Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have reported two cases of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) associated with Graves' disease. Case 1: a 45-year-old woman noticed a diffuse goiter, palpitation and emaciation in 1977. Laboratory studies confirmed that she had Graves' disease, and she was treated with antithyroid drug. In 1986, when the hyperthyroidism was subsided, she showed progressive symmetrical weakness and numbness in her limbs, and she was almost in tetraplegia at 1987. Markedly slowed motor and sensory nerve conductions and elevated CSF proteins as well as clinical manifestations confirmed the diagnosis of CIDP. Following corticosteroid-pulse therapy and plasmapheresis resulted in good recovery in both motor and sensory impairment, though two-times of relapses were observed. Case 2: a 33-year-old man first noticed weakness in his legs in 1977, motor and sensory disturbances progressed for 12 years. Slowed nerve conduction, high CSF proteins and two-times of relapses in early phase indicated that the CIDP was the diagnosis. In 1989 he complained general fatigue, hyperhidrosis and body-weight loss. The serum thyroid hormone levels were high, and other laboratory studies confirmed the presence of Graves' disease. The cases with both CIDP and Graves' disease has rarely been reported. The background mechanism of this association is not well understood, but the susceptibility to CIDP and Graves' disease may be related to the HLA antigens and immunoglobulin Gm allotypes of which are the genes linked to the major histocompatibility complex and controlling immune responses. The present two cases commonly shared several HLA-DR antigens, but their significance should be confirmed by examining many cases.
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PMID:[Two cases of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) associated with Graves' disease]. 178 65

In vivo therapy with monoclonal antibody (mAb) GK1.5, which recognizes a glycoprotein antigen designated L3T4 on murine helper T lymphocytes, either prevented or suppressed the development of murine lupus, autoimmune encephalomyelitis, and collagen arthritis. The L3T4 antigen in the mouse is analogous to the human Leu-3/T4 antigen expressed on helper T lymphocytes, because they both participate in the T cell response to class II major histocompatibility complex (MHC) antigens. Class II MHC genes and I-A antigens mediate murine experimental autoimmune myasthenia gravis (EAMG) induced by acetylcholine receptor (AChR) autoimmunity. We studied the efficacy of mAb GK1.5 as an immunotherapeutic agent for murine EAMG. Therapy with mAb GK1.5 not only suppressed established autoimmunity to AChR but also prevented loss of muscle AChR in mice with EAMG. Moreover, permanent remission of clinical muscle weakness was induced if mAb GK1.5 therapy was initiated after the onset of clinical disease. Because the function of the Leu-3/T4 determinant on human helper T lymphocytes is analogous to the murine L3T4 determinant, use of antibody to the Leu-3/T4 determinant as an immunotherapeutic agent may provide a way to control the progression of human MG.
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PMID:Immunotherapy for myasthenia gravis: a murine model. 241 35

Myasthenia gravis (MG) is an autoimmune neuromuscular disease manifested by muscle weakness and fatiguability. The primary pathology in MG is antibody and complement-mediated destruction of muscle acetylcholine receptor (AChR). Like other autoimmune diseases, MG is associated with certain HLA antigens, particularly HLA-B8 and DR3 in Caucasians. Also, certain GM antigens and complotypes are associated with MG. Therefore, it is crucial to study the immunogenetic aspect of MG in animal models to evaluate disease etiopathogenesis and eventual strategy for specific therapy. In the introduction of this review article, I focus on the association of HLA and GM antigens in MG and emphasize the mouse model of experimental autoimmune myasthenia gravis (EAMG) as an ideal model to study the immunogenetic aspect of MG. The following sections deal with the role of (1) major histocompatibility complex (MHC), (2) immune response gene, (3) the IA molecule, (4) the Igl locus, (5) the complement genes, and (6) non-MHC genes on EAMG pathogenesis. The review concludes with future immunogenetic analysis and eventual strategy for specific therapy from an immunogeneticist's point of view.
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PMID:Immunogenetics of experimental autoimmune myasthenia gravis. 267 61

The rat CT antigens are a system of medial histocompatibility antigens linked to RT1, the rat major histocompatibility complex (MHC). They have aroused interest firstly because, despite their extreme serological weakness, they are targets for 'unrestricted' cytotoxic T lymphocytes (CTL); and secondly because they have appeared to represent a complex genetic system in terms both of the number of genetic loci involved and the number of distinguishable antigenic specificities expressed. The CT system was originally defined by the reactions of LEW anti-F344 (RT1l anti-RT1lv1) secondary in vitro CTL. These CTL reacted strongly on DA(RT1av1) targets, but much more weakly on AUG or PVG (RT1c) targets. We have used the recently derived RT1 recombinant rat strains PVG.R19 (RT1.Aav1Iav1Cc) and PVG.R20 (RT1.AcIcCav1) to investigate the genetic control of this system. Contrary to previous interpretations, the results are consistent with a model in which CT is a single locus, which maps to the RT1.C region. In addition, our results demonstrate that there is cross-reactivity of anti-RT1C CTLs on RT1A products, and we suggest that the earlier placement of a CT locus in the RT1.A region was probably incorrect and a consequence of this cross-reactivity.
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PMID:Genetics of the rat CT system: its apparent complexity is a consequence of cross-reactivity between the distinct MHC class I antigens RT1.C and RT1.A. 387 78

Gene(s) at the I-A subregion of the murine major histocompatibility complex influence susceptibility to experimental autoimmune myasthenia gravis. C57Bl/6 mice immunized with acetylcholine receptors (AChR) in complete Freund's adjuvant demonstrated cellular and humoral immune responses to AChR. They developed muscle weakness characteristic of myasthenia gravis and demonstrated a reduction in the muscle AChR content. The kinetics of AChR-specific lymphocyte proliferation generally correlate with anti-AChR antibody response. AChR-specific lymphocyte proliferation was also observed in C57Bl/6 splenocytes after secondary immunization with AChR. The in vitro cellular reactivity to AChR in experimental autoimmune myasthenia gravis (EAMG) mice (C57Bl/6) was suppressed by monoclonal anti-I-Ab antibodies directed against private (Ia20) or public (Ia8) specificities, suggesting a critical role for these Ia determinants in the cellular immune response to AChR in murine EAMG.
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PMID:Cellular immune response to acetylcholine receptors in murine experimental autoimmune myasthenia gravis: inhibition with monoclonal anti-I-A antibodies. 657 68

Mice immunized with acetylcholine receptor (AChR) purified from Torpedo californica form anti-AChR antibodies and often develop muscular weakness and flaccid paralysis closely resembling the human disease myasthenia gravis. This condition, termed experimental myasthenia gravis (EMG), is strain dependent in that the frequency of paralysis is much greater in some strains than in others. Differences in the frequency of EMG might result from differences in the immune system or the neuromuscular junction. In these studies, we have identified two loci, the major histocompatibility complex (H-2) region on chromosome 17 and the region that contains the structural genes for the constant region of immunoglobulin heavy chains (IgCH region) on chromosome 12, which significantly effect the probability with which a mouse immunized with T. californica AChR can be expected to become paralyzed. One genotype (H-2b, Ig-1b) correlated with high susceptibility to EMG in four strains with three dissimilar backgrounds. These studies demonstrate that susceptibility to EMG is a heritable trait determined by at least two distinct loci that are linked to regions of the mouse genome that regulate immune responsiveness.
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PMID:Linkage between the frequency of muscular weakness and loci that regulate immune responsiveness in murine experimental myasthenia gravis. 677 45

Infection of outbred CD-1 mice with the Tucson strain of coxsackievirus B1 (CVB1T) leads to the development of chronic hind limb weakness and associated inflammatory muscle disease. Host factors that influence susceptibility have not been studied in this mouse model of chronic inflammatory myopathy (IM). Therefore, the pathogenesis was examined by using different inbred strains of mice. Initially, seven strains of mice with either the H-2d or H-2b major histocompatibility complex (MHC) haplotype were evaluated. All strains showed similar levels of acute mortality caused by viral infection, but chronic weakness or inflammation did not develop in two strains with the B6 background, regardless of their MHC haplotype. In susceptible mice, weakness was more likely to develop in the H-2d strains than in mice with the H-2b haplotype. Based on these results, H-2 congenic strains of the susceptible B10 background (C57BL/10 and B10.D2) and the resistant B6 background (C57BL/6 and B6.C-H2d) were examined in greater detail. During acute infection, the kinetics and degree of viral replication in hind limb muscle were similar among B6 and B10 strains. By 4 weeks after infection, more intense chronic muscle inflammation and pathology were observed in susceptible B10 mice of the H-2d haplotype than in those of the H-2b haplotype. Resistant B6 mice did not show signs of inflammation or calcification, but they did exhibit some myopathic features, including centralized nuclei and variations in myofiber size and shape. These changes were less common in resistant B6 mice than in B10 strains but were significant when compared with changes in uninfected controls. Viral RNA persistence and elevated titers of antiviral IgG were more prevalent in but not restricted to susceptible strains. These studies demonstrate that host background genes confer resistance to chronic IM but also that MHC genes influence disease severity. They also reveal that susceptibility to acute CVB1T infection is under different genetic control than that which mediates development of chronic post-viral IM.
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PMID:Genetic determinants of susceptibility to coxsackievirus B1-induced chronic inflammatory myopathy: effects of host background and major histocompatibility complex genes. 878 35

Sporadic inclusion body myositis (IBM) is the most common inflammatory myopathy affecting patients over the age of 50 years. Dysimmune and degenerative aetiologies have been postulated, but viral infections have not been associated with the disease. Two HIV-I (human immunodeficiency virus type 1) infected men and one woman infected with HTLV-1 (human T cell leukaemia virus type 1) developed progressive proximal muscle weakness unrelated to antiretroviral therapy. Their muscle biopsies were studied by light and electron microscopy, by immunocytochemistry to determine the expression of major histocompatibility complex (MHC) molecules and identify the type of infiltrating cells and T cell receptor (TCR) subunits, and by reverse transcription-polymerase chain reaction (RT-PCR) and single or double immunocytochemistry to search for retrovirally infected endomysial cells. The clinical features were consistent with sporadic IBM. The muscle biopsies showed primary endomysial inflammation, red-rimmed vacuoles, amyloid deposits, eosinophilic inclusions, and small round fibres in groups, all diagnostic of IBM. The muscle fibres expressed MHC class-1 antigens and were invaded primarily by CD8+ T-lymphocytes preferentially bearing TCR V beta 5.1 and V beta 13 chains. The HIV-1 or HTLV-1 antigens were detected only on endomysial macrophages on or around muscle fibres, but not within the muscle fibres. We conclude that IBM occurs in HIV-1 and HTLV-1 infected individuals and has a clinical, histological and immunological pattern identical to sporadic IBM in the non-retrovirally infected patients. Retroviruses do not directly infect the muscle, but persistent retroviral infections may provide superantigenic stimulation and trigger an endomysial inflammatory response identical to that occurring in sporadic IBM.
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PMID:Inclusion body myositis in HIV-1 and HTLV-1 infected patients. 900 95

In 14 patients with polymyositis (PM), 5 patients (2 males and 3 females) were positive for anti-hepatitis C virus (HCV) antibody measured by a second generation assay. We analysed the clinical characteristics and histopathological findings of the biopsied muscles from those 5 patients. They aged from 42 to 65 years averaging 53.6 years. Two asymptomatic patients visited our hospital due to elevated muscle enzyme levels, who had slight weakness in their orbicularis oculi and neck muscles on physical examination. The other 3 patients had moderate weakness of the proximal muscles. Anti-nuclear antibody was positive in 2 of the 5 patients and anti-Jo 1 antibody was negative in all patients. The serum enzymes elevated were creatine kinase (215-2, 207 (IU/l)) and glutamate oxaloacetate transaminase (40-119 (KU)). HCV-RNA was positive in the sera of 4 patients examined. All muscle biopsy specimens revealed variation in fiber size with inflammatory cellular infiltration and observed degenerating and regenerating fibers. The scant infiltration type was observed in 2 asymptomatic patients in whom the infiltrated cells were CD4 positive. The endomysial infiltration type was observed in 3 symptomatic patients; CD8 positive cells were found focally to diffusely in 2 patients examined. The expression of class 1 molecules from the major histocompatibility complex was detected mainly in infiltrated fibers to variable degrees. All of the patients showed a good response to the initial steroid therapy. The present study suggests that autoimmune reaction related to HCV infection causes myositis, therefore anti-HCV antibody should be checked in cases of PM.
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PMID:[Clinical characteristics and muscle histopathology in polymyositis positive anti-hepatitis with C virus antibody]. 921 18

The optic nerve of rats with EAE was examined at various times to determine the integrity of the blood-brain barrier (BBB) and to assess monocyte-macrophage, T cell, and microglial responses. In naive control animals, leakage of horseradish peroxidase (HRP) and the presence of cells expressing major histocompatibility complex (MHC) class II antigen were evident in the meninges of the retrobulbar optic nerve. In rats with EAE, microglia in the region of the lamina cribrosa and in the regions adjacent to the meninges became activated from day 7 to 8 postinduction (pi). HRP leakage was also evident in the region of the lamina cribrosa from day 7 to 8 pi. On day 8 pi, infiltration of inflammatory cells and Monastral blue leakage were apparent in the myelinated region of the optic nerve. The intensity of these cellular and vascular changes peaked at day 12 pi, when signs of clinical disease became manifest. Monocytes-macrophages expressing MHC class II and the ED1 antigen, together with lymphocytes expressing the alphabetaT cell receptor, constituted the major proportion of cells associated with inflammatory lesions. Thus: (i) the inherent weakness of the BBB as well as the presence of both antigen (myelin) and MHC class II+ cells in the retrobulbar optic nerve are likely susceptibility factors for the frequent involvement of this region in EAE and multiple sclerosis; and (ii) activation of microglia occurs early in the pathogenesis of experimental optic neuritis.
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PMID:Microvascular and cellular responses in the optic nerve of rats with acute experimental allergic encephalomyelitis (EAE). 966 98


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