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 the present work, using an immunological approach, we have investigated the existence of common epitopes between two receptors of the glycoprotein hormone family, lutropin (LH) and thyrotropin (TSH) receptors. We have immunized high responder mice with purified porcine LH receptors obtained by successive affinity chromatographies on agarose-human chorionic gonadotropin (hCG) gels. From one fusion of splenocytes with the murine myeloma NSC1, secreting hybridomas were tested for their anti-LH receptor specificities. During sequential selection for this activity including direct recognition of the purified LH receptors in dot-blot assays and displacement experiments of 125I-pLH and 125I-hCG binding to different sources of receptors, we performed a parallel investigation of their anti-porcine TSH receptor activities. Purified immunoglobulins from two of them showed a TSH-like activity on the iodide metabolism of porcine thyroid cell, this activity being related to the phosphoinositide breakdown pathway; moreover, these antibodies obtained after immunization with porcine LH receptors were able to immunopurify human TSH receptors. The double selection process led us to characterize three groups of immunoglobulins: exclusive specificities for lutropin receptors or thyrotropin receptors and cross-reactive specificities. Our results demonstrate the possibility of sequence homologies at the protein and the gene levels between the receptors for the glycoprotein hormone family supporting the hypothesis of a common origin in evolution.
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PMID:Lutropin receptor and thyrotropin receptor share a common epitope. 247 48

Evaluation of double-stranded RNA by flow cytometric analysis is an important parameter for discriminating quantitatively between human tumoral and normal cells. We studied double-stranded RNA (ds-RNA) measurements using propidium-iodide after DNase treatment in bone marrow and in peripheral blood cells from patients with acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia and multiple myeloma. The highest incidence of ds-RNA excess (greater than 30%) was observed in patients with acute leukemia (75%), while those displaying it in complete remission phase were 20-25% and in relapse about 80%. A high incidence was also noted in patients with chronic myeloid leukemia in blastic crisis (100%) and in patients with multiple myeloma with heavy tumor stage myeloma (78%). We never observed an elevated ds-RNA excess in the control group, formed by normal peripheral blood lymphocytes. Indeed the specificity of this tumor marker is attested to not only by its high levels in various hematologic malignancies, but also by its absence in normal cells. Hence the importance of its clinical implications in malignant hematologic diseases is confirmed.
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PMID:Double-stranded RNA excess in hematologic diseases: clinical implications. 263 84

Tumor cell-associated expression of multidrug resistance (MDR) was quantitated in 22 patients with DNA-aneuploid myeloma using 2-parameter flow cytometry with monoclonal antibody (MoAb) C-219 for the detection of cytoplasmic p-170 and propidium iodide for nuclear DNA content. The proportion of cells expressing p-170 and the intensity of p-170-related fluorescence were determined for each patient. Among the 14 patients treated with vincristine-adriamycin-dexamethasone (VAD), the proportion of p-170-positive cells distinguished sensitive from resistant disease (P less than .01). Among a subgroup of seven patients with MDR analysis available prior to VAD therapy, two subsequent nonresponders had high proportions of C-219-reactive cells. The presence de novo of high proportions of p-170-expressing cells in another still untreated patient and in a further individual with resistance to dexamethasone and interferon (not associated with MDR) warrants systematic analysis of p-170 expression prior to therapy to determine its clinical implications for response to MDR-associated drugs as combined in the VAD regimen. Concurrent MDR expression by aneuploid tumor cells and cells in the diploid subcompartment may represent involvement of diploid cells in the myeloma disease process.
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PMID:P-glycoprotein expression in plasma-cell myeloma is associated with resistance to VAD. 256 64

Using a recently described cell line derived from the fusion of human thyroid and human myeloma cells, we studied the effects of TSH on cell growth, iodide organification, and cAMP production. Although these cells grow in the absence of TSH, when incubated for 2 days in serum-free medium containing purified human or bovine TSH, there was a significant increase in cellular DNA content. The stimulatory effect was observed at concentrations as low as 0.5 microU/ml, which produced a significant increase in DNA content, and was maximal with 5 microU/ml. This effect was still present after 6 days of incubation. Electron microscopy performed by an unbiased observer on cells incubated in the presence of TSH showed an increase in the calculated size of the cells and the nucleus which was significant at 0.1 microU/ml and maximal at 1 microU/ml. Stimulation of 125I organification and hormone production was observed at TSH concentrations as low as 1 microU/ml and was maximal at 10 microU/ml. However, neither TSH (1-50 microU/ml) nor forskolin (10(-6) M) stimulated cAMP production. These data suggest that these cells lack a functional adenylate cyclase pathway and that growth and iodide organification are mediated by other second messenger systems. Such a cell line could yield new insights into the mechanisms of TSH action and may provide a sensitive bioassay for TSH and other thyrotropic factors.
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PMID:Thyrotropin induces growth and iodothyronine production in a human thyroid cell line without affecting adenosine 3',5'-monophosphate production. 284 54

We analyzed 49 patients with multiple myeloma (MM) using propidium iodide (PI) staining and flow cytometry to assess DNA content of MM cells in bone marrow. In 12 patients the presence or absence of DNA content aneuploidy could not be determined by analysis of single-parameter DNA histograms alone. Using forward light scatter measurement, resolution of ploidy was readily obtained in all but three cases. Assuming the DNA content of the low light scatter population to be diploid, we were able to classify 7 cases as hypodiploid and 39 as hyperdiploid or diploid. Hyperdiploid or diploid patients survived a median of 24 months and hypodiploid patients only 2.5 months. We conclude that multiparameter analysis of DNA content and light scatter provides easier analysis for the presence or absence of aneuploidy. Patients with DNA content hypodiploidy have a short survival.
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PMID:Detection of hypodiploidy using multi-parameter flow cytometric analysis: a prognostic indicator in multiple myeloma. 292 79

Data collected by the Cancer Registry of the Canton of Vaud, Switzerland, were used to estimate proportional mortality ratios (PMR) and mortality odds ratios (MOR) for various neoplasms according to social class and sector of occupation (agriculture versus others). Mortality ratios were elevated in lower social classes for cancers of the lung (MOR = 1.18 for social class IV or V vs I or II) and other sites strictly related to tobacco (mouth or pharynx, oesophagus and larynx; MOR = 1.70), and (though not significantly) for cancers of the stomach (MOR = 1.16) and uterus (MOR = 1.30 for cervix and 1.47 for corpus uteri). Furthermore, there was a strong negative social class gradient for thyroid cancer (a neoplasm with particularly elevated incidence and mortality in Switzerland), probably attributable to higher prevalence of iodine deficiency in lower social classes (MOR = 3.17). Positive social class gradients emerged for cancers of the intestines (MOR = 0.77 for social class IV or V), skin (MOR = 0.74) and prostate (MOR = 0.87). Agricultural workers showed decreased ratios for cancers of the lung (MOR = 0.75), cervix uteri (MOR = 0.72) and prostate (MOR = 0.80), and excess mortality from cancers of the upper digestive and respiratory sites (MOR = 1.22), stomach (MOR = 1.18), testis (MOR = 2.05) and lympho-haematopoietic neoplasms, particularly myeloma (MOR = 2.14).
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PMID:Socioeconomic groups and cancer risk at death in the Swiss Canton of Vaud. 322 77

We have assessed the tumoricidal potential of enzyme-antibody conjugates on murine myeloma cells. Conjugates of glucose oxidase (EC 1.1.3.4) and lactoperoxidase (EC 1.11.1.7) were specifically targeted on the NSO tumor cells. Optimal conditions for tumor cell killing, as assayed by [51Cr] release required the binding of both antibody conjugates to the cell membrane. This is followed by washing and incubation in medium containing glucose and 0.1 mM iodide. Under these conditions 90% of the incorporated [51Cr] labeled is released from the cells, and NSO clonogenicity is reduced by a factor greater than 5 logs by 2 h of incubation.
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PMID:In-vitro cytolysis of myeloma tumor cells with glucose oxidase and lactoperoxidase antibody conjugates. 376 10

In an effort to develop a new tumor marker suitable for flow cytometric analysis, we examined the value of double-stranded ribonucleic acid (ds-RNA) measurements using propidium iodide after DN'ase treatment. Cellular ds-RNA content was evaluated both in experimental cell lines and in clinical specimens. Higher levels of ds-RNA were present in tumor cells as compared with normal cells. In tumor cells, fluorescence was intensely localized in the nucleolus and was more diffuse in the cytoplasm. Change of less than 10% in the ds-RNA levels was observed in cell lines as a function of cytokinetic determinants such as cycle phase, culture age, and cycle traverse rate. Tumor differentiation by dimethylsulfoxide resulted in a significant decrease in cellular ds-RNA content. For quantitative comparison of clinical material, a ds-RNA excess was defined in relationship to normal peripheral blood lymphocytes. ds-RNA excess greater than 30% was observed in only one of 34 normal tissues (3%) as compared with 124 of 201 neoplastic tissue samples (62%). This incidence was higher in patients with acute leukemia (76%), high-grade and intermediate-grade lymphoma (75%), and high tumor stage myeloma (83%), as compared with chronic leukemia (20%), low-grade lymphoma (25%), and intermediate or low tumor mass myeloma (43%). Prognostically, a high pretreatment ds-RNA excess in myeloma was associated with a lower remission rate. The persistence of ds-RNA excess in the bone marrow of patients with acute myelogenous leukemia in remission predicted for a shorter remission duration (seven v 22 months; P = .05). We conclude that ds-RNA excess, as readily measured objectively and quantitatively by flow cytometry, may have important diagnostic and prognostic implications for the management of patients with malignant disease.
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PMID:Preferential expression of double-stranded ribonucleic acid in tumor versus normal cells: biological and clinical implications. 400 32

The DNA content of human plasma cells from myeloma patients relative to that of leukocytes was determined by flow and microscopic cytofluorometry after propidium iodide and fluorescent Feulgen staining, respectively. Mononucleated myeloma plasma cells from all of the 17 patients studied contained more DNA (17 to 58%) than the leukocytes from the patient. The binucleated and trinucleated plasma cells, which were more prevalent in advanced cases, contained up to two and three times, respectively, the amount of DNA determined in the mononucleated plasma cells. These observations suggest that the ploidy abnormalities of myeloma plasma cells are even more extensive than the numerous karyotypic studies have indicated.
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PMID:The DNA content of human plasma cells. 616 50

A rapid reproducible method yielding high resolution analysis of DNA and protein in human hematopoietic cell samples has been developed by modification of the propidium iodide and fluorescein isothiocyanate procedure. Cell staining involves sequential addition of each reagent (RNase, fluorescein isothiocyanate and propidium iodide) to ethanol-fixed cells and requires no centrifugation steps. Stained cells are analyzed in the reagent solutions. Analysis of bone marrow samples from multiple myeloma patients showed mixed normal and aneuploid populations with a major portion of the aneuploid cells having a significantly higher protein content. This approach permitted differential cell cycle analysis of normal and the aneuploid populations.
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PMID:Simplified method for DNA and protein staining of human hematopoietic cell samples. 616 93


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