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)

Histochemical and ultrastructural analyses were performed postflight on hind limb skeletal muscles of rats orbited for 12.5 days aboard the unmanned Cosmos 1887 biosatellite and returned to Earth 2 days before sacrifice. The antigravity adductor longus (AL), soleus, and plantaris muscles atrophied more than the non-weight-bearing extensor digitorum longus, and slow muscle fibers were more atrophic than fast fibers. Muscle fiber segmental necrosis occurred selectively in the AL and soleus muscles; primarily, macrophages and neutrophils infiltrated and phagocytosed cellular debris. Granule-rich mast cells were diminished in flight AL muscles compared with controls, indicating the mast cell secretion contributed to interstitial tissue edema. Increased ubiquitination of disrupted myofibrils implicated ubiquitin in myofilament degradation. Mitochondrial content and succinic dehydrogenase activity were normal, except for subsarcolemmal decreases. Myofibrillar ATPase activity of flight AL muscle fibers shifted toward the fast type. Absence of capillaries and extravasation of red blood cells indicated failed microcirculation. Muscle fiber regeneration from activated satellite cells was detected. About 17% of the flight AL end plates exhibited total or partial denervation. Thus, skeletal muscle weakness associated with spaceflight can result from muscle fiber atrophy and segmental necrosis, partial motor denervation, and disruption of the microcirculation.
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PMID:Skeletal muscle fiber, nerve, and blood vessel breakdown in space-flown rats. 215 85

Two female infants who developed normally during infancy began to have progressive muscle hypotonia and weakness from 2 years 10 months and 2 years 3 months of ages, respectively. Both patients had rapidly progressive muscle weakness with death from respiratory failure at 4 years 11 months and 3 years 9 months, respectively. In addition to mild inflammation in their muscle biopsies, the most striking finding was the presence of numerous reducing bodies (RB) in almost all degenerating fibers. By electron microscopy, these bodies consisted of fine granular material, usually located around the degenerating nucleus. These bodies showed no immunohistochemical reaction to antibodies against structural, cytoskeletal and membrane proteins and a histone-specific antibody against nuclei and chromosomes. They were occasionally positively stained with a ubiquitin antibody. Although the origin of these bodies remains unknown, they appeared to be related to active myofibrillar degeneration, probably resulting from primary nuclear degeneration.
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PMID:Fatal reducing body myopathy. Ultrastructural and immunohistochemical observations. 772 35

A 74-year-old woman with corticobasal degeneration (CBD) had a 9-year history of progressive loss of strength and rigidity of her right hand and then arm, followed by speech difficulties, dyskinesia, rigidity, spasticity and weakness of the ipsilateral lower limb, ultimately also involving the opposite side. She later developed supranuclear gaze palsy. Her memory remained intact during most of the duration of her disease. Laboratory tests and anti-Parkinsonian medications were not helpful. At autopsy, frontal lobe atrophy, discoloration of putamen (Pt) and pallor of substantia nigra (Sn) were observed. Neuronal loss and gliosis were extensive in motor cortex and milder in frontal cortex, abruptly ending at the central sulcus and junction of cingulate gyrus. "Achromatic" neurons were present. Neuronal loss and gliosis were seen in Pt and Sn and corticobasal inclusions in Sn. Numerous Gallyas/tau-positive, Bielschowsky/ubiquitin-negative coil, sickle, or coma-shaped tangles and thread-like processes were found in affected cortex, Pt and Sn. Some of the tangles were in neurons, but most occurred in astroglia, and their processes. The presence of Gallyas/tau-positive glia in CBD may have the same diagnostic significance as in progressive supranuclear palsy, analogous to the argyrophilic ubiquinated inclusions in oligodendroglia in multisystem atrophy. We suggest that in CBD: (1) cytoskeletal protein metabolism in neurons and glia can simultaneously be perturbed in certain neurodegenerative diseases, and (2) the astrocytosis in CBD may not be simply a reactive process but an integral part of the disease.
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PMID:Unusual case of corticobasal degeneration with tau/Gallyas-positive neuronal and glial tangles. 787 9

IBM has emerged as a clinicopathological entity during the past 25 years but with increasing complexity. It occurs primarily in elderly persons (over the sixth decade of life, with 3:1 male preponderance), but young adults or children may also be affected in some families. FIBM is by and large non-inflammatory though some autosomal dominant FIBM cases have inflammatory cell infiltrates. In IBM, slowly progressive weakness of proximal as well as distal muscle groups occurs and is usually not associated with skin rash or malignancy. The incidence of associated collagen-vascular disease is thought to be lower than in DM or PM but is reported to be as high as 15%. It is generally refractory to treatment with corticosteroids or other immunosuppressants. Muscle biopsy and electromyography may suggest a neurogenic process mixed with myopathic features. None of the histopathological features is specific enough to be a diagnostic criterion. The diagnostic criteria have to be collective, encompassing both clinical and pathological criteria in different combinations. The presence of eosinophilic intranuclear or cytoplasmic inclusions immunoreactive for both beta-amyloid and ubiquitin in affected myofibres may facilitate the diagnosis of IBM. The diagnosis no longer depends on the ultrastructural demonstration of characteristic microtubular filaments as previously thought. The identification of both beta-amyloid and ubiquitin may provide a new concept for the disease process in IBM. A chronic persistent intracytoplasmic synthesis of abnormal amyloid protein in IBM is suspected to be similar to that in Alzheimer's disease. IBM is considered to be intimately related to a heterogenous group of non-inflammatory IBMD, including DMY, OPMD, and both autosomal recessive and dominant FIBM. An inflammatory response has been seen, however, in muscles of both OPMD and autosomal dominant FIBM. The pathogenesis in IBM and in IBMD may not be the same. Unlike IBM, there is no abnormal sarcolemmal expression of MHC-I antigen in IBMD as a sign of T-cell-mediated cytotoxicity causing myofibre destruction. The prion theory derived from identification of amyloidogenic protein in the filament inclusions in the rimmed vacuoles is provocative. If one believes in the contention that the amyloidogenic filaments are the primary pathogen of either IBM or IBMD, one must account for the fact that these filaments are originally derived from sarcolemmal nuclei and not from autophagic vacuoles. Until this is clarified, the possibility that the filaments represent either abnormal or defective 'slow' virus nucleocapsids cannot be completely ruled out.
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PMID:Inclusion body myositis. 815 43

A 9-year-old male horse showed emaciation, weakness and trembling and was euthanatized. Histopathological examinations revealed loss, swelling and chromatolysis of motor neurons throughout the spinal ventral horns, axonal degeneration of the ventral spinal roots. Eosinophilic cytoplasmic inclusions were distributed in degenerated spinal ventral neurons. Ultrastructurally, the inclusions consisted of aggregations of granular dense material and a few vesicles. They reacted positively with polyclonal antibody against ubiquitin. The present case was diagnosed as equine motor neuron disease, which has recently been reported in North America and the United Kingdom.
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PMID:The first case of equine motor neuron disease in Japan. 820 55

Two siblings developed cardiomyopathy several years before slowly progressive muscle weakness. Skeletal muscle biopsy specimens showed subsarcolemmal crescents of dark eosinophilic material in both type I and type II fibres. Immunohistochemically the subsarcolemmal material stained positively for the intermediate filament protein desmin and for the heat shock protein ubiquitin but for no other cytoskeletal proteins. Ultrastructurally the subsarcolemmal deposits consisted of aggregates of granular and filamentous material arising from Z-bands. Follow up muscle biopsies six years later showed an increased number of the muscle fibres that contained subsarcolemmal aggregates that stained positively for desmin and ubiquitin. These clinical and pathological features characterise a rare familial myopathy associated with an unusual distribution of desmin intermediate filament proteins in skeletal and probably also cardiac muscle.
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PMID:Familial desminopathy: myopathy with accumulation of desmin-type intermediate filaments. 850 78

Inclusion body myositis has been recently recognized as a clinical entity although its exact definition remains uncertain. Initially considered to be an inflammatory dermatomyositis, inclusion body myositis can actually take on three specific forms: disseminated muscle atrophy and weakness, pseudopolymyositis, or pseudo-degenerative disease. Inclusion body myositis is different from non-inflammatory neuromuscular diseases with vacuoles. Abnormal deposits are seen within the muscle fiber may contain amyloid substance, beta-amyloid precursor, ubiquitin, antichymotrypsin, protein tau, apolipoprotein E and even prions. The signification of these deposits is unknown. Deletions in mitochondrial DNA have been demonstrated but do not appear to play a causal role. More and more hereditary forms are being recognized and certain may be related to an abnormality in chromosome 9.
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PMID:[Inclusion body myositis]. 869 77

We present the clinical, molecular genetic and neuropathological findings of an 81-year-old man with concurrent Huntington's disease (HD) and familial amyotrophic lateral sclerosis (FALS). His mother had been diagnosed clinically as having ALS. There was no known family history of HD, but a maternal uncle had died in a chronic care psychiatric hospital. The diagnosis of HD in the patient was suspected at age 66, after 8 years of personality change, hallucinations, agitation, cognitive decline and choreoathetosis. No symptoms of motor neuron disease were noticed at that time, but progressive weakness developed later. Postmortem examination revealed cerebral atrophy, marked atrophy of basal ganglia (grade 3), and atrophy of brain stem and spinal cord. The neostriatum displayed massive neuronal loss and gliosis. The neocortex showed changes characteristic of Alzheimer's disease. Pathological lesions also included loss of neurons and gliosis in the anterior horns, Clarke's columns and the hypoglossal nuclei; degeneration of the lateral corticospinal tracts, dorsal spinocerebellar tracts and fasciculus gracilis; and rare Bunina bodies and ubiquitin-positive filamentous skeins in motor-neuron perikarya. Molecular analysis demonstrated chromosome 4p16.3 expansion of trinucleotide repeats characteristic of HD. Analysis of Cu,Zn superoxide dismutase gene and heavy neurofilament subunit gene failed to demonstrate mutations. The concurrence of HD and FALS in our patient and three previously reported cases did not appear to be associated with cosegregation in other family members.
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PMID:Coexistence of Huntington's disease and familial amyotrophic lateral sclerosis: case presentation. 889 Oct 76

The subject presented with intellectual decline followed by progressive muscle weakness of the bilateral upper limbs when he was 60 years old. He had a point mutation (methionin-valine) at 129 prion protein codon. He died at the age of 63 and necropsy revealed bilateral frontal lobe atrophy. The frontal cortex showed neuronal cell loss in layers II and III with spongiform change. Reusche silver impregnation technique for beta-peptide combined with ubiquitin immunostaining revealed perineuronal structures encircling degenerated neurons and ubiquitin-immunoreactive (IR) dot-like deposits. They were distributed particularly in the temporal neocortex and entorhinal cortex. They differed from either classic senile or diffuse plaque by the absence of amyloid core in the center and of amyloid fibrils. Ubiquitin-IR materials were also found as neuronal inclusions in the hippocampal granular cells. Nigral degeneration and neuronal loss in the hypoglossal nerve nucleus and in the anterior horn of the spinal cord were also found and spinal cord motoneurons had Bunina body inclusions. The clinical features and pathological findings were consistent with non-Alzheimer dementia with status spongiosus and neuronal cell loss. The unusual perineuronal structures found in our case might be a specific cellular pathology of dementia of the frontal lobe type.
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PMID:Non-Alzheimer dementia with status spongiosus and neuronal cell loss showing unusual perineuronal structures and point mutation at 129 codon of prion protein. 899 53

This report concerns a case of sporadic amyotrophic lateral sclerosis (ALS) with dementia and Lewy body-like hyaline inclusions (LBHIs). The patient was a 70-year-old woman who initially showed memory disturbance and later developed bulbar palsy, muscle atrophy and weakness. The total clinical course was 51 months. The postmortem examination revealed superficial sponginess and subcortical gliosis in the frontotemporal cortices. Ubiquitin-positive intraneuronal inclusions were found in small cortical neurons of the frontotemporal lobe. Neuronal loss was marked in the spinal anterior horn with degeneration of the pyramidal tracts. The anterior horn cells had ubiquitin-immunoreactive skein-like inclusions and Bunina bodies. LBHIs were present in the lumbar horn; ultrastructurally they were composed of randomly arranged thick filamentous structures studded with granules. The LBHIs were intensely stained with anti-ubiquitin antibody. As in familial ALS and in certain cases of sporadic ALS, some of these inclusions reacted with an antibody against Cu/Zn superoxide dismutase, the enzyme whose gene was recently found to be mutated in some forms of familial ALS.
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PMID:Sporadic amyotrophic lateral sclerosis with dementia and Cu/Zn superoxide dismutase-positive Lewy body-like inclusions. 899 56


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