Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression "immunocompromised host" refers to an individual who has one or more defects in the body's natural defense, which leads to severe, often life-threatening, infections. Alcoholism, diabetes mellitus, advanced age, the use of antacids, and viral infections have immune-modulating effects. The human immunodeficiency virus, cytomegalovirus, Epstein-Barr virus, and Non A, Non B hepatitis virus also contribute to immunosuppression. The lung has a special vulnerability to infection, and pneumonia accounts for more than 40% of deaths in the immunosuppressed population. Diagnostic methods include detection of microbial antigens by monoclonal antibodies, DNA sequences by the polymerase chain-reactions or DNA probes, and unique metabolites of pathogens by gas chromatography. Transtracheal aspiration was used to obtain uncontaminated respiratory secretions, but fiberoptic bronchoscopy with shielded brush and bronchoalveolar lavage (BAL) is a better means of diagnosis because of a 90% sensitivity in diagnosing pneumocystis infection. Percutaneous aspiration and open lung biopsy are reserved for more complicated cases. Empiric treatment is justified in far advanced AIDS or relapsed myelogenous leukemia with limited life expectancy, or when there is uncontrollable bleeding diathesis or impaired pulmonary function as invasion diagnostic procedures will not be tolerated. The most important antiinfective measure is careful hand washing, while prophylactic antibiotics, selective decontamination, and antifungal, antiviral, and antiparasitic agents can be used. Active and passive immunization against specific pathogens, immunological reconstitution with granulocyte-macrophage colony-stimulating factor (GM-CSF) and reducing the dosage of immunosuppression are the other strategies for prevention. In the last several decades there has been substantial progress in the management of chronic diseases which used to be fatal.
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PMID:Pulmonary infections in the immunocompromised host. 166 54

The pathogenic effects of human cytomegalovirus (CMV) infection in vitro on hematopoiesis were investigated. Normal human bone marrow cells from both seronegative and seropositive donors were challenged with CMV (Towne or wild-type strain) and tested for their responsiveness to the recombinant hematopoietic growth factors granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-CSF (G-CSF), respectively. Regardless of the serostatus of the donor, infection with CMV resulted in a significant decrease in the proliferation and colony formation of hematopoietic progenitor cells in response to both growth factors, with more pronounced suppression in response to G-CSF being observed. Evaluation of the colony composition revealed a profound decrease in colonies of the granulocytic (CFU-G), or granulocyte-macrophage (CFU-GM) lineages, while suppression of multipotential (CFU-GEMM) and erythroid (BFU-E) colony-forming cells occurred after infection with wild-type but not the laboratory strain of CMV. Although no evidence of productive virus infection could be seen in colony-forming cells, in situ hybridization studies and immunohistochemical staining revealed the presence of CMV-specific mRNA and immediate-early antigens, demonstrating that a small proportion of cells were abortively infected. These studies demonstrate that CMV can infect bone marrow progenitor cells and interfere with normal hematopoiesis in vitro, which may help to explain the hematologic defects seen during acute infections with CMV in vivo.
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PMID:Preferential suppression of myelopoiesis in normal human bone marrow cells after in vitro challenge with human cytomegalovirus. 169 91

Ganciclovir is effective in halting or delaying the progression of cytomegalovirus (CMV) retinitis in patients with acquired immune deficiency syndrome (AIDS). However, the development of neutropenia necessitates the interruption of ganciclovir therapy in 40-50% of AIDS patients. In an ongoing randomized, controlled trial, AIDS patients with CMV retinitis are receiving standard ganciclovir therapy or ganciclovir plus recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF). rHuGM-CSF is administered by daily subcutaneous injections and is given in ascending doses based on the neutrophil response in the individual patient. Preliminary data obtained from 36 evaluable patients (21 receiving ganciclovir alone, 15 receiving ganciclovir plus rHuGM-CSF) suggest that rHuGM-CSF administration is associated with a trend toward a decrease in the proportion of patients developing an absolute neutrophil count (ANC) of less than 750 cells/microliter (40% vs. 59%), in the overall incidence of such neutropenic episodes (20 vs. 68), and in the duration of ganciclovir treatment interruption due to the development of an ANC of less than 500 cells/microliter (5.5 days vs. 10.1 days). rHuGM-CSF administration has been generally well tolerated, and no consistent proliferative effect of this agent on human immunodeficiency virus infection has been observed. Definitive conclusions regarding the coadministration of rHuGM-CSF and ganciclovir await completion of the trial.
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PMID:Combined ganciclovir and recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of cytomegalovirus retinitis in AIDS patients. 184 18

Ganciclovir currently is the only agent approved for use in the treatment of cytomegalovirus (CMV) retinitis in immunocompromised patients, including those with the acquired immune deficiency syndrome (AIDS). Its effect against CMV in vitro and in vivo suggests its usefulness in other types of CMV infection as well. Investigations of the use of this agent in the treatment of AIDS patients with CMV gastrointestinal disease and in the treatment or prevention of CMV disease in transplant recipients are ongoing. In other studies, issues important to the management of patients receiving ganciclovir therapy are being addressed. Particular objectives include characterizing the scope of ganciclovir resistance in CMV, detailing the prospects for the tolerance of coadministered ganciclovir and zidovudine, and determining the plausibility of enhancing drug delivery through the concomitant use of recombinant human granulocyte-macrophage colony-stimulating factor and through oral administration of the agent.
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PMID:Future directions in the management of cytomegalovirus infections. 184 23

Immunotherapy can be defined as treatment directed at augmenting host immune defence mechanisms. Non-antimicrobial therapies and immunoprophylaxis in bone marrow transplantation (BMT) can be subdivided into three broad categories: passive immunotherapy with intravenous immunoglobulin (IVIG); cytokine therapy; and anti-endotoxin-directed treatments. Most studies using IVIG in BMT are prophylactic and suffer from variability in study design, type of IVIG and dosing regimens. Various effects on viral and bacterial infections and graft-versus-host disease (GVHD) have been reported but few if any have shown benefit in terms of improved patient survival. Moreover the immunomodulatory effect of immunoglobulin G preparations is frequently overlooked. With the exception of cytomegalovirus (CMV) pneumonitis, there is little evidence of benefit in the treatment of established infections and the relative benefits of hyperimmune preparations are poorly established. The development of haemopoietic growth factors has led to the widespread use of cytokines in BMT. The benefits of these agents both in the prevention of fever and infection and as adjuvants to standard antimicrobial therapy in established infection (e.g. invasive mycoses) are rapidly becoming apparent. Both human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and granulocyte colony-stimulating factor (rhG-CSF) have been shown to accelerate granulocyte recovery following BMT and reduce fever days, antibiotic usage and hospitalization. RhGM-CSF appears superior in these respects. The roles of interleukin 1 (IL1), IL3, IL6 and interferons are also under evaluation. As with the much publicised studies using anti-endotoxin antibodies as therapy in sepsis, there is little evidence of benefit in the few studies performed in BMT patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunotherapy and immunoprophylaxis in bone marrow transplantation. 756 Sep 54

The efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in graft failure after bone marrow transplantation (BMT) has been evaluated in 25 patients. rhGM-CSF was administered intravenously at a dose of 5 or 10 micrograms/kg. Fourteen patients (seven allogeneic BMT [allo-BMT], seven autologous BMT [ABMT]) were treated for primary bone marrow failure (no granulocyte recovery after BMT), and 11 cases (all allo-BMT) received rhGM-CSF for secondary bone marrow failure (absolute neutrophil count lower than 0.5 x 10(9)/L after a previously sustained granulocyte recovery). Two allo-BMT and three ABMT patients with primary bone marrow failure achieved a granulocyte response to rhGM-CSF. In contrast, nine patients with primary graft failure did not respond to rhGM-CSF (four ABMT, three HLA-identical T-depleted BMT, one minor mismatch BMT, one unrelated BMT). Ten of 11 allo-BMT patients treated for secondary bone marrow failure attained an ANC higher than 0.5 x 10(9)/L, but most became severely neutropenic again at a median time of 4 weeks. The possible cause triggering graft failure (graft-vs.-host disease [GVHD], cytomegalovirus [CMV] infection) remained unsolved in most of these cases. Actuarial probability of survival of the entire series was 16 +/- 9% at 15 months. The severity of graft failure and the presence of other concomitant complications in most of our patients may justify these poor results. In conclusion, rhGM-CSF had less efficacy in patients with primary bone marrow failure than in those with secondary bone marrow failure. In the latter setting, measures addressed to correct the initial cause of graft failure are mandatory.
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PMID:Different response to recombinant human granulocyte-macrophage colony-stimulating factor in primary and secondary graft failure after bone marrow transplantation. 801 72

Recently, considerable interest has arisen as to use cord blood (CB) as a source of hematopoietic stem cells for allogenic transplantation when bone marrow (BM) from a familial HLA-matched donor is not available. Because human cytomegalovirus (HCMV) has been shown to inhibit the proliferation of BM progenitors in vitro, it was important to examine whether similar effect could be observed in HCMV-infected CB cells. Therefore, the effect of HCMV challenge on the proliferation of myeloid progenitors from BM and CB was compared using both mononuclear cells (MNC) and purified CD34+ cells. A clinical isolate of HCMV inhibited the colony formation of myeloid BM progenitors responsive to granulocyte-macrophage colony-stimulating factor (CSF), granulocyte-CSF, macrophage-CSF, interleukin-3 (IL-3) and the combination of IL-3 and stem cell factor (SCF). In contrast, colony growth of CB progenitors was not affected. In addition, HCMV inhibited directly the growth of purified BM CD34+ cells responsive to IL-3 and SCF in single cell assay by 40%, wheras the growth of CD34+ progenitors obtained from CB was not suppressed. The HCMV lower matrix structural protein pp65 and HCMV DNA were detected in both CB and BM CD34+ cells after in vitro challenge. However, neither immediate early (IE)-mRNA nor IE proteins were observed in infected cells. Cell cyclus examination of BM and CB CD34+ cells revealed that 25.7% of BM progenitors were in S + G2/ M phase wheras only 10.7% of the CB progenitors. Thus, a clinical isolate of HCMV directly inhibited the proliferation of myeloid BM progenitors in vitro wheras CB progenitors were not affected. This difference in the susceptibility of CB and BM cells to HCMV may partly be caused by the slow cycling rate of naive CB progenitors compared to BM progenitors at the time of infection.
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PMID:Direct growth suppression of myeloid bone marrow progenitor cells but not cord blood progenitors by human cytomegalovirus in vitro. 883 43

Macrophages are putative target cells for expressing an exogenous gene with therapeutical effects. Knowing that macrophages express membrane lectins mediating endocytosis of their ligands, DNA/glycosylated polylysine complexes were used to transfect human blood monocyte-derived macrophages. Monocytes from human peripheral blood were matured in culture for 7 days to differentiate into macrophage-like cells in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF). Adherent cells, which displayed characteristic macrophage markers, CD 14, CD 11b, HLA-DR, and HLA-ABC antigens and mannose receptor, were transfected by DNA/glycosylated polylysine complexes in the presence of chloroquine. The luciferase reporter gene expression was maximal 24 hr after transfection with a DNA/mannosylated polylysine complex and by using plasmids in which the promoters (either the long terminal repeat of the human immunodeficiency virus or the human cytomegalovirus) drove the luciferase gene expression. Luciferase gene expression was lower when the promoter was the early region of the large T antigen of SV40 virus. Transfection mediated by DNA/mannosylated polylysine complexes was much more efficient than with DEAE-dextran or lipofectin. The possibility of transferring and expressing an exogenous gene into macrophage-like cells by using a nonimmunogenic synthetic vector as a DNA carrier opens new ways to develop nonviral gene therapy strategies.
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PMID:Gene transfer by DNA/glycosylated polylysine complexes into human blood monocyte-derived macrophages. 891 94

Selective lineage differentiation depends upon the combined action of several colony-stimulating factors. Here we describe 3 human granulocyte-macrophage colony-stimulating factor-erythropoietin (GM-CSF-EPO) hybrid proteins generated by recombination of the relevant cDNAs. The expression vector containing the murine cytomegalovirus (mCMV) promoter and dihydrofolate reductase (DHFR) gene was used for the expression of the hybrid genes in Chinese hamster ovary (CHO) cells. Purified hybrid proteins from CHO transfectant cultures induced proliferation of both EPO and GM-CSF dependent cell lines. The clonogenic test, performed on purified human hematopoietic precursor cells, indicates that the hybrid proteins are more efficient at inducing erythroid differentiation compared with the equimolar mixture of GM-CSF and EPO.
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PMID:Production of recombinant human GM-CSF-EPO hybrid proteins: in vitro biological characterization. 933 22

Induction or short-term transgenic expression of specific cytokines, growth factors, or other candidate therapeutic genes in hematopoietic progenitor or stem cells is potentially applicable to gene therapy for cancer. In this study, we explored the application of a gene gun technique, as an alternative to viral vectors, for ex vivo gene transfer into and transient gene expression in highly enriched CD34+ cells derived from human umbilical cord blood. Twenty-four hours posttransfection, 32.6 to 1500 pg/l x 10(6) CD34+ cells of transient gene expression was routinely obtained for specific cytokine and reporter genes. Transgene expression at the single-cell level was revealed by X-Gal staining of lacZ cDNA-transfected CD34+ cells. Expression of four candidate therapeutic genes, namely human granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha, interleukin 2, and interferon gamma, was detectable for 4 to 7 days in CD34+ cells. A human elongation factor 1alpha promoter/intron 1 transcription unit was identified as a strong cellular promoter for CD34+ cells, exhibiting strength similar to that of the commonly employed cytomegalovirus immediate-early promoter. These results suggest that the nonviral, gene gun technique offers an efficient alternative approach for transient transgenic studies of hematopoietic cells and may provide new possibilities for certain cancer gene therapy strategies using CD34+ cells.
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PMID:Cytokine transgene expression and promoter usage in primary CD34+ cells using particle-mediated gene delivery. 979 4


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