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)

Dendritic spheroid bodies (SBs) and Lewy bodies (LBs) were identified in comparable numbers in the substantia nigra pars compacta (SBC) of nine parkinsonian cases and one case of striatonigral degeneration but were not found in cases of Huntington's disease or neurologically normal controls. The immunohistochemical profile of the SBs in dystrophic dendrites of nigrostriatal dopaminergic neurons was remarkably similar to that of the LBs found within dendrites or free of the SNC neuropil. Both types of inclusions stained positively with antibodies to tyrosine hydroxylase, ubiquitin and microtubule-associated protein-2 (MAP2), and negatively for Tau-2, although they had different ultrastructural appearances. A few intracellular LBs were stained by antibodies to neurofilament proteins (NFs) 68, 160, and 200 kD, but dendritic SBs and extracellular LBs were not so stained. These data indicate that dendritic SBs and extracellular LBs may have a common molecular pathogenetic origin in Parkinson's disease. On the other hand, the SBs seen in the pars reticulata (SNR) and in the distal nigrostriatal axons even in control cases were generally stained by antibodies to NFs and ubiquitin but not to MAP2. This latter staining pattern in similar to that shown by SBs in the anterior horn in ALS and in the cerebellum of neurologically normal brains and is believed typical of axonal as opposed to dendritic SBs.
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PMID:Two types of spheroid bodies in the nigral neurons in Parkinson's disease. 191 62

Several degenerative diseases of the central nervous system are characterized by the presence of neuronal inclusions. One of these inclusions, neurofibrillary tangles in Alzheimer's disease, has been shown to contain ubiquitin that belongs to a group of proteins known as heat shock proteins. Subsequent studies revealed that ubiquitin is also associated with various neuronal inclusions including Lewy bodies, Pick bodies and hyaline inclusions. Very recently, ubiquitin has been found also to be associated with glial inclusions that are unique to multiple system atrophy. The close association of ubiquitin with varying cellular inclusions, together with its function in the proteolytic process, raised the hypothesis that ubiquitin may be involved in the degradation of abnormal proteins appearing in the damaged neurons and glial cells. In central nervous system, a group of heat shock proteins collectively known as HSP 70 is also present which is constitutive and/or inducible. Since HSP 70 has been suspected to play a crucial role degradation and repair of abnormal intracellular proteins, we hypothesized that HSP 70 may be associated with those inclusions, as the case with ubiquitin. To test this we performed immunohistochemical studies on brain tissues from patients with various neurodegenerative conditions by using specific polyclonal antibody to HSP 70. Brain tissues were obtained at autopsy from each three patients with Alzheimer's disease, Pick's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS) and multiple system atrophy. Tissues were fixed in buffered formalin and embedded in paraffin. Immunostaining was performed by the standard ABC method using diaminobenzidine as a chromogen. Sections were lightly stained with hematoxylin. Polyclonal antibodies were raised in rabbits against mouse HSP 70.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[HSP 70 is associated with abnormal cytoplasmic inclusions characteristic of neurodegenerative diseases]. 205 24

Neuronal inclusions in lower motor neurons in 23 cases of adult-onset sporadic amyotrophic lateral sclerosis were studied immunocytochemically and ultrastructurally. Monoclonal and polyclonal antiubiquitin antibodies recognized four structures in the neuronal perikarya: (1) all Lewy body-like inclusions in 6 cases with a relatively short clinical course, (2) a small percentage of Bunina bodies in 4 cases with abundant Bunina bodies, (3) ill-defined structures closely associated with Bunina bodies (Bunina body-related structures) in 15 cases, and (4) a focally aggregated meshwork of fine filamentous structures not associated with Bunina bodies in all cases. These four structures were not recognized by the antibodies raised against cytoskeletal proteins (neurofilament, tubulin, microtubule-associated protein 2, and phosphorylated tau). Electron microscopy revealed Lewy body-like inclusions to be accumulations of randomly oriented filaments, approximately 15 nm in diameter, covered by fine granules. Bundles of coated filaments 12 nm in diameter that sometimes formed Bunina body-like structures were also observed in the perikarya. Immunoelectron microscopy showed the reaction product with antiubiquitin to be on the filaments, 15 nm in diameter, of Lewy body-like inclusions. Our study revealed the existence of two types of filaments in lower motor neurons of patients with amyotrophic lateral sclerosis: (1) ubiquitin-positive, granule-associated filaments, approximately 15 nm in diameter, that form Lewy body-like inclusions; and (2) 12 nm coated filaments that may be a candidate for another ubiquitin-positive structure and possibly a precursor of Bunina bodies. These two types of filaments may represent early pathological changes of lower motor neurons in amyotrophic lateral sclerosis.
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PMID:Immunocytochemical and ultrastructural studies of lower motor neurons in amyotrophic lateral sclerosis. 215 79

We studied the topographic distribution and immunohistochemical characteristics of spinal cord neurofibrillary tangles (NFTs) in 6 patients with Guamanian amyotrophic lateral sclerosis (ALS) and 6 patients with parkinsonismdementia complex (PD) on Guam, using antibodies to tau protein and ubiquitin. The NFTs were immunoreactive with both antibodies, but staining for tau was more pronounced. As identified by this reactivity, all the Guamanian ALS and PD cases examined showed spinal cord NFTs. The posterior horn had the most and the anterior horn the least. In the posterior horn the NFTs were located mainly in the marginal areas. Large anterior horn cells showed few, if any, NFTs. In addition to perikaryal NFTs, we observed tau-reactive neurites. Our results provide evidence that spinal cord NFTs are not uncommon in Guamanian ALS and PD on Guam and that they are more numerous than previously found with conventional methods.
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PMID:Spinal cord neurofibrillary tangles of Guamanian amyotrophic lateral sclerosis and parkinsonism-dementia complex: an immunohistochemical study. 216 Oct 95

The ultrastructural localization of ubiquitin (Ubq) in spinal cord of 2 cases of amyotrophic lateral sclerosis was studied, using immunoperoxidase and immunogold labeling on Vibratome sections or on sections cut from paraffin blocks. Two different types of ubiquitinated cytoplasmic inclusions were observed: (1) bundles composed of 10-15 nm filaments; (2) small rounded bodies without a limiting membrane. A panel of antibodies to neurofilaments (NFs) did not stain the ubiquitinated bundles, and decorated only axonal swellings. Ubq-positive filamentous deposits could be identified with inclusions previously described ultrastructurally. The absence of staining with antibodies to NFs might be due to abnormalities of the filaments, possibly because of a dysfunction of the ubq proteolytic system.
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PMID:Ubiquitinated filamentous inclusions in spinal cord of patients with motor neuron disease. 216 61

Immunohistochemical studies with an antibody to ubiquitin revealed the presence of filamentous inclusions in spinal anterior horn cells in all of six patients with Guamanian amyotrophic lateral sclerosis (ALS) and one of six cases of parkinsonism-dementia complex (PD) on Guam. Similar ubiquitin-reactive filamentous inclusions were found in all of seven non-Guamanian sporadic ALS patients examined. No similar inclusions were seen in six normal controls or in non-ALS patients who had chromatolytic neurons. The filamentous inclusions differed from spinal neurofibrillary tangles, a characteristic feature of Guamanian ALS and PD, since they were restricted to anterior horn cells and did not react with anti-tau antibody. The chromatolytic neurons of non-ALS patients occasionally had weak diffuse immunoreactivity, but no focal inclusions were detected. These results suggest that ubiquitin-reactive focal filamentous inclusions may reflect a characteristic degenerative process of anterior horn cells of motor neuron disease.
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PMID:Ubiquitin-immunoreactive filamentous inclusions in anterior horn cells of Guamanian and non-Guamanian amyotrophic lateral sclerosis. 216 72

Lewy body-like hyaline inclusion (LI) in the neuronal soma and swollen cord-like processes is a characteristic feature in the anterior horn cells and neurons in thoracic nucleus (Clarke) of familial amyotrophic lateral sclerosis (ALS) with posterior column involvement. We have studied the LI in the case of two sisters with this disorders. Microscopically the LI consists of an eosinophilic "core" surrounded by a basophilic "halo". Ultrastructurally the core consists of granule-associated filaments, while the halo consists of normal-looking neurofilament. Immunocytochemistry with anti-ubiquitin antibody shows that these granule-associated filaments in the core are highly ubiquitinated, while the normal-looking neurofilaments in the halo are not recognized by anti-ubiquitin antibody. Our study proves that LI consists of an aggregation of ubiquitinated filaments among a neurofilamentous accumulation, possibly representing a form of neuronal cytoskeletal disorganization in familial ALS.
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PMID:Immunocytochemical and ultrastructural study of Lewy body-like hyaline inclusions in familial amyotrophic lateral sclerosis. 247 94

Histological sections of cerebral motor cortex, brainstem, and spinal cord from 10 cases of clinically diagnosed motor neurone disease (MND) and 10 control cases were examined by conventional histology and immunocytochemical methods to localise ubiquitin. Intracytoplasmic inclusion bodies were identified in motor neurones of hypoglossal nuclei and appeared specific for MND. Similar inclusions were found in both large pyramidal cells and small neurones in the motor cortex, and were restricted to 4 cases having the amyotrophic lateral sclerosis form of MND with severe degeneration of corticospinal tracts. As reported in earlier studies, cellular inclusion bodies were identified in motor neurones of spinal cord from cases of MND but not in control material. Ubiquitin inclusions in motor neurones appear to be markers for the degenerative process causing neuronal loss in MND and there appears to be a close association between the anatomical location of inclusions and clinical manifestations of disease.
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PMID:Inclusion bodies in motor cortex and brainstem of patients with motor neurone disease are detected by immunocytochemical localisation of ubiquitin. 248 32

The clinical and neuropathological features of a case of a neurodegenerative disorder with pronounced and progressive head drooping, in Japanese Kubisagari, are reported. This female patient died at the age of 72 years after an approximately 20-year history of peculiar posture with progressive head drooping (Kubisagari) and lordosis (bowed posture), parkinsonism, dysphonia and slight muscle wasting of the face, tongue, neck, and distal portions of the upper extremities. She did not display mental deterioration until the terminal stage of the illness. A simple macroscopic inspection formalin-fixed sections of the central nervous system (CNS) showed prominent atrophic frontal and temporal lobes, brownish discoloration of the putamen and an atrophic pyramidal tract. Light microscopy revealed severe neuron loss with fibrillary gliosis at both the above-mentioned lobes and the putamen. Both the facial and hypoglossal nuclei had almost disappeared. Motor neurons in the spinal cord were moderately to markedly decreased. Neither Bunina nor Lewy bodies, senile plaque, nor Pick's argyrophilic neuronal inclusions were observed, but very occasionally ubiquitin-positive neurons were found in the temporal cortex. In conclusion, the hitherto-unrecognized neuropathological findings in the CNS corresponding to progressive head drooping (Kubisagari) suggest that this is a neurodegenerative disorder of the CNS, possibly an atypical form of amyotrophic lateral sclerosis.
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PMID:Clinical and neuropathological features of a neurodegenerative disorder in the central nervous system with progressive head drooping (Kubisagari). 748 99

This study addresses the suggested possible pathogenetic relationship between the late-onset muscular atrophy in patients with the prior diagnosis of poliomyelitis and amyotrophic lateral sclerosis (ALS). For this purpose we applied immunohistochemical techniques to determine the presence of pathological structures that were stained for ubiquitin (a protein involved in degenerative processes) in the spinal cords of patients with a history of poliomyelitis and compared the results with those of ALS, a condition in which cytoplasmic ubiquitin-positive inclusions are invariably found in the anterior horn cells. Our results indicate that post-poliomyelitis patients have no ubiquitin-reactive inclusion bodies in these cells; however, some immunopositive globular and cord-shaped structures are seen in less-affected areas. Similar structures were also found in the spinal cords from patients with ALS and from normal individuals. Our findings would suggest that the pathogenesis of late muscular atrophy in post-poliomyelitis patients is dissimilar to that of ALS.
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PMID:Comparative study of spinal cord ubiquitin expression in post-poliomyelitis and sporadic amyotrophic lateral sclerosis. 751 92


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