Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of proteins associated with immune function was investigated immunohistochemically in postmortem brain and spinal cord of patients with amyotrophic lateral sclerosis (ALS). Reactive microglia/macrophages displaying high levels of leukocyte common antigen (LCA), the immunoglobulin receptor Fc gamma R1, lymphocyte function associated molecule-1 (LFA-1), the complement receptors CR3 and CR4, the class II major histocompatibility complex molecules HLA-DR, HLA-DP and HLA-DQ and common determinants of the class I HLA-A,B,C complex were abundant in affected areas in ALS. These areas included the primary motor cortex, motor nuclei of the brain stem, the anterior horn of the spinal cord, and the full extent of the corticospinal tract. A significant number of T lymphocytes of the helper/inducer (CD4+) and cytotoxic/suppressor (CD8+) subtypes were observed marginating along the walls of capillaries and venules and extending into the parenchyma of affected areas. Clusters of complement activated oligodendroglia as well as degenerating neurites positive for C3d and C4d were frequently detected in ALS-affected areas. These data provide evidence of immune-effector changes in ALS. They are consistent with an autoimmune or slow virus theory of the disorder, but may reflect only secondary changes.
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PMID:Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue. 134 73

Features common to amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD) are reviewed. Shared epidemiological aspects include an increasing frequency which is proportional for each disease. We draw attention to geographic non-uniform distribution which, for ALS and PD, correlates positively with latitude. Clinical and pathological overlap occurs in the same patients, and in members of the same family. A high early morning plasma cysteine/sulphate ratio possibly related to the development of proteinacious inclusions, as well as ubiquinated neuronal inclusions, characterize ALS, PD and AD. HLA-DR (the human group II major histocompatibility class) staining is marked in ALS, PD and AD and may represent autoimmunity-incited by-products of neuronal degeneration. Based upon demonstrated glutaminergic connections between the neocortex and anterior horn cells, the entorhinal cortex and the basal ganglia we hypothesize that ALS, AD and PD are phylogenetic disturbances of the neocortical cell. The postsynaptic neuron may degenerate secondarily to anterograde effects of deranged glutamate metabolism. Future therapeutic strategies should be directed to agents that decrease transmission induced by excitatory amino-acids.
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PMID:Amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease: phylogenetic disorders of the human neocortex sharing many characteristics. 157 56

Elements consistent with a cell mediated immune response were identified immunohistochemically in amyotrophic lateral sclerosis (ALS) spinal cord and Alzheimer disease (AD) hippocampus. T helper/inducer and cytotoxic/suppressor lymphocytes were detected in affected tissues in both diseases. In addition, abundant reactive microglia were found expressing the major histocompatibility glycoproteins HLA-A,B,C and HLA-DR, as well as receptors for the Fc chain (Fc gamma R1), for complement 3 and 4, and for vitronectin. In AD, the complement proteins C1q, C4d, C3d and C5b-9 were found on dystrophic neurites, neuropile threads and some neurofibrillary tangles. In ALS, the only complement proteins identified were C4d and C3d. The integrin ligands vitronectin and ICAM-1 were also identified in affected tissues in both diseases.
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PMID:Reactions of the immune system in chronic degenerative neurological diseases. 193 84

The spinal cord and motor cortex of patients with amyotrophic lateral sclerosis (ALS) were examined with immunohistochemical methods for the presence of IgG. In 13 of 15 spinal cords, a population of motoneurons stained positively for IgG in a granular pattern, characteristic of binding to the rough endoplasmic reticulum. In 6 of 11 motor cortices, a proportion of pyramidal cells also stained positively for IgG. No such reactivity was noted in motoneurons of control human tissues, although positive IgG staining was present in astrocytes of ALS and control specimens. Reactive microglia and/or macrophages were detected in the territory of degenerating pyramidal tracts and ventral horns. The surface of most of these cells stained positively for IgG, and 50% stained positively for HLA-DR. The accumulation of IgG in motoneurons and the presence of immunologically active macrophages provide additional evidence for the participation of immunologic factors in the pathogenesis of ALS.
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PMID:IgG reactivity in the spinal cord and motor cortex in amyotrophic lateral sclerosis. 212 77

In order to test the hypothesis that the immune system plays a role in the pathogenesis of amyotrophic lateral sclerosis (ALS), the cellular composition of the spinal cord inflammatory infiltrate was analysed in eight cases of sporadic ALS by a panel of monoclonal antibodies. The majority of the many diffusely scattered lymphocytes seen in the anterior and lateral corticospinal tracts and anterior horns belonged to the suppressor/cytotoxicity T-cell subset and were admixed with variable numbers of macrophages. Helper-inducer T-cells were rare and B-cells were conspicuously absent. Compared to controls, ALS specimens exhibited an increase in major histocompatibility complex (MHC) products or human leucocyte antigens (HLA) in the corticospinal tracts and anterior horns. HLA-ABC antigens were expressed in the honeycomb pattern of the glial matrix of the spinal cord, and HLA-DR antigens were strongly expressed by large dendritic cells. In addition, macrophages and endothelial cells were labelled by HLA-DR. These findings suggest that an autoimmune process or infectious agent may play a role in ALS.
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PMID:Immunohistochemical characterization of the inflammatory infiltrate in amyotrophic lateral sclerosis. 226 15

Reactive microglia or macrophages expressing the histocompatibility glycoprotein HLA-DR were detected in many neurological diseases including Alzheimer's, Parkinson's, Pick's and Huntington's diseases, parkinsonism-dementia of Guam, amyotrophic lateral sclerosis, Shy-Drager syndrome, multiple sclerosis and AIDS encephalopathy. Reactive astrocytes, also present in these conditions, were established as a population distinct from the HLA-DR positive microglia by double immunostaining for glial fibrillary acidic protein and HLA-DR. A distinctive pattern of HLA-DR positive cells was seen in each disease entity. Areas known to contain pathology always stained positively, and, in several cases, reactive microglia appeared in areas that would otherwise not have been suspected of being involved in the pathological process. HLA-DR staining, which outlines the surface membranes of positive cells, was so strong that lesioned areas could frequently be identified in sections with the naked eye. In adjacent sections stained with H&E or sections destained of HLA-DR and then restained with H&E, gliosis was often hard to identify except on close microscopic inspection. The results suggest that HLA-DR staining may be a valuable addition to standard neuropathological methods and might be useful in investigating diseases where pathology has not yet been identified.
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PMID:Expression of the histocompatibility glycoprotein HLA-DR in neurological disease. 297 27

To investigate the possibility of local antigen presentation within the peripheral nerve in amyotrophic lateral sclerosis (ALS), cryostat sections of 83 peripheral nerve biopsies were stained for the demonstration of HLA-DR using a monoclonal antibody. Forty samples showed increased expression of HLA-DR in endoneurium. The phenotypic characteristics of the HLA-DR positive cells are chiefly Schwann cells, using S-100 protein as a marker. We did not detect any co-expression between HLA-DR and NF (axons) and HLA-DR and myelin marker. We also detected co-expression between HLA-DR and NGFr in a majority of HLA-DR positive cells. Inflammatory cells were infrequent, being detected only in 11 cases, predominantly around epineurial blood vessels. Motor and sensory nerve biopsies performed simultaneously showed higher expression of HLA-DR in motor nerves in 2 out of 4 patients. The significance of these findings is not clear. The presence of endoneurial cells expressing HLA-DR suggests that an autoimmune mechanism may be involved in ALS having Schwann as the main target.
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PMID:Expression of HLA-DR in peripheral nerve of amyotrophic lateral sclerosis. 761 42

In a 2-year hospital-based study in Jordan 131 Arab multiple sclerosis patients were identified including 84 Palestinians and 36 Jordanians. Based on MS/ALS case ratio, multiple sclerosis was found to be twice as common among Palestinians than Jordanians. Other than the less marked female preponderance among Jordanian patients, the disease had the same clinical and paraclinical characteristics in both groups. It was more likely for Palestinian and Jordanian patients to originate from the northern parts of their countries, to be Rh negative and to be HLA-DR2 positive than their controls. Palestinians (patients and controls) did not show significant differences from Jordanians (patients and controls) in relation to their eye color, ABO and Rh blood groups distribution nor the HLA-DR or HLA-DQ (apart from HLA-DQ3) epitopes frequency, thus not offering any significant difference in the genetic-racial markers studies to explain the difference in the observed disease susceptibility. Previous studies demonstrated that 2 racially different populations sharing the same environment can have different risk of developing multiple sclerosis, but this study has shown that this can also be true for 2 racially similar populations sharing the same environment.
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PMID:Epidemiology of multiple sclerosis in Arabs in Jordan: a comparative study between Jordanians and Palestinians. 886 73

Enriched populations of human microglial cells were isolated from mixed cell cultures prepared from embryonic human telencephalon tissues. Human microglial cells exhibited cell type-specific antigens for macrophage-microglia lineage cells including CD11b (Mac-1), CD68, B7-2 (CD86), HLA-ABC, HLA-DR and ricinus communis aggulutinin lectin-1 (RCA-1), and actively phagocytosed latex beads. Gene expression and protein production of cytokines, chemokines and cytokine/chemokine receptors were investigated in the purified populations of human microglia. Normal unstimulated human microglia expressed constitutively mRNA transcripts for interleukin- 1beta (IL-1beta) -6, -8, -10, -12, -15, tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and monocyte chemoattractant protein-1 (MCP-1), while treatment with lipopolysaccharide (LPS) or amyloid beta peptides (Abeta) led to increased expression of mRNA levels of IL-8, IL-10, IL-12, TNF-alpha, MIP-1alpha, MIP-1beta, and MCP-1. Human microglia, in addition, expressed mRNA transcripts for IL-1RI, IL-1RII, IL-5R, IL-6R, IL-8R, IL-9R, IL-10R, IL-12R, IL-13R, and IL-15R. Enzyme-linked immunosorbent assays (ELISA) showed increased protein levels in culture media of IL-1beta, IL-8, TNF-alpha, and MIP-1alpha in human microglia following treatment with LPS or Abeta. Increased TNF-alpha release from human microglia following LPS treatment was completely inhibited with IL-10 pretreatment, but not with IL-6, IL-9, IL-12, IL-13, or transforming growth factor-beta (TGF-beta). Present results should help in understanding the basic microglial biology, but also the pathophysiology of activated microglia in neurological diseases such as Alzheimer disease, Parkinson disease, Huntington disease, amyotrophic lateral sclerosis, stroke, and neurotrauma.
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PMID:Cytokines, chemokines, and cytokine receptors in human microglia. 1211 20

An immunological function has been proposed for the choroid plexus (CP). In multiple sclerosis (MS) brains, CPs show (immunohistochemistry to HLA-DR, CD3, CD20, CD68, VCAM-1, CD138) T lymphocytes in vessels and stroma, VCAM-1 expression on endothelia, intense HLA-DR immunostaining on cells in CP stroma, among CP epithelium and on epiplexus cells. CPs in control or amyotrophic lateral sclerosis brains do not show such inflammatory changes. Intense CP inflammation is observed in viral encephalitis. Changes in MS CPs suggest persisting immune activation, with intensity similar to acute encephalitis, even in MS phases in which neurodegeneration prevails. In MS, CPs could represent a site for lymphocyte entry in the CSF and for CSF antigens presentation.
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PMID:Involvement of the choroid plexus in multiple sclerosis autoimmune inflammation: a neuropathological study. 1853 42


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