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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression and function of CSF-1 and its receptor were studied in tumors of the human breast, ovary, and endometrium. CSF-1 and its receptor, initially implicated as essential to normal monocyte development and trophoblastic implantation, have been more recently shown to be expressed by carcinomas of the breast and other epithelia of the female reproductive tract where activation of the receptor by ligand produced either by the tumor cells or by stromal elements stimulates tumor cell invasion by a urokinase-dependent mechanism. Breast carcinomas express wild-type CSF-1 receptors (CSF-1R) at levels comparable to those observed in trophoblast and monocytes. Ovarian and endometrial carcinomas express significantly lower levels of wild-type, functional CSF-1Rs, while ovarian carcinomas also express unusual transcripts that diverge from the wild-type CSF-1R transcript in their 5' extracellular domain sequences. Tumor cell expression of CSF-1R is under the control of several steroid hormones (glucocorticoids and progestins) and the binding of several bHLH transcription factors, while tumor cell expression of CSF-1 appears to be regulated by other hormones, some of which are involved in normal lactogenic differentiation. In addition, tumor cells often produce CSF-1 at such high levels that the cytokine spills into the extracellular fluid and circulation. Measurements of circulating levels of CSF-1 have proved useful in patients with ovarian, endometrial, and breast carcinoma both for disease detection and monitoring of response to therapy. CSF-1 and its receptor appear to be an important receptor/ligand pair in the biology of breast cancers and tumors of the female reproductive tract where they may regulate functions similar to those they control during macrophage activation and placental implantation.
Mol Reprod Dev 1997 Jan
PMID:CSF-1 and its receptor in breast carcinomas and neoplasms of the female reproductive tract. 898 66

Infiltration of monocytes into arteries is an early event in the pathogenesis of atherosclerosis. This recruitment is interpreted as enhancing lesion development, but it could also be a host response limiting lipid accumulation. The ability of macrophages to limit cholesterol uptake, however, can be reduced by the impaired mobility and metabolic activity associated with foam cell development. As lesions enlarge, foam cells die and become the nidus for the necrotic core. Treatments to improve viability might improve foam cell function and promote regression. Macrophage colony-stimulating factor (M-CSF) is vital to monocyte/macrophage differentiation, proliferation, and activation. We found that foam cells of Watanabe heritable hyperlipidemic (WHHL) rabbits had faint staining for M-CSF. Treatment of rabbits with recombinant human M-CSF (rhM-CSF) increased M-CSF staining, which correlated with reduced cholesterol content of these foam cells.
Mol Reprod Dev 1997 Jan
PMID:Immunoreactive macrophage colony-stimulating factor is increased in atherosclerotic lesions of Watanabe heritable hyperlipidemic rabbits after recombinant human macrophage colony-stimulating factor therapy. 898 69

A human tryptophan hydroxylase intron seven polymorphism previously associated with low CSF 5-HIAA and suicidal behavior was sequenced and characterized for its potential role in TPH pre-mRNA splicing. Two polymorphic sites were identified: A218C and A779C. The 779A allelic frequency in various populations ranged from 0.43 to 0.61 and was in strong linkage disequilibrium with the A218C site. A218C provides a site for restriction fragment length polymorphism analysis. TPH mRNA was reverse-transcribed and sequenced. No aberrant splice products from the 779A or 779G TPH genes were detected nor were any other polymorphic nucleotides found.
Brain Res Mol Brain Res 1997 Apr
PMID:Sequence, splice site and population frequency distribution analyses of the polymorphic human tryptophan hydroxylase intron 7. 910 82

A profound inflammatory response is initiated immediately following traumatic brain injury (TBI) and is characterized by the release of several cytokines with pro- and anti-inflammatory functions. In order to elucidate which cytokines are released in the human brain in response to injury as well as in the peripheral compartment, IL-1, IL-6, IL-8, IL-10, TNF-alpha and TGF-beta were monitored in CSF and serum of severely brain-injured patients. Furthermore, we investigated the possible modulation of systemic reactions by IL-6 and the ability of IL-6 and IL-8 to promote the synthesis of nerve growth factor.
Mol Psychiatry 1997 Mar
PMID:Production of cytokines following brain injury: beneficial and deleterious for the damaged tissue. 910 36

Abnormal deposition and accumulation of Alzheimer's amyloid beta-protein (A beta) and degeneration of forebrain cholinergic neurons are among the principal features of Alzheimer's disease. Studies in rat model systems have shown that forebrain cholinergic deficits are accompanied by induction of cortical beta-amyloid precursor protein (beta-APP) mRNAs and increased levels of secreted beta-APP in the CSF. The studies reported here determined whether the CSF levels of secreted beta-APP could be altered pharmacologically. In different experiments, rats with lesions of the forebrain cholinergic system received injections of vehicle, a muscarinic receptor antagonist scopolamine, or one of two cholinesterase inhibitors - diisopropyl phosphorofluoridate (DFP) or phenserine. Scopolamine was administered to determine whether the levels of beta-APP in the CSF could be increased by anticholinergic agents. The cholinesterase inhibitors were administered to determine whether the forebrain cholinergic system lesion-induced increases in CSF beta-APP could be reduced by cholinergic augmentation. Scopolamine administration led to a significant increase in the CSF levels of secreted beta-APP in sham-lesioned rats. Phenserine, a novel, reversible acetyl-selective cholinesterase inhibitor, significantly decreased the levels of secreted beta-APP in the CSF of forebrain cholinergic system-lesioned rats whereas DFP, a relatively non-specific cholinesterase inhibitor, failed to affect CSF levels of secreted beta-APP. These results suggest that the levels of secreted beta-APP in the CSF can be pharmacologically modulated but that this modulation is dependent upon the status of the forebrain cholinergic system and the pharmacological properties of the drugs used to influence it.
Brain Res Mol Brain Res 1997 Jun
PMID:Pharmacological modulation of Alzheimer's beta-amyloid precursor protein levels in the CSF of rats with forebrain cholinergic system lesions. 919 Oct 90

We compared the production of recombinant human granulocyte colony-stimulating factor (rhG-CSF) by Chinese hamster ovary (CHO) cells in a transient expression system, using different analogous vectors carrying a human G-CSF-encoding cDNA under the transcriptional control of the murine cytomegalovirus (CMV) major immediate early promoter. Comparison of two transcription units carrying a human (h)G-CSF cDNA deleted of 3'-untranslated (UTR) sequences containing AT-rich elements (ARE) and using 3'-UTR sequences for processing of transcripts from the SV40 early region or from the rabbit beta 1-globin gene showed that use of the sequences from the rabbit beta 1-globin gene resulted in 7- to 12-fold higher levels of rhG-CSF production. Deletion of ARE of hG-CSF cDNA resulted in increased rhG-CSF synthesis when transcription units using 3'-UTR sequences from the rabbit beta 1-globin gene were compared. By contrast, deletion of ARE did not appear to affect rhG-CSF production when 3'-UTR sequences from the SV40 early region were used. The most efficient G-CSF transcription unit, fused to a dihydrofolate reductase (DHFR) marker gene and transfected into a CHO cell line, yielded initial transfectant CHO cell lines secreting up to 21 micrograms rhG-CSF/1 x 10(6) cells in 24 h. After two rounds of DHFR gene amplification, a cell line was isolated that contains approx 12 copies of the vector and produces rhG-CSF at a rate of 90 micrograms/1 x 10(6) cells in 24 h.
Mol Biotechnol 1997 Jun
PMID:High-level expression of a cDNA for human granulocyte colony-stimulating factor in Chinese hamster ovary cells. Effect of 3'-noncoding sequences. 921 37

We present here the case of a Japanese female patient with aplastic anemia who developed monosomy 7 and clonal evolution following a treatment with recombinant human granulocyte colony-stimulating factor (rhG-CSF). At the onset of aplastic anemia, cytogenetic analysis was 46, XX and X-inactivation/methylation analysis revealed a polyclonal pattern. After 4 months of administration of rhG-CSF, she had 45, XX, -7 and a clonal pattern, although there were no morphological evidence of a myelodysplastic syndrome or leukemia. The ratio of monosomy 7 to normal analyzed by fluorescence in situ hybridization decreased after discontinuation of rhG-CSF and there were still no dysplastic changes and/or increased numbers of blasts. These results indicate that the acquisition of monosomy 7 following rhG-CSF treatment dose not always cause clonal evolution to induce hematological malignancies.
Blood Cells Mol Dis 1997 Aug
PMID:The evidence of clonal evolution with monosomy 7 in aplastic anemia following granulocyte colony-stimulating factor using the polymerase chain reaction. 923 59

The existence of a biochemical network of embryo-maternal communication implies that various secreted molecules constitute a signal-response mechanism, important for the process of embryo implantation in mammals. Here we report the purification of a protein with an apparent molecular weight of 136 kDa, responsible for a 2000-fold increase in embryo-derived histamine-releasing factor (EHRF) activity. This protein, purified from medium from the in-vitro culture of 2-8-cell human embryos, by means of affinity chromatography, was capable of binding immunoglobulin (Ig)E as demonstrated by immunoblotting and enzyme-linked immunosorbent assays. We found EHRF was capable of inducing release of histamine and cytokines in vitro from rat uterine tissue, collected on day 4 of pregnancy (preimplantation stage of embryo development). When EHRF was used as a secretagogue, granulocyte macrophage-colony stimulating factor (GM-CSF) release increased from 3 to 55 pg/g (P < 0.01) and tumour necrosis factor-alpha (TNF-alpha) release increased from 0 to 2.1 ng/g (P < 0.01), as detected by enzyme-linked immunosorbent assay. A simple method was used to purify uterine mast cells using an IgE-Sepharose affinity chromatography column and the purity (90%) was checked with Dynabeads coupled to specific rat IgE antibody. When purified mast cells were stimulated with EHRF in the same way as the uterine explants, a similar pattern of GM-CSF and TNF-alpha release was obtained. We also describe the reverse transcription-polymerase chain reaction (RT-PCR) of GM-CSF and TNF-alpha mRNA from purified uterine mast cells. On day 4 of pregnancy only the mRNA of TNF-alpha was found and this increased after stimulation with the EHRF. In conclusion, the data presented suggest that uterine mast cells isolated during the preimplantation stage release cytokines in vitro following interaction with an embryo factor.
Mol Hum Reprod 1996 Oct
PMID:A factor secreted by human embryo stimulates cytokine release by uterine mast cell. 923 97

Anesthetic agent, arterial pCO2 level, and opioid peptides have all been implicated in the pathophysiology of experimental stroke models. The effects of halothane, alpha-chloralose, and differing concentrations of arterial pCO2 on injury volume and CSF beta-endorphin levels were studied in a feline model of experimental focal cerebral ischemia. The type of anesthetic agent used had no effect on injury volume following 6 h of focal cerebral ischemia. Over a 6-h period, beta-endorphin levels significantly increased from 10.1 +/- 5.0 fmol/mL at zero time to 14.4 +/- 7.2 fmol/mL at 6 h under halothane anesthesia (p < 0.05), whereas they did not significantly change (10.1 +/- 6.7 to 7.8 +/- 4.7 fmol/mL) under alpha-chloralose anesthesia. In contrast, hypercapnia had no effect on beta-endorphin levels, but significantly increased injury volume from 30.6 +/- 5.7% of the ipsilateral hemisphere under normocapnic conditions to 37.1 +/- 5.9% under hypercapnic conditions (p < 0.05). These results suggest that hypercapnia increases injury volume in a feline model of focal cerebral ischemia, and pCO2 should be controlled in experimental focal cerebral ischemia models.
Mol Chem Neuropathol 1997 May
PMID:Effects of halothane, alpha-chloralose, and pCO2 on injury volume and CSF beta-endorphin levels in focal cerebral ischemia. 927 Oct 3

In an attempt to find new agents that promote differentiation and have therapeutic potential in acute myeloid leukemias, we have studied the effect of recombinant human granulocyte colony stimulating factor (rhG-CSF) on the Kasumi-1 AML2 t(8; 21) cell line. Upon incubation with rhG-CSF (0.2-2000 ng/ml), Kasumi-1 cells showed a peak of cell growth, with a subsequent decrease of cell survival after 4 days of culture. At that time, more than 80% of the cell population expressed myeloid differentiation antigens (CD11b, CD13, CD15 and CDw85), and increased G-CSF receptors. Gel shift assays were performed with nuclear extracts of Kasumi-1 cells after 1, 5, 10, 15, 30 and 60 min incubations with G-CSF and oligonucleotides containing the high-affinity SIF-binding site. At least three specific complexes were obtained, and shown by supershift assays to be STAT3/STAT3, STAT1/STAT3 and STAT1/STAT1 dimers. These results suggest that in G-CSF-sensitive Kasumi-1 cells, normal JAK-STAT pathways are activated, providing a further molecular basis for the effect of G-CSF in these cells.
Cytokines Cell Mol Ther 1997 Jun
PMID:G-CSF activates STAT pathways in Kasumi-1 myeloid leukemic cells with the t(8; 21) translocation: basis for potential therapeutic efficacy. 928 46


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