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)

To investigate the structure-function relationship in tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), four hybrid sequences were amplified and overexpressed in a mouse myeloma cell line. The following constructs were made starting from cDNA encoding human t-PA and u-PA: (i) a hybrid in which amino acids (AA) 1-262 of the A-chain of t-PA is fused to AA 139-411 of the B-chain of u-PA; (ii) a hybrid in which the kringle 2 region of t-PA (AA 173-262) is inserted between amino acids 130 and 139 of u-PA; (iii) hybrid #2 having amino acids 1 to 10 deleted and replaced by the finger region of t-PA (AA 1-50); and (iv) a chimera in which the finger region of t-PA is followed by amino acids 10-411 of u-PA and where the lysine residues at positions 135 and 136 of u-PA are replaced by glutamines. These four hybrids were efficiently secreted into the culture medium as single-chain polypeptides of the expected molecular weights and had fully functional catalytic activity. Replacement of the A-chain of u-PA by that of t-PA leads to increased fibrin binding, whereas additions of finger and kringle domains do not. These data suggest that structural domains in serine proteases may not fold and/or function autonomously.
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PMID:Production in eukaryotic cells and characterization of four hybrids of tissue-type and urokinase-type plasminogen activators. 250 71

A radioimmunoassay for glycated serum protein (GSP) was developed using monoclonal antibody to glucitollysine and polystyrene beads coated with Coomassie-Brilliant-Blue (CBB) as adsorbent for serum protein. The monoclonal antibody was raised by immunizing BALB/c mice with reduced glycated LDL and fusing their spleen cells with mouse myeloma cells. CBB-coated polystyrene beads were introduced to absorb a constant amount of serum protein. The protein adsorbed on the CBB-coated beads was reduced by NaHB4, and after treatment with radiolabeled antibody, the radioactivity of each bead was counted with an automatic gamma-counter. The standard glycated protein used was reduced glycated human serum albumin, in which 8 of 59 lysine residues were glycated. The intra- and interassay coefficients of variation of GSP were 4.8-6.5% and 1.6-6.0%, respectively. The GSP level of diabetic patients was significantly higher than that of normal controls (1.97 +/- 1.23 vs. 0.47 +/- 0.21 nmol/mg-protein; mean +/- SD, p less than 0.001). The GSP levels of patients with insulin-dependent and non-insulin-dependent diabetes mellitus were 3.03 +/- 1.05 and 1.51 +/- 1.00 nmol/mg-protein, respectively. A good correlation was found between the levels of GSP and hemoglobin A1c (HbA1c) (r = 0.85, p less than 0.001). In patients admitted to the hospital for diabetes education and glycemic control, the GSP level decreased 43 +/- 12% with the decrease in the fasting plasma glucose level (39 +/- 13%) and the mean daily plasma glucose level (MPG, 47 +/- 15%) in a four week period after admission, whereas the HbA1c level decreased only 13 +/- 6% during this period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Radioimmunoassay of glycated serum protein using monoclonal antibody to glucitollysine and coomassie-brilliant-blue-coated polystyrene beads. 251 33

Ornithine decarboxylase (ODC), a key enzyme in the biosynthesis of polyamines in mammalian cells is characterized by an extremely short half-life. In the present study, ODC degradation was investigated in 653-1 mouse myeloma cells that overproduce ODC and in ts85 cells that are thermosensitive for conjunction of ubiquitin to target proteins. Addition of 2-deoxyglucose and dinitrophenol (agents that efficiently deplete cellular ATP) to the growth medium of these cells inhibited ODC degradation. In contrast, chloroquine and leupeptin, inhibitors of intralysosomal proteolysis, did not affect ODC degradation. Shifting ts85 cells to 42 degrees C (a non-permissive temperature that inhibited conjugation of ubiquitin to target proteins) did not prevent ODC degradation. The ATP-dependent degradation of ODC in 653-1 cells was inhibited substantially by N alpha-tosyl-L-lysine chloromethane (TosPheMeCl), iodoacetamide and o-phenanthroline. These results suggest that ODC degradation occurs via a non-lysosomal. ATP-requiring and ubiquitin-independent cellular proteolytic mechanism, and that serine proteases and enzymes containing sulphydryl groups and metalloenzyme(s) may be involved in this process.
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PMID:Degradation of ornithine decarboxylase in mammalian cells is ATP dependent but ubiquitin independent. 255 93

The immunoglobulin Kol was the first intact antibody molecule which was characterized by high-resolution X-ray crystallography. Furthermore the complete amino-acid sequence of the heavy (H)-chain is known. Here we report the complete amino-acid sequence of the light (L)-chain of the monoclonal immunoglobulin Kol (IgG1). The polypeptide has an Mr of 22,781, consists of 216 amino acids and due to its structure is of the lambda-type. With the characteristic amino acids threonine, asparagine, threonine, glycine and lysine in positions 101, 114, 116, 154, and 165, respectively the Kol L-chain is of the Mcg isotype. With the proteins Mcg, Mot, Bur, Loc and Mem six myeloma-derived amino-acid sequences of the same isotype are known. The amino-acid sequence of the N-terminal variable part is characteristic of subgroup 1. This contribution completes the primary structure of IgG1 Kol.
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PMID:[The primary structure of crystallizable monoclonal immunoglobulin IgG1 Kol. II. Amino acid sequence of the L-chain, gamma-type, subgroup I]. 271 5

The urinary light chain dimer and serum monoclonal IgG1 protein from a patient (Mcg) with multiple myeloma and amyloidosis were systematically tested for their binding activities to peptides presented on solid supports. The system was validated using a series of enkephalins, beta-casomorphins and DNP-lysine derivatives which were known to complex with the dimer. Sets of peptide ligands binding to the proteins were constructed by incremental additions of amino acid residues to minimal binding units [Geysen et al., J. Immun. Meth. 102, 259-274 (1987)]. Both the amino acid sequences and the combinations of optical isomers were optimized at each stage of the syntheses. Binding could be demonstrated for ligands ranging in size from a tethered single amino acid to pentapeptides. At the dipeptide levels, the dimer and the IgG1 protein showed different preferences (Hp versus qf, where lower case letters designate D-amino acid residues). However, in a tetrapeptide ligand (qfHp) for the dimer, both of these initial preferences had converged. With few exceptions, the IgG1 molecule showed binding activity for the ligands developed for the dimer. Two sets of selected peptides, one based on Hp and the other on mW, were synthesized for diffusion into crystals of the dimer. X-ray analyses showed that these peptides bound exclusively in the main binding cavity between the "variable" domains of the dimer. As predicted from the ELISA results with tethered ligands, the relative occupancies in the crystals followed the order of tetrapeptide greater than tripeptide much greater than dipeptide. The crystallographic studies confirmed that peptides with very different sequences can bind in the same cavity.
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PMID:Similar binding properties of peptide ligands for a human immunoglobulin and its light chain dimer. 277 86

Hybridomas secreting monoclonal antibodies specific for nonenzymatically glycated albumin were produced by fusion of SP2/0 myeloma cells with spleen cells from BALB/c mice immunized with unreduced nonenzymatically glycated albumin prepared from human plasma. Wells containing hybridomas secreting antibodies against glycoalbumin were identified by binding, in an enzyme-linked immunosorbent assay, to glycoalbumin isolated from human plasma or to albumin that had been glycated in vitro. The colony designated A717, which secreted antibodies discriminating between glycated versus unglycated albumin, was cloned four times by limiting dilution and used for further study, performed with monoclonal antibody purified from mouse ascites fluid. Specificity of A717 was demonstrated by immunoblotting and by ELISA, wherein the monoclonal antibody reacted preferentially with glycated albumin but insignificantly with unglycated albumin. Immunoblotting of human plasma with A717 on nitrocellulose yielded a single band, the electrophoretic mobility of which corresponded with that of authentic glycated albumin, indicating site specificity for glycated epitopes residing in albumin but not in other nonenzymatically glycated serum proteins. A717 differs from other antibodies raised against glycated albumin and other proteins, which recognize glycated residues only after reductive conversion to glucitol-lysine and which do not discriminate between different glycated proteins. Thus, this report describes the establishment of the first hybridoma secreting monoclonal antibody raised against unreduced glycated albumin, which is the physiologic form occurring in vivo, and for the epitope when it resides in albumin but not other proteins.
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PMID:Production and characterization of monoclonal antibodies against human glycoalbumin. 291 57

Several animal studies have demonstrated that pain is modulated by spinal mechanisms involving prostaglandins and that acetylsalicylic acid (ASA) administered intrathecally has an analgesic effect. We report our experience of this treatment in 60 patients with proven and advanced cancer. An isobaric solution of lysine acetylsalicylate was administered by lumbar puncture in doses ranging from 120 to 720 mg of ASA. The results were evaluated using the habitual criteria: scoring system, behaviour, consumption of analgesic drugs. In this trial the method proved astonishingly effective (78% of the cases). Analgesia was strong, almost immediate and without influence on motricity. No thermic or neurovegetative changes were noted. The effect of one injection lasted from 3 weeks to 1 month on average; it was reproduced and often more prolonged after a repeat injection. Pain associated with bone metastases seems to constitute the best indication, notably in breast and lung cancer and in myeloma. Visceral (pancreas) or neural pain requires higher doses to respond. Failures (22%) were due to such factors as insufficient dosage at the very beginning of our experience or severe depressive syndrome. The perineal and sphincteral pain of rectal cancer often resists treatment. This simple, inexpensive and very effective method with no other complication than a frequent tendency to fatigue should rank among other analgesic measures in cancer. The lack of respiratory depression is a major advantage over catheter spinal opiate analgesia. We consider that its main indications are pain associated with osteolytic metastases of adenocarcinomas, and myelomas. Owing to the absence of formal toxicological data, its use must be limited to cancer pain and to patients with a life expectancy of less than 2 years.
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PMID:[Chronic refractory pain in cancer patients. Value of the spinal injection of lysine acetylsalicylate. 60 cases]. 295 75

Monoclonal antibodies to chicken riboflavin carrier protein have been produced by fusing immunized mouse spleen cells with myeloma SP2/O-Ag 14. The three different monoclonal antibodies specifically bound 125I-labelled chicken riboflavin carrier protein and were characterized with respect to their affinities to bind the antigen, subclass and isotype. These three monoclonal antibodies had similar affinities for holo-, apo- and SDS-denatured riboflavin carrier protein but were unable to recognize the reduced and carboxymethylated protein indicating that they were directed to specific conformational epitopes on the native avian protein. Succinylation of the vitamin carrier protein while still retaining flavin binding characteristics totally abolished the cross-reactivity with all the three monoclonal antibodies indicating that lysine residues were involved at the antigenic sites of the protein. This shows that the antigenic loci may be distinct from the flavin binding sites in the protein. All three antibodies were able to recognize riboflavin carrier protein present in the sera of pregnant rats, monkeys and humans indicating that the epitopes to which they are directed are conserved throughout evolution. These antibodies can therefore be effectively used for radioimmunoassays and further studies on the functional aspects of this protein in higher mammals.
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PMID:Immunological characterization of riboflavin carrier proteins using monoclonal antibodies. 311 15

Balb/c mice were immunized with affinity purified Ro(SS-A) from human origin in order to allow the preparation of monoclonal anti-Ro(SS-A) antibodies. After fusion of mouse myeloma cells (line Sp2/0 A914) with spleen cells from one of these mice, anti-Ro(SS-A) monoclonals were not obtained, but, instead, two IgM producing hybridomas reactive with histone H1 and one with histone H2B. The specificity of the anti-H1 monoclonals was investigated by means of immunoblotting of very lysine-rich histone variants from mouse which were separated by two-dimensional gelelectrophoresis. One of them (CLB-ANA 105) has H1(0) specificity with respect to the histone variants of mouse and man, but recognizes H5 as well as H1 from Xenopus laevis. Another monoclonal (CLB-ANA 108) reacts with the variant H1c from mouse, exclusively. From the way these monoclonals were produced, we postulate that they were not the result of immunization, but comprise specificities of naturally occurring autoantibodies.
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PMID:Monoclonal autoantibodies recognizing histone variants. 341 May 13

Microimmunofluorescence using Terasaki plates and a direct plate freezing method were combined for effective screening of hybridoma supernatants. The microplates, in which the fused cells (myeloma and spleen cells) were cultured and hybridoma colonies were growing, were frozen after harvest of supernatants and saved at -80 C for several weeks without affecting antibody production ability of hybridomas. Microimmunofluorescence was performed in Terasaki plates on which target cells were attached by poly-L-lysine and glutaraldehyde or by short time culture of the cells in Terasaki plates. The direct plate freezing method prevented initial hybridoma cells from changes or disappearance of antibody productions during screening of hybridoma supernatants; the microimmunofluorescence staining method permits fast and detailed estimation of specificity of antibodies of hybridomas by saving time and minimal consumption of supernatant for checking. The combination of these two methods is a powerful tool for obtaining desired monoclonal antibodies.
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PMID:Microimmunofluorescence using Terasaki plates and direct plate freezing method--rapid and reliable screening system of hybridomas. 354 26


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