Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sera from 14 patients with an IgA M-component, six of whom had myelomatosis and eight with benign monoclonal gammopathy (BMG) were analysed. All six sera from patients with high IgA (greater than 40 g/l) and total protein (greater than 100 g/l) concentrations were hyperviscous (HV). Four of these six patients also had hyperviscosity syndrome (HVS). There was no correlation between the quantity of IgA dimers or polymers and the presentation of HV and HVS. The binding between IgA and albumin and alpha 1-anti-trypsin was not covalent. Differences in the microenvironment of S-S bonds or of aromatic amino acids between isolated monoclonal monomeric and dimeric IgA were demonstrated with circular dichroism. Besides that, differences in hydrophobicity (exposure of aromatic amino acids) between IgA from normal serum and monomeric and dimeric IgA from a myeloma serum were revealed using hydrophobic interaction chromatography. The significance of hydrophobic interactions involving IgA and the influence of such forces on the circulation of the molecules are discussed.
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PMID:Factors affecting IgA related hyperviscosity. 685 Dec 49

In the rat, dimeric immunoglobulin A (dIgA) is cleared rapidly from the systemic circulation into bile by vesicular transport through the hepatocyte. Whether such transfer of dIgA occurs in man is controversial. The fate of dIgA and monomeric IgA (mIgA) was studied in rats with biliary drainage, and in parallel in 4 patients, 3 of whom had biliary drainage. Human dIgA and mIgA were prepared from myeloma sera and labeled with radioisotopes of iodine. Ten microcuries each of 125I-dIgA and 131I-mIgA (2 to 4 microgram protein) were given i.v. simultaneously. In the four patients, 125I-dIgA disappeared more rapidly from the serum than did 131I-mIgA. Biliary recovery of 125I-dIgA (expressed as per cent total dose given) was only 0.2 to 0.9% in 8 8 hr while that of 131I-mIgA was 0.1 to 0.2%. In contrast, biliary recovery over the same period in rats was 21 to 32% for 125I-dIgA and 3.0 to 4.6% for 131I-mIgA. The data show that in man after injection of a trace amount of human myeloma IgA, rapid transport of dIgA into bile, as observed in the rat, was not seen. Although selective transport of dIgA over mIgA into bile occurred in man, the total amount of dIgA transported was small, and it is suggested that under physiological conditions, the major part of human biliary IgA is derived from local synthesis.
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PMID:A comparative study of the biliary secretion of human dimeric and monomeric IgA in the rat and in man. 707 14

The solution properties of five samples of human immunoglobulin A (IgA) were investigated with covalent and hydrophobic fluorescence probes. The immunoglobulins included a secretory IgA and four myeloma proteins of both IgA1 and IgA2 subclasses in the monomeric and dimeric forms. The probe 8-anilinonaphthalene-1-sulfonate (ANS) was found to bind to both monomeric and dimeric IgA with comparable affinity. Pyrenesulfonyl chloride covalently linked to the proteins exhibited multiexponential decays. The decay of ANS complexed to the same proteins showed similar multiple exponential character. The rotational motions of the immunoglobulins were investigated by the nanosecond fluorescence anisotropy decay method. The decay of both probes attached to these proteins was characterized by a fast component followed by a slow component. The rapid component was in the range 14-26 ns for th covalent conjugates and 26-41 ns for the ANS complexes. These results are interpreted in terms of a segmental motion arising from a mass in the range 60 000-100 000 daltons, If the decrease in the anisotropy value at long times is taken as a measure of restricted diffusion of the mobile fragment, the half-angle of a cone within which the fragment traverses may provide a qualitative measure of the extent of flexibility. By this criterion, monomeric and dimeric IgA's of the same subclass appear to be qualitatively similar in flexibility.
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PMID:Nanosecond fluorescence spectroscopy of human immunoglobulin A. 722 69

Samples of the urine of 10 myeloma patients with proteinuria were examined by SDS-PAGE. Light chain proteins of Bence Jones (B.J.) type were excreted by 7 patients as monomer (m.w. 20--26.5 x 10(3) Dalton, by 2 patients as a mixture of monomer and dimer and by one patient as dimer. By two-dimensional electrophoresis in SDS-PAG and subsequent electrophoresis in agarose containing kappa and lambda chain specific antibodies the immunological identity of monomeric and dimeric B.J. protein of one patient has been shown. The two-dimensional analysis has been proven a valuable procedure in cases with the excretion of complete monoclonal protein and B.J. protein at the same time.
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PMID:Study of uroproteins in myeloma patients by sodium dodecyl sulfate-polyacrylamide gel electrohporesis (SDS-PAGE). 739 39

The existence of two IgA subclasses in humans has been reliably shown by biochemical, immunochemical and genetic means. IgA is unique among immunoglobulins in the regular occurrence of both monomeric and polymeric forms. In order to be able to study the relationship between monomeric and polymeric IgA1 and IgA2 concentrations in the circulation and mucosal compartment i.e. secretions, it is essential that the methods used are not biased by the molecular size of the IgA under investigation. We validated IgA and IgA subclass measurements in serum and saliva by sandwich enzyme-linked immunosorbent assay (ELISA). Coating reagents were specific mAbs against IgA (clone 4E8), IgA1 (clone 69-11.4) or IgA2 (clone 16-512-H5 and clone IF8.58). Pooled normal human serum and purified dimeric IgA1 (d-IgA1) or IgA2 (d-IgA2) myeloma proteins were used to standardize the assays. Polymeric and monomeric forms of IgA in sera from volunteers and patients with myelomatosis were assayed in fractions separated by high performance liquid chromatography (HPLC). Dithioerythritol (DTE) was used to determine the influence of the quarternary structure of IgA on its detection by mAbs. We found that mAbs 4E8, 69-11.4 and 16-512-H5 reliably measured d-IgA, d-IgA1 and d-IgA2 respectively, independent of the standard employed. Clone IF8.58 underestimated the concentration of d-IgA2 (correction factor +/- 2) with increased sensitivity in the presence of DTE. This difference is probably explained by the composition of the immunogen against which the mAb was raised. We conclude that no reliable conclusions can be made concerning the subclass ratio in biological fluids unless the monoclonal antibodies used have been appropriately validated.
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PMID:Immunoglobulin A subclass measurement in serum and saliva: sensitivity of detection of dimeric IgA2 in ELISA depends on the antibody used. 749 81

Using a synthetic peptide with the amino acid sequence corresponding to residues 78-109 of human TGF-beta 1 (A78/109 peptide) as an immunogen, we generated and characterized monoclonal antibodies (Mabs) against transforming growth factor-beta 1 (TGF-beta 1). Spleen cells from a mouse immunized with carrier-free A78/109 peptide were fused with a myeloma cell line, P3U1. Two hybridoma cell lines were selected with A78/109 peptide used as the antigen, and the Mabs were designated as 3H10 and 4C10. Mab 4C10 recognized TGF-beta 1 only in immunoblotting analysis, but not in ELISA. In contrast, Mab 3H10 recognized it in not only ELISA but also immunoblotting analysis. Neither Mab was capable of recognizing both porcine TGF-beta 2 and chicken TGF-beta 3, and, therefore, both Mabs were TGF-beta 1 specific. From the results of epitope-mapping analysis, both Mab 3H10 and Mab 4C10 recognized the 78-87 portion of TGF-beta 1. The epitope recognized by Mab 4C10 was mapped specifically to amino acids 85-87. These results suggest that the region within 78-87 is exposed in the dimeric TGF-beta 1 and is one of the antigenic determinants in this molecule.
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PMID:Synthetic peptide-generated monoclonal antibodies to transforming growth factor-beta 1. 750 42

To determine the role of humoral mucosal immune response in protection against shigellosis, we have obtained a monoclonal dimeric immunoglobulin A (IgA) antibody specific for Shigella flexneri serotype 5a lipopolysaccharide (mIgA) and used a murine pulmonary infection model that mimics the lesions occurring in natural intestinal infection. Adult BALB/c mice challenged with 10(7) S. flexneri organisms developed a rapid inflammatory response characterized by polymorphonuclear cell infiltration around and within the bronchi and strong systemic interleukin 6 response. Implantation of hybridoma cells in the back of mice, resulting in the development of a myeloma tumor producing mIgA in the serum and subsequently secretory mIgA in local secretions, or direct intranasal administration of these antibodies, protected the animals against subsequent intranasal challenge with S. flexneri serotype 5a. Absence of histopathological lesion and significant decrease in bacterial load of the lungs and of systemic interleukin 6 response were the three major criteria of protection. This protection was shown to be serotype-specific and dependent on local concentration of mIgA. These data demonstrate that mucosal antibodies directed against a single polysaccharidic surface epitope of Shigella can protect against the disease.
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PMID:Monoclonal immunoglobulin A antibody directed against serotype-specific epitope of Shigella flexneri lipopolysaccharide protects against murine experimental shigellosis. 754 97

Kidney tubule dysfunction and lesions are frequent complications of myeloma, related to unknown properties of the monoclonal light chain. We have analyzed protease sensitivity and binding properties of urinary light chains from four patients with Fanconi's syndrome, 12 with cast nephropathy, and four control patients without myeloma-associated tubulopathy. All light chains were normal-sized, monomeric and/or dimeric, and none was N-glycosylated. Kinetic studies of light chain digestion by pepsin and the lysosomal enzyme cathepsin B showed the generation of a protease-resistant 12 kDa fragment, corresponding to the V domain of the kappa chain in the four Fanconi's syndrome patients; in two out of four the V domain was also completely resistant to trypsin. Western and dot blots revealed similar patterns of reactivity of light chains from patients with the Fanconi's syndrome towards other light chains. Properties of cast-nephropathy light chains were more heterogeneous but clearly differed from those of Fanconi's syndrome: (i) 9 out of 12 were of the lambda-type; (ii) only four yielded a transient 12 kDa fragment after cathepsin B digestion, but all showed some resistance to proteolysis of the entire molecule or a fragment thereof to at least one protease, at variance with control light chains; (iii) they displayed various patterns of reactivity with other light chains; (iv) 7 out of 12 reacted specifically with Tamm-Horsfall protein (THP) by ELISA, in contrast with those of Fanconi's syndrome. In one patient who presented with cast nephropathy and the Fanconi's syndrome, the light chain exhibited both partial resistance of the V kappa domain to cathepsin B and the highest reactivity with THP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protease resistance and binding of Ig light chains in myeloma-associated tubulopathies. 756 94

The baculovirus expression system has been used for the production of a variety of proteins, including antibodies. Two single-gene constructs encoding single-chain immunoglobulins have recently been developed. The antibody employed was monoclonal antibody (MAb) CC49 which reacts with the pancarcinoma antigen, tumor associated glycoprotein, TAG-72. One, single-chain construct designated SCA delta CLCH1 (SCIg), consists of the CC49 sFv covalently joined to the human Fc (gamma 1) through the hinge region. The other, SCA delta CLCH1-IL-2 (SCIg-IL-2), has a human IL-2 molecule attached to the carboxyl end of the SCIg. These constructs have been used to test the feasibility of producing biologically active antibodies using the baculovirus expression system. Both constructs have been successfully expressed in insect cells and purified. The baculovirus recombinant single-chain antibodies have been designated, bV-SCA delta CLCH1 (bV-SCIg) and bV-SCA delta CLCH1-IL-2 (bV-SCIg-IL-2) they have been shown to be secreted in the culture supernatant as dimeric molecules of approximately 115 kDa and 140 kDa, respectively. The specificity and antibody dependent cellular cytolytic activity of the baculovirus recombinant single-chain antibodies were shown to be similar to that of the myeloma derived molecules. Glycosylation analysis showed that baculovirus derived proteins were N-glycosylated, but carried few if any high mannose residues. The biological activity of the IL-2 moiety was retained in bV-SCIg-IL-2, as evidenced by its stimulatory effect on the proliferation of the IL-2 dependent cell line HT-2. The observation that a significantly shorter time is required to develop baculovirus recombinant molecules as compared to myeloma derived molecules and that insect cells express single chain MAbs at acceptable levels may have implications for the production of these molecules for clinical use.
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PMID:Baculovirus expression of a functional single-chain immunoglobulin and its IL-2 fusion protein. 759 24

Starting from two IgA1 myeloma sera, the isolation of monoclonal monomeric, dimeric, trimeric and tetrameric IgA in a high state of purity and size homogeneity for each serum is described. The method combined repetitive gel filtrations on Ultrogel AcA22 with affinity chromatography on Jacalin-Sepharose. These various forms of pure polymeric IgA obtained from the same monoclonal IgA should allow a precise comparison of their respective structure and reactivity with different IgA-binding proteins, such as IgA Fc-receptors, the polymeric Ig receptor, and lectins.
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PMID:Homogenous IgA monomers, dimers, trimers and tetramers from the same IgA myeloma serum. 762 99


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