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)

Presented are the steps in creating a recombinant DNA molecule, examples of recombinant drug products, a description of DNA fingerprinting methods for diagnosing diseases, a discussion of the patenting of recombinant drugs, and a look to the future of this revolutionary biotechnology. Constructing a recombinant DNA molecule involves cutting the DNA into fragments with restriction endonucleases and rejoining the fragments in novel arrangements with ligase. Propagating the molecule in a microorganism, or cloning, is necessary to increase the number of gene copies to facilitate detection of the gene of interest and to produce the protein it encodes. Recombinant DNA drug products have been developed that represent the communicator, structural, and modifier classes of proteins. Recombinant communicator proteins include interferons alfa-2a and alfa-2b and granulocyte-macrophage colony-stimulating factor (immune system modulators); epidermal growth factor and erythropoietin (tissue repair promoters); and human insulin, growth hormone, and atrial peptide (metabolism modulators). Recombinant structural proteins include hepatitis B virus vaccine and CD4 protein, and recombinant modifier proteins include tissue plasminogen activator and superoxide dismutase (agents that split or splice organic molecules). In the future, gene defects associated with genetic diseases will be unraveled, leading to the production of new therapeutic agents designed to counteract or actually reverse those defects. Recombinant protein drugs will be further tailored to enhance their activity and specificity. These advances are so novel and momentous that patent protection has been extended not only to recombinant drugs but to the recombinant microorganisms in which they are manufactured. In cloning genes, investigators directly use the protein designs that occur naturally. Basic research will soon lead to the engineering of novel proteins with specified functions.
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PMID:Drug products of recombinant DNA technology. 267 63

To investigate whether there is any evidence of an immune stimulation against hepatitis B virus surface antigen (HBsAg) in asymptomatic HBsAg carriers, proliferative and cytotoxic responses to HBsAg were measured in their peripheral blood lymphocytes. Although the majority of asymptomatic carriers had no proliferative response to HBsAg, 3 (25%) of 12 carriers showed significant T cell proliferation against HBsAg. In addition, using HBsAg-expressing autologous lymphoblastoid cell line (LCL) as target cells, HBsAg-specific cytotoxic activity was found in 2 of 3 asymptomatic HBsAg carriers who had a proliferative response against HBsAg. Furthermore, 6 cytotoxic T lymphocyte (CTL) clones were isolated from 1 asymptomatic carrier. The epitope recognized by 2 CTL clones was mapped to the major HBsAg residues 158-172. These CTL clones were able to produce interferon-gamma, tumor necrosis factor-alpha, or granulocyte-macrophage colony-stimulating factor. These findings demonstrate the presence of HBsAg-specific, major histocompatibility complex class I-restricted CTL in asymptomatic HBsAg carriers.
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PMID:Presence of hepatitis B surface antigen (HBsAg)-specific cytotoxic T cells in asymptomatic HBsAg carriers. 751 10

Interleukin-8 (IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are important mediators of inflammation and immune response in human disease. To demonstrate their importance in pathophysiological processes in liver disease, we measured the circulating levels of IL-8 and GM-CSF in patients with hepatocellular carcinoma (HCC) and chronic active hepatitis (CAH). IL-8 and GM-CSF levels in serum samples were determined with highly specific and sensitive enzyme-linked immunosorbent assays. IL-8 levels were more elevated in serum samples of patients with HCC and CAH associated with hepatitis C virus infection than HCC and CAH associated with hepatitis B virus infection. However, in all patients with autoimmune CAH and in some patients with HCC and CAH, GM-CSF levels were elevated over the baseline levels measured in all of the normals, but this difference was not statistically significant for any group. We conclude that IL-8 and GM-CSF are increased in some patients with liver diseases, and as such they may play a significant role in host defense and disease.
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PMID:Interleukin-8 and granulocyte-macrophage colony-stimulating factor secretion in hepatocellular carcinoma and viral chronic active hepatitis. 785 12

Recombinant human granulocyte-macrophage colony-stimulating factor therapy significantly reduces serum hepatitis B virus DNA levels, associated with increased 2',5'-oligoadenylate synthetase activity in cultured mononuclear cells of patients with chronic hepatitis B. To assess changes in immune function during therapy of chronic hepatitis B patients, spontaneous and mitogen-induced production of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interferon-alpha and interferon-gamma were measured-along with serum levels of soluble CD4, soluble CD8, soluble interleukin-2 receptor and beta 2-microglobulin-before, during and after a 6-wk course of granulocyte-macrophage colony-stimulating factor in nine patients with chronic hepatitis B. Treatment statistically enhanced spontaneous production of tumor necrosis factor-alpha (p < 0.05) and interleukin-1 beta (p < 0.02). Furthermore, spontaneous interleukin-6 production correlated negatively with hepatitis B virus DNA levels (p < 0.03), and spontaneous interleukin-1 beta production correlated positively with 2',5'-oligoadenylate synthetase activity (p < 0.0005). In addition, statistically significant increases were found during therapy in serum levels of soluble interleukin-2 receptor (p < 0.01), soluble CD4 (p < 0.01) and beta 2-microglobulin (p < 0.05). Levels of soluble interleukin-2 receptor and soluble CD4 correlated negatively with levels of hepatitis B virus DNA (p < 0.05), and levels of soluble interleukin-2 receptor and beta 2-microglobulin correlated positively with 2',5'-oligoadenylate synthetase activity (p < 0.003 and p < 0.02, respectively). Thus recombinant human granulocyte-macrophage colony-stimulating factor administration may induce reductions in hepatitis B virus DNA levels, perhaps by altering the immune status and increasing cytokine production.
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PMID:Changes in cytokine production during therapy with granulocyte-macrophage colony-stimulating factor in patients with chronic hepatitis B. 792 47

An expression system combining a unit for the expression of the gene of interest reinforced by the hepatitis B virus X transactivator and a selectable gene weakened by the insertion of an A+T-rich sequence derived from the 3'-untranslated region of the granulocyte-macrophage colony-stimulating factor mRNA is described. This vector allows rapid one-step isolation of highly productive Chinese hamster ovary clones.
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PMID:Rapid isolation of highly productive recombinant Chinese hamster ovary cell lines. 795 14

Recombinant human granulocyte-macrophage colony-stimulating factor is being used to improve the immunological function of patients with various diseases and to ameliorate hematological disorders. We investigated the tolerance and possible antiviral effect of the administration of daily doses of recombinant human granulocyte-macrophage colony-stimulating factor (3, 1 or 0.5 micrograms/kg body wt) to nine patients with chronic hepatitis B, alone or in combination with 5 MU interferon-alpha 2b. Recombinant human GM-CSF reduced significantly (p < 0.02) hepatitis B virus DNA levels. The three doses used were equally effective. Of the eight patients who completed the study, four became negative for HBV DNA and HBeAg; two of them seroconverted to HBe antibody. These four patients showed improvement in the histological activity of their liver disease. Ultimately, two patients regained normal ALT values. 2',5'-Oligoadenylate synthetase activity increased significantly (p < 0.01) in cell lysates of mononuclear cells cultured in vitro, coinciding with the reductions in hepatitis B virus DNA levels. Recombinant human granulocyte-macrophage colony-stimulating factor was well tolerated but produced a dose-dependent increase in white blood cell counts. It became intolerable at doses of 3 micrograms (and was reduced to 1.5 microgram); this effect was reversible after cessation of recombinant human granulocyte-macrophage colony-stimulating factor treatment. No remarkable variations occurred in other parameters. In conclusion, recombinant human granulocyte-macrophage colony-stimulating factor administration is safe and tolerable at doses of 0.5 to 1 microgram/kg body wt and may exert an antiviral effect in chronic hepatitis B.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pilot study of recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of chronic hepatitis B. 840 50

Haemodialysis patients often fail to respond to hepatitis B vaccination. In this pilot study, 15 patients previously non-responsive to at least three 40 micrograms doses of hepatitis B vaccine were given 0.5, 5 or 10 micrograms kg-1 granulocyte-macrophage colony-stimulating factor (GM-CSF) subcutaneously 24 h prior to booster vaccination with a hepatitis B vaccine. Seven of the 15 patients developed antibody to hepatitis B surface antigen (HBsAb) (35-7240 IU L-1) upon initial vaccination with GM-CSF and two of four individuals responded with low HBsAb titres of 15 and 60 IU L-1 when revaccinated with hepatitis B surface antigen (HBsAg) and twice the dose of GM-CSF. The application of GM-CSF was associated with adverse effects that were, in general, mild to moderate in severity and appeared to be dose dependent. Two patients, both receiving 10 micrograms kg-1 GM-CSF discontinued the study because of severe hypotension.
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PMID:The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on hepatitis B vaccination in haemodialysis patients. 887 74

The response to vaccination with recombinant hepatitis B virus (HBV) vaccine is poor in haemodialysis patients. A defect in the antigen-presenting cells may be responsible for this hyporesponsiveness. To overcome this and to improve the response to HBV vaccine in dialysis patients, we used granulocyte-macrophage colony-stimulating factor (GM-CSF) as a vaccine adjuvant. Fifteen consecutive patients with chronic renal failure (CRF), commenced on dialysis, were stratified to receive either 40microg HBV vaccine (Engerix-B) at 0, 1, 2 and 6 months (group A, n=9) or 3microg kg-1 GM-CSF (Leucomax) on day 1 followed by the vaccination schedule described above (group B, n=6). All patients were negative for hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCV) and human immunodeficiency virus (HIV) serology. Titres of antibody to HBsAg (HBsAb) were quantitatively assayed, using enzyme-linked immunosorbent assay (ELISA), at 1, 2, 6 and 7 months from the first dose of vaccination. Only 44% of the patients in group A developed protective antibody levels (mean HBsAb: 22 IU l-1) Fifty per cent of responders developed protective antibody levels (HBsAb >10 IU l-1) only after the fourth dose of vaccination. In contrast, all six patients (100%) in group B developed protective levels of HBsAb (mean HBsAb: 70 IU l-1) (P<0.02). Sixty-seven per cent of the responders were protected after only the second dose of vaccination (P=0.046). No serious adverse effects of GM-CSF were observed in group B. Hence, haemodialysis patients respond poorly to HBV vaccine. GM-CSF is a safe vaccine adjuvant capable of stimulating an earlier and a stronger antibody response to HBV vaccine in haemodialysis patients.
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PMID:Granulocyte-macrophage colony-stimulating factor enhances the efficacy of hepatitis B virus vaccine in previously unvaccinated haemodialysis patients. 1060 57

Patients on maintenance hemodialysis (HD) have poor seroconversion rate after hepatitis B vaccination. The present study was designed to test the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjuvant to hepatitis B vaccination for improving seroconversion rate in maintenance HD patients. Twelve chronic HD patients were randomly assigned to receive either hepatitis B vaccination alone or hepatitis B vaccination 24 h after 1 dose of GM-CSF for primary immunization. A group of 16 chronic HD patients who had not seroconverted after a standard two-dose hepatitis B vaccination were randomly assigned either to a booster dose of hepatitis B vaccine alone or a booster dose given 24 h after one dose of GM-CSF. In the primary immunization group only 2 of 6 patients (33%) who had received vaccination alone, versus 5 of 6 patients (83%) who had received hepatitis B vaccine after one dose of GM-CSF, developed seroprotective antibody titers. Moreover, seroprotective antibody titers (IU/ml) were significantly higher in the latter group (275 +/- 286.5 vs. 14 +/- 22, p < 0.05). In patients who had not seroconverted with prior hepatitis B vaccination, GM-CSF adjuvant therapy significantly increased the seroconversion rate versus booster dose alone (87.5 vs. 25%, respectively, p < 0.02), with significantly higher seroprotective antibody titers (84 +/- 80 vs. 19 +/- 33 IU/ml, respectively, p < 0. 05). These findings suggest that administration of one dose of GM-CSF, as adjuvant therapy, prior to primary or booster dose hepatitis B vaccination may significantly increase seroconversion rate and seroprotective antibody titers in chronic HD patients.
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PMID:Granulocyte-macrophage colony-stimulating factor as an adjuvant to hepatitis B vaccination in maintenance hemodialysis patients. 1064 69

The genetic immunization of rodents with a plasmid coding for a Plasmodium chabaudi merozoite surface protein 1 (C terminus)-hepatitis B virus surface fusion protein (pPcMSP1(19)-HBs) provided protection of mice against subsequent lethal challenge with P. chabaudi chabaudi PC1-infected red blood cells. The percentage of survivor mice was higher in DNA-immunized mice than in animals immunized with a recombinant rPcMSP1(19)- glutathione S-transferase fusion protein administered in Freund adjuvant. In all mice immunized with the pPcMSP1(19)-HBs, a Th1-specific response, including the production of anti-MSP1(19)-specific immunoglobulins predominantly of the immunoglobulin G2a subtype and reacting almost exclusively against discontinuous epitopes, was elicited. The coinjection of Th1-type cytokine-expressing plasmids (gamma interferon, interleukin-2, and granulocyte-macrophage colony-stimulating factor) mostly abolished protection and boosting of MSP1(19)-specific antibodies. The inclusion of a lymph node-targeting signal did not significantly increase protection. These data provide further evidence that MSP1(19)-HBs DNA constructs might be useful as components of a genetic vaccine against the asexual blood stages of Plasmodium.
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PMID:Genetic immunization of BALB/c mice with a plasmid bearing the gene coding for a hybrid merozoite surface protein 1-hepatitis B virus surface protein fusion protects mice against lethal Plasmodium chabaudi chabaudi PC1 infection. 1099 93


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