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

Many renal diseases involving the tubular epithelium appear to preferentially affect certain nephron segments. While major portions of the nephron, such as proximal and distal convoluted tubules and collecting ducts, can be identified in the normal kidney, the distinction of diseased nephron segments can be difficult in tissue sections. Thus, to identify which nephron segments are involved in pathologic changes is usually impossible by routine histologic examination alone. Recently antibody and lectin probes that react with specific nephron segment-specific epitopes and carbohydrates, respectively, have become available. Some of these antibodies and lectins can be used on formalin-fixed, paraffin-embedded, archival tissues. Because renal tubules appear to retain their nephron segment-specific epitopes and glycoprotein moieties under most pathologic conditions, these nephron segment-specific tubular epithelial markers provide a method to study renal diseases involving the tubular system also in archival material. Such nephron segment-specific tubular epithelial markers are: the lectins, Tetragonolobus purpuras and Phaseolus vulgaris erythroagglutinin (proximal tubular markers); antibodies to low-molecular-weight cytokeratin (AE1/AE3); epithelial membrane antigen and the lectin Arachis hypogaea (distal nephron [distal convoluted tubule and collecting duct] markers); and antibodies to Tamm-Horsfall protein (labeling the thick ascending limb of Henle). We review the application of these and other renal tubular epithelial markers in the normal kidney and in various renal diseases including cystic disease of the kidney, interstitial nephritis, tubular atrophy, acute tubular necrosis, myeloma cast nephropathy, and renal tumors.
 ...
PMID:Immunohistochemical and lectin dissection of the human nephron in health and disease. 825 Jun 94

Macrophage cell-surface protein 2 (Mac-2), a galactose specific S-type lectin identified in inflammatory macrophages, presents a high degree of homology with the rat IgE-binding protein (epsilon BP). In the present study, we show by different experimental approaches that human eosinophils can express Mac-2/epsilon BP. Flow cytometry analysis revealed that a large proportion of eosinophilic patients expressing binding sites for IgE on their eosinophil membrane, were able to bind anti-Mac-2 monoclonal antibody (mAb). Northern blot performed with eosinophil RNA hybridized with the human Mac-2 or epsilon BP cDNA probes revealed that eosinophils presented a unique transcript at 1.2 kb. Immunoprecipitation of eosinophil extracts with anti-Mac-2 mAb revealed the presence of a molecule of 29 kDa corresponding to Mac-2 protein, as well as one additional molecule of 15 kDa, absent from control alveolar macrophages. The function of these molecules was investigated in a radiolabeled IgE binding assay. Anti-Mac-2 mAb as well as galactose and lactose saccharides significantly inhibited the binding of radiolabeled human myeloma IgE protein to eosinophils. Moreover, the dose-dependent inhibition by anti-Mac-2 mAb of IgE-dependent eosinophil-mediated cytotoxicity towards parasite targets indicated the role of these IgE-binding molecules in the function of human eosinophils. These results suggest that in addition to transmembrane receptors, lectin-type molecules can participate in the IgE-dependent effector function of eosinophils.
 ...
PMID:IgE-binding molecules (Mac-2/epsilon BP) expressed by human eosinophils. Implication in IgE-dependent eosinophil cytotoxicity. 825 38

It has been shown previously that secretory IgA interacts with the mannose-specific lectin of Escherichia coli. The purpose of the study described here was to evaluate whether the N-linked oligosaccharide chains of the human IgA isotypes IgA1 and IgA2 differ in lectin receptor activity. A range of plant lectins specific for N-linked oligosaccharide chains were tested for their ability to precipitate IgA1 and IgA2 myeloma proteins, secretory IgA and free secretory component. IgA2 myeloma proteins reacted more strongly than IgA1 with the mannose-specific lectin ConA, whereas IgA1 myeloma proteins reacted more strongly than IgA2 with two galactose-specific lectins, Ricinus communis agglutinin I and Abrus precatorius agglutinin. This suggests that IgA2 possesses a larger proportion of short truncated complex type oligosaccharide chains and/or oligomannose type chains than IgA1. Further, IgA2 reacted more strongly than IgA1 myeloma proteins with Lens culinaris (lentil) lectin, and Pisum sativum (pea) lectin, suggesting that IgA2 exposes more of short, complex type chains fucosylated on the core than IgA1. The differences demonstrated in receptor activity between IgA1 and IgA2 may be important in their interaction with the microbial flora, as well with endogenous lectins, such as phagocyte receptors.
 ...
PMID:Lectin receptors on IgA isotypes. 829 63

A better understanding of the pathophysiological role of Langerhans cells (LC) in atopic diseases is dictated by the characterization of the structures involved in immunoglobulin (IgE)-binding on their cell surface. We previously reported that human LC express the high affinity receptor for IgE (Fc epsilon RI), as well as the low affinity receptor for IgE (Fc epsilon RII/CD23). In the present study, we document the presence of a third IgE-binding structure on human LC, the IgE-binding protein (epsilon BP), an endogenous soluble beta-galactoside binding lectin. Immunohistochemical studies performed on normal human skin revealed an anti-epsilon BP reactivity in the cytoplasm of keratinocytes and in that of acinous cells of eccrine sweat glands. epsilon BP was also found on the cell surface of LC, as shown by anti-epsilon BP/anti-CD1a double labeling and flow cytometric analysis. Anti-epsilon BP binding to the surface of LC was completely abolished by preincubation with lactose and restored by addition of recombinant human epsilon BP, indicating that epsilon BP binds to LC surface by virtue of its lectin property. Immunoblot analysis of anti-epsilon BP-reactive material in keratinocytes and purified LC disclosed a protein with an apparent molecular weight of 33,000 consistent with epsilon BP. Interestingly, mRNA transcripts for epsilon BP were detected only in keratinocytes but not in purified LC isolated from normal skin. epsilon BP was found to be released in culture supernatants of keratinocytes. Incubation of LC with these supernatants resulted in epsilon BP-binding to LC surface via protein-carbohydrate interaction. Most importantly, we could show that binding of human myeloma IgE to LC was inhibited by epsilon BP. In contrast, neuraminidase-treated human myeloma IgE binds to LC only in the presence of epsilon BP. In situ binding studies revealed that keratinocytes, although containing epsilon BP intracytoplasmatically, failed to exhibit any IgE-binding properties. Collectively, our results suggest that human keratinocytes produce the beta-galactoside-binding lectin epsilon BP, which subsequently binds to the surface of LC where it is functional in modulating their binding capacity for IgE glycoforms.
 ...
PMID:Human keratinocytes release the endogenous beta-galactoside-binding soluble lectin immunoglobulin E (IgE-binding protein) which binds to Langerhans cells where it modulates their binding capacity for IgE glycoforms. 835 53

A clinically euthyroid 53-year-old woman with an IgA-lambda-secreting multiple myeloma presented with increased serum concentrations of thyroid hormones. Laboratory studies revealed increased total thyroxine (T4) and triiodothyronine (T3) concentrations, a high-normal free T4 concentration, and a normal basal thyrotropin (TSH) concentration with a normal response to thyroliberin (TRH). Her serum concentration of IgA was 11,040 mg/L (normal range 900-4500 mg/L) and immunoelectrophoresis revealed it to be monoclonal. This monoclonal IgA bound both T4 and T3, as determined by serum immunoelectrophoresis and direct binding studies. Immunoelectrophoresis in the presence of [125I]T4 or [125I]T3 localized the radiolabeled iodothyronines to a band corresponding exactly to the precipitin arc of the monoclonal IgA. We performed direct binding studies with IgA purified by affinity chromatography with the lectin jacalin. Purified IgA (50 micrograms) bound both [125I]T4 (12.3%) and [125I]T3 (2.7%) specifically and in a dose-dependent manner. Scatchard analysis of competitive-binding data utilizing [125I]T4 and unlabeled T4 revealed a Kd of 2.2 x 10(-7) mol/L. The binding capacity for T4 was approximately 7 mumol/L. Thus, in this case of IgA-secreting myeloma, the monoclonal IgA acts as an additional thyroid hormone-binding protein in serum that interferes in the T4 and T3 RIAs. This is the first report of a monoclonal IgA producing an apparent euthyroid hyperthyroxinemia.
 ...
PMID:Factitious hyperthyroxinemia due to a monoclonal IgA in a case of multiple myeloma. 835 66

It has been suggested that neutrophils may be involved in the late-phase reaction of immunoglobulin E (IgE)-dependent hypersensitivity states. However, the identity of neutrophil-associated molecules inducing the release of mediators remains unclear. In this report, we demonstrate that human neutrophils from normal donors or from patients with inflammatory disorders could bind myeloma IgE proteins, especially after desialylation. Northern blot, immunoprecipitation, and flow cytometry analyses revealed that neutrophils did not express Fc epsilon RII/CD23, but rather Mac-2/epsilon binding protein (BP), belonging to the S-type lectin family. Similarly to IgA used as positive control, myeloma IgE proteins, as well as polyclonal IgE antibodies with or without antibody specificity, were both capable of inducing a neutrophil respiratory burst. Anti-Mac-2 but not anti-CD23 mAb strongly decreased the IgE-dependent activation of neutrophils, induced either by the specific antigen or by anti-IgE antibodies. These findings open new perspectives on the functional role of neutrophils in IgE-associated diseases including allergic states or parasitic infections.
 ...
PMID:Human neutrophils express immunoglobulin E (IgE)-binding proteins (Mac-2/epsilon BP) of the S-type lectin family: role in IgE-dependent activation. 841 6

A human monoclonal IgA1-IgA2 lambda hybrid molecule was detected in a myeloma patient homozygous for the A2m(1) allotype during a systematic study of monoclonal IgA with subclass-specific monoclonal antibodies (mAb) and the lectin jacalin. This monoclonal immunoglobulin (GAU) reacted with both, although not with all, anti-alpha 1 and anti-alpha 2 mAb. Its heavy (H) chain contained an alpha 1 hinge region as shown by jacalin reactivity, the presence of disulfide-linked H and light chains in spite of its belonging to the IgA2m(1) allotype and amino acid composition of the isolated hinge region. The complete sequence of the H chain was deduced from that of complementary DNA clones from bone marrow cells. The CH1 domain, hinge region and beginning of the CH2 domain and the membrane peptide were encoded by the alpha 1 gene, with an insertion of an alpha 2m(1) gene sequence accounting for the end of the CH2 and part or all of the CH3 domain (sequence identity between the two normal genes precludes a precise definition of breakpoints). The region of the 5' recombination site included a repeat of a six base pair sequence which might play a role in the genetic exchange. The GAU hybrid alpha gene was undetectable in the patient's genomic DNA from polymorphonuclear cells. The genetic event which occurred at the level of the proliferating plasma cell clone is most likely to be a gene conversion.
 ...
PMID:A human myeloma IgA with a hybrid heavy chain resulting from putative somatic gene conversion. 843 72

A series of 12 cell fusions of BALB/c mice spleen cells with the SP2/O-Ag14 mouse myeloma cell line were performed after immunizations with normal human pancreas to generate monoclonal antibodies (mAbs) with high affinity against antigens of the exocrine pancreas. The immunohistologic tissue screening resulted in the selection of 14 clones that were further characterized on frozen tissues, tumor cell lines, and lectin binding assays. Four mAbs reacting with pancreatic acini detected granular antigens and three mAbs reacted with acinar cell membrane antigens. Six other clones reacted with pancreatic ducts; among these were three clones positive with antigens in both acini and ducts. Among the clones reactive with secretory products, there was one pair of mAbs identified as pancreas specific (P78C9/P79D4); the other secretory antigens (identified by P97F3 and P109H1) were also detectable in other exocrine organs, but were absent from the gastrointestinal mucosa. Two clones reactive with acinar cell membranes (P96H2 and P100H1) were also positive with hepatocytes. All but four antigens were detectable in pancreatic cancer cell lines Capan-1, Capan-2, and DAN-G. On the whole, immunizations were more effective using whole pancreatic tissues (eight clones selected) compared with single-cell suspensions as immunogen (four clones) or cell membrane preparations (two clones). Therefore, the immunization and screening strategies used in this study resulted in the generation of new mAbs against specific substructures of the exocrine pancreas. The shared expression of some of these antigens with other exocrine organs and pancreatic adenocarcinoma cell lines suggests that these mAbs detect antigens that are characteristic for the exocrine system and could therefore be useful for the study of the exocrine pancreas and pancreatic adenocarcinomas.
 ...
PMID:Characterization of new monoclonal antibodies directed against normal human exocrine pancreas and pancreatic adenocarcinomas. 848 69

Plasma cells within bone marrow aspirates from multiple myeloma patients have been shown to be reactive with the lectin peanut agglutinin (PNA). This has been recently exploited by using PNA for purging bone marrow of malignant cells in autotransplantation therapy of the disease. The purpose of this investigation was to isolate and characterize the PNA-binding proteins of myeloma cells. We used the malignant plasma cell-derived line Karpas-620 (K620) as a model, and showed by affinity chromatography, SDS-PAGE, and immunoprecipitation that, among several PNA-binding proteins, a major one is an incompletely sialylated form of CD44. CD44 is a well-known homing receptor protein which is rich in carbohydrate and usually completely sialylated so that it does not react with PNA. We have then examined the PNA reactivity of myeloma cells from different patients and showed a clear difference in the profile of PNA-binding proteins from case to case. Moreover, in contrast to K620 cells, some of the patient plasma cells tested did not have a PNA-binding form of CD44. In conclusion, therefore, we have shown that a number of different proteins participate in PNA binding by malignant plasma cells. Moreover, we have demonstrated a novel, incompletely sialylated form of CD44 on a myeloma cell line. It is known that the level of glycosylation of CD44 and other proteins may affect their function, but how this relates to the malignant behaviour of plasma cells remains to be determined.
 ...
PMID:The peanut-agglutinin (PNA)-binding surface components of malignant plasma cells. 851 74

Expression plasmids carrying a humanized N901 immunoglobulin heavy chain gene (hN901HC) fused to a gene encoding the native B chain of ricin toxin (RTB), hN901HC-RTB, or a sugar binding mutant of RTB, hN901HC-RTB delta gly, were constructed. In each case, the fused gene constructions were co-expressed in murine myeloma cells (Sp2/0) with the gene for humanized N901 immunoglobulin light chain to produce the secreted recombinant products hN901-RTB and hN901-RTB delta gly, respectively. When purified by affinity chromatography, both the hN901-RTB and hN901-RTB delta gly products were found to have an apparent molecular mass of M(r) = 210,000 and to be composed of two hN901 antibody heavy chains each fused to a full-length copy of RTB and two hN901 antibody light chains. In each of the recombinant fusions the hN901 antibody moiety retained the full binding affinity and specificity for its cognate antigen, CD56. Moreover, when mixtures of hN901-RTB and native ricin A chain were incubated in the presence of the antigen-positive target cell line SW-2, antigen-specific potentiation of ricin A chain cytotoxicity was observed. It has been demonstrated previously that lectin activity of the B chain is essential for A chain cytotoxicity, and we conclude that the fused wild-type B chain was properly folded and maintained lectin activity. These data demonstrate that feasibility of using recombinant ricin B chain in an immunotoxin and of using mammalian cell culture for its expression. The use of recombinant hN901-RTB fusion protein to evaluate the contribution of the lectin activity of ricin B chain in the penetration of cell membranes by ricin A chain is proposed.
 ...
PMID:Expression and secretion of a recombinant ricin immunotoxin from murine myeloma cells. 853 70


<< Previous 1 2 3 4 5 6 7 8 9 Next >>