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)

Serum beta 2-microglobulin (beta 2m) levels were followed in eight patients with multiple myeloma who were treated with leucocyte alpha interferon (alpha IFN) 6 x 10(6) IU daily for 1-2 weeks before chemotherapy. Serial measurements of serum beta 2m were carried out regularly during the first week on alpha IFN. A rise in beta 2m was observed in all patients. with maximum increments ranging from 29% to 185% (mean 109%). The increase in beta 2m was most marked in patients with elevated pretreatment levels of serum beta 2m and creatinine. In six patients the peak value was reached between the third and the fifth day, after which the levels decreased. In two patients serum beta 2m remained elevated for 3 and 4 months, respectively. A marked increase in serum beta 2m can be induced by alpha IFN in myeloma, which should be taken into consideration when using beta 2m for the assessment of tumour response during alpha IFN therapy.
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PMID:Alpha interferon raises serum beta-2-microglobulin in patients with multiple myeloma. 201 58

Interleukin-6 (IL-6) is a multifunctional cytokine involved in the regulation of the terminal differentiation pathway of B lymphocytes. Recent reports revealed its potential role in the in vitro and in vivo growth of human multiple myeloma cells. The mechanism, however, by which IL-6 triggers proliferation of malignant plasma cells remains controversial. Using the very sensitive 7TD 1 bioassay we quantified endogenous circulating IL-6 levels in serum samples of 104 patients suffering from monoclonal gammopathies and other hematological disorders [47 with multiple myeloma (MM), 24 with monoclonal gammopathy of unknown significance (MGUS), 8 with myeloproliferative disease, and 25 suffering from low-grade non-Hodgkin's lymphoma (NHL)]. Elevated serum levels of IL-6 (greater than 5 pg/ml) were detected in 42% of the patients with MM, in 13% with MGUS, in 15% with low-grade B-NHL, and in 1 patient with T-NHL. In patients suffering from chronic myeloproliferative diseases, IL-6 levels were within the normal range. In patients with myeloma, IL-6 levels were significantly higher at advanced stages (II/III) or with progressive disease than in patients with MM stage I, MGUS, or at the plateau phase (P less than 0.01). In patients with monoclonal gammopathies including MGUS, serum IL-6 levels correlated with neopterin, tumor necrosis factor alpha and beta 2-microglobulin. An inverse correlation was found with hemoglobin levels. From these results, we propose that in myeloma patients serum IL-6 levels may reflect disease activity and tumor cell mass. The correlation with serum neopterin, a macrophage product, also suggests its origin in an activated immune system.
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PMID:Serum levels of interleukin-6 in multiple myeloma and other hematological disorders: correlation with disease activity and other prognostic parameters. 203 68

The authors evaluated in a group of 89 patients with monoclonal gammapathy (18 patients with monoclonal gammapathy of undermined significance, 34 patients examined at the time of diagnosis of multiple myeloma (MM) and in a group of 71 patients with MM examined in different stages of the disease) the serum beta 2-microglobulin. It was revealed that the mentioned indicator is of no differential diagnostic value, it is not related to sex nor to the immunochemical type of monoclonal immunoglobulin. A relationship of serum beta 2-microglobulin to age, serum urea and serum creatinine, to the severity of anaemia, serum albumin, sedimentation rate of red cells, degree of infiltration of bone marrow by myeloma plasmocytes and the stage of the disease, evaluated by the systems of Durie-Salmon and Medical Research Council, was found. The authors tested the importance of serum levels of this indicator for the prognosis of the disease.
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PMID:[Serum beta 2-microglobulin in multiple myeloma. I. Relation to selected indicators, clinical stage and disease prognosis]. 205 4

We selected 37 cases, followed-up for more than 36 months or until death, from a series of 45 patients affected by acute renal failure due to multiple myeloma in order to identify the parameters that could allow the outcome to be predicted. The patients were allocated to group 1, consisting of 27 patients who died within one year and to group 2, consisting of 10 patients who survived for more than 36 months. Renal failure was severe enough to require dialysis in 28 patients, 16 of whom were oliguric. Renal biopsy was performed in 23 cases, whereas light chain isoelectric point and serum beta 2-microglobulin levels were evaluated in each patient. All the patients underwent chemotherapy, which was associated with plasma exchange in 16 patients. Statistical analysis of the potential prognostic factors in the 2 groups showed that the incidence of hypercalcemia, infection, irreversible renal failure and severe tubulo-interstitial damage was significantly higher in group 1. Sex, tumor load, severity of renal failure and light chain isoelectric point had no prognostic significance. Finally, the number of patients treated by plasma exchange was significantly higher in group 2. Our results underline the prognostic role of both hypercalcemia and infection and justify aggressive treatment consisting of chemotherapy, plasma exchange and dialysis, even in cases of severe renal failure and high tumor load.
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PMID:Long-term survival patients with acute and severe renal failure due to multiple myeloma. 207 67

The levels of TNF-alpha and IFN-gamma were examined in serum from 32 patients with multiple myeloma and 33 healthy controls using sensitive enzyme-linked immunosorbent assays (ELISA). The detection limits for TNF-alpha and IFN-gamma were 80 pg/ml and 200 pg/ml, respectively. All samples were obtained at the time of diagnosis, before treatment. In sera from 8 of the myeloma patients the TNF-alpha concentrations were above the detection limit with a maximum value of 1.0 ng/ml. Overall, the TNF-alpha levels of the myeloma patients did not differ from the levels of the control group. Detectable amounts of IFN-gamma were found in 17 of the patient sera with 10.7 ng/ml as the top value. In contrast, the control group showed significantly lower s-IFN-gamma levels without detectable amounts in any of the samples (p less than 0.01). High IFN-alpha levels in 4 patients coincided with intercurrent infections but were not accompanied by a parallel increase of the TNF-alpha levels. The TNF-alpha and IFN-gamma values were compared with the serum levels of beta 2-microglobulin, calcium and creatinine, the M-component, the erythrocyte sedimentation rate, the degree of plasma cell infiltration of the bone marrow, the degree of skeletal destructions and with patients survival. No significant correlations could be observed between TNF-alpha or IFN-gamma and these variables of myeloma activity. We conclude that detection of serum TNF-alpha and IFN-gamma levels in multiple myeloma appears to be without any clinical value.
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PMID:Tumor necrosis factor-alpha and interferon-gamma in serum of multiple myeloma patients. 211 19

Between January 1987 and October 1989, 561 consecutive untreated patients with monoclonal gammopathy of undetermined clinical importance (MGUS) (n = 295) or with multiple myeloma (n = 266) were evaluated in a multicentre trial. Both bone marrow biopsy and aspiration (performed at different anatomical sites) were required at presentation. Bone marrow biopsy data indicated that changes in bone marrow composition from MGUS to early multiple myeloma and to advanced multiple myeloma followed a precise pattern, including an increased percentage of bone marrow plasma cells (BMPC%), a shift from plasmocytic to plasmoblastic cytology, an increase in bone marrow cellularity and fibrosis, a change in bone marrow infiltration (becoming diffuse rather than interstitial), a decrease in residual haemopoiesis and an increase in osteoclasts. In multiple myeloma the BMPC% of biopsy specimens and aspirate were closely related, although in 5% of cases the difference between the two values was greater than 20%. Some histological features were remarkably associated with each other. For example, BMPC% was higher in cases with plasmoblastic cytology, heavy fibrosis, or reduced residual haemopoiesis. Anaemia was the clinical characteristic most influenced by bone marrow histology. The BMPC% was the only histological variable which affected the greatest number of clinical and laboratory characteristics, including, besides haemoglobin concentration, erythrocyte sedimentation rate, radiographic skeletal bone disease, and serum concentrations of monoclonal component, calcium, beta 2-microglobulin and thymidine kinase activity. These data indicate that comparative bone marrow histology in monoclonal gammopathies has clinical importance.
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PMID:Bone marrow biopsy in monoclonal gammopathies: correlations between pathological findings and clinical data. The Cooperative Group for Study and Treatment of Multiple Myeloma. 219 32

The prognostic value of the multiple myeloma (MM) immunological type, of 20 different single prognostic variables, of 11 clinical staging systems, and of 6 morphological classification systems was evaluated in 121 patients (71 males and 50 females, 75 MM IgG, 26 MM IgA, and 20 MM micromolecular), who were followed from diagnosis to demise. The values of the prognostic variables related to diagnosis were correlated with survival by means of univariate analysis; multivariate analysis according to Cox's model was employed to select highly-significant parameters correlated with survival among these variables. Every patient was retrospectively staged according to each clinical and morphological system. Mean survivals were computed for each group on the basis of immunological type, mean value of each prognostic factor, clinical and morphological stage. Survival curves were computed and compared. All prognostic parameters showed a significant relationship with survival, even though p-value differed. Multivariate analysis according to Cox's model has indicated the following variables as significantly correlated with survival: bone marrow plasma cell percentage, degree of lytic bone lesions, hemoglobinemia value, and serum levels of beta 2-microglobulin. Each clinical and morphological staging system, as well as immunological types and mean value of single prognostic parameters, have divided patients into separate groups with significant differences in mean survival and in survival curves. All of these factors could be taken into account for correct prognostic evaluation, and, if they were applied in different steps of diagnosis and therapy, it would be possible to study the MM patient under different perspectives, in order to have a more complete picture of the disease and of the patient.
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PMID:[Prognostic evaluation in multiple myeloma. Relationship between immunological types, single prognostic factors, clinical staging systems, morphological classification systems and survival]. 228 22

CD4 is a cell surface glycoprotein that identifies the subset of human T lymphocytes that induces sIg+ B lymphocytes to differentiate and secrete Ig after intimate T-B cell contact. In the course of studying a recombinant, truncated form of CD4 (rT4) we noticed that goat antibodies of apparently irrelevant specificities bound to immobilized rT4. To directly study whether rT4 interacts with Ig molecules, purified human IgG was added to rT4-coated wells and a dose-dependent interaction between IgG and rT4 was observed by ELISA. Purified myeloma IgG proteins bound to immobilized rT4 with the same avidity as polyclonal IgG that suggests that rT4-IgG binding was not due to the presence of anti-rT4 antibodies in the IgG fraction. IgG from 6 sera bound to rT4 in concentration dependent manner similar to purified IgG. Immobilized rT4 specifically bound IgG, and not IgM, IgA, IgD, or beta 2-microglobulin. The specific interaction of rT4 and IgG was also observed when IgG or IgM were immobilized, demonstrating that IgG binding was not a unique property of immobilized rT4. As with low affinity receptors for IgG, rT4 bound heat aggregated IgG with increased avidity. Neither anti-CD4 mAb nor dextran sulfate inhibited rT4-IgG binding. rT4 bound Fc but not F(ab)2 fragments. Each of the purified IgG subclasses; IgG1, 2, 3, and 4 bound to rT4 with similar avidity. Taken together, these data suggest that rT4 specifically interacts with a public structure on IgG Fc.
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PMID:Recombinant, truncated CD4 molecule (rT4) binds IgG. 229 93

We studied the influence of plasmapheresis on the plasma concentrations of proteins (IgG, IgA, beta 2-microglobulin) used for estimation of tumour cell mass in patients with multiple myeloma. Simultaneously, the effects of plasmapheresis on plasma concentrations of proteins (CRP, alpha 1-antitrypsin, haptoglobin) used for the assessment of inflammatory processes were studied. Also, changes in the plasma concentration of protein HC, a recently described protein occurring both as a free protein and as an IgA complex, were studied. The influence of plasmapheresis varied for the different proteins. The plasma levels of IgG, IgA, CRP, alpha 1-antitrypsin, and haptoglobin decreased during plasmapheresis. The simultaneous reduction of the level of protein HC was smaller than that of IgG, IgA and haptoglobin. The plasma concentration of beta 2-microglobulin did not decrease during plasmapheresis. The recovery rates of the proteins were found to be approximately inversely related to their molecular weights.
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PMID:Effects of plasmapheresis on the plasma concentration of proteins used to monitor the disease process in multiple myeloma. 245 97

The expression of early and mature B cell markers, surface beta 2-microglobulin (B2M) and cytoplasmic immunoglobulin (clg) by aneuploid tumor cells in bone marrow aspirates from 44 patients with multiple myeloma was evaluated by correlated DNA immunofluorescence flow cytometry. Myeloma tumor cells of almost 90% of the patients contained monoclonal clg and expressed the mature plasma cell antigen R1-3 as well as surface B2M; common acute lymphoblastic leukemia antigen (CALLA) was present in 55%, B2 in 17%, and B4 in 23% of samples studied. Coexpression of CALLA and clg in 46% of all patients identified a novel myeloma phenotype without known counterpart in the normal differentiation of B cells. CALLA and clg were independently expressed and gave rise to CALLA+/clg-, CALLA+/clg+, and CALLA-/clg+ cells. The association of CALLA and mature plasma cell markers may define discrete stages of neoplastic plasma cell differentiation.
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PMID:Phenotypic heterogeneity in aneuploid multiple myeloma indicates pre-B cell involvement. 245 50


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