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)

In untreated patients with inoperable lung cancer, serum levels of alpha1-antitrypsin were found significantly increased in comparison to patients with non malignant diseases of the lung, alpha2-macroglobulin levels were unchanged in both groups of patients. There was also no difference in alpha2-macroglobulins in cancer patients reacting with DNCB and in non-reactors. Thus alpha2-macroglobulin levels do not seem to correlate with the immunestatus of cancer patients. Proteinase inhibitors are involved in a variety of biological processes including blood, clotting, digestion, and sperm capacitation. alpha1-antitrypsin, a alpha-globulin with a molecular weight of about 60,000 has been found to be decreased in patients' serum under several pathological conditions. A clear correlation exists between alpha1-antitrypsin deficiency and hereditary pulmonary emphysema (1, 2), respiratory distress syndrome (3), and juvenile cirrhoses of the liver (4). Elevated serum levels of alpha1-antitrypsin have also been found in some cancer cases. Thirty years ago a cancer test was developed on the basis of differences in the antiproteolytic activity in cancer patients' sera and in patients with other non-neoplastic diseases (5, 6). Several authors have tried to confirm these early data regarding specifity and sensitivity with respect to a screening test for cancer (7, 8). Methods of these authors were based mainly on enzyme substrate inhibition assays by addition of the patients' sera. Recently a commercially available test, based on immune-precipitation according to Mancini (9), has been developed (Behring-Werke, Partigen). By using this standardized method for determinating alpha1-antitrypsin, Harris et al. have recently demonstrated that patients with inoperable lung cancer have significantly elevated levels of this antiprotease in their sera (10), in comparison to patients with non malignant diseases of the lung. alpha2-macroglobulin is a serum protein with a molecular weight of 800,000 and with known antiprotease activity and can therefore bind trypsin, plasmin, elastase, and collagenase and it is known that alpha2-macroglobulin decreases with increasing of age. Changes of alpha-macroglobulin have also been observed in several pathological conditions (11). James et al. 4ave found decreases in serum of myeloma patients (12). An association between the development and function of lymphocytes and alpha2-macroglobulin has been suggested by several authors (13, 14). This alpha2-globulin has also been demonstrated on the surface of peripheral blood lymphocytes (15) and there is evidence that it is synthesized by lymphocytes (16). The purpose of the present study was to determine serum alpha1-antitrypsin levels in patients with inoperable lung cancer and to determine whether there is also an inverse correlation to alpha2-macroglobulin. It was further attempted to correlate alpha2-macroglobulin with general immunological parameters, as it is known that patients with lung cancer show a decreased general immune-reactivity (17).
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PMID:Serum levels of alpha1-antitrypsin and alpha2-macroglobulin in lung cancer. 6 86

High anti-staphylolysin activity was found in the serum from a patient with multiple myeloma. The activity was confined to the monoclonal IgA protein and was dependent on an intact Fc part of the molecule. An Fc-dependent interaction with protein A was also demonstrated. In addition, a part of the monoclonal IgA was found to be complexed with alpha2-macroglobulin. The results imply an unusual Fc-reactivity of the IgA protein.
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PMID:A human IgA myeloma protein interacting with staphylococcal alpha-toxin and protein A. 86 31

One class of genes coding for the acute-phase proteins (acute-phase genes) is induced by interleukin 6 (IL-6) through the human transcription factor NF-IL-6 and its rat homolog IL-6-DBP/LAP. A second class, represented by the rat alpha 2 macroglobulin gene, utilizes a different IL-6 response element (IL-6-RE) and different DNA-binding proteins interacting with this element, the so-called IL-6-RE binding proteins (IL-6 RE-BPs). Human Hep3B and HepG2 hepatoma, U266 myeloma, and CESS lymphoblastoid cells contain IL-6 RE-BPs that form complexes, with the IL-6-RE, with gel mobilities indistinguishable from those of the corresponding complexes of rat liver cells. The ability to form these complexes was induced by IL-6 in human hepatoma cells with a maximum reached after 4 h and required ongoing protein synthesis. Multiple copies of an 18-bp element containing the IL-6-RE core were sufficient to confer both induction by IL-6 and a synergistic induction by IL-6 plus glucocorticoids to minimal promoters. The synergism was blocked by the receptor antagonist RU486 and thus was dependent on the glucocorticoid receptor (GR). However, the 18-bp element contained no consensus GR-binding site, and recombinant GR did not bind at this sequence. Therefore, the synergism was probably achieved by an indirect effect of a glucocorticoid-activated intermediate gene on the IL-6 RE-BPs. The rat IL-6 RE-BP had a molecular weight of 102 +/- 10 kDa and was thus distinct from NF-IL-6 and IL-6-DBP/LAP. Therefore, IL-6 must activate two different classes of liver acute-phase genes through at least two different nuclear DNA-binding proteins: NF-IL-6/IL-6-DBP/LAP and the IL-6 RE-BP.
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PMID:Synergistic action of interleukin-6 and glucocorticoids is mediated by the interleukin-6 response element of the rat alpha 2 macroglobulin gene. 137 12

The interaction between purified Agaricus bisporus lectin and several human proteins was studied using the Ouchterlony double diffusion and immunoelectrophoresis techniques. Only one precipitation line was observed with normal human serum, normal human colostrum, IgA1 myeloma serum, both serum monoclonal and secretory IgA1 and monoclonal IgD. No reaction was observed with monoclonal and secretory IgA2, IgG, IgM, alpha 2 macroglobulin or pregnancy-associated alpha 2 glycoprotein. These results were confirmed by hemagglutination inhibition assays when IgA1, IgA2 and IgD were tested. On the basis of this reactivity, ABL could be a useful tool for distinguishing and isolating human IgA subclasses.
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PMID:Differential reactivity of Agaricus bisporus lectin with human IgA subclasses in gel precipitation. 147 57

Five allotypic determinants controlled by independent genes have been identified in goat. Of these determinants, four have been detected with alloimmune antisera and one with monoclonal antibodies. The specificities A1, C1 and D1 are lipoproteins; B1 is possibly an alpha 2 macroglobulin and E1 and IgG2. The specificity B1 is not expressed until the age of 3-4 months. The gene controlling the specificity E1 is present at about the same frequency (0.38-0.41) in goat, sheep, cattle and water buffalo. Stable hybridomas secreting goat IgG2 have been obtained by the fusion of goat peripheral lymphocytes with mouse myeloma cells.
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PMID:Identification of goat allotypic determinants and generation of goat-mouse hybridomas secreting goat IgG2. 238 13

In 13 specimens of renal tissue from 11 patients, deposits of monoclonal immunoglobulin light chains and continuous granular electron-dense material within tubular basement membranes and in association with the glomerular basement membrane were identified. All but one patient were men n the fifth to seventh decades of life, and each presented with azotemia and features of glomerular rather than tubulointerstitial disease. Osteolytic bone lesions occurred in only three patients, and a bone marrow plasmacytosis greater than 30 percent consistent with plasma cell myeloma was identified in only four patients. Light chain distribution in the nephron was confirmed with immunoelectron microscopy and was not associated with deposition of other serum proteins such as immunoglobulin heavy chains, complement, transferrin, alpha 2 macroglobulin and albumin. The electron dense deposits differed in distribution and character from those associated with membranoproliferative glomerulonephritis type II (dense deposit disease), amyloidosis, cryoglobulinemia, macroglobulinemia and benign monoclonal gammopathy. Serum from six of these patients did not bind to normal human or rat renal parenchyma in vitro. Kappa light chain nephropathy was characterized by predominant linear tubular basement membrane kappa deposits, and nodular mesangial and linear glomerular basement membrane kappa immunostaining. Lambda light chain nephropathy was characterized by linear lambda glomerular basement membrane and tubular basement membrane immunostaining. Manifestations of glomerular dysfunction dominated the clinical presentation of light chain nephropathy, and most patients did not have typical features of multiple myeloma. The diagnosis was predicated upon thorough immmunohistologic assessment of renal biopsy material.
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PMID:Light chain nephropathy. 678 78

The polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes (POEMS) syndrome is a rare multisystem disorder of obscure pathogenesis associated with osteosclerotic myeloma. Circulating levels of proinflammatory cytokines (tumor necrosis factor-alpha (TNF-alpha) interleukin-1 beta [IL-1 beta], IL-2, IL-6, and interferon-gamma [IFN-gamma]), anti-inflammatory cytokines (transforming growth factor beta 1 [TGF beta 1], IL-4, IL-10, and IL-13), the cytokine carrier protein alpha 2 macroglobulin, IL-1 receptor antagonist (IL-1ra), soluble TNF receptors (sTNFr) p55 and p75, and soluble IL-6 receptor (sIL-6r) were determined in 15 patients with POEMS syndrome and 15 with multiple myeloma. Patients with POEMS syndrome had higher serum levels of IL-1 beta, TNF-alpha, and IL-6 and lower serum levels of TGF beta 1 than did patients with multiple myeloma. Serum levels of IL-2, IL-4, IL-10, IL-13, IFN-gamma, alpha 2 macroglobulin, and sIL-6r were similar in both groups. IL-1ra and sTNFrs were increased in POEMS syndrome, but out of proportion to the increase of IL-1 beta and TNF-alpha. Serial evaluations in 1 patient showed that proinflammatory cytokine serum levels paralleled disease activity assessed by platelet count and neurologic involvement. Our results suggest that the manifestations of POEMS syndrome might be regarded as the result of a marked activation of the proinflammatory cytokine network (IL-1 beta, IL-6, and TNF-alpha) associated with a weak or even decreased (TGF beta 1) antagonistic reaction insufficient to counteract the noxious effects of cytokines.
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PMID:Overproduction of proinflammatory cytokines imbalanced by their antagonists in POEMS syndrome. 860 36

New technological evolutions have enabled new diagnostic approaches in urinalysis. Urinary flow cytometry and automated microscopic pattern recognition are two new techniques that are characterised by a much better imprecision and a higher throughput as compared to conventional microscopy of the urine sediment. Although these new techniques are well suited for the routine clinical laboratory for screening and diagnostic purposes, trained technicians are still required to verify, and if necessary, to correct the results by visual microscopy. On the other hand, automated urinary test strip analysis offers analytical, clinical, and labour cost-saving advantages. Furthermore, determination of specific urinary proteins offer interesting alternatives for diagnosis. In diabetics, the clinical significance of non-immunoreactive microalbumin needs to be established. Furthermore, the determination of specific urinary proteins alpha 1 microglobulin (as a tubular marker protein), alpha 2 macroglobulin (as a haematuria location marker) and light chains (myeloma monitoring) offer interesting diagnostic perspectives. As the information content obtained by urinalysis is complex, expert systems that make use of the various chemical and morphological parameters can offer an interesting help in the interpretation.
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PMID:New screening diagnostic techniques in urinalysis. 1767 79