Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have examined basal and lipopolysaccharide (LPS)-induced release of epidermal growth factor (EGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), growth-regulated peptide alpha (GRO alpha), leukaemia inhibitory factor (LIF), macrophage inflammatory protein-1a (MIP-1 alpha) and platelet-derived growth factor-AB (PDGF-AB) in peripheral blood mononuclear cells (PBMC) from 20 persons with either high (n = 10) or low (n = 10) levels of high-density lipoprotein (HDL). PBMC were incubated with 100 ng LPS/ml for up to 160 h, and showed a significantly higher release of the chemokines GRO alpha (P = 0.04) and MIP-1 alpha (P < 0.01) in persons with high HDL, whereas levels of GM-CSF were similar. Levels of EGF, LIF and PDGF-AB were always low, and remained unaltered during 160 h of incubation. These findings indicate that PBMC from persons with high or low levels of HDL have different functional properties, of importance in cell recruitment and activation.
 ...
PMID:LPS-induced release of EGF, GM-CSF, GRO alpha, LIF, MIP-1 alpha and PDGF-AB in PBMC from persons with high or low levels of HDL lipoprotein. 858 Mar 73

We examined the effect of diffusible factors generated during the culture of the KM102 stromal cell line as well as in long-term bone marrow culture (LTBMC) on K562 leukemia cells, with respect to proliferation of clonogenic cells as well as total cells, and compared it with the effect on normal myeloid progenitors (CFU-GM). Proliferation of K562 cells plated in diffusion chambers was inhibited by coculture for 3-5 days in the fluid phase of stromal cell cultures or stromal cell-conditioned medium (CM), while CFU-GM proliferation was not inhibited under the same culture conditions. The inhibitory action was not attributed to the exhaustion of nutrients or growth promoting factors such as stem cell factor. These findings suggest that bone marrow stromal cells secrete diffusible molecule(s) which exert a preferential inhibitory effect on K562 leukemic cells vs. normal CFU-GM. Neutralization with antibodies against hematopoiesis-inhibiting cytokines such as TGF-beta 1, IFN-gamma, MIP-1 alpha and IL-4 which were detected in stromal cell-CM, failed to abrogate the inhibitory effect of KM102-CM on K562 cells. IL-1, TNF-alpha, IFN-alpha and lipopolysaccharides, known as stimulators of various cytokines from stromal cells, could not enhance the inhibitory activity. Further characterization of the factors may have implications for the treatment of leukemias.
 ...
PMID:Preferential inhibitory effect of soluble factor(s) in human bone marrow stromal cells on proliferation of K562 leukemia cells versus normal myeloid progenitor cells. 893 34

We have previously reported that oral administration of hot water extract of Chlorella vulgaris (CVE) enhances resistance to Listeria monocytogenes through augmentation of Listeria-specific cell-mediated immunity in normal mice and mice with murine acquired immunodeficiency syndrome (MAIDS) caused by murine leukemia virus (MuLV) LP-BM5. To elucidate the mechanisms whereby CVE augments the cell-mediated immunity, we examined the expression patterns of mRNA for cytokines in normal and MAIDS mice given CVE orally after L. monocytogenes infection. The expression levels of IL-1 alpha, IL-12, GM-CSF, MIP and TNF alpha genes were significantly augmented in the peritoneal adherent cells by oral administration of CVE for 2 weeks before Listeria infection. The expression levels of gamma IFN and IL-12 mRNA were significantly higher in the spleen after Listeria infection in CVE-treated mice than in normal mice, while the expression of IL-10 mRNA in the spleen was decreased by CVE administration. In MAIDS mice, oral administration of CVE also augmented the expression of gamma IFN and IL-12 mRNA in the spleen after Listeria infection, while it rather reduced the expression of IL-10 mRNA. These results suggest that CVE may preferentially augment THI responses against Listeria via activation of macrophages to produce IL-12 and enhance host defence against Listeria infection both in normal and MAIDS mice.
 ...
PMID:Effect of hot water extract of Chlorella vulgaris on cytokine expression patterns in mice with murine acquired immunodeficiency syndrome after infection with Listeria monocytogenes. 904 41

Adult T cell leukemia (ATL) cells show a mature helper-inducer T cell phenotype and are thought to secrete many kinds of cytokines in vivo, complicating the clinical features in these patients. In an attempt to specify the cytokines produced by ATL cells, we measured the cytokine concentration in the culture supernatants of three ATL cell lines, all of which were confirmed to be true peripheral blood ATL cell in origin. All these cell lines showed the same cytokine production profile, secreting IL1-alpha, IL1-beta, LD78(MIP-l alpha), TNF-alpha, IFN-gamma, and GM-CSF, but not secreting IL-1 alpha, IL-1 beta, IL-1 receptor antagonist (IL-1 Ra), IL-4, IFN-alpha, and G-CSF irrespective of the stimulatory agents used. Such limited cytokine production may indicate the specific origin of ATL cells within the helper-inducer T cell subtypes. Moreover, these results explain some of the unusual clinical features of ATL patients.
 ...
PMID:Features of the cytokines secreted by adult T cell leukemia (ATL) cells. 917 9

In two lines of transgenic rats (pX rats) from WKAH and F344 strains and carrying the HTLV-I pX gene under control of the mouse H-2Kd promoter, mammary carcinomas developed predominantly in females starting at about 5 months of age. The incidence of the tumor reached about 40% when the rats were 12 months old. Histology of the tumor was undifferentiated carcinoma with massive infiltration of granulocytes into the tumor tissue. Systemic granulocytosis and hepato-splenomegaly due to extramedullary granulocytopoiesis were seen in pX rats and nude mice bearing pX mammary tumor. mRNAs of both pX and host genes, Gro and MIP-2, which are granulocyte chemoattractants of the IL-8 family, were highly expressed in the tumor tissue. Since expression and point mutation of several oncogenes and anti-oncogene, related with mammary carcinomas, were not demonstrated, hitherto unidentified novel oncogenic pathways may be transactivated by the pX transgene in these pX rats. pX mammary carcinoma cell lines, which have similar characteristics to the primary tumor, were established and the cells underwent apoptosis under the serum deprived conditions. The pX rats and the pX mammary carcinomas appear to be suitable models for analyses of HTLV-I pX oncogenesis and immune pathogenesis in vivo and in vitro.
Leukemia 1997 Apr
PMID:HTLV-I pX transgenic rats: development of cytokine-producing mammary carcinomas and establishment of the pX mammary carcinoma cell lines. 920 2

Flt3-ligand (FL) is a cytokine that is of paramount importance in the proliferation of primitive hematopoietic progenitors. In this study, we show that endothelial cells (EC) produce large amounts of soluble FL and express a membrane-bound form of the molecule. Bone marrow microvascular EC also produce FL, suggesting that EC are an important source of FL in the bone marrow. High concentrations of FL in EC supernatants contrast with its undetectable levels in long-term bone marrow cultures. A single mRNA for FL is detected, suggesting that soluble FL derives from the membrane-bound species by proteolytic release. FL mRNA is stable with a half-life of about 3 h. II-1alpha increases FL mRNA levels and membrane and soluble FL expression. Glucocorticoids, known inhibitors for many hematopoietic growth factors do not down-regulate the expression of FL. On the contrary, GC increase the expression of both species of FL. The neutralization of FL in cocultures EC/ hematopoietic progenitors results in an acceleration of the maturation of the progenitors. IFN-alpha, MIP-1 alpha and TGF-beta stimulate production of membrane-bound and soluble FL. This stimulation is essential to explain their modulatory effect on the generation of clonogenic cells in cocultures EC/hematopoietic progenitors. Leukemia (2000) 14, 153-162.
Leukemia 2000 Jan
PMID:Expression of Flt3-ligand by the endothelial cell. 1063 91

Multiple myeloma (MM) is a B cell tumor characterized by its selective localization in the bone marrow. The mechanisms that contribute to the multiple myeloma cell recruitment to the bone marrow microenvironment are not well understood. Chemokines play a central role for lymphocyte trafficking and homing. In this study we have investigated expression and functional importance of chemokine receptors in MM-derived cell lines and primary MM cells. We found that MM cell lines express functional CCR1, CXCR3 and CXCR4 receptors, and some also CCR6. Although only a minority of the cell lines responded by calcium mobilization after agonist stimulation, a migratory response to the CCR1 ligands RANTES and MIP-1 alpha was obtained in 5/6 and 4/6, respectively, of the cell lines tested. Five out of six cell lines showed a response to the CXCR4 ligand SDF-1. In addition, 3/6 cell lines migrated in response to MIP-3 alpha and IP-10, ligands for CCR6 and CXCR3, respectively. The expression of CXCR4 and CCR1 and the migration to their ligands, SDF-1, and RANTES and MIP-1 alpha, respectively, were also demonstrated in primary MM cells. These findings suggest that chemokine receptor expression and the migratory capacity of MM cells to their ligands are relevant for the compartmentalization of MM cells in the bone marrow.
Leukemia 2003 Jan
PMID:Expression and function of chemokine receptors in human multiple myeloma. 1252 79

Using rat peritoneal neutrophils, the complete nucleotide sequence of rat macrophage inflammatory protein-2 (MIP-2) mRNA including 5'untranslated region (UTR) and 3'UTR was determined (GenBank Accession number, AB060092). It was found that the MIP-2 mRNA has a 70 bp 5'UTR, a 303 bp coding region and a 728 bp 3'UTR which contains adenylate/uridylate (AU)-rich areas defined as AU-rich elements (AREs). Site-directed mutagenesis studies using the tetracycline-sensitive transactivator protein-expressing rat basophilic leukemia cells (RBL-2H3-TO cells) revealed that MIP-2 mRNA mutants which lack the 3'UTR are more stable than MIP-2-wild-type (wt) mRNA. A MIP-2 mRNA mutant in which some mutations were introduced to the ARE was also stable. The stability of MIP-2 mRNA was low in untreated RBL-2H3-TO cells, but it increased in the antigen-stimulated immunoglobulin E (IgE)-sensitized cells. The antigen-induced MIP-2 mRNA stabilization was counteracted by the highly specific p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 and the MAPK/ERK kinase (MEK-1) inhibitor PD98059. These findings indicate that ARE is the cis-element which mediates the rapid decay of MIP-2 mRNA, and the antigen stimulation stabilizes MIP-2 mRNA and the p38 MAPK and p44/42 MAPK pathways are involved in the antigen-induced stabilization of MIP-2 mRNA.
 ...
PMID:Analysis of the mechanism regulating the stability of rat macrophage inflammatory protein-2 mRNA in RBL-2H3 cells. 1462 57

All-trans retinoic acid (ATRA) induces complete remission in patients with acute promyelocytic leukemia (APL). However, ATRA sometimes causes retinoic acid syndrome (RAS) characterized by respiratory distress, pleural effusions, fever and weight gain. To investigate the pathophysiology of RAS, we generated an animal model by injecting an APL cell line, NB4, into immunodeficient mice. When NOD/scid mice were injected intravenously with fully differentiated NB4 cells (1 x 10(7)) and then given a daily administration of ATRA, three of 12 mice died of pulmonary edema within 14 days. Pathologically, dilated lung capillary vessels and alveolar effusions were observed. After the injection, NB4 cells were detected in the lung within 2 days and in the pleural effusion later on. The gene expression levels of CXC chemokines (MIP-2 and KC) and ICAM-1 were increased in the lung and heart by the ATRA administration. In immunohistochemical analyses, MIP-2 was clearly detected in alveolar macrophages of the lung in mice with RAS. Dexamethasone treatment prevented the development of RAS and decreased the CXC chemokine mRNA expression in the lung. These findings suggested that the activation of adhesion molecules for leukocytes and expression of CXC chemokines in the lung are closely involved in triggering RAS.
Leukemia 2004 Mar
PMID:Retinoic acid syndrome in NOD/scid mice induced by injecting an acute promyelocytic leukemia cell line. 1474 6

Those inhabitants of Hiroshima and Nagasaki who were affected by the A-bomb explosions, were exposed to a mixed neutron and gamma radiation field. Few years later about 120,000 survivors of both cities were selected, and since then radiation-induced late effects such as leukemia and solid tumors are being investigated in this cohort. When the present study was initiated, the fast neutron fluences that caused the neutron doses of these survivors had never been determined experimentally. In principle, this would have been possible if radioisotopes produced by fast neutrons from the A-bomb explosions had been detected in samples from Hiroshima and Nagasaki at distances where the inhabitants survived. However, no suitable radioisotope had so far been identified. As a contribution to a large international effort to re-evaluate the A-bomb dosimetry, the concentration of the radionuclide (63)Ni (half-life 100.1 years) has been measured in copper samples from Hiroshima and Nagasaki. These measurements were mainly performed at the Maier-Leibnitz-Laboratory in Munich, Germany, by means of accelerator mass spectrometry. Because the (63)Ni had been produced in these samples by fast A-bomb neutrons via the reaction (63)Cu(n,p)(63)Ni, these measurements allow direct experimental validation of calculated neutron doses to the members of the LSS cohort, for the first time. The results of these efforts have already been published in a compact form. A more detailed discussion of the methodical aspects of these measurements and their results are given in the present paper. Eight copper samples that had been significantly exposed to fast neutrons from the Hiroshima A-bomb explosion were investigated. In general, measured (63)Ni concentrations decreased in these samples with increasing distance to the hypocenter, from 4 x 10(6 ) (63)Ni nuclei per gram copper at 391 m, to about 1 x 10(5 ) (63)Ni nuclei per gram copper at about 1,400 m. Additional measurements performed on three large-distant copper samples from Hiroshima (distance to the hypocenter 1,880-7,500 m) and on three large-distant copper samples from Nagasaki (distance to the hypocenter 3,931-4,428 m) that were not exposed significantly to A-bomb neutrons, suggest a typical background concentration of about 8 x 10(4 ) (63)Ni nuclei per gram copper. If the observed background is accounted for, the results are consistent with state-of-the-art neutron transport calculations for Hiroshima, in particular for those distances where the victims survived and were included in the life span study cohort.
 ...
PMID:Neutron-induced 63Ni in copper samples from Hiroshima and Nagasaki: a comprehensive presentation of results obtained at the Munich Maier-Leibnitz Laboratory. 1839 35


<< Previous 1 2 3 4 5 Next >>