Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The importance of the consideration of micro-anatomical and cytological observation for the oxygen utilization by hybridoma cells are emphasized. Tumor cells have considerably lower content of mitochondria and that cells metabolize much of their carbon source by anaerobic pathway, therefore, consumes much less oxygen. Because of the fact that hybridoma cells are derived from a myeloma cell, which is a type of tumor cell, there may be possibility that the oxygen demand could be closely related to mitochondrial content of the resulting cell. Possible correlation between the optimum DOT and mitochondrial content of the hybridoma cells is hypothesized. By simulating oxygen transport inside of a single hybridoma cells for the cases of three different mitochondrial contents, possible differences in the optimum DOT according to the mitochondrial contents were studied and the results reported.
 ...
PMID:Structured modeling and simulation of oxygen transport to hybridoma cell in a suspension culture: theoretical analysis. 278 46

Eosinophils like neutrophils possess an oxidative metabolism which is activated by phagocytosis and cell membrane activation. Since eosinophils may take part in inflammatory reactions by releasing oxygen species and have membrane receptors for immunoglobulins, immune complexes may activate their respiratory burst. We compared the ability of phorbol myristate acetate (PMA) and immunoglobulin G (IgG) and immunoglobulin E (IgE) immune complexes to stimulate hydrogen peroxide (H2O2) release from circulating eosinophils and neutrophils. PMA was able to stimulate a significant respiratory burst in both cell types, PMA-induced H2O2 production being higher in eosinophils than in neutrophils (p less than 0.05). Similar results were obtained when the cells were stimulated by IgG (p less than 0.05). In contrast, aggregated human myeloma IgE induced a detectable H2O2 release only from peripheral blood eosinophils. We conclude that H2O2 release from eosinophils may play a role in parenchymal injury associated with hypereosinophilic disorders and the presence of immune complexes at sites of disease activity.
 ...
PMID:Oxidative metabolism of human peripheral blood eosinophils and neutrophils: H2O2 production after stimulation with phorbol myristate acetate and immune complexes. 280 4

Human alveolar macrophages were obtained during diagnostic bronchoalveolar lavage. Cells were cultured, and morphological examination (including electron microscopy) revealed that not more than 5% of the cultured cells were identifiable as cells other than alveolar macrophages. The cells were sensitized with human myeloma immunoglobulin E. and then challenged with anti-immunoglobulin E anti-sera. The experiments employed a highly specific monoclonal antibody and three affinity purified reagents. The formation of immunoglobulin E/anti-immunoglobulin E complexes facilitated release from alveolar macrophages of leukotriene B4, prostaglandin F2 alpha, thromboxane B2 and the lysosomal hydrolase N-acetyl-beta-D-glucosaminidase. There was no release of active oxygen species, with this stimulus, as measured by lucigenin chemiluminescence. Immunoglobulin E receptors were identified histochemically on the surface of human alveolar macrophages, and were visualized as conjugates with colloidal gold by electron microscopy. These results support the view that human alveolar macrophages may contribute to type 1 hypersensitivity reactions in the lung.
 ...
PMID:Immunoglobulin E-dependent stimulation of human alveolar macrophages: significance in type 1 hypersensitivity. 294 65

Neutrophil chemiluminescence (CL) as a measure of oxygen-dependent killing activity was evaluated in 3 groups of patients: (a) 63 patients with multiple myeloma (MM); (b) 31 subjects with monoclonal gammopathy of undetermined significance (MGUS); (c) 32 healthy controls. Neutrophil CL response was shown to be significant reduced both in patients with MM (p less than 0.001) and in subjects with MGUS (p less than 0.001). A significant difference was also observed between the results obtained in MM and those of MGUS (p less than 0.001). Treated MM patients showed a more severe impairment of neutrophil chemiluminescence response than that observed in untreated patients (p less than 0.001). It is suggested that the impairment of neutrophil CL response, possibly related to decreased killing activity, may play a role, along with other known causes, in the increased susceptibility to infection observed in MM patients.
 ...
PMID:Impaired chemiluminescence response by neutrophils in patients with multiple myeloma. 302 7

The antitumor antibiotic mitomycin C (MMC) was studied in vitro using L1210 leukemia and 8226 human myeloma cells. Cytotoxicity was evaluated by colony formation in soft agar, and DNA damage was analyzed using alkaline elution filter assays. The purposes of these studies were: (a) to characterize the time course of MMC-DNA damage; (b) to characterize the type of DNA damage [DNA-DNA interstrand cross-links (ISC), DNA-protein cross-links (DPC), single and double strand breaks (SSBs, DSBs)]; and (c) to correlate this damage with cytotoxicity in vitro. Colony-forming assays showed the D0 value for 1 h MMC to be 15.0 microM for L1210 cells and 17 microM for 8226 cells. Alkaline elution studies showed that dose-dependent ISCs and DPCs formed rapidly following MMC exposure. Removal of cross-links was delayed, with only 50% repaired 32 h after exposure. There was a good correlation between ISCs and cytotoxicity in dose-response studies in each cell line. ISCs appeared to comprise most of the MMC-DNA lesions in both cell lines. No DNA SSBs or DSBs were observed following MMC exposure. Nuclei isolated from both cell lines and exposed to MMC produced less MMC alkylation than whole cells but, again, no strand breaks were evident. These results demonstrate that MMC is principally an alkylating agent when used at pharmacological (cytotoxic) concentrations in vitro. The lack of evidence for DNA strand breaks discounts a significant role for putative quinone-generated oxygen free radicals in the production of MMC cytotoxicity.
 ...
PMID:Interactions of mitomycin C with mammalian DNA detected by alkaline elution. 392 1

The viability of neutrophils in the condition under which they kill neoplastic cells was studied. In the presence of phorbol myristate acetate (PMA) the 51Cr-release by human neutrophils was markedly stimulated. The PMA-induced 51Cr-release by neutrophils correlated well with the number of nonviable neutrophils as determined by the uptake of trypan blue. Phorbol myristate acetate had no effect on the 51Cr-release by lymphocytes, LPC-1 myeloma cells, ovarian ascites tumor cells, or neutrophils from a patient with chronic granulomatous disease. This suggests that the effect of PMA is not due to its nonspecific toxic effect; instead, it is dependent on the reactive oxygen species produced by the normal neutrophils. Catalase, cytochrome C, histidine, and methionine inhibited the PMA-induced 51Cr-release by human neutrophils, whereas superoxide dismutase, myeloperoxidase inhibitors, and some hydroxyl radical scavengers or singlet oxygen quenchers had no effect. The clumping of neutrophils induced by PMA was also important in the PMA-induced 51Cr-release by human neutrophils.
 ...
PMID:Phorbol myristate acetate induced neutrophil autotoxicity. 719 15

Alpha-linolenic acid (ALA) and eicosapentaenoic acid (EPA) exhibited potent cytotoxic action on SP 2/0 mouse myeloma cells in vitro. Both SOD and vitamin E could inhibit the action of ALA and EPA indicating a role for reactive oxygen species and lipid peroxides. In addition, both ALA and EPA enhanced the formation of superoxide anion, hydrogen peroxide and lipid peroxides, and caused a reduction in the levels of antioxidant enzymes: SOD, catalase and glutathione peroxidase and induced significant damage to DNA in SP 2/0 cells. Thus, ALA and EPA inhibit antioxidant defenses of the cell and damage the DNA, which can ultimately lead to tumor cell lysis.
 ...
PMID:Free radical-dependent suppression of growth of mouse myeloma cells by alpha-linolenic and eicosapentaenoic acids in vitro. 775 58

It is now well documented that apoptosis represents the prevalent mode of cell death in hybridoma cultures. Apoptotic or programmed cell death occurs spontaneously in late exponential phase of batch cultures. Until lately, no specific triggering factors had been identified. Recently, we observed that glutamine, cystine or glucose deprivation induced apoptosis in both hybridoma and myeloma cell lines whereas accumulation of toxic metabolites induced necrotic cell death in these cells. Other triggering factors such as oxygen deprivation might also be responsible for induction of apoptosis. In the present study, induction of cell death by exposure to anoxia was examined in batch culture of the SP2/0-derived hybridoma D5 clone. The mode of cell death was studied by morphological examination of acridine orange-ethidium bromide stained cells in a 1.5 L bioreactor culture grown under anoxic conditions for 75 hours. Under such conditions, viable cell density levelled off rapidly and remained constant for 25 hours. After 45 hours of anoxia, cell viability had decreased to 30% and the dead cell population was found to be 90% apoptotic. In terms of cellular metabolism, anoxia resulted in an increase in the utilization rates of glucose and arginine, and in a decrease in the utilization rate of glutamine. The lactate production rate and the yield of lactate on glucose increased significantly while the MAb production rate decreased. These results demonstrate that glycolysis becomes the main source of energy under anoxic conditions. Cells incubated for 10 hours or less under anoxic conditions were able to recuperate almost immediately and displayed normal growth rates when reincubated in oxic conditions whereas cells incubated for 22 hours or more displayed reduced growth rates. Nonetheless, even after 22 h or 29 h of anoxia, cells reincubated in oxic conditions showed no further progression into apoptosis. Therefore, upon removal of the triggering signal, induction of apoptosis ceased.
 ...
PMID:Induction of apoptosis in oxygen-deprived cultures of hybridoma cells. 776 24

Monoclonal antibodies to polyribosylribitolphosphate (PRP), the capsular polysaccharide of Haemophilus influenzae type b (Hib), are useful tools in the investigation of the molecular and cellular mechanisms causing Hib meningitis. A better understanding of these mechanisms may lead to improved therapeutic strategies. A number of different in vivo immunization techniques in BALB/c mice were used, which did not however reveal detectable serum levels of antibodies to PRP. Therefore a modified in vitro immunization technique, originally established for in vitro immunization of human B lymphocytes, was used for this weak immunogen in mice. After 5 days of in vitro stimulation with purified PRP the splenic lymphocytes of BALB/c mice were fused with the mouse myeloma line P3-X63-Ag8.653. One hybridoma produced an IgM antibody (12E7) which recognized the capsular polysaccharide in ELISA and specifically labelled all tested Hib strains in immune fluorescent microscopy. The blotted polysaccharide PRP was immunostained with monoclonal antibody 12E7. Preincubation of Hib with this antibody enhanced the oxygen radical metabolism of polymorphnuclear leucocytes in a chemiluminescence assay. There was no cross-reactivity with the supernatants of other Haemophilus influenzae serotypes and other bacterial species, as shown by counterimmunoelectrophoresis.
 ...
PMID:Characterization of a monoclonal antibody to the capsule of Haemophilus influenzae type b, generated by in vitro immunization. 782 41

The diameter and sphericity of alginate-poly-L-lysine-alginate microcapsules, which was determined by the size and shape of calcium alginate microspheres, affected durability and biocompatibility of microcapsules and the result of transplantation. The commonly used airjet spray method generated microspheres with wide variation in diameter and sphericity. In order to overcome these drawbacks, we designed a field effect microparticle generator which established a stable electric field. This generated calcium alginate microspheres with an adjustable diameter (range, 50-350 microns). Factors which influenced the diameter and sphericity of microspheres included the percentage of alginate, field strength, speed of extrusion of alginate, needle gauge, field distance, and cell density in sodium alginate. The conditions used for microencapsulation of rat, pig, and human islets were 5500-6500 volts, 22 gauge needle with blunt end, 1-cm field distance, 1.5% sodium alginate, and 0.57 mL/min extrusion speed. These combinations would give most of the islet-containing microcapsules a diameter of 300-450 microns when alginate microspheres were incubated with calcium chloride solution for a total of six minutes. If individual cells (eg, NS-1) were microencapsulated, a larger gauge needle resulted in smaller microcapsules. Field strength of 6500 volts at a distance of 1 cm did not change the doubling time of NS-1 myeloma cells. By using the electric field microparticle generator, encapsulated cells were distributed around the periphery of the microspheres and thus improved the oxygen and nutrient supply of these encapsulated cells.
 ...
PMID:The use of field effects to generate calcium alginate microspheres and its application in cell transplantation. 792 65


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>