Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Murine peritoneal thioglycollate-elicited macrophages were cultured for 3 days in the presence or absence of highly purified human macrophage colony stimulating factor (CSF-1). The cells were then challenged with vesicular stomatitis virus (VSV) for 24 hr. Ability to resist viral infection was measured in two ways. First, macrophage viability after infection with VSV was measured by washing to remove dead cells, staining the remaining cells with crystal violet, and reading absorbance. Second, a yield reduction assay was used to measure viral replication in the macrophage cultures. Cells treated with CSF-1 (500 to 2000 U/ml) and infected with VSV looked similar microscopically to uninfected cells and had absorbance values twofold to threefold higher than those of infected cultures not treated with CSF-1. The CSF-1-treated cultures also had a virus titer one log lower than that of the untreated cultures. Treatment with partially purified murine CSF-1 induced a similar reduction in virus titer, whereas other murine CSF tested (purified murine GM-CSF, lung-conditioned medium that contains GM-CSF and G-CSF, and WEHI-3B-conditioned medium as a source of IL 3) had little to no effect on virus titer. Antibody to murine IFN-alpha/beta added to the macrophage cultures inhibited the protective effect of CSF-1, indicating that the CSF-1 effect was due to induction of endogenous IFN. Treatment with lipopolysaccharide (1 ng/ml) had some protective effect, which was blocked with polymyxin B. Polymyxin B did not inhibit the effect of CSF-1.
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PMID:CSF-1-induced resistance to viral infection in murine macrophages. 303 81

We retrospectively reviewed the regimen-related toxicity associated with busulphan (1 mg/kg orally QID days -7 to -4) and cyclophosphamide (60 mg/kg IV days -3 and -2) (Bu/Cy) chemotherapy in 69 consecutive patients who underwent autologous bone marrow transplantation (ABMT). Twenty-four patients received bone marrow (BM) alone, 22 received BM plus post-transplant granulocyte-colony stimulating factor (G-CSF) and 23 received peripheral blood progenitor cells (PBPC) +/- BM plus post-transplant G-CSF. Toxicity was scored using the criteria of Bearman. Grade II and III toxicities included mucosa (38%), liver (8%), central nervous system (5%), kidney (5%), heart (3%), pericardium (2%), bladder (2%) and lung (2%). There were five treatment related deaths (7%) from pneumonitis (2) and veno-occlusive disease, pulmonary hemorrhage and sepsis (1 each). Post-transplant G-CSF (+/- PBPC) resulted in a trend (p = 0.07) towards a reduction in post-transplant stomatitis, but did not impact on the already low incidence of other organ toxicities. As Bu/Cy for ABMT is associated with minimal non-hemopoietic toxicity, the addition of other cytotoxic agents is justified in an attempt to augment the anti-tumour effect of this conditioning regimen.
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PMID:High dose busulphan/cyclophosphamide for autologous bone marrow transplantation is associated with minimal non-hemopoietic toxicity. 752 88

To confirm the reported correlation of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) serum concentrations with nonhematologic toxicity after cytotoxic chemotherapy and to examine their possible effects on hematopoiesis, we evaluated serum TNF-alpha and IL-6 concentrations every 3 days during 21 chemotherapy cycles in 11 patients with acute myelogenous leukemia (AML) and one patient with chronic myelogenous leukemia in blast crisis (CML-BC). All patients developed grade IV hematologic toxicity. In 13 patient cycles, grade III-IV nonhematologic toxicity developed: hepatic (nine), pulmonary (six), and stomatitis (five). In these patient cycles, IL-6 concentrations increased from 10.1 pg/mL (4.6-15.6, 95% CI) before nonhematologic toxicity to 64.8 (5.3-124.2, 95% CI) at the onset of toxicity (p = 0.02). TNF-alpha concentrations were not detectable before nonhematologic toxicity but increased to 20.4 pg/mL (not detectable [ND]-45.5, 95% CI) at the onset of grade III-IV toxicity. In six patient cycles, grade II nonhematologic toxicity developed: hepatic (five), pulmonary (one), and stomatitis (two). In these six, IL-6 concentrations increased from 12.1 pg/mL (6.8-17.4, 95% CI) before toxicity to 21.4 (11-31.8, 95% CI) at the onset of toxicity (p = 0.03). TNF-alpha concentrations were detectable in one patient cycle before toxicity and detectable in only two patient cycles at the onset of toxicity. The peak IL-6 and TNF-alpha concentrations did not correlate with the onset of nonhematologic toxicity in 87% of patient cycles. In patient cycles with a cumulative IL-6 area-under-the-serum concentration vs. time curve (AUC) > 1000 pg/mL.d, platelet recovery (> 30 x 10(9)/L and platelet transfusion-independent) occurred earlier at 21.9 days (18.7-25.1, 95% CI) compared to the 30.6 days (23.6-37.5, 95% CI, p = 0.02) in patient cycles with an IL-6 AUC < 1000 pg/mL.d. Patient cycles with a cumulative TNF-alpha AUC > 150 pg/mL.d required a mean of 17.5 units of red blood cells (RBCs) (9.3-25.7, 95% CI) compared to patient cycles with an AUC < 150 pg/mL.d, which required only 8.9 units of RBCs (6.2-11.7, 95% CI, p = 0.03). The peak concentration and AUC for IL-6 and TNF-alpha were not significantly different between those receiving growth factors (G-CSF, six; GM-CSF, one) and those not receiving growth factors (14). Endogenous IL-6 and TNF-alpha serum concentrations increase in patients who experience nonhematologic toxicity and correlate with hematologic recovery after chemotherapy.
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PMID:The influence of serum tumor necrosis factor-alpha and interleukin-6 concentrations on nonhematologic toxicity and hematologic recovery in patients with acute myelogenous leukemia. 758 79

We determined the effective method of administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in patients with transitional cell carcinoma of the urothelium receiving methotrexate, etoposide and cisplatinum (MEC) therapy. Recombinant human G-CSF was administered at 2 micrograms/kg subcutaneously starting after the white blood cell count was less than 3,000/mm3 (short administration) or starting immediately after finishing MEC therapy (prophylactic administration). The median white blood cell nadir for the control group, short administration group and prophylactic administration group, was 275 +/- 77, 250 +/- 317 and 2,066 +/- 47/mm3, respectively. The number of days with a white blood count of less than 1,000/mm3 for the control group, short administration group and prophylactic administration group was 6.6 +/- 0.6, 4 +/- 2 and 0.9 +/- 0.5 days, respectively. The difference between the control group and prophylactic administration group was statistically significant (p < 0.01). These findings indicated that the prophylactic administration of rhG-CSF following MEC therapy was effective for preventing leukopenia. Other side effects of stomatitis, diarrhea and pneumonia were also decreased using rhG-CSF after MEC therapy.
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PMID:[Effect of recombinant human granulocyte colony stimulating factor in patients with transitional cell carcinoma of the urothelium receiving methotrexate, etoposide and cisplatinum combination chemotherapy]. 768 38

Double hemibody irradiation (DHBI) is an alternative treatment of stage III multiple myeloma (MM) in patients aged over 55 years. Toxic side-effects such as myelosuppression are a severe limiting factor to its use. We performed DHBI associated with human recombinant granulocyte-macrophage colony stimulating factor (hrGM-CSF) as support therapy in 10 patients with stage III MM to improve the tolerance to this treatment. Ten patients received subcutaneously 5 micrograms/kg/d of hrGM-CSF during 2 weeks after each course of hemibody irradiation. All these patients had stage III MM: eight previously received chemotherapy, six of them were regarded as patients with refractory MM and two with relapse. Two patients received DHBI as first-line treatment. hrGM-CSF increased safety and tolerance of DHBI. GM-CSF support reduced the mean time between upper body irradiation (UBI) and lower body irradiation (LBI): 41 v 108 d in a cohort of 32 patients previously treated without growth factor support. Overall there was no lethal infection with hrGM-CSF or granulocytopenia (5.0 x 10(9)/l v 0.4 x 10(9)/l at day 15 in patients without growth factor). hrGM-CSF also reduced stomatitis grading and thrombocytopenia (90 x 10(9)/l v 45 x 10(9)/l at day 15). Furthermore, hrGM-CSF increased blood colony forming unit-granulocyte macrophage (CFU-GM) and was well tolerated in all but one patient. hrGM-CSF reduces toxic side-effects of DHBI, thus providing an effective treatment in patients with advanced and resistant MM.
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PMID:Human recombinant granulocyte-macrophage colony stimulating factor (hrGM-CSF) improves double hemibody irradiation (DHBI) tolerance in patients with stage III multiple myeloma: a pilot study. 783 62

A prospective randomized study on the administration of recombinant granulocyte colony stimulating factor (rG-CSF) was conducted on 15 patients with testicular germ cell tumors. The clinical stagings of all patients except one were minimal to moderate extent according to the Indiana University staging system. Combination chemotherapy using bleomycin, etoposide and cisplatinum (BEP) was performed as the initial treatment on the eligible patients. rG-CSF was administered by two different methods; 1) routine administration on the 6th day after BEP chemotherapy (group A), and 2) the same method, but after granulocytopenia of 1,500/mm3 had developed (group B). The administration of rG-CSF in group A significantly reduced the severity of leucocytopenia and also the incidence of stomatitis compared with group B. Although rG-CSF produced no significant side effects, the thrombocytopenia was prominent in the group A patients (not significant). BEP chemotherapy itself is an easily-tolerable and well established method for treating young adult patients. The method used in group B seems to be suitable in situations where thrombocytopenia and cost effectiveness.
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PMID:[Effective administration of recombinant granulocyte colony-stimulating factor to prevent granulocytopenia due to combination chemotherapy for testicular germ cell tumors]. 891 74

Plaque-periplaque areas from MS brain tissue were explanted and propagated in tissue culture. The same in vitro techniques that successfully rescued measles virus from SSPE brain, papovavirus from PML brain, and HSV from normal human trigeminal ganglia, were applied. MS brain cells were also inoculated into chimpanzees, multiple rodent species, and embryonated hens eggs. No neurologic disease developed in experimentally infected animals, and no cytopathic effect was observed in explanted cells, or after cocultivation or fusion of MS brain cells with indicator cells. Further analysis of explanted and cocultivated cells by indirect immunofluorescence with various antiviral antisera prepared against viruses associated with post-infectious encephalomyelitis, as well as antisera to other ubiquitous viruses, failed to detect viral antigen. Finally, attempts to detect a latent enveloped virus in MS brain cells by 'superinfecting' MS brain cells in culture with vesicular stomatitis virus (VSV) did not reveal a VSV non-neutralizable fraction. Nevertheless, since oligoclonal bands (OGBs) in the CSF of patients with chronic infectious diseases of the CNS are directed against the causative agent, it is likely that OGBs in MS CSF are antibody directed against the agent or antigen that triggered disease. Although the relevant antibody may be scarce relative to irrelevant antibody in MS CSF, and only small amounts of an MS-specific antigen may be present in brain, this report provides a rationale for strategies proposed in our companion report by Owens et al which will allow detection of an MS-specific antigen or its cognate RNA in brain.
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PMID:The search for virus in multiple sclerosis brain. 934 71

Professional antigen-presenting cells, such as dendritic cells (DCs) and macrophages, are target cells for gene therapy of infectious disease and cancer. However, transduction of DCs and macrophages has proved difficult by most currently available gene transfer methods. Several recent studies have shown that lentiviral vector systems can efficiently transduce many nondividing and differentiated cell types. In this study, we examined the gene transfer to DCs and macrophages using a lentiviral vector system. Human DCs were propagated from the adherent fraction of peripheral blood mononuclear cells (PBMCs) by culture in medium containing GM-CSF, IL-4, and TNF-alpha. Human macrophages were propagated from adherent PBMCs in medium containing GM-CSF. High titers of a replication-defective vesicular stomatitis virus glycoprotein G pseudotyped HIV-1-based vector encoding the enhanced yellow fluorescent protein were produced. In immature DCs (culture days 3 and 5), transduction efficiencies of 25 to 35% were achieved at a multiplicity of infection of 100. However, the transduction efficiency was decreased in more mature DCs (culture day 8 or later). Furthermore, monocyte-derived macrophages were also transduced by the lentiviral vector system. In addition, Alu-LTR PCR demonstrated the integration of the HIV-1 provirus into the cellular genome of the transduced DCs and macrophages. Allogeneic mixed lymphocyte reactions revealed similar antigen-presenting functions of untransduced and lentivirally transduced DCs. Thus, the results of this study demonstrate that both PBMC-derived DCs and macrophages can be transduced by lentiviral vectors.
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PMID:Transduction of human PBMC-derived dendritic cells and macrophages by an HIV-1-based lentiviral vector system. 1093 28

Cell vaccines engineered to express immunomodulators have shown feasibility in eliminating leukemia in murine models. Vectors for efficient gene delivery to primary human leukemia cells are required to translate this approach to clinical trials. In this study, second-generation lentiviral vectors derived from human immunodeficiency virus 1 were evaluated, with the cytomegalovirus (CMV) promoter driving expression of granulocyte-macrophage-colony-stimulating factor (GM-CSF) and CD80 in separate vectors or in a bicistronic vector. The vectors were pseudotyped with vesicular stomatitis virus G glycoprotein and concentrated to high titers (10(8)-10(9) infective particles/mL). Human acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia cell lines transduced with the monocistronic pHR-CD80 vector or the bicistronic pHR-GM/CD vector became 75% to 95% CD80 positive (CD80(+)). More important, transduction of primary human ALL and AML blasts with high-titer lentiviral vectors was consistently successful (40%-95% CD80(+)). The average amount of GM-CSF secretion by the leukemia cell lines transduced with the pHR-GM-CSF monocistronic vector was 2182.9 pg/10(6) cells per 24 hours. Secretion was markedly lower with the bicistronic pHR-GM/CD vector (average, 225.7 pg/10(6) cells per 24 hours). Lower amounts of CMV-driven messenger RNA were detected with the bicistronic vector, which may account for its poor expression of GM-CSF. Primary ALL cells transduced to express CD80 stimulated T-cell proliferation in an autologous mixed lymphocyte reaction. This stimulation was specifically blocked with monoclonal antibodies reactive against CD80 or by recombinant cytotoxic T-lymphocyte antigen 4-immunoglobulin fusion protein. These results show the feasibility of efficiently transducing primary leukemia cells with lentiviral vectors to express immunomodulators to elicit antileukemic immune responses. (Blood. 2000;96:1317-1326)
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PMID:Lentiviral vectors for efficient delivery of CD80 and granulocyte-macrophage- colony-stimulating factor in human acute lymphoblastic leukemia and acute myeloid leukemia cells to induce antileukemic immune responses. 1094 73

Dendritic cells (DCs) are potent antigen-presenting cells and are capable of activating naive T cells. Gene transfer of tumor antigen and cytokine genes into DCs could be an important strategy for immunotherapeutic applications. Dendritic cells derived from peripheral blood monocytes do not divide and are therefore poor candidates for gene transfer by Moloney murine leukemia virus (Mo-MuLV)-based retroviral vectors. Lentiviral vectors are emerging as a powerful tool for gene delivery into dividing and nondividing cells. A three-plasmid expression system pseudotyped with the envelope from vesicular stomatitis virus (VSV-G) was used to generate lentiviral vector particles expressing enhanced green fluorescent protein (EGFP). Peripheral blood monocyte-derived DCs were cultured in the presence of GM-CSF and IL-4 and transduced with lentiviral or Mo-MuLV-based vectors expressing EGFP. FACS analysis of lentiviral vector-transduced DCs derived either from normal healthy volunteers or from melanoma patients demonstrated transduction efficiency ranging from 70 to 90% compared with 2-8% using Mo-MuLV-based vectors pseudotyped with VSV-G. Comparison of lentiviral vectors expressing EGFP driven by CMV or human PGK promoters showed similar levels of transgene expression. Lentiviral vector preparations produced in the absence of HIV accessory proteins transduced DCs at efficiencies equal to vectors produced with accessory proteins. Alu-HIV-1 LTR PCR demonstrated the genomic integration of the lentiviral vector in the transduced DCs. Transduced cells showed characteristic dendritic cell phenotype and strong allostimulatory capacity and maintained the ability to respond to activation signals such as CD40 ligand and lipopolysaccharide. These results provide evidence that lentiviral vectors are efficient tools for gene transfer and expression in monocyte-derived DCs that could be useful for immunotherapeutic applications.
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PMID:Efficient gene transfer to human peripheral blood monocyte-derived dendritic cells using human immunodeficiency virus type 1-based lentiviral vectors. 1098 62


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