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)

1. A series of Dnp (dinitrophenyl) nitroxide spin labels was used to map the dimensions of the combining site of the Dnp-binding immunoglobulin A myeloma protein MOPC 315. The method compares the observed e.s.r. (electron-spin-resonance) hyperfine splittings with those calculated on the basis of different postulated motions for the spin label. The analysis is complicated by the sensitivity of the e.s.r. hyperfine splitting to the overall ;tumbling' time of the antibody-hapten complex and the polarity of the spin-label's environment. When these effects are considered quantitatively, it is then possible to determine the degree of mobility of each hapten which is allowed by the shape of the combining site. 2. The dinitrophenyl ring is rigidly held, and the depth of the site is 1.1-1.2nm and has lateral dimensions at the entrance to the site >/=0.6nmx0.9nm. The analysis of the results for spin-labelled haptens with chiral centres allows these lateral dimensions to be refined to 0.8nm and 1.1nm, and it is shown that the site is asymmetric with respect to the plane of the dinitrophenyl ring. 3. A polarity profile of the combining site was also obtained and a positively charged amino acid residue, possibly arginine-95(L) (light chain), was located at the entrance to the site. 4. The binding of Gd(III) to the antibody-hapten complexes results in quenching of the e.s.r. signal of the nitroxide. By using La(III) as a control, the paramagnetic contribution to the quenching is measured. 5. Analysis of the differential quenchings of the enantiomers of two five-membered nitroxide ring spin labels gives two possible locations of the metal-binding site. One of these is equidistant (0.7nm) from each of the three dinitrophenyl aromatic protons, and nuclear-magnetic-resonance relaxation studies, at 270MHz, on solutions of dinitrobenzene, Gd(III) and the Fv fragment (variable region of heavy and light chain) from protein MOPC 315 support this location for the metal site. 6. The e.s.r. and metal-binding data were then compared with the results of a model of the combining site constructed on the basis of framework invariance in immunoglobulins [Padlan, Davies, Pecht, Givol & Wright (1976) Cold Spring Harbor Symp. Quant. Biol.41, in the press]. The overall agreement is very good. Assignments of possible chelating groups for the metal can be made.
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PMID:The gross architecture of an antibody-combining site as determined by spin-label mapping. 20 Feb 19

A bone biopsy specimen from a patient with multiple myeloma showed numerous Gaucher-like cells scattered throughout a homogeneous background of plasma cells. Further studies using histochemical stains, immunofluorescence, and light and electron microscopy were carried out to further define these cells. Light microscopy of Wright-stained and hematoxylin and eosin-stained marrow preparations showed large, round cells with fibrillar appearing cytoplasm and eccentric, pyknotic nuclei. These cells were periodic acid-Schiff positive, resistant to diastase digestion. Electron microscopy demonstrated plasma cells containing crystals in membrane-bound vesicles. Also, large macrophages among these plasma cells contained similar crystals surrounded by a single limiting membrane. Immunofluorescence staining of thin sections of marrow with fluorescein-labelled specific antiserums showed fluorescence of these large cells. Strong immunofluorescence was seen with polyvalent kappa and gamma antiserums but not with anti-albumin or serums with anti-lambda, mu or alpha specificity. It appears that these large cells have the light microscopic and histochemical characteristics of true Gaucher cells but, when studied with immunofluorescence and electron microscopy, it appears that the pseudo-Gaucher cells of multiple myeloma are bone marrow macrophages engorged with immunoglobulin.
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PMID:Pseudo-Gaucher cells in multiple myeloma. 38 Mar 39

Multiple myeloma is a disease that infrequently involves nonreticuloendothelial tissues and rarely causes pleural effusion. A 59-year-old woman had pleural effusion as the major manifestation of multiple myeloma. Light microscopy of her pleural fluid with Wright stained preparations showed all cells to be bizarre and often multinucleated plasmacytes. Electron microscopy confirmed these results. Intracellular immunofluorescence revealed IgG-kappa immunoglobulin (Ig) in greater than 90% of these cells. Surface immunofluorescence using anti-Ig sera was seen on less than 5% of the pleural fluid cells. 3H leucine incorporation into Ig in vitro was measured for these cells, and secretory curves were obtained that have the typical secretory kinetics of bone marrow plasmacytes. This demonstrates that such cells are viable and are able to synthesize and release immunoglobulin. Treatment of our patient with prednisone, melphalan, and cyclophosphamide resulted in symptomatic improvement and complete resolution of her pleural effusion. Pleural effusion is an unusual but important complication of multiple myeloma and does not necessarily carry the grave prognosis implied in previous reports.
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PMID:Myelomatous pleural effusion: clinical course and immunologic characterization of the pleural fluid cells. 38 84

Alterations in affinity of amyloid for Congo red after incubation of tissue sections with potassium permanganate, as described by Wright el al, were studied. The affinity of amyloid for Congo red after incubation with potassium permanganate did not change in patients with myeloma-associated amyloidosis, familial amyloidotic polyneuropathy, medullary carcinoma of the thyroid, pancreatic island amyloid, and cerebral amyloidosis. Affinity for Congo red was lost after incubation with potassium permanganate in tissue sections from patients with secondary amyloidosis and amyloidosis complicating familial Mediterranean fever (consisting of amyloid AA). Patients with primary amyloidosis could be divided into two groups, one with potassium-permanganate--sensitive and one with potassium-permanganate--resistant amyloid deposits. These two groups correlated with the clinical classification in typical organ distribution (presenting with nephropathy) and atypical organ distribution (presenting with cardiomyopathy, nephropathy, and glossopathy) and the expected presence of amyloid AA or amyloid AL. Potassium permanganate sensitivity seems to be restricted to amyloid AA. The potassium permanganate method can be important in dividing the major forms of generalized amyloidosis in AA amyloid and non-AA amyloid. This can be used for differentiating early stages of the disease and cases otherwise difficult to classify. It is important to define patient groups properly, especially in evaluating the effect of therapeutic measures. (Am J Pathol 97:43--58, 1979).
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PMID:The potassium permanganate method. A reliable method for differentiating amyloid AA from other forms of amyloid in routine laboratory practice. 49 95

A patient with multiple myeloma and a normal spleen died with high-grade pneumococcal bacteremia diagnosed by routine examination of a Wright-stained peripheral blood smear. In earlier reports, this finding has been described only in patients with abnormal or absent spleens. We review the proposed mechanisms of high-grade pneumococcal bacteremia in these patients and the immunologic abnormalities in patients with multiple myeloma that may result in increased susceptibility to this infection.
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PMID:Pneumococcal bacteremia diagnosed by peripheral blood smear in multiple myeloma. 71 28

Magnetic-resonance techniques are used to refine the model of the combining site of the Fv fragment of the dinitrophenyl-binding mouse myeloma protein MOPC 315 constructed by Padlan, Davies, Pecht, Givol & Wright (1976) (Cold Spring Harbor Symp. Quant. Biol.41, in the press). Light-absorption studies indicate a dinitrophenyl-tryptophan interaction in the Fv fragment of the type occurring in free solution. The Dnp-aspartate-tryptophan complex is therefore used as a starting point for the n.m.r. (nuclear-magnetic-resonance) analysis of the dinitrophenyl-Fv fragment interaction. Ring-current calculations are used to determine the geometry of the complex. The specificity of complex-formation between dinitrophenyl and tryptophan is confirmed by the lack of ring-current shifts of the dinitrophenyl resonances when tryptophan is replaced by any other aromatic amino acid. Proton n.m.r. difference spectra (at 270MHz), resulting from the addition of a variety of haptens to the Fv fragment, show that the combining site is highly aromatic in nature. Calculations on the basis of ring-current shifts define the geometry of the combining site, which involves a dinitrophenyl ring in van der Waals contact with four aromatic amino acid residues on the protein. The observation of a nuclear Overhauser effect on the H((3)) resonance of the dinitrophenyl ring provides additional constraints on the relative geometry of the H((3)) proton and an aromatic amino acid residue on the Fv fragment. The specificity of the Fv fragment for dinitrophenyl ligands arises from a stacking interaction of the dinitrophenyl ring with tryptophan-93(L), in an ;aromatic box' of essentially tryptophan-93(L), phenylalanine-34(H) and tyrosine-34(L); asparagine-36(L) and tyrosine-34(L) also contribute by forming hydrogen bonds with the nitro groups on the dinitrophenyl ring. The n.m.r. results also confirm that the antibody-hapten reaction may be visualized as a single encounter step. An Appendix shows the method of calculation of ring currents for the four aromatic amino acids and their use in calculating structures.
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PMID:The combining site of the dinitrophenyl-binding immunoglobulin A myeloma protein MOPC 315. 92 44

The pKa values of the three histidine residues in the Fv fragment (variable region of the heavy and light chains) of the mouse myeloma protein MOPC 315, measured by high resolution n.m.r. (nuclear magnetic resonance), are 5.9, 6.9 and 8.2. The perturbation of the pKa of one of the histidines (pKa 6.9) on the addition of hapten and the narrow linewidth of its proton resonances suggests that it is at the edge of the combining site. References to the model of the Fv fragment [Padlan, Davies, Pecht, Givol & Wright (1976) Cold Spring Harbor Symp. Quant. Biol. 41, in the press] allows assignment of the three histidine residues, histidine-102H, histidine-97L and histidine-44L. The determination of the pKa of the phosphorus group, by 31P n.m.r., of a homologous series of Dnp- and Tnp- (di- and tri-nitrophenyl) haptens has located a positively charged residue. Molecular-model studies on the conformations of these haptens show that the residue is at the edge of the site. The model suggests that the positively charged residue is either arginine-95L or lysine-52H.
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PMID:Specificity of interactions of hapten side chains with the combining site of the myeloma protein MOPC 315. 92 46

These studies indicate that monoclonal plasma cells can be detected in the peripheral blood of patients with active myeloma even when they are not detectable by routine WBC differentials performed on Wright-stained blood smears. These cells are usually not present in patients with MGUS and true SMM. They are detected in approximately 60% of patients with new, active MM and over 90% of patients with relapsed or refractory MM. If treatment is effective, they tend to decrease or disappear from the blood. When immunological, molecular, or cytogenetic studies are performed on peripheral blood cells from patients with MM, it must be realized that monoclonal plasma cells may be present and that they can influence the results of these tests. Although monoclonal plasma cells can circulate in the peripheral blood, it is not yet clear whether this cell represents the myeloma stem cell. It is possible that there are precursor cells that do not have plasma cell morphology in the blood or marrow that then differentiate into plasma cells. This question can only be answered by first depleting the plasma cells and then examining the remaining B-cells with appropriate immunological and molecular techniques.
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PMID:Circulating peripheral blood plasma cells in multiple myeloma. 149 Mar 54

The low frequency of plasma cells and the lack of specific cell surface markers has been a major obstacle for a detailed characterization of plasma cells in normal human bone marrow. Multiparameter flow cytometry enabled the identification of plasma cells in normal bone marrow aspirates. The plasma cells were located in a unique position in the correlation of forward light scattering, orthogonal light scattering, and immunofluorescent-labeled CD38. The identity of the sorted cell populations was confirmed by microscopic examination of Wright's stained slides and slides stained for cytoplasmic immunoglobulin using polyclonal antibodies reactive with light chains; ie, anti-kappa fluorescein isothiocyanate and anti lambda phycoerythrin (PE). The purity of the sorted plasma cells was greater than 97% (n = 4). The average frequency of plasma cells in normal bone marrow aspirates was low--0.25% of the nucleated cells (n = 7)--but surprisingly consistent between individuals (SD = .05; range 0.14% to 0.30%). A detailed analysis showed two distinct populations of plasma cells: (1) A population relatively smaller by forward light scattering expressed CD22, CD35, and sigE and was identified as early plasma cells (ie, lymphoplasmacytoid), and (2) a population larger by forward light scattering lacked these markers and was identified as mature plasma cells. The antigenic profile of the normal plasma cells was determined in two-color immunofluorescence studies. The expression of cell surface immunoglobulin G (IgG), IgA, IgE, IgD, IgM, and the cell surface antigens CD10, CD11b, CD13, CD11c, CD14, CD15, CD16, CD19, CD22, CD20, CD33, CD35, CD45, and HLA-DR was determined on the plasma cells. A significant heterogeneity in cell surface antigen expression was observed within the plasma cell population. Unexpectedly, myeloid-specific cell surface antigens such as CD33 and CD13 and the early B-cell antigen identified by CD10 were expressed on a proportion of plasma cells. These observations imply that the association of myeloid and early B-cell markers described in multiple myeloma may not be associated with the neoplasia but is a normal phenomenon.
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PMID:Identification and characterization of plasma cells in normal human bone marrow by high-resolution flow cytometry. 222 23

Aspirates obtained from bone marrow were prepared for routine Papanicolaou staining and screened by a cytologist. As a preliminary study, 100 consecutive bone marrow aspirations were examined. It was shown that metastatic carcinoma and primary bone marrow disorders (including leukemia, myelodysplastic syndromes, and multiple myeloma) can be recognized on Papanicolaou-stained marrow aspirates using the same cytologic criteria employed in the evaluation of cells from any site. Evaluation of bone marrow aspirates in the cytology laboratory is feasible and can be used to augment parallel services employing air-dried Wright-Giemsa-stained specimens in the hematology laboratory.
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PMID:Cytologic evaluation of Papanicolaou-stained bone marrow aspirates. 248 55


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