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)

Amyloidosis is the name given to a group of clinically protean diseases whose common feature is the tissue accumulation of amyloid fibrils which have specific optical and staining properties, and are both insoluble in physiological solvents and resistant to proteolytic enzymes. Fibril deposition and progressive extracellular infiltration eventually result in atrophy due to compression. The structure of these fibrils embraces a wide range: immunoglobulin light chain or their fragments, acute phase proteins, hormones, protease inhibitors, beta 2-microglobulin, natriuretic peptides, and proteins whose function is still unknown. Despite this heterogeneity, however, they share a common crystallographic beta-pleated sheet structure. The clinical spectrum includes apparently primary forms, amyloidosis of myeloma, forms secondary to familial Mediterranean fever, Alzheimer's disease, forms associated with type 2 diabetes or medullary carcinoma of the thyroid, inherited-familial amyloidosis, and other less common conditions. Two pathogenetic phases are involved: enhanced production of precursor proteins and their abnormal enzyme cleavage, resulting in the formation of intermediate products corresponding to the amyloid fibrils. The results of treatment are still disappointing: alkylating agents and/or cortico-steroids are used in primary forms and for amyloidosis of myeloma; colchicine in familial Mediterranean fever; DMSO in renal amyloidosis; plasmapheresis in inherited-familial forms, together with the supportive management obviously dictated by clinical manifestations.
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PMID:Amyloidosis: clinical picture, immunological and biomolecular features, treatment prospects. 174 46

Synthesis of alpha- and beta-globin RNA in DMSO-induced Friend's erythroleukemia cells and synthesis of immunoglobulin gamma- and kappa-chain RNA, total RNA, 5S RNA, and tRNA in mouse myeloma cells (MPC-11) was inhibited by gamma-irradiation. For all RNA species, synthesis decreased nearly exponentially as a function of radiation dose, whereas RNA size distributions, turnover rates, and specific activities of radioactively labeled RNA were affected only insignificantly. D37 values for the loss of synthesis of various RNA species correspond to target sizes ranging from 21,000 to 53,000 kd, or 30-80 kbp of DNA. These target sizes are several-fold larger than the structural genes in question; however, they correspond well with the size of DNA loops, or "domains" constrained by the nuclear matrix. The data suggest that the eukaryotic transcription unit is the torsionally constrained chromatin loop, transcription of which may be inactivated, or significantly reduced by a DNA single-strand break.
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PMID:Structure of transcriptionally active chromatin: radiological evidence for requirement of torsionally constrained DNA. 247 70

A new and highly selective procedure is described for the rapid selection and cloning of antibody-secreting hybridomas with antigen-coated magnetic beads. Immune splenocytes were fused to Sp2 myeloma cells with a PEG/DMSO mixture. Cells were cultured in HAT and screened for the presence of specific antibody after 7-10 days. Hybridomas from the positive colonies were mixed with antigen-coated magnetic polymer beads and antigen-specific cells separated on a magnet. Cloning was carried out directly by limiting dilution with the magnetic beads still bound on the cells. No obvious toxic effects were observed. The antibodies established by this technique were of a high affinity (greater than 10(9) l/mol) and were generated in 50% of the usual process time. The procedure described here should greatly facilitate the process of obtaining hybridomas and expand the range of monoclonal antibodies available.
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PMID:A new and rapid method for the selection and cloning of antigen-specific hybridomas with magnetic microspheres. 248 Sep 79

Amyloid is a beta-pleated fibrillar protein principally constituted of light chains of immunoglobulins (kappa or lambda) in primary or myeloma-associated amyloidosis, of AA proteins in secondary amyloidosis and familial. Mediterranean fever, and of variants of prealbumin - now called transthyretin - in senile amyloidosis and in familial polyneuropathies. Other identified amyloidogenic proteins involve APUD protein derivatives (calcitonin), beta 2 microglobulin in chronic hemodialysis-related amyloidosis and beta protein in Alzheimer disease. After a short review of experimental findings and theories concerning the pathogenesis of amyloid deposition, the clinical aspects of amyloidosis are discussed stressing their great diversity. The diagnostic approach is also examined, with particular emphasis on rectal and kidney biopsy and subcutaneous adipose tissue aspirates. Finally, some comments on the treatment of amyloidosis (role of colchicine and DMSO) are made.
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PMID:Amyloid proteins and amyloidoses: complexity updated. 266 33

Most mammalian cells respond to brief incubation at elevated temperatures by enhanced or new synthesis of a set of heat-shock proteins (hsp). In mouse cells, as determined by SDS--one-dimensional gel electrophoresis, the most prominent hsps have molecular masses of approximately 89,000, 70,000, and 68,000 Da. When the heat-shock response of the mouse erythroleukemia cell line D1B, or two other DBA/2 cell lines (707C1 and 745C2), was examined by [35S]methionine labelling, following heat shocks of 10 min at 42 or 44 degrees C, or 1 h at 45 degrees C, no protein band corresponding to hsp 68 was observed. However, the synthesis of both hsp 89 and hsp 70 was enhanced. Northern blot analysis of cytoplasmic RNA extracted from control and stressed cells indicated that hsp 68 mRNA was absent, even after stresses of up to 1 h at 45 degrees C. Differentiation induced by dimethyl sulphoxide (DMSO) (monitored by the induction of globin synthesis) had no effect on hsp 68 expression in D1B cells; also, hsp 68 could not be induced at various stages of differentiation (0-72 h). Southern blot analysis showed that all three hsp-68 genes were present and not rearranged, and apparently did not carry any deletion in their 5' ends. To determine whether methylation could be involved in maintaining the genes in their silent state, we treated cells with 10 microM 5-azacytidine for 48 h. No hsp 68 expression was observed following such treatment in either undifferentiated or DMSO-induced differentiated D1B cells. Furthermore, Southern blot analysis of MspI/HpaII-digested genomic D1B DNA did not display any differences in methylation patterns around the promoter region of the probed gene compared with control cells, indicating that methylation is not involved in hsp-68 repression. When chimeric plasmids carrying the bacterial chloramphenicol acetyl transferase gene under regulation of the mouse hsp-68 or Drosophila hsp-70 promoters were transfected into D1B cells, minimal (2-fold) or no induction was observed, in contrast with the 60-fold induction seen in a control myeloma cell line. These results suggest a trans-acting mechanism of hsp-68 repression in erythroleukemia cells.
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PMID:The major heat-shock protein hsp 68 is not induced by stress in mouse erythroleukemia cell lines. 317 16

Four human B cell lines with a mature phenotype (immunoglobulin secretion and expression of membrane markers associated with maturation) were cultured in the presence of phorbol ester (PMA), dimethyl sulphoxide (DMSO) and two conditioned media. PMA and DMSO led to changes in phenotype which suggested the cells were being activated, whilst the conditioned media resulted in increased immunoglobulin secretion, accompanied by phenotypic changes more consistent with maturation towards the plasma cell stage. The four cell lines, which had different origins (EBV-transformed normal B cell, Burkitt's lymphoma, prolymphocytic leukaemia and multiple myeloma) responded differently to the culture stimuli. These differences suggest that the changes associated with transformation affect the way in which these cells respond to agents which stimulate activation and maturation.
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PMID:Responses of 'mature' human B lymphocyte lines to inducers of maturation and activation. 349

Murine erythropoiesis represents a favourable system in which to investigate the coordinate regulation of gene expression due to the availability of erythroid precursor cells at various stages of differentiation. In this report, we investigate the biosynthesis and cell specificity of two characteristic murine RBC membrane glycoproteins that resemble the human RBC glycophorins: a major component of apparent molecular mass 31 kD (glycophorin MA) and a minor 46 kD component (glycophorin MB). Both glycophorins bind to wheat germ lectin and share a common protein antigenic determinant recognised by a monoclonal antibody (GP 29.4), but they differ significantly in their carbohydrate components: whilst both glycophorins contain mainly O-linked sugars, glycophorin MA contains in addition at least one N-linked carbohydrate residue and terminal sialic acid residues. Pulse-chase in vivo labelling experiments combined with in vitro translations of glycophorin mRNAs show that the initial precursor to glycophorin MA is a 24.5 kD polypeptide which is subsequently processed and glycosylated to give the mature 31 kD molecule via a 21.5 kD polypeptide intermediate. Both glycophorins MA and MB are synthesized most actively in early to mid erythroblasts (e.g., Friend cells induced for 3 days with DMSO) but their synthesis is considerably reduced by the reticulocyte stage. However, of the other cell types tested (neuroblastoma, myeloma, fibroblasts, epithelial cells and T-lymphoma cells), none synthesizes glycophorin with the possible exception of a low level in thymus tissue. Thus murine glycophorins, in contrast to the RBC cytoskeletal proteins (spectrin, ankyrin, band 4.1) seem to be restricted to the erythroid cell lineage like human glycophorin.
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PMID:The cell specificity and biosynthesis of mouse glycophorins studied with monoclonal antibodies. 385 53

The objective of this study was to review (1) the factors that have been linked to prediction of clinical outcome and survival in amyloidosis and (2) the available studies on the therapy for localized and systemic forms of amyloidosis. We made a retrospective review of the relevant literature on treatment and prognosis in localized and systemic amyloidosis dating back to 1975. The most important prognostic factors in amyloidosis are the presence of congestive heart failure, beta 2-microglobulin, and whether peripheral neuropathy dominates the presentation. The presence of a monoclonal light chain in serum or urine, multiple myeloma, and hepatic involvement are also important adverse factors. Colchicine is beneficial in treating familial Mediterranean fever and may play a role in managing secondary amyloidosis in inflammatory bowel disease. Chlorambucil is particularly useful in juvenile rheumatoid arthritis with amyloidosis. Dimethyl sulfoxide provides benefit in bladder and lichen amyloidosis. A trial of alkylating agent-based chemotherapy is reasonable in symptomatic primary systemic amyloidosis. Advances have been made in the treatment of amyloidosis and include chemotherapy, dialysis, transplantation, and improved supportive care. Definite disease regressions with long-term survival (> 10 years) are seen. Unfortunately, alternatives still need to be developed: Of 859 patients with primary systemic amyloidosis seen at the Mayo Clinic from 1982 to 1992, the median survival was 2.1 years.
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PMID:Amyloidosis: prognosis and treatment. 783 54

A 57-year-old man with IgG multiple myeloma developed pulmonary infiltration caused by pulmonary amyloidosis, for which continuous transdermal dimethyl sulfoxide (DMSO) treatment was given. After 8 weeks from the start of DMSO treatment, a dramatic reduction of pulmonary infiltration as determined by chest roentgenogram was observed, and arterial blood gas levels were improved. No serious side effect of DMSO was encountered. We conclude that a therapeutic trial with transdermal DMSO administration brought about a marked regression of the pulmonary infiltrate.
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PMID:A case of pulmonary amyloidosis associated with multiple myeloma successfully treated with dimethyl sulfoxide. 802 51

Fusions were made between thymidine kinase deficient (TK-) Friend Cells inducible for hemoglobin production, and immunoglobulin-producing, hypoxanthine-guanine phosphoribosyltransferase-deficient (HGPRT-) myeloma cells. Hybrids were selected in hypoxanthine-aminopterin-thymidine (HAT) and identified by isozyme analysis and chromosome counts. All hybrids resembled the myeloma cell line in mode of growth and were immunoglobulin secretors. All hybrids did not express hemoglobin and were uninducible for hemoglobin production with dimethyl sulfoxide (DMSO). Hybridization of genomic globin DNA probes with hybrid-derived nuclear and cytoplasmic mRNAs blotted to nitrocellulose filter indicated that lack of expression of the globin genes in the hybrids was due to lack of transcription.
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PMID:Transcriptional control of the expression of mouse globin genes in myeloma x erythroleukemia cell hybrids. 973 46


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