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)

A case of fatal pulmonary fibrosis and atypical epithelial proliferation (AEP) in a patient with multiple myeloma treated with melphalan is presented. Review of 10 other autopsied patients with myeloma treated with melphalan but no thoracic radiation, other cytotoxic agents, or highdose oxygen therapy revealed one other patient who died with extensive pulmonary fibrosis and AEP. Four other patients with AEP not associated with pneumonitis or fibrosis were also found, while no such changes were found in 11 autopsy controls or 11 patients with myeloma who did not receive cytotoxic agents. Melphalan should be added to the growing list of agents capable of causing severe fibrotic pulmonary reactions.
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PMID:Pulmonary histopathologic changes associated with melphalan therapy. 35 22

The physicochemical methods showed that in the blood serum of patients with different forms of malignant growth, including myeloma, there exists protein which cannot be detected by the same methods in the serum of healthy people. Using ion-exchange chromatography protein was isolated and characterized by some physicochemical and biological parameters. The protein is established to belong to immunoglobulins G but it does not represent the whole function in reactions with antisera, it reacts only against gamma-heavy chains. The sedimentation constant and molecular weight testify to this fact as well. Peculiarities of amino acidic composition, conformation and structure are typical of the protein. The characteristic immunoglobulin G has a unique property of activating glycolysis and inhibiting oxygen uptake as well as of removing the Paster reaction. The physicochemical and biological peculiarities features are peculiar not only to the whole molecule but also to Fab fragment of characteristic immunoglobulin G. By using immunosorbents it was possible to show that a part of characteristic protein is in the composition of the immune complexes. The results of the model experiments with rats on studying biosynthesis of proteins peculiar to the malignant growth give reasons to suggest that proteins peculiar to these processes are synthetized anew. A correlation is found between the processes of protein synthesis and changes in mRNA transcription. On the basis of the data presented a conclusion is drawn on community of the malignant growth at the level of biosynthesis and ejection into the blood bed the peculiar proteins--malignancy markers.
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PMID:[Immunoglobulin G peculiar to cancer]. 81 32

Six months after a pneumonectomy for myeloma, which had preoperatively been indistinguishable from bronchial carcinoma, a 50-year-old man presented with shortage of breath, cyanosis and episodes of syncope on standing or walking, symptoms which improved on lying down (platypnea). On one occasion these symptoms necessitated controlled artificial ventilation, but even at an inspiratory oxygen saturation of 100%, blood gases only partially improved (pCO2 27 mm Hg, pO2 67 mm Hg, O2 saturation 93%). Right heart catheterization in recumbency revealed a right to left shunt at atrial level of 37% of systemic flow. Contrast medium injection into the inferior vena cava near the heart demonstrated cardiac displacement and rotation. Part of the inferior vena cava flow passed into the left atrium via a patent foramen ovale: it is likely that this shunt increased in the upright position. After surgical closure of the patent foramen ovale and partial relocation of the heart (with a vicryl net) the patient has now remained free of symptoms for 5 years.
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PMID:[Patent foramen ovale and platypnea after pneumonectomy]. 145 15

Seven patients with necrotizing soft tissue infections of the perineum are described. Predisposing factors related to infection were present in four patients (diabetes mellitus, multiple myeloma, HIV, and a poorly defined immunodeficiency syndrome). Anaerobic and facultative anaerobic bacteria were cultured in each case. Two patients required skin graft closure of the debrided wounds, with the remaining wounds closed by contracture and epithelialization. A diverting sigmoid colostomy to facilitate wound care was performed on one patient who had complete dissolution of all anal sphincters. The role of hyperbaric oxygen therapy in four patients was of uncertain value.
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PMID:Synergistic soft tissue infections of the perineum. 161 51

Benzene, a common industrial chemical and a component of gasoline, is radiomimetic and exposure may lead progressively to aplastic anaemia, leukaemia, and multiple myeloma. Although benzene has been shown to cause many types of genetic damage, it has consistently been classified as a non-mutagen in the Ames test, possibly because of the inadequacy of the S9 microsomal activation system. The metabolism of benzene is complex, yielding glucuronide and sulphate conjugates of phenol, quinol, and catechol, L-phenylmercapturic acid, and muconaldehyde and trans, trans-muconic acid by ring scission. Quinol is oxidised to p-benzoquinone, which binds to vital cellular components or undergoes redox cycling to generate oxygen radicals; muconaldehyde, like p-benzoquinone, is toxic through depletion of intracellular glutathione. Exposure to benzene may also induce the microsomal mixed function oxidase, cytochrome P450 IIE1, which is probably responsible for the oxygenation of benzene, but also has a propensity to generate oxygen radicals. The radiomimetic nature of benzene and its ability to induce different sites of neoplasia indicate that formation of oxygen radicals is a major cause of benzene toxicity, which involves multiple mechanisms including synergism between arylating and glutathione-depleting reactive metabolites and oxygen radicals. The occupational exposure limit in the United Kingdom (MEL) and the United States (PEL) was 10 ppm based on the association of benzene exposure with aplastic anaemia, but recently was lowered to 5 ppm and 1 ppm respectively, reflecting a concern for the risk of neoplasia. The American Conference of Governmental Industrial Hygienists (ACGIH) has even more recently recommended that, as benzene is considered an A1 carcinogen, the threshold limit value (TLV) should be decreased to 0.1 ppm. Only one study in man, based on nine cases of benzene associated fatal neoplasia, has been considered suitable for risk assessment. Recent re-evaluation of these data indicated that past assessments may have overestimated the risk, and different authors have considered that lifetime exposure to benzene at 1 ppm would result in an excess of leukaemia deaths of 9.5 to 1.0 per 1000. Although in this study, deaths at low levels of benzene exposure were associated with multiple myeloma and a long latency period, instead of leukaemia, which might justify further lowering of the exposure limit, the risk assessment model has been found to be non-significant for response at low levels of exposure. The paucity of data for man, the complexity of the metabolic activation of benzene, the interactive and synergistic mechanisms of benzene toxicity and carcinogenicity, the different disease endpoints (aplastic anaemia, leukaemia, and multiple myeloma), and different individual susceptibilities, all indicate that in such a complex scenario, regulators should proceed with caution before making further changes to the exposure limit for this chemical.
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PMID:The toxicity of benzene and its metabolism and molecular pathology in human risk assessment. 185 46

Described herein are structure-activity studies of new antitumor agents based on the pyrrolo[1,2-a]benzimidazole (PBI) ring system. These compounds were designed as new DNA cross-linkers mimicking the mitomycin antitumor agents. Actually, the PBI derivatives were found to have anthracycline-like features: (i) shared cross resistance with doxorubicin in a human myeloma line, (ii) cardiotoxicity, and (iii) excellent DNA strand cleaving capability. The DNA strand cleavage is thought to result from reductive alkylation of DNA followed by the generation of reactive oxygen radicals. The best antitumor agent studied is 6-N-aziridinyl-3-hydroxy-7-methyl-2,3-dihydro-1H-pyrrolo- [1,2-a]benzimidazole-5,8-dione 3-acetate (PBI-A), which possesses nanomolar IC50 values against various human ovarian and colon cancer cell lines.
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PMID:Structure-activity studies of antitumor agents based on pyrrolo[1,2-a]benzimidazoles: new reductive alkylating DNA cleaving agents. 192 Mar 49

Ten patients with severe hematologic malignancies (four with acute leukemia, three with multiple myeloma, one with prolymphocytic leukemia, one with malignant lymphoma and one with blastic crisis of chronic myelogenous leukemia) developed respiratory failure during the period between April 1986 and May 1990. Clinically, the patients manifested high-fever, dyspnea refractory to oxygen therapy, diffuse pulmonary rales and severe hypoxemia without evidence of cardiogenic pulmonary edema. Chest roentgenograms displayed diffuse alveolar infiltrates. Respiratory failure occurred as early as 48 hours and as late as 66 days after the administration of intensive anti-neoplastic chemotherapy. At that time leukocyte count was between 100/microliters and 54,900/microliters. Marked leukocytosis was observed in two patients with AML and PLL. Respiratory failure was preceded by sepsis in one patient with AML and by pneumonia in nine patients. DIC was diagnosed in four patients. All patients treated with high dose methyl prednisolone (mPSL) within 12 hours after the onset of respiratory failure. Only one patient required assisted ventilation. High dose mPSL had significant effect on seven of ten patients. But three patients died from progressive respiratory failure, sepsis, pneumonia and multi-organ failure.
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PMID:[Clinical investigation on acute respiratory failure in patients with severe hematologic malignancy]. 194 22

Multiple myeloma (MM) is characterized by an increased susceptibility to infections and to other malignancies. Selected related immune functions were studied. Spontaneous and interleukin-2-stimulated natural killer (NK) cell activities were normal in 19 patients with MM compared with 62 controls. In contrast, interferon-stimulated NK cells had a significantly lower increase in activity in MM than in controls. The normal improvement in lytic NK cell activity after addition of indomethacin to the mononuclear cell cultures (to inhibit prostaglandin-mediated suppression) was not observed in cultures from MM patients. As reported for other lymphoproliferative disorders, the levels of soluble interleukin-2 receptors in serum were significantly higher in MM (600 U/ml median value) compared with controls (317 U/ml median value), P less than 0.0001, and the concentration of interleukin-2 receptors was significantly correlated with the concentration of monoclonal immunoglobulin in serum. Blood monocyte chemotactic responsiveness was significantly lower in MM patients with both zymosan-activated serum and f-Met-Leu-Phe as cytotaxins, suggesting reduced ability to accumulate at inflammatory foci. In contrast, release of reactive oxygen radicals, believed to be associated with the killing ability of monocytes, was normal after in vitro stimulation.
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PMID:Immune dysfunction in multiple myeloma. Reduced natural killer cell activity and increased levels of soluble interleukin-2 receptors. 203 17

Mineral dust-induced production of reactive oxygen metabolites (ROMs) by human monocyte-derived macrophages was investigated using lucigenin-dependent chemiluminescence. Chrysotile asbestos alone caused only weak ROM production by macrophages, but the addition of polyclonal immunoglobulin enhanced the reaction strongly. The phenomenon was seen with 1-, 4-, and 7-day-old cell cultures. Polyclonal immunoglobulin also slightly enhanced the ROM responses induced by amosite, crocidolite, and quartz dust. The enhancing effect could be achieved with several monoclonal immunoglobulins (isolated from the sera of myeloma patients), but IgA and IgG had the strongest effects. We suggest that immunoglobulins may interact with mineral dusts in a "nonimmunological," antigen-independent way and that the so-formed dust-immunoglobulin complexes may amplify the production of ROMs by inflammatory cells. This may explain a number of in vivo phenomena in which immune responses (for instance hypergammaglobulinemia and the presence of autoantibodies) have been shown to relate to the progression of mineral dust-induced pulmonary disease.
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PMID:Effect of immunoglobulins on mineral dust-induced production of reactive oxygen metabolites by human macrophages. 209 May 82

Multiple myeloma is characterized by an increased susceptibility to infections and to other malignancies. In a double-blind, placebo-controlled study the potential impact of immunomodulation by ranitidine was studied in 20 patients with multiple myeloma. Three patients were untreated, while 17 after previous cytotoxic therapy were in a stable phase of their disease. All were without clinical signs of infections and at that time had not been treated with other immunomodulating agents. The patients were randomized to oral ranitidine 300 mg twice a day for 21 days or placebo, and several immunological parameters related to multiple myeloma were studied. The blood monocyte chemotactic response was improved in patients treated with ranitidine, and superoxide anion production increased from 2.02 nmol/min to 3.86 nmol/min (median values), while it was unchanged in patients given placebo (2.19-2.25 nmol/min) (P less than 0.005 between groups). Among ranitidine-treated patients spontaneous NK cell activity was unchanged, while in vitro interleukin-2- and interferon-alpha-stimulated NK cell activity decreased (P less than 0.03, respectively). As production of oxygen radicals constitutes an important mechanism of monocyte killing activity against microorganisms and probably against malignant cells, it is suggested that ranitidine may be of beneficial impact in the treatment of multiple myeloma.
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PMID:The effect of ranitidine on cellular immunity in patients with multiple myeloma. 228 14


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