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)

Fluorescence photobleaching recovery and immunofluorescence methods have been used to study the lateral mobility and topographical distribution of a major cell surface glycoprotein (CSP). Both endogenous CSP and fluorescent-labeled exogenous CSP bind to the cell surface in a fibrillar pattern and are immobile on the experimental time scale. Azide, vinblastine, and cytochalasin B do not alter the immobility and cell surface distribution of the CSP molecules. Therefore, oxidative phosphorylation and the cytoskeleton do not seem to be responsible for the properties of the bound glycoprotein. The presence of immobile CSP fibrils does not, however, impede the diffusion of a lipid probe, a ganglioside analogue, or various surface antigens. Therefore, the fibrils apparently do not form a "barrier" across the lipid phase of the plasma membrane. In contrast, concanavalin A binds to CSP and is largely immobile in regions rich in CSP. The presence of immobile concanavalin A receptors in areas or on cells lacking CSP indicates that other types of immobile concanavalin A receptors also exist.CSP does not bind to lipid bilayers composed of phosphatidylcholine or oxidized cholesterol. It does bind to dextran-coated bilayers as a diffuse distribution of mobile molecules that can patch after addition of antibodies to CSP. The latter result suggests that CSP molecules do not interact strongly with other CSP molecules under these conditions. Exogenous CSP binds to regions on the cell surface that already bear CSP. In view of the apparent weakness of CSP-CSP interactions on the lipid bilayer, it seems possible that the assembly of CSP fibrils is nucleated by cell surface components in addition to CSP.
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PMID:Mobility and distribution of a cell surface glycoprotein and its interaction with other membrane components. 33 20

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

The Ss sialoglycoprotein (glycophorin B) and its antigens in Rhnull erythrocytes, which lack the Rhesus blood group antigens, due to apparently silent (amorphic type) or independent suppressor (regulator type) genes, were investigated. The quantity of the molecule in amorphic and in regulator type red cell membranes was found to be decreased by about 60%-70%, as judged from sodium-dodecylsulfate polyacrylamide gel electrophoresis. The Ss glycoprotein content in the erythrocytes from heterozygotes (regulator type) was diminished to an extent of about 30%. Confirming and extending previous studies, the S, s, Ux, Uz and 'N' antigens were slightly weakened in Rhnull erythrocytes. The U and Duclos receptors were only slightly or not depressed in amorphic Rhnull cells, but almost absent from or not detectable in those of the regulator type. This demonstrates that an additional alteration, apart from the decreased Ss glycoprotein content of the membranes, accounts for the weakness of these receptors in regulator type cells. We propose the hypothesis that (a) protein(s) encoded by the Rhesus locus form(s) a complex with the Ss glycoprotein. Thus, it (they) might facilitate the incorporation of the Ss glycoprotein into the membrane and also contribute to the complete expression of the U and Duclos antigens in normal cells.
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PMID:Characterization of the Ss sialoglycoprotein and its antigens in Rhnull erythrocytes. 309 64

Acetylcholine receptors in skeletal muscle and fish electric organs are intrinsic membrane proteins whose function is to bind acetylcholine released from the nerve ending and trigger the opening of a cation-specific channel in the postsynaptic membrane, thereby facilitating transmission of the nerve signal to the muscle. Investigations from several laboratories indicate that acetylcholine receptors from fish electric organs are composed of four homologous glycoprotein subunits of apparent relative molecular masses (Mr) approximating 40, 50, 57 and 64 x 10(3) designated, respectively, alpha, beta, gamma and delta. These subunits are present in receptor monomers in the mole ratio alpha 2 beta gamma delta. Receptor purified from skeletal muscle appears to have a similar structure. The alpha subunits are unknown. It is known that the cation channel regulated by acetylcholine binding is located within the receptor monomer. Experimental autoimmune myasthenia gravis (EAMG) is induced by immunizing animals with purified receptor. The mechanisms by which neuromuscular transmission is impaired in this model are very similar to those in myasthenia gravis (MG). Although there are many immunogenic determinants on receptors, and EAMG can be induced in rats by any of the denatured subunits, there is a main immunogenic region at which most of the antibodies to native receptors are directed. The main immunogenic region is a conformationally dependent part of the external surface of alpha subunits other than the acetylcholine-binding site or the attached carbohydrate. Antisera from MG patients are also directed primarily at this region. No correlation was detected between the specificities of antibodies to receptor in patients' sera and the severity of their weakness.
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PMID:Structure of the acetylcholine receptor and specificities of antibodies to it in myasthenia gravis. 692 7

The expression of dystrophin, the dystrophin-associated proteins and utrophin has been studied immunocytochemically in three young, manifesting carriers of Duchenne muscular dystrophy, aged 3, 5 and 12 yrs, one adult manifesting carrier, aged 60 yrs, and one presumptive carrier with a raised serum creatine kinase, aged 24 yrs, the mother of the 5-yr-old manifesting carrier. The manifesting carriers had variable degrees of weakness; the presumptive carrier had no weakness. Morphological abnormalities were also variable and were most marked in the young manifesting carriers. The three young manifesting carriers and the presumptive carrier had a mosaic pattern of dystrophin-positive and dystrophin-negative fibres. All the dystrophin-associated proteins were reduced in the dystrophin-deficient fibres, giving a similar mosaic pattern to dystrophin. Expression of dystrophin and the dystrophin-associated proteins was normal in the adult manifesting carrier. Utrophin was detected on the sarcolemma of fibres both with and without dystrophin and the dystrophin-associated proteins. Thus, dystrophin and utrophin are co-expressed in several fibres in carriers. The results emphasize the close association between dystrophin and the glycoprotein complex and their role in the pathogenesis of muscle damage. In addition, the presence of utrophin in fibres with greatly reduced glycoproteins suggests that very little of the glycoprotein complex may be required to anchor the amount of utrophin expressed at the sarcolemma in these particular cases.
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PMID:Expression of dystrophin-associated glycoproteins and utrophin in carriers of Duchenne muscular dystrophy. 788 Dec 85

The term limb girdle muscular dystrophy (LGMD) has been introduced to delineate a distinct form of muscular dystrophy with predominantly proximal upper and lower extremity weakness. Families with evidence of both autosomal recessive and autosomal dominant modes of inheritance have been described. The recognition of other disorders presenting with weakness in a limb girdle distribution, such as the spinal muscular atrophies, dystrophinopathies, inflammatory and metabolic myopathies, casted doubt on the existence of LGMD as a separate entity. Recent linkage studies showing association between various forms of LGMD and loci on chromosome 15, 13 and 5 respectively, and the demonstration of 50K dystrophin associated glycoprotein deficiency in some cases of LGMD, strongly support the notion that limb girdle muscular dystrophy constitutes a separate group of phenotypically and genotypically distinct disorders. Further investigations are necessary to recognize the different subtypes of this disease and to identify the underlying mutations.
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PMID:Limb girdle muscular dystrophy: reappraisal of a rejected entity. 798 88

Adrenal epithelioid angiosarcomas (AEA) are rare neoplasms. We report the clinicopathologic features of nine cases of AEA. AEA occurred most frequently in the sixth and seventh decades of life (age range, 45-85 years; median, 60); five cases occurred in men and four in women. Presenting symptoms included abdominal mass with or without pain, weight loss, fever, and weakness. Two cases were asymptomatic; one was discovered during evaluation for other disease(s) and the other at autopsy. All neoplasms were nonfunctioning. Radiographic evaluation demonstrated suprarenal or retroperitoneal neoplasms ranging in size from 6 to 10 cm in greatest dimension. Histologically, the neoplasms were invasive, predominantly arranged in solid sheets or nests, and composed of epithelioid cells. Endothelial cell differentiation was suggested by the transition areas between dilated anastomotic vascular spaces and the sheet-like growth, the cytomorphologic similarity between the endothelial cells lining the discernible vascular spaces and those seen in the solid foci, and the presence of intracytoplasmic vacuolization occasionally containing red blood cells. Endothelial derivation was confirmed by immunohistochemistry including Factor VIII-related antigen (FVIII), CD-34 (hematopoetic progenitor cell antigen), and/or Ulex europaeus agglutinin-1 lectin immunoreactivity (UEA-1) and by ultrastructural findings, including rod-shaped microtubulated bodies and intracytoplasmic lumen formation. In addition, cytokeratin reactivity was seen in seven cases, and B72.3 (tumor-associated glycoprotein-72) reactivity was seen in six. Surgical resection was the treatment of choice, occasionally supplemented by chemotherapy. Three patients are presently alive, free of disease, at 13, 11, and 6 years following diagnosis. Three died with metastatic AEA of the lung, and three died of unrelated causes.
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PMID:Epithelioid angiosarcoma of the adrenal glands. A clinicopathologic study of nine cases with a discussion of the implications of finding "epithelial-specific" markers. 827 29

Muscular dystrophies primarily affect skeletal muscle and are characterized by progressive muscle wasting and weakness. Although these diseases have been clinically recognized for some time, genetic defects in a number of muscular dystrophies only recently have been identified. One of the most important advances in understanding the molecular genetics of neuromuscular diseases has been the cloning of the gene encoding dystrophin, the protein that is absent in the muscle of patients with Duchenne and Becker muscular dystrophy. Several dystrophin-associated proteins have been identified. Components of the dystrophin-glycoprotein complex are being characterized, and evidence indicates that proteins of this complex may be responsible for other forms of muscular dystrophy.
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PMID:Dystrophinopathies and related disorders. 857 67

A single intraperitoneal dose of 300 mg/kg of p-bromophenylacetylurea (BPAU) induced progressive distal neuropathy in rats, prominently involving peripheral nerves and long central nervous system myelinated tracts such as the fasciculus gracilis and spinocerebellar pathways. Clinical signs assessed using a Functional Observational Battery (FOB) and in-cage observation included weakness and deficits in motor and sensory integration, definitively noted on post-dosing day 7. The signs were more pronounced upon repetition of the FOB on post-dosing day 12. The neuropathological substrate of these signs was a progressive axonopathy with regional swelling, leading to Wallerian-like degeneration of affected myelinated fibers. Immunocytochemical staining for synaptophysin revealed often striking increase in immunoreactivity for this synaptic vesicle glycoprotein in swollen and otherwise injured axons. Such accumulations were considered consistent with interruption of anterograde (and possibly retrograde) fast axonal transport systems secondary to toxicant-induced nerve fiber breakdown.
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PMID:Synaptophysin immunoreactive axonal swelling in p-bromophenylacetylurea-induced neuropathy. 921 98

The muscle weakness in myasthenia gravis (MG) is caused by heterogeneous high-affinity IgG autoantibodies to the nicotinic acetylcholine receptor (AChR), a complex ion channel glycoprotein. These antibodies are clearly responsible for reducing AChR numbers at the neuromuscular junction in myasthenia; however, the origins, diversity, specificity and pathogenicity of individual antibodies have not yet been established. We have cloned and characterized four different AChR-specific Fab from an MG patient's thymus by screening an IgG1/kappa gene combinatorial lambda phage library with soluble human AChR labeled with [125I] alpha-bungarotoxin. Unlike most previously cloned human antibodies, all four Fab immunoprecipitated soluble human muscle AChR. Two Fab strongly inhibited binding of mAb to the main immunogenic region on the alpha subunits and one Fab bound to an epitope on the fetal-specific gamma subunit. In sensitivity and fine specificity, these Fab resembled the anti-AChR antibodies found in many MG patients, including the donor. The closest germline counterparts for their heavy chains were in VH families 1, 3 and 4; however, there were many differences consistent with an antigen-driven response of diverse B cell clones. The combinatorial approach holds promise for further analysis of human autoantibodies.
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PMID:Diverse Fab specific for acetylcholine receptor epitopes from a myasthenia gravis thymus combinatorial library. 931 Aug 34


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