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 expression of HLA class II molecules is mainly regulated transcriptionally and this regulation is thought to play an important role to the control of immune response. In this report, we have studied the effect of adenylate cyclase activator, forskolin, to the expression of HLA class II molecules on the cell surface of an human multiple myeloma cell line, RPMI8226. On the northern blot analysis and FACS analysis, we have revealed that forskolin upregulated the expression of mRNAs of DQB and DRB gene and their products on its surface. On the sequence analysis of upstream of HLA-DQB gene, we have identified not only Y-,X-, W-box, which were thought to regulatory region of truncated gene, but also cAMP responsible element (CRE) like regulatory region, which located upstream of W-box. On the gel retardation assay, when we used DNA probes that were specific for CRE like region and Y-box, we have found newly detectable bands, which appeared by forskolin treatment. These data suggest that forskolin upregulates HLA class II molecules by means of the interaction between CRE and cAMP responsible element binding protein (CREB).
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PMID:[Analysis of the regulation of HLA class II genes by forskolin]. 132 79

The human spermidine synthase (EC 2.5.1.16) gene was isolated from a genomic library constructed with DNA obtained from a human immunoglobulin G (IgG) myeloma cell line. Subsequent sequence analyses revealed that the gene comprised of 5,818 nucleotides from the cap site to the last A of the putative polyadenylation signal with 8 exons and 7 intervening sequences. The 5'-flanking region of the gene was extremely GC rich, lacking any TATA box but containing CCAAT consensus sequences. No perfect consensus sequence for the cAMP-responsive element for the AP-1 binding site was found, yet the gene contained seven AP-2 binding site consensus sequences. The putative polyadenylation signal was an unusual AATACA instead of AATAAA. Polymerase chain reaction analysis with DNA obtained from human x hamster somatic cell hybrids indicated that human spermidine synthase genomic sequences segregate with human chromosome 1. Transfection of the genomic clone into Chinese hamster ovary cells displaying a low endogenous spermidine synthase activity revealed that the gene was transiently expressed and hence in all likelihood represents a functional gene.
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PMID:Human spermidine synthase gene: structure and chromosomal localization. 206 20

Mobilization of sequestered intracellular Ca2+ with EGTA or Ca2+ ionophores severely depresses rates of translational initiation in various mammalian cell types including C6 glial, GH3 pituitary and P3X63Ag8 myeloma cells. Within 2-3 h of continuous exposure to either chelator or ionophore, cells adapt or accommodate such that their rates of amino acid incorporation are restored to 40-70% of those of untreated controls. In GH3 and P3X63Ag8 cells, treatment with either a phorbol ester or a cAMP-elevating agent was required to obtain maximal degrees of accommodation of translational initiation. Following the development of accommodation, cells restored with optimal Ca2+ exhibited rates of amino acid incorporation identical with those of nontreated controls but remained resistance to inhibition on subsequent challenge with EGTA or ionophore. Development of translational tolerance to agents depleting Ca2+ stores did not involve alterations in cellular capacity or affinity for the cation. Invariably, the development of tolerance was preceded by transcriptionally dependent, preferential synthesis of the reticuloplasmin GRP78/BiP. In Ca2(+)-deprived GH3 cells, the synthesis of GRP78 was promoted by phorbol ester and cAMP with the extent of induction correlating directly with the degree of translational tolerance to ionophore. Cells pretreated with dithiothreitol, an alternate inducer of GRP78, also became tolerant to translational inhibition by Ca2+ ionophore or EGTA. Amino acid incorporation in nonsecreting NS-1-cloned myeloma cells, which constitutively express high levels of GRP78 and its mRNA, resisted inhibition by EGTA, ionophore, and dithiothreitol. Antisense oligodeoxynucleotides directed against GRP78 mRNA reduced amino acid incorporation in tolerant, but not in non-tolerant, preparations. These results predicate the existence of a mechanism whereby mammalian cells are capable of rapidly developing translational cross-tolerance to either depletion of sequestered Ca2+ or a reducing environment. A role for nascent GRP78 is strongly implicated in this accommodation mechanism.
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PMID:Accommodation of protein synthesis to chronic deprivation of intracellular sequestered calcium. A putative role for GRP78. 212 77

Previous studies have shown that human ornithine decarboxylase (ODC)-encoding sequences map to two chromosome regions: 2pter-p23 and 7cen-qter. In the present work we have cloned the expressed human ODC gene from a genomic library of myeloma cells that overproduce ODC protein due to selective gene amplification and determined its entire nucleotide sequence. The gene comprises 12 exons and 11 introns and spans about 8 kb of chromosome 2 DNA. The organization of the human gene is very similar to that of the mouse and rat, with the major difference being the presence of longer intronic sequences in the human gene. Some of these differences can be accounted for by the insertion of four Alu sequences in the human gene. Several potential regulatory elements are present in the promoter region and in 5'-proximal introns, including a TATA box; GC boses; AP-1-, AP-2- and NF-1-binding sites; and a cAMP-responsive element. The 5'-untranslated sequence of ODC mRNA is extremely GC-rich, and computer predictions suggest a very stable secondary structure for this region, with an overall free energy of formation of -225.4 kcal/mol. In addition to the active ODC gene on chromosome 2, ODC gene-related sequences were isolated from human chromosome 7-specific libraries and shown to represent a processed ODC pseudogene.
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PMID:Human ornithine decarboxylase-encoding loci: nucleotide sequence of the expressed gene and characterization of a pseudogene. 222 39

Using the whole-cell variation of the patch-clamp technique, we have demonstrated that retinoic acid (RA) blocks Ca channels and inhibits cell proliferation in a mouse hybridoma cell line (MHY206) derived from a fusion of murine myeloma and splenic B cells. In 25 mM external Ca, and with an Na internal solution containing aspartate, cAMP, and Mg-ATP, inward currents were activated in these cells from holding potentials more negative than -70 mV, peaked at voltage steps up to -20 mV, and were voltage-inactivated within the 125-msec duration of the pulse. With more positive pulses, outward current carried by Na ions permeating through the Ca channels were seen. Application of RA blocked both inward and outward current through the Ca channels in a dose-dependent manner, with 50% block at a concentration of around 5 x 10(-5) M. Proliferation was blocked by 75% at that concentration, and the same relation between the reduction in current and proliferation was seen throughout the concentration range. A similar reduction of Ca currents and proliferation was demonstrated with octanol, a long-chain alcohol that has recently been reported to block Ca channels. These results suggest a role for Ca channels in the proliferation of MHY206 cells and implicate blockage of these channels as contributing to the antiproliferative activity of RA.
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PMID:Retinoic acid inhibits Ca2+ currents and cell proliferation in a B-lymphocyte cell line. 245 24

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

Impaired platelet aggregation, normal shape change, and agglutination and normal ATP secretion and thromboxane synthesis in response to high concentrations of thrombin or arachidonic acid were found in a patient with multiple myeloma and hemorrhagic tendency. The purified IgG1 kappa or its F(ab1)2 fragments induced similar changes when added in vitro to platelet-rich plasma from normal subjects. In addition, the paraprotein inhibited adhesion to glass microbeads, fibrin clot retraction, and binding of radiolabeled fibrinogen or von Willebrand factor to platelets exposed to thrombin or arachidonic acid without affecting intraplatelet levels of cAMP. The radiolabeled para-protein bound to an average of 35,000 sites on normal platelets but it bound to less than 2,000 sites on the platelets from a patient with Glanzmann's thrombasthenia. Immunoprecipitation studies showed that the platelet antigen identified by the paraprotein was the glycoprotein IIIa. Furthermore, binding of radiolabeled prostaglandin E1 (PGE1) to resting platelets as well as binding of von Willebrand factor to platelets stimulated with ristocetin were entirely normal in the presence of patient's inhibitor. These studies indicate that bleeding occurring in dysproteinemia may be the result of a specific interaction of monoclonal paraproteins with platelets. In addition, our data support the concept that the interaction of fibrinogen and/or von Willebrand factor with the platelet glycoprotein IIb-IIIa complex is essential for effective hemostasis.
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PMID:A myeloma paraprotein with specificity for platelet glycoprotein IIIa in a patient with a fatal bleeding disorder. 293 59

We have developed two types of hybridomas producing monoclonal antibodies to the turkey erythrocyte beta 1-adrenergic receptor in order to study the beta-adrenergic-cAMP system of epidermis. Splenic cells from BALB/c mice immunized with partially purified turkey erythrocyte beta 1-receptors were fused with mouse myeloma cell line SP2/0-Ag14. Five hybridomas of 17 positive cells producing antibodies which could precipitate soluble turkey erythrocyte beta 1-receptors were cloned by the limiting dilution method. The antibodies cross-reacted with beta 1- and beta 2-adrenergic receptors and stained epidermal basal cells with immunocytochemical techniques. Neither type of antibody interfered with the antagonist binding, i.e., all antibodies bound to sites other than the ligand binding site on the surface. One type of antibody inhibited epinephrine-stimulated adenylate cyclase activity in our "leaky" epidermal cell system. The data suggest that the antibody interferes with the coupling of the receptor to the regulatory protein.
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PMID:Monoclonal antibodies to the beta-adrenergic receptor: modulation of catecholamine-sensitive adenylate cyclase by the antibody. 301 55

The protein B of group B streptococci can bind in a nonimmune reaction to Ig of the IgG and IgM classes of various mammalian species (i.e., human, mouse, rabbit, and bovine). Protein B binding involves the Fc parts of both IgG and IgM molecules. Monoclonal or polyclonal IgG or IgM and the IgM-FC5 mu fragment of human myeloma protein combined with the protein B thereby inhibiting protein B-induced hemolysis in the CAMP reaction. The protein B/Ig complex can be dissociated with 1% Triton or guanidine-HCl (6 M). Mice infected intraperitoneally with sublethal doses of group B streptococci (GBS) and that received seven repeated intravenous injections of highly purified protein B during the first 9 h of infection developed fatal septicemia within 24 h with colony counts of up to 10(8) CFU/ml in the blood. Animals treated in the same way with either PBS or trypsinized protein B recovered. The protein B itself was not pathogenic when injected into healthy mice. Tissue sections of liver or spleen from mice infected with a lethal dose of GBS revealed the presence of protein B together with large numbers of cocci when stained by the peroxidase method using specific antibodies raised against purified protein B in the rabbit.
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PMID:Unspecific binding of group B streptococcal cocytolysin (CAMP factor) to immunoglobulins and its possible role in pathogenicity. 354 80

After confirming hypercalcemia by 3 successive measurements of the total plasma calcium corrected for a plasma protein concentration of 72 g/l, which excludes spurious hypercalcemia due to dehydration, the physician orientates the aetiological diagnosis bearing in mind that primary hyperparathyroidism PHPT is the cause of 85 p. 100 of all asymptomatic forms of hypercalcaemia whilst overt or occult malignancy is the main cause (60 p. 100) of symptomatic forms of hypercalcaemia with PHPT responsible for 20 p. 100 of cases. Other causes, including drug toxicity with Vit D, calcium, Vit A, lithium, thiazide and aluminium hydroxide, sarcoidosis, hyperthyroidism, Addison's disease, pheochromocytoma and familial endocrine disorders are much rarer. Nevertheless, these rarer causes must be excluded on the clinical history and examination followed by radiological (chest X ray, plain abdomen X ray, bone X rays) and simple biological tests. The latter and/or scans tests should also help in a rapid diagnosis of metastatic carcinoma and multiple myeloma, so that the major diagnostic problem is to distinguish primary HPT from occult malignancy. This problem is greatly facilitated by reliable assays of C terminal or medium PTH rather than renal CAMP which is increased in 80 p. 100 of occult malignancies. When PTH assays is unavailable or unreliable Dent's hydrocortisone suppression test may be useful as a fall in'serum calcium is associated with occult malignancy in 70 p. 100 of cases and non-suppression is associated with PHPT in 91 p. 100 of cases. Discriminant analysis of the usual biochemical parameters may be helpful in this differential diagnosis and is accurate in about 90 p. 100 of cases. However, the association of PHPT and malignancy is also possible and not fortuitous.
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PMID:[Stages of the etiological diagnosis of hypercalcemia]. 389 Jun 61


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