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)

The bone marrow of a patient with multiple myeloma of the IgG2 Kappa type with spontaneously crystallizing cryoglobulin was studied by electron microscopy. The ultrastructure of the myeloma cells disclosed the presence of a crystalline material in the cytoplasm within the rough endoplasmic reticulum (RER) as well as in extracisternal sites. The crystalline material was also seen extracellulary with a distinctly unique subunit structure. The tubular units measured 200 +/- A (SEM) externally with an internal diameter of 100 +/- A (SEM). The intracellular distribution did not indicate a characteristic organelle association usually observed in protein synthesizing cells. It is suggested, based on the present observations and the findings of others, that the crystalline material may represent polymerized protein synthesized by free ribosomes mostly in extracisternal locations, a pattern often seen in neoplastic plasma cells. Diffusion to extracisternal sites of precrystalline material through the membranes of the RER is a possible alternative mechanism.
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PMID:Ultrastructure of myeloma cells in a case with crystalcryoglobulinemia. 40 21

Plasma cells isolated from bone marrow (BM) aspirates of 15 patients with active multiple myeloma (MM) were cultured and analysed for in vitro proliferative response and Ig-synthesis upon stimulation with interleukin-3 (IL-3), interleukin-4 (IL-4) and interleukin-6 (IL-6). The proliferative response, determined as Ki-67 positivity in concentrated plasma cells, was increased by IL-6 (Stimulation Index, SI = 1.77 +/- 0.21 (M +/- SEM] but not by IL-3 or IL-4. This proliferation could be blocked by anti-IL-6. In vitro Ig-synthesis was stimulated by IL-4 (SI = 1.62 +/- 0.12 (M +/- SEM) P less than 0.05) but not by IL-6 or IL-3. This effect was not antagonized by anti-IL-6. An inverse correlation was found in this group of patients between the IL-6 induced stimulation of plasma cell proliferative activity and the IL-4 induced increase of Ig-synthesis (P = 0.027). These data indicate in MM that Ig-synthesis and the in vitro proliferative activity may be stimulated by different haematopoietic growth factors, which may reflect the involvement of different responding cells.
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PMID:In vitro Ig-synthesis and proliferative activity in multiple myeloma are stimulated by different growth factors. 177 80

Review of direct antiglobulin testing (DAT) in 88 patients with multiple myeloma (MM) and five with Waldenstrom's macroglobulinemia revealed 26 cases with a positive DAT. Twenty-two of these had immunoglobulin G-M protein, three had light chain MM, and one had immunoglobulin A-MM protein. None of the immunoglobulin GD-MM (n = 2), nonsecretory MM (n = 5), or Waldenstrom's macroglobulinemia patients (n = 5) were positive. None of the patients had hemolysis attributable to the adsorption of the M protein. The serum concentration of M protein was higher in DAT-positive patients (57.6 +/- 3.8 g/L, mean +/- SEM) than in the negative ones (35.7 +/- 6.4 g/L; probability value of the difference was less than 0.01). The erythrocyte eluates from DAT-positive patients contained a single immunoglobulin, of the same class as the M protein, and did not react with a panel of ABO-compatible erythrocytes. Addition of melphalan during incubation did not affect the results. The M protein of DAT-positive patients was of immunoglobulin G-3 subclass in 7 of 10 patients. A positive direct antiglobulin test frequently is seen in patients with multiple myeloma, the reaction is due to passive adsorption of the M protein onto the erythrocytes, is most frequently observed with immunoglobulin G3-MM, and usually does not produce hemolysis.
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PMID:Positive direct antiglobulin tests in myeloma patients. Occurrence, characterization, and significance. 190 37

A monoclonal antibody-based immunoenzymometric assay (IEMA) for the measurement of human serum growth hormone is described. Two high-affinity and complementary monoclonal antibodies were selected from a panel of 9 obtained upon fusion of SP2/O myeloma cells with spleen cells from a Balb/c mouse immunized against human growth hormone of pituitary origin. One monoclonal antibody was immobilized by attaching it to the walls of microtiter wells and the second was biotinylated. The reaction was quantitated by the addition of streptavidin-peroxidase. The sensitivity of the assay was 0.2 mIU/l and the intra- and interassay coefficients of variation for 4.6 to 46 mIU/l were less than 8.3 and 17.3%, respectively. Cross-reaction with human placental lactogen, human prolactin and rat growth hormone was less than 0.1% (w/w). Comparison of results obtained for 180 routine serum assays by radioimmunoassay and the assay described here had a correlation coefficient of 0.94 with a mean value of 16.3 +/- 1.3 (mean +/- SEM) and 13.3 +/- 1.2 mIU/l, with the IEMA providing values 18% lower than the RIA. The discrepancy emphasizes the necessity of redefining normal ranges before immunometric assays, like the one described, can be used routinely.
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PMID:Monoclonal antibody-based immunoenzymometric assay for serum human growth hormone. 209 41

In vitro perfused kidneys of ovalbumin-sensitized guinea-pigs consistently released relatively large quantities of histamine when challenged with the specific antigen (mean +/- SEM in twelve experiments was 37.7 +/- 6.0% of total kidney histamine, maximum 70.6%, compared with a basal release of 0.5 +/- 0.46% over a comparable period) but not with non-cross-reacting antigens. There was also no release from non-sensitized kidney. Rabbit antisera to guinea pig IgG1 and IgG2 immunoglobulins (but not normal rabbit serum) also consistently released histamine from perfused kidneys of sensitized guinea-pigs, but the release was smaller than with antigen, and could also be obtained from kidneys of non-sensitized guinea-pigs (maximum release 62.4% with the most potent antiserum). Guinea-pig kidney cell suspensions prepared by collagenase dispersion in vitro responded similarly, but the release with antigen was small (less than 10% net release, minus the spontaneous release 9.46% on average) as compared to anti-IgG1 (net release up to 38%) or anti-IgG2 (up to 44%). Rat kidney cells prepared by a similar procedure, and passively sensitized in vitro by incubation with rat immunoglobulin E (IgE) myeloma protein also responded to the addition of antiserum to rat IgE by releasing substantial amounts of histamine (up to 44% net release). In addition, heparin-containing cells (presumably mast cells or equivalent) in the enzyme-dispersed kidney cell preparations in both species were identified and counted by an adaptation of the Technicon H 6000 system used for counting blood basophils, and shown to represent 1 in 10,000 or less of the total cell population, which was not different from the count of similar cells in lung and heart tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal histamine: release by immune stimuli. 243 15

Patients with myeloma have a depressed capacity to respond to antigenic challenge. Studies in this laboratory have previously described an unclassified lymphoid cell which binds human erythrocytes coated with human immunoglobulin G (IgG) anti-D antibody (EA) as important in the inhibition of Ig synthesis in myeloma patients. Using monoclonal antibodies, two-color fluorescence studies, and flow cytometry, we characterized this EA cell as a Leu-1+ (cluster designation (CD) 5), Leu-12+ (CD 19), Leu-16+ (CD 20), B2+ (CD 21), Leu-14+ (CD 22), and HLA-DR+ B cell. The cell was negative for antibodies to Leu-2 (CD 8), Leu-3 (CD 4), Leu-4 (CD 3), Leu-5 (CD 2), Leu-7, Leu-8, Leu-11 (CD 16), Leu-M1 (CD 15), Leu-M3, and CALLA (CD 10). This profile is consistent with a Leu-1+ B cell and excludes a T cell, natural killer cell, and monocyte. Comparison of the relative role of these cells to the role of monocytes in the suppression of pokeweed mitogen-stimulated Ig synthesis was determined in serial studies on 19 myeloma patients. The mean (+/- SEM) percentage of inhibition of Ig synthesis by monocytes from stage I myeloma patients was 14 +/- 2.2%, from stage II patients was 37 +/- 3.5%, and from stage III patients was 51 +/- 4.7%. Inhibition of Ig synthesis by Leu-1+ EA cells was 46 +/- 1.5%, 48 +/- 1.6%, and 43 +/- 3.7% in stage I, II, and III patients, respectively. Immunosuppressive B cells are an important component of inhibition of Ig synthesis in the immunodeficiency of myeloma.
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PMID:Multiple myeloma: an immunologic profile. IV. The EA rosette-forming cell is a Leu-1 positive immunoregulatory B cell. 295 12

Increased bone resorption (BR) and increased renal tubular reabsorption of calcium (TRCa) may both be involved in the pathogenesis of hypercalcemia of malignancy (HM). We have evaluated the relative importance of these two mechanisms in 33 patients with HM after extracellular volume expansion and after single infusion of clodronate (C12MDP: 500 mg iv over 8 h). The fasting urine Ca/creatinine ratio was taken as an index of BR (BRI). An index of TRCa was calculated (TRCaI) from a nomogram based on the relationship between urine Ca excretion per unit of glomerular filtration rate and plasma Ca (PCa). Mean (+/- SEM) PCa fell from 3.29 +/- 0.07 to 2.69 +/- 0.05 mmol/l three days after C12MDP (n = 33, p less than 0.001), a response similar to that obtained with repeated daily iv injections of 500 to 1000 mg C12MDP. The pathogenesis of hypercalcemia varied according to the type of neoplasm. BRI was the highest in multiple myeloma and breast tumors. TRCaI was markedly increased in squamous-cells lung, bladder, kidney and liver carcinomas, reaching levels observed in primary hyperparathyroidism. TRCaI was normal in most cases of multiple myeloma. Breast tumors appeared to be heterogeneous with respect to TRCaI. The fall in PCa in response to a single infusion of C12MDP was usually most marked in cancer patients with elevated BRI and normal TRCaI. It was very modest in patients with high TRCaI and slightly elevated BRI. In conclusion, this study confirms that stimulation of bone resorption is not the only mechanism of the maintenance of hypercalcemia of malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone and renal components in hypercalcemia of malignancy and responses to a single infusion of clodronate. 297 82

A cell type-specific monoclonal antibody (Mab) against a cell surface antigen of rat anterior pituitary somatotrophs has been generated by fusion of a nonsecreting mouse myeloma line with spleen cells from a mouse immunized with enzymatically dispersed anterior pituitary cells of adult random cycling female rats. Hybridomas were initially screened for antibodies to cell surface antigens by an enzyme-linked immunosorbant assay using rat anterior pituitary cells and smooth muscle cells of aorta as positive and negative controls, respectively. Positive clones were further checked for cell type specificity by immunofluorescence. Mab WHC-1 is an immunoglobulin M (IgM) with kappa-light chains and is cytotoxic in the presence of complement. Based on double immunofluorescence, this Mab reacted with 22.5 +/- 2.0% (+/- SEM) of the anterior pituitary cells of adult random cycling female rats. Among them, about 93.5 +/- 1.4% were somatotrophs, and only 4.1 +/- 1.2% were mammotrophs. Approximately two thirds of the somatotrophs were Mab WHC-1-positive. The reaction of this Mab with gonadotrophs, thyrotrophs, or corticotrophs were negligible. The percentage of Mab WHC-1-positive cells derived from immunoperoxidase staining was significantly greater than that from immunofluorescence. The cell surface antigen defined by Mab WHC-1 is expressed heavily on GH3 cells, but not on smooth muscle cells. It is resistant to trypsin digestion, but sensitive to ethanol treatment, and exhibits the solubility property of a glycolipid. Mab WHC-1 cross-reacts with the anterior pituitary cell of rabbits, but not mice. These results provide the immunological evidence for heterogeneity among somatotrophs and demonstrate the feasibility of making pituitary cell type-specific Mabs.
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PMID:Production and partial characterization of a monoclonal antibody to rat anterior pituitary somatotrophs. 327 36

Serum osteocalcin (BGP) is a new marker of bone turnover that reportedly evaluates bone formation. Thus, its measurement could assess the bone formation rate in tumor-associated hypercalcemia. We measured concentrations of BGP and other parameters of bone metabolism in 54 untreated hypercalcemic cancer patients as compared to 109 healthy subjects. Primary tumor sites were breast (19), lung (11), head and neck (6), multiple myeloma (3), kidney (2), and various (11) or multiple (2). Mean BGP levels were higher in the hypercalcemic subjects, 4.6 +/- 0.4 (SEM) ng/ml, than in the normal subjects, 3.6 +/- 0.1 ng/ml (p less than .05), and were normalized in the 22 patients who could be reevaluated after successful treatment of hypercalcemia with intravenous aminohydroxypropylidene diphosphonate (APD). There was no correlation of BGP levels with age, sex, or renal function. Compared with the Gaussian distribution in the normal subjects, there was a considerable scatter of the data in hypercalcemic patients, suggesting the existence of defined subgroups with abnormally low or abnormally high values. However, we found no significant relationship of BGP concentrations with tumor site or histology or with bone metastatic involvement. We found also no significant correlation between concentrations of serum BGP and total or ionized calcium, alkaline phosphatase, parameters of bone resorption, and indices of parathyroid function. In summary, serum BGP levels were slightly elevated in tumor-associated hypercalcemia and were normalized after successful treatment of hypercalcemia. More importantly, BGP concentrations varied widely even in the subgroups of patients with hypercalcemia accompanying massive bone metastatic involvement or in the patients without detectable skeletal metastases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum osteocalcin (BGP) in tumor-associated hypercalcemia. 350 43

In order to define the ultrastructure of the hybridoma cell and to learn more about the plasmocytic differentiation process, a scanning (SEM) and transmission (TEM) electron microscopy study of several cell types involved in the production of monoclonal antibodies was performed. Cells of the three different stages in hybridoma process were studied. These cells included NS/1 murine myeloma cells, 40-3A4 in vitro cultured hybridoma and 33-1D2 ascitic tumor hybridoma cells. A stereological analysis of the Sv parameter (surface of RER per volume unit of cytoplasm) was performed in the murine myeloma line, the in vitro cultured hybridoma and the ascitic tumor hybridoma. In order to comparatively evaluate the plasmocytic differentiation of these cells the same methodology was applied to splenic lymphocytes from immunized mouse and to mature human myelomatous plasma cells. As expected, during the hybridoma process, a progressive increase in the amount of RER was detected. This was in contrast with the surface characteristics of the cells which become progressively smooth when the hybridoma was cloned, either in vitro or in vivo. From these results it can be inferred that the amount of RER is a more reliable parameter than surface blebs as a morphological element indicative of plasmocytic differentiation. On the other hand, numerous viral particles were present not only in murine myeloma line but also in hybridoma clones secreting monoclonal antibodies.
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PMID:Hybridoma process: ultrastructural cytology of different stages. 356 Feb 92


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