.9%, respectively, in the control group. There is no linear relationship between OHI scores and prevalence of periodontitis (CPI and LOA scores) in the case group. Patients suffering from systemic autoimmune diseases showed more prevalence of periodontal diseases irrespective of oral hygiene scores. It is postulated that the presence of systemic autoimmune diseases may pose a risk for the development of periodontal diseases.

  16. Comparative assessment of the prevalence of periodontal disease in subjects with and without systemic autoimmune diseases: A case–control study

    Directory of Open Access Journals (Sweden)

    S G Ramesh Kumar

    2016-01-01

    Full Text Available Background: Immune mechanism shares a common pathway both for systemic autoimmune diseases and periodontal diseases. Scientific exploration of literature revealed limited studies on the association between systemic autoimmune diseases and periodontal diseases in India. Aim: The aim of the study is to find whether the presence of systemic autoimmune diseases in an individual is a risk factor for the development of periodontal disease. Settings and Design: This was a hospital-based case–control study. Materials and Methods: A sample of 253 patients with systemic autoimmune diseases, attending the Rheumatology Department of Government General Hospital, Chennai-3, and 262 patients without systemic autoimmune diseases, attending the outpatient department of the Tamil Nadu Government Dental College and Hospital, Chennai-3, constituted the case and control groups, respectively. Age, gender, and oral hygiene status matching was done. Oral hygiene status was assessed using oral hygiene index (OHI and periodontal status was assessed using community periodontal index (CPI and loss of attachment (LOA index. Statistical Analysis: Statistical analysis was done using SPSS version 15 (SPSS Inc, 2006, Chicago. Results: Results showed 99.2% and 73.9% prevalence of gingivitis and periodontitis, respectively, in the case group as compared to 85.5% and 14.9%, respectively, in the control group. There is no linear relationship between OHI scores and prevalence of periodontitis (CPI and LOA scores in the case group. Patients suffering from systemic autoimmune diseases showed more prevalence of periodontal diseases irrespective of oral hygiene scores. Conclusion: It is postulated that the presence of systemic autoimmune diseases may pose a risk for the development of periodontal diseases.

  17. The roles of PDGF in development and during neurogenesis in the normal and diseased nervous system.

    Science.gov (United States)

    Funa, Keiko; Sasahara, Masakiyo

    2014-03-01

    The four platelet-derived growth factor (PDGF) ligands and PDGF receptors (PDGFRs), α and β (PDGFRA, PDGFRB), are essential proteins that are expressed during embryonic and mature nervous systems, i.e., in neural progenitors, neurons, astrocytes, oligodendrocytes, and vascular cells. PDGF exerts essential roles from the gastrulation period to adult neuronal maintenance by contributing to the regulation of development of preplacodal progenitors, placodal ectoderm, and neural crest cells to adult neural progenitors, in coordinating with other factors. In adulthood, PDGF plays critical roles for maintenance of many specific cell types in the nervous system together with vascular cells through controlling the blood brain barrier homeostasis. At injury or various stresses, PDGF modulates neuronal excitability through adjusting various ion channels, and affecting synaptic plasticity and function. Furthermore, PDGF stimulates survival signals, majorly PI3-K/Akt pathway but also other ways, rescuing cells from apoptosis. Studies imply an involvement of PDGF in dendrite spine morphology, being critical for memory in the developing brain. Recent studies suggest association of PDGF genes with neuropsychiatric disorders. In this review, we will describe the roles of PDGF in the nervous system, from the discovery to recent findings, in order to understand the broad spectrum of PDGF in the nervous system. Recent development of pharmacological and replacement therapies targeting the PDGF system is discussed.

  18. Pathology of the Nervous System in Von Hippel-Lindau Disease

    Directory of Open Access Journals (Sweden)

    Alexander O. Vortmeyer

    2015-06-01

    Full Text Available Von Hippel-Lindau (VHL disease is a tumor syndrome that frequently involves the central nervous system (CNS. It is caused by germline mutation of the VHL gene. Subsequent VHL inactivation in selected cells is followed by numerous well-characterized molecular consequences, in particular, activation and stabilization of hypoxia-inducible factors HIF1 and HIF2. The link between VHL gene inactivation and tumorigenesis remains poorly understood. Hemangioblastomas are the most common manifestation in the CNS; however, CNS invasion by VHL disease-associated endolymphatic sac tumors or metastatic renal cancer also occur, and their differentiation from primary hemangioblastoma may be challenging. Finally, in this review, we present recent morphologic insights on the developmental concept of VHL tumorigenesis which is best explained by pathologic persistence of temporary embryonic progenitor cells. 

  19. The Central Nervous System of Box Jellyfish

    DEFF Research Database (Denmark)

    Garm, Anders Lydik; Ekström, Peter

    2008-01-01

    of behaviors in the box jellyfish such as obstacle avoidance and navigation. The need to process the visual information and turn it into the appropriate behavior puts strong demands on the nervous system of box jellyfish, which appears more elaborate than in other cnidarians. Here, the central part...... of this nervous system is described. Each rhopalium holds a separate part of the CNS with 1,000 nerve cells and a large amount of neuropil. The rhopalial nervous system has several subsystems defined by the anatomy, location, and immunocytochemistry of the cells. Most of the subsystems connect to one or more...... of the eye types, and it is likely that the rhopalial nervous system accounts for most of the visual processing. The major part of the CNS is made up of a ring nerve encircling the bell shaped body. The ring nerve holds around 10,000 cells and is directly connected to all four rhopalial nervous systems...

  20. THE POLYPEPTIDE STIMULATOR APPLICATION IN COMPLEX TREATMENT OF COGNITIVE DISORDERS IN CHILDREN WITH DISEASES OF THE CENTRAL NERVOUS SYSTEM

    Directory of Open Access Journals (Sweden)

    S. A. Nemkova

    2012-01-01

    Full Text Available The results of the review of studies on the polypeptide nootropic neurometabolic stimulator in a complex correction of cognitive impairment in children with diseases of the central nervous system are given in the article. It is shown that cognitive-modulating effect is the leading feature of the drug, and in a combination with nootropic, neurotrophic, neuroprotective, reparative and anticonvulsive effects, as well as antioxidant, anti-stress and metabolic actions, which determines its high therapeutic efficacy in a complex correction of cognitive impairment in various central nervous system diseases in children.

  1. Premature atherosclerosis in systemic autoimmune diseases

    NARCIS (Netherlands)

    Leeuw, Karina de

    2008-01-01

    Systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and Wegener’s granulomatosis (WG) are associated with a significantly increased prevalence of cardiovascular disease (CVD) compared to age- and sex-matched controls. Many risk factors are involved in the pathogenesis of

  2. The role of melatonin in autoimmune and atopic diseases

    Directory of Open Access Journals (Sweden)

    J.R. Calvo

    2016-04-01

    Full Text Available Melatonin is the main secretory product synthesized and secreted by the pineal gland during the night. Melatonin is a pleitropic molecule with a wide distribution within phylogenetically distant organisms and has a great functional versatility, including the regulation of circadian and seasonal rhythms and antioxidant and anti-inflammatory properties. It also possesses the capacity to modulate immune responses by regulation of the TH1/TH2 balance and cytokine production. Immune system eradicates infecting organisms without serious injury to host tissues, but sometimes these responses are inadequately controlled, giving rise to called hypersensitivity diseases, or inappropriately targeted to host tissues, causing the autoimmune diseases. In clinical medicine, the hypersensitivity diseases include the allergic or atopic diseases and the hallmarks of these diseases are the activation of TH2 cells and the production of IgE antibody. Regarding autoimmunity, at the present time we know that the key events in the development of autoimmunity are a failure or breakdown of the mechanisms normally responsible for maintaining self-tolerance in B lymphocytes, T lymphocytes, or both, the recognition of self-antigens by autoreactive lymphocytes, the activation of these cells to proliferate and differentiate into effector cells, and the tissue injury caused by the effector cells and their products. Melatonin treatment has been investigated in atopic diseases, in several animal models of autoimmune diseases, and has been also evaluated in clinical autoimmune diseases. This review summarizes the role of melatonin in atopic diseases (atopic dermatitis and asthma and in several autoimmune diseases, such as arthritis rheumatoid, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes mellitus, and inflammatory bowel diseases.

  3. Sirolimus for Autoimmune Disease of Blood Cells

    Science.gov (United States)

    2017-11-02

    Autoimmune Pancytopenia; Autoimmune Lymphoproliferative Syndrome (ALPS); Evans Syndrome; Idiopathic Thrombocytopenic Purpura; Anemia, Hemolytic, Autoimmune; Autoimmune Neutropenia; Lupus Erythematosus, Systemic; Inflammatory Bowel Disease; Rheumatoid Arthritis

  4. Intrathecal Fas ligand infusion strengthens immunoprivilege of central nervous system and suppresses experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Zhu, Bing; Luo, Liqing; Chen, Yongliang; Paty, Donald W; Cynader, Max S

    2002-08-01

    Fas ligand (FasL) is an essential molecule strongly expressed in some immunoprivileged sites, but is expressed at very low levels in normal CNS. In this study, acute experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats with guinea pig myelin basic protein. Intrathecal infusion of recombinant FasL before EAE onset dose dependently suppressed acute EAE and alleviated pathological inflammation in lumbosacral spinal cord. This treatment greatly increased apoptosis in CNS inflammatory cells, but did not inhibit systemic immune response to myelin basic protein. Systemic administration of a similar dose of rFasL was ineffective. In vitro, encephalitogenic T cells were highly sensitive to rFasL-induced cell death, and activated macrophages were also susceptible. In addition, in vitro rFasL treatment potentiated the immunosuppressive property of rat cerebrospinal fluid. We conclude that intrathecal infusion of rFasL eliminated the initial wave of infiltrating T cells and macrophages, and therefore blocked the later recruitment of inflammatory cells into CNS. Although Fas receptor expression was observed on spinal cord neurons, astrocytes, and oligodendrocytes, no damage to these cells or to the myelin structure was detected after rFasL infusion.

  5. Headache in autoimmune diseases.

    Science.gov (United States)

    John, Seby; Hajj-Ali, Rula A

    2014-03-01

    Autoimmune diseases are a group of heterogeneous inflammatory disorders characterized by systemic or localized inflammation, leading to ischemia and tissue destruction. These include disorders like systemic lupus erythematosus and related diseases, systemic vasculitides, and central nervous system (CNS) vasculitis (primary or secondary). Headache is a very common manifestation of CNS involvement of these diseases. Although headache characteristics can be unspecific and often non-diagnostic, it is important to recognize because headache can be the first manifestation of CNS involvement. Prompt recognition and treatment is necessary not only to treat the headache, but also to help prevent serious neurological sequelae that frequently accompany autoimmune diseases. In this review, we discuss headache associated with autoimmune diseases along with important mimics. © 2014 American Headache Society.

  6. The Roles of PDGF in Development and During Neurogenesis in the Normal and Diseased Nervous System

    OpenAIRE

    Funa, Keiko; Sasahara, Masakiyo

    2013-01-01

    The four platelet-derived growth factor (PDGF) ligands and PDGF receptors (PDGFRs), α and β (PDGFRA, PDGFRB), are essential proteins that are expressed during embryonic and mature nervous systems, i.e., in neural progenitors, neurons, astrocytes, oligodendrocytes, and vascular cells. PDGF exerts essential roles from the gastrulation period to adult neuronal maintenance by contributing to the regulation of development of preplacodal progenitors, placodal ectoderm, and neural crest cells to adu...

  7. Systemic autoimmune disease and Raynaud's phenomonen.

    NARCIS (Netherlands)

    Kallenberg, Cornelis

    1982-01-01

    Systemic autoimmune diseases (AID) are clinically characterized by the involvement of multiple organ systems in the desease process, and immunologically by immune responsiveness against "self". The constitute a heterogenous group of disorders wich are presented to the clinician in a wide variety of

  8. The central nervous system manifestation and CT findings of Fabry's disease

    International Nuclear Information System (INIS)

    Toyonaga, Kazutaka; Nishihira, Takeo

    1983-01-01

    A case of Fabry's disease with central nervous system dysfunction is reported. This 27-year-old man had recurrent episodes of pains in the extremities when he was a child. Spontaneous clinical remission occured around puberty. He had been well until age 22 when he experienced transient weakness of the left arm. The following year he developed transient blindness of the right eye. Then, he developed weakness in the extremities, dysphagia, dysarthria, and was brought to the hospital in unconscious state. Several members of his family are affected with the same disease presenting leg pains, kidney disease and angiokeratoma. Physical examination disclosed an optic atrophy, pseudobulbar palsy with spastic weakness in the all extremities and multiple angiokeratoma in the flank, buttocks and thighs. Abnormal laboratory findings included leukocytosis, increased ESR and strongly positive CRP. Biopsy of the skin disclosed dilated capilaries with numerous vacuoles in the cytoplasm of the epithelial cells. Thin-layer chromatography of the urine sediment showed a marked increase in ceramide trihexoside. Leukocyte alphagalactosidase level was abnormally low. CT scan showed diffuse cerebral atrophy and multiple low density areas in the thalamus, ventral pons and centrum semiovale. The CT findings and possible mechanism of the response to predonisolone were also discussed. (author)

  9. Pregnancy and the risk of autoimmune disease.

    LENUS (Irish Health Repository)

    Khashan, Ali S

    2012-01-31

    Autoimmune diseases (AID) predominantly affect women of reproductive age. While basic molecular studies have implicated persisting fetal cells in the mother in some AID, supportive epidemiological evidence is limited. We investigated the effect of vaginal delivery, caesarean section (CS) and induced abortion on the risk of subsequent maternal AID. Using the Danish Civil Registration System (CRS) we identified women who were born between 1960 and 1992. We performed data linkage between the CRS other Danish national registers to identify women who had a pregnancy and those who developed AID. Women were categorised into 4 groups; nulligravida (control group), women who had 1st child by vaginal delivery, whose 1st delivery was by CS and who had abortions. Log-linear Poisson regression with person-years was used for data analysis adjusting for several potential confounders. There were 1,035,639 women aged >14 years and 25,570 developed AID: 43.4% nulligravida, 44.3% had their first pregnancy delivered vaginally, 7.6% CS and 4.1% abortions. The risk of AID was significantly higher in the 1st year after vaginal delivery (RR = 1.1[1.0, 1.2]) and CS (RR = 1.3[1.1, 1.5]) but significantly lower in the 1st year following abortion (RR = 0.7[0.6, 0.9]). These results suggest an association between pregnancy and the risk of subsequent maternal AID. Increased risks of AID after CS may be explained by amplified fetal cell traffic at delivery, while decreased risks after abortion may be due to the transfer of more primitive fetal stem cells. The increased risk of AID in the first year after delivery may also be related to greater testing during pregnancy.

  10. Pregnancy and the risk of autoimmune disease.

    Directory of Open Access Journals (Sweden)

    Ali S Khashan

    Full Text Available Autoimmune diseases (AID predominantly affect women of reproductive age. While basic molecular studies have implicated persisting fetal cells in the mother in some AID, supportive epidemiological evidence is limited. We investigated the effect of vaginal delivery, caesarean section (CS and induced abortion on the risk of subsequent maternal AID. Using the Danish Civil Registration System (CRS we identified women who were born between 1960 and 1992. We performed data linkage between the CRS other Danish national registers to identify women who had a pregnancy and those who developed AID. Women were categorised into 4 groups; nulligravida (control group, women who had 1st child by vaginal delivery, whose 1st delivery was by CS and who had abortions. Log-linear Poisson regression with person-years was used for data analysis adjusting for several potential confounders. There were 1,035,639 women aged >14 years and 25,570 developed AID: 43.4% nulligravida, 44.3% had their first pregnancy delivered vaginally, 7.6% CS and 4.1% abortions. The risk of AID was significantly higher in the 1st year after vaginal delivery (RR = 1.1[1.0, 1.2] and CS (RR = 1.3[1.1, 1.5] but significantly lower in the 1st year following abortion (RR = 0.7[0.6, 0.9]. These results suggest an association between pregnancy and the risk of subsequent maternal AID. Increased risks of AID after CS may be explained by amplified fetal cell traffic at delivery, while decreased risks after abortion may be due to the transfer of more primitive fetal stem cells. The increased risk of AID in the first year after delivery may also be related to greater testing during pregnancy.

  11. Psychiatric disorders in children with demyelinating diseases of the central nervous system.

    Science.gov (United States)

    Pakpoor, Julia; Goldacre, Raph; Schmierer, Klaus; Giovannoni, Gavin; Waubant, Emmanuelle; Goldacre, Michael J

    2017-07-01

    The profile of psychiatric disorders associated with multiple sclerosis (MS) may differ in children. We aimed to assess the risk of psychiatric disorders in children with MS and other demyelinating diseases, and vice versa. We analyzed linked English Hospital Episode Statistics, and mortality data, 1999-2011. Cohorts were constructed of children admitted with MS and other central nervous system (CNS) demyelinating diseases. We searched for any subsequent episode of care with psychiatric disorders in these cohorts and compared to a reference cohort. Children with CNS demyelinating diseases had an increased rate of psychotic disorders (rate ratio (RR) = 5.77 (95% confidence interval (CI) = 2.48-11.41)); anxiety, stress-related, and somatoform disorders (RR = 2.38 (1.39-3.81)); intellectual disability (RR = 6.56 (3.66-10.84)); and other behavioral disorders (RR = 8.99 (5.13-14.62)). In analysis of the pediatric MS cohort as the exposure, there were elevated rates of psychotic disorders (RR = 10.76 (2.93-27.63)), mood disorders (RR = 2.57 (1.03-5.31)), and intellectual disability (RR = 6.08 (1.25-17.80)). In reverse analyses, there were elevated rates of a recorded hospital episode with CNS demyelinating disease after a previous recorded episode with anxiety, stress-related, and somatoform disorders; attention-deficit hyperactivity disorder (ADHD); autism; intellectual disability; and other behavioral disorders. This analysis of a national diagnostic database provides strong evidence for an association between pediatric CNS demyelinating diseases and psychiatric disorders, and highlights a need for early involvement of mental health professionals.

  12. Parkinson disease: the enteric nervous system spills its guts.

    Science.gov (United States)

    Derkinderen, P; Rouaud, T; Lebouvier, T; Bruley des Varannes, S; Neunlist, M; De Giorgio, R

    2011-11-08

    Lewy pathology in Parkinson disease (PD) extends well beyond the CNS, also affecting peripheral autonomic neuronal circuits, especially the enteric nervous system (ENS). The ENS is an integrative neuronal network also referred to as "the brain in the gut" because of its similarities to the CNS. We have recently shown that the ENS can be readily analyzed using routine colonic biopsies. This led us to propose that the ENS could represent a unique window to assess the neuropathology in living patients with PD. In this perspective, we discuss current evidence which indicates that the presence of ENS pathology may by exploited to improve our understanding and management of PD and likely other neurodegenerative disorders.

  13. Selected Aspects in the Pathogenesis of Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    György Nagy

    2015-01-01

    Full Text Available Autoimmune processes can be found in physiological circumstances. However, they are quenched with properly functioning regulatory mechanisms and do not evolve into full-blown autoimmune diseases. Once developed, autoimmune diseases are characterized by signature clinical features, accompanied by sustained cellular and/or humoral immunological abnormalities. Genetic, environmental, and hormonal defects, as well as a quantitative and qualitative impairment of immunoregulatory functions, have been shown in parallel to the relative dominance of proinflammatory Th17 cells in many of these diseases. In this review we focus on the derailed balance between regulatory and Th17 cells in the pathogenesis of autoimmune diseases. Additionally, we depict a cytokine imbalance, which gives rise to a biased T-cell homeostasis. The assessment of Th17/Treg-cell ratio and the simultaneous quantitation of cytokines, may give a useful diagnostic tool in autoimmune diseases. We also depict the multifaceted role of dendritic cells, serving as antigen presenting cells, contributing to the development of the pathognomonic cytokine signature and promote cellular and humoral autoimmune responses. Finally we describe the function and role of extracellular vesicles in particular autoimmune diseases. Targeting these key players of disease progression in patients with autoimmune diseases by immunomodulating therapy may be beneficial in future therapeutic strategies.

  14. [Treatment of autoimmune hepatic diseases].

    Science.gov (United States)

    Bueverov, A O

    2004-01-01

    The immunosuppresive drugs, primarily glucocorticosteroids, serve as the basis for the pathogenetic treatment of autoimmune diseases of the liver. In autoimmune hepatitis, immunosuppressive therapy induces and maintains persistent remission in most patients while in primary biliary cirrhosis and primary sclerosing cholangitis, its capacities are substantially limited. Ursodeoxycholic acid is used as the basic drug in predominantly occurring intrahepatic cholestasis. The treatment of cross autoimmune syndromes generally requires the choice of a combination of drugs.

  15. Dapsone in the management of the autoimmune bullous diseases

    Science.gov (United States)

    Piette, Evan W.

    2013-01-01

    Synopsis Dapsone is occasionally used in the treatment of the autoimmune bullous diseases, a group of disorders resulting from autoimmunity directed against basement membrane and/or intercellular adhesion molecules on cutaneous and mucosal surfaces. This review will summarize the limited published data evaluating dapsone as a therapy for the AIBD. PMID:22560144

  16. Primary angiitis of the central nervous system presenting with subacute and fatal course of disease: a case report

    Directory of Open Access Journals (Sweden)

    Börnke Christian

    2005-09-01

    Full Text Available Abstract Background Primary angiitis of the central nervous system is an idiopathic disorder characterized by vasculitis within the dural confines. The clinical presentation shows a wide variation and the course and the duration of disease are heterogeneous. This rare but treatable disease provides a diagnostic challenge owing to the lack of pathognomonic tests and the necessity of a histological confirmation. Case presentation A 28-year-old patient presenting with headache and fluctuating signs of encephalopathy was treated on the assumption of viral meningoencephalitis. The course of the disease led to his death 10 days after hospital admission. Postmortem examination revealed primary angiitis of the central nervous system. Conclusion Primary angiitis of the central nervous system should always be taken into consideration when suspected infectious inflammation of the central nervous system does not respond to treatment adequately. In order to confirm the diagnosis with the consequence of a modified therapy angiography and combined leptomeningeal and brain biopsy should be considered immediately.

  17. IFN-gamma signaling in the central nervous system controls the course of experimental autoimmune encephalomyelitis independently of the localization and composition of inflammatory foci

    Directory of Open Access Journals (Sweden)

    Lee Eunyoung

    2012-01-01

    Full Text Available Abstract Background Murine experimental autoimmune encephalomyelitis (EAE, a model for multiple sclerosis, presents typically as ascending paralysis. However, in mice in which interferon-gamma (IFNγ signaling is disrupted by genetic deletion, limb paralysis is accompanied by atypical deficits, including head tilt, postural imbalance, and circling, consistent with cerebellar/vestibular dysfunction. This was previously attributed to intense cerebellar and brainstem infiltration by peripheral immune cells and formation of neutrophil-rich foci within the CNS. However, the exact mechanism by which IFNγ signaling prohibits the development of vestibular deficits, and whether the distribution and composition of inflammatory foci within the CNS affects the course of atypical EAE remains elusive. Methods We induced EAE in IFNγ-/- mice and bone marrow chimeric mice in which IFNγR is not expressed in the CNS but is intact in the periphery (IFNγRCNSKO and vice versa (IFNγRperiKO. Blood-brain barrier permeability was determined by Evans blue intravenous administration at disease onset. Populations of immune cell subsets in the periphery and the CNS were quantified by flow cytometry. CNS tissues isolated at various time points after EAE induction, were analyzed by immunohistochemistry for composition of inflammatory foci and patterns of axonal degeneration. Results Incidence and severity of atypical EAE were more pronounced in IFNγRCNSKO as compared to IFNγRperiKO mice. Contrary to what we anticipated, cerebella/brainstems of IFNγRCNSKO mice were only minimally infiltrated, while the same areas of IFNγRperiKO mice were extensively populated by peripheral immune cells. Furthermore, the CNS of IFNγRperiKO mice was characterized by persistent neutrophil-rich foci as compared to IFNγRCNSKO. Immunohistochemical analysis of the CNS of IFNγ-/- and IFNγR chimeric mice revealed that IFNγ protective actions are exerted through microglial STAT1

  18. The role of human endogenous retroviruses in the pathogenesis of autoimmune diseases.

    Science.gov (United States)

    Brodziak, Andrzej; Ziółko, Ewa; Muc-Wierzgoń, Małgorzata; Nowakowska-Zajdel, Ewa; Kokot, Teresa; Klakla, Katarzyna

    2012-06-01

    This paper presents a new, recently formulated theory, which concerns the etiopathological process of autoimmune diseases. This theory takes into account the existence in the human genome, since approximately 40 million years, of so-called human endogenous retroviruses (HERVs), which are transmitted to descendants "vertically" by the germ cells. It was recently established that these generally silent sequences perform some physiological roles, but occasionally become active and influence the development of some chronic diseases like diabetes, some neoplasms, chronic diseases of the nervous system (eg, sclerosis multiplex), schizophrenia and autoimmune diseases. We present a short synopsis of immunological processes involved in the pathogenesis of autoimmune diseases, such as molecular mimicry, epitope spreading and activation of the superantigen. We then focus on experimental findings related to systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome and some diseases of hepar and otorhinal tissues. We conclude the outline of this new model of the development of chronic diseases and indicate the conclusions important for the teaching of the basis of pathology.

  19. The therapeutic potential of epigenetics in autoimmune diseases.

    Science.gov (United States)

    De Santis, Maria; Selmi, Carlo

    2012-02-01

    Autoimmune diseases now include over 100 conditions and are estimated to affect over 20 million people in the United States or 5% of the world population with numerous geographical differences coined as geoepidemiology. Further, concordance rates in monozygotic twins are significantly higher compared to dizygotic sets while being significantly below 50% for most autoimmune diseases. These lines of evidence suggest that additional mechanisms are needed to link the individual susceptibility with the proposed chemical and infectious factors in the environment. Epigenetics may well constitute this missing link to include DNA methylation, histone changes, and microRNA which contribute to the epigenome characterizing specific diseases. Importantly, these epigenetic changes may be ideal targets for new personalized treatments as suggested by data in cancer. A number of chemical and physical factors, along with proposed infectious agents or aging, are involved in the etiopathogenesis of autoimmune diseases through epigenetic changes. The most prominent evidence on the association between environment and autoimmunity has been reported in systemic lupus erythematosus, but similar mechanisms were proposed in rheumatoid arthritis, systemic sclerosis, and type 1 diabetes.

  20. Explanation of diagnostic criteria for radiation-induced nervous system disease

    International Nuclear Information System (INIS)

    Xing Zhiwei; Jiang Enhai

    2012-01-01

    National occupational health standard-Diagnostic Criteria for Radiation-Induced Nervous System Disease has been issued and implemented by the Ministry of health. This standard contained three independent criteria of the brain, spinal cord and peripheral nerve injury. These three kinds of disease often go together in clinic,therefore,the three diagnostic criteria were merged into radioactive nervous system disease diagnostic criteria for entirety and maneuverability of the standard. This standard was formulated based on collection of the clinical practice experience, extensive research of relevant literature and foreign relevant publications. It is mainly applied to diagnosis and treatment of occupational radiation-induced nervous system diseases, and to nervous system diseases caused by medical radiation exposure as well. In order to properly implement this standard, also to correctly deal with radioactive nervous system injury, the main contents of this standard including dose threshold, clinical manifestation, indexing standard and treatment principle were interpreted in this article. (authors)

  1. Infectious and inflammatory diseases of the central nervous system-the spectrum of imaging findings and differential diagnosis.

    Science.gov (United States)

    Rozell, Joseph M; Mtui, Edward; Pan, Yu-Ning; Li, Shan

    2017-12-01

    The infectious and inflammatory diseases of the central nervous system (CNS) including the brain and spine can present with a wide spectrum of clinical symptoms, locations, and appearance. The purpose of this exhibit is to review the different patterns of their presentations, to illustrate their imaging characteristics and techniques, and to discuss their clinical features and pathology so that the correct diagnosis can be made and prompt intervention can be initiated on a timely fashion.

  2. Dapsone in the management of autoimmune bullous diseases.

    Science.gov (United States)

    Piette, Evan W; Werth, Victoria P

    2012-05-01

    Dapsone is used in the treatment of autoimmune bullous diseases (AIBD), a group of disorders resulting from autoimmunity directed against basement membrane and/or intercellular adhesion molecules on cutaneous and mucosal surfaces. This review summarizes the limited published data evaluating dapsone as a therapy for AIBD. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. The evolution of the serotonergic nervous system

    DEFF Research Database (Denmark)

    Hay-Schmidt, Anders

    2000-01-01

    Anatomy, serotonergic nervous system, neurons, invertebrates, phylogeny, development, apical ganglion......Anatomy, serotonergic nervous system, neurons, invertebrates, phylogeny, development, apical ganglion...

  4. Restrained Th17 response and myeloid cell infiltration into the central nervous system by human decidua-derived mesenchymal stem cells during experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Bravo, Beatriz; Gallego, Marta I; Flores, Ana I; Bornstein, Rafael; Puente-Bedia, Alba; Hernández, Javier; de la Torre, Paz; García-Zaragoza, Elena; Perez-Tavarez, Raquel; Grande, Jesús; Ballester, Alicia; Ballester, Sara

    2016-03-17

    Multiple sclerosis is a widespread inflammatory demyelinating disease. Several immunomodulatory therapies are available, including interferon-β, glatiramer acetate, natalizumab, fingolimod, and mitoxantrone. Although useful to delay disease progression, they do not provide a definitive cure and are associated with some undesirable side-effects. Accordingly, the search for new therapeutic methods constitutes an active investigation field. The use of mesenchymal stem cells (MSCs) to modify the disease course is currently the subject of intense interest. Decidua-derived MSCs (DMSCs) are a cell population obtained from human placental extraembryonic membranes able to differentiate into the three germ layers. This study explores the therapeutic potential of DMSCs. We used the experimental autoimmune encephalomyelitis (EAE) animal model to evaluate the effect of DMSCs on clinical signs of the disease and on the presence of inflammatory infiltrates in the central nervous system. We also compared the inflammatory profile of spleen T cells from DMSC-treated mice with that of EAE control animals, and the influence of DMSCs on the in vitro definition of the Th17 phenotype. Furthermore, we analyzed the effects on the presence of some critical cell types in central nervous system infiltrates. Preventive intraperitoneal injection of DMSCs resulted in a significant delay of external signs of EAE. In addition, treatment of animals already presenting with moderate symptoms resulted in mild EAE with reduced disease scores. Besides decreased inflammatory infiltration, diminished percentages of CD4(+)IL17(+), CD11b(+)Ly6G(+) and CD11b(+)Ly6C(+) cells were found in infiltrates of treated animals. Early immune response was mitigated, with spleen cells of DMSC-treated mice displaying low proliferative response to antigen, decreased production of interleukin (IL)-17, and increased production of the anti-inflammatory cytokines IL-4 and IL-10. Moreover, lower RORγT and higher GATA-3

  5. [Tumors of the central nervous system].

    Science.gov (United States)

    Alegría-Loyola, Marco Antonio; Galnares-Olalde, Javier Andrés; Mercado, Moisés

    2017-01-01

    Central nervous system (CNS) tumors constitute a heterogeneous group of neoplasms that share a considerable morbidity and mortality rate. Recent advances in the underlying oncogenic mechanisms of these tumors have led to new classification systems, which, in turn, allow for a better diagnostic approach and therapeutic planning. Most of these neoplasms occur sporadically and several risk factors have been found to be associated with their development, such as exposure to ionizing radiation or electromagnetic fields and the concomitant presence of conditions like diabetes, hypertension and Parkinson's disease. A relatively minor proportion of primary CNS tumors occur in the context of hereditary syndromes. The purpose of this review is to analyze the etiopathogenesis, clinical presentation, diagnosis and therapy of CNS tumors with particular emphasis in the putative risk factors mentioned above.

  6. Kaleidoscope of autoimmune diseases in HIV infection.

    Science.gov (United States)

    Roszkiewicz, Justyna; Smolewska, Elzbieta

    2016-11-01

    Within the last 30 years, the human immunodeficiency virus (HIV) infection has changed its status from inevitably fatal to chronic disorder with limited impact on life span. However, this breakthrough was mainly the effect of introduction of the aggressive antiviral treatment, which has led to the clinically significant increase in CD4+ cell count, resulting in fewer cases of the acquired immunodeficiency syndrome (AIDS) and improved management of opportunistic infections occurring in the course of the disease. The occurrence of a particular autoimmune disease depends on degree of immunosuppression of the HIV-positive patient. In 2002, four stages of autoimmunity were proposed in patients infected by HIV, based on the absolute CD4+ cell count, feature of AIDS as well as on the presence of autoimmune diseases. Spectrum of autoimmune diseases associated with HIV infection seems to be unexpectedly wide, involving several organs, such as lungs (sarcoidosis), thyroid gland (Graves' disease), liver (autoimmune hepatitis), connective tissue (systemic lupus erythematosus, rheumatoid arthritis, polyarteritis nodosa and other types of vasculitis, antiphospholipid syndrome) or hematopoietic system (autoimmune cytopenias). This paper contains the state of art on possible coincidences between HIV infection and a differential types of autoimmune diseases, including the potential mechanisms of this phenomenon. As the clinical manifestations of autoimmunization often mimic those inscribed in the course of HIV infection, health care providers should be aware of this rare but potentially deadly association and actively seek for its symptoms in their patients.

  7. The importance of the autonomic nervous system for the development and treatment of dental and periodontal diseases

    OpenAIRE

    Batig, V. M.

    2017-01-01

    One of the mechanisms of the organism's adaptation to environmental changes and the pathological processes development is the reaction of the autonomic nervous system. It is considered as one of the constitutional characteristics of the organism that determines the type of its response to various physiological and pathological stimuli. Analysis of published data showed a significant influence of the autonomic nervous system to stressful situations, especially among young people and the elderl...

  8. The pleiotropic role of HDL in autoimmune diseases.

    Science.gov (United States)

    Parra, Sandra; Castro, Antoni; Masana, Luis

    2015-01-01

    As is widely known, the classic function of HDL is reverse cholesterol transport (RCT), thus removing cholesterol from peripheral tissues. Early epidemiological studies, such as Framingham's, stated that increased HDL levels were associated with a significant decrease in relative risk for cardiovascular disease (CVD) mortality. However, those with heightened expectations in recent years for the development of therapeutic targets to increase HDL levels have been disappointed, because efforts have demonstrated the opposite effect on cardiovascular and global mortality. However, in contrast, studies have highlighted the complexity and the intriguing role of HDL in different pathological conditions, such as infections, neoplasms, and autoimmune diseases. In this review an attempt is made to summarize some biological pathways that link HDL function with the immune system, and its possible clinical repercussions in autoimmune diseases. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  9. Involvement of endocrine system in a patient affected by glycogen storage disease 1b: speculation on the role of autoimmunity.

    Science.gov (United States)

    Melis, Daniela; Della Casa, Roberto; Balivo, Francesca; Minopoli, Giorgia; Rossi, Alessandro; Salerno, Mariacarolina; Andria, Generoso; Parenti, Giancarlo

    2014-03-19

    Glycogen storage disease type 1b (GSD1b) is an inherited metabolic defect of glycogenolysis and gluconeogenesis due to mutations of the SLC37A4 gene and to defective transport of glucose-6-phosphate. The clinical presentation of GSD1b is characterized by hepatomegaly, failure to thrive, fasting hypoglycemia, and dyslipidemia. Patients affected by GSD1b also show neutropenia and/or neutrophil dysfunction that cause increased susceptibility to recurrent bacterial infections. GSD1b patients are also at risk for inflammatory bowel disease. Occasional reports suggesting an increased risk of autoimmune disorders in GSD1b patients, have been published. These complications affect the clinical outcome of the patients. Here we describe the occurrence of autoimmune endocrine disorders including thyroiditis and growth hormone deficiency, in a patient affected by GSD1b. This case further supports the association between GSD1b and autoimmune diseases.

  10. Current practice in laboratory diagnostics of autoimmune diseases in Croatia. 
Survey of the Working group for laboratory diagnostics of autoimmune diseases of the Croatian Society of Medical Biochemistry and Laboratory Medicine

    Science.gov (United States)

    Kuna, Andrea Tešija; Đerek, Lovorka; Kozmar, Ana; Drvar, Vedrana

    2016-01-01

    Introduction With the trend of increasing incidence of autoimmune diseases, laboratories are faced with exponential growth of the requests for tests relating the diagnosis of these diseases. Unfortunately, the lack of laboratory personnel experienced in this specific discipline of laboratory diagnostic, as well as an unawareness of a method limitation often results in confusion for clinicians. The aim was to gain insight into number and type of Croatian laboratories that perform humoral diagnostics with the final goal to improve and harmonize laboratory diagnostics of autoimmune diseases in Croatia. Materials and methods In order to get insight into current laboratory practice two questionnaires, consisting of 42 questions in total, were created. Surveys were conducted using SurveyMonkey application and were sent to 88 medical biochemistry laboratories in Croatia for the first survey. Out of 33 laboratories that declared to perform diagnostic from the scope, 19 were selected for the second survey based on the tests they pleaded to perform. The survey comprised questions regarding autoantibody hallmarks of systemic autoimmune diseases while regarding organ-specific autoimmune diseases was limited to diseases of liver, gastrointestinal and nervous system. Results Response rate was high with 80 / 88 (91%) laboratories which answered the first questionnaire, and 19 / 19 (1.0) for the second questionnaire. Obtained results of surveys indicate high heterogeneity in the performance of autoantibody testing among laboratories in Croatia. Conclusions Results indicate the need of creating recommendations and algorithms in order to harmonize the approach to laboratory diagnostics of autoimmune diseases in Croatia. PMID:27812306

  11. Targeting of prion-infected lymphoid cells to the central nervous system accelerates prion infection

    Directory of Open Access Journals (Sweden)

    Friedman-Levi Yael

    2012-03-01

    Full Text Available Abstract Background Prions, composed of a misfolded protein designated PrPSc, are infectious agents causing fatal neurodegenerative diseases. We have shown previously that, following induction of experimental autoimmune encephalomyelitis, prion-infected mice succumb to disease significantly earlier than controls, concomitant with the deposition of PrPSc aggregates in inflamed white matter areas. In the present work, we asked whether prion disease acceleration by experimental autoimmune encephalomyelitis results from infiltration of viable prion-infected immune cells into the central nervous system. Methods C57Bl/6 J mice underwent intraperitoneal inoculation with scrapie brain homogenates and were later induced with experimental autoimmune encephalomyelitis by inoculation of MOG35-55 in complete Freund's adjuvant supplemented with pertussis toxin. Spleen and lymph node cells from the co-induced animals were reactivated and subsequently injected into naïve mice as viable cells or as cell homogenates. Control groups were infected with viable and homogenized scrapie immune cells only with complete Freund's adjuvant. Prion disease incubation times as well as levels and sites of PrPSc deposition were next evaluated. Results We first show that acceleration of prion disease by experimental autoimmune encephalomyelitis requires the presence of high levels of spleen PrPSc. Next, we present evidence that mice infected with activated prion-experimental autoimmune encephalomyelitis viable cells succumb to prion disease considerably faster than do mice infected with equivalent cell extracts or other controls, concomitant with the deposition of PrPSc aggregates in white matter areas in brains and spinal cords. Conclusions Our results indicate that inflammatory targeting of viable prion-infected immune cells to the central nervous system accelerates prion disease propagation. We also show that in the absence of such targeting it is the load of PrPSc in the

  12. Analysis of gene expression in the nervous system identifies key genes and novel candidates for health and disease.

    Science.gov (United States)

    Carpanini, Sarah M; Wishart, Thomas M; Gillingwater, Thomas H; Manson, Jean C; Summers, Kim M

    2017-04-01

    The incidence of neurodegenerative diseases in the developed world has risen over the last century, concomitant with an increase in average human lifespan. A major challenge is therefore to identify genes that control neuronal health and viability with a view to enhancing neuronal health during ageing and reducing the burden of neurodegeneration. Analysis of gene expression data has recently been used to infer gene functions for a range of tissues from co-expression networks. We have now applied this approach to transcriptomic datasets from the mammalian nervous system available in the public domain. We have defined the genes critical for influencing neuronal health and disease in different neurological cell types and brain regions. The functional contribution of genes in each co-expression cluster was validated using human disease and knockout mouse phenotypes, pathways and gene ontology term annotation. Additionally a number of poorly annotated genes were implicated by this approach in nervous system function. Exploiting gene expression data available in the public domain allowed us to validate key nervous system genes and, importantly, to identify additional genes with minimal functional annotation but with the same expression pattern. These genes are thus novel candidates for a role in neurological health and disease and could now be further investigated to confirm their function and regulation during ageing and neurodegeneration.

  13. CT diagnosis of congenital anomalies of the central nervous system

    International Nuclear Information System (INIS)

    Mori, Koreaki

    1980-01-01

    In the diagnosis of central nervous system congenital anomalies, understanding of embryology of the central nervous system and pathophysiology of each anomaly are essential. It is important for clinical approach to central nervous system congenital anomalies to evaluate the size of the head and tention of the anterior fontanelle. Accurate diagnosis of congenital anomalies depends on a correlation of CT findings to clinical pictures. Clinical diagnosis of congenital anomalies should include prediction of treatability and prognosis, in addition to recognition of a disease. (author)

  14. Ginger extract modulates the expression of IL-12 and TGF-β in the central nervous system and serum of mice with experimental autoimmune encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Abdollah Jafarzadeh

    2017-01-01

    Full Text Available Objective: The main function of IL-12 is differentiation of naive T cells intoTh1 cells and TGF-β is a powerful immunoregulatory cytokine. The immunomodulatory and anti-inflammatory properties of ginger have also been reported in some studies. The aim of this study was to evaluate the effects of ginger extract on the expression of IL-12 and TGF-β in a model of experimental autoimmune encephalomyelitis (EAE.Materials and Methods: EAE was induced in C57BL/6 mice by immunization with myelin oligodendroglial glycoprotein emulsified in complete Freund's adjuvant. The mice were administered intra-peritoneally with ginger extracts or PBS, from day +3 to +30. On day 31, mice were scarified and the expression of IL-12 and TGF-β mRNA in the spinal cord were determined by using real time-PCR. The serum levels of cytokines were measured by ELISA.Results: In PBS-treated EAE mice, the expression of IL-12 P35 and IL-12 P40 mRNA in the CNS and the mean serum levels of IL-12 were significantly higher than those of healthy group (p

  15. A Tol2 Gateway-Compatible Toolbox for the Study of the Nervous System and Neurodegenerative Disease.

    Science.gov (United States)

    Don, Emily K; Formella, Isabel; Badrock, Andrew P; Hall, Thomas E; Morsch, Marco; Hortle, Elinor; Hogan, Alison; Chow, Sharron; Gwee, Serene S L; Stoddart, Jack J; Nicholson, Garth; Chung, Roger; Cole, Nicholas J

    2017-02-01

    Currently there is a lack in fundamental understanding of disease progression of most neurodegenerative diseases, and, therefore, treatments and preventative measures are limited. Consequently, there is a great need for adaptable, yet robust model systems to both investigate elementary disease mechanisms and discover effective therapeutics. We have generated a Tol2 Gateway-compatible toolbox to study neurodegenerative disorders in zebrafish, which includes promoters for astrocytes, microglia and motor neurons, multiple fluorophores, and compatibility for the introduction of genes of interest or disease-linked genes. This toolbox will advance the rapid and flexible generation of zebrafish models to discover the biology of the nervous system and the disease processes that lead to neurodegeneration.

  16. The central nervous system

    International Nuclear Information System (INIS)

    Holmes, R.A.

    1984-01-01

    The first section presents a comprehensive evaluation of radionuclide imaging of the central nervous system and provides a comparison of the detection accuracies of radionuclide imaging (RNI) and XCT in certain lesions, realizing that the XCT results may vary when radiocontrast or newer generation XCT scanners are used. Although conventional radionuclide imaging of the central nervous system has experienced no significant changes over the last 7 years except for mild refinements, a new section has been added on positron emission tomography (PET). Most positron radiopharmaceuticals passively cross the intact blood-brain barrier, and their localization has catalyzed renewed interest in our ability to metabolically study and obtain images of the central nervous system. The section on radionuclide cisternography has been rewritten to reflect present day practice and the wider application of XCT in describing conditions affecting the ventricular system

  17. Antibody response against gastrointestinal antigens in demyelinating diseases of the central nervous system

    DEFF Research Database (Denmark)

    Banati, M; Csecsei, P; Koszegi, E

    2013-01-01

    BACKGROUND: Antibodies against gastrointestinal antigens may indicate altered microbiota and immune responses in the gut. Recent experimental data suggest a connection between gastrointestinal immune responses and CNS autoimmunity. METHODS: Antibodies against gliadin, tissue transglutaminase (tTG...

  18. Chemokines and chemokine receptors in inflammation of the nervous system

    DEFF Research Database (Denmark)

    Huang, D; Han, Yong-Chang; Rani, M R

    2000-01-01

    This article focuses on the production of chemokines by resident glial cells of the nervous system. We describe studies in two distinct categories of inflammation within the nervous system: immune-mediated inflammation as seen in experimental autoimmune encephalomyelitis (EAE) or multiple sclerosis...... (MS) and post-traumatic inflammation. We provide evidence that chemokines play a role in amplifying the inflammatory reaction in EAE (and, probably, MS). In the context of neural trauma, chemokines appear to be primary stimuli for leukocyte recruitment. Strikingly, expression of monocyte...... that produce aggregates of simultaneous stimuli. These characteristics, in turn, mirror the expression patterns of the endogenous genes: MCP-1 is expressed under a variety of circumstances, while IP-10 appears primarily during immune-mediated processes that feature exposure of resident neuroglia to high levels...

  19. The autoimmune concept of multiple sclerosis.

    Science.gov (United States)

    Nicol, Bryan; Salou, Marion; Laplaud, David-Axel; Wekerle, Hartmut

    2015-04-01

    Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system (CNS). With growing evidence for environmental and genetic factors, MS is now accepted as an autoimmune disease. This complex disease seems to implicate various cell types in both innate and adaptive compartments. Here, we discuss recent advances in the immunological field of MS research. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  20. Beta-endorphin and the immune system--possible role in autoimmune diseases

    DEFF Research Database (Denmark)

    Mørch, H; Pedersen, B K

    1995-01-01

    The immune system and the neuroendocrine system are closely interconnected having such means of bidirectional communication and regulation. In this review, a hypothesis is put forward regarding the possible role of beta-endorphins in the pathogenesis of autoimmune diseases: It is suggested...

  1. Associated Autoimmune Diseases

    Science.gov (United States)

    ... celiac disease are type 1 diabetes and autoimmune thyroid disease. The tendency to develop autoimmune diseases is believed ... confusion, weight loss, and coma (if left untreated). Thyroid Disease There are two common forms of autoimmune thyroid ...

  2. NETs: The missing link between cell death and systemic autoimmune diseases?

    Directory of Open Access Journals (Sweden)

    Felipe eAndrade

    2013-01-01

    Full Text Available For almost 20 years, apoptosis and secondary necrosis have been considered the major source of autoantigens and endogenous adjuvants in the pathogenic model of systemic autoimmune diseases. This focus is justified in part because initial evidence in systemic lupus erythematosus (SLE guided investigators toward the study of apoptosis, but also because other forms of cell death were unknown. To date, it is known that many other forms of cell death occur, and that they vary in their capacity to stimulate as well as inhibit the immune system. Among these, NETosis (an antimicrobial form of death in neutrophils in which nuclear material is extruded from the cell forming extracellular traps, is gaining major interest as a process that may trigger some of the immune features found in SLE, granulomatosis with polyangiitis (formerly Wegener’s granulomatosis and Felty’s syndrome. Although there have been volumes of very compelling studies published on the role of cell death in autoimmunity, no unifying theory has been adopted nor have any successful therapeutics been developed based on this important pathway. The recent inclusion of NETosis into the pathogenic model of autoimmune diseases certainly adds novel insights into this paradigm, but also reveals a previously unappreciated level of complexity and raises many new questions. This review discusses the role of cell death in systemic autoimmune diseases with a focus on apoptosis and NETosis, highlights the current short comings in our understanding of the vast complexity of cell death, and considers the potential shift in the cell death paradigm in autoimmunity. Understanding this complexity is critical in order to develop tools to clearly define the death pathways that are active in systemic autoimmune diseases, identify drivers of disease propagation, and develop novel therapeutics.

  3. Recent advances in understanding autoimmune thyroid disease

    DEFF Research Database (Denmark)

    Bliddal, Sofie; Nielsen, Claus Henrik; Feldt-Rasmussen, Ulla

    2017-01-01

    Autoimmune thyroid disease (AITD) is often observed together with other autoimmune diseases. The coexistence of two or more autoimmune diseases in the same patient is referred to as polyautoimmunity, and AITD is the autoimmune disease most frequently involved. The occurrence of polyautoimmunity has...... led to the hypothesis that the affected patients suffer from a generalized dysregulation of their immune system. The present review summarizes recent discoveries unravelling the immunological mechanisms involved in autoimmunity, ranging from natural autoimmunity to disease-specific autoimmunity...

  4. Palivizumab Exposure and the Risk of Autoimmune Disease

    DEFF Research Database (Denmark)

    Haerskjold, Ann; Linder, Marie; Henriksen, Lonny

    2016-01-01

    of autoimmune disease were diagnosed among palivizumab-exposed children during the period of observation. Among the children exposed to palivizumab, one child in Denmark developed inflammatory bowel disease; in Sweden, children developed juvenile arthritis (one child), diabetes mellitus (two children), celiac......BACKGROUND: Treatment with biologic pharmaceuticals may be associated with an increased risk of immune-mediated disease. Palivizumab is a humanized monoclonal antibody designed to provide passive immunity against respiratory syncytial virus infection. Palivizumab is primarily used in preterm...... children known to be immunologically immature. The long-term effect of palivizumab in terms of autoimmune diseases has not yet been investigated. AIM: Our objective was to investigate whether exposure to palivizumab was associated with the development of autoimmune diseases in children. METHODS...

  5. DAMAGE OF NERVOUS SYSTEM IN TICK-BITE BORRELIOSIS (LYME DISEASE IN СHILDREN IN THE KIROV REGION

    Directory of Open Access Journals (Sweden)

    T. V. Egorova

    2017-01-01

    Full Text Available During 1993—2016 there were treated 1255 children 9 months — 14 ages old with tick-bite infections in Kirov Infectious Clinical Hospital and 1214 children from them with the verified diagnosis of Lyme disease. Damage of nervous system was detected in 98 (8.1% patients in the forms of serous meningitis, meningoencephalitis, polyneuropathies, neuropathies, disseminated encephalomyelitis, diencephalic syndrome with impaired thermal regulation. 45.9 % of cases were mixed-infection (tick-bite encephalitis and Lyme disease

  6. The role of microbiome in central nervous system disorders

    Science.gov (United States)

    Wang, Yan; Kasper, Lloyd H.

    2014-01-01

    Mammals live in a co-evolutionary association with the plethora of microorganisms that reside at a variety of tissue microenvironments. The microbiome represents the collective genomes of these co-existing microorganisms, which is shaped by host factors such as genetics and nutrients but in turn is able to influence host biology in health and disease. Niche-specific microbiome, prominently the gut microbiome, has the capacity to effect both local and distal sites within the host. The gut microbiome has played a crucial role in the bidirectional gut-brain axis that integrates the gut and central nervous system (CNS) activities, and thus the concept of microbiome-gut-brain axis is emerging. Studies are revealing how diverse forms of neuro-immune and neuro-psychiatric disorders are correlated with or modulated by variations of microbiome, microbiota-derived products and exogenous antibiotics and probiotics. The microbiome poises the peripheral immune homeostasis and predisposes host susceptibility to CNS autoimmune diseases such as multiple sclerosis. Neural, endocrine and metabolic mechanisms are also critical mediators of the microbiome-CNS signaling, which are more involved in neuro-psychiatric disorders such as autism, depression, anxiety, stress. Research on the role of microbiome in CNS disorders deepens our academic knowledge about host-microbiome commensalism in central regulation and in practicality, holds conceivable promise for developing novel prognostic and therapeutic avenues for CNS disorders. PMID:24370461

  7. Encephalopathy Associated With Autoimmune Thyroid Disease

    OpenAIRE

    li A. Raouf; Gianluca Tamagno

    2014-01-01

    Autoimmune thyroid diseases (ATDs) are immune-endocrine disorders affecting the thyroid gland and, eventually, also a number of other systemic targets, including the brain and the nervous system. Encephalopathy associated with autoimmune thyroid disease (EAATD) is a rare, heterogeneous condition arising from the background of an ATD. It is characterised by neurological and/or psychiatric symptoms with acute or sub-acute onset, and virtually any neurological or psychiatric symptom can appear. ...

  8. When do the symptoms of autonomic nervous system malfunction appear in patients with Parkinson’s disease?

    Directory of Open Access Journals (Sweden)

    De Luka Silvio R.

    2014-01-01

    Full Text Available Background/Aim. Dysautonomia appears in almost all patients with Parkinson’s disease (PD in a certain stage of their condition. The aim of our study was to detect the development and type of autonomic disorders, find out the factors affecting their manifestation by analyzing the potential association with demographic variables related to clinical presentation, as well as the symptoms of the disease in a PD patient cohort. Methods. The patients with PD treated at the Clinic of Neurology in Belgrade during a 2-year period, divided into 3 groups were studied: 25 de novo patients, 25 patients already treated and had no long-term levodopa therapy-related complications and 22 patients treated with levodopa who manifested levodopa-induced motor complications. Simultaneously, 35 healthy control subjects, matched by age and sex, were also analyzed. Results. Autonomic nervous system malfunction was defined by Ewing diagnostic criteria. The tests, indicators of sympathetic and parasympathetic nervous systems, were significantly different in the PD patients as compared with the controls, suggesting the failure of both systems. However, it was shown, in the selected groups of patients, that the malfunction of both systems was present in two treated groups of PD patients, while de novo group manifested only sympathetic dysfunction. For this reason, the complete autonomic neuropathy was diagnosed only in the treated PD patients, while de novo patients were defined as those with the isolated sympathetic dysfunction. The patients with the complete autonomic neuropathy differed from the subjects without such neuropathy in higher cumulative and motor unified Parkinson’s disease rating score (UPDRS (p < 0.01, activities of daily living scores (p < 0.05, Schwab-England scale (p < 0.001 and Hoehn-Yahr scale. There was no difference between the patients in other clinical-demographic characteristics (sex, age at the time of diagnosis, actual age, duration of

  9. Autoimmune liver disease panel

    Science.gov (United States)

    Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cholangitis (formerly called primary biliary cirrhosis). This group of tests ...

  10. Chagas disease and systemic autoimmune diseases among Bolivian patients in Switzerland

    Directory of Open Access Journals (Sweden)

    Yves Jackson

    2018-02-01

    Full Text Available BACKGROUND Chronic cardiomyopathy occurs in 20-40% of the patients with Chagas disease. Autoimmune mechanisms may contribute to its pathogenesis. We diagnosed several cases of systemic autoimmune diseases among Bolivian migrants in Geneva with a high prevalence of Chagas disease. OBJECTIVES We tested the hypothesis of a clinical association between systemic autoimmune diseases and Chagas disease, particularly with the development of cardiomyopathy. METHODS We retrospectively searched the medical records of all Bolivian patients visiting Geneva University Hospitals between 2012 and 2015 for diagnosis of Chagas disease or systemic autoimmune diseases. FINDINGS Of the 2,189 eligible patients, 28 [1.3%; 95% confidence interval (CI = 0.9-1.9%] presented with systemic autoimmune disease. The Chagas status was known in 903 (41.3% patient, of whom 244 (27.0%; 95% CI = 24.2-30.0% were positive. Eight (28.6%; 95% CI = 15.3-47.1% of the 28 cases of systemic autoimmune disease had Chagas disease. We found no association between both entities (p = 1.000 or with Chagasic cardiomyopathy (p = 0.729. Moreover, there was no evidence of a temporal relationship between antiparasitic chemotherapy and the development of systemic autoimmune diseases. CONCLUSIONS Our results do not support a clinical association between chronic Chagas disease and systemic autoimmune diseases. However, prospective studies in areas endemic for Chagas disease should better assess the prevalence of systemic autoimmune diseases and thus a possible relationship with this infection.

  11. Chagas disease and systemic autoimmune diseases among Bolivian patients in Switzerland.

    Science.gov (United States)

    Jackson, Yves; Pula, Drenusha Vieira de Mello; Finckh, Axel; Chizzolini, Carlo; Chappuis, François

    2018-02-05

    Chronic cardiomyopathy occurs in 20-40% of the patients with Chagas disease. Autoimmune mechanisms may contribute to its pathogenesis. We diagnosed several cases of systemic autoimmune diseases among Bolivian migrants in Geneva with a high prevalence of Chagas disease. We tested the hypothesis of a clinical association between systemic autoimmune diseases and Chagas disease, particularly with the development of cardiomyopathy. We retrospectively searched the medical records of all Bolivian patients visiting Geneva University Hospitals between 2012 and 2015 for diagnosis of Chagas disease or systemic autoimmune diseases. Of the 2,189 eligible patients, 28 [1.3%; 95% confidence interval (CI) = 0.9-1.9%] presented with systemic autoimmune disease. The Chagas status was known in 903 (41.3%) patient, of whom 244 (27.0%; 95% CI = 24.2-30.0%) were positive. Eight (28.6%; 95% CI = 15.3-47.1%) of the 28 cases of systemic autoimmune disease had Chagas disease. We found no association between both entities (p = 1.000) or with Chagasic cardiomyopathy (p = 0.729). Moreover, there was no evidence of a temporal relationship between antiparasitic chemotherapy and the development of systemic autoimmune diseases. Our results do not support a clinical association between chronic Chagas disease and systemic autoimmune diseases. However, prospective studies in areas endemic for Chagas disease should better assess the prevalence of systemic autoimmune diseases and thus a possible relationship with this infection.

  12. Clinical aspects of autoimmune rheumatic diseases.

    Science.gov (United States)

    Goldblatt, Fiona; O'Neill, Sean G

    2013-08-31

    Multisystem autoimmune rheumatic diseases are heterogeneous rare disorders associated with substantial morbidity and mortality. Efforts to create international consensus within the past decade have resulted in the publication of new classification or nomenclature criteria for several autoimmune rheumatic diseases, specifically for systemic lupus erythematosus, Sjögren's syndrome, and the systemic vasculitides. Substantial progress has been made in the formulation of new criteria in systemic sclerosis and idiopathic inflammatory myositis. Although the autoimmune rheumatic diseases share many common features and clinical presentations, differentiation between the diseases is crucial because of important distinctions in clinical course, appropriate drugs, and prognoses. We review some of the dilemmas in the diagnosis of these autoimmune rheumatic diseases, and focus on the importance of new classification criteria, clinical assessment, and interpretation of autoimmune serology. In this era of improvement of mortality rates for patients with autoimmune rheumatic diseases, we pay particular attention to the effect of leading complications, specifically cardiovascular manifestations and cancer, and we update epidemiology and prognosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. The Nervous System Game

    Science.gov (United States)

    Corbitt, Cynthia; Carpenter, Molly

    2006-01-01

    For many children, especially those with reading difficulties, a motor-kinesthetic learning activity may be an effective tool to teach complex concepts. With this in mind, the authors developed and tested a game designed to teach fourth- to sixth-grade children some basic principles of nervous system function by allowing the children themselves to…

  14. The role of monocytes and monocyte-derived dendritic cells in type 1 diabetes mellitus and autoimmune thyroid disease

    NARCIS (Netherlands)

    W.K. Lam-Tse

    2003-01-01

    textabstractType 1 diabetes mellitus (DM1) and autoimmune thyroid disease (AITD) are organ specific autoimmune diseases in which the immune system is directed against the ß cells and the thyrocytes respectively. The etio-pathogenesis of organ-specific or endocrine autoimmune diseases is complex,

  15. Family history of systemic lupus erythematosus and risk of autoimmune disease

    DEFF Research Database (Denmark)

    Ulff-Møller, Constance Jensina; Simonsen, Jacob; Kyvik, Kirsten Ohm

    2017-01-01

    Objective.: To provide population-based estimates of relative risk of SLE and other autoimmune diseases (ADs) in relatives of SLE patients. Methods.: A cohort of 5 237 319 Danish residents identified through the Civil Registration System was coupled to their relatives through the parental link...

  16. Role of glutamatergic neurotransmission in the enteric nervous system and brain-gut axis in health and disease.

    Science.gov (United States)

    Filpa, Viviana; Moro, Elisabetta; Protasoni, Marina; Crema, Francesca; Frigo, Gianmario; Giaroni, Cristina

    2016-12-01

    Several studies have been carried out in the last 30 years in the attempt to clarify the possible role of glutamate as a neurotransmitter/neuromodulator in the gastrointestinal tract. Such effort has provided immunohistochemical, biomolecular and functional data suggesting that the entire glutamatergic neurotransmitter machinery is present in the complex circuitries of the enteric nervous system (ENS), which participates to the local coordination of gastrointestinal functions. Glutamate is also involved in the regulation of the brain-gut axis, a bi-directional connection pathway between the central nervous system (CNS) and the gut. The neurotransmitter contributes to convey information, via afferent fibers, from the gut to the brain, and to send appropriate signals, via efferent fibers, from the brain to control gut secretion and motility. In analogy with the CNS, an increasing number of studies suggest that dysregulation of the enteric glutamatergic neurotransmitter machinery may lead to gastrointestinal dysfunctions. On the whole, this research field has opened the possibility to find new potential targets for development of drugs for the treatment of gastrointestinal diseases. The present review analyzes the more recent literature on enteric glutamatergic neurotransmission both in physiological and pathological conditions, such as gastroesophageal reflux, gastric acid hypersecretory diseases, inflammatory bowel disease, irritable bowel syndrome and intestinal ischemia/reperfusion injury. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Longitudinal analysis of hearing loss in a case of hemosiderosis of the central nervous system.

    NARCIS (Netherlands)

    Weekamp, H.; Huygen, P.L.M.; Merx, J.L.; Kremer, H.P.H.; Cremers, C.W.R.J.; Longridge, N.S.

    2003-01-01

    OBJECTIVE: To describe cochleovestibular aspects of superficial hemosiderosis of the central nervous system. BACKGROUND: Superficial hemosiderosis of the central nervous system is a rare disease in which cochleovestibular impairment, cerebellar ataxia, and myelopathy are the most frequent signs.

  18. Longitudinal analysis of hearing loss in a case of hemosiderosis of the central nervous system

    NARCIS (Netherlands)

    Weekamp, H H; Huygen, P L M; Merx, J L; Kremer, H P H; Cremers, Cor W R J; Longridge, Neil S

    OBJECTIVE: To describe cochleovestibular aspects of superficial hemosiderosis of the central nervous system. BACKGROUND: Superficial hemosiderosis of the central nervous system is a rare disease in which cochleovestibular impairment, cerebellar ataxia, and myelopathy are the most frequent signs.

  19. Hypogonadism and the risk of rheumatic autoimmune disease.

    Science.gov (United States)

    Baillargeon, Jacques; Al Snih, Soham; Raji, Mukaila A; Urban, Randall J; Sharma, Gulshan; Sheffield-Moore, Melinda; Lopez, David S; Baillargeon, Gwen; Kuo, Yong-Fang

    2016-12-01

    Testosterone deficiency has been linked with autoimmune disease and an increase in inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor, and interleukin-6 (IL-6). However, no large-scale longitudinal studies have examined this association. We examined whether untreated hypogonadism was associated with an increased risk of rheumatic autoimmune disease in a large nationally representative cohort. Using one of the nation's largest commercial insurance databases, we conducted a retrospective cohort study in which we identified 123,460 men diagnosed with hypogonadism between January 1, 2002 and December 31, 2014 and with no prior history of rheumatic autoimmune disease. We matched this cohort to 370,380 men without hypogonadism, at a 1 to 3 ratio, on age and index/diagnosis date. All patients were followed until December 31, 2014 or until they lost insurance coverage or were diagnosed with a rheumatic autoimmune disease. Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHRs). Untreated hypogonadism was associated with an increased risk of developing any rheumatic autoimmune disease (HR = 1.33, 95 % CI = 1.28, 1.38), rheumatoid arthritis (HR = 1.31, 95 % CI = 1.22, 1.44), and lupus (HR = 1.58, 95 % CI = 1.28, 1.94). These findings persisted using latency periods of 1 and 2 years. Hypogonadism was not associated with the control outcome, epilepsy (HR = 1.04, 95 % CI = 0.96, 1.15). Patients diagnosed with hypogonadism who were not treated with testosterone had an increased risk of developing any rheumatic autoimmune disease, rheumatoid arthritis, and lupus. Future research should further examine this association, with particular attention to underlying mechanisms.

  20. Hypogonadism and the risk of rheumatic autoimmune disease

    Science.gov (United States)

    Snih, Soham Al; Raji, Mukaila A.; Urban, Randall J.; Sharma, Gulshan; Sheffield-Moore, Melinda; Lopez, David S.; Baillargeon, Gwen; Kuo, Yong-Fang

    2017-01-01

    Testosterone deficiency has been linked with autoimmune disease and an increase in inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor, and interleukin-6 (IL-6). However, no large-scale longitudinal studies have examined this association. We examined whether untreated hypogonadism was associated with an increased risk of rheumatic autoimmune disease in a large nationally representative cohort. Using one of the nation’s largest commercial insurance databases, we conducted a retrospective cohort study in which we identified 123,460 men diagnosed with hypogonadism between January 1, 2002 and December 31, 2014 and with no prior history of rheumatic autoimmune disease. We matched this cohort to 370,380 men without hypogonadism, at a 1 to 3 ratio, on age and index/diagnosis date. All patients were followed until December 31, 2014 or until they lost insurance coverage or were diagnosed with a rheumatic autoimmune disease. Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHRs). Untreated hypogonadism was associated with an increased risk of developing any rheumatic autoimmune disease (HR = 1.33, 95 % CI = 1.28, 1.38), rheumatoid arthritis (HR = 1.31, 95 % CI = 1.22, 1.44), and lupus (HR = 1.58, 95 % CI = 1.28, 1.94). These findings persisted using latency periods of 1 and 2 years. Hypogonadism was not associated with the control outcome, epilepsy (HR = 1.04, 95 % CI = 0.96, 1.15). Patients diagnosed with hypogonadism who were not treated with testosterone had an increased risk of developing any rheumatic autoimmune disease, rheumatoid arthritis, and lupus. Future research should further examine this association, with particular attention to underlying mechanisms. PMID:27325124

  1. Metallothionein expression in the central nervous system of multiple sclerosis patients

    DEFF Research Database (Denmark)

    Penkowa, M; Espejo, C; Ortega-Aznar, A

    2003-01-01

    Multiple sclerosis (MS) is a major chronic demyelinating and inflammatory disease of the central nervous system (CNS) in which oxidative stress likely plays a pathogenic role in the development of myelin and neuronal damage. Metallothioneins (MTs) are antioxidant proteins induced in the CNS...... by tissue injury, stress and some neurodegenerative diseases, which have been postulated to play a neuroprotective role. In fact, MT-I+II-deficient mice are more susceptible to developing experimental autoimmune encephalomyelitis (EAE), and treatment of Lewis rats with Zn-MT-II reduces EAE severity. We show...

  2. Is Alzheimer's Disease Autoimmune Inflammation of the Brain That Can be Treated With Nasal Nonsteroidal Anti-Inflammatory Drugs?

    Science.gov (United States)

    Lehrer, Steven; Rheinstein, Peter H

    2015-05-01

    The Alzheimer's Association recently reported that a woman's estimated lifetime risk of developing Alzheimer's at age 65 is 1 in 6, compared to nearly 1 in 11 for a man (ie, female to male ratio 1.8). Based on female to male ratio, Alzheimer's disease could well be an autoimmune disorder. Like Alzheimer's, multiple sclerosis, an autoimmune inflammation of the central nervous system, has a female to male ratio of 2.3. Also based on female to male ratio, Alzheimer's resembles the autoimmune inflammatory disease rheumatoid arthritis, which has a female to male ratio of 2.7. The reasons for the female preponderance in autoimmune disease are unclear, but nonsteroidal anti-inflammatory drugs (NSAIDs) are widely and successfully employed to treat autoimmune anti-inflammatory disease and dramatically relieve symptoms. Moreover, oral NSAIDs consistently reduce the risk of Alzheimer's disease, although they have been totally ineffective as a treatment in multiple failed clinical trials. A basis for this failure might well be that the brain dose after oral administration is too small and not sufficiently early in the pathogenesis of the disorder. But NSAID brain dose could be significantly increased by delivering the NSAIDs intranasally. © The Author(s) 2014.

  3. Congenital tumors of the central nervous system

    International Nuclear Information System (INIS)

    Severino, Mariasavina; Schwartz, Erin S.; Thurnher, Majda M.; Rydland, Jana; Nikas, Ioannis; Rossi, Andrea

    2010-01-01

    Congenital tumors of the central nervous system (CNS) are often arbitrarily divided into ''definitely congenital'' (present or producing symptoms at birth), ''probably congenital'' (present or producing symptoms within the first week of life), and ''possibly congenital'' (present or producing symptoms within the first 6 months of life). They represent less than 2% of all childhood brain tumors. The clinical features of newborns include an enlarged head circumference, associated hydrocephalus, and asymmetric skull growth. At birth, a large head or a tense fontanel is the presenting sign in up to 85% of patients. Neurological symptoms as initial symptoms are comparatively rare. The prenatal diagnosis of congenital CNS tumors, while based on ultrasonography, has significantly benefited from the introduction of prenatal magnetic resonance imaging studies. Teratomas constitute about one third to one half of these tumors and are the most common neonatal brain tumor. They are often immature because of primitive neural elements and, rarely, a component of mixed malignant germ cell tumors. Other tumors include astrocytomas, choroid plexus papilloma, primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumors, and medulloblastomas. Less common histologies include craniopharyngiomas and ependymomas. There is a strong predilection for supratentorial locations, different from tumors of infants and children. Differential diagnoses include spontaneous intracranial hemorrhage that can occur in the presence of coagulation factor deficiency or underlying vascular malformations, and congenital brain malformations, especially giant heterotopia. The prognosis for patients with congenital tumors is generally poor, usually because of the massive size of the tumor. However, tumors can be resected successfully if they are small and favorably located. The most favorable outcomes are achieved with choroid plexus tumors, where aggressive surgical treatment leads to disease

  4. Congenital tumors of the central nervous system

    Energy Technology Data Exchange (ETDEWEB)

    Severino, Mariasavina [G. Gaslini Children' s Hospital, Department of Neuroradiology, Genoa (Italy); Schwartz, Erin S. [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Thurnher, Majda M. [Medical University of Vienna, Department of Radiology, Vienna (Austria); Rydland, Jana [MR Center, St. Olav' s Hospital HF, Trondheim (Norway); Nikas, Ioannis [Agia Sophia Children' s Hospital, Imaging Department, Athens (Greece); Rossi, Andrea [G. Gaslini Children' s Hospital, Department of Neuroradiology, Genoa (Italy); G. Gaslini Children' s Hospital, Department of Pediatric Neuroradiology, Genoa (Italy)

    2010-06-15

    Congenital tumors of the central nervous system (CNS) are often arbitrarily divided into ''definitely congenital'' (present or producing symptoms at birth), ''probably congenital'' (present or producing symptoms within the first week of life), and ''possibly congenital'' (present or producing symptoms within the first 6 months of life). They represent less than 2% of all childhood brain tumors. The clinical features of newborns include an enlarged head circumference, associated hydrocephalus, and asymmetric skull growth. At birth, a large head or a tense fontanel is the presenting sign in up to 85% of patients. Neurological symptoms as initial symptoms are comparatively rare. The prenatal diagnosis of congenital CNS tumors, while based on ultrasonography, has significantly benefited from the introduction of prenatal magnetic resonance imaging studies. Teratomas constitute about one third to one half of these tumors and are the most common neonatal brain tumor. They are often immature because of primitive neural elements and, rarely, a component of mixed malignant germ cell tumors. Other tumors include astrocytomas, choroid plexus papilloma, primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumors, and medulloblastomas. Less common histologies include craniopharyngiomas and ependymomas. There is a strong predilection for supratentorial locations, different from tumors of infants and children. Differential diagnoses include spontaneous intracranial hemorrhage that can occur in the presence of coagulation factor deficiency or underlying vascular malformations, and congenital brain malformations, especially giant heterotopia. The prognosis for patients with congenital tumors is generally poor, usually because of the massive size of the tumor. However, tumors can be resected successfully if they are small and favorably located. The most favorable outcomes are achieved with choroid plexus tumors

  5. Primary central nervous system lymphomas and related diseases: Pathological characteristics and discussion of the differential diagnosis.

    Science.gov (United States)

    Sugita, Yasuo; Muta, Hiroko; Ohshima, Koichi; Morioka, Motohiro; Tsukamoto, Yoshihiro; Takahashi, Hitoshi; Kakita, Akiyoshi

    2016-08-01

    Although primary diffuse large B-cell lymphomas of the CNS are designated as primary CNS lymphomas according to the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue in 2008, a variety of other lymphomas (Burkitt lymphomas, EBV-positive diffuse large B-cell lymphoma of the elderly) and related diseases (lymphomatoid granulomatosis) that are also found in the CNS have been spotlighted in recent years. The histopathology of primary CNS Burkitt lymphomas mimics that of primary diffuse large B-cell lymphomas of the CNS after steroid administration. Therefore, for correct diagnosis of the involved lymphoma, comprehensive fluorescent in situ hybridization analysis for c-MYC and BCL2 is recommended in all primary CNS lymphoma cases with aggressive clinical course, multifocal involvement of the CNS, and a high proliferation index. The pathological characteristics of primary CNS EBV-positive diffuse large B-cell lymphoma of the elderly have similarities with those of the latency phenotype III, EBV lymphoproliferative disorders that arise in the setting of immunodeficiency. These age-related lymphomas usually occur in elderly immunocompetent patients, and the incidence of this disease was estimated to range from 4.0% to 13.6% of all primary CNS lymphomas. Shorter overall survival has been reported for patients with this disease. Lymphomatoid granulomatosis (LYG) is a systemic, EBV-driven, angiocentric and angiodestructive lymphoproliferative disorder. Primary LYG that shows distinct clinicopathological features compared with systemic LYG was recently reported. Finally, this review focuses on the relationship between primary CNS lymphomas and demyelinating diseases, and the concomitant use of intraoperative cytology and frozen sections that are helpful in rapid intraoperative diagnosis. © 2015 Japanese Society of Neuropathology.

  6. Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells.

    Science.gov (United States)

    Kleinewietfeld, Markus; Manzel, Arndt; Titze, Jens; Kvakan, Heda; Yosef, Nir; Linker, Ralf A; Muller, Dominik N; Hafler, David A

    2013-04-25

    There has been a marked increase in the incidence of autoimmune diseases in the past half-century. Although the underlying genetic basis of this class of diseases has recently been elucidated, implicating predominantly immune-response genes, changes in environmental factors must ultimately be driving this increase. The newly identified population of interleukin (IL)-17-producing CD4(+) helper T cells (TH17 cells) has a pivotal role in autoimmune diseases. Pathogenic IL-23-dependent TH17 cells have been shown to be critical for the development of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, and genetic risk factors associated with multiple sclerosis are related to the IL-23-TH17 pathway. However, little is known about the environmental factors that directly influence TH17 cells. Here we show that increased salt (sodium chloride, NaCl) concentrations found locally under physiological conditions in vivo markedly boost the induction of murine and human TH17 cells. High-salt conditions activate the p38/MAPK pathway involving nuclear factor of activated T cells 5 (NFAT5; also called TONEBP) and serum/glucocorticoid-regulated kinase 1 (SGK1) during cytokine-induced TH17 polarization. Gene silencing or chemical inhibition of p38/MAPK, NFAT5 or SGK1 abrogates the high-salt-induced TH17 cell development. The TH17 cells generated under high-salt conditions display a highly pathogenic and stable phenotype characterized by the upregulation of the pro-inflammatory cytokines GM-CSF, TNF-α and IL-2. Moreover, mice fed with a high-salt diet develop a more severe form of EAE, in line with augmented central nervous system infiltrating and peripherally induced antigen-specific TH17 cells. Thus, increased dietary salt intake might represent an environmental risk factor for the development of autoimmune diseases through the induction of pathogenic TH17 cells.

  7. The role of complement in autoimmune renal disease

    NARCIS (Netherlands)

    Seelen, M. A.; Daha, M. R.

    The predominance of renal involvement in autoimmune diseases can most likely be assigned to the specialised function of the kidneys filtrating over 120 ml plasma per minute. Complement activation by autoantibodies directed against planted antigens or antigens already present in renal tissue in the

  8. The use of stem cells for the treatment of autoimmune diseases

    Directory of Open Access Journals (Sweden)

    S.B. Rosa

    2007-12-01

    Full Text Available Autoimmune diseases constitute a heterogeneous group of conditions commonly treated with anti-inflammatory, immunosuppressant and immunomodulating drugs, with satisfactory results in most cases. Nevertheless, some patients become resistant to conventional therapy. The use of high doses of drugs in such cases results in the need for bone marrow reconstitution, a situation which has stimulated research into the use of hematopoietic stem cells in autoimmune disease therapy. Stem cell transplantation in such diseases aims to destroy the self-reacting immune cells and produce a new functional immune system, as well as substitute cells for tissue damaged in the course of the disease. Significant results, such as the reestablishment of tolerance and a decrease in the recurrence of autoimmune disease, have been reported following stem cell transplantation in patients with autoimmune disease in Brazil and throughout the world. These results suggest that stem cell transplantation has the potential to become an important therapeutic approach to the treatment of various autoimmune diseases including rheumatoid arthritis, juvenile idiopathic arthritis, systemic lupus erythematosus, multiple sclerosis, systemic sclerosis, Crohn's disease, autoimmune blood cytopenias, and type I diabetes mellitus.

  9. The central nervous system phenotype of X-linked Charcot-Marie-Tooth disease: a transient disorder of children and young adults.

    Science.gov (United States)

    Al-Mateen, Majeed; Craig, Alexa Kanwit; Chance, Phillip F

    2014-03-01

    We describe 2 patients with X-linked Charcot-Marie-Tooth disease, type 1 (CMTX1) disease and central nervous system manifestations and review 19 cases from the literature. Our first case had not been previously diagnosed with Charcot-Marie-Tooth disease, and the second case, although known to have Charcot-Marie-Tooth disease, was suspected of having CMTX1 after presentation with central nervous system manifestations. The most common central nervous system manifestations were transient and included dysarthria, ataxia, hemiparesis, and tetraparesis resembling periodic paralysis. Of the 21 patients, 19 presented at 21 years of age or younger, implicating CMTX1 with transient central nervous system manifestations as a disorder that predominantly affects children and adolescents. CMTX1 should be included in the differential diagnosis of patients who present with transient central nervous system phenomena, including stroke-like episodes, tetraparesis suggestive of periodic paralysis, dysarthria, ataxia, or combinations of these deficits. Reversible, bilateral, nonenhancing white matter lesions and restricted diffusion on magnetic resonance imaging are characteristic features of the central nervous system phenotype of CMTX1.

  10. Antagonizing the alpha(4)beta(1) Integrin, but Not alpha(4)beta(7), Inhibits Leukocytic Infiltration of the Central Nervous System in Rhesus Monkey Experimental Autoimmune Encephalomyelitis

    NARCIS (Netherlands)

    Haanstra, Krista G.; Hofman, Sam O.; Estevao, Dave M. Lopes; Blezer, Erwin L. A.; Bauer, Jan; Yang, Li-Li; Wyant, Tim; Csizmadia, Vilmos; 't Hart, Bert A.; Fedyk, Eric R.

    2013-01-01

    The immune system is characterized by the preferential migration of lymphocytes through specific tissues (i.e., tissue tropism). Tissue tropism is mediated, in part, by the alpha(4) integrins expressed by T lymphocytes. The alpha(4)beta(1) integrin mediates migration of memory T lymphocytes into the

  11. SJL mice infected with Acanthamoeba castellanii develop central nervous system autoimmunity through the generation of cross-reactive T cells for myelin antigens

    DEFF Research Database (Denmark)

    Massilamany, Chandirasegaran; Marciano-Cabral, Francine; Rocha-Azevedo, Bruno da

    2014-01-01

    ) in SJL mice reminiscent of the diseases induced with their corresponding cognate peptides. We now demonstrate that mice infected with ACA also show the generation of cross-reactive T cells, predominantly for PLP 139-151, as evaluated by T cell proliferation and IAs/dextramer staining. We verified...

  12. Hypersensitivity Responses in the Central Nervous System

    DEFF Research Database (Denmark)

    Khorooshi, Reza; Asgari, Nasrin; Mørch, Marlene Thorsen

    2015-01-01

    of pathology in neuromyelitis optica (NMO), a central nervous system (CNS) demyelinating disease where activated neutrophils infiltrate, unlike in MS. The most widely used model for MS, experimental autoimmune encephalomyelitis, is an autoantigen-immunized disease that can be transferred to naive animals......Immune-mediated tissue damage or hypersensitivity can be mediated by autospecific IgG antibodies. Pathology results from activation of complement, and antibody-dependent cellular cytotoxicity, mediated by inflammatory effector leukocytes include macrophages, natural killer cells, and granulocytes...... injection of antibody and complement to the CNS, or experimental manipulations to induce BBB breakdown. We here review studies in MS and NMO that elucidate roles for IgG and complement in the induction of BBB breakdown, astrocytopathy, and demyelinating pathology. These studies point to significance of T...

  13. microRNA involvement in developmental and functional aspects of the nervous system and in neurological diseases

    DEFF Research Database (Denmark)

    Christensen, Mette; Schratt, Gerhard M

    2009-01-01

    microRNAs, small non-coding RNAs that regulate gene expression at the post-transcriptional level, are emerging as important regulatory molecules involved in the fine-tuning of gene expression during neuronal development and function. microRNAs have roles during neuronal stem cell commitment...... and early differentiation as well as in later stages of neuronal development, such as dendritogenesis and synaptic plasticity. A link between microRNAs and neurological diseases, such as neurodegeneration or synaptic dysfunction, is becoming increasingly clear. This review summarizes the current knowledge...... of the function of microRNAs in the developing and adult nervous system and their potential contribution to the etiology of neurological diseases....

  14. The curiously suspicious: infectious disease may ameliorate an ongoing autoimmune destruction in systemic lupus erythematosus patients.

    Science.gov (United States)

    Praprotnik, Sonja; Sodin-Semrl, Snezna; Tomsic, Matija; Shoenfeld, Yehuda

    2008-01-01

    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, which can arise from a combination of genetic and environmental factors. In the past, infections (Epstein Barr virus, parvovirus B-19) have been indicated to play a causative role in the development of autoimmune diseases, such as SLE. On the other hand, with the emergence of the "hygiene hypothesis" infections have also shown to play a protective role in autoimmune diseases. Two case studies are presented which provide clinical evidence of SLE patients with severe, long-term disease, despite immunosuppresive therapy. The course of both diseases changed remarkably after they experienced infections with multiple microbes (bacterial, viral and fungal). Surprisingly, their clinical and laboratory signs of SLE normalized and they are now symptom-free after 5 and 3year follow-ups. The second patient has even had a normal pregnancy, which was a trigger factor for disease flare in the past. The infections presumably changed the host immune systems and the mechanisms of their protective effects are most likely multifactorial. Our cases illustrate that infections could be beneficial in SLE patients and re-directing research toward novel innate-based SLE therapy should be explored.

  15. The role of transposable elements in health and diseases of the central nervous system.

    Science.gov (United States)

    Reilly, Matthew T; Faulkner, Geoffrey J; Dubnau, Joshua; Ponomarev, Igor; Gage, Fred H

    2013-11-06

    First discovered in maize by Barbara McClintock in the 1940s, transposable elements (TEs) are DNA sequences that in some cases have the ability to move along chromosomes or "transpose" in the genome. This revolutionary finding was initially met with resistance by the scientific community and viewed by some as heretical. A large body of knowledge has accumulated over the last 60 years on the biology of TEs. Indeed, it is now known that TEs can generate genomic instability and reconfigure gene expression networks both in the germline and somatic cells. This review highlights recent findings on the role of TEs in health and diseases of the CNS, which were presented at the 2013 Society for Neuroscience meeting. The work of the speakers in this symposium shows that TEs are expressed and active in the brain, challenging the dogma that neuronal genomes are static and revealing that they are susceptible to somatic genomic alterations. These new findings on TE expression and function in the CNS have major implications for understanding the neuroplasticity of the brain, which could hypothetically have a role in shaping individual behavior and contribute to vulnerability to disease.

  16. "How I treat" autoimmune diseases: State of the art on the management of rare rheumatic diseases and ANCA-associated systemic idiopathic vasculitis.

    Science.gov (United States)

    Roccatello, Dario

    2017-10-01

    This Special Issue of Autoimmunity Reviews constitutes summaries of presentations at the 20th International Meeting on Immunopathology and Orphan Diseases, held in Torino, Italy, 25-28th January 2017. As such, these presentations represent the state of the art on the pathophysiology of autoimmune diseases as well as the most recent insights into the management of these pathologic conditions. The latter includes both the optimal use of established drugs and approaches as well as novel knowledge on the means and consequences of targeted blocking of molecules or cellular mechanisms. The 2nd Turin Congress on systemic idiopathic vasculitis concluded the works of the International Meeting on Immune Pathology and Orphan Diseases. This Satellite Congress was mainly addressed to the management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitis: advances on induction therapy and maintenance treatment. Guidelines and recommendations were critically discussed, reviewing available evidence and providing experts' insights. New intensive therapeutic approaches had been also reported. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Investigating the autonomic nervous system and cognitive functions as potential mediators of an association between cardiovascular disease and driving performance.

    Science.gov (United States)

    Gaudet, Jeffrey; Bélanger, Mathieu F; Corriveau, Hélène; Mekary, Said; Hay, Dean; Johnson, Michel J

    2013-05-01

    Cardiovascular disease (CVD) impacts the autonomic nervous system and cognitive functions related to activities of daily living, including driving an automobile. Although CVD has been linked to unsafe driving, mechanisms underlying this relationship remain elusive. The aim of this study was to examine the role of cognitive functions and the autonomic nervous system as potential mediators of driving performance. Nineteen individuals having recently suffered a cardiac event and 16 individuals with no history of CVD completed a simulated drive using a STISIM simulator to assess driving performance. Heart rate was recorded throughout testing using a Polar RS800CX heart rate monitor, and measures of executive, orienting, and alerting functions were obtained through the Attention Network Test. We used the Baron and Kenny analysis method to assess potential mediating effects of the relationship between CVD and driving performance. Executive function was the only potential mediator investigated to be associated with driving (p driving and that further research is needed to better understand the mechanisms underlying this relationship.

  18. [Autoimmune thyroid disease and other non-endocrine autoimmune diseases].

    Science.gov (United States)

    Dilas, Ljiljana Todorović; Icin, Tijana; Paro, Jovanka Novaković; Bajkin, Ivana

    2011-01-01

    Autoimmune diseases are chronic conditions initiated by the loss of immunological tolerance to self-antigens. They constitute heterogeneous group of disorders, in which multiple alterations in the immune system result in a spectrum of syndromes that either target specific organs or affect the body systematically. Recent epidemiological studies have shown a possible shift of one autoimmune disease to another or the fact that more than one autoimmune disease may coexist in a single patient or in the same family. Numerous autoimmune diseases have been shown to coexist frequently with thyroid autoimmune diseases. AUTOIMMNUNE THYROID DISEASE AND OTHER ORGAN SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: This part of the study reviews the prevalence of autoimmune thyroid disease coexisting with: pernicious anaemia, vitiligo, celiac disease, autoimmune liver disease, miastenia gravis, alopecia areata and sclerosis multiplex, and several recommendations for screening have been given. AUTOIMMUNE THYROID DISEASE AND OTHER ORGAN NON-SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: Special attention is given to the correlation between autoimmune thyroid disease and rheumatoid arthritis, systemic lupus erythematosus, syndrome Sjögren, systemic sclerosis and mixed connective tissue disease. Screening for autoimmune thyroid diseases should be recommended in everyday clinical practice, in patients with primary organ-specific or organ non-specific autoimmune disease. Otherwise, in patients with primary thyroid autoimmune disease, there is no good reason of seeking for all other autoimmune diseases, although these patients have a greater risk of developing other autoimmune disease. Economic aspects of medicine require further analyzing of these data, from cost/benefit point of view to justified either mandatory screening or medical practitioner judgment.

  19. Inflammatory cells in the peripheral nervous system in motor neuron disease

    NARCIS (Netherlands)

    Kerkhoff, H.; Troost, D.; Louwerse, E. S.; van Dijk, M.; Veldman, H.; Jennekens, F. G.

    1993-01-01

    We examined post-mortem material of the peripheral nervous system of 26 cases of motor neuron disease (MND) for the presence of lymphocyte subsets and macrophages. Findings were quantified and compared with those in control nerves. Lymphocytes in chronic and acute axonal degeneration were studied in

  20. RGS10 deficiency ameliorates the severity of disease in experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Lee, Jae-Kyung; Kannarkat, George T; Chung, Jaegwon; Joon Lee, Hyun; Graham, Kareem L; Tansey, Malú G

    2016-02-01

    Regulator of G-protein signaling (RGS) family proteins, which are GTPase accelerating proteins (GAPs) that negatively regulate G-protein-coupled receptors (GPCRs), are known to be important modulators of immune cell activation and function. Various single-nucleotide polymorphisms in RGS proteins highly correlate with increased risk for multiple sclerosis (MS), an autoimmune, neurodegenerative disorder. An in-depth search of the gene expression omnibus profile database revealed higher levels of RGS10 and RGS1 transcripts in peripheral blood mononuclear cells (PBMCs) in MS patients, suggesting potential functional roles for RGS proteins in MS etiology and/or progression. To define potential roles for RGS10 in regulating autoimmune responses, we evaluated RGS10-null and wild-type (WT) mice for susceptibility to experimental autoimmune encephalomyelitis (EAE), a widely studied model of MS. Leukocyte distribution and functional responses were assessed using biochemical, immunohistological, and flow cytometry approaches. RGS10-null mice displayed significantly milder clinical symptoms of EAE with reduced disease incidence and severity, as well as delayed onset. We observed fewer CD3+ T lymphocytes and CD11b+ myeloid cells in the central nervous system (CNS) tissues of RGS10-null mice with myelin oligodendrocyte protein (MOG)35-55-induced EAE. Lymph node cells and splenocytes of immunized RGS10-null mice demonstrated decreased proliferative and cytokine responses in response to in vitro MOG memory recall challenge. In adoptive recipients, transferred myelin-reactive RGS10-null Th1 cells (but not Th17 cells) induced EAE that was less severe than their WT counterparts. These data demonstrate a critical role for RGS10 in mediating autoimmune disease through regulation of T lymphocyte function. This is the first study ever conducted to elucidate the function of RGS10 in effector lymphocytes in the context of EAE. The identification of RGS10 as an important regulator of

  1. Determination of autoantibodies to annexin XI in systemic autoimmune diseases

    DEFF Research Database (Denmark)

    Jorgensen, C S; Levantino, G; Houen, Gunnar

    2000-01-01

    of 282 sera from patients with systemic rheumatic diseases. The highest number of annexin XI positive sera were found in primary antiphospholipid syndrome (3/17), and in subacute lupus erythematosus (1/6), while lower frequencies of positive sera were found in patients with systemic sclerosis (5...

  2. Modelling of pathologies of the nervous system by the example of computational and electronic models of elementary nervous systems

    International Nuclear Information System (INIS)

    Shumilov, V. N.; Syryamkin, V. I.; Syryamkin, M. V.

    2015-01-01

    The paper puts forward principles of action of devices operating similarly to the nervous system and the brain of biological systems. We propose an alternative method of studying diseases of the nervous system, which may significantly influence prevention, medical treatment, or at least retardation of development of these diseases. This alternative is to use computational and electronic models of the nervous system. Within this approach, we represent the brain in the form of a huge electrical circuit composed of active units, namely, neuron-like units and connections between them. As a result, we created computational and electronic models of elementary nervous systems, which are based on the principles of functioning of biological nervous systems that we have put forward. Our models demonstrate reactions to external stimuli and their change similarly to the behavior of simplest biological organisms. The models possess the ability of self-training and retraining in real time without human intervention and switching operation/training modes. In our models, training and memorization take place constantly under the influence of stimuli on the organism. Training is without any interruption and switching operation modes. Training and formation of new reflexes occur by means of formation of new connections between excited neurons, between which formation of connections is physically possible. Connections are formed without external influence. They are formed under the influence of local causes. Connections are formed between outputs and inputs of two neurons, when the difference between output and input potentials of excited neurons exceeds a value sufficient to form a new connection. On these grounds, we suggest that the proposed principles truly reflect mechanisms of functioning of biological nervous systems and the brain. In order to confirm the correspondence of the proposed principles to biological nature, we carry out experiments for the study of processes of

  3. Modelling of pathologies of the nervous system by the example of computational and electronic models of elementary nervous systems

    Energy Technology Data Exchange (ETDEWEB)

    Shumilov, V. N., E-mail: vnshumilov@rambler.ru; Syryamkin, V. I., E-mail: maximus70sir@gmail.com; Syryamkin, M. V., E-mail: maximus70sir@gmail.com [National Research Tomsk State University, 634050, Tomsk, Lenin Avenue, 36 (Russian Federation)

    2015-11-17

    The paper puts forward principles of action of devices operating similarly to the nervous system and the brain of biological systems. We propose an alternative method of studying diseases of the nervous system, which may significantly influence prevention, medical treatment, or at least retardation of development of these diseases. This alternative is to use computational and electronic models of the nervous system. Within this approach, we represent the brain in the form of a huge electrical circuit composed of active units, namely, neuron-like units and connections between them. As a result, we created computational and electronic models of elementary nervous systems, which are based on the principles of functioning of biological nervous systems that we have put forward. Our models demonstrate reactions to external stimuli and their change similarly to the behavior of simplest biological organisms. The models possess the ability of self-training and retraining in real time without human intervention and switching operation/training modes. In our models, training and memorization take place constantly under the influence of stimuli on the organism. Training is without any interruption and switching operation modes. Training and formation of new reflexes occur by means of formation of new connections between excited neurons, between which formation of connections is physically possible. Connections are formed without external influence. They are formed under the influence of local causes. Connections are formed between outputs and inputs of two neurons, when the difference between output and input potentials of excited neurons exceeds a value sufficient to form a new connection. On these grounds, we suggest that the proposed principles truly reflect mechanisms of functioning of biological nervous systems and the brain. In order to confirm the correspondence of the proposed principles to biological nature, we carry out experiments for the study of processes of

  4. Bistability in autoimmune diseases

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Mosekilde, Erik; Lund, Ole

    2011-01-01

    Autoimmune diseases damage host tissue, which, in turn, may trigger a stronger immune response. Systems characterized by such positive feedback loops can display co-existing stable steady states. In a mathematical model of autoimmune disease, one steady state may correspond to the healthy state...... and another to an autoimmune steady state characterized by widespread tissue damage and immune activation. We show how a triggering event may move the system from the healthy to the autoimmune state and how transient immunosuppressive treatment can move the system back to the healthy state....

  5. Identification models of the nervous system.

    Science.gov (United States)

    Zipser, D

    1992-01-01

    It has been widely observed that when artificial neural networks are trained by supervised learning to do computations that also occur in the nervous system, the behavior of the model neurons often closely resembles that of the real neurons involved in the task. It is not immediately clear why this should be the case or what use can be made of models generated by supervised learning. Here, recent developments are reviewed and analysed in an attempt to clarify these issues. This analysis is facilitated by treating supervised learning models of the brain as a special case of system identification, a general and well-studied modeling paradigm. The neural systems identification paradigm provides a systematic way to generate realistic models starting with a high-level description of a hypothesized computation and some architectural and physiological constraints about the area being modeled. There is no inherent limitation to the realism that can be incorporated into identification models. This approach eliminates the need to find neural implementation algorithms by ad hoc means and provides neuroscientists with a convenient way to build models that account for observed data.

  6. CT and MRI analysis of central nervous system Rosai-Dorfman disease

    International Nuclear Information System (INIS)

    Zhang Jiatang; Lang Senyang; Pu Chuanqiang; Zhu Ruyuan; Wang Dianjun

    2008-01-01

    Objective: To study the CT and MRI imaging features of central nervous system Rosai-Dorfman disease and to enhance knowledge and differential diagnostic ability for central nervous system Rosai-Doffman disease. Methods: The CT and MRI imaging appearances in 4 cases of pathologically proven Rosai-Dorfman disease were retrospectively evaluated and the literature of central nervous system Rosai- Dorfman disease were reviewed. Results: Two cases had cranial CT scans, 4 cases had cranial MRI scans. On CT scans, cerebral edema was demonstrated in one case and the other case was normal. MRI scans showed the lesions were solitary in saddle area in 3 cases, and multiple in anterior cranial fossa in 1 case. The lesions exhibited iso- to hypointensity on both T 1 WI and T 2 WI images. Following intravenous injection of contrast medium, ring-like enhancement was seen in 2 cases and homogeneous enhancement in 1 case. Nodular enhancement was seen in the case of multiple lesions in the anterior cranial fossa. All lesions were dural-based. Conclusions: In patients with fever, headache, elevation of the erythrocyte sedimentation rate (ESR) and a polyclonal increase in γ-globulins, the possibility of central nervous system Rosai-Dorfman disease should be considered when single or multiple dural-based mass lesions, especially in sellar region, were identified by CT and MRI. (authors)

  7. [Thymoma and autoimmune diseases].

    Science.gov (United States)

    Jamilloux, Y; Frih, H; Bernard, C; Broussolle, C; Petiot, P; Girard, N; Sève, P

    2018-01-01

    The association between thymoma and autoimmunity is well known. Besides myasthenia gravis, which is found in 15 to 20% of patients with thymoma, other autoimmune diseases have been reported: erythroblastopenia, systemic lupus erythematosus, inflammatory myopathies, thyroid disorders, Isaac's syndrome or Good's syndrome. More anecdotally, Morvan's syndrome, limbic encephalitis, other autoimmune cytopenias, autoimmune hepatitis, and bullous skin diseases (pemphigus, lichen) have been reported. Autoimmune diseases occur most often before thymectomy, but they can be discovered at the time of surgery or later. Two situations require the systematic investigation of a thymoma: the occurrence of myasthenia gravis or autoimmune erythroblastopenia. Nevertheless, the late onset of systemic lupus erythematosus or the association of several autoimmune manifestations should lead to look for a thymoma. Neither the characteristics of the patients nor the pathological data can predict the occurrence of an autoimmune disease after thymectomy. Thus, thymectomy usefulness in the course of the autoimmune disease, except myasthenia gravis, has not been demonstrated. This seems to indicate the preponderant role of self-reactive T lymphocytes distributed in the peripheral immune system prior to surgery. Given the high infectious morbidity in patients with thymoma, immunoglobulin replacement therapy should be considered in patients with hypogammaglobulinemia who receive immunosuppressive therapy, even in the absence of prior infection. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  8. The Epidemiologic Evidence Linking Autoimmune Diseases and Psychosis

    DEFF Research Database (Denmark)

    Benros, Michael E; Eaton, William W; Mortensen, Preben B

    2014-01-01

    This review summarizes the epidemiologic evidence linking autoimmune diseases and psychosis. The associations between autoimmune diseases and psychosis have been studied for more than a half century, but research has intensified within the last decades, since psychosis has been associated...... with genetic markers of the immune system and with excess autoreactivity and other immune alterations. A range of psychiatric disorders, including psychosis, have been observed to occur more frequently in some autoimmune diseases, such as systemic lupus erythematosus and multiple sclerosis. Many autoimmune......, there is some evidence of associations of psychosis with a family history of autoimmune disorders and vice versa. Additionally, several autoimmune diseases, individually and in aggregate, have been identified as raising the risk for psychotic disorders in longitudinal studies. The associations have been...

  9. Epigenetic mechanisms underlying nervous system diseases.

    Science.gov (United States)

    Qureshi, Irfan A; Mehler, Mark F

    2018-01-01

    Epigenetic mechanisms act as control systems for modulating genomic structure and activity in response to evolving profiles of cell-extrinsic, cell-cell, and cell-intrinsic signals. These dynamic processes are responsible for mediating cell- and tissue-specific gene expression and function and gene-gene and gene-environmental interactions. The major epigenetic mechanisms include DNA methylation and hydroxymethylation; histone protein posttranslational modifications, nucleosome remodeling/repositioning, and higher-order chromatin reorganization; noncoding RNA regulation; and RNA editing. These mechanisms are intimately involved in executing fundamental genomic programs, including gene transcription, posttranscriptional RNA processing and transport, translation, X-chromosome inactivation, genomic imprinting, retrotransposon regulation, DNA replication, and DNA repair and the maintenance of genomic stability. For the nervous system, epigenetics offers a novel and robust framework for explaining how brain development and aging occur, neural cellular diversity is generated, synaptic and neural network connectivity and plasticity are mediated, and complex cognitive and behavioral phenotypes are inherited transgenerationally. Epigenetic factors and processes are, not surprisingly, implicated in nervous system disease pathophysiology through several emerging paradigms - mutations and genetic variation in genes encoding epigenetic factors; impairments in epigenetic factor expression, localization, and function; epigenetic mechanisms modulating disease-associated factors and pathways; and the presence of deregulated epigenetic profiles in central and peripheral tissues. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Glial Cells: The Other Cells of the Nervous System ...

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 7; Issue 6. Glial Cells: The Other Cells of the Nervous System - Oligodendrocytes – Ensheathers of the CNS. Yasmin Khan Medha S Rajadhyaksha. Series Article Volume 7 Issue 6 June 2002 pp 6-13 ... Keywords. Glia; myelin; central nervous system.

  11. Regulatory Roles of Long Non-Coding RNAs in the Central Nervous System and Associated Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Zhenzhen Quan

    2017-06-01

    Full Text Available Accumulating studies have revealed that the human genome encodes tens of thousands of long non-coding RNAs (lncRNAs, which participate in multiple biological networks modulating gene expression via transcriptional, post-transcriptional and epigenetic regulation. Strikingly, a large fraction of tissue-specific lncRNAs are expressed in the Central Nervous System (CNS with precisely regulated temporal and spatial expression patterns. These brain-specific lncRNAs are also featured with the cell-type specificity, the highest signals of evolutionary conservation, and their preferential location adjacent to brain-expressed protein-coding genes. Mounting evidence has indicated dysregulation or mutations in lncRNA gene loci are associated with a variety of CNS-associated neurodegenerative disorders, such as Alzheimer’s, Parkinson’s, Huntington’s diseases, Amyotrophic Lateral Sclerosis and others. However, how lncRNAs contribute to these disorders remains to be further explored and studied. In this review article, we systematically and comprehensively summarize the current studies of lncRNAs, demonstrate the specificity of lncRNAs expressed in the brain, their functions during neural development and expression profiles in major cell types of the CNS, highlight the regulatory mechanisms of several studied lncRNAs that may play essential roles in the pathophysiology of neurodegenerative diseases, and discuss the current challenges and future perspectives of lncRNA studies involved in neurodegenerative and other diseases.

  12. [Medicinal cannabis for diseases of the nervous system: no convincing evidence of effectiveness].

    Science.gov (United States)

    Killestein, J; Bet, P M; van Loenen, A C; Polman, C H

    2004-11-27

    --In 1996, the Netherlands Health Council issued a negative recommendation regarding the use of medication on the basis of cannabis (marihuana). However, interest in medicinal cannabis has certainly not waned since. --The neurological diseases for which cannabis could presently be used therapeutically are: multiple sclerosis, chronic (neuropathic) pain and the syndrome of Gilles de la Tourette. --Since September 2003, the Dutch Ministry of Health, Welfare and Sport delivers medicinal cannabis to Dutch pharmacies, so that now for the first time, medicinal cannabis can be given to patients on a prescription basis within the framework of the Opium Law. The result of this is that doctors and patients now assume that this is a medication for which the efficacy and safety have been established. --The question arises whether new scientific data have become available since 1996 that provide scientific support for the current Governmental policy. --In a recent clinical trial that has aroused much discussion, patients with multiple sclerosis and problematic spasticity were treated with oral cannabis or a placebo. There was no significant effect of treatment on the primary outcome measure, i.e. objectively determined spasticity. Nevertheless, it was concluded that the mobility was improved and that the pain was subjectively decreased. --Until now, convincing scientific evidence that cannabinoids are effective in neurological conditions is still lacking. --However, it is also not possible to conclude definitely that cannabinoids are ineffective; still, this is no basis for official stimulation of their use.

  13. Diverse roles of neurotensin agonists in the central nervous system

    Directory of Open Access Journals (Sweden)

    Mona eBoules

    2013-03-01

    Full Text Available NT is a tridecapeptide that is found in the central nervous system and the gastrointestinal tract. NT behaves as a neurotransmitter in the brain and as a hormone in the gut. Additionally, NT acts as a neuromodulator to several neurotransmitter systems including dopaminergic, sertonergic, GABAergic, glutamatergic and cholinergic systems. Due to its association with such a wide variety of neurotransmitters, NT has been implicated in the pathophysiology of several central nervous system (CNS disorders such as schizophrenia, drug abuse, Parkinson’s disease, pain, central control of blood pressure, eating disorders, as well as, cancer and inflammation. The present review will focus on the role that NT and its analogs play in schizophrenia, endocrine function, pain, psychostimulant abuse, and Parkinson’s disease.

  14. 50-57 Effects of the Autonomic Nervous System, Centra

    African Journals Online (AJOL)

    admin

    The gastrointestinal tract is chiefly involved in the digestion of ingested food, facilitation of absorption process and expulsion of the undigested food material through motility process. Motility is influenced by neurohormonal system which is associated with the enteric nervous system , autonomic nervous system and the ...

  15. Glial biomarkers in human central nervous system disease.

    Science.gov (United States)

    Garden, Gwenn A; Campbell, Brian M

    2016-10-01

    There is a growing understanding that aberrant GLIA function is an underlying factor in psychiatric and neurological disorders. As drug discovery efforts begin to focus on glia-related targets, a key gap in knowledge includes the availability of validated biomarkers to help determine which patients suffer from dysfunction of glial cells or who may best respond by targeting glia-related drug mechanisms. Biomarkers are biological variables with a significant relationship to parameters of disease states and can be used as surrogate markers of disease pathology, progression, and/or responses to drug treatment. For example, imaging studies of the CNS enable localization and characterization of anatomical lesions without the need to isolate tissue for biopsy. Many biomarkers of disease pathology in the CNS involve assays of glial cell function and/or response to injury. Each major glia subtype (oligodendroglia, astroglia and microglia) are connected to a number of important and useful biomarkers. Here, we describe current and emerging glial based biomarker approaches for acute CNS injury and the major categories of chronic nervous system dysfunction including neurodegenerative, neuropsychiatric, neoplastic, and autoimmune disorders of the CNS. These descriptions are highlighted in the context of how biomarkers are employed to better understand the role of glia in human CNS disease and in the development of novel therapeutic treatments. GLIA 2016;64:1755-1771. © 2016 Wiley Periodicals, Inc.

  16. Electrocardiographic changes in central nervous system disease.

    Science.gov (United States)

    Valeriano, J; Elson, J

    1993-05-01

    This article gives a basic description of neurophysiologic control of cardiac function. Specific electrocardiographic abnormalities related to various central nervous system insults are discussed also.

  17. Schistosome-Derived Molecules as Modulating Actors of the Immune System and Promising Candidates to Treat Autoimmune and Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Luis Janssen

    2016-01-01

    Full Text Available It is long known that some parasite infections are able to modulate specific pathways of host’s metabolism and immune responses. This modulation is not only important in order to understand the host-pathogen interactions and to develop treatments against the parasites themselves but also important in the development of treatments against autoimmune and inflammatory diseases. Throughout the life cycle of schistosomes the mammalian hosts are exposed to several biomolecules that are excreted/secreted from the parasite infective stage, named cercariae, from their tegument, present in adult and larval stages, and finally from their eggs. These molecules can induce the activation and modulation of innate and adaptive responses as well as enabling the evasion of the parasite from host defense mechanisms. Immunomodulatory effects of helminth infections and egg molecules are clear, as well as their ability to downregulate proinflammatory cytokines, upregulate anti-inflammatory cytokines, and drive a Th2 type of immune response. We believe that schistosomes can be used as a model to understand the potential applications of helminths and helminth-derived molecules against autoimmune and inflammatory diseases.

  18. The immunobiology of Campylobacter jejuni: Innate immunity and autoimmune diseases.

    Science.gov (United States)

    Phongsisay, Vongsavanh

    2016-04-01

    The Gram-negative bacterium Campylobacter jejuni causes gastroenteritis and Guillain-Barré syndrome in humans. Recent advances in the immunobiology of C. jejuni have been made. This review summarizes C. jejuni-binding innate receptors and highlights the role of innate immunity in autoimmune diseases. This human pathogen produces a variety of glycoconjugates, including human ganglioside-like determinants and multiple activators of Toll-like receptors (TLRs). Furthermore, C. jejuni targets MyD88, NLRP3 inflammasome, TIR-domain-containing adapter-inducing interferon-β (TRIF), sialic acid-binding immunoglobulin-like lectins (Siglecs), macrophage galactose-type lectin (MGL), and immunoglobulin-like receptors (TREM2, LMIR5/CD300b). The roles of these innate receptors and signaling molecules have been extensively studied. MyD88-mediated TLR activation or inflammasome-dependent IL-1β secretion is essential for autoimmune induction. TRIF mediates the production of type I interferons that promote humoral immune responses and immunoglobulin class-switching. Siglec-1 and Siglec-7 interact directly with gangliosides. Siglec-1 activation enhances phagocytosis and inflammatory responses. MGL internalizes GalNAc-containing glycoconjugates. TREM2 is well-known for its role in phagocytosis. LMIR5 recognizes C. jejuni components and endogenous sulfoglycolipids. Several lines of evidence from animal models of autoimmune diseases suggest that simultaneous activation of innate immunity in the presence of autoreactive lymphocytes or antigen mimicry may link C. jejuni to immunopathology. Copyright © 2015 Elsevier GmbH. All rights reserved.

  19. Extraversion, Neuroticism and Strength of the Nervous System

    Science.gov (United States)

    Frigon, Jean-Yves

    1976-01-01

    The hypothesized identity of the dimensions of extraversion-introversion and strength of the nervous system was tested on four groups of nine subjects (neurotic extraverts, stable extraverts, neurotic introverts, stable introverts). Strength of the subjects' nervous system was estimated using the electroencephalographic (EEG) variant of extinction…

  20. Radiation response of the central nervous system

    International Nuclear Information System (INIS)

    Schultheiss, T.E.; Kun, L.E.; Ang, K.K.; Stephens, L.C.

    1995-01-01

    This report reviews the anatomical, pathophysiological, and clinical aspects of radiation injury to the central nervous system (CNS). Despite the lack of pathognomonic characteristics for CNS radiation lesions, demyelination and malacia are consistently the dominant morphological features of radiation myelopathy. In addition, cerebral atrophy is commonly observed in patients with neurological deficits related to chemotherapy and radiation, and neurocognitive deficits are associated with diffuse white matter changes. Clinical and experimental dose-response information have been evaluated and summarized into specific recommendations for the spinal cord and brain. The common spinal cord dose limit of 45 Gy in 22 to 25 fractions is conservative and can be relaxed if respecting this limit materially reduces the probability of tumor control. It is suggested that the 5% incidence of radiation myelopathy probably lies between 57 and 61 Gy to the spinal cord in the absence of dose modifying chemotherapy. A clinically detectable length effect for the spinal cord has not been observed. The effects of chemotherapy and altered fractionation are also discussed. Brain necrosis in adults is rarely noted below 60 Gy in conventional fractionation, with imaging and clinical changes being observed generally only above 50 Gy. However, neurocognitive effects are observed at lower doses, especially in children. A more pronounced volume effect is believed to exist in the brain than in the spinal cord. Tumor progression may be hard to distinguish from radiation and chemotherapy effects. Diffuse white matter injury can be attributed to radiation and associated with neurological deficits, but leukoencephalopathy is rarely observed in the absence of chemotherapy. Subjective, objective, management, and analytic (SOMA) parameters related to radiation spinal cord and brain injury have been developed and presented on ordinal scales

  1. Radiation response of the central nervous system

    International Nuclear Information System (INIS)

    Schultheiss, T.E.; Kun, L.E.; Stephens, L.C.

    1995-01-01

    This report reviews the anatomical, pathophysiological, and clinical aspects of radiation injury to the central nervous system (CNS). Despite the lack of pathoGyomonic characteristics for CNS radiation lesions, demyelination and malacia are consistently the dominant morphological features of radiation myelopathy. In addition, cerebral atrophy is commonly observed in patients with neurological deficits related to chemotherapy and radiation, and neurocognitive deficits are associated with diffuse white matter changes. Clinical and experimental dose-response information have been evaluated and summarized into specific recommendations for the spinal cord and brain. The common spinal cord dose limit of 45 Gn in 22 to 25 fractions is conservative and can be relaxed if respecting this limit materially reduces the probability of tumor control. It is suggested that the 5% incidence of radiation myelopathy probably lies between 57 and 61 Gy to the spinal cord in the absence of dose modifying chemotherapy. A clinically detectable length effect for the spinal cord has not been observed. The effects of chemotherapy and altered fractionation are also discussed. Brain necrosis in adults is rarely noted below 60 Gy in conventional fractionation, with imaging and clinical changes being observed generally only above 50 Gy. However, neurocognitive effects are observed at lower doses, especially in children. A more pronounced volume effect is believed to exist in the brain than in the spinal cord. Tumor progression may be hard to distinguish from radiation and chemotherapy effects. Diffuse white matter injury can be attributed to radiation and associated with neurological deficits, but leukoencephalopathy is rarely observed in the absence of chemotherapy. Subjective, objective, management, and analytic (SOMA) parameters related to radiation spinal cord and brain injury have been developed and presented on ordinal scales. 140 refs., 3 figs., 6 tabs

  2. Alpha7 neuronal nicotinic receptor: a pluripotent target for diseases of the central nervous system.

    Science.gov (United States)

    Bencherif, Merouane; Narla, Sridhar T; Stachowiak, Michal S

    2014-01-01

    Twenty years ago the alpha7 nicotinic acetylcholine receptor (nAChR) was thought to be vestigial with little biological relevance, but in recent years it has emerged as a functional target with ubiquitous localization and biological roles. In the last decade more than two thousand manuscripts have been published unraveling the multi-dimensional complexity of this target, the heterogeneity of its genetic variants, the spectrum of transducing signals, and the critical roles it plays in pivotal biological functions in the protection and maturation of neurons and stems cells, immune and inflammatory responses, sensory gating, mnemonic and attentional processes. In addition research and development of novel drugs has also promoted an intense debate on the role of activation, desensitization, β -amyloid oligomers, glutamate, and alpha7 nAChR, in cognition, neuronal survival, and neurodegeneration. The initial alpha7 nAChRs transducing enzyme, aptly named after Janus the two-faced roman deity for crossroads and gateways, reflects the dichotomy of reports on alpha7 nAChRs in promoting neuronal survival and cognitive processes, or as the target of β- amyloid oligomers to destabilize neuronal homeostasis leading to an irreversible neurochemical demise and dementia. It is therefore important to understand the functional neural bases of alpha7 nAChRs-mediated improvement of biological functions. The promise of alpha7 nAChR-directed drugs has already recently translated into proof-of-concept in controlled clinical trials but the full promise of this target(s) will be fully unraveled when its impact on neuronal health and survival is tested in controlled long-term clinical trials of disease progression.

  3. The Adverse Effects of Air Pollution on the Nervous System

    Science.gov (United States)

    Genc, Sermin; Zadeoglulari, Zeynep; Fuss, Stefan H.; Genc, Kursad

    2012-01-01

    Exposure to ambient air pollution is a serious and common public health concern associated with growing morbidity and mortality worldwide. In the last decades, the adverse effects of air pollution on the pulmonary and cardiovascular systems have been well established in a series of major epidemiological and observational studies. In the recent past, air pollution has also been associated with diseases of the central nervous system (CNS), including stroke, Alzheimer's disease, Parkinson's disease, and neurodevelopmental disorders. It has been demonstrated that various components of air pollution, such as nanosized particles, can easily translocate to the CNS where they can activate innate immune responses. Furthermore, systemic inflammation arising from the pulmonary or cardiovascular system can affect CNS health. Despite intense studies on the health effects of ambient air pollution, the underlying molecular mechanisms of susceptibility and disease remain largely elusive. However, emerging evidence suggests that air pollution-induced neuroinflammation, oxidative stress, microglial activation, cerebrovascular dysfunction, and alterations in the blood-brain barrier contribute to CNS pathology. A better understanding of the mediators and mechanisms will enable the development of new strategies to protect individuals at risk and to reduce detrimental effects of air pollution on the nervous system and mental health. PMID:22523490

  4. Modeling systemic autoimmune rheumatic disease in rats under the adverse weather conditions

    Directory of Open Access Journals (Sweden)

    Yegudina Ye.D.

    2017-04-01

    Full Text Available Changes in the lungs, heart and kidneys are found in all animals with experimental systemic autoimmune rheumatic disease and respectively in 47%, 47% and 40% of cases of intact rats in a hostile environment with xenobiotics air pollution (ammonia + benzene + formalin, herewith in every third or fourth individual lesions of visceral vessels developed. The negative environmental situation increases the frequency of morphological signs of the disease, such as proliferation of endothelial vessels of the heart by 68% and renal arterioles by 52%, in addition, there are direct correlations of angiopathy degree in individual organs; this depends on the nature of pathological process modeling and demonstrates air pollution as a risk factor of disease in humans. The impact of pulmonary vessels sclerosis on the development of bronhosclerosis, perivascular infiltration of the heart muscle on the lymphocyte-macrophage infiltration of the stroma of the myocardium and sclerosis of renal arterioles on the degree of nephroslerosis of stroma is directly associated, with the model of systemic autoimmune rheumatic diseases whereas air pollution by xenobiotics determines dependences of the degree of cellular infiltration of alveolar septa from perivascular pulmonary infiltration, the development of cardiomyocytes hypertrophy from proliferation of the heart endothelial vessels, increase of kidney mesangial matrix from the proliferation of endothelial glomerular capillaries.

  5. Maternal history of autoimmune disease in children presenting with tics and/or obsessive-compulsive disorder.

    Science.gov (United States)

    Murphy, T K; Storch, E A; Turner, A; Reid, J M; Tan, J; Lewin, A B

    2010-12-15

    A commonality across a number of pediatric neuropsychiatric disorders is a higher than typical rate of familial - and especially maternal - autoimmune disease. Of recent interest, a subtype of obsessive-compulsive disorder (OCD) and tic disorders known collectively as Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) is believed to be secondary to central nervous system (CNS) autoimmunity that occurs in relation to group A streptococcal infection. Thus, we hypothesized that a sample of children with OCD and/or tics would have an increased maternal risk for an autoimmune response relative to population norms. We also expected maternal prevalence of various autoimmune diseases to be higher among those participants that met the putative criteria for PANDAS. We examined, via structured interview, the medical history of the biological mothers of 107 children with OCD and/or tics. Autoimmune disorders were reported in 17.8% of study mothers, which is significantly greater than the general prevalence among women in the United States (approximately 5%). Further, study mothers were more likely to report having an autoimmune disease if their children were considered "likely PANDAS" cases versus "unlikely PANDAS" cases. The results offer preliminary support for hypothesized links between maternal autoimmune disease and both OCD/tics and PANDAS in youth. Further research is necessary to clarify these general associations; links to specific autoimmune disease; and relevance of autoimmune disease in other family members (e.g., fathers). Copyright © 2010 Elsevier B.V. All rights reserved.

  6. Diagnosis abnormalities of limb movement in disorders of the nervous system

    Science.gov (United States)

    Tymchik, Gregory S.; Skytsiouk, Volodymyr I.; Klotchko, Tatiana R.; Bezsmertna, Halyna; Wójcik, Waldemar; Luganskaya, Saule; Orazbekov, Zhassulan; Iskakova, Aigul

    2017-08-01

    The paper deals with important issues of diagnosis early signs of diseases of the nervous system, including Parkinson's disease and other specific diseases. Small quantities of violation trajectory of spatial movement of the extremities of human disease at the primary level as the most appropriate features are studied. In modern medical practice is very actual the control the emergence of diseases of the nervous system, including Parkinson's disease. In work a model limbs with six rotational kinematic pairs for diagnosis of early signs of diseases of the nervous system is considered. subject.

  7. Occupational therapy for patients with chronic diseases: CVA, rheumatoid arthritis and progressive diseases of the central nervous system.

    NARCIS (Netherlands)

    Driessen, M.J.; Dekker, J.; Lankhorst, G.; Zee, J. van der

    1997-01-01

    A substantial proportion of the patients treated by occupational therapists have a chronic disease. The aim of this study was to describe the outlines of occupational therapy treatment for three specific groups of chronic diseases: progressive neurological diseases, cerebrovascular accident and

  8. MRT of the central nervous system. 2. rev. and enl. ed.; MRT des Zentralnervensystems

    Energy Technology Data Exchange (ETDEWEB)

    Forsting, Michael [Universitaetsklinikum Essen (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie und Neuroradiologie; Jansen, Olav (ed.) [Universitaetsklinikum Schleswig-Holstein, Kiel (Germany). Klinik fuer Radiologie und Neuroradiologie

    2014-11-01

    The book on MRT of the central nervous system includes the following chapters: anatomy, vascular diseases, brain tumors, craniocerebral injuries, infectious diseases, multiple sclerosis and related diseases, metabolic diseases, degenerative diseases, malformations and developmental disorders, hydrocephalus and intracranial hypertension, spinal marrow, degenerative caused spinal and foraminal stenosis, traumata, tumors and tumor-like neoplasm, vascular diseases, inflammations, infections and related diseases, diseases of the peripheral nervous system.

  9. The critical role of epigenetics in systemic lupus erythematosus and autoimmunity.

    Science.gov (United States)

    Long, Hai; Yin, Heng; Wang, Ling; Gershwin, M Eric; Lu, Qianjin

    2016-11-01

    One of the major disappointments in human autoimmunity has been the relative failure on genome-wide association studies to provide "smoking genetic guns" that would explain the critical role of genetic susceptibility to loss of tolerance. It is well known that autoimmunity refers to the abnormal state that the dysregulated immune system attacks the healthy cells and tissues due to the loss of immunological tolerance to self-antigens. Its clinical outcomes are generally characterized by the presence of autoreactive immune cells and (or) the development of autoantibodies, leading to various types of autoimmune disorders. The etiology and pathogenesis of autoimmune diseases are highly complex. Both genetic predisposition and environmental factors such as nutrition, infection, and chemicals are implicated in the pathogenic process of autoimmunity, however, how much and by what mechanisms each of these factors contribute to the development of autoimmunity remain unclear. Epigenetics, which refers to potentially heritable changes in gene expression and function that do not involve alterations of the DNA sequence, has provided us with a brand new key to answer these questions. In the recent decades, increasing evidence have demonstrated the roles of epigenetic dysregulation, including DNA methylation, histone modification, and noncoding RNA, in the pathogenesis of autoimmune diseases, especially systemic lupus erythematosus (SLE), which have shed light on a new era for autoimmunity research. Notably, DNA hypomethylation and reactivation of the inactive X chromosome are two epigenetic hallmarks of SLE. We will herein discuss briefly how genetic studies fail to completely elucidate the pathogenesis of autoimmune diseases and present a comprehensive review on landmark epigenetic findings in autoimmune diseases, taking SLE as an extensively studied example. The epigenetics of other autoimmune diseases such as rheumatic arthritis, systemic sclerosis and primary biliary

  10. Pathogenesis of thyroid autoimmune disease: the role of cellular mechanisms.

    Science.gov (United States)

    Ramos-Leví, Ana Maria; Marazuela, Mónica

    2016-10-01

    Hashimoto's thyroiditis (HT) and Graves' disease (GD) are two very common organ-specific autoimmune diseases which are characterized by circulating antibodies and lymphocyte infiltration. Although humoral and cellular mechanisms have been classically considered separately in the pathogenesis of autoimmune thyroid diseases (AITD), recent research suggests a close reciprocal relationship between these two immune pathways. Several B- and T-cell activation pathways through antigen-presenting cells (APCs) and cytokine production lead to specific differentiation of T helper (Th) and T regulatory (Treg) cells. This review will focus on the cellular mechanisms involved in the pathogenesis of AITD. Specifically, it will provide reasons for discarding the traditional simplistic dichotomous view of the T helper type 1 and 2 pathways (Th1/Th2) and will focus on the role of the recently characterized T cells, Treg and Th17 lymphocytes, as well as B lymphocytes and APCs, especially dendritic cells (DCs). Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Assistive technology in occupational therapy practice with a child with degenerative disease of the central nervous system

    Directory of Open Access Journals (Sweden)

    Tácia Caroline de Lima Rodrigues

    2015-07-01

    Full Text Available This paper aims to report the effects of the interventions, using the resource of assistive technology, carried out with a child with degenerative disease of the central nervous system at his home. This is a study case, which was conducted in seven meetings, addressing the child and his caregivers during a process of evaluation, preparation of assistive devices, family orientation, and evaluation of the family environment repercussion. The results showed that the child presents significant motor, cognitive, and psychosocial impairments, resulting in difficulties in performing activities of daily living, communication, and play. Adjustments were proposed to facilitate the child’s involvement and alleviate family difficulties on equipment and environments, such as wheelchair, bedroom, bathroom, orthosis, toys and communication. Finally, it was possible to note that the assistive technology resources were used according to the child’s needs and his own reality, and that the domiciliary visits contributed positively to the family’s life because they facilitated the child’s care, despite the limitations faced.

  12. Familial risk of systemic sclerosis and co-aggregation of autoimmune diseases in affected families.

    Science.gov (United States)

    Kuo, Chang-Fu; Luo, Shue-Fen; Yu, Kuang-Hui; See, Lai-Chu; Zhang, Weiya; Doherty, Michael

    2016-10-12

    Systemic sclerosis (SSc) is a rare and devastating disease affecting skin and internal organs. Familial aggregation of SSc and co-aggregation with other autoimmune diseases is rarely reported. We identified 23,658,577 beneficiaries registered with the National Health Insurance database in 2010, 1891 of whom had SSc. We identified 21,009,551 parent-child relationships and 17,168,340 full sibling pairs. The familial risks of SSc and other autoimmune diseases and familial transmission were estimated. The prevalence of SSc in the general population was 0.008 %. There are 3801 individuals had at least one first-degree relative with SSc, among them 3 people had SSc which was equivalent to a prevalence of 0.08 %. The adjusted relative risk (RR) (95 % CI) for SSc was 81.21 (11.40-579.72) for siblings of SSc patients. The familial transmission (genetic plus shared environmental contribution to total phenotypic variance of SSc) was 0.72. However, 84.1 % of patients were expected to be sporadic cases. The RR (95 % CI) in first-degree relatives of SSc patients was 2.64 (1.46-4.75) for rheumatoid arthritis, 6.51 (4.05-10.46) for systemic lupus erythematosus, 2.77 (1.04-7.35) for Sjögren's syndrome, 8.05 (2.03-31.92) for idiopathic inflammatory myositis, and 1.52 (1.15-2.01) for psoriasis. The risks of SSc and other autoimmune diseases are increased in relatives of people with SSc, and family factors explain over two-thirds of the phenotypic variance of the disease. These findings may be useful in counselling families of patients with SSc and for further genetic studies.

  13. Evasion and interactions of the humoral innate immune response in pathogen invasion, autoimmune disease, and cancer.

    Science.gov (United States)

    Rettig, Trisha A; Harbin, Julie N; Harrington, Adelaide; Dohmen, Leonie; Fleming, Sherry D

    2015-10-01

    The humoral innate immune system is composed of three major branches, complement, coagulation, and natural antibodies. To persist in the host, pathogens, such as bacteria, viruses, and cancers must evade parts of the innate humoral immune system. Disruptions in the humoral innate immune system also play a role in the development of autoimmune diseases. This review will examine how Gram positive bacteria, viruses, cancer, and the autoimmune conditions systemic lupus erythematosus and anti-phospholipid syndrome, interact with these immune system components. Through examining evasion techniques it becomes clear that an interplay between these three systems exists. By exploring the interplay and the evasion/disruption of the humoral innate immune system, we can develop a better understanding of pathogenic infections, cancer, and autoimmune disease development. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Effect of hyperthermia on the central nervous system: a review

    NARCIS (Netherlands)

    Sminia, P.; van der Zee, J.; Wondergem, J.; Haveman, J.

    1994-01-01

    Experimental data show that nervous tissue is sensitive to heat. Animal data indicate that the maximum tolerated heat dose after local hyperthermia of the central nervous system (CNS) lies in the range of 40-60 min at 42-42 x 5 degrees C or 10-30 min at 43 degrees C. No conclusions concerning the

  15. Psychosis: an autoimmune disease?

    Science.gov (United States)

    Al-Diwani, Adam A J; Pollak, Thomas A; Irani, Sarosh R; Lennox, Belinda R

    2017-11-01

    Psychotic disorders are common and disabling. Overlaps in clinical course in addition to epidemiological and genetic associations raise the possibility that autoimmune mechanisms may underlie some psychoses, potentially offering novel therapeutic approaches. Several immune loci including the major histocompatibility complex and B-cell markers CD19 and CD20 achieve genome-wide significance in schizophrenia. Emerging evidence suggests a potential role via neurodevelopment in addition to classical immune pathways. Additionally, lymphocyte biology is increasingly investigated. Some reports note raised peripheral CD19 + and reduced CD3 + lymphocyte counts, with altered CD4 : CD8 ratios in acute psychosis. Also, post-mortem studies have found CD3 + and CD20 + lymphocyte infiltration in brain regions that are of functional relevance to psychosis. More specifically, the recent paradigm of neuronal surface antibody-mediated (NSAb) central nervous system disease provides an antigen-specific model linking adaptive autoimmunity to psychopathology. NSAbs bind extracellular epitopes of signalling molecules that are classically implicated in psychosis such as NMDA and GABA receptors. This interaction may cause circuit dysfunction leading to psychosis among other neurological features in patients with autoimmune encephalitis. The detection of these cases is crucial as autoimmune encephalitis is ameliorated by commonly available immunotherapies. Meanwhile, the prevalence and relevance of these antibodies in people with isolated psychotic disorders is an area of emerging scientific and clinical interest. Collaborative efforts to achieve larger sample sizes, comparison of assay platforms, and placebo-controlled randomized clinical trials are now needed to establish an autoimmune contribution to psychosis. © 2017 John Wiley & Sons Ltd.

  16. Porous silicon biosensor for the detection of autoimmune diseases

    Science.gov (United States)

    Jane, Andrew O.; Szili, Endre J.; Reed, Joanne H.; Gordon, Tom P.; Voelcker, Nicolas H.

    2007-12-01

    Advances in porous silicon (pSi) technology have led to the development of new sensitive biosensors. The unique optical properties of pSi renders the material a perfect candidate for optical transducers exploiting photoluminescence or white light interference effects. The ability of biosensors exploiting these transduction mechanisms to quickly and accurately detect biological target molecules affords an alternative to current bioassays such as enzyme-linked immunosorbent assays (ELISAs). Here, we present a pSi biosensor that was developed to detect antibodies against the autoimmune protein La. This protein is associated with autoimmune diseases including rheumatic disorders, systematic lupus erythematosus (SLE) and Sjogren's syndrome (SS). A fast and sensitive detection platform such as the one described here can be applied to the rapid diagnosis of these debilitating autoimmune diseases. The immobilisation of the La protein onto pSi films gave a protein receptor-decorated sensor matrix. A cascade of immunological reactions was then initiated to detect anti-La antibody on the functionalised pSi surface. In the presence of o-phenylenediamine (OPD), horseradish peroxidase (HRP)/H IIO II catalysed the formation of an oxidised radical species that accelerated pSi corrosion. pSi corrosion was detected as a blue-shift in the generated interference pattern, corresponding to a decrease in the effective optical thickness (EOT) of the pSi film. Compared to an ELISA, the pSi biosensor could detect the anti-La antibody at a similar concentration (500 - 125 ng/ml). Furthermore, we found that the experimental process can be significantly shortened resulting in detection of the anti-La antibody in 80 minutes compared to a minimum of 5 hours required for ELISA.

  17. The glia of the adult Drosophila nervous system

    Science.gov (United States)

    Kremer, Malte C.; Jung, Christophe; Batelli, Sara; Rubin, Gerald M.

    2017-01-01

    Glia play crucial roles in the development and homeostasis of the nervous system. While the GLIA in the Drosophila embryo have been well characterized, their study in the adult nervous system has been limited. Here, we present a detailed description of the glia in the adult nervous system, based on the analysis of some 500 glial drivers we identified within a collection of synthetic GAL4 lines. We find that glia make up ∼10% of the cells in the nervous system and envelop all compartments of neurons (soma, dendrites, axons) as well as the nervous system as a whole. Our morphological analysis suggests a set of simple rules governing the morphogenesis of glia and their interactions with other cells. All glial subtypes minimize contact with their glial neighbors but maximize their contact with neurons and adapt their macromorphology and micromorphology to the neuronal entities they envelop. Finally, glial cells show no obvious spatial organization or registration with neuronal entities. Our detailed description of all glial subtypes and their regional specializations, together with the powerful genetic toolkit we provide, will facilitate the functional analysis of glia in the mature nervous system. GLIA 2017 GLIA 2017;65:606–638 PMID:28133822

  18. [Glycosylation of autoantibodies in autoimmunes diseases].

    Science.gov (United States)

    Goulabchand, R; Batteux, F; Guilpain, P

    2013-12-01

    Protein glycosylation is one of the most common post-translational modifications, involved in the well described protein biosynthesis process. Protein glycosylation seems to play a major role in the pathogenesis of auto-immune diseases. Herein are described the main alterations of autoantibody glycosylation associated with autoimmunes diseases such as rheumatoid arthritis, IgA glomerulonephritis, Schoenlein-Henoch purpura, Sjögren's syndrome, systemic scleroderma, systemic lupus erythematosus, myasthenia gravis and granulomatosis with polyangiitis (Wegener). Molecular identification of altered immunoglobulin glycosylation could lead to a better understanding of the pathogenesis of those diseases, might allow an evaluation of their biological activity and could even be a new therapeutic target. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  19. The Autoimmune diseases

    National Research Council Canada - National Science Library

    Rose, Noel R; Mackay, Ian R

    1985-01-01

    ..., O R ANY INFORMATION STORAGE AND RETRIEVAL SYSTEM, W I T H O U T PERMISSION IN WRITING FROM THE PUBLISHER. ACADEMIC PRESS, INC. Orlando, Florida 32887 United Kingdom Edition published by ACADEMIC ...

  20. Human genome-microbiome interaction: metagenomics frontiers for the aetiopathology of autoimmune diseases

    Science.gov (United States)

    Nalbantoglu, Ufuk

    2017-01-01

    A short while ago, the human genome and microbiome were analysed simultaneously for the first time as a multi-omic approach. The analyses of heterogeneous population cohorts showed that microbiome components were associated with human genome variations. In-depth analysis of these results reveals that the majority of those relationships are between immune pathways and autoimmune disease-associated microbiome components. Thus, it can be hypothesized that autoimmunity may be associated with homeostatic disequilibrium of the human-microbiome interactome. Further analysis of human genome–human microbiome relationships in disease contexts with tailored systems biology approaches may yield insights into disease pathogenesis and prognosis. PMID:28785422

  1. How the immune and nervous systems interact during disease-associated anorexia.

    Science.gov (United States)

    Konsman, J P; Dantzer, R

    2001-01-01

    Anorexia is one of the most common symptoms associated with illness and constitutes an adaptive strategy in fighting acute infectious diseases. However, prolonged reduction in food intake and an increase in metabolic rate, as seen in the anorexia-cachexia syndrome, lead to depletion of body fat and protein reserves, thus worsening the organism's condition. Because the central nervous system controls many aspects of food intake, soluble factors known as cytokines that are secreted by immune cells might act on the brain to induce anorexia during disease. This review focuses on the communication pathways from the immune system to the brain that might mediate anorexia during disease. The vagus nerve is a rapid route of communication from the immune system to the brain, as subdiaphragmatic vagotomy attenuates the decrease in food-motivated behavior and c-Fos expression in the central nervous system in response to peripheral administration of the proinflammatory cytokine, interleukin-1beta, or bacterial lipopolysaccharide. At later time points after peripheral lipopolysaccharide administration, interleukin-1 itself acts in the brain to mediate anorexia and is found in the arcuate nucleus of the hypothalamus. The mechanisms by which interleukin-1beta gains access to the brain and the potential role of neuropeptide-Y-containing neurons in the arcuate hypothalamus in mediating anorexia during disease are discussed.

  2. Development of a disease registry for autoimmune bullous diseases: initial analysis of the pemphigus vulgaris subset.

    Science.gov (United States)

    Shah, Amit Aakash; Seiffert-Sinha, Kristina; Sirois, David; Werth, Victoria P; Rengarajan, Badri; Zrnchik, William; Attwood, Kristopher; Sinha, Animesh A

    2015-01-01

    Pemphigus vulgaris (PV) is a rare, potentially life threatening, autoimmune blistering skin disease. The International Pemphigus and Pemphigoid Foundation (IPPF) has recently developed a disease registry with the aim to enhance our understanding of autoimmune bullous diseases with the long-term goal of acquiring information to improve patient care. Patients were recruited to the IPPF disease registry through direct mail, e-mail, advertisements, and articles in the IPPF-quarterly, -website, -Facebook webpage, and IPPF Peer Health Coaches to complete a 38-question survey. We present here the initial analysis of detailed clinical information collected on 393 PV patients. We report previously unrecognized gender differences in terms of lesion location, autoimmune comorbidity, and delay in diagnosis. The IPPF disease registry serves as a useful resource and guide for future clinical investigation.

  3. [The interface between the immune system and autonomic nervous system].

    Science.gov (United States)

    Nakane, Shunya; Mukaino, Akihiro; Ando, Yukio

    2017-01-01

      The nervous system and the immune system are two major systems in human body. Although it was revealed these two systems correlated, the control of immune cell dynamics by the nervous system has come to draw a lot of attention at the present time. Recent advances in basic and preclinical science reveal that reflex neural circuits inhibit the production of cytokines and inflammation in several animal models. One well-characterized cytokine-inhibiting mechanism, termed the "inflammatory reflex", is dependent upon vagus nerve stimulation that inhibits cytokine production and attenuates the inflammation. And the mechanism for controlling lymphocyte trafficking becomes clear, and molecular basis of immune regulation by the nervous system was reported. On the other hand, the nervous system is protected from the invasion of harmful agents by the barrier. However, there are neuroimmunological disorders, which is associated with autoimmunity, tumor immunity, and infection immunity. Autoimmune autonomic ganglionopathy (AAG) is an acquired immune-mediated disorder that leads to widespread autonomic manifestations, in which autoantibodies to ganglionic nicotinic acetylcholine receptors play a central role. Previously, we elucidated the prevalence of extra-autonomic manifestations in patients with AAG. It is necessary to establish the new systems for the detection of autoantibodies to other subunits of acetylcholine receptor.

  4. Pregnancy and the risk of autoimmune disease: An exploration.

    LENUS (Irish Health Repository)

    2012-01-31

    Fetal microchimerism is the study of persisting fetal cells in the mother years after pregnancy and the purported implications for her health and longevity. Due to the association between pregnancy and autoimmune disease (AID), and the preponderance of these diseases in women, laboratory studies have for years attempted to link microchimeric fetal cells with the onset of AID after pregnancy. This new study gave us the opportunity to examine for the first time if this theory could be proven clinically in a large cohort of women. By examining whether different types of delivery affected the onset of AID, we also aimed to indirectly relate this finding to fetal microchimerism. The results did suggest an association between pregnancy and the risk of subsequent maternal AID, with increased risks noted after caesarean section (CS) and decreased risks after abortion. This is the first epidemiological study on the risk of AID following pregnancy.

  5. Experimental transmission of systemic AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice

    Science.gov (United States)

    Maeda, Mayuko; Murakami, Tomoaki; Muhammad, Naeem; Inoshima, Yasuo; Ishiguro, Naotaka

    2016-01-01

    AA amyloidosis is a protein misfolding disease characterized by extracellular deposition of amyloid A (AA) fibrils. AA amyloidosis has been identified in food animals, and it has been postulated that AA amyloidosis may be transmissible to different animal species. Since the precursor protein of AA fibrils is serum amyloid A (SAA), which is an inflammatory acute phase protein, AA amyloidosis is considered to be associated with inflammatory diseases such as rheumatoid arthritis. Chronic diseases such as autoimmune disease and type 2 diabetes mellitus could be potential factors for AA amyloidosis. In this study, to examine the relationship between the induction of AA amyloidosis and chromic abnormalities such as autoimmune disease or type 2 diabetes mellitus, amyloid fibrils from mice, cattle, or chickens were experimentally injected into disease model mice. Wild-type mice were used as controls. The concentrations of SAA, IL-6, and IL-10 in autoimmune disease model mice were higher than those of control mice. However, induction of AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice was lower than that in control mice, and the amount of amyloid deposits in the spleens of both mouse models was lower than that of control mice according to Congo red staining and immunohistochemistry. These results suggest that factors other than SAA levels, such as an inflammatory or anti-inflammatory environment in the immune response, may be involved in amyloid deposition. PMID:27321428

  6. Experimental transmission of systemic AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice.

    Science.gov (United States)

    Maeda, Mayuko; Murakami, Tomoaki; Muhammad, Naeem; Inoshima, Yasuo; Ishiguro, Naotaka

    2016-11-01

    AA amyloidosis is a protein misfolding disease characterized by extracellular deposition of amyloid A (AA) fibrils. AA amyloidosis has been identified in food animals, and it has been postulated that AA amyloidosis may be transmissible to different animal species. Since the precursor protein of AA fibrils is serum amyloid A (SAA), which is an inflammatory acute phase protein, AA amyloidosis is considered to be associated with inflammatory diseases such as rheumatoid arthritis. Chronic diseases such as autoimmune disease and type 2 diabetes mellitus could be potential factors for AA amyloidosis. In this study, to examine the relationship between the induction of AA amyloidosis and chromic abnormalities such as autoimmune disease or type 2 diabetes mellitus, amyloid fibrils from mice, cattle, or chickens were experimentally injected into disease model mice. Wild-type mice were used as controls. The concentrations of SAA, IL-6, and IL-10 in autoimmune disease model mice were higher than those of control mice. However, induction of AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice was lower than that in control mice, and the amount of amyloid deposits in the spleens of both mouse models was lower than that of control mice according to Congo red staining and immunohistochemistry. These results suggest that factors other than SAA levels, such as an inflammatory or anti-inflammatory environment in the immune response, may be involved in amyloid deposition.

  7. Involvement of central nervous system in the schistosomiasis.

    Science.gov (United States)

    Ferrari, Teresa Cristina de Abreu

    2004-01-01

    The involvement of the central nervous system (CNS) by schistosomes may or may not determine clinical manifestations. When symptomatic, neuroschistosomiasis (NS) is one of the most severe presentations of schistosomal infection. Considering the symptomatic form, cerebral involvement is almost always due to Schistosoma japonicum and the spinal cord disease, caused by S. mansoni or S. haematobium. Available evidence suggests that NS depends basically on the presence of parasite eggs in the nervous tissue and on the host immune response. The patients with cerebral NS usually have the clinical manifestations of increased intracranial pressure associated with focal neurological signs; and those with schistosomal myeloradiculopathy (SMR) present rapidly progressing symptoms of myelitis involving the lower cord, usually in association with the involvement of the cauda esquina roots. The diagnosis of cerebral NS is established by biopsy of the nervous tissue and SMR is usually diagnosed according to a clinical criterion. Antischistosomal drugs, corticosteroids and surgery are the resources available for treating NS. The outcome is variable and is better in cerebral disease.

  8. Involvement of central nervous system in the schistosomiasis

    Directory of Open Access Journals (Sweden)

    Teresa Cristina de Abreu Ferrari

    2004-08-01

    Full Text Available The involvement of the central nervous system (CNS by schistosomes may or may not determine clinical manifestations. When symptomatic, neuroschistosomiasis (NS is one of the most severe presentations of schistosomal infection. Considering the symptomatic form, cerebral involvement is almost always due to Schistosoma japonicum and the spinal cord disease, caused by S. mansoni or S. haematobium. Available evidence suggests that NS depends basically on the presence of parasite eggs in the nervous tissue and on the host immune response. The patients with cerebral NS usually have the clinical manifestations of increased intracranial pressure associated with focal neurological signs; and those with schistosomal myeloradiculopathy (SMR present rapidly progressing symptoms of myelitis involving the lower cord, usually in association with the involvement of the cauda esquina roots. The diagnosis of cerebral NS is established by biopsy of the nervous tissue and SMR is usually diagnosed according to a clinical criterion. Antischistosomal drugs, corticosteroids and surgery are the resourses available for treating NS. The outcome is variable and is better in cerebral disease.

  9. The complex simplicity of the brittle star nervous system.

    Science.gov (United States)

    Zueva, Olga; Khoury, Maleana; Heinzeller, Thomas; Mashanova, Daria; Mashanov, Vladimir

    2018-01-01

    Brittle stars (Ophiuroidea, Echinodermata) have been increasingly used in studies of animal behavior, locomotion, regeneration, physiology, and bioluminescence. The success of these studies directly depends on good working knowledge of the ophiuroid nervous system. Here, we describe the arm nervous system at different levels of organization, including the microanatomy of the radial nerve cord and peripheral nerves, ultrastructure of the neural tissue, and localization of different cell types using specific antibody markers. We standardize the nomenclature of nerves and ganglia, and provide an anatomically accurate digital 3D model of the arm nervous system as a reference for future studies. Our results helped identify several general features characteristic to the adult echinoderm nervous system, including the extensive anatomical interconnections between the ectoneural and hyponeural components, neuroepithelial organization of the central nervous system, and the supporting scaffold of the neuroepithelium formed by radial glial cells. In addition, we provide further support to the notion that the echinoderm radial glia is a complex and diverse cell population. We also tested the suitability of a range of specific cell-type markers for studies of the brittle star nervous system and established that the radial glial cells are reliably labeled with the ERG1 antibodies, whereas the best neuronal markers are acetylated tubulin, ELAV, and synaptotagmin B. The transcription factor Brn1/2/4 - a marker of neuronal progenitors - is expressed not only in neurons, but also in a subpopulation of radial glia. For the first time, we describe putative ophiuroid proprioceptors associated with the hyponeural part of the central nervous system. Together, our data help establish both the general principles of neural architecture common to the phylum Echinodermata and the specific ophiuroid features.

  10. Cutting-edge issues in autoimmunity and allergy of the digestive system.

    Science.gov (United States)

    Selmi, Carlo

    2012-06-01

    Autoimmunity and allergy involving the digestive system may be considered as paradigmatic for numerous common themes of complex diseases secondary to tolerance breakdown. Among gastrointestinal autoimmune diseases, for example, we encounter diseases in which a clear environmental trigger is identified (i.e., celiac disease), serum autoantibodies are most specific (i.e., primary biliary cirrhosis), or in which the disease pathophysiology is clearly understood (i.e., autoimmune gastritis). Similarly, it is intriguing that the gastrointestinal tract and the liver circulation represent the crucial environment for the development of immune tolerance. This issue is dedicated to the discussion of recent concepts while identifying two major common issues, i.e., the need for serum biomarkers and the role of vitamin D. Other common themes characterize the etiology and effector mechanisms of these and other autoimmune diseases and are discussed in each cutting-edge overview.

  11. The potential for induction of autoimmune disease by a randomly-mutated self-antigen

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm

    2007-01-01

    -antigens can be immunogenic and lead to autoimmunity against wildtype self-antigens. In theory, modified self-antigens can arise by random errors and mutations during protein synthesis and would be recognized as foreign antigens by naïve B and T lymphocytes. Here, it is postulated that the initial auto......-antigen is not a germline self-antigen, but rather a mutated self-antigen. This mutated self-antigen might interfere with peripheral tolerance if presented to the immune system during an infection. The infection lead to bystander activation of naïve T and B cells with specificity for mutated self-antigen and this can lead......The pathology of most autoimmune diseases is well described. However, the exact event that triggers the onset of the inflammatory cascade leading to disease is less certain and most autoimmune diseases are complex idiopathic diseases with no single gene known to be causative. In many cases...

  12. Bioengineered cell culture systems of central nervous system injury and disease

    OpenAIRE

    Teixeira, Fábio Gabriel Rodrigues; Vasconcelos, Natália L.; Gomes, Eduardo Domingos Correia; Marques, Fernanda; Sousa, João Carlos; Sousa, Nuno; Silva, Nuno A.; Silva, Rita Catarina Assunção Ribeiro; Lima, Rui Augusto Ribeiro; Salgado, A. J.

    2016-01-01

    Cell culture systems, either 2D or explant based, have been pivotal to better understand the pathophysiology of several central nervous system (CNS) disorders. Recently, bioengineered cell culture systems have been proposed as an alternative to the traditional setups. These innovative systems often combine different cell populations in 3D environments that more closely recapitulate the different niches that exist within the developing or adult CNS. Given the importance of such systems for the...

  13. Role of nervous system on immunological response of animal

    International Nuclear Information System (INIS)

    Elssayed, A.E.A.

    1980-01-01

    Autoantibodies occur more frequently in old age. Both organ and non organ specific antibodies have been reported to occur in increasing frequency in sera of diseased free men and mice relatively late in life. The prevalence of auto-anti-thyroglobulin antibodies in various thyroid abnormalities are common regardless of age. The investigation reported in the present study was aimed to provide some insights on virtually unexplored area of auto-anti-thyroglobulin as related to central nervous system using various radio immunological and serological techniques for the determination of antibody formation and toter, in artificial case of auto-immunity developed by induced T G immunity in rabbits

  14. Hyaluronan Anchored to Activated CD44 on Central Nervous System Vascular Endothelial Cells Promotes Lymphocyte Extravasation in Experimental Autoimmune Encephalomyelitis*

    Science.gov (United States)

    Winkler, Clayton W.; Foster, Scott C.; Matsumoto, Steven G.; Preston, Marnie A.; Xing, Rubing; Bebo, Bruce F.; Banine, Fatima; Berny-Lang, Michelle A.; Itakura, Asako; McCarty, Owen J. T.; Sherman, Larry S.

    2012-01-01

    The extravasation of lymphocytes across central nervous system (CNS) vascular endothelium is a key step in inflammatory demyelinating diseases including multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). The glycosaminoglycan hyaluronan (HA) and its receptor, CD44, have been implicated in this process but their precise roles are unclear. We find that CD44−/− mice have a delayed onset of EAE compared with wild type animals. Using an in vitro lymphocyte rolling assay, we find that fewer slow rolling (<1 μm/s) wild type (WT) activated lymphocytes interact with CD44−/− brain vascular endothelial cells (ECs) than with WT ECs. We also find that CD44−/− ECs fail to anchor HA to their surfaces, and that slow rolling lymphocyte interactions with WT ECs are inhibited when the ECs are treated with a pegylated form of the PH20 hyaluronidase (PEG-PH20). Subcutaneous injection of PEG-PH20 delays the onset of EAE symptoms by ∼1 day and transiently ameliorates symptoms for 2 days following disease onset. These improved symptoms correspond histologically to degradation of HA in the lumen of CNS blood vessels, decreased demyelination, and impaired CD4+ T-cell extravasation. Collectively these data suggest that HA tethered to CD44 on CNS ECs is critical for the extravasation of activated T cells into the CNS providing new insight into the mechanisms promoting inflammatory demyelinating disease. PMID:22865853

  15. Biomarkers of Alzheimer's Disease: From Central Nervous System to Periphery?

    Directory of Open Access Journals (Sweden)

    Enrico Mossello

    2011-01-01

    Full Text Available Alzheimer's Disease (AD is the most frequent form of dementia and represents one of the main causes of disability among older subjects. Up to now, the diagnosis of AD has been made according to clinical criteria. However, the use of such criteria does not allow an early diagnosis, as pathological alterations may be apparent many years before the clear-cut clinical picture. An early diagnosis is even more valuable to develop new treatments, potentially interfering with the pathogenetic process. During the last decade, several neuroimaging and cerebrospinal fluid (CSF parameters have been introduced to allow an early and accurate detection of AD patients, and, recently, they have been included among research criteria for AD diagnosis. However, their use in clinical practice suffers from limitations both in accuracy and availability. The increasing amount of knowledge about peripheral biomarkers will possibly allow the future identification of reliable and easily available diagnostic tests.

  16. Epidemiology of autoimmune diseases in Denmark

    DEFF Research Database (Denmark)

    Eaton, William W.; Rose, N.R.; Kalaydijan, A.

    2007-01-01

    An epidemiologic study of the autoimmune diseases taken together has not been done heretofore. The National Patient Register of Denmark is used to estimate the population prevalence of 31 possible or probable autoimmune diseases. Record linkage is used to estimate 465 pairwise co...... diseases and weak across diseases. These data confirm the importance of the autoimmune diseases as a group and suggest that common etiopathologies exist among them......-morbidities in individuals among the 31 diseases, and familial aggregation among sibs, parents and offspring. The prevalence of any of the 31 diseases in the population is more than 5%. Within individuals, there is extensive comorbidity across the 31 diseases. Within families, aggregation is strongest for individual...

  17. The paradox of chronic neuroinflammation, systemic immune suppression, autoimmunity after traumatic chronic spinal cord injury.

    Science.gov (United States)

    Schwab, Jan M; Zhang, Yi; Kopp, Marcel A; Brommer, Benedikt; Popovich, Phillip G

    2014-08-01

    During the transition from acute to chronic stages of recovery after spinal cord injury (SCI), there is an evolving state of immunologic dysfunction that exacerbates the problems associated with the more clinically obvious neurologic deficits. Since injury directly affects cells embedded within the "immune privileged/specialized" milieu of the spinal cord, maladaptive or inefficient responses are likely to occur. Collectively, these responses qualify as part of the continuum of "SCI disease" and are important therapeutic targets to improve neural repair and neurological outcome. Generic immune suppressive therapies have been largely unsuccessful, mostly because inflammation and immunity exert both beneficial (plasticity enhancing) and detrimental (e.g. glia- and neurodegenerative; secondary damage) effects and these functions change over time. Moreover, "compartimentalized" investigations, limited to only intraspinal inflammation and associated cellular or molecular changes in the spinal cord, neglect the reality that the structure and function of the CNS are influenced by systemic immune challenges and that the immune system is 'hardwired' into the nervous system. Here, we consider this interplay during the progression from acute to chronic SCI. Specifically, we survey impaired/non-resolving intraspinal inflammation and the paradox of systemic inflammatory responses in the context of ongoing chronic immune suppression and autoimmunity. The concepts of systemic inflammatory response syndrome (SIRS), compensatory anti-inflammatory response syndrome (CARS) and "neurogenic" spinal cord injury-induced immune depression syndrome (SCI-IDS) are discussed as determinants of impaired "host-defense" and trauma-induced autoimmunity. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Treatment of autoimmune inflammation by a TLR7 ligand regulating the innate immune system.

    Directory of Open Access Journals (Sweden)

    Tomoko Hayashi

    Full Text Available The Toll-like receptors (TLR have been advocated as attractive therapeutic targets because TLR signaling plays dual roles in initiating adaptive immune responses and perpetuating inflammation. Paradoxically, repeated stimulation of bone marrow mononuclear cells with a synthetic TLR7 ligand 9-benzyl-8-hydroxy-2-(2-methoxyethoxy adenine (called 1V136 leads to subsequent TLR hyporesponsiveness. Further studies on the mechanism of action of this pharmacologic agent demonstrated that the TLR7 ligand treatment depressed dendritic cell activation, but did not directly affect T cell function. To verify this mechanism, we utilized experimental allergic encephalitis (EAE as an in vivo T cell dependent autoimmune model. Drug treated SJL/J mice immunized with proteolipid protein (PLP(139-151 peptide had attenuated disease severity, reduced accumulation of mononuclear cells in the central nervous system (CNS, and limited demyelination, without any apparent systemic toxicity. Splenic T cells from treated mice produced less cytokines upon antigenic rechallenge. In the spinal cords of 1V136-treated EAE mice, the expression of chemoattractants was also reduced, suggesting innate immune cell hyposensitization in the CNS. Indeed, systemic 1V136 did penetrate the CNS. These experiments indicated that repeated doses of a TLR7 ligand may desensitize dendritic cells in lymphoid organs, leading to diminished T cell responses. This treatment strategy might be a new modality to treat T cell mediated autoimmune diseases.

  19. The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases

    Directory of Open Access Journals (Sweden)

    Maulilio John Kipanyula

    2016-01-01

    Full Text Available The ongoing epidemics of metabolic diseases and increase in the older population have increased the incidences of neurodegenerative diseases. Evidence from murine and cell line models has implicated calcineurin-nuclear factor of activated T-lymphocytes (NFAT signaling pathway, a Ca2+/calmodulin-dependent major proinflammatory pathway, in the pathogenesis of these diseases. Neurotoxins such as amyloid-β, tau protein, and α-synuclein trigger abnormal calcineurin/NFAT signaling activities. Additionally increased activities of endogenous regulators of calcineurin like plasma membrane Ca2+-ATPase (PMCA and regulator of calcineurin 1 (RCAN1 also cause neuronal and glial loss and related functional alterations, in neurodegenerative diseases, psychotic disorders, epilepsy, and traumatic brain and spinal cord injuries. Treatment with calcineurin/NFAT inhibitors induces some degree of neuroprotection and decreased reactive gliosis in the central and peripheral nervous system. In this paper, we summarize and discuss the current understanding of the roles of calcineurin/NFAT signaling in physiology and pathologies of the adult and developing nervous system, with an emphasis on recent reports and cutting-edge findings. Calcineurin/NFAT signaling is known for its critical roles in the developing and adult nervous system. Its role in physiological and pathological processes is still controversial. However, available data suggest that its beneficial and detrimental effects are context-dependent. In view of recent reports calcineurin/NFAT signaling is likely to serve as a potential therapeutic target for neurodegenerative diseases and conditions. This review further highlights the need to characterize better all factors determining the outcome of calcineurin/NFAT signaling in diseases and the downstream targets mediating the beneficial and detrimental effects.

  20. Experimental models of autoimmune inflammatory ocular diseases

    Directory of Open Access Journals (Sweden)

    Fabio Gasparin

    2012-04-01

    Full Text Available Ocular inflammation is one of the leading causes of blindness and loss of vision. Human uveitis is a complex and heterogeneous group of diseases characterized by inflammation of intraocular tissues. The eye may be the only organ involved, or uveitis may be part of a systemic disease. A significant number of cases are of unknown etiology and are labeled idiopathic. Animal models have been developed to the study of the physiopathogenesis of autoimmune uveitis due to the difficulty in obtaining human eye inflamed tissues for experiments. Most of those models are induced by injection of specific photoreceptors proteins (e.g., S-antigen, interphotoreceptor retinoid-binding protein, rhodopsin, recoverin, phosducin. Non-retinal antigens, including melanin-associated proteins and myelin basic protein, are also good inducers of uveitis in animals. Understanding the basic mechanisms and pathogenesis of autoimmune ocular diseases are essential for the development of new treatment approaches and therapeutic agents. The present review describes the main experimental models of autoimmune ocular inflammatory diseases.

  1. Outbreak of central nervous system disease associated with hand, foot, and mouth disease in Japan during the summer of 2000: detection and molecular epidemiology of enterovirus 71.

    Science.gov (United States)

    Fujimoto, Tsuguto; Chikahira, Masatsugu; Yoshida, Shigeru; Ebira, Hitomi; Hasegawa, Ayako; Totsuka, Atsuko; Nishio, Osamu

    2002-01-01

    Few outbreaks of the serious enterovirus 71 (EV71) infections, which affect the central nervous system (CNS), had been reported in Japan before 2000. During June through August 2000, a patient died of pulmonary edema caused by brainstem encephalitis accompanied by EV71-induced hand, foot, and mouth disease (HFMD), and many patients complicated by serious CNS disease, including paralysis, were hospitalized in a restricted area in Hyogo Prefecture, Japan (K-area). During the same period, endemics of HFMD were reported in other areas in Hyogo Prefecture, where EV71 was isolated from HFMD patients, but few patients developed aseptic meningitis. The isolations of EV71 from K-area patients were difficult with the use of Vero cells, so the strains were isolated by use of GL37 cells; Vero cells, however, could isolate EV71 strains from other areas in Hyogo Prefecture. We sequenced VP4 coding regions of these EV71 isolates and found that the isolates from K-area had the same sequence, which, except for one isolate, was different from the sequences of EV71 strains isolated from other areas of Hyogo Prefecture. Although these results were not enough to state that EV71 from K-area was a virulent strain, it seemed reasonable to conclude that serious CNS diseases in K-area were caused by EV71 because it was the only infectious agent detected in the inpatients of K-area.

  2. How Does Age at Onset Influence the Outcome of Autoimmune Diseases?

    Directory of Open Access Journals (Sweden)

    Manuel J. Amador-Patarroyo

    2012-01-01

    Full Text Available The age at onset refers to the time period at which an individual experiences the first symptoms of a disease. In autoimmune diseases (ADs, these symptoms can be subtle but are very relevant for diagnosis. They can appear during childhood, adulthood or late in life and may vary depending on the age at onset. Variables like mortality and morbidity and the role of genes will be reviewed with a focus on the major autoimmune disorders, namely, systemic lupus erythematosus (SLE, rheumatoid arthritis (RA, multiple sclerosis (MS, type 1 diabetes mellitus (T1D, Sjögren's syndrome, and autoimmune thyroiditis (AITD. Early age at onset is a worst prognostic factor for some ADs (i.e., SLE and T1D, while for others it does not have a significant influence on the course of disease (i.e., SS or no unanimous consensus exists (i.e., RA and MS.

  3. Poisoning or primary nervous system disease?--difficulties of the differential diagnosis exemplified by four different clinical cases.

    Science.gov (United States)

    Magdalan, Jan; Antończyk, Andrzej; Kochman, Krystyna; Porebska, Barbara

    2005-01-01

    Acute or chronic injury of the nervous system caused by xenobiotics can resemble primary disorders of the nervous system. In this study, four different cases that are characterized by unclear clinical presentation have been discussed; they required a detailed differential diagnostics using modern radiologic and electrophysiologic studies. Case 1. A young alcohol abuser was referred to the Acute Poisonings Unit at Wrocław with a presumptive diagnosis of methanol poisoning. Neither methanol nor ethylene glycol were detected in patient's serum and urine. During hospitalization in our ward he lost vision completely, and neurologic examination was consistent with a transverse spinal cord injury. Traumatic spinal cord injury coexisting with methanol poisoning, or even Devic's syndrome were considered in differential diagnosis. The MRI did not reveal a spinal cord injury, and the EMG showed severe demyelinating-axonal polyneuropathy. Finally the patient was diagnosed with methanol poisoning complicated by both loss of vision and severe alcoholic polyneuropathy. Case 2. A 27-year-old man was found unconscious in a street. A head CT revealed numerous small intracerebral hemorrhages, and patient's urine contained high concentration of amphetamine. A presumptive diagnosis of amphetamine poisoning complicated by intracranial hemorrhage was proposed. The repeat head CT revealed traumatic injury of the skull in a form of depression. Based on this result, the patient was diagnosed with a posttraumatic intracranial hemorrhage. Case 3. A young man with history of schizophrenia was transferred to our ward from a psychiatric hospital with a presumptive diagnosis of neuroleptic malignant syndrome complicated by rhabdomyolysis. Infection of the nervous system and focal lesions in the brain were ruled out with help of lumbar puncture and a brain MRI. After having obtained additional details of patient's history, it appeared that the patient had not been taking neuroleptics, and

  4. Evaluation of central nervous system in patients with glycogen storage disease type 1a.

    Science.gov (United States)

    Aydemir, Yusuf; Gürakan, Figen; Saltık Temizel, İnci Nur; Demir, Hülya; Oğuz, Kader Karlı; Yalnızoğlu, Dilek; Topçu, Meral; Özen, Hasan; Yüce, Aysel

    2016-01-01

    We aimed to evaluate structure and functions of central nervous system (CNS) in children with glycogen storage disease (GSD) type 1a. Neurological examination, psychometric tests, electroencephalography (EEG), magnetic resonance imaging (MRI), visual evoked potentials (VEP) and brainstem auditory evoked potentials (BAEP) were performed. The results were compared between patients with good and poor metabolic control and healthy children. Twenty-three patients with GSD type 1a were studied. Twelve patients were in poor metabolic control group and 11 patients in good metabolic control group. Five patients had intellectual disability, 10 had EEG abnormalities, seven had abnormal VEP and two had abnormal BAEP results. MRI was abnormal in five patients. There was significant correlation between the number of hypoglycemic attacks and MRI abnormalities. Central nervous system may be affected in GSD type 1a even in patients with normal neurologic examination. Accumulation of abnormal results in patients with poor metabolic control supports the importance of metabolic control in GSD type 1a.

  5. Congenital and acquired mitochondrial disorders of the central nervous system

    Directory of Open Access Journals (Sweden)

    V. V. Nikitina

    2014-01-01

    Full Text Available Clinical presentations of disorders of the nervous system manifest in young and middle-aged patients with congenital and acquired mitochondrial dysfunctions and cognitive disorders manifest in patients with mitochondrial diseases more often. Nowadays the effective methods of initial diagnosing of these conditions are neurological and neuropsychological examination of patients, using of biochemical markers of mitochondrial diseases: the indices of lactate, total homocysteine in plasma and liquor. Neuro-visual study (Magnetic resonance imaging of the brain, MR spectroscopy, tractography, diffusion-weighted magnetic resonance imaging of the brain, mitochondrial DNA typing is actually used for the differential diagnosing of mitochondrial diseases with other disorders that are accompanied by demyelinating disorders.

  6. MRI of central nervous system anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Izawa, M.; Oikawa, A.; Matoba, A.

    1987-05-01

    MRI was very useful in the evaluation of congenital anomalies of central nervous system as well as other nervous system disease with three-dimensional spatial resolution. We had experienced MRI of central nervous system anomalies, demonstrated characterisitic findings in each anomaly. MRI is useful to observe the coronal, horizontal and sagittal images of the brain and spinal cord in order to discuss the etiological mechanisms of spinal dysraphysm and its associated anomalies. In case of spina bifida cystica MRI was available to decide operative indication for radical operation and tetherd cord developed from postoperative scar or accompanied intraspinal lesions.

  7. Menopause in patients with autoimmune diseases.

    Science.gov (United States)

    Sammaritano, Lisa R

    2012-05-01

    Menopause represents a time of significant clinical and hormonal change. Given the incompletely understood interrelationship between gonadal hormones and the immune system, it is possible that menopause may affect, or be affected by, the presence of autoimmune disease. Menopause has significant effects on a number of organ systems including the cardiovascular, skeletal, central nervous and genitourinary systems. Premature ovarian failure is related to autoimmune factors in a proportion of cases, but is not generally associated with systemic autoimmune disorders unless secondary to treatment with alkylating agents such as cyclophosphamide. Gonadal hormones have been suggested to relate to both onset and activity in certain autoimmune diseases. For patients with systemic lupus erythematosus, disease activity is lower, and damage accrual higher, in the postmenopausal years, but the mechanisms responsible may relate to age, duration of disease, menopause changes, long-term effects of therapy, or some combination of these factors. Early menopause is a risk factor for rheumatoid arthritis, and post-menopausal status in RA is associated with greater damage and disability. Systemic sclerosis and giant cell arteritis may also be adversely affected by onset of menopause. Importantly, autoimmune disease and menopause may have an additive effect on risk for common comorbidities such as cardiovascular disease and osteoporosis. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Autonomic nervous system function in Huntington's disease.

    Science.gov (United States)

    Andrich, J; Schmitz, T; Saft, C; Postert, T; Kraus, P; Epplen, J T; Przuntek, H; Agelink, M W

    2002-06-01

    To investigate whether Huntington's disease (HD) affects autonomic nervous system (ANS) functioning. Twenty patients with HD who had positive genetic test results underwent standardised ANS function tests including sympathetic skin responses (SSRs) of the hands and feet, measurements of heart rate variability (HRV), both during five minutes of resting and deep respiration, and an orthostatic blood pressure test. Patients were classified according to the motor subscale of the unified Huntington's disease rating scale (UHDRS; mean (SD) score 26.4 (13.6)) and divided into two subgroups: UHDRS or =25 points (mid stages, M-HD). Autonomic indices were compared with those obtained for a group of well matched healthy controls (n=60). Overall, patients showed lower HRV indices than controls. Multivariate analysis with the independent factor of "group" (controls, E-HD, M-HD) showed a significant group effect on both the high frequency power (F=4.32, p=0.017) and the coefficient of variation (F=4.23, p=0.018), indicating a significant reduction in vagal modulation in the M-HD group. There was a shift in autonomic neurocardiac balance towards sympathetic predominance in the M-HD group compared with controls (F=2.89, p=0.062). Moreover, we found an inverse correlation between the severity of clinical HD symptoms (assessed by the UHDRS) and the modulation of cardiovagal activity (p=0.028). Vagal dysregulation was present in two patients; one of them also showed a pathological blood pressure test and a latency prolongation in the SSRs of the hands. Two other patients had pathologically reduced SSR amplitudes. Only patients of the M-HD group were affected. Autonomic dysfunction is present even in the middle stages of HD and affects both the sympathetic and parasympathetic branch of the ANS.

  9. Peripheral nervous system manifestations of Chediak-Higashi disease.

    Science.gov (United States)

    Lehky, Tanya J; Groden, Catherine; Lear, Barbara; Toro, Camilo; Introne, Wendy J

    2017-03-01

    Chediak-Higashi disease (CHD) is a rare autosomal recessive disorder with hematologic, infectious, pigmentary, and neurologic manifestations. Classic CHD (C-CHD) presents in early childhood with severe infectious or hematologic complications unless treated with bone marrow transplantation. Atypical CHD (A-CHD) has less severe hematologic and infectious manifestations. Both C-CHD and A-CHD develop neurological problems. Eighteen patients with CHD (9 A-CHD and 9 C-CHD) underwent electrodiagnostic studies as part of a natural history study (NCT 00005917). Longitudinal studies were available for 10 patients. All A-CHD patients had either sensory neuropathy, sensorimotor neuropathy, and/or diffuse neurogenic findings. In C-CHD, 3 adults had sensorimotor neuropathies with diffuse neurogenic findings, and 1 adult had a sensory neuropathy. The 5 children with C-CHD had normal electrodiagnostic findings. CHD can result in sensory or sensorimotor neuropathies and/or a diffuse motor neuronopathy. It may take 2-3 decades for the neuropathic findings to develop, because children appear to be spared. Muscle Nerve 55: 359-365, 2017. © 2016 Wiley Periodicals, Inc.

  10. Cyclophosphamide: As bad as its reputation? Long-term single centre experience of cyclophosphamide side effects in the treatment of systemic autoimmune diseases.

    Science.gov (United States)

    Dan, Diana; Fischer, Rahel; Adler, Sabine; Förger, Frauke; Villiger, Peter M

    2014-01-01

    Despite new treatment modalities, cyclophosphamide (CYC) remains a cornerstone in the treatment of organ or life-threatening vasculitides and connective tissue disorders. We aimed at analysing the short- and long-term side-effects of CYC treatment in patients with systemic autoimmune diseases. Chart review and phone interviews regarding side effects of CYC in patients with systemic autoimmune diseases treated between 1984 and 2011 in a single university centre. Adverse events were stratified according to the "Common Terminology Criteria for Adverse Events" version 4. A total of 168 patients were included. Cumulative CYC dose was 7.45 g (range 0.5-205 g). Gastro-intestinal side effects were seen in 68 events, hair loss occurred in 38 events. A total of 58 infections were diagnosed in 44/168 patients (26.2%) with 9/44 suffering multiple infections. Severity grading of infections was low in 37/58 cases (63.8%). One CYC-related infection-induced death (0.6%) was registered. Amenorrhoea occurred in 7/92 females (7.6%) with 5/7 remaining irreversible. In females with reversible amenorrhoea, prophylaxis with nafarelin had been administered. Malignancy was registered in 19 patients after 4.7 years (median, range 0.25-22.25) presenting as 4 premalignancies and 18 malignancies, 3 patients suffered 2 premalignancies/malignancies each. Patients with malignancies were older with a higher cumulative CYC dose. Death was registered in 28 patients (16.6%) with 2/28 probably related to CYC. Considering the organ or life-threatening conditions which indicate the use of CYC, severe drug-induced health problems were rare. Our data confirm the necessity to follow-up patients long-term for timely diagnosis of malignancies. CYC side-effects do not per se justify prescription of newer drugs or biologic agents in the treatment of autoimmune diseases.

  11. [Panarteritis nodosa: infection of the central nervous system with headache and clinical symptoms].

    Science.gov (United States)

    Müller, H

    1981-01-29

    Headache in various forms is frequent in panarteritis nodosa and possibly is an early symptom of affection of the central nervous system. 2 typical cases are described. In up to 13% of patients with panarteritis nodosa the central nervous system is affected, the forms of the disease are described as well as development of prognosis under today's therapy.

  12. Monophyletic Origin of the Metazoan Nervous System: Characterizing

    Science.gov (United States)

    Watkins, Russell; Beckenbach, Andrew

    In the absence of additional cases to be studied, our understanding of the likelihood of intelligent life evolving elsewhere in the universe must be framed within the context of the evolution of intelligence on this planet. Towards this end a valid model of the evolution of animal life, and in particular of the nervous system, is key. Models which describe the development of complexity within the nervous system can be positively misleading if they are not grounded in an accurate model of the true relationships of the animal phyla. If fact the evolution of animal life at its earliest stages, from protists to the sponges, Cnidaria, and Ctenophora and onward to the bilateral animal phyla is poorly characterized. Recently numerous phylogenies of the early animal radiation have been published based upon DNA sequence data, with conflicting and poorly supported results. A polyphyletic origin for the animal nervous system has been implied by the results of several studies, which would lead to the conclusion that some characteristics of the nervous systems of higher and lower animals could be convergent. We show that an equally parsimonious interpretation of the molecular sequence data published thus far is that it reflects rapid speciation events early in animal evolution among the classical ``diploblast'' phyla, as well as accelerated DNA sequence divergence among the higher animals. This could be interpreted as support for a classical phylogeny of the animal kingdom, and thus of a strictly monophyletic origin for the nervous system.

  13. Effects of Brazilian scorpion venoms on the central nervous system.

    Science.gov (United States)

    Nencioni, Ana Leonor Abrahão; Neto, Emidio Beraldo; de Freitas, Lucas Alves; Dorce, Valquiria Abrão Coronado

    2018-01-01

    In Brazil, the scorpion species responsible for most severe incidents belong to the Tityus genus and, among this group, T. serrulatus , T. bahiensis , T. stigmurus and T. obscurus are the most dangerous ones. Other species such as T. metuendus , T. silvestres, T. brazilae , T. confluens , T. costatus , T. fasciolatus and T. neglectus are also found in the country, but the incidence and severity of accidents caused by them are lower. The main effects caused by scorpion venoms - such as myocardial damage, cardiac arrhythmias, pulmonary edema and shock - are mainly due to the release of mediators from the autonomic nervous system. On the other hand, some evidence show the participation of the central nervous system and inflammatory response in the process. The participation of the central nervous system in envenoming has always been questioned. Some authors claim that the central effects would be a consequence of peripheral stimulation and would be the result, not the cause, of the envenoming process. Because, they say, at least in adult individuals, the venom would be unable to cross the blood-brain barrier. In contrast, there is some evidence showing the direct participation of the central nervous system in the envenoming process. This review summarizes the major findings on the effects of Brazilian scorpion venoms on the central nervous system, both clinically and experimentally. Most of the studies have been performed with T. serrulatus and T. bahiensis . Little information is available regarding the other Brazilian Tityus species.

  14. The environment and autoimmune thyroid diseases

    NARCIS (Netherlands)

    Prummel, Mark F.; Strieder, Thea; Wiersinga, Wilmar M.

    2004-01-01

    Genetic factors play an important role in the pathogenesis of autoimmune thyroid disease (AITD) and it has been calculated that 80% of the susceptibility to develop Graves' disease is attributable to genes. The concordance rate for AITD among monozygotic twins is, however, well below I and

  15. Phototherapeutic treatment of patients with peripheral nervous system diseases by means of LED arrays

    Science.gov (United States)

    Zharov, Vladimir P.; Kalinin, Konstantin L.; Menyaev, Yulian A.; Zmievskoy, Gregory N.; Savin, Alexei A.; Stulin, Igor D.; Shihkerimov, Raphiz K.; Shapkina, Alla V.; Velsher, Leonid Z.; Stakhanov, Mikhail L.

    2001-05-01

    The further development of new method of phototherapy based on use of light-emitting diodes (LED) arrays has been presented. LEDs array distribution is side of cylindrical surface, covering pathology region, was used for treatment group of patients with an affected peripheral nervous system. The main group consisted of patients with humeral plexopathy - one of possible neurological manifestation of postmastectomic syndrome as result of breast cancer radical treatment. This disease was accompanied also by some other peripheral nervous system diseases: diabetic polyneuropathy, compression ischemic mononeuropathy, festering wounds and others. The phototherapeutic method is just directed on improvement of patient's conditions in combination with other traditional methods of treatment. The main parameters of photomatrix therapeutic system: wavelength - 660 nm, line width - no more than 20 nm, intensity of radiation on the surface of edema - 0.5-3 mW/cm2 (in dependence of apparatuses type). To control and study efficiency of phototreatment ultrasonic dopplerography, thermography, electromyography and viscosimetry have been used.

  16. Linking autoimmunity to the origin of the adaptive immune system.

    Science.gov (United States)

    Bayersdorf, Robert; Fruscalzo, Arrigo; Catania, Francesco

    2018-01-01

    In jawed vertebrates, the adaptive immune system (AIS) cooperates with the innate immune system (IIS) to protect hosts from infections. Although targeting non-self-components, the AIS also generates self-reactive antibodies which, when inadequately counter-selected, can give rise to autoimmune diseases (ADs). ADs are on the rise in western countries. Why haven't ADs been eliminated during the evolution of a ∼500 million-year old system? And why have they become more frequent in recent decades? Self-recognition is an attribute of the phylogenetically more ancient IIS and empirical data compellingly show that some self-reactive antibodies, which are classifiable as elements of the IIS rather then the AIS, may protect from (rather than cause) ADs. Here, we propose that the IIS's self-recognition system originally fathered the AIS and, as a consequence of this relationship, its activity is dampened in hygienic environments. Rather than a mere breakdown or failure of the mechanisms of self-tolerance, ADs might thus arise from architectural constraints.

  17. Glial Cells: The Other Cells of the Nervous System

    Indian Academy of Sciences (India)

    Carl Ludwig Schleich (1859-1922) was an anaesthetist and a surgeon who for the first time emphasized the role of neuroglia in brain function. In an era that was dominated by the idea that neurons alone were functional units of the nervous system and that glial cells were a mere glue holding neurons in place, Schleich ...

  18. LGI Proteins in the Nervous System

    Directory of Open Access Journals (Sweden)

    Linde Kegel

    2013-05-01

    Full Text Available The development and function of the vertebrate nervous system depend on specific interactions between different cell types. Two examples of such interactions are synaptic transmission and myelination. LGI1-4 (leucine-rich glioma inactivated proteins play important roles in these processes. They are secreted proteins consisting of an LRR (leucine-rich repeat domain and a so-called epilepsy-associated or EPTP (epitempin domain. Both domains are thought to function in protein–protein interactions. The first LGI gene to be identified, LGI1, was found at a chromosomal translocation breakpoint in a glioma cell line. It was subsequently found mutated in ADLTE (autosomal dominant lateral temporal (lobe epilepsy also referred to as ADPEAF (autosomal dominant partial epilepsy with auditory features. LGI1 protein appears to act at synapses and antibodies against LGI1 may cause the autoimmune disorder limbic encephalitis. A similar function in synaptic remodelling has been suggested for LGI2, which is mutated in canine Benign Familial Juvenile Epilepsy. LGI4 is required for proliferation of glia in the peripheral nervous system and binds to a neuronal receptor, ADAM22, to foster ensheathment and myelination of axons by Schwann cells. Thus, LGI proteins play crucial roles in nervous system development and function and their study is highly important, both to understand their biological functions and for their therapeutic potential. Here, we review our current knowledge about this important family of proteins, and the progress made towards understanding their functions.

  19. LGI proteins in the nervous system.

    Science.gov (United States)

    Kegel, Linde; Aunin, Eerik; Meijer, Dies; Bermingham, John R

    2013-06-25

    The development and function of the vertebrate nervous system depend on specific interactions between different cell types. Two examples of such interactions are synaptic transmission and myelination. LGI1-4 (leucine-rich glioma inactivated proteins) play important roles in these processes. They are secreted proteins consisting of an LRR (leucine-rich repeat) domain and a so-called epilepsy-associated or EPTP (epitempin) domain. Both domains are thought to function in protein-protein interactions. The first LGI gene to be identified, LGI1, was found at a chromosomal translocation breakpoint in a glioma cell line. It was subsequently found mutated in ADLTE (autosomal dominant lateral temporal (lobe) epilepsy) also referred to as ADPEAF (autosomal dominant partial epilepsy with auditory features). LGI1 protein appears to act at synapses and antibodies against LGI1 may cause the autoimmune disorder limbic encephalitis. A similar function in synaptic remodelling has been suggested for LGI2, which is mutated in canine Benign Familial Juvenile Epilepsy. LGI4 is required for proliferation of glia in the peripheral nervous system and binds to a neuronal receptor, ADAM22, to foster ensheathment and myelination of axons by Schwann cells. Thus, LGI proteins play crucial roles in nervous system development and function and their study is highly important, both to understand their biological functions and for their therapeutic potential. Here, we review our current knowledge about this important family of proteins, and the progress made towards understanding their functions.

  20. Bullous Skin Diseases: Classical Types of Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Jan Damoiseaux

    2013-01-01

    Full Text Available The prototypic bullous skin diseases, pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid, are characterized by the blister formation in the skin and/or oral mucosa in combination with circulating and deposited autoantibodies reactive with (hemidesmosomes. Koch’s postulates, adapted for autoimmune diseases, were applied on these skin diseases. It appears that all adapted Koch’s postulates are fulfilled, and, therefore, these bullous skin diseases are to be considered classical autoimmune diseases within the wide and expanding spectrum of autoimmune diseases.

  1. Rapid infusion with rituximab: short term safety in systemic autoimmune diseases

    DEFF Research Database (Denmark)

    Larsen, Janni Lisander; Jacobsen, Soren

    2013-01-01

    To describe the incidence, types and severity of adverse events, related to an accelerated regime of rituximab infusion in patients with various autoimmune diseases. Fifty-four patients with systemic autoimmune disease, to be treated with 1,000 mg of rituximab twice 2 weeks apart, participated. Pre...

  2. The role of epigenetic mechanisms and processes in autoimmune disorders

    Directory of Open Access Journals (Sweden)

    Greer JM

    2012-09-01

    Full Text Available Judith M Greer, Pamela A McCombeThe University of Queensland, UQ Centre for Clinical Research, Brisbane, Queensland, AustraliaAbstract: The lack of complete concordance of autoimmune disease in identical twins suggests that nongenetic factors play a major role in determining disease susceptibility. In this review, we consider how epigenetic mechanisms could affect the immune system and effector mechanisms in autoimmunity and/or the target organ of autoimmunity and thus affect the development of autoimmune diseases. We also consider the types of stimuli that lead to epigenetic modifications and how these relate to the epidemiology of autoimmune diseases and the biological pathways operative in different autoimmune diseases. Increasing our knowledge of these epigenetic mechanisms and processes will increase the prospects for controlling or preventing autoimmune diseases in the future through the use of drugs that target the epigenetic pathways.Keywords: twins, concordance, autoimmune disease, nongenetic factors, immune system, epigenetic modifications

  3. Glial Cells: The Other Cells of the Nervous System

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 7; Issue 1. Glial Cells: The Other Cells of the Nervous System - An Introduction to Glial Cells. Medha S Rajadhyaksha Yasmin Khan. Series Article Volume 7 Issue 1 January 2002 pp 4-10 ...

  4. Autoimmune Abnormalities of Postpartum Thyroid Diseases.

    Science.gov (United States)

    Di Bari, Flavia; Granese, Roberta; Le Donne, Maria; Vita, Roberto; Benvenga, Salvatore

    2017-01-01

    The year following parturition is a critical time for the de novo appearance or exacerbation of autoimmune diseases, including autoimmune thyroid disease. The vast majority of postpartum thyroid disease consists of postpartum thyroiditis (PPT) and the minority by Graves' disease and non-autoimmune thyroiditis. PPT has a worldwide prevalence ranging from 1 to 22% and averaging 5% based on a review published in 2012. Several factors confer risk for the development of PPT. Typically, the clinical course of PPT is characterized by three phases: thyrotoxic, hypothyroid, and euthyroid phase. Approximately half of PPT women will have permanent hypothyroidism. The best humoral marker for predictivity, already during the first trimester of gestation, is considered positivity for thyroperoxidase autoantibodies (TPOAb), though only one-third to half of such TPOAb-positive pregnant women will develop PPT. Nutraceuticals (such as selenium) or omega-3-fatty acid supplements seem to have a role in prevention of PPT. In a recent study on pregnant women with stable dietary habits, we found that the fish consumers had lower rates of positivity (and lower serum levels) of both TPOAb and thyroglobulin Ab compared to meat eaters. Finally, we remind the reader of other diseases that can be observed in the postpartum period, either autoimmune or non-autoimmune, thyroid or non-thyroid.

  5. Systemic autoimmune diseases are associated with an increased risk of bipolar disorder: A nationwide population-based cohort study.

    Science.gov (United States)

    Wang, Ling-Yi; Chiang, Jen-Huai; Chen, Shih-Fen; Shen, Yu-Chih

    2018-02-01

    Studies suggested autoimmunity plays a role in the etiology of bipolar disorder (BD). This study aimed to investigate the association between systemic autoimmune diseases (SADs) and the subsequent development of BD, and examine the potential risk factors for developing BD. Patients with SADs were identified in the Taiwan National Health Insurance Program (NHIP). A comparison cohort was created by matching patients without SADs with age. The SADs cohort consisted of 65,498 while the comparison cohort consisted of 261,992 patients. The incidence of BD was evaluated in both cohorts. The major finding was the discovery of a higher incidence of subsequent BD among patients with SADs (adjusted hazard ratio: 1.98). Specifically, the risk of BD was observed to be significant increase in systemic lupus erythematosus, rheumatoid arthritis, autoimmune vasculitis, Sicca syndrome and Crohn's disease. Furthermore, our study revealed some potential risk factors for developing BD including female, younger age and patients who lived in eastern Taiwan. Also, some comorbidities including dyslipidemia, chronic obstructive pulmonary disease, diabetes mellitus, asthma, cerebrovascular disease, alcohol used disorder, liver cirrhosis, and malignancies were potential risk factors for incident BD. The diagnosis of SADs was based on the catastrophic illness certificate defined by Taiwanese NHIP. Thus, not every form of SADs was explored for subsequent developing BD. This study confirms that SADs are associated with higher incidence of BD, suggesting that abnormal autoimmune process is associated with increased expression of psychiatric disturbances. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Different response to glucocorticoid therapy in autoimmune diseases of CNS

    Directory of Open Access Journals (Sweden)

    Stanojević Željka

    2016-01-01

    Full Text Available Th17 cells and interleukin (IL-17, their signature cytokine, have the main role in the pathogenesis of autoimmune diseases of the central nervous system such as multiple sclerosis and experimental autoimmune encephalomyelitis (EAE. The effect of glucocorticoids (GC on expression and production of IL-17 has not been thoroughly tested yet. Also, the site of action of GC is not precisely defined. This paper presents the main results of the Doctoral thesis devoted to studies of GC on the production of IL-17 in the model of EAE, induced in susceptible laboratory animals. Methylprednisolone (MP, a synthetic glucocorticoid, inhibit in vitro production of IL-17 in mitogen-stimulated lymph node cells (LNC as well as in myelin basic protein (MBP-stimulated draining LNC in dose- dependent manner. However, under the same conditions inhibitory effect of the MP on production and expression of the genes for IFN-γ, a cytokine that TH1 cells generate, is significantly more pronounced. Interestingly, when we analyzed effects of MP applied in vivo in EAE, the same phenomenon was observed: the proportion of IFN-γ producing, but not all of IL-17 cells were reduced in cells isolated from MP treated rats in comparison to control rats which indicates that MP achieves its effects not only in the peripheral lymphoid tissues, but also in target tissue. Different sensitivities of Th1 and Th17 cells that are major cellular sources of IFN-γ or IL-17 in the effect of the GC has been observed in other animal models and in human disease. Understanding the molecular mechanisms underlying the relative resistance of Th17 cells on the operation of GC is very important for the development of new strategies in the treatment of those forms of autoimmune and chronic diseases that are resistant to the effect of glucocorticoids.

  7. Role of neuroactive steroids in the peripheral nervous system

    Directory of Open Access Journals (Sweden)

    Roberto Cosimo eMelcangi

    2011-12-01

    Full Text Available Several reviews have so far pointed out on the relevant physiological and pharmacological role exerted by neuroactive steroids in the central nervous system. In the present review we summarize observations indicating that synthesis and metabolism of neuroactive steroids also occur in the peripheral nerves. Interestingly, peripheral nervous system is also a target of their action. Indeed, as here reported neuroactive steroids are physiological regulators of peripheral nerve functions and they may also represent interesting therapeutic tools for different types of peripheral neuropathy.

  8. Nuclear magnetic resonance imaging of the central nervous system

    International Nuclear Information System (INIS)

    Knaap, M.S. van der; Valk, J.

    1989-01-01

    In this article a review is given of the use of magnetic resonance imaging for the central nervous system. An example of the screening of the population for multiple scelerosis is given. A good preliminary examination and the supply of relevant information to the person which performs the imaging is necessary. (R.B.). 9 figs.; 4 tabs

  9. FMRFamide-like immunoreactivity in the nervous system of Hydra

    DEFF Research Database (Denmark)

    Grimmelikhuijzen, C J; Dockray, G J; Schot, L P

    1982-01-01

    FMRFamide-like immunoreactivity has been localized in different parts of the hydra nervous system. Immunoreactivity occurs in nerve perikarya and processes in the ectoderm of the lower peduncle region near the basal disk, in the ectoderm of the hypostome and in the ectoderm of the tentacles...

  10. Microtubule-Targeting Agents Enter the Central Nervous System (CNS): Double-edged Swords for Treating CNS Injury and Disease.

    Science.gov (United States)

    Hur, Eun-Mi; Lee, Byoung Dae

    2014-12-01

    Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs) are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS) are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been postulated that exogenous application of MTAs might prevent the breakdown or degradation of microtubules after injury or during neurodegeneration, which will thereby aid in preserving the structural integrity and function of the nervous system. Here we review recent evidence that supports this notion and also discuss potential risks of targeting microtubules as a therapy for treating nerve injury and neurodegenerative diseases.

  11. Smoke and autoimmunity: The fire behind the disease.

    Science.gov (United States)

    Perricone, Carlo; Versini, Mathilde; Ben-Ami, Dana; Gertel, Smadar; Watad, Abdulla; Segel, Michael J; Ceccarelli, Fulvia; Conti, Fabrizio; Cantarini, Luca; Bogdanos, Dimitrios P; Antonelli, Alessandro; Amital, Howard; Valesini, Guido; Shoenfeld, Yehuda

    2016-04-01

    The association between smoke habit and autoimmunity has been hypothesized a long time ago. Smoke has been found to play a pathogenic role in certain autoimmune disease as it may trigger the development of autoantibodies and act on pathogenic mechanism possibly related with an imbalance of the immune system. Indeed, both epidemiological studies and animal models have showed the potential deleterious effect caused by smoke. For instance, smoke, by provoking oxidative stress, may contribute to lupus disease by dysregulating DNA demethylation, upregulating immune genes, thereby leading to autoreactivity. Moreover, it can alter the lung microenvironment, facilitating infections, which, in turn, may trigger the development of an autoimmune condition. This, in turn, may result in a dysregulation of immune system leading to autoimmune phenomena. Not only cigarette smoke but also air pollution has been reported as being responsible for the development of autoimmunity. Large epidemiological studies are needed to further explore the accountability of smoking effect in the pathogenesis of autoimmune diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. The challenge of identification of autoantibodies specific to systemic autoimmune rheumatic diseases in high throughput operation: proposal of reliable and feasible strategies.

    Science.gov (United States)

    Pereira, Kaline Medeiros Costa; Dellavance, Alessandra; Andrade, Luis Eduardo Coelho

    2014-11-01

    Autoantibodies to extractable nuclear antigens (ENA) are good biomarkers for systemic autoimmune rheumatic diseases (SARD), but no one assay for the detection of these antibodies provides satisfactory sensitivity and positive predictive value (PPV). Here we evaluate current assays and propose novel strategies to detect anti-ENA antibodies. Diagnostic performance of double immunodiffusion (DID) and several enzyme immunoassays (EIA) for the detection of anti-ENA autoantibodies was determined using samples from 144 patients with a previous clinical diagnosis of SARD and 121 non-autoimmune individuals. A 2-step assay combining EIA and DID was developed and tested on 16,458 serum samples. EIA was more sensitive than DID for all anti-ENA antibodies, but yielded lower PPV (mean=66%) than DID (mean=96%) and a higher percentage of unexpected positive results. ROC-curve guided cut-off adjustments improved PPV for most EIA kits. Using the 2-step assay, over 80% of the samples were screened out by the first step (EIA), with results available within 24h, leaving only about 20% to be confirmed by DID. 2.9% of the 16,485 samples were found to be positive. A 2-step assay combining the speed and potential for automation of EIA with the high specificity and PPV of DID allows efficient and reliable detection of anti-ENA antibodies. Alternatively, improved PPV can be achieved by adjusting cut-off values for EIA assay results. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Autoimmune thyroiditis perdating the presentation of systemic lupus erythematosus: Two cases and a review of literature

    Directory of Open Access Journals (Sweden)

    Dhir Rajeev

    2002-01-01

    Full Text Available Autoimmune diseases are commonly encountered in dermatology practice. While the association of two autoimmune diseases in the same individual is not unknown, it is relatively rare for the second disease to be suspected based on cutaneous manifestations. We present two such cases wherein cutaneous manifestations were the first clue to the development of lupus erythematosus in a setting of autoimmune thyroiditis. Further, we have reviewed literature on this uncommon occurrence and discuss various aspects of this association.

  14. Primary granulomatous angeitis of the central nervous system

    International Nuclear Information System (INIS)

    Barrena, R.; Sevilla, G.; Olivan, M.; Gutierrez, P.; Guelbenzo, S.; Ayuso, T.

    1995-01-01

    A case of a young man with primary granulomatous angeitis of the central nervous system manifesting as a seizure is presented. The patient did not show previous pathology. Laboratory tests, computed tomography and magnetic resonance imaging were performed, but the definitive diagnosis was made only by means of brain biopsy. Administration of steroids showed and improvement in symptoms. 8 refs

  15. NSDNA: a manually curated database of experimentally supported ncRNAs associated with nervous system diseases.

    Science.gov (United States)

    Wang, Jianjian; Cao, Yuze; Zhang, Huixue; Wang, Tianfeng; Tian, Qinghua; Lu, Xiaoyu; Lu, Xiaoyan; Kong, Xiaotong; Liu, Zhaojun; Wang, Ning; Zhang, Shuai; Ma, Heping; Ning, Shangwei; Wang, Lihua

    2017-01-04

    The Nervous System Disease NcRNAome Atlas (NSDNA) (http://www.bio-bigdata.net/nsdna/) is a manually curated database that provides comprehensive experimentally supported associations about nervous system diseases (NSDs) and noncoding RNAs (ncRNAs). NSDs represent a common group of disorders, some of which are characterized by high morbidity and disabilities. The pathogenesis of NSDs at the molecular level remains poorly understood. ncRNAs are a large family of functionally important RNA molecules. Increasing evidence shows that diverse ncRNAs play a critical role in various NSDs. Mining and summarizing NSD-ncRNA association data can help researchers discover useful information. Hence, we developed an NSDNA database that documents 24 713 associations between 142 NSDs and 8593 ncRNAs in 11 species, curated from more than 1300 articles. This database provides a user-friendly interface for browsing and searching and allows for data downloading flexibility. In addition, NSDNA offers a submission page for researchers to submit novel NSD-ncRNA associations. It represents an extremely useful and valuable resource for researchers who seek to understand the functions and molecular mechanisms of ncRNA involved in NSDs. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. Diagnosis and Management of Pediatric Autoimmune Liver Disease : ESPGHAN Hepatology Committee Position Statement

    NARCIS (Netherlands)

    Mieli-Vergani, Giorgina; Vergani, Diego; Baumann, Ulrich; Czubkowski, Piotr; Debray, Dominique; Dezsofi, Antal; Fischler, Björn; Gupte, Girish; Hierro, Loreto; Indolfi, Giuseppe; Jahnel, Jörg; Smets, Françoise; Verkade, Henkjan J; Hadžić, Nedim

    Paediatric autoimmune liver disease is characterised by inflammatory liver histology, circulating autoantibodies and increased levels of IgG, in the absence of a known etiology. Three conditions have a likely autoimmune pathogenesis: autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis

  17. The autoimmune puzzle - shared and specific genetics of immune-related diseases

    NARCIS (Netherlands)

    Zhernakova, A.P.

    2009-01-01

    Immune-mediated disorders are common diseases affecting 5-10% of the population. They include two sets of diseases: the classical autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis and coeliac disease; and inflammatory diseases, such as inflammatory bowel disease, psoriasis, asthma

  18. Role of semaphorins in the adult nervous system

    NARCIS (Netherlands)

    de Wit, Joris; Verhaagen, J.

    2003-01-01

    In the developing nervous system, extending axons are directed towards their appropriate targets by a myriad of attractive and repulsive guidance cues. Work in the past decade has significantly advanced our understanding of these molecules and has made it increasingly clear that their function is

  19. Role of Nuclear Receptors in Central Nervous System Development and Associated Diseases

    Directory of Open Access Journals (Sweden)

    Ana Ana Maria

    2015-01-01

    Full Text Available The nuclear hormone receptor (NHR superfamily is composed of a wide range of receptors involved in a myriad of important biological processes, including development, growth, metabolism, and maintenance. Regulation of such wide variety of functions requires a complex system of gene regulation that includes interaction with transcription factors, chromatin-modifying complex, and the proper recognition of ligands. NHRs are able to coordinate the expression of genes in numerous pathways simultaneously. This review focuses on the role of nuclear receptors in the central nervous system and, in particular, their role in regulating the proper development and function of the brain and the eye. In addition, the review highlights the impact of mutations in NHRs on a spectrum of human diseases from autism to retinal degeneration.

  20. Superficial siderosis of the central nervous system

    African Journals Online (AJOL)

    The term superficial siderosis is used to describe the haemosiderin deposition on the surface of the brain, spinal cord, brainstem and cranial nerve leptomeninges following recurrent subarachnoid haemorrhage. The concern is the cytotoxic nature of the haemosiderin on the under- lying tissue causing slow but progressive ...

  1. Echography of congenital malformations of the central nervous system

    International Nuclear Information System (INIS)

    Toirac Romani, Carlos Andres; Salmon Cruzata, Acelia; Musle Acosta, Mirelvis; Rosales Fargie, Yamile; Dosouto Infante, Vivian

    2010-01-01

    A descriptive and prospective study was conducted in 173 pregnant women attended at the Provincial Department of Clinical Genetics of Santiago de Cuba, from January, 2000 to December, 2004, to identify congenital malformations of the central nervous system detected by means of echography. The most frequent malformation was the hydrocephaly, followed by the fusion defects of the spine, associated with the hydrocephaly and the absence of cranial cavity. There was a prevalence of altered alpha fetoprotein and of elevated amniotic fluid

  2. Paracoccidioidomycosis of the central nervous system: CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Rodacki, M.A. [Section of Neuroradiology, Service of Radiology, Sta Isabel Hospital, Sta Catarina (Brazil); Toni, G. de [University Hospital, Medical School of Curitiba, Parana (Brazil); Borba, L.A. [Division of Neurosurgery, Sta Isabel Hospital, Blumenau, Sta Catarina (Brazil); Oliveira, G.G. [Division of Pathology, Sta Isabel Hospital, Blumenau, Sta Catarina (Brazil)

    1995-11-01

    A retrospective analisis of six cases of central nervous system paracoccidioidomycosis, all but one proven by biopsy and surgery, was carried out to study the CT and clinical data and pathological correlation. Most of the patients were from the country. Headache, vomiting, seizures and hemiparesis were the most frequent symptoms. Papilloedema was present in four patients with raised intracranial pressure. Five patients had chronic lung disease and two with advanced systemic disease, skin and mucous membrane lesions were also observed. The neurological disturbance was sometimes the presenting features and the diagnosis was discovered incidentally after surgery. Both solitary and multiple parenchymal lesions were observed and the cerebral hemispheres were more commonly involved in four patients. Local meningeal involvement was observed in one with a single cortical granuloma. We enphasise the usefulness of CT, showing a rounded or lobulated mass with an isodense or radiolucent centre after contrast enhancement, surrounded by an irregular wall of varying thickness. There was always moderate oedema, extending peripherally. Other infections or neoplastic diseases may present similar findings. Preoperative diagnosis should rest on integration of clinical data, chest films, laboratory and neuroimaging studies. (orig.). With 4 figs., 2 tabs.

  3. Nanomedicine and the nervous system

    CERN Document Server

    Martin, Colin R; Hunter, Ross J

    2012-01-01

    The nanosciences encompass a variety of technologies ranging from particles to networks and nanostructures. Nanoparticles can be suitable carriers of therapeutic agents, and nanostructures provide suitable platforms and scaffolds for sub-micro bioengineering. This book focuses on nanomedicine and nanotechnology as applied to the nervous system and the brain. It covers nanoparticle-based immunoassays, nanofiber microbrush arrays, nanoelectrodes, protein nanoassemblies, nanoparticles-assisted imaging, nanomaterials, and ion channels. Additional topics include stem cell imaging, neuronal performa

  4. Clinical implications of shared genetics and pathogenesis in autoimmune diseases

    NARCIS (Netherlands)

    Zhernakova, Alexandra; Withoff, Sebo; Wijmenga, Cisca

    2013-01-01

    Many endocrine diseases, including type 1 diabetes mellitus, Graves disease, Addison disease and Hashimoto disease, originate as an autoimmune reaction that affects disease-specific target organs. These autoimmune diseases are characterized by the development of specific autoantibodies and by the

  5. Smart electromechanical systems the central nervous system

    CERN Document Server

    Kurbanov, Vugar

    2017-01-01

    This book describes approaches to solving the problems of developing the central nervous system of robots (CNSR) based on smart electromechanical systems (SEMS) modules, principles of construction of the various modules of the central nervous system and variants of mathematical software CNSR in control systems for intelligent robots. It presents the latest advances in theory and practice at the Russian Academy of Sciences. Developers of intelligent robots to solve modern problems in robotics are increasingly addressing the use of the bionic approach to create robots that mimic the complexity and adaptability of biological systems. These have smart electromechanical system (SEMS), which are used in various cyber-physical systems (CPhS), and allow the functions of calculation, control, communications, information storage, monitoring, measurement and control of parameters and environmental parameters to be integrated. The behavior of such systems is based on the information received from the central nervous syst...

  6. PET Imaging of Disease Progression and Treatment Effects in the Experimental Autoimmune Encephalomyelitis Rat Model

    NARCIS (Netherlands)

    Faria, Daniele de Paula; Vlaming, Maria L. H.; Copray, Sjef C. V. M.; Tielen, Frans; Anthonijsz, Herma J. A.; Sijbesma, Jurgen W. A.; Buchpiguel, Carlos A.; Dierckx, Rudi A. J. O.; van der Hoorn, Jose W. A.; de Vries, Erik F. J.

    The experimental autoimmune encephalomyelitis model is a model of multiple sclerosis that closely mimics the disease characteristics in humans. The main hallmarks of multiple sclerosis are neuroinflammation (microglia activation, monocyte invasion, and T-cell infiltration) and demyelination. PET

  7. Herpes Simplex Virus Infections of the Central Nervous System.

    Science.gov (United States)

    Whitley, Richard J

    2015-12-01

    This article summarizes knowledge of herpes simplex virus (HSV) infections of the central nervous system (CNS). Disease pathogenesis, detection of DNA polymerase chain reaction (PCR) for diagnosis and prognosis, and approaches to therapy warrant consideration. HSV infection of the CNS is one of few treatable viral diseases. Clinical trials indicate that outcome following neonatal herpes simplex virus type 2 (HSV-2) infections of the CNS is significantly improved when 6 months of suppressive oral acyclovir therapy follows IV antiviral therapy. In contrast, herpes simplex virus type 1 (HSV-1) infections of the brain do not benefit from extended oral antiviral therapy. This implies a difference in disease pathogenesis between HSV-2 and HSV-1 infections of the brain. PCR detection of viral DNA in the CSF is the gold standard for diagnosis. Use of PCR is now being adopted as a basis for determining the duration of therapy in the newborn. HSV infections are among the most common encountered by humans; seropositivity occurs in 50% to 90% of adult populations. Herpes simplex encephalitis, however, is an uncommon result of this infection. Since no new antiviral drugs have been introduced in nearly 3 decades, much effort has focused on learning how to better use acyclovir and how to use existing databases to establish earlier diagnosis.

  8. Overview of the Anatomy, Physiology, and Pharmacology of the Autonomic Nervous System.

    Science.gov (United States)

    Wehrwein, Erica A; Orer, Hakan S; Barman, Susan M

    2016-06-13

    Comprised of the sympathetic nervous system, parasympathetic nervous system, and enteric nervous system, the autonomic nervous system (ANS) provides the neural control of all parts of the body except for skeletal muscles. The ANS has the major responsibility to ensure that the physiological integrity of cells, tissues, and organs throughout the entire body is maintained (homeostasis) in the face of perturbations exerted by both the external and internal environments. Many commonly prescribed drugs, over-the-counter drugs, toxins, and toxicants function by altering transmission within the ANS. Autonomic dysfunction is a signature of many neurological diseases or disorders. Despite the physiological relevance of the ANS, most neuroscience textbooks offer very limited coverage of this portion of the nervous system. This review article provides both historical and current information about the anatomy, physiology, and pharmacology of the sympathetic and parasympathetic divisions of the ANS. The ultimate aim is for this article to be a valuable resource for those interested in learning the basics of these two components of the ANS and to appreciate its importance in both health and disease. Other resources should be consulted for a thorough understanding of the third division of the ANS, the enteric nervous system. © 2016 American Physiological Society. Compr Physiol 6:1239-1278, 2016. Copyright © 2016 John Wiley & Sons, Inc.

  9. The Multifactorial role of Peripheral Nervous System in Bone Growth

    Science.gov (United States)

    Gkiatas, Ioannis; Papadopoulos, Dimitrios; Pakos, Emilios E.; Kostas-Agnantis, Ioannis; Gelalis, Ioannis; Vekris, Marios; Korompilias, Anastasios

    2017-09-01

    Bone alters its metabolic and anabolic activities in response to the variety of systemic and local factors such as hormones and growth factors. Classical observations describing abundance of the nerve fibers in bone also predict a paradigm that the nervous system influences bone metabolism and anabolism. Since 1916 several investigators tried to analyze the effect of peripheral nervous system in bone growth and most of them advocated for the positive effect of innervation in the bones of growing organisms. Moreover, neuronal tissue controls bone formation and remodeling. The purpose of this mini-review is to present the most recent data concerning the influence of innervation on bone growth, the current understanding of the skeletal innervation and their proposed physiological effects on bone metabolism as well as the implication of denervation in human skeletal biology in the developing organism since the peripheral neural trauma as well as peripheral neuropathies are common and they have impact on the growing skeleton.

  10. Functional structure and dynamics of the human nervous system

    Science.gov (United States)

    Lawrence, J. A.

    1981-01-01

    The status of an effort to define the directions needed to take in extending pilot models is reported. These models are needed to perform closed-loop (man-in-the-loop) feedback flight control system designs and to develop cockpit display requirements. The approach taken is to develop a hypothetical working model of the human nervous system by reviewing the current literature in neurology and psychology and to develop a computer model of this hypothetical working model.

  11. Haemangiopericytoma of central nervous system

    Energy Technology Data Exchange (ETDEWEB)

    Borg, M.F.; Benjamin, C.S. [Auckland Hospital, Auckland (New Zealand). Dept. of Clinical Oncology

    1995-02-01

    The records of four patients presenting with a histological diagnosis of haemangiopericytoma of the central nervous system, in Auckland, New Zealand, between 1970 and 1990 were reviewed retrospectively, with the aim of determining the natural history of the disease and response to various treatment modalities. Three out of the four patients reviewed presented with primary cerebral disease and the fourth with a primary spinal cord tumour. All three cerebral primary patients were initially treated with local surgical excision. All three patients received radical radiotherapy following local recurrence. The first two patients remained disease-free locally although one patient developed a solitary liver metastasis 5 years after radiotherapy. The third patient was referred with multiple cerebral metastases and failed to respond to radiotherapy. The patient with the primary lesion in the spinal cord was treated with local excision followed by postoperative radiotherapy and remains disease-free 17 years after treatment. One patient failed to respond to chemotherapy, prescribed to treat a local recurrence adjacent to the previous radiotherapy field. This was successfully excised subsequently. The patient presenting with multiple cerebral metastases was the only patient to die of this disease. Results suggest that local recurrence is avoidable with adequate wide excision of the primary tumour followed by local radical radiotherapy. The role of chemotherapy remains controversial and no conclusion could be drawn regarding the role of palliative radiotherapy from this study. Active treatment and long-term follow-up are necessary because of the relative aggressiveness of this disease and the propensity for late relapses. 22 refs., 2 tabs., 6 figs.

  12. Pathophysiology of Resistant Hypertension: The Role of Sympathetic Nervous System

    Directory of Open Access Journals (Sweden)

    Costas Tsioufis

    2011-01-01

    Full Text Available Resistant hypertension (RH is a powerful risk factor for cardiovascular morbidity and mortality. Among the characteristics of patients with RH, obesity, obstructive sleep apnea, and aldosterone excess are covering a great area of the mosaic of RH phenotype. Increased sympathetic nervous system (SNS activity is present in all these underlying conditions, supporting its crucial role in the pathophysiology of antihypertensive treatment resistance. Current clinical and experimental knowledge points towards an impact of several factors on SNS activation, namely, insulin resistance, adipokines, endothelial dysfunction, cyclic intermittent hypoxaemia, aldosterone effects on central nervous system, chemoreceptors, and baroreceptors dysregulation. The further investigation and understanding of the mechanisms leading to SNS activation could reveal novel therapeutic targets and expand our treatment options in the challenging management of RH.

  13. Pathophysiology of Resistant Hypertension: The Role of Sympathetic Nervous System

    OpenAIRE

    Tsioufis, Costas; Kordalis, Athanasios; Flessas, Dimitris; Anastasopoulos, Ioannis; Tsiachris, Dimitris; Papademetriou, Vasilios; Stefanadis, Christodoulos

    2011-01-01

    Resistant hypertension (RH) is a powerful risk factor for cardiovascular morbidity and mortality. Among the characteristics of patients with RH, obesity, obstructive sleep apnea, and aldosterone excess are covering a great area of the mosaic of RH phenotype. Increased sympathetic nervous system (SNS) activity is present in all these underlying conditions, supporting its crucial role in the pathophysiology of antihypertensive treatment resistance. Current clinical and experimental knowledge po...

  14. Alteration of the spontaneous systemic autoimmune disease in (NZB x NZW)F1 mice by treatment with thimerosal (ethyl mercury)

    International Nuclear Information System (INIS)

    Havarinasab, S.; Hultman, P.

    2006-01-01

    Inorganic mercury may aggravate murine systemic autoimmune diseases which are either spontaneous (genetically determined) or induced by non-genetic mechanisms. Organic mercury species, the dominating form of mercury exposure in the human population, have not been examined in this respect. Therefore, ethyl mercury in the form of thimerosal, a preservative recently debated as a possible health hazard when present in vaccines, was administered in a dose of 0.156-5 mg/L drinking water to female (NZB x NZW)F1 (ZBWF1) mice. These mice develop an age-dependent spontaneous systemic autoimmune disease with high mortality primarily due to immune-complex (IC) glomerulonephritis. Five mg thimerosal/L drinking water (295 μg Hg/kg body weight (bw)/day) for 7 weeks induced glomerular, mesangial and systemic vessel wall IC deposits and antinuclear antibodies (ANA) which were not present in the untreated controls. After 22-25 weeks, the higher doses of thimerosal had shifted the localization of the spontaneously developing renal glomerular IC deposits from the capillary wall position seen in controls to the mesangium. The altered localization was associated with less severe histological kidney damage, less proteinuria, and reduced mortality. The effect was dose-dependent, lower doses having no effect compared with the untreated controls. A different effect of thimerosal treatment was induction of renal and splenic vessel walls IC deposits. Renal vessel wall deposits occurred at a dose of 0.313-5 mg thimerosal/L (18-295 μg Hg/kg bw/day), while splenic vessel wall deposits developed also in mice given the lowest dose of thimerosal, 0.156 mg/L (9 μg Hg/kg bw/day). The latter dose is 3- and 15-fold lower than the dose of Hg required to induce vessel wall IC deposits in genetically susceptible H-2 s mice by HgCl 2 and thimerosal, respectively. Further studies on the exact conditions needed for induction of systemic IC deposits by low-dose organic mercurials in autoimmune

  15. Interaction of pregnancy and autoimmune rheumatic disease.

    Science.gov (United States)

    Østensen, Monika; Villiger, Peter M; Förger, Frauke

    2012-05-01

    During pregnancy, the fetus represents a natural allograft that is not normally rejected. While the maternal immune system retains the ability to respond to foreign antigens, tolerance mechanisms are up-regulated to protect the fetus from immunologic attacks by the mother. The profound immunologic adaptations during and after pregnancy do influence maternal autoimmune rheumatic diseases in several ways. One is triggering the onset of a rheumatic disease in the post partum period, the other influencing disease activity of established rheumatic disease. The review will discuss the mechanisms of increased susceptibility of rheumatoid arthritis (RA) in the first year post partum with a specific emphasis on the role of fetal cells or antigens persisting in the maternal circulation (so called microchimerism). Furthermore, the different influences of pregnancy on established rheumatic diseases will be highlighted. A marked beneficial effect of pregnancy is observed on RA whereas several other rheumatic diseases as ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE) show either no particular effect or an aggravation of symptoms during pregnancy. Differences emerging in regard to modulation of disease symptoms during pregnancy seem related to response to hormones, the type of cytokine profile and immune response prevailing as well as further downstream interactions of molecular pathways that are important in disease pathogenesis. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. THE CLINICAL PRESENTATION OF AUTOIMMUNE THYROID DISEASE IN MEN IS ASSOCIATED WITH IL12B GENOTYPE

    DEFF Research Database (Denmark)

    Walsh, John P; Berry, Jemma; Liu, Shu

    2011-01-01

    hypothesized that IL12B genotype may influence the clinical presentation of autoimmune thyroid disease. Objective.  We tested for differences in IL12B genotype between Graves' disease and Hashimoto's disease. Patients.  We studied a discovery cohort of 203 Australian women and 37 men with autoimmune thyroid.......034). This result was confirmed in the European males (MAF 24% and 41%; P=0.013). On combined analysis of Australian, European and Chinese men (N=285), the difference was highly significant (MAF 23% and 45%; P=3x10(-5) ). In 233 males without thyroid disease, the MAF was 34%, significantly different from Graves......' disease (P=0.005) and Hashimoto's disease (P=0.029). Conclusion.  In men with autoimmune thyroid disease, a common variant located upstream of the IL12B coding region may influence whether patients present with Graves' disease or Hashimoto's disease....

  17. Study of cytokines microenvironment during autoimmune diseases ...

    African Journals Online (AJOL)

    22, IL-23, TNF-α and TGF-β) were determined. We used the immunoenzymatic technology to assess the titer of cytokines. We found that there was no significant variation of TNF-α level in normal controls and autoimmune diseases ...

  18. [Pregnancy in systemic autoimmune diseases: Myths, certainties and doubts].

    Science.gov (United States)

    Danza, Álvaro; Ruiz-Irastorza, Guillermo; Khamashta, Munther

    2016-10-07

    Systemic autoimmune diseases especially affect young women during childbearing age. The aim of this review is to update systemic lupus erythematosus, antiphospholipid syndrome and systemic sclerosis management during pregnancy. These diseases present variable maternal and fetal risks. Studies show that an appropriate disease control and a reasonable remission period prior to pregnancy are associated with satisfactory obstetric outcomes. Antiphospholipid autoantibodies profile, anti-Ro/anti-La antibodies, pulmonary pressure and activity evaluation are crucial to assess the pregnancy risk. Monitoring requires a multidisciplinary team, serial analytic controls and Doppler ultrasound of maternal and fetal circulation. Evaluation of the activity of the disease is essential. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  19. Autoimmunity in X-linked agammaglobulinemia: Kawasaki disease and review of the literature.

    Science.gov (United States)

    Behniafard, Nasrin; Aghamohammadi, Asghar; Abolhassani, Hassan; Pourjabbar, Sarvenaz; Sabouni, Farah; Rezaei, Nima

    2012-02-01

    Although autoimmunity phenotype is surprisingly common in patients with different types of primary antibody deficiency, it is much less frequent in X-linked agammaglobulinemia (XLA). Herein, we report on a 15-month-old boy with XLA who also suffered from Kawasaki disease. The current case presentation is the first report of an association between Kawasaki disease and XLA. XLA could be considered as a special opportunity to understand autoimmunity in the near absence of immunoglobulins.

  20. Epstein-Barr Virus in Systemic Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Anette Holck Draborg

    2013-01-01

    Full Text Available Systemic autoimmune diseases (SADs are a group of connective tissue diseases with diverse, yet overlapping, symptoms and autoantibody development. The etiology behind SADs is not fully elucidated, but a number of genetic and environmental factors are known to influence the incidence of SADs. Recent findings link dysregulation of Epstein-Barr virus (EBV with SAD development. EBV causes a persistent infection with a tight latency programme in memory B-cells, which enables evasion of the immune defence. A number of immune escape mechanisms and immune-modulating proteins have been described for EBV. These immune modulating functions make EBV a good candidate for initiation of autoimmune diseases and exacerbation of disease progression. This review focuses on systemic lupus erythematosus (SLE, rheumatoid arthritis (RA, and Sjögren’s syndrome (SS and sum up the existing data linking EBV with these diseases including elevated titres of EBV antibodies, reduced T-cell defence against EBV, and elevated EBV viral load. Together, these data suggest that uncontrolled EBV infection can develop diverse autoreactivities in genetic susceptible individuals with different manifestations depending on the genetic background and the site of reactivation.

  1. Gross anatomy and development of the peripheral nervous system.

    Science.gov (United States)

    Catala, Martin; Kubis, Nathalie

    2013-01-01

    The nervous system is divided into the central nervous system (CNS) composed of the brain, the brainstem, the cerebellum, and the spinal cord and the peripheral nervous system (PNS) made up of the different nerves arising from the CNS. The PNS is divided into the cranial nerves III to XII supplying the head and the spinal nerves that supply the upper and lower limbs. The general anatomy of the PNS is organized according to the arrangement of the fibers along the rostro-caudal axis. The control of the development of the PNS has been unravelled during the last 30 years. Motor nerves arise from the ventral neural tube. This ventralization is induced by morphogenetic molecules such as sonic hedgehog. In contrast, the sensory elements of the PNS arise from a specific population of cells originating from the roof of the neural tube, namely the neural crest. These cells give rise to the neurons of the dorsal root ganglia, the autonomic ganglia and the paraganglia including the adrenergic neurons of the adrenals. Furthermore, the supportive glial Schwann cells of the PNS originate from the neural crest cells. Growth factors as well as myelinating proteins are involved in the development of the PNS. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. The MicroRNA-21 in Autoimmune Diseases.

    Science.gov (United States)

    Wang, Shaowen; Wan, Xiaochun; Ruan, Qingguo

    2016-06-03

    MicroRNA-21 (miR-21) is an oncomiR and significantly upregulated in a wide range of cancers. It is strongly involved in apoptosis and oncogenesis, since most of its reported targets are tumor suppressors. Recently, miR-21 was found to be correlated with the pathogenesis of autoimmune diseases and may play an essential role in regulating autoimmune responses. In particular, miR-21 promotes Th17 cell differentiation, which mediates the development of multiple autoimmune diseases. In this article, we review the current research on the mechanisms that regulate miR-21 expression, the potential of miR-21 as a diagnostic biomarker for autoimmune disease and the mechanisms by which miR-21 promotes the development of autoimmune disease. We also discussed the therapeutic potential of targeting miR-21 in treating patients with autoimmune disease.

  3. Sexual dimorphism of miRNA expression: a new perspective in understanding the sex bias of autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Dai R

    2014-03-01

    Full Text Available Rujuan Dai, S Ansar Ahmed Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA Abstract: Autoimmune diseases encompass a diverse group of diseases which emanate from a dysregulated immune system that launches a damaging attack on its own tissues. Autoimmune attacks on self tissues can occur in any organ or body system. A notable feature of autoimmune disease is that a majority of these disorders occur predominantly in females. The precise basis of sex bias in autoimmune diseases is complex and potentially involves sex chromosomes, sex hormones, and sex-specific gene regulation in response to internal and external stimuli. Epigenetic regulation of genes, especially by microRNAs (miRNAs, is now attracting significant attention. miRNAs are small, non-protein-coding RNAs that are predicted to regulate a majority of human genes, including those involved in immune regulation. Therefore, it is not surprising that dysregulated miRNAs are evident in many diseases, including autoimmune diseases. Because there are marked sex differences in the incidence of autoimmune diseases, this review focuses on the role of sex factors on miRNA expression in the context of autoimmune diseases, an aspect not addressed thus far. Here, we initially review miRNA biogenesis and miRNA regulation of immunity and autoimmunity. We then summarize the recent findings of sexual dimorphism of miRNA expression in diverse tissues, which imply a critical role of miRNA in sex differentiation and in sex-specific regulation of tissue development and/or function. We also discuss the important contribution of the X chromosome and sex hormones to the sexual dimorphism of miRNA expression. Understanding sexually dimorphic miRNA expression in sex-biased autoimmune diseases not only offers us new insight into the mechanism of sex bias of the disease but will also aid us in developing new sex

  4. Autoimmune diseases and pregnancy: analysis of a series of cases.

    Science.gov (United States)

    Gomes, Vânia; Mesquita, Alexandra; Capela, Carlos

    2015-06-04

    An autoimmune disease is characterized by tissue damage, caused by self-reactivity of different effector mechanisms of the immune system, namely antibodies and T cells. All autoimmune diseases, to some extent, have implications for fertility and obstetrics. Currently, due to available treatments and specialised care for pregnant women with autoimmune disease, the prognosis for both mother and child has improved significantly. However these pregnancies are always high risk. The purpose of this study is to analyse the fertility/pregnancy process of women with systemic and organ-specific autoimmune diseases and assess pathological and treatment implications. The authors performed an analysis of the clinical records and relevant obstetric history of five patients representing five distinct autoimmune pathological scenarios, selected from Autoimmune Disease Consultation at the Hospital of Braga, and reviewed the literature. The five clinical cases are the following: Case 1-28 years old with systemic lupus erythematosus, and clinical remission of the disease, under medication with hydroxychloroquine, prednisolone and acetylsalicylic acid, with incomplete miscarriage at 7 weeks of gestation without signs of thrombosis. Case 2-44 years old with history of two late miscarriages, a single preterm delivery (33 weeks) and multiple thrombotic events over the years, was diagnosed with antiphospholipid syndrome after acute myocardial infarction. Case 3-31 years old with polymyositis, treated with azathioprine for 3 years with complete remission of the disease, took the informed decision to get pregnant after medical consultation and full weaning from azathioprine, and gave birth to a healthy term new-born. Case 4-38 years old pregnant woman developed Behcet's syndrome during the final 15 weeks of gestation and with disease exacerbation after delivery. Case 5-36 years old with autoimmune thyroiditis diagnosed during her first pregnancy, with difficult control over the thyroid

  5. The endocannabinoid system and its therapeutic exploitation in multiple sclerosis : Clues for other neuroinflammatory diseases.

    NARCIS (Netherlands)

    Chiurchiù, V.; Stelt, van der M.; Centonze, D.; Maccarrone, M.

    2017-01-01

    Multiple sclerosis is the most common inflammatory demyelinating disease of the central nervous system, caused by an autoimmune response against myelin that eventually leads to progressive neurodegeneration and disability. Although the knowledge on its underlying neurobiological mechanisms has

  6. Incidence of neoplasms in the most prevalent autoimmune rheumatic diseases: a systematic review.

    Science.gov (United States)

    Machado, Roberta Ismael Lacerda; Braz, Alessandra de Sousa; Freire, Eutilia Andrade Medeiros

    2014-01-01

    This article is a systematic review of the literature about the coexistence of cancer and autoimmune rheumatic diseases, their main associations, cancers and possible risk factors associated, with emphasis on existing population-based studies, besides checking the relation of this occur with the use of the drugs used in the treatment of autoimmune diseases. A search was conducted of scientific articles indexed in the Cochrane / BVS, Pubmed / Medline and Scielo / Lilacs in the period from 2002 to 2012. Also consulted was the IB-ICT (Brazilian digital library of theses and Masters), with descriptors in Portuguese and English for "Systemic sclerosis", "Rheumatoid Arthritis", " Systemic Lupus Erythematosus" and "Sjögren's syndrome", correlating each one with the descriptor AND "neoplasms". The results showed that in the database IBICT a thesis and a dissertation for the descriptor SLE met the inclusion criteria, none met RA one thesis to SS. Lilacs in the database/Scielo found two articles on "Rheumatoid Arthritis" AND "neoplasms". In Pubmed/Medline the inicial search resulted in 118 articles, and 41 were selected. The review noted the relationship between cancer and autoimmune rheumatic diseases, as well as a risk factor for protection, although the pathophysiological mechanisms are not known.

  7. IMMUNOHISTOCHEMISTRY VERSUS IMMUNOFLUORESENCE IN THE DIAGNOSIS OF AUTOIMMUNE BLISTERING DISEASES

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2013-11-01

    Full Text Available Introduction: In patients with autoimmune skin blistering diseases (ABDs, the diagnostic gold standard has classically been direct and indirect immunofluorescence (DIF and IIF, despite inherent technical problems of autofluorescence. Aim: We sought to overcome autofluorescence issues and compare the reliability of immunofluorescence versus immunohistochemistry (IHC staining in the diagnoses of these diseases. Methods: We tested via IHC for anti-human IgG, IgM, IgA, IgD, IgE, Kappa light chains, Lambda light chains, Complement/C3c, Complement/C1q, Complement/C3d, albumin and fibrinogen in 30 patients affected by a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre-EPF, and 30 control biopsies from the endemic area. We also tested archival biopsies from patients with ABDs whose diagnoses were made clinically, histopathologically and by DIF/IIF studies from 2 independent dermatopathology laboratories in the USA. Specifically, we tested 34 patients with bullous pemphigoid (BP, 18 with pemphigus vulgaris (PV, 8 with pemphigus foliaceus (PF, 14 with dermatitis herpetiformis (DH and 30 control skin samples from plastic esthetic surgery reduction surgeries. Results: The diagnostic correlation between IHC and DIF-IIF was almost 98% in most cases. IHC revealed evidence of autofluorescence around dermal blood vessels, dermal eccrine glands and neurovascular packages feeding skin appendices in ABDs; this autofluorescence may represent a non-specific immune response. Strong patterns of positivity were seen also in endothelial-mesenchymal cell junction-like structures, as well as between dermal fibrohistiocytic cells. In PV, we noted strong reactivity to neurovascular packages supplying sebaceous glands, as well as apocrine glands with edematous changes. Conclusions: We suggest that IHC is as reliable as DIF or IIF for the diagnosis of ABDs; our findings further suggest that what has previously been considered DIF/IIF autofluorescence

  8. Familial systemic autoimmune rheumatic disease in Nigerians: a ...

    African Journals Online (AJOL)

    Systemic Autoimmune Rheumatic Diseases (SARD) are chronic disorders affecting multiple organs. Most SARDs have a female preponderance. SARDs have rarely been reported in African blacks, although there is increasing reportage of recent. Different SARDs are believed to have genetic predisposition and familial ...

  9. Genetics Home Reference: autoimmune Addison disease

    Science.gov (United States)

    ... of each kidney. It is classified as an autoimmune disorder because it results from a malfunctioning immune system ... disease or their family members can have another autoimmune disorder, most commonly autoimmune thyroid disease or type 1 ...

  10. AIRE genetic variants and predisposition to polygenic autoimmune disease: The case of Graves' disease and a systematic literature review.

    Science.gov (United States)

    Colobran, Roger; Giménez-Barcons, Mireia; Marín-Sánchez, Ana; Porta-Pardo, Eduard; Pujol-Borrell, Ricardo

    2016-08-01

    Autoimmune Regulator (AIRE) is a transcriptional regulator that is crucial for establishing central tolerance as illustrated by the Mendelian Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) syndrome associated with AIRE-inactivating recessive or dominant mutations. Polymorphisms in AIRE have been proposed to be implicated in genetic susceptibility to non-Mendelian organ specific autoimmune diseases. Because there is evidence that in predisposition to Graves' disease (GD) central tolerance is crucial, we investigated whether AIRE polymorphisms could modulate risk of GD. A case-control association study using 29 variants and conducted in 150 GD patients and 200 controls did not detect any significant association. This result is not exceptional: a systematic review of the literature, including GWAS, on the association of AIRE variants with organ specific autoimmune diseases did not show clear associations; similarly heterozygous recessive mutations are not associated to non-Mendelian autoimmunity. Dominant negative mutations of AIRE are associated to autoimmunity but as mild forms of APECED rather than to non-Mendelian organ specific autoimmunity. The lack of association of common AIRE polymorphisms with polygenic autoimmune diseases is counterintuitive as many other genes less relevant for immunological tolerance have been found to be associated. These findings give rise to the intriguing possibility that evolution has excluded functionally modifying polymorphisms in AIRE. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  11. Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin antigens: IV. Suppression of chronic relapsing disease in the Lewis rat and strain 13 guinea pig.

    Science.gov (United States)

    Brod, S A; al-Sabbagh, A; Sobel, R A; Hafler, D A; Weiner, H L

    1991-06-01

    Oral administration of proteins is a long-recognized method of inducing antigen-specific peripheral immune tolerance. We previously showed that oral administration of myelin basic protein suppresses monophasic experimental autoimmune encephalomyelitis in the Lewis rat when it is given in association with immunization and prior to disease onset. As a potential therapy for human autoimmune disease, it is crucial to determine whether oral tolerance can ameliorate an ongoing immune response. We therefore asked whether oral administration of myelin antigens, after sensitization and disease expression has occurred, could affect immunological, clinical, or pathological features of experimental autoimmune encephalomyelitis. Chronic relapsing experimental autoimmune encephalomyelitis was induced in the Lewis rat and strain 13 guinea pig by immunization with whole guinea pig cord homogenate, complete Freund's adjuvant, and Mycobacterium tuberculosis. Following recovery from the first attack, animals were orally given bovine myelin, guinea pig myelin, or guinea pig myelin basic protein three times per week for up to 3 months. Animals receiving myelin products orally had decreased severity and frequency of clinical relapses, decreased delayed-type hypersensitivity responses to myelin antigens, diminished inflammation in the central nervous system (CNS), and decreased areas of CNS demyelination. In the rat, guinea pig myelin basic protein was as effective as guinea pig myelin in ameliorating the disease and also resulted in decreased serum anti-myelin basic protein antibody levels. No exacerbation of disease or worsening of pathological findings occurred in the animals given myelin products. These results demonstrate that oral administration of myelin antigens can suppress chronic relapsing experimental autoimmune encephalomyelitis and have direct relevance to therapy of human demyelinating disorders such as multiple sclerosis.

  12. A history of the autonomic nervous system: part II: from Reil to the modern era.

    Science.gov (United States)

    Oakes, Peter C; Fisahn, Christian; Iwanaga, Joe; DiLorenzo, Daniel; Oskouian, Rod J; Tubbs, R Shane

    2016-12-01

    The history of the study of the autonomic nervous system is rich. At the beginning of the nineteenth century, scientists were beginning to more firmly grasp the reality of this part of the human nervous system. The evolution of our understanding of the autonomic nervous system has a rich history. Our current understanding is based on centuries of research and trial and error.

  13. Autonomic Nervous System Disorders

    Science.gov (United States)

    Your autonomic nervous system is the part of your nervous system that controls involuntary actions, such as the beating of your heart ... breathing and swallowing Erectile dysfunction in men Autonomic nervous system disorders can occur alone or as the result ...

  14. Distribution of enteroviruses in hospitalized children with hand, foot and mouth disease and relationship between pathogens and nervous system complications

    Directory of Open Access Journals (Sweden)

    Xu Wei

    2012-01-01

    Full Text Available Abstract Background To explore the relationship between enteroviruses and hospitalized children with hand, foot and mouth disease (HFMD complicated with nervous system disease. 234 hospitalized HFMD patients treated in Shengjing Hospital, Liaoning Province were analyzed retrospectively. Based on the presence and severity of nervous system disease, the patients were grouped as follows: general patients, severely ill patients, critically ill patients and fatal patients. Based on the detected pathogen, the patients were grouped as follows: Enterovirus 71 (EV71 infection, coxsackie A16 (CA16 infection and other enterovirus (OE infection. Results Of the 423 hospitalized patients, most were admitted in July 2010(129/423, 30.5%. Enteroviruses were detected in 177(41.8%. 272/423 patients were male (64.3%, and fatal patients had the greatest proportion of male patients (p p p p p p Conclusion The disease progresses faster in EV71-infected HFMD patients. These patients are more likely to suffer nervous system damage, neurogenic pulmonary edema, severe sequelae or death. CA16 and other enteroviruses can also cause HFMD with severe nervous system complications.

  15. Neuronal expression of muskelin in the rodent central nervous system

    Directory of Open Access Journals (Sweden)

    Georges-Labouesse Elisabeth

    2007-05-01

    Full Text Available Abstract Background The kelch repeat protein muskelin mediates cytoskeletal responses to the extracellular matrix protein thrombospondin 1, (TSP1, that is known to promote synaptogenesis in the central nervous system (CNS. Muskelin displays intracellular localization and affects cytoskeletal organization in adherent cells. Muskelin is expressed in adult brain and has been reported to bind the Cdk5 activator p39, which also facilitates the formation of functional synapses. Since little is known about muskelin in neuronal tissues, we here analysed the tissue distribution of muskelin in rodent brain and analysed its subcellular localization using cultured neurons from multiple life stages. Results Our data show that muskelin transcripts and polypeptides are expressed throughout the central nervous system with significantly high levels in hippocampus and cerebellum, a finding that resembles the tissue distribution of p39. At the subcellular level, muskelin is found in the soma, in neurite projections and the nucleus with a punctate distribution in both axons and dendrites. Immunostaining and synaptosome preparations identify partial localization of muskelin at synaptic sites. Differential centrifugation further reveals muskelin in membrane-enriched, rather than cytosolic fractions. Conclusion Our results suggest that muskelin represents a multifunctional protein associated with membranes and/or large protein complexes in most neurons of the central nervous system. These data are in conclusion with distinct roles of muskelin's functional interaction partners.

  16. Histophysiology of the vegetative peripheral nervous system of skin.

    Science.gov (United States)

    Förster, F J; Heine, H; Schaeg, G

    1975-12-31

    Preterminal nerve fibers of the peripheral vegetative nervous system make inmediate contact (neuro-effector-areas) to interstitial cells (I.C.). This connection is characterized through a common glycocalyx with the nerve fiber. The I.C. are specific innervated cells and differ morphologically from Schwann-cells, fibrocytes, and histiocytes. The I.C. are able to come into morphologically different contacts with neighbouring cells by microvilli-like cell protrusions. These neighbouring cells then are able to contact other cells by themselves. The results are interpreted in the sense of electro-mechanical feed-back system of information processing in the vegetative periphery.

  17. Radon exposure and tumors of the central nervous system.

    Science.gov (United States)

    Ruano-Ravina, Alberto; Dacosta-Urbieta, Ana; Barros-Dios, Juan Miguel; Kelsey, Karl T

    2017-03-15

    To review the published evidence of links between radon exposure and central nervous system tumors through a systematic review of the scientific literature. We performed a thorough bibliographic search in Medline (PubMed) and EMBASE. We combined MeSH (Medical Subject Heading) terms and free text. We developed a purpose-designed scale to assess the quality of the included manuscripts. We have included 18 studies, 8 performed on miners, 3 on the general population and 7 on children, and the results have been structured using this classification. The results are inconclusive. An association between radon exposure and central nervous system tumors has been observed in some studies on miners, but not in others. The results observed in the general adult population and in children are also mixed, with some research evincing a statistically significant association and others showing no effect. We cannot conclude that there is a relationship between radon exposure and central nervous system tumors. The available studies are extremely heterogeneous in terms of design and populations studied. Further research is needed in this topic, particularly in the general population residing in areas with high levels of radon. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Elevated Adiponectin Serum Levels in Women with Systemic Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Éric Toussirot

    2010-01-01

    Full Text Available Adipose tissue produces a wide range of proteins that may influence the immune system. In this study, we assessed the serum levels of leptin, adiponectin, and ghrelin, in association with the measurements of body composition, in 15 female patients with various autoimmune diseases (systemic lupus erythematosus, primary Sjögren's syndrome, sarcoidosis, mixed connective tissue disease, vasculitis, CREST syndrome, and polymyositis and in 15 healthy female controls. There were no statistically significant differences between the patients and controls with regard to serum leptin, serum ghrelin, global fat mass, adiposity, and fat mass in the android or gynoid regions, whereas serum adiponectin levels were higher in patients than controls (16.3±1.6 μg/mL versus 9.7±0.6 μg/mL; =.01. As adiponectin is known to exhibit potent anti-inflammatory properties, a high adiponectinemia in patients with systemic autoimmune disease may mitigate the inflammatory response. However, the precise consequences of these elevated serum adiponectin levels on the metabolic syndrome development and atherosclerotic cardiovascular risk in this patient population still needs to be determined.

  19. Abnormal hyperintensity within the subarachnoid space evaluated by fluid-attenuated inversion-recovery MR imaging: a spectrum of central nervous system diseases

    International Nuclear Information System (INIS)

    Maeda, M.; Sakuma, H.; Takeda, K.; Yagishita, A.; Yamamoto, T.

    2003-01-01

    A variety of central nervous system (CNS) diseases are associated with abnormal hyperintensity within the subarachnoid space (SAS) by fluid-attenuated inversion-recovery (FLAIR) MR imaging. Careful attention to the SAS can provide additional useful information that may not be available with conventional MR sequences. The purpose of this article is to provide a pictorial essay about CNS diseases and FLAIR images with abnormal hyperintensity within the SAS. We present several CNS diseases including subarachnoid hemorrhage, meningitis, leptomeningeal metastases, acute infarction, and severe arterial occlusive diseases such as moya-moya disease. We also review miscellaneous diseases or normal conditions that may exhibit cerebrospinal fluid hyperintensity on FLAIR images. Although the detection of abnormal hyperintensity suggests the underlying CNS diseases and narrows differential diagnoses, FLAIR imaging sometimes presents artifactual hyperintensity within the SAS that can cause the misinterpretation of normal SAS as pathologic conditions; therefore, radiologists should be familiar with such artifactual conditions as well as pathologic conditions shown as hyperintensity by FLAIR images. This knowledge is helpful in establishing the correct diagnosis. (orig.)

  20. Extranodal Marginal Zone Lymphoma of the Central Nervous System.

    Science.gov (United States)

    Ayanambakkam, Adanma; Ibrahimi, Sami; Bilal, Khalid; Cherry, Mohamad A

    2018-01-01

    Extranodal marginal zone lymphoma of the central nervous system (CNS EMZBL) is a rare disease. We present a review of the literature and describe its presentation, differential diagnosis, treatment options, and outcomes. Systematic search of PubMed, Medline, and Embase databases via the Ovid engine for primary articles and case reports yielded 37 unduplicated peer-reviewed articles of CNS EMZBL. We identified 69 cases in these articles and 1 unreported case at our institution, which were included for this review's analysis. Median age at diagnosis was 55 years (range, 18-78 years), with a female preponderance of 77% (n = 54). Most common presenting symptoms were headache in 43% (n = 30), seizures in 31% (n = 22), and visual defects in 27% (n = 19). The most common treatment modalities were localized therapies, which were provided to 67% (n = 47) of cases. These included radiotherapy in 27% (n = 19), radiotherapy with surgery in 24% (n = 17), and surgery alone in 16% (n = 11). Ninety percent (n = 63) of patients had a median follow-up of 23 months. Complete remission was experienced by 77% (n = 49) patients, and 22% (n = 14) were alive with disease. Three patients had evidence of relapse, and one patient died. CNS EMZBL is an indolent, low-grade, radiosensitive lymphoma with good treatment outcomes and prognosis. It is an important differential to consider in extra-axial dural-based masses. Individualized management plans, with preference given to localized treatment options, should be considered after factoring in the site and extent of disease, its resectability, and the expected adverse effects of systemic therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Multiple autoimmune syndrome with celiac disease.

    Science.gov (United States)

    Harpreet, Singh; Deepak, Jain; Kiran, B

    Multiple autoimmune syndrome (MAS) is a condition characterised by three or more autoimmune disorders in a same individual. Familial, immunologic and infectious factors are implicated in the development of MAS. Here we report a case of a 32-year-old woman with co-existence of four auto-immune diseases, namely autoimmune hypothyroidism, Sjögren's syndrome, systemic lupus erythematosus (SLE) and celiac disease which leads to the final diagnosis of multiple autoimmune syndrome type 3 with celiac disease. Patients with single autoimmune disorder are at 25% risk of developing other autoimmune disorders. The present case emphasises to clinicians that there is a need for continued surveillance for the development of new autoimmune disease in predisposed patients.

  2. Central nervous system manifestation and CT findings of Fabry's disease. Case report

    Energy Technology Data Exchange (ETDEWEB)

    Toyonaga, Kazutaka; Nishihira, Takeo (Okinawa Central Hospital (Japan))

    1983-11-01

    A case of Fabry's disease with central nervous system dysfunction is reported. This 27-year-old man had recurrent episodes of pains in the extremities when he was a child. Spontaneous clinical remission occured around puberty. He had been well until age 22 when he experienced transient weakness of the left arm. The following year he developed transient blindness of the right eye. Then, he developed weakness in the extremities, dysphagia, dysarthria, and was brought to the hospital in unconscious state. Several members of his family are affected with the same disease presenting leg pains, kidney disease and angiokeratoma. Physical examination disclosed an optic atrophy, pseudobulbar palsy with spastic weakness in the all extremities and multiple angiokeratoma in the flank, buttocks and thighs. Abnormal laboratory findings included leukocytosis, increased ESR and strongly positive CRP. Biopsy of the skin disclosed dilated capilaries with numerous vacuoles in the cytoplasm of the epithelial cells. Thin-layer chromatography of the urine sediment showed a marked increase in ceramide trihexoside. Leukocyte alphagalactosidase level was abnormally low. CT scan showed diffuse cerebral atrophy and multiple low density areas in the thalamus, ventral pons and centrum semiovale. The CT findings and possible mechanism of the response to predonisolone were also discussed.

  3. The zebrafish as a gerontology model in nervous system aging, disease, and repair.

    Science.gov (United States)

    Van Houcke, Jessie; De Groef, Lies; Dekeyster, Eline; Moons, Lieve

    2015-11-01

    Considering the increasing number of elderly in the world's population today, developing effective treatments for age-related pathologies is one of the biggest challenges in modern medical research. Age-related neurodegeneration, in particular, significantly impacts important sensory, motor, and cognitive functions, seriously constraining life quality of many patients. Although our understanding of the causal mechanisms of aging has greatly improved in recent years, animal model systems still have much to tell us about this complex process. Zebrafish (Danio rerio) have gained enormous popularity for this research topic over the past decade, since their life span is relatively short but, like humans, they are still subject to gradual aging. In addition, the extensive characterization of its well-conserved molecular and cellular physiology makes the zebrafish an excellent model to unravel the underlying mechanisms of aging, disease, and repair. This review provides a comprehensive overview of the progress made in zebrafish gerontology, with special emphasis on nervous system aging. We review the evidence that classic hallmarks of aging can also be recognized within this small vertebrate, both at the molecular and cellular level. Moreover, we illustrate the high level of similarity with age-associated human pathologies through a survey of the functional deficits that arise as zebrafish age. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Recent Advances in the Pathogenesis of Autoimmune Hair Loss Disease Alopecia Areata

    Directory of Open Access Journals (Sweden)

    Taisuke Ito

    2013-01-01

    Full Text Available Alopecia areata is considered to be a cell-mediated autoimmune disease, in which autoreactive cytotoxic T cells recognize melanocyte-associated proteins such as tyrosinase. This review discusses recent advances in the understanding of the pathogenesis of alopecia areata, focusing on immunobiology and hormonal aspects of hair follicles (HFs. The HF is a unique “miniorgan” with its own immune and hormonal microenvironment. The immunosuppressive milieu of the anagen hair bulb modulated by immunosuppressive factors is known as “hair follicle immune privilege.” The collapse of the hair follicle immune privilege leads to autoimmune reactions against hair follicle autoantigens. Alopecia areata is sometimes triggered by viral infections such as influenza that causes excess production of interferons (IFN. IFN-γ is one of the key factors that lead to the collapse of immune privilege. This paper reviews the interactions between the endocrine and immune systems and hair follicles in the pathogenesis of alopecia areata.

  5. On cerebrae blood circulation from data of radiocirculography in some diseases of central nervous system in children

    International Nuclear Information System (INIS)

    Dolgov, A.G.; Stroganova, L.I.; Chirkin, N.I.

    1980-01-01

    Results of radioisotope investigation of cerebral blood circulation in 202 children with different pathology of central nervous system are presented. Velocity of cerebral blood flow and time of semiaccumulation and semimoving a preparate were investigated by means of sup(113m)In. It is established that radiocirculography shows clearly the changes in the system of cerebral blood supply and in such diseases as vegetovascular distonia and hypertension syndrome, the radiocirculography data pass ahead the clinical picture

  6. Tuberculosis of the central nervous system: overview of neuroradiological findings

    International Nuclear Information System (INIS)

    Bernaerts, A.; Vanhoenacker, F.M.; Parizel, P.M.; Goethem, J.W.M. van; De Roeck, J.; De Schepper, A.M.; Altena, R. van; Laridon, A.; Coeman, V.

    2003-01-01

    This article presents the range of manifestations of tuberculosis (TB) of the craniospinal axis. Central nervous system (CNS) infection with Mycobacterium tuberculosis occurs either in a diffuse form as basal exudative leptomeningitis or in a localized form as tuberculoma, abscess, or cerebritis. In addition to an extensive review of computed tomography and magnetic resonance features, the pathogenesis and the relevant clinical setting are discussed. Modern imaging is a cornerstone in the early diagnosis of CNS tuberculosis and may prevent unnecessary morbidity and mortality. Contrast-enhanced MR imaging is generally considered as the modality of choice in the detection and assessment of CNS tuberculosis. (orig.)

  7. The effect of space radiation of the nervous system

    Science.gov (United States)

    Gauger, Grant E.; Tobias, Cornelius A.; Yang, Tracy; Whitney, Monroe

    The long-term effects of irradiation by accelerated heavy ions on the structure and function of the nervous system have not been studied extensively. Although the adult brain is relatively resistant to low LET radiation, cellular studies indicate that individual heavy ions can produce serious membrane lesions and multiple chromatin breaks. Capillary hemorrhages may follow high LET particle irradiation of the developing brain as high RBE effects. Evidence has been accumulating that the glial system and blood-brain barrier (BBB) are relatively sensitive to injury by ionizing radiation. While DNA repair is active in neural systems, it may be assumed that a significant portion of this molecular process is misrepair. Since the expression of cell lethality usually requires cell division, and nerve cells have an extremely low rate of division, it is possible that some of the characteristic changes of premature aging may represent a delayed effect of chromatin misrepair in brain. Altered microcirculation, decreased local metabolism, entanglement and reduction in synaptic density, premature loss of neurons, myelin degeneration, and glial proliferation are late signs of such injuries. HZE particles are very efficient in producing carcinogenic cell transformation, reaching a peak for iron particles. The promotion of viral transformation is also efficient up to an energy transfer of approximately 300 keV/micron. The RBE for carcinogenesis in nerve tissues remains unknown. On the basis of available information concerning HZE particle flux in interplanetary space, only general estimates of the magnitude of the effects of long-term spaceflight on some nervous system parameters may be constructed.

  8. Innate immune responses in central nervous system inflammation

    DEFF Research Database (Denmark)

    Finsen, Bente; Owens, Trevor

    2011-01-01

    In autoimmune diseases of the central nervous system (CNS), innate glial cell responses play a key role in determining the outcome of leukocyte infiltration. Access of leukocytes is controlled via complex interactions with glial components of the blood-brain barrier that include angiotensin II...

  9. Mechanisms of villous atrophy in autoimmune enteropathy and coeliac disease

    Science.gov (United States)

    CICCOCIOPPO, R; D'ALÒ, S; DI SABATINO, A; PARRONI, R; ROSSI, M; DOGLIONI, C; CIFONE, M G; CORAZZA, G R

    2002-01-01

    Since in coeliac disease mucosal flattening has been suggested to result from an increased enterocyte apoptosis triggered by Fas/Fas ligand system and perforin cytolytic granules, we looked for a similar mechanism in autoimmune enteropathy. Moreover, we tried to assess whether enterocyte autoantibodies, which are the hallmark of autoimmune enteropathy, may be involved in triggering enterocyte apoptosis in this condition. Immunohistochemical staining with anti-Fas,-FasL and-perforin MoAb, and TUNEL technique were applied on endoscopic duodenal biopsies of two autoimmune enteropathy patients, two untreated coeliac patients and two biopsied controls. Cytotoxicity assays were carried out by incubating peripheral blood mononuclear cells from a healthy subject (effectors) with enterocytes primed with patient or control sera (targets). In autoimmune enteropathy a large number of enterocytes were apoptotic, as in coeliac disease, whereas neither Fas/Fas ligand or perforin expressions were up-regulated. On the other hand, antibody-dependent cellular cytotoxicity assay revealed the ability of sera from patients with autoimmune enteropathy to mediate enterocyte death through apoptosis. These results point to enterocyte autoantibody-dependent cellular cytotoxicity as the prevalent mechanism of increased enterocyte apoptosis in autoimmune enteropathy but not in coeliac disease. PMID:11982595

  10. VITILIGO AND THE PREVALENCE OF AUTOIMMUNE THYROID DISEASE AND DIABETIS MELLITUS IN VITILIGO

    Directory of Open Access Journals (Sweden)

    Melathil Sadanandan Sadeep

    2017-11-01

    Full Text Available BACKGROUND Vitiligo is an acquired pigmentary disorder characterised by the development of white macules related to the selective loss of melanocytes residing in the interfollicular epidermis and occasionally in the hair follicles as well. Exact aetiology of vitiligo is not known. A convergence theory, which states that stress, infection, mutations, autoimmunity, accumulation of toxic compounds, altered cellular environment and impaired melanocyte migration or proliferation- all can contribute to development of vitiligo. However, most favoured hypothesis is autoimmune because vitiligo is frequently associated with other disorders, which have an autoimmune origin such as Autoimmune Thyroid Disease (AITD and Diabetes Mellitus (DM. Recent studies suggest that vitiligo is not just a cutaneous disorder, but a systemic disorder of the pigmentary system. MATERIALS AND METHODS This is a hospital-based one year cross-sectional study of all vitiligo patients attending the outpatient wing of a tertiary care centre in Kerala. Patients were included after getting the written consent and those patients who had under gone thyroid surgery and on drugs that can interfere with thyroid function were excluded. RESULTS After meeting the criteria, only 122 patients out of 61,750 outpatients (0.19% were included in this study. The youngest participant was 4 years, while the eldest was 69 years old. Most common age group- 10-19 years. 56.6% were females. Duration of disease was less than 2 years in 61.8%. Majority (36.9% patients were students. A personal history of thyroid disease was obtained in 12.29%. 55.7% had positive family history of diseases like diabetes, thyroid disease, vitiligo and rheumatoid arthritis. Among the diseases noted in family members, diabetes was the commonest accounting for 32%. Though vitiligo vulgaris was common, percentage of focal and acrofacial vitiligo was higher than other studies. Vitiligo vulgaris was more commonly seen among females

  11. Neutron activation analysis in the central nervous system tissues of neurological diseases and rats maintained on minerally unbalanced diets

    International Nuclear Information System (INIS)

    Yasui, Masayuki; Ota, Kiichiro; Sasajima, Kazuhisa.

    1995-01-01

    Epidemiological surveys on Guam have suggested that low calcium (Ca), magnesium (Mg) and high Al and Mn in river, soil and drinking water may be implicated in the pathogenesis of PD. Experimentally, low Ca-Mg diets with or without added Al have been found to accelerate Al deposition in the CNS of rats and monkeys. Although excessive deposition of Mn produces neurotoxic action similar to Al in CNS tissues, the mechanism of Mn deposition coupled with Al loading in the presence of low Ca-Mg intake is not yet known. In this animal study, the deposition and metal-metal interaction of both Al and Mn in the CNS, visceral organs and bones of rats fed unbalanced mineral diets were analyzed. Male Wistar rats, weighing 200 g, were maintained for 90 days on the following diets: (A) standard diet, (B) low Ca diet, (C) low Ca-Mg diet, (D) low Ca-Mg diet with high Al. Al and Mn content were determined in the frontal cortex, spinal cord, kidney, muscle, abdominal aorta, femur and lumbar spine using neutron activation analysis (NAA). Intake of low Ca and Mg with added Al in rats led to the high concentrations of Mn and Al in bones and in the frontal cortex. It is likely that unbalanced mineral diets and metal-metal interactions may lead to the unequal distribution of Al and Mn in bones and ultimately in the CNS inducing CNS degeneration. On the other hand, concentrations of copper (Cu), calcium (Ca) and aluminum (Al) for 26 subanatomical regions of the CNS were measured by neutron activation analysis (NAA) in two cases of Wilson's disease, two of portal systemic encephalopathy, six pathologically verified cases of ALS, four of Parkinson's disease and five neurologically normal controls. Also zinc (Zn) and iron (Fe) concentrations were measured by NAA for frontal and occipital lobes of parkinsonism-dementia. (author)

  12. Metabolic disorders of purine metabolism affecting the nervous system.

    Science.gov (United States)

    Jinnah, H A; Sabina, Richard L; Van Den Berghe, Georges

    2013-01-01

    The purines are a group of molecules used by all cells for many vital biochemical processes including energy-requiring enzymatic reactions, cofactor-requiring reactions, synthesis of DNA or RNA, signaling pathways within and between cells, and other processes. Defects in some of the enzymes of purine metabolism are known to be associated with specific clinical disorders, and neurological problems may be a presenting sign or the predominant clinical problem for several of them. This chapter describes three disorders for which the clinical features and metabolic basis are well characterized. Deficiency of adenylosuccinate-lyase (ADSL) causes psychomotor retardation, epilepsy, and autistic features. Lesch-Nyhan disease is caused by deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) and is characterized by hyperuricemia, motor and cognitive disability, and self-injurious behavior. Deficiency of myoadenylate deaminase (mAMPD) is associated with myopathic features. In addition to these disorders, several other disorders are briefly summarized. These include defects of phosphoribosylpyrophosphate synthase, adenosine deaminase (ADA), purine nucleoside phosphorylase (PND), deoxyguanosine kinase (dGK), or IMP dehydrogenase (IMPDH). Each of these disorders provides an unusual window on the unique importance of purine metabolism for function of different parts of the nervous system. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Understanding and controlling the enteric nervous system

    NARCIS (Netherlands)

    Boeckxstaens, G. E.

    2002-01-01

    The enteric nervous system or the `Little Brain' of the gut controls gastrointestinal motility and secretion, and is involved in visceral sensation. In this chapter, new developments in understanding the function of the enteric nervous system are described. In particular, the interaction of this

  14. New insights into immune mechanisms underlying autoimmune diseases of the gastrointestinal tract.

    Science.gov (United States)

    Di Sabatino, Antonio; Lenti, Marco Vincenzo; Giuffrida, Paolo; Vanoli, Alessandro; Corazza, Gino Roberto

    2015-12-01

    Recent progresses in the immune mechanisms implicated in chronic inflammatory disorders have led to a more in-depth knowledge of the pathogenesis of autoimmune diseases of the gastrointestinal tract, including autoimmune atrophic gastritis, celiac disease, autoimmune enteropathy and ulcerative colitis. While the pathogenic role of specific circulating autoantibodies, i.e., respectively anti-parietal cell, anti-tissue transglutaminase, anti-enterocyte and anti-neutrophil cytoplasmic, is still controversial, some common T-cell mediated mechanisms for inflammation - increase in T helper cell type 1/type 17 pro-inflammatory cytokines- or losing self-tolerance-abnormal regulatory T cell function - are recognized as crucial mediators of the tissue damage causing atrophy of the stomach mucosa in autoimmune atrophic gastritis, villous flattening of the small bowel in celiac disease and autoimmune enteropathy, and mucosal ulceration of the colon in ulcerative colitis. This review deals with novel advances in the immunological bases of the aforementioned autoimmune gastrointestinal disorders, and it also highlights immune mechanisms of progression from chronic inflammation to cancer and implications for new therapeutic targets. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Moving towards a molecular taxonomy of autoimmune rheumatic diseases

    NARCIS (Netherlands)

    Barturen, Guillermo; Beretta, Lorenzo; Cervera, Ricard; van Vollenhoven, Ronald; Alarcón-Riquelme, Marta E.

    2018-01-01

    Autoimmune rheumatic diseases pose many problems that have, in general, already been solved in the field of cancer. The heterogeneity of each disease, the clinical similarities and differences between different autoimmune rheumatic diseases and the large number of patients that remain without a

  16. Central nervous system frontiers for the use of erythropoietin

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal

    2003-01-01

    Recombinant human erythropoietin (r-HuEPO; epoetin alfa) is well established as safe and effective for the treatment of anemia. In addition to the erythropoietic effects of endogenous erythropoietin (EPO), recent evidence suggests that it may elicit a neuroprotective effect in the central nervous...... system (CNS). Preclinical studies have demonstrated the presence of EPO receptors in the brain that are up-regulated under hypoxic or ischemic conditions. Intracerebral and systemic administration of epoetin alfa have been demonstrated to elicit marked neuroprotective effects in multiple preclinical...

  17. Cryptic etiopathological conditions of equine nervous system with special emphasis on viral diseases

    Directory of Open Access Journals (Sweden)

    Rakesh Kumar

    2017-12-01

    Full Text Available The importance of horse (Equus caballus to equine practitioners and researchers cannot be ignored. An unevenly distributed population of equids harbors numerous diseases, which can affect horses of any age and breed. Among these, the affections of nervous system are potent reason for death and euthanasia in equids. Many episodes associated with the emergence of equine encephalitic conditions have also pose a threat to human population as well, which signifies their pathogenic zoonotic potential. Intensification of most of the arboviruses is associated with sophisticated interaction between vectors and hosts, which supports their transmission. The alphaviruses, bunyaviruses, and flaviviruses are the major implicated groups of viruses involved with equines/humans epizootic/epidemic. In recent years, many outbreaks of deadly zoonotic diseases such as Nipah virus, Hendra virus, and Japanese encephalitis in many parts of the globe addresses their alarming significance. The equine encephalitic viruses differ in their global distribution, transmission and main vector species involved, as discussed in this article. The current review summarizes the status, pathogenesis, pathology, and impact of equine neuro-invasive conditions of viral origin. A greater understanding of these aspects might be able to provide development of advances in neuro-protective strategies in equine population.

  18. Cystic Fibrosis and the Nervous System.

    Science.gov (United States)

    Reznikov, Leah R

    2017-05-01

    Cystic fibrosis (CF) is a life-shortening autosomal recessive disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is an anion channel that conducts bicarbonate and chloride across cell membranes. Although defective anion transport across epithelial cells is accepted as the basic defect in CF, many of the features observed in people with CF and organs affected by CF are modulated by the nervous system. This is of interest because CFTR expression has been reported in both the peripheral and central nervous systems, and it is well known that the transport of anions, such as chloride, greatly modulates neuronal excitability. Thus it is predicted that in CF, lack of CFTR in the nervous system affects neuronal function. Consistent with this prediction, several nervous system abnormalities and nervous system disorders have been described in people with CF and in animal models of CF. The goal of this special feature article is to highlight the expression and function of CFTR in the nervous system. Special emphasis is placed on nervous system abnormalities described in people with CF and in animal models of CF. Finally, features of CF that may be modulated by or attributed to faulty nervous system function are discussed. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  19. Prevalence of Celiac Disease in Children with Autoimmune Hepatitis and vice versa

    OpenAIRE

    Najafi, Mehri; Sadjadei, Nooshin; Eftekhari, Kambiz; Khodadad, Ahmad; Motamed, Farzaneh; Fallahi, Gholam-Hossain; Farahmand, Fatemeh

    2014-01-01

    Objective: Celiac disease is an autoimmune disorder in which the risk of autoimmune liver disease is high. Autoimmune hepatitis is a chronic and progressive entity and the risk of its being associated with other autoimmune disorders such as celiac disease is high also. The aim of this study was to determine the prevalence of celiac disease in patients with autoimmune hepatitis and vice versa. Methods: In a cross-sectional study children with autoimmune hepatitis underwent serological screenin...

  20. Microbiota-gut-brain axis and the central nervous system.

    Science.gov (United States)

    Zhu, Xiqun; Han, Yong; Du, Jing; Liu, Renzhong; Jin, Ketao; Yi, Wei

    2017-08-08

    The gut and brain form the gut-brain axis through bidirectional nervous, endocrine, and immune communications. Changes in one of the organs will affect the other organs. Disorders in the composition and quantity of gut microorganisms can affect both the enteric nervous system and the central nervous system (CNS), thereby indicating the existence of a microbiota-gut-brain axis. Due to the intricate interactions between the gut and the brain, gut symbiotic microorganisms are closely associated with various CNS diseases, such as Parkinson's disease, Alzheimer's disease, schizophrenia, and multiple sclerosis. In this paper, we will review the latest advances of studies on the correlation between gut microorganisms and CNS functions & diseases.

  1. Arteriovenous Malformations and Other Vascular Lesions of the Central Nervous System

    Science.gov (United States)

    ... Arteriovenous Malformations and Other Vascular Lesions of the Central Nervous System Fact Sheet What are arteriovenous malformations? What are ... What other types of vascular lesions affect the central nervous system? Besides AVMs, three other main types of vascular ...

  2. Clinical and electrodiagnostic findings in a cohort of 61 dogs with peripheral nervous system diseases - a retrospective study

    Directory of Open Access Journals (Sweden)

    EG Giza, JE Nicpon and MA Wrzosek

    2014-04-01

    Full Text Available The electrodiagnostic examination provides the basis for a diagnostic workup in diseases involving nerve roots, peripheral nerves, neuromuscular junctions and muscles in humans and animals. It is a functional test that enables identification, localization and characterization of the disease within the peripheral nervous system. The study was carried out retrospectively on a group of 61 dogs of different breeds referred for an electrodiagnostic examination because of local or generalized peripheral nervous system impairment. The electrodiagnostic examination consisted of electromyography, electroneurography, F-wave and repetitive nerve stimulation testing. The results of electrodiagnostic studies and their impact on the diagnosis of neuromuscular diseases of different etiology is presented in the study. The lesion was localized to peripheral nerves in 38%, nerve roots in 34%, skeletal muscles in 18% and the neuromuscular junction in 10% of cases. Electrodiagnostics enabled an objective assessment of the extent, distribution and nature of the disease in the study group. However, only when it is used in conjunction with a complete physical and neurological examination and appropriate laboratory or imaging studies, it may be helpful in determining the etiological diagnosis in patients with peripheral nervous system disease.

  3. [Treatment with immunosuppressive and biologic drugs of pregnant women with systemic rheumatic or autoimmune disease].

    Science.gov (United States)

    Alijotas-Reig, Jaume; Esteve-Valverde, Enrique; Ferrer-Oliveras, Raquel

    2016-10-21

    Rheumatic and systemic autoimmune diseases occur in women and, to a lesser degree, men of reproductive age. These disorders have to be clinically nonactive before conception, which is usually only possible after anti-inflammatory and immunosuppressive treatment. We must be alert since 50% of pregnancies are unplanned. Physicians should know the embryo-foetal toxicity of these drugs during pregnancy and lactation. This January 2016-updated review allows us to conclude that the majority of immunosuppressives available -anti-TNF inhibitors included- can be used before and during pregnancy, with the exception of cyclophosphamide, methotrexate, mycophenolate and leflunomide. Lactation is permitted with all drugs except methotrexate, leflunomide, mycophenolate and cyclophosphamide. Although data on abatacept, belimumab, rituximab, tocilizumab and anakinra are scant, preliminary reports agree on their safety during pregnancy and, probably, lactation. Cyclophosphamide and sulfasalazine apart, no negative effects on sperm quality, or embryo-foetal anomalies in men treated with immunosuppressives have been described. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  4. Applications of Nanotechnology to the Central Nervous System

    Science.gov (United States)

    Blumling, James P., II

    Nanotechnology and nanomaterials, in general, have become prominent areas of academic research. The ability to engineer at the nano scale is critical to the advancement of the physical and medical sciences. In the realm of physical sciences, the applications are clear: smaller circuitry, more powerful computers, higher resolution intruments. However, the potential impact in the fields of biology and medicine are perhaps even grander. The implementation of novel nanodevices is of paramount importance to the advancement of drug delivery, molecular detection, and cellular manipulation. The work presented in this thesis focuses on the development of nanotechnology for applications in neuroscience. The nervous system provides unique challenges and opportunities for nanoscale research. This thesis discusses some background in nanotechnological applications to the central nervous system and details: (1) The development of a novel calcium nanosenser for use in neurons and astrocytes. We implemented the calcium responsive component of Dr. Roger Tsien's Cameleon sensor, a calmodulin-M13 fusion, in the first quantum dot-based calcium sensor. (2) The exploration of cell-penetrating peptides as a delivery mechanism for nanoparticles to cells of the nervous system. We investigated the application of polyarginine sequences to rat primary cortical astrocytes in order to assess their efficacy in a terminally differentiated neural cell line. (3) The development of a cheap, biocompatible alternative to quantum dots for nanosensor and imaging applications. We utilized a positively charged co-matrix to promote the encapsulation of free sulforhodamine B in silica nanoparticles, a departure from conventional reactive dye coupling to silica matrices. While other methods have been invoked to trap dye not directly coupled to silica, they rely on positively charged dyes that typically have a low quantum yield and are not extensively tested biologically, or they implement reactive dyes bound

  5. INSULIN AND INSULIN RESISTANCE: NEW MOLECULE MARKERS AND TARGET MOLECULE FOR THE DIAGNOSIS AND THERAPY OF DISEASES OF THE CENTRAL NERVOUS SYSTEM

    Directory of Open Access Journals (Sweden)

    A. B. Salmina

    2013-01-01

    Full Text Available The review summarizes current data on the role of insulin in the regulation of t glucose metabolism in the central nervous system at physiologic and pathologic conditions. For many years, the brain has been considered as an insulin-independent organ which utilizes glucose without insulin activity. However, it is become clear now that insulin not only regulates glucose transport and metabolism, but also has modulatory efftects in impact on excitability, proliferation and differentiation of brain progenitor cells, synaptic plasticity and memory formation, secretion of neurotransmitters, apoptosis. We have critically reviewed literature information and our own data on the role of insulin and insulin resistance in neuron-glia metabolic coupling, regulation of NAD+ metabolism and action of NAdependent enzymes, neurogenesis, brain development in (pathophysiological conditions. The paper clarifies interrelations between alterations in glucose homeostasis, development of insulin resistance and development of neurodegeneration (Alzheimer's disease and Parkinson's disease, autism, stroke, and depression. We discuss the application of novel molecular markers of insulin resistance (adipokines, α-hydroxybutyrate, BDNF, insulin-regulated aminopeptidase, provasopressin and molecular targets for diagnostics and treatment of brain disorders associated with insulin resistance.

  6. Tendencies the treatment of the central nervous system (CNS) tumors

    International Nuclear Information System (INIS)

    Alert Silva, Jose; Jimenez Medina, Jose

    2004-01-01

    It is known that the treatment of the central nervous system (CNS) tumors is based on the use of surgery and radiotherapy (RT) and that chemotherapy (QMT) is used even more, as well as the other drugs. A bibliographic review was made to update the knowledge on the current trends and perspectives of RT applied to CNS tumors. The following were found among them: a) combinations of RT and CMT; b) radiosensitizers incorporated to the radiant treatment; c) angiogenesis inhibitors associated with RT; d) the scale-up or increase of the RT doses thanks to the development of new technologies, such as 3 D conformal radiotherapy, intensity- modulated radiotherapy, surgery and others. Another field of research is that of the changes in the rhythm or fractioning of the RT: hyperfractionated, accelerated, combinations of both, etc., which will allow mainly to increase the dosage scale-up

  7. The clinical value of detection of serum TGAb and TPOAb level in autoimmune thyroid diseases

    International Nuclear Information System (INIS)

    Min Xiaoxia; Huang Xingming

    2008-01-01

    To study the clinical value of serum TGAb and TPOAb levels in the diagnosis of patients with autoimmune thyroid diseases (AITD), the serum levels of TGAb and TPOAb in 175 patients with AITD and 64 non-AITD patients and 57 health controls were measured by RIA. The results showed that the serum levels of TGAb and TPOAb in AITD patients with GD and HT were significantly higher than that of control group (P 0.05). The detection of serum TGAb and TPOAb levels may have clinical value in the diagnosis, treatment and prognosis of autoimmune thyroid diseases. (authors)

  8. Autoimmune Subepidermal Bullous Diseases of the Skin and Mucosae: Clinical Features, Diagnosis, and Management.

    Science.gov (United States)

    Amber, Kyle T; Murrell, Dedee F; Schmidt, Enno; Joly, Pascal; Borradori, Luca

    2018-02-01

    Autoimmune subepidermal blistering diseases of the skin and mucosae constitute a large group of sometimes devastating diseases, encompassing bullous pemphigoid, gestational pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita, and anti-p200 pemphigoid. Their clinical presentation is polymorphic. These autoimmune blistering diseases are associated with autoantibodies that target distinct components of the basement membrane zone of stratified epithelia. These autoantigens represent structural proteins important for maintenance of dermo-epidermal integrity. Bullous pemphigoid (BP) is the most common subepidermal autoimmune blistering disease of the skin and mucosae. Although the disease typically presents with a generalized blistering eruption associated with itch, atypical variants with either localized bullous lesions or "non-bullous" presentations are observed in approximately 20% of patients. A peculiar form of BP typically associated with pregnancy is pemphigoid gestationis. In anti-p200 pemphigoid, patients present with tense blisters on erythematosus or normal skin resembling BP, with a predilection for acral surfaces. These patients have antibodies targeting the 200-kDa basement membrane protein. Epidermolysis bullosa is a rare autoimmune blistering disease associated with autoantibodies against type VII collagen that can have several phenotypes including a classical form mimicking dystrophic epidermolysis bullosa, an inflammatory presentation mimicking BP, or mucous membrane pemphigoid-like lesions. Mucous membrane pemphigoid (MMP) is the term agreed upon by international consensus for an autoimmune blistering disorder, which affects one or more mucous membrane and may involve the skin. The condition involves a number of different autoantigens in the basement membrane zone. It may result in severe complications from scarring, such as blindness and strictures. Diagnosis of these diseases relies on direct immunofluorescence microscopy studies

  9. Some Central Nervous System Effects of the aqueous Extract of the ...

    African Journals Online (AJOL)

    The leaves of Phyllanthus amarus is used in Southern Nigeria to treat variety of diseases including epilepsy. The aqueous extract of the leaves of Phyllanthus amarus was investigated for some central nervous system effects. Two animals models (maximal electroshock and pentylenetetrazol-induced convulsion), were used ...

  10. Inhibition of Myeloperoxidase at the Peak of Experimental Autoimmune Encephalomyelitis Restores Blood-Brain-Barrier Integrity and Ameliorates Disease Severity.

    Science.gov (United States)

    Zhang, Hao; Ray, Avijit; Miller, Nichole M; Hartwig, Danielle; Pritchard, Kirkwood A; Dittel, Bonnie N

    2015-11-12

    Oxidative stress is thought to contribute to disease pathogenesis in the central nervous system (CNS) disease multiple sclerosis (MS). Myeloperoxidase (MPO), a potent peroxidase that generates toxic radicals and oxidants, is increased in the CNS during MS. However, the exact mechanism whereby MPO drives MS pathology is not known. We addressed this question by inhibiting MPO in mice with experimental autoimmune encephalomyelitis (EAE) using our non-toxic MPO inhibitor KYC. We found that therapeutic administration of KYC for five days starting at the peak of disease significantly attenuated EAE disease severity, reduced myeloid cell numbers and permeability of the blood-brain-barrier (BBB). These data indicate that inhibition of MPO by KYC restores BBB integrity thereby limiting migration of myeloid cells into the CNS that drive EAE pathogenesis. In addition, these observations indicate that KYC may be an effective therapeutic agent for the treatment of MS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. Bone involvement in clusters of autoimmune diseases: just a complication?

    Science.gov (United States)

    Lombardi, Francesca; Franzese, Adriana; Iafusco, Dario; del Puente, Antonio; Esposito, Antonella; Prisco, Francesco; Troncone, Riccardo; Valerio, Giuliana

    2010-02-01

    Bone loss, described in individual groups of patients with Type 1 diabetes (T1D), autoimmune thyroid disease (ATD) or celiac disease (CD) is usually viewed as a complication of these diseases. There is increasing evidence that alterations in the immune system may directly affect bone mass. Clustering of autoimmune diseases in the same individual might predispose to higher risk of osteopenia due to imbalance in immune regulation. The aim of this study was to evaluate bone involvement in clusters of the most common autoimmune diseases (T1D, ATD and CD) in children. The study was performed at a tertiary care center for the care of pediatric diabetes. One-hundred-two patients with T1D alone or associated with ATD and/or CD were studied; 13 patients had cluster of three autoimmune diseases. Amplitude-dependent speed of sound (AD-SoS) was measured by phalangeal quantitative ultrasound and expressed as standard deviation score (SDS). AD-SoS SDS diseases. Poor compliance to gluten-free diet increased osteopenia to 18.8% in patients with T1D and CD and 80% in patients with three autoimmune disorders. No difference among groups was found with regard to gluco-metabolic control, calcium metabolism, thyroid function. In conclusion bone impairment in multiple autoimmune diseases might be considered not only a complication due to endocrine or nutritional mechanisms, but also a consequence of an immunoregulatory imbalance. Alterations of homeostatic mechanisms might explain an imbalance of osteoclast activity leading to osteopenia. (c) 2009 Elsevier Inc. All rights reserved.

  12. Role of the Enteric Nervous System in the Fluid and Electrolyte Secretion of Rotavirus Diarrhea

    Science.gov (United States)

    Lundgren, Ove; Peregrin, Attila Timar; Persson, Kjell; Kordasti, Shirin; Uhnoo, Ingrid; Svensson, Lennart

    2000-01-01

    The mechanism underlying the intestinal fluid loss in rotavirus diarrhea, which often afflicts children in developing countries, is not known. One hypothesis is that the rotavirus evokes intestinal fluid and electrolyte secretion by activation of the nervous system in the intestinal wall, the enteric nervous system (ENS). Four different drugs that inhibit ENS functions were used to obtain experimental evidence for this hypothesis in mice in vitro and in vivo. The involvement of the ENS in rotavirus diarrhea indicates potential sites of action for drugs in the treatment of the disease.

  13. Developmental markers of ganglion cells in the enteric nervous system and their application for evaluation of Hirschsprung disease.

    Science.gov (United States)

    Kawai, Hitomi; Satomi, Kaishi; Morishita, Yukio; Murata, Yoshihiko; Sugano, Masato; Nakano, Noriyuki; Noguchi, Masayuki

    2014-09-01

    Hirschsprung disease (HSCR) is a congenital disease resulting from failure of neural crest-derived ganglion cells to colonize the colon. Conventional diagnostic methods are insufficient for evaluating the 'functional' prognosis of HSCR. In order to elucidate the maturation of ganglion cells, 17 immunohistochemical markers were examined. We examined the digestive tracts of 2 human early delivery patients, 2 miniature swine fetuses, 4 little infants, 3 infants, 3 children, 6 adults, and 3 aged individuals. With increasing age, the labeling index (LI) for both calretinin and tyrosine hydroxylase (TH) increased, whereas that for SOX10 decreased. We then examined the 'transitional zone' of HSCR in 21 affected patients and 18 controls for these three markers. The LI of calretinin and TH were significantly lower than in the controls (median: 3.7 in HSCR and 8.2 in controls, P ganglion cells are present in the transitional zone of HSCR, and that HSCR may have two different pathophysiological processes. © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

  14. Clinical Review 160: Postpartum autoimmune thyroid disease: the potential role of fetal microchimerism.

    Science.gov (United States)

    Ando, Takao; Davies, Terry F

    2003-07-01

    Fetal microchimerism is defined as the presence of fetal cells in maternal tissues established during pregnancy. Immune suppression of maternal immunity during pregnancy by the placenta may play an important role in allowing the establishment of such fetal microchimerism. However, peripheral blood fetal microchimerism that persists in the postpartum period is considered a natural event and implies the induction of tolerance during pregnancy. Identification of fetal cells that persist preferentially in maternal tissues subject to autoimmunity, such as skin and thyroid, has also suggested the possible immune modulation of the autoimmune response at the target tissue by fetal cells. Accumulating evidence suggests that fetal immune cells may be reactive to maternal antigens and, therefore, have the capacity to trigger graft vs. host reactions. This would provide a mechanism for the initiation and/or exacerbation of autoimmune disease. The course and severity of autoimmune thyroid disease have long been known to be profoundly influenced by pregnancy, with disease suppression prepartum and exacerbation postpartum. However, the precise mechanisms involved have not been fully understood. Here we have reviewed recent information on the possible role of fetal microchimerism in autoimmune thyroid disease, focusing on the immunological consequences of intrathyroidal fetal cells and their contribution to postpartum exacerbations.

  15. Extending the enteric nervous system.

    Science.gov (United States)

    Sbarbati, Andrea; Osculati, Francesco

    2007-08-01

    The work reviews the evidence suggesting that lingual components of the autonomic system may be considered the most rostral portion of the enteric nervous system (ENS) defining the concept of lingual ENS (LENS). The LENS is not dissimilar from the more distally located portions of the ENS, however, it is characterized by a massive sensory input generated by collaterals of gustatory and trigeminal fibers. The different neuronal subpopulations that compose the LENS operate reflexes involved in regulation of secretion and vasomotility. Systemic reflexes on the digestive and respiratory apparatus are operated by means of neural connections through the pharynx or larynx. The LENS can modulate the activity of distally located organs by means of the annexed glands.The LENS seems therefore to be a "chemical eye" located at the beginning of the digestive apparatus which analyses the foods before their ingestion and diffuses this information distally. The definition of the LENS supports the concept of an elevated degree of autonomy in the ENS and puts in a new light the role of the gustatory system in modulation of the digestive functions. For its characteristics, the LENS appears to be an ideal model to study the elementary connectivity of the ENS.

  16. Blocking neurogenic inflammation for the treatment of acute disorders of the central nervous system.

    Science.gov (United States)

    Lewis, Kate Marie; Turner, Renée Jade; Vink, Robert

    2013-01-01

    Classical inflammation is a well-characterized secondary response to many acute disorders of the central nervous system. However, in recent years, the role of neurogenic inflammation in the pathogenesis of neurological diseases has gained increasing attention, with a particular focus on its effects on modulation of the blood-brain barrier BBB. The neuropeptide substance P has been shown to increase blood-brain barrier permeability following acute injury to the brain and is associated with marked cerebral edema. Its release has also been shown to modulate classical inflammation. Accordingly, blocking substance P NK1 receptors may provide a novel alternative treatment to ameliorate the deleterious effects of neurogenic inflammation in the central nervous system. The purpose of this paper is to provide an overview of the role of substance P and neurogenic inflammation in acute injury to the central nervous system following traumatic brain injury, spinal cord injury, stroke, and meningitis.

  17. Blocking Neurogenic Inflammation for the Treatment of Acute Disorders of the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Kate Marie Lewis

    2013-01-01

    Full Text Available Classical inflammation is a well-characterized secondary response to many acute disorders of the central nervous system. However, in recent years, the role of neurogenic inflammation in the pathogenesis of neurological diseases has gained increasing attention, with a particular focus on its effects on modulation of the blood-brain barrier BBB. The neuropeptide substance P has been shown to increase blood-brain barrier permeability following acute injury to the brain and is associated with marked cerebral edema. Its release has also been shown to modulate classical inflammation. Accordingly, blocking substance P NK1 receptors may provide a novel alternative treatment to ameliorate the deleterious effects of neurogenic inflammation in the central nervous system. The purpose of this paper is to provide an overview of the role of substance P and neurogenic inflammation in acute injury to the central nervous system following traumatic brain injury, spinal cord injury, stroke, and meningitis.

  18. Interaction between Tat and Drugs of Abuse during HIV-1 Infection and Central Nervous System Disease.

    Science.gov (United States)

    Maubert, Monique E; Pirrone, Vanessa; Rivera, Nina T; Wigdahl, Brian; Nonnemacher, Michael R

    2015-01-01

    In many individuals, drug abuse is intimately linked with HIV-1 infection. In addition to being associated with one-third of all HIV-1 infections in the United States, drug abuse also plays a role in disease progression and severity in HIV-1-infected patients, including adverse effects on the central nervous system (CNS). Specific systems within the brain are known to be damaged in HIV-1-infected individuals and this damage is similar to that observed in drug abuse. Even in the era of anti-retroviral therapy (ART), CNS pathogenesis occurs with HIV-1 infection, with a broad range of cognitive impairment observed, collectively referred to as HIV-1-associated neurocognitive disorders (HAND). A number of HIV-1 proteins (Tat, gp120, Nef, Vpr) have been implicated in the etiology of pathogenesis and disease as a result of the biologic activity of the extracellular form of each of the proteins in a number of tissues, including the CNS, even in ART-suppressed patients. In this review, we have made Tat the center of attention for a number of reasons. First, it has been shown to be synthesized and secreted by HIV-1-infected cells in the CNS, despite the most effective suppression therapies available to date. Second, Tat has been shown to alter the functions of several host factors, disrupting the molecular and biochemical balance of numerous pathways contributing to cellular toxicity, dysfunction, and death. In addition, the advantages and disadvantages of ART suppression with regard to controlling the genesis and progression of neurocognitive impairment are currently under debate in the field and are yet to be fully determined. In this review, we discuss the individual and concerted contributions of HIV-1 Tat, drug abuse, and ART with respect to damage in the CNS, and how these factors contribute to the development of HAND in HIV-1-infected patients.

  19. Epigenetics as biomarkers in autoimmune diseases.

    Science.gov (United States)

    Wu, Haijing; Liao, Jieyue; Li, Qianwen; Yang, Ming; Zhao, Ming; Lu, Qianjin

    2018-03-21

    Autoimmune diseases are immune system disorders in which immune cells cannot distinguish self-antigens from foreign ones. The current criteria for autoimmune disease diagnosis are based on clinical manifestations and laboratory tests. However, none of these markers shows both high sensitivity and specificity. In addition, some autoimmune diseases, for example, systemic lupus erythematosus (SLE), are highly heterogeneous and often exhibit various manifestations. On the other hand, certain autoimmune diseases, such as Sjogren's syndrome versus SLE, share similar symptoms and autoantibodies, which also causes difficulties in diagnosis. Therefore, biomarkers that have both high sensitivity and high specificity for diagnosis, reflect disease activity and predict drug response are necessary. An increasing number of publications have proposed the abnormal epigenetic modifications as biomarkers of autoimmune diseases. Therefore, this review will comprehensively summarize the epigenetic progress in the pathogenesis of autoimmune disorders and unearth potential biomarkers that might be appropriate for disease diagnosis and prediction. Copyright © 2018. Published by Elsevier Inc.

  20. Possible pathogenic nature of the recently discovered TT virus: does it play a role in autoimmune rheumatic diseases?

    Science.gov (United States)

    Gergely, Peter; Perl, Andras; Poór, Gyula

    2006-11-01

    Pathogenesis of viral origin has long been suggested in autoimmune rheumatic diseases. Beside the well-defined virus induced transient or chronic rheumatic diseases often resembling systemic autoimmune disorders such as rheumatoid arthritis, viruses can contribute to disease pathogenesis by several different pathomechanisms. TT virus is a recently discovered virus of extremely high genetic diversity which commonly infects humans. Despite accumulated evidence on the biological characteristics of TTV, its pathogenicity is still in question; many consider TTV as a harmless endosymbiont. The recent paper overviews the biology of TT virus and investigates the hypothesis that TTV might have a causative role in human diseases with special attention to the possibility that TTV might trigger autoimmunity in rheumatic disorders.

  1. Neural stem cells and neuro/gliogenesis in the central nervous system: understanding the structural and functional plasticity of the developing, mature, and diseased brain.

    Science.gov (United States)

    Yamaguchi, Masahiro; Seki, Tatsunori; Imayoshi, Itaru; Tamamaki, Nobuaki; Hayashi, Yoshitaka; Tatebayashi, Yoshitaka; Hitoshi, Seiji

    2016-05-01

    Neurons and glia in the central nervous system (CNS) originate from neural stem cells (NSCs). Knowledge of the mechanisms of neuro/gliogenesis from NSCs is fundamental to our understanding of how complex brain architecture and function develop. NSCs are present not only in the developing brain but also in the mature brain in adults. Adult neurogenesis likely provides remarkable plasticity to the mature brain. In addition, recent progress in basic research in mental disorders suggests an etiological link with impaired neuro/gliogenesis in particular brain regions. Here, we review the recent progress and discuss future directions in stem cell and neuro/gliogenesis biology by introducing several topics presented at a joint meeting of the Japanese Association of Anatomists and the Physiological Society of Japan in 2015. Collectively, these topics indicated that neuro/gliogenesis from NSCs is a common event occurring in many brain regions at various ages in animals. Given that significant structural and functional changes in cells and neural networks are accompanied by neuro/gliogenesis from NSCs and the integration of newly generated cells into the network, stem cell and neuro/gliogenesis biology provides a good platform from which to develop an integrated understanding of the structural and functional plasticity that underlies the development of the CNS, its remodeling in adulthood, and the recovery from diseases that affect it.

  2. High prevalence of autoimmune disease in the rare inflammatory bone disorder sternocostoclavicular hyperostosis: survey of a Dutch cohort.

    Science.gov (United States)

    Valkema, Pieter A; Luymes, Clare H; Witteveen, Janneke E; le Cessie, Saskia; Appelman-Dijkstra, Natasha M; Hogendoorn, Pancras C W; Hamdy, Neveen A T

    2017-01-25

    Sternocostoclavicular hyperostosis (SCCH; ORPHA178311) is a rare inflammatory disorder of the axial skeleton, the precise pathophysiology of which remains to be established. We addressed the potential association of SCCH with autoimmune processes by evaluating the lifetime prevalence of autoimmune disease in 70 patients with adult-onset SCCH and 518 SCCH-unaffected first-degree relatives (parents, siblings and children). Danish hospital registry data for autoimmune diseases were used as reference data. The mean age of interviewed patients was 56.3 years (range 26-80 years) and 86% were female. Interviewed patients belonged to 63 families, with four families having clusters of 2-3 patients. A diagnosis of at least one autoimmune disease was reported in 20 SCCH patients (29%) and in 47 relatives (9.1%), compared to an estimated 3.9% prevalence of autoimmune disease in the Danish reference population. A diversity of autoimmune diseases was reported in SCCH patients and relatives, most frequently psoriasis vulgaris (14%). Palmoplantar pustulosis was reported by 28 patients (40%). In SCCH patients, inclusion of palmoplantar pustulosis as putative autoimmune disease increased the overall prevalence to 54%. The high prevalence of autoimmune disease in patients with sternocostoclavicular hyperostosis and their first-degree relatives suggests that autoimmunity may play a role in the still elusive pathophysiology of the intriguing osteogenic response to inflammation observed in this rare bone disorder.

  3. An overview of travel-associated central nervous system infectious diseases: risk assessment, general considerations and future directions

    Directory of Open Access Journals (Sweden)

    Morteza Izadi

    2014-08-01

    Full Text Available Nervous system infections are among the most important diseases in travellers. Healthy travellers might be exposed to infectious agents of central nervous system, which may require in-patient care. Progressive course is not uncommon in this family of disorders and requires swift diagnosis. An overview of the available evidence in the field is, therefore, urgent to pave the way to increase the awareness of travel-medicine practitioners and highlights dark areas for future research. In November 2013, data were collected from PubMed, Scopus, and Web of Knowledge (1980 to 2013 including books, reviews, and peer-reviewed literature. Works pertained to pre-travel care, interventions, vaccinations related neurological infections were retrieved. Here we provide information on pre-travel care, vaccination, chronic nervous system disorders, and post-travel complications. Recommendations with regard to knowledge gaps, and state-of-the-art research are made. Given an increasing number of international travellers, novel dynamic ways are available for physicians to monitor spread of central nervous system infections. Newer research has made great progresses in developing newer medications, detecting the spread of infections and the public awareness. Despite an ongoing scientific discussion in the field of travel medicine, further research is required for vaccine development, state-of-the-art laboratory tests, and genetic engineering of vectors.

  4. Involvement of the central nervous system in myotonic dystrophy

    International Nuclear Information System (INIS)

    Fukui, Ritsuko; Tobimatsu, Shozo; Kuroiwa, Yoshigoro; Iwashita, Hiroshi; Kato, Motohiro.

    1985-01-01

    In order to evaluate the central nervous system involvement in myotonic dystrophy, intelligence quotient (IQ), brain CT scan, EEG and pattern-reversal visual evoked potential (VEP) were analyzed in 10 patients with myotonic dystrophy. Impaired intelligence was observed in 9 out of 10 patients, abnormal brain CT in 7, and EEG abnormality in 7. The brain CT showed a diffuse cortical atrophy, a dilatation of the ventricles, and a periventricular lucency, mainly around the anterior horn of the lateral ventricle. The EEG findings showed a tendency toward generalized slowing of the background activity. These abnormal findings were well related to the clinical severity of MD, indicating that there is a diffuse cerebral involvement in the majority of the MD patients. VEP showed a prolonged P100 latency in 5 out of 10 patints, or 7 out of 19 eyes examined. These prolonged latency of the P100 component was considered to be due to dysfunctions of the visual pathway in the cerebral hemisphere, rather than due to cataracts and retinal dysfunctions because it was observed only in moderate and severe cases. These severe and moderate cases showed abnormalities in all four examinations. It was concluded that combination of different parameters might be useful to evaluate the central nervous system involvement in patients with MD. (author)

  5. Doenças do sistema nervoso de bovinos no semiárido nordestino Diseases of the nervous system of cattle in the semiarid of Northeastern Brazil

    Directory of Open Access Journals (Sweden)

    Glauco J.N. Galiza

    2010-03-01

    Full Text Available Para determinar as doenças que ocorrem no sistema nervoso de bovinos no semiárido nordestino, foi realizado um estudo retrospectivo em 411 necropsias de bovinos realizadas no Hospital Veterinário da Universidade Federal de Campina Grande, Patos, Paraíba, entre janeiro de 2000 a dezembro de 2008. Dos 411 casos analisados 139 (33,81% apresentaram alterações clínicas do sistema nervoso e as fichas foram revisadas para determinar os principais achados referentes à epidemiologia, aos sinais clínicos e às alterações macroscópicas e microscópicas. Em 28 (20,14% casos o diagnóstico foi inconclusivo. As principais enfermidades foram raiva (48,7% dos casos com sinais nervosos, abscessos cerebrais (7,2% incluindo três casos de abscesso da pituitária, febre catarral maligna (6,3%, botulismo (6,3%, alterações congênitas (4,5%, traumatismo (4,5%, tuberculose (2,7%, tétano (2,7%, infecção por herpesvírus bovino-5 (2,7%, encefalomielite não supurativa (2,7%, intoxicação por Prosopis juliflora (2,7%, status spongiosus congênito de causa desconhecida (1,8% e polioencefalomalacia (1,8%. Outras doenças diagnosticadas numa única oportunidade (0,9% foram criptococose, listeriose, encefalite tromboembólica, linfossarcoma, tripanossomíase e babesiose por Babesia bovis.Diseases of the nervous system of cattle in the semiarid region of northeastern Brazil were evaluated by a retrospective study of 411 cattle necropsies performed in the Veterinary Hospital of the Federal University of Campina Grande, Patos, Paraíba, from January 2000 to December 2008. Of the 411 cases analyzed, 139 (33.81% were from cattle that presented nervous signs and the records were reviewed to determine the epidemiological, clinical, and macroscopic and histologic main features. Diagnosis was inconclusive in 28 cases (20.14%. In cases with diagnosis the main diseases were rabies (48.7% of the cases with nervous signs, brain abscesses (7.2% including three cases of

  6. Iron Oxide Magnetic Nanoparticles Highlight Early Involvement of the Choroid Plexus in Central Nervous System Inflammation

    Directory of Open Access Journals (Sweden)

    Jason M. Millward

    2013-03-01

    Full Text Available Neuroinflammation during multiple sclerosis involves immune cell infiltration and disruption of the BBB (blood–brain barrier. Both processes can be visualized by MRI (magnetic resonance imaging, in multiple sclerosis patients and in the animal model EAE (experimental autoimmune encephalomyelitis. We previously showed that VSOPs (very small superparamagnetic iron oxide particles reveal CNS (central nervous system lesions in EAE which are not detectable by conventional contrast agents in MRI. We hypothesized that VSOP may help detect early, subtle inflammatory events that would otherwise remain imperceptible. To investigate the capacity of VSOP to reveal early events in CNS inflammation, we induced EAE in SJL mice using encephalitogenic T-cells, and administered VSOP prior to onset of clinical symptoms. In parallel, we administered VSOP to mice at peak disease, and to unmanipulated controls. We examined the distribution of VSOP in the CNS by MRI and histology. Prior to disease onset, in asymptomatic mice, VSOP accumulated in the choroid plexus and in spinal cord meninges in the absence of overt inflammation. However, VSOP was undetectable in the CNS of non-immunized control mice. At peak disease, VSOP was broadly distributed; we observed particles in perivascular inflammatory lesions with apparently preserved glia limitans. Moreover, at peak disease, VSOP was prominent in the choroid plexus and was seen in elongated endothelial structures, co-localized with phagocytes, and diffusely disseminated in the parenchyma, suggesting multiple entry mechanisms of VSOP into the CNS. Thus, using VSOP we were able to discriminate between inflammatory events occurring in established EAE and, importantly, we identified CNS alterations that appear to precede immune cell infiltration and clinical onset.

  7. [Immunomodulatory properties of stem mesenchymal cells in autoimmune diseases].

    Science.gov (United States)

    Sánchez-Berná, Isabel; Santiago-Díaz, Carlos; Jiménez-Alonso, Juan

    2015-01-20

    Autoimmune diseases are a cluster of disorders characterized by a failure of the immune tolerance and a hyperactivation of the immune system that leads to a chronic inflammation state and the damage of several organs. The medications currently used to treat these diseases usually consist of immunosuppressive drugs that have significant systemic toxic effects and are associated with an increased risk of opportunistic infections. Recently, several studies have demonstrated that mesenchymal stem cells have immunomodulatory properties, a feature that make them candidates to be used in the treatment of autoimmune diseases. In the present study, we reviewed the role of this therapy in the treatment of systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, Crohn's disease and multiple sclerosis, as well as the potential risks associated with its use. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  8. Phosphoprotein phosphatase in the central nervous system of Manduca sexta.

    Science.gov (United States)

    Albin, E E; Newburgh, R W

    1975-02-19

    The existence and some enzymological properties of phosphoprotein phosphatase (EC 3.1.3.16) have been established in the larval central nervous system of the tobacco hornworm, Manduca sexta (Lepidoptera: Sphingidae). A simple, sensitive and reproducible assay employing 32-P-labeled protamine as a phosphoprotein substrate was employed to measure phosphatase activity in both soluble and particulate fractions of the insect nerve cord. The specific activity of soluble phosphatase in the Manduca sexta central nervous system is of the same order of magnitude as that in mammalian brain. Nerve cord phosphoprotamine phosphatase activity may be stimulated by a variety of monovalent salts, the optimal concentration of NaCl or KCl being 0.2 molar. Activity does not appear to be dependent on bivalent metals and is stimulated by EDTA. A reduced sulfhydryl group is obligatory for maximum activity. Phosphatase could be greatly inhibited by sodium fluoride, ATP and GTP. Cyclic AMP and cyclic GMP are without effect on enzyme activity. Although most of the phosphatase activity in the insect nerve cord appears to be of cytosolic origin, much latent activity can be unmasked by incubating membranous fractions with Triton X-100. In contrast to soluble phosphatase, the detergent-solubilized activity is moderately stimulated by Mn-2+.?

  9. Morphological changes in the enteric nervous system caused by carcinoma of the human large intestine.

    Directory of Open Access Journals (Sweden)

    Janusz Godlewski

    2010-06-01

    Full Text Available The innervations of the large intestine is responsible for it peristalsis and contractibility. Investigations of the enteric nervous system in many colon diseases have revealed changes in this structure. No study has been carried out on morphological changes of the enteric nervous system in the human large intestine with carcinoma. The aim of this study was to investigate potential changes in the structure of the enteric neurons in patients with sigmoid and rectal cancer. Material for the study was obtained from patients undergoing operations due to carcinoma of the sigmoid colon and rectum. Microscopic observation of the cancerous tumor of the human large intestine revealed changes in the enteric nervous system innervating this part of the gastrointestinal tract. In the region of the enteric plexuses located close to the tumour, disruption of their correct placement and structure was observed. The changes also consisted of the disappearance of neurons and nerve fibers forming these plexuses. In the solid cancerous tumour, elements of the enteric nervous system were not present. Destruction of the enteric nervous system in the course of carcinoma of the large intestine may cause disruption of proper intestinal function and may be responsible for part of symptoms which the patients suffer.

  10. Distribution of the Endocannabinoid System in the Central Nervous System.

    Science.gov (United States)

    Hu, Sherry Shu-Jung; Mackie, Ken

    2015-01-01

    The endocannabinoid system consists of endogenous cannabinoids (endocannabinoids), the enzymes that synthesize and degrade endocannabinoids, and the receptors that transduce the effects of endocannabinoids. Much of what we know about the function of endocannabinoids comes from studies that combine localization of endocannabinoid system components with physiological or behavioral approaches. This review will focus on the localization of the best-known components of the endocannabinoid system for which the strongest anatomical evidence exists.

  11. Autoimmune diseases in the TH17 era

    Directory of Open Access Journals (Sweden)

    D. Mesquita Jr.

    2009-06-01

    Full Text Available A new subtype of CD4+ T lymphocytes characterized by the production of interleukin 17, i.e., TH17 cells, has been recently described. This novel T cell subset is distinct from type 1 and type 2 T helper cells. The major feature of this subpopulation is to generate significant amounts of pro-inflammatory cytokines, therefore appearing to be critically involved in protection against infection caused by extracellular microorganisms, and in the pathogenesis of autoimmune diseases and allergy. The dynamic balance among subsets of T cells is important for the modulation of several steps of the immune response. Disturbances in this balance may cause a shift from normal immunologic physiology to the development of immune-mediated disorders. In autoimmune diseases, the fine balance between the proportion and degree of activation of the various T lymphocyte subsets can contribute to persistent undesirable inflammatory responses and tissue replacement by fibrosis. This review highlights the importance of TH17 cells in this process by providing an update on the biology of these cells and focusing on their biology and differentiation processes in the context of immune-mediated chronic inflammatory diseases.

  12. Diagnosis of leptomeningeal disease in diffuse large B-cell lymphomas of the central nervous system by flow cytometry and cytopathology.

    Science.gov (United States)

    Schroers, Roland; Baraniskin, Alexander; Heute, Christoph; Vorgerd, Matthias; Brunn, Anna; Kuhnhenn, Jan; Kowoll, Annika; Alekseyev, Andriy; Schmiegel, Wolff; Schlegel, Uwe; Deckert, Martina; Pels, Hendrik

    2010-12-01

    Reliable detection of leptomeningeal disease has the potential of facilitating the diagnosis of central nervous system (CNS) lymphoma and is important for therapeutic considerations. Currently, the standard diagnostic procedure for the detection of lymphoma in the cerebrospinal fluid is cytopathology. To improve the limited specificity and sensitivity of cytopathology, flow cytometry has been suggested as an alternative. Here, we evaluated multi-parameter flow cytometry in combination with conventional cytopathology in cerebrospinal fluid (CSF) samples from 30 patients with primary CNS lymphoma and seven patients with secondary CNS lymphoma. Overall, in 11 of 37 (29.7%) patients with CNS lymphoma, lymphoma cells were detected in CSF by flow cytometry, while cytopathology was less sensitive displaying unequivocally malignant CSF cells in only seven of all 37 (18.9%) patients. Six (16.2%) patients showed cytopathological results suspicious of lymphoma; however, in only one of these patients, the diagnosis of CSF lymphoma cells could be confirmed by flow cytometry. In primary CNS lymphomas (PCNSL), seven of 30 (23.3%) patients were positive for CSF lymphoma cells in flow cytometry, in contrast to four (13.3%) patients with PCNSL with definitely positive cytopathology. In summary, our results suggest that multi-parameter flow cytometry increases the sensitivity and specificity of leptomeningeal disease detection in CNS lymphomas. Both methods should be applied concurrently for complementary diagnostic assessment in patients with CNS lymphoma. © 2010 John Wiley & Sons A/S.

  13. APPEARANCE OF AUTOIMMUNE DISEASES IN PATIENTS WITH ENDOMETRIOSIS

    Directory of Open Access Journals (Sweden)

    Nina Slabe

    2018-02-01

    Full Text Available Background. Endometriosis is a comon, complex gynecological syndrom defined as the growth of endometrial glands and stroma in an extra-uterine location. It affects 5 – 20 % of women of reproductive age.1 Nowadays, prevailing opinion about endometriosis is based on presumption, that endometriosis is a result of changed immune system, according to autoimmune theory.2, 3 Characteristics of autoimmune disease that are also found in endometriosis are female preponderance, multiorgan involvement, family occurence, possible genetic basis, response to hormonal manipulation, tissue damage, polyclonal B lymphocite activation, immunological abnormalities in T lymphocite and B lymphocite function and associated autoimmune disease. Women with endometriosis are more frequently affected by asthma, rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrom and Hashimoto’s thyroiditis. Autoimmune disease is characterized by the production of autoantibodies against components of apoptotic cells. Anti-endometrial antibodies of IgG and IgM classes could be detected in 60 % of endometriosis patients. They show reactivity in glandular epithelium and stroma. Anti-endothelial antibodies specifically react with vascular endothelium and might be with anti-endometrial antibodies partially responsible for failure of implantation leading to infertility, wich is common in endometriosis patients. Anti-nuclear antibodies are frequent serological findings in patients with autoimmune disease, and could be detected in 29–47 % of women with endometriosis.4 Generation of anti-nuclear antibodies is a risk factor for development of other autoimmune disease in women of reproductive age. Studies have shown conflicting results on the presence of anti-ovarian antibodies in the serum of endometriosis patients and in the peritoneal fluid. Their presence is one of the possible causes of infertility. Conclusions. Ethiopathogenesis of endometriosis still remains uncelar but

  14. Suppression of systemic autoimmunity by the innate immune adaptor STING

    Science.gov (United States)

    Sharma, Shruti; Campbell, Allison M.; Chan, Jennie; Schattgen, Stefan A.; Orlowski, Gregory M.; Nayar, Ribhu; Huyler, Annie H.; Nündel, Kerstin; Mohan, Chandra; Berg, Leslie J.; Shlomchik, Mark J.; Marshak-Rothstein, Ann; Fitzgerald, Katherine A.

    2015-01-01

    Cytosolic DNA-sensing pathways that signal via Stimulator of interferon genes (STING) mediate immunity to pathogens and also promote autoimmune pathology in DNaseII- and DNaseIII-deficient mice. In contrast, we report here that STING potently suppresses inflammation in a model of systemic lupus erythematosus (SLE). Lymphoid hypertrophy, autoantibody production, serum cytokine levels, and other indicators of immune activation were markedly increased in STING-deficient autoimmune-prone mice compared with STING-sufficient littermates. As a result, STING-deficient autoimmune-prone mice had significantly shorter lifespans than controls. Importantly, Toll-like receptor (TLR)-dependent systemic inflammation during 2,6,10,14-tetramethylpentadecane (TMPD)-mediated peritonitis was similarly aggravated in STING-deficient mice. Mechanistically, STING-deficient macrophages failed to express negative regulators of immune activation and thus were hyperresponsive to TLR ligands, producing abnormally high levels of proinflammatory cytokines. This hyperreactivity corresponds to dramatically elevated numbers of inflammatory macrophages and granulocytes in vivo. Collectively these findings reveal an unexpected negative regulatory role for STING, having important implications for STING-directed therapies. PMID:25646421

  15. Vascular supply of the central nervous system of the land snail Megalobulimus oblongus (Gastropoda, Pulmonata)

    OpenAIRE

    Noblega, Hector Gabriel; Missaglia, Vivian; Stenert, Cristina; Heuser, Maria Cristina Faccioni; Achaval-Elena, Matilde

    2003-01-01

    The vascularization of the central nervous system of the snail Megalobulimus oblongus was studied by injection of carmine-gelatin solution into the arterial system and using a histochemical technique for the detection of alkaline phosphatase. The central nervous system of M. oblongus is irrigated by the anterior aorta, from which a series of small branches emerge that supply the subesophageal nervous ganglia. In turn, these branches give rise to a series of smaller vessels that irrigate the b...

  16. The role of the autonomic nervous system in Tourette Syndrome

    Directory of Open Access Journals (Sweden)

    Jack eHawksley

    2015-05-01

    Full Text Available Tourette Syndrome (TS is a neurodevelopmental disorder, consisting of multiple involuntary movements (motor tics and one or more vocal (phonic tics. It affects up to one percent of children worldwide, of whom about one third continue to experience symptoms into adulthood. The central neural mechanisms of tic generation are not clearly understood, however recent neuroimaging investigations suggest impaired cortico-striato-thalamo-cortical activity during motor control. In the current manuscript, we will tackle the relatively under-investigated role of the peripheral autonomic nervous system, and its central influences, on tic activity. There is emerging evidence that both sympathetic and parasympathetic nervous activity influences tic expression. Pharmacological treatments which act on sympathetic tone are often helpful: for example, Clonidine (an alpha-2 adrenoreceptor agonist is often used as first choice medication for treating TS in children due to its good tolerability profile and potential usefulness for co-morbid attention-deficit and hyperactivity disorder. Clonidine suppresses sympathetic activity, reducing the triggering of motor tics. A general elevation of sympathetic tone is reported in patients with TS compared to healthy people, however this observation may reflect transient responses coupled to tic activity. Thus the presence of autonomic impairments in patients with TS remains unclear. Effect of autonomic afferent input to cortico-striato-thalamo-cortical circuit will be discussed schematically. We additionally review how TS is affected by modulation of central autonomic control through biofeedback and Vagus Nerve Stimulation (VNS. Biofeedback training can enable a patient to gain voluntary control over covert physiological responses by making these responses explicit. Electrodermal biofeedback training to elicit a reduction in sympathetic tone has a demonstrated association with reduced tic frequency. VNS, achieved through an

  17. Immunofluorescence of Autoimmune Bullous Diseases

    NARCIS (Netherlands)

    Diercks, Gilles F; Pas, Hendri H; Jonkman, Marcel F

    Autoimmmune bullous diseases of skin and mucosa are uncommon, disabling, and potentially lethal diseases. For a quick and reliable diagnosis immunofluorescence is essential. This article describes two variants of immunofluorescence. The direct method uses a skin or mucosal biopsy of the patient to

  18. Aging changes in the nervous system

    Science.gov (United States)

    ... ency/article/004023.htm Aging changes in the nervous system To use the sharing features on this page, please enable JavaScript. The brain and nervous system are your body's central control center. They control ...

  19. Measuring of quality of life in autoimmune blistering disorders in Poland. Validation of disease - specific Autoimmune Bullous Disease Quality of Life (ABQOL) and the Treatment Autoimmune Bullous Disease Quality of Life (TABQOL) questionnaires.

    Science.gov (United States)

    Kalinska-Bienias, Agnieszka; Jakubowska, Beata; Kowalewski, Cezary; Murrell, Dedee F; Wozniak, Katarzyna

    2017-03-01

    Autoimmune bullous dermatoses (AIBD) are rare, severe diseases resulting from some antibodies activity against the different adhesion structures within the skin and/or mucosa. Few studies investigated quality of life (QOL) in AIBD by generic and dermatology-specific instruments, all reporting strong impact on QOL. Recently, disease-specific measurement tools have been developed: Autoimmune Bullous Disease Quality of Life (ABQOL) and Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL) questionnaires. The aim of this study was to test the reliability and validity of ABQOL and TABQOL by developing the first foreign language versions and to evaluate ABQOL and TABQOL in Polish patients. The study enrolled 80 patients from the tertiary referral center for AIBD at the outpatient clinic or on admission to the hospital. Sixty six patients completed the 17-item questionnaires of each ABQOL and TABQOL at day 0 and after 5-7 days. Both questionnaires were translated into Polish according to protocol. The internal consistency and test-retest reliability were high (Cronbach α=0.95 for ABQOL, α=0.87 for TABQOL), (R=0.98 for ABQOL, R=0.86 for TABQOL). In convergent validity, the correlation of ABQOL and TABQOL was strong (R=0.81), but low with objective disease activity scales. The strongest impact of AIBD on QOL has been observed in flares and in patients with the onset below 70 years of age. The patients with bullous pemphigoid had the highest QOL compared to other AIBD patients. The ABQOL and TABQOL are reliable and valid instruments for the assessment of QOL in AIBD. Copyright © 2016 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

  20. Liver biopsy interpretation in the differential diagnosis of autoimmune liver disease in children

    Directory of Open Access Journals (Sweden)

    Clara Gerosa

    2013-06-01

    Full Text Available Autoimmune liver disease  (AILD represents a group of complex inflammatory liver diseases, all characterized by an aberrant autoreactivity against hepatocytes and/or biliary structures. AILD may be subclassified into four major diseases: autoimmune hepatitis (AIH, primary biliary cirrhosis (PBC, primary sclerosing cholangitis (PSC, and autoimmune cholangitis (AIC. Recently a new entity frequently associated with autoimmune pancreatitis and defined IgG4-related cholangitis (IgG4-RC,  has been added to the spectrum of AILD. The most frequent autoimmune liver diseases  of the AILD spectrum occurring in children and in young adults are  AIH  and PSC, overlap syndrome between AIH and PSC, also defined as autoimmune sclerosing cholangitis (ASC, representing a frequent finding in pediatric patients. Here,  the morphological findings that may help liver pathologists in the differential diagnosis of AILD in pediatric patients are reviewed, underlying the frequency in liver biopsy interpretation of complex cases in which a precise diagnosis may remain controversial, due to overlap of hepatocytic and bile duct cell lesions. Among the multiple morphological changes typical of AILD,  the detection of an high number of plasma cell clusters in the portal and periportal regions is generally considered one of the main clue for the diagnosis of AIH. The recent report in a 13-year old  boy of IgG4-associated cholangitis, induces  pathologists when detecting a huge number of plasmacells, to consider the differential diagnosis between AIH and IgG4-RC.Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research

  1. Low prevalence of hepatitis B virus infection in patients with autoimmune diseases in a Chinese patient population.

    Science.gov (United States)

    Sui, M; Wu, R; Hu, X; Zhang, H; Jiang, J; Yang, Y; Niu, J

    2014-12-01

    Hepatitis B is a very common communicable disease in China but the prevalence of hepatitis B virus (HBV) infection in patients with autoimmune diseases is unknown. We retrospectively investigated the prevalence of autoimmune diseases in patients with HBV infection. The medical records of 4060 patients with autoimmune or nonautoimmune diseases were reviewed. A positive test result for hepatitis B surface antigen (HBsAg) was used to indicate the presence of HBV infection. Autoimmune diseases included autoimmune hepatitis, primary biliary cirrhosis, systemic lupus erythematosus and ulcerative colitis. Nonautoimmune conditions included inguinal hernia, appendicitis and pregnant or postpartum women. The proportion of autoimmune disease patients who were HBsAg positive (2.24%) was significantly lower than that of nonautoimmune disease patients who were HBsAg positive (4.58%; P = 0.0014). Regarding hepatic autoimmune diseases, the positivity rates for HBsAg in autoimmune hepatitis patients (0.83%) and primary biliary cirrhosis patients (1.02%) were both significantly lower than in nonautoimmune patients (4.58%; P = 0.006 and 0.004, respectively). Patients with hepatic autoimmune disease were significantly less likely to be HBsAg positive (0.93%) than patients with non-hepatic autoimmune disease (3.99%; P = 0.002). Patients with autoimmune diseases, especially those with hepatic autoimmune disease, may more efficiently clear HBV than patients with nonautoimmune diseases. © 2014 John Wiley & Sons Ltd.

  2. Association between allelic variants of the human glucocorticoid receptor gene and autoimmune diseases: A systematic review and meta-analysis.

    Science.gov (United States)

    Herrera, Cristian; Marcos, Miguel; Carbonell, Cristina; Mirón-Canelo, José Antonio; Espinosa, Gerard; Cervera, Ricard; Chamorro, Antonio-Javier

    2018-03-08

    The human glucocorticoid receptor gene (NR3C1) is considered to play a role in the differences and sensitivities of the glucocorticoid response in individuals with autoimmune diseases. The objective of this study was to examine by means of a systematic review previous findings regarding allelic variants of NR3C1 in relation to the risk of developing systemic autoimmune diseases. Studies that analysed the genotype distribution of NR3C1 allelic variants among patients with systemic autoimmune diseases were retrieved. A meta-analysis was conducted with a random effects model. Odds ratios (ORs) and their confidence intervals (CIs) were calculated. In addition, sub-analysis by ethnicity, sensitivity analysis and tests for heterogeneity of the results were performed. Eleven studies met the inclusion criteria for meta-analysis. We found no evidence that the analysed NR3C1 polymorphisms, rs6198, rs56149945, and rs6189/rs6190, modulate the risk of developing a systemic autoimmune disease. Nonetheless, a protective role for the minor allele of rs41423247 was found among Caucasians (OR = 0.78; 95% CI: 0.65, 0.92; P = 0.004). A subgroup analysis according to underlying diseases revealed no significant association either for Behçet's disease or rheumatoid arthritis, while correlations between NR3C1 polymorphisms and disease activity or response to glucocorticoids could not be evaluated due to insufficient data. There is no clear evidence that the analysed NR3C1 allelic variants confer a risk for developing systemic autoimmune diseases although the minor G allele of rs41423247 may be protective among Caucasians. Copyright © 2018. Published by Elsevier B.V.

  3. Eosinophils in Autoimmune Diseases.

    Science.gov (United States)

    Diny, Nicola L; Rose, Noel R; Čiháková, Daniela

    2017-01-01

    Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs.

  4. Eosinophils in Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Daniela Čiháková

    2017-04-01

    Full Text Available Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs.

  5. A neurochemical map of the developing amphioxus nervous system

    Directory of Open Access Journals (Sweden)

    Candiani Simona

    2012-06-01

    Full Text Available Abstract Background Amphioxus, representing the most basal group of living chordates, is the best available proxy for the last invertebrate ancestor of the chordates. Although the central nervous system (CNS of amphioxus comprises only about 20,000 neurons (as compared to billions in vertebrates, the developmental genetics and neuroanatomy of amphioxus are strikingly vertebrate-like. In the present study, we mapped the distribution of amphioxus CNS cells producing distinctive neurochemicals. To this end, we cloned genes encoding biosynthetic enzymes and/or transporters of the most common neurotransmitters and assayed their developmental expression in the embryo and early larva. Results By single and double in situ hybridization experiments, we identified glutamatergic, GABAergic/glycinergic, serotonergic and cholinergic neurons in developing amphioxus. In addition to characterizing the distribution of excitatory and inhibitory neurons in the developing amphioxus CNS, we observed that cholinergic and GABAergic/glycinergic neurons are segmentally arranged in the hindbrain, whereas serotonergic, glutamatergic and dopaminergic neurons are restricted to specific regions of the cerebral vesicle and the hindbrain. We were further able to identify discrete groups of GABAergic and glutamatergic interneurons and cholinergic motoneurons at the level of the primary motor center (PMC, the major integrative center of sensory and motor stimuli of the amphioxus nerve cord. Conclusions In this study, we assessed neuronal differentiation in the developing amphioxus nervous system and compiled the first neurochemical map of the amphioxus CNS. This map is a first step towards a full characterization of the neurotransmitter signature of previously described nerve cell types in the amphioxus CNS, such as motoneurons and interneurons.

  6. Tumor-Like Presentation of Primary Angiitis of the Central Nervous System.

    Science.gov (United States)

    de Boysson, Hubert; Boulouis, Grégoire; Dequatre, Nelly; Godard, Sophie; Néel, Antoine; Arquizan, Caroline; Detante, Olivier; Bloch-Queyrat, Coralie; Zuber, Mathieu; Touzé, Emmanuel; Bienvenu, Boris; Aouba, Achille; Guillevin, Loïc; Naggara, Olivier; Pagnoux, Christian

    2016-09-01

    We aimed to describe the clinical and imaging features of patients with tumor-like presentation of primary angiitis of the central nervous system. We retrospectively analyzed 10 patients enrolled in the French primary angiitis of the central nervous system cohort, who initially presented tumor-like brain lesions and compared them with other patients within the cohort. The 10 patients with tumor-like presentation in the cohort were younger and had more seizures at diagnosis than the other 75 patients (median of 37 [30-48] years versus 46 [18-79] years; P=0.008; 9 [90%] with seizures versus 22 [29%], Pcentral nervous system represent a subgroup characterized with mainly small-sized vessel disease that requires histological confirmation because vascular imaging is often normal. Although relapses are not uncommon, global outcomes are good under treatment with glucocorticoids and cyclophosphamide. © 2016 American Heart Association, Inc.

  7. Optical cuff for optogenetic control of the peripheral nervous system

    Science.gov (United States)

    Michoud, Frédéric; Sottas, Loïc; Browne, Liam E.; Asboth, Léonie; Latremoliere, Alban; Sakuma, Miyuki; Courtine, Grégoire; Woolf, Clifford J.; Lacour, Stéphanie P.

    2018-02-01

    Objective. Nerves in the peripheral nervous system (PNS) contain axons with specific motor, somatosensory and autonomic functions. Optogenetics offers an efficient approach to selectively activate axons within the nerve. However, the heterogeneous nature of nerves and their tortuous route through the body create a challenging environment to reliably implant a light delivery interface. Approach. Here, we propose an optical peripheral nerve interface—an optocuff—, so that optogenetic modulation of peripheral nerves become possible in freely behaving mice. Main results. Using this optocuff, we demonstrate orderly recruitment of motor units with epineural optical stimulation of genetically targeted sciatic nerve axons, both in anaesthetized and in awake, freely behaving animals. Behavioural experiments and histology show the optocuff does not damage the nerve thus is suitable for long-term experiments. Significance. These results suggest that the soft optocuff might be a straightforward and efficient tool to support more extensive study of the PNS using optogenetics.

  8. Prospective population-based study of the association between vitamin D status and incidence of autoimmune disease

    DEFF Research Database (Denmark)

    Skaaby, Tea; Husemoen, Lise Lotte Nystrup; Thuesen, Betina Heinsbæk

    2015-01-01

    Beside its traditional role in skeletal health, vitamin D is believed to have multiple immunosuppressant properties, and low vitamin D status has been suggested to be a risk factor in the development of autoimmune disease. We investigated the association between vitamin D status and development...... of autoimmune disease. We included a total of 12,555 individuals from three population-based studies with measurements of vitamin D status (25-hydroxy vitamin D). We followed the participants by linkage to the Danish National Patient Register (median follow-up time 10.8 years). Relative risks of autoimmune...... disease were estimated by Cox regression and expressed as hazard ratios, HRs (95 % confidence intervals CIs). There were 525 cases of incident autoimmune disease. The risk for a 10 nmol/l higher vitamin D was: for any autoimmune disease (HR = 0.94 % CI 0.90, 0.98); thyrotoxicosis (HR = 0.83, 95 % CI 0...

  9. MRT of the central nervous system; MRT des Zentralnervensystems

    Energy Technology Data Exchange (ETDEWEB)

    Forsting, M.; Jansen, O. (eds.)

    2006-07-01

    The book presents the state of the art of MRT imaging of the central nervous system. Detailed information is presented in order to provide sufficient knowledge for the medical diagnostician to discuss any case encountered at eye level with the clinical physician. The book is an indispensable reference manual and a quick orientation already during examination in difficult cases. It contains images made with the most recent technology and with excellent representation of details. Even rare findings are described in detail. The imaging principle is illustrated by more than 1000 pictures and graphical representations as well as more than 100 complementary tables. Findings are classified by regions, i.e. 'brain' and 'spinal cord', including anatomical descriptions. (orig.)

  10. ELR chemokine signaling in host defense and disease in a viral model of central nervous system disease

    Directory of Open Access Journals (Sweden)

    Martin P Hosking

    2014-06-01

    Full Text Available Intracranial infection of the neurotropic JHM strain of mouse hepatitis virus (JHMV into the central nervous system (CNS of susceptible strains of mice results in an acute encephalomyelitis, accompanied by viral replication in glial cells and robust infiltration of virus-specific T cells that contribute to host defense through cytokine secretion and cytolytic activity. Mice that survive the acute stage of disease develop an immune-mediated demyelinating diseases characterized by viral persistence in white matter tracts and a chronic neuroinflammatory response dominated by T cells and macrophages. Early following JHMV infection, there is a dynamic expression of chemokines and chemokine receptors that contribute to neuroinflammation by regulating innate and adaptive immune responses as well influencing glial biology. In response to JHMV infection, we have shown that signaling through the chemokine receptor CXCR2 contributes to host defense through recruitment of polymorphonuclear cells (PMNs to the CNS that enhance permeability of the blood-brain-barrier (BBB and facilitating entry of virus-specific T cells into the parenchyma. Further, CXCR2 promotes the protection of oligodendroglia from cytokine-induced apoptosis and restricts the severity of demyelination. This review covers aspects related to the role of CXCR2 in host defense and disease in response to JHMV infection.

  11. Development of autoantibodies precedes clinical manifestations of autoimmune diseases: A comprehensive review.

    Science.gov (United States)

    Ma, Wen-Tao; Chang, Christopher; Gershwin, M Eric; Lian, Zhe-Xiong

    2017-09-01

    The etiology of autoimmune diseases is due to a combination of genetic predisposition and environmental factors that alter the expression of immune regulatory genes through various mechanisms including epigenetics. Both humoral and cellular elements of the adaptive immune system play a role in the pathogenesis of autoimmune diseases and the presence of autoantibodies have been detected in most but not all autoimmune diseases before the appearance of clinical symptoms. In some cases, the presence or levels of these autoantibodies portends not only the risk of developing a corresponding autoimmune disease, but occasionally the severity as well. This observation is intriguing because it suggests that we can, to some degree, predict who may or may not develop autoimmune diseases. However, the role of autoantibodies in the pathogenesis of autoimmune diseases, whether they actually affect disease progression or are merely an epiphenomenon is still not completely clear in many autoimmune diseases. Because of these gaps in our knowledge, the ability to accurately predict a future autoimmune disease can only be considered a relative risk factor. Importantly, it raises the critical question of defining other events that may drive a patient from a preclinical to a clinical phase of disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Focal lesions in the central nervous system

    International Nuclear Information System (INIS)

    Fabrikant, J.I.; Budinger, T.F.; Tobias, C.A.; Born, J.L.

    1980-01-01

    This report reviews the animal and human studies currently in progress at LBL with heavy-ion beams to induce focal lesions in the central nervous system, and discusses the potential future prospects of fundamental and applied brain research with heavy-ion beams. Methods are being developed for producing discrete focal lesions in the central nervous system using the Bragg ionization peak to investigate nerve pathways and neuroendocrine responses, and for treating pathological disorders of the brain

  13. Multiple myeloma invasion of the central nervous system

    Directory of Open Access Journals (Sweden)

    Marjanović Slobodan

    2012-01-01

    Full Text Available Introduction. Multiple myeloma (MM is characterized by the presence of neoplastic proliferating plasma cells. The tumor is generally restricted to the bone marrow. The most common complications include renal insufficiency, hypercalcemia, anemia and reccurent infections. The spectrum of MM neurological complications is diverse, however, involvement of MM in the cerebrospinal fluid (CSF and leptomeningeal infiltration are rare considered. In about 1% of the cases, the disease affects the central nervous system (CNS and presents itself in the form of localized intraparenchymal lesions, solitary cerebral plasmocytoma or CNS myelomatosis (LMM. Case report. We presented the clinical course of a 55-year-old man with MM and LMM proven by malignant plasma cells in the CSF, hospitalized with the pain in the thoracic spine. His medical history was uneventful. There had been no evidence of mental or neurological impairment prior to the seizures. Physical examination showed no abnormalities. After a complete staging, the diagnosis of MM type biclonal gammopathia IgG lambda and free lambda light chains in the stage III was confirmed. The treatment started with systemic chemotherapy (with vincristine, doxorubicin plus high-dose dexamethasone - VAD protocol, radiotherapy and bisphosphonate. The patient developed weakness, nausea, febrility, dispnea, bilateral bronchopneumonia, acute renal insufficiency, confusions, headaches and soon thereafter sensomotor aphasias and right hemiparesis. The patient was treated with the adequate therapy including one hemodyalisis. His neurological status was deteriorated, so Multislice Computed Tomography (MSCT of the head was performed and the findings were normal. Analysis of CSF showed pleocytosis, 26 elements/ mL and increased concentrations of proteins. Cytological analysis revealed an increased number of plasma cells (29%. Electrophoretic analysis of proteins disclosed the existance of monoclonal components in the serum

  14. Nanotechnologies for the study of the central nervous system.

    Science.gov (United States)

    Ajetunmobi, A; Prina-Mello, A; Volkov, Y; Corvin, A; Tropea, D

    2014-12-01

    The impact of central nervous system (CNS) disorders on the human population is significant, contributing almost €800 billion in annual European healthcare costs. These disorders not only have a disabling social impact but also a crippling economic drain on resources. Developing novel therapeutic strategies for these disorders requires a better understanding of events that underlie mechanisms of neural circuit physiology. Studying the relationship between genetic expression, synapse development and circuit physiology in CNS function is a challenging task, involving simultaneous analysis of multiple parameters and the convergence of several disciplines and technological approaches. However, current gold-standard techniques used to study the CNS have limitations that pose unique challenges to furthering our understanding of functional CNS development. The recent advancement in nanotechnologies for biomedical applications has seen the emergence of nanoscience as a key enabling technology for delivering a translational bridge between basic and clinical research. In particular, the development of neuroimaging and electrophysiology tools to identify the aetiology and progression of CNS disorders have led to new insights in our understanding of CNS physiology and the development of novel diagnostic modalities for therapeutic intervention. This review focuses on the latest applications of these nanotechnologies for investigating CNS function and the improved diagnosis of CNS disorders. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Accelerated Central Nervous System Autoimmunity in BAFF-Receptor-Deficient Mice

    OpenAIRE

    Kim, Susan S.; Richman, David P.; Zamvil, Scott S.; Agius, Mark A.

    2011-01-01

    B cell activating factor (BAFF) is critical for B cell survival, a function that is mediated by BAFF receptor, (BAFF-R). The role of BAFF (or BAFF-R) in the multiple sclerosis model, experimental autoimmune encephalomyelitis (EAE), was examined using BAFF-R-deficient mice. BAFF-R deficiency resulted in paradoxically increased severity of EAE induced by myelin-oligodendrocyte glycoprotein (MOG) peptide 35-55. Inflammatory foci in BAFF-R-deficient mice comprised increased numbers of activated m...

  16. Nanotechnologies for the study of the central nervous system.

    LENUS (Irish Health Repository)

    Ajetunmobi, A

    2014-12-01

    The impact of central nervous system (CNS) disorders on the human population is significant, contributing almost €800 billion in annual European healthcare costs. These disorders not only have a disabling social impact but also a crippling economic drain on resources. Developing novel therapeutic strategies for these disorders requires a better understanding of events that underlie mechanisms of neural circuit physiology. Studying the relationship between genetic expression, synapse development and circuit physiology in CNS function is a challenging task, involving simultaneous analysis of multiple parameters and the convergence of several disciplines and technological approaches. However, current gold-standard techniques used to study the CNS have limitations that pose unique challenges to furthering our understanding of functional CNS development. The recent advancement in nanotechnologies for biomedical applications has seen the emergence of nanoscience as a key enabling technology for delivering a translational bridge between basic and clinical research. In particular, the development of neuroimaging and electrophysiology tools to identify the aetiology and progression of CNS disorders have led to new insights in our understanding of CNS physiology and the development of novel diagnostic modalities for therapeutic intervention. This review focuses on the latest applications of these nanotechnologies for investigating CNS function and the improved diagnosis of CNS disorders.

  17. Development, Sensibility, and Validity of a Systemic Autoimmune Rheumatic Disease Case Ascertainment Tool.

    Science.gov (United States)

    Armstrong, Susan M; Wither, Joan E; Borowoy, Alan M; Landolt-Marticorena, Carolina; Davis, Aileen M; Johnson, Sindhu R

    2017-01-01

    Case ascertainment through self-report is a convenient but often inaccurate method to collect information. The purposes of this study were to develop, assess the sensibility, and validate a tool to identify cases of systemic autoimmune rheumatic diseases (SARD) in the outpatient setting. The SARD tool was administered to subjects sampled from specialty clinics. Determinants of sensibility - comprehensibility, feasibility, validity, and acceptability - were evaluated using a numeric rating scale from 1-7. Comprehensibility was evaluated using the Flesch Reading Ease and the Flesch-Kincaid Grade Level. Self-reported diagnoses were validated against medical records using Cohen's κ statistic. There were 141 participants [systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis, Sjögren syndrome (SS), inflammatory myositis (polymyositis/dermatomyositis; PM/DM), and controls] who completed the questionnaire. The Flesch Reading Ease score was 77.1 and the Flesch-Kincaid Grade Level was 4.4. Respondents endorsed (mean ± SD) comprehensibility (6.12 ± 0.92), feasibility (5.94 ± 0.81), validity (5.35 ± 1.10), and acceptability (3.10 ± 2.03). The SARD tool had a sensitivity of 0.91 (95% CI 0.88-0.94) and a specificity of 0.99 (95% CI 0.96-1.00). The agreement between the SARD tool and medical record was κ = 0.82 (95% CI 0.77-0.88). Subgroup analysis by SARD found κ coefficients for SLE to be κ = 0.88 (95% CI 0.79-0.97), SSc κ = 1.0 (95% CI 1.0-1.0), PM/DM κ = 0.72 (95% CI 0.49-0.95), and SS κ = 0.85 (95% CI 0.71-0.99). The screening questions had sensitivity ranging from 0.96 to 1.0 and specificity ranging from 0.88 to 1.0. This SARD case ascertainment tool has demonstrable sensibility and validity. The use of both screening and confirmatory questions confers added accuracy.

  18. The role of the nervous system in fish evolution

    Directory of Open Access Journals (Sweden)

    Michael H Hofmann

    2015-12-01

    Full Text Available The nervous system plays an important role in the evolution and adaptation of animals. All sensory and motor functions as well as cognitive abilities are organized in the brain and spinal cord. Volumetric measurements of different brain regions were made in more than 150 species of ray finned fishes as well as in several outgroups. In Actanthopterygii, the hypothalamus shows greatest enlargement most likely due to an enormous visual input via the nucleus glomerulosos. The telencephalon is highly differentiated in many acanthopterygii, mostly coral reef species, but its relative size is not much effected. There is, however, a clear shift from olfactory to visual functions in ray finned fishes. In species with a highly differentiated telencephalon, the area where place memory may be located is very prominent. In basal ray finned fishes, lungfish, amphibia and elasmobranchs, the olfactory bulb is relatively large and the ratio of the olfactory bulb and telencephalon large as well. This holds also for elopomorpha and spiny eels, but in most other groups vision dominates. Apart from differences between larger clades, variation in brain architecture are also seen in closely related species and even between sexes of the same species. Profound differences are present in the cerebellum between male and female swordtails and in the telencephalon of sticklebacks. Morphometric analysis of brain architecture turned out to be an important tool to study the evolution and adaptations of the brain in fishes.

  19. NEUROGENETIC ASPECTS OF PERINATAL HYPOXIC-ISCHEMIC AFFECTIONS OF THE CENTRAL NERVOUS SYSTEM

    OpenAIRE

    George A. Karkashadze; Kirill V. Savostianov; Svetlana G. Makarova; Leyla S. Namazova-Baranova; Olga I. Maslova; Galina V. Yatsyk

    2016-01-01

    Neurogenetics is a thriving young science greatly contributing to the generally accepted concept of the brain development in health and disease. Thereby; scientists are not only able to highlight new key points in traditional ideas about the origin of diseases; but also to completely rethink their view on the problem of pathology development. In particular; new data on neurogenetics of perinatal affections of the central nervous system (CNS) has appeared. Genetic factors in varying degrees af...

  20. Ocular inflammation in the setting of concomitant systemic autoimmune conditions in an older male population

    Science.gov (United States)

    Levitt, Alexandra E.; McManus, Katherine T.; McClellan, Allison L.; Davis, Janet; Goldhardt, Raquel; Galor, Anat

    2015-01-01

    Purpose This retrospective cross-sectional study was designed to investigate the frequency and types of inflammatory ocular manifestations of specific systemic autoimmune diseases in a South Florida Veterans Affairs Hospital population. Methods Demographic and medical diagnosis information was extracted from the Veterans Administration database for 1225 patients. These patients were seen in Miami and Broward Veterans Affairs hospitals between 4/18/2008 and 4/17/2013 and were diagnosed with at least one of the following: systemic lupus erythematosus, sarcoid, rheumatoid arthritis, polymyalgia rheumatica, Takayasu arteritis, giant cell arteritis, Kawasaki disease, polyarteritis nodosa, Buerger disease, Henoch-Schonlein purpura, Behcet syndrome, granulomatosis with polyangiitis, other polyarteritis nodosa associated vasculitides, or arteritis NOS. Results Of 1225 patients, 618 were seen in the VA eye clinic, and 25 were diagnosed with concomitant inflammatory ocular conditions. Uveitis was the most common, and included 8 cases of anterior, 1 anterior-intermediate, 1 intermediate, 2 panuveitis, and 3 unspecified. Other manifestations included 7 cases of keratitis and 2 each of scleritis, episcleritis and AION. The overall frequency of inflammatory ocular disease was 2%. The diseases associated with the highest frequency of ocular involvement were granulomatosis with polyangiitis (1/8), sarcoid (9/198), giant cell arteritis (2/68), and rheumatoid arthritis (11/576). Of these 25 patients, 9 were diagnosed with eye prior to systemic disease. Conclusions In this population, ocular manifestations were rarely the presenting feature of systemic disease, but autoimmune disorders are an important underlying cause of inflammatory eye disease that should be considered on first evaluation, even in this “non-traditional”, predominantly male, autoimmune disease population. PMID:26053887

  1. Role of Human Leukocyte Antigens (HLA) in Autoimmune Diseases.

    Science.gov (United States)

    Bodis, Gergely; Toth, Victoria; Schwarting, Andreas

    2018-03-07

    Since the discovery of HLA 60 years ago, it has contributed to the understanding of the immune system as well as of the pathogenesis of several diseases. Aside from its essential role in determining donor-recipient immune compatibility in organ transplantation, HLA genotyping is meanwhile performed routinely as part of the diagnostic work-up of certain autoimmune diseases. Considering the ability of HLA to influence thymic selection as well as peripheral anergy of T cells, its role in the pathogenesis of autoimmunity is understandable. The aim of this paper is to provide a brief overview of the role and current clinical relevance of HLA-B27 in spondyloarthritis and HLA-B51 in Behçet's disease as well as HLA-DQ2/DQ8 in celiac disease and HLA-DRB1 in rheumatoid arthritis and to discuss possible future implications.

  2. Role of extracellular vesicles in autoimmune diseases.

    Science.gov (United States)

    Turpin, Delphine; Truchetet, Marie-Elise; Faustin, Benjamin; Augusto, Jean-François; Contin-Bordes, Cécile; Brisson, Alain; Blanco, Patrick; Duffau, Pierre

    2016-02-01

    Extracellular vesicles (EVs) consist of exosomes released upon fusion of multivesicular bodies with the cell plasma membrane and microparticles shed directly from the cell membrane of many cell types. EVs can mediate cell-cell communication and are involved in many processes including inflammation, immune signaling, angiogenesis, stress response, senescence, proliferation, and cell differentiation. Accumulating evidence reveals that EVs act in the establishment, maintenance and modulation of autoimmune processes among several others involved in cancer and cardiovascular complications. EVs could also present biomedical applications, as disease biomarkers and therapeutic targets or agents for drug delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. [Assessment of endothelial function in autoimmune diseases].

    Science.gov (United States)

    Benhamou, Y; Bellien, J; Armengol, G; Gomez, E; Richard, V; Lévesque, H; Joannidès, R

    2014-08-01

    Numerous autoimmune-inflammatory rheumatic diseases have been associated with accelerated atherosclerosis or other types of vasculopathy leading to an increase in cardiovascular disease incidence. In addition to traditional cardiovascular risk factors, endothelial dysfunction is an important early event in the pathogenesis of atherosclerosis, contributing to plaque initiation and progression. Endothelial dysfunction is characterized by a shift of the actions of the endothelium toward reduced vasodilation, a proinflammatory and a proadhesive state, and prothrombic properties. Therefore, assessment of endothelial dysfunction targets this vascular phenotype using several biological markers as indicators of endothelial dysfunction. Measurements of soluble adhesion molecules (ICAM-1, VCAM-1, E-selectin), pro-thrombotic factors (thrombomodulin, von Willebrand factor, plasminogen activator inhibitor-1) and inflammatory cytokines are most often performed. Regarding the functional assessment of the endothelium, the flow-mediated dilatation of conduit arteries is a non-invasive method widely used in pathophysiological and interventional studies. In this review, we will briefly review the most relevant information upon endothelial dysfunction mechanisms and explorations. We will summarize the similarities and differences in the biological and functional assessments of the endothelium in different autoimmune diseases. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  4. The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system.

    Science.gov (United States)

    Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Belau, Nele M; Zimmermann, Martin; Wirbelauer, Tim; Spielberg, Steffi; Vossen-Gajcy, Michaela; Cario, Gunnar; Schrappe, Martin; Schewe, Denis M

    2017-02-01

    Central nervous system infiltration and relapse are poorly understood in childhood acute lymphoblastic leukemia. We examined the role of zeta-chain-associated protein kinase 70 in preclinical models of central nervous system leukemia and performed correlative studies in patients. Zeta-chain-associated protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via activation of extracellular signal-regulated kinases. High expression of zeta-chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted in a higher proportion of central nervous system leukemia in xenografts as compared to zeta-chain-associated protein kinase 70 low expressing counterparts. High zeta-chain-associated protein kinase 70 also enhanced the migration potential towards CCL19/CXCL12 gradients in vitro CCR7 blockade almost abrogated homing of acute lymphoblastic leukemia cells to the central nervous system in xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70 and CCR7/CXCR4 expression levels were significantly correlated. Zeta-chain-associated protein kinase 70 expression correlated with central nervous system disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4 correlated with central nervous system involvement in T-cell acute lymphoblastic leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase 70 expression levels in the upper third and fourth quartiles were associated with central nervous system involvement in B-cell precursor acute lymphoblastic leukemia (odds ratio=7.48, 95% confidence interval, 2.06-27.17; odds ratio=6.86, 95% confidence interval, 1.86-25.26, respectively). CCR7 expression in the upper fourth quartile correlated with central

  5. Antigen discovery in chronic human inflammatory central nervous system disease: panning phage-displayed antigen libraries identifies the targets of central nervous system-derived IgG in subacute sclerosing panencephalitis.

    Science.gov (United States)

    Burgoon, M P; Owens, G P; Carlson, S; Maybach, A L; Gilden, D H

    2001-11-15

    The presence of increased IgG in the brains of humans with infectious and inflammatory CNS diseases of unknown etiology such as multiple sclerosis may be a clue to the cause of disease. For example, the intrathecally synthesized oligoclonal bands in diseases such as subacute sclerosing panencephalitis (SSPE) or cryptococcal meningitis have been shown to represent Ab directed against the causative agents, measles virus (MV), or Cryptococcus neoformans, respectively. Using SSPE as a model system, we developed a strategy to identify the antigenic targets of the intrathecal disease-relevant IgG in chronic human inflammatory and demyelinating diseases of the CNS. Libraries of cDNA Ags were displayed on the surface of T7Select bacteriophage and biopanned on IgG extracted from the brain of an SSPE patient, or on a monospecific recombinant Fab identified from SSPE brain. After three or six rounds of biopanning on either Ab, positive phage-displayed Ags reacting with IgG were enriched to 35-77% of all panned clones. Sequence analysis of the positive clones identified fragments of the nucleocapsid protein of MV, the cause of SSPE. The sensitivity of the system was determined by diluting the positive clones from this SSPE phage-displayed library at a ratio of 10(-6) into another phage-displayed library that did not contain any detectable MV Ags; after six rounds of panning, the positive clones comprised 34% of all phage and were also shown to be MV nucleocapsid specific. This strategy will be useful to identify potentially rare Ags in diseases of unknown cause.

  6. Selenium status and over-expression of interleukin-15 in celiac disease and autoimmune thyroid diseases

    Directory of Open Access Journals (Sweden)

    Anna Velia Stazi

    2010-12-01

    Full Text Available In celiac disease (CD, for its multifactorial nature, the target organs are not limited to the gut, but include thyroid, liver, skin and reproductive and nervous systems. Between the extraintestinal symptoms associated with CD, autoimmune thyroid diseases (AITDs are more evident, underlining as CD-related autoimmune alterations can be modulated not only by gluten but also by various concurrent endogenous (genetic affinity, over-expression of cytokines and exogenous (environment, nutritional deficiency factors. In their pathogenesis a central role for over-expression of interleukin-15 (IL-15 is shown, by inhibiting apoptosis, leading to the perpetuation of inflammation and tissue destruction. Thyroid is particularly sensitive to selenium deficiency because selenoproteins are significant in biosynthesis and activity of thyroid hormones; besides, some selenoproteins as glutathione peroxidase are involved in inhibiting apoptosis. Thus, selenium malabsorption in CD can be thought as a key factor directly leading to thyroid and intestinal damage. Considering the complexity of this interaction and on the basis of available evidence, the aim of this review is to assess as preventive and therapeutic target the role of IL-15 and selenium in the pathogeneses of both CD and AITD.

  7. Molecular and cellular analyses of HLA class II-associated susceptibility to autoimmune diseases in the Japanese population.

    Science.gov (United States)

    Nishimura, Y; Ito, H; Fujii, S; Tabata, H; Tokano, Y; Chen, Y Z; Matsuda, I; Mitsuya, H; Kira, J; Hashimoto, H; Senju, S; Matsushita, S

    2001-06-01

    Abstract It is well known that individuals who are positive for particular HLA class II alleles show a high risk of developing autoimmune diseases. HLA class II molecules expressed on antigen-presenting cells present antigenic peptides to CD4(+) T cells. Their extensive polymorphism affects the structures of peptides bound to HLA class II molecules to create individual differences in immune responses to antigenic peptides. In order to gain a better understanding of mechanisms of the association between HLA class II alleles and susceptibility to autoimmune diseases, it is important to identify self-peptides presented by disease-susceptible HLA class II molecules and triggering disease-causative T cells. Many of the autoimmune diseases are observed in all ethnic groups, whereas the incidence of diseases, clinical manifestations and disease-susceptible HLA class II alleles are different among various ethnic groups for some autoimmune diseases. These phenomena suggest that differences in autoimmune self-peptide(s) in the context of disease-susceptible HLA class II molecules may cause these differences. Therefore, comparisons among disease-susceptible HLA class II alleles, autoantigenic peptides, and clinical manifestations of autoimmune diseases in different ethnic groups would be helpful in elucidating the pathogenesis of the diseases. In this review, we describe our recent findings on (1) the uniqueness of both clinical manifestations and the HLA-linked genetic background of Asian-type (opticospinal form) multiple sclerosis, (2) the characteristics of glutamic acid decarboxylase 65 (GAD65) or β2-glycoprotein I (β2-GPI) autoreactive T cells in Japanese patients with insulin-dependent diabetes mellitus (IDDM) or anti-β2-GPI antibody-associated autoimmunity, respectively, and (3) the generation of an efficient delivery system of peptides to the HLA class II-restricted antigen presentation path-way by utilizing a class II-associated invariant chain peptide (CLIP

  8. Prevalence and characteristics of central nervous system involvement by chronic lymphocytic leukemia.

    Science.gov (United States)

    Strati, Paolo; Uhm, Joon H; Kaufmann, Timothy J; Nabhan, Chadi; Parikh, Sameer A; Hanson, Curtis A; Chaffee, Kari G; Call, Timothy G; Shanafelt, Tait D

    2016-04-01

    Abroad array of conditions can lead to neurological symptoms in chronic lymphocytic leukemia patients and distinguishing between clinically significant involvement of the central nervous system by chronic lymphocytic leukemia and symptoms due to other etiologies can be challenging. Between January 1999 and November 2014, 172 (4%) of the 4174 patients with chronic lymphocytic leukemia followed at our center had a magnetic resonance imaging of the central nervous system and/or a lumbar puncture to evaluate neurological symptoms. After comprehensive evaluation, the etiology of neurological symptoms was: central nervous system chronic lymphocytic leukemia in 18 patients (10% evaluated by imaging and/or lumbar puncture, 0.4% overall cohort); central nervous system Richter Syndrome in 15 (9% evaluated, 0.3% overall); infection in 40 (23% evaluated, 1% overall); autoimmune/inflammatory conditions in 28 (16% evaluated, 0.7% overall); other cancer in 8 (5% evaluated, 0.2% overall); and another etiology in 63 (37% evaluated, 1.5% overall). Although the sensitivity of cerebrospinal fluid analysis to detect central nervous system disease was 89%, the specificity was only 42% due to the frequent presence of leukemic cells in the cerebrospinal fluid in other conditions. No parameter on cerebrospinal fluid analysis (e.g. total nucleated cells, total lymphocyte count, chronic lymphocytic leukemia cell percentage) were able to offer a reliable discrimination between patients whose neurological symptoms were due to clinically significant central nervous system involvement by chronic lymphocytic leukemia and another etiology. Median overall survival among patients with clinically significant central nervous system chronic lymphocytic leukemia and Richter syndrome was 12 and 11 months, respectively. In conclusion, clinically significant central nervous system involvement by chronic lymphocytic leukemia is a rare condition, and neurological symptoms in patients with chronic lymphocytic

  9. Effect of TACI Signaling on Humoral Immunity and Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    2015-01-01

    Full Text Available Transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI is one of the receptors of B cell activating factor of the tumor necrosis factor family (BAFF and a proliferation-inducing ligand (APRIL. TACI is a regulator in the immune responses. TACI inhibits B cell expansion and promotes the differentiation and survival of plasma cells. The mechanisms underlying these effects probably involve changed expressions of some crucial molecules, such as B lymphocyte induced maturation protein-1 (Blimp-1 and inducible T-cell costimulator ligand (ICOSL in B cells and/or plasma cells. However, abnormal TACI signaling may relate to autoimmune disorders. Common variable immune deficiency (CVID patients with heterozygous mutations in TACI alleles increase susceptibility to autoimmune diseases. Taci−/− mice and BAFF transgenic mice both develop signs of human SLE. These findings that indicate inappropriate levels of TACI signaling may disrupt immune system balance, thereby promoting the development of autoimmune diseases. In this review, we summarize the basic characteristics of the TACI ligands BAFF and APRIL, and detail the research findings on the role of TACI in humoral immunity. We also discuss the possible mechanisms underlying the susceptibility of CVID patients with TACI mutations to autoimmune diseases and the role of TACI in the pathogenesis of SLE.

  10. Dysregulation of Autonomic Nervous System in Chagas’ Heart Disease Is Associated with Altered Adipocytokines Levels

    Science.gov (United States)

    Barbosa-Ferreira, João Marcos; Mady, Charles; Ianni, Barbara Maria; Lopes, Heno Ferreira; Ramires, Felix José Alvarez; Salemi, Vera Maria Cury; Grupi, Cesar José; Hachul, Denise Tessariol; Fernandes, Fábio

    2015-01-01

    Background Chagas disease (CD) induces autonomic dysfunction and inflammatory activity, which may promote metabolic abnormalities. We studied metabolism and his correlation with Autonomic Nervous System (ANS) and inflammation in CD. Methods and Results Sixty subjects were divided into 4 groups: control group (CG), IF (indeterminate form) group; ECG group (ECG abnormalities and normal left ventricular systolic function), and LVD group (left ventricular sistolic dysfunction). Levels of adiponectin, leptin, insulin, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were assayed in serum samples by ELISA. ANS was assessed by heart rate variability in frequency domain in 24-hour Holter and postural tilt test (rest and orthostatic position). High frequency (HFr) component values were used to estimate parasympathetic activity and low frequency (LFr) component, sympathetic activity. Analyzes were made of the correlations of each of the metabolic parameters (leptin and adiponectin) with the inflammatory cytokines (interleukin-6 and TNF- alpha) and with the ANS assessment measurements. No significant differences were observed in leptin and insulin levels. Adiponectin was higher in ECG and LVD groups: [CG = 4766.5 (5529.5), IF = 4003.5 (2482.5), ECG = 8376.5 (8388.5), LVD = 8798 (4188.0) ng/mL, p<0.001)]. IL-6 and TNF-alpha were higher in LVD group: [IL-6: CG = 1.85 (6.41); IF = 1.58 (1.91); ECG = 1.0 (1.57); LVD= 31.44 (72.19) pg/ml; p = 0.001. TNF-alpha: CG = 22.57 (88.2); IF = 19.31 (33.16); ECG = 12.45 (3.07); LVD = 75.15 (278.57) pg/ml; p = 0.04]. Adiponectin levels had a positive association with the HFr component (r = 0.539; p = 0.038) and an inverse association with the LFr component (r = - 0.539; p = 0.038) in ECG group. Leptin levels had a negative association with the HFr component (r= - 0.632; p = 0.011) and a positive association with the LFr component (r = 0.632; p = 0.011) in LVD group. Conclusions We found increased adiponectin levels in

  11. Dysregulation of Autonomic Nervous System in Chagas' Heart Disease Is Associated with Altered Adipocytokines Levels.

    Directory of Open Access Journals (Sweden)

    João Marcos Barbosa-Ferreira

    Full Text Available Chagas disease (CD induces autonomic dysfunction and inflammatory activity, which may promote metabolic abnormalities. We studied metabolism and his correlation with Autonomic Nervous System (ANS and inflammation in CD.Sixty subjects were divided into 4 groups: control group (CG, IF (indeterminate form group; ECG group (ECG abnormalities and normal left ventricular systolic function, and LVD group (left ventricular sistolic dysfunction. Levels of adiponectin, leptin, insulin, interleukin-6 (IL-6, and tumor necrosis factor-alpha (TNF-alpha were assayed in serum samples by ELISA. ANS was assessed by heart rate variability in frequency domain in 24-hour Holter and postural tilt test (rest and orthostatic position. High frequency (HFr component values were used to estimate parasympathetic activity and low frequency (LFr component, sympathetic activity. Analyzes were made of the correlations of each of the metabolic parameters (leptin and adiponectin with the inflammatory cytokines (interleukin-6 and TNF- alpha and with the ANS assessment measurements. No significant differences were observed in leptin and insulin levels. Adiponectin was higher in ECG and LVD groups: [CG = 4766.5 (5529.5, IF = 4003.5 (2482.5, ECG = 8376.5 (8388.5, LVD = 8798 (4188.0 ng/mL, p<0.001]. IL-6 and TNF-alpha were higher in LVD group: [IL-6: CG = 1.85 (6.41; IF = 1.58 (1.91; ECG = 1.0 (1.57; LVD= 31.44 (72.19 pg/ml; p = 0.001. TNF-alpha: CG = 22.57 (88.2; IF = 19.31 (33.16; ECG = 12.45 (3.07; LVD = 75.15 (278.57 pg/ml; p = 0.04]. Adiponectin levels had a positive association with the HFr component (r = 0.539; p = 0.038 and an inverse association with the LFr component (r = - 0.539; p = 0.038 in ECG group. Leptin levels had a negative association with the HFr component (r= - 0.632; p = 0.011 and a positive association with the LFr component (r = 0.632; p = 0.011 in LVD group.We found increased adiponectin levels in Chagas' heart disease with systolic dysfunction and in

  12. Innate sensing of the gut microbiota: modulation of inflammatory and autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Aline eIgnacio

    2016-02-01

    Full Text Available The mammalian gastrointestinal tract harbors a diverse microbial community with which dynamic interactions have been established over millennia of co-evolution. Commensal bacteria and their products are sensed by innate receptors expressed in gut epithelia and in gut-associated immune cells thereby promoting the proper development of mucosal immune system and host homeostasis. Many studies have demonstrated that host-microbiota interactions play a key role during local and systemic immunity. Therefore, this review will focus on how innate sensing of the gut-microbiota and their metabolites through inflammasome and toll-like receptors impact the modulation of a distinct set of inflammatory and autoimmune diseases. We believe that a better understanding of the fine-tuning that governs host-microbiota interactions will further improve common prophylactic and therapeutic applications.

  13. Effects of radiation on development, especially of the nervous system

    International Nuclear Information System (INIS)

    Hicks, S.P.; D'Amato, C.J.

    1980-01-01

    Humans and other organisms are exposed to ionizing radiations from a variety of natural and man-made sources. Radiation may cause mutations and chromosome abnormalities, cell-killing, alterations and transformations in cell growth, and carcinogenetic changes. This paper considers principally the cell-killing and nonlethal cell alterations in developing laboratory mammals and humans, especially the nervous system, that follow irradiation and often lead to malformation and disturbed function, but at certain stages to restitution of the injury. Most of what researchers know about the mechanisms of these radiation effects in man is derived from animal experiments, especially with rats. The few observations in humans have corresponded closely to them. Researchers illustrate the cellular effects and malformative results with an example of cell-killing in the developing cortex of a human fetus exposed to therapeutic radiation in utero; a current timetable of the malformative and other effects of radiation on rats during development from which expectations of human effects might be extrapolated; examples of hydrocephalus produced in rats; low-dose alterations of nerve cells in rats; and a microcephalic Japanese boy exposed in utero to the atomic bomb at Hiroshima in 1945

  14. Successful treatment with Ipilimumab and Interleukin‑2 in two patients with metastatic melanoma and systemic autoimmune disease

    DEFF Research Database (Denmark)

    Pedersen, Magnus; Andersen, Rikke; Larsen, Peter Nørgaard

    2014-01-01

    Two patients were treated with immunotherapy for metastatic malignant melanoma (MM) despite suffering from systemic autoimmune disease, i.e., ulcerative colitis (UC) and Behcets disease (BD), respectively. Both patients benefitted from the treatment. The patient with UC achieved partial remission...... of all measurable parameters after treatment with Ipilimumab, while the patient with BD achieved a complete remission of MM after treatment with Interleukin-2 (IL-2) and Interferon-α (IFN-α). Moreover, no aggravation of symptoms related to the autoimmune diseases was seen during treatment, in contrast......, clinical indications of improvement were observed. These two cases illustrate that the presence of autoimmune disease does not necessarily predict increased autoimmune toxicity in connection with immunotherapy. They also raise the question of whether autoimmune disease should continue to be an absolute...

  15. Association between demyelinating disease and autoimmune rheumatic disease in a pediatric population.

    Science.gov (United States)

    Amorim, Ana Luiza M; Cabral, Nadia C; Osaku, Fabiane M; Len, Claudio A; Oliveira, Enedina M L; Terreri, Maria Teresa

    Multiple sclerosis (MS) and neuromyelitis optica (NMO) are demyelinating diseases of the central nervous system. Autoimmunity in patients with demyelinating disease and in their families has been broadly investigated and discussed. Recent studies show a higher incidence of rheumatic autoimmune diseases among adult patients with MS or NMO and their families, but there are no studies in the pediatric population. To evaluate an association of MS and NMO with autoimmune rheumatic diseases in pediatric patients. 22 patients younger than 21 years old with MS or NMO diagnosed before the age of 18 years were evaluated regarding epidemiological data, clinical presentation, association with autoimmune diseases, family history of autoimmune diseases, laboratory findings, imaging studies and presence of auto-antibodies. Among the patients studied, there was a prevalence of females (68.1%). The mean age of symptoms onset was 8 years and 9 months and the mean current age was 16 years and 4 months. Two patients (9%) had a history of associated autoimmune rheumatic disease: one case of juvenile dermatomyositis in a patient with NMO and another of systemic lupus erythematosus in a patient with MS. Three patients (13%) had a family history of autoimmunity in first-degree relatives. Antinuclear antibody was found positive in 80% of patients with NMO and 52% of patients with MS. About 15% of antinuclear antibody-positive patients were diagnosed with rheumatologic autoimmune diseases. Among patients with demyelinating diseases diagnosed in childhood included in this study there was a high frequency of antinuclear antibody positivity but a lower association with rheumatologic autoimmune diseases than that observed in studies conducted in adults. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

  16. Autoimmune Disease in First-Degree Relatives and Spouses of Individuals With Celiac Disease.

    Science.gov (United States)

    Emilsson, Louise; Wijmenga, Cisca; Murray, Joseph A; Ludvigsson, Jonas F

    2015-07-01

    First-degree relatives of individuals with celiac disease are at increased risk for this disorder, but little is known about their risk for other autoimmune diseases. We assessed the risk of nonceliac autoimmune disease in first-degree relatives and spouses of people with celiac disease. We identified individuals with celiac disease by searching computerized duodenal and jejunal biopsies, collected from 1969 through 2008, at 28 pathology departments in Sweden. Celiac disease was identified based on biopsy reports of villous atrophy (equal to Marsh grade 3; n = 29,096). Individuals with celiac disease were matched with up to 5 controls (people without celiac disease) for sex, age, county, and calendar year (total, 144,522 controls). Through Swedish health care registries, we identified all first-degree relatives (fathers, mothers, siblings, and offspring) and spouses of individuals with celiac disease (n = 84,648) and controls (n = 430,942). We used Cox regression analysis to calculate hazard ratios (HRs) for nonceliac autoimmune disease (Crohn's disease, type 1 diabetes mellitus, hypothyroidism, hyperthyroidism, psoriasis, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, or ulcerative colitis) in these groups. During the follow-up period (median, 10.8 y), 3333 of the first-degree relatives of patients with celiac disease (3.9%) and 12,860 relatives of controls (3.0%) had an autoimmune disease other than celiac disease. First-degree relatives of people with celiac disease were at increased risk of nonceliac autoimmune disease, compared with controls (HR, 1.28; 95% confidence interval, 1.23-1.33), as were spouses (HR, 1.20; 95% confidence interval, 1.06-1.35). Risk estimates for nonceliac autoimmune disease did not differ between first-degree relatives and spouses of individuals with celiac disease (interaction test: P = .11). HRs for nonceliac autoimmune disease were highest in the first 2 years of follow-up evaluation. First-degree relatives and

  17. Hemostasis and Alterations of the Central Nervous System

    Science.gov (United States)

    del Zoppo, Gregory J.; Izawa, Yoshikane; Hawkins, Brian T.

    2014-01-01

    Modulation of coagulation has been successfully applied to ischemic disorders of the central nervous system (CNS). Some components of the coagulation system have been identified in the CNS, yet with limited exception their functions have not been clearly defined. Little is known about how events within the cerebral tissues affect hemostasis. Nonetheless, the interaction between cerebral cells and vascular hemostasis and the possibility that endogenous coagulation factors can participate in functions within the neurovascular unit provide intriguing possibilities for deeper insight into CNS functions and the potential for treatment of CNS injuries. Here, we consider the expression of coagulation factors in the CNS, the coagulopathy associated with focal cerebral ischemia (and its relationship to hemorrhagic transformation), the use of recombinant tissue plasminogen activator (rt-PA) in ischemic stroke and its study in animal models, the impact of rt-PA on neuron and CNS structure and function, and matrix protease generation and matrix degradation and hemostasis. Interwoven among these topics is evidence for interactions of coagulation factors with and within the CNS. How activation of hemostasis occurs in the cerebral tissues and how the brain responds are difficult questions that offer many research possibilities. PMID:24166247

  18. Triggers and drivers of autoimmunity: lessons from coeliac disease

    Science.gov (United States)

    Sollid, Ludvig M.; Jabri, Bana

    2013-01-01

    Preface Coeliac disease, an inflammatory disease of the small intestine, shares key features with autoimmune disorders, such as susceptibility genes, presence of autoantibodies and T cell-mediated destruction of specific cells. Strikingly, however, continuous exposure to the exogenous dietary antigen gluten and gluten-specific adaptive immunity are required to maintain immunopathology. These observations challenge the notion that autoimmunity requires adaptive immune activation towards self-antigens. Using coeliac disease as an example, we propose that other exogenous factors might be identified as drivers of autoimmune processes, in particular when evidence for T cells with specificity for self-antigens is lacking. PMID:23493116

  19. Expert Panel Workshop Consensus Statement on the Role of the Environment in the Development of Autoimmune Disease

    Science.gov (United States)

    Parks, Christine G.; Miller, Frederick W.; Pollard, Kenneth Michael; Selmi, Carlo; Germolec, Dori; Joyce, Kelly; Rose, Noel R.; Humble, Michael C.

    2014-01-01

    Autoimmune diseases include 80 or more complex disorders characterized by self-reactive, pathologic immune responses in which genetic susceptibility is largely insufficient to determine disease onset. In September 2010, the National Institute of Environmental Health Sciences (NIEHS) organized an expert panel workshop to evaluate the role of environmental factors in autoimmune diseases, and the state of the science regarding relevant mechanisms, animal models, and human studies. The objective of the workshop was to analyze the existing data to identify conclusions that could be drawn regarding environmental exposures and autoimmunity and to identify critical knowledge gaps and areas of uncertainty for future study. This consensus document summarizes key findings from published workshop monographs on areas in which “confident” and “likely” assessments were made, with recommendations for further research. Transcribed notes and slides were reviewed to synthesize an overview on exposure assessment and questions addressed by interdisciplinary panels. Critical advances in the field of autoimmune disease research have been made in the past decade. Collaborative translational and interdisciplinary research is needed to elucidate the role of environmental factors in autoimmune diseases. A focus on exposure assessment methodology is needed to improve the effectiveness of human studies, and more experimental studies are needed to focus on causal mechanisms underlying observed associations of environmental factors with autoimmune disease in humans. PMID:25196523

  20. Electromagnetic fields and health effects-epidemiologic studies of cancer, diseases of the central nervous system and arrhythmia-related heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Johansen, C.

    2004-07-01

    cohort of mobile phone subscribers comprising some 420 000 persons. No increased risk was observed for the cancers considered a priori to be possibly associated with the radiofrequency fields emitted by mobile phones, which