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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human-human hybridomas producing monoclonal antibodies (MoAbs) specific for five major serotypes of Pseudomonas aeruginosa were developed by fusing P. aeruginosa primed and Epstein-Barr virus-transformed cells with human myeloma P109 cells using polyethyleneglycol. The MoAbs which were produced by the hybridomas were protective against lethal intraperitoneal (i.p.) challenge of P. aeruginosa (10 LD50) in mice. The 50% effective dose (ED50) values of MoAbs ranged from 0.5 to 10.2 micrograms/mouse and were 26 to 240 times more protective than a commercial human IgG preparation. MoAb administration to mice promoted bacterial clearance in peritoneal cavity, and prevented bacterial invasion into blood in the way of increasing both the number of bacteria trapped by a macrophage and the ratio of macrophages that trapped bacteria. MoAbs also showed protective effects against lethal infection of P. aeruginosa in the mice which were decreased in polymorphonuclear cells (PMN) by cyclophosphamide (CY). All MoAbs showed serotype-specific binding to the clinical isolates of P. aeruginosa as well as to the immunized strains. The hybridoma cell lines maintained their capacity to produce MoAb continuously for more than 12 months and produced 10 to 60 micrograms MoAbs per 10(6) cells in 24 hr. It is practicable to use these cell lines for large-scale production of anti-P. aeruginosa MoAbs and such MoAbs must be useful for the therapeutics of patients with P. aeruginosa infection.
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PMID:Establishment of stable cell lines producing anti-Pseudomonas aeruginosa monoclonal antibodies and their protective effects for the infection in mice. 128 5

In a patient with multiple myeloma, numerous indurated, subcutaneous nodules and pyomyositis due to Pseudomonas aeruginosa were noted. These lesions resolved with ciprofloxacin plus ceftazidime therapy without surgical incision and drainage. Despite another course of cancer chemotherapy after total disappearance, there were no recurrences at the end of 3 months. Quinolones initially combined with other antipseudomonal beta-lactam agents may be the drugs of choice in the management of patients with subcutaneous nodules caused by P. aeruginosa.
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PMID:Subcutaneous nodules caused by Pseudomonas aeruginosa: healing without incision and drainage. 140 78

IL-6-PE4E is a recombinant protein consisting of interleukin-6 (IL-6) fused to a mutant form of Pseudomonas exotoxin in which four basic amino acids are changed to glutamate (PE4E). The chimeric toxin has been previously shown to specifically kill malignant hepatic, prostatic, epidermoid, and myeloma cell lines in vitro. To explore the possible clinical utility of IL-6-PE4E, particularly as an agent for ex vivo purging of marrow for autologous bone marrow transplantation (ABMT), we tested malignant cells from patients with multiple myeloma for sensitivity to this chimeric toxin. Ficoll-purified bone marrow cells were incubated with and without IL-6-toxin for 2 to 3 days. Eight of the 15 myeloma patients had cells that were sensitive to IL-6-toxin as measured by a decrease in the level of protein synthesis. Cells from five patients were very sensitive to IL-6-PE4E, with 50% inhibition of protein synthesis (ID50) achieved at or below 6 ng/mL (7 x 10(-11) mol/L). Cells from three additional patients showed moderate sensitivity, with ID50s between 30 and 140 ng/mL. The remaining seven samples showed little or no sensitivity, with ID50s greater than or equal to 400 ng/mL. Normal bone marrow cells or normal BFU-E and CFU-GM were resistant to the IL-6-toxin even at 1,000 ng/mL. Neither IL-6, IL-2-PE4E, nor an enzymatically deficient mutant of IL-6-PE4E was cytotoxic toward the myeloma cells, indicating that the cytotoxic effect of IL-6-PE4E required the adenosine diphosphate-ribosylation function as well as the specific ligand. Our data suggest that IL-6-toxin could be effective in ex vivo marrow purging in selected multiple myeloma patients who are candidates for ABMT, and that this toxin should also be investigated further for in vivo therapy.
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PMID:Interleukin-6 fused to a mutant form of Pseudomonas exotoxin kills malignant cells from patients with multiple myeloma. 155 71

Monoclonal antibodies against the elastase of Pseudomonas aeruginosa were produced from spleen cells of BALB/c mice primed with purified elastase of P. aeruginosa and P3-X63-Ag8-U1 myeloma cells. The six clones established generated antibodies which reacted with a 33,000-Da peptide and recognized four different elastase epitopes by a competitive binding enzyme-linked immunosorbent assay. The monoclonal antibodies designated as ELA-17 and ELA-42 that recognize two different epitopes reacted by dot-enzyme immunoassay and by Western immunoblotting with all clinical and International Antigen Typing Scheme strains of P. aeruginosa positive for elastase.
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PMID:Four epitopes of Pseudomonas aeruginosa elastase defined by monoclonal antibodies. 170 68

We reported the production of monoclonal antibodies (McAbs) against chorionic gonadotropin hormone (CG) receptor by fusing spleen cells of BALB/c mice which had been immunized by purified bacteria (Pseudomonas maltophilia) CG receptor with mouse myeloma line SP2/0. Four hybridoma cell lines secreting CG receptor McAbs were obtained (ED490 DG390, AB890 and GE590). The titers of specific antibodies of both mice ascites and culture supernatant were 10(-2)-10(-6) and 1-10(-2) respectively, by solid phase ELISA. Double-Immunodiffusion test showed that the McAb GE590 was IgG1, and the McAbs ED490, DG390 and AB890 were IgG2b Immunoprecipitation indicated that 125I-HCG could bind the HCG receptor which had reacted with McAbs ED490, AB890 and DG390, suggesting that they may recognize the receptor with different antigenic determinant. Interaction of McAb GE590 with the receptor showed that the increased concentration of GE590 was in inverse proportion to the amount of 125I-HCG binding receptor, indicating that both the McAb and 125I-HCG could recognize a common site of receptor and that increased concentration of McAb GE590 may induce some change in conformation and structure of the receptor. Our study suggested that these McAbs may be used for studying structure of CG receptor.
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PMID:[Preparation of monoclonal antibodies against chorionic gonadotropin receptor and study of its characteristics]. 181 14

Three stable hybridoma cell lines, IN-2A8, IN-5D6, and ZI-3A8, that secrete human monoclonal antibodies (MAbs) specific for b-type flagella of Pseudomonas aeruginosa were established by fusing peripheral blood lymphocytes from healthy volunteers with murine myeloma P3X63-Ag8.653 cells. The immunoglobulin M MAbs reacted specifically with flagellin (Mr, 52,000) by Western blotting (immunoblotting) analysis and bound specifically to clinical isolates belonging to Homma serotypes A, B, H, I, and M at frequencies of 58, 50, 46, 30, and 35%, respectively, but did not bind to any serotype E or G isolates. Overall, the MAbs bound to 31% of the clinical isolates. MAb IN-2A8 strongly protected burned mice challenged with P. aeruginosa bearing b-type flagella from death following parenteral administration of 0.1 microgram per mouse. This MAb also inhibited P. aeruginosa colony spreading in soft agar at a concentration of more than 1 microgram/ml but only slightly enhanced opsonophagocytosis by human polymorphonuclear leukocytes. A line of evidence suggests that the potent in vivo activity of MAb IN-2A8 in the burned-mouse model is likely to be caused by its inhibition of bacterial motility after binding to flagella.
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PMID:Inhibitory activity on bacterial motility and in vivo protective activity of human monoclonal antibodies against flagella of Pseudomonas aeruginosa. 189 8

BALB/c mice were immunized intraperitoneally with outer envelopes of serogroup icterohaemorrhagiae lai serovar strain 017 leptospires. Monoclonal antibodies against outer envelopes (IgG, agglutinating titre 1:25,600) were produced by hybridoma technique. The monoclonal antibodies ascites (diluted 1:100) 1 ml administered intraperitoneally 1 hour before the intraperitoneal injection of 2 x 10(8) leptospires of strain 017 and the subsequent daily administration of McAb in similar doses for five days protected 80% of guinea pigs. Survival rates of three control groups which received physiological saline, ascites of BALB/c mouse myeloma cell lines SP2/0, and monoclonal antibodies against Pseudomonas aeruginosa in place of monoclonal antibodies against outer envelopes of strain 017 leptospires were 10%, 20% and 10% respectively. When killed 20 days after challenge, guinea pigs of experiment group were normal at autopsy. Old pulmonary haemorrhage were present in the animals of three control groups. Passive immunoprotection experiments have demonstrated immunoprotection of monoclonal antibodies against outer envelopes of strain 017 leptospires. It will be valuable for separating protective antigen fraction of outer envelopes and studying new vaccine of leptospira.
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PMID:[Investigation on the immunoprotection of monoclonal antibodies against outer envelopes of serogroup Icterohaemorrhagiae serovar lai strain 017 leptospires]. 209 58

Human colostral IgA and myeloma proteins of both IgA1 and IgA2 subclasses were susceptible to cleavage by Pseudomonas aeruginosa elastase. Detailed analysis of the cleavage products of IgA myeloma proteins revealed complete degradation of Fab with no evidence of intact Fab fragments as intermediate cleavage products. In contrast, both IgA1 and IgA2 proteins were resistant to cleavage by alkaline protease from P. aeruginosa. The susceptibility of human IgA proteins to elastase suggests a mechanism by which P. aeruginosa might evade the potentially protective function of IgA by producing this enzyme.
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PMID:Degradation of IgA proteins by Pseudomonas aeruginosa elastase. 210 56

The chimeric toxin IL6-PE40, which is composed of interleukin 6 (IL6) fused to a mutant form of Pseudomonas exotoxin (PE) devoid of its native cell recognition domain, can kill myeloma and hepatoma cells which express high levels of IL6 receptors. To enhance the usefulness of IL6-PE40 on potential target cells, we have attempted to develop more potent IL6-PE derivatives. We have developed nine new IL6-PE derivatives and assessed their cytotoxicity on human myeloma cells. Two of these new forms, IL6-domain II-PE40 and IL6-PE664Glu were more toxic to myeloma cells bearing IL6 receptors than was IL6-PE40. These two chimeric toxins were compared with IL6-PE40 for cytotoxicity toward a variety of tumor cell lines. We found that most tumor cell lines which are sensitive to IL6-PE40 are more sensitive to IL6-domain II-PE40 and IL6-PE664Glu. Cells with as few as 200-600 IL6 receptors/cell could be killed. The specificity of these chimeric toxins was shown through competition with recombinant IL6. Toxicity studies in mice demonstrated that the two new molecules had an LD50 of 10-20 micrograms/mouse. This compares to an IL6-PE40 LD50 of 20 micrograms/mouse. The new IL6-toxins could be detected in the serum up to 8 h after intraperitoneal administration with a peak at 1 h. These data suggest that IL6-domain II-PE40 and IL6-PE664Glu may be more useful than IL6-PE40 in killing IL6 receptor-bearing tumor cells in animals.
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PMID:Cytotoxicity of IL6-PE40 and derivatives on tumor cells expressing a range of interleukin 6 receptor levels. 211 4

IL6-PE40 is a chimeric toxin composed of human interleukin-6 (IL6) linked by a peptide bond to PE40, a form of Pseudomonas exotoxin (PE) devoid of its cell recognition domain. To identify cancer cell lines with high numbers of IL6 receptors and to assess the usefulness of IL6-PE40 as a possible anticancer agent, we evaluated the toxicity of IL6-PE40 on a variety of tumor cell lines and demonstrated that certain human myeloma and hepatoma cell lines were particularly sensitive. IL6 binding to selected hepatoma and myeloma cell lines were determined by using [125I]IL6. IL6 receptor mRNA levels were measured by polymerase chain reactions. When comparisons were made among different hepatoma cell lines, the sensitivity to IL6-PE40 correlated with the number of IL6 receptors. However, the hepatoma line PLC/PRF/5, which contains 2,300 IL6 receptors, was more sensitive to IL6-PE40 (amount of protein required to inhibit protein synthesis by 50% was 5 ng/ml) than both the myeloma cell lines U266 and H929 (for both cell lines, the 50% inhibitory dose was 8 ng/ml), which contain 15,500 and 16,500 IL6 receptors, respectively. RNA analysis confirmed that the sensitivity of these cells to IL6-PE40 and the amount of IL6 receptor RNA detected did not correlate. These data suggest that factors in addition to the number of IL6-binding sites contribute to the sensitivity of cells to IL6-PE40.
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PMID:Cell-specific toxicity of a chimeric protein composed of interleukin-6 and Pseudomonas exotoxin (IL6-PE40) on tumor cells. 216 May 79


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