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Sample records for neuromyelitis optica pathogenesis

  1. Molecular Pathogenesis of Neuromyelitis Optica

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    Simon A Broadley

    2012-10-01

    Full Text Available Neuromyelitis optica (NMO is a rare autoimmune disorder, distinct from multiple sclerosis, causing inflammatory lesions in the optic nerves and spinal cord. An autoantibody (NMO IgG against aquaporin-4 (AQP4, a water channel expressed on astrocytes is thought to be causative. Peripheral production of the antibody is triggered by an unknown process in genetically susceptible individuals. Anti-AQP4 antibody enters the central nervous system (CNS when the blood brain barrier is made permeable and has high affinity for orthogonal array particles of AQP4. Like other autoimmune diseases, Th17 cells and their effector cytokines (such as interleukin 6 have been implicated in pathogenesis. AQP4 expressing peripheral organs are not affected by NMO IgG, but the antibody causes extensive astrocytic loss in specific regions of the CNS through complement mediated cytotoxicity. Demyelination occurs during the inflammatory process and is probably secondary to oligodendrocyte apoptosis subsequent to loss of trophic support from astrocytes. Ultimately, extensive axonal injury leads to severe disability. Despite rapid advances in the understanding of NMO pathogenesis, unanswered questions remain, particularly with regards to disease mechanisms in NMO IgG seronegative cases. Increasing knowledge of the molecular pathology is leading to improved treatment strategies.

  2. Systemic manifestations and pathogenesis exploration of neuromyelitis optica spectrum disorders

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    Hong JIANG

    2014-09-01

    Full Text Available Objective To investigate the immunological abnormalities beyond central nervous system (CNS associated with neuromyelitis optica spectrum disorders (NMOSDs.  Methods Clinical data of 56 patients with NMOSDs from January 2010 to December 2013 enrolled in Department of Neurology at Peking University People's Hospital were analyzed retrospectively. All patients were divided into 2 groups: neuromyelitis optica (N = 33 and non-neuromyelitis optica (N = 23. Each patient underwent detailed physical examination including internal medicine and nervous system. Records of complicated autoimmune diseases as well as scoring of Expanded Disability Status Scale (EDSS were used to evaluate disease severity. Part of patients received detection of multiple immunological indicators.  Results In all patients with NMOSDs, there were 3 cases with Hashimoto thyroiditis, one case with systemic lupus erythematosus (SLE and Sjögren's syndrome (SS, asthma, hyperthyroidism, rheumatoid arthritis and iridocyclitis, respectively. In patients whose immunological indices were available, the first three abnormal immunological changes were abnormal thyroid function (10/17, positive anti-nuclear antibody (14/28 and positive complement 3 (8/19. In addition, NMOSDs got worsen in 2 cases after delivery.  Conclusions NMOSDs coexist with many kinds of autoimmune diseases and multiple autoantibodies. The above-mentioned autoimmunity may be related to the pathogenesis of NMOSDs. Besides, pregnancy or delivery may aggravate the disease severity of NMOSDs. doi: 10.3969/j.issn.1672-6731.2014.09.009

  3. Spectrum of pediatric neuromyelitis optica.

    Science.gov (United States)

    Lotze, Timothy E; Northrop, Jennifer L; Hutton, George J; Ross, Benjamin; Schiffman, Jade S; Hunter, Jill V

    2008-11-01

    Our goal was to describe the spectrum of clinical phenotypes, laboratory and imaging features, and treatment in pediatric patients with neuromyelitis optica. The study consisted of a retrospective chart review of patients followed in a pediatric multiple sclerosis center with a diagnosis of neuromyelitis optica spectrum disorder. Nine patients with neuromyelitis optica spectrum disorders were included, all of whom were female. There were 4 black children, 2 Latin American children, 2 white children, and 1 child of mixed Latin American/white heritage. Median age at initial attack was 14 years (range: 1.9-16 years). Median disease duration was 4 years (range: 0.6-9 years). Tests for neuromyelitis optica immunoglobulin G were positive for 7 patients. Eight patients had transverse myelitis and optic neuritis, and 1 patient had longitudinally extensive transverse myelitis without optic neuritis but had a positive neuromyelitis optica immunoglobulin G antibody titer. Cerebral involvement on MRI was found in all subjects, 5 of whom were symptomatic with encephalopathy, seizures, hemiparesis, aphasia, vomiting, or hiccups. Immunosuppressive therapy reduced attack frequency and progression of disability. Pediatric neuromyelitis optica has a diverse clinical presentation and may be difficult to distinguish from multiple sclerosis in the early stages of the disease. The recognition of the broad spectrum of this disease to include signs and symptoms of brain involvement is aided by the availability of a serum biomarker: neuromyelitis optica immunoglobulin G. Early diagnosis and immunosuppresive treatment may help to slow the accumulation of severe disability.

  4. Genetics Home Reference: neuromyelitis optica

    Science.gov (United States)

    ... expand/collapse boxes. Description Neuromyelitis optica is an autoimmune disorder that affects the nerves of the eyes and ... system, which includes the brain and spinal cord. Autoimmune disorders occur when the immune system malfunctions and attacks ...

  5. Seronegative Neuromyelitis Optica Spectrum - The challenges on disease definition and pathogenesis

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    Douglas Kazutoshi Sato

    2014-06-01

    Full Text Available Neuromyelitis optica spectrum disorders (NMOSD are characterized by severe optic neuritis and/or longitudinally extensive transverse myelitis, and some brain lesions are also unique to NMOSD. Serum autoantibodies against aquaporin-4 (AQP4 are detected in most cases of NMOSD. However, some patients with NMOSD remain seronegative despite repetitive testing during attacks with highly sensitive cell-based assays. The differential diagnosis of NMOSD is not restricted to multiple sclerosis and it includes many diseases that can produce longitudinally extensive myelitis and/or optic neuritis. We review the clinical features, imaging, and laboratory findings that can be helpful on the diagnostic work-up, discuss the differences between AQP4 antibody positive and negative patients with NMOSD, including features of NMOSD with antibodies against myelin oligodendrocyte glycoprotein.

  6. Neuromyelitis Optica Lesion Mimicking Brainstem Glioma

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    J Gordon Millichap

    2007-12-01

    Full Text Available A 12-year-old girl who presented with weakness of the left extremities and right sided sixth cranial nerve palsy had neuromyelitis optica (NMO mistaken for brainstem glioma on MRI, in a report from Brain Research Institute, Yonsei University College of Medicine,Seoul, Republic of KoreaNeuromyelitis Optica, Optic-Spinal Syndrome, Spectroscopy.

  7. Cognitive impairment in Chinese neuromyelitis optica

    NARCIS (Netherlands)

    Zhang, N.; Li, Y.J.; Fu, Y.; Shao, J.H.; Luo, L.L.; Yang, L.; Shi, F.D.; Liu, Y.

    2015-01-01

    Background: Cognitive dysfunction is frequently seen in neuromyelitis optica (NMO). However, the features and influencing factors of cognitive impairment of Chinese NMO patients are unclear. Objective: To investigate the patterns of cognitive impairment in Chinese NMO patients, and correlate the

  8. Neuromyelitis Optica: A Case Report

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    Wei-Chia Chia

    2010-12-01

    Full Text Available Neuromyelitis optica (NMO, Devic's syndrome is a demyelinating disease of the central nervous system that predominantly affects the spinal cord and optic nerves. It is often confused with multiple sclerosis. Early discrimination between NMO and multiple sclerosis is important because the two diseases have different natural histories and treatment regimens. Seropositivity for NMO-IgG and longitudinally extensive spinal cord lesions (3 or more spinal segments are characteristic of NMO. Despite the absence of a definitive therapeutic strategy for NMO syndrome, methylprednisolone pulse therapy is recommended in the acute phase. Treatment strategies in relapse phases are aimed at preventing relapses, and increasing evidence shows a better clinical response of immunosuppressive therapy than immuno-modulating therapy (a standard multiple sclerosis-modulating therapy. We describe a 10-year-old girl who had visual loss due to acute optic neuritis at 6 years old and suffered repetitive myelitis 2 years later. NMO was diagnosed because of characteristic longitudinal myelitis and positive NMO-IgG. After combining therapy with prednisolone and an immunosuppressant (cyclophosphamide, the patient's medical condition was stable and no relapse symptoms were observed.

  9. A population-based study of neuromyelitis optica in Caucasians

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    Asgari, N; Lillevang, S T; Skejoe, H P B

    2011-01-01

    Epidemiologic studies have suggested different prevalence of neuromyelitis optica (NMO) in different ethnic groups. However, data on the incidence and prevalence of NMO in Caucasians are scarce.......Epidemiologic studies have suggested different prevalence of neuromyelitis optica (NMO) in different ethnic groups. However, data on the incidence and prevalence of NMO in Caucasians are scarce....

  10. Demographic and clinical features of neuromyelitis optica

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    Pandit, L.; Asgari, Nasrin; Apiwattanakul, M.

    2015-01-01

    The comparative clinical and demographic features of neuromyelitis optica (NMO) are not well known. In this review we analyzed peer-reviewed publications for incidence and prevalence, clinical phenotypes, and demographic features of NMO. Population-based studies from Europe, South East and Southern...... course, particularly in anti-aquaporin 4 antibody (anti AQP4-IgG)-positive patients. Ethnicity may have a bearing on disease phenotype and clinical outcome. Despite limitations inherent to the review process, themes noted in clinical and demographic features of NMO among different populations promote...

  11. EFNS guidelines on diagnosis and management of neuromyelitis optica

    DEFF Research Database (Denmark)

    Sellner, J; Boggild, M; Clanet, M

    2010-01-01

    Neuromyelitis optica (NMO) or Devic's disease is a rare inflammatory and demyelinating autoimmune disorder of the central nervous system (CNS) characterized by recurrent attacks of optic neuritis (ON) and longitudinally extensive transverse myelitis (LETM), which is distinct from multiple sclerosis...

  12. Brain MRI abnormalities in neuromyelitis optica

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    Wang Fei, E-mail: feiwang1973@gmail.com [Department of Radiology, Xuanwu Hospital, Capital University of Medical Sciences, 45 Chang-Chun St, Xuanwu District, Beijing 100053 (China); Liu Yaou, E-mail: asiaeurope80@gmail.com [Department of Radiology, Xuanwu Hospital, Capital University of Medical Sciences, 45 Chang-Chun St, Xuanwu District, Beijing 100053 (China); Duan Yunyun, E-mail: duanyun2003@sohu.com [Department of Radiology, Xuanwu Hospital, Capital University of Medical Sciences, 45 Chang-Chun St, Xuanwu District, Beijing 100053 (China); Li Kuncheng, E-mail: kunchengli@yahoo.com.cn [Department of Radiology, Xuanwu Hospital, Capital University of Medical Sciences, 45 Chang-Chun St, Xuanwu District, Beijing 100053 (China); Education Ministry Key Laboratory for Neurodegenerative Disease, Xuanwu Hospital, Capital University of Medical Sciences, 45 Chang-Chun St, Xuanwu District, Beijing 100053 (China)

    2011-11-15

    Objective: The purpose of this study was to explore brain MRI findings in neuromyelitis optica (NMO) and to investigate specific brain lesions with respect to the localization of aquaporin-4 (AQP-4). Materials and methods: Forty admitted patients (36 women) who satisfied the 2006 criteria of Wingerchuk et al. for NMO were included in this study. All patients received a neurological examination and MRI scanning including brain and spinal cord. MRIs were classified as normal, nonspecific, multiple sclerosis-like, typical abnormalities. MS-like lesions were too few to satisfy the Barkhof et al. criteria for MS. Confluent lesions involving high AQP-4 regions were considered typical. Non-enhancing deep white matter lesions other than MS-like lesions or typical lesions were classified as nonspecific. Results: Brain MRI lesions were delineated in 12 patients (25%). Four patients (10%) had hypothalamus, brainstem or periventricle lesions. Six (15%) patients were nonspecific, and 2 (5%) patients had multiple sclerosis-like lesions. Conclusion: Brain MRIs are negative in most NMO, and brain lesions do not exclude the diagnosis of NMO. Hypothalamus, brainstem or periventricle lesions, corresponding to high sites of AQP-4 in the brain, are indicative of lesions of NMO.

  13. Immunopathogenesis in Myasthenia Gravis and Neuromyelitis Optica

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    Zhen Wang

    2017-12-01

    Full Text Available Myasthenia gravis (MG and neuromyelitis optica (NMO are autoimmune channelopathies of the peripheral neuromuscular junction (NMJ and central nervous system (CNS that are mainly mediated by humoral immunity against the acetylcholine receptor (AChR and aquaporin-4 (AQP4, respectively. The diseases share some common features, including genetic predispositions, environmental factors, the breakdown of tolerance, the collaboration of T cells and B cells, imbalances in T helper 1 (Th1/Th2/Th17/regulatory T cells, aberrant cytokine and antibody secretion, and complement system activation. However, some aspects of the immune mechanisms are unique. Both targets (AChR and AQP4 are expressed in the periphery and CNS, but MG mainly affects the NMJ in the periphery outside of CNS, whereas NMO preferentially involves the CNS. Inflammatory cells, including B cells and macrophages, often infiltrate the thymus but not the target—muscle in MG, whereas the infiltration of inflammatory cells, mainly polymorphonuclear leukocytes and macrophages, in NMO, is always observed in the target organ—the spinal cord. A review of the common and discrepant characteristics of these two autoimmune channelopathies may expand our understanding of the pathogenic mechanism of both disorders and assist in the development of proper treatments in the future.

  14. Interferon Alpha Association with Neuromyelitis Optica

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    Nasrin Asgari

    2013-01-01

    Full Text Available Interferon-alpha (IFN-α has immunoregulatory functions in autoimmune inflammatory diseases. The goal of this study was to determine occurrence and clinical consequences of IFN-α in neuromyelitis optica (NMO patients. Thirty-six NMO and 41 multiple sclerosis (MS patients from a population-based retrospective case series were included. Expanded Disability Status Scale (EDSS score and MRI findings determined disease activity. Linear regression was used to assess the effects of the level of IFN-α on disability (EDSS. IFN-α was determined by sensitive ELISA assays. IFN-α was detectable in sera from 9/36 NMO patients, significantly more often than in the MS group (2/41 (P=0.0197. A higher frequency of IFN-α was observed in NMO patients with acute relapse compared to NMO patients in remission (P<0.001 and compared to the MS patients with relapse (P=0.010. In NMO patients, the levels of IFN-α were significantly associated with EDSS (P=0.0062. It may be concluded that IFN-α was detectable in a subgroup of NMO patients. Association of IFN-α levels with clinical disease activity and severity suggests a role for IFN-α in disease perpetuation and may provide a plausible explanation for a negative effect of IFN-1 treatment in NMO patients.

  15. Brain Abnormalities in Neuromyelitis Optica Spectrum Disorder

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    Woojun Kim

    2012-01-01

    Full Text Available Neuromyelitis optica (NMO is an idiopathic inflammatory syndrome of the central nervous system that is characterized by severe attacks of optic neuritis (ON and myelitis. Until recently, NMO was considered a disease without brain involvement. However, since the discovery of NMO-IgG/antiaqaporin-4 antibody, the concept of NMO was broadened to NMO spectrum disorder (NMOSD, and brain lesions are commonly recognized. Furthermore, some patients present with brain symptoms as their first manifestation and develop recurrent brain symptoms without ON or myelitis. Brain lesions with characteristic locations and configurations can be helpful in the diagnosis of NMOSD. Due to the growing recognition of brain abnormalities in NMOSD, these have been included in the NMO and NMOSD diagnostic criteria or guidelines. Recent technical developments such as diffusion tensor imaging, MR spectroscopy, and voxel-based morphometry reveal new findings related to brain abnormalities in NMOSD that were not identified using conventional MRI. This paper focuses on the incidence and characteristics of the brain lesions found in NMOSD and the symptoms that they cause. Recent studies using advanced imaging techniques are also introduced.

  16. Magnetic Resonance Imaging Features of Neuromyelitis Optica

    International Nuclear Information System (INIS)

    You, Sun Kyung; Song, Chang June; Park, Woon Ju; Lee, In Ho; Son, Eun Hee

    2013-01-01

    To report the magnetic resonance (MR) imaging features of the spinal cord and brain in patients of neuromyelitis optica (NMO). Between January 2001 and March 2010, the MR images (spinal cord, brain, and orbit) and the clinical and serologic findings of 11 NMO patients were retrospectively reviewed. The contrast-enhancement of the spinal cord was performed (20/23). The presence and pattern of the contrast-enhancement in the spinal cord were classified into 5 types. Acute myelitis was monophasic in 8 patients (8/11, 72.7%); and optic neuritis preceded acute myelitis in most patients. Longitudinally extensive cord lesion (average, 7.3 vertebral segments) was involved. The most common type was the diffuse and subtle enhancement of the spinal cord with a multifocal nodular, linear or segmental intense enhancement (45%). Most of the brain lesions (5/11, 10 lesions) were located in the brain stem, thalamus and callososeptal interphase. Anti-Ro autoantibody was positive in 2 patients, and they showed a high relapse rate of acute myelitis. Anti-NMO IgG was positive in 4 patients (4/7, 66.7%). The imaging findings of acute myelitis in NMO may helpful in making an early diagnosis of NMO which can result in a severe damage to the spinal cord, and to make a differential diagnosis of multiple sclerosis and inflammatory diseases of the spinal cord such as toxocariasis.

  17. Magnetic Resonance Imaging Features of Neuromyelitis Optica

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    You, Sun Kyung; Song, Chang June; Park, Woon Ju; Lee, In Ho; Son, Eun Hee [Chungnam National University College of Medicine, Chungnam National University Hospital, Daejeon (Korea, Republic of)

    2013-03-15

    To report the magnetic resonance (MR) imaging features of the spinal cord and brain in patients of neuromyelitis optica (NMO). Between January 2001 and March 2010, the MR images (spinal cord, brain, and orbit) and the clinical and serologic findings of 11 NMO patients were retrospectively reviewed. The contrast-enhancement of the spinal cord was performed (20/23). The presence and pattern of the contrast-enhancement in the spinal cord were classified into 5 types. Acute myelitis was monophasic in 8 patients (8/11, 72.7%); and optic neuritis preceded acute myelitis in most patients. Longitudinally extensive cord lesion (average, 7.3 vertebral segments) was involved. The most common type was the diffuse and subtle enhancement of the spinal cord with a multifocal nodular, linear or segmental intense enhancement (45%). Most of the brain lesions (5/11, 10 lesions) were located in the brain stem, thalamus and callososeptal interphase. Anti-Ro autoantibody was positive in 2 patients, and they showed a high relapse rate of acute myelitis. Anti-NMO IgG was positive in 4 patients (4/7, 66.7%). The imaging findings of acute myelitis in NMO may helpful in making an early diagnosis of NMO which can result in a severe damage to the spinal cord, and to make a differential diagnosis of multiple sclerosis and inflammatory diseases of the spinal cord such as toxocariasis.

  18. Immunopathogenesis in Myasthenia Gravis and Neuromyelitis Optica

    Science.gov (United States)

    Wang, Zhen; Yan, Yaping

    2017-01-01

    Myasthenia gravis (MG) and neuromyelitis optica (NMO) are autoimmune channelopathies of the peripheral neuromuscular junction (NMJ) and central nervous system (CNS) that are mainly mediated by humoral immunity against the acetylcholine receptor (AChR) and aquaporin-4 (AQP4), respectively. The diseases share some common features, including genetic predispositions, environmental factors, the breakdown of tolerance, the collaboration of T cells and B cells, imbalances in T helper 1 (Th1)/Th2/Th17/regulatory T cells, aberrant cytokine and antibody secretion, and complement system activation. However, some aspects of the immune mechanisms are unique. Both targets (AChR and AQP4) are expressed in the periphery and CNS, but MG mainly affects the NMJ in the periphery outside of CNS, whereas NMO preferentially involves the CNS. Inflammatory cells, including B cells and macrophages, often infiltrate the thymus but not the target—muscle in MG, whereas the infiltration of inflammatory cells, mainly polymorphonuclear leukocytes and macrophages, in NMO, is always observed in the target organ—the spinal cord. A review of the common and discrepant characteristics of these two autoimmune channelopathies may expand our understanding of the pathogenic mechanism of both disorders and assist in the development of proper treatments in the future. PMID:29312313

  19. Neuromyelitis optica-- en vigtig differentialdiagnose til multipel sklerose

    DEFF Research Database (Denmark)

    Holbech, Jakob Vormstrup; Falah, Masoud

    2009-01-01

    Neuromyelitis optica (Devic's disease) is a rare autoimmune neuroinflammatory disease. The disease can often be difficult to distinguish from multiple sclerosis. It is important to be familiar with the disease because of the risk of rapid progression to disability or even death. We describe a 15...

  20. Neuro-ophthalmic manifestation of neuromyelitis optica spectrum disorders

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    Xiao-jun ZHANG

    2014-10-01

    Full Text Available Neuromyelitis optica spectrum disorders (NMOSDs include classic neuromyelitis optica (NMO, opticospinal multiple sclerosis (OSMS, limited form of NMO and isolated optic neuritis or myelitis accompanied by either systemic autoimmune diseases or typical MRI findings of NMO. The common neuro-ophthalmic features of NMOSDs include simultaneous or consecutive bilateral optic neuritis, more commonly seen optic disk edema and surrounding exudate, poor visual recovery, steroid responsiveness and dependency. Combined with serum aquaporin 4 (AQP4 antibody and brain MRI examination, these clinical features can be helpful to the early differential diagnosis between NMOSDs and MS. Some types of eye movement abnormalities have been reported in patients with NMOSDs, but further investigation needs to be done before the specificity of these features are confirmed. doi: 10.3969/j.issn.1672-6731.2014.10.003

  1. Neuromyelitis optica spectrum disorders without and with autoimmune diseases

    OpenAIRE

    Zhang, Bingjun; Zhong, Yi; Wang, Yanqiang; Dai, Yongqiang; Qiu, Wei; Zhang, Lei; Li, Haiyan; Lu, Zhengqi

    2014-01-01

    Background Neuromyelitis optica spectrum disorder (NMOSD) can coexist with non-organ-specific or organ-specific autoimmune diseases. The aim of this study was to investigate and compare the features between NMOSD without and with autoimmune diseases, and NMOSD with non-organ-specific and organ-specific autoimmune diseases. Methods One hundred and fifty five NMOSD patients without autoimmune diseases (n = 115) and with autoimmune diseases (n = 40) were enrolled. NMOSD with autoimmune diseases ...

  2. Autoimmune AQP4 channelopathies and neuromyelitis optica spectrum disorders.

    Science.gov (United States)

    Hinson, Shannon R; Lennon, Vanda A; Pittock, Sean J

    2016-01-01

    Neuromyelitis optica (NMO) spectrum disorders (SD) represent an evolving group of central nervous system (CNS)-inflammatory autoimmune demyelinating diseases unified by a pathogenic autoantibody specific for the aquaporin-4 (AQP4) water channel. It was historically misdiagnosed as multiple sclerosis (MS), which lacks a distinguishing biomarker. The discovery of AQP4-IgG moved the focus of CNS demyelinating disease research from emphasis on the oligodendrocyte and myelin to the astrocyte. NMO is recognized today as a relapsing disease, extending beyond the optic nerves and spinal cord to include brain (especially in children) and skeletal muscle. Brain magnetic resonance imaging abnormalities, identifiable in 60% of patients at the second attack, are consistent with MS in 10% of cases. NMOSD-typical lesions (another 10%) occur in AQP4-enriched regions: circumventricular organs (causing intractable nausea and vomiting) and the diencephalon (causing sleep disorders, endocrinopathies, and syndrome of inappropriate antidiuresis). Advances in understanding the immunobiology of AQP4 autoimmunity have necessitated continuing revision of NMOSD clinical diagnostic criteria. Assays that selectively detect pathogenic AQP4-IgG targeting extracellular epitopes of AQP4 are promising prognostically. When referring to AQP4 autoimmunity, we suggest substituting the term "autoimmune aquaporin-4 channelopathy" for the term "NMO spectrum disorders." Randomized clinical trials are currently assessing the efficacy and safety of newer immunotherapies. Increasing therapeutic options based on understanding the molecular pathogenesis is anticipated to improve the outcome for patients with AQP4 channelopathy. © 2016 Elsevier B.V. All rights reserved.

  3. Neuromyelitis optica-like pathology is dependent on type I interferon response

    DEFF Research Database (Denmark)

    Khorooshi, Reza; Wlodarczyk, Agnieszka; Asgari, Nasrin

    2013-01-01

    Neuromyelitis optica is an antibody-mediated autoimmune inflammatory disease of the central nervous system. Reports have suggested that interferon beta which is beneficial for multiple sclerosis, exacerbates neuromyelitis optica. Our aim was to determine whether type I interferon plays a role in ...

  4. A Case of Neuromyelitis Optica Masquerading as Miller Fisher Syndrome

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    Yuka Furutani

    2014-10-01

    Full Text Available A 22-year-old woman presented with double vision that she had experienced since an infection 2 weeks previously. A neurological examination showed limited bilateral eye abduction, mimicking Miller Fisher syndrome. However, T2-weighted magnetic resonance imaging of her brain revealed hyperintense areas in the tegmentum of the pons, including the abducens nucleus, and her serum anti-aquaporin-4 antibody test was positive. She was finally diagnosed with neuromyelitis optica. Intravenous high-dose steroid therapy immediately improved the patient's abduction palsy, but bilateral optic neuritis manifested during the treatment. Subsequent treatment with plasma exchange improved her optic neuritis symptoms.

  5. Use of advanced magnetic resonance imaging techniques in neuromyelitis optica spectrum disorder

    NARCIS (Netherlands)

    S. Kremer (Stephane); F. Renard (Felix); S. Achard (Sophie); M.A. Lana-Peixoto (Marco A.); J. Palace (Jacqueline); N. Asgari (Nasrin); E.C. Klawiter (Eric C.); S. Tenembaum (Silvia); B. Banwell (Brenda); B.M. Greenberg (Benjamin M.); J.L. Bennett (Jeffrey); M. Levy (Michael); P. Villoslada (Pablo); A. Saiz (Albert Abe); K. Fujihara (Kazuo); K.H. Chan (Koon Ho); S. Schippling (Sven); F. Paul (Friedemann); H.J. Kim (Ho Jin); J. De Seze (Jerome); J.T. Wuerfel (Jens T.); P. Cabre (Philippe); R. Marignier (Romain); T. Tedder (Thomas); E.D. van Pelt - Gravesteijn (Daniëlle); S. Broadley (Simon); T. Chitnis (Tanuja); D. Wingerchuk (Dean); L. Pandit (Lekha); M.I. Leite (M. Isabel); M. Apiwattanakul (Metha); I. Kleiter (Ingo); N. Prayoonwiwat (Naraporn); M. Han (May); K. Hellwig (Kerstin); K. Van Herle (Katja); G. John (Gareth); D.C. Hooper (D. Craig); I. Nakashima (Ichiro); D. Sato (Douglas); M.R. Yeaman (Michael R.); E. Waubant (Emmanuelle); S. Zamvil (Scott); O. Stüve (Olaf); O. Aktas (Orhan); T.J. Smith (Terry J.); A. Jacob (Anu); K. O'Connor (Kevin)

    2015-01-01

    textabstractBrain parenchymal lesions are frequently observed on conventional magnetic resonance imaging (MRI) scans of patients with neuromyelitis optica (NMO) spectrum disorder, but the specific morphological and temporal patterns distinguishing them unequivocally from lesions caused by other

  6. Neuromyelitis optica and neuromyelitis optica spectrum disorder: Natural history and long-term outcome, an Indian experience

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    Sujit Abajirao Jagtap

    2015-01-01

    Full Text Available Background: Neuromyelitis optica (NMO has evolved from devic′s classical description to a broader disease spectrum, from monophasic illness to a polyphasic illness with multiple recurrences, disease confined to optic nerve and spinal cord to now brain stem, cerebrum and even endocrinopathy due to hypothalamic involvement. Objectives: To report, the epidemiological characteristics, clinical presentations, recurrence rate, treatment and response to therapy in 26 patients with NMO and NMO spectrum disorder among the Indian population. Methods: We performed observational, retrospective analysis of our prospectively maintained data base of patients with NMO, longitudinally extensive transverse myelitis during the period of January 2003-December 2012 who satisfied the national multiple sclerosis society (NMSS task force criteria for diagnosis of NMO and NMO spectrum disorder. Results: There were 26 patients (female: male, 21:5, the mean age of onset of symptom was 27 years (range 9-58, standard deviation = 12. Twenty-one patients (80% fulfilled NMSS criteria for NMO while rest 5 patients (20% were considered as NMO spectrum disorder. Seven patients (27% had a monophasic illness, 19 patients (73% had a polyphasic illness with recurrences. The Median recurrence rate was 4/patient in the polyphasic group. 13 (50% patient were tested for aquaporin 4 antibody, 8 (61% were positive while 5 patients (39% were negative. All patients received intravenous methyl prednisolone, 9 patients (35% required further treatment for acute illness in view of unresponsiveness to steroids. Thirteen patients (50% received disease-modifying agents for recurrences. Mean duration of follow-up was 5 years. All patients had a good outcome (modified Rankin scale, <3 except one who had poor visual recovery. Conclusion: Neuromyelitis optica/NMO spectrum disorder is demyelinating disorder with female predominance, polyphasic course, myelitis being most common event although brain

  7. 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....

  8. Treatment of neuromyelitis optica: an evidence based review

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    Douglas Sato

    2012-01-01

    Full Text Available Neuromyelitis optica (NMO is an inflammatory disease of the central nervous system characterized by severe optic neuritis and transverse myelitis, usually with a relapsing course. Aquaporin-4 antibody is positive in a high percentage of NMO patients and it is directed against this water channel richly expressed on foot processes of astrocytes. Due to the severity of NMO attacks and the high risk for disability, treatment should be instituted as soon as the diagnosis is confirmed. There is increasing evidence that NMO patients respond differently from patients with multiple sclerosis (MS, and, therefore, treatments for MS may not be suitable for NMO. Acute NMO attacks usually are treated with high dose intravenous corticosteroid pulse and plasmapheresis. Maintenance therapy is also required to avoid further attacks and it is based on low-dose oral corticosteroids and non-specific immunosuppressant drugs, like azathioprine and mycophenolate mofetil. New therapy strategies using monoclonal antibodies like rituximab have been tested in NMO, with positive results in open label studies. However, there is no controlled randomized trial to confirm the safety and efficacy for the drugs currently used in NMO.

  9. NMO-IgG: A Specific Biomarker for Neuromyelitis Optica

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    Brian G. Weinshenker

    2006-01-01

    Full Text Available Neuromyelitis optica (NMO is an inflammatory demyelinating disease that principally targets the optic nerves and spinal cord and often leads to severe disability and occasionally life threatening respiratory failure. Although its clinical manifestations overlap with those of multiple sclerosis (MS, in established cases these two conditions can be distinguished on the basis of clinical, radiological, and routine spinal fluid studies. The diagnosis in early cases or limited forms of NMO is difficult. We recently discovered a unique IgG autoantibody (NMO-IgG that is highly specific to patients with NMO and thus a valuable diagnostic aid. Its antigen, aquaporin-4 (AQP4, is the central nervous system’s predominant water channel protein. This antibody has not yet been proven to be pathogenic, but several facts suggest that it might be, including the similarity of the immunohistochemical pattern of NMO-(AQP4 IgG binding to mouse CNS tissues to the pattern of immune complex deposition in autopsied patients’ spinal cord tissue. The spectrum of diseases identified by NMO-IgG is broader than has previously been recognized clinically and includes incomplete forms of NMO, such as recurrent transverse myelitis without optic neuritis and recurrent optic neuritis without myelitis.

  10. Rituximab in Neuromyelitis Optica Spectrum Disorders: Our Experience.

    Science.gov (United States)

    Jade, Jui Dilip; Bansi, Srishti; Singhal, Bhim

    2017-01-01

    Neuromyelitis optica (NMO) is an inflammatory demyelinating central nervous system disease, with recurrent attacks of severe bilateral optic neuritis and longitudinally extensive transverse myelitis. Aggressive immunosuppression is essential to prevent clinical relapses and permanent disability. Rituximab, a monoclonal antibody to CD20, has been found effective in several reports and small uncontrolled studies. There is a paucity of data regarding its use in Indian patients. The aim of this study was to report the results of rituximab treatment in NMO spectrum disorders (NMOSDs) in the Indian scenario. This study is a retrospective, observational study including 13 NMOSD patients treated with rituximab. After initial therapy in the acute episode with IV methylprednisolone and if needed plasma exchange, therapy was initiated as a cycle of intravenous rituximab, two doses 2 weeks apart of 1 g each. Subsequent cycles were advised at intervals of every 6 months. The primary outcome measure was annualized relapse rate (ARR), defined as a number of clinical attacks per year. Clinical adverse events were recorded throughout the study. In the study, mean ARR reduced from 2.61 to 0.09 after therapy ( P = 0.000685). Of 13 patients, 8 (61.54%) were completely relapse free after starting treatment with rituximab. Treatment was well tolerated and no serious adverse events were noted. The treatment of NMOSDs with rituximab in Indian patients reduces the frequency of relapses and is well tolerated.

  11. Paraneoplastic neuromyelitis optica spectrum disorder associated with stomach carcinoid tumor.

    Science.gov (United States)

    Al-Harbi, Talal; Al-Sarawi, Adnan; Binfalah, Mohamed; Dermime, Said

    2014-09-01

    Neuromyelitis optica (NMO), or Devic's syndrome, is an autoimmune central nervous system demyelinating disorder primarily affecting the spinal cord and the optic nerves. It is characterized by the presence of NMO antibodies, alongside clinical and radiological findings. NMO and NMO-spectrum disorders (NMO-SD) have been reported in autoimmune disorders, and are infrequently described as a paraneoplastic syndrome with cancers of lung, breast, and carcinoid tumors of the thyroid. We report a patient who presented with severe vomiting, blurring of vision, vertigo, diplopia, left hemiparesis and hemisensory loss and ataxia. She was found to have a longitudinally-extensive demyelinating lesion extending from the medulla to the upper cervical spinal cord on MRI. Her gastric endoscopy revealed carcinoid tumor of the stomach, and classic paraneoplastic antibodies in the serum were negative. She had extremely high serum gastrin level and high titer of NMO IgG autoantibody. The patient made an excellent recovery with tumor resection and immunotherapy, with both clinical and radiological improvement. On rare instances, NMO or NMO-SD may present as a paraneoplastic neurological syndrome associated with carcinoid tumor of the stomach. Copyright © 2014 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

  12. Seronegative Neuromyelitis Optica Spectrum Disorder following Exposure to Hepatitis B Vaccination

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    Richard Heekin

    2015-04-01

    Full Text Available Controversy exists regarding a potential link between exposure to recombinant hepatitis B vaccine (HBV and central nervous system demyelinating diseases. Here, we present a case of seronegative neuromyelitis optica spectrum disorder (NMOSD following exposure to HBV. A 28-year-old man developed painful eye movements 11 days after exposure to HBV. Within 24 h, he experienced vision loss, ascending numbness, and ataxia. T-spine MRI showed a cord lesion spanning T6-T9. Brain MRI showed bilateral optic nerve contrast enhancement and a right-sided internal capsule lesion. Cerebrospinal fluid analysis was normal, including negative oligoclonal bands and normal IgG index. AQP4-IgG serology was negative. The patient's visual symptoms improved after treatment with steroids and plasma exchange. He received plasma exchange weekly for 4 weeks with decreased numbness and tingling as well as improved coordination. Treatment with mycophenolate mofetil was started, and the patient remains clinically stable with near resolution of his prior symptoms. Neuromyelitis optica is characterized by optic neuritis and/or longitudinally extensive transverse myelitis. While our patient tested seronegative for AQP4-IgG (which remains negative in 10-50% of NMOSD cases, despite testing with the most sensitive assays available, he did meet NMOSD diagnostic criteria. In a literature review, we found 7 cases of NMOSD onset or relapse associated with exposure to various vaccines, but to our knowledge this represents the first published report of NMOSD onset following exposure to HBV. While causality between vaccination and CNS demyelinating disease remains elusive, it is important to report these cases to help develop safer vaccinations and provoke further inquiry into the pathogenesis of NMOSD.

  13. Seronegative Neuromyelitis Optica Spectrum Disorder following Exposure to Hepatitis B Vaccination.

    Science.gov (United States)

    Heekin, Richard; Gandhy, Chetan; Robertson, Derrick

    2015-01-01

    Controversy exists regarding a potential link between exposure to recombinant hepatitis B vaccine (HBV) and central nervous system demyelinating diseases. Here, we present a case of seronegative neuromyelitis optica spectrum disorder (NMOSD) following exposure to HBV. A 28-year-old man developed painful eye movements 11 days after exposure to HBV. Within 24 h, he experienced vision loss, ascending numbness, and ataxia. T-spine MRI showed a cord lesion spanning T6-T9. Brain MRI showed bilateral optic nerve contrast enhancement and a right-sided internal capsule lesion. Cerebrospinal fluid analysis was normal, including negative oligoclonal bands and normal IgG index. AQP4-IgG serology was negative. The patient's visual symptoms improved after treatment with steroids and plasma exchange. He received plasma exchange weekly for 4 weeks with decreased numbness and tingling as well as improved coordination. Treatment with mycophenolate mofetil was started, and the patient remains clinically stable with near resolution of his prior symptoms. Neuromyelitis optica is characterized by optic neuritis and/or longitudinally extensive transverse myelitis. While our patient tested seronegative for AQP4-IgG (which remains negative in 10-50% of NMOSD cases, despite testing with the most sensitive assays available), he did meet NMOSD diagnostic criteria. In a literature review, we found 7 cases of NMOSD onset or relapse associated with exposure to various vaccines, but to our knowledge this represents the first published report of NMOSD onset following exposure to HBV. While causality between vaccination and CNS demyelinating disease remains elusive, it is important to report these cases to help develop safer vaccinations and provoke further inquiry into the pathogenesis of NMOSD.

  14. Continuous Positive Airway Pressure (CPAP for prevention of recurrent pneumonia in the Neuromyelitis Optica patient

    Directory of Open Access Journals (Sweden)

    James A. Welker

    2014-01-01

    Conclusions: Patients with Neuromyelitis Optica differ from those with traumatic spinal cord injury as they have a chronic progressive systemic illness that causes continued deterioration of their nervous system resulting in the need for routine monitoring that ensures the timely addition of CPAP for the prevention of pneumonia and its associated medical expenses.

  15. Disruption of the leptomeningeal blood barrier in neuromyelitis optica spectrum disorder

    DEFF Research Database (Denmark)

    Asgari, Nasrin; Flanagan, Eoin P.; Fujihara, Kazuo

    2017-01-01

    Objective: To describe leptomeningeal blood-barrier impairment reflected by MRI gadoliniumenhanced lesions in patients with aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD). Methods: A retrospective case series of 11 AQP4-IgG-positive NMOSD patients ...

  16. Diagnosis of neuromyelitis optica (NMO) spectrum disorders: is MRI obsolete?

    Energy Technology Data Exchange (ETDEWEB)

    Downer, Jonathan James; Carter, Ranjana; Kueker, Wilhelm; Quaghebeur, Gerardine [John Radcliffe Hospital, Department of Neuroradiology, Oxford (United Kingdom); Leite, Maria Isabel; Palace, Jacqueline [Oxford University, Department of Clinical Neurology, Oxford (United Kingdom)

    2012-04-15

    Neuromyelitis optica (NMO) is a severe demyelinating disease that preferentially involves spinal cord and optic nerve. It is part of a spectrum of neurological conditions associated with antibodies to aquaporin-4 (AQP4). This study investigates the role of MRI where novel, more sensitive AQP4 antibody immunoassay techniques are being used. Retrospective review of neuroimaging in 69 patients (25 antibody positive, 44 antibody negative), investigated in the context of suspected NMO or NMO spectrum disorder, was performed independently by two consultant neuroradiologists. Longitudinally extensive, central spinal cord lesions were more frequent in AQP4 positive patients (95.2% vs 35.5%, p < 0.0001; 85.7% vs 45.2%, p = 0.015). Multiple sclerosis diagnostic criteria were less frequently fulfilled on brain MRI in antibody positive patients (5.6% vs 33.3%, p = 0.035). Juxtacortical and corpus callosal lesions were also less common in this group (16.7% vs 46.7%, p = 0.063; 5.6% vs 46.7%, p = 0.0034). Hypothalamic and periependymal disease related to the aqueduct was not seen in antibody negative patients. T1 hypointensity was more common in cord lesions of antibody positive patients (75.0% vs 35.3%, p = 0.037). However, this characteristic did not discriminate antibody positive and negative longitudinally extensive cord lesions (73.3% vs 62.5%, p = 0.66). The NMO spectrum of diseases are among an increasing number of neurological conditions defined by serological tests. However, despite improved immunoassay techniques, MRI of the brain and spinal cord continues to be among the first-line investigations in these patients, providing valuable diagnostic information that will help guide patient management. (orig.)

  17. Neuromyelitis optica: association with paroxysmal painful tonic spasms.

    Science.gov (United States)

    Carnero Contentti, E; Leguizamón, F; Hryb, J P; Celso, J; Pace, J L Di; Ferrari, J; Knorre, E; Perassolo, M B

    2016-10-01

    Paroxysmal painful tonic spasms (PPTS) were initially described in multiple sclerosis (MS) but they are more frequent in neuromyelitis optica (NMO). The objective is to report their presence in a series of cases of NMO and NMO spectrum disorders (NMOSD), as well as to determine their frequency and clinical features. We conducted a retrospective assessment of medical histories of NMO/NMOSD patients treated in 2 hospitals in Buenos Aires (Hospital Durand and Hospital Álvarez) between 2009 and 2013. Out of 15 patients with NMOSD (7 with definite NMO and 8 with limited NMO), 4 presented PPTS (26.66%). PPTS frequency in the definite NMO group was 57.14% (4/7). Of the 9 patients with longitudinally extensive transverse myelitis (LETM), 44.44% (9/15) presented PPTS. Mean age was 35 years (range, 22-38 years) and all patients were women. Mean time between NMO diagnosis and PPTS onset was 7 months (range, 1-29 months) and mean time from last relapse of LETM was 30 days (range 23-40 days). LETM (75% cervicothoracic and 25% thoracic) was observed by magnetic resonance imaging (MRI) in all patients. Control over spasms and pain was achieved in all patients with carbamazepine (associated with gabapentin in one case). No favourable responses to pregabalin, gabapentin, or phenytoin were reported. PPTS are frequent in NMO. Mean time of PPTS onset is approximately one month after an LETM relapse, with extensive cervicothoracic lesions appearing on the MRI scan. They show an excellent response to carbamazepine but little or no response to pregabalin and gabapentin. Prospective studies with larger numbers of patients are necessary in order to confirm these results. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. White matter atrophy and cognitive dysfunctions in neuromyelitis optica.

    Directory of Open Access Journals (Sweden)

    Frederic Blanc

    Full Text Available Neuromyelitis optica (NMO is an inflammatory disease of central nervous system characterized by optic neuritis and longitudinally extensive acute transverse myelitis. NMO patients have cognitive dysfunctions but other clinical symptoms of brain origin are rare. In the present study, we aimed to investigate cognitive functions and brain volume in NMO. The study population consisted of 28 patients with NMO and 28 healthy control subjects matched for age, sex and educational level. We applied a French translation of the Brief Repeatable Battery (BRB-N to the NMO patients. Using SIENAx for global brain volume (Grey Matter, GM; White Matter, WM; and whole brain and VBM for focal brain volume (GM and WM, NMO patients and controls were compared. Voxel-level correlations between diminished brain concentration and cognitive performance for each tests were performed. Focal and global brain volume of NMO patients with and without cognitive impairment were also compared. Fifteen NMO patients (54% had cognitive impairment with memory, executive function, attention and speed of information processing deficits. Global and focal brain atrophy of WM but not Grey Matter (GM was found in the NMO patients group. The focal WM atrophy included the optic chiasm, pons, cerebellum, the corpus callosum and parts of the frontal, temporal and parietal lobes, including superior longitudinal fascicle. Visual memory, verbal memory, speed of information processing, short-term memory and executive functions were correlated to focal WM volumes. The comparison of patients with, to patients without cognitive impairment showed a clear decrease of global and focal WM, including brainstem, corticospinal tracts, corpus callosum but also superior and inferior longitudinal fascicles. Cognitive impairment in NMO patients is correlated to the decreased of global and focal WM volume of the brain. Further studies are needed to better understand the precise origin of cognitive impairment in

  19. Brain magnetic resonance imaging findings in relapsing neuromyelitis optica.

    Science.gov (United States)

    Cabrera-Gómez, José A; Quevedo-Sotolongo, L; González-Quevedo, A; Lima, S; Real-González, Y; Cristófol-Corominas, M; Romero-García, K; Ugarte-Sánchez, C; Jordán-González, J; de la Nuez, J E González; Lahera, J García; Tellez, R; Pedroso-Ibañez, I; Roca, R Rodríguez; Cabrera-Núñez, A Y

    2007-03-01

    Some studies showed abnormalities in brain magnetic resonance imaging (MRI) of relapsing neuromyelitis optica (R-NMO) from 12 to 46%. These abnormalities are described as compatible/non-compatible with multiple sclerosis (MS). To describe the abnormal brain MRI lesions in R-NMO with imaging studies conducted with more sensitive white matter change techniques. Thirty patients with R-NMO were selected. All MRI brain studies were performed with a 1.5-T Siemens MRI system according to the Standardized MR Imaging Protocol for Multiple Sclerosis from the Consortium of MS Centers Consensus Guidelines. Brain MRI images were evaluated in 29 R-NMO cases because in one case the MRI images were not appropriate for the study. Of these 29 brain MRI studies, 19 cases (65.5%) had at least one or more lesions (1-57) and 10 were negative (34.4%). Brain MRI findings in 19 cases were characterized in T2/fluid-attenuated inversion-recovery (FLAIR) by the presence of subcortical/deep white matter lesions in 16 (84.2%) cases (1-50), most of them 3 mm, were observed in 4 (21.05%) cases without cerebellar involvement. T1 studies demonstrated absence of hypointense regions. Optic nerve enhancement was observed in 6/19 patients (31.5%). None of the brain MRI abnormalities observed were compatible with Barkhof et al. criteria of MS. This study, based on a Cuban patient population, with long duration of disease, good sample size and detailed characterization by MRI, demonstrated the brain MRI pattern of R-NMO patients, which is different from MS.

  20. Neuromyelitis optica med udtalte cerebrale magnetisk resonans-skannings-forandringer hos en niårig pige

    DEFF Research Database (Denmark)

    Trautner, Simon; Pedersen, Hans Peder; Bendtson, Inger

    2009-01-01

    Neuromyelitis optica (NMO) is a rare inflammatory disorder characterised by optic neuritis and transverse myelitis. We report a severe pediatric case presenting with impaired vision, tetraparesis, bladder retention and lower extremity pain. Magnetic resonance imaging demonstrated longitudinally e...

  1. Neuromyelitis optica-IgG testing in an Indian cohort with neuromyelitis optica and related demyelinating disorders: Our experience

    Directory of Open Access Journals (Sweden)

    Narayanan Unni

    2013-01-01

    Full Text Available Background: Neuromyelitis optica (NMO is an immune-mediated inflammatory demyelinating disorder of the central nervous system with a predilection for the optic nerves and the spinal cord. Immunopathological evidence suggests that the target antigen of the disease is aquaporin-4. An IgG antibody against this protein has been explored as a molecular marker for the disease and as a diagnostic tool due to its high sensitivity and specificity in various populations. Objective: To assess the value of NMO-IgG testing in Indian patients with clinical and magnetic resonance imaging features consistent with NMO and longitudinally extensive transverse myelitis (LETM. Materials and Methods: Forty-five patients with clinical and magnetic resonance imaging features consistent with NMO, LETM, and MS were tested for serum NMO-IgG. Of these patients, 22 patients satisfied revised (2006 Wingerchuk criteria for NMO (excluding NMO-IgG status and 11 patients had LETM. Twelve patients satisfied the revised (2010 McDonald criteria for multiple sclerosis (MS. Results: Of the 21 patients, satisfying the criteria for NMO and for whom the test results were available, 17 were positive for NMO-IgG (80.9%, and of the 11 patients having LETM, 6 (54.5% were positive for NMO-IgG. In one patient with NMO, the test result was not available. None of the 12 patients satisfying McDonald criteria for MS showed NMO-IgG seropositivity. Conclusion: Our study suggests that it is worthwhile to pursue NMO-IgG testing as a diagnostic tool for patients with clinical and Magnetic Resonance Imaging (MRI features consistent with NMO and LETM in the Indian population.

  2. Adult methylmalonic acidemia presented as neuromyelitis optica: one case report

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    Sheng-de LI

    2015-10-01

    Full Text Available A 26-year-old male was admitted to our department, complaining of cognitive impairment, urine incontinence for 3 months, blurred vision for one month and numbness of bilateral lower limbs for 20 days. Presumed as “depression” and “viral encephalitis”, antidepressant and dexamethasone had been given but had no response. Neurological examination demonstrated impaired orientation to time and place; hearing impairment of right ear; normal muscle force in upper limbs, proximal lower muscle force was 2 and distal was 0; normal tendon reflex in both upper limbs; diminished tendon reflex in both lower limbs; left palmomental reflex (+; bilateral Babinski sign (+. Below T10: diminished superficial, deep sensation and cortical sensory. Cranial MRI on admission revealed widened sulci in bilateral cleft and frontal, temporal and insular lobes, indicating brain atrophy. Spinal MRI revealed high-intensity signals of C3-7 level and T1-12 level. The patient was diagnosed as “neuromyelitis optica (NMO” at first, but cognitive impairment is really rare in NMO. It finally turned out to be “inherited metabolic diseases” with the negative results of aquaporin 4 (AQP4, NMO-IgG, GM1, voltage-gated potassium channel (VGKC from serum and cerebrospinal fluid (CSF. The elevated level of plasm homocysteine [30.79 mmol/L (5-20 mmol/L] and urine methylmalonic acid [0.40 mmol/L (0.001 mmol/L] ascertained the diagnosis of methylmalonic acidemia. The patient was given oral treatment of folate 5 mg (3 times a day, 13 days and levocarnitine 1 g (3 times a day, 8 days and intramuscular injection of mecobalamine 1mg (once a day, 4 days or 0.50 mg (once a day, 8 days and adenosylcobalamine 0.50 mg (once a day, 8 days. Sixteen days on discharge, the patient’s neurological examination revealed no obvious recovery of vision; lower muscle force: about Ⅳ, right sensory level: T12-L1, and left sensory level lowered to L3. Reexamination of MRI revealed brain atrophy

  3. Cognitive performance of neuromyelitis optica patients: comparison with multiple sclerosis

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    Sandra Vanotti

    2013-06-01

    Full Text Available The aim of the present research was to investigate cognitive pattern of patients with neuromyelitis optica (NMO and to compare it with multiple sclerosis (MS patients' performance. Methods: Fourteen NMO, 14 relapsing remitting multiple sclerosis (RRMS, and 14 healthy control patients participated in the investigation. Neuropsychological functions were evaluated with the Brief Repeatable Neuropsychological Battery for MS; Symbol Digit Modalities Test; Digit Span; and Semantic Fluency. Results: Fifty-seven percent of NMO patients and 42.85% of the MS ones had abnormal performance in at least two cognitive tests. The NMO Group showed abnormal performance in verbal fluency, verbal and visual memories, with greater attention deficits. NMO patients outperformed healthy control in the paced auditory serial addition test (PASAT. However, no difference was found between NMO and RRMS patients. Conclusions: The NMO Group showed more dysfunction in attention and verbal fluencies than in verbal and visual memories. When compared with the MS patients, a similar dysfunction pattern was found. O objetivo da presente pesquisa foi investigar o padrão cognitivo de pacientes com neuromielite óptica (NMO e compará-lo com o desempenho de pacientes com esclerose múltipla (EM. Métodos: Quatorze pacientes com NMO, 14 com esclerose múltipla recorrente remitente (EMRR e 14 participantes do Controle saudáveis participaram da presente investigação. As funções neuropsicológicas foram avaliadas com a Bateria Breve de Testes Neuropsicológicos de Rao, Teste Símbolo Digit e a Fluência Semântica. Resultados: Cinquenta e sete por cento dos pacientes com NMO e 42,85% daqueles com EM apresentaram desempenho anormal em pelo menos dois testes cognitivos. O Grupo NMO apresentarou desempenho anormal na fluência verbal e nas memórias visual e verbal, com maiores déficits de atenção. Pacientes com NMO superaram os controles saudáveis em PASAT. No entanto, não foi

  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. Diffusion tensor imaging of brain in relapsing neuromyelitis optica

    International Nuclear Information System (INIS)

    Yu Chunshui; Li Kuncheng; Qin Wen; Lin Fuchun; Jiang Tianzi

    2007-01-01

    Objective: To investigate the presence of occult brain tissue damage in patients with relapsing neuromyelitis optica (RNMO) and its possible mechanism by using diffusion tensor imaging (DTI). Methods: DTI scans were performed in 16 patients with RNMO and 16 sex- and age-matched healthy controls. Histogram analysis of mean diffusivity (MD) and fractional anisotropy (FA) was performed in brain tissue (BT), white matter (WM) and gray matter (GM) to detect the presence of occult brain tissue damage in RNMO patients. Region of interest (ROI) analysis of MD and FA was also performed in 6 dedicated regions with or without direct connection with spinal cord or optic nerve to determine the relationship between occult brain tissue damage and the damage of spinal cord and optic nerve. Results Patients with RNMO had a significantly higher average MD of the BT [RNMO (0.95 ± 0.02) x 10 -3 mm 2 /s, controls (0.91 ± 0.03) x 10 -3 mm 2 /s, t=3.940, P -3 mm 2 /s, controls(0.80 ± 0.02) x 10 -3 mm 2 /s, t=3.117, P=0.004] an.d GM [RNMO (1.06 ± 0.04) x 10 -3 mm 2 /s, controls (0.88 ± 0.05) x 10 -3 mm 2 /s, t=4.031, P -3 mm 2 /s, controls (0.81 ± 0.02) x 10 -3 mm 2 /s, t=4.373, P -3 mm 2 /s, controls (1.11 ± 0.10) x 10 -3 mm 2 /s, t=4.260, P -3 mm 2 /s, controls (0.87 ± 0.05) x 10 -3 mm 2 /s, t4.391, P -3 mm 2 /s, controls (0.72 ± O.01) x 10 -3 mm 2 /s, t=4.683, P -3 mm 2 /s, controls (0.82+0.03) x 10-3 mm2/s, t = 4. 619, P -3 mm 2 /s, controls (0.73±0.03) x 10 -3 mm 2 /s, t =2.804, P=0.009 and splenium of corpus callosum: RNMO(0.77 ± 0.05) x 10 -3 mm 2 /s, controls (0.73 ± 0.04) x 10 -3 mm 2 /s, t=2.234, P=0.033] and FA [genu of corpus callosum: RNMO 0.82± 0.03 ,controls 0.82 ± 0.03, t=0.196, P=0.846 and splenium of corpus caltosum: RNMO 0.83±0.03, controls 0.83 ± 0.02, t=0.333, P=0.741] between RNMO patients and controls. Conclusion: RNMO patients have occult brain tissue damage, which might be related to the antegrade and retrograde degeneration secondary to lesions in

  6. A Rare Case of Neuromyelitis Optica Spectrum Disorder in Patient with Sjogren’s Syndrome

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    Supat Thongpooswan

    2014-01-01

    Full Text Available We report a 48-year-old female with the history of Sjogren’s syndrome who presented with 3-week history of tingling, numbness, and shooting back, waist, and bilateral leg pain and numbness in the pelvic region with urinary and bowel incontinence. Physical examination was remarkable for reduced motor power in both lower extremities with spasticity. Sensory deficit was noted at the T6 level. Laboratory investigation revealed elevated ESR and CRP and positive serum antiaquaporin-4 IgG. Thoracic and lumbar magnetic resonance imaging revealed abnormal patchy areas, leptomeningeal enhancement through the thoracic cord extending from T3 through T6 levels, without evidence of cord compression. Impression of neuromyelitis optica spectrum disorder was made and patient was treated with methylprednisolone intravenously followed by tapering oral prednisone. Neurological symptoms gradually improved with resolution of bowel and urinary incontinence. In a patient with Sjogren’s syndrome who presents with neurological complaints, the possibility of neuromyelitis optica or neuromyelitis optica spectrum disorder should be considered. Awareness of the possibility of CNS disease is important due to the serious nature of CNS complications, some of which are treatable with immunosuppressants. Our patient with Sjogren’s syndrome who presented with myelopathy benefited from early recognition and institution of appropriate therapy.

  7. Comparison of the efficacy of azathioprine and rituximab in neuromyelitis optica spectrum disorder

    DEFF Research Database (Denmark)

    Nikoo, Zahra; Badihian, Shervin; Shaygannejad, Vahid

    2017-01-01

    Neuromyelitis optica spectrum disorder (NMOSD) often follows a relapsing course. As disability in NMOSD is attack-related, effective treatments are needed. We aimed to compare the efficacy of azathioprine (AZA) and rituximab (RIT) as maintenance therapy in NMOSD patients. An open, randomized...... clinical trial was conducted during September 2015 to December 2016, in Isfahan, Iran. Initially, 100 NMOSD patients were approached, 86 entered the study, and 68 cases completed the trial. All patients had a relapsing–remitting course with expanded disability extended scale (EDSS) ≤7 (median 2.75, range...

  8. Convergence spasm due to aquaporin-positive neuromyelitis optica spectrum disorder

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    Pınar Özçelik

    2017-06-01

    Full Text Available A female 27 presented with nausea and diplopia for 1 week. On examination she had normal vertical gaze but would develop convergence with miosis whenever she made horizontal saccades. Pupils were 6 mm and unreactive to light. MRI showed extensive hyperintensity in the dorsal midbrain and thalamus. Spinal MRI and CSF were both normal. Serum aquaporin-4-antibody was positive. She was treated with steroids and plasmapheresis and after 3 months convergence spasm resolved but pupils remained unreactive. Neuromyelitis optica often presents with brainstem signs, rarely a dorsal midbrain syndrome. Convergence spasm is occasionally of organic neurologic origin.

  9. A systematic analysis of the complement pathways in patients with neuromyelitis optica indicates alteration but no activation during remission

    DEFF Research Database (Denmark)

    Veszeli, Nóra; Füst, György; Csuka, Dorottya

    2014-01-01

    Neuromyelitis optica (NMO) is an autoimmune demyelinating inflammatory disorder, mediated by pathogenic autoantibodies against aquaporin 4 (AQP4), the main water channel of the central nervous system (CNS). NMO is characterized by local IgG deposition and complement activation within the CNS, but...

  10. Endocrinopathies in paediatric-onset neuromyelitis optica spectrum disorder with aquaporin 4 (AQP4) antibody.

    Science.gov (United States)

    Hacohen, Yael; Messina, Silvia; Gan, Hoong-Wei; Wright, Sukhvir; Chandratre, Saleel; Leite, Maria Isabel; Fallon, Penny; Vincent, Angela; Ciccarelli, Olga; Wassmer, Evangeline; Lim, Ming; Palace, Jacqueline; Hemingway, Cheryl

    2017-08-01

    The involvement of the diencephalic regions in neuromyelitis optica spectrum disorder (NMOSD) may lead to endocrinopathies. In this study, we identified the following endocrinopathies in 60% (15/25) of young people with paediatric-onset aquaporin 4-Antibody (AQP4-Ab) NMOSD: morbid obesity ( n = 8), hyperinsulinaemia ( n = 5), hyperandrogenism ( n = 5), amenorrhoea ( n = 5), hyponatraemia ( n = 4), short stature ( n = 3) and central hypothyroidism ( n = 2) irrespective of hypothalamic lesions. Morbid obesity was seen in 88% (7/8) of children of Caribbean origin. As endocrinopathies were prevalent in the majority of paediatric-onset AQP4-Ab NMOSD, endocrine surveillance and in particular early aggressive weight management is required for patients with AQP4-Ab NMOSD.

  11. Anti-N-methyl-d-aspartate receptor encephalitis in a patient with neuromyelitis optica spectrum disorders.

    Science.gov (United States)

    Luo, Jing-Jing; Lv, He; Sun, Wei; Zhao, Juan; Hao, Hong-Jun; Gao, Feng; Huang, Yi-Ning

    2016-07-01

    We described a female patient with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis occurring sequentially with neuromyelitis optica spectrum disorders (NMOSD). The 19-year-old patient initially presented a diencephalic syndrome with aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) and brain lesions which involving bilateral medial temporal lobes and periependymal surfaces of the third ventricle on magnetic resonance imaging (MRI). Ten months later, the patient developed cognitive impairment, psychiatric symptoms and dyskinesia with left basal ganglia lesions on brain MRI. Meanwhile, the anti-NMDAR antibodies were positive in the patient's serum and cerebrospinal fluid, while the screening tests for an ovarian teratoma and other tumors were all negative. Hence, the patient was diagnosed NMOSD and anti-NMDAR encephalitis followed by low-dose rituximab treatment with a good response. This case was another evidence for demyelinating syndromes overlapping anti-NMDAR encephalitis in Chinese patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Posterior reversible encephalopathy syndrome masquerading as progressive multifocal leukoencephalopathy in rituximab treated neuromyelitis optica.

    Science.gov (United States)

    Berger, Joseph R; Neltner, Janna; Smith, Charles; Cambi, Franca

    2014-11-01

    Both progressive multifocal leukoencephalopathy (PML) and posterior reversible encephalopathy syndrome (PRES) have been reported as complications of rituximab therapy. These disorders may appear indistinguishable on magnetic resonance imaging (MRI). We report on a 42 year old woman with neuromyelitis optica (NMO) of 10 years duration who developed extensive white matter disease affecting chiefly both parietal lobes 6 months after her first and only dose of rituximab. The MRI findings suggested the diagnosis of PML, but her history was more consistent with PRES. Ultimately, a brain biopsy was performed which was consistent with the diagnosis of PRES. PRES and PML may have overlapping symptomatology and be indistinguishable on MRI. An approach to distinguishing between these two disorders is addressed. Copyright © 2014. Published by Elsevier B.V.

  13. Neuromyelitis optica spectrum disorder in patient with systemic lupus erythematosus - our experience

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    Božić Ksenija

    2018-01-01

    Full Text Available Introduction. Neuromyelitis optica spectrum disorder (NMOSD is a rare demyelinating immune-mediated central nervous system disease. It is extremely rare to occur in patients with systemic lupus erythematosus (SLE, and it represents a diagnostic and therapeutic challenge. Case report. A 38-year-old Caucasian woman with medical history of SLE and new onset of flaccid paraparesis, fecal and urinary incontinence, persistent nausea and vomiting was admitted to our hospital. Based on the clinical presentation, magnetic resonance imaging findings and positive aquaporin 4 (AQP4 antibodies, a NMOSD with coexisting SLE were diagnosed. Pulse-doses of cyclophosphamide and glucocorticoids were efficient in patient treatment. Conclusion. In a patient with SLE and symptoms of longitudinal extensive transverse myelitis and/or optic neuritis and area postrema syndrome, assessment of AQP4 antibodies is neccessary for diagnosing NMOSD. Accurate diagnosis, and timely and long-term administration of immunosuppressive therapy are crucial for favorable outcome of these two coexisting diseases.

  14. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients

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    Jarius Sven

    2012-01-01

    Full Text Available Abstract Background The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab in patients with neuromyelitis optica spectrum disorders (NMOSD has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. Objective To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. Methods Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%. Results Seropositive patients were found to be predominantly female (p 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome. Conclusion This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients.

  15. Neuromyelitis optica IgG in the cerebrospinal fluid induces astrocytopathy in optic nerve

    DEFF Research Database (Denmark)

    Soelberg, Kerstin; Lillevang, Søren Thue; Mørch, Marlene

    was coincident with deposition of complement. Histopathological lesions were markedly enhanced with extensive/long-segment astrocytopathy of optic nerve and optic chiasm involvement in AQP4- IgG+ C + anti-CD59a treated mice. Such pathology was not seen in mice receiving normal human IgG, C and anti-CD59a......Background: Serum immunoglobulin G targeting the astrocyte water channel aquaporin-4 (AQP4) in the central nervous system (CNS) is a biomarker for neuromyelitis optica spectrum disease (NMOSD). Optic neuritis (ON) is believed to be immune-mediated and is associated with AQP4-IgG in NMOSD......-ON. The predilection of the optic nerve in NMOSD may partly be explained by the dense expression of AQP4 in the optic nerve. We previously reported that AQP4-IgG in cerebrospinal fluid (CSF) becomes widely distributed in the brain and causes complementdependent astrocyte injury in periventricular areas and brain...

  16. Neuromyelitis optica spectrum disease characteristics in Isfahan, Iran: A cross-sectional study

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    Fereshte Ashtari

    2017-01-01

    Full Text Available Background: Neuromyelitis optica spectrum disease (NMOSD is a severe autoimmune demyelinating disorder of the central nervous system that throughout epidemiological data, it has not been completely determined. The aim of this study was to assess characteristics of NMOSD patients in Isfahan as one of the most prevalent cities for multiple sclerosis in Iran. Materials and Methods: Forty-five patients diagnosed as neuromyelitis optica (NMO disease through 5 years enrolled in this study. Demographics and characteristics of disease such as Expanded Disability Status Scale (EDSS score, disease duration, clinical symptoms, laboratory data, and magnetic resonance imaging findings (including T1, T2, and flair protocols were recorded. NMO-immunoglobulin G serology assay was done in all of the patients by ELISA test. Results: Female to male ratio was 5.4:1. The mean age of disease onset was 29.8 ± 11.2 years. NMO antibody was positive in 24.4% of patients. The presenting symptoms were optic neuritis (55.5%, transverse myelitis (40%, and brainstem symptoms (4.5%. The interval between the first and second attack was 19.28 ± 31.27 months (range: 1 month to 17 years. The mean EDSS score of the patients was 2.8 ± 2.25. Frequency of long-extending cervical plaque was higher among men than women (85.7% vs. 57.9%. Conclusion: Based on this study, the mean age of NMOSD onset among Isfahan population was considerably lower than other studies, and there was higher frequency of long-extending cervical lesion among male patients which needs more consideration in further studies.

  17. An update on the evidence for the efficacy and safety of rituximab in the management of neuromyelitis optica.

    Science.gov (United States)

    Collongues, Nicolas; de Seze, Jérôme

    2016-05-01

    Neuromyelitis optica spectrum disorders (NMOSDs) is a new concept which includes classical neuromyelitis optica (NMO) and partial forms of NMO such as recurrent optic neuritis with positive aquaporin-4 antibodies (AQP4) or brainstem symptoms (intractable hiccups or vomiting). This disease is clearly distinguished from multiple sclerosis (MS) and the therapeutic approach is clearly different. Rituximab is actually considered to be one of the most efficient treatments of NMOSD, even if class I studies are clearly lacking. In the present review, we describe the state of the art about rituximab treatment in NMOSD, including adults and children, plus its efficacy and tolerance and we also underline the questions that should be addressed in the near future.

  18. Successful treatment for psychomotor agitation in neuromyelitis optica spectrum disorder with trazodone–risperidone combination: a case report

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    Narita Z

    2017-03-01

    Full Text Available Zui Narita,1 Harumasa Takano,1 Tomiki Sumiyoshi2 1Department of Psychiatry, National Center Hospital, 2Department of Clinical Epidemiology, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan Abstract: Neuromyelitis optica (NMO is a relapsing disease that typically affects the spinal cord and optic nerves. So far, a few studies have reported pharmacologic treatment for psychiatric symptoms in patients with NMO spectrum disorder (NMOSD. However, no literature has described psychomotor agitation associated with the disease and its treatment. We report an 84-year-old woman with NMOSD whose psychomotor agitation was effectively treated with a combination of trazodone and risperidone. Our observation suggests the ability of augmentation of antipsychotic drugs with antidepressants to ameliorate psychotic symptoms associated with NMOSD. Keywords: neuromyelitis optica, multiple sclerosis, psychomotor agitation, trazodone, risperidone

  19. [Diagnostic criteria in acute neuromyelitis].

    Science.gov (United States)

    Panea, Cristina; Petrescu, Simona; Monica, Pop; Voinea, Liliana; Dascălu, Ana-Maria; Nicolae, Miruna; Ungureanu, E; Panca, Aida; Grădinaru, Sânziana

    2007-01-01

    Neuromyelitis optica, also known as Devic disease, was identified in the 19th century, is one of the inflammatory idiopathic demyelinating diseases of the central nervous system, often mistaken for severe multiple sclerosis. In 1999 it had been proposed diagnostic criteria for neuromyelitis optica, but in 2006 these criteria were revised by Dean Wingerchuck. These criteria are 99% sensitive and 90% specific for differentiating neuromyelitis optica from multiple sclerosis that present with optic neuritis or a myelitis syndrome. In the following article we present clinical, spinal and cerebral MR imaging, serological and aspects of cerebrospinal fluid examination features of neuromyelitis optica and the revised criteria of neuromyelitis optica established in 2006. The recently identified serum antibody biomarker: neuromyelitis optica immunoglobulin G (NMO Ig G), which target aquaporin 4 water channel, distinguish neuromyelitis optica from multiple sclerosis, is one of the revised criteria of neuromyelitis optica.

  20. The Contribution of Optical Coherence Tomography in Neuromyelitis Optica Spectrum Disorders

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    Javier Mateo

    2017-09-01

    Full Text Available Neuromyelitis optica spectrum disorders (NMOSD comprises a group of central nervous system disorders of inflammatory autoimmune origin that mainly affect the optic nerves and the spinal cord and can cause severe visual and general disability. The clinical signs are similar to those of multiple sclerosis (MS, with the result that it is often difficult to differentiate between the two, thus leading to misdiagnosis. As the treatment and prognosis of NMOSD and MS are different, it is important to make an accurate and early diagnosis of NMOSD. Optical coherence tomography (OCT is a non-invasive technique that enables a quantitative study of the changes that the optic nerve and the macula undergo in several neurodegenerative diseases. Many studies have shown that some of these changes, such as retinal nerve fiber layer thinning or microcystic macular edema, can be related to alterations in the brain due to neurodegenerative disorders. The purpose of this mini-review is to show how OCT can be useful for the diagnosis of NMOSD and follow-up of affected patients, as well as for the differential diagnosis with MS.

  1. Recent insights into the pathology of multiple sclerosis and neuromyelitis optica.

    Science.gov (United States)

    Wegner, Christiane

    2013-12-01

    Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system. Traditionally, demyelinating lesions in the white matter have been regarded as the most important pathological feature in MS, but recent pathological and imaging studies confirmed substantial changes in grey matter and normal-appearing white matter. MS lesions are characterized by inflammation, demyelination, axonal damage and astrogliosis. During early MS lesion formation acute axonal injury is extensive and correlates with inflammation. In addition to focal lesions, diffuse wide-spread changes including neuroaxonal degeneration and compartmentalized inflammation are likely to contribute to increasing disability in progressive MS. Neuromyelitis optica (NMO) is classically characterized by severe transverse myelitis and optic neuritis, but brain lesions are also present in the majority of NMO patients. The discovery of the NMO-specific antibody demonstrated that NMO is a disease entity distinct from MS. This antibody binds to aquaporin-4 expressed in astrocytes and ependymal cells. NMO lesions are characterized by inflammation, demyelination, axonal damage and a marked loss of aquaporin-4. Early NMO lesions demonstrate a pronounced humoral inflammatory response and astrocytic cell death with loss of aquaporin-4, followed by inflammatory demyelination and axonal damage. These recent findings contribute to a better understanding of different mechanisms leading to inflammatory demyelination. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. The Contribution of Optical Coherence Tomography in Neuromyelitis Optica Spectrum Disorders.

    Science.gov (United States)

    Mateo, Javier; Esteban, Olivia; Martínez, Mireya; Grzybowski, Andrzej; Ascaso, Francisco Javier

    2017-01-01

    Neuromyelitis optica spectrum disorders (NMOSD) comprises a group of central nervous system disorders of inflammatory autoimmune origin that mainly affect the optic nerves and the spinal cord and can cause severe visual and general disability. The clinical signs are similar to those of multiple sclerosis (MS), with the result that it is often difficult to differentiate between the two, thus leading to misdiagnosis. As the treatment and prognosis of NMOSD and MS are different, it is important to make an accurate and early diagnosis of NMOSD. Optical coherence tomography (OCT) is a non-invasive technique that enables a quantitative study of the changes that the optic nerve and the macula undergo in several neurodegenerative diseases. Many studies have shown that some of these changes, such as retinal nerve fiber layer thinning or microcystic macular edema, can be related to alterations in the brain due to neurodegenerative disorders. The purpose of this mini-review is to show how OCT can be useful for the diagnosis of NMOSD and follow-up of affected patients, as well as for the differential diagnosis with MS.

  3. Neuromyelitis optica and the evolving spectrum of autoimmune aquaporin-4 channelopathies: a decade later.

    Science.gov (United States)

    Pittock, Sean J; Lucchinetti, Claudia F

    2016-02-01

    The discovery of AQP4-IgG (a pathogenic antibody that targets the astrocytic water channel aquaporin-4), as the first sensitive and specific biomarker for any inflammatory central nervous system demyelinating disease (IDD), has shifted emphasis from the oligodendrocyte and myelin to the astrocyte as a central immunopathogenic player. Neuromyelitis optica (NMO) spectrum disorders (SDs) represent an evolving spectrum of IDDs extending beyond the optic nerves and spinal cord to include the brain (especially in children) and, rarely, muscle. NMOSD typical brain lesions are located in areas that highly express the target antigen, AQP4, including the circumventricular organs (accounting for intractable nausea and vomiting) and the diencephalon (accounting for sleep disorders, endocrinopathies, and syndrome of inappropriate antidiuresis). Magnetic resonance imaging brain abnormalities fulfill Barkoff criteria for multiple sclerosis in up to 10% of patients. As the spectrum broadens, the importance of highly specific assays that detect pathogenic AQP4-IgG targeting extracellular epitopes of AQP4 cannot be overemphasized. The rapid evolution of our understanding of the immunobiology of AQP4 autoimmunity necessitates continuing revision of NMOSD diagnostic criteria. Here, we describe scientific advances that have occurred since the discovery of NMO-IgG in 2004 and review novel targeted immunotherapies. We also suggest that NMOSDs should now be considered under the umbrella term autoimmune aquaporin-4 channelopathy. © 2015 New York Academy of Sciences.

  4. Altered topological organization of white matter structural networks in patients with neuromyelitis optica.

    Directory of Open Access Journals (Sweden)

    Yaou Liu

    Full Text Available OBJECTIVE: To investigate the topological alterations of the whole-brain white-matter (WM structural networks in patients with neuromyelitis optica (NMO. METHODS: The present study involved 26 NMO patients and 26 age- and sex-matched healthy controls. WM structural connectivity in each participant was imaged with diffusion-weighted MRI and represented in terms of a connectivity matrix using deterministic tractography method. Graph theory-based analyses were then performed for the characterization of brain network properties. A multiple linear regression analysis was performed on each network metric between the NMO and control groups. RESULTS: The NMO patients exhibited abnormal small-world network properties, as indicated by increased normalized characteristic path length, increased normalized clustering and increased small-worldness. Furthermore, largely similar hub distributions of the WM structural networks were observed between NMO patients and healthy controls. However, regional efficiency in several brain areas of NMO patients was significantly reduced, which were mainly distributed in the default-mode, sensorimotor and visual systems. Furthermore, we have observed increased regional efficiency in a few brain regions such as the orbital parts of the superior and middle frontal and fusiform gyri. CONCLUSION: Although the NMO patients in this study had no discernible white matter T2 lesions in the brain, we hypothesize that the disrupted topological organization of WM networks provides additional evidence for subtle, widespread cerebral WM pathology in NMO.

  5. Brain parenchymal damage in neuromyelitis optica spectrum disorder - A multimodal MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Pache, F.; Paul, F. [Max Delbrueck Center for Molecular Medicine and Charite Universitaetsmedizin Berlin, NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Berlin (Germany); Charite Universitaetsmedizin Berlin, Department of Neurology, Berlin (Germany); Zimmermann, H.; Lacheta, A.; Papazoglou, S.; Kuchling, J.; Wuerfel, J.; Brandt, A.U. [Max Delbrueck Center for Molecular Medicine and Charite Universitaetsmedizin Berlin, NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Berlin (Germany); Finke, C. [Charite Universitaetsmedizin Berlin, Department of Neurology, Berlin (Germany); Humboldt-Universitaet zu Berlin, Berlin School of Mind and Brain, Berlin (Germany); Hamm, B. [Charite Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany); Ruprecht, K. [Charite Universitaetsmedizin Berlin, Department of Neurology, Berlin (Germany); Scheel, M. [Max Delbrueck Center for Molecular Medicine and Charite Universitaetsmedizin Berlin, NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Berlin (Germany); Charite Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany)

    2016-12-15

    To investigate different brain regions for grey (GM) and white matter (WM) damage in a well-defined cohort of neuromyelitis optica spectrum disorder (NMOSD) patients and compare advanced MRI techniques (VBM, Subcortical and cortical analyses (Freesurfer), and DTI) for their ability to detect damage in NMOSD. We analyzed 21 NMOSD patients and 21 age and gender matched control subjects. VBM (GW/WM) and DTI whole brain (TBSS) analyses were performed at different statistical thresholds to reflect different statistical approaches in previous studies. In an automated atlas-based approach, Freesurfer and DTI results were compared between NMOSD and controls. DTI TBSS and DTI atlas based analysis demonstrated microstructural impairment only within the optic radiation or in regions associated with the optic radiation (posterior thalamic radiation p < 0.001, 6.9 % reduction of fractional anisotropy). VBM demonstrated widespread brain GM and WM reduction, but only at exploratory statistical thresholds, with no differences remaining after correction for multiple comparisons. Freesurfer analysis demonstrated no group differences. NMOSD specific parenchymal brain damage is predominantly located in the optic radiation, likely due to a secondary degeneration caused by ON. In comparison, DTI appears to be the most reliable and sensitive technique for brain damage detection in NMOSD. (orig.)

  6. Use of Advanced Magnetic Resonance Imaging Techniques in Neuromyelitis Optica Spectrum Disorder

    Science.gov (United States)

    Kremer, Stephane; Renard, Felix; Achard, Sophie; Lana-Peixoto, Marco A.; Palace, Jacqueline; Asgari, Nasrin; Klawiter, Eric C.; Tenembaum, Silvia N.; Banwell, Brenda; Greenberg, Benjamin M.; Bennett, Jeffrey L.; Levy, Michael; Villoslada, Pablo; Saiz, Albert; Fujihara, Kazuo; Chan, Koon Ho; Schippling, Sven; Paul, Friedemann; Kim, Ho Jin; de Seze, Jerome; Wuerfel, Jens T.

    2016-01-01

    Brain parenchymal lesions are frequently observed on conventional magnetic resonance imaging (MRI) scans of patients with neuromyelitis optica (NMO) spectrum disorder, but the specific morphological and temporal patterns distinguishing them unequivocally from lesions caused by other disorders have not been identified. This literature review summarizes the literature on advanced quantitative imaging measures reported for patients with NMO spectrum disorder, including proton MR spectroscopy, diffusion tensor imaging, magnetization transfer imaging, quantitative MR volumetry, and ultrahigh-field strength MRI. It was undertaken to consider the advanced MRI techniques used for patients with NMO by different specialists in the field. Although quantitative measures such as proton MR spectroscopy or magnetization transfer imaging have not reproducibly revealed diffuse brain injury, preliminary data from diffusion-weighted imaging and brain tissue volumetry indicate greater white matter than gray matter degradation. These findings could be confirmed by ultrahigh-field MRI. The use of nonconventional MRI techniques may further our understanding of the pathogenic processes in NMO spectrum disorders and may help us identify the distinct radiographic features corresponding to specific phenotypic manifestations of this disease. PMID:26010909

  7. European ancestry predominates in neuromyelitis optica and multiple sclerosis patients from Brazil.

    Directory of Open Access Journals (Sweden)

    Doralina Guimarães Brum

    Full Text Available BACKGROUND: Neuromyelitis optica (NMO is considered relatively more common in non-Whites, whereas multiple sclerosis (MS presents a high prevalence rate, particularly in Whites from Western countries populations. However, no study has used ancestry informative markers (AIMs to estimate the genetic ancestry contribution to NMO patients. METHODS: Twelve AIMs were selected based on the large allele frequency differences among European, African, and Amerindian populations, in order to investigate the genetic contribution of each ancestral group in 236 patients with MS and NMO, diagnosed using the McDonald and Wingerchuck criteria, respectively. All 128 MS patients were recruited at the Faculty of Medicine of Ribeirão Preto (MS-RP, Southeastern Brazil, as well as 108 healthy bone marrow donors considered as healthy controls. A total of 108 NMO patients were recruited from five Neurology centers from different Brazilian regions, including Ribeirão Preto (NMO-RP. PRINCIPAL FINDINGS: European ancestry contribution was higher in MS-RP than in NMO-RP (78.5% vs. 68.7% patients. In contrast, African ancestry estimates were higher in NMO-RP than in MS-RP (20.5% vs. 12.5% patients. Moreover, principal component analyses showed that groups of NMO patients from different Brazilian regions were clustered close to the European ancestral population. CONCLUSIONS: Our findings demonstrate that European genetic contribution predominates in NMO and MS patients from Brazil.

  8. Default-mode network and deep gray-matter analysis in neuromyelitis optica patients.

    Science.gov (United States)

    Rueda-Lopes, Fernanda C; Pessôa, Fernanda M C; Tukamoto, Gustavo; Malfetano, Fabíola Rachid; Scherpenhuijzen, Simone Batista; Alves-Leon, Soniza; Gasparetto, Emerson L

    2018-02-20

    The aim of our study was to detect functional changes in default-mode network of neuromyelitis optica (NMO) patients using resting-state functional magnetic resonance images and the evaluation of subcortical gray-matter structures volumes. NMO patients (n=28) and controls patients (n=19) were enrolled. We used the integrated registration and segmentation tool, part of FMRIB's Software Library (FSL) to segment subcortical structures including the thalamus, caudate nucleus, putamen, hippocampus and amygdalae. Resting-state functional magnetic resonance images were post-processed using the Multivariate Exploratory Linear Optimized Decomposition into Independent Components, also part of FSL. Average Z-values extracted from the default-mode network were compared between patients and controls using t-tests (P values default-mode network of patients compared to controls, notably in the precuneus and right hippocampus (corrected Pdefault-mode network. The hyperactivity of certain default-mode network areas may reflect cortical compensation for subtle structural damage in NMO patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  9. A voxel-based morphometry study of brain volume changes in patients with neuromyelitis optica

    International Nuclear Information System (INIS)

    Duan Yunyun; Liu Yaou; Liang Peipeng; Huang Jing; Ren Zhuoqiong; Ye Jing; Dong Huiqing; Chen Hai; Li Kuncheng

    2012-01-01

    Objective: To detect changes of regional grey matter and white matter volume in patients of neuromyelitis optica (NMO) by voxel-based morphometry (VBM), and investigate its relationship with clinical variables. Methods: Conventional magnetic resonance imaging (MRI) and structural three-dimensional MRI were obtained from 20 NMO and 20 sex-and age-matched healthy volunteers. The comparison of grey matter and white matter volume between the two groups was analyzed by VBM tools of statistical parametric mapping (SPM) 5. Pearson correlation analysis was used to assess correlations between regional volume decrease and disease duration and expanded disability status scale (EDSS) scores in NMO patients. Results: Compared with normal controls, NMO patients had grey matter atrophy in several cortical regions, such as right inferior frontal gyrus (cluster size 514), left superior temporal gyrus (282), right middle temporal gyrus (229) and right insula (211) (t=3.58-5.11, AlphaSim corrected, P<0.05). White matter atrophy was found in several subcortical regions in NMO patients, such as right precentral and postcentral gyrus (cluster size 457, 110), left middle frontal gyrus (285), and right inferior parietal lobule (231) (t=2.90-4.25, AlphaSim corrected, P<0.05). Grey matter and white matter volume loss were not significantly correlated with clinical duration or EDSS score in NMO. Conclusion: By means of VBM, regional atrophy of grey matter and white matter is found in NMO patients, which may provide evidence for brain structural abnormality in NMO. (authors)

  10. [A case of neuromyelitis optica presenting ileus as a neurologic finding].

    Science.gov (United States)

    Takayama, Kei; Kojima, Akihiro; Kanda, Takayuki; Takeuchi, Masaru

    2012-10-01

    To report an atypical case of neuromyelitis optica (NMO) with Sjögren syndrome that presented only ileus as a neurologic finding. A thirty two-year-old woman was hospitalized for abnormal abdominal symptoms, and was diagnosed as having paralytic ileus. Dry eye symptoms due to Sjogren syndrome were also observed, and visual acuity OU decreased suddenly 10 days after hospitalization. The best corrected visual acuity was 0.04 OD and 0.6 OS, and the optic discs OU were swollen and red. Although no neurologic signs were found, pleocytosis and abnormal MRI findings suggested NMO. Steroid pulse therapy was performed, and after three cycles, the ileus symptoms disappeared, and the disturbed visual acuity OU returned to normal. Because the anti-aquaporin 4 antibody was positive and no abnormal abdominal findings that might have caused ileus were found, we diagnosed NMO presenting only paralytic ileus as a neurologic finding. Differential diagnosis is important for NMO initiated by ileus as the only neurologic sign.

  11. The expanded spectrum of neuromyelitis optica: evidences for a new definition

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    Marco A Lana-Peixoto

    2012-10-01

    Full Text Available Neuromyelitis optica (NMO has been traditionally described as the association of recurrent or bilateral optic neuritis and longitudinally extensive transverse myelitis (LETM. Identification of aquaporin-4 antibody (AQP4-IgG has deeply changed the concept of NMO. A spectrum of NMO disorders (NMOSD has been formulated comprising conditions which include both AQP4-IgG seropositivity and one of the index events of the disease (recurrent or bilateral optic neuritis and LETM. Most NMO patients harbor asymptomatic brain MRI lesions, some of them considered as typical of NMO. Some patients with aquaporin-4 autoimmunity present brainstem, hypothalamic or encephalopathy symptoms either preceding an index event or occurring isolatedly with no evidence of optic nerve or spinal involvement. On the opposite way, other patients have optic neuritis or LETM in association with typical lesions of NMO on brain MRI and yet are AQP4-IgG seronegative. An expanded spectrum of NMO disorders is proposed to include these cases.

  12. Multifrequency magnetic resonance elastography of the brain reveals tissue degeneration in neuromyelitis optica spectrum disorder

    Energy Technology Data Exchange (ETDEWEB)

    Streitberger, Kaspar-Josche [Charite - Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany); Charite - Universitaetsmedizin Berlin, Department of Neurology with Experimental Neurology, Berlin (Germany); Fehlner, Andreas; Sack, Ingolf [Charite - Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany); Pache, Florence [Charite - Universitaetsmedizin Berlin, Department of Neurology with Experimental Neurology, Berlin (Germany); Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Lacheta, Anna; Papazoglou, Sebastian; Brandt, Alexander [Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Bellmann-Strobl, Judith [Max Delbrueck Center for Molecular Medicine and Charite - Universitaetsmedizin Berlin, Experimental and Clinical Research Center, Berlin (Germany); Ruprecht, Klemens [Charite - Universitaetsmedizin Berlin, Department of Neurology with Experimental Neurology, Berlin (Germany); Braun, Juergen [Charite - Universitaetsmedizin Berlin, Institute of Medical Informatics, Berlin (Germany); Paul, Friedemann [Charite - Universitaetsmedizin Berlin, Department of Neurology with Experimental Neurology, Berlin (Germany); Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Max Delbrueck Center for Molecular Medicine and Charite - Universitaetsmedizin Berlin, Experimental and Clinical Research Center, Berlin (Germany); Wuerfel, Jens [Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Max Delbrueck Center for Molecular Medicine and Charite - Universitaetsmedizin Berlin, Experimental and Clinical Research Center, Berlin (Germany); Medical Image Analysis Center (MIAC AG), Basel (Switzerland)

    2017-05-15

    Application of multifrequency magnetic resonance elastography (MMRE) of the brain parenchyma in patients with neuromyelitis optica spectrum disorder (NMOSD) compared to age matched healthy controls (HC). 15 NMOSD patients and 17 age- and gender-matched HC were examined using MMRE. Two three-dimensional viscoelastic parameter maps, the magnitude G* and phase angle φ of the complex shear modulus were reconstructed by simultaneous inversion of full wave-field data in 1.9-mm isotropic resolution at 7 harmonic drive frequencies from 30 to 60 Hz. In NMOSD patients, a significant reduction of G* was observed within the white matter fraction (p = 0.017), predominantly within the thalamic regions (p = 0.003), compared to HC. These parameters exceeded the reduction in brain volume measured in patients versus HC (p = 0.02 whole-brain volume reduction). Volumetric differences in white matter fraction and the thalami were not detectable between patients and HC. However, phase angle φ was decreased in patients within the white matter (p = 0.03) and both thalamic regions (p = 0.044). MMRE reveals global tissue degeneration with accelerated softening of the brain parenchyma in patients with NMOSD. The predominant reduction of stiffness is found within the thalamic region and related white matter tracts, presumably reflecting Wallerian degeneration. (orig.)

  13. Low T3 syndrome in neuromyelitis optica spectrum disorder: Associations with disease activity and disability.

    Science.gov (United States)

    Cho, Eun Bin; Min, Ju-Hong; Cho, Hye-Jin; Seok, Jin Myoung; Lee, Hye Lim; Shin, Hee Young; Lee, Kwang-Ho; Kim, Byoung Joon

    2016-11-15

    Neuromyelitis optica (NMO) sometimes coexists with serological marker-positive, non-organ-specific autoimmune disorders. We evaluated the prevalence of thyroid dysfunction and anti-thyroid antibodies in patients with NMO spectrum disorder (NMOSD) and investigated the associations between thyroid dysfunction/autoimmunity and clinical features of NMOSD. Forty-nine NMOSD patients with anti-aquaporin-4 antibody and 392 age- and sex-matched healthy controls were included. We measured the levels of thyroid hormones and anti-thyroid antibodies. The prevalence of clinical hypothyroidism, subclinical hyperthyroidism, and low T3 syndrome were higher in patients with NMOSD (4.1%, 12.2%, and 20.4%, respectively) compared with healthy controls (0.3%, 2.8%, and 0.5%, respectively; p=0.034, p=0.001, and poral prednisolone use, iv methylprednisolone use, other immunosuppressive agents use, and the location of lesion (ρ=-0.416, p=0.010). Our study suggests that thyroid dysfunction is frequent in patients with NMOSD; particularly, serum T3 levels may be a useful indicator of disease activity and disability in NMOSD. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Comparison of grey matter atrophy between patients with neuromyelitis optica and multiple sclerosis: A voxel-based morphometry study

    International Nuclear Information System (INIS)

    Duan Yunyun; Liu Yaou; Liang Peipeng; Jia Xiuqin; Yu Chunshui; Qin Wen; Sun Hui; Liao Zhangyuan; Ye Jing; Li Kuncheng

    2012-01-01

    Purpose: Previous studies have established regional grey matter (GM) loss in multiple sclerosis (MS). However, whether there is any regional GM atrophy in neuromyelitis optica (NMO) and the difference between NMO and MS is unclear. The present study addresses this issue by voxel-based morphometry (VBM). Methods: Conventional magnetic resonance imaging (MRI) and T1-weighted three-dimensional MRI were obtained from 26 NMO patients, 26 relapsing–remitting MS (RRMS) patients, and 26 normal controls. An analysis of covariance model assessed with cluster size inference was used to compare GM volume among three groups. The correlations of GM volume changes with disease duration, expanded disability status scale (EDSS) and brain T2 lesion volume (LV) were analyzed. Results: GM atrophy was found in NMO patients in several regions of frontal, temporal, parietal lobes and insula (uncorrected, p < 0.001). While extensive GM atrophy was found in RRMS patients, including most cortical regions and the deep grey matter (corrected for multiple comparisons, p < 0.01). Compared with NMO, those with RRMS had significant GM loss in bilateral thalami, caudate, left parahippocampal gyrus, right hippocampus and insula (corrected, p < 0.01). In RRMS group, regional GM loss in right caudate and bilateral thalami were strongly correlated with brain T2LV. Conclusions: Our study found the difference of GM atrophy between NMO and RRMS patients mainly in deep grey matter. The correlational results suggested axonal degeneration from lesions on T2WI may be a key pathogenesis of atrophy in deep grey matter in RRMS.

  15. Quantitative MRI analysis of the brain after twenty-two years of neuromyelitis optica indicates focal tissue damage

    DEFF Research Database (Denmark)

    Aradi, Mihaly; Koszegi, Edit; Orsi, Gergely

    2013-01-01

    BACKGROUND: The long-term effect of neuromyelitis optica (NMO) on the brain is not well established. METHODS: After 22 years of NMO, a patient's brain was examined by quantitative T1- and T2-weighted mono- and biexponential diffusion and proton spectroscopy. It was compared to 3 cases with short......, and they were also not quantitatively different from the controls. CONCLUSION: After NMO of 22-year duration, metabolic changes, altered diffusivity and magnetic resonance relaxation features of patchy brain areas may suggest tissue damage in NAWM that persist for at least 6 months....

  16. Gray matter MRI differentiates neuromyelitis optica from multiple sclerosis using random forest

    Science.gov (United States)

    Wottschel, Viktor; Cortese, Rosa; Calabrese, Massimiliano; Sahraian, Mohammad Ali; Thompson, Alan J.; Alexander, Daniel C.; Ciccarelli, Olga

    2016-01-01

    Objective: We tested whether brain gray matter (GM) imaging measures can differentiate between multiple sclerosis (MS) and neuromyelitis optica (NMO) using random-forest classification. Methods: Ninety participants (25 patients with MS, 30 patients with NMO, and 35 healthy controls [HCs]) were studied in Tehran, Iran, and 54 (24 patients with MS, 20 patients with NMO, and 10 HCs) in Padua, Italy. Participants underwent brain T1 and T2/fluid-attenuated inversion recovery MRI. Volume, thickness, and surface of 50 cortical GM regions and volumes of the deep GM nuclei were calculated and used to construct 3 random-forest models to classify patients as either NMO or MS, and separate each patient group from HCs. Clinical diagnosis was the gold standard against which the accuracy was calculated. Results: The classifier distinguished patients with MS, who showed greater atrophy especially in deep GM, from those with NMO with an average accuracy of 74% (sensitivity/specificity: 77/72; p < 0.01). When we used thalamic volume (the most discriminating GM measure) together with the white matter lesion volume, the accuracy of the classification of MS vs NMO was 80%. The classifications of MS vs HCs and NMO vs HCs achieved higher accuracies (92% and 88%). Conclusions: GM imaging biomarkers, automatically obtained from clinical scans, can be used to distinguish NMO from MS, even in a 2-center setting, and may facilitate the differential diagnosis in clinical practice. Classification of evidence: This study provides Class II evidence that GM imaging biomarkers can distinguish patients with NMO from those with MS. PMID:27807185

  17. Fatigue in patients with neuromyelitis optica spectrum disorder and its impact on quality of life.

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    Jin Myoung Seok

    Full Text Available Fatigue is a prevalent symptom and major burden in neuroimmunological diseases. In neuromyelitis optica spectrum disorder (NMOSD, a severe autoimmune central nervous system (CNS inflammatory disease with autoantibodies reactive to aquaporin-4, there are few reports about fatigue and quality of life (QOL. We aimed to evaluate the severity of fatigue and its relationship with QOL in patients with NMOSD. We prospectively studied patients with NMOSD who were in remission and seropositive for anti-aquaporin-4 antibody, and they were divided into 2 groups based on the presence of fatigue assessed using the Functional Assessment of Chronic Illness Therapy-fatigue score. Sleep quality, depression, pain, and QOL were also evaluated. A total of 35 patients were enrolled (mean age, 46.5 ± 14.1 years; female: male = 29:6, and the median Expanded Disability Status Scale (EDSS score was 2.0 (range, 0 to 8.0. The patients with fatigue (N = 25, 71.4% had poorer sleep quality and more severe depression than those without fatigue (p = 0.009 and p = 0.001. Both the physical and mental QOL scores were lower in patients with fatigue than in those without fatigue (p = 0.033 and p = 0.004. Multiple linear regression analyses showed that the degree of fatigue with EDSS score and pain were independent predictors of physical aspects of QOL (B = 0.382, p = 0.001, whereas depression was the only predictor of the mental components of QOL (B = -0.845, p = <0.001. Fatigue is a common symptom and an important predictor of QOL in patients with NMOSD.

  18. Elderly-Onset Neuromyelitis Optica Spectrum Disorder with Pre-Existing Prednisone Allergy

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    Christopher Hollen

    2018-01-01

    Full Text Available We present a case of an 82-year-old man with new-onset neuromyelitis optica (NMO spectrum disorder, the treatment of which was complicated by a severe pre-existing prednisone allergy. His age caused much initial doubt about his diagnosis, and his corticosteroid allergy altered our management as we attempted to minimize risk to the patient. Our patient was a healthy 82-year-old, right-handed man who presented with sensory loss of the bilateral lower extremities and progressive, painless vision loss. MRI showed bilateral pre-chiasmatic optic nerve and optic chiasm enhancement, along with enhancement within the thoracic spinal cord from T3 to T7. Serum NMO-IgG was positive with a titer >1: 100,000. Due to concern of allergic reaction, our patient initially refused high-dose Solu-Medrol and opted to try plasma exchange alone, but due to worsening of his symptoms we attempted to use dexamethasone as it had a theoretically lower risk of adverse reaction with a known prednisone allergy. There are several cases of elderly-onset NMO in the literature but this is the only case we could find of NMO accompanied by a rare severe allergy to prednisone. This case demonstrates the relative safety of dexamethasone as an alternative to methylprednisolone for acute management of NMO spectrum disorder, though efficacy has not been established in major trials. Cross-reactivity between various systemic corticosteroids is not as well established as topical corticosteroids, so it is difficult to assess the probability of a reaction between prednisone and methylprednisolone.

  19. Clinical and imaging characteristics and autoantibody analysis of neuromyelitis optica spectrum disorders

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    Nan LIU

    2014-09-01

    Full Text Available Objective To observe the clinical and imaging characteristics and the changes of autoimmune antibodies in the serum and cerebrospinal fluid (CSF of patients with neuromyelitis optica spectrum disorders (NMOSDs.  Methods The data of 10 patients with NMOSDs in Aviation General Hospital of China Medical University from January 2011 to June 2014 were collected. The clinical and imaging features were retrospectively reviewed, and NMO-IgG in serum and CSF, anti-nuclear antibody (ANA, homocysteine (Hcy and thyroid function were analyzed.  Results Cranial and spinal MRI of these patients showed that brain stem was involved in 3 cases, cervical cord in 3 cases, thoracic cord in 6 cases, and cervical-thoracic cord in one case. Serum NMO-IgG were tested in 8 cases, among whom 3 patients were positive (3/8 and 5 were negative (5/8. ANA was positive in one case (1/3, and thyroglobulin (TG antibody and thyroid peroxidase (TPO antibody were positive in 2 cases (2/3. Hypothyroidism occured in 2 cases, hyperthyroidism occured in one case, and Hcy rised in 2 cases.  Conclusions NMOSDs frequently occur in young and middle-aged women. Patients who were highly suspected with NMOSDs should receive tests of autoimmune antibodies in the serum and CSF, and cranial and spinal MRI examination, in order to make a definite diagnosis and receive appropriate treatment. Retesting the autoimmune antibodies should be done in catabasis, in order to identify the relationship between autoimmune antibodies and NMOSDs. doi: 10.3969/j.issn.1672-6731.2014.09.010

  20. Elevated Plasma Chemokines for Eosinophils in Neuromyelitis Optica Spectrum Disorders during Remission

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    Yanping Tong

    2018-02-01

    Full Text Available BackgroundA prominent pathological feature of neuromyelitis optica spectrum disorders (NMOSD is markedly greater eosinophilic infiltration than that seen in other demyelinating diseases, like multiple sclerosis (MS. Eosinophils express the chemokine receptor CCR3, which is activated by eotaxins (CCL11/eotaxin-1, CCL24/eotaxin-2, CCL26/eotaxin-3 and CCL13 [monocyte chemoattractant protein (MCP-4]. Moreover, CCL13 is part of the chemokine set that activates CCR2. The present study aimed to evaluate plasma levels of eotaxins (CCL11, CCL24, and CCL26 and MCPs (CCL13, CCL2, CCL8, and CCL7 in patients with NMOSD during remission.MethodsHealthy controls (HC; n = 30 and patients with MS (n = 47 and NMOSD (n = 58 in remission were consecutively enrolled in this study between January 2016 and August 2017. Plasma CCL11, CCL24, CCL26, CCL2, CCL8, CCL7, CCL13, tumor necrosis factor (TNF-α, and interleukin (IL-1β levels were detected using the human cytokine multiplex assay.ResultsPlasma CCL13, CCL11, and CCL26 levels were all significantly higher in patients with NMOSD than in HC and patients with MS. No significant differences were found in the CCL13, CCL11, or CCL26 levels between patients with NMOSD receiving and not receiving immunosuppressive therapy. The plasma levels of TNF-α and IL-1β, which stimulate the above chemokines, were higher in patients with NMOSD than in HC. There was no difference in CCL24 levels among the three groups. In most cases, the CCL7 levels were below the threshold value of the human cytokine multiplex assay, which is in line with other studies. Adjusted multiple regression analyses showed a positive association of CCL13 levels with the number of relapses after controlling gender, age, body mass index, and disease duration in patients with NMOSD.ConclusionThe study indicates that in NMOSD, the overproduction of cytokines such as IL-1β and TNF-α during remission stimulates eosinophilic chemoattractants such as

  1. Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders

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    Mader Simone

    2011-12-01

    Full Text Available Abstract Background Serum autoantibodies against the water channel aquaporin-4 (AQP4 are important diagnostic biomarkers and pathogenic factors for neuromyelitis optica (NMO. However, AQP4-IgG are absent in 5-40% of all NMO patients and the target of the autoimmune response in these patients is unknown. Since recent studies indicate that autoimmune responses to myelin oligodendrocyte glycoprotein (MOG can induce an NMO-like disease in experimental animal models, we speculate that MOG might be an autoantigen in AQP4-IgG seronegative NMO. Although high-titer autoantibodies to human native MOG were mainly detected in a subgroup of pediatric acute disseminated encephalomyelitis (ADEM and multiple sclerosis (MS patients, their role in NMO and High-risk NMO (HR-NMO; recurrent optic neuritis-rON or longitudinally extensive transverse myelitis-LETM remains unresolved. Results We analyzed patients with definite NMO (n = 45, HR-NMO (n = 53, ADEM (n = 33, clinically isolated syndromes presenting with myelitis or optic neuritis (CIS, n = 32, MS (n = 71 and controls (n = 101; 24 other neurological diseases-OND, 27 systemic lupus erythematosus-SLE and 50 healthy subjects for serum IgG to MOG and AQP4. Furthermore, we investigated whether these antibodies can mediate complement dependent cytotoxicity (CDC. AQP4-IgG was found in patients with NMO (n = 43, 96%, HR-NMO (n = 32, 60% and in one CIS patient (3%, but was absent in ADEM, MS and controls. High-titer MOG-IgG was found in patients with ADEM (n = 14, 42%, NMO (n = 3, 7%, HR-NMO (n = 7, 13%, 5 rON and 2 LETM, CIS (n = 2, 6%, MS (n = 2, 3% and controls (n = 3, 3%, two SLE and one OND. Two of the three MOG-IgG positive NMO patients and all seven MOG-IgG positive HR-NMO patients were negative for AQP4-IgG. Thus, MOG-IgG were found in both AQP4-IgG seronegative NMO patients and seven of 21 (33% AQP4-IgG negative HR-NMO patients. Antibodies to MOG and AQP4 were predominantly of the IgG1 subtype, and were able

  2. Ring-enhancing spinal cord lesions in neuromyelitis optica spectrum disorders.

    Science.gov (United States)

    Zalewski, Nicholas L; Morris, Padraig P; Weinshenker, Brian G; Lucchinetti, Claudia F; Guo, Yong; Pittock, Sean J; Krecke, Karl N; Kaufmann, Timothy J; Wingerchuk, Dean M; Kumar, Neeraj; Flanagan, Eoin P

    2017-03-01

    We assessed the frequency and characteristics of ring-enhancing spinal cord lesions in neuromyelitis optica spectrum disorder (NMOSD) myelitis and myelitis of other cause. We reviewed spinal cord MRIs for ring-enhancing lesions from 284 aquaporin-4 (AQP4)-IgG seropositive patients at Mayo Clinic from 1996 to 2014. Inclusion criteria were as follows: (1) AQP4-IgG seropositivity, (2) myelitis attack and (3) MRI spinal cord demonstrating ring-enhancement. We identified two groups of control patients with: (1) longitudinally extensive myelopathy of other cause (n=66) and (2) myelitis in the context of a concurrent or subsequent diagnosis of multiple sclerosis (MS) from a population-based cohort (n=30). Ring-enhancement was detected in 50 of 156 (32%) myelitis episodes in 41 patients (83% single; 17% multiple attacks). Ring-enhancement was noted on sagittal and axial images in 36 of 43 (84%) ring enhancing myelitis episodes and extended a median of two vertebral segments (range, 1-12); in 21 of 48 (44%) ring enhancing myelitis episodes, the ring extended greater than or equal to three vertebrae. Ring-enhancement was accompanied by longitudinally extensive (greater than or equal to three vertebral segments) T2-hyperintensity in 44 of 50 (88%) ring enhancing myelitis episodes. One case of a spinal cord biopsy during ring-enhancing myelitis revealed tissue vacuolation and loss of AQP4 immunoreactivity with preserved axons. The clinical characteristics of ring-enhancing myelitis episodes did not differ from non-ring-enhancing episodes. Ring-enhancing spinal cord lesions were more common in NMOSD than other causes of longitudinally extensive myelopathy (50/156 (32%) vs 0/66 (0%); p≤0.001) but did not differ between NMOSD and MS (50/156 (32%) vs 6/30 (20%); p=0.20). Spinal cord ring-enhancement accompanies one-third of NMOSD myelitis episodes and distinguishes NMOSD from other causes of longitudinally extensive myelopathies but not from MS. Published by the BMJ Publishing

  3. Retinal ganglion cell-inner plexiform and nerve fiber layers in neuromyelitis optica.

    Science.gov (United States)

    Hu, Sai-Jing; Lu, Pei-Rong

    2018-01-01

    To determine the thickness of the retinal ganglion cell-inner plexiform layer (GCIPL) and the retinal nerve fiber layer (RNFL) in patients with neuromyelitis optica (NMO). We conducted a cross-sectional study that included 30 NMO patients with a total of 60 eyes. Based on the presence or absence of optic neuritis (ON), subjects were divided into either the NMO-ON group (30 eyes) or the NMO-ON contra group (10 eyes). A detailed ophthalmologic examination was performed for each group; subsequently, the GCIPL and the RNFL were measured using high-definition optical coherence tomography (OCT). In the NMO-ON group, the mean GCIPL thickness was 69.28±21.12 µm, the minimum GCIPL thickness was 66.02±10.02 µm, and the RNFL thickness were 109.33±11.23, 110.47±3.10, 64.92±12.71 and 71.21±50.22 µm in the superior, inferior, temporal and nasal quadrants, respectively. In the NMO-ON contra group, the mean GCIPL thickness was 85.12±17.09 µm, the minimum GCIPL thickness was 25.39±25.1 µm, and the RNFL thicknesses were 148.33±23.22, 126.36±23.45, 82.21±22.30 and 83.36±31.28 µm in the superior, inferior, temporal and nasal quadrants, respectively. In the control group, the mean GCIPL thickness was 86.98±22.37 µm, the minimum GCIPL thickness was 85.28±10.75 µm, and the RNFL thicknesses were 150.22±22.73, 154.79±60.23, 82.33±7.01 and 85.62±13.81 µm in the superior, inferior, temporal and nasal quadrants, respectively. The GCIPL and RNFL were thinner in the NMO-ON contra group than in the control group ( P deviation (MD) and corrected pattern standard deviation (PSD) in the NMO-ON group ( P <0.05). The thickness of the GCIPL and RNFL, as measured using OCT, may indicate optic nerve damage in patients with NMO.

  4. In vivo imaging reveals rapid astrocyte depletion and axon damage in a model of neuromyelitis optica-related pathology

    DEFF Research Database (Denmark)

    Herwerth, Marina; Kalluri, Sudhakar Reddy; Srivastava, Rajneesh

    2016-01-01

    OBJECTIVE: Neuromyelitis optica (NMO) is an autoimmune disease of the CNS, which resembles multiple sclerosis (MS). NMO differs from MS, however, in the distribution and histology of neuroinflammatory lesions and shows a more aggressive clinical course. Moreover, the majority of NMO patients carry...... of astrocyte injury in NMO and the mechanisms by which toxicity spreads to axons are not understood. METHODS: Here, we establish in vivo imaging of the spinal cord, one of the main sites of NMO pathology, as a powerful tool to study the formation of experimental NMO-related lesions caused by human AQP4...... antibody concentration and complement, specifically C1q. INTERPRETATION: In vivo imaging of the spinal cord reveals the swift development of NMO-related acute axon injury following AQP4 antibody-mediated astrocyte depletion. This approach will be useful in studying the mechanisms underlying the spread...

  5. Retinal ganglion cell-inner plexiform and nerve fiber layers in neuromyelitis optica

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    Sai-Jing Hu

    2018-01-01

    Full Text Available AIM: To determine the thickness of the retinal ganglion cell-inner plexiform layer (GCIPL and the retinal nerve fiber layer (RNFL in patients with neuromyelitis optica (NMO. METHODS: We conducted a cross-sectional study that included 30 NMO patients with a total of 60 eyes. Based on the presence or absence of optic neuritis (ON, subjects were divided into either the NMO-ON group (30 eyes or the NMO-ON contra group (10 eyes. A detailed ophthalmologic examination was performed for each group; subsequently, the GCIPL and the RNFL were measured using high-definition optical coherence tomography (OCT. RESULTS: In the NMO-ON group, the mean GCIPL thickness was 69.28±21.12 μm, the minimum GCIPL thickness was 66.02±10.02 μm, and the RNFL thickness were 109.33±11.23, 110.47±3.10, 64.92±12.71 and 71.21±50.22 μm in the superior, inferior, temporal and nasal quadrants, respectively. In the NMO-ON contra group, the mean GCIPL thickness was 85.12±17.09 μm, the minimum GCIPL thickness was 25.39±25.1 μm, and the RNFL thicknesses were 148.33±23.22, 126.36±23.45, 82.21±22.30 and 83.36±31.28 μm in the superior, inferior, temporal and nasal quadrants, respectively. In the control group, the mean GCIPL thickness was 86.98±22.37 μm, the minimum GCIPL thickness was 85.28±10.75 μm, and the RNFL thicknesses were 150.22±22.73, 154.79±60.23, 82.33±7.01 and 85.62±13.81 μm in the superior, inferior, temporal and nasal quadrants, respectively. The GCIPL and RNFL were thinner in the NMO-ON contra group than in the control group (P<0.05; additionally, the RNFL was thinner in the inferior quadrant in the NMO-ON group than in the control group (P<0.05. Significant correlations were observed between the GCIPL and RNFL thickness measurements as well as between thickness measurements and the two visual field parameters of mean deviation (MD and corrected pattern standard deviation (PSD in the NMO-ON group (P<0.05. CONCLUSION: The thickness of the GCIPL

  6. The major brain endocannabinoid 2-AG controls neuropathic pain and mechanical hyperalgesia in patients with neuromyelitis optica.

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    Hannah L Pellkofer

    Full Text Available Recurrent myelitis is one of the predominant characteristics in patients with neuromyelitis optica (NMO. While paresis, visual loss, sensory deficits, and bladder dysfunction are well known symptoms in NMO patients, pain has been recognized only recently as another key symptom of the disease. Although spinal cord inflammation is a defining aspect of neuromyelitis, there is an almost complete lack of data on altered somatosensory function, including pain. Therefore, eleven consecutive patients with NMO were investigated regarding the presence and clinical characteristics of pain. All patients were examined clinically as well as by Quantitative Sensory Testing (QST following the protocol of the German Research Network on Neuropathic Pain (DFNS. Additionally, plasma endocannabinoid levels and signs of chronic stress and depression were determined. Almost all patients (10/11 suffered from NMO-associated neuropathic pain for the last three months, and 8 out of 11 patients indicated relevant pain at the time of examination. Symptoms of neuropathic pain were reported in the vast majority of patients with NMO. Psychological testing revealed signs of marked depression. Compared to age and gender-matched healthy controls, QST revealed pronounced mechanical and thermal sensory loss, strongly correlated to ongoing pain suggesting the presence of deafferentation-induced neuropathic pain. Thermal hyperalgesia correlated to MRI-verified signs of spinal cord lesion. Heat hyperalgesia was highly correlated to the time since last relapse of NMO. Patients with NMO exhibited significant mechanical and thermal dysesthesia, namely dynamic mechanical allodynia and paradoxical heat sensation. Moreover, they presented frequently with either abnormal mechanical hypoalgesia or hyperalgesia, which depended significantly on plasma levels of the endogenous cannabinoid 2-arachidonoylglycerole (2-AG. These data emphasize the high prevalence of neuropathic pain and hyperalgesia

  7. Frequency of brain MRI abnormalities in neuromyelitis optica spectrum disorder at presentation: A cohort of Latin American patients.

    Science.gov (United States)

    Carnero Contentti, Edgar; Daccach Marques, Vanessa; Soto de Castillo, Ibis; Tkachuk, Veronica; Antunes Barreira, Amilton; Armas, Elizabeth; Chiganer, Edson; de Aquino Cruz, Camila; Di Pace, José Luis; Hryb, Javier Pablo; Lavigne Moreira, Carolina; Lessa, Carmen; Molina, Omaira; Perassolo, Monica; Soto, Arnoldo; Caride, Alejandro

    2018-01-01

    Brain magnetic resonance imaging (BMRI) lesions were classically not reported in neuromyelitis optica (NMO). However, BMRI lesions are not uncommon in NMO spectrum disorder (NMOSD) patients. To report BMRI characteristic abnormalities (location and configuration) in NMOSD patients at presentation. Medical records and BMRI characteristics of 79 patients with NMOSD (during the first documented attack) in Argentina, Brazil and Venezuela were reviewed retrospectively. BMRI abnormalities were observed in 81.02% of NMOSD patients at presentation. Forty-two patients (53.1%) showed typical-NMOSD abnormalities. We found BMRI abnormalities at presentation in the brainstem/cerebellum (n = 26; 32.9%), optic chiasm (n = 16; 20.2%), area postrema (n = 13; 16.4%), thalamus/hypothalamus (n = 11; 13.9%), corpus callosum (n = 11; 13.9%), periependymal-third ventricle (n = 9; 11.3%), corticospinal tract (n = 7; 8.8%), hemispheric white matter (n = 1; 1.2%) and nonspecific areas (n = 49; 62.03%). Asymptomatic BMRI lesions were more common. The frequency of brain MRI abnormalities did not differ between patients who were positive and negative for aquaporin 4 antibodies at presentation. Typical brain MRI abnormalities are frequent in NMOSD at disease onset. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Patient with neuromyelitis optica and inflammatory demyelinating lesions comprising whole spinal cord from C2 level till conus: case report

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    Pavlisa Goran

    2009-10-01

    Full Text Available Abstract Background Neuromyelitis optica (NMO is an idiopathic, severe, inflammatory demyelinating disease of the central nervous system, that causes severe optic neuritis and myelitis attacks. Early discrimination between multiple sclerosis (MS and NMO is important, as optimum treatment for both diseases may differ considerably. Case Presentation We report a case of a patient who initially presented as longitudinally extensive transverse myelitis (LETM, having spastic upper extremities diparesis and spastic paraplegia, C2/C3 sensory level and urinary incontinence, as well as extensive inflammatory spinal cord lesions from C2 level to conus. After 5 months the patient had another attack of transverse myelitis, had electrophysiological findings consistent with optic neuritis, was seropositive for NMO-IgG (aquaporin-4 IgG and thus fulfilled NMO diagnostic criteria. Following treatment of disease attacks with pulse corticosteroid therapy and intravenous immunoglobulins, we included oral azathioprine in a combination with oral prednisone in the therapy. Since there was no significant clinical improvement, we decided to use cyclophosphamide therapy, which resulted in good clinical improvement and gradual decrease of cord swelling. Conclusion In this NMO case report we wanted to emphasize the extensiveness of inflammatory spinal cord changes in our patient, from C2 level to conus. In the conclusion it is important to say that accurate, early diagnosis and distinction from MS is critical to facilitate initiation of immunosuppressive therapy for attack prevention.

  9. Sudden hearing loss as the initial symptom in Japanese patients with multiple sclerosis and seropositive neuromyelitis optica spectrum disorders.

    Science.gov (United States)

    Tanaka, Masami; Tanaka, Keiko

    2016-09-15

    Sudden hearing loss may occur in rare cases of relapsing-remitting multiple sclerosis (RRMS). There have also been reports of idiopathic sudden sensorineural hearing loss (SNHL) in patients with neuromyelitis optica spectrum disorders (NMOSD), but the frequency of such cases is unclear. We conducted a retrospective analysis of the medical records of 173 consecutive patients with multiple sclerosis (MS) and 101 consecutive patients with NMOSD who tested positive for anti-aquaporin-4 antibodies in addition to 37 consecutive patients with clinically isolated syndromes (CIS) to investigate the frequency and onset timing of SNHL. SNHL was observed in six (3.5%) of the RRMS cases, one (1.0%) of the seropositive NMOSD cases, and three (8.1%) of the CIS cases. SNHL occurred ahead of onset in 4/6 MS patients and in all of 3 CIS patients. Patient with NMOSD exhibited SNHL 6years after the onset of NMOSD. Although SNHL is rare, these results suggest the risk of developing demyelinating lesions in the central nervous system and further conversion to MS in the future. Copyright © 2016. Published by Elsevier B.V.

  10. Interleukin-6 analysis of 572 consecutive CSF samples from neurological disorders: A special focus on neuromyelitis optica.

    Science.gov (United States)

    Uzawa, Akiyuki; Mori, Masahiro; Masuda, Hiroki; Ohtani, Ryohei; Uchida, Tomohiko; Sawai, Setsu; Kuwabara, Satoshi

    2017-06-01

    Elevation of cerebrospinal fluid (CSF) interleukin (IL)-6 has been reported in various neurological disorders but has never been systematically analyzed. Our main objectives are to compare the CSF IL-6 levels among various neurological disorders and to evaluate the significance of CSF IL-6 measurements for the diagnosis of neuromyelitis optica (NMO). We retrospectively investigated the IL-6 levels of 572 consecutive CSF samples in patients with various neurological disorders. Additionally, the associations between clinical manifestations in NMO patients and CSF IL-6 levels were closely investigated. Among the neurological disorders, patients with NMO had the highest CSF IL-6 level. Receiver operating characteristic analysis found the optimal cutoff CSF IL-6 value for diagnosing NMO as 7.8pg/ml, and the sensitivity and specificity were 0.7317 and 0.7694, respectively. In NMO, CSF IL-6 levels were correlated with the length of the spinal cord lesion and anti-aquaporin-4 antibody-positivity and decreased after treatment. CSF IL-6 can be high in various inflammatory and non-inflammatory CNS disorders, but its upregulation appears to be the most remarkable in NMO. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. The cervical spinal cord in neuromyelitis optica patients: A comparative study with multiple sclerosis using diffusion tensor imaging

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    Pessôa, Fernanda Miraldi Clemente, E-mail: fernandamiraldi@hotmail.com [Federal University of Rio de Janeiro, Medical Student, Rua Rodolpho Paulo Rocco, 255, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, RJ (Brazil); Lopes, Fernanda Cristina Rueda, E-mail: frueda81@hotmail.com [Department of Radiology, Federal University of Rio de Janeiro, Avenida das Américas, 4666 sl 325, Barra da Tijuca, Rio de Janeiro, RJ (Brazil); Costa, João Victor Altamiro, E-mail: victoraltamiro@gmail.com [Department of Radiology, Federal University of Rio de Janeiro, Rua Rodolpho Paulo Rocco, 255, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, RJ (Brazil); Leon, Soniza Vieira Alves, E-mail: sonizavleon@globo.com [Department of Neurology, Federal University of Rio de Janeiro, Rua Rodolpho Paulo Rocco, 255, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, RJ (Brazil); Domingues, Romeu Côrtes, E-mail: romeu@CDPi.com.br [CDPI – Clínica de Diagnóstico Por Imagem, Avenida das Américas, 4666 sl 325, Barra da Tijuca, Rio de Janeiro, RJ (Brazil); Gasparetto, Emerson Leandro, E-mail: egasparetto@gmail.com [Department of Radiology, Federal University of Rio de Janeiro, Avenida das Américas, 4666 sl 325, Barra da Tijuca, Rio de Janeiro, RJ (Brazil); CDPI – Clínica de Diagnóstico Por Imagem, Avenida das Américas, 4666 sl 325, Barra da Tijuca, Rio de Janeiro, RJ (Brazil)

    2012-10-15

    Introduction: This study aims to evaluate “in vivo” the integrity of the normal-appearing spinal cord in patients with neuromyelitis optica (NMO), using diffusion tensor MR imaging, comparing to controls and patients with multiple sclerosis (MS). Materials and methods: We studied 8 patients with NMO and 17 without any neurologic disorder. Also, 32 MS patients were selected. Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) were calculated within regions of interest at C2 and C7 levels in the four columns of the spinal cord. Results: At C2, the FA value was decreased in NMO patients compared to MS and controls in the anterior column. Also in this column, RD value showed increase in NMO compared to MS and to controls. The FA value of the posterior column was decreased in NMO in comparison to controls. At C7, AD value was higher in NMO than in MS in the right column. At the same column, MD values were increased in NMO compared to MS and to controls. Conclusions: There is extensive NASC damage in NMO patients, including peripheral areas of the cervical spinal cord, affecting the white matter, mainly caused by demyelination. This suggests a new spinal cord lesion pattern in NMO in comparison to MS.

  12. MR imaging findings of the corpus callosum region in the differentiation between multiple sclerosis and neuromyelitis optica

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    Chen, Zhiye, E-mail: yyqf@hotmail.com [Department of Radiology, PLA General Hospital, 28 Fuxing Road, Beijing 100853 (China); Feng, Feng, E-mail: cjr.fengfeng@vip.163.com [Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Shuaifuyuan, Wangfujing, Beijing 100730 (China); Yang, Yang, E-mail: whitean0584@sina.com.cn [Department of Neurology, PLA General Hospital, 28 Fuxing Road, Beijing 100853 (China); Li, Jinfeng, E-mail: lijf_301@163.com [Department of Radiology, PLA General Hospital, 28 Fuxing Road, Beijing 100853 (China); Ma, Lin, E-mail: cjr.malin@vip.163.com [Department of Radiology, PLA General Hospital, 28 Fuxing Road, Beijing 100853 (China)

    2012-11-15

    Purpose: To evaluate MR imaging findings in corpus callosum region for the discrimination between opticospinal multiple sclerosis (OSMS) and neuromyelitis optica (NMO). Materials and methods: Forty-two definite OSMS with seronegative NMO-IgG and 23 NMO with seropositive NMO-IgG, and 27 age-matched normal controls (NC) were recruited. Sagittal T2-FLAIR images with 2-mm slice thickness were obtained. Subcallosal dot-dash (SCDD) sign and subcallosal striations (SCS) sign were reviewed. Results: SCDD was more commonly detected in OSMS (28 of 42 patients) than in NMO (5 of 23 patients) (P < 0.05). SCS showed no difference between OSMS (31 of 42 patients) and NMO (12 of 23 patients) (P > 0.05). For comparing ROC analysis among SCDD, SCS, and SCDD + SCS for predicted probability through binary logistic regression analysis, SCDD + SCS had the largest area under ROC curve (0.777) than SCDD (0.725) and SCS (0.608). Conclusion: SCDD may be helpful in distinguishing OSMS from NMO. The regression equation may also be a simple and effective method of choice for the differentiation between OSMS and NMO.

  13. Abnormal baseline brain activity in patients with neuromyelitis optica: A resting-state fMRI study

    International Nuclear Information System (INIS)

    Liu Yaou; Liang Peipeng; Duan Yunyun; Jia Xiuqin; Wang Fei; Yu Chunshui; Qin Wen; Dong Huiqing; Ye Jing; Li Kuncheng

    2011-01-01

    Purpose: Recent immunopathologic and MRI findings suggest that tissue damage in neuromyelitis optica (NMO) is not limited to spinal cord and optic nerve, but also in brain. Baseline brain activity can reveal the brain functional changes to the tissue damages and give clues to the pathophysiology of NMO, however, it has never been explored by resting-state functional MRI (fMRI). We used regional amplitude of low frequency fluctuation (ALFF) as an index in resting-state fMRI to investigate how baseline brain activity changes in patients with NMO. Methods: Resting-state fMRIs collected from seventeen NMO patients and seventeen age- and sex-matched normal controls were compared to investigate the ALFF difference between the two groups. The relationships between ALFF in regions with significant group differences and the EDSS (Expanded Disability Status Scale), disease duration were further explored. Results: Our results showed that NMO patients had significantly decreased ALFF in precuneus, posterior cingulate cortex (PCC) and lingual gyrus; and increased ALFF in middle frontal gyrus, caudate nucleus and thalamus, compared to normal controls. Moderate negative correlations were found between the EDSS and ALFF in the left middle frontal gyrus (r = -0.436, p = 0.040) and the left caudate (r = -0.542, p = 0.012). Conclusion: The abnormal baseline brain activity shown by resting-state fMRI in NMO is relevant to cognition, visual and motor systems. It implicates a complex baseline brain status of both functional impairments and adaptations caused by tissue damages in these systems, which gives clues to the pathophysiology of NMO.

  14. Variants of Interleukin-7/Interleukin-7 Receptor Alpha are Associated with Both Neuromyelitis Optica and Multiple Sclerosis Among Chinese Han Population in Southeastern China

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    Jing-Cong Zhuang

    2015-01-01

    Full Text Available Background: Neuromyelitis optica (NMO and multiple sclerosis (MS are autoimmune demyelinating diseases of the central nerve system. Interleukin-7 (IL-7 and interleukin-7 receptor alpha (IL-7Rα were proved to be important in the pathogenesis of both diseases because of the roles they played in the differentiations of autoimmune lymphocytes. The variants of both genes had been identified to be associated with MS susceptibility in Caucasian, Japanese and Korean populations. However, the association of these variants with NMO and MS has not been well studied in Chinese Southeastern Han population. Here, we aimed to evaluate the association of six IL-7 variants (rs1520333, rs1545298, rs4739140, rs6993386, rs7816065, and rs2887502 and one variant of IL-7RA (rs6897932 with NMO and MS among Chinese Han population in southeastern China. Methods: Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MassARRAY system and Sanger sequencing were used to determine the variants of IL-7 and IL-7RA in 167 NMO patients, 159 MS patients and 479 healthy controls among Chinese Han population in southeastern China. Samples were excluded if the genotyping success rate <90%. Results: Statistical differences were observed in the genotypes of IL-7 rs1520333 in MS patients and IL-7RA rs6897932 in NMO patients, compared with healthy controls (P = 0.035 and 0.034, respectively. There was a statistically significant difference in the genotypes of IL-7 rs2887502 between MS and NMO patients (P = 0.014. And there were statistically significant differences in the rs6897932 genotypes (P = 0.004 and alleles (P = 0.042 between NMO-IgG positive patients and healthy controls. Conclusions: The study suggested that among Chinese Han population in southeastern China, the variant of IL-7RA (rs6897932 was associated with NMO especially NMO-IgG positive patients while the variant of IL-7 (rs1520333 with MS patients. And the genotypic differences of IL-7 rs2887502

  15. Aquaporin-4 autoantibodies in neuromyelitis optica spectrum disorders: comparison between tissue-based and cell-based indirect immunofluorescence assays

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    Chan Koon H

    2010-09-01

    Full Text Available Abstract Background Neuromyelitis optica spectrum disorders (NMOSD are severe central nervous system inflammatory demyelinating disorders (CNS IDD characterized by monophasic or relapsing, longitudinally extensive transverse myelitis (LETM and/or optic neuritis (ON. A significant proportion of NMOSD patients are seropositive for aquaporin-4 (AQP4 autoantibodies. We compared the AQP4 autoantibody detection rates of tissue-based indirect immunofluorescence assay (IIFA and cell-based IIFA. Methods Serum of Chinese CNS IDD patients were assayed for AQP4 autoantibodies by tissue-based IIFA using monkey cerebellum and cell-based IIFA using transfected HEK293 cells which express human AQP4 on their cell membranes. Results In total, 128 CNS IDD patients were studied. We found that 78% of NMO patients were seropositive for AQP4 autoantibodies by cell-based IIFA versus 61% by tissue-based IFA (p = 0.250, 75% of patients having relapsing myelitis (RM with LETM were seropositive by cell-based IIFA versus 50% by tissue-based IIFA (p = 0.250, and 33% of relapsing ON patients were seropositive by cell-based IIFA versus 22% by tissue-based IIFA (p = 1.000; however the differences were not statistically significant. All patients seropositive by tissue-based IIFA were also seropositive for AQP4 autoantibodies by cell-based IIFA. Among 29 NMOSD patients seropositive for AQP4 autoantibodies by cell-based IIFA, 20 (69% were seropositive by tissue-based IIFA. The 9 patients seropositive by cell-based IIFA while seronegative by tissue-based IIFA had NMO (3, RM with LETM (3, a single attack of LETM (1, relapsing ON (1 and a single ON attack (1. Among 23 NMO or RM patients seropositive for AQP4 autoantibodies by cell-based IIFA, comparison between those seropositive (n = 17 and seronegative (n = 6 by tissue-based IIFA revealed no differences in clinical and neuroradiological characteristics between the two groups. Conclusion Cell-based IIFA is slightly more sensitive

  16. Factors associated with the effectiveness of plasma exchange for the treatment of NMO-IgG-positive neuromyelitis optica spectrum disorders.

    Science.gov (United States)

    Lim, Young-Min; Pyun, So Young; Kang, Bong-Hui; Kim, Jimin; Kim, Kwang-Kuk

    2013-08-01

    To identify factors associated with plasma exchange response in neuromyelitis optica (NMO) spectrum disorders, the clinical and magnetic resonance imaging (MRI) features of 31 NMO-IgG-positive patients receiving plasma exchange for steroid-resistant exacerbations were analyzed. Functional improvement was observed in 65% of the patients. A lower baseline Expanded Disability Status Scale score was associated with favorable response (p = 0.040). Patients without cord atrophy had a higher success rate than patients with atrophy (p = 0.016). Levels of NMO-IgG did not differ between responders and non-responders before and after plasma exchange. In conclusion, a minimal pre-existing disability is the primary determinant of the effectiveness of plasma exchange.

  17. Quantitative study of the cervical spinal cord damage in patients with multiple sclerosis and neuromyelitis optica using diffusion tensor imaging

    International Nuclear Information System (INIS)

    Hou Huanxin; Li Yongmei; Lu Fajin; Luo Tianyou; Ouyang Yu; Zeng Chun; Zhang Zhiwei

    2012-01-01

    Objective: To investigate the changes of the cervical spinal cord in patients with relapsing-remitting multiple sclerosis (RRMS) and relapsing neuromyelitis optica (RNMO) using diffusion tensor imaging (DTI) and to analyze its correlations with clinical disability scores. Methods: Thirty patients with MS (MS group),28 patients with NMO (NMO group) and 20 healthy volunteers were imaged using DTI on a 3.0 Tesla scanner. DTI indices of cervical spinal cord from all participants were measured, including mean diffusivity (MD) and fractional anisotropy (FA), and the correlations between the DTI metrics and the expanded disability status scale (EDSS) scores were assessed. One-way ANOVA, Dunnett-t test and Spearman correlation analysis were used for statistics. Results: (1) The values of MD among three groups were different at C3 level for left lateral and dorsal columns, C4 level for the central gray substance and dorsal columns, and C5-C6 level for all structures. There were significant differences among them (F=4.006-36.814, P<0.05). The values of FA were significantly different at all levels (F=5.561-98.128, P<0.05). (2) Compared with the control group, the values of MD were increased and FA were decreased for both MS and NMO groups, there were significant differences among them (t=-0.320-3.138, P<0.05). In MS and NMO groups, there were no significant differences of MD (t=-1.183-0.069, P>0.05), while the FA at C4-C6 levels (including the central gray substance, dorsal columns,right lateral columns and left lateral columns) for NMO group were 0.57 ± 0.09, 0.56 ± 0.11, 0.54 ±0.10, 0.57±0.09, 0.55 ±0.11, 0.52 ±0.13, 0.55 ±0.11, 0.54 ±0.13, 0.54±0.10, 0.54±0.11, 0.53 ±0.13, 0.52 ±0.11; and for MS group were 0.67 ±0.10, 0.68 ±0.10, 0.68 ±0.10, 0.70 ±0.12, 0.68 ±0.11, 0.69±0.10, 0.68 ±0.11, 0.69 ±0.12, 0.67 ±0.14, 0.68 ±0.15, 0.69 ±0.14, 0.69 ±0.16, and there were significant differences between two groups (t=-0.011-0.169, P<0.05). (3) Univariate

  18. Anti-N-methyl-D-aspartate receptor(NMDAR) antibody encephalitis presents in atypical types and coexists with neuromyelitis optica spectrum disorder or neurosyphilis.

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    Qin, Kaiyu; Wu, Wenqing; Huang, Yuming; Xu, Dongmei; Zhang, Lei; Zheng, Bowen; Jiang, Meijuan; Kou, Cheng; Gao, Junhua; Li, Wurong; Zhang, Jinglin; Wang, Sumei; Luan, Yanfei; Yan, Chaoling; Xu, Dan; Zheng, Xinmei

    2017-01-05

    Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a clinically heterogeneous disorder characterized by epileptic seizures, psychosis, dyskinesia, consciousness impairments, and autonomic instability. Symptoms are always various. Sometimes it presents in milder or incomplete forms. We report 4 cases of anti-NMDAR encephalitis with incomplete forms, 3 cases of which were accompanied by neuromyelitis optica spectrum disorder or neurosyphilis respectively. A 33-year-old man presented with dysarthria, movement disorder and occasional seizures. He had 6 relapses in 28 years. When suffered from upper respiratory tract syndrome, he developed behavioral and consciousness impairment. Cranial MRI was normal. Viral PCR studies and oncologic work-up were negative. Anti-NMDAR antibody was detected in CSF and serum. A 21-year-old female manifested dizziness and diplopia ten months and six months before, respectively. Both responded to steroid therapy and improved completely. This time she presented with progressive left limb and facial anesthesia, walking and holding unsteadily. Spinal cord MRI follow-up showed abnormality of medulla oblongata and cervical cord(C1). Anti-AQP4 and anti-NMDAR were positive in CSF. Steroid-pulse therapy ameliorated her symptoms. A 37-year-old male experienced worsening vision. He was confirmed neurosyphilis since the CSF tests for syphilis were positive. Protein was elevated and the oligoclonal IgG bands(OB) and anti-NMDAR was positive in CSF. Anti-aquaporin 4(AQP4) antibodies and NMO-IgG were negative. Cranial MRI showed high FLAIR signal on frontal lobe and low T2 signal adjacent to the right cornu posterious ventriculi lateralis. Treatment for neurosyphlis was commenced with gradual improvement. A 39-year-old male, developed serious behavioral and psychiatric symptoms. Examination showed abnormal pupils and unsteady gait. He was confirmed neurosyphilis according to the CSF tests for syphilis. Anti-NMDAR was positive in CSF and serum

  19. The frequency of anti-aquaporin-4 Ig g antibody in neuromyelitis optica and its spectrum disorders at a single tertiary referral center in malaysia.

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    Viswanathan, Shanthi; Arip, Masita; Mustafa, Norhazlin; Dhaliwal, Jasbir S; Rose, Norzainie; Muda, Sobri; Puvanarajah, Santhi Datuk; Rafia, Mohammad Hanip; Wing Loong, Mark Cheong

    2014-01-01

    Background. In the past the occurrence of neuromyelitis optica in Malaysia was thought to be uncommon and the frequency of anti-aquaporin-4 Ig G antibody was unknown. Objective. To evaluate the frequency of anti-aquaporin-4 Ig G antibody (Anti-AQP4 antibody) amongst patients with neuromyelitis optica (NMO) and its spectrum disorders (NMOSD) and the differences between the seropositive and seronegative groups. Methods. Retrospectively, 96 patients with NMO/high risk syndromes for NMOSD (HRS-NMOSD) were identified out of 266 patients with idiopathic inflammatory demyelinating disease from a single center hospital based registry. Anti-AQP4 seropositivity was found in 38/48 (79.2%) with NMO, 12/21 (57.1%) with brain involvement at high risk for NMOSD, 12/15 (80%) with transverse myelitis (i.e., 11/15 with relapsing transverse myelitis and one with monophasic transverse myelitis), and 3/7 (42.8%) with relapsing optic neuritis. Sixty-five out of 96 patients, that is, 67.7%, with NMO/HRS for NMOSD were seropositive. Seropositivity was significantly associated with female gender, a higher number of mean relapses, that is, 5.15 ± 4.42 versus 2.10 ± 1.68, longer length of spinal cord lesions, that is, 6.6 ± 4.9 versus 2.9 ± 2.5, vertebral bodies, higher EDSS, 4.5 ± 2.4 versus 2.4 ± 2.6, presence of paroxysmal tonic spasms, and blindness (unilateral/bilateral); P < 0.001. Longitudinally extensive cord lesions (contiguous or linear), presence of lesions in the cervical and thoracic regions, and involvement of the central gray matter or holocord regions on axial scans, were also significantly associated with seropositivity; P < 0.001. Conclusion. NMO and HRS for NMOSD are present in larger numbers than previously thought in Malaysia. More than 2/3rds are seropositive. Seropositive and seronegative NMO/NMOSD have differences that are useful in clinical practice.

  20. Neuromyelitis optica spectrum disorder: 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography findings--case report.

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    Oyama, Hirofumi; Miwa, Shigeru; Noda, Tomoyuki; Sobajima, Atsuhiro; Kito, Akira; Maki, Hideki; Hattori, Kenichi; Wada, Kentaro

    2012-01-01

    A 51-year-old female with a history of rheumatoid arthritis rapidly developed anterior neck pain and paresis in the left upper and lower extremities and right lower extremity, sensory disturbance in the left upper and lower extremities, and bladder and rectal disorder. Adduction of the left eye and abduction of the right eye were also disturbed. Spinal magnetic resonance imaging demonstrated severe edema in the C1-T5 levels, which then deteriorated rapidly over 3 days, and lesions enhanced with gadolinium in the C1-C3 and C5-T3 levels. 2-Deoxy-2-[18F]fluoro-D-glucose positron emission tomography study demonstrated the inflammatory sites as segmental enhanced accumulation in the C1-C3, C5-C6, and T1 levels. The serum anti-aquaporin 4 antibody level was positive and she was diagnosed with neuromyelitis optica spectrum disorder. Marked improvement in the neurological conditions, concomitant with reduced spinal cord edema, was obtained by steroid pulse therapy.

  1. Anti-Aquaporin-4 Antibody-Positive Neuromyelitis Optica Presenting with Syndrome of Inappropriate Antidiuretic Hormone Secretion as an Initial Manifestation

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    H. Nakajima

    2011-10-01

    Full Text Available The distribution of neuromyelitis optica (NMO-characteristic brain lesions corresponds to sites of high aquaporin-4 (AQP4 expression, and the brainstem and hypothalamus lesions that express high levels of AQP4 protein are relatively characteristic of NMO. The syndrome of inappropriate antidiuretic hormone secretion (SIADH is one of the important causes of hyponatremia and results from an abnormal production or sustained secretion of antidiuretic hormone (ADH. SIADH has been associated with many clinical states or syndromes, and the hypothalamic-neurohypophyseal system regulates the feedback control system for ADH secretion. We report the case of a 63-year-old man with NMO, whose initial manifestation was hyponatremia caused by SIADH. Retrospective analysis revealed that the serum anti-AQP4 antibody was positive, and an MRI scan showed a unilateral lesion in the hypothalamus. SIADH recovered completely with regression of the hypothalamic lesion. As such, NMO should even be considered in patients who develop SIADH and have no optic nerve or spinal cord lesions but have MRI-documented hypothalamic lesions.

  2. Pattern electroretinogram in neuromyelitis optica and multiple sclerosis with or without optic neuritis and its correlation with FD-OCT and perimetry.

    Science.gov (United States)

    Hokazono, Kenzo; Raza, Ali S; Oyamada, Maria K; Hood, Donald C; Monteiro, Mário L R

    2013-12-01

    To evaluate the ability of transient pattern electroretinogram (PERG) parameters to differentiate between eyes of patients with neuromyelitis optica (NMO), longitudinally extensive transverse myelitis (LETM), multiple sclerosis with optic neuritis (MS + ON), multiple sclerosis without optic neuritis (MS - ON), and controls, to compare PERG and OCT with regard to discrimination ability, and to assess the correlation between PERG, FD-OCT, and visual field measurements (VFs). Visual field measurements and full-field stimulation PERGs based on both 48- and 14-min checks were obtained from patients with MS (n = 28), NMO (n = 20), LETM (n = 18), and controls (n = 26). In addition, FD-OCT peripapillary retinal nerve fiber layer (RNFL) and segmented macular layer measurements were obtained and their correlation coefficients were determined. Compared to controls, PERG amplitude measurements were significantly reduced in eyes with NMO and MS + ON, but not in eyes with LETM and MS - ON. PERG amplitudes were significantly smaller in NMO and MS + ON eyes than in MS - ON eyes. PERG and OCT performance was similar except in NMO eyes where macular thickness parameters were more efficient at detecting abnormalities. A significant correlation was found between N95 amplitude values and OCT-measured macular ganglion cell layer thickness, total retinal thickness, and temporal peripapillary RNFL thickness. PERG amplitude was also significantly associated with VF sensitivity loss. No statistically significant difference was observed with regard to the best-performing parameters of the two methods. Pattern electroretinogram measurements were able to detect RNFL loss in MS + ON and NMO eyes, with a performance comparable to OCT. PERG amplitude measurements were reasonably well correlated with OCT-measured parameters.

  3. Autologous mesenchymal stem cells applied on the pressure ulcers had produced a surprising outcome in a severe case of neuromyelitis optica

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    Adriana Octaviana Dulamea

    2015-01-01

    Full Text Available Recent studies provided evidence that mesenchymal stem cells (MSCs have regenerative potential in cutaneous repair and profound immunomodulatory properties making them a candidate for therapy of neuroimmunologic diseases. Neuromyelitis optica (NMO is an autoimmune, demyelinating central nervous system disorder characterized by a longitudinally extensive spinal cord lesion. A 46-year-old male diagnosed with NMO had relapses with paraplegia despite treatment and developed two stage IV pressure ulcers (PUs on his legs. The patient consented for local application of autologous MSCs on PUs. MSCs isolated from the patient′s bone marrow aspirate were multiplied in vitro during three passages and embedded in a tridimensional collagen-rich matrix which was applied on the PUs. Eight days after MSCs application the patient showed a progressive healing of PUs and improvement of disability. Two months later the patient was able to walk 20 m with bilateral assistance and one year later he started to walk without assistance. For 76 months the patient had no relapse and no adverse event was reported. The original method of local application of autologous BM-MSCs contributed to healing of PUs. For 6 years the patient was free of relapses and showed an improvement of disability. The association of cutaneous repair, sustained remission of NMO and improvement of disability might be explained by a promotion/optimization of recovery mechanisms in the central nervous system even if alternative hypothesis should be considered. Further studies are needed to assess the safety and efficacy of mesenchymal stem cells in NMO treatment.

  4. Cognitive impairment in neuromyelitis optica spectrum disorders: A comparison of the Wechsler Adult Intelligence Scale-III and the Wechsler Memory Scale Revised with the Rao Brief Repeatable Neuropsychological Battery

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    Juichi Fujimori

    2017-12-01

    Full Text Available Background: Approximately 55% of patients with neuromyelitis optica spectrum disorder (NMOSD show cognitive impairment as evaluated using the Rao Brief Repeatable Neuropsychological Battery (BRBN, but this frequency appears to be higher than the frequency of specific brain lesions in NMOSD. Objective: We studied whether cognitive impairment could be observed in NMOSD patients with no or minor non-specific brain lesions. Methods: We evaluated cognitive function in 12 NMOSD and 14 MS patients using the Wechsler Adult Intelligence Scale-III (WAIS-III, the Wechsler Memory Scale-Revised (WMS-R, and the BRBN. We judged as cognitively impaired patients whose scores were below the average by 2 standard deviations or greater in 2 or more cognitive domains. Results: Cognitive impairment was observed in 5 MS patients (35.7% and in the only NMOSD patient (8.3% with symptomatic brain lesions, but not in the other NMOSD patients who had no or minor non-specific brain lesions. Meanwhile, 5 NMOSD (41.7% and 4 MS (28.6% patients who had normal cognition according to the WAIS-III and WMS-R were assessed as cognitively impaired by the BRBN (which is not standardized for age. Conclusions: Cognitive function in NMOSD patients with no or mild non-specific brain lesions was preserved according to the WAIS-III and WMS-R. Keywords: Neuromyelitis Optica, Cognitive impairment, Wechsler Adult Intelligence Scale-III, Wechsler Memory Scale-Revised, Rao Brief Repeatable Neuropsychological Battery, Multiple sclerosis

  5. Recurrent neuromyelitis optica with diffuse central nervous system involvement: case report Neuromielite óptica recorrente com envolvimento difuso do sistema nervoso central: relato de caso

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    Renan B. Domingues

    2004-06-01

    Full Text Available Several demyelinating disorders can affect children. The differential diagnosis between these diseases is usually an arduous task. Diagnostic criteria have been proposed for some of these disorders, however most of them have not yet been clinically and prospectively validated. Here we present a case of a ten year-old boy with recurrent bilateral optic neuritis and spinal cord involvement. Clinical and cerebrospinal fluid data have fulfilled diagnostic criteria for Devic's neuromyelitis optica (NMO. The differential diagnosis with multiple sclerosis (MS has become troublesome since not only optic nerves and spinal cord were involved. In one of the relapses a left hemiparesis with facial involvement was registered. Magnetic resonance imaging was also compatible with MS. This case illustrates that CNS demyelinating disorders can fulfill diagnostic criteria for more than one demyelinating disease, making the clinical judgment an important tool in the management of these patients.Diversas doenças desmielinizantes podem ocorrer em crianças, sendo muitas vezes o diagnóstico diferencial entre elas difícil. Critérios diagnósticos têm sido propostos para algumas destas entidades, entretanto nenhum deles pode ser considerado definitivo. O objetivo deste trabalho é apresentar o caso de um paciente de 10 anos de idade, com quadro recorrente de neurite óptica bilateral e mielopatia. Os dados clínicos e liquóricos preencheram critérios para o diagnóstico de neuromielite óptica de Devic. O diagnóstico diferencial foi especialmente difícil em relação à esclerose múltipla, pois não apenas os nervos ópticos e medula foram acometidos, visto que em um dos surtos registrou-se hemiparesia, com acometimento facial. A ressonância magnética foi também compatível com esclerose múltipla. Este caso ilustra que pacientes com doenças desmielinizantes do SNC podem preencher critérios diagnósticos para mais de uma delas, o que torna o julgamento cl

  6. The neuromyelitis optica presentation and the aquaporin-4 antibody in HIV-seropositive and seronegative patients in KwaZulu-Natal, South Africa

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    Ahmed I. Bhigjee

    2017-01-01

    Full Text Available Background: The association of the anti-aquaporin-4 (AQP-4 water channel antibody with neuromyelitis optica (NMO syndrome has been described from various parts of the world. There has been no large study describing this association from southern Africa, an HIV endemic area. HIV patients often present with visual disturbance or features of a myelopathy but seldom both either simultaneously or consecutively. We report our experience of NMO in the era of AQP-4 testing in HIV-positive and HIV-negative patients seen in KwaZulu-Natal, South Africa. Methods: A retrospective chart review was undertaken of NMO cases seen from January 2005 to April 2016 in two neurology units serving a population of 7.1 million adults. The clinical, radiological and relevant laboratory data were extracted from the files and analysed. Results: There were 12 HIV-positive patients (mean age 33 years, 9 (75% were women and all 12 were black patients. Of the 17 HIV-negative patients (mean age 32 years, 15 (88% were women and 10 (59% were black people. The clinical features in the two groups ranged from isolated optic neuritis, isolated longitudinally extensive myelitis or combinations. Recurrent attacks were noted in six HIV-positive patients and six HIV-negative patients. The AQP-4 antibody was positive in 4/10 (40% HIV-positive patients and 11/13 (85% HIV-negative patients. The radiological changes ranged from longitudinal hyperintense spinal cord lesions and long segment enhancing lesions of the optic nerves. Three patients, all HIV-positive, had tumefactive lesions with incomplete ring enhancement. Conclusion: This study confirms the presence of AQP-4-positive NMO in southern Africa in both HIV-positive and HIV-negative patients. The simultaneous or consecutive occurrence of optic neuritis and myelitis in an HIV-positive patient should alert the clinician to test for the AQP-4 antibody. It is important to recognise this clinical syndrome as specific therapy is available

  7. Tonic spasms are a common clinical manifestation in patients with neuromyelitis optica Espasmos tônicos são manifestações clínicas frequentes em pacientes com neuromielite óptica

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    Luz Abaroa

    2013-05-01

    Full Text Available Tonic spasms have been most commonly associated with multiple sclerosis. To date, few reports of series of patients with neuromyelitis optica and tonic spasms have been published. Methods: We analyzed the characteristics and frequency of tonic spasms in 19 subjects with neuromyelitis optica. Data was collected using a semi-structured questionnaire for tonic spasms, by both retrospectively reviewing medical records and performing clinical assessment. Results: All patients except one developed this symptom. The main triggering factors were sudden movements and emotional factors. Spasms were commonly associated to sensory disturbances and worsened during the acute phases of the disease. Carbamazepine was most commonly used to treat the symptom and patients showed good response to the drug. Conclusions: Tonic spasms are a common clinical manifestation in patients with neuromyelitis optica.Espasmos tônicos têm sido mais frequentemente associados com esclerose múltipla. Foram publicados até agora poucos relatos de série de pacientes com neuromielite óptica e espasmos tônicos. Métodos: Foram analisadas as características e a frequência de espasmos tônicos em 19 indivíduos com neuromielite óptica. Os dados foram coletados por meio de um questionário semiestruturado para espasmos tônicos, mediante a avaliação retrospectiva dos prontuários e a análise dos dados clínicos Resultados: Todos os pacientes com neuromielite óptica exceto um apresentaram espasmos tônicos. Os principais fatores desencadeantes foram movimentos bruscos e fatores emocionais. Espasmos foram frequentemente associados a perturbações sensoriais e se agravaram durante a fase aguda da doença. A carbamazepina foi utilizada frequentemente para tratar os sintomas, com boa resposta. Conclusões: Os espasmos tônicos são manifestações clínicas frequentes em pacientes com neuromielite óptica.

  8. Devic’s neuromyelitis optica: a critical review Neuromielite óptica de Devic: revisão crítica

    Directory of Open Access Journals (Sweden)

    Marco Aurélio Lana-Peixoto

    2008-03-01

    Full Text Available Devic's neuromyelitis optica (NMO is an idiopathic inflammatory demyelinating and necrotizing disease characterized by predominant involvement of the optic nerves and spinal cord. In Asian countries relapsing NMO has been known as opticospinal multiple sclerosis. It has long been debated if NMO is a variant of multiple sclerosis (MS or a distinct disease. Recent studies have shown that NMO has more frequently a relapsing course, and results from attack to aquaporin-4 which is the dominant water channel in the central nervous system, located in foot processes of the astrocytes. Distinctive pathological features of NMO include perivascular deposition of IgG and complement in the perivascular space, granulocyte and eosinophil infiltrates and hyalinization of the vascular walls. These features distinguish NMO from other demyelinating diseases such as MS and acute demyelinating encephalomyelopathy. An IgG-antibody that binds to aquaporin-4, named NMO-IgG has high sensitivity and specificity. Magnetic resonance imaging (MRI studies have revealed that more frequently there is a long spinal cord lesion that extends through three or more vertebral segments in length. Brain MRI lesions atypical for MS are found in the majority of cases. Treatment in the acute phase includes intravenous steroids and plasma exchange therapy. Immunosupressive agents are recommended for prophylaxis of relapses.Neuromielite óptica ou doença de Devic (NMO é uma doença inflamatória com desmielinização e necrose envolvendo preferencialmente os nervos ópticos e a medula espinal. Desde sua descrição inicial tem havido controvérsia se a NMO é uma variante da esclerose múltipla (EM ou se é uma entidade independente. Na Ásia a doença é conhecida como esclerose múltipla óptico-espinal. Recentes avanços tem demonstrado que na maioria dos casos a NMO é recorrente e resulta de alterações inflamatórias por ataque à aquaporina-4, uma proteína localizada nos p

  9. Neuromyelitis optica and multiple sclerosis

    DEFF Research Database (Denmark)

    Bennett, J. L.; de Seze, J.; Lana-Peixoto, M.

    2015-01-01

    aquaporin-4 present in up to 80% of NMO patients enables distinction from MS. Optic neuritis may occur in either condition resulting in neuro-anatomical retinal changes. Optical coherence tomography (OCT) has become a useful tool for analyzing retinal damage both in MS and NMO. Numerous studies showed...... that optic neuritis in NMO typically results in more severe retinal nerve fiber layer (RNFL) and ganglion cell layer thinning and more frequent development of microcystic macular edema than in MS. Furthermore, while patients' RNFL thinning also occurs in the absence of optic neuritis in MS, subclinical...

  10. Comparison of spontaneous brain activity revealed by regional homogeneity in AQP4-IgG neuromyelitis optica-optic neuritis versus MOG-IgG optic neuritis patients: a resting-state functional MRI study

    Directory of Open Access Journals (Sweden)

    Wang J

    2017-10-01

    Full Text Available Junqing Wang,1,* Yuan Tian,2,* Yi Shao,3,* Hui Feng,1 Limin Qin,1 Weiwei Xu,1 Hongjuan Liu,1 Quangang Xu,1 Shihui Wei,1 Lin Ma2 1Department of Ophthalmology, 2Department of Radiology, Chinese PLA General Hospital, Beijing, 3Department of Ophthalmology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China *These authors contributed equally to this work Objective: Many previous studies have demonstrated that neuromyelitis optica (NMO patients have abnormalities of brain anatomy and function. However, differences in spontaneous brain activity between myelin oligodendrocyte glycoprotein (MOG-IgG ON and aquaporin 4(AQP4-neuromyelitis optica-optic neuritis (ON remain unknown. In the current study, we investigated the brain neural homogeneity in MOG-IgG ON versus AQP4-IgG NMO-ON subjects by regional homogeneity (ReHo method using magnetic resonance imaging (MRI. Patients and methods: A total of 32 NMO-ON and ON subjects (21 with AQP4-IgG+NMO-ON and 11 with MOG-IgG+ON and 34 healthy controls (HCs closely matched for age were recruited, and scans were performed for all subjects. A one-way analysis of variance (ANOVA was performed to determine the regions in which the ReHo was different across the three groups. NMO-ON and ON subjects were distinguished from HCs by a receiver operating characteristic (ROC curve. The relationship between the mean ReHo in many brain regions and clinical features in NMO subjects was calculated by Pearson correlation analysis. Results: Compared with HCs, MOG-IgG+ON subjects had significantly decreased ReHo values in the posterior lobe of the left cerebellum and increased ReHo values in the left inferior frontal gyrus, right prefrontal gyrus, and left precentral/postcentral gyrus. AQP4-IgG+NMO-ON subjects showed higher ReHo values in the left inferior frontal gyrus and right middle temporal/occipital gyrus. Compared with MOG-IgG+ON subjects, AQP4-IgG+NMO-ON subjects had lower Re

  11. An unusual chiasmal visual defect in a patient with neuromyelitis optica: case report Comprometimento quiasmático incomum em um paciente com neuromielite óptica: relato de caso

    Directory of Open Access Journals (Sweden)

    Roberta Martins da Silva Costa

    2007-02-01

    Full Text Available PURPOSE: To report the unusual visual field finding due to a chiasmal neuritis in a 33-year-old female with the diagnosis of optic neuromyelitis optica (Devic's syndrome. METHODS: We report a case of a 33 years old female with limb paraesthesias, weakness in the legs, bowel and bladder dysfunction that was referred to the "Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo" in October 1995. Six years and four months later she had an acute visual involvement. Ophthalmologic examination, laboratory studies, magnetic resonance imaging (MRI and a 24-2 threshold visual field in the Humphrey field analyzer were performed. RESULTS: The MRI scan showed enlargement and cavitation on the spinal cord and chiasmal involvement (thickening of the chiasm with contrast enhancement and no demyelinating lesions in the brain, brainstem, or cerebellum. The central 24-degree threshold field examination showed an inferior visual field defect bitemporally, disclosing a chiasmal involvement. CONCLUSION: Chiasmal involvement may occur in neuromyelitis optica, probably due to a plaque within the chiasm. The authors call attention to the importance of visual field examination with particular regard to quantifying the visual impairment and follow-up of these patients.OBJETIVO: Relatar o caso de uma mulher de 33 anos de idade, com o diagnóstico de neuromielite óptica (síndrome de Devic acometendo o quiasma óptico que apresentou um escotoma incomum no exame de campo visual. MÉTODOS: Uma paciente do sexo feminino, portadora de parestesias nos membros inferiores, fraqueza nas pernas, disfunção da defecação e disfunção urinária, foi encaminhada para o Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo em outubro do ano de 1995. Seis anos e quatro meses mais tarde ela sofreu acometimento visual agudo. Foram realizados exame oftalmológico completo, exame de líquor, resson

  12. [Proportion and significance of CD1d(hi)CD5⁺CD19⁺ regulatory B cell in peripheral blood of patients with neuromyelitis optica].

    Science.gov (United States)

    Yang, Fen; Huang, Dehui; Cheng, Chen; Wu, Weiping

    2015-03-01

    To detect the proportion of CD1d(hi)CD5⁺CD19⁺ regulatory B cells (Bregs) in peripheral blood of the patients with neuromyelitis optica (NMO), and explore whether CD1d(hi)CD5⁺CD19⁺ Bregs can play a role as a biomarker in the diagnosis of NMO versus multiple sclerosis (MS). Flow cytometry was performed to detect the proportion of CD1d(hi)CD5⁺CD19⁺ Bregs in peripheral blood from 44 cases of NMO, 38 cases of MS, and 30 healthy controls. The serum level of aquaporin-4 antibody (AQP4-Ab) of patients with NMO was detected by indirect immunofluorescence assay. The proportion of CD1d(hi)CD5⁺CD19⁺ Bregs in CD19⁺ B cells and lymphocytes was significantly lower in NMO group than in MS and control groups; however, there was no significant difference between MS group and control group. The proportion of CD1d(hi)CD5⁺CD19⁺ Bregs in CD19⁺ B cells and lymphocytes was lower in AQP4-Ab-positive NMO patients than in AQP4-Ab-negative NMO patients, and the difference was statistically significant. CD1d(hi)CD5⁺CD19⁺ Bregs may be a biomarker in the differential diagnosis of NMO versus MS.

  13. Immune system markers of neuroinflammation in patients with clinical diagnose of neuromyelitis optica Marcadores imunológicos em pacientes com diagnóstico de neuromielite óptica

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    Soniza Vieira Alves-Leon

    2008-01-01

    Full Text Available Neuromyelitis optica (NMO is an inflammatory, demyelinating disease of the central nervous system characterized by the association of a serious myelitis and unilateral or bilateral optic neuritis. The present study aimed to analyze the immunological parameters of NMO patients with diagnosis established based on Wingerchuck et al. (1999 criteria. Production of IgG and IgA antibodies to antigens of MBP, PLP 95-116, MOG 92-106, and the cytokines interleukin-4 (IL-4 and interferon-γ (INF-γ were assessed by Elisa assay. The cohort was formed by 28 NMO patients and a matched healthy control group. NMO patients had significant high levels of IgG to MOG (pA neuromielite óptica (NMO é doença inflamatória do sistema nervoso central, caracterizada por mielite aguda ou subaguda grave e neurite óptica unilateral ou bilateral. Este estudo objetiva analisar parâmetros imunológicos de pacientes com critérios de Wingerchuck et al. (1999 para NMO. O método de ELISA avaliou a produção de IgG e IgA para antígenos da proteína básica da mielina (MBP, o proteolipídeo (PLP 95-116, a glicoproteina associada ao oligodendrócito (MOG 92-106 e as citocinas interleucina-4 (IL-4 e interferon-gama (INF-γ. Foram incluνdos 28 pacientes com NMO pareados com controles saudáveis. Pacientes com NMO apresentaram níveis significativamente elevados de imunoglobulinas reativas dos isotipos IgG para MOG (p<0,0001, PLP (p=0,0002 e MBP (p<0,0001 e IgA somente para MBP (p<0,0001. Os níveis de INF-γ (p=0,61 foram semelhantes aos controles. A produção elevada de IL-4 (p=0,0084 indica papel importante na ativação de células regulatórias Th2 e linfócitos B produtores de IgA e da ativação da imunidade humoral.

  14. Neuromielitis óptica con alta expresión de acuaporina-4 y anticuerpos anti-acuaporina-4 positivos en suero Neuromyelitis optica with high aquaporin-4 expression and positive serum aquaporin-4 autoantibodies

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    Alejandra Báez

    2012-04-01

    Full Text Available La presencia de anticuerpos IgG en suero, con blanco en los canales de acuaporina-4, es específica de la neuromielitis óptica (NMO. El 60% de los pacientes con NMO presentan lesiones cerebrales en la resonancia magnética (RM; en un 8% (mayoría niños estas lesiones se consideraron "atípicas". Presentamos dos pacientes con NMO y lesiones en el SNC de alta expresión de acuaporina-4. Caso 1: varón de 50 años, que comenzó con pérdida de visión en ojo derecho (OD. Recibió tratamiento empírico con metilprednisolona 1 g/d x 3 días. Al mes presentó dolor generalizado y hemiparesia derecha; nuevamente recibió metilprednisolona 1 g/d x 5 días e IgG IV 400 mg/kg/d × 5 días. Recuperó la deambulación persistiendo el dolor y fenómenos paroxísticos en los 4 miembros. Potenciales evocados visuales: P100, ojo izquierdo (OI 123 mseg. OD sin respuesta. La RM de cerebro (FLAIR mostró hiperintensidad en nervio óptico derecho, hipotálamo y comisura blanca anterior. RM cervical: lesión medular extensa (5 cuerpos vertebrales. Caso 2: mujer de 53 años, con disminución de la agudeza visual en ambos ojos y parestesias en miembros inferiores que remitieron espontáneamente. Evolucionó al mes con cuadriparesia e incontinencia esfinteriana. Recibió metilprednisolona 1 g/d x 5 días, sin mejoría. Potenciales evocados visuales: P100 OI 124 mseg. OD 128 mseg. RM cerebro: (FLAIR hiperintensidad hipotalámica y periacueductal. RM cervical: lesión medular extensa (7 cuerpos vertebrales. Anticuerpos anti-acuaporina-4 positivos en ambos pacientes (inmunofluorescencia indirecta. Las lesiones consideradas "atípicas", como aquí, en sitios con alta densidad de proteínas canales de agua AQP4 deberán considerarse para el diagnóstico diferencial.Disease-specific aquaporin-4 antibodies (NMO-IgG are the main effector of lesions in neuromyelitis optica (NMO patients. Brain MRI lesions are detected in 60% of them, with 8% (almost infants at sites of high

  15. MRI characteristics of neuromyelitis optica spectrum disorder An international update

    DEFF Research Database (Denmark)

    Kim, H. J.; Paul, F.; Lana-Peixoto, M. A.

    2015-01-01

    location without optic nerve and spinal cord involvement. Thus, characteristics of brain abnormalities in such patients have become of increased interest. In this regard, MRI has an increasingly important role in the differential diagnosis of NMO and its spectrum disorder (NMOSD), particularly from...

  16. A Urinary Metabolic Signature for Multiple Sclerosis and Neuromyelitis Optica

    DEFF Research Database (Denmark)

    Gebregiworgis, Teklab; Nielsen, Helle H; Massilamany, Chandirasegaran

    2016-01-01

    Urine is a metabolite-rich biofluid that reflects the body's effort to maintain chemical and osmotic homeostasis. Clinical diagnosis routinely relies on urine samples because the collection process is easy and noninvasive. Despite these advantages, urine is an under-investigated source of biomark......Urine is a metabolite-rich biofluid that reflects the body's effort to maintain chemical and osmotic homeostasis. Clinical diagnosis routinely relies on urine samples because the collection process is easy and noninvasive. Despite these advantages, urine is an under-investigated source...

  17. Antibodies against interferon-beta in neuromyelitis optica patients

    DEFF Research Database (Denmark)

    Asgari, Nasrin; Kyvik, Kirsten Ohm; Steenstrup, Troels

    2014-01-01

    -negative patients were anti-AQP4 antibody-positive. Eleven patients (three NAbs-positive, eight NAbs-negative) developed cerebral lesions and 12 patients (four NAbs-positive, eight NAbs-negative) spinal cord lesions on magnetic resonance imaging as gadolinium positive lesions or T2-weighted lesions...... of IFN-neutralizing antibodies (NAbs) in 15 IFN-ß treated NMO-patients from a population-based retrospective case series cohort. NMO patients not treated with IFN-ß acted as a reference group. IFN-ß antibody determinations included binding antibodies (BAbs) measured by immunoassay and NAbs measured...

  18. Epidemiological, clinical and immunological aspects of neuromyelitis optica (NMO)

    DEFF Research Database (Denmark)

    Asgari, Nasrin

    2013-01-01

    than earlier believed. Clinical, radiologic and serological data were reviewed in order to establish the diagnostic accuracy of anti-AQP4 antibodies/NMO-IgG for specific syndromes in NMO. We observed assay characteristics with a sensitivity of 62% and a specificity of 100%. The diagnosis of NMO based...... of the brainstem, cerebellum and periventricular areas. The lesions were characterized by deposition of immunoglobulin and complement, loss of AQP-4 expression and loss of reactive astrocytes co-localizing with inflammatory cell infiltration. This pattern is similar to the characteristic histological...

  19. Diagnosis and management of Neuromyelitis Optica Spectrum Disorder (NMOSD) in Iran

    DEFF Research Database (Denmark)

    Sahraian, Mohammad Ali; Moghadasi, Abdorreza Naser; Azimi, Amir Reza

    2017-01-01

    their practice and unify the treatment approaches in different communities. In order to develop a national consensus and recommendations for the diagnosis and management of NMOSD in Iran, a group of neurologists with long term experience in management of NMOSD were gathered to develop this consensus based...... on available national and international data. The primary draft was prepared and discussed to suggest the most appropriate treatment for these patients. We propose strategies for early diagnosis and treatment for prevention of relapses and minimizing consequences of attacks as a primary therapeutic goal...... in order to reduce attack frequency. The current consensus reviews the previous data and provides the clinicians with practical recommendations and advices for the diagnosis and management of NMOSD based on scientific data and clinical experience....

  20. Clinical Features of Patients with Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Hai Chen

    2016-01-01

    Conclusion: The different CSF features combined with clinical, magnetic resonance imaging, and serum characteristics between Chinese patients with MS and NMOSD could assist in the differential diagnosis.

  1. Neuromyelitis optica IgG in the cerebrospinal fluid induces astrocytopathy in optic nerve

    DEFF Research Database (Denmark)

    Soelberg, Kerstin; Lillevang, Søren Thue; Mørch, Marlene

    -ON. The predilection of the optic nerve in NMOSD may partly be explained by the dense expression of AQP4 in the optic nerve. We previously reported that AQP4-IgG in cerebrospinal fluid (CSF) becomes widely distributed in the brain and causes complementdependent astrocyte injury in periventricular areas and brain...... of brain-specific antibodies in cerebrospinal fluid. Journal of neuroimmunology 2013;254:76-82....

  2. Use of Advanced Magnetic Resonance Imaging Techniques in Neuromyelitis Optica Spectrum Disorder

    DEFF Research Database (Denmark)

    Kremer, S.; Renard, F.; Achard, S.

    2015-01-01

    not been identified. This literature review summarizes the literature on advanced quantitative imaging measures reported for patients with NMO spectrum disorder, including proton MR spectroscopy, diffusion tensor imaging, magnetization transfer imaging, quantitative MR voltametry, and ultrahigh...

  3. Experimental Neuromyelitis Optica Induces a Type I Interferon Signature in the Spinal Cord

    DEFF Research Database (Denmark)

    Oji, Satoru; Nicolussi, Eva-Maria; Kaufmann, Nathalie

    2016-01-01

    ) on astrocytes. When these antibodies gain access to the CNS, they mediate astrocyte destruction by complement-dependent and by antibody-dependent cellular cytotoxicity. In contrast to multiple sclerosis (MS) patients who benefit from therapies involving type I interferons (I-IFN), NMO patients typically do......, when the blood-brain barrier was open. With this treatment regimen, we could amplify possible effects of the I-IFN induced genes on the transmigration of infiltrating cells through the blood brain barrier, and on lesion formation and expansion, but could avoid effects of I-IFN on the differentiation...

  4. Anti Myelin Oligodendrocyte Glycoprotein associated Immunoglobulin G (AntiMOG-IgG)-associated Neuromyelitis Optica Spectrum Disorder with Persistent Disease Activity and Residual Cognitive Impairment.

    Science.gov (United States)

    Pandit, Lekha; Nakashima, Ichiro; Mustafa, Sharik; Takahashi, Toshiyuki; Kaneko, Kimhiko

    2017-01-01

    Antibodies targeting myelin oligodendrocyte glycoprotein (MOG) have been recently reported in association with idiopathic inflammatory central nervous system disorders. Initially believed to be a benign disorder, anti MOG-IgG was noted to cause steroid responsive recurrent optic neuritis and isolated longitudinally extensive myelitis. However, there is growing evidence that the disease may be predominantly relapsing, often producing severe visual loss and involving regions other than the spinal cord and optic nerve. We report an adolescent male with an aggressive disease course previously undescribed in anti MOG-IgG-associated disease that left him with residual cognitive dysfunction.

  5. Astrovirus Pathogenesis

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    Cydney Johnson

    2017-01-01

    Full Text Available Astroviruses are a major cause of diarrhea in the young, elderly, and the immunocompromised. Since the discovery of human astrovirus type 1 (HAstV-1 in 1975, the family Astroviridae has expanded to include two more human clades and numerous mammalian and avian-specific genotypes. Despite this, there is still little known about pathogenesis. The following review highlights the current knowledge of astrovirus pathogenesis, and outlines the critical steps needed to further astrovirus research, including the development of animal models of cell culture systems.

  6. Multicentre comparison of a diagnostic assay

    DEFF Research Database (Denmark)

    Waters, Patrick; Reindl, Markus; Saiz, Albert

    2016-01-01

    ) assays in neuromyelitis optica spectrum disorders (NMOSD). METHODS: Coded samples from patients with neuromyelitis optica (NMO) or NMOSD (101) and controls (92) were tested at 15 European diagnostic centres using 21 assays including live (n=3) or fixed cell-based assays (n=10), flow cytometry (n=4...

  7. Pathogenesis of Parkinson's disease

    OpenAIRE

    Riederer, Peter; Lange, Klaus W.

    1992-01-01

    The importance of genetic aspects, ageing, environmental factors, head trauma, defective mitochondrial respiration, altered iron metabolism, oxidative stress and glutamatergic overactivity of the basal ganglia in the pathogenesis of Parkinson's disease (PD) are considered in this review.

  8. Viral pathogenesis in diagrams

    National Research Council Canada - National Science Library

    Tremblay, Michel; Berthiaume, Laurent; Ackermann, Hans-Wolfgang

    2001-01-01

    .... The 268 diagrams in Viral Pathogenesis in Diagrams were selected from over 800 diagrams of English and French virological literature, including one derived from a famous drawing by Leonardo da Vinci...

  9. Pathogenesis of Hepatic Encephalopathy

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    Irena Ciećko-Michalska

    2012-01-01

    Full Text Available Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy.

  10. The Pathogenesis of Autism

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    Timothy John Watts

    2008-01-01

    Full Text Available Autism is well known as a complex developmental disorder with a seemingly confusing and uncertain pathogenesis. The definitive mechanisms that promote autism are poorly understood and mostly unknown, yet available theories do appear to focus on the disruption of normal cerebral development and its subsequent implications on the functional brain unit. This mini-review aims solely to discuss and evaluate the most prominent current theories regarding the pathogenesis of autism. The main conclusion is that although there is not a clear pathway of mechanisms directed towards a simple pathogenesis and an established link to autism on the symptomatic level; there are however several important theories (neural connectivity, neural migration, excitatory-inhibitory neural activity, dendritic morphology, neuroimmune; calcium signalling and mirror neurone which appear to offer an explanation to how autism develops. It seems probable that autism's neurodevelopmental defect is ‘multi-domain’ in origin (rather than a single anomaly and is hence distributed across numerous levels of study (genetic, immunopathogenic, etc.. A more definitive understanding of the pathogenesis could facilitate the development of better treatments for this complex psychiatric disorder.

  11. Molecular Pathogenesis of Spondyloarthritis

    DEFF Research Database (Denmark)

    Carlsen, Thomas Gelsing

    This dissertation includes a presentation of knowledge on the molecular pathogenesis of spondyloarthritis achieved through a PhD programme at Aalborg University from 1.12.2011 - 1.12.2014. Work was carried out in the Laboratory of Medical Mass Spectrometry, headed by: Professor Svend Birkelund...

  12. Complement and Viral Pathogenesis

    Science.gov (United States)

    Stoermer, Kristina A.; Morrison, Thomas E.

    2011-01-01

    The complement system functions as an immune surveillance system that rapidly responds to infection. Activation of the complement system by specific recognition pathways triggers a protease cascade, generating cleavage products that function to eliminate pathogens, regulate inflammatory responses, and shape adaptive immune responses. However, when dysregulated, these powerful functions can become destructive and the complement system has been implicated as a pathogenic effector in numerous diseases, including infectious diseases. This review highlights recent discoveries that have identified critical roles for the complement system in the pathogenesis of viral infection. PMID:21292294

  13. Pathogenesis of microbial keratitis.

    Science.gov (United States)

    Lakhundi, Sahreena; Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed

    2017-03-01

    Microbial keratitis is a sight-threatening ocular infection caused by bacteria, fungi, and protist pathogens. Epithelial defects and injuries are key predisposing factors making the eye susceptible to corneal pathogens. Among bacterial pathogens, the most common agents responsible for keratitis include Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumonia and Serratia species. Fungal agents of corneal infections include both filamentous as well as yeast, including Fusarium, Aspergillus, Phaeohyphomycetes, Curvularia, Paecilomyces, Scedosporium and Candida species, while in protists, Acanthamoeba spp. are responsible for causing ocular disease. Clinical features include redness, pain, tearing, blur vision and inflammation but symptoms vary depending on the causative agent. The underlying molecular mechanisms associated with microbial pathogenesis include virulence factors as well as the host factors that aid in the progression of keratitis, resulting in damage to the ocular tissue. The treatment therefore should focus not only on the elimination of the culprit but also on the neutralization of virulence factors to minimize the damage, in addition to repairing the damaged tissue. A complete understanding of the pathogenesis of microbial keratitis will lead to the rational development of therapeutic interventions. This is a timely review of our current understanding of the advances made in this field in a comprehensible manner. Coupled with the recently available genome sequence information and high throughput genomics technology, and the availability of innovative approaches, this will stimulate interest in this field. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Application of unimodal optic fiber to communications among electric substations; Aplicacion de fibra optica unimodal a comunicaciones entre subestaciones electricas

    Energy Technology Data Exchange (ETDEWEB)

    Martinez Pinon, Fernando; Hernandez Juarez, Taide [Instituto de Investigaciones Electricas, Cuernavaca (Mexico)

    1992-07-01

    The utilization of the unimodal fiber optics technology in the electric power systems, represents one of the best communication options because of its multiple advantages, that results in a better coordination of the technical and administrative activities, needed to carry the electric energy from its generation site to the most remote locations. In this document a study, in accordance with the available options for the design of communication systems via unimodal optic fiber, is presented. With this technology, ties of more than 100 kilometers without the need of repeating stations, can be made. [Espanol] La utilizacion de la tecnologia de fibra optica unimodal en los sistemas electricos de potencia representa una de las mejores alternativas de comunicacion por sus multiples ventajas que se traducen en una mejor coordinacion de las acitividades tecnicas y administrativas necesarias para llevar la energia electrica desde el lugar de generacion hasta los puntos mas distantes. En este documento se presenta un estudio de acuerdo a las opciones disponibles para el diseno de sistemas de comunicacion por fibra optica unimodal. Con esta tecnologia se pueden realizar enlaces mayores que 100 km sin necesidad de repetidores.

  15. Molecular Pathogenesis of NASH

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    Alessandra Caligiuri

    2016-09-01

    Full Text Available Nonalcoholic steatohepatitis (NASH is the main cause of chronic liver disease in the Western world and a major health problem, owing to its close association with obesity, diabetes, and the metabolic syndrome. NASH progression results from numerous events originating within the liver, as well as from signals derived from the adipose tissue and the gastrointestinal tract. In a fraction of NASH patients, disease may progress, eventually leading to advanced fibrosis, cirrhosis and hepatocellular carcinoma. Understanding the mechanisms leading to NASH and its evolution to cirrhosis is critical to identifying effective approaches for the treatment of this condition. In this review, we focus on some of the most recent data reported on the pathogenesis of NASH and its fibrogenic progression, highlighting potential targets for treatment or identification of biomarkers of disease progression.

  16. Pathogenesis of Candida infections.

    Science.gov (United States)

    Odds, F C

    1994-09-01

    Candida infections of the skin and superficial mucosal sites are the result of an interplay between fungal virulence and host defenses. Epidermal proliferation and T-lymphocyte immune responses are expressed by the host to combat fungal invasion, but inflammatory responses and nonspecific inhibitors also probably play a role. Candida albicans can express at least three types of surface adhesion molecules to colonize epithelial surfaces, plus an aspartyl proteinase enzyme able to facilitate initial penetration of keratinized cells. Deeper penetration of keratinized epithelia is assisted by hypha formation, and C. albicans hyphae may use contact sensing (thigmotropism) as a guiding mechanism. Pathogenesis requires differential expression of virulence factors at each new stage of the process: a propensity for rapid alteration of the expressed phenotype in C. albicans may therefore be a significant factor in establishing the comparatively high pathogenic potential of this species.

  17. Pathogenesis of Takotsubo syndrome

    Directory of Open Access Journals (Sweden)

    Daniele Masarone

    2017-01-01

    Full Text Available Takotsubo syndrome (TTS is an enigmatic disease with a multifactorial and still unresolved pathogenesis. Postulated mechanisms include catecholamine excess, coronary artery spasm, and microvascular dysfunction, however catecholamines seem to play a central role in the pathophysiology of TTS. In facts catecholamines have relevant effects on the vasculature and myocardium. Toxic direct effects of catecholamine on myocardium are mediated by multiple pathway including functional hypoxia, metabolic changes and changes in membrane permeability leading to various electrolytic imbalances. Recently report of familial cases has suggested a genetic component. Further research is required to help clarify the proposed hypotheses and to increase our understanding of the cardiovascular responses to acute stress and the pathophysiology underpinning TTS.

  18. Pathogenesis of Mucormycosis

    Science.gov (United States)

    Spellberg, Brad; Walsh, Thomas J.; Kontoyiannis, Dimitrios P.

    2012-01-01

    Mucormycosis is a life-threatening infection that occurs in patients who are immunocompromised because of diabetic ketoacidosis, neutropenia, organ transplantation, and/or increased serum levels of available iron. Because of the increasing prevalence of diabetes mellitus, cancer, and organ transplantation, the number of patients at risk for this deadly infection is increasing. Despite aggressive therapy, which includes disfiguring surgical debridement and frequently adjunctive toxic antifungal therapy, the overall mortality rate is high. New strategies to prevent and treat mucormycosis are urgently needed. Understanding the pathogenesis of mucormycosis and the host response to invading hyphae ultimately will provide targets for novel therapeutic interventions. In this supplement, we review the current knowledge about the virulence traits used by the most common etiologic agent of mucormycosis, Rhizopus oryzae. Because patients with elevated serum levels of available iron are uniquely susceptible to mucormycosis and these infections are highly angioinvasive, emphasis is placed on the ability of the organism to acquire iron from the host and on its interactions with endothelial cells lining blood vessels. Several promising therapeutic strategies in preclinical stages are identified. PMID:22247441

  19. Kaposi sarcoma herpesvirus pathogenesis.

    Science.gov (United States)

    Mariggiò, Giuseppe; Koch, Sandra; Schulz, Thomas F

    2017-10-19

    Kaposi sarcoma herpesvirus (KSHV), taxonomical name human gammaherpesvirus 8, is a phylogenetically old human virus that co-evolved with human populations, but is now only common (seroprevalence greater than 10%) in sub-Saharan Africa, around the Mediterranean Sea, parts of South America and in a few ethnic communities. KSHV causes three human malignancies, Kaposi sarcoma, primary effusion lymphoma, and many cases of the plasmablastic form of multicentric Castleman's disease (MCD) as well as occasional cases of plasmablastic lymphoma arising from MCD; it has also been linked to rare cases of bone marrow failure and hepatitis. As it has colonized humans physiologically for many thousand years, cofactors are needed to allow it to unfold its pathogenic potential. In most cases, these include immune defects of genetic, iatrogenic or infectious origin, and inflammation appears to play an important role in disease development. Our much improved understanding of its life cycle and its role in pathogenesis should now allow us to develop new therapeutic strategies directed against key viral proteins or intracellular pathways that are crucial for virus replication or persistence. Likewise, its limited (for a herpesvirus) distribution and transmission should offer an opportunity for the development and use of a vaccine to prevent transmission.This article is part of the themed issue 'Human oncogenic viruses'. © 2017 The Authors.

  20. Pathogenesis and biology.

    Science.gov (United States)

    Winkler, Frank

    2018-01-01

    Metastasis to the brain is an increasing complication of solid cancers. Fortunately, our understanding of its pathogenesis has greatly increased in the last decade, with crucial insights into the molecular and cellular determinants of successful brain colonization; some aspects remain less well understood. The latter include the exact features of brain metastasis-initiating cancer cells, and a potential premetastatic niche. It is clear that a brain-arrested cancer cell has to master a sequence of steps to eventually grow to a clinically relevant brain metastasis. Various brain-specific cell types and molecular niches promote or hinder brain colonization in a dynamic and reciprocal manner. After mandatory extravasation and colonization of a brain-specific perivascular niche, the cancer cell can stay dormant, or further grow by dynamic interactions with cerebral blood vessels. In addition, the activation of certain molecular pathways on site of the cancer cell which are related to growth, motility, survival, and adaptation to the brain environment appears also important, given their characteristic modification in brain metastases of patients. A deeper understanding of the most vulnerable steps of the brain metastatic cascade may foster the development of novel preventive approaches, and that of core biologic mechanisms for macrometastatic growth and persistence will help to develop better therapeutics. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Pathogenesis of rhinitis.

    Science.gov (United States)

    Eifan, A O; Durham, S R

    2016-09-01

    Rhinitis is a heterogeneous condition that has been associated with inflammatory responses as in allergic rhinitis but can also occur in the absence of inflammation such as in so-called idiopathic (previously 'vasomotor') rhinitis. Allergic rhinitis affects approximately one in four of the population of westernized countries and is characterized by typical symptoms of nasal itching, sneezing, watery discharge and congestion. The intention of this review is to illustrate key concepts of the pathogenesis of rhinitis. Imbalance in innate and adaptive immunity together with environmental factors is likely to play major roles. In allergic rhinitis, initial allergen exposure and sensitization involves antigen-presenting cells, T and B lymphocytes and results in the generation of allergen-specific T cells and allergen-specific IgE antibodies. On re-exposure to relevant allergens, cross-linking of IgE on mast cells results in the release of mediators of hypersensitivity such as histamine and immediate nasal symptoms. Within hours, there is an infiltration by inflammatory cells, particularly Th2 T lymphocytes, eosinophils and basophils into nasal mucosal tissue that results in the late-phase allergic response. Evidence for nasal priming and whether or not remodelling may be a feature of allergic rhinitis will be reviewed. The occurrence of so-called local allergic rhinitis in the absence of systemic IgE will be discussed. Non-allergic (non-IgE-mediated) rhinitis will be considered in the context of inflammatory and non-inflammatory disorders. © 2016 John Wiley & Sons Ltd.

  2. Pathogenesis of bovine neosporosis.

    Science.gov (United States)

    Dubey, J P; Buxton, D; Wouda, W

    2006-05-01

    The protozoan parasite Neospora caninum is a major pathogen of cattle and dogs, being a significant cause of abortion in cattle in many countries. It is one of the most efficiently transmitted parasites, with up to 90% of cattle infected in some herds. The pathogenesis of abortion due to Neospora is complex and only partially understood. Losses occur after a primary infection during pregnancy but more commonly as the result of recrudescence of a persistent infection during pregnancy. Parasitaemia is followed by invasion of the placenta and fetus. It is suggested that abortion occurs when primary parasite-induced placental damage jeopardises fetal survival directly or causes release of maternal prostaglandins that in turn cause luteolysis and abortion. Fetal damage may also occur due to primary tissue damage caused by the multiplication of N. caninum in the fetus or due to insufficient oxygen/nutrition, secondary to placental damage. In addition, maternal immune expulsion of the fetus may occur associated with maternal placental inflammation and the release of maternal pro-inflammatory cytokines in the placenta. Thus N. caninum is a primary pathogen capable of causing abortion either through maternal placental inflammation, maternal and fetal placental necrosis, fetal damage, or a combination of all three. The question of how N. caninum kills the fetus exposes the complex and finely balanced biological processes that have evolved to permit bovine and other mammalian pregnancies to occur. Defining these immunological mechanisms will shed light on potential methods of control of bovine neosporosis and enrich our understanding of the continuity of mammalian and protozoal survival.

  3. Pathogenesis of Acanthamoeba Keratitis

    Science.gov (United States)

    Panjwani, Noorjahan

    2010-01-01

    Acanthamoeba keratitis (AK) is a serious infection of the cornea. At present, diagnosis of the disease is not straightforward and treatment is very demanding. While contact lens wear is the leading risk factor for AK, Acanthamoeba parasites are increasingly recognized as an important cause of keratitis in non-contact lens wearers. The first critical step in the pathogenesis of infection is the adhesion of the microbe to the surface of the host tissues. Acanthamoebae express a major virulence protein, the mannose-binding protein (MBP), which mediates the adhesion of amoebae to the surface of the cornea. The MBP is a transmembrane protein with characteristics of a typical cell surface receptor. Subsequent to the MBP-mediated adhesion to host cells, the amoebae produce a contact-dependent metalloproteinase and several contact-independent serine proteinases. These proteinases work in concert to produce a potent cytopathic effect (CPE) involving killing of the host cells, degradation of epithelial basement membrane and underlying stromal matrix, and penetration into the deeper layers of the cornea. In the hamster animal model, oral immunization with the recombinant MBP protects against AK, and this protection is associated with an increased level of anti-MBP IgA in tears of protected animals. Normal human tear fluid contains IgA antibodies against Acanthamoeba MBP that is likely to provide protection by inhibiting the adhesion of parasites to host cells. Indeed, in in vitro CPE assays, even a low concentration of tears (10 [MU]μL of undiluted tears per milliliter of media) almost completely inhibits Acanthamoeba-induced CPE. In addition to adherence-inhibiting, IgA-mediated protection, human tears also contain IgA-independent factors that provide protection against Acanthamoeba-induced CPE by inhibiting the activity of cytotoxic proteinases. Characterization of the CPE-inhibitory factors of human tears should lead to a better understanding of the mechanism by which the

  4. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... d Other Conditions to Rule Out Lyme Disease Lupus Neuromyelitis Optica Acute Disseminated Encephalomyelitis (ADEM) d For ... with MS d Diet, Exercise & Healthy Behaviors Diet & Nutrition Exercise Heat & Temperature Sensitivity Sleep Vaccinations Women's Health ...

  5. Frequency and prognostic impact of antibodies to aquaporin-4 in patients with optic neuritis

    DEFF Research Database (Denmark)

    Jarius, Sven; Frederiksen, Jette Lautrup Battistini; Waters, Patrick

    2010-01-01

    Antibodies to aquaporin-4 (AQP4-Ab) are found in 60-80% of patients with neuromyelitis optica (NMO), a severely disabling inflammatory CNS disorder of putative autoimmune aetiology, which predominantly affects the optic nerves and spinal cord....

  6. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... progressive MS (SPMS) d Related Conditions Acute Disseminated Encephalomyelitis (ADEM) Balo’s Disease HTLV-I Associated Myelopathy (HAM) ... Out Lyme Disease Lupus Neuromyelitis Optica Acute Disseminated Encephalomyelitis (ADEM) d For Clinicians d Treating MS d ...

  7. Molecular mechanisms of rosacea pathogenesis

    Directory of Open Access Journals (Sweden)

    Davydova A.M.

    2013-09-01

    Full Text Available The article presents possible molecular mechanisms for rosacea pathogenesis from current domestic and foreign clinical observations and laboratory research: regulation and expression defects of antimicrobial peptides, vascular endothelial growth factor, the effect of serine proteases, oxidative stress, reactive oxygen species and ferritin on the occurrence and course of rosacea. New developments in molecular biology and genetics are advanced for researching the interaction of multiple factors involved in rosacea pathogenesis, as well as providing the bases for potentially new therapies.

  8. Concepts in viral pathogenesis II

    Energy Technology Data Exchange (ETDEWEB)

    Notkins, A.L.; Oldstone, M.B.A.

    1986-01-01

    This paper contains papers divided among 10 sections. The section titles are: Viral Structure and Function; Viral Constructs; Oncogenes, Transfection, and Differentiation; Viral Tropism and Entry into Cells; Immune Recognition of Viruses; Evolving Concepts in Viral Pathogenesis Illustrated by Selected Plant and Animal Models; Evolving Concepts in Viral Pathogenesis Illustrated by Selected Diseases in Humans; New Trends in Diagnosis and Epidemiology; and Vaccines and Antiviral Therapy.

  9. Review: pathogenesis of gallstones.

    Science.gov (United States)

    Dowling, R H

    2000-05-01

    The aim of this article is to review selected aspects of the pathogenesis of cholesterol-rich, gall-bladder stones (GBS)--with emphasis on recent developments in biliary cholesterol saturation, cholesterol microcrystal nucleation, statis within the gall-bladder and, particularly, on the roles of intestinal transit and altered deoxycholic acid (DCA) metabolism, in GBS development. In biliary cholesterol secretion, transport and saturation, recent developments include evidence in humans and animals, that bile lipid secretion is under genetic control. Thus in mice the md-2 gene, and in humans the MDR-3 gene, encodes for a canalicular protein that acts as a 'flippase' transporting phospholipids from the inner to the outer hemi-leaflet of the canalicular membrane. In the absence of this gene, there is virtually no phospholipid or cholesterol secretion into bile. Furthermore, when inbred strains of mice that have 'lith genes' are fed a lithogenic diet, they become susceptible to high rates of GBS formation. The precipitation/nucleation of cholesterol microcrystals from supersaturated bile remains a critical step in gallstone formation. methods of studying this phenomenon have now been refined from the original 'nucleation time' to measurement of cholesterol appearance/detection times, and crystal growth assays. Furthermore, the results of recent studies indicate that, in addition to classical Rhomboid-shape monohydrate crystals, cholesterol can also crystallize, transiently, as needle-, spiral- and tubule-shaped crystals of anhydrous cholesterol. A lengthy list of promoters, and a shorter list of inhibitors, has now been defined. There are many situations where GB stasis in humans is associated with an increased risk of gallstone formation--including iatrogenic stone formation in acromegalic patients treated chronically with octreotide (OT). As well as GB stasis, however, OT-treated patients all have 'bad' bile which is supersaturated with cholesterol, has excess

  10. Frequency and prognostic impact of antibodies to aquaporin-4 in patients with optic neuritis

    DEFF Research Database (Denmark)

    Jarius, Sven; Frederiksen, Jette Lautrup Battistini; Waters, Patrick

    2010-01-01

    Antibodies to aquaporin-4 (AQP4-Ab) are found in 60-80% of patients with neuromyelitis optica (NMO), a severely disabling inflammatory CNS disorder of putative autoimmune aetiology, which predominantly affects the optic nerves and spinal cord.......Antibodies to aquaporin-4 (AQP4-Ab) are found in 60-80% of patients with neuromyelitis optica (NMO), a severely disabling inflammatory CNS disorder of putative autoimmune aetiology, which predominantly affects the optic nerves and spinal cord....

  11. Genes contributing to prion pathogenesis

    DEFF Research Database (Denmark)

    Tamgüney, Gültekin; Giles, Kurt; Glidden, David V

    2008-01-01

    incubation times, indicating that the conversion reaction may be influenced by other gene products. To identify genes that contribute to prion pathogenesis, we analysed incubation times of prions in mice in which the gene product was inactivated, knocked out or overexpressed. We tested 20 candidate genes...... show that many genes previously implicated in prion replication have no discernible effect on the pathogenesis of prion disease. While most genes tested did not significantly affect survival times, ablation of the amyloid beta (A4) precursor protein (App) or interleukin-1 receptor, type I (Il1r1...

  12. Huntington disease: pathogenesis and treatment.

    Science.gov (United States)

    Dayalu, Praveen; Albin, Roger L

    2015-02-01

    Huntington disease (HD) is an autosomal dominant inherited neurodegenerative disease characterized by progressive motor, behavioral, and cognitive decline, culminating in death. It is caused by an expanded CAG repeat in the huntingtin gene. Even years before symptoms become overt, mutation carriers show subtle but progressive striatal and cerebral white matter atrophy by volumetric MRI. Although there is currently no direct treatment of HD, management options are available for several symptoms. A better understanding of HD pathogenesis, and more sophisticated clinical trials using newer biomarkers, may lead to meaningful treatments. This article reviews the current knowledge of HD pathogenesis and treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Pathogenesis of giant colonic diverticula

    International Nuclear Information System (INIS)

    Muhletaler, C.A.; Berger, J.L.; Robinette, C.L. Jr.

    1981-01-01

    The clinical, radiographic, and pathologic findings of 3 patients with giant colonic diverticula are presented. Although several theories have been proposed for the formation of these diverticula, they have not been fully documented. One of our cases illustrates the evolution of this disorder following typical colonic diverticulitis. The pathogenesis and differential diagnosis of this unusual entity are discussed. (orig.)

  14. Molecular pathogenesis of intrahepatic cholangiocarcinoma

    DEFF Research Database (Denmark)

    Andersen, Jesper Bøje

    2014-01-01

    Cholangiocarcinoma (CCA) is an orphan cancer of the hepatobiliary tract, the incidence of which has increased in the past decade. The molecular pathogenesis of this treatment-refractory disease is poorly understood. Desmoplasia is a key causal feature of CCA; however, a majority of tumors develop...

  15. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... Encephalomyelitis (ADEM) Balo’s Disease HTLV-I Associated Myelopathy (HAM) Neuromyelitis Optica (NMO) Schilder's Disease Transverse Myelitis d ... Optica (NMO) Learn More HTLV-I Associated Myelopathy (HAM) Learn More Clinically Isolated Syndrome (CIS) Learn More ...

  16. Epigenetics and Colorectal Cancer Pathogenesis

    International Nuclear Information System (INIS)

    Bardhan, Kankana; Liu, Kebin

    2013-01-01

    Colorectal cancer (CRC) develops through a multistage process that results from the progressive accumulation of genetic mutations, and frequently as a result of mutations in the Wnt signaling pathway. However, it has become evident over the past two decades that epigenetic alterations of the chromatin, particularly the chromatin components in the promoter regions of tumor suppressors and oncogenes, play key roles in CRC pathogenesis. Epigenetic regulation is organized at multiple levels, involving primarily DNA methylation and selective histone modifications in cancer cells. Assessment of the CRC epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has thousands of abnormally methylated genes. Although relatively less is known about the patterns of specific histone modifications in CRC, selective histone modifications and resultant chromatin conformation have been shown to act, in concert with DNA methylation, to regulate gene expression to mediate CRC pathogenesis. Moreover, it is now clear that not only DNA methylation but also histone modifications are reversible processes. The increased understanding of epigenetic regulation of gene expression in the context of CRC pathogenesis has led to development of epigenetic biomarkers for CRC diagnosis and epigenetic drugs for CRC therapy

  17. Epigenetics and Colorectal Cancer Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Bardhan, Kankana; Liu, Kebin, E-mail: Kliu@gru.edu [Department of Biochemistry and Molecular Biology, Medical College of Georgia, and Cancer Center, Georgia Regents University, Augusta, GA 30912 (United States)

    2013-06-05

    Colorectal cancer (CRC) develops through a multistage process that results from the progressive accumulation of genetic mutations, and frequently as a result of mutations in the Wnt signaling pathway. However, it has become evident over the past two decades that epigenetic alterations of the chromatin, particularly the chromatin components in the promoter regions of tumor suppressors and oncogenes, play key roles in CRC pathogenesis. Epigenetic regulation is organized at multiple levels, involving primarily DNA methylation and selective histone modifications in cancer cells. Assessment of the CRC epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has thousands of abnormally methylated genes. Although relatively less is known about the patterns of specific histone modifications in CRC, selective histone modifications and resultant chromatin conformation have been shown to act, in concert with DNA methylation, to regulate gene expression to mediate CRC pathogenesis. Moreover, it is now clear that not only DNA methylation but also histone modifications are reversible processes. The increased understanding of epigenetic regulation of gene expression in the context of CRC pathogenesis has led to development of epigenetic biomarkers for CRC diagnosis and epigenetic drugs for CRC therapy.

  18. Pathogenesis of oral FIV infection

    Science.gov (United States)

    Miller, Craig; Boegler, Karen; Carver, Scott; MacMillan, Martha; Bielefeldt-Ohmann, Helle

    2017-01-01

    Feline immunodeficiency virus (FIV) is the feline analogue of human immunodeficiency virus (HIV) and features many hallmarks of HIV infection and pathogenesis, including the development of concurrent oral lesions. While HIV is typically transmitted via parenteral transmucosal contact, recent studies prove that oral transmission can occur, and that saliva from infected individuals contains significant amounts of HIV RNA and DNA. While it is accepted that FIV is primarily transmitted by biting, few studies have evaluated FIV oral infection kinetics and transmission mechanisms over the last 20 years. Modern quantitative analyses applied to natural FIV oral infection could significantly further our understanding of lentiviral oral disease and transmission. We therefore characterized FIV salivary viral kinetics and antibody secretions to more fully document oral viral pathogenesis. Our results demonstrate that: (i) saliva of FIV-infected cats contains infectious virus particles, FIV viral RNA at levels equivalent to circulation, and lower but significant amounts of FIV proviral DNA; (ii) the ratio of FIV RNA to DNA is significantly higher in saliva than in circulation; (iii) FIV viral load in oral lymphoid tissues (tonsil, lymph nodes) is significantly higher than mucosal tissues (buccal mucosa, salivary gland, tongue); (iv) salivary IgG antibodies increase significantly over time in FIV-infected cats, while salivary IgA levels remain static; and, (v) saliva from naïve Specific Pathogen Free cats inhibits FIV growth in vitro. Collectively, these results suggest that oral lymphoid tissues serve as a site for enhanced FIV replication, resulting in accumulation of FIV particles and FIV-infected cells in saliva. Failure to induce a virus-specific oral mucosal antibody response, and/or viral capability to overcome inhibitory components in saliva may perpetuate chronic oral cavity infection. Based upon these findings, we propose a model of oral FIV pathogenesis and suggest

  19. Pathogenesis of oral FIV infection.

    Directory of Open Access Journals (Sweden)

    Craig Miller

    Full Text Available Feline immunodeficiency virus (FIV is the feline analogue of human immunodeficiency virus (HIV and features many hallmarks of HIV infection and pathogenesis, including the development of concurrent oral lesions. While HIV is typically transmitted via parenteral transmucosal contact, recent studies prove that oral transmission can occur, and that saliva from infected individuals contains significant amounts of HIV RNA and DNA. While it is accepted that FIV is primarily transmitted by biting, few studies have evaluated FIV oral infection kinetics and transmission mechanisms over the last 20 years. Modern quantitative analyses applied to natural FIV oral infection could significantly further our understanding of lentiviral oral disease and transmission. We therefore characterized FIV salivary viral kinetics and antibody secretions to more fully document oral viral pathogenesis. Our results demonstrate that: (i saliva of FIV-infected cats contains infectious virus particles, FIV viral RNA at levels equivalent to circulation, and lower but significant amounts of FIV proviral DNA; (ii the ratio of FIV RNA to DNA is significantly higher in saliva than in circulation; (iii FIV viral load in oral lymphoid tissues (tonsil, lymph nodes is significantly higher than mucosal tissues (buccal mucosa, salivary gland, tongue; (iv salivary IgG antibodies increase significantly over time in FIV-infected cats, while salivary IgA levels remain static; and, (v saliva from naïve Specific Pathogen Free cats inhibits FIV growth in vitro. Collectively, these results suggest that oral lymphoid tissues serve as a site for enhanced FIV replication, resulting in accumulation of FIV particles and FIV-infected cells in saliva. Failure to induce a virus-specific oral mucosal antibody response, and/or viral capability to overcome inhibitory components in saliva may perpetuate chronic oral cavity infection. Based upon these findings, we propose a model of oral FIV pathogenesis

  20. Biology and pathogenesis of Acanthamoeba

    Directory of Open Access Journals (Sweden)

    Siddiqui Ruqaiyyah

    2012-01-01

    Full Text Available Abstract Acanthamoeba is a free-living protist pathogen, capable of causing a blinding keratitis and fatal granulomatous encephalitis. The factors that contribute to Acanthamoeba infections include parasite biology, genetic diversity, environmental spread and host susceptibility, and are highlighted together with potential therapeutic and preventative measures. The use of Acanthamoeba in the study of cellular differentiation mechanisms, motility and phagocytosis, bacterial pathogenesis and evolutionary processes makes it an attractive model organism. There is a significant emphasis on Acanthamoeba as a Trojan horse of other microbes including viral, bacterial, protists and yeast pathogens.

  1. Biology and pathogenesis of Acanthamoeba

    Science.gov (United States)

    2012-01-01

    Acanthamoeba is a free-living protist pathogen, capable of causing a blinding keratitis and fatal granulomatous encephalitis. The factors that contribute to Acanthamoeba infections include parasite biology, genetic diversity, environmental spread and host susceptibility, and are highlighted together with potential therapeutic and preventative measures. The use of Acanthamoeba in the study of cellular differentiation mechanisms, motility and phagocytosis, bacterial pathogenesis and evolutionary processes makes it an attractive model organism. There is a significant emphasis on Acanthamoeba as a Trojan horse of other microbes including viral, bacterial, protists and yeast pathogens. PMID:22229971

  2. Analysis of the thermal and optical properties of some construction materials; Analisis de las propiedades termicas y opticas de algunos materiales de construccion

    Energy Technology Data Exchange (ETDEWEB)

    Marroquin Hernandez, Karla F. [Universidad Nacional Autonoma de Mexico, Huauchinango, Puebla (Mexico)

    2000-07-01

    In this paper the optical and thermal properties of some materials of construction of greater application in a region of the state of Puebla, are obtained and presented, with the purpose of extending the bibliography and at the same time to analyze the importance that these properties have in the field of energy saving and to know the normative aspects in Mexico, as well as the control that is held of the construction materials. The properties that were analyzed are: Optical (Transmittance, reflectance, absorbency and emittance), Thermal (Thermal conductivity). [Spanish] En este trabajo se obtienen y se presentan las propiedades opticas y termicas de algunos materiales de construccion de mayor aplicacion en una region del estado de Puebla, con el fin de ampliar la bibliografia y al mismo tiempo de analizar la importancia que dichas propiedades tienen en el campo del ahorro energetico y de conocer los aspectos de la normativa en Mexico, asi como el control que se tiene de los materiales de construccion. Las propiedades que se analizaron son: Opticas (Transmitancia, reflectancia, absortancia y emitancia) Termica (Conductividad termica).

  3. Ion channelopathies and migraine pathogenesis.

    Science.gov (United States)

    Albury, Cassie L; Stuart, Shani; Haupt, Larisa M; Griffiths, Lyn R

    2017-08-01

    Migraine is a common neurological disorder that affects approximately 12-20% of the general adult population. Migraine pathogenesis is complex and not wholly understood. Molecular genetic investigations, imaging and biochemical studies, have unveiled a number of interconnected neurological pathways which seem to have a cause and effect component integral to its cause. Much weight of migraine attack initiation can be placed on the initial trigger and the pathways involved in its neuronal counter reaction. Ion channels play a large role in the generation, portrayal and mitigation of the brains response to external triggers. Several genetic studies have identified and implicated a number of ion channelopathy genes which may contribute to this generalised process. This review will focus on the genetics of migraine with particular emphasis placed on the potentially important role genes HEPH (responsible for iron transport and homeostasis) and KCNK18 (important for the transport and homeostasis of potassium) play in migraine cause.

  4. The pathogenesis of cardiac fibrosis.

    Science.gov (United States)

    Kong, Ping; Christia, Panagiota; Frangogiannis, Nikolaos G

    2014-02-01

    Cardiac fibrosis is characterized by net accumulation of extracellular matrix proteins in the cardiac interstitium, and contributes to both systolic and diastolic dysfunction in many cardiac pathophysiologic conditions. This review discusses the cellular effectors and molecular pathways implicated in the pathogenesis of cardiac fibrosis. Although activated myofibroblasts are the main effector cells in the fibrotic heart, monocytes/macrophages, lymphocytes, mast cells, vascular cells and cardiomyocytes may also contribute to the fibrotic response by secreting key fibrogenic mediators. Inflammatory cytokines and chemokines, reactive oxygen species, mast cell-derived proteases, endothelin-1, the renin/angiotensin/aldosterone system, matricellular proteins, and growth factors (such as TGF-β and PDGF) are some of the best-studied mediators implicated in cardiac fibrosis. Both experimental and clinical evidence suggests that cardiac fibrotic alterations may be reversible. Understanding the mechanisms responsible for initiation, progression, and resolution of cardiac fibrosis is crucial to design anti-fibrotic treatment strategies for patients with heart disease.

  5. Rosacea: Epidemiology, pathogenesis, and treatment

    Science.gov (United States)

    Rainer, Barbara M.; Kang, Sewon; Chien, Anna L.

    2017-01-01

    ABSTRACT Rosacea is a chronic relapsing inflammatory skin disease with a high prevalence among adults of Northern European heritage with fair skin. Symptoms present in various combinations and severity, often fluctuating between periods of exacerbation and remission. Based on morphological characteristics, rosacea is generally classified into four major subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular. Diverse environmental and endogenous factors have been shown to stimulate an augmented innate immune response and neurovascular dysregulation; however, rosacea's exact pathogenesis is still unclear. An evidence-based approach is essential in delineating differences between the many available treatments. Because of the diverse presentations of rosacea, approaches to treatment must be individualized based on the disease severity, quality-of-life implications, comorbidities, trigger factors, and the patient's commitment to therapy. PMID:29484096

  6. Pathogenesis of Idiopathic Pulmonary Fibrosis

    Science.gov (United States)

    Wolters, Paul J.; Collard, Harold R.; Jones, Kirk D.

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease associated with aging that is characterized by the histopathological pattern of usual interstitial pneumonia. Although an understanding of the pathogenesis of IPF is incomplete, recent advances delineating specific clinical and pathologic features of IPF have led to better definition of the molecular pathways that are pathologically activated in the disease. In this review we highlight several of these advances, with a focus on genetic predisposition to IPF and how genetic changes, which occur primarily in epithelial cells, lead to activation of profibrotic pathways in epithelial cells. We then discuss the pathologic changes within IPF fibroblasts and the extracellular matrix, and we conclude with a summary of how these profibrotic pathways may be interrelated. PMID:24050627

  7. The Pathogenesis of Nontraumatic Osteonecrosis

    Directory of Open Access Journals (Sweden)

    Jesse Seamon

    2012-01-01

    Full Text Available Nontraumatic osteonecrosis continues to be a challenging problem causing debilitating major joint diseases. The etiology is multifactorial, but steroid- and alcohol-induced osteonecrosis contribute to more than two thirds of all cases with genetic risk factors playing an important role in many other cases, especially when they contribute to hypercoagulable states. While the exact mechanisms remain elusive, many new insights have emerged from research in the last decade that have given us a clearer picture of the pathogenesis of nontraumatic osteonecrosis of the femoral head. Progression to end stage osteonecrosis of the femoral head appears to be related to four main factors: interactions involving the differentiation pathway of osteoprogenitor cells that promote adipogenesis, decreased angiogenesis, direct suppression of osteogenic gene expression and proliferation of bone marrow stem cells, and genetic anomalies or other diseases that promote hypercoagulable states.

  8. Etiology and Pathogenesis of Psoriasis.

    Science.gov (United States)

    Boehncke, Wolf-Henning

    2015-11-01

    Psoriasis is a common, chronic inflammatory skin disease most often appearing in the form of well-demarcated, scaly plaques. These lesions highlight the fundamental processes underlying its pathogenesis, namely, inflammation and epidermal hyperproliferation. Both phenomena are considered consequences of an intimate interplay between the innate and the adaptive immune system. This concept is supported by results of genetic studies, pointing toward the signaling pathways of nuclear factor-κB, interferon-γ, and interleukin (IL)-23 as well as antigen presentation as central axes of the psoriatic inflammation. Efficacy of biologics targeting tumor necrosis factor-α, IL-23, or IL-17 provides further evidence in favor of this model. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Molecular Pathogenesis of MALT Lymphoma

    Directory of Open Access Journals (Sweden)

    Katharina Troppan

    2015-01-01

    Full Text Available Approximately 8% of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT, also known as MALT lymphoma, which was first described in 1983 by Isaacson and Wright. MALT lymphomas arise at a wide range of different extranodal sites, with the highest frequency in the stomach, followed by lung, ocular adnexa, and thyroid, and with a low percentage in the small intestine. Interestingly, at least 3 different, apparently site-specific, chromosomal translocations and missense and frameshift mutations, all pathway-related genes affecting the NF-κB signal, have been implicated in the development and progression of MALT lymphoma. However, these genetic abnormalities alone are not sufficient for malignant transformation. There is now increasing evidence suggesting that the oncogenic product of translocation cooperates with immunological stimulation in oncogenesis, that is, the association with chronic bacterial infection or autoaggressive process. This review mainly discusses MALT lymphomas in terms of their genetic aberration and association with chronic infections and summarizes recent advances in their molecular pathogenesis.

  10. Achondroplasia: Development, pathogenesis, and therapy.

    Science.gov (United States)

    Ornitz, David M; Legeai-Mallet, Laurence

    2017-04-01

    Autosomal dominant mutations in fibroblast growth factor receptor 3 (FGFR3) cause achondroplasia (Ach), the most common form of dwarfism in humans, and related chondrodysplasia syndromes that include hypochondroplasia (Hch), severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), and thanatophoric dysplasia (TD). FGFR3 is expressed in chondrocytes and mature osteoblasts where it functions to regulate bone growth. Analysis of the mutations in FGFR3 revealed increased signaling through a combination of mechanisms that include stabilization of the receptor, enhanced dimerization, and enhanced tyrosine kinase activity. Paradoxically, increased FGFR3 signaling profoundly suppresses proliferation and maturation of growth plate chondrocytes resulting in decreased growth plate size, reduced trabecular bone volume, and resulting decreased bone elongation. In this review, we discuss the molecular mechanisms that regulate growth plate chondrocytes, the pathogenesis of Ach, and therapeutic approaches that are being evaluated to improve endochondral bone growth in people with Ach and related conditions. Developmental Dynamics 246:291-309, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Molecular Pathogenesis of MALT Lymphoma

    Science.gov (United States)

    Troppan, Katharina; Wenzl, Kerstin; Neumeister, Peter; Deutsch, Alexander

    2015-01-01

    Approximately 8% of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT), also known as MALT lymphoma, which was first described in 1983 by Isaacson and Wright. MALT lymphomas arise at a wide range of different extranodal sites, with the highest frequency in the stomach, followed by lung, ocular adnexa, and thyroid, and with a low percentage in the small intestine. Interestingly, at least 3 different, apparently site-specific, chromosomal translocations and missense and frameshift mutations, all pathway-related genes affecting the NF-κB signal, have been implicated in the development and progression of MALT lymphoma. However, these genetic abnormalities alone are not sufficient for malignant transformation. There is now increasing evidence suggesting that the oncogenic product of translocation cooperates with immunological stimulation in oncogenesis, that is, the association with chronic bacterial infection or autoaggressive process. This review mainly discusses MALT lymphomas in terms of their genetic aberration and association with chronic infections and summarizes recent advances in their molecular pathogenesis. PMID:25922601

  12. The Pathogenesis of Lupus Nephritis

    Science.gov (United States)

    Lech, Maciej

    2013-01-01

    Lupus nephritis is an immune complex GN that develops as a frequent complication of SLE. The pathogenesis of lupus nephritis involves a variety of pathogenic mechanisms. The extrarenal etiology of systemic lupus is based on multiple combinations of genetic variants that compromise those mechanisms normally assuring immune tolerance to nuclear autoantigens. This loss of tolerance becomes clinically detectable by the presence of antinuclear antibodies. In addition, nucleic acids released from netting or apoptotic neutrophils activate innate and adaptive immunity via viral nucleic acid-specific Toll-like receptors. Therefore, many clinical manifestations of systemic lupus resemble those of viral infection. In lupus, endogenous nuclear particles trigger IFN-α signaling just like viral particles during viral infection. As such, dendritic cells, T helper cells, B cells, and plasma cells all contribute to the aberrant polyclonal autoimmunity. The intrarenal etiology of lupus nephritis involves antibody binding to multiple intrarenal autoantigens rather than the deposition of circulating immune complexes. Tertiary lymphoid tissue formation and local antibody production add to intrarenal complement activation as renal immunopathology progresses. Here we provide an update on the pathogenic mechanisms that lead to lupus nephritis and provide the rationale for the latest and novel treatment strategies. PMID:23929771

  13. Pathogenesis of ovarian cancer: current perspectives | Chesang ...

    African Journals Online (AJOL)

    Objective: To present a review of current knowledge of the pathogenesis of ovarian cancer and its clinical implications. Data Source: Extensive literature search was conducted to identify relevant studies. Study Selection: Studies in the English language about or related to pathogenesis of ovarian cancer were selected.

  14. CONFERENCE NOTE: CETO—Centro de Ciências e Tecnologias Opticas, Trends in Optical Fibre Metrology and Standards

    Science.gov (United States)

    1994-01-01

    requirements of the new generation of analogue and digital fibre optical systems, which require sophisticated measurement techniques employing complex instruments unique to optical measurements. The school will foster and enhance the interaction between material, devices, systems, and standards-oriented R&D communities, as well as between engineers concerned with design and manufacturers of systems and instrumentation. Topics Review of optical fibre communication technology and systems Measurement techniques for fibre characterization: Reliability and traceability Reference fibres and calibration artefacts Ribbon fibres Mechanical and environmental testing Fibre reliability Polarimetric measurements Passive components characterization: Splices and connectors Couplers, splitters, taps and WDMs Optical fibres and isolators WDM technologies and applications: WDM technologies Tunable optical filters Fibre amplifiers and sources: Performances and characterization Design and standards Nonlinear effects Subsystem design and standards: Design and fabrication techniques Performance degradation and reliability Evaluation of costs/performance/technology Sensors IR - optical fibres Plastic fibres Instrumentation Registration Participation free of charge for postgraduate students, with some grants available for travel and lodging expenses. All correspondence should be addressed to: Secretariat, Trends in Optical Fibre Metrology and Standards, a/c Prof. Olivério D D Soares, Centro de Ciências e Tecnologias Opticas, Lab. Fisica - Faculdade de Ciências, Praça Gomes Teixeira, P-4000 Porto, Portugal. Tel: 351-2-310290, 351-2-2001648; Fax: 351-2-319267.

  15. An Odyssey to Viral Pathogenesis.

    Science.gov (United States)

    Oldstone, Michael B A

    2016-05-23

    polishing by Karl Habel (a superb senior virologist who left the National Institutes of Health and came to Scripps), and the gifted postdoctoral fellows who joined my laboratory over four decades form the log of my scientific voyage. The strong friendships and collaborations developed with other young but growing experimentalists like Bernie Fields and Abner Notkins are the fabric of the tale I will weave and were pivotal in the establishment of viral pathogenesis as a discipline.

  16. Current understanding in pathogenesis of atopic dermatitis

    Directory of Open Access Journals (Sweden)

    Tess McPherson

    2016-01-01

    Full Text Available There have been advances in our understanding of the complex pathogenesis of atopic eczema over the past few decades. This article examines the multiple factors which are implicated in this process.

  17. Autophagy in lung disease pathogenesis and therapeutics

    Directory of Open Access Journals (Sweden)

    Stefan W. Ryter

    2015-04-01

    Full Text Available Autophagy, a cellular pathway for the degradation of damaged organelles and proteins, has gained increasing importance in human pulmonary diseases, both as a modulator of pathogenesis and as a potential therapeutic target. In this pathway, cytosolic cargos are sequestered into autophagosomes, which are delivered to the lysosomes where they are enzymatically degraded and then recycled as metabolic precursors. Autophagy exerts an important effector function in the regulation of inflammation, and immune system functions. Selective pathways for autophagic degradation of cargoes may have variable significance in disease pathogenesis. Among these, the autophagic clearance of bacteria (xenophagy may represent a crucial host defense mechanism in the pathogenesis of sepsis and inflammatory diseases. Our recent studies indicate that the autophagic clearance of mitochondria, a potentially protective program, may aggravate the pathogenesis of chronic obstructive pulmonary disease by activating cell death programs. We report similar findings with respect to the autophagic clearance of cilia components, which can contribute to airways dysfunction in chronic lung disease. In certain diseases such as pulmonary hypertension, autophagy may confer protection by modulating proliferation and cell death. In other disorders, such as idiopathic pulmonary fibrosis and cystic fibrosis, impaired autophagy may contribute to pathogenesis. In lung cancer, autophagy has multiple consequences by limiting carcinogenesis, modulating therapeutic effectiveness, and promoting tumor cell survival. In this review we highlight the multiple functions of autophagy and its selective autophagy subtypes that may be of significance to the pathogenesis of human disease, with an emphasis on lung disease and therapeutics.

  18. Quo vadis optica quantorum?

    International Nuclear Information System (INIS)

    Lewenstein, M.

    2005-01-01

    In my talk I will present the recent developments of quantum optics, and in particular physics of ultra-cold gases that occur at the interplay between quantum optics, atomic physics, quantum information, statistical mechanics, condensed matter physics and even high energy physics, and touch the same frontiers and challenges of modern physics. In particular I will discuss the possibility of studying and discovering new phenomena in physics of frustrated anti-ferromagnets, and about possibility of studying some aspects of abelian and non-abelian gauge field theories. (author)

  19. Animal models of papillomavirus pathogenesis.

    Science.gov (United States)

    Campo, M Saveria

    2002-11-01

    Tumorigenesis due to papillomavirus (PV) infection was first demonstrated in rabbits and cattle early last century. Despite the evidence obtained in animals, the role of viruses in human cancer was dismissed as irrelevant. It took a paradigm shift in the late 1970s for some viruses to be recognised as 'tumour viruses' in humans, and in 1995, more than 60 years after Rous's first demonstration of CRPV oncogenicity, WHO officially declared that 'HPV-16 and HPV-18 are carcinogenic to humans'. Experimental studies with animal PVs have been a determining factor in this decision. Animal PVs have been studied both as agents of disease in animals and as models of human PV infection. In addition to the study of PV infection in whole animals, in vitro studies with animal PV proteins have contributed greatly to the understanding of the mechanisms of cell transformation. Animal PVs cause distressing diseases in both farm and companion animals, such as teat papillomatosis in cattle, equine sarcoids and canine oral papillomatosis and there is an urgent need to understand the pathogenesis of these problematic infections. Persistent and florid teat papillomatosis in cows can lead to mastitis, prevent the suckling of calves and make milking impossible; heavily affected animals are culled and so occasionally are whole herds. Equine sarcoids are often recurrent and untreatable and lead to loss of valuable animals. Canine oral papillomatosis can be very extensive and persistent and lead to great distress. Thus the continuing research in the biology of animal PVs is amply justified. BPVs and CRPV have been for many years the model systems with which to study the biology of HPV. Induction of papillomas and their neoplastic progression has been experimentally demonstrated and reproduced in cattle and rabbits, and virus-cofactor interactions have been elucidated in these systems. With the advancements in molecular and cell culture techniques, the direct study of HPV has become less

  20. Trichomonas vaginalis Pathogenesis: a Narrative Review

    Directory of Open Access Journals (Sweden)

    Zahra Arab-Mazar

    2015-07-01

    Full Text Available In the latest articles which were published during 2013-2014, Trichomonas vaginalis (T. vaginalis was mentioned as a neglected sexual transmission disease (STD, while the exact mechanism of its pathogenesis has not been cleared yet. Although trichomonasiasis is easy curable, there is concern that resistance to drug are increasing. This common infection as concerning the important public health implications needs more research to be done for understanding the diagnosis, treatment, immunology and pathogenesis. In this review we searched all valuable and relevant information considering the pathogenesis of T. vaginalis. We referred to the information databases of Medline, PubMed, Scopus and Google scholar. The used keywords were the combinations of T. vaginalis and words associated with pathogenicity. This review discusses the host-parasite interaction and pathogenicity of this parasite.

  1. Bordetella pertussis pathogenesis: current and future challenges

    Science.gov (United States)

    Melvin, Jeffrey A.; Scheller, Erich V.; Miller, Jeff F.; Cotter, Peggy A.

    2014-01-01

    Pertussis, or whooping cough, has recently reemerged as a major public health threat despite high levels of vaccination against the etiological agent, Bordetella pertussis. In this Review, we describe the pathogenesis of this disease, with a focus on recent mechanistic insights into virulence factor function. We also discuss the changing epidemiology of pertussis and the challenges of vaccine development. Despite decades of research, many aspects of B. pertussis physiology and pathogenesis remain poorly understood. We highlight knowledge gaps that must be addressed to develop improved vaccines and therapeutic strategies. PMID:24608338

  2. Pathogenesis of helicobacter pylori infection involves interaction ...

    African Journals Online (AJOL)

    It is now clear that both bacterial virulence factors and host susceptibility play key roles in disease pathogenesis. The nature and levels of these interactions between these major factors has been found to determine the spectrum of clinical outcomes of the infection with this important bacterium. Virulence factors include the ...

  3. Immunological pathogenesis of inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Seung Hoon Lee

    2018-01-01

    Full Text Available Inflammatory bowel disease (IBD is a chronic inflammatory state of the gastrointestinal tract and can be classified into 2 main clinical phenomena: Crohn's disease (CD and ulcerative colitis (UC. The pathogenesis of IBD, including CD and UC, involves the presence of pathogenic factors such as abnormal gut microbiota, immune response dysregulation, environmental changes, and gene variants. Although many investigations have tried to identify novel pathogenic factors associated with IBD that are related to environmental, genetic, microbial, and immune response factors, a full understanding of IBD pathogenesis is unclear. Thus, IBD treatment is far from optimal, and patient outcomes can be unsatisfactory. As result of massive studying on IBD, T helper 17 (Th17 cells and innate lymphoid cells (ILCs are investigated on their effects on IBD. A recent study of the plasticity of Th17 cells focused primarily on colitis. ILCs also emerging as novel cell family, which play a role in the pathogenesis of IBD. IBD immunopathogenesis is key to understanding the causes of IBD and can lead to the development of IBD therapies. The aim of this review is to explain the pathogenesis of IBD, with a focus on immunological factors and therapies.

  4. Pathogenesis of nosocomial infections with Enterococcus faecalis

    NARCIS (Netherlands)

    Waar, Karola

    2004-01-01

    In this thesis, we analyzed the role of the different virulence factors of E. faecalis known in literature in the pathogenesis of infections. We investigated the prevalence of virulence factors in E. faecalis isolates from different hosts as well as their role in biomaterial related infections. The

  5. Frontoethmoidal encephaloceles, a study of their pathogenesis

    NARCIS (Netherlands)

    Hoving, Eelco; Vermeij-Keers, C

    1997-01-01

    A prospective clinical study of 30 patients with frontoethmoidal encephaloceles was performed in order to find support for a proposed theory concerning its pathogenesis, based on a previously performed embryological study and relevant findings in the literature. According to this proposed theory the

  6. Fungal Plant Pathogenesis Mediated by Effectors

    NARCIS (Netherlands)

    Wit, de P.J.G.M.; Testa, A.; Oliver, R.

    2016-01-01

    The interactions between fungi and plants encompass a spectrum of ecologies ranging from saprotrophy (growth on dead plant material) through pathogenesis (growth of the fungus accompanied by disease on the plant) to symbiosis (growth of the fungus with growth enhancement of the plant). We consider

  7. Pathogenesis of bovine spongiform encephalopathy in sheep

    NARCIS (Netherlands)

    Keulen, van L.J.M.; Vromans, M.E.W.; Dolstra, C.H.; Bossers, A.; Zijderveld, van F.G.

    2008-01-01

    The pathogenesis of bovine spongiform encephalopathy (BSE) in sheep was studied by immunohistochemical detection of scrapie-associated prion protein (PrPSc) in the gastrointestinal, lymphoid and neural tissues following oral inoculation with BSE brain homogenate. First accumulation of PrPSc was

  8. [Purulent corneal ulcers: etiology, pathogenesis, classification].

    Science.gov (United States)

    Kasparova, Evg A; Kasparova, Evg A

    2015-01-01

    Advanced purulent corneal ulcer, as well as abscess, is a serious vision-threatening condition notable for its fulminant course and possible loss of the eye due to endophthalmitis. Its leading causes, pathogenesis, and classifications are described and analyzed in this paper.

  9. [The etiology and pathogenesis of Sprengel's disease].

    Science.gov (United States)

    Skopichenko, D N

    1999-01-01

    Basing on the analysis of clinico-radiological and functional signs, electromyographic and histological changes in the shoulder girdle (SG) upper extremities muscles, macro- and microscopic investigations of omovertebral formations in the patients with Sprengel disease, and the literature data there was formulated the scheme of etiology and pathogenesis of the inborn high position of shoulder blade. The leading role in the Sprengel disease etiology plays teratogenic exo- or endogenous harmful agent, affecting mesenchymal tissue in the moment of the vertebral column and SG inlay on the 4-5th week of embryogenesis. Underdevelopment and degeneration of the SG muscles, creation of fibrous, fibrous-cartilaginous and osteal tissues due to the embryogenesis disorder occurrence, are playing essential role in pathogenesis of anatomic-functional disorders, causing occurrence of the inborn high position of shoulder blade.

  10. Theories on the Pathogenesis of Endometriosis

    Directory of Open Access Journals (Sweden)

    Samer Sourial

    2014-01-01

    Full Text Available Endometriosis is a common, chronic inflammatory disease defined by the presence of extrauterine endometrial tissue. The aetiology of endometriosis is complex and multifactorial, where several not fully confirmed theories describe its pathogenesis. This review examines existing theories on the initiation and propagation of different types of endometriotic lesions, as well as critically appraises the myriad of biologically relevant evidence that support or oppose each of the proposed theories. The current literature suggests that stem cells, dysfunctional immune response, genetic predisposition, and aberrant peritoneal environment may all be involved in the establishment and propagation of endometriotic lesions. An orchestrated scientific and clinical effort is needed to consider all factors involved in the pathogenesis of this multifaceted disease and to propose novel therapeutic targets to reach effective treatments for this distressing condition.

  11. The epigenetic paradigm in periodontitis pathogenesis

    Directory of Open Access Journals (Sweden)

    Vamsi Lavu

    2015-01-01

    Full Text Available Epigenome refers to "epi" meaning outside the "genome." Epigenetics is the field of study of the epigenome. Epigenetic modifications include changes in the promoter CpG Islands, modifications of histone protein structure, posttranslational repression by micro-RNA which contributes to the alteration of gene expression. Epigenetics provides an understanding of the role of gene-environment interactions on disease phenotype especially in complex multifactorial diseases. Periodontitis is a chronic inflammatory disorder that affects the supporting structures of the tooth. The role of the genome (in terms of genetic polymorphisms in periodontitis pathogenesis has been examined in numerous studies, and chronic periodontitis has been established as a polygenic disorder. The potential role of epigenetic modifications in the various facets of pathogenesis of periodontitis is discussed in this paper based on the available literature.

  12. [The pathogenesis of small-plaque parapsoriasis].

    Science.gov (United States)

    Olisova, O Iu; Kop'eva, T N

    1994-01-01

    The paper deals with the origin of parapsoriasis nodularis, which in its micronodular variant belongs to chronic dermatosis and has a clear-cut clinical and histological appearance. The disease arises most frequently after stress and occurs for the most part in middle-aged males. The leading role in pathogenesis of parapsoriasis nodularis is played by cellular immunity as indicated by reduced count of T-lymphocytes, active T-lymphocytes as well as the emergence of delayed hypersensitivity.

  13. Osmotin, a Pathogenesis-Related Protein

    Czech Academy of Sciences Publication Activity Database

    Viktorová, J.; Krásný, Lukáš; Kamlar, M.; Nováková, M.; Macková, M.; Macek, T.

    2012-01-01

    Roč. 13, č. 7 (2012), s. 672-681 ISSN 1389-2037 Grant - others:GA ČR(CZ) GAP501/11/1654; GA ČR(CZ) GA522/09/1693 Program:GA; GA Institutional support: RVO:61388971 Keywords : osmotin * pathogenesis-related proteins * antifungal activity Subject RIV: CE - Biochemistry Impact factor: 2.326, year: 2012

  14. Acute pancreatitis: Etiology and common pathogenesis

    OpenAIRE

    Wang, Guo-Jun; Gao, Chun-Fang; Wei, Dong; Wang, Cun; Ding, Si-Qin

    2009-01-01

    Acute pancreatitis is an inflammatory disease of the pancreas. The etiology and pathogenesis of acute pancreatitis have been intensively investigated for centuries worldwide. Many causes of acute pancreatitis have been discovered, but the pathogenetic theories are controversial. The most common cause of acute pancreatitis is gallstone impacting the distal common bile-pancreatic duct. The majority of investigators accept that the main factors for acute billiary pancreatitis are pancreatic hype...

  15. [Anatomy and pathogenesis of diverticular disease].

    Science.gov (United States)

    Wedel, T; Böttner, M

    2014-04-01

    Although diverticular disease is one of the most frequent gastrointestinal disorders the pathogenesis is not yet sufficiently clarified. The aim is to define the anatomy and pathogenesis of diverticular disease considering the risk factors and description of structural and functional alterations of the bowel wall. This article gives an appraisal of the literature, presentation and evaluation of classical etiological factors, analysis and discussion of novel pathogenetic concepts. Colonic diverticulosis is defined as an acquired out-pouching of multiple and initially asymptomatic pseudodiverticula through muscular gaps in the colon wall. Diverticular disease is characterized by diverticular bleeding and/or inflammatory processes (diverticulitis) with corresponding complications (e.g. abscess formation, fistula, covered and open perforation, peritonitis and stenosis). Risk factors for diverticular disease include increasing age, genetic predisposition, congenital connective tissue diseases, low fiber diet, high meat consumption and pronounced overweight. Alterations of connective tissue cause a weakening of preformed exit sites of diverticula and rigidity of the bowel wall with reduced flexibility. It is assumed that intestinal innervation disorders and structural alterations of the musculature induce abnormal contractile patterns with increased intraluminal pressure, thereby promoting the development of diverticula. Moreover, an increased release of pain-mediating neurotransmitters is considered to be responsible for persistent pain in chronic diverticular disease. According to the present data the pathogenesis of diverticular disease cannot be attributed to a single factor but should be considered as a multifactorial event.

  16. Pathogenesis of Acute Respiratory Distress Syndrome

    Directory of Open Access Journals (Sweden)

    A. M. Golubev

    2012-01-01

    Full Text Available Acute respiratory distress syndrome (ARDS is a common complication of many diseases. Its polyetiological pattern determines the specific features of lung morphological changes and the clinical course of ARDS. Objective: to analyze the pathogenesis of ARDS in the context of the general pathological processes underlying its development. Material and methods. More than 200 lungs from the people who had died from severe concomitant injury or ARDS-complicated pneumonia were investigated. More than 150 rat experiments simulated various types of lung injury: ventilator-induced lung injury with different ventilation parameters; reperfusion injuries (systemic circulation blockade due to 12-minute vascular fascicle ligation, followed by the recovery of cardiac performance and breathing; microcirculatory disorder (injection of a thromboplastin solution into the jugular vein; blood loss; betaine-pepsin aspiration; and closed chest injury. Different parts of the right and left lungs were histologically examined 1 and 3 hours and 1 and 3 days after initiation of the experiment. Lung pieces were fixed in 10% neutral formalin solution and embedded in paraffin. Histological sections were stained with hematoxylin and eosin and using the van Gieson and Weigert procedures; the Schiff test was used. Results. The influence of aggression factors (trauma, blood loss, aspiration, infection, etc. results in damage to the lung and particularly air-blood barrier structures (endothelium, alveolar epithelium, their basement membrane. In turn the alteration of cellular and extracellular structures is followed by the increased permeability of hemomicrocirculatory bed vessels, leading to the development of non-cardiogenic (interstitial, alveolar pulmonary edema that is a central component in the pathogenesis of ARDS. Conclusion. The diagnosis of the early manifestations of ARDS must account for the nature of an aggression factor, the signs confirming the alteration of the lung

  17. The pathogenesis of progressive multifocal leukoencephalopathy.

    Science.gov (United States)

    Berger, Joseph R; Khalili, Kamel

    2011-12-01

    Interest in pathogenesis of progressive multifocal leukoencephalopathy (PML) followed the observation of the high risk for the disease in HIV infection and the recent observation of an association with a variety of newer therapeutic modalities, e.g., natalizumab, an α4β1 integrin inhibitor, and efalizumab, an anti-CD11a monoclonal antibody. Any hypothesis of PML pathogenesis must account for a number of facts. Firstly, the causative agent JC virus is ubiquitously present, yet only a vanishingly small number of infected persons develop the disease. Secondly, disorders of cell-mediated immunity increase the risk of the disease, particularly HIV infection. Impaired innate immunity is not a risk for PML, and antibodies against JC virus are not protective. Thirdly, a latent period of several months appears necessary following the administration of natalizumab and efalizumab before PML develops. Fourthly, restoration of the immune system can arrest the PML. It is possible that infection with JC virus occurs with a form of the virus shed in the urine of as many as 40% of all adults and present in sewage worldwide. Once acquired, perhaps through an oropharyngeal route, it may replicate and disseminate. A neurotropic form of JC virus that replicates in glial tissues causes PML when immunosurveillance is impaired. There are many unanswered questions with respect to PML pathogenesis. How is virus acquired? What tissues are infected? What is the origin of the neurotropic form? When does virus enter brain? What is the role of central nervous system immunosurveillance? The lack of an animal model has made answering these questions challenging. © Discovery Medicine

  18. Inflammatory Bowel Disease: Genetics, Epigenetics and Pathogenesis

    Directory of Open Access Journals (Sweden)

    Italia eLoddo

    2015-11-01

    Full Text Available Inflammatory Bowel Diseases (IBDs are complex, multifactorial disorders characterized by chronic relapsing intestinal inflammation. Although aetiology remains largely unknown, recent research has suggested that genetic factors, environment, microbiota and immune response are involved in the pathogenesis.Epidemiological evidence for a genetic contribution is defined: 15% of patients with Crohn’s Disease (CD have an affected family member with IBD, and twin studies for CD have shown 50% concordance in monozygotic twins compared to less than 10% in dizygotics. The most recent and largest genetic association studies, which employed genome-wide association data for over 75,000 patients and controls, identified 163 susceptibility loci for IBD. More recently, a trans-ethnic analysis, including over 20,000 individuals, identified an additional 38 new IBD loci.Although most cases are correlated with polygenic contribution toward genetic susceptibility, there is a spectrum of rare genetic disorders that can contribute to early onset IBD (before 5 years or very early IBD (before 2 years. Genetic variants that cause these disorders have a wide effect on gene function. These variants are so rare in allele frequency that the genetic signals are not detected in genome-wide association studies of patients with IBD. With recent advances in sequencing techniques, approximately 50 genetic disorders have been identified and associated with IBD-like immunopathology. Monogenic defects have been found to alter intestinal immune homeostasis through many mechanisms. Candidate gene resequencing should be carried out in early-onset patients in clinical practice.The evidence that genetic factors contribute in small part to disease pathogenesis confirms the important role of microbial and environmental factors. Epigenetic factors can mediate interactions between environment and genome. Epigenetic mechanisms could affect development and progression of IBD. Epigenomics is

  19. Urinary tract infection pathogenesis: host factors.

    Science.gov (United States)

    Stapleton, Ann E

    2014-03-01

    Clinically, host factors in the pathogenesis of urinary tract infection (UTI) may be considered as modifiable (eg, behaviors associated with increased risk of UTI, anatomic and functional problems of the urinary tract) and thus potentially amenable to a change in patient behavior or treatment approach, or as intrinsic and nonmodifiable host factors that neither the patient nor the clinician can influence (eg, gender and genetic influences associated with UTI). Although considering nonmodifiable host factors may be discouraging to patients and clinicians at present, some genetic associations have the potential for future predictive value and may interface with future treatments. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Treacher Collins syndrome: etiology, pathogenesis and prevention

    Science.gov (United States)

    Trainor, Paul A; Dixon, Jill; Dixon, Michael J

    2009-01-01

    Treacher Collins syndrome (TCS) is a rare congenital disorder of craniofacial development that arises as the result of mutations in the TCOF1 gene, which encodes a nucleolar phosphoprotein known as Treacle. Individuals diagnosed with TCS frequently undergo multiple reconstructive surgeries, which are rarely fully corrective. Identifying potential avenues for rescue and/or repair of TCS depends on a profound appreciation of the etiology and pathogenesis of the syndrome. Recent research using animal models has not only determined the cellular basis of TCS but also, more importantly, unveiled a successful avenue for therapeutic intervention and prevention of the craniofacial anomalies observed in TCS. PMID:19107148

  1. Urinary Tract Infection: Pathogenesis and Outlook.

    Science.gov (United States)

    McLellan, Lisa K; Hunstad, David A

    2016-11-01

    The clinical syndromes comprising urinary tract infection (UTI) continue to exert significant impact on millions of patients worldwide, most of whom are otherwise healthy women. Antibiotic therapy for acute cystitis does not prevent recurrences, which plague up to one fourth of women after an initial UTI. Rising antimicrobial resistance among uropathogenic bacteria further complicates therapeutic decisions, necessitating new approaches based on fundamental biological investigation. In this review, we highlight contemporary advances in the field of UTI pathogenesis and how these might inform both our clinical perspective and future scientific priorities. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Pathogenesis and treatment of diabetic glomerulopathy

    International Nuclear Information System (INIS)

    Marre, M.; Le Jeune, J.J.

    1995-01-01

    Diabetic glomerulopathy is the consequence, at the glomerular level, of diabetes. Diagnosis is based on the association of proteinuria, arterial hypertension and an early reduction of glomerular filtration in a diabetic patient, generally insulin-dependent. Diabetic glomerulopathy is a complication of type I diabetes, which begins in childhood or adolescence, but can also be discovered in type II diabetes. A definite diagnosis requires histological evidences ; glomerular clearance measurements ( 125 I-iodothalamate or 51 Cr-EDTA) yield important information concerning glomerular filtration. The authors subsequently address pathogenesis and therapeutic regimens, and they report on the particularities of this condition in type II diabetes. (authors). 30 refs., 2 tabs

  3. Biology and pathogenesis of Naegleria fowleri.

    Science.gov (United States)

    Siddiqui, Ruqaiyyah; Ali, Ibne Karim M; Cope, Jennifer R; Khan, Naveed Ahmed

    2016-12-01

    Naegleria fowleri is a protist pathogen that can cause lethal brain infection. Despite decades of research, the mortality rate related with primary amoebic meningoencephalitis owing to N. fowleri remains more than 90%. The amoebae pass through the nose to enter the central nervous system killing the host within days, making it one of the deadliest opportunistic parasites. Accordingly, we present an up to date review of the biology and pathogenesis of N. fowleri and discuss needs for future research against this fatal infection. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Etiology and pathogenesis of periodontal diseases.

    Science.gov (United States)

    Tatakis, Dimitris N; Kumar, Purnima S

    2005-07-01

    The two most prevalent and most investigated periodontal diseases are dental plaque-induced gingivitis and chronic periodontitis. The last 10 to 15 years have seen the emergence of several important new findings and concepts regarding the etiopathogenesis of periodontal diseases. These findings include the recognition of dental bacterial plaque as a biofilm, identification and characterization of genetic defects that predispose individuals to periodontitis, host-defense mechanisms implicated in periodontal tissue destruction, and the interaction of risk factors with host defenses and bacterial plaque. This article reviews current aspects of the etiology and pathogenesis of periodontal diseases.

  5. The fascinating germ theories on cancer pathogenesis.

    Science.gov (United States)

    Tsoucalas, G; Laios, K; Karamanou, M; Gennimata, V; Androutsos, G

    2014-01-01

    For more than 100 years, the germ theory of cancer, proposing that microorganisms were at the origin of the disease, dominated medicine. Several eminent scientists like Etienne Burnet, Mikhail Stepanovich Voronin, Charles-Louis Malassez, and Francis-Peyton Rous argued on the pathogenesis presenting their theories that implicated cocci, fungi and parasites. The impact of these theories was culminated by the Nobel Prize in 1926 that was attributed to the Danish scientist Johannes Fibiger for his work on the nematode Spiroptera as a causative agent in cancer. Even if those theories were the result of fantasy and misinterpretation, they paved the way for the scientific research in oncology.

  6. Molecular pathogenesis and mechanisms of thyroid cancer

    Science.gov (United States)

    Xing, Mingzhao

    2013-01-01

    Thyroid cancer is a common endocrine malignancy. There has been exciting progress in understanding its molecular pathogenesis in recent years, as best exemplified by the elucidation of the fundamental role of several major signalling pathways and related molecular derangements. Central to these mechanisms are the genetic and epigenetic alterations in these pathways, such as mutation, gene copy-number gain and aberrant gene methylation. Many of these molecular alterations represent novel diagnostic and prognostic molecular markers and therapeutic targets for thyroid cancer, which provide unprecedented opportunities for further research and clinical development of novel treatment strategies for this cancer. PMID:23429735

  7. Penile cancer: epidemiology, pathogenesis and prevention.

    Science.gov (United States)

    Bleeker, M C G; Heideman, D A M; Snijders, P J F; Horenblas, S; Dillner, J; Meijer, C J L M

    2009-04-01

    Penile cancer is a disease with a high morbidity and mortality. Its prevalence is relatively rare, but the highest in some developing countries. Insight into its precursor lesions, pathogenesis and risk factors offers options to prevent this potentially mutilating disease. This review presents an overview of the different histologically and clinically identified precursor lesions of penile cancer and discusses the molecular pathogenesis, including the role of HPV in penile cancer development. A systematic review of the literature evaluating penile carcinogenesis, risk factors and molecular mechanisms involved. Careful monitoring of men with lichen sclerosis, genital Bowen's disease, erythroplasia of Queyrat and bowenoid papulosis seems useful, thereby offering early recognition of penile cancer and, subsequently, conservative therapeutic options. Special attention is given to flat penile lesions, which contain high numbers of HPV. Their role in HPV transmission to sexual partners is highlighted, but their potential to transform as a precursor lesion into penile cancer has been unsatisfactorily explored. Further research should not only focus on HPV mediated pathogenic pathways but also on the non-HPV related molecular and genetic factors that play a role in penile cancer development. Options for prevention of penile cancer include (neonatal) circumcision, limitation of penile HPV infections (either by prophylactic vaccination or condom use), prevention of phimosis, treatment of chronic inflammatory conditions, limiting PUVA treatment, smoking cessation and hygienic measures.

  8. Non Melanoma Skin Cancer Pathogenesis Overview.

    Science.gov (United States)

    Didona, Dario; Paolino, Giovanni; Bottoni, Ugo; Cantisani, Carmen

    2018-01-02

    (1) Background: Non-melanoma skin cancer is the most frequently diagnosed cancer in humans. The process of skin carcinogenesis is still not fully understood. However, several studies have been conducted to better explain the mechanisms that lead to malignancy; (2) Methods: We reviewed the more recent literature about the pathogenesis of non-melanoma skin cancer focusing on basal cell carcinomas, squamous cell carcinoma and actinic keratosis; (3) Results: Several papers reported genetic and molecular alterations leading to non-melanoma skin cancer. Plenty of risk factors are involved in non-melanoma skin cancer pathogenesis, including genetic and molecular alterations, immunosuppression, and ultraviolet radiation; (4) Conclusion: Although skin carcinogenesis is still not fully understood, several papers demonstrated that genetic and molecular alterations are involved in this process. In addition, plenty of non-melanoma skin cancer risk factors are now known, allowing for an effective prevention of non-melanoma skin cancer development. Compared to other papers on the same topic, our review focused on molecular and genetic factors and analyzed in detail several factors involved in non-melanoma skin cancer.

  9. Pathogenesis of Apical Periodontitis: a Literature Review

    Directory of Open Access Journals (Sweden)

    Indre Graunaite

    2011-09-01

    Full Text Available Objectives: This review article discusses the host response in apical periodontitis with the main focus on cytokines, produced under this pathological condition and contributing to the degradation of periradicular tissues. The pace of research in this field has greatly accelerated in the last decade. Here we provide an analysis of studies published in this area during this period.Material and methods: Literature was selected through a search of PubMed electronic database. The keywords used for search were pathogenesis of apical periodontitis cytokines, periapical granuloma cytokines, inflammatory infiltrate apical periodontitis. The search was restricted to English language articles, published from 1999 to December 2010. Additionally, a manual search in the cytokine production, cytokine functions and periapical tissue destruction in the journals and books was performed.Results: In total, 97 literature sources were obtained and reviewed. The topics covered in this article include cellular composition of an inflammatory infiltrate in the periapical lesions, mechanisms of the formation of the innate and specific immune response. Studies which investigated cytokine secretion and functions were identified and cellular and molecular interactions in the course of apical periodontitis described.Conclusions: The abundance and interactions of various inflammatory and anti-inflammatory molecules can influence and alter the state and progression of the disease. Therefore, periapical inflammatory response offers a model, suited for the study of many facets of pathogenesis, biocompatibility of different materials to periapical tissues and development of novel treatment methods, based on the regulation of cytokines expression.

  10. Pathogenesis of apical periodontitis: a literature review.

    Science.gov (United States)

    Graunaite, Indre; Lodiene, Greta; Maciulskiene, Vita

    2012-01-01

    This review article discusses the host response in apical periodontitis with the main focus on cytokines, produced under this pathological condition and contributing to the degradation of periradicular tissues. The pace of research in this field has greatly accelerated in the last decade. Here we provide an analysis of studies published in this area during this period. Literature was selected through a search of PubMed electronic database. The keywords used for search were pathogenesis of apical periodontitis cytokines, periapical granuloma cytokines, inflammatory infiltrate apical periodontitis. The search was restricted to English language articles, published from 1999 to December 2010. Additionally, a manual search in the cytokine production, cytokine functions and periapical tissue destruction in the journals and books was performed. In total, 97 literature sources were obtained and reviewed. The topics covered in this article include cellular composition of an inflammatory infiltrate in the periapical lesions, mechanisms of the formation of the innate and specific immune response. Studies which investigated cytokine secretion and functions were identified and cellular and molecular interactions in the course of apical periodontitis described. The abundance and interactions of various inflammatory and anti-inflammatory molecules can influence and alter the state and progression of the disease. Therefore, periapical inflammatory response offers a model, suited for the study of many facets of pathogenesis, biocompatibility of different materials to periapical tissues and development of novel treatment methods, based on the regulation of cytokines expression.

  11. Channelopathy Pathogenesis in Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Galina eSchmunk

    2013-11-01

    Full Text Available Autism spectrum disorder (ASD is a syndrome that affects normal brain development and is characterized by impaired social interaction as well as verbal and non-verbal communication and by repetitive, stereotypic behavior. ASD is a complex disorder arising from a combination of multiple genetic and environmental factors that are independent from racial, ethnic and socioeconomical status. The high heritability of ASD suggests a strong genetic basis for the disorder. Furthermore, a mounting body of evidence implies a role of various ion channel gene defects (channelopathies in the pathogenesis of autism. Indeed, recent genome-wide association, and whole exome- and whole- genome resequencing studies linked polymorphisms and rare variants in calcium, sodium and potassium channels and their subunits with susceptibility to ASD, much as they do with bipolar disorder, schizophrenia and other neuropsychiatric disorders, and animal models with these genetic variations recapitulate endophenotypes considered to be correlates of autistic behavior seen in patients. An ion flux across the membrane regulates a variety of cell functions, from generation of action potentials to gene expression and cell morphology, thus it is not surprising that channelopathies have profound effects on brain functions. In the present work, we summarize existing evidence for the role of ion channel gene defects in the pathogenesis of autism with a focus on calcium signaling and its downstream effects.

  12. Transport proteins promoting Escherichia coli pathogenesis

    Science.gov (United States)

    Tang, Fengyi; Saier, Milton H.

    2014-01-01

    Escherichia coli is a genetically diverse species infecting hundreds of millions of people worldwide annually. We examined seven well-characterized E. coli pathogens causing urinary tract infections, gastroenteritis, pyelonephritis and haemorrhagic colitis. Their transport proteins were identified and compared with each other and a non-pathogenic E. coli K12 strain to identify transport proteins related to pathogenesis. Each pathogen possesses a unique set of protein secretion systems for export to the cell surface or for injecting effector proteins into host cells. Pathogens have increased numbers of iron siderophore receptors and ABC iron uptake transporters, but the numbers and types of low-affinity secondary iron carriers were uniform in all strains. The presence of outer membrane iron complex receptors and high-affinity ABC iron uptake systems correlated, suggesting co-evolution. Each pathovar encodes a different set of pore-forming toxins and virulence-related outer membrane proteins lacking in K12. Intracellular pathogens proved to have a characteristically distinctive set of nutrient uptake porters, different from those of extracellular pathogens. The results presented in this report provide information about transport systems relevant to various types of E. coli pathogenesis that can be exploited in future basic and applied studies. PMID:24747185

  13. Transport proteins promoting Escherichia coli pathogenesis.

    Science.gov (United States)

    Tang, Fengyi; Saier, Milton H

    2014-01-01

    Escherichia coli is a genetically diverse species infecting hundreds of millions of people worldwide annually. We examined seven well-characterized E. coli pathogens causing urinary tract infections, gastroenteritis, pyelonephritis and haemorrhagic colitis. Their transport proteins were identified and compared with each other and a non-pathogenic E. coli K12 strain to identify transport proteins related to pathogenesis. Each pathogen possesses a unique set of protein secretion systems for export to the cell surface or for injecting effector proteins into host cells. Pathogens have increased numbers of iron siderophore receptors and ABC iron uptake transporters, but the numbers and types of low-affinity secondary iron carriers were uniform in all strains. The presence of outer membrane iron complex receptors and high-affinity ABC iron uptake systems correlated, suggesting co-evolution. Each pathovar encodes a different set of pore-forming toxins and virulence-related outer membrane proteins lacking in K12. Intracellular pathogens proved to have a characteristically distinctive set of nutrient uptake porters, different from those of extracellular pathogens. The results presented in this report provide information about transport systems relevant to various types of E. coli pathogenesis that can be exploited in future basic and applied studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Irritable bowel syndrome: Diagnosis and pathogenesis

    Science.gov (United States)

    El-Salhy, Magdy

    2012-01-01

    Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder that considerably reduces the quality of life. It further represents an economic burden on society due to the high consumption of healthcare resources and the non-productivity of IBS patients. The diagnosis of IBS is based on symptom assessment and the Rome III criteria. A combination of the Rome III criteria, a physical examination, blood tests, gastroscopy and colonoscopy with biopsies is believed to be necessary for diagnosis. Duodenal chromogranin A cell density is a promising biomarker for the diagnosis of IBS. The pathogenesis of IBS seems to be multifactorial, with the following factors playing a central role in the pathogenesis of IBS: heritability and genetics, dietary/intestinal microbiota, low-grade inflammation, and disturbances in the neuroendocrine system (NES) of the gut. One hypothesis proposes that the cause of IBS is an altered NES, which would cause abnormal GI motility, secretions and sensation. All of these abnormalities are characteristic of IBS. Alterations in the NES could be the result of one or more of the following: genetic factors, dietary intake, intestinal flora, or low-grade inflammation. Post-infectious IBS (PI-IBS) and inflammatory bowel disease-associated IBS (IBD-IBS) represent a considerable subset of IBS cases. Patients with PI- and IBD-IBS exhibit low-grade mucosal inflammation, as well as abnormalities in the NES of the gut. PMID:23066308

  15. MOG-IgG in NMO and related disorders

    DEFF Research Database (Denmark)

    Pache, Florence; Zimmermann, Hanna; Mikolajczak, Janine

    2016-01-01

    BACKGROUND: Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been reported in patients with aquaporin-4 antibody (AQP4-IgG)-negative neuromyelitis optica spectrum disorders (NMOSD). The objective of this study was to describe optic neuritis (ON)-induced neuro-axonal damage in...

  16. Status of diagnostic approaches to AQP4-IgG seronegative NMO and NMO/MS overlap syndromes

    DEFF Research Database (Denmark)

    Juryńczyk, Maciej; Weinshenker, Brian; Akman-Demir, Gulsen

    2016-01-01

    Distinguishing aquaporin-4 IgG(AQP4-IgG)-negative neuromyelitis optica spectrum disorders (NMOSD) from opticospinal predominant multiple sclerosis (MS) is a clinical challenge with important treatment implications. The objective of the study was to examine whether expert clinicians diagnose and t...

  17. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... Multiple Sclerosis and Your Emotions (.pdf) Download Brochure Disease Modifying Therapies Overview (.pdf) Download Document Pediatric MS Learn More Transverse Myelitis Learn More Neuromyelitis Optica (NMO) Learn More HTLV-I ... Learn More Acute Disseminated Encephalomyelitis (ADEM) Learn More ...

  18. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... MS? d Definition of MS Myelin Immune-Mediated Disease T Cells d What Causes MS? Disproved Theories ... d Related Conditions Acute Disseminated Encephalomyelitis (ADEM) Balo’s Disease HTLV-I Associated Myelopathy (HAM) Neuromyelitis Optica (NMO) ...

  19. Astrocyte loss and astrogliosis in neuroinflammatory disorders

    NARCIS (Netherlands)

    Hostenbach, Stephanie; Cambron, Melissa; D'haeseleer, Miguel; Kooijman, Ron; De Keyser, Jacques

    2014-01-01

    Neuroinflammation can lead to either damage of astrocytes or astrogliosis. Astrocyte loss may be caused by cytotoxic T cells as seen in Rasmussen encephalitis, auto-antibodies such as in neuromyelitis optica (aquaporin-4 antibodies), or cytokines such as TNF-alpha in major depressive disorder.

  20. Ubiquitination in melanoma pathogenesis and treatment.

    Science.gov (United States)

    Ma, Jinyuan; Guo, Weinan; Li, Chunying

    2017-06-01

    Melanoma is one of the most aggressive skin cancers with fiercely increasing incidence and mortality. Since the progressive understanding of the mutational landscape and immunologic pathogenic factors in melanoma, the targeted therapy and immunotherapy have been recently established and gained unprecedented improvements for melanoma treatment. However, the prognosis of melanoma patients remains unoptimistic mainly due to the resistance and nonresponse to current available drugs. Ubiquitination is a posttranslational modification which plays crucial roles in diverse cellular biological activities and participates in the pathogenesis of various cancers, including melanoma. Through the regulation of multiple tumor promoters and suppressors, ubiquitination is emerging as the key contributor and therefore a potential therapeutic target for melanoma. Herein, we summarize the current understanding of ubiquitination in melanoma, from mechanistic insights to clinical progress, and discuss the prospect of ubiquitination modification in melanoma treatment. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  1. Foodborne Campylobacter: Infections, Metabolism, Pathogenesis and Reservoirs

    Science.gov (United States)

    Epps, Sharon V. R.; Harvey, Roger B.; Hume, Michael E.; Phillips, Timothy D.; Anderson, Robin C.; Nisbet, David J.

    2013-01-01

    Campylobacter species are a leading cause of bacterial-derived foodborne illnesses worldwide. The emergence of this bacterial group as a significant causative agent of human disease and their propensity to carry antibiotic resistance elements that allows them to resist antibacterial therapy make them a serious public health threat. Campylobacter jejuni and Campylobacter coli are considered to be the most important enteropathogens of this genus and their ability to colonize and survive in a wide variety of animal species and habitats make them extremely difficult to control. This article reviews the historical and emerging importance of this bacterial group and addresses aspects of the human infections they cause, their metabolism and pathogenesis, and their natural reservoirs in order to address the need for appropriate food safety regulations and interventions. PMID:24287853

  2. Origin and pathogenesis of antiphospholipid antibodies

    Directory of Open Access Journals (Sweden)

    C.M. Celli

    1998-06-01

    Full Text Available Antiphospholipid antibodies (aPL are a heterogeneous group of antibodies that are detected in the serum of patients with a variety of conditions, including autoimmune (systemic lupus erythematosus, infectious (syphilis, AIDS and lymphoproliferative disorders (paraproteinemia, myeloma, lymphocytic leukemias. Thrombosis, thrombocytopenia, recurrent fetal loss and other clinical complications are currently associated with a subgroup of aPL designating the antiphospholipid syndrome. In contrast, aPL from patients with infectious disorders are not associated with any clinical manifestation. These findings led to increased interest in the origin and pathogenesis of aPL. Here we present the clinical features of the antiphospholipid syndrome and review the origin of aPL, the characteristics of experimentally induced aPL and their historical background. Within this context, we discuss the most probable pathogenic mechanisms induced by these antibodies.

  3. Ovarian Cancer Pathogenesis: A Model in Evolution

    Directory of Open Access Journals (Sweden)

    Alison M. Karst

    2010-01-01

    Full Text Available Ovarian cancer is a deadly disease for which there is no effective means of early detection. Ovarian carcinomas comprise a diverse group of neoplasms, exhibiting a wide range of morphological characteristics, clinical manifestations, genetic alterations, and tumor behaviors. This high degree of heterogeneity presents a major clinical challenge in both diagnosing and treating ovarian cancer. Furthermore, the early events leading to ovarian carcinoma development are poorly understood, thus complicating efforts to develop screening modalities for this disease. Here, we provide an overview of the current models of ovarian cancer pathogenesis, highlighting recent findings implicating the fallopian tube fimbria as a possible site of origin of ovarian carcinomas. The ovarian cancer model will continue to evolve as we learn more about the genetics and etiology of this disease.

  4. Update on bacterial pathogenesis in BRD.

    Science.gov (United States)

    Confer, Anthony W

    2009-12-01

    Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, Mycoplasma bovis and Arcanobacterium pyogenes are all frequently implicated in bovine respiratory disease (BRD). M. haemolytica is considered the most important of the group. These bacteria are commensals in the nasopharynx and establish infection in the lungs of cattle that are subjected to a variety of stresses. Factors that permit adherence to and proliferation in the lungs and factors that cause tissue destruction and inflammation have been identified as having major roles in pathogenesis. These virulence factors include protein adhesins, capsular polysaccharide, outer membrane proteins, iron-binding proteins, lipopolysacharide or lipooligosaccharide, enzymes and toxins. These bacterial products function to evade the immune system, damage the immune system and induce a severe inflammatory response.

  5. Vibrio cholerae Biofilms and Cholera Pathogenesis.

    Directory of Open Access Journals (Sweden)

    Anisia J Silva

    2016-02-01

    Full Text Available Vibrio cholerae can switch between motile and biofilm lifestyles. The last decades have been marked by a remarkable increase in our knowledge of the structure, regulation, and function of biofilms formed under laboratory conditions. Evidence has grown suggesting that V. cholerae can form biofilm-like aggregates during infection that could play a critical role in pathogenesis and disease transmission. However, the structure and regulation of biofilms formed during infection, as well as their role in intestinal colonization and virulence, remains poorly understood. Here, we review (i the evidence for biofilm formation during infection, (ii the coordinate regulation of biofilm and virulence gene expression, and (iii the host signals that favor V. cholerae transitions between alternative lifestyles during intestinal colonization, and (iv we discuss a model for the role of V. cholerae biofilms in pathogenicity.

  6. Apnea of prematurity: pathogenesis and management strategies.

    Science.gov (United States)

    Mathew, O P

    2011-05-01

    Apnea of prematurity (AOP) is a significant clinical problem manifested by an unstable respiratory rhythm reflecting the immaturity of respiratory control systems. This review will address the pathogenesis of and treatment strategies for AOP. Although the neuronal mechanisms leading to apnea are still not well understood, recent decades have provided better insight into the generation of the respiratory rhythm and its modulation in the neonate. Ventilatory responses to hypoxia and hypercarbia are impaired and inhibitory reflexes are exaggerated in the neonate. These unique vulnerabilities predispose the neonate to the development of apnea. Treatment strategies attempt to stabilize the respiratory rhythm. Caffeine remains the primary pharmacological treatment modality and is presumed to work through blockade of adenosine receptors A(1) and A(2). Recent evidences suggest that A(2A) receptors may have a greater role than previously thought. AOP typically resolves with maturation suggesting increased myelination of the brainstem.

  7. Pathogenesis of Staphylococcus aureus Bloodstream Infections

    Science.gov (United States)

    Thomer, Lena; Schneewind, Olaf; Missiakas, Dominique

    2016-01-01

    Staphylococcus aureus , a Gram-positive bacterium colonizing nares, skin, and the gastrointestinal tract, frequently invades the skin, soft tissues, and bloodstreams of humans. Even with surgical and antibiotic therapy, bloodstream infections are associated with significant mortality. The secretion of coagulases, proteins that associate with and activate the host hemostatic factor prothrombin, and the bacterial surface display of agglutinins, proteins that bind polymerized fibrin, are key virulence strategies for the pathogenesis of S. aureus bloodstream infections, which culminate in the establishment of abscess lesions. Pathogen-controlled processes, involving a wide spectrum of secreted factors, are responsible for the recruitment and destruction of immune cells, transforming abscess lesions into purulent exudate, with which staphylococci disseminate to produce new infectious lesions or to infect new hosts. Research on S. aureus bloodstream infections is a frontier for the characterization of protective vaccine antigens and the development of immune therapeutics aiming to prevent disease or improve outcomes. PMID:26925499

  8. Vibrio cholerae Biofilms and Cholera Pathogenesis

    Science.gov (United States)

    Silva, Anisia J.; Benitez, Jorge A.

    2016-01-01

    Vibrio cholerae can switch between motile and biofilm lifestyles. The last decades have been marked by a remarkable increase in our knowledge of the structure, regulation, and function of biofilms formed under laboratory conditions. Evidence has grown suggesting that V. cholerae can form biofilm-like aggregates during infection that could play a critical role in pathogenesis and disease transmission. However, the structure and regulation of biofilms formed during infection, as well as their role in intestinal colonization and virulence, remains poorly understood. Here, we review (i) the evidence for biofilm formation during infection, (ii) the coordinate regulation of biofilm and virulence gene expression, and (iii) the host signals that favor V. cholerae transitions between alternative lifestyles during intestinal colonization, and (iv) we discuss a model for the role of V. cholerae biofilms in pathogenicity. PMID:26845681

  9. [Etiology and pathogenesis of overactive bladder].

    Science.gov (United States)

    Bschleipfer, T; Wagenlehner, F; Weidner, W

    2011-04-01

    The symptom complex"overactive bladder" (OAB) affects more than 10% of adult individuals. The etiopathology is complex and multifactorial. Foremost, urinary tract infection, bladder cancer, foreign bodies, and history of radiation or intravesical instillation of chemotherapeutics must be excluded. In many cases, OAB is caused by neurogenic disorders that activate involuntary detrusor contractions (detrusor overactivity, DO). Also, non-neurogenic disorders such as bladder outlet obstruction or dysfunctions of the female pelvic floor/slack ligaments that affect the urothelium, suburothelium, detrusor and bladder afferents are substantially involved in the pathogenesis of OAB. Until now, circulatory disorders have not been adequately taken into consideration but seem to be another etiological factor that causes OAB. Henceforth, molecular changes of bladder afferents and circulatory disorders in patients suffering from OAB have to be investigated in more detail.

  10. Pathogenesis of Insulin Resistance in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Muhammad A. Abdul-Ghani

    2010-01-01

    Full Text Available Insulin resistance in skeletal muscle is manifested by decreased insulin-stimulated glucose uptake and results from impaired insulin signaling and multiple post-receptor intracellular defects including impaired glucose transport, glucose phosphorylation, and reduced glucose oxidation and glycogen synthesis. Insulin resistance is a core defect in type 2 diabetes, it is also associated with obesity and the metabolic syndrome. Dysregulation of fatty acid metabolism plays a pivotal role in the pathogenesis of insulin resistance in skeletal muscle. Recent studies have reported a mitochondrial defect in oxidative phosphorylation in skeletal muscle in variety of insulin resistant states. In this review, we summarize the cellular and molecular defects that contribute to the development of insulin resistance in skeletal muscle.

  11. Cellular and molecular mechanisms of chikungunya pathogenesis.

    Science.gov (United States)

    Lum, Fok-Moon; Ng, Lisa F P

    2015-08-01

    Chikungunya virus (CHIKV) is an arthropod-borne virus that causes chikungunya fever, a disease characterized by the onset of fever and rashes, with arthralgia as its hallmark symptom. CHIKV has re-emerged over the past decade, causing numerous outbreaks around the world. Since late 2013, CHIKV has reached the shores of the Americas, causing more than a million cases of infection. Despite concentrated efforts to understand the pathogenesis of the disease, further outbreaks remain a threat. This review highlights important findings regarding CHIKV-associated immunopathogenesis and offers important insights into future directions. This article forms part of a symposium in Antiviral Research on "Chikungunya discovers the New World." Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Oxidative stress in the pathogenesis of psoriasis.

    Science.gov (United States)

    Zhou, Qiang; Mrowietz, Ulrich; Rostami-Yazdi, Martin

    2009-10-01

    Psoriasis is a chronic immune-mediated hyperproliferative inflammatory skin disease in which a cytokine network concept is well established. Skin is a major target of oxidative stress mainly due to reactive oxygen species (ROS) originating from the environment and skin metabolism itself. Although endogenous antioxidants attenuate the harmful effects of ROS, increased or prolonged presence of free radicals can override ROS defense mechanisms and mediate numerous cellular responses that contribute to the development of a variety of skin disorders, including psoriasis. Regarding psoriasis, antioxidant strategies have proven to be beneficial therapeutics. The cellular signaling pathways such as mitogen-activated protein kinase/activator protein 1, nuclear factor kappaB, and Janus kinase-signal transducers and activators of transcription are known to be redox sensitive and proven to be involved in the progress of psoriasis. This review summarizes the current knowledge of the role of the redox system in regulating these signaling pathways related to the pathogenesis of psoriasis.

  13. Psoriatic arthritis: from pathogenesis to therapy.

    LENUS (Irish Health Repository)

    Fitzgerald, Oliver

    2012-02-01

    Psoriatic arthritis is a multigenic autoimmune disease that involves synovial tissue, entheseal sites and skin, and that may result in significant joint damage. Although there are no diagnostic tests for psoriatic arthritis, research has identified consistent features that help to distinguish the condition from other common rheumatic diseases. Comparison of HLA-B and HLA-C regions in psoriatic arthritis with those in psoriasis without joint involvement demonstrates significant differences, such that psoriatic arthritis cannot be viewed simply as a subset of genetically homogeneous psoriasis. T-cell receptor phenotypic studies have failed to identify antigen-driven clones, and an alternative hypothesis for CD8 stimulation involving innate immune signals is proposed. Finally, imaging studies have highlighted entheseal involvement in psoriatic arthritis, and it is possible that entheseal-derived antigens may trigger an immune response that is critically involved in disease pathogenesis.

  14. Mathematical models of HIV replication and pathogenesis.

    Science.gov (United States)

    Wodarz, Dominik

    2014-01-01

    This review outlines how mathematical models have been helpful, and continue to be so, for obtaining insights into the in vivo dynamics of HIV infection. The review starts with a discussion of a basic mathematical model that has been frequently used to study HIV dynamics. Some crucial results are described, including the estimation of key parameters that characterize the infection, and the generation of influential theories which argued that in vivo virus evolution is a key player in HIV pathogenesis. Subsequently, more recent concepts are reviewed that have relevance for disease progression, including the multiple infection of cells and the direct cell-to-cell transmission of the virus through the formation of virological synapses. These are important mechanisms that can influence the rate at which HIV spreads through its target cell population, which is tightly linked to the rate at which the disease progresses towards AIDS.

  15. Innate immunity in the pathogenesis of psoriasis.

    LENUS (Irish Health Repository)

    Sweeney, Cheryl M

    2011-12-01

    Psoriasis is a common, immune-mediated inflammatory skin disorder. T helper(h)1 and Th17 lymphocytes contribute to the pathogenesis of psoriasis through the release of inflammatory cytokines that promote further recruitment of immune cells, keratinocyte proliferation and sustained inflammation. The innate immune system is the first line of defence against infection and plays a crucial role in the initiation of the adaptive immune response. The presence of innate immune cells and their products in psoriatic skin plaques suggests a role for innate immunity in this disease. In addition, the innate immune system can direct the development of pathogenic Th cells in psoriasis. In this article, we will summarise the role of the innate immune system in psoriasis with particular emphasis on the role of cytokines, signalling pathways and cells of the innate immune system.

  16. Some aspects of periodontitis pathogenesis in children

    Directory of Open Access Journals (Sweden)

    Shcherbina I.N.

    2013-12-01

    Full Text Available Inflammatory processes in the tissues surrounding tooth root are frequent enough and develop as the direct complication of caries. As acute periodontitis is manifested with grinding toothache and violation of ph¬y¬sio¬logical act of chewing, symptoms of general intoxication, the continuous sluggish chronic periodontitis is harmful and dangerous to the organism as well. It forms the state of chronic оdontogenetic intoxication and chroneosepsis with wrong functioning of some internal organs and body systems. The like complications can cause significant disturbance to the function of kidneys, liver, heart, joints and their treatment without ablating focus of inflammation is often in- effective; this must be taken into account by doctors-interns. However, scanning of the oral cavity by conservative means has its difficulties mostly because of ignoring pathogenesis of such inflammation. That is why activity of ferments of blood dehydrogenases from the periapical tissues of the teeth affected with the chronic periodontitis was studied. The level of succinate dehydrogenase and alpha-glycerophosphate degydrogenase of lymphocytes of 110 schoolchildren aged 13-17 years old was studied. The main group of examined individuals included those of infected with tuber¬culousis – 50 individuals, and the control group (60 individuals – clinically healthy ones without tuberculousis desease. All schoolchildren had 1 or 2 teeth affected with chronic periodontitis of the apical localization. The researchers found that a significant inhibition of activity of succinate dehydrogenase and alpha-glycerophosphate degydrogenase ferments occurs in the inflammatory periodontal tissues, which indicates to local immunity decline, and as a consequence, pathogenic bacteria activation. In people infected with tuberculousis these violations were more developed. Such features of periodontitis pathogenesis must be taken into account when providing a combined treatment.

  17. Research advances in the pathogenesis of nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    WANG Hu

    2017-04-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD has been developing rapidly in recent years and has become one of the most common liver diseases. However, its pathogenesis remains unclear, and there are no widely accepted therapeutic regimens. NAFLD has a complex pathogenesis with multiple factors involved, including insulin resistance, oxidative stress, bile acid metabolic disorders, and autophagy. This article reviews the pathogenesis of NAFLD in order to provide a reference for further research and clinical treatment in the future.

  18. Preeclampsia: Updates in Pathogenesis, Definitions, and Guidelines.

    Science.gov (United States)

    Phipps, Elizabeth; Prasanna, Devika; Brima, Wunnie; Jim, Belinda

    2016-06-06

    Preeclampsia is becoming an increasingly common diagnosis in the developed world and remains a high cause of maternal and fetal morbidity and mortality in the developing world. Delay in childbearing in the developed world feeds into the risk factors associated with preeclampsia, which include older maternal age, obesity, and/or vascular diseases. Inadequate prenatal care partially explains the persistent high prevalence in the developing world. In this review, we begin by presenting the most recent concepts in the pathogenesis of preeclampsia. Upstream triggers of the well described angiogenic pathways, such as the heme oxygenase and hydrogen sulfide pathways, as well as the roles of autoantibodies, misfolded proteins, nitric oxide, and oxidative stress will be described. We also detail updated definitions, classification schema, and treatment targets of hypertensive disorders of pregnancy put forth by obstetric and hypertensive societies throughout the world. The shift has been made to view preeclampsia as a systemic disease with widespread endothelial damage and the potential to affect future cardiovascular diseases rather than a self-limited occurrence. At the very least, we now know that preeclampsia does not end with delivery of the placenta. We conclude by summarizing the latest strategies for prevention and treatment of preeclampsia. A better understanding of this entity will help in the care of at-risk women before delivery and for decades after. Copyright © 2016 by the American Society of Nephrology.

  19. Recent advances in understanding ichthyosis pathogenesis

    Science.gov (United States)

    Marukian, Nareh V.; Choate, Keith A.

    2016-01-01

    The ichthyoses, also known as disorders of keratinization (DOK), encompass a heterogeneous group of skin diseases linked by the common finding of abnormal barrier function, which initiates a default compensatory pathway of hyperproliferation, resulting in the characteristic clinical manifestation of localized and/or generalized scaling. Additional cutaneous findings frequently seen in ichthyoses include generalized xerosis, erythroderma, palmoplantar keratoderma, hypohydrosis, and recurrent infections. In 2009, the Ichthyosis Consensus Conference established a classification consensus for DOK based on pathophysiology, clinical manifestations, and mode of inheritance. This nomenclature system divides DOK into two main groups: nonsyndromic forms, with clinical findings limited to the skin, and syndromic forms, with involvement of additional organ systems. Advances in next-generation sequencing technology have allowed for more rapid and cost-effective genetic analysis, leading to the identification of novel, rare mutations that cause DOK, many of which represent phenotypic expansion. This review focuses on new findings in syndromic and nonsyndromic ichthyoses, with emphasis on novel genetic discoveries that provide insight into disease pathogenesis. PMID:27408699

  20. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Nandy, Debashis; Mukhopadhyay, Debabrata, E-mail: mukhopadhyay.debabrata@mayo.edu [Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, 200 First Street SW, Guggenheim 1321C, Rochester, MN 55905 (United States)

    2011-02-24

    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed.

  1. New Insights into the Pathogenesis of Pancreatitis

    Science.gov (United States)

    Sah, Raghuwansh P.; Dawra, Rajinder K.; Saluja, Ashok K.

    2014-01-01

    Purpose of review In this article, we review important advances in our understanding of the mechanisms of pancreatitis. Recent Findings The relative contribution of intra-pancreatic trypsinogen activation and NFκB activation, the two major early independent cellular events in the etiology of pancreatitis, have been investigated using novel genetic models. Trypsinogen activation has traditionally held the spotlight for many decades as it is believed to be the central pathogenic event of pancreatitis However, recent experimental evidence points to the role of trypsin activation in early acinar cell damage but not in the inflammatory response of acute pancreatitis through NFκB activation. Further, chronic pancreatitis in the caerulein model develops independently of typsinogen activation. Sustained activation of the NFκB pathway, but not persistent intra-acinar expression of active trypsin, was shown to result in chronic pancreatitis. Calcineurin-NFAT signaling was shown to mediate downstream effects of pathologic rise in intracellular calcium. IL-6 was identified as a key cytokine mediating pancreatitis-associated lung injury. Summary Recent advances challenge the long-believed trypsin-centered understanding of pancreatitis. It is becoming increasingly clear that activation of intense inflammatory signaling mechanisms in acinar cells is crucial to the pathogenesis of pancreatitis, which may explain the strong systemic inflammatory response in pancreatitis. PMID:23892538

  2. Premature ovarian insufficiency: Pathogenesis and management

    Directory of Open Access Journals (Sweden)

    Anna J Fenton

    2015-01-01

    Full Text Available The term premature ovarian insufficiency (POI describes a continuum of declining ovarian function in a young woman, resulting in an earlier than average menopause. It is a term that reflects the variable nature of the condition and is substantially less emotive than the formerly used "premature ovarian failure" which signaled a single event in time. Contrary to the decline in the age of menarche seen over the last 3-4 decades there has been no similar change in the age of menopause. In developed nations, the average age for cessation of menstrual cycles is 50-52 years. The age is younger among women from developing nations. Much has been written about POI despite a lack of good data on the incidence of this condition. It is believed that 1% of women under the age of 40 years and 0.1% under the age of 30 years will develop POI. Research is increasingly providing information about the pathogenesis and treatments are being developed to better preserve ovarian function during cancer treatment and to improve fertility options. This narrative review summarizes the current literature to provide an approach to best practice management of POI.

  3. Pain and the pathogenesis of biceps tendinopathy

    Science.gov (United States)

    Raney, Elise B; Thankam, Finosh G; Dilisio, Matthew F; Agrawal, Devendra K

    2017-01-01

    Biceps tendinopathy is a relatively common ailment that typically presents as pain, tenderness, and weakness in the tendon of the long head of the biceps brachii. Though it is often associated with degenerative processes of the rotator cuff and the joint, this is not always the case, thus, the etiology remains considerably unknown. There has been recent interest in elucidating the pathogenesis of tendinopathy, since it can be an agent of chronic pain, and is difficult to manage. The purpose of this article is to critically evaluate relevant published research that reflects the current understanding of pain and how it relates to biceps tendinopathy. A review of the literature was conducted to create an organized picture of how pain arises and manifests itself, and how the mechanism behind biceps tendinopathy possibly results in pain. Chronic pain is thought to arise from neurogenic inflammation, central pain sensitization, excitatory nerve augmentation, inhibitory nerve loss, and/or dysregulation of supraspinal structures; thus, the connections of these theories to the ones regarding the generation of biceps tendinopathy, particularly the neural theory, are discussed. Pain mediators such as tachykinins, CGRP, and alarmins, in addition to nervous system ion channels, are highlighted as possible avenues for research in tendinopathy pain. Recognition of the nociceptive mechanisms and molecular of biceps tendinopathy might aid in the development of novel treatment strategies for managing anterior shoulder pain due to a symptomatic biceps tendon. PMID:28670360

  4. Pathogenesis of trypanosome infections in cattle

    International Nuclear Information System (INIS)

    Murray, M.; Morrison, W.I.; Emery, D.L.; Akol, G.W.O.; Masake, R.A.; Moloo, S.K.

    1980-01-01

    The potential application of radioisotopes are not discussed in this review of trypanosome pathogenesis in cattle. Initially, structural changes in the lymphoid system are characterized by marked proliferation and germinal centre formation, whereas in long-standing infections the lymphoid organs become depleted. These changes appear associated with immunodepression. Anaemia dominates the clinical disease syndrome in bovine trypanosomiasis. It develops with the onset of parasitaemia and is largely haemolytic, resulting from increased red blood cell destruction by phagocytosis. Several factors may be involved in this process including haemolysins produced by the trypanosome, immunological mechanisms, fever, disseminated intravascular coagulation and an expanded and active mononuclear phagocytic system. During this phase of the disease, cattle respond well to chemotherapy. However, in later phases of the disease, when trypanosomes cannot be detected, the anaemia sometimes persists and animals do not respond to treatment. Concerning the underlying mechanisms responsible for the anaemia, continued red cell destruction combined with some dyshaemopoiesis, associated with a defect in iron metabolism, appears responsible. Widespread tissue degeneration occurs. Organs particularly severely affected include the heart. Death in bovine trypanosomiasis is presumably due to a combination of anaemia, microcirculatory disturbances and myocardial damage. The factors incriminated in tissue damage probably vary with the species of trypanosome involved, although under natural field conditions it is common to find T. congolense, T. vivax and T. brucei in one animal. Likely pathogenic mechanisms in bovine include anoxia as a result of anaemia, microcirculatory disorders and hypersensitivity reactions

  5. Achondroplasia: pathogenesis and implications for future treatment.

    Science.gov (United States)

    Laederich, Melanie B; Horton, William A

    2010-08-01

    Although the genetic defect underlying achondroplasia has been known for over a decade, no effective therapies to stimulate bone growth have emerged. Here we review the recent literature and summarize the molecular mechanisms underlying disease pathology and examine their potential as therapeutic targets. Currently used preclinical models are discussed in the context of recent advances with a special focus on C-type natriuretic peptide. Research on the mutation in Fibroblast Growth Factor Receptor 3 (FGFR3) that causes achondroplasia suggests that disease results from increased signal transduction from the mutant receptor. Thus, current therapeutic strategies have focused on reducing signals emanating from FGFR3. First-generation therapies directly targeting FGFR3, such as kinase inhibitors and neutralizing antibodies, designed for targeting FGFR3 in cancer, are still in the preclinical phase and have yet to translate into the management of achondroplasia. Counteracting signal transduction pathways downstream of FGFR3 holds promise with the discovery that administration of C-type natriuretic peptide to achondroplastic mice ameliorates their clinical phenotype. However, more research into long-term effectiveness and safety of this strategy is needed. Direct targeting of therapeutic agents to growth plate cartilage may enhance efficacy and minimize side effects of these and future therapies. Current research into the pathogenesis of achondroplasia has expanded our understanding of the mechanisms of FGFR3-induced disease and has increased the number of approaches that we may use to potentially correct it. Further research is needed to validate these approaches in preclinical models of achondroplasia.

  6. Apoptosis in cancer: from pathogenesis to treatment

    Directory of Open Access Journals (Sweden)

    Wong Rebecca SY

    2011-09-01

    Full Text Available Abstract Apoptosis is an ordered and orchestrated cellular process that occurs in physiological and pathological conditions. It is also one of the most studied topics among cell biologists. An understanding of the underlying mechanism of apoptosis is important as it plays a pivotal role in the pathogenesis of many diseases. In some, the problem is due to too much apoptosis, such as in the case of degenerative diseases while in others, too little apoptosis is the culprit. Cancer is one of the scenarios where too little apoptosis occurs, resulting in malignant cells that will not die. The mechanism of apoptosis is complex and involves many pathways. Defects can occur at any point along these pathways, leading to malignant transformation of the affected cells, tumour metastasis and resistance to anticancer drugs. Despite being the cause of problem, apoptosis plays an important role in the treatment of cancer as it is a popular target of many treatment strategies. The abundance of literature suggests that targeting apoptosis in cancer is feasible. However, many troubling questions arise with the use of new drugs or treatment strategies that are designed to enhance apoptosis and critical tests must be passed before they can be used safely in human subjects.

  7. Fibromyalgia Pathogenesis and Treatment Options Update.

    Science.gov (United States)

    Chinn, Steven; Caldwell, William; Gritsenko, Karina

    2016-04-01

    This review article presents and summarizes up-to-date literature on the clinical manifestations, diagnosis, pathophysiological mechanisms, and treatment options for fibromyalgia patients. First, the most recent diagnostic criteria for fibromyalgia, as put forth by the American College of Rheumatology will be summarized. Clinical features, including chronic widespread pain, hyperalgesia, mood disorders, anxiety, and disturbed sleep patterns will be explored in-depth. The pathogenesis and pathophysiology of fibromyalgia involves alterations in multiple ascending and descending central nervous system pathways, as well as peripheral pathways, leading to heightened pain sensitivity. Risk factors have been studied extensively, and the most recent research focuses on various genetic influences and the contributions of stress and poor sleep. Lastly, the discussion in this article focuses on treatment options for fibromyalgia; some have been mainstay options for many years. Pharmacological agents include tricyclic antidepressants, anti-epileptic drugs, selective serotonin reuptake inhibitors, norepinephrine/serotonin reuptake inhibitors, as well as some investigational agents. The evidence behind non-pharmacologic treatments, including massage therapy, exercise, and acupuncture, are discussed.

  8. [Transthyretin: it's miracle function and pathogenesis].

    Science.gov (United States)

    Ando, Yukio

    2009-03-01

    Transthyretin (TTR) was previously called prealbumin because the band it formed on agarose gel electrophoresis at pH 8.6 was at the prealbumin position. However, it has been well documented that TTR of rodents does not show a prealbumin position on electrophoresis. Now, its name describes its function, binding to retinol binding protein (RBP) and T4. The serum concentration of the protein is 20-40 mg/dl, and TTR forms a tetramer. The plasma half life of the protein is 1.9 days. TTR is synthesized by the liver, retina, pancreas, and choroid plexus. In cerebro-spinal fluid (CSF), it is the second most abundant protein, and is considered as an important protein in the pathogenesis of Alzheimer's disease, depression, and lead intoxication. In addition, TTR is a tryptophan-rich protein, it is used as one of the nutrition assessment proteins, it acts as an anti acute phase protein, and its plasma concentration decreases during inflammation and bacterial infection. Since TTR is a highly amyloidogenic protein because it contains a beta-sheet structure, it becomes a precursor protein in familial amyloidotic polyneuropathy(FAP). Moreover, TTR plays important roles in various CNS disorders, diabetes melitus, and lipid metabolism.

  9. Zika virus genome biology and molecular pathogenesis.

    Science.gov (United States)

    Wang, Anyou; Thurmond, Stephanie; Islas, Leonel; Hui, Kingyung; Hai, Rong

    2017-03-22

    Zika virus (ZIKV) is an emerging RNA virus in the widespread Flavivirus genus. Recently, ZIKV has rapidly spread around the world and has been implicated in human disease, including neurological disorders, triggering public and scientific attention. Understanding how ZIKV causes disease is the highest priority, yet little is known about this virus. Here we examine the currently published data from ZIKV studies to provide the latest understanding of ZIKV genome biology and molecular pathogenesis. The ZIKV genome evolved rapidly from the Flavivirus genus and diverged from the members of this genus, even within the dengue virus cluster to which ZIKV belongs. Genome variations and divergences also exist among ZIKV strains/isolates. These genome divergences might account for the uniqueness of Zika disease. ZIKV infection activates not only the antiviral immune response but also the pro-inflammatory responses associated with disease symptoms. Strikingly, ZIKV activates protein complexes that are functionally associated with disease process, such as glial cell activation and proliferation (for example, Toll-like receptors), apoptosis and cell death, and inflammation. The activation of these complexes may critically contribute to Zika disease. The novel insights into ZIKV genome divergence and disease mechanisms summarized in this review will help accelerate the development of anti-ZIKV strategies.

  10. Naegleria fowleri: pathogenesis, diagnosis, and treatment options.

    Science.gov (United States)

    Grace, Eddie; Asbill, Scott; Virga, Kris

    2015-11-01

    Naegleria fowleri has generated tremendous media attention over the last 5 years due to several high-profile cases. Several of these cases were followed very closely by the general public. N. fowleri is a eukaryotic, free-living amoeba belonging to the phylum Percolozoa. Naegleria amoebae are ubiquitous in the environment, being found in soil and bodies of freshwater, and feed on bacteria found in those locations. While N. fowleri infection appears to be quite rare compared to other diseases, the clinical manifestations of primary amoebic meningoencephalitis are devastating and nearly always fatal. Due to the rarity of N. fowleri infections in humans, there are no clinical trials to date that assess the efficacy of one treatment regimen over another. Most of the information regarding medication efficacy is based on either case reports or in vitro studies. This review will discuss the pathogenesis, diagnosis, pharmacotherapy, and prevention of N. fowleri infections in humans, including a brief review of all survivor cases in North America. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  11. UPDATED MOLECULAR GENETICS AND PATHOGENESIS OF ICHTHYOSES

    Science.gov (United States)

    AKIYAMA, MASASHI

    2011-01-01

    ABSTRACT Research into the molecular genetics and pathomechanisms of ichthyoses have advanced considerably, resulting in the identification of several causative genes and molecules underlying the disease. In 2009, the First Ichthyosis Consensus Conference was held to establish a consensus for the nomenclature and classification of inherited ichthyoses, by which an international consensus for the classification of inherited ichthyosis was achieved. In this review, the pathogeneses of various ichthyoses are summarized based on their revised classification and terminology. Skin barrier defects are involved in the pathogenesis of various types of ichthyosis. The known causative molecules underlying ichthyosis include ABCA12, lipoxygenase-3, 12R-lipoxygenase, CYP4F22, ichthyin and steroid sulfatase, all of which are thought to be related to the intercellular lipid layers. ABCA12 is a known keratinocyte lipid transporter associated with lipid transport in lamellar granules and a loss of ABCA12 function leads to defective lipid transport in the keratinocytes, resulting in the most severe, harlequin ichthyosis phenotype. Other causative molecules for ichthyoses are transglutaminase 1, keratins and filaggrin. Transglutaminase 1 plays a role in cornified cell envelope formation. Keratins 1, 10 and 2 are involved in the keratin network of suprabasal keratinocytes and filaggrin is essential for the formation of keratohyalin granules. It is important to obtain information concerning genetic defects and to elucidate ichthyotic disease pathomechanisms for the establishment of an effective therapy and beneficial genetic counseling, including a prenatal diagnosis for families affected by ichthyotic disease. PMID:21928690

  12. Preeclampsia: Updates in Pathogenesis, Definitions, and Guidelines

    Science.gov (United States)

    Phipps, Elizabeth; Prasanna, Devika; Brima, Wunnie

    2016-01-01

    Preeclampsia is becoming an increasingly common diagnosis in the developed world and remains a high cause of maternal and fetal morbidity and mortality in the developing world. Delay in childbearing in the developed world feeds into the risk factors associated with preeclampsia, which include older maternal age, obesity, and/or vascular diseases. Inadequate prenatal care partially explains the persistent high prevalence in the developing world. In this review, we begin by presenting the most recent concepts in the pathogenesis of preeclampsia. Upstream triggers of the well described angiogenic pathways, such as the heme oxygenase and hydrogen sulfide pathways, as well as the roles of autoantibodies, misfolded proteins, nitric oxide, and oxidative stress will be described. We also detail updated definitions, classification schema, and treatment targets of hypertensive disorders of pregnancy put forth by obstetric and hypertensive societies throughout the world. The shift has been made to view preeclampsia as a systemic disease with widespread endothelial damage and the potential to affect future cardiovascular diseases rather than a self-limited occurrence. At the very least, we now know that preeclampsia does not end with delivery of the placenta. We conclude by summarizing the latest strategies for prevention and treatment of preeclampsia. A better understanding of this entity will help in the care of at-risk women before delivery and for decades after. PMID:27094609

  13. Coronary heart disease: dietary links and pathogenesis.

    Science.gov (United States)

    Renaud, S; Lanzmann-Petithory, D

    2001-04-01

    For decades it has been postulated that the main environmental factor for coronary heart disease (CHD) was the intake of saturated fatty acids (SFA). Nevertheless, confirmation of the role of SFA in CHD through intervention trials has been disappointing. It was only when the diet was enriched in n-3 fatty acids that CHD was significantly prevented, especially cardiac death. In addition to n-3 fatty acids, many other foodstuffs or nutrients such as fibers, antioxidants, folic acid, calcium and even alcohol contribute to prevent CHD. Thus the relationship between diet and CHD morbidity and mortality appears to be much more complex than formerly suspected considering as key factors only SFA, linoleic acid, cholesterol and atherosclerosis. Some of the mechanisms are briefly described, but many additional nutrients (or non nutrients) may also play an important role in the pathogenesis of CHD. Finally, as a result of the most recent epidemiologic studies the ideal diet may comprise: 8% energy from SFA, 5% from polyunsaturated fatty acids with a ratio 5/1 of linoleic/alpha-linolenic acid+longer chains n-3, oleic acid as desired, large intake of cereals, vegetables, legumes and fruits, fish twice a week, cheese and yogurt as dairy products, rapeseed and olive oils as edible fat. Without side effects, such a diet can be highly palatable, easily enjoyed by many populations and may prevent effectively and rapidly (within a few weeks or months) CHD.

  14. Canine neosporosis: perspectives on pathogenesis and management

    Directory of Open Access Journals (Sweden)

    Silva RC

    2016-04-01

    Full Text Available Rodrigo C Silva,1 Gustavo P Machado2 1Department of Pathobiology and Population Medicine, College of Veterinary Medicine, Mississippi State University, Starkville, MS, USA; 2Department of Internal Medicine and Surgery of Small Animals, Dr Munhoz Veterinary Hospital, Itápolis, Brazil Abstract: Canine neosporosis is a worldwide disease caused by the obligate intracellular parasite protozoan Neospora caninum, manifesting mainly neurological symptoms. N. caninum has a heteroxenous life cycle and affects a wide range of warm-blooded animals. The domestic and wild canids are the definitive host of the parasite. They shed oocysts after ingestion of tissue cysts from infected intermediate hosts (ovine, equine, bovine, canine, and many other species, containing bradyzoites, or oocyst-contaminated water and food. The presence of dogs in farms is considered a risk factor for production animals. A wide range of diagnostic methods are currently available, but the most used is serology, ie, indirect fluorescent antibody test specific to the antibody detection in blood serum samples. No vaccine is available, but control strategies should be focused on the vertical and horizontal transmission of the parasite, ie, avoid feeding dogs with raw or undercooked meat, and taking care with water for human and animal consumption. No medicines to control the transplacental transmission are available yet. Keywords: neosporosis, Neospora caninum, pathogenesis, management, dogs

  15. Infantile hemangiomas: from pathogenesis to clinical features

    Directory of Open Access Journals (Sweden)

    Rosenblatt A

    2012-06-01

    Full Text Available Adena Rosenblatt,1 Erin F Mathes,2 Kristina W Rosbe31Department of Pediatrics, University of California, San Francisco, 2Division of Pediatric Dermatology, Departments of Dermatology and Pediatrics, University of California, San Francisco, 3Division of Pediatric Otolaryngology, Department of Otolaryngology – Head and Neck Surgery, University of California, San Francisco, CA, USAAbstract: Infantile hemangiomas (IH are benign vascular tumors consisting of a collection of immature cells, including progenitor stem cells and disorganized blood vessels. They are the most common benign tumors in childhood. Recently, there have been significant, exciting advancements in the understanding of the pathogenesis and treatment of infantile hemangiomas, which are discussed in this review. The decision to initiate treatment for IH is based on many factors, including size and location, functional compromise, psychosocial implications, and risks and benefits of the proposed therapy. For most families of children with hemangiomas, education about the natural history of IH and reassurance are often the only "treatment" required. A minority of patients with large, complex lesions or lesions that cause functional compromise require early intervention. These patients and families benefit from a multidisciplinary approach to care in vascular birthmark centers. Ongoing multi-institutional clinical trials will provide further important data on the efficacy and safety of hemangioma treatments.Keywords: progenitor stem cell, glucose transporter 1, PHACES, LUMBAR, infantile hemangioma

  16. The Pathogenesis of Ebola Virus Disease.

    Science.gov (United States)

    Baseler, Laura; Chertow, Daniel S; Johnson, Karl M; Feldmann, Heinz; Morens, David M

    2017-01-24

    For almost 50 years, ebolaviruses and related filoviruses have been repeatedly reemerging across the vast equatorial belt of the African continent to cause epidemics of highly fatal hemorrhagic fever. The 2013-2015 West African epidemic, by far the most geographically extensive, most fatal, and longest lasting epidemic in Ebola's history, presented an enormous international public health challenge, but it also provided insights into Ebola's pathogenesis and natural history, clinical expression, treatment, prevention, and control. Growing understanding of ebolavirus pathogenetic mechanisms and important new clinical observations of the disease course provide fresh clues about prevention and treatment approaches. Although viral cytopathology and immune-mediated cell damage in ebolavirus disease often result in severe compromise of multiple organs, tissue repair and organ function recovery can be expected if patients receive supportive care with fluids and electrolytes; maintenance of oxygenation and tissue perfusion; and respiratory, renal, and cardiovascular support. Major challenges for managing future Ebola epidemics include establishment of early and aggressive epidemic control and earlier and better patient care and treatment in remote, resource-poor areas where Ebola typically reemerges. In addition, it will be important to further develop Ebola vaccines and to adopt policies for their use in epidemic and pre-epidemic situations.

  17. Psychological Stress in Pathogenesis of Essential Hypertension.

    Science.gov (United States)

    Ushakov, Alexey V; Ivanchenko, Vera S; Gagarina, Alina A

    2016-01-01

    The article represents literature review and provides evidence for psychological stress to play essential role in the development of arterial hypertension. The pathogenesis of hypertension is complex with a significant diversity and variability of the mechanisms involved in individual patient. In this regard, the determination of specific pathogenic pathways underlying sustained blood pressure elevation in each patient would substantially individualize therapeutic approaches, and hence increase the effectiveness of treatment. Psychological stress is proposed as a significant factor contributing to the development of hypertension. Global urbanization, sedentary lifestyle, daily stress at workplace, lack of physical activity and social support lead to increased anxiety, uncertainty, and finally to chronic mental and emotional stress. This review provides information about alterations in neuroendocrine and immune systems as the main pathogenic pathways linking psychological stress and hypertension. Endothelial dysfunction is considered not only as a consequence but also a primary factor causing prohypertensive state. Moreover, physical inactivity is discussed as one of the plausible mechanisms playing a key role in the development of hypertension in modern lifestyle conditions. Particularly the loss of connection between psychosocial strain and physical activity may underlie the deleterious effect of stress on cardiovascular and metabolic health. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    International Nuclear Information System (INIS)

    Nandy, Debashis; Mukhopadhyay, Debabrata

    2011-01-01

    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed

  19. Pathogenesis of odontogenic cysts: an update.

    Science.gov (United States)

    Chindia, M L

    1991-04-01

    This article briefly reviews the origin, classification and pathogenesis of the various odontogenic cysts. Keratocysts and follicular cysts are said to be developmental lesions arising from the remnants of the dental lamina and the cell rests of the dental follicle respectively. The radicular cysts are the most commonly occurring lesions associated with the apices of non-vital teeth. They are said to arise from proliferation of the cell rests of Malassez in chronically inflamed granulomata. It is noted that bone resorption is the major requirement for any bony lesion to expand; hence the interest in the role of diverse cellular and chemical mediators of bone resorption in disease. The current concepts of the role, in cyst initiation and growth, of enzymes including cellular metabolites and cytokines are presented. Evidence on the activities of collagenase, arachidonic acid metabolites, leukotrienes, hydroxyeicosatetraenoic acids, interleukin--1 and prostaglandins is cited. It is observed that the understanding of these cellular and molecular biological behaviour patterns may yield more appropriate information necessary for the development of more effective management modalities for such tissue degrading lesions as odontogenic cysts.

  20. Tryptophan-induced pathogenesis of breast cancer | Cao | African ...

    African Journals Online (AJOL)

    Background: The pathogenesis of breast cancer remains unclear. Aims: To investigate the pathogenesis of breast cancer through targeted metabolomics of amino acids components in serum of patients with breast cancer. Methods: Patients with breast cancers were enrolled in our hospital between year January 1st, 2013 ...

  1. Aetio-pathogenesis of breast cancer | Abdulkareem | Nigerian ...

    African Journals Online (AJOL)

    This is a literature review on the aetiology and pathogenesis of breast cancer, which is the most common cancer worldwide, and the second leading cause of cancer death, especially in Western countries. Several aetiological factors have been implicated in its pathogenesis, and include age, genetics, family history, diet, ...

  2. Necrotizing enterocolitis. New thoughts about pathogenesis and potential treatments.

    Science.gov (United States)

    MacKendrick, W; Caplan, M

    1993-10-01

    Necrotizing enterocolitis (NEC) remains a major cause of morbidity and mortality in premature infants. An incomplete understanding of its pathogenesis has hampered efforts to devise an effective preventative strategy. New insights into the pathogenesis of NEC, particularly at the cellular and biochemical level, however, offer a rational basis for the development of new approaches to this disease.

  3. Role of Endogenous Peptides and Enzymes in the Pathogenesis of ...

    African Journals Online (AJOL)

    pathogenesis mechanism of acute pancreatitis that are related to various inflammatory and pro- inflammatory mediators. Keywords: Acute ... cytokines which are released by neutrophils and macrophages during acute pancreatitis, ... platelet activating factor have been shown to play significant roles in the pathogenesis of ...

  4. Cytokines in Gaucher disease: Role in the pathogenesis of bone ...

    African Journals Online (AJOL)

    Azza A.G. Tantawy

    2015-03-03

    Mar 3, 2015 ... Cytokines in Gaucher disease: Role in the pathogenesis of bone and pulmonary ... Studies are increasingly recognizing the role of immune dysregulation and inflammation in the pathogenesis of Gaucher disease. ..... by various other cells of the immune system [11]. Recent work in a murine model of ...

  5. Demonstrating concepts of pathogenesis using effectors of Phytophthora infestans

    Science.gov (United States)

    Pathogenesis, or how pathogens cause disease, is an important concept in plant pathology. The study of pathogenesis in plant pathology has rapidly expanded and is now a significant portion of plant pathology research (especially research at the molecular level of host-pathogen interaction). With the...

  6. Pathogenesis of Noroviruses, Emerging RNA Viruses

    Directory of Open Access Journals (Sweden)

    Stephanie M. Karst

    2010-03-01

    Full Text Available Human noroviruses in the family Caliciviridae are a major cause of epidemic gastroenteritis. They are responsible for at least 95% of viral outbreaks and over 50% of all outbreaks worldwide. Transmission of these highly infectious plus-stranded RNA viruses occurs primarily through contaminated food or water, but also through person-to-person contact and exposure to fomites. Norovirus infections are typically acute and self-limited. However, disease can be much more severe and prolonged in infants, elderly, and immunocompromised individuals. Norovirus outbreaks frequently occur in semi-closed communities such as nursing homes, military settings, schools, hospitals, cruise ships, and disaster relief situations. Noroviruses are classified as Category B biodefense agents because they are highly contagious, extremely stable in the environment, resistant to common disinfectants, and associated with debilitating illness. The number of reported norovirus outbreaks has risen sharply since 2002 suggesting the emergence of more infectious strains. There has also been increased recognition that noroviruses are important causes of childhood hospitalization. Moreover, noroviruses have recently been associated with multiple clinical outcomes other than gastroenteritis. It is unclear whether these new observations are due to improved norovirus diagnostics or to the emergence of more virulent norovirus strains. Regardless, it is clear that human noroviruses cause considerable morbidity worldwide, have significant economic impact, and are clinically important emerging pathogens. Despite the impact of human norovirus-induced disease and the potential for emergence of highly virulent strains, the pathogenic features of infection are not well understood due to the lack of a cell culture system and previous lack of animal models. This review summarizes the current understanding of norovirus pathogenesis from the histological to the molecular level, including

  7. [Evolution of pathogenesis of atherosclerosis in phylogenesis].

    Science.gov (United States)

    Titov, V N

    2014-01-01

    The first atherosclerosis pandemics developed in phylogenesis when animals went out of the ocean, the second coincided with mutations of proteins that transferred zero-cholesterol esters, the third (present-day pandemics) results from disturbed biological function of trophology, abnormally high content of saturated fatty acids and their trans-forms in food, and blockade of bioavailability of polyenic FA (PNFA) for cells. The blood pool of ligand-free lipoproteins, phylogenetically early macrophages are only partly utilized in intima giving rise to atheromatosis. When active absorption of w-3 and w-6 PNFA is blocked, the cells synthesize by way of compensation non-physiological w-9 eicosanoids which creates the basis of pathogenesis of atherosclerosis, pathology ofautocrine regulation, and paracrine humoral regulation of cell communities and the body. A rise in the frequency of non-infectious diseases above 5-7% is regarded as pathology of biological functions and reactions. Non-physiological environmental effects should be neutralized by normalization of tropholgy function, exotrophic biological reaction. Metabolic pandemics may have two outcomes. First: (a) effective reduction to a minimum of infavourable environmental effects, i.e. normalization of the nutritive function, (b) matching it with possibilities of lipoproteins, (c) reduction of morbidity and mortality from atherosclerosis. Second: man continues to develop as in phylogenesis and adapts himself to nonphysiological nutrition. Mortality from infarction and stroke will remain high during the next 40-50 thousand years. Increased content of w-3 PNFA in food without reduction of NAF with blockade of bioavailability will further facilitate atheromatosis. Man should rely on physiological nutrition, there is no reason to rely on hypolipidemic agents. Otherwise, the second outcome awaits the mankind. Tertium non datum.

  8. Pathogenesis of reduced or increased bladder sensation.

    Science.gov (United States)

    Tsunoyama, Kuniko; Sakakibara, Ryuji; Yamaguchi, Chiharu; Uchiyama, Tomoyuki; Yamamoto, Tatsuya; Yamanishi, Tomonori; Takahashi, Osamu; Sugiyama, Megumi; Kishi, Masahiko; Ogawa, Emina

    2011-03-01

    Pathogenesis of reduced or increased bladder sensation is not well known. Hence, we systematically investigated the frequency of reduced or increased bladder sensation in neurologic/mental diseases. We analyzed 911 patients who were referred from within our hospital. Data registries included a diagnosis, a lower urinary tract symptom questionnaire, a urodynamic study, and neurological examinations. Reduced bladder sensation is defined as bladder volume at the first sensation >300 ml. Increased bladder sensation is defined as bladder volume at the first sensation sensation (33.3-43.8% in diabetic neuropathy, etc.). Myelopathies are the second most common cause (17.4-25.0% in multiple sclerosis, etc.). Less common is brain diseases (9.6% in multiple system atrophy, etc.). In contrast, myelopathies are the most common cause of increased bladder sensation without DO (25.0-40.0% in spinal forms of systemic lupus erythematosus, Sjogren's syndrome, etc.). Neuropathies are the second most common (17.3-22.2% in post-pelvic organ surgery, diabetic neuropathy, etc.). Less common is brain/mental diseases (20.0% in psychogenic bladder dysfunction, 8.1% in Parkinson's disease, etc.). The present study revealed that neuropathies are the most common cause of reduced bladder sensation in neurologic/mental diseases. Increased bladder sensation without DO occurs mainly in peripheral and central sensory pathway lesions, as well as in basal ganglia lesions and psychogenic bladder dysfunction. Reduced and increased bladder sensation should be a major treatment target for maximizing patients' quality of life. Copyright © 2011 Wiley-Liss, Inc.

  9. Pathogenesis of diverticulosis and diverticular disease.

    Science.gov (United States)

    Walker, Marjorie M; Harris, Angela K

    2017-06-01

    Diverticulosis is defined by the presence of diverticula due to herniation of mucosa and muscularis mucosa through the muscularis propria at sites of vascular penetration in the colon and is asymptomatic in the vast majority affected. There are global differences of distribution, in Western industrialized societies, the most common site is in the left colon, but in Asia right sided diverticulosis predominates. Whilst present in 17.5% of a general population and 42% of all comers at endoscopy it is seen in 71% of those aged ≥80 years. Diverticular disease is defined as clinically significant and symptomatic diverticulosis, which may have an absence of macroscopically overt colitis and in true diverticulitis there is macroscopic inflammation of diverticula with related acute or chronic complications. Whilst overall, diverticulitis affects only 4% of those with diverticulosis, in younger patients (aged 40-49 years) this peaks at 11%. Diverticulosis is one of the most common chronic diseases, yet research in this field on pathogenesis has lagged behind other common conditions such as diabetes mellitus. However, in the last decade there have been major advances in taxonomy that can be used to relate to patients' outcome and treatment in both medicine and surgery. It has been shown there is an association with age, diet, drugs and smoking. Genetic studies have shown a familial association and a specific gene, TNFSF 15 may predict severity of disease. The role of the microbiome has been explored and microbial and metabolomic signatures are also important in predicting disease severity. That diverticulosis is a chronic disease is shown by mucosal pathology with subtle chronic inflammation present in those with asymptomatic diverticulosis and inflammation may lead to muscular hypertrophy, enteric nerve remodeling with disordered motility. The diverticulitis quality of life instrument shows that this condition impacts markedly on patients' well-being and prevention and

  10. Obesity Pathogenesis: An Endocrine Society Scientific Statement.

    Science.gov (United States)

    Schwartz, Michael W; Seeley, Randy J; Zeltser, Lori M; Drewnowski, Adam; Ravussin, Eric; Redman, Leanne M; Leibel, Rudolph L

    2017-08-01

    Obesity is among the most common and costly chronic disorders worldwide. Estimates suggest that in the United States obesity affects one-third of adults, accounts for up to one-third of total mortality, is concentrated among lower income groups, and increasingly affects children as well as adults. A lack of effective options for long-term weight reduction magnifies the enormity of this problem; individuals who successfully complete behavioral and dietary weight-loss programs eventually regain most of the lost weight. We included evidence from basic science, clinical, and epidemiological literature to assess current knowledge regarding mechanisms underlying excess body-fat accumulation, the biological defense of excess fat mass, and the tendency for lost weight to be regained. A major area of emphasis is the science of energy homeostasis, the biological process that maintains weight stability by actively matching energy intake to energy expenditure over time. Growing evidence suggests that obesity is a disorder of the energy homeostasis system, rather than simply arising from the passive accumulation of excess weight. We need to elucidate the mechanisms underlying this "upward setting" or "resetting" of the defended level of body-fat mass, whether inherited or acquired. The ongoing study of how genetic, developmental, and environmental forces affect the energy homeostasis system will help us better understand these mechanisms and are therefore a major focus of this statement. The scientific goal is to elucidate obesity pathogenesis so as to better inform treatment, public policy, advocacy, and awareness of obesity in ways that ultimately diminish its public health and economic consequences. Copyright © 2017 Endocrine Society.

  11. Pathogenesis of glucose intolerance in uremia.

    Science.gov (United States)

    DeFronzo, R A

    1978-12-01

    The pathogenesis of glucose intolerance in uremia was examined with the glucose clamp technique. Hyperglycemic clamp (n = 8): The plasma glucose concentration is acutely raised and maintained at 125 mg/dl above basal levels. Under these steady state conditions the glucose infusion rate, M, equals the amount of glucose metabolized: Predialysis M averaged 4.23 +/- 0.36 mg/kg/min and increased to 7.71 +/- 0.43 postdialysis (p less than 0.001). The plasma insulin response predialysis was 90 +/- 20 microU/ml and decreased to 80 +/- 23 microU/ml following dialysis. Consequently the M/l ratio, a measure of tissue sensitivity to insulin, increased by 80% +/- 25% (p less than 0.001) but still remained less than controls (p less than 0.01). Euglycemic insulin clamp (n = 10): The plasma insulin concentration is acutely raised by 100 microU/ml and the plasma glucose concentration is held constant at the basal level. Predialysis both M (3.37 +/- 0.36 mg/kg/min) and M/l (3.56 +/- 0.33 mg/kg/min per microU/ml X 100) were significantly less than controls (p less than 0.01). Postdialysis both M and M/l increased significantly (p less than 0.01) to a mean that was not significantly different from controls. Basal hepatic glucose production (n = 6), 2.15 +/- 0.09 mg/kg/min, was similar to controls and fell (87% +/- 4%) normally during the insulin clamp. In five uremic subjects in wom insulin binding to monocytes was measured, there was no correlation with tissue sensitivity to insulin (M/l). Significant abnormalities in both growth hormone and glucagon physiology were present in uremic individuals, but no correlation with either the presence or degree of glucose intolerance was demonstrable. In conclusion, glucose intolerance is universally present in uremic subjects and results primarily from peripheral tissue insensitivity to insulin. Insulin secretion is usually enhanced in an attempt to compensate for this insulin resistance but in occasional subjects uremia also inhibits beta

  12. Modifier genes: Moving from pathogenesis to therapy.

    Science.gov (United States)

    McCabe, Edward R B

    2017-09-01

    This commentary will focus on how we can use our knowledge about the complexity of human disease and its pathogenesis to identify novel approaches to therapy. We know that even for single gene Mendelian disorders, patients with identical mutations often have different presentations and outcomes. This lack of genotype-phenotype correlation led us and others to examine the roles of modifier genes in the context of biological networks. These investigations have utilized vertebrate and invertebrate model organisms. Since one of the goals of research on modifier genes and networks is to identify novel therapeutic targets, the challenges to patient access and compliance because of the high costs of medications for rare genetic diseases must be recognized. A recent article explored protective modifiers, including plastin 3 (PLS3) and coronin 1C (CORO1C), in spinal muscular atrophy (SMA). SMA is an autosomal recessive deficit of survival motor neuron protein (SMN) caused by mutations in SMN1. However, the severity of SMA is determined primarily by the number of SMN2 copies, and this results in significant phenotypic variability. PLS3 was upregulated in siblings who were asymptomatic compared with those who had SMA2 or SMA3, but identical homozygous SMN1 deletions and equal numbers of SMN2 copies. CORO1C was identified by interrogation of the PLS3 interactome. Overexpression of these proteins rescued endocytosis in SMA models. In addition, antisense RNA for upregulation of SMN2 protein expression is being developed as another way of modifying the SMA phenotype. These investigations suggest the practical application of protective modifiers to rescue SMA phenotypes. Other examples of the potential therapeutic value of novel protective modifiers will be discussed, including in Duchenne muscular dystrophy and glycerol kinase deficiency. This work shows that while we live in an exciting era of genomic sequencing, a functional understanding of biology, the impact of its

  13. Role of perfumes in pathogenesis of autism.

    Science.gov (United States)

    Bagasra, Omar; Golkar, Zhabiz; Garcia, Miranda; Rice, Lakya N; Pace, Donald Gene

    2013-06-01

    Autism spectrum disorders (ASDs) are developmental conditions characterized by deficits in social interaction, verbal and nonverbal communication, and obsessive/stereotyped patterns of behavior. Although there is no reliable neurophysiological marker associated with ASDs, dysfunction of the parieto-frontal mirror neuron system and underdeveloped olfactory bulb (OB) has been associated with the disorder. It has been reported that the number of children who have ASD has increased considerably since the early 1990 s. In developed countries, it is now reported that 1-1.5% of children have ASD, and in the US it is estimated that one in 88 children suffer from ASD. Currently, there is no known cause for ASD. During the last three decades, the most commonly accepted paradigm about autism is that it is a genetically inherited disease. The recent trio analyses, in which both biological parents and the autistic child's exomes are sequenced, do not support this paradigm. On the other hand, the environmental factors that may induce genetic mutations in vitro have not been clearly identified, and there is little irrefutable evidence that pesticides, water born chemicals, or food preservatives play critical roles in inducing the genetic mutations associated with known intellectual deficiencies that have been linked to autism spectrum disorder (ASD). Here, we hypothesize and provide scientific evidence that ASD is the result of exposure to perfumes and cosmetics. The highly mutagenic, neurotoxic, and neuromodulatory chemicals found in perfumes are often overlooked and ignored as a result of a giant loophole in the Federal Fair Packaging and Labeling Act of 1973, which explicitly exempts fragrance producers from having to disclose perfume ingredients on product labels. We hypothesize that perfumes and cosmetics may be important factors in the pathogenesis of ASD. Synthetic perfumes have gained global utility not only as perfumes but also as essential chemicals in detergents

  14. Water hardness influences Flavobacterium columnare pathogenesis in channel catfish

    Science.gov (United States)

    Studies were conducted to determine aspects of water chemistry responsible for large differences in pathogenesis and mortality rates in challenges of channel catfish Ictalurus punctatus with Flavobacterium columnare; challenges were conducted in water supplying the Stuttgart National Aquaculture Res...

  15. Oral candidiasis: pathogenesis, clinical presentation, diagnosis and treatment strategies.

    Science.gov (United States)

    Lalla, Rajesh V; Patton, Lauren L; Dongari-Bagtzoglou, Anna

    2013-04-01

    Oral candidiasis is a clinical fungal infection that is the most common opportunistic infection affecting the human oral cavity. This article reviews the pathogenesis, clinical presentations, diagnosis and treatmentstrategies for oral candidiasis.

  16. Current insights in sepsis: from pathogenesis to new treatment targets

    NARCIS (Netherlands)

    Wiersinga, W. Joost

    2011-01-01

    Sepsis continues to be a leading cause of ICU death. This review summarizes current knowledge on sepsis pathogenesis and new therapeutical strategies. Although systemic inflammatory response syndrome predominates in early sepsis, the compensatory anti-inflammatory response syndrome causes

  17. Signaling Pathways in Pathogenesis of Diamond Blackfan Anemia

    Science.gov (United States)

    2015-12-01

    AWARD NUMBER: W81XWH-12-1-0590 TITLE: SIGNALING PATHWAYS IN PATHOGENESIS OF DIAMOND BLACKFAN ANEMIA PRINCIPAL INVESTIGATOR: KATHLEEN M...SUBTITLE 5a. CONTRACT NUMBER W81XWH-12-1-0590 SIGNALING PATHWAYS IN PATHOGENESIS OF DIAMOND BLACKFAN ANEMIA 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER...Unlimited 13. SUPPLEMENTARY NOTES None 14. ABSTRACT: Diamond Blackfan Anemia (DBA) is a disorder that results in pure red cell aplasia, congenital

  18. Cardiac syndrome X. Diagnosis, pathogenesis and management.

    Science.gov (United States)

    Kaski, Juan Carlos; Aldama, Guillermo; Cosín-Sales, Juan

    2004-01-01

    Patients with cardiac syndrome X (typical chest pain and normal coronary arteriograms) represent a heterogeneous syndrome, which encompasses different pathogenic mechanisms. Although symptoms in most patients with cardiac syndrome X are non-cardiac, a sizable proportion of them have angina pectoris due to transient myocardial ischemia. Thus radionuclide myocardial perfusion defects, coronary sinus oxygen saturation abnormalities and pH changes, myocardial lactate production and stress-induced alterations of cardiac high energy phosphate suggest an ischemic origin of symptoms in at least a proportion of patients with cardiac syndrome X. Microvascular abnormalities, caused by endothelial dysfunction, appear to be responsible for myocardial ischemia in patients with cardiac syndrome X. Endothelial dysfunction is likely to be multifactorial in these patients and it is conceivable that risk factors such as hypertension, hypercholesterolemia, diabetes mellitus and smoking can contribute to its development. Most patients with cardiac syndrome X are postmenopausal women and estrogen deficiency has been therefore proposed as a pathogenic factor in female patients. Additional factors such as abnormal pain perception may contribute to the pathogenesis of chest pain in patients with angina pectoris and normal coronary angiograms. Although prognosis is good regarding survival, patients with cardiac syndrome X have an impaired quality of life. Management of this syndrome represents a major challenge to the treating physician. Understanding the mechanism underlying the condition is of vital importance for patient management. Thus diagnostic tests should aim at identifying the cause of the symptoms in the individual patient, i.e. myocardial ischemia, increased pain perception, abnormalities of adrenergic tone, non-cardiac mechanisms, etc. Moreover, it is important to bear in mind that treatment of cardiac syndrome X should be mainly directed towards improving quality of life, as

  19. CSF cytokines/chemokines as biomarkers in neuroinflammatory CNS disorders: A systematic review.

    Science.gov (United States)

    Kothur, Kavitha; Wienholt, Louise; Brilot, Fabienne; Dale, Russell C

    2016-01-01

    Despite improved understanding of the pathogenesis of neuroinflammatory disorders of the brain and development of new diagnostic markers, our biomarker repertoire to demonstrate and monitor inflammation remains limited. Using PubMed database, we reviewed 83 studies on CSF cytokines and chemokines and describe the pattern of elevation and possible role of cytokines/chemokines as biomarkers in viral and autoimmune inflammatory neurological disorders of the CNS. Despite inconsistencies and overlap of cytokines and chemokines in different neuroinflammation syndromes, there are some trends regarding the pattern of cytokines/chemokine elevation. Namely B cell markers, such as CXCL13 and BAFF are predominantly investigated and found to be elevated in autoantibody-associated disorders, whereas interferon gamma (IFN-γ) is elevated mainly in viral encephalitis. Th2 and Th17 cytokines are frequently elevated in acute disseminated encephalomyelitis (ADEM) and neuromyelitis optica (NMO), whereas Th1 and Th17 cytokines are more commonly elevated in multiple sclerosis (MS). Cytokine/chemokine profiling might provide new insights into disease pathogenesis, and improve our ability to monitor inflammation and response to treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Rheumatic fever pathogenesis: Approach in research needs change

    Directory of Open Access Journals (Sweden)

    Rajendra Tandon

    2012-01-01

    Full Text Available Despite identifying that rheumatic fever (RF is the result of an immunological reaction following group-A beta-hemolytic streptococcal infection, the pathogenesis remains elusive. RF has been incorrectly designated as causing pancarditis, since it does not cause myocarditis. Research directed toward myocarditis, targeting myosin to unravel the pathogenesis has not succeeded in more than 60 years. RF causes permanent damage to cardiac valves. The mitral valve (MV, derived from the wall of the left ventricle, is composed of a central core of connective tissue, covered on both sides by endothelium. The left ventricle does not have either myocardial or intermyocardial connective tissue involvement in RF. By exclusion, therefore, the primary site of RF damage appears to be the endothelium. Evaluation of the histopathology and immunopathology indicates that RF is a disease of the valvular and vascular endothelium. It is not a connective tissue disorder. Research to identify pathogenesis needs to be focused toward valvular endothelium.

  1. The Role of Caveolin 1 in HIV Infection and Pathogenesis.

    Science.gov (United States)

    Mergia, Ayalew

    2017-05-26

    Caveolin 1 (Cav-1) is a major component of the caveolae structure and is expressed in a variety of cell types including macrophages, which are susceptible to human immunodeficiency virus (HIV) infection. Caveolae structures are present in abundance in mechanically stressed cells such as endothelial cells and adipocytes. HIV infection induces dysfunction of these cells and promotes pathogenesis. Cav-1 and the caveolae structure are believed to be involved in multiple cellular processes that include signal transduction, lipid regulation, endocytosis, transcytosis, and mechanoprotection. Such a broad biological role of Cav-1/caveolae is bound to have functional cross relationships with several molecular pathways including HIV replication and viral-induced pathogenesis. The current review covers the relationship of Cav-1 and HIV in respect to viral replication, persistence, and the potential role in pathogenesis.

  2. The epidemiology, pathogenesis and histopathology of fatty liver disease.

    Science.gov (United States)

    Levene, Adam P; Goldin, Robert D

    2012-08-01

    Fatty liver disease includes non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD), each of which is increasing in prevalence. Each represents a histological spectrum that extends from isolated steatosis to steatohepatitis and cirrhosis. NAFLD is associated with obesity, diabetes, and insulin resistance, and is considered to be the liver manifestation of the metabolic syndrome. The pathogenesis of NAFLD and ALD involves cytokines, adipokines, oxidative stress, and apoptosis. Histopathology is the gold standard for assessing the severity of liver damage in NAFLD and ALD. We have reviewed the literature, and described and compared the epidemiology, natural disease history, pathogenesis and histopathology of NAFLD and ALD. © 2012 Blackwell Publishing Ltd.

  3. Modern views on the epidemiology, etiology and pathogenesis of gynecomastia

    Directory of Open Access Journals (Sweden)

    Yu. N. Yashina

    2014-01-01

    Full Text Available The review deals with one of the pressing andrological issues – gynecomastia, its etiology and pathogenesis. Based on the current epidemiological and experimental data, most common etiological factors of gynecomastia were investigated. A multiple-valued role of various causes of gynecomastia in several age-groups was revealed. Literature data show that gynecomastia may be a manifestation of various diseases: endocrine, genetic, systematic. As well as that, gynecomastia may occur in patients with oncological diseases. However, gynecomastia can be an iatrogenic complication. Currently, we continue to make insights to the problem of gynecomastia in order to be able to classify its etiological factors and determine its basic pathogenesis pathways.

  4. The role of EPCR in the pathogenesis of severe malaria

    DEFF Research Database (Denmark)

    Mosnier, Laurent O; Lavstsen, Thomas

    2016-01-01

    malaria syndromes and that these PfEMP1 variants contain EPCR binding domains provides new opportunities to improve our understanding of the molecular mechanisms responsible for the pathogenesis of severe malaria. EPCR is known for its essential role in the protein C (PC) system and for its ability...... the new paradigm that EPCR plays a central role in the pathogenesis of severe malaria. Thus, targeting of the PfEMP1-EPCR interaction and restoring the functionality of the PC system may provide new strategies for the development of novel adjuvant therapies for severe malaria....

  5. Immunomodulatory role of vitamin D in the pathogenesis of preeclampsia.

    Science.gov (United States)

    Smith, Tyler A; Kirkpatrick, Daniel R; Kovilam, Oormila; Agrawal, Devendra K

    2015-01-01

    Worldwide, preeclampsia is a significant health risk to both pregnant women and their unborn children. Despite scientific advances, the exact pathogenesis of preeclampsia is not yet fully understood. Meanwhile, the incidence of preeclampsia is expected to increase. A series of potential etiologies for preeclampsia has been identified, including endothelial dysfunction, immunological dysregulation and trophoblastic invasion. In this literature review, we have critically reviewed existing literature regarding the research findings that link the role of vitamin D to the pathogenesis and immunoregulation of preeclampsia. The relationship of vitamin D with the suspected etiologies of preeclampsia underscores its clinical potential in the diagnosis and treatment of preeclampsia.

  6. ROLE OF UBIQUITIN PROTEASOME SYSTEM IN GASTRIC CANCER PATHOGENESIS

    Directory of Open Access Journals (Sweden)

    E. V. Ivanova

    2014-01-01

    Full Text Available The review presents data on the ubiquitin-proteasome system participation in pathogenesis of gastric cancer. The role of proteasome system in regulation of cell cycle, angiogenesis and tumor metastasis has been shown. The aspects of the participation of ubiquitin-proteasome proteolytic system in the pathogenesis of intensive muscle protein degradation in cancer cachexia are analyzed. The role of proteasome system in the development of H. Pylori-induced gastric cancer is discussed. The clinical assessment of selective proteasome inhibitor (bortezomib is a promising area of research for metastatic gastric cancer.

  7. Recent advances in dengue pathogenesis and clinical management.

    Science.gov (United States)

    Simmons, Cameron P; McPherson, Kirsty; Van Vinh Chau, Nguyen; Hoai Tam, D T; Young, Paul; Mackenzie, Jason; Wills, Bridget

    2015-12-10

    This review describes and commentates on recent advances in the understanding of dengue pathogenesis and immunity, plus clinical research on vaccines and therapeutics. We expand specifically on the role of the dermis in dengue virus infection, the contribution of cellular and humoral immune responses to pathogenesis and immunity, NS1 and mechanisms of virus immune evasion. Additionally we review a series of therapeutic intervention trials for dengue, as well as recent clinical research aimed at improving clinical diagnosis, risk prediction and disease classification. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. On the Pathogenesis of Alzheimer's Disease: The MAM Hypothesis.

    Science.gov (United States)

    Area-Gomez, Estela; Schon, Eric A

    2017-03-01

    The pathogenesis of Alzheimer's disease (AD) is currently unclear and is the subject of much debate. The most widely accepted hypothesis designed to explain AD pathogenesis is the amyloid cascade, which invokes the accumulation of extracellular plaques and intracellular tangles as playing a fundamental role in the course and progression of the disease. However, besides plaques and tangles, other biochemical and morphological features are also present in AD, often manifesting early in the course of the disease before the accumulation of plaques and tangles. These include altered calcium, cholesterol, and phospholipid metabolism; altered mitochondrial dynamics; and reduced bioenergetic function. Notably, these other features of AD are associated with functions localized to a subdomain of the endoplasmic reticulum (ER), known as mitochondria-associated ER membranes (MAMs). The MAM region of the ER is a lipid raft-like domain closely apposed to mitochondria in such a way that the 2 organelles are able to communicate with each other, both physically and biochemically, thereby facilitating the functions of this region. We have found that MAM-localized functions are increased significantly in cellular and animal models of AD and in cells from patients with AD in a manner consistent with the biochemical findings noted above. Based on these and other observations, we propose that increased ER-mitochondrial apposition and perturbed MAM function lie at the heart of AD pathogenesis.-Area-Gomez, E., Schon, E. A. On the pathogenesis of Alzheimer's disease: the MAM hypothesis. © FASEB.

  9. Role of free radicals in pathogenesis of diabetes nephropathy ...

    African Journals Online (AJOL)

    However, the pathogenesis of diabetes nephropathy remains illusive, notwithstanding, free radicals seem to be the most favorable linkage between all the associated factors suggested. Consequently, free radicals, oxidative stress and antioxidants have become commonly used terms in modern discussions of renal disease ...

  10. Etiology and pathogenesis of anterior open bite: A review | Wanjau ...

    African Journals Online (AJOL)

    Objective: To review the etiology and pathogenesis of anterior open bite malocclusion. Data source: Review of literature was affected through Pubmed, Google scholar and Science direct. References identified from articles found from the primary search were also reviewed. Study selection: Published data on etiology and ...

  11. Tick-borne encephalitis: Pathogenesis and clinical implications

    Czech Academy of Sciences Publication Activity Database

    Růžek, Daniel; Dobler, G.; Mantke, O. D.

    2010-01-01

    Roč. 8, č. 4 (2010), s. 223-232 ISSN 1477-8939 R&D Projects: GA ČR GPP302/10/P438; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z60220518 Keywords : Tick-borne encephalitis * Tick-borne encephalitis virus * Pathogenesis * Clinical data Subject RIV: EE - Microbiology, Virology

  12. Deciphering the pathogenesis of tendinopathy: a three-stages process

    Directory of Open Access Journals (Sweden)

    Fu Sai-Chuen

    2010-12-01

    Full Text Available Abstract Our understanding of the pathogenesis of "tendinopathy" is based on fragmented evidences like pieces of a jigsaw puzzle. We propose a "failed healing theory" to knit these fragments together, which can explain previous observations. We also propose that albeit "overuse injury" and other insidious "micro trauma" may well be primary triggers of the process, "tendinopathy" is not an "overuse injury" per se. The typical clinical, histological and biochemical presentation relates to a localized chronic pain condition which may lead to tendon rupture, the latter attributed to mechanical weakness. Characterization of pathological "tendinotic" tissues revealed coexistence of collagenolytic injuries and an active healing process, focal hypervascularity and tissue metaplasia. These observations suggest a failed healing process as response to a triggering injury. The pathogenesis of tendinopathy can be described as a three stage process: injury, failed healing and clinical presentation. It is likely that some of these "initial injuries" heal well and we speculate that predisposing intrinsic or extrinsic factors may be involved. The injury stage involves a progressive collagenolytic tendon injury. The failed healing stage mainly refers to prolonged activation and failed resolution of the normal healing process. Finally, the matrix disturbances, increased focal vascularity and abnormal cytokine profiles contribute to the clinical presentations of chronic tendon pain or rupture. With this integrative pathogenesis theory, we can relate the known manifestations of tendinopathy and point to the "missing links". This model may guide future research on tendinopathy, until we could ultimately decipher the complete pathogenesis process and provide better treatments.

  13. The Roles of Environmental Pollutants in the Pathogenesis and ...

    African Journals Online (AJOL)

    ADOWIE PERE

    researchers have tried to explain the association between pollutants and diabetes using human and animal studies. Evidence from Human Studies: A study from Chile found elevated levels of particulate matter in children that developed type 1 diabetes, suggesting pollutants may play a role in the pathogenesis of diabetes.

  14. Renin-sodium profile and renal prostaglandins in the pathogenesis ...

    African Journals Online (AJOL)

    Renin-sodium profile and renal prostaglandins in the pathogenesis of systemic arterial hypertension in blacks. L. Somova, J. Mufunda. Thirteen black women with systemic (essential) arterial hypertension, age-matched with normotensives, were examined during two protocols inducing sodium depletion and sodium loading ...

  15. Molecular cloning and characterization of pathogenesis-related ...

    African Journals Online (AJOL)

    We described the cloning and characterization of pathogenesis-related protein 5 gene in maize, named ZmPR5 (GenBank Accession Number: HM230665). Molecular and bioinformatic analyses of ZmPR5 revealed an open reading frame (ORF) of 525 bp, encoding a protein of 175 amino acids (aa) and a deduced ...

  16. ALCOHOLIC CARDIOMYOPATHY: BASIC ASPECTS OF EPIDEMIOLOGY, PATHOGENESIS AND PHARMACOTHERAPY

    Directory of Open Access Journals (Sweden)

    A. O. Yusupova

    2014-01-01

    Full Text Available Data on the epidemiology and pathogenesis of alcoholic cardiomyopathy (ACMP are presented. Special aspects of clinical manifestations as well as management of these patients are considered. Psychotropic therapy aimed at reduction in motivation to alcohol consumption in patients with ACMP is discussed separately.

  17. Advances in understanding the pathogenesis of pneumococcal otitis media.

    NARCIS (Netherlands)

    Tonnaer, E.L.G.M.; Graamans, K.; Sanders, E.A.M.; Curfs, J.H.A.J.

    2006-01-01

    In this review, a state of the art on otitis media research is provided with emphasis on the role of Streptococcus pneumoniae in the pathogenesis of this disease. Articles have been selected by MEDLINE search supplemented with a manual crosscheck of bibliographies. Pathogenic mechanisms in middle

  18. A review of the Pathogenesis and Pathology of Bovine Schistosomosis

    African Journals Online (AJOL)

    Keywords: Schistosomosis, zoonosis, cattle, pathology, pathogenesis. Schistosomes are trematodes of separate sex living in blood vessels. They have part of their life cycle in a snail before becoming cercariae, and they reach the final host. Schistosomosis is a zoonosis. Several aspects of schistosomosis and Schistosoma ...

  19. The puzzle of polymorphous light eruption : Patients and pathogenesis

    NARCIS (Netherlands)

    Schornagel, I.J.

    2007-01-01

    Polymorphous light eruption (PLE) is a photosensitivity disorder of which the pathogenesis is not fully understood. Patient history in PLE is important since lesions are transient and often not present at time of consultation. Phototesting is done to reproduce the PLE skin lesions and to obtain

  20. Review: Cytokines in Gaucher disease: Role in the pathogenesis of ...

    African Journals Online (AJOL)

    Review: Cytokines in Gaucher disease: Role in the pathogenesis of bone and pulmonary disease. AAG Tantawy. Abstract. Gaucher disease (GD) is the most frequently encountered lysosomal storage disease caused by inborn defects of themembrane-bound lysosomal enzyme, acid b-glucosidase or glucocerebrosidase.

  1. Role of Endogenous Peptides and Enzymes in the Pathogenesis of ...

    African Journals Online (AJOL)

    Acute pancreatitis is an inflammatory disease with the clinical manifestation of acute abdominal pain. Several factors are involved in the pathogenesis of acute pancreatitis. The exact mechanism(s) by which diverse etiological factors induce an attack are still unclear. However, one of the proposed mechanisms for induction ...

  2. Radiation-induced carcinogenesis: Pathogenesis of bone tumors

    International Nuclear Information System (INIS)

    Goessner, W.

    1984-01-01

    The occurrence of bone tumours after incorporation of bone-seeking radionuclides in humans is reported with special emphasis on the observations after incorporation of the short-lived Radium-224 (Thorium X). In addition some general remarks concerning the pathogenesis of tumour development after internal irradiation are discussed. (orig.) [de

  3. Leprosy and the eye a review of epidemiology, pathogenesis, ocular ...

    African Journals Online (AJOL)

    Objectives: 1. To update knowledge on the current trends in the epidemiology, pathogenesis, and treatment of leprosy 2. To highlight the ocular complications associated with leprosy. Methodology:Current literature on various aspects of leprosy research obtained from the Internet and supplemented by available journals ...

  4. The roles of environmental pollutants in the pathogenesis and ...

    African Journals Online (AJOL)

    ... rise worldwide with a growing suspicion of association between environmental pollutants and diabetes. This paper reviewed the roles of environmental pollutants in the pathogenesis and increasing incidence of diabetes. Relevant information was retrieved from reliable sources in the internet using Google search engine.

  5. Autoimmune pathogenesis of Chagas heart disease: looking back, looking ahead.

    Science.gov (United States)

    Bonney, Kevin M; Engman, David M

    2015-06-01

    Chagas heart disease is an inflammatory cardiomyopathy that develops in approximately one-third of individuals infected with the protozoan parasite Trypanosoma cruzi. Since the discovery of T. cruzi by Carlos Chagas >100 years ago, much has been learned about Chagas disease pathogenesis; however, the outcome of T. cruzi infection is highly variable and difficult to predict. Many mechanisms have been proposed to promote tissue inflammation, but the determinants and the relative importance of each have yet to be fully elucidated. The notion that some factor other than the parasite significantly contributes to the development of myocarditis was hypothesized by the first physician-scientists who noted the conspicuous absence of parasites in the hearts of those who succumbed to Chagas disease. One of these factors-autoimmunity-has been extensively studied for more than half a century. Although questions regarding the functional role of autoimmunity in the pathogenesis of Chagas disease remain unanswered, the development of autoimmune responses during infection clearly occurs in some individuals, and the implications that this autoimmunity may be pathogenic are significant. In this review, we summarize what is known about the pathogenesis of Chagas heart disease and conclude with a view of the future of Chagas disease diagnosis, pathogenesis, therapy, and prevention, emphasizing recent advances in these areas that aid in the management of Chagas disease. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  6. Genetic approaches to defining pathogenesis of Toxoplasma gondii

    Science.gov (United States)

    Toxoplasma gondii is a widespread parasite of warm-blooded vertebrates that also causes opportunistic infections in humans. Rodents are a natural host for transmission to cats, which serve as the definitive host for sexual development. The laboratory mouse provides a model to study pathogenesis. Str...

  7. Recovery of active pathogenesis-related enzymes from the apoplast ...

    African Journals Online (AJOL)

    Overall protease activity intensity was higher in the symplast. Maximum symplast contamination of the apoplast was 2% as estimated by glucose 6-phosphate dehydrogenase activity, a biochemical marker for symplast. Accumulation of pathogenesis-related enzymatic activities in the apoplast of M. acuminata leaf tissue was ...

  8. [New knowledge of the pathogenesis of Crohn's disease].

    Science.gov (United States)

    Ambrůzová, B; Rédová, M; Michálek, J; Sachlová, M; Slabý, O

    2012-04-01

    Crohns disease is a complex chronic inflammatory disease of the gastrointestinal tract with multifactorial pathogenesis. Over the recent years, there has been rather a sharp increase in the incidence of Crohn's disease and, even though this disease had been known for some time, the cause remains unknown. Studies exploring genetic basis of Crohn's disease have provided new knowledge of the pathogenesis of this disease, suggesting that this may be associated with a failure of mechanisms behind symbiosis of gut microflora and intestinal mucosal immune system. Crohn's disease seems to be caused by inadequate immune response to intestinal flora in genetically predisposed individuals. Crohn's disease has been linked to a number of genes. Many of them are related to the modulation of non-specific immune response, defects of which are considered to be key in Crohn's disease pathogenesis. The aim of this review paper is to summarize the new knowledge on the pathogenesis of Crohn's disease at the level of polymorphisms of the NOD2, ATG16L1 genes and the IL23-Th17-lymfocytes signalling pathway genes and to consider further research directions in this disease.

  9. Influenza A Virus-Host Protein Interactions Control Viral Pathogenesis.

    Science.gov (United States)

    Zhao, Mengmeng; Wang, Lingyan; Li, Shitao

    2017-08-01

    The influenza A virus (IAV), a member of the Orthomyxoviridae family, is a highly transmissible respiratory pathogen and represents a continued threat to global health with considerable economic and social impact. IAV is a zoonotic virus that comprises a plethora of strains with different pathogenic profiles. The different outcomes of viral pathogenesis are dependent on the engagement between the virus and the host cellular protein interaction network. The interactions may facilitate virus hijacking of host molecular machinery to fulfill the viral life cycle or trigger host immune defense to eliminate the virus. In recent years, much effort has been made to discover the virus-host protein interactions and understand the underlying mechanisms. In this paper, we review the recent advances in our understanding of IAV-host interactions and how these interactions contribute to host defense and viral pathogenesis.

  10. Multiple pathways contribute to the pathogenesis of Huntington disease

    Directory of Open Access Journals (Sweden)

    Li Xiao-Jiang

    2006-12-01

    Full Text Available Abstract Huntington disease (HD is caused by expansion of a polyglutamine (polyQ domain in the protein known as huntingtin (htt, and the disease is characterized by selective neurodegeneration. Expansion of the polyQ domain is not exclusive to HD, but occurs in eight other inherited neurodegenerative disorders that show distinct neuropathology. Yet in spite of the clear genetic defects and associated neurodegeneration seen with all the polyQ diseases, their pathogenesis remains elusive. The present review focuses on HD, outlining the effects of mutant htt in the nucleus and neuronal processes as well as the role of cell-cell interactions in HD pathology. The widespread expression and localization of mutant htt and its interactions with a variety of proteins suggest that mutant htt engages multiple pathogenic pathways. Understanding these pathways will help us to elucidate the pathogenesis of HD and to target therapies effectively.

  11. MODERN IDEA ON THE PATHOGENESIS OF SPONDYLOARTHRITIS: MOLECULAR MECHANISMS

    Directory of Open Access Journals (Sweden)

    E. L. Nasonov

    2015-01-01

    Full Text Available As of now, impaired immune homeostasis of the intestinal mucosa in genetically predisposed individuals is considered to be one of the major components in the pathogenesis of spondyloarthritis (SpA, which leads to systemic chronic inflammation. The results of recent studies may suggest that the interleukin-23/interleukin-17 (IL-23/IL-17 axis plays a leading role in the development of these diseases. The multifactorial components of the pathogenesis of SpA are characterized by not only the hyperproduction of IL-23, but also by the change in cell target susceptibility to this cytokine with aconcurrent increase in their number, resulting in the chronic autoinflammatory process that occurs via a wide spectrum of clinical manifestations of different types of SpA

  12. Comparative Pathogenesis and Systems Biology for Biodefense Virus Vaccine Development

    Directory of Open Access Journals (Sweden)

    Gavin C. Bowick

    2010-01-01

    Full Text Available Developing vaccines to biothreat agents presents a number of challenges for discovery, preclinical development, and licensure. The need for high containment to work with live agents limits the amount and types of research that can be done using complete pathogens, and small markets reduce potential returns for industry. However, a number of tools, from comparative pathogenesis of viral strains at the molecular level to novel computational approaches, are being used to understand the basis of viral attenuation and characterize protective immune responses. As the amount of basic molecular knowledge grows, we will be able to take advantage of these tools not only to rationally attenuate virus strains for candidate vaccines, but also to assess immunogenicity and safety in silico. This review discusses how a basic understanding of pathogenesis, allied with systems biology and machine learning methods, can impact biodefense vaccinology.

  13. New discoveries in the pathogenesis and classification of vitiligo.

    Science.gov (United States)

    Rodrigues, Michelle; Ezzedine, Khaled; Hamzavi, Iltefat; Pandya, Amit G; Harris, John E

    2017-07-01

    Vitiligo is a common autoimmune disease that progressively destroys melanocytes in the skin, resulting in the appearance of patchy depigmentation. This disfiguring condition frequently affects the face and other visible areas of the body, which can be psychologically devastating. The onset of vitiligo often occurs in younger individuals and progresses for life, resulting in a heavy burden of disease and decreased quality of life. Presentation patterns of vitiligo vary, and recognition of these patterns provides both diagnostic and prognostic clues. Recent insights into disease pathogenesis offer a better understanding of the natural history of the disease, its associations, and potential for future treatments. The first article in this continuing medical education series outlines typical and atypical presentations of vitiligo, how they reflect disease activity, prognosis, and response to treatment. Finally, we discuss disease associations, risk factors, and our current understanding of disease pathogenesis. Copyright © 2016 American Academy of Dermatology, Inc. All rights reserved.

  14. Progress towards understanding the pathogenesis of dengue hemorrhagic fever.

    Science.gov (United States)

    Pang, Xiaojing; Zhang, Rudian; Cheng, Gong

    2017-02-01

    Dengue virus (DENV) is a mosquito-borne virus belonging to the Flaviviridae family. There are 4 serotypes of DENV that cause human disease through transmission by mosquito vectors. DENV infection results in a broad spectrum of clinical symptoms, ranging from mild fever to dengue hemorrhagic fever (DHF), the latter of which can progress to dengue shock syndrome (DSS) and death. Researchers have made unremitting efforts over the last half-century to understand DHF pathogenesis. DHF is probably caused by multiple factors, such as virus-specific antibodies, viral antigens and host immune responses. This review summarizes the current progress of studies on DHF pathogenesis, which may provide important information for achieving effective control of dengue in the future.

  15. Peripheral Ulcerative Keratitis Associated with Autoimmune Disease: Pathogenesis and Treatment

    Directory of Open Access Journals (Sweden)

    Yan Cao

    2017-01-01

    Full Text Available Peripheral ulcerative keratitis (PUK is type of crescent-shaped inflammatory damage that occurs in the limbal region of the cornea. PUK is always combined with an epithelial defect and the destruction of the peripheral corneal stroma. PUK may have a connection to systemic conditions, such as long-standing rheumatoid arthritis (RA, systemic lupus erythematosus (SLE, Wegener granulomatosis (WG, relapsing polychondritis, classic polyarteritis nodosa and its variants, microscopic polyangiitis, and Churg-Strauss syndrome. However, the most common connection is with RA, which is also the focus of this review. The pathogenesis of PUK is still unclear. It is thought that circulating immune complexes and cytokines exert an important influence on the progression of this syndrome. Treatment is applied to inhibit certain aspects of PUK pathogenesis.

  16. Peripheral Ulcerative Keratitis Associated with Autoimmune Disease: Pathogenesis and Treatment

    Science.gov (United States)

    Cao, Yan; Zhang, Wensong; Wu, Jie; Zhang, Hong

    2017-01-01

    Peripheral ulcerative keratitis (PUK) is type of crescent-shaped inflammatory damage that occurs in the limbal region of the cornea. PUK is always combined with an epithelial defect and the destruction of the peripheral corneal stroma. PUK may have a connection to systemic conditions, such as long-standing rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Wegener granulomatosis (WG), relapsing polychondritis, classic polyarteritis nodosa and its variants, microscopic polyangiitis, and Churg-Strauss syndrome. However, the most common connection is with RA, which is also the focus of this review. The pathogenesis of PUK is still unclear. It is thought that circulating immune complexes and cytokines exert an important influence on the progression of this syndrome. Treatment is applied to inhibit certain aspects of PUK pathogenesis. PMID:28785483

  17. Persistent perineal sinus. Incidence, pathogenesis, risk factors, and management

    International Nuclear Information System (INIS)

    Lohsiriwat, V.

    2009-01-01

    This review discusses the incidence, pathogenesis, risk factors, diagnosis, and therapeutic options for persistent perineal sinus (PPS), defined as a perineal wound that remains unhealed more than 6 months after surgery. The incidence of PPS after surgery for inflammatory bowel disease (IBD) ranges from 3% to 70% and after abdominoperineal resection (APR) for Low rectal cancer, it can be up to 30%. These unhealed wounds are frequently related to perioperative pelvic or perineal sepsis. Crohn's disease (CD) and neoadjuvant radiation therapy are also important risk factors. The management of PPS is based on an understanding of pathogenesis and clinical grounds. The advantages and disadvantages of the current therapeutic approaches, including the topical administration of various drugs, vacuum-assisted closure, and perineal reconstruction with a muscle flap or a myocutaneous flap are also discussed. (author)

  18. Animal Models of Zika Virus Infection, Pathogenesis, and Immunity.

    Science.gov (United States)

    Morrison, Thomas E; Diamond, Michael S

    2017-04-15

    Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that now causes epidemics affecting millions of people on multiple continents. The virus has received global attention because of some of its unusual epidemiological and clinical features, including persistent infection in the male reproductive tract and sexual transmission, an ability to cross the placenta during pregnancy and infect the developing fetus to cause congenital malformations, and its association with Guillain-Barré syndrome in adults. This past year has witnessed an intensive effort by the global scientific community to understand the biology of ZIKV and to develop pathogenesis models for the rapid testing of possible countermeasures. Here, we review the recent advances in and utility and limitations of newly developed mouse and nonhuman primate models of ZIKV infection and pathogenesis. Copyright © 2017 American Society for Microbiology.

  19. Epigenetic mechanisms in the pathogenesis of diabetic retinopathy.

    Science.gov (United States)

    Zeng, Jun; Chen, Baihua

    2014-01-01

    Diabetic retinopathy (DR), which arises as a result of an increasing incidence of diabetes mellitus, has gradually become a common disease. Due to its complex pathogenesis, the treatment means of DR are very limited. The findings of several studies have shown that instituting tight glycemic control in diabetic patients does not immediately benefit the progression of retinopathy, and the benefits of good control persist beyond the period of good glycemic control. This has led to the concept of persistent epigenetic changes. Epigenetics has now become an increasingly important area of biomedical research. Recently, important roles of various epigenetic mechanisms have been identified in the pathogenesis of diabetes and its complications. The aim of this review is to provide an overview of the epigenetics and epigenetic mechanisms in diabetes and diabetes complications, and the focus is on the emerging evidence for aberrant epigenetic mechanisms in DR. © 2014 S. Karger AG, Basel.

  20. MicroRNAs in the Cholangiopathies: Pathogenesis, Diagnosis, and Treatment

    Directory of Open Access Journals (Sweden)

    Maria Jose Lorenzo Pisarello

    2015-08-01

    Full Text Available The cholangiopathies are a group of liver diseases resulting from different etiologies but with the cholangiocyte as the primary target. As a group, the cholangiopathies result in significant morbidity and mortality and represent one of the main indications for liver transplant in both children and adults. Contributing to this situation is the absence of a thorough understanding of their pathogenesis and a lack of adequate diagnostic and prognostic biomarkers. MicroRNAs are small non-coding RNAs that modify gene expression post-transcriptionally. They have been implicated in the pathogenesis of many diseases, including the cholangiopathies. Thus, in this review we provide an overview of the literature on miRNAs in the cholangiopathies and discuss future research directions.

  1. HIV Infection of Macrophages: Implications for Pathogenesis and Cure

    Directory of Open Access Journals (Sweden)

    Kiera Leigh Clayton

    2017-05-01

    Full Text Available Although CD4+ T cells represent the major reservoir of persistent HIV and SIV infection, accumulating evidence suggests that macrophages also contribute. However, investigations of the role of macrophages are often underrepresented at HIV pathogenesis and cure meetings. This was the impetus for a scientific workshop dedicated to this area of study, held in Cambridge, MA in January 2017. The workshop brought together experts in the fields of HIV/SIV immunology/virology, macrophage biology and immunology, and animal models of HIV/SIV infection to facilitate discussions regarding the role of macrophages as a physiologically relevant viral reservoir, and the implications of macrophage infection for HIV pathogenesis and cure strategies. An emerging consensus that infected macrophages likely persist in the setting of combination antiretroviral therapy, driving persistent inflammation and contributing to the viral reservoir, indicate the importance of addressing macrophages as well as CD4+ T cells with future therapeutic strategies.

  2. Genes, autoimmunity and pathogenesis of rheumatic heart disease

    International Nuclear Information System (INIS)

    Guilherme, L; Köhler, K F; Postol, E; Kalil, J

    2011-01-01

    Pathogenesis of rheumatic heart disease (RHD) remains incompletely understood. Several genes associated with RHD have been described; most of these are involved with immune responses. Single nucleotide polymorphisms in a number of genes affect patients with RHD compared to controls. Molecular mimicry between streptococcal antigens and human proteins, including cardiac myosin epitopes, vimentin and other intracellular proteins is central to the pathogenesis of RHD. Autoreactive T cells migrate from the peripheral blood to the heart and proliferate in the valves in response to stimulation with specific cytokines. The types of cells involved in the inflammation as well as different cytokine profiles in these patients are being investigated. High TNF alpha, interferon gamma, and low IL4 are found in the rheumatic valve suggesting an imbalance between Th1 and Th2 cytokines and probably contributing to the progressive and permanent valve damage. Animal model of ARF in the Lewis rat may further contribute towards understanding the ARF

  3. Pathogenesis of pulmonary emphysema – cellular and molecular events

    Directory of Open Access Journals (Sweden)

    Antonio Di Petta

    2010-06-01

    Full Text Available Pulmonary emphysema is a chronic obstructive disease, resulting fromimportant alterations in the whole distal structure of terminal bronchioles, either by enlargement of air spaces or by destruction of the alveolar wall, leading to loss of respiratory surface, decreased elastic recoil and lung hyperinflation. For many years, the hypothesis of protease-antiprotease unbalance prevailed as the central theme in the pathogenesis of pulmonary emphysema. According to this hypothesis, the release of active proteolytic enzymes, produced mainly by neutrophils and macrophages, degrades the extracellular matrix, affecting the integrity of its components, especially collagen and elastic fibers. However, new concepts involving cellular and molecular events were proposed, including oxidative stress, cell apoptosis, cellular senescence and failed lung tissue repair. The aim of this review paper was to evaluate the cellular and molecular mechanisms seen in the pathogenesis of pulmonary emphysema.

  4. Propionibacterium acnes in the pathogenesis and immunotherapy of acne vulgaris.

    Science.gov (United States)

    Liu, Pei-Feng; Hsieh, Yao-Dung; Lin, Ya-Ching; Two, Aimee; Shu, Chih-Wen; Huang, Chun-Ming

    2015-01-01

    Acne vulgaris, a multi-factorial disease, is one of the most common skin diseases, affecting an estimated 80% of Americans at some point during their lives. The gram-positive and anaerobic Propionibacterium acnes (P. acnes) bacterium has been implicated in acne inflammation and pathogenesis. Therapies for acne vulgaris using antibiotics generally lack bacterial specificity, promote the generation of antibiotic-resistant bacterial strains, and cause adverse effects. Immunotherapy against P. acnes or its antigens (sialidase and CAMP factor) has been demonstrated to be effective in mice, attenuating P. acnes-induced inflammation; thus, this method may be applied to develop a potential vaccine targeting P. acnes for acne vulgaris treatment. This review summarizes reports describing the role of P. acnes in the pathogenesis of acne and various immunotherapy-based approaches targeting P. acnes, suggesting the potential effectiveness of immunotherapy for acne vulgaris as well as P. acnes-associated diseases.

  5. Understanding Anaplasmataceae pathogenesis using ‘Omics’ approaches

    Directory of Open Access Journals (Sweden)

    Ludovic ePruneau

    2014-07-01

    Full Text Available This paper examines how Omics approaches improve our understanding of Anaplasmataceae pathogenesis, through a global and integrative strategy to identify genes and proteins involved in biochemical pathways key for pathogen-host-vector interactions.The Anaplasmataceae family comprises obligate intracellular bacteria mainly transmitted by arthropods. These bacteria are responsible for major human and animal endemic and emerging infectious diseases with important economic and public health impacts. In order to improve disease control strategies, it is essential to better understand their pathogenesis. Our work focused on four Anaplasmataceae, which cause important animal, human and zoonotic diseases: Anaplasma marginale, A. phagocytophilum, Ehrlichia chaffeensis and E. ruminantium. Wolbachia spp. an endosymbiont of arthropods was also included in this review as a model of a non-pathogenic Anaplasmataceae.A gap analysis on Omics approaches on Anaplasmataceae was performed, which highlighted a lack of studies on the genes and proteins involved in the infection of hosts and vectors. Furthermore, most of the studies have been done on the pathogen itself, mainly on infectious free-living forms and rarely on intracellular forms. In order to perform a transcriptomic analysis of the intracellular stage of development, researchers developed methods to enrich bacterial transcripts from infected cells. These methods are described in this paper. Bacterial genes encoding outer membrane proteins, post-translational modifications, eukaryotic repeated motif proteins, proteins involved in osmotic and oxidative stress and hypothetical proteins have been identified to play a key role in Anaplasmataceae pathogenesis. Further investigations on the function of these outer membrane proteins and hypothetical proteins will be essential to confirm their role in the pathogenesis. Our work underlines the need for further studies in this domain and on host and vector responses

  6. Pathogenesis: common pathways between hidradenitis suppurativa and Crohn disease.

    Science.gov (United States)

    García Martínez, F J; Menchén, L

    2016-09-01

    Both hidradenitis suppurativa and Crohn disease are considered chronic inflammatory diseases due to immune dysregulation. The high prevalence of Crohn disease patients diagnosed with hidradenitis suppurativa suggests the existence of common pathogenic links. The present literature review analyses the similarities and differences in the pathogenesis of the two diseases, in the search for new research and knowledge targets. Copyright © 2016 Elsevier España, S.L.U. y AEDV. All rights reserved.

  7. [Monoamine-hormonal interactions in the pathogenesis of anxious depression].

    Science.gov (United States)

    Uzbekov, M G; Maximova, N M

    2015-01-01

    Biochemical aspects of the relationship between monoaminergic and hormonal systems in the pathogenesis of anxious depression are analyzed on the basis of literature and own results published earlier. Significant alterations in biogenic monoamine metabolism and changes in the hormonal status, that reflects homeostasis disturbance in whole, are inherent to anxious depression. The biochemical mechanisms of imbalance between serotonergic and noradrenergic systems and a role of cortisol in this process are discussed.

  8. [EBOLA HEMORRHAGIC FEVER; ETIOLOGY, EPIDEMIOLOGY, PATHOGENESIS, AND CLINICAL SYMPTOMS].

    Science.gov (United States)

    Zhdanov, K W; Zakharenko, S M; Kovalenko, A N; Semenov, A V; Fusin, A Ya

    2015-01-01

    The data on the prevalence of disease caused by Ebola virus, biological features of its pathogen, character of the epidemiological process, pathogenesis and clinical symptoms are presented. The disease is characterized by suppression of protective immunological mechanisms and systemic inflammatory reaction accounting for the lesions of vascular endothelium, hemostatic and immune systems. It eventually leads to polyorgan insufficiency and severe shock. Lethality amounts to 50%.

  9. The pathogenesis of tendinopathy: balancing the response to loading

    DEFF Research Database (Denmark)

    Magnusson, S Peter; Jørgensen, Henning Langberg; Kjaer, Michael

    2010-01-01

    , such as tendinopathy, which is characterized by pain during activity, localized tenderness upon palpation, swelling and impaired performance. Tendon histological changes include reduced numbers and rounding of fibroblasts, increased content of proteoglycans, glycosaminoglycans and water, hypervascularization......, thus implying that one or more 'weak links' are present in the structure. Understanding how tendon tissue adapts to mechanical loading will help to unravel the pathogenesis of tendinopathy....

  10. Immunomodulatory Role of Vitamin D in the Pathogenesis of Preeclampsia

    OpenAIRE

    Smith, Tyler A.; Kirkpatrick, Daniel R.; Kovilam, Oormila; Agrawal, Devendra K.

    2015-01-01

    Worldwide, preeclampsia is a significant health risk to both pregnant women and their unborn children. Despite scientific advances, the exact pathogenesis of preeclampsia is not yet fully understood. Meanwhile, the incidence of preeclampsia is expected to increase. A series of potential etiologies for preeclampsia have been identified, including endothelial dysfunction, immunological dysregulation, and trophoblastic invasion. In this literature review, we have critically reviewed existing lit...

  11. Correlation between mitochondrial dysfunction and the pathogenesis of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Xiao-yu LIU

    2014-02-01

    Full Text Available Parkinson's disease (PD is a progressive neurodegenerative disease. A growing number of studies have shown that mitochondrial dysfunction plays an important role in the pathogenesis of PD. Therefore, this review will mainly discuss the research progress on the correlation between PD and abnormal mitochondrial dynamics, mitochondrial autophapy as well as mitochondrial DNA mutations and mitochondrial complex Ⅰ inhibition.doi:10.3969/j.issn.1672-6731.2014.02.012

  12. Therapeutic implications from the pathogenesis of Raynaud's phenomenon

    OpenAIRE

    Herrick, Ariane L

    2017-01-01

    INTRODUCTION: Raynaud's phenomenon (RP) can be either primary (idiopathic) or secondary to a number of different diseases/conditions, when vasopasm can be superimposed upon structural vascular abnormality or a hyperviscosity state and may then lead to severe ischaemia with tissue damage. Treatment must be tailored to the individual. Areas covered: This review discusses how increased understanding of the pathogenesis of RP has driven and is driving new approaches to therapy, and how we are now...

  13. Pathogenesis of apical periodontal cysts: guidelines for diagnosis in palaeopathology

    OpenAIRE

    Dias, G. J.; Prasad, K.; Santos, A. L.

    2007-01-01

    Apical periodontal cysts are benign lesions developing in relation to the apices of non-vital teeth due to inflammatory response from the infective pulp. These are epithelium-lined bony cavities containing fluid. Despite being widely reported in medical/dental literature, this common condition is poorly diagnosed and documented in the archaeological literature. We aim to clarify the correct terminology, demonstrate bony manifestations at different stages of pathogenesis of chronic periapical ...

  14. The fundamental role of endothelial cells in hantavirus pathogenesis

    Directory of Open Access Journals (Sweden)

    Jussi eHepojoki

    2014-12-01

    Full Text Available Hantavirus, a genus of rodent- and insectivore-borne viruses in the family Bunyaviridae, is a group of emerging zoonotic pathogens. Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS and hantavirus cardiopulmonary syndrome (HCPS in man, often with severe consequences. Vascular leakage is evident in severe hantavirus infections, and increased permeability contributes to the pathogenesis. This review summarizes the current knowledge on hantavirus interactions with endothelial cells, and their effects on the increased vascular permeability.

  15. The fundamental role of endothelial cells in hantavirus pathogenesis

    OpenAIRE

    Hepojoki, Jussi; Vaheri, Antti; Strandin, Tomas

    2014-01-01

    Hantavirus, a genus of rodent- and insectivore-borne viruses in the family Bunyaviridae, is a group of emerging zoonotic pathogens. Hantaviruses cause hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome in man, often with severe consequences. Vascular leakage is evident in severe hantavirus infections, and increased permeability contributes to the pathogenesis. This review summarizes the current knowledge on hantavirus interactions with hematopoietic and endothelial ...

  16. Cellulite: a review of pathogenesis-directed therapy.

    Science.gov (United States)

    Callaghan, Daniel J; Robinson, Deanne Mraz; Kaminer, Michael S

    2017-12-01

    Cellulite is a condition that affects the majority of postpubertal women and can negatively impact quality of life. This review discusses several proposed pathophysiologies of cellulite, and examines treatment options that have been utilized, focusing on the etiologic factor targeted by the therapies. This approach aims to help clarify the pathogenesis of cellulite and provide a road map for developing effective treatment paradigms for patients. ©2017 Frontline Medical Communications.

  17. The role of extracellular vesicles in malaria biology and pathogenesis.

    Science.gov (United States)

    Sampaio, Natalia Guimaraes; Cheng, Lesley; Eriksson, Emily M

    2017-06-09

    In the past decade, research on the functions of extracellular vesicles in malaria has expanded dramatically. Investigations into the various vesicle types, from both host and parasite origin, has revealed important roles for extracellular vesicles in disease pathogenesis and susceptibility, as well as cell-cell communication and immune responses. Here, work relating to extracellular vesicles in malaria is reviewed, and the areas that remain unknown and require further investigations are highlighted.

  18. Molecular mechanisms involved in the pathogenesis of septic shock.

    Science.gov (United States)

    López-Bojórquez, Lucia Nikolaia; Dehesa, Alejandro Zentella; Reyes-Terán, Gustavo

    2004-01-01

    Pathogenesis of the development of sepsis is highly complex and has been the object of study for many years. The inflammatory phenomena underlying septic shock are described in this review, as well as the enzymes and genes involved in the cellular activation that precedes this condition. The most important molecular aspects are discussed, ranging from the cytokines involved and their respective transduction pathways to the cellular mechanisms related to accelerated catabolism and multi-organic failure.

  19. Interferons and Alphavirus Pathogenesis: Implications for Developing Medical Countermeasures

    Science.gov (United States)

    2005-12-01

    ines qui interferent avec la croissance d’un virus. Depuis cette d~couverte, on a trouv6 plusieurs sortes d’INF que lPon a classifid en trois types...Defence Research and Recherche et developpement Development Canada pour la defense Canada DEFENCE •DFFENSE a Interferons and Alphavirus Pathogenesis...majestd la reine, reprdsentde par le ministre de la DMfense nationale, 2005 Abstract Our immune system can launch a quick defence against a large

  20. Inclusion body myositis: diagnosis, pathogenesis, and treatment options.

    Science.gov (United States)

    Solorzano, Guillermo E; Phillips, Lawrence H

    2011-05-01

    Inclusion body myositis (IBM) is the most common acquired myopathy in people older than 50 years. IBM typically presents with distal upper extremity weakness accompanied by proximal lower extremity muscle weakness. Associated clinical findings include asymmetric weakness, foot drop, and dysphagia. The pathogenesis of IBM is not clear. In this article the authors briefly discuss postulated pathogenic mechanisms. Although no proven pharmacotherapy exists, some promising candidates are discussed. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Understanding rare disease pathogenesis: a grand challenge for model organisms.

    Science.gov (United States)

    Hieter, Philip; Boycott, Kym M

    2014-10-01

    In this commentary, Philip Hieter and Kym Boycott discuss the importance of model organisms for understanding pathogenesis of rare human genetic diseases, and highlight the work of Brooks et al., "Dysfunction of 60S ribosomal protein L10 (RPL10) disrupts neurodevelopment and causes X-linked microcephaly in humans," published in this issue of GENETICS. Copyright © 2014 by the Genetics Society of America.

  2. The pathogenesis, diagnosis and treatment of Raynaud phenomenon.

    Science.gov (United States)

    Herrick, Ariane L

    2012-08-01

    The past 10 years have seen the publication of results from several multicentre clinical trials in primary and systemic sclerosis (SSc)-related Raynaud phenomenon. The publication of these studies has occurred as a result of new insights into the pathogenesis of Raynaud phenomenon, which are directing new treatment approaches, and increased international collaboration between clinicians and scientists. Although the pathogenesis of Raynaud phenomenon is complex, abnormalities of the blood vessel wall, of neural control mechanisms and of intravascular (circulating) factors are known to interact and contribute. Key players relevant in drug development include nitric oxide, endothelin-1, alpha adrenergic receptor activation, abnormal signal transduction in vascular smooth muscle, oxidative stress and platelet activation. The main advances in diagnosis have been a clearer understanding of autoantibodies and of abnormal nailfold capillary patterns as independent predictors of SSc, and widespread use and increased availability of capillaroscopy. The ultimate aim is to translate the advances made in the pathophysiology and early diagnosis into development of treatments to prevent and reverse digital vascular dysfunction and injury. This Review provides an update of the pathogenesis, diagnosis and treatment of Raynaud phenomenon. Current and future treatment approaches are discussed, and some key unanswered questions are highlighted.

  3. Significance of Inactivated Genes in Leukemia: Pathogenesis and Prognosis

    Science.gov (United States)

    Heidari, Nazanin; Abroun, Saeid; Bertacchini, Jessika; Vosoughi, Tina; Rahim, Fakher; Saki, Najmaldin

    2017-01-01

    Epigenetic and genetic alterations are two mechanisms participating in leukemia, which can inactivate genes involved in leukemia pathogenesis or progression. The purpose of this review was to introduce various inactivated genes and evaluate their possible role in leukemia pathogenesis and prognosis. By searching the mesh words “Gene, Silencing AND Leukemia” in PubMed website, relevant English articles dealt with human subjects as of 2000 were included in this study. Gene inactivation in leukemia is largely mediated by promoter’s hypermethylation of gene involving in cellular functions such as cell cycle, apoptosis, and gene transcription. Inactivated genes, such as ASPP1, TP53, IKZF1 and P15, may correlate with poor prognosis in acute lymphoid leukemia (ALL), chronic lymphoid leukemia (CLL), chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML), respectively. Gene inactivation may play a considerable role in leukemia pathogenesis and prognosis, which can be considered as complementary diagnostic tests to differentiate different leukemia types, determine leukemia prognosis, and also detect response to therapy. In general, this review showed some genes inactivated only in leukemia (with differences between B-ALL, T-ALL, CLL, AML and CML). These differences could be of interest as an additional tool to better categorize leukemia types. Furthermore; based on inactivated genes, a diverse classification of Leukemias could represent a powerful method to address a targeted therapy of the patients, in order to minimize side effects of conventional therapies and to enhance new drug strategies. PMID:28580304

  4. Molecular Determinants of Influenza Virus Pathogenesis in Mice

    Science.gov (United States)

    Katz, Jaqueline M.; York, Ian A.

    2015-01-01

    Mice are widely used for studying influenza virus pathogenesis and immunology because of their low cost, the wide availability of mouse-specific reagents, and the large number of mouse strains available, including knockout and transgenic strains. However, mice do not fully recapitulate the signs of influenza infection of humans: transmission of influenza between mice is much less efficient than in humans, and influenza viruses often require adaptation before they are able to efficiently replicate in mice. In the process of mouse adaptation, influenza viruses acquire mutations that enhance their ability to attach to mouse cells, replicate within the cells, and suppress immunity, among other functions. Many such mouse-adaptive mutations have been identified, covering all 8 genomic segments of the virus. Identification and analysis of these mutations have provided insight into the molecular determinants of influenza virulence and pathogenesis, not only in mice but also in humans and other species. In particular, several mouse-adaptive mutations of avian influenza viruses have proved to be general mammalian-adaptive changes that are potential markers of pre-pandemic viruses. As well as evaluating influenza pathogenesis, mice have also been used as models for evaluation of novel vaccines and anti-viral therapies. Mice can be a useful animal model for studying influenza biology as long as differences between human and mice infections are taken into account. PMID:25038937

  5. [The pathogenesis and prevention of urinary tract infection in women].

    Science.gov (United States)

    Shabad, A L; Minakov, N K; Mkrtchan, G G; Zabirov, K I; Vasil'ev, M M; Khodyreva, L A; Tolstova, S S; Kisina, V I

    1995-01-01

    Urinary tract infection (UTI) in females occurs significantly more frequently than in males because of specific anatomical and functional features of female urinary system, sequelae of pregnancy, delivery, gynecological diseases. Much controversy still exists as to pathogenesis of UTI and UTI-induced urinary inflammation. We have examined 233 females of different age with UTI and obtained evidence which shows participation of such factors as early and intensive sex, ignorance of sex hygiene, multiple pregnancies, deliveries, abortions, inflammatory gynecological diseases, anogenital infection in its pathogenesis. These factors were registered 2-4 times more frequently in UTI females than in controls without UTI. Bacteriological urinary and genital findings coincide in 80% of cases in terms of an infective agent. This suggests that it is essential to detect urogenital infection in girls and females as early as possible and to treat it adequately with antibacterial and other drugs. The leading role of an ascending urinogenic route in urinary tract infection from local sources in anogenital zone, sexual factor and the absence of relevant hygienic habits proved most contributing to UTI pathogenesis. This concept serves the basis for UTI prevention in females.

  6. Advances in hepatitis E - I: virology, pathogenesis and diagnosis.

    Science.gov (United States)

    Aggarwal, Rakesh; Goel, Amit

    2016-09-01

    Infection with hepatitis E virus (HEV) is the commonest cause of acute hepatitis worldwide. HEV was discovered in 1980s and is known to have small non-enveloped virions with single-stranded RNA genome of positive polarity. In recent years. In recent years, availability of new information has changed our understanding of this virus and the pathogenesis of the related disease. This article reviews the current knowledge about structure, genomic organization, taxonomy, genetic epidemiology, host specificity and replication of the human HEV and of various closely-related viruses that infect other animals. In addition, the models available for the study of HEV infection, the available information on the pathogenesis of this infection and the techniques available for its diagnosis are also reviewed. Expert commentary: A circulating, enveloped form of the human HEV has been recently recognized. Originally believed to naturally infect only humans and possibly primates, HEV-like viruses are now known to infect several vertebrate animals. Based on this, phylogenetic classification of these viruses has recently been revised. In vitro replicons and infection systems have been developed, which have improved our understanding about the virus and the pathogenesis of infection with it. Recent development of mouse models with chimeric livers that contain human hepatocytes provides another avenue for further advancement of this knowledge.

  7. Eosinophils in vasculitis: characteristics and roles in pathogenesis

    Science.gov (United States)

    Khoury, Paneez; Grayson, Peter C.; Klion, Amy D.

    2016-01-01

    Eosinophils are multifunctional granular leukocytes that are implicated in the pathogenesis of a wide variety of disorders, including asthma, helminth infection, and rare hypereosinophilic syndromes. Although peripheral and tissue eosinophilia can be a feature of many types of small-vessel and medium-vessel vasculitis, the role of eosinophils has been best studied in eosinophilic granulomatosis with polyangiitis (EGPA), where eosinophils are a characteristic finding in all three clinical stages of the disorder. Whereas numerous studies have demonstrated an association between the presence of eosinophils and markers of eosinophil activation in the blood and tissues of patients with EGPA, the precise role of eosinophils in disease pathogenesis has been difficult to ascertain owing to the complexity of the disease process. In this regard, results of clinical trials using novel agents that specifically target eosinophils are providing the first direct evidence of a central role of eosinophils in EGPA. This Review focuses on the aspects of eosinophil biology most relevant to the pathogenesis of vasculitis and provides an update of current knowledge regarding the role of eosinophils in EGPA and other vasculitides. PMID:25003763

  8. Diverticular Disease: An Update on Pathogenesis and Management.

    Science.gov (United States)

    Rezapour, Mona; Ali, Saima; Stollman, Neil

    2018-03-15

    Diverticular disease is one of the most common conditions in the Western world and one of the most common findings identified at colonoscopy. Recently, there has been a significant paradigm shift in our understanding of diverticular disease and its management. The pathogenesis of diverticular disease is thought to be multifactorial and include both environmental and genetic factors in addition to the historically accepted etiology of dietary fiber deficiency. Symptomatic uncomplicated diverticular disease (SUDD) is currently considered a type of chronic diverticulosis that is perhaps akin to irritable bowel syndrome. Mesalamine, rifaximin and probiotics may achieve symptomatic relief in some patients with SUDD, although their role(s) in preventing complications remain unclear. Antibiotic use for acute diverticulitis and elective prophylactic resection surgery are considered more individualized treatment modalities that take into account the clinical status, comorbidities and lifestyle of the patient. Our understanding of the pathogenesis of diverticular disease continues to evolve and is likely to be diverse and multifactorial. Paradigm shifts in several areas of the pathogenesis and management of diverticular disease are explored in this review.

  9. Adherence and pathogenesis of Salmonella enteritidis in mice.

    Science.gov (United States)

    Aslanzadeh, J; Paulissen, L J

    1990-01-01

    Adherence of many pathogenic organisms to the host cells has been associated with the presence of fimbriae. The exact role of these organelles in the adherence and pathogenesis of Salmonella enteritidis is not well established. Utilizing hemagglutination tests, S. enteritidis was shown to possess type 1 and type 3 fimbriae. Polyacrylamide gel electrophoresis of the isolated fimbriae showed that type 1 and 3 fimbriae of S. enteritidis had subunit M.r of 17 and 22 kDa, respectively. In vitro adherence assays suggested that S. enteritidis utilized type 1 fimbriae to adhere to human buccal and mouse small intestine epithelial cells. In addition, antibody produced against type 1 and type 3 fimbriae protected the mice from infection with a lethal dose of S. enteritidis. These results suggest that type 1 and possibly type 3 fimbriae are involved in the adherence and pathogenesis of S. enteritidis. The data further suggest that they may have a role in the adherence and pathogenesis of the other enteric organisms.

  10. Protection against retrovirus pathogenesis by SR protein inhibitors.

    Directory of Open Access Journals (Sweden)

    Anne Keriel

    Full Text Available Indole derivatives compounds (IDC are a new class of splicing inhibitors that have a selective action on exonic splicing enhancers (ESE-dependent activity of individual serine-arginine-rich (SR proteins. Some of these molecules have been shown to compromise assembly of HIV infectious particles in cell cultures by interfering with the activity of the SR protein SF2/ASF and by subsequently suppressing production of splicing-dependent retroviral accessory proteins. For all replication-competent retroviruses, a limiting requirement for infection and pathogenesis is the expression of the envelope glycoprotein which strictly depends on the host splicing machinery. Here, we have evaluated the efficiency of IDC on an animal model of retroviral pathogenesis using a fully replication-competent retrovirus. In this model, all newborn mice infected with a fully replicative murine leukemia virus (MLV develop erythroleukemia within 6 to 8 weeks of age. We tested several IDC for their ability to interfere ex vivo with MLV splicing and virus spreading as well as for their protective effect in vivo. We show here that two of these IDC, IDC13 and IDC78, selectively altered splicing-dependent production of the retroviral envelope gene, thus inhibiting early viral replication in vivo, sufficiently to protect mice from MLV-induced pathogenesis. The apparent specificity and clinical safety observed here for both IDC13 and IDC78 strongly support further assessment of inhibitors of SR protein splicing factors as a new class of antiretroviral therapeutic agents.

  11. T cell-dependence of Lassa fever pathogenesis.

    Directory of Open Access Journals (Sweden)

    Lukas Flatz

    2010-03-01

    Full Text Available Lassa virus (LASV, the causative agent of Lassa fever (LF, is endemic in West Africa, accounting for substantial morbidity and mortality. In spite of ongoing research efforts, LF pathogenesis and mechanisms of LASV immune control remain poorly understood. While normal laboratory mice are resistant to LASV, we report that mice expressing humanized instead of murine MHC class I (MHC-I failed to control LASV infection and develop severe LF. Infection of MHC-I knockout mice confirmed a key role for MHC-I-restricted T cell responses in controlling LASV. Intriguingly we found that T cell depletion in LASV-infected HHD mice prevented disease, irrespective of high-level viremia. Widespread activation of monocyte/macrophage lineage cells, manifest through inducible NO synthase expression, and elevated IL-12p40 serum levels indicated a systemic inflammatory condition. The absence of extensive monocyte/macrophage activation in T cell-depleted mice suggested that T cell responses contribute to deleterious innate inflammatory reactions and LF pathogenesis. Our observations in mice indicate a dual role for T cells, not only protecting from LASV, but also enhancing LF pathogenesis. The possibility of T cell-driven enhancement and immunopathogenesis should be given consideration in future LF vaccine development.

  12. Update of enterovirus 71 infection: epidemiology, pathogenesis and vaccine.

    Science.gov (United States)

    Wang, Shih-Min; Liu, Ching-Chuan

    2014-04-01

    Enterovirus 71 (EV71) is a neurotropic human pathogen that is the causative agent of hand foot and mouth disease (HFMD), herpangina and brain stem encephalitis. Recurrent EV71 epidemics of various scales have occurred in the Asia-Pacific region. Several specific cell surface molecules serve as the receptors for EV71. Identification of the receptors is an important step to understand EV71 disease. Cytokines, lymphocytes and monocytes contribute significantly to EV71 pathogenesis. The interaction of EV71 and receptors may be associated with the cytokines immunopathogenesis. Some animal models have been established and aim to explore the pathogenesis of EV71 infections. EV71 antibodies can neutralize or enhance infection at subneutralizing levels. These results are important for EV71 vaccine and therapeutics design. Several clinical trials of human inactivated EV71 vaccine have recently been completed. The purpose of this review is to summarize recent discoveries about the epidemiology and pathogenesis of EV71 and provide insights into human vaccine development.

  13. DMPD: Role of Toll-like receptor responses for sepsis pathogenesis. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18086373 Role of Toll-like receptor responses for sepsis pathogenesis. Weighardt H, Holzmann B. Immunobiolog... responses for sepsis pathogenesis. Authors Weighardt H, Holzmann B. Publication Immunobiology

  14. Demyelinating syndrome in SLE: review of different disease subtypes and report of a case series

    Directory of Open Access Journals (Sweden)

    E. Chessa

    2017-12-01

    Full Text Available Demyelinating syndrome (DS is a rare manifestation of systemic lupus erythematosus (SLE (1% with high clinical heterogeneity and potentially severe prognosis. It can represent a diagnostic and therapeutic challenge for clinicians. A recent study described 5 different patterns of demyelinating disease presentation, characterised by specific clinical, laboratory and brain and spine magnetic resonance imaging abnormalities: 1 neuromyelitis optica; 2 neuromyelitis optica spectrum disorders; 3 DS prevalently involving the brain; 4 DS prevalently involving the brainstem; 5 clinically isolated syndrome. In this review we briefly discuss typical characteristics of each DS presentation in SLE and we describe 5 illustrative clinical cases, one for each subset of DS, considering both diagnostic and therapeutic options.

  15. Demyeliniserende sygdom hos børn med akutte neurologiske symptomer

    DEFF Research Database (Denmark)

    Olofsson, Isa Amalie; Skov, Liselotte; Miranda, Maria Jose

    2015-01-01

    Demyelinating diseases in children is a broad group of illnesses, which affect the central nervous system. Demyelinating diseases can be monophasic or chronic and comprise acute disseminated encephalomyelitis, optic neuritis, transverse myelitis, multiple sclerosis and neuromyelitis optica....... Demyelinating diseases are rare, but it is important for the physician to recognize these diseases, as well as to understand the differential diagnoses. This review summarizes the current knowledge of demyelinating disorders in children, focusing on an approach to diagnosis and management....

  16. Demyeliniserende sygdom hos børn med akutte neurologiske symptomer

    DEFF Research Database (Denmark)

    Olofsson, Isa Amalie; Skov, Liselotte; Miranda, Maria Jose

    2015-01-01

    . Demyelinating diseases are rare, but it is important for the physician to recognize these diseases, as well as to understand the differential diagnoses. This review summarizes the current knowledge of demyelinating disorders in children, focusing on an approach to diagnosis and management.......Demyelinating diseases in children is a broad group of illnesses, which affect the central nervous system. Demyelinating diseases can be monophasic or chronic and comprise acute disseminated encephalomyelitis, optic neuritis, transverse myelitis, multiple sclerosis and neuromyelitis optica...

  17. Structural studies of human glioma pathogenesis-related protein 1

    Energy Technology Data Exchange (ETDEWEB)

    Asojo, Oluwatoyin A., E-mail: oasojo@unmc.edu [College of Medicine, Nebraska Medical Center, Omaha, NE 68198-6495 (United States); Koski, Raymond A.; Bonafé, Nathalie [L2 Diagnostics LLC, 300 George Street, New Haven, CT 06511 (United States); College of Medicine, Nebraska Medical Center, Omaha, NE 68198-6495 (United States)

    2011-10-01

    Structural analysis of a truncated soluble domain of human glioma pathogenesis-related protein 1, a membrane protein implicated in the proliferation of aggressive brain cancer, is presented. Human glioma pathogenesis-related protein 1 (GLIPR1) is a membrane protein that is highly upregulated in brain cancers but is barely detectable in normal brain tissue. GLIPR1 is composed of a signal peptide that directs its secretion, a conserved cysteine-rich CAP (cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 proteins) domain and a transmembrane domain. GLIPR1 is currently being investigated as a candidate for prostate cancer gene therapy and for glioblastoma targeted therapy. Crystal structures of a truncated soluble domain of the human GLIPR1 protein (sGLIPR1) solved by molecular replacement using a truncated polyalanine search model of the CAP domain of stecrisp, a snake-venom cysteine-rich secretory protein (CRISP), are presented. The correct molecular-replacement solution could only be obtained by removing all loops from the search model. The native structure was refined to 1.85 Å resolution and that of a Zn{sup 2+} complex was refined to 2.2 Å resolution. The latter structure revealed that the putative binding cavity coordinates Zn{sup 2+} similarly to snake-venom CRISPs, which are involved in Zn{sup 2+}-dependent mechanisms of inflammatory modulation. Both sGLIPR1 structures have extensive flexible loop/turn regions and unique charge distributions that were not observed in any of the previously reported CAP protein structures. A model is also proposed for the structure of full-length membrane-bound GLIPR1.

  18. Enterobacterial involvement in the pathogenesis of secondary ankylosing spondylitis.

    Science.gov (United States)

    van Bohemen, C G; Weterings, E; Goei The, H S; Grumet, F C; Zanen, H C

    1988-01-01

    Ankylosing spondylitis (AS) is closely associated with the histocompatibility antigen HLA-B27. Pathogenesis of AS is thought to involve interactions between B27 and certain enterobacterial antigens. However, this is uncertain and contested by some. The present paper argues that the presence of statistically raised specific serum IgA to a common enterobacterial heat modifiable major outer membrane protein (h-momp; Mr 35,000) in active AS (N = 25; IgA = 1485 +/- 20) in comparison to controls, most notably hospital patients without known arthropathies or gastrointestinal disease (N = 12; IgA = 548 +/- 59), supports an inductive contribution of enterobacterial antigens to the pathogenesis of secondary AS. Serum IgG and IgM did not statistically differ. Raised specific serum IgA to h-momp might indicate enterobacterial antigenic stimulation from the gastrointestinal tract. It does not necessarily imply direct involvement in the pathogenesis of primary AS. H-momp appears to be a convenient tool for serological studies of AS and at present is likely to be more suitable than other bacterial antigens, notably those with B27-like epitopes. Namely, the confirmed presence in AS of enterobacteria with freely accessible B27-like antigenic epitopes on their cell surface might induce unusual tolerance to these organisms in B27 positive hosts, thus causing chronic inflammation, initially sacroiliitis (and spondylitis) due to the proximity of presacral and para-aortic colon draining lymph nodes, later becoming more generalized (for reasons unclear) to include other lesions (e.g. peripheral arthritis, uveitis, enthesopathies). Thus, antibodies to B27-like antigenic epitopes need not be detectable or may be absent. Also, cellular immune responsiveness to these antigens might be involved.

  19. Ebolavirus: An Overview of Molecular and Clinical Pathogenesis.

    Science.gov (United States)

    Vine, Veronica; Scott, Dana P; Feldmann, Heinz

    2017-01-01

    Ebolaviruses cause severe, often fatal hemorrhagic fever in Central, East, and West Africa. Until recently, they have been viewed as rare but highly pathogenic infections with regional, but limited, global public health impact. This view has changed with the emergence of the first epidemic of Ebola hemorrhagic fever in West Africa. In this chapter we provide an introduction of the pathogenesis of ebolaviruses as well as a description of clinical disease features. We also describe the current animal models used in ebolavirus research, detailing each model's unique strengths and weaknesses. We focus on Ebola virus representing the type species Zaire ebolavirus of the genus Ebolavirus, as most work relates to this pathogen.

  20. Roles of Rack1 Proteins in Fungal Pathogenesis

    Directory of Open Access Journals (Sweden)

    Xue Zhang

    2016-01-01

    Full Text Available Pathogenic fungi cause diseases on various organisms. Despite their differences in life cycles, fungal pathogens use well-conserved proteins and pathways to regulate developmental and infection processes. In this review, we focus on Rack1, a multifaceted scaffolding protein involved in various biological processes. Rack1 is well conserved in eukaryotes and plays important roles in fungi, though limited studies have been conducted. To accelerate the study of Rack1 proteins in fungi, we review the functions of Rack1 proteins in model and pathogenic fungi and summarize recent progress on how Rack1 proteins are involved in fungal pathogenesis.

  1. Review of Critical Issues in the Pathogenesis of Atopic Dermatitis.

    Science.gov (United States)

    Irvine, Alan D; Eichenfield, Lawrence F; Friedlander, Sheila F; Simpson, Eric L

    2016-06-01

    About a decade age, loss-of-function mutations in the filaggrin molecule were first implicated in the pathogenesis of ichthyosis vulgaris and, subsequently, of atopic dermatitis and other atopic diseases. Since then, intensive study of the role of filaggrin null mutations have led to other milestones in understanding the pathologic pathways in these diseases, including the initiation, maintenance, and promotion of the disease processes. The result has been new and emerging clinical and pharmacologic strategies for early identification of and intervention in atopic diseases. Semin Cutan Med Surg 35(supp5):S89-S91. 2016 published by Frontline Medical Communications.

  2. [The pathogenesis of periodontal disease: a paradigm shift].

    Science.gov (United States)

    Ekstein, J; Shapira, L; Van Dyke, T E

    2010-07-01

    Periodontitis is a family of related diseases that differ in etiology, natural history, disease progression and response to therapy, but have a common underlying chain of events, thatareinfluenced by disease modifiers. The clinical manifestations observed are a result of the complex interplay of these factors. The pathogenesis of human periodontitis was placed on a rational footing for the first time by Page & Schroeder in 1976 and the general principles and the overall conclusions reached in that article are still largely acceptable today. Still, an enormous amount has been learned about all aspects of human periodontitis, including its pathogenesis, since 1976. A critical evaluation of the literature regarding the complex relationship between the microbial factor, the host factor and the occurrence of a disease, might be leading us over a surge of a paradigm shift in our understanding the pathogenesis of the disease. It is well acknowledged that while the etiology of periodontitis is bacterial, the pathogenesis is inflammatory. The understanding of regulation of inflammation in periodontitis is far from complete; however, as the understanding of periodontal inflammation increases, the current understanding of the microbiology of periodontitis becomes less clear. While we think we know that bacteria initiate the disease, the role of specific bacteria is still unknown. The current knowledge of the microbiology of periodontitis is based on large cross-sectional and association studies. Periodontitis is seen as the direct consequence of bacterial invasion and is regarded as an infectious disease. It is however, not possible to draw cause and- effect inferences from these studies. One might state that the inflammation precedes the overgrowth of the bacteria. In this scenario, the initiator of the disease might be early, gram-positive colonizers that elicit a profound inflammatory response in the susceptible host. The implication of that paradigm shift outlined above

  3. Molecular Pathogenesis and Current Therapy in Intrahepatic Cholangiocarcinoma

    DEFF Research Database (Denmark)

    Høgdall, Dan Taksony Solyom; O'Rourke, Colm J; Taranta, Andrzej

    2016-01-01

    Intrahepatic cholangiocarcinoma (iCCA) comprises one of the most rapidly evolving cancer types. An underlying chronic inflammatory liver disease that precedes liver cancer development for several decades and creates a pro-oncogenic microenvironment frequently impairs progress in therapeutic...... approaches. Depending on the cellular target of malignant transformation, a large spectrum of molecular and morphological patterns is observed. As such, it is crucial to advance our existing understanding of the molecular pathogenesis of iCCA, particularly its genomic heterogeneity, to improve current...

  4. Rosacea: part I. Introduction, categorization, histology, pathogenesis, and risk factors.

    Science.gov (United States)

    Two, Aimee M; Wu, Wiggin; Gallo, Richard L; Hata, Tissa R

    2015-05-01

    Rosacea is a chronic inflammatory skin condition that affects approximately 16 million Americans. Four distinct subtypes of rosacea have been recognized, with transient and nontransient facial flushing, telangiectasia, and inflammatory papules and pustules being among the more commonly recognized features. Although the exact pathogenesis of rosacea is unknown, dysregulation of the innate immune system, overgrowth of commensal skin organisms, and aberrant neurovascular signaling may all have a role in promoting the clinical features of rosacea. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  5. Implication of microRNAs in the Pathogenesis of MDS

    Science.gov (United States)

    Fang, Jing; Varney, Melinda; Starczynowski, Daniel T.

    2016-01-01

    MicroRNAs (miRNAs) are significant regulators of human hematopoietic stem cells (HSC), and their deregulation contributes to hematological malignancies. Myelodysplastic syndromes (MDS) represent a spectrum of hematological disorders characterized by dysfunctional HSC, ineffective blood cell production, progressive marrow failure, and an increased risk of developing acute myeloid leukemia (AML). Although miRNAs have been primarily studied in AML, only recently have similar studies been performed on MDS. In this review, we describe the normal function and expression of miRNAs in human HSC, and describe mounting evidence that deregulation of miRNAs contributes to the pathogenesis of MDS. PMID:22571695

  6. The HBZ gene, a key player in HTLV-1 pathogenesis

    Directory of Open Access Journals (Sweden)

    Green Patrick L

    2009-08-01

    Full Text Available Abstract Human T-cell leukemia virus type 1 (HTLV-1 causes adult T-cell leukemia/lymphoma (ATL and is also associated with a variety of lymphocyte-mediated diseases. The HTLV-1 basic leucine zipper (HBZ gene, found to be consistently expressed in ATL, has recently been the subject of intensive research efforts. In this review, we summarize recent findings about HBZ and discuss its roles and functions not only in the virus life cycle, but also in HTLV-1 disease pathogenesis.

  7. CYTOMEGALOVIRUS: A REVIEW OF PATHOGENESIS, EPIDEMIOLOGY AND DIAGNOSIS OF INFECTION

    Directory of Open Access Journals (Sweden)

    Sócrates Bezerra de Matos

    2011-05-01

    Full Text Available The cytomegalovirus (CMV is a human β-herpesvirus ubiquitous and has high worldwide prevalence. The transmission occurs through contact with biological fluids, such as: saliva, semen, vaginal secretions, urine and breast milk, as well as transplacental, blood transfusion or organ transplantation. The most CMV infected individuals remains asymptomatic, however, some patients, especially the immunosuppressed, can develop severe infection with serious clinical signs, like the transplant recipients, HIV positive, leukemic or newborn. This review aims, among other things, discuss the pathogenesis and highlight important sites of immunology and diagnosis of CMV infection.

  8. Cytomegalovirus: a review of pathogenesis, epidemiology and diagnosis of infection

    Directory of Open Access Journals (Sweden)

    Sócrates Bezerra de Matos

    2011-01-01

    Full Text Available The cytomegalovirus (CMV is a human β-herpesvirus ubiquitous and has high worldwide prevalence. The transmission occurs through contact with biological fluids, such as: saliva, semen, vaginal secretions, urine and breast milk, as well as trans placental, blood transfusion or organ transplantation. The most CMV infected individuals remains asymptomatic, however, some patients, especially the immunosuppressed, can develop severe infection with serious clinical signs, like the transplant recipients, HIV positive, leukemic or newborn. This review aims, among other things, discuss the pathogenesis and highlight important sites of immunology and diagnosis of CMV infection.

  9. The dynamics and pathogenesis of traumatic subdural hygromas

    International Nuclear Information System (INIS)

    Kopp, W.

    1988-01-01

    Of 2005 patients, who had suffered blunt skull trauma, 108 developed post-traumatic subdural hygromas (TSH). CT was used to observe the course of subdural hygromas not treated surgically, with particular reference to the time of their appearance and regression. The relative incidence of TSH, and of the severity of head trauma quanitified on a 5-grade scale was determined in different age groups. From the traumatic changes demonstrated on CT, some conclusions could be drawn regarding the pathogenesis. A hypothetical model has been developed which explains TSH as a result of shearing forces. (orig.) [de

  10. The role of inflammation in the pathogenesis of glaucoma

    DEFF Research Database (Denmark)

    Vohra, Rupali; Tsai, James C; Kolko, Miriam

    2013-01-01

    Glaucoma is an ocular disorder characterized by the progressive loss of retinal ganglion cells (RGC) and their axons. There are various hypotheses concerning the cause of RGC death. Previously, glaucoma was defined by high intraocular pressure (IOP); during the past decade, however, glaucoma...... specialists have acknowledged that elevated IOP is the most important risk factor for glaucoma, but does not define the disease. Other factors such as genetics, blood flow, and excitotoxicity are suggested as potential causal factors for progressive RGC death observed in glaucoma. We review recent studies...... elucidating a possible role of low-grade inflammation as a causal factor in the pathogenesis of glaucoma....

  11. Pathogenesis and symptomatics of the acute radiation syndrome

    International Nuclear Information System (INIS)

    Fliedner, T.M.; Haen, M.; Carbonell, F.

    1980-01-01

    The pathogenesis and symptomatics of the acute radiation syndrome are discussed. Diagnosis and therapy would be impossible without detailed knowledge in these fields. The concept of acute radiation syndrome is explained, and a pathophysiological analysis of the various forms of radiation syndrome - haematological, intestinal and affecting the central nervous system is attempted. The developments in the diagnosis and therapy of acute radiation syndrome since its first description - 35 years ago - are reviewed. Today, whole-body doses of 100 rd and more can be treated by radiotherapy. (orig./MG) [de

  12. Oral lichen planus: An update on pathogenesis and treatment

    Science.gov (United States)

    Lavanya, N; Jayanthi, P; Rao, Umadevi K; Ranganathan, K

    2011-01-01

    Oral lichen planus (OLP) is a chronic inflammatory disease that affects the mucus membrane of the oral cavity. It is a T-cell mediated autoimmune disease in which the cytotoxic CD8+ T cells trigger apoptosis of the basal cells of the oral epithelium. Several antigen-specific and nonspecific inflammatory mechanisms have been put forward to explain the accumulation and homing of CD8+ T cells subepithelially and the subsequent keratinocyte apoptosis. A wide spectrum of treatment modalities is available, from topical corticosteroids to laser ablation of the lesion. In this review, we discuss the various concepts in the pathogenesis and current treatment modalities of OLP. PMID:22529568

  13. A new direction in the pathogenesis of idiopathic pulmonary fibrosis?

    Directory of Open Access Journals (Sweden)

    Kolb Martin

    2002-01-01

    Full Text Available Abstract A recent review article suggested that idiopathic pulmonary fibrosis (IPF is a disease that is associated more with abnormal wound healing than with inflammation. Data derived from transgenic and gene transfer rodent models suggest that lung inflammation may be a necessary but insufficient component of IPF, and that at some point in the natural history of the disease IPF becomes no longer dependent on the inflammatory response for propagation. Altered microenvironment and involvement of epithelial cell/mesenchymal cell interaction are the most likely contributors to the pathogenesis of this chronic progressive disorder.

  14. Apoptosis and pathogenesis of viral hepatitis C--an update.

    Science.gov (United States)

    Nasir, A; Arora, H S; Kaiser, H E

    2000-01-01

    Hepatitis C virus is a major causative agent of chronic liver disease. Viral genotype, mutations, virus-host interaction, expression of viral proteins and host immune-reaction are important factors in the pathogenesis of HCV infection. Precise pathogenesis and perpetuation of hepatocellular injury in hepatitis C viral infection remain unclear. Proposed mechanisms include direct viropathic effect, the host immune response mediated through cytotoxic T lymphocytes, both viropathic and cytopathic effects, and macrophages/monocytes. Apoptosis occurs both in acute or chronic hepatitis and has been suggested to be mediated through Fas antigen. In HCV infection, Fas expression is up-regulated in the liver cells in line with the severity of liver inflammation. When HCV-specific T cells migrate into hepatocytes and recognize the viral antigen via the T cell receptor, they become activated and express Fas ligand that transduces the apoptotic death signal to Fas-bearing hepatocytes resulting in their destruction. Thus, the Fas system plays an important role in liver cell injury by HCV infection. Possible inducers of apoptosis in hepatitis C include cytokines, especially tumor necrosis factor-alpha (TNF-alpha), released by inflammatory cells, and acting through TNF and other cytokine receptors.

  15. Pathogenic Leptospira: Advances in understanding the molecular pathogenesis and virulence

    Directory of Open Access Journals (Sweden)

    Ciamak Ghazaei

    2018-01-01

    Full Text Available Leptospirosis is a common zoonotic disease has emerged as a major public health problem, with developing countries bearing disproportionate burdens. Although the diverse range of clinical manifestations of the leptospirosis in humans is widely documented, the mechanisms through which the pathogen causes disease remain undetermined. In addition, leptospirosis is a much-neglected life-threatening disease although it is one of the most important zoonoses occurring in a diverse range of epidemiological distribution. Recent advances in molecular profiling of pathogenic species of the genus Leptospira have improved our understanding of the evolutionary factors that determine virulence and mechanisms that the bacteria employ to survive. However, a major impediment to the formulation of intervention strategies has been the limited understanding of the disease determinants. Consequently, the association of the biological mechanisms to the pathogenesis of Leptospira, as well as the functions of numerous essential virulence factors still remain implicit. This review examines recent advances in genetic screening technologies, the underlying microbiological processes, the virulence factors and associated molecular mechanisms driving pathogenesis of Leptospira species.

  16. Molecular pathogenesis of long QT syndrome type 1

    Directory of Open Access Journals (Sweden)

    Jie Wu, PhD

    2016-10-01

    Full Text Available Long QT syndrome type 1 (LQT1 is a subtype of a congenital cardiac syndrome caused by mutation in the KCNQ1 gene, which encodes the α-subunit of the slow component of delayed rectifier K+ current (IKs channel. Arrhythmias in LQT1 are characterized by prolongation of the QT interval on ECG, as well as the occurrence of life-threatening cardiac events, frequently triggered by adrenergic stimuli (e.g., physical or emotional stress. During the past two decades, much advancement has been made in understanding the molecular pathogenesis underlying LQT1. Uncovering the genotype-phenotype correlations in LQT1 is of clinical importance to better understand the gene-specific differences that may influence the propensity for developing life-threatening arrhythmias under specific conditions. Elucidation of these mechanisms will also help to improve the diagnosis and management of this cardiac disorder based on gene-specific considerations. This review describes the current medical consensus and recent developments regarding the molecular pathogenesis of LQT1 and provides a novel insight into the adrenergic regulation of this disease.

  17. Immunogenetics and genetic susceptibility in the pathogenesis of autoimmune hepatitis

    Directory of Open Access Journals (Sweden)

    Das Anup K

    2014-11-01

    Full Text Available vAutoimmune hepatitis is a progressive liver disease. Its pathogenesis is unclear, but needs a ‘trigger’ to initiate the disease in a genetically susceptible person. The susceptibility is partly related to MHCII class genes, and more so with human leukocyte antigen (HLA. Several mechanisms have been proposed which, however, cannot fully explain the immunologic findings in autoimmune hepatitis. The susceptibility to any autoimmune disease is determined by several factors where genetic and immunological alterations, along with, environmental factor are active. MHCII antigens as a marker for AIH, or a predictor of treatment response and prognosis has been investigated. Since MHCII antigens show significant ethnic heterogeneity, mutations in MHCII may merely act as only precursors of the surface markers of immune cells, which can be of significance, because the changes in HLA and MHC are missing in certain populations. One such marker is the CTLA-4 (CD152 gene mutation, reported in the phenotypes representing susceptibility to AIH. Other candidate genes of cytokines, TNF, TGF-beta1 etc, have also been investigated but with unvalidated results. Paediatric AIH show differences in genetic susceptibility. Genetic susceptibility or resistance to AIH may be associated with polypeptides in DRB1 with certain amino-acid sequences. Understanding which genes are implicated in genesis and/or disease progression will obviously help to identify key pathways in AIH and provide better insights into its pathogenesis. But studies to identify responsible genes are complex because of the complex trait of AIH.

  18. Glia: silent partners in energy homeostasis and obesity pathogenesis.

    Science.gov (United States)

    Douglass, John D; Dorfman, Mauricio D; Thaler, Joshua P

    2017-02-01

    Body weight stability requires homeostatic regulation to balance energy intake and energy expenditure. Research on this system and how it is affected by obesity has largely focused on the role of hypothalamic neurons as integrators of information about long-term fuel storage, short-term nutrient availability and metabolic demand. Recent studies have uncovered glial cells as additional contributors to energy balance regulation and obesity pathogenesis. Beginning with early work on leptin signalling in astrocytes, this area of research rapidly emerged after the discovery of hypothalamic inflammation and gliosis in obese rodents and humans. Current studies have revealed the involvement of a wide variety of glial cell types in the modulation of neuronal activity, regulation of hormone and nutrient availability, and participation in the physiological regulation of feeding behaviour. In addition, one glial type, microglia, has recently been implicated in susceptibility to diet-induced obesity. Together, these exciting new findings deepen our understanding of energy homeostasis regulation and raise the possibility of identifying novel mechanisms that contribute to the pathogenesis of obesity.

  19. Nucleus accumbens core and pathogenesis of compulsive checking

    Science.gov (United States)

    Ballester González, Javier; Dvorkin-Gheva, Anna; Silva, Charmaine; Foster, Jane A.

    2015-01-01

    To investigate the role of the nucleus accumbens core (NAc) in the development of quinpirole-induced compulsive checking, rats received an excitotoxic lesion of NAc or sham lesion and were injected with quinpirole (0.5 mg/kg) or saline; development of checking behavior was monitored for 10 biweekly tests. The results showed that even after the NAc lesion, quinpirole still induced compulsive checking, suggesting that the pathogenic effects produced by quinpirole lie outside the NAc. Although the NAc lesion did not prevent the induction of compulsive checking, it altered how quickly it develops, suggesting that the NAc normally contributes toward the induction of compulsive checking. Saline-treated rats with an NAc lesion were hyperactive, but did not develop compulsive checking, indicating that hyperactivity by itself is not sufficient for the pathogenesis of compulsive checking. It is proposed that compulsive checking is the exaggerated output of a security motivation system and that the NAc serves as a neural hub for coordinating the orderly activity of neural modules of this motivational system. Evidence is considered suggesting that the neurobiological condition for the pathogenesis of compulsive checking is two-fold: activation of dopamine D2/D3 receptors without concurrent stimulation of D1-like receptors and long-term plastic changes related to quinpirole-induced sensitization. PMID:25426580

  20. Diet, gut microbes, and the pathogenesis of inflammatory bowel diseases.

    Science.gov (United States)

    Dolan, Kyle T; Chang, Eugene B

    2017-01-01

    The rising incidence of inflammatory bowel diseases in recent decades has notably paralleled changing lifestyle habits in Western nations, which are now making their way into more traditional societies. Diet plays a key role in IBD pathogenesis, and there is a growing appreciation that the interaction between diet and microbes in a susceptible person contributes significantly to the onset of disease. In this review, we examine what is known about dietary and microbial factors that promote IBD. We summarize recent findings regarding the effects of diet in IBD epidemiology from prospective population cohort studies, as well as new insights into IBD-associated dysbiosis. Microbial metabolism of dietary components can influence the epithelial barrier and the mucosal immune system, and understanding how these interactions generate or suppress inflammation will be a significant focus of IBD research. Our knowledge of dietary and microbial risk factors for IBD provides important considerations for developing therapeutic approaches through dietary modification or re-shaping the microbiota. We conclude by calling for increased sophistication in designing studies on the role of diet and microbes in IBD pathogenesis and disease resolution in order to accelerate progress in response to the growing challenge posed by these complex disorders. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Endometriosis: etiology, pathogenesis, diagnostics, modern aspects of treatment

    Directory of Open Access Journals (Sweden)

    N. V. Avramenko

    2014-08-01

    Full Text Available Aim. To analyze the data of the current scientific literature on the etiology, pathogenesis, diagnosis, clinic and modern therapy of genital endometriosis, which is one of the most urgent problems of modern gynecological practice. Methods and results. The main role in the process of growth and development of endometriosis is currently attributed to changes in the function of the immune system, possibly genetically determined. Currently, it is proved that endometriosis develops immune processes against endometrial tissue. There is every reason to believe that endometrium in its unusual places can acquire antigenic properties that stimulates the body's immune system reaction. Hyperandrogenism, early menarche, heavy and prolonged menstruation, disorders of the outflow of menstrual blood, adverse environment, obesity, smoking, stress are considered as the risk factors for the development of endometriosis. Revised diagnosis is possible with laparoscopic visualization (ideally with confirming histological research. A presumptive diagnosis is based on typical clinical symptoms and signs. Laboratory methods of diagnosis: magnetic resonance imaging and ultrasound. The main methods of treatment of endometriosis are surgical, medication, combined. Conclusion. Endometriosis remains unresolved scientific and clinical problem characterized by the paradoxical aspects of the pathogenesis and clinical contrasts of course without found explanation yet.

  2. 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.

  3. Pathogenic Leptospira: Advances in understanding the molecular pathogenesis and virulence

    Science.gov (United States)

    Ghazaei, Ciamak

    2018-01-01

    Leptospirosis is a common zoonotic disease has emerged as a major public health problem, with developing countries bearing disproportionate burdens. Although the diverse range of clinical manifestations of the leptospirosis in humans is widely documented, the mechanisms through which the pathogen causes disease remain undetermined. In addition, leptospirosis is a much-neglected life-threatening disease although it is one of the most important zoonoses occurring in a diverse range of epidemiological distribution. Recent advances in molecular profiling of pathogenic species of the genus Leptospira have improved our understanding of the evolutionary factors that determine virulence and mechanisms that the bacteria employ to survive. However, a major impediment to the formulation of intervention strategies has been the limited understanding of the disease determinants. Consequently, the association of the biological mechanisms to the pathogenesis of Leptospira, as well as the functions of numerous essential virulence factors still remain implicit. This review examines recent advances in genetic screening technologies, the underlying microbiological processes, the virulence factors and associated molecular mechanisms driving pathogenesis of Leptospira species. PMID:29445617

  4. Update on ankylosing spondylitis: current concepts in pathogenesis.

    Science.gov (United States)

    Smith, Judith A

    2015-01-01

    Ankylosing spondylitis is an insidiously progressive and debilitating form of arthritis involving the axial skeleton. The long delay in diagnosis and insufficient response to currently available therapeutics both advocate for a greater understanding of disease pathogenesis. Genome-wide association studies of this highly genetic disease have implicated specific immune pathways, including the interleukin (IL)-17/IL-23 pathway, control of nuclear factor kappa B (NF-κB) activation, amino acid trimming for major histocompatibility complex (MHC) antigen presentation, and other genes controlling CD8 and CD4 T cell subsets. The relevance of these pathways has borne out in animal and human subject studies, in particular, the response to novel therapeutic agents. Genetics and the findings of autoantibodies in ankylosing spondylitis revisit the question of autoimmune vs. autoinflammatory etiology. As environmental partners to genetics, recent attention has focused on the roles of microbiota and biomechanical stress in initiating and perpetuating inflammation. Herein, we review these current developments in the investigation of ankylosing spondylitis pathogenesis.

  5. MDS: Recent progress in molecular pathogenesis and clinical aspects.

    Science.gov (United States)

    Harada, Hironori

    2017-01-01

    Myelodysplastic syndromes (MDS) are defined as hematopoietic stem cell disorders caused by various gene abnormalities. Recent analysis using next generation sequencing has provided great progress in identifying relationships between gene mutations and clinical phenotypes of MDS. It is estimated that one or more gene mutations occur in greater than 90% of MDS patients. More than 50 gene mutations affecting RNA splicing machinery, DNA methylation, histone modifications, transcription factors, signal transduction proteins, and components of the cohesion complex participate in the pathogenesis of MDS. The sequential accumulation of additional cooperating mutations drives disease evolution from clonal hematopoiesis of indeterminate potential (CHIP) to symptomatic MDS and from MDS to acute myelogenous leukemia (AML). Mutations in RNA splicing and DNA methylation occur early and are considered founding mutations, whereas others that occur later are regarded as subclonal mutations. RUNX1 mutations are more likely to be subclonal; however, they apparently play a pivotal role in familial MDS. In addition, large alterations of chromosomes are involved in the pathogenesis of MDS. 5q- syndrome, which leads to haploinsufficiency of the located genes, has consistent clinical features. Understanding gene abnormalities of MDS patients can provide clinical information, including diagnosis, prognostic score, and prediction of response to therapy.

  6. Fetal/Neonatal Alloimmune Thrombocytopenia: Pathogenesis, Diagnostics and Prevention.

    Science.gov (United States)

    Brojer, Ewa; Husebekk, Anne; Dębska, Marzena; Uhrynowska, Małgorzata; Guz, Katarzyna; Orzińska, Agnieszka; Dębski, Romuald; Maślanka, Krystyna

    2016-08-01

    Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a relatively rare condition (1/1000-1/2000) that was granted orphan status by the European Medicines Agency in 2011. Clinical consequences of FNAIT, however, may be severe. A thrombocytopenic fetus or new-born is at risk of intracranial hemorrhage that may result in lifelong disability or death. Preventing such bleeding is thus vital and requires a solution. Anti-HPA1a antibodies are the most frequent cause of FNAIT in Caucasians. Its pathogenesis is similar to hemolytic disease of the newborn (HDN) due to anti-RhD antibodies, but is characterized by platelet destruction and is more often observed in the first pregnancy. In 75 % of these women, alloimmunization by HPA-1a antigens, however, occurs at delivery, which enables development of antibody-mediated immune suppression to prevent maternal immunization. As for HDN, the recurrence rate of FNAIT is high. For advancing diagnostic efforts and treatment, it is thereby crucial to understand the pathogenesis of FNAIT, including cellular immunity involvement. This review presents the current knowledge on FNAIT. Also described is a program for HPA-1a screening in identifying HPA-1a negative pregnant women at risk of immunization. This program is now performed at the Institute of Hematology and Transfusion Medicine in cooperation with the Department of Obstetrics and Gynecology of the Medical Centre of Postgraduate Education in Warsaw as well as the UiT The Arctic University of Norway.

  7. The Role of Extracellular Histones in Influenza Virus Pathogenesis.

    Science.gov (United States)

    Ashar, Harshini K; Mueller, Nathan C; Rudd, Jennifer M; Snider, Timothy A; Achanta, Mallika; Prasanthi, Maram; Pulavendran, Sivasami; Thomas, Paul G; Ramachandran, Akhilesh; Malayer, Jerry R; Ritchey, Jerry W; Rajasekhar, Rachakatla; Chow, Vincent T K; Esmon, Charles T; Teluguakula, Narasaraju

    2018-01-01

    Although exaggerated host immune responses have been implicated in influenza-induced lung pathogenesis, the etiologic factors that contribute to these events are not completely understood. We previously demonstrated that neutrophil extracellular traps exacerbate pulmonary injury during influenza pneumonia. Histones are the major protein components of neutrophil extracellular traps and are known to have cytotoxic effects. Here, we examined the role of extracellular histones in lung pathogenesis during influenza. Mice infected with influenza virus displayed high accumulation of extracellular histones, with widespread pulmonary microvascular thrombosis. Occluded pulmonary blood vessels with vascular thrombi often exhibited endothelial necrosis surrounded by hemorrhagic effusions and pulmonary edema. Histones released during influenza induced cytotoxicity and showed strong binding to platelets within thrombi in infected mouse lungs. Nasal wash samples from influenza-infected patients also showed increased accumulation of extracellular histones, suggesting a possible clinical relevance of elevated histones in pulmonary injury. Although histones inhibited influenza growth in vitro, in vivo treatment with histones did not yield antiviral effects and instead exacerbated lung pathology. Blocking with antihistone antibodies caused a marked decrease in lung pathology in lethal influenza-challenged mice and improved protection when administered in combination with the antiviral agent oseltamivir. These findings support the pathogenic effects of extracellular histones in that pulmonary injury during influenza was exacerbated. Targeting histones provides a novel therapeutic approach to influenza pneumonia. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  8. Hepatic encephalopathy: An updated approach from pathogenesis to treatment

    Science.gov (United States)

    Toris, Giannakis T.; Bikis, Christos N.; Tsourouflis, Gerasimos S.; Theocharis, Stamatios E.

    2011-01-01

    Summary One of the most serious complications of chronic or fulminant liver failure is hepatic encephalopathy (HE), associated most commonly with cirrhosis. In the presence of chronic liver disease, HE is a sign of decompensation, while in fulminant liver failure its development represents a worrying sign and usually indicates that transplantation will be required. Despite the significance of HE in the course of liver disease, the progress in development of new therapeutic options has been unremarkable over the last 20 years. An up-to-date review regarding HE, including both research and review articles. HE is a serious and progressive, but potentially reversible, disorder with a wide spectrum of neuropsychiatric abnormalities and motor disturbances that ranges from mild alteration of cognitive and motor function to coma and death. Although a clear pathogenesis is yet to be determined, elevated ammonia in serum and the central nervous system is the mainstay for pathogenesis and treatment of HE. Management includes early diagnosis and prompt treatment of precipitating factors. Clinical trials and extensive clinical experience have established the efficacy of diverse substances in HE treatment. Novel therapies with clinical promise include: L-ornithine L-aspartate, sodium benzoate, phenylacetate, AST-120, and the molecular adsorbent recirculating system. Eventually, liver transplantation is often the most successful long-term therapy for HE. PMID:21278704

  9. Abnormal epidermal barrier in the pathogenesis of psoriasis.

    Science.gov (United States)

    Wolf, Ronni; Orion, Edith; Ruocco, Eleonora; Ruocco, Vincenzo

    2012-01-01

    Almost 2 decades ago, Williams and Elias suggested a unifying concept for the pathogenesis of disorders of cornification, according to which the integrity of the epidermal barrier and its effective function is an important factor in the regulation of epidermal DNA synthesis. Interference with the barrier integrity or function will result in epidermal hyperplasia and may be the primary event leading to hyperproliferative skin diseases, such as psoriasis. We have analyzed alterations to several structures of the epidermal barrier that might be responsible for barrier dysfunction and thus lead to hyperproliferation of the epidermis in an attempt to repair the barrier and, as a result, might be inducers of psoriasis. There are several convincing reports indicating that inhibiting of epidermal transglutaminase may lead to epidermal hyperproliferation and that this stimulus might trigger psoriasis among genetically predisposed patients. Disturbance of epidermal barrier function caused by derangement of lipid or cholesterol or ceramide synthesis leads to increased DNA synthesis and epidermal hyperplasia and as a result might be an inducer of psoriasis. We could find little evidence to show that defective defense of the epidermis or an abnormal response of it to bacteria plays a role in the pathogenesis of psoriasis. Accumulating data indicate that there is an association of psoriasis and mutations of genes within the epidermal differentiation complex, which are crucial for the development, maturation, cornification, cross-linking, and terminal differentiation of the epidermis, called psoriasis susceptibility locus 4. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Pathogenesis of minimal change nephrotic syndrome: an immunological concept

    Science.gov (United States)

    Kim, Seong Heon; Park, Se Jin; Han, Kyoung Hee; Kronbichler, Andreas; Saleem, Moin A.; Oh, Jun; Lim, Beom Jin

    2016-01-01

    Idiopathic nephrotic syndrome (INS) in children is characterized by massive proteinuria and hypoalbuminemia. Minimal change nephrotic syndrome (MCNS) is the most common form of INS in children. The pathogenesis of MCNS still remains unclear, however, several hypotheses have been recently proposed. For several decades, MCNS has been considered a T-cell disorder, which causes the impairment of the glomerular filtration barrier with the release of different circulating factors. Increased levels of several cytokines are also suggested. Recently, a "two-hit" theory was proposed that included the induction of CD80 (B7-1) and regulatory T-cell (Treg) dysfunction, with or without impaired autoregulatory functions of the podocyte. In contrast to the well-established involvement of T cells, the role of B cells has not been clearly identified. However, B-cell biology has recently gained more attention, because rituximab (a monoclonal antibody directed against CD20-bearing cells) demonstrated a very good therapeutic response in the treatment of childhood and adult MCNS. Here, we discuss recent insights into the pathogenesis of MCNS in children. PMID:27279884

  11. Salivary proteomics in lichen planus: A relationship with pathogenesis?

    Science.gov (United States)

    Souza, M M; Florezi, G P; Nico, Mms; de Paula, F; Paula, F M; Lourenço, S V

    2018-01-30

    Oral lichen planus is a chronic, T-cell-mediated, inflammatory disease that affects the oral cavity. The oral lichen planus pathogenesis is still unclear, however, the main evidence is that the mechanisms of activation of different T lymphocyte pathway induce apoptosis with an increase in Th1 and Th17 subtypes cells, triggered by the release of cytokines. This study analysed saliva proteomics to identify protein markers that might be involved in the pathogenesis and development of the disease. Proteins differentially expressed by oral lichen planus and healthy controls were screened using mass spectrometry; the proteins found in oral lichen planus were subjected to bioinformatics analysis, including gene ontology and string networks analysis. The multiplex analysis validation allowed the correlation between the proteins identified and the involved cytokines in Th17 response. One hundred and eight proteins were identified in oral lichen planus, of which 17 proteins showed a high interaction between them and indicated an association with the disease. Expression of these proteins was correlated with the triggering of cytokines, more specifically the Th17 cells. Proteins, such as S100A8, S100A9, haptoglobin, can trigger cytokines and might be associated with a pathological function and antioxidant activities in oral lichen planus. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

  12. MicroRNAs in the pathogenesis of cystic kidney disease.

    Science.gov (United States)

    Phua, Yu Leng; Ho, Jacqueline

    2015-04-01

    Cystic kidney diseases are common renal disorders characterized by the formation of fluid-filled epithelial cysts in the kidneys. The progressive growth and expansion of the renal cysts replace existing renal tissue within the renal parenchyma, leading to reduced renal function. While several genes have been identified in association with inherited causes of cystic kidney disease, the molecular mechanisms that regulate these genes in the context of post-transcriptional regulation are still poorly understood. There is increasing evidence that microRNA (miRNA) dysregulation is associated with the pathogenesis of cystic kidney disease. In this review, recent studies that implicate dysregulation of miRNA expression in cystogenesis will be discussed. The relationship of specific miRNAs, such as the miR-17∼92 cluster and cystic kidney disease, miR-92a and von Hippel-Lindau syndrome, and alterations in LIN28-LET7 expression in Wilms tumor will be explored. At present, there are no specific treatments available for patients with cystic kidney disease. Understanding and identifying specific miRNAs involved in the pathogenesis of these disorders may have the potential to lead to the development of novel therapies and biomarkers.

  13. Membranous nephropathy: A review on the pathogenesis, diagnosis, and treatment

    Directory of Open Access Journals (Sweden)

    Wei Ling Lai

    2015-02-01

    Full Text Available In adults, membranous nephropathy (MN is a major cause of nephrotic syndrome. However, the etiology of approximately 75% of MN cases is idiopathic. Secondary causes of MN are autoimmune diseases, infection, drugs, and malignancy. The pathogenesis of MN involves formation of immune complex in subepithelial sites, but the definite mechanism is still unknown. There are three hypotheses about the formation of immune complex, including preformed immune complex, in situ immune-complex formation, and autoantibody against podocyte membrane antigen. The formation of immune complex initiates complement activation, which subsequently leads to glomerular damage. Recently, the antiphospholipase A2 receptor antibody was found to be associated with idiopathic MN. This finding may be useful in the diagnosis and prognosis of MN. The current treatment includes best supportive care, which consists of the use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, lipid-lowering agents, and optimal control of blood pressure. Immunosuppressive agents should be used for patients who suffer from refractory proteinuria or complications associated with nephrotic syndrome. Existing evidence supports the use of a combination of steroid and alkylating agents. This article reviews the epidemiology, pathogenesis, diagnosis, and the treatment of MN.

  14. Microbiome in interstitial lung disease: from pathogenesis to treatment target.

    Science.gov (United States)

    Salisbury, Margaret L; Han, MeiLan K; Dickson, Robert P; Molyneaux, Philip L

    2017-09-01

    This review summarizes current knowledge of the role of the lung microbiome in interstitial lung disease and poses considerations of the microbiome as a therapeutic target. Although historically considered sterile, bacterial communities have now been well documented in lungs in health and disease. Studies in idiopathic pulmonary fibrosis (IPF) suggest that increased bacterial burden and/or abundance of potentially pathogenic bacteria may drive disease progression, acute exacerbations, and mortality. More recent work has highlighted the interaction between the lung microbiome and the innate immune system in IPF, strengthening the argument for the role of both host and environment interaction in disease pathogenesis. In support of this, studies of interstitial lung diseases other than IPF suggest that it may be the host immune response, which shapes the microbiome in these diseases. Some clinical and mouse model data also suggest that the lung microbiome may represent a therapeutic target, via antibiotic administration, immunization against pathogenic organisms, or treatment directed at gastroesophageal reflux. Evidence suggests that the lung microbiome may serve as a prognostic biomarker, a therapeutic target, or provide an explanation for disease pathogenesis in IPF.

  15. Neutralizing Antibodies and Pathogenesis of Hepatitis C Virus Infection

    Directory of Open Access Journals (Sweden)

    Françoise Stoll-Keller

    2012-10-01

    Full Text Available Hepatitis C virus (HCV infection is a major cause of chronic liver disease worldwide. The interplay between the virus and host innate and adaptive immune responses determines the outcome of infection. There is increasing evidence that host neutralizing responses play a relevant role in the resulting pathogenesis. Furthermore, viral evasion from host neutralizing antibodies has been revealed to be an important contributor in leading both to viral persistence in acute liver graft infection following liver transplantation, and to chronic viral infection. The development of novel model systems to study HCV entry and neutralization has allowed a detailed understanding of the molecular mechanisms of virus-host interactions during antibody-mediated neutralization. The understanding of these mechanisms will ultimately contribute to the development of novel antiviral preventive strategies for liver graft infection and an urgently needed vaccine. This review summarizes recent concepts of the role of neutralizing antibodies in viral clearance and protection, and highlights consequences of viral escape from neutralizing antibodies in the pathogenesis of HCV infection.

  16. Inflammatory Bowel Disease: Autoimmune or Immune-mediated Pathogenesis?

    Directory of Open Access Journals (Sweden)

    Zhonghui Wen

    2004-01-01

    Full Text Available The pathogenesis of Crohn's disease (CD and ulcerative colitis (UC, the two main forms of inflammatory bowel disease (IBD, is still unclear, but both autoimmune and immune-mediated phenomena are involved. Autoimmune phenomena include the presence of serum and mucosal autoantibodies against intestinal epithelial cells in either form of IBD, and against human tropomyosin fraction five selectively in UC. In addition, perinuclear antineutrophil cytoplasmic antibodies (pANCA are common in UC, whereas antibodies against Saccharomyces cerevisiae (ASCA are frequently found in CD. Immune-mediate phenomena include a variety of abnormalities of humoral and cell-mediated immunity, and a generalized enhanced reactivity against intestinal bacterial antigens in both CD and UC. It is currently believed that loss of tolerance against the indigenous enteric flora is the central event in IBD pathogenesis. Various complementary factors probably contribute to the loss of tolerance to commensal bacteria in IBD. They include defects in regulatory T-cell function, excessive stimulation of mucosal dendritic cells, infections or variants of proteins critically involved in bacterial antigen recognition, such as the products of CD-associated NOD2/CARD15 mutations.

  17. Molecular Pathogenesis of Liver Steatosis Induced by Hepatitis C Virus

    Directory of Open Access Journals (Sweden)

    Cheng Jun

    2012-09-01

    Full Text Available Liver steatosis is a pathological hallmark in patients with chronic hepatitis C (CHC. Increased lipid uptake, decreased lipid secretion, increased lipid synthesis and decreased lipid degradation are all involved in pathogenesis of steatosis induced by hepatitic C virus (HCV infection. Level of low density lipoprotein receptor (LDL-R and activity of peroxisome proliferator-activated receptor (PPAR α is related to liver uptake of lipid from circulation, and affected by HCV. Secretion via microsomal triglyceride transfer protein (MTTP, and formation of very low density lipoprotein (VLDL have been hampered by HCV infection. Up-regulation of lipid synthesis related genes, such as sterol regulatory element-binding protein (SREBP-1, SREBP-2, SREBP-1c, fatty acid synthase (FASN, HMG CoA reductase (HMGCR, liver X receptor (LXR, acetyl-CoA carboxylase 1 (ACC1, hepatic CB (1 receptors, retinoid X receptor (RXR α, were the main stay of liver steatosis pathogenesis. Degradation of lipid in liver is decreased in patients with CHC. There is strong evidence that heterogeneity of HCV core genes of different genotypes affect their effects of liver steatosis induction. A mechanism in which steatosis is involved in HCV life cycle is emerging.

  18. The role of the gastrointestinal microbiome in Helicobacter pylori pathogenesis

    Science.gov (United States)

    Sheh, Alexander; Fox, James G

    2013-01-01

    The discovery of Helicobacter pylori overturned the conventional dogma that the stomach was a sterile organ and that pH values pylori are an etiological agent associated with gastritis, hypochlorhydria, duodenal ulcers, and gastric cancer. It is now appreciated that the human stomach supports a bacterial community with possibly 100s of bacterial species that influence stomach homeostasis. Other bacteria colonizing the stomach may also influence H. pylori-associated gastric pathogenesis by creating reactive oxygen and nitrogen species and modulating inflammatory responses. In this review, we summarize the available literature concerning the gastric microbiota in humans, mice, and Mongolian gerbils. We also discuss the gastric perturbations, many involving H. pylori, that facilitate the colonization by bacteria from other compartments of the gastrointestinal tract, and identify risk factors known to affect gastric homeostasis that contribute to changes in the microbiota. PMID:23962822

  19. Liver injury and disease pathogenesis in chronic hepatitis C.

    Science.gov (United States)

    Yamane, Daisuke; McGivern, David R; Masaki, Takahiro; Lemon, Stanley M

    2013-01-01

    Chronic hepatitis C virus (HCV) infection is a leading cause of liver-specific morbidity and mortality in humans, including progressive liver fibrosis, cirrhosis, and hepatocellular carcinoma. It has also been associated with altered function in other organs, including those of the endocrine, hematopoietic, and nervous systems. Disease results from both direct regulation of cellular metabolism and signaling pathways by viral proteins as well as indirect consequences of the host response to HCV infection, including inflammatory responses stemming from immune recognition of the virus. Recent in vitro studies have begun to reveal molecular mechanisms responsible for virus-induced changes in cell metabolism and cellular kinase cascades that culminate in pathologic consequences in the liver, such as steatosis, insulin resistance, and carcinogenesis. Here we discuss how these findings may be relevant to disease pathogenesis in patients, and suggest future directions in the field.

  20. Patterns of evolution of host proteins involved in retroviral pathogenesis

    Directory of Open Access Journals (Sweden)

    Kaessmann Henrik

    2006-02-01

    Full Text Available Abstract Background Evolutionary analysis may serve as a useful approach to identify and characterize host defense and viral proteins involved in genetic conflicts. We analyzed patterns of coding sequence evolution of genes with known (TRIM5α and APOBEC3G or suspected (TRIM19/PML roles in virus restriction, or in viral pathogenesis (PPIA, encoding Cyclophilin A, in the same set of human and non-human primate species. Results and conclusion This analysis revealed previously unidentified clusters of positively selected sites in APOBEC3G and TRIM5α that may delineate new virus-interaction domains. In contrast, our evolutionary analyses suggest that PPIA is not under diversifying selection in primates, consistent with the interaction of Cyclophilin A being limited to the HIV-1M/SIVcpz lineage. The strong sequence conservation of the TRIM19/PML sequences among primates suggests that this gene does not play a role in antiretroviral defense.

  1. [Pathogenesis of lipodystrophy and metabolic syndromes associated with HIV infection].

    Science.gov (United States)

    Muñoz-Sanz, Agustín; Rodríguez-Vidigal, Francisco F; Domingo, Pere

    2006-09-30

    Lipodystrophy, and the metabolic alterations (dislipemia, insulin-resistance) associated with human immunodeficiency virus (HIV) infection, is a multifactorial syndrome due to the interaction of host related factors (cellular immune status, diet, gene mutations), viral factors (cytokine synthesis, polyunsaturated fatty acid or PUFA depletion), and pharmacological effects (mitochondrial DNA-polymerase inhibition, lipolysis inhibition, adiponectin synthesis reduction). HIV probably modifies the adipocyte differentiation and the lipid metabolism. This retroviral effect is mediated by proinflammatory cytokines (tumor necrosis factor) and the participation of other factors (drugs, diet), all in the context of a particular host genetic setting. The adipocyte (and several cellular receptors, fatty acids, membrane proteins, and cytokines) plays a central role in the pathogenesis of HIV-associated lipodystrophy.

  2. Pathogenesis and biomarkers of carcinogenesis in ulcerative colitis

    DEFF Research Database (Denmark)

    Thorsteinsdottir, Sigrun; Gudjonsson, Thorkell; Nielsen, Ole Haagen

    2011-01-01

    One of the most serious complications of ulcerative colitis is the development of colorectal cancer. Screening patients with ulcerative colitis by standard histological examination of random intestinal biopsy samples might be inefficient as a method of cancer surveillance. This Review focuses...... on the current understanding of the pathogenesis of ulcerative colitis-associated colorectal cancer and how this knowledge can be transferred into patient management to assist clinicians and pathologists in identifying patients with ulcerative colitis who have an increased risk of colorectal cancer. Inflammation....... Although progress has been made in the understanding of inflammation-driven carcinogenesis, markers based on these findings possess insufficient sensitivity or specificity to be usable as reliable biomarkers for risk of colorectal cancer development in patients with ulcerative colitis. However, screening...

  3. Cellular microparticles in the pathogenesis of pulmonary hypertension.

    Science.gov (United States)

    Amabile, Nicolas; Guignabert, Christophe; Montani, David; Yeghiazarians, Yerem; Boulanger, Chantal M; Humbert, Marc

    2013-07-01

    Pulmonary hypertension (PH) is a fatal disease with no treatment options, characterised by elevated pulmonary vascular resistanzce and secondary right ventricular failure. The aetiology of pulmonary arterial hypertension is multiple and its pathogenesis is complex. Although the exact role of cellular microparticles remains partially understood, there is increasing evidence to suggest an active role for microparticles in PH pathophysiology. Patients with PH exhibited higher circulating levels of microparticles compared to control subjects and in vitro or in vivo generated microparticles can induce endothelial dysfunction, interfere with coagulation pathways or modulate inflammatory phenomenon. Whether or not these new conveyors of biological information contribute to the acquisition and/or maintenance of the altered endothelial phenotype is unexplored in PH and requires further study.

  4. Advances in canine distemper virus pathogenesis research: a wildlife perspective.

    Science.gov (United States)

    Loots, Angelika K; Mitchell, Emily; Dalton, Desiré L; Kotzé, Antoinette; Venter, Estelle H

    2017-03-01

    Canine distemper virus (CDV) has emerged as a significant disease of wildlife, which is highly contagious and readily transmitted between susceptible hosts. Initially described as an infectious disease of domestic dogs, it is now recognized as a global multi-host pathogen, infecting and causing mass mortalities in a wide range of carnivore species. The last decade has seen the effect of numerous CDV outbreaks in various wildlife populations. Prevention of CDV requires a clear understanding of the potential hosts in danger of infection as well as the dynamic pathways CDV uses to gain entry to its host cells and its ability to initiate viral shedding and disease transmission. We review recent research conducted on CDV infections in wildlife, including the latest findings on the causes of host specificity and cellular receptors involved in distemper pathogenesis.

  5. [Primary biliary cirrhosis (PBC): concept, pathogenesis and classification].

    Science.gov (United States)

    Aizawa, Y; Toda, G

    1994-01-01

    Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by inflammatory destruction of median size intrahepatic bile ducts. The characteristic histological process is described as chronic nonsuppurative destractive cholangitis (CNSDC). Our knowledge for the pathogenesis of PBC remains incomplete. However, immunological mechanisms seems to play one of the most important role. The immunohistochemical examination represents accumulation of stimmulated T lymphocytes in the portal area. Attachment of CD8 positive T cells to bile duct epithelial cells is observed. The animal model of PBC indicates autoreactive CD4 positive T cells seems to be important at the early stage of PBC and CD8 positive cytotoxic T cells are essential for the progression of the disease. PBC is histologically classified into four overlapping stages by Scheuer. Clinically, PBC is classified into asymptomatic PBC (aPBC), PBC with itching alone (s1PBC) and with jaundice (s2PBC).

  6. The role of the kidney in the pathogenesis of hypertension

    DEFF Research Database (Denmark)

    Evans, Roger G; Bie, Peter

    2016-01-01

    develop to hypertension characterized by increased peripheral resistance remain enigmatic. Finally, by definition, animal models of hypertension are not 'essential hypertension'; progress in our understanding of essential hypertension depends on new results on system functions in patients.......The 'Guytonian paradigm' places the direct effect of arterial pressure, on renal excretion of salt and water, at the center of long-term control of blood pressure and thus the pathogenesis of hypertension. It originated in the sixties and remains influential within the field of hypertension...... cardiac output induced by high salt intake do not necessarily lead to increased arterial pressure. Indeed, in multiple models of salt-sensitive hypertension the major abnormality appears to be failure of the vasodilator response to increased cardiac output, seen in salt-resistant animals, rather than...

  7. Pathogenesis of Hendra and Nipah virus infection in humans.

    Science.gov (United States)

    Escaffre, Olivier; Borisevich, Viktoriya; Rockx, Barry

    2013-04-17

    Hendra virus (HeV) and Nipah virus (NiV) are emerging zoonotic viruses that cause severe and often lethal respiratory illness and encephalitis in humans. Henipaviruses can infect a wide range of species and human-to-human transmission has been observed for NiV. While the exact route of transmission in humans is not known, experimental infection in different animal species suggests that infection can be efficiently initiated after respiratory challenge. The limited data on histopathological changes in fatal human cases of HeV and NiV suggest that endothelial cells are an important target during the terminal stage of infection; however, it is unknown where these viruses initially establish infection and how the virus disseminates from the respiratory tract to the central nervous system and other organs. Here we review the current concepts in henipavirus pathogenesis in humans.

  8. Co-infections and Pathogenesis of KSHV-Associated Malignancies

    Directory of Open Access Journals (Sweden)

    Suhani eThakker

    2016-02-01

    Full Text Available Kaposi’s sarcoma-associated herpesvirus (KSHV, also known as human herpes virus 8 (HHV-8 is one of the several carcinogenic viruses that infect humans. KSHV infection has been implicated in the development of Kaposi’s sarcoma (KS, primary effusion lymphoma (PEL, and multicentric Castleman’s Disease (MCD. While KSHV infection is necessary for the development of KSHV associated malignancies, it is not sufficient to induce tumoriegenesis. Evidently, other co-factors are essential for the progression of KSHV induced malignancies. One of the most important co-factors, necessary for the progression of KSHV induced tumors, is immune suppression that frequently arises during co-infection with HIV and also by other immune suppressants. In this mini-review, we discuss the roles of co-infection with HIV and other pathogens on KSHV infection and pathogenesis.

  9. Dengue Hemorrhagic Fever: Epidemiology, Pathogenesis, and Its Transmission Risk Factors

    Directory of Open Access Journals (Sweden)

    Aryu Candra

    2010-12-01

    Full Text Available Dengue hemorrhagic fever is an infectious disease resulting spectrum of clinical manifestations that vary from the lightest, dengue fever, hemorrhagic fever and dengue fever are accompanied by shock or dengue shock syndrome. Its caused by dengue virus, transmitted by Aedes mosquitoes. The case is spread in the tropics, especially in Southeast Asia, Central America, America and the Caribbean, many causes of death in children 90% of them attacking children under 15 years old. Until now pathogenesis is unclear. There are two theories or hypotheses immuno-patogenesis DHF and DSS is still controversial which secondary infections (secondary heterologus infection and antibody-dependent enhancement. Risk factors for dengue transmission are rapid urban population growth, mobilization of the population because of improved transportation facilities and disrupted or weakened so that population control. Another risk factor is poverty which result in people not has the ability to provide a decent home and healthy, drinking water supply and proper waste disposal.

  10. Recent advances in the pathogenesis and treatment of osteoporosis.

    Science.gov (United States)

    Curtis, Elizabeth M; Moon, Rebecca J; Dennison, Elaine M; Harvey, Nicholas C; Cooper, Cyrus

    2016-08-01

    Over recent decades, the perception of osteoporosis has changed from that of an inevitable consequence of ageing, to that of a well characterised and treatable chronic non-communicable disease, with major impacts on individuals, healthcare systems and societies. Characterisation of its pathophysiology from the hierarchical structure of bone and the role of its cell population, development of effective strategies for the identification of those most appropriate for treatment, and an increasing armamentarium of efficacious pharmacological therapies, have underpinned this evolution. Despite this marked progress, individuals who experience a fragility fracture remain under-treated in many areas of the world, and there is substantial need for investment both in secondary and primary prevention globally. In this brief article, we give an overview of the pathogenesis of osteoporosis, and summarise current and future approaches to its assessment and -treatment. © 2016 Royal College of Physicians.

  11. Amyloid cascade hypothesis: Pathogenesis and therapeutic strategies in Alzheimer's disease.

    Science.gov (United States)

    Barage, Sagar H; Sonawane, Kailas D

    2015-08-01

    Alzheimer's disease is an irreversible, progressive neurodegenerative disorder. Various therapeutic approaches are being used to improve the cholinergic neurotransmission, but their role in AD pathogenesis is still unknown. Although, an increase in tau protein concentration in CSF has been described in AD, but several issues remains unclear. Extensive and accurate analysis of CSF could be helpful to define presence of tau proteins in physiological conditions, or released during the progression of neurodegenerative disease. The amyloid cascade hypothesis postulates that the neurodegeneration in AD caused by abnormal accumulation of amyloid beta (Aβ) plaques in various areas of the brain. The amyloid hypothesis has continued to gain support over the last two decades, particularly from genetic studies. Therefore, current research progress in several areas of therapies shall provide an effective treatment to cure this devastating disease. This review critically evaluates general biochemical and physiological functions of Aβ directed therapeutics and their relevance. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Asthma in elite athletes: pathogenesis, diagnosis, differential diagnoses, and treatment

    DEFF Research Database (Denmark)

    Pedersen, Lars; Elers, Jimmi; Backer, Vibeke

    2011-01-01

    is essential when treating elite athletes. This article is aimed at physicians who diagnose and treat athletes with respiratory symptoms. It focuses on the pathogenesis of asthma and exercise-induced bronchoconstriction in elite athletes and how the diagnosis can be made. Furthermore, treatment of elite......Elite athletes have a high prevalence of asthma and exercise-induced bronchoconstriction. Although respiratory symptoms can be suggestive of asthma, the diagnosis of asthma in elite athletes cannot be based solely on the presence or absence of symptoms; diagnosis should be based on objective...... measurements, such as the eucapnic voluntary hyperpnea test or exercise test. When considering that not all respiratory symptoms are due to asthma, other diagnoses should be considered. Certain regulations apply to elite athletes who require asthma medication for asthma. Knowledge of these regulations...

  13. Atretic encephalocele/myelocele--case reports with emphasis on pathogenesis.

    Science.gov (United States)

    Hong, E. K.; Kim, N. H.; Lee, J. D.

    1996-01-01

    Atretic encephaloceles or myelomeningoceles are frequently solid due to hamartomatous proliferation of fibrous tissue and blood vessels. Because of the fibrous nature of the tumor with no cystic cavity and unusual location with no connection to CNS, they are frequently regarded as insignificant hamartomas. Apart from this terminology, they are also described as cutaneous meningiomas or hamartomas with ectopic meningothelial elements by the presence of meningothelial cells. We report a case of atretic encephalocele in the parietal scalp of an 8 year-old boy and a case of myelomeningocele in the posterior mediastinum of a 31 year-old woman. The terms atretic encephalocele and myelomeningocele are more appropriate for these cases because they include their pathogenesis and the non-neoplastic nature of the lesion. PMID:8878809

  14. MicroRNAs in the pathogenesis of malignant melanoma

    DEFF Research Database (Denmark)

    Glud, M; Gniadecki, R

    2013-01-01

    Cutaneous malignant melanoma is the most aggressive and lethal form of skin cancer. Over the past decades, its incidence has been increasing by 3-8% per year in western countries while mortality has stabilized. Melanoma is a heterogenous disease and can be subclassified based on distinct clinical...... to play a crucial role in cell homeostasis and carcinogenesis. MiRNAs might prove to be powerful cancer biomarkers and future therapeutic targets. In this review, we focused on the miRNA involvement in four molecular pathways known to be deregulated in malignant melanoma, including the RAS...... characteristics, histopathological features and mutation patterns within NRAS and BRAF genes. Recent data indicate that microRNAs (miRNAs) are involved in the pathogenesis of malignant melanoma. MiRNAs are small, non-coding, regulatory RNA molecules expressed in a tissue and cell specific manner and are known...

  15. Immuno-pathogenesis of Periodontal Disease: Current and Emerging Paradigms.

    Science.gov (United States)

    Huang, Nasi; Gibson, Frank C

    2014-06-01

    Periodontal disease (PD) is a highly complex disease involving many factors; however, two principal facets central to initiation and progression of the majority of PD are the composition of the microbes in the sub-gingival plaque, and the host immune response to these organisms. Numerous studies point to the complexity of PD, and to the fact that despite innate and adaptive immune activation, and resultant inflammation, our immune response fails to cure disease. Stunning new findings have begun to clarify several complexities of the host-pathogen interaction of PD pointing to key roles for microbial dysboisis and immune imbalance in the pathogenesis of disease. Furthermore, these investigations have identified novel translational opportunities to intercede in PD treatment. In this review we will highlight a select few recent findings in innate and adaptive immunity, and host pathogen interactions of PD at a micro-environmental level that may have profound impact on PD progression.

  16. Influenza pathogenesis: mechanisms of modulation by agent proteins

    Directory of Open Access Journals (Sweden)

    M. Yu. Shchelkanov

    2015-01-01

    Full Text Available Modern concepts of the influence of the proteins from viruses-etiological agents of flu – Influenzavirus A, B and C (Orthomyxoviridae – on the development of different elements of the main disease pathogenesis are analyzed in the review. In particular, the short description of life cycle of Influenza viruses is alleguered with special attention to those its stages which are capable to modulate pathogenetic mechanisms. The interrelation between the structure of hemagglutinin receptor-binding site and virus tropism as well as the influence of the receptor-destroying virus proteins on this phenomenon is described. The mechanism of suppression of interferon production in the infected cell by virus NS1 protein is presented. The induction of apoptosis by nonstructural PB1-F2 protein of Influenza A virusis described. 

  17. Therapeutic implications from the pathogenesis of Raynaud's phenomenon.

    Science.gov (United States)

    Herrick, Ariane L

    2017-07-01

    Raynaud's phenomenon (RP) can be either primary (idiopathic) or secondary to a number of different diseases/conditions, when vasopasm can be superimposed upon structural vascular abnormality or a hyperviscosity state and may then lead to severe ischaemia with tissue damage. Treatment must be tailored to the individual. Areas covered: This review discusses how increased understanding of the pathogenesis of RP has driven and is driving new approaches to therapy, and how we are now better able to predict which patients presenting with RP are likely to have an underlying disease requiring specific intervention. Medline searches (1946 to August 2016) were conducted for 'Raynaud's' in combination with relevant terms including different drugs. All papers identified were English language, with abstracts. Expert commentary: Randomised controlled trials of RP present particular challenges. The major aim must continue to be development of safe, effective treatments for patients across the spectrum of RP.

  18. Pathogenesis of the Metabolic Syndrome: Insights from Monogenic Disorders

    Directory of Open Access Journals (Sweden)

    Rinki Murphy

    2013-01-01

    Full Text Available Identifying rare human metabolic disorders that result from a single-gene defect has not only enabled improved diagnostic and clinical management of such patients, but also has resulted in key biological insights into the pathophysiology of the increasingly prevalent metabolic syndrome. Insulin resistance and type 2 diabetes are linked to obesity and driven by excess caloric intake and reduced physical activity. However, key events in the causation of the metabolic syndrome are difficult to disentangle from compensatory effects and epiphenomena. This review provides an overview of three types of human monogenic disorders that result in (1 severe, non-syndromic obesity, (2 pancreatic beta cell forms of early-onset diabetes, and (3 severe insulin resistance. In these patients with single-gene defects causing their exaggerated metabolic disorder, the primary defect is known. The lessons they provide for current understanding of the molecular pathogenesis of the common metabolic syndrome are highlighted.

  19. Pathogenesis of ankylosing spondylitis - recent advances and future directions.

    Science.gov (United States)

    Ranganathan, Vidya; Gracey, Eric; Brown, Matthew A; Inman, Robert D; Haroon, Nigil

    2017-06-01

    Over the past 5 years, advances in high-throughput techniques and studies involving large cohorts of patients have led to considerable advances in the identification of novel genetic associations and immune pathways involved in ankylosing spondylitis (AS). These discoveries include genes encoding cytokine receptors, transcription factors, signalling molecules and transport proteins. Although progress has been made in understanding the functions and potential pathogenic roles of some of these molecules, much work remains to be done to comprehend their complex interactions and therapeutic potential in AS. In this Review, we outline the current knowledge of AS pathogenesis, including genetic risk associations, HLA-B27-mediated pathology, perturbations in antigen-presentation pathways and the contribution of the type 3 immune response.

  20. Rosacea – new data on pathogenesis and treatment

    Directory of Open Access Journals (Sweden)

    Waldemar Placek

    2016-10-01

    Full Text Available Rosacea is a common dermatosis more prevalent in females, significantly impairing quality of life. Currently erythematous, papulo-pustular and phymatous subtypes are distinguished, which do not necessarily represent consecutive stages. Recent findings indicate in the pathogenesis of rosacea the role of the impaired innate immune system and vascular abnormalities. Additionally, the role of genetic and infectious factors is suggested. The therapy of rosacea is directed not only against inflammatory changes but also anti-parasitic. In topical treatment the most commonly used are metronidazole and azelaic acid. Other drugs are topical antibiotics, antiparasitic agents such as ivermectin and preparations directly influencing erythema. In more severe cases tetracyclines or macrolides are used, and in the most severe cases, isotretinoine. As ultraviolet light is a recognized trigger for rosacea, regular sunscreen use is necessary. Also, proper diet is indicated. Presently in the treatment of rosacea more and more techniques using different lights are employed.

  1. Molecular basis of pathogenesis of emerging viruses infecting aquatic animals

    Directory of Open Access Journals (Sweden)

    Lang Gui

    2018-01-01

    Full Text Available Aquatic vertebrates are very abundant in the world, and they are of tremendous importance in providing global food security and nutrition. However, emergent and resurgent viruses, such as ranavirus (e.g., Rana grylio virus, RGV and Andriasd avidianus ranavirus, ADRV, herpesvirus (e.g., Carassius carassius herpesvirus, CaHV, reovirus (e.g., grass carp reovirus 109, GCRV-109, Scophthal musmaximus reovirus, SMReV and Micropterus salmoides reovirus, MsReV, and rhabdovirus (e.g., Siniper cachuatsi rhabdovirus, SCRV and Scophthal musmaximus rhabdovirus, SMRV can cause severe diseases in aquaculture animals and wild lower vertebrates, such as frogs, giant salamanders, fish, and so on. Here, we will briefly describe the symptoms produced by the aforementioned viruses and the molecular basis of the virus–host interactions. This manuscript aims to provide an overview of viral diseases in lower vertebrates with an emphasis on visible symptomatic manifestations and pathogenesis.

  2. The role of platelets in the pathogenesis of systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Giuseppe A. eRamirez

    2012-06-01

    Full Text Available Systemic sclerosis (SSc is an inflammatory disease of unknown etiology characterized by widespread organ dysfunction due to fibrosis and ischemia. Its nebulous pathogenic background and the consequent absence of an etiological therapy prevent the adoption of satisfying treatment strategies, able to improve patients' quality of life and survival and stimulate researchers to identify a unifying pathogenic target. Platelets show a unique biological behavior, lying at the crossroads between vascular function, innate and adaptive immunity and regulation of cell proliferation. Consequently they are also emerging players in the pathogenesis of many inflammatory diseases, including systemic sclerosis. In the setting of SSc platelets are detectable in a persistent activated state, which is intimately linked to the concomitant presence of an injured endothelium and to the widespread activation of the innate and adaptive immune system. As a consistent circulating source of bioactive compounds platelets contribute to the development of many characteristic phenomena of SSc, such as fibrosis and impaired vascular tone.

  3. Pathogenesis of optic disc edema in raised intracranial pressure.

    Science.gov (United States)

    Hayreh, Sohan Singh

    2016-01-01

    Optic disc edema in raised intracranial pressure was first described in 1853. Ever since, there has been a plethora of controversial hypotheses to explain its pathogenesis. I have explored the subject comprehensively by doing basic, experimental and clinical studies. My objective was to investigate the fundamentals of the subject, to test the validity of the previous theories, and finally, based on all these studies, to find a logical explanation for the pathogenesis. My studies included the following issues pertinent to the pathogenesis of optic disc edema in raised intracranial pressure: the anatomy and blood supply of the optic nerve, the roles of the sheath of the optic nerve, of the centripetal flow of fluids along the optic nerve, of compression of the central retinal vein, and of acute intracranial hypertension and its associated effects. I found that, contrary to some previous claims, an acute rise of intracranial pressure was not quickly followed by production of optic disc edema. Then, in rhesus monkeys, I produced experimentally chronic intracranial hypertension by slowly increasing in size space-occupying lesions, in different parts of the brain. Those produced raised cerebrospinal fluid pressure (CSFP) and optic disc edema, identical to those seen in patients with elevated CSFP. Having achieved that, I investigated various aspects of optic disc edema by ophthalmoscopy, stereoscopic color fundus photography and fluorescein fundus angiography, and light microscopic, electron microscopic, horseradish peroxidase and axoplasmic transport studies, and evaluated the effect of opening the sheath of the optic nerve on the optic disc edema. This latter study showed that opening the sheath resulted in resolution of optic disc edema on the side of the sheath fenestration, in spite of high intracranial CSFP, proving that a rise of CSFP in the sheath was the essential pre-requisite for the development of optic disc edema. I also investigated optic disc edema with

  4. Mannose receptor may be involved in small ruminant lentivirus pathogenesis

    Directory of Open Access Journals (Sweden)

    Crespo Helena

    2012-05-01

    Full Text Available Abstract Thirty-one sheep naturally infected with small ruminant lentiviruses (SRLV of known genotype (A or B, and clinically affected with neurological disease, pneumonia or arthritis were used to analyse mannose receptor (MR expression (transcript levels and proviral load in virus target tissues (lung, mammary gland, CNS and carpal joints. Control sheep were SRLV-seropositive asymptomatic (n = 3, seronegative (n = 3 or with chronic listeriosis, pseudotuberculosis or parasitic cysts (n = 1 in each case. MR expression and proviral load increased with the severity of lesions in most analyzed organs of the SRLV infected sheep and was detected in the affected tissue involved in the corresponding clinical disease (CNS, lung and carpal joint in neurological disease, pneumonia and arthritis animal groups, respectively. The increased MR expression appeared to be SRLV specific and may have a role in lentiviral pathogenesis.

  5. Asthma in elite athletes: pathogenesis, diagnosis, differential diagnoses, and treatment

    DEFF Research Database (Denmark)

    Pedersen, Lars; Elers, Jimmi; Backer, Vibeke

    2011-01-01

    Elite athletes have a high prevalence of asthma and exercise-induced bronchoconstriction. Although respiratory symptoms can be suggestive of asthma, the diagnosis of asthma in elite athletes cannot be based solely on the presence or absence of symptoms; diagnosis should be based on objective...... measurements, such as the eucapnic voluntary hyperpnea test or exercise test. When considering that not all respiratory symptoms are due to asthma, other diagnoses should be considered. Certain regulations apply to elite athletes who require asthma medication for asthma. Knowledge of these regulations...... is essential when treating elite athletes. This article is aimed at physicians who diagnose and treat athletes with respiratory symptoms. It focuses on the pathogenesis of asthma and exercise-induced bronchoconstriction in elite athletes and how the diagnosis can be made. Furthermore, treatment of elite...

  6. Epigenetic mechanisms underlying the pathogenesis of neurogenetic diseases.

    Science.gov (United States)

    Qureshi, Irfan A; Mehler, Mark F

    2014-10-01

    There have been considerable advances in uncovering the complex genetic mechanisms that underlie nervous system disease pathogenesis, particularly with the advent of exome and whole genome sequencing techniques. The emerging field of epigenetics is also providing further insights into these mechanisms. Here, we discuss our understanding of the interplay that exists between genetic and epigenetic mechanisms in these disorders, highlighting the nascent field of epigenetic epidemiology-which focuses on analyzing relationships between the epigenome and environmental exposures, development and aging, other health-related phenotypes, and disease states-and next-generation research tools (i.e., those leveraging synthetic and chemical biology and optogenetics) for examining precisely how epigenetic modifications at specific genomic sites affect disease processes.

  7. Copper in microbial pathogenesis: meddling with the metal.

    Science.gov (United States)

    Samanovic, Marie I; Ding, Chen; Thiele, Dennis J; Darwin, K Heran

    2012-02-16

    Transition metals such as iron, zinc, copper, and manganese are essential for the growth and development of organisms ranging from bacteria to mammals. Numerous studies have focused on the impact of iron availability during bacterial and fungal infections, and increasing evidence suggests that copper is also involved in microbial pathogenesis. Not only is copper an essential cofactor for specific microbial enzymes, but several recent studies also strongly suggest that copper is used to restrict pathogen growth in vivo. Here, we review evidence that animals use copper as an antimicrobial weapon and that, in turn, microbes have developed mechanisms to counteract the toxic effects of copper. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Contribution of pertussis toxin to the pathogenesis of pertussis disease

    Science.gov (United States)

    Carbonetti, Nicholas H.

    2015-01-01

    Pertussis toxin (PT) is a multisubunit protein toxin secreted by Bordetella pertussis, the bacterial agent of the disease pertussis or whooping cough. PT in detoxified form is a component of all licensed acellular pertussis vaccines, since it is considered to be an important virulence factor for this pathogen. PT inhibits G protein-coupled receptor signaling through Gi proteins in mammalian cells, an activity that has led to its widespread use as a cell biology tool. But how does this activity of PT contribute to pertussis, including the severe respiratory symptoms of this disease? In this minireview, the contribution of PT to the pathogenesis of pertussis disease will be considered based on evidence from both human infections and animal model studies. Although definitive proof of the role of PT in humans is lacking, substantial evidence supports the idea that PT is a major contributor to pertussis pathology, including the severe respiratory symptoms associated with this disease. PMID:26394801

  9. Livedoid vasculopathy: A review of pathogenesis and principles of management.

    Science.gov (United States)

    Vasudevan, Biju; Neema, Shekhar; Verma, Rajesh

    2016-01-01

    Livedoid vasculopathy is a rare cutaneous disease manifesting as recurrent ulcers on the lower extremities. The ulceration results in atrophic, porcelain white scars termed as atrophie blanche. The pathogenesis is yet to be understood with the main mechanism being hypercoagulability and inflammation playing a secondary role. The important procoagulant factors include protein C and S deficiency, factor V Leiden mutation, antithrombin III deficiency, prothrombin gene mutation and hyperhomocysteinemia. Histopathology of livedoid vasculopathy is characterized by intraluminal thrombosis, proliferation of the endothelium and segmental hyalinization of dermal vessels. The treatment is multipronged with anti-thrombotic measures such as anti-platelet drugs, systemic anticoagulants and fibrinolytic therapy taking precedence over anti-inflammatory agents. Colchicine, hydroxychloroquine, vasodilators, intravenous immunoglobulin, folic acid, immunosuppressive therapy and supportive measures are also of some benefit. A multidisciplinary approach would go a long way in the management of these patients resulting in relief from pain and physical as well as psychological scarring.

  10. Type I Interferon in the Pathogenesis of Lupus

    Science.gov (United States)

    Crow, Mary K.

    2014-01-01

    Investigations of patients with systemic lupus erythematosus (SLE) have applied insights from studies of the innate immune response to define type I interferon (IFN-I), with IFN-α the dominant mediator, as central to the pathogenesis of this prototype systemic autoimmune disease. Genetic association data identify regulators of nucleic acid degradation and components of TLR-independent, endosomal TLR-dependent, and IFN-I signaling pathways as contributors to lupus disease susceptibility. Together with a gene expression signature characterized by IFNI-induced gene transcripts in lupus blood and tissue, those data support the conclusion that many of the immunologic and pathologic features of this disease are a consequence of a persistent self-directed immune reaction driven by IFN-I and mimicking a sustained anti-virus response. This expanding knowledge of the role of IFN-I and the innate immune response suggests candidate therapeutic targets that are being tested in lupus patients. PMID:24907379

  11. Further insights into the pathogenesis of primary hyperparathyroidism

    DEFF Research Database (Denmark)

    Rejnmark, Lars; Amstrup, Anne Kristine; Mollerup, Charlotte

    2013-01-01

    CONTEXT: The pathogenesis of primary hyperparathyroidism (PHPT) is largely unknown. OBJECTIVE: The objective of the study was to ascertain the plasma levels of calcium, PTH, and 25-hydroxyvitamin D (25OHD) as measured prior to a clinical diagnosis of PHPT. STUDY SUBJECTS: Within three population......, undiagnosed PHPT was present in 63% of the cases. Among those without PHPT at inclusion (n = 43), 55% had normocalcemic hyperparathyroidism (vs. 21% in the matched controls, P ... controls, 25OHD levels were lower in normocalcemic hyperparathyroidism but not in normoparathyroid hypercalcemia. An adenoma was removed from 78% of the cases with normocalcemic hyperparathyroidism, whereas 39% of the cases with normoparathyroid hypercalcemia had parathyroid hyperplasia (P = 0.02). Overlap...

  12. Dengue Virus Structural Differences That Correlate with Pathogenesis

    Science.gov (United States)

    Leitmeyer, Katrin C.; Vaughn, David W.; Watts, Douglas M.; Salas, Rosalba; Villalobos , Iris; de Chacon; Ramos, Celso; Rico-Hesse, Rebeca

    1999-01-01

    The understanding of dengue virus pathogenesis has been hampered by the lack of in vitro and in vivo models of disease. The study of viral factors involved in the production of severe dengue, dengue hemorrhagic fever (DHF), versus the more common dengue fever (DF), have been limited to indirect clinical and epidemiologic associations. In an effort to identify viral determinants of DHF, we have developed a method for comparing dengue type 2 genomes (reverse transcriptase PCR in six fragments) directly from patient plasma. Samples for comparison were selected from two previously described dengue type 2 genotypes which had been shown to be the cause of DF or DHF. When full genome sequences of 11 dengue viruses were analyzed, several structural differences were seen consistently between those associated with DF only and those with the potential to cause DHF: a total of six encoded amino acid charge differences were seen in the prM, E, NS4b, and NS5 genes, while sequence differences observed within the 5′ nontranslated region (NTR) and 3′ NTR were predicted to change RNA secondary structures. We hypothesize that the primary determinants of DHF reside in (i) amino acid 390 of the E protein, which purportedly alters virion binding to host cells; (ii) in the downstream loop (nucleotides 68 to 80) of the 5′ NTR, which may be involved in translation initiation; and (iii) in the upstream 300 nucleotides of the 3′ NTR, which may regulate viral replication via the formation of replicative intermediates. The significance of four amino acid differences in the nonstructural proteins NS4b and NS5, a presumed transport protein and the viral RNA polymerase, respectively, remains unknown. This new approach to the study of dengue virus genome differences should better reflect the true composition of viral RNA populations in the natural host and permit their association with pathogenesis. PMID:10233934

  13. An O antigen capsule modulates bacterial pathogenesis in Shigella sonnei.

    Science.gov (United States)

    Caboni, Mariaelena; Pédron, Thierry; Rossi, Omar; Goulding, David; Pickard, Derek; Citiulo, Francesco; MacLennan, Calman A; Dougan, Gordon; Thomson, Nicholas R; Saul, Allan; Sansonetti, Philippe J; Gerke, Christiane

    2015-03-01

    Shigella is the leading cause for dysentery worldwide. Together with several virulence factors employed for invasion, the presence and length of the O antigen (OAg) of the lipopolysaccharide (LPS) plays a key role in pathogenesis. S. flexneri 2a has a bimodal OAg chain length distribution regulated in a growth-dependent manner, whereas S. sonnei LPS comprises a monomodal OAg. Here we reveal that S. sonnei, but not S. flexneri 2a, possesses a high molecular weight, immunogenic group 4 capsule, characterized by structural similarity to LPS OAg. We found that a galU mutant of S. sonnei, that is unable to produce a complete LPS with OAg attached, can still assemble OAg material on the cell surface, but a galU mutant of S. flexneri 2a cannot. High molecular weight material not linked to the LPS was purified from S. sonnei and confirmed by NMR to contain the specific sugars of the S. sonnei OAg. Deletion of genes homologous to the group 4 capsule synthesis cluster, previously described in Escherichia coli, abolished the generation of the high molecular weight OAg material. This OAg capsule strongly affects the virulence of S. sonnei. Uncapsulated knockout bacteria were highly invasive in vitro and strongly inflammatory in the rabbit intestine. But, the lack of capsule reduced the ability of S. sonnei to resist complement-mediated killing and to spread from the gut to peripheral organs. In contrast, overexpression of the capsule decreased invasiveness in vitro and inflammation in vivo compared to the wild type. In conclusion, the data indicate that in S. sonnei expression of the capsule modulates bacterial pathogenesis resulting in balanced capabilities to invade and persist in the host environment.

  14. An O antigen capsule modulates bacterial pathogenesis in Shigella sonnei.

    Directory of Open Access Journals (Sweden)

    Mariaelena Caboni

    2015-03-01

    Full Text Available Shigella is the leading cause for dysentery worldwide. Together with several virulence factors employed for invasion, the presence and length of the O antigen (OAg of the lipopolysaccharide (LPS plays a key role in pathogenesis. S. flexneri 2a has a bimodal OAg chain length distribution regulated in a growth-dependent manner, whereas S. sonnei LPS comprises a monomodal OAg. Here we reveal that S. sonnei, but not S. flexneri 2a, possesses a high molecular weight, immunogenic group 4 capsule, characterized by structural similarity to LPS OAg. We found that a galU mutant of S. sonnei, that is unable to produce a complete LPS with OAg attached, can still assemble OAg material on the cell surface, but a galU mutant of S. flexneri 2a cannot. High molecular weight material not linked to the LPS was purified from S. sonnei and confirmed by NMR to contain the specific sugars of the S. sonnei OAg. Deletion of genes homologous to the group 4 capsule synthesis cluster, previously described in Escherichia coli, abolished the generation of the high molecular weight OAg material. This OAg capsule strongly affects the virulence of S. sonnei. Uncapsulated knockout bacteria were highly invasive in vitro and strongly inflammatory in the rabbit intestine. But, the lack of capsule reduced the ability of S. sonnei to resist complement-mediated killing and to spread from the gut to peripheral organs. In contrast, overexpression of the capsule decreased invasiveness in vitro and inflammation in vivo compared to the wild type. In conclusion, the data indicate that in S. sonnei expression of the capsule modulates bacterial pathogenesis resulting in balanced capabilities to invade and persist in the host environment.

  15. Pathogenesis study of enterovirus 71 infection in rhesus monkeys.

    Science.gov (United States)

    Zhang, Ying; Cui, Wei; Liu, Longding; Wang, Jingjing; Zhao, Hongling; Liao, Yun; Na, Ruixiong; Dong, Chenghong; Wang, Lichun; Xie, Zhongping; Gao, Jiahong; Cui, Pingfang; Zhang, Xuemei; Li, Qihan

    2011-09-01

    Enterovirus 71 (EV71), a major pathogen that is responsible for causing hand-foot-and-mouth disease (HFMD) worldwide, is a member of the Human Enterovirus species A, family Picornaviridae. HFMD that is caused by EV71 is usually characterized by vesicular lesions on the skin and oral mucosa and high morbidity rates in children; additionally, occasional fatal cases have been reported involving brainstem encephalitis and myelitis associated with cardiopulmonary collapse. Although viral pathogenesis in humans is unclear, previous animal studies have indicated that EV71, inoculated via various routes, is capable of targeting and injuring the central nervous system (CNS). We report here the pathogenic process of systemic EV71 infection in rhesus monkeys after inoculation via intracerebral, intravenous, respiratory and digestive routes. Infection with EV71 via these routes resulted in different rates of targeting to and injury of the CNS. Intracerebral inoculation resulted in pulmonary edema and hemorrhage, along with impairment of neurons. However, intravenous and respiratory inoculations resulted in a direct infection of the CNS, accompanied by obvious inflammation of lung tissue, as shown by impairment of the alveoli structure and massive cellular infiltration around the terminal bronchioles and small vessels. These pathological changes were associated with a peak of viremia and dynamic viral distribution in organs over time in the infected monkeys. Our results suggest that the rhesus monkey model may be used to study not only the basic pathogenesis of EV71 viral infections, but also to examine clinical features, such as neurological lesions, in the CNS and pathological changes in associated organs.

  16. Study of camelpox virus pathogenesis in athymic nude mice.

    Directory of Open Access Journals (Sweden)

    Sophie Duraffour

    Full Text Available Camelpox virus (CMLV is the closest known orthopoxvirus genetically related to variola virus. So far, CMLV was restricted to camelids but, recently, three human cases of camelpox have been described in India, highlighting the need to pursue research on its pathogenesis, which has been hampered by the lack of small animal models. Here, we confirm that NMRI immunocompetent mice are resistant to intranasal (i.n. CMLV infection. However, we demonstrate that CMLV induced a severe disease following i.n. challenge of athymic nude mice, which was accompanied with a failure in gaining weight, leading to euthanasia of the animals. On the other hand, intracutaneous (i.c. infection resulted in disease development without impacting the body weight evolution. CMLV replication in tissues and body fluids was confirmed in the two models. We further analyzed innate immune and B cell responses induced in the spleen and draining lymph nodes after exposure to CMLV. In both models, strong increases in CD11b(+F4/80(+ macrophages were seen in the spleen, while neutrophils, NK and B cell responses varied between the routes of infection. In the lymph nodes, the magnitude of CD11c(+CD8α(+ lymphoid and CD11c(+CD11b(+ myeloid dendritic cell responses increased in i.n. challenged animals. Analysis of cytokine profiles revealed significant increases of interleukin (IL-6 and IL-18 in the sera of infected animals, while those of other cytokines were similar to uninfected controls. The efficacy of two antivirals (cidofovir or HPMPC, and its 2, 6-diaminopurine analog was evaluated in both models. HPMPC was the most effective molecule affording 100% protection from morbidity. It appeared that both treatments did not affect immune cell responses or cytokine expression. In conclusion, we demonstrated that immunodeficient mice are permissive for CMLV propagation. These results provide a basis for studying the pathogenesis of CMLV, as well as for evaluating potential antiviral

  17. MicroRNAs in inflammatory bowel disease--pathogenesis, diagnostics and therapeutics

    DEFF Research Database (Denmark)

    Coskun, Mehmet; Bjerrum, Jacob Tveiten; Seidelin, Jakob Benedict

    2012-01-01

    The pathogenesis of inflammatory bowel disease (IBD) is complex and largely unknown. Until recently, research has focused on the study of protein regulators in inflammation to reveal the cellular and molecular networks in the pathogenesis of IBD. However, in the last few years, new and promising...... diagnosis of IBD, and in the development of personalized therapies. Here, we provide a short review of the current state-of-the-art of miRNAs in IBD pathogenesis, diagnostics and therapeutics....

  18. Pathogenesis of Arterial Hypertension in the Pregnant Females

    Directory of Open Access Journals (Sweden)

    N. V. Kabanova

    2007-01-01

    Full Text Available Objective: to study the pathogenetic mechanisms of development of arterial hypertension (AH in pregnant females and to develop clinical and laboratory criteria that may determine the type of AH in them on the basis of a comprehensive study of hemostatic parameters.Subjects and materials. A hundred and seventy-two pregnant females with AH (a study group and 54 healthy pregnant ones (a control group were examined in the third trimester of pregnancy. In all, biochemical blood and urinary analyses determining the concentrations of urea, creatinine, sodium, and protein, followed by the calculation of partial renal functions, were made by the unified method. Enzyme radioimmunoassay was used to determine plasma renin activity. The concentrations of angiotensin-2, aldosterone, thyroxine-binding globulin, testosterone, estriol, estradiol, progesterone, and placental lactogen were measured by enzyme radioimmunoassay. Enzyme immunoassay was employed to estimate the levels of prostanoids. The activity of membranous lipid peroxidation was assessed by the level of its metabolites; the state of the antioxidative system was evaluated. The degree of endogenous intoxication was determined. Central hemodynamic parameters were estimated by tetrapolar rheography. Statistical processing used IBM 384/387 and the statistical package «Stadia».Results. Arterial hypertension caused by pregnancy was ascertained to involve pathogenetical-ly different types: low-, normal-, and high-renin ones. According to its type, the mechanisms of AH were variable. The pressor mechanisms in the pathogenesis of AH were sodium and water retention and elevated total peripheral resistance due to the activation of extrarenal (placental hormonal imbalance, increases in cortisol and angiotensin-2 and renal (increased ARP pressor systems. The renal depressor system was presented by prostaglandins, the extrarenal depressor system by thyroxine.Conclusion. Activation of the extrarenal depressor

  19. New Aspects of the Pathogenesis of Canine Distemper Leukoencephalitis

    Science.gov (United States)

    Lempp, Charlotte; Spitzbarth, Ingo; Puff, Christina; Cana, Armend; Kegler, Kristel; Techangamsuwan, Somporn; Baumgärtner, Wolfgang; Seehusen, Frauke

    2014-01-01

    Canine distemper virus (CDV) is a member of the genus morbillivirus, which is known to cause a variety of disorders in dogs including demyelinating leukoencephalitis (CDV-DL). In recent years, substantial progress in understanding the pathogenetic mechanisms of CDV-DL has been made. In vivo and in vitro investigations provided new insights into its pathogenesis with special emphasis on axon-myelin-glia interaction, potential endogenous mechanisms of regeneration, and astroglial plasticity. CDV-DL is characterized by lesions with a variable degree of demyelination and mononuclear inflammation accompanied by a dysregulated orchestration of cytokines as well as matrix metalloproteinases and their inhibitors. Despite decades of research, several new aspects of the neuropathogenesis of CDV-DL have been described only recently. Early axonal damage seems to represent an initial and progressive lesion in CDV-DL, which interestingly precedes demyelination. Axonopathy may, thus, function as a potential trigger for subsequent disturbed axon-myelin-glia interactions. In particular, the detection of early axonal damage suggests that demyelination is at least in part a secondary event in CDV-DL, thus challenging the dogma of CDV as a purely primary demyelinating disease. Another unexpected finding refers to the appearance of p75 neurotrophin (NTR)-positive bipolar cells during CDV-DL. As p75NTR is a prototype marker for immature Schwann cells, this finding suggests that Schwann cell remyelination might represent a so far underestimated endogenous mechanism of regeneration, though this hypothesis still remains to be proven. Although it is well known that astrocytes represent the major target of CDV infection in CDV-DL, the detection of infected vimentin-positive astrocytes in chronic lesions indicates a crucial role of this cell population in nervous distemper. While glial fibrillary acidic protein represents the characteristic intermediate filament of mature astrocytes

  20. [Pathogenesis and therapy of hydronephrosis after hematopoietic stem cell transplantation].

    Science.gov (United States)

    Yu, Lu-ping; Xu, Tao; Huang, Xiao-bo; Wang, Xiao-feng

    2014-08-18

    To investigate the pathogenesis and therapy of hydronephrosis after hematopoietic stem cell transplantation (HSCT). From March 2004 to March 2014, 23 patients with hydronephrosis after HSCT were identified. With these data, the pathogenesis of hydronephrosis after HSCT were analyzed. According to the surgical intervention of hydronephrosis and ureteral dialation of ureteral stricture, the patients were divided into two groups, rank-sum test and exact probability test were used to evaluate whether there were significant differences in the time of hemorrhagic cystitis (HC) occurred, ureteritis and viremia. HC, ureteritis, ureteral stenosis were all the causes of hydronephrosis after HSCT. In this study, 69.6% (16/23) of the patients suffered from HSCT were cured by conservative treatment, 30.4% (7/23) by surgical intervention, and 13.0% (3/23) by insertion DJ stent or nephrostomy.Of the patients [17.4% (4/23)] who suffered ureteral stenosis, 2 were cured after the balloon dialation of ureter, 1 needed DJ tube long-term insertion, and 1 was still followed-up. rank-sum test and exact probability test results showed that the patients who needed surgical intervention might suffer from HC later than other patients, and their incidences of viremia and ureteritis were higher, but the differences between the two groups were not statistically significant (P = 0.524, P = 0.169, and P = 0.124, respectively). The results also showed that the ureteritis incidences of the patients who suffered from ureteral stricture and needed ureteral dialation were higher than that of the other patients, and the difference between the two groups was statistically significant (P = 0.024). The patients who needed ureteral dialation suffered from HC later and their incidences of viremia was higher, but the differences between the two groups were not statistically significant (P = 0.73 and P = 0.27). HC, ureteritis and ureteral stenosis may cause hydronephrosis after HSCT. Patients may treated by

  1. New aspects of the pathogenesis of canine distemper leukoencephalitis.

    Science.gov (United States)

    Lempp, Charlotte; Spitzbarth, Ingo; Puff, Christina; Cana, Armend; Kegler, Kristel; Techangamsuwan, Somporn; Baumgärtner, Wolfgang; Seehusen, Frauke

    2014-07-02

    Canine distemper virus (CDV) is a member of the genus morbillivirus, which is known to cause a variety of disorders in dogs including demyelinating leukoencephalitis (CDV-DL). In recent years, substantial progress in understanding the pathogenetic mechanisms of CDV-DL has been made. In vivo and in vitro investigations provided new insights into its pathogenesis with special emphasis on axon-myelin-glia interaction, potential endogenous mechanisms of regeneration, and astroglial plasticity. CDV-DL is characterized by lesions with a variable degree of demyelination and mononuclear inflammation accompanied by a dysregulated orchestration of cytokines as well as matrix metalloproteinases and their inhibitors. Despite decades of research, several new aspects of the neuropathogenesis of CDV-DL have been described only recently. Early axonal damage seems to represent an initial and progressive lesion in CDV-DL, which interestingly precedes demyelination. Axonopathy may, thus, function as a potential trigger for subsequent disturbed axon-myelin-glia interactions. In particular, the detection of early axonal damage suggests that demyelination is at least in part a secondary event in CDV-DL, thus challenging the dogma of CDV as a purely primary demyelinating disease. Another unexpected finding refers to the appearance of p75 neurotrophin (NTR)-positive bipolar cells during CDV-DL. As p75NTR is a prototype marker for immature Schwann cells, this finding suggests that Schwann cell remyelination might represent a so far underestimated endogenous mechanism of regeneration, though this hypothesis still remains to be proven. Although it is well known that astrocytes represent the major target of CDV infection in CDV-DL, the detection of infected vimentin-positive astrocytes in chronic lesions indicates a crucial role of this cell population in nervous distemper. While glial fibrillary acidic protein represents the characteristic intermediate filament of mature astrocytes

  2. New Aspects of the Pathogenesis of Canine Distemper Leukoencephalitis

    Directory of Open Access Journals (Sweden)

    Charlotte Lempp

    2014-07-01

    Full Text Available Canine distemper virus (CDV is a member of the genus morbillivirus, which is known to cause a variety of disorders in dogs including demyelinating leukoencephalitis (CDV-DL. In recent years, substantial progress in understanding the pathogenetic mechanisms of CDV-DL has been made. In vivo and in vitro investigations provided new insights into its pathogenesis with special emphasis on axon-myelin-glia interaction, potential endogenous mechanisms of regeneration, and astroglial plasticity. CDV-DL is characterized by lesions with a variable degree of demyelination and mononuclear inflammation accompanied by a dysregulated orchestration of cytokines as well as matrix metalloproteinases and their inhibitors. Despite decades of research, several new aspects of the neuropathogenesis of CDV-DL have been described only recently. Early axonal damage seems to represent an initial and progressive lesion in CDV-DL, which interestingly precedes demyelination. Axonopathy may, thus, function as a potential trigger for subsequent disturbed axon-myelin-glia interactions. In particular, the detection of early axonal damage suggests that demyelination is at least in part a secondary event in CDV-DL, thus challenging the dogma of CDV as a purely primary demyelinating disease. Another unexpected finding refers to the appearance of p75 neurotrophin (NTR-positive bipolar cells during CDV-DL. As p75NTR is a prototype marker for immature Schwann cells, this finding suggests that Schwann cell remyelination might represent a so far underestimated endogenous mechanism of regeneration, though this hypothesis still remains to be proven. Although it is well known that astrocytes represent the major target of CDV infection in CDV-DL, the detection of infected vimentin-positive astrocytes in chronic lesions indicates a crucial role of this cell population in nervous distemper. While glial fibrillary acidic protein represents the characteristic intermediate filament of mature

  3. CREB Signaling Is Involved in Rett Syndrome Pathogenesis.

    Science.gov (United States)

    Bu, Qian; Wang, Anxin; Hamzah, Hamdi; Waldman, Alex; Jiang, Keer; Dong, Qiping; Li, Ronghui; Kim, Jason; Turner, Daniel; Chang, Qiang

    2017-03-29

    Rett syndrome (RTT) is a debilitating neurodevelopmental disorder caused by mutations in the MECP2 gene. To facilitate the study of cellular mechanisms in human cells, we established several human stem cell lines: human embryonic stem cell (hESC) line carrying the common T158M mutation ( MECP2 T158M/T158M ), hESC line expressing no MECP2 ( MECP2-KO ), congenic pair of wild-type and mutant RTT patient-specific induced pluripotent stem cell (iPSC) line carrying the V247fs mutation (V247fs-WT and V247fs-MT), and iPSC line in which the V247fs mutation was corrected by CRISPR/Cas9-based genome editing (V247fs-MT-correction). Detailed analyses of forebrain neurons differentiated from these human stem cell lines revealed genotype-dependent quantitative phenotypes in neurite growth, dendritic complexity, and mitochondrial function. At the molecular level, we found a significant reduction in the level of CREB and phosphorylated CREB in forebrain neurons differentiated from MECP2 T158M/T158M , MECP2-KO , and V247fs-MT stem cell lines. Importantly, overexpression of CREB or pharmacological activation of CREB signaling in those forebrain neurons rescued the phenotypes in neurite growth, dendritic complexity, and mitochondrial function. Finally, pharmacological activation of CREB in the female Mecp2 heterozygous mice rescued several behavioral defects. Together, our study establishes a robust in vitro platform for consistent quantitative evaluation of genotype-dependent RTT phenotypes, reveals a previously unappreciated role of CREB signaling in RTT pathogenesis, and identifies a potential therapeutic target for RTT. SIGNIFICANCE STATEMENT Our study establishes a robust human stem cell-based platform for consistent quantitative evaluation of genotype-dependent Rett syndrome (RTT) phenotypes at the cellular level. By providing the first evidence that enhancing cAMP response element binding protein signaling can alleviate RTT phenotypes both in vitro and in vivo , we reveal a

  4. 'Omics investigations of HIV and SIV pathogenesis and innate immunity.

    Science.gov (United States)

    Palermo, Robert E; Fuller, Deborah H

    2013-01-01

    In the 30 years since the advent of the AIDS epidemic, the biomedical community has put forward a battery of molecular therapies that are based on the accumulated knowledge of a limited number of viral targets. Despite these accomplishments, the community still confronts unanswered foundational questions about HIV infection. What are the cellular or biomolecular processes behind HIV pathogenesis? Can we elucidate the characteristics that distinguish those individuals who are naturally resistant to either infection or disease progression? The discovery of simian immunodeficiency viruses (SIVs) and the ensuing development of in vivo, nonhuman primate (NHP) infection models was a tremendous advance, especially in abetting the exploration of vaccine strategies. And while there have been numerous NHP infection models and vaccine trials performed, fundamental questions remain regarding host-virus interactions and immune correlates of protection. These issues are, perhaps, most starkly illustrated with the appreciation that many species of African nonhuman primates are naturally infected with strains of SIV that do not cause any appreciable disease while replicating to viral loads that match or exceed those seen with pathogenic SIV infections in Asian species of nonhuman primates. The last decade has seen the establishment of high-throughput molecular profiling tools, such as microarrays for transcriptomics, SNP arrays for genome features, and LC-MS techniques for proteins or metabolites. These provide the capacity to interrogate a biological model at a comprehensive, systems level, in contrast to historical approaches that characterized a few genes or proteins in an experiment. These methods have already had revolutionary impacts in understanding human diseases originating within the host genome such as genetic disorders and cancer, and the methods are finding increasing application in the context of infectious disease. We will provide a review of the use of such 'omics

  5. Pulmonary hypertension in rheumatic diseases: epidemiology and pathogenesis.

    Science.gov (United States)

    Shahane, Anupama

    2013-07-01

    The focus of this review is to increase awareness of pulmonary arterial hypertension (PAH) in patients with rheumatic diseases. Epidemiology and pathogenesis of PAH in rheumatic diseases is reviewed, with recommendations for early screening and diagnosis and suggestion of possible role of immunosuppressive therapy in treatment for PAH in rheumatic diseases. A MEDLINE search for articles published between January 1970 and June 2012 was conducted using the following keywords: pulmonary hypertension, scleroderma, systemic sclerosis, pulmonary arterial hypertension, connective tissues disease, systemic lupus erythematosus, mixed connective tissue disease, rheumatoid arthritis, Sjogren's syndrome, vasculitis, sarcoidosis, inflammatory myopathies, dermatomyositis, ankylosing spondylitis, spondyloarthropathies, diagnosis and treatment. Pathogenesis and disease burden of PAH in rheumatic diseases was highlighted, with emphasis on early consideration and workup of PAH. Screening recommendations and treatment were touched upon. PAH is most commonly seen in systemic sclerosis and may be seen in isolation or in association with interstitial lung disease. Several pathophysiologic processes have been identified including an obliterative vasculopathy, veno-occlusive disease, formation of microthrombi and pulmonary fibrosis. PAH in systemic lupus erythematosus is associated with higher prevalence of antiphospholipid and anticardiolipin antibodies and the presence of Raynaud's phenomenon. Endothelial proliferation with vascular remodeling, abnormal coagulation with thrombus formation and immune-mediated vasculopathy are the postulated mechanisms. Improvement with immunosuppressive medications has been reported. Pulmonary fibrosis, extrinsic compression of pulmonary arteries and granulomatous vasculitis have been reported in patients with sarcoidosis. Intimal and medial hyperplasia with luminal narrowing has been observed in Sjogren's syndrome, mixed connective tissue disease and

  6. Pilonidal sinus disease - Etiological factors, pathogenesis and clinical features

    Directory of Open Access Journals (Sweden)

    Kazim Duman

    2016-12-01

    Full Text Available and lsquo;Pilonidal sinus' disease, which is most commonly seen in reproductive populations, such as young adults - mostly in males who are in their twenties - is actually a controversial disease in that there is no consensus on its many facets. It is sometimes seen as an infected abscess draining from an opening or a lesion extending to the perineum. It may also present as a draining fistula opening to skin. In terms of etiological factors, various theories (main theories being congenital and acquired have been established since it was first described, no universal understanding achieved. A long and significant post-operative care period with different lengths of recovery depending on the type of operation are quite prevalent with regards to recurrence and complication status. In order to prevent recurrence and improve the quality of life, etiological and predisposing factors as well as clinical features of sacrococcygeal pilonidal disease should be well known, a detailed differential diagnosis should be made, and a suitable and timely intervention should be performed. It was aimed here to explain the etiological factors, pathogenesis and clinical features of the disease that may present with various clinical symptoms. [Arch Clin Exp Surg 2016; 5(4.000: 228-232

  7. Huntington Disease: Linking Pathogenesis to the Development of Experimental Therapeutics.

    Science.gov (United States)

    Mestre, Tiago A; Sampaio, Cristina

    2017-02-01

    Huntington disease (HD) is an autosomal dominant neurodegenerative condition caused by a CAG trinucleotide expansion in the huntingtin gene. At present, the HD field is experiencing exciting times with the assessment for the first time in human subjects of interventions aimed at core disease mechanisms. Out of a portfolio of interventions that claim a potential disease-modifying effect in HD, the target huntingtin has more robust validation. In this review, we discuss the spectrum of huntingtin-lowering therapies that are currently being considered. We provide a critical appraisal of the validation of huntingtin as a drug target, describing the advantages, challenges, and limitations of the proposed therapeutic interventions. The development of these new therapies relies strongly on the knowledge of HD pathogenesis and the ability to translate this knowledge into validated pharmacodynamic biomarkers. Altogether, the goal is to support a rational drug development that is ethical and cost-effective. Among the pharmacodynamic biomarkers under development, the quantification of mutant huntingtin in the cerebral spinal fluid and PET imaging targeting huntingtin or phosphodiesterase 10A deserve special attention. Huntingtin-lowering therapeutics are eagerly awaited as the first interventions that may be able to change the course of HD in a meaningful way.

  8. Differential Virulence and Pathogenesis of West Nile Viruses

    Directory of Open Access Journals (Sweden)

    Emilie Donadieu

    2013-11-01

    Full Text Available West Nile virus (WNV is a neurotropic flavivirus that cycles between mosquitoes and birds but that can also infect humans, horses, and other vertebrate animals. In most humans, WNV infection remains subclinical. However, 20%–40% of those infected may develop WNV disease, with symptoms ranging from fever to meningoencephalitis. A large variety of WNV strains have been described worldwide. Based on their genetic differences, they have been classified into eight lineages; the pathogenic strains belong to lineages 1 and 2. Ten years ago, Beasley et al. (2002 found that dramatic differences exist in the virulence and neuroinvasion properties of lineage 1 and lineage 2 WNV strains. Further insights on how WNV interacts with its hosts have recently been gained; the virus acts either at the periphery or on the central nervous system (CNS, and these observed differences could help explain the differential virulence and neurovirulence of WNV strains. This review aims to summarize the current state of knowledge on factors that trigger WNV dissemination and CNS invasion as well as on the inflammatory response and CNS damage induced by WNV. Moreover, we will discuss how WNV strains differentially interact with the innate immune system and CNS cells, thus influencing WNV pathogenesis.

  9. Proteome catalog of Zymoseptoria tritici captured during pathogenesis in wheat.

    Science.gov (United States)

    Ben M'Barek, Sarrah; Cordewener, Jan H G; van der Lee, Theo A J; America, Antoine H P; Mirzadi Gohari, Amir; Mehrabi, Rahim; Hamza, Sonia; de Wit, Pierre J G M; Kema, Gerrit H J

    2015-06-01

    Zymoseptoria tritici is an economically important pathogen of wheat. However, the molecular basis of pathogenicity on wheat is still poorly understood. Here, we present a global survey of the proteins secreted by this fungus in the apoplast of resistant (cv. Shafir) and susceptible (cv. Obelisk) wheat cultivars after inoculation with reference Z. tritici strain IPO323. The fungal proteins present in apoplastic fluids were analyzed by gel electrophoresis and by data-independent acquisition liquid chromatography/mass spectrometry (LC/MS(E)) combined with data-dependent acquisition LC-MS/MS. Subsequent mapping mass spectrometry-derived peptide sequence data against the genome sequence of strain IPO323 identified 665 peptides in the MS(E) and 93 in the LC-MS/MS mode that matched to 85 proteins. The identified fungal proteins, including cell-wall degrading enzymes and proteases, might function in pathogenicity, but the functions of many remain unknown. Most fungal proteins accumulated in cv. Obelisk at the onset of necrotrophy. This inventory provides an excellent basis for future detailed studies on the role of these genes and their encoded proteins during pathogenesis in wheat. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. The role of astrocytes in multiple sclerosis pathogenesis.

    Science.gov (United States)

    Guerrero-García, J J

    2017-09-25

    Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system (CNS), in which astrocytes play an important role as CNS immune cells. However, the activity of astrocytes as antigen-presenting cells (APC) continues to be subject to debate. This review analyses the existing evidence on the participation of astrocytes in CNS inflammation in MS and on several mechanisms that modify astrocyte activity in the disease. Astrocytes play a crucial role in the pathogenesis of MS because they express toll-like receptors (TLR) and major histocompatibility complex (MHC) classI andII. In addition, astrocytes participate in regulating the blood-brain barrier (BBB) and in modulating T cell activity through the production of cytokines. Future studies should focus on the role of astrocytes in order to find new therapeutic targets for the treatment of MS. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Thrombotic thrombocytopenic purpura: pathogenesis, diagnosis and potential novel therapeutics.

    Science.gov (United States)

    Saha, M; McDaniel, J K; Zheng, X L

    2017-10-01

    Thrombotic thrombocytopenic purpura (TTP), a potentially fatal clinical syndrome, is primarily caused by autoantibodies against the von Willebrand factor (VWF)-cleaving metalloprotease ADAMTS-13. In general, severe deficiency of plasma ADAMTS-13 activity ( 10 IU dL -1 ) in a similar clinical context supports an alternative diagnosis such as atypical hemolytic uremic syndrome (aHUS) or other types of TMA. Prompt differentiation of TTP from other causes of TMA is crucial for the initiation of an appropriate therapy to reduce morbidity and mortality. Although plasma infusion is often sufficient for prophylaxis or treatment of hereditary TTP due to ADAMTS-13 mutations, daily therapeutic plasma exchange remains the initial treatment of choice for acquired TTP with demonstrable autoantibodies. Immunomodulatory therapies, including corticosteroids, rituximab, vincristine, cyclosporine, cyclophosphamide and splenectomy, etc., should be considered to eliminate autoantibodies for a sustained remission. Other emerging therapeutic modalities, including recombinant ADAMTS-13, adeno-associated virus (AAV) 8-mediated gene therapy, platelet-delivered ADAMTS-13, and antagonists targeting the interaction between platelet glycoprotein 1b and VWF are under investigation. This review highlights the recent progress in our understanding of the pathogenesis and diagnosis of, and current and potential novel therapies for, hereditary and acquired TTP. © 2017 International Society on Thrombosis and Haemostasis.

  12. Candida albicans secreted aspartyl proteinases in virulence and pathogenesis.

    Science.gov (United States)

    Naglik, Julian R; Challacombe, Stephen J; Hube, Bernhard

    2003-09-01

    Candida albicans is the most common fungal pathogen of humans and has developed an extensive repertoire of putative virulence mechanisms that allows successful colonization and infection of the host under suitable predisposing conditions. Extracellular proteolytic activity plays a central role in Candida pathogenicity and is produced by a family of 10 secreted aspartyl proteinases (Sap proteins). Although the consequences of proteinase secretion during human infections is not precisely known, in vitro, animal, and human studies have implicated the proteinases in C. albicans virulence in one of the following seven ways: (i) correlation between Sap production in vitro and Candida virulence, (ii) degradation of human proteins and structural analysis in determining Sap substrate specificity, (iii) association of Sap production with other virulence processes of C. albicans, (iv) Sap protein production and Sap immune responses in animal and human infections, (v) SAP gene expression during Candida infections, (vi) modulation of C. albicans virulence by aspartyl proteinase inhibitors, and (vii) the use of SAP-disrupted mutants to analyze C. albicans virulence. Sap proteins fulfill a number of specialized functions during the infective process, which include the simple role of digesting molecules for nutrient acquisition, digesting or distorting host cell membranes to facilitate adhesion and tissue invasion, and digesting cells and molecules of the host immune system to avoid or resist antimicrobial attack by the host. We have critically discussed the data relevant to each of these seven criteria, with specific emphasis on how this proteinase family could contribute to Candida virulence and pathogenesis.

  13. Pathogenesis of and unifying hypothesis for idiopathic pouchitis.

    LENUS (Irish Health Repository)

    Coffey, J Calvin

    2009-04-01

    Ileal pouch-anal anastomosis is the procedure of choice in the surgical management of refractory ulcerative colitis. Pouchitis affects up to 60% of patients following ileal pouch-anal anastomosis for ulcerative colitis. It overlaps significantly with ulcerative colitis such that improvements in our understanding of one will impact considerably on the other. The symptoms are distressing and impinge significantly on patients\\' quality of life. Despite 30 years of scientific and clinical investigation, the pathogenesis of pouchitis is unknown; however, recent advances in molecular and cell biology make a synergistic hypothesis possible. This hypothesis links interaction between epithelial metaplasia, changes in luminal bacteria (in particular sulfate-reducing bacteria), and altered mucosal immunity. Specifically, colonic metaplasia supports colonization by sulfate-reducing bacteria that produce hydrogen sulfide. This causes mucosal depletion and subsequent inflammation. Although in most cases antibiotics lead to bacterial clearance and symptom resolution, immunogenetic subpopulations can develop a chronic refractory variant of pouchitis. The aims of this paper are to discuss proposed pathogenic mechanisms and to describe a novel mechanism that combines many hypotheses and explains several aspects of pouchitis. The implications for the management of both pouchitis and ulcerative colitis are discussed.

  14. Pathogenesis of and unifying hypothesis for idiopathic pouchitis.

    LENUS (Irish Health Repository)

    Coffey, J Calvin

    2012-02-01

    Ileal pouch-anal anastomosis is the procedure of choice in the surgical management of refractory ulcerative colitis. Pouchitis affects up to 60% of patients following ileal pouch-anal anastomosis for ulcerative colitis. It overlaps significantly with ulcerative colitis such that improvements in our understanding of one will impact considerably on the other. The symptoms are distressing and impinge significantly on patients\\' quality of life. Despite 30 years of scientific and clinical investigation, the pathogenesis of pouchitis is unknown; however, recent advances in molecular and cell biology make a synergistic hypothesis possible. This hypothesis links interaction between epithelial metaplasia, changes in luminal bacteria (in particular sulfate-reducing bacteria), and altered mucosal immunity. Specifically, colonic metaplasia supports colonization by sulfate-reducing bacteria that produce hydrogen sulfide. This causes mucosal depletion and subsequent inflammation. Although in most cases antibiotics lead to bacterial clearance and symptom resolution, immunogenetic subpopulations can develop a chronic refractory variant of pouchitis. The aims of this paper are to discuss proposed pathogenic mechanisms and to describe a novel mechanism that combines many hypotheses and explains several aspects of pouchitis. The implications for the management of both pouchitis and ulcerative colitis are discussed.

  15. Epidemiology and pathogenesis of osteonecrosis of the jaw.

    Science.gov (United States)

    Reid, Ian R; Cornish, Jillian

    2011-11-29

    Osteonecrosis of the jaw (ONJ) is defined as exposed bone in the oral cavity that persists despite appropriate therapy. Over the past decade, ONJ has been reported in about 5% of patients with cancer receiving high-dose intravenous bisphosphonates, and more recently in similar patients treated with denosumab, another potent inhibitor of osteoclastic bone resorption. The condition has also been described in patients treated with bisphosphonates for benign diseases, such as osteoporosis, but whether bisphosphonates or denosumab increase the incidence above that seen in untreated patients of comparable age and frailty is yet to be established. The pathogenesis of ONJ is uncertain: the toxic effects of bisphosphonates in a wide variety of cells could increase susceptibility to infections in the oral cavity or impair mucosal healing, and denosumab might interfere with monocyte and macrophage function. Local osteolysis is an important defense against infection on bone surfaces that is blocked by both bisphosphonates and denosumab. Preventive dentistry prior to high-dose antiresorptive therapy is a critical measure in cancer patients, but is not usually justified in patients with osteoporosis. The management of established ONJ lesions is problematic: the greatest success seems to come from vigorous antimicrobial therapy with judicious use of surgical debridement.

  16. Peroxiredoxin 6, a novel player in the pathogenesis of diabetes.

    Science.gov (United States)

    Pacifici, Francesca; Arriga, Roberto; Sorice, Gian Pio; Capuani, Barbara; Scioli, Maria Giovanna; Pastore, Donatella; Donadel, Giulia; Bellia, Alfonso; Caratelli, Sara; Coppola, Andrea; Ferrelli, Francesca; Federici, Massimo; Sconocchia, Giuseppe; Tesauro, Manfredi; Sbraccia, Paolo; Della-Morte, David; Giaccari, Andrea; Orlandi, Augusto; Lauro, Davide

    2014-10-01

    Enhanced oxidative stress contributes to the pathogenesis of diabetes and its complications. Peroxiredoxin 6 (PRDX6) is a key regulator of cellular redox balance, with the peculiar ability to neutralize peroxides, peroxynitrite, and phospholipid hydroperoxides. In the current study, we aimed to define the role of PRDX6 in the pathophysiology of type 2 diabetes (T2D) using PRDX6 knockout (-/-) mice. Glucose and insulin responses were evaluated respectively by intraperitoneal glucose and insulin tolerance tests. Peripheral insulin sensitivity was analyzed by euglycemic-hyperinsulinemic clamp, and molecular tools were used to investigate insulin signaling. Moreover, inflammatory and lipid parameters were evaluated. We demonstrated that PRDX6(-/-) mice developed a phenotype similar to early-stage T2D caused by both reduced glucose-dependent insulin secretion and increased insulin resistance. Impaired insulin signaling was present in PRDX6(-/-) mice, leading to reduction of muscle glucose uptake. Morphological and ultrastructural changes were observed in islets of Langerhans and livers of mutant animals, as well as altered plasma lipid profiles and inflammatory parameters. In conclusion, we demonstrated that PRDX6 is a key mediator of overt hyperglycemia in T2D glucose metabolism, opening new perspectives for targeted therapeutic strategies in diabetes care. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  17. Pathogenesis and Diagnostic Approaches of Avian Infectious Bronchitis.

    Science.gov (United States)

    Bande, Faruku; Arshad, Siti Suri; Omar, Abdul Rahman; Bejo, Mohd Hair; Abubakar, Muhammad Salisu; Abba, Yusuf

    2016-01-01

    Infectious bronchitis (IB) is one of the major economically important poultry diseases distributed worldwide. It is caused by infectious bronchitis virus (IBV) and affects both galliform and nongalliform birds. Its economic impact includes decreased egg production and poor egg quality in layers, stunted growth, poor carcass weight, and mortality in broiler chickens. Although primarily affecting the respiratory tract, IBV demonstrates a wide range of tissues tropism, including the renal and reproductive systems. Thus, disease outcome may be influenced by the organ or tissue involved as well as pathotypes or strain of the infecting virus. Knowledge on the epidemiology of the prevalent IBV strains in a particular region is therefore important to guide control and preventions. Meanwhile previous diagnostic methods such as serology and virus isolations are less sensitive and time consuming, respectively; current methods, such as reverse transcription polymerase chain reaction (RT-PCR), Restriction Fragment Length Polymorphism (RFLP), and sequencing, offer highly sensitive, rapid, and accurate diagnostic results, thus enabling the genotyping of new viral strains within the shortest possible time. This review discusses aspects on pathogenesis and diagnostic methods for IBV infection.

  18. A Periplasmic Polymer Curves Vibrio cholerae and Promotes Pathogenesis.

    Science.gov (United States)

    Bartlett, Thomas M; Bratton, Benjamin P; Duvshani, Amit; Miguel, Amanda; Sheng, Ying; Martin, Nicholas R; Nguyen, Jeffrey P; Persat, Alexandre; Desmarais, Samantha M; VanNieuwenhze, Michael S; Huang, Kerwyn Casey; Zhu, Jun; Shaevitz, Joshua W; Gitai, Zemer

    2017-01-12

    Pathogenic Vibrio cholerae remains a major human health concern. V. cholerae has a characteristic curved rod morphology, with a longer outer face and a shorter inner face. The mechanism and function of this curvature were previously unknown. Here, we identify and characterize CrvA, the first curvature determinant in V. cholerae. CrvA self-assembles into filaments at the inner face of cell curvature. Unlike traditional cytoskeletons, CrvA localizes to the periplasm and thus can be considered a periskeletal element. To quantify how curvature forms, we developed QuASAR (quantitative analysis of sacculus architecture remodeling), which measures subcellular peptidoglycan dynamics. QuASAR reveals that CrvA asymmetrically patterns peptidoglycan insertion rather than removal, causing more material insertions into the outer face than the inner face. Furthermore, crvA is quorum regulated, and CrvA-dependent curvature increases at high cell density. Finally, we demonstrate that CrvA promotes motility in hydrogels and confers an advantage in host colonization and pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Advances in the cellular immunological pathogenesis of type 1 diabetes.

    Science.gov (United States)

    Li, Min; Song, Lu-Jun; Qin, Xin-Yu

    2014-05-01

    Type 1 diabetes is an autoimmune disease caused by the immune-mediated destruction of insulin-producing pancreatic β cells. In recent years, the incidence of type 1 diabetes continues to increase. It is supposed that genetic, environmental and immune factors participate in the damage of pancreatic β cells. Both the immune regulation and the immune response are involved in the pathogenesis of type 1 diabetes, in which cellular immunity plays a significant role. For the infiltration of CD4(+) and CD8(+) T lymphocyte, B lymphocytes, natural killer cells, dendritic cells and other immune cells take part in the damage of pancreatic β cells, which ultimately lead to type 1 diabetes. This review outlines the cellular immunological mechanism of type 1 diabetes, with a particular emphasis to T lymphocyte and natural killer cells, and provides the effective immune therapy in T1D, which is approached at three stages. However, future studies will be directed at searching for an effective, safe and long-lasting strategy to enhance the regulation of a diabetogenic immune system with limited toxicity and without global immunosuppression. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  20. An update on Acanthamoeba keratitis: diagnosis, pathogenesis and treatment

    Directory of Open Access Journals (Sweden)

    Lorenzo-Morales Jacob

    2015-01-01

    Full Text Available Free-living amoebae of the genus Acanthamoeba are causal agents of a severe sight-threatening infection of the cornea known as Acanthamoeba keratitis. Moreover, the number of reported cases worldwide is increasing year after year, mostly in contact lens wearers, although cases have also been reported in non-contact lens wearers. Interestingly, Acanthamoeba keratitis has remained significant, despite our advances in antimicrobial chemotherapy and supportive care. In part, this is due to an incomplete understanding of the pathogenesis and pathophysiology of the disease, diagnostic delays and problems associated with chemotherapeutic interventions. In view of the devastating nature of this disease, here we present our current understanding of Acanthamoeba keratitis and molecular mechanisms associated with the disease, as well as virulence traits of Acanthamoeba that may be potential targets for improved diagnosis, therapeutic interventions and/or for the development of preventative measures. Novel molecular approaches such as proteomics, RNAi and a consensus in the diagnostic approaches for a suspected case of Acanthamoeba keratitis are proposed and reviewed based on data which have been compiled after years of working on this amoebic organism using many different techniques and listening to many experts in this field at conferences, workshops and international meetings. Altogether, this review may serve as the milestone for developing an effective solution for the prevention, control and treatment of Acanthamoeba infections.

  1. Ebola haemorrhagic fever virus: pathogenesis, immune responses, potential prevention.

    Science.gov (United States)

    Marcinkiewicz, Janusz; Bryniarski, Krzysztof; Nazimek, Katarzyna

    2014-01-01

    Ebola zoonotic RNA filovirus represents human most virulent and lethal pathogens, which induces acute hemorrhagic fever and death within few days in a range of 60-90% of symptomatic individuals. Last outbreak in 2014 in West Africa caused panic that Ebola epidemic can be spread to other continents. Number of deaths in late December reached almost 8,000 individuals out of more than 20,000 symptomatic patients. It seems that only a coordinated international response could counteract the further spread of Ebola. Major innate immunity mechanisms against Ebola are associated with the production of interferons, that are inhibited by viral proteins. Activation of host NK cells was recognized as a leading immune function responsible for recovery of infected people. Uncontrolled cell infection by Ebola leads to an impairment of immunity with cytokine storm, coagulopathy, systemic bleeding, multi-organ failure and death. Tested prevention strategies to induce antiviral immunity include: i. recombinant virus formulations (vaccines); ii. cocktail of monoclonal antibodies (serotherapy); iii. alternative RNA-interference-based antiviral methods. Maintaining the highest standards of aseptic and antiseptic precautions is equally important. Present brief review summarizes a current knowledge concerning pathogenesis of Ebola hemorrhagic disease and the virus interaction with the immune system and discusses recent advances in prevention of Ebola infection by vaccination and serotherapy.

  2. Pseudomonas syringae Catalases Are Collectively Required for Plant Pathogenesis

    Science.gov (United States)

    Guo, Ming; Block, Anna; Bryan, Crystal D.; Becker, Donald F.

    2012-01-01

    The bacterial pathogen Pseudomonas syringae pv. tomato DC3000 must detoxify plant-produced hydrogen peroxide (H2O2) in order to survive in its host plant. Candidate enzymes for this detoxification include the monofunctional catalases KatB and KatE and the bifunctional catalase-peroxidase KatG of DC3000. This study shows that KatG is the major housekeeping catalase of DC3000 and provides protection against menadione-generated endogenous H2O2. In contrast, KatB rapidly and substantially accumulates in response to exogenous H2O2. Furthermore, KatB and KatG have nonredundant roles in detoxifying exogenous H2O2 and are required for full virulence of DC3000 in Arabidopsis thaliana. Therefore, the nonredundant ability of KatB and KatG to detoxify plant-produced H2O2 is essential for the bacteria to survive in plants. Indeed, a DC3000 catalase triple mutant is severely compromised in its ability to grow in planta, and its growth can be partially rescued by the expression of katB, katE, or katG. Interestingly, our data demonstrate that although KatB and KatG are the major catalases involved in the virulence of DC3000, KatE can also provide some protection in planta. Thus, our results indicate that these catalases are virulence factors for DC3000 and are collectively required for pathogenesis. PMID:22797762

  3. Role of genetic factors in the pathogenesis of aggressive periodontitis.

    Science.gov (United States)

    Vieira, Alexandre R; Albandar, Jasim M

    2014-06-01

    This article critically reviews the evidence for a role of genetic factors in the pathogenesis of aggressive periodontitis and discusses the study approaches commonly used to identify genetic risk factors of this disease. Available data suggest that aggressive periodontitis is caused by mutations in multiple genes, combined with environmental effects. Syndromic periodontal diseases include certain monogenic disorders that express phenotypes showing aggressive forms of periodontitis, and the genetic triggering factors of most of these syndromes have been identified. Other periodontal disease phenotypes seem to occur through different genetic predisposition patterns. Case-control and genome-wide studies have been used to investigate the association with gene polymorphisms. Association studies and the familial aggregation of aggressive periodontitis suggest a significant genetic component in the increased predisposition to this disease. There is evidence to support the contribution of a few major genes or of multiple small-effects genes. In addition, there is evidence of gene-gene and gene-environment interaction effects. Early studies suggested an X-linked mode of transmission of aggressive periodontitis, and subsequent studies support an autosomal mode. Genetic studies have the potential to improve the screening programs of subjects at risk for developing aggressive periodontitis and may enhance treatment outcome through gene therapy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Molecular Pathogenesis of Familial Wolff-Parkinson-White Syndrome.

    Science.gov (United States)

    Licht, Miyamotoa

    2018-01-01

    Familial Wolff-Parkinson-White (WPW) syndrome is an autosomal dominant inherited disease and consists of a small percentage of WPW syndrome which exhibits ventricular pre-excitation by development of accessory atrioventricular pathway. A series of mutations in PRKAG2 gene encoding gamma2 subunit of 5'AMP-activated protein kinase (AMPK) has been identified as the cause of familial WPW syndrome. AMPK is one of the most important metabolic regulators of carbohydrates and lipids in many types of tissues including cardiac and skeletal muscles. Patients and animals with the mutation in PRKAG2 gene exhibit aberrant atrioventricular conduction associated with cardiac glycogen overload. Recent studies have revealed "novel" significance of canonical pathways leading to glycogen synthesis and provided us profound insights into molecular mechanism of the regulation of glycogen metabolism by AMPK. This review focuses on the molecular basis of the pathogenesis of cardiac abnormality due to PRKAG2 mutation and will provide current overviews of the mechanism of glycogen regulation by AMPK. J. Med. Invest. 65:1-8, February, 2018.

  5. Prion pathogenesis in the absence of NLRP3/ASC inflammasomes.

    Directory of Open Access Journals (Sweden)

    Mario Nuvolone

    Full Text Available The accumulation of the scrapie prion protein PrPSc, a misfolded conformer of the cellular prion protein PrPC, is a crucial feature of prion diseases. In the central nervous system, this process is accompanied by conspicuous microglia activation. The NLRP3 inflammasome is a multi-molecular complex which can sense heterogeneous pathogen-associated molecular patterns and culminates in the activation of caspase 1 and release of IL 1β. The NLRP3 inflammasome was reported to be essential for IL 1β release after in vitro exposure to the amyloidogenic peptide PrP106-126 and to recombinant PrP fibrils. We therefore studied the role of the NLRP3 inflammasome in a mouse model of prion infection. Upon intracerebral inoculation with scrapie prions (strain RML, mice lacking NLRP3 (Nlrp3-/- or the inflammasome adaptor protein ASC (Pycard-/- succumbed to scrapie with attack rates and incubation times similar to wild-type mice, and developed the classic histologic and biochemical features of prion diseases. Genetic ablation of NLRP3 or ASC did not significantly impact on brain levels of IL 1β at the terminal stage of disease. Our results exclude a significant role for NLRP3 and ASC in prion pathogenesis and invalidate their claimed potential as therapeutic target against prion diseases.

  6. Host Genetic Variants in the Pathogenesis of Hepatitis C

    Directory of Open Access Journals (Sweden)

    Monika Rau

    2012-11-01

    Full Text Available Direct-acting antiviral drugs (DAAs are currently replacing antiviral therapy for Hepatitis C infection. Treatment related side effects are even worse and the emergence of resistant viruses must be avoided because of the direct-antiviral action. Altogether it remains a challenge to take treatment decisions in a clinical setting with cost restrictions. Genetic host factors are hereby essential to implement an individualized treatment concept. In recent years results on different genetic variants have been published with a strong association with therapy response, fibrosis and treatment-related side effects. Polymorphisms of the IL28B gene were identified as accurate predictors for therapy response and spontaneous clearance of HCV infection and are already used for diagnostic decisions. For RBV-induced side effects, such as hemolytic anemia, associations to genetic variants of inosine triphosphatase (ITPA were described and different SLC28 transporters for RBV-uptake have been successfully analyzed. Fibrosis progression has been associated with variants of Vitamin D receptor (VDR and ABCB11 (bile salt export pump. Cirrhotic patients especially have a high treatment risk and low therapy response, so that personalized antiviral treatment is mandatory. This review focuses on different host genetic variants in the pathogenesis of Hepatitis C at the beginning of a new area of treatment.

  7. Traumatic ulcerative granuloma with stromal eosinophilia - Mystery of pathogenesis revisited.

    Science.gov (United States)

    Sarangarajan, R; Vaishnavi Vedam, V K; Sivadas, G; Sarangarajan, Anuradha; Meera, S

    2015-08-01

    Oral ulcers are a common symptom in clinical practice. Among various causative factors, different types of ulcers in oral cavity exist. Among this, traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) appears to be quite neglected by the clinicians due to the limited knowledge and awareness. On reviewing with a detailed approach to titles and abstracts of articles eliminating duplicates, 40 relevant articles were considered. Randomized studies, review articles, case reports and abstracts were included while conference papers and posters were excluded. Of importance, TUGSE cases been reported only to a minimal extent in the literature. Lack of its awareness tends to lead clinicians to a misconception of cancer. Thus, this particular lesion needs to be differentiated from other malignant lesions to provide a proper mode of treatment. The present article reviews various aspects of the TUGSE with emphasis on the clinical manifestation, pathogenesis, histological, and immunohistochemical study. This study provides the clinician contemporaries, a humble expansion to their knowledge of the disease, based on the searched literature, enabling a more comprehensive management of this rare occurrence.

  8. Role of Helicobacter pylori infection in pathogenesis of gastric carcinoma

    Science.gov (United States)

    Zhang, Rong-Guang; Duan, Guang-Cai; Fan, Qing-Tang; Chen, Shuai-Yin

    2016-01-01

    Gastric cancer (GC) is one of the most common carcinoma and the second leading cause of cancer-related deaths worldwide. Helicobacter pylori (H. pylori) infection causes a series of precancerous lesions like gastritis, atrophy, intestinal metaplasia and dysplasia, and is the strongest known risk factor for GC, as supported by epidemiological, preclinical and clinical studies. However, the mechanism of H. pylori developing gastric carcinoma has not been well defined. Among infected individuals, approximately 10% develop severe gastric lesions such as peptic ulcer disease, 1%-3% progresses to GC. The outcomes of H. pylori infection are determined by bacterial virulence, genetic polymorphism of hosts as well as environmental factors. It is important to gain further understanding of the pathogenesis of H. pylori infection for developing more effective treatments for this common but deadly malignancy. The recent findings on the bacterial virulence factors, effects of H. pylori on epithelial cells, genetic polymorphism of both the bacterium and its host, and the environmental factors for GC are discussed with focus on the role of H. pylori in gastric carcinogenesis in this review. PMID:26909232

  9. Role of perceived family environment in the pathogenesis of schizophrenia

    Directory of Open Access Journals (Sweden)

    Roshan Lal Dewangan

    2018-01-01

    Full Text Available Background: Family plays an important role in mental health of its member, thus its contribution can also be discerned in pathogenesis. Maintenance and relapse of several mental illnesses have been also attributed to the family environment (FE. This study explores FE as perceived by schizophrenia patients. Methodology: A case–control study was conducted in Chhattisgarh, India, to measure the association of perceived FE with schizophrenia. Between February 2014 and January 2015, 100 paranoid schizophrenia patients and 100 neighborhood-based healthy (based on 28-item General Health Questionnaire controls were recruited. Minimum school-educated individuals aged 20–35 years were eligible if they/their caregivers provided consent. Interpersonal relationships and FE were assessed by an interviewer-administered 69-item FE scale. Results: The odds of suffering from schizophrenia increased with age, decreased with education, income, and found to be less among married. Schizophrenia risk was negatively associated with mean scores for cohesion, acceptance/caring, active-recreational orientation, and organization. Negative symptoms of schizophrenia were less pronounced among patients belonging to joint families. Conclusion: Thus, to minimize the burden and morbidity associated with schizophrenia, interventions to improve FE by minimizing conflict and improving cohesion, acceptance/caring, active-recreational orientation, and organization, and specifically targeting older, less-educated, poor, and married individuals in nuclear families seemed necessary.

  10. TNFα gene polymorphisms in the pathogenesis of acne vulgaris.

    Science.gov (United States)

    Szabó, Kornélia; Tax, Gábor; Teodorescu-Brinzeu, Dragos; Koreck, Andrea; Kemény, Lajos

    2011-01-01

    Inflammation plays an important role in acne pathogenesis, and pro-inflammatory cytokines are key factors in these events. Tumor necrosis factor alpha (TNFα) is a central molecule coded by a gene that shows high level of genetic polymorphisms especially in its promoter region. Single nucleotide polymorphisms (SNPs) of the TNFα gene have been shown to be associated with an increased risk to develop chronic inflammatory diseases. In order to find out if known TNFα regulatory SNPs (-1031T>C, -857C>T, -863C>A, -308G>A, -238G>A) have a role in the development of the inflammatory reactions in acne vulgaris, we analyzed our genomic collection in a retrospective case-control study using the PCR-RFLP method, and we compared the resulting genotype and allele frequencies. There were no significant differences in the observed genotype or allele frequencies between the control and acne group in case of the -1031, -863, -238 SNPs; however, the TNFα -857 minor T allele was found to act as a protective factor in our study population in acne, and a higher occurrence of the minor -308 A allele in female acne patients was also noted. Genetic variants of the TNFα gene may affect the risk of acne vulgaris. Our results can help to elucidate the molecular events leading to acne development.

  11. Multifocal motor neuropathy: a review of pathogenesis, diagnosis, and treatment

    Directory of Open Access Journals (Sweden)

    Lawson VH

    2014-04-01

    Full Text Available Victoria H Lawson,1 W David Arnold1,2 1Division of Neuromuscular Disorders, Department of Neurology, 2Department of Physical Medicine and Rehabilitation, Wexner Medical Center at The Ohio State University, Columbus, Ohio, USA Abstract: Multifocal motor neuropathy (MMN is an uncommon, purely motor neuropathy associated with asymmetric deficits with predilection for upper limb involvement. Even in the early descriptions of MMN, the associations of anti-GM1 antibodies and robust response to immunomodulatory treatment were recognized. These features highlight the likelihood of an underlying autoimmune etiology of MMN. The clinical presentation of MMN can closely mimic several neurological conditions including those with more malignant prognoses such as motor neuron disease. Therefore early and rapid recognition of MMN is critical. Serological evidence of anti GM-1 antibodies and electrodiagnostic findings of conduction block are helpful diagnostic clues for MMN. Importantly, these diagnostic features are not universally present, and patients lacking these characteristic findings can demonstrate similar robust response to immunodulatory treatment. In the current review, recent research in the areas of diagnosis, pathogenesis, and treatment of MMN and needs for the future are discussed. The characteristic findings of MMN and treatment implications are reviewed and contrasted with other mimicking disorders. Keywords: autoimmune, conduction block, electrodiagnosis, motor neuron, nerve, inflammatory

  12. Are infectious agents involved in the pathogenesis of postpartum psychosis?

    Science.gov (United States)

    de Witte, Lot D; Snijders, Gijsje; Litjens, Manja; Kamperman, Astrid M; Kushner, Steven A; Kahn, René S; Bergink, Veerle

    2018-03-15

    Since postpartum psychosis has been linked to activation of the immune system, it has been hypothesized that infectious agents may be involved in the pathogenesis of this disorder. We therefore investigated whether exposure to pathogens that can infect the central nervous system is increased in patients with postpartum psychosis. We measured the prevalence and titers of immunoglobulin G (IgG) and M (IgM) to herpes simplex virus type 1 (HSV-1) and 2 (HSV-2), Epstein-Barr virus (EBV), cytomegalovirus (CMV) and Toxoplasma Gondii (TG) in a cohort of patients with postpartum psychosis (n = 81) and compared these to matched postpartum controls. We did not find significant differences in seroprevalence or antibody titers for any of these pathogens. Limitations of this study include the indirect measurement of infectious disease and the cross-sectional design. Our results do not support the hypothesis that exposure to these neurotropic pathogens is involved in postpartum psychosis. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Cavitating pulmonary tuberculosis in children: correlating radiology with pathogenesis

    International Nuclear Information System (INIS)

    Griffith-Richards, S.B.; Andronikou, Savvas; Przybojewski, Stefan J.; Strachan, Melanie; Vadachia, Yousuf; Kathan, David L.; Goussard, Pierre; Gie, Robert P.

    2007-01-01

    Cavitating pulmonary tuberculosis (PTB) is generally known as a disease of adults, with children typically having features of primary PTB. To group children with PTB and cavities according to possible pathogenesis by evaluating the clinical and radiological findings. The clinical and radiological findings in ten randomly selected children with PTB and cavitations on chest radiographs were retrospectively reviewed and evaluated. Three groups emerged: group 1 (four children) had cavities, usually single and unilateral in the classic upper lobe distribution of postprimary PTB; group 2 (three children) developed progressive primary spread of disease with extensive and bilateral pulmonary cavities; and group 3 (three children) developed cavities secondary to airway obstruction by mediastinal lymph nodes with consequent distal collapse and consolidation. Children in group 1 responded well to treatment and had unremarkable recoveries. Children in group 2 were all below 2 years of age with complicated recoveries. Children in group 3 had frequent complications resulting in one fatality. Cavities in PTB in children may arise by one of three possible mechanisms with a relatively equal incidence. A study is underway to determine the incidence of cavity formation associated with mediastinal lymphadenopathy and airway obstruction. (orig.)

  14. Bone mineral measurements and the pathogenesis of osteoporosis

    International Nuclear Information System (INIS)

    Aloia, J.F.; Vaswani, A.N.; Ellis, K.J.; Cohn, S.H.

    1986-01-01

    Low bone mass (osteopenia) is a major factor in the development of osteoporotic fractures in women after the menopause. The pathogenesis of postmenopausal osteoporosis has been pursued by dual lines of investigation: (1) development of a model to describe involutional bone loss, (2) identification of those factors which result in some healthy women having a greater risk for osteoporosis than others. Bone mineral measurements have been made using in vivo neutron activation analysis and whole body counting for the measurement of total body calcium (TBCa), single photon absorptiometry for the measurement of bone mineral content of the distal radius and dual photon absorptiometry for measurement of the bone density of the spine. TBCa is higher in men than women and is lost at a slow linear rate in men. Blacks have a skeletal mass about 8-9% higher than Caucasians. Women have a similar loss of TBCa to men prior to menopause, but then have an accelerated rate of loss after menopause. The change in bone density of the radius and spine with increasing age is also best described by a 2 phase regression in women, with appreciable loss after age 50

  15. [Advances in the pathogenesis of non alcoholic fatty liver disease].

    Science.gov (United States)

    Pár, Alajos; Pár, Gabriella

    2017-06-01

    Non alcoholic fatty liver disease is the hepatic manifestation of metabolic syndrome, and the most common liver disease. Its more aggressive form is the non alcoholic steatohepatitis. Multiple genetic and environmental factors lead to the accumulation of triglicerides and the inflammatory cascade. High fat diet, obesity, adipocyte dysfunction with cytokine production, insulin resistance and increased lipolysis with free fatty acid flux into the liver - all are the drivers of liver cell injury. Activation of inflammasome by damage- or pathogen-associated molecular patterns results in "steril inflammation" and immune response, while the hepatic stellate cells and progenitor cells lead to fibrogenesis. Small intestinal bacterial overgrowth and gut dysbiosis are also of pivotal importance in the inflammation. Among the susceptible genetic factors, mutations of patatin-like phospholipase domain containing 3 and the transmembrane 6 superfamily 2 genes play a role in the development and progression of the disease, similarly as do epigenetic regulators such as microRNAs and extracellular vesicles. Better understanding of the pathogenesis of non alcoholic fatty liver disease may identify novel therapeutic agents that improve the outcome of the disease. Orv Hetil. 2017; 158(23): 882-894.

  16. The Potential Roles of Bisphenol A (BPA Pathogenesis in Autoimmunity

    Directory of Open Access Journals (Sweden)

    Datis Kharrazian

    2014-01-01

    Full Text Available Bisphenol A (BPA is a monomer found in commonly used consumer plastic goods. Although much attention in recent years has been placed on BPA’s impact as an endocrine disruptor, it also appears to activate many immune pathways involved in both autoimmune disease development and autoimmune reactivity provocation. The current scientific literature is void of research papers linking BPA directly to human or animal onset of autoimmunity. This paper explores the impact of BPA on immune reactivity and the potential roles these mechanisms may have on the development or provocation of autoimmune diseases. Potential mechanisms by which BPA may be a contributing risk factor to autoimmune disease development and progression include its impact on hyperprolactinemia, estrogenic immune signaling, cytochrome P450 enzyme disruption, immune signal transduction pathway alteration, cytokine polarization, aryl hydrocarbon activation of Th-17 receptors, molecular mimicry, macrophage activation, lipopolysaccharide activation, and immunoglobulin pathophysiology. In this paper a review of these known autoimmune triggering mechanisms will be correlated with BPA exposure, thereby suggesting that BPA has a role in the pathogenesis of autoimmunity.

  17. Studies on the pathogenesis and immunology of African trypanosomiasis

    International Nuclear Information System (INIS)

    Assoku, R.K.G.

    1981-01-01

    Within the past few years evidence has accumulated which indicates that at least some of the African trypanosomes are capable of generating potent, biologically active factors or 'toxins'. The importance of these trypanosome-derived biological factors is not firmly established, yet when acting together they may account for some of the lesions observed and for the deaths of trypanosome-infected individuals. One group of factors generated by autolysing trypanosomes includes the phospholipases, lysophospholipases and free fatty acids. Both T. congolense and T. brucei, on autolysis for 8-24 h at 20 0 C, greatly increase their phospholipase activity which reaches 40-times the level in fresh organisms by 24 h. The phospholipase, acting on trypanosome phosphatidylcholine, yields great quantities of free fatty acids and lysophosphatidylcholine, the latter being further degraded by lysophospholipase to yield more free fatty acids. It is suggested that the free fatty acids generated in this way are of major significance in the pathogenesis of African trypanosomiasis. (author)

  18. Pathogenesis of hyperinflation in chronic obstructive pulmonary disease

    Science.gov (United States)

    Gagnon, Philippe; Guenette, Jordan A; Langer, Daniel; Laviolette, Louis; Mainguy, Vincent; Maltais, François; Ribeiro, Fernanda; Saey, Didier

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a preventable and treatable lung disease characterized by airflow limitation that is not fully reversible. In a significant proportion of patients with COPD, reduced lung elastic recoil combined with expiratory flow limitation leads to lung hyperinflation during the course of the disease. Development of hyperinflation during the course of COPD is insidious. Dynamic hyperinflation is highly prevalent in the advanced stages of COPD, and new evidence suggests that it also occurs in many patients with mild disease, independently of the presence of resting hyperinflation. Hyperinflation is clinically relevant for patients with COPD mainly because it contributes to dyspnea, exercise intolerance, skeletal muscle limitations, morbidity, and reduced physical activity levels associated with the disease. Various pharmacological and nonpharmacological interventions have been shown to reduce hyperinflation and delay the onset of ventilatory limitation in patients with COPD. The aim of this review is to address the more recent literature regarding the pathogenesis, assessment, and management of both static and dynamic lung hyperinflation in patients with COPD. We also address the influence of biological sex and obesity and new developments in our understanding of hyperinflation in patients with mild COPD and its evolution during progression of the disease. PMID:24600216

  19. A STAT-1 knockout mouse model for Machupo virus pathogenesis

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    Shurtleff Amy C

    2011-06-01

    Full Text Available Abstract Background Machupo virus (MACV, a member of the Arenaviridae, causes Bolivian hemorrhagic fever, with ~20% lethality in humans. The pathogenesis of MACV infection is poorly understood, and there are no clinically proven treatments for disease. This is due, in part, to a paucity of small animal models for MACV infection in which to discover and explore candidate therapeutics. Methods Mice lacking signal transducer and activator of transcription 1 (STAT-1 were infected with MACV. Lethality, viral replication, metabolic changes, hematology, histopathology, and systemic cytokine expression were analyzed throughout the course of infection. Results We report here that STAT-1 knockout mice succumbed to MACV infection within 7-8 days, and presented some relevant clinical and histopathological manifestations of disease. Furthermore, the model was used to validate the efficacy of ribavirin in protection against infection. Conclusions The STAT-1 knockout mouse model can be a useful small animal model for drug testing and preliminary immunological analysis of lethal MACV infection.

  20. Molecular concepts in the pathogenesis of ameloblastoma: implications for therapeutics.

    Science.gov (United States)

    Jhamb, Tania; Kramer, Jill M

    2014-12-01

    Ameloblastoma is a benign odontogenic neoplasm that may exhibit aggressive biological behavior as evidenced by its rapid growth and significance recurrence rates following initial surgical resection. Currently, the only therapy for ameloblastoma is surgical, and adjunctive treatment modalities are needed to mitigate tumor growth and to reduce the need for extensive and disfiguring surgeries. Many studies have identified markers expressed by ameloblastoma and these lend insight to our understanding of tumor progression. This review provides a summary of the specific molecular pathways implicated in tumor pathogenesis, including those involved in bone remodeling, apoptosis, cell signaling, and tumor suppression. Based on these data, we identify several prognostic or therapeutic markers that have been used successfully in the treatment of other neoplastic processes that may also have diagnostic and prognostic utility for ameloblastoma. Thus, it is important to determine which markers hold the greatest promise for clinical management of this benign neoplasm in order to improve treatment options, particularly in patients with aggressive forms of ameloblastoma. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Selected Aspects in the Pathogenesis of Autoimmune Diseases

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    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.

  2. Role of Helicobacter pylori in the pathogenesis of hyperemesis gravidarum.

    Science.gov (United States)

    Mansour, Ghada M; Nashaat, Ehab H

    2011-10-01

    To evaluate the role of Helicobacter pylori (H. pylori) in the pathogenesis of hyperemesis gravidarum (HG) and the value of adding a non teratogenic regimen for its treatment in intractable cases. Eighty hyperemesis gravidarum cases were recruited from Ain Shams University out patient clinics. A complete history was taken including history of medical disorders and chronic medications intake as non steroidal anti-inflammatory drugs. After general and local examination, ultrasound was done for all cases to exclude obstetric causes of hyperemesis. Eighty normal pregnant women acted as control. Serum test for H. pylori IgG antibody titre was done for all patients and controls. Seventy-one cases among the 80 HG cases and twenty-four out of the 80 controls were H. pylori positive. Eight HG cases developed severe intractable vomiting. Three of them developed attacks of hematemesis. Gastroscopy done for the eight cases revealed antral gastritis and duodenitis. Gastric and duodenal erosions were found in two cases. The eight patients received a non teratogenic regimen for treatment. Attacks of vomiting decreased and pregnancy continued till delivery of healthy newborns. Screening for H. pylori should be added to the investigations of hyperemesis gravidarum cases. Non teratogenic treatment can be considered in intractable cases.

  3. Genetics of ankylosing spondylitis--insights into pathogenesis.

    Science.gov (United States)

    Brown, Matthew A; Kenna, Tony; Wordsworth, B Paul

    2016-02-01

    Ankylosing spondylitis (AS), an immune-mediated arthritis, is the prototypic member of a group of conditions known as spondyloarthropathies that also includes reactive arthritis, psoriatic arthritis and enteropathic arthritis. Patients with these conditions share a clinical predisposition for spinal and pelvic joint dysfunction, as well as genetic associations, notably with HLA-B(*)27. Spondyloarthropathies are characterized by histopathological inflammation in entheses (regions of high mechanical stress where tendons and ligaments insert into bone) and in the subchondral bone marrow, and by abnormal osteoproliferation at involved sites. The association of AS with HLA-B(*)27, first described >40 years ago, led to hope that the cause of the disease would be rapidly established. However, even though many theories have been advanced to explain how HLA-B(*)27 is involved in AS, no consensus about the answers to this question has been reached, and no successful treatments have yet been developed that target HLA-B27 or its functional pathways. Over the past decade, rapid progress has been made in discovering further genetic associations with AS that have shed new light on the aetiopathogenesis of the disease. Some of these discoveries have driven translational ideas, such as the repurposing of therapeutics targeting the cytokines IL-12 and IL-23 and other factors downstream of this pathway. AS provides an excellent example of how hypothesis-free research can lead to major advances in understanding pathogenesis and to the development of innovative therapeutic strategies.

  4. An update on Acanthamoeba keratitis: diagnosis, pathogenesis and treatment.

    Science.gov (United States)

    Lorenzo-Morales, Jacob; Khan, Naveed A; Walochnik, Julia

    2015-01-01

    Free-living amoebae of the genus Acanthamoeba are causal agents of a severe sight-threatening infection of the cornea known as Acanthamoeba keratitis. Moreover, the number of reported cases worldwide is increasing year after year, mostly in contact lens wearers, although cases have also been reported in non-contact lens wearers. Interestingly, Acanthamoeba keratitis has remained significant, despite our advances in antimicrobial chemotherapy and supportive care. In part, this is due to an incomplete understanding of the pathogenesis and pathophysiology of the disease, diagnostic delays and problems associated with chemotherapeutic interventions. In view of the devastating nature of this disease, here we present our current understanding of Acanthamoeba keratitis and molecular mechanisms associated with the disease, as well as virulence traits of Acanthamoeba that may be potential targets for improved diagnosis, therapeutic interventions and/or for the development of preventative measures. Novel molecular approaches such as proteomics, RNAi and a consensus in the diagnostic approaches for a suspected case of Acanthamoeba keratitis are proposed and reviewed based on data which have been compiled after years of working on this amoebic organism using many different techniques and listening to many experts in this field at conferences, workshops and international meetings. Altogether, this review may serve as the milestone for developing an effective solution for the prevention, control and treatment of Acanthamoeba infections. © J. Lorenzo-Morales et al., published by EDP Sciences, 2015.

  5. Role of leptin in the pathogenesis of breast cancer

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    Thayse Fachin Cormanique

    2015-12-01

    Full Text Available Leptin is a small polypeptide codified by the Obese Gene (OB, deeply related with the body fat mass and energetic balance. Due to its diverse biological effects and downstream signal transducers, multiple classifications have been attributed to leptin, as hormone, cytokine, adypokine, growth factor, and developmental factor, among others. This scenario gives us an idea of the size of the potential biological effects generated by this molecule. The concentration of leptin in the body is determined by the amount of adipose tissue; therefore, hyperleptinemia is a common finding in obese individuals. In addition, high levels of circulating leptin may confer a poor prognosis for any pathological condition. Although leptin history has been reported for more than 20 years, its relationship with cancer has gained notoriety in the past ten years, where studies focused on discussing the issue of obesity as a strong risk factor for cancer developing. Further, growing evidences have pointed leptin as a pivotal mediator of immune response, which aggravates the scenario of cancer occurrence in the presence of obesity. Therefore, leptin can present at least two faces in the pathogenesis of breast cancer, acting by immune and non-immune mechanisms. In this paper we review the dynamic of the leptin axis in breast cancer and further discuss its role in disease, immunopathogenesis and prognosis.

  6. Some aspects of the pathogenesis and pathomorphology of leprosy*

    Science.gov (United States)

    Ivanova, N. A.

    1972-01-01

    The results of bacteriological and histological examinations of the organs of mice infected in the footpad with human leprosy bacilli by the Shepard method are summarized. The periods of observation ranged from a few days to 2 years. The disease developed in mice as a chronic infection with a lengthy “incubation” period of 3-4 months or more without symptoms. Usually about 2 years after inoculation, or in some cases after a shorter interval, the disease became generalized. Different types of tissue reaction occurred: simple inflammatory infiltration, tuberculoid granuloma, and leproma-like granuloma, similar to the clinical types of leprosy in man. When the infection became general, cells resembling lepra cells formed in the internal organs and at the site of infection. These cells contained massive intracellular aggregations of mycobacteria and compact globi with lipids and a vacuolized protoplasm, similar in origin and morphology to the lepra cells in human lesions. Changes were found in the neuroreceptor apparatus of the skin of the mice, with groups of leprosy bacilli in the endoneurium, the Schwann cells, and the perineural spaces. The length of the experiments and the histological examination of material from the sacrificed mice at different stages of the infective process revealed biological parallels with human leprosy and threw light on a number of aspects of the pathogenesis of leprosy. ImagesFig. 2Fig. 3Fig. 4Fig. 5Fig. 1 A-DFig. 10Fig. 11Fig. 12Fig. 13Fig. 6Fig. 7Fig. 8Fig. 9 PMID:4538195

  7. Pathogenesis of biliary atresia: defining biology to understand clinical phenotypes

    Science.gov (United States)

    Asai, Akihiro; Miethke, Alexander; Bezerra, Jorge A.

    2016-01-01

    Biliary atresia is a severe cholangiopathy of early infancy that destroys extrahepatic bile ducts and disrupts bile flow. With a poorly defined disease pathogenesis, treatment consists of the surgical removal of duct remnants followed by hepatoportoenterostomy. Although this approach can improve the short-term outcome, the liver disease progresses to end-stage cirrhosis in most children. Further improvement in outcome will require a greater understanding of the mechanisms of biliary injury and fibrosis. Here, we review progress in the field, which has been fuelled by collaborative studies in larger patient cohorts and the development of cell culture and animal model systems to directly test hypotheses. Advances include the identification of phenotypic subgroups and stages of disease based on clinical, pathological and molecular features. Stronger evidence exists for viruses, toxins and gene sequence variations in the aetiology of biliary atresia, triggering a proinflammatory response that injures the duct epithelium and produces a rapidly progressive cholangiopathy. The immune response also activates the expression of type 2 cytokines that promote epithelial cell proliferation and extracellular matrix production by nonparenchymal cells. These advances provide insight into phenotype variability and might be relevant to the design of personalized trials to block progression of liver disease. PMID:26008129

  8. Role of serotonin in pathogenesis of analgesic induced headache

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    Srikiatkhachorn, A.

    1999-12-16

    Analgesic abuse has recently been recognized as a cause of deterioration in primary headache patients. Although the pathogenesis of this headache transformation is still obscure, and alteration of central pain control system is one possible mechanism. A number of recent studies indicated that simple analgesics exert their effect by modulating the endogenous pain control system rather than the effect at the peripheral tissue, as previously suggested. Serotonin (5-hydroxytryptamine ; 5-HT) has long been known to play a pivotal role in the pain modulatory system in the brainstem. In the present study, we investigated the changes in 5-HT system in platelets and brain tissue. A significant decrease in platelet 5-HT concentration (221.8{+-}30.7, 445.3{+-}37.4 and 467.2{+-}38.5 ng/10{sup 9} platelets, for patients with analgesic-induced headache and migraine patients, respectively, p<0.02) were evident in patients with analgesic induced headache. Chronic paracetamol administration induced a decrease in 5-HT{sub 2} serotonin receptor in cortical and brain stem tissue in experimental animals (B{sub max}=0.93{+-}0.04 and 1.79{+-}0.61 pmol/mg protein for paracetamol treated rat and controls, respectively, p<0.05). Our preliminary results suggested that chronic administration of analgesics interferes with central and peripheral 5-HT system and therefore possibly alters the 5-HT dependent antinociceptive system. (author)

  9. Current concepts of the pathogenesis of inflammatory bowel disease.

    LENUS (Irish Health Repository)

    Shanahan, F

    2012-02-03

    Although the cause of inflammatory bowel disease is not known, the pathogenesis involves an immune-mediated tissue damage that is the result of an interaction among genetic predisposing factors, exogenous triggers and endogenous modifying influences. Multiple genes are involved and operate at the level of the immune response and at the target organ. Exogenous triggers include the enteric microflora which might stimulate the mucosal immune system in genetically predisposed individuals. Endogenous modifying factors such as the psychoneuroendocrine system have regulatory effects on the immune system and the inflammatory response, and may influence the course of the disease. While autoimmune phenomena do occur, particularly in ulcerative colitis, there is no evidence that they are directly responsible for the tissue damage. It appears more likely, particularly in Crohn\\'s disease, that tissue injury may occur as an indirect or "bystander" effect of mucosal T-cell hyperactivation, perhaps in response to a normal enteric microbial antigen. Most of the immunologic and histologic features of Crohn\\'s disease can be explained by the effects of T-cell derived and other cytokines on the epithelium, the local immune system, the microvasculature, and the recruitment of auxiliary effector cells such as neutrophils.

  10. Role of nitric oxide in the pathogenesis of alloxan diabetes.

    Science.gov (United States)

    Belkina, L M; Smirnova, E A; Terekhina, O L; Kruglov, S V; Boichuk, E S

    2013-03-01

    We studied the effects of N(w)-nitro-L-arginine (L-NNA), a nonselective inhibitor of NO synthases, on the severity of type 1 diabetes mellitus induced by subcutaneous injection of 130 mg/kg alloxan in August rats with high activity of NO system and in Wistar rats. Five days after alloxan injection, hyperglycemia levels after overnight fasting in August and Wistar rats were 27.1±3.7 and 22.0±1.1 mmol/liter, respectively (p<0.03). The mortality over 15 days after alloxan injection in August rats was higher than in Wistar rats (36 and 26%, respectively). L-NNA normalized glucose levels in diabetics of both groups. It completely prevented mortality in August and reduced it to 13% in Wistar rats. Body weight loss and polydipsia after L-NNA injection were also less pronounced in August rats. Plasma nitrite/nitrate concentrations in August rats were 32% higher than in Wistar rats, both in intact and diabetic rats. These data attest to an important role of NO in the pathogenesis of alloxan diabetes.

  11. Mouse models to study dengue virus immunology and pathogenesis

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    Raphaël M. Zellweger

    2014-04-01

    Full Text Available The development of a compelling murine model of dengue virus (DENV infection has been challenging, because dengue virus clinical isolates do not readily replicate or cause pathology in immunocompetent mice. However, research using immunocompromised mice and/or mouse-adapted viruses allows to investigate questions that may be impossible to address in human studies. In this review, we discuss the potential strengths and limitations of existing mouse models of dengue disease. Human studies are descriptive by nature; moreover, the strain, time, and sequence of infection are often unknown. In contrast, in mice, the conditions of infection are well defined and a large number of experimental parameters can be varied at will. Therefore, mouse models offer an opportunity to experimentally test hypotheses that are based on epidemiological observations. In particular, gain-of-function or loss-of-function models can be established to assess how different components of the immune system (either alone or in combination contribute to protection or pathogenesis during secondary infections or after vaccination. In addition, mouse models have been used for pre-clinical testing of antiviral drug or for vaccine development studies. Conclusions based on mouse experiments must be extrapolated to DENV infection in humans with caution due to the inherent limitations of animal models. However, research in mouse models is a useful complement to in vitro and epidemiological data, and may delineate new areas that deserve attention during future human studies.

  12. Pathogenesis of Paget's disease based on viral etiology.

    Science.gov (United States)

    Mirra, J M

    1987-04-01

    It has been slightly over 100 years since Sir James Paget's classic descriptions of "osteitis deformans" first appeared. He had described the mid- to late stages of patients with the chronic, debilitating, rare, and polyostotic forms of the disease. It is now known that the milder forms of the disease are quite common particularly in those of Anglo-Saxon ancestry. He believed the condition to be a chronic inflammation of unknown etiology because of its asymmetrical skeletal distribution, chronicity, and the gross appearance of the bones. With regard to the possible etiology of Paget's disease of bone, nothing worthy of note had been discovered until 1974 when viral-like inclusions were reported within the osteoclasts of all Paget's disease patients. In the ensuing decade, a great deal more circumstantial evidence from electron microscopic and immunologic studies supports the view that Paget's disease represents a slow virus infection. This article deals with the possible to probable viral etiology of Paget's disease with respect to its pathogenesis and its potential for eventual eradication. For many years Paget's disease was considered a disease almost exclusively confined to adulthood. Evidence now suggests that "familial chronic hyperphosphatasemia" represents the childhood form of Paget's disease.

  13. Role of Vpma phase variation in Mycoplasma agalactiae pathogenesis

    Science.gov (United States)

    Chopra-Dewasthaly, Rohini; Baumgartner, Martina; Gamper, Erika; Innerebner, Carmen; Zimmermann, Martina; Schilcher, Franz; Tichy, Alexander; Winter, Petra; Rosengarten, Renate; Spergser, Joachim

    2015-01-01

    Compared with other bacterial pathogens, the molecular mechanisms of mycoplasma pathogenicity are largely unknown. Several studies in the past have shown that pathogenic mycoplasmas are equipped with sophisticated genetic systems that allow them to undergo high-frequency surface antigenic variations. Although never clearly proven, these variable mycoplasma surface components are often implicated in host immune evasion and adaptation. Vpma surface lipoproteins of the ruminant pathogen Mycoplasma agalactiae are encoded on a genomic pathogenicity island–like locus and are considered as one of the well-characterized model systems of mycoplasma surface antigenic variation. The present study assesses the role of these phase-variable Vpmas in the molecular pathogenesis of M. agalactiae by testing the wild-type strain PG2 in comparison with the xer1-disrupted Vpma ‘phase-locked’ mutants in sheep infection models. The data clearly illustrate that although Xer1 recombinase is not a virulence factor of M. agalactiae and Vpma phase variation is not necessary for establishing an infection, it might critically influence the survival and persistence of the pathogen under natural field conditions, mainly due to a better capacity for dissemination and evoking systemic responses. This is the first study where mycoplasma ‘phase-locked’ mutants are tested in vivo to elucidate the role of phase variation during infection. PMID:22809092

  14. Role of matrix metalloproteinases in the pathogenesis of childhood gastroenteritis.

    Science.gov (United States)

    Kawamura, Yoshiki; Gotoh, Kensei; Takeuchi, Nao; Miura, Hiroki; Nishimura, Naoko; Ozaki, Takao; Yoshikawa, Tetsushi

    2016-08-01

    Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been implicated in the pathogenesis of gastrointestinal diseases, such as rotavirus gastroenteritis (GE). Kinetics of these biomarkers were examined in paired serum samples collected from bacterial enteritis patients with Campylobacter (n = 2) and Salmonella (n = 4) and viral GE patients with rotavirus (n = 27), norovirus (n = 25), and adenovirus (n = 11). At the time of hospital admission, all viral GE patients demonstrated increased MMP-9 and decreased MMP-2 and TIMP-2 serum levels. In contrast to viral GE patients, serum MMP-9 levels were not elevated at the time of hospital admission but elevated at the time of discharge; serum MMP-2 and TIMP-2 levels were decreased both at the time of admission and discharge in bacterial enteritis patients. Interestingly, the kinetics of serum MMP-2, MMP-9, and TIMP-2 levels were similar among the viral GE patients but distinct from bacterial enteritis patients. Thus, the involvement of MMPs and TIMPs in the pathophysiology of gastrointestinal symptoms likely varies depending on the etiological agent. Further studies are required to verify whether the extent of the bacterial enteritis or age of the patients influences these serum biomarkers. J. Med. Virol. 88:1341-1346, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Role of Collecting Duct Renin in the Pathogenesis of Hypertension.

    Science.gov (United States)

    Gonzalez, Alexis A; Lara, Lucienne S; Prieto, Minolfa C

    2017-08-01

    The presence of renin production by the principal cells of the collecting duct has opened new perspectives for the regulation of intrarenal angiotensin II (Ang II). Angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) are present in the tubular fluid coming from the proximal tubule and collecting duct. All the components needed for Ang II formation are present along the nephron, and much is known about the mechanisms regulating renin in juxtaglomerular cells (JG); however, those in the collecting duct remain unclear. Ang II suppresses renin via protein kinase C (PKC) and calcium (Ca 2+ ) in JG cells, but in the principal cells, Ang II increases renin synthesis and release through a pathophysiological mechanism that increases further intratubular Ang II de novo formation to enhance distal Na + reabsorption. Transgenic mice overexpressing renin in the collecting duct demonstrate the role of collecting duct renin in the development of hypertension. The story became even more interesting after the discovery of a specific receptor for renin and prorenin: the prorenin receptor ((P)RR), which enhances renin activity and fully activates prorenin. The interactions between (P)RR and prorenin/renin may further increase intratubular Ang II levels. In addition to Ang II, other mechanisms have been described in the regulation of renin in the collecting duct, including vasopressin (AVP), bradykinin (BK), and prostaglandins. Current active investigations are aimed at elucidating the mechanisms regulating renin in the distal nephron segments and understand its role in the pathogenesis of hypertension.

  16. The role of neurosteroids in the pathogenesis of hepatic encephalopathy

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    Mladenović Dušan

    2016-01-01

    Full Text Available Hepatic Encephalopathy (HE represents a neuropsychiatric syndrome caused by acute or chronic liver failure. Hyperammonemia plays a pivotal role in the development of HE through modulation of neurotransmission, oxidative stress, neuroinflammation, mitochondrial dysfunction, and energy deficit. Neurosteroids contribute significantly to increased GABAergic tone in HE. Ammonia, in combination with manganese and proinflammatory cytokines, stimulate neurosteroid synthesis by up-regulation of translocator protein, a component of multiprotein complex that stimulate cholesterol transport into astrocytic mitochondria. Cholesterol serves as a substrate for the synthesis of neurosteroids allopregnanolone and tetrahydro-deoxycorticosterone. After release from astrocytes, allopregnanolone and tetrahydro-deoxycorticosterone potentiate GABAergic transmission by positive allosteric modulation of GABAA receptor, thus contributing to cognitive deficit and alterations in sleep-wake cycle. Additional potential mechanisms of neurosteroid action in HE include modulation of serotoninergic, cholinergic, glutamatergic, glycinergic, and opioid receptor activities, as well as modulation of gene expression. This review aimed to summarize current knowledge of the role of neurosteroids in the pathogenesis of HE.

  17. Role of Autophagy in HIV Pathogenesis and Drug Abuse.

    Science.gov (United States)

    Cao, Lu; Glazyrin, Alexey; Kumar, Santosh; Kumar, Anil

    2017-10-01

    Autophagy is a highly regulated process in which excessive cytoplasmic materials are captured and degraded during deprivation conditions. The unique nature of autophagy that clears invasive microorganisms has made it an important cellular defense mechanism in a variety of clinical situations. In recent years, it has become increasingly clear that autophagy is extensively involved in the pathology of HIV-1. To ensure survival of the virus, HIV-1 viral proteins modulate and utilize the autophagy pathway so that biosynthesis of the virus is maximized. At the same time, the abuse of illicit drugs such as methamphetamine, cocaine, morphine, and alcohol is thought to be a significant risk factor for the acquirement and progression of HIV-1. During drug-induced toxicity, autophagic activity has been proved to be altered in various cell types. Here, we review the current literature on the interaction between autophagy, HIV-1, and drug abuse and discuss the complex role of autophagy during HIV-1 pathogenesis in co-exposure to illicit drugs.

  18. Oligodendrocyte Injury and Pathogenesis of HIV-1-Associated Neurocognitive Disorders

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    Han Liu

    2016-07-01

    Full Text Available Oligodendrocytes wrap neuronal axons to form myelin, an insulating sheath which is essential for nervous impulse conduction along axons. Axonal myelination is highly regulated by neuronal and astrocytic signals and the maintenance of myelin sheaths is a very complex process. Oligodendrocyte damage can cause axonal demyelination and neuronal injury, leading to neurological disorders. Demyelination in the cerebrum may produce cognitive impairment in a variety of neurological disorders, including human immunodeficiency virus type one (HIV-1-associated neurocognitive disorders (HAND. Although the combined antiretroviral therapy has markedly reduced the incidence of HIV-1-associated dementia, a severe form of HAND, milder forms of HAND remain prevalent even when the peripheral viral load is well controlled. HAND manifests as a subcortical dementia with damage in the brain white matter (e.g., corpus callosum, which consists of myelinated axonal fibers. How HIV-1 brain infection causes myelin injury and resultant white matter damage is an interesting area of current HIV research. In this review, we tentatively address recent progress on oligodendrocyte dysregulation and HAND pathogenesis.

  19. Genetics and pathogenesis of systemic lupus erythematosus and lupus nephritis.

    Science.gov (United States)

    Mohan, Chandra; Putterman, Chaim

    2015-06-01

    Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder that has a broad spectrum of effects on the majority of organs, including the kidneys. Approximately 40-70% of patients with SLE will develop lupus nephritis. Renal assault during SLE is initiated by genes that breach immune tolerance and promote autoantibody production. These genes might act in concert with other genetic factors that augment innate immune signalling and IFN-I production, which in turn can generate an influx of effector leucocytes, inflammatory mediators and autoantibodies into end organs, such as the kidneys. The presence of cognate antigens in the glomerular matrix, together with intrinsic molecular abnormalities in resident renal cells, might further accentuate disease progression. This Review discusses the genetic insights and molecular mechanisms for key pathogenic contributors in SLE and lupus nephritis. We have categorized the genes identified in human studies of SLE into one of four pathogenic events that lead to lupus nephritis. We selected these categories on the basis of the cell types in which these genes are expressed, and the emerging paradigms of SLE pathogenesis arising from murine models. Deciphering the molecular basis of SLE and/or lupus nephritis in each patient will help physicians to tailor specific therapies.

  20. Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

    Science.gov (United States)

    Teixeira, Antonio R. L.; Hecht, Mariana M.; Guimaro, Maria C.; Sousa, Alessandro O.; Nitz, Nadjar

    2011-01-01

    Summary: Acute Trypanosoma cruzi infections can be asymptomatic, but chronically infected individuals can die of Chagas' disease. The transfer of the parasite mitochondrial kinetoplast DNA (kDNA) minicircle to the genome of chagasic patients can explain the pathogenesis of the disease; in cases of Chagas' disease with evident cardiomyopathy, the kDNA minicircles integrate mainly into retrotransposons at several chromosomes, but the minicircles are also detected in coding regions of genes that regulate cell growth, differentiation, and immune responses. An accurate evaluation of the role played by the genotype alterations in the autoimmune rejection of self-tissues in Chagas' disease is achieved with the cross-kingdom chicken model system, which is refractory to T. cruzi infections. The inoculation of T. cruzi into embryonated eggs prior to incubation generates parasite-free chicks, which retain the kDNA minicircle sequence mainly in the macrochromosome coding genes. Crossbreeding transfers the kDNA mutations to the chicken progeny. The kDNA-mutated chickens develop severe cardiomyopathy in adult life and die of heart failure. The phenotyping of the lesions revealed that cytotoxic CD45, CD8+ γδ, and CD8α+ T lymphocytes carry out the rejection of the chicken heart. These results suggest that the inflammatory cardiomyopathy of Chagas' disease is a genetically driven autoimmune disease. PMID:21734249