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 assessed the limitations of the polymerase chain reaction (PCR) as a semiquantitative technique for assessing very low level gene expression. Using PCR, the in vivo expression patterns of the cytokines Leukaemia Inhibitory Factor (LIF) and Interleukin 6 (IL-6) in the normal adult mouse, have been examined. We show that both LIF and IL-6 mRNA are constitutively expressed, albeit at extremely low levels, in most tissues. While it is unclear whether this low level of expression is of biological significance, it is possible that it reflects a local mode of action of these potent polyfunctional molecules. Lipopolysaccharide, the bacterial cell wall product responsible for endotoxic shock, when administered in vivo, was capable of inducing the expression of both LIF and IL-6 in all of the tissues examined. In addition, LIF and IL-6 expression was induced in lung tissue by in vitro culturing in serum-free media. This induction of LIF and IL-6, by LPS and culturing, may reflect the role of these molecules as mediators of the acute phase response to tissue damage.
Cytokine 1994 May
PMID:Leukaemia inhibitory factor and interleukin 6 are expressed at very low levels in the normal adult mouse and are induced by inflammation. 805 87

A murine acquired immunodeficiency syndrome (MAIDS) is induced in genetically susceptible strains of mice inoculated with LP-BM5 murine leukemia virus. It is characterized by progressive lymphoproliferation, profound immunodeficiency, and the subsequent loss of resistance to opportunistic pathogens, including intestinal pathogens. Cellular and/or humoral immunity of gut-associated lymphoid tissues may play a key role in the elimination of these pathogens. We have previously demonstrated reductions in the number of mucosal T and B cells in MAIDS. In this study, the cytokine production by mesenteric lymph nodes (MLN) cells and their proliferative response to mitogens during MAIDS were investigated. Alterations were observed in the kinetics of MLN cell proliferation and cytokine secretion by in vitro mitogen-stimulated MLN cells during the retrovirus infection. Cytokine production was abnormally changed, with a gradual decrease in interleukin-2 (IL-2) production as well as an increase in IL-5 and IL-6 secretion. Interferon-gamma production was increased during the progression to MAIDS. The dysregulated release of cytokines by MLN cells due to retrovirus infection could lead to immune dysfunction. These data indicate that dysregulated cytokine secretion by MLN cells may be responsible for impaired mucosal immunity in AIDS, explaining the dramatic increase of opportunistic intestinal pathogens in individuals with AIDS.
 ...
PMID:The kinetics of cytokine secretion and proliferation by mesenteric lymph node cells during the progression to murine AIDS, caused by LP-BM5 murine leukemia virus infection. 806 35

Cytokine treatment in patients with myelodysplastic syndrome (MDS) aims to overcome the maturation defects of myeloid lineage cells associated with cytopenia and cellular dysfunction of mature cells. Since phagocytes play a major role in host defense against microbial infection, we investigated cytokine secretion and oxygen radical release (ORR) from peripheral blood monocytes (PBMC) in a total of 16 MDS patients, 12 patients with refractory anemia (RA) and four patients with RA and excess of blasts (RAEB). Interleukin (IL-6), tumour necrosis factor alpha (TNF alpha), IL-1 beta, and IL-8 secretion from monocytes in response to lipopolysaccharide (LPS) was significantly reduced in the 12 patients with RA compared to 12 healthy controls, whereas no difference was seen in ORR. We further assessed cytokine secretion from monocytes of 10 MDS patients before and after therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, or a combination therapy with GM-CSF and cytosine arabinoside (AraC). In all 10 patients, secretion of IL-1 beta, IL-6, and TNF alpha from PBMC increased after cytokine therapy, whereas IL-8 secretion increased only in five patients with GM-CSF or IL-3 therapy receiving a dosage > or = 250 micrograms/m2 per day but decreased in all other patients. ORR increased in all patients on either GM-CSF or IL-3 therapy. These data indicate that the ability of monocytes to secrete secondary cytokines is impaired in MDS patients but can be restored by in vivo administration of GM-CSF and IL-3.
Leukemia 1993 Nov
PMID:Restoration of impaired cytokine secretion from monocytes of patients with myelodysplastic syndromes after in vivo treatment with GM-CSF or IL-3. 823 Dec 42

Leukaemia inhibitory factor (LIF) is a multifunctional growth and differentiation factor with activities in both the adult and the embryo. The expression of LIF appears to be tightly regulated, as the levels of constitutive expression in most tissues and cell lines is extremely low. In this report we have identified three sequence elements within the 5'-flanking region of the murine LIF gene which control the constitutive action of the LIF promoter. A nested set of DNA fragments from the LIF gene 5'-flanking region was placed upstream of the chloramphenicol acetyltransferase (CAT) gene and assayed for their ability to direct chloramphenicol acetyltransferase (CAT) expression in STO-fibroblasts. The essential promoter of the LIF-gene, giving rise to low levels of CAT expression, was found to require the major start-site of transcription (+1), a TATA-box (-31) and up to 72 additional 5' nucleotides (-32 to -103). A negative regulatory element which abolished CAT-activity was identified between positions -360 and -249. The SV40 enhancer element was able to override this apparent negative element. In addition, an apparent positive control element in the LIF 5'-flanking region, between positions -860 and -661 was identified which was also able to override this negative effect.
Cytokine 1993 Jul
PMID:Delineation of positive and negative control elements within the promoter region of the murine leukemia inhibitory factor (LIF) gene. 826 Jun 5

Secretion of different cytokines may be an important T-cell effector mechanism for bone marrow engraftment, graft versus host disease and graft versus leukaemia effects after allogeneic bone marrow transplantation (BMT). Cytokine secretion and autocrine proliferative capacity of T-cell clones derived from leukaemia patients 3-6 weeks after allogeneic bone marrow transplantation were investigated. Only a minority of post-transplant T-cell clones (23/120; 19%) was capable of undergoing autocrine proliferation. By contrast, 21/65 (32%) normal control clones from the marrow donors derived under the same conditions were autocrine proliferative. All clones were interleukin-2 (IL-2) responsive. A majority (12/17; 71%) of autocrine proliferating post-transplant clones secreted detectable IL-2. Compared with control clones, CD4+ T-cell clones derived early after BMT produced decreased levels of interleukin-4 (IL-4) and interleukin-6 (IL-6), whereas secretion of interleukin-3 (IL-3) and granulocyte/macrophage colony-stimulating factor (GM-CSF) showed no significant difference. The small number (n = 8) of posttransplant CD8+ clones showed decreased production of IL-3, IL-4 and IL-6 compared with control clones, but normal secretion of GM-CSF. Neither CD4+ nor CD8+ T-cell clones secreted interleukin-7 (IL-7).
 ...
PMID:Secretion of IL-2, IL-3, IL-4, IL-6 and GM-CSF by CD4+ and CD8+ TCR alpha beta+ T-cell clones derived early after allogeneic bone marrow transplantation. 832 61

Short-term liquid marrow culture (STLMC) is a potential source for autografting in leukemia. In a preclinical setting, including candidates for autologous marrow transplantation, we have studied STLMC supported by a selected mixture of clinical available recombinant human haematopoietic growth factors. STLMC of leukemic marrow cells were prospectively performed to evaluate the purging effect. Bone marrow cells cultured and supported by the selected mixture of rhIL-3/rhGM-CSF/rhEpo revealed an increased number of day 10-12 cultured cells, parallelled by an increased proliferation rate when compared to unstimulated cultures. The median number of myeloid progenitors recognized as day 7 and day 14 granulocyte-macrophage colony-forming units (day 7/14 GM-CFU) was significantly increased in the supported STLMC to 145/305 from 105/115 per ml culture (n = 7, p < 0.01). Further addition of rhKL did not enhance the numbers of day 7 or day 14 GM-CFUs per ml culture. In no instance was the number of clonogenic cells at the end of culture greater than the input day 0, except in cultures of purified CD34-positive marrow progenitors which resulted in an expansion of late myeloid progenitors. Cytokine-supported cultures of leukemic marrow cells from acute myeloid (n = 14) and lymphoblastic (n = 7) leukemia patients were established at the time of diagnosis. In the supported cultures, the cell number increased for myeloblast but was unchanged for lymphoblast leukemic marrow cells compared to non-supported cultures. Immunophenotypic and cytogenetic studies of selected leukemic cell samples identified unchanged myeloid or slightly reduced frequencies of lymphoblastic leukemic cells at the end of culture. This preclinical study supports the idea that the addition of a mixture of clinical available haemopoietic cytokines to STLMC increases the recovery of detectable myeloid progenitors which may enhance myeloid regeneration after autografting. No substantial selective loss of myeloid leukemic cells was found in the cytokine-supported short-term culture system.
Leukemia 1993 Sep
PMID:Short-term liquid marrow cultures are supported by a mixture of haematopoietic cytokines but do not purge for acute myeloid or lymphoid leukemic marrow cells. 837 91

An adoptive transfer immunization/fusion protocol in mice has been successfully used to raise a series of monoclonal antibodies directed against the Human Interleukin for DA-1a (HILDA)/Leukemia Inhibitory Factor (LIF) cytokine. These antibodies which were raised using recombinant HILDA/LIF purified from conditioned medium of transfected Chinese Hamster Ovary (CHO) cells also react with natural HILDA/LIF from the HSB2 T lymphoma cell line and unglycosylated HILDA/LIF produced in E. coli. They define four separate epitopes, one of which is involved in receptor binding and induction of biological activity. A sensitive sandwich immunoradiometric assay which is linear up to 5 ng/ml HILDA/LIF and can detect as low as 25 pg/ml of the cytokine has been developed.
Cytokine 1993 Jan
PMID:Generation of monoclonal antibodies against HILDA/LIF and their use in the quantitative assay of the cytokine. 848 3

The beta-type receptor of platelet-derived growth factor (beta PDGFR) is a class III transmembrane receptor with tyrosine kinase activity. The beta PDGFR gene is located on mouse chromosome 18 close to the c-fms gene which codes for the colony stimulating factor-1 receptor (CSF-1R). We previously reported that in a high percentage of myeloblastic leukemias induced by the Friend helper murine leukemia virus (F-MuLV), proviruses were integrated in the first intron of the c-fms gene leading to an enhanced expression of c-fms mRNA. Since activation by proviral insertion can act at long distance, we studied beta PDGF receptor gene expression in murine myeloblastic leukemias. This gene was found to be frequently expressed but the level of beta PDGF receptor mRNA was weak and not related to proviral activation. High affinity binding sites were expressed on myeloblastic cells and ligand binding induced cell proliferation. To determine whether beta PDGFR expression is a common feature in hematopoietic cells, we tested cell lines belonging to other hematopoietic lineages. We found that multipotent stem and mast cell lines also expressed the beta PDGF receptor gene. This suggests that PDGF, known as a mitogen for connective tissue cells, could also play a role in normal hematopoiesis.
Cytokine 1993 Jan
PMID:Expression of functional beta-platelet-derived growth factor receptors on hematopoietic cell lines. 848 8

Leukaemia Inhibitory Factor (LIF), an interleukin 6 (IL-6)-type cytokine, is an essential growth factor for murine embryonal stem cells. The LIF-receptor was known in these cells, but the cell-internal part of the signal cascade and the transcription factors through which LIF controls its growth-promoting target genes in embryonal stem cells, had not been identified. This study shows that the type II IL-6-response element of the rat alpha 2 macroglobulin (alpha 2M) gene, which mediates IL-6- and LIF-responses in hepatic cells, also functioned as a LIF-response element (LIF-RE) in ES1 embryonal stem cells and P19 embryonal carcinoma cells. It conferred transcriptional activation by LIF of transfected reporter constructs in these cells. A characteristic DNA-binding activity interacting with this LIF-RE was induced by treatment of these cells with LIF. The complex between this activity and the LIF-RE had identical electrophoretic mobility, sequence-specificity and kinetics of induction as the complex with the corresponding LIF-response factor (LIF-RF) from hepatic cells. The transcription factor STAT3 was part of this complex, as shown by its reactivity with anti-STAT3 antibodies. Withdrawal of LIF from ES1 cells caused the induction of differentiation and the disappearance of this DNA-binding activity. Simultaneously, the surface density of high-affinity LIF receptors was reduced approximately 10-fold.
Cytokine 1995 Aug
PMID:The LIF response element of the alpha 2 macroglobulin gene confers LIF-induced transcriptional activation in embryonal stem cells. 858 Mar 64

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.
Cytokine 1995 Aug
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


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