Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We carried out a study in patients with severe neutropenia from hematologic malignancy and suspected gram-negative sepsis to evaluate the clinical significance of endotoxin concentrations in plasma before and during a therapeutic intervention with a human polyclonal immunoglobulin M (IgM)-enriched immunoglobulin preparation (Pentaglobin; Biotest, Dreieich, Germany). Twenty-one patients with acute leukemia or non-Hodgkin's lymphoma entered the study upon the development of clinical signs of gram-negative sepsis and received the IgM-enriched immunoglobulin preparation every 6 h for 3 days (total dose, 1.3 liter with 7.8 g of IgM, 7.8 g of IgA, and 49.4 g of IgG), in addition to standardized antibiotic treatment. Concentrations of endotoxin and IgM and IgG antibodies against lipid A and Re lipopolysaccharide (LPS) in plasma were determined by a modified chromogenic Limulus amebocyte lysate test and semiquantitative enzyme linked immunosorbent assay, respectively, before each immunoglobulin infusion and during the following 25 days. Seventeen patients were endotoxin positive; in five of these patients, gram-negative infection was confirmed by microbiologic findings. Prior to therapy, endotoxemia correlated significantly with the occurrence of fever, and a quantitative correlation between the endotoxin concentration and body temperature was found during the individual course of infection in 8 of the 17 patients. Overall mortality from endotoxin-positive sepsis was 41% (7 of 17) and 64% (7 of 11) in patients with symptoms of septic shock. Nonsurvivors had significantly higher maximum concentration of endotoxin in plasma compared with those of survivors at the first study day (median of 126 versus 34 pg/ml; P < 0.05) and during the whole septic episode (median of 126 versus 61 pg/ml; P < 0.05). In survivors, immunoglobulin therapy resulted in a significant decrease in endotoxin levels in plasma within the initial 18-h treatment period, from a pretreatment median value of 28 pg/ml to a value of 8 pg/ml (P< 0.05). In the seven patients who died from uncontrollable infection, no effect of therapy on endotoxin levels in plasma was observed. IgM and IgG antibodies against lipid A and Re LPS increased significantly under immunoglobulin treatment, with significant correlations between antibodies against lipid A and Re LPS. These data strongly suggest a prognostic significance of the endotoxin levels in plasma and a potential effect of treatment with a polyclonal IgM-enriched immunoglobulin preparation. Further studies are needed to substantiate these findings and to assess the impact on the clinical course by way of a prospective placebo-controlled clinical trial.
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PMID:Endotoxin concentration in neutropenic patients with suspected gram-negative sepsis: correlation with clinical outcome and determination of anti-endotoxin core antibodies during therapy with polyclonal immunoglobulin M-enriched immunoglobulins. 144 93

Previously we described a cell line OCI-LY3 derived from a patient with non-Hodgkin's lymphoma. The cell line produced interleukin-6 (IL-6) mRNA and protein and demonstrated an autocrine pattern of growth for IL-6. Southern blot analysis of the IL-6 gene did not reveal any rearrangement. To determine whether the production of IL-6 by OCI-LY3 was due to subtle changes in the promoter of IL-6 or due to the expression of trans-acting factors chloramphenicol acetyltransferase (CAT) reporter constructs containing from -1,180 to +13 to -112 to +13 of a normal IL-6 gene were electroporated into the cell line. When these constructs are transferred into unstimulated fibroblasts, no CAT activity is seen; however, CAT activity is induced when the cells are stimulated with either IL-1 alpha, lipopolysaccharide (LPS), or cyclic adenosine monophosphate (cAMP) analogues. When the cell line OCI-LY3 was transfected with these constructs, CAT activity was observed; it was not necessary to stimulate the cells with exogenous factors to observe this activity. No CAT activity was observed in a second lymphoma cell line, OCI-LY13.1, that does not produce IL-6. These results suggest that the constitutive production of IL-6 by the cell line OCI-LY3 is due to the presence of trans-acting factors that stimulate the expression of IL-6 and not due to a cis-acting mutation of the IL-6 promoter.
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PMID:Regulation of interleukin-6 expression in the lymphoma cell line OCI-LY3. 191 71

One of the major tenets of current non-Hodgkin's lymphoma classifications is the relationship of morphologic subtypes to stages in the sequence of normal B-lymphocyte transformation occurring in the germinal follicle. To test this hypothesis, quantitative morphometric image analysis was carried out on in vivo and in vitro samples of mouse splenic lymphocytes in which transformation was induced by bacterial lipopolysaccharide (LPS), a specific B-cell mitogen. The results were compared with a similar analysis of germinal center lymphocyte populations of normal human spleen. In the in vivo mouse model, initial stages of B-cell transformation were detectable as early as 4 hours after LPS injection, and the process was essentially fully developed by 48-72 hours. Quantitative evaluation revealed that the majority of nuclear profiles were nearly spherical or only slightly eccentric and that no major alteration in nuclear contour occurred during any phase of the progressive increase in nuclear size following mitogen-induced lymphocyte transformation. In fact, in this system, B lymphocytes with a nuclear profile cleft of greater than or equal to 0.4 mu accounted for only 3% of the combined unstimulated and LPS-activated population assessed (N = 9936). This compared with normal human spleen, in which 16% of germinal center lymphocyte populations had similarly cleft nuclear profiles. Sequential alterations in the organization of condensed chromatin occurred concomitant with gradual nuclear enlargement during mitogen-induced mouse spleen lymphocyte transformation. A comparative morphologic and morphometric assessment of nuclear profiles of lymphocyte populations in germinal centers of normal human spleen provides indirect evidence for a similar pattern of nuclear alterations in human B lymphocytes. Autoradiographic data obtained from LPS-activated mouse splenic lymphocytes indicate that nuclear morphologic aspects of the transformation process can occur entirely within the G1 phase of the cell cycle. The results of this study suggest that subtypes of non-Hodgkin's lymphoma largely composed of neoplastic lymphocytes with extensively convoluted or cleft nuclei do not reflect a morphologic stage in the transformation of normal lymphocytes. In addition, the heterogeneous nuclear forms of follicular center cell lymphocytes would appear to result from parallel transformation processes involving cleaved and noncleaved nucleated lymphocytes and not the sequential pathway proposed by Lukes and Collins.
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PMID:Nuclear morphology and morphometry of B-lymphocyte transformation. Implications for follicular center cell lymphomas. 634 May 18

The motility of circulating neutrophils from seven patients affected by intermediate and high-grade non-Hodgkin's lymphoma was investigated before and after rhG-CSF administration (5 micrograms/kg/d for 5 d subcutaneously) in the course of chemotherapy. Random motility and bacterial lipopolysaccharide-induced chemotaxis were studied by the micropore filter technique in a Boyden chamber. These functions were evaluated by a very sensitive technique, based on a computer-assisted image processing system, capable of giving several parameters about the kinetics of cell migration. Along with a significant increase in neutrophil number, a significant decrease both in random and stimulated motility was found. The kinetics of cell migration showed that the cells maintained the typical gaussian pattern of random motility. On the contrary, neutrophils were found to have lost the typical stimulated migration peak. These findings are consistent with a rhG-CSF-induced impairment of the directional movement, rather than of the ability of moving at random. These effects were found in patients who, in the same experimental conditions, had displayed an enhanced phagocytosis and phagocytosis-associated chemiluminescence along with an enhanced CD32 expression, not due to an aspecific cell manipulation. Two hypotheses may be taken into account: (i) an increased adhesiveness due to a direct or an indirect activity of the cytokine; (ii) an abnormality in the cytoskeleton maturation and/or rearrangement during the accelerated bone marrow transit of myeloid cells. These findings emphasize that rh-GCSF administration can modulate several functions which play an important role in host defence, and suggest the utility of carrying out further studies to investigate the optimum dosage both to correct neutrophil number and preserve neutrophil functional activities.
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PMID:Motility of rhG-CSF-induced neutrophils in patients undergoing chemotherapy: evidence for inhibition detected by image analysis. 856 91

Translocations involving the BCL-6 gene are common in the diffuse large cell subtype of non-Hodgkin's lymphoma. Invariably, the BCL-6 coding region is intact, but its 5' untranslated region is replaced with sequences from the translocation partner. The present study shows that BCL-6 expression is regulated in lymphocytes during mitogenic stimulation. Resting B and T lymphocytes contain high levels of BCL-6 mRNA. Stimulation of mouse B cells with anti-IgM or IgD antibodies, bacterial lipopolysaccharide, phorbol 12-myristate 13-acetate plus ionomycin, or CD40 ligand led to a five-fold to 35-fold decrease in BCL-6 mRNA levels. Similar downregulation of BCL-6 mRNA was seen in human B cells stimulated with Staphylococcus aureus plus interleukin-2 or anti-IgM antibodies and in human T lymphocytes stimulated with phytohemagglutinin. BCL-6 mRNA levels began to decrease 8 to 16 hours after stimulation, before cells entered S phase. Although polyclonal activation of B cells in vitro invariably decreased BCL-6 MRNA expression, activated B cells from human germinal centers expressed BCL-6 mRNA at levels comparable to the levels in resting B cells. Despite these similar mRNA levels, BCL-6 protein expression was threefold to 34-fold higher in germinal center B cells than in resting B cells, suggesting that BCL-6 protein levels are controlled by translational or posttranslational mechanisms. These observations suggest that the germinal center reaction provides unique activation signals to B cells that allow for continued, high-level BCL-6 expression.
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PMID:BCL-6 expression during B-cell activation. 865 41

This study was designed to investigate the immunomodulatory effect of low-dose IL-2 therapy (100 microg/day for 3 weeks) on interferon (IFN), tumor necrosis factor (TNF) production in vivo and in vitro and on the expression of IL-2Ralpha/beta and soluble form of IL-2Ralpha. Patients enrolled in the study suffered from multiple myeloma (MM), Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) All of them were in remission after chemotherapy or radiotherapy. Our results indicated that IL-2 given subcutaneously at a low dose of 100 microg/day for 3 weeks induced IFN-gamma and TNF-alpha in plasma (measured 24 hrs after the last dose of IL-2) and affected the ability of blood leukocytes to produce cytokines. Production of IFN-gamma induced in vitro with PHA was enhanced, but TNF-alpha production induced by lipopolysaccharide (LPS) and virus (Newcastle Disease Virus) was depressed. The expression of both: surface IL-2R, especially beta subunit on total population of lymphocytes and NK cells, and soluble form of IL-2R, of chain were significantly enhanced after low-dose IL-2 therapy. Low dose IL-2 therapy was well tolerated by all patients, and side effects not exceeding II grade of toxicity according to WHO scale were observed. Five patients with MM relapsed 3-10 month after cessation of IL-2 therapy, but all patients with Hodgkin's and non-Hodgkin's lymphomas are still in remission (20 months of observation).
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PMID:Influence of low dose rIL-2 treatment on endogenous cytokine production, expression of surface IL-2R and the level of soluble IL-2R in patients with minimal residual disease. 1070 60

TNF synthesis depends on many controls at transcriptional and post-transcriptional levels, including in particular mRNA stability and translational efficiency through the AU-rich elements (ARE) in the 3'untranslated region (3'UTR) of mRNA. We have previously reported that upon lipopolysaccharide (LPS) stimulation, TNF protein secreted by normal peripheral blood cells (PBC) from non-Hodgkin's lymphoma patients was slightly, but not significantly increased when compared to healthy control donors. In contrast, the relative amounts of TNF mRNA were significantly higher in lymphoma patients. Thus, the implication of TNF mRNA stability has been explored by investigating the decay rate of LPS-induced TNF mRNA and the expression of tristetraprolin (TTP), one of the factors involved in the destabilization of TNF mRNA. After LPS incubation, peak levels of TTP mRNA preceded those of TNF mRNA, supporting its implication in the control of TNF mRNA levels in human PBC. Furthermore, similar TTP expression in both groups correlated with an identical decay rate of TNF mRNA, which excludes this pathway for the higher LPS-induced TNF mRNA levels in PBC from lymphoma patients.
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PMID:Tumor necrosis factor-alpha mRNA stability in human peripheral blood cells after lipopolysaccharide stimulation. 1195 26

This study found that oridonin, a natural diterpenoid purified from Rabdosia rubescens, inhibited growth of multiple myeloma (MM; U266, RPMI8226), acute lymphoblastic T-cell leukemia (Jurkat), and adult T-cell leukemia (MT-1) cells with an effective dose that inhibited 50% of target cells (ED50) ranging from 0.75 to 2.7 microg/mL. Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining showed that oridonin caused apoptosis of MT-1 cells in a time-dependent manner. We explored effects of oridonin on antiapoptotic Bcl-2 family members and found that it down-regulated levels of Mcl-1 and BCL-x(L), but not Bcl-2 protein, in both MT-1 and RPMI8226 cells. Further studies found that oridonin inhibited nuclear factor-kappa B (NF-kappa B) DNA-binding activity in these cells as measured by luciferase reporter gene, ELISA-based, and electrophoretic mobility shift assays. Oridonin also blocked tumor necrosis factor-alpha- and lipopolysaccharide-stimulated NF-kappa B activity in Jurkat cells as well as RAW264.7 murine macrophages. Of note, oridonin decreased survival of freshly isolated adult T-cell leukemia (three samples), acute lymphoblastic leukemia (one sample), chronic lymphocytic leukemia (one sample), non-Hodgkin's lymphoma (three samples), and MM (four samples) cells from patients in association with inhibition of NF-kappa B DNA-binding activity. On the other hand, oridonin did not affect survival of normal lymphoid cells from healthy volunteers. Taken together, oridonin might be useful as adjunctive therapy for individuals with lymphoid malignancies, including the lethal disease adult T-cell leukemia.
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PMID:Oridonin, a diterpenoid purified from Rabdosia rubescens, inhibits the proliferation of cells from lymphoid malignancies in association with blockade of the NF-kappa B signal pathways. 1582 31

Using biopsy specimens from patients with B-cell non-Hodgkin's lymphoma, we observed a significantly low frequency of T(H)17 cells, including several samples with no detectable amount of interleukin (IL)-17-producing cells present in the tumor microenvironment. We found that, in the absence of lymphoma B cells, treatment with IL-1beta/IL-6 or lipopolysaccharide (LPS) enhanced IL-17 expression in CD4(+) T cells and this enhancement was attenuated when CD4(+) T cells were cocultured with lymphoma B cells. Blockade of CD27-CD70 or CD28-CD80/86 interactions by anti-CD70 or anti-CD80/86 antibodies restored LPS-mediated induction of IL-17 expression in CD4(+) T cells cocultured with lymphoma B cells. Because a subset of lymphoma B cells express IL-2 and given that IL-2 signaling is critically important in the development of regulatory T (T(reg)) cells, we tested the role of IL-2 signaling in T(H)17 cell development. We found that treatment with anti-IL-2 antibody to interrupt IL-2 signaling significantly inhibited Foxp3 expression in CD4(+) T cells. In contrast, interruption of IL-2 signaling up-regulated IL-17 expression in CD4(+) T cells and restored lymphoma-mediated down-regulation of IL-17-producing cells. Furthermore, the reversal of T(reg) cell activity by LPS or CpG-A resulted in an enhancement of IL-17-producing cells. Taken together, our study indicated that lymphoma B cells play an important role in skewing the balance between T(reg) and T(H)17 cells resulting in the establishment of a profoundly inhibitory tumor microenvironment.
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PMID:Malignant B cells skew the balance of regulatory T cells and TH17 cells in B-cell non-Hodgkin's lymphoma. 1950 24

Objective To investigate the potential association of cytotoxic T lymphocyte associated protein 4 (CTLA4) polymorphisms with non-Hodgkin's lymphoma (NHL) risk. Methods Two reviewers independently searched the PubMed, MEDLINE, China National Knowledge Infrastructure (CNKI), Chinese WanFang databases and Database of Chinese Scientific and Technical Periodicals (VIP) for relevant studies from January 1, 1990 to May 25, 2016. Odds ratios (OR) with 95% confidence intervals (CI) for CTLA4 polymorphism and HNL risk were used to evaluate the strength of association. Meta-analysis was performed using SATA (v12.0) software. Results A total of 6 case-control studies concerning the CTLA4 +49A/G, -318T/C, and CT60A/G polymorphisms were included in the meta-analysis. The polymorphisms of the three alleles were not associated with genetic susceptibility to NHL (PZ>0.05 or 95%CI contains 1). In the subgroup analysis of CTLA4 +49A/G gene polymorphism, we found that AA was a risk factor for mixed type lymphoma (AA vs GG: OR=4.181, 95%CI: 1.362-12.833; AA+AG vs GG: OR=3.217, 95%CI: 1.055-9.810; AA vs AG+GG: OR=2.827, 95%CI: 1.345-5.940), but was a protect factor for B cell lymphoma (AA vs GG: OR=0.465, 95%CI: 0.251-0.863; AA vs AG+GG: OR=0.534, 95%CI: 0.362-0.788); AA was a risk factor in Italians (AA vs GG: OR=4.181, 95%CI: 1.362-12.833; AA+AG vs GG: OR=3.217, 95%CI: 1.055-9.810; AA vs AG+GG: OR=2.827, 95%CI: 1.345-5.940), but was a protect factor in Chinese (AA vs GG: OR=0.643, 95%CI: 0.417-0.992; AA vs AG+GG, OR=0.601, 95%CI: 0.395-0.913). Conclusion This meta-analysis suggests that the polymorphisms of the three alleles are not associated with genetic susceptibility to NHL.
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PMID:[Association between cytotoxic T lymphocyte protein-4 polymorphisms and non-Hodgkin's lymphoma risk: a meta-analysis]. 2741 43


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