Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The preparation, properties, and some applications of ferritin conjugates of two plant agglutinins, concanavalin A and Ricinus communis agglutinin, are reported. These conjugates serve as specific electron-dense stains for cell- and membrane-bound saccharide residues of the alpha-D-mannopyranosyl and beta-D-galactopyranosyl configurations, respectively, and as examples of a wide range of ferritin-plant agglutinin conjugates useful as high resolution saccharide stains. By using a technique for preparing flattened membrane specimens, it was found with a variety of mammalian cell plasma membranes (lymphocyte, lymphoma, and myeloma and normal, spontaneously and virally transformed fibroblasts) that the ferritin conjugates were localized exclusively to the exterior face of the membrane, with essentially none found on the cytoplasmic face. On the exterior face the topographical distribution of ferritin conjugates appeared to be random. The asymmetrical distribution of saccharide residues to the outer membrane face can be explained by an "assembly line" process whereby new plasma membrane is made from intracellular precursor membranes. It also suggests that the saccharide-containing components of the plasma membrane do not rotate at any appreciable rate from one membrane surface to the other.
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PMID:The distribution and asymmetry of mammalian cell surface saccharides utilizing ferritin-conjugated plant agglutinins as specific saccharide stains. 412 77

The hyperviscosity syndrome is an uncommon complication in IgG myeloma. Its occurrence has been ascribed to the presence in the serum of high molecular weight polymers of the IgG proteins. Three patients with IgG myeloma and the clinical hyperviscosity syndrome were investigated, none of whom had IgG polymers in the serum by analytical ultracentrifugation. Relative serum viscosity in these patients ranged from 10 to 17.4 (normal 1.4-1.8). The total serum proteins ranged from 14 to 19 g/100 ml of which 10 to 17 g/100 ml was IgG globulin. Physicochemical studies of two of the isolated myeloma proteins indicated that they were of normal molecular weight (near 158,000 and 162,000). Protein Ca had a normal molecular radius (52.2 A) and configuration, (intrinsic viscosity of 5.5 cc/g, frictional ratio 1.48), but was present in very high concentration in the serum. Protein Pur had an increased molecular radius (58.2 A) and was asymmetrical (intrinsic viscosity 10.2 cc/g, frictional ratio 1.63). These results indicate that the concentration and molecular configuration of the myeloma protein are important determinants of the presence or absence of the hyperviscosity syndrome.
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PMID:The hyperviscosity syndrome. I. In IgG myeloma. The role of protein concentration and molecular shape. 540 3

Cerebral infarction is an uncommon complication in multiple myeloma with hyperviscosity. Serum hyperviscosity may cause a variety of clinical manifestations including bleeding from mucosal membranes, congestive heart failure, retinopathy, and various neurologic deficits. These manifestations have been attributed to the presence of large quantities of asymmetrical molecules of high molecular weight in the serum. We recently experienced a case of multiple myeloma with acute cerebral infarction, which caused by hyperviscosity, as an initial manifestation in IgG multiple myeloma, and reviewed the relevant literature of myeloma presenting with the stroke. A 68-yr-old woman abruptly developed hypesthesia and monoplegia in the left leg. The stroke confirmed by the brain MRI and MR angiography, which revealed acute infarction at the right anterior cerebral artery territory. On admission, routine blood tests showed a slight decrease in hemoglobin and a marked increase in erythrocyte sedimentation rate. Peripheral blood smear, serum protein electrophoresis, serum visocity, and bone marrow aspiration showed that she had IgG multiple myeloma with hyperviscosity. She was treated by chemotherapy with cyclophosphamide and discharged with the improved clinical condition.
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PMID:Cerebral infarction in IgG multiple myeloma with hyperviscosity. 1610 Apr 71

In this work, we present studies of the covalent structure of human IgG2 molecules. Detailed analysis showed that recombinant human IgG2 monoclonal antibody could be partially resolved into structurally distinct forms caused by multiple disulfide bond structures. In addition to the presently accepted structure for the human IgG2 subclass, we also found major structures that differ from those documented in the current literature. These novel structural isoforms are defined by the light chain constant domain (C(L)) and the heavy chain C(H)1 domain covalently linked via disulfide bonds to the hinge region of the molecule. Our results demonstrate the presence of three main types of structures within the human IgG2 subclass, and we have named these structures IgG2-A, -B, and -A/B. IgG2-A is the known classic structure for the IgG2 subclass defined by structurally independent Fab domains and hinge region. IgG2-B is a structure defined by a symmetrical arrangement of a (C(H)1-C(L)-hinge)(2) complex with both Fab regions covalently linked to the hinge. IgG2-A/B represents an intermediate form, defined by an asymmetrical arrangement involving one Fab arm covalently linked to the hinge through disulfide bonds. The newly discovered structural isoforms are present in native human IgG2 antibodies isolated from myeloma plasma and from normal serum. Furthermore, the isoforms are present in native human IgG2 with either kappa or lambda light chains, although the ratios differ between the light chain classes. These findings indicate that disulfide structural heterogeneity is a naturally occurring feature of antibodies belonging to the human IgG2 subclass.
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PMID:Human IgG2 antibodies display disulfide-mediated structural isoforms. 1833 24

A 67-year-old man affected by moderate weight loss, acral paresthesia and plantar burning sensation was admitted to our department. Electromyographic (EMG) and electroneurographic (ENG) studies confirmed a peripheral, asymmetrical, motor-sensorial polyneuropathy (PPN). Hematological data and bone marrow biopsy discovered a non-secerning multiple myeloma (MM). All other probable causes of peripheral neuropathy could be excluded, and the possible relationship between nerve damage and neoplasia was confirmed. Furthermore, all possibilities of association of MM with PPn, namely the osteosclerotic variant, the Crow-Fukase syndrome, and the amyloid one have been evaluated. The only finding of osteolytic bone areas by radiology, the absence of organomegaly, diabetes mellitus, skin alterations, and of amyloid deposition in muscles and nerves, exclude the possible connection of the case to any of the listed possibilities. On the other hand, some clinical aspects differ, in part, to others described in the literature. In conclusion, the association between PPN and MM as the result of multiform clinical variants could be considered.
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PMID:Peripheral neuropathy and multiple myeloma in aging: a case report. 1864 92

Multiple myeloma (MM) is an incurable B-cell neoplasia in which progressive skeletal lesions are a characteristic feature. Earlier we established an animal model for human MM in the immune-deficient RAG2(-/-)gammac(-/-) mouse, in which the growth of luciferase-transduced MM cells was visualized using noninvasive bioluminescence imaging (BLI). This model appeared well suited to study disease progression and response to therapy by identifying the location of various foci of MM tumor growth scattered throughout the skeleton and at subsequent time points the quantitative assessment of the tumor load by using BLI. We report here on the corresponding high-resolution X-ray micro-computed tomographic (micro-CT) analysis to study skeletal defects in the mice with full-blown MM. Several anatomical derangements were observed, including abnormalities in geometry and morphology, asymmetrical bone structures, decreased overall density in the remaining bone, loss of trabecular bone mass, destruction of the inner microarchitecture, as well as cortical perforations. Using the combination of BLI, micro-CT imaging, and immune-histopathological techniques, we found a high correlation between the micro-CT-identified lesions, exact tumor location, and infiltration leading to structural lesions and local bone deformation. This confirms that this animal model strongly resembles human MM and has the potential for studying the biology of MM growth and for preclinical testing of novel therapies for MM and for repair of MM-induced bone lesions.
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PMID:Correlation of high-resolution X-ray micro-computed tomography with bioluminescence imaging of multiple myeloma growth in a xenograft mouse model. 1981 49

The spectrum of chronic dysimmune neuropathies has widened well beyond chronic demyelinating polyradiculoneuropathy (CIDP). Pure motor (multifocal motor neuropathy), sensorimotor with asymmetrical involvement (multifocal acquired demylinating sensory and motor neuropathy), exclusively distal sensory (distal acquired demyelinating sensory neuropathy) and very proximal sensory (chronic immune sensory polyradiculopathy) constitute the variants of CIDP. Correct diagnosis of these entities is of importance in terms of initiation of appropriate therapy as well as prognostication of these patients. The rates of detection of immune-mediated neuropathies with monoclonal cell proliferation (monoclonal gammopathy of unknown significance, multiple myeloma, etc.) have been facilitated as better diagnostic tools such as serum immunofixation electrophoresis are being used more often. Immune neuropathies associated with malignancies and systemic vasculitic disorders are being defined further and treated early with better understanding of the disease processes. As this field of dysimmune neuropathies will evolve in the future, some of the curious aspects of the clinical presentations and response patterns to different immunosuppressants or immunomodulators will be further elucidated. This review also discusses representative case studies.
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PMID:Chronic dysimmune neuropathies: Beyond chronic demyelinating polyradiculoneuropathy. 2180 68

This paper demonstrates membrane poration of a single suspension cell due to a fast liquid microjet. The jet is formed during the collapse of a laser induced bubble created at a variable stand-off distance from the target cell. The cell is trapped by a converging structure within a microfluidic chip. The asymmetrical growth and collapse of the cavitation bubble next to the cell lead to the microjetting, which deforms and porates the cell membrane. In the experiments, the membrane porations of myeloma cells are probed with the uptake of trypan blue. Time-resolved studies of the diffusion of trypan blue show a marked dependency on the bubble dynamics, i.e. the stand-off distance. The penetration length of the dye increases with shorter distances. Numerical simulations of the diffusion process agree with larger pores formed on the cell membrane. This method allows for a fast, repeatable, and localized rupture of membranes of individual cells in suspension.
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PMID:Single cell membrane poration by bubble-induced microjets in a microfluidic chip. 2336 62

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is probably the best recognized progressive immune-mediated peripheral neuropathy. It is characterized by a symmetrical, motor-predominant peripheral neuropathy that produces both distal and proximal weakness. Large-fiber abnormalities (weakness and ataxia) predominate, whereas small-fiber abnormalities (autonomic and pain) are less common. The pathophysiology of CIDP is inflammatory demyelination that manifests as slowed conduction velocities, temporal dispersion, and conduction block on nerve conduction studies and as segmental demyelination, onion-bulb formation, and endoneurial inflammatory infiltrates on nerve biopsies. Although spinal fluid protein levels are generally elevated, this finding is not specific for the diagnosis of ClDP. Other neuropathies can resemble CIDP, and it is important to identify these to ensure correct treatment of these various conditions. Consequently, metastatic bone surveys (for osteosclerotic myeloma), serum electrophoresis with immunofixation (for monoclonal gammopathies), and human immunodeficiency virus testing should be considered for testing in patients with suspected CIDP. Chronic inflammatory demyelinating polyradiculoneuropathy can present as various subtypes, the most common being the classical symmetrical polyradiculoneuropathy and the next most common being a localized asymmetrical form, multifocal CIDP. There are 3 well-established, first-line treatments of CIDP-corticosteroids, plasma exchange, and intravenous immunoglobulin-with most experts using intravenous immunoglobulin as first-line therapy. Newer immune-modulating drugs can be used in refractory cases. Treatment response in CIDP should be judged by objective measures (improvement in the neurological or electrophysiological examination), and treatment needs to be individualized to each patient.
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PMID:History, Diagnosis, and Management of Chronic Inflammatory Demyelinating Polyradiculoneuropathy. 2986 82