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1

Correlation of osteoprotegerin and sRANKL concentrations in serum and bone marrow of multiple myeloma patients

100%
Kraj M., Owczarska K., Sokolowska U., Centkowski P., Poglod R., Kruk B.
Archivum Immunologiae et Therapiae Experimentalis
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2005
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vol. 53
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issue 5
454-464
EN
Summary Recent studies suggest that multiple myeloma (MM) triggers osteoclastogenesis by disrupting the balance between the receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG), its natural antagonist. Determinations of bone marrow (BM) and serum OPG and sRANKL concentrations were performed in 133 MM patients and 42 healthy subjects by the ELISA method using Osteoprotegerin ELISA and sRANKL ELISA kits. MM patients had elevated serum levels of OPG compared with controls (p<0.0001) and OPG levels were higher in patients with renal failure and patients with hipercalcemia (p<0.001 and p=0.04, respectively). Serum OPG levels correlated with age, serum ?2-microglobulin, and BM OPG concentrations and did not correlate with the presence of osteolysis or with stage of disease. sRANKL serum levels in MM patients and in controls were not statistically different (p=0.42). In MM patients, serum OPG and sRANKL levels were similar at diagnosis and in the plateau phase of disease. There was a correlation between BM and serum sRANKL concentrations (p<0.001). Median values of the sRANKL/OPG ratio for BM and serum of MM patients were 0.14 and 0.11, respectively. The median value of the sRANKL/OPG ratio for the serum of controls was 0.11. In 20% of MM patients, serum OPG levels are elevated, and this may be a compensative reaction related to increased bone destruction. There is not statistically significant relationship between sRANKL serum and BM levels and the main clinical and laboratory parameters of the disease. Determination of BM and the serum sRANKL/OPG ratio seems to have no clinical value.
2

The use of the Congo red-related dye DBACR to recognize the heavy chain-derived abnormality of myeloma immunoglobulins

88%
Spolnik P., Konieczny L., Piekarska B., Rybarska J., Stopa B., Zemanek G., Drozd A., Krol M., Roterman I., Wolska-Smolen T., Skotnicki A. B.
Archivum Immunologiae et Therapiae Experimentalis
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2006
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vol. 54
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issue 3
217-221
EN
Introduction: The aim of this study was to differentiate heavy and light chain-derived instability of monoclonal myeloma immunoglobulins by complexation of matched supramolecular dyes. These are composed of several micellar pieces of self-assembled dye molecules which may penetrate the protein interior of the binding locus with polypeptide chains. These dyes were used to elicit, by precipitation, the postulated higher aggregation tendency of the heavy chain derived from its higher hydrophobicity. Materials and Methods: Agarose gel electrophoresis was used to create conditions for dye complexation and to reveal the precipitation. Results: Congo red derivatives with aromatic ring substitutes, BACR and DBACR, of increased penetrating capability were chosen to provoke the precipitation of abnormal immunoglobulins by displacing association-prone polypeptide chains from the protein interior. Conclusions: The results of this study confirm the heavy chain-related propensity of some monoclonal immunoglobulins to aggregate and precipitate. The simplicity of the technique may improve clinical diagnosis and facilitate predictions of disease complications.
3

Matrix metalloproteinase and cytokine production by bone marrow adherent cells from multiple myeloma patients

75%
Zdzisinska B., Walter-Croneck A., Dmoszynska A., Kandefer-Szerszen M.
Archivum Immunologiae et Therapiae Experimentalis
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2006
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vol. 54
|
issue 4
289-296
EN
Introduction: Cultures of bone marrow stromal cells derived from the bone marrow of multiple myeloma (MM) patients were shown to exhibit several abnormalities compared with control cultures from healthy subjects. The aim of the study was to examine whether cultures of bone marrow adherent cells, at low passage level, exhibit differences in matrix metalloproteinases (MMPs) and cytokine production compared with cultures from normal donors. Materials and Methods: MMP production was evaluated by gel zymography and by ELISA in supernatants of serum-free cultures of bone marrow adherent cells derived from 20 MM patients and 23 healthy controls. Spontaneous and lipopolysaccharide (LPS)- or Newcastle disease virus (NDV)-induced cytokine release was assessed in the supernatants of the cultures by the ELISA method. Results: Both cultures produced MMP-1, -2, -3, and -9 under serum-free conditions; however, the levels of MMP-1 and MMP-2 were significantly higher in cultures derived from MM patients, while MMP-3 was significantly higher in control cultures. The level of MMP-9 was comparable in the cultures derived from MM patients and controls. All cultures produced interleukin (IL)-10 and IL-11 spontaneously, but after LPS or NDV induction the levels of IL-10, IL-11, interferon , and tumor necrosis factor , were significantly higher in the cultures derived from MM patients than in control cultures. Conclusions: The results indicate that both the abnormalities in MMP production and the overproduction of cytokines (in the presence of LPS or virus, which mimic inflammatory conditions) may be involved in bone destruction and tumor spread in multiple myeloma.
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