Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of rHuGM-CSF has resulted in patient benefit as shown by reduced infections (MDS and AA), reduced days in intensive care (ABM transplant), better adherence to cancer chemotherapy protocols, and the ability to use full doses of antiviral drugs in AIDS and cytomegalovirus retinitis. The adverse reactions are significant when high doses are used, therefore high doses should be avoided (there is a plateau in the dose-effective biological responses). At recommended doses, GM-CSF is well tolerated and is a valuable adjunctive therapy in the management of patients with conditions of dysmyelopoiesis and myeloid hypoplasia associated with myelotoxic therapy, or after bone marrow transplantation.
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PMID:Clinical experience with Escherichia coli rHuGM-CSF. 845 14

Multinucleated giant cell formation (MNGC) occurs in central nervous system AIDS. The mechanism of fusion of microglia in these cases is unknown. We investigated the ability of lymphokines to induce fusion and found that interleukin-3 (IL-3), interleukin-4 (IL-4), gamma interferon (gamma-IFN), and granulocyte-macrophage colony stimulating factor (GM-CSF) induced MNGC formation in cultures of rat microglia in vitro. The diacylglycerol analogue phorbol myristate acetate (PMA) also induced MNGC. Interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF alpha) failed to induce fusion. Preincubation of the IL-3 treated cultures with anti-IL-3, anti-leukocyte function associated antigen-1 (LFA-1) alpha-chain (CD11a), and anti-intercellular adhesion molecule-1 (ICAM-1) inhibited cell fusion. Antibody to polymorphic Class II major histocompatibility complex (MHC) determinants also inhibited MNGCs. Cell surface LFA-1 was predominantly observed on MNGC, suggesting that LFA-1 expression is involved in microglia fusion. We thus propose that MNGC formation of microglia result from the effects of T cell-derived cytokines probably through the induction of cell surface adhesion molecules.
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PMID:Lymphokine induction of rat microglia multinucleated giant cell formation. 850 64

HIV encephalitis is unusual in that neurologic damage occurs in the absence of significant infection of neuronal or glial cells. Because the predominant infected cell in the brain is the macrophage, it has been proposed that release of viral or immune activation factors from macrophages may mediate neurologic damage. Numerous studies have examined the concentration of immune activation factors in the cerebrospinal fluid (CSF), however, there has been no correlation between these CSF measurements and severity of HIV encephalitis (Wiley, C.A., C.L. Achim, R.D. Schrier, M.P. Heyes, J.A. McCutchen, and I. Grant. 1992. AIDS (Phila.). 6:1299-1307. Because CSF measurements may not represent tissue concentrations of these factors, we examined the concentrations of HIV p24, quinolinic acid (QUIN), IL-1, IL-3, IL-6, TNF-alpha, and GMCSF within the brains of 10 AIDS autopsies. Homogenization and extraction of cortical gray, cortical white and deep gray matter showed a good correlation between the amount of HIV gp41 immunostaining and extracted HIV gag protein p24. The concentrations of cytokines were low in the tissue extracts and showed no correlation with severity of HIV encephalitis. Brain extracts from mild cases of HIV encephalitis showed elevated levels of TNF-alpha in deep gray matter, while in more severe cases, elevated TNF-alpha levels were also found within cortical white and cortical gray matter. Brain tissue and CSF QUIN concentrations were substantially increased compared to control values. QUIN concentrations were not correlated with the severity of HIV encephalitis. We conclude that increased tissue levels of TNF-alpha and QUIN may have a role in the etiology of HIV-related neurologic dysfunction.
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PMID:Quantitation of human immunodeficiency virus, immune activation factors, and quinolinic acid in AIDS brains. 851 84

An in vitro culture system was developed that facilitates detailed studies of the interaction of Human Immunodeficiency Virus (HIV) with dendritic cells (DC). Cultured immature DC were generated from adherent peripheral blood mononuclear cells in the presence of GM-CSF and IL-4. These cells were non-adherent, non-phagocytic and had a veiled surface appearance. They expressed high levels of MHC class I and II proteins, CD1a, B7/BB1 and low levels of CD4, and were known to possess a potent soluble antigen presenting capacity. Upon infection with the HIV-1 strains Lai (lymphocytotropic) and BaL (monocytotropic), the viral RNA was reverse transcribed to complete DNA provirus. However the infection was non-productive as judged from measuring the activity of the virus encoded reverse transcriptase in the culture supernatant. Thus HIV infection was restricted at a step post entry.
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PMID:Infection of cultured immature dendritic cells with human immunodeficiency virus type 1. 852 22

Restoration of bone marrow and immune function by means of allogeneic bone marrow transplantation has been attempted in AIDS patients but has not been successful as the donor-derived cells, or their progeny, inevitably became infected. A hairpin ribozyme that specifically cleaves HIV-1 RNA has been developed by F. Wong-Staal et al. and has been demonstrated to confer resistance against HIV-1 infection. Allogeneic transplantation of CD34+ cells or their pluripotent subsets, transduced by vectors bearing this ribozyme gene, can protect the stem cells and their progeny from HIV-1 infection and eventually restores immune function. We have provided evidence that long-term repopulating stem cells can be mobilized into peripheral blood by growth factors. The combination of G-CSF and GM-CSF seems to yield a high frequency of pluripotent stem cells with a CD34+ subset profile that is similar to placental and umbilical cord blood (PUCB). We have then demonstrated a highly efficient transduction of CD34+ cells from PUCB and mobilized leukapheresis products by retroviral vectors bearing the ribozyme gene. Expression of the ribozyme gene, as shown by reverse transcriptase-polymerase chain reaction, was of similar magnitude (70%-90% of cells that grow into colonies). Challenge of the progeny macrophages from such transduced CD34+ cells with monocyte-trophic strains of HIV-1 showed that they were resistant to infection. Thus allogeneic transplantation of CD34+ cells or their pluripotent subsets, transduced with ribozyme gene, can be a promising strategy for the treatment of HIV infection.
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PMID:Stem cells as vehicles for gene therapy: novel strategy for HIV infection. 874 96

Combination therapy with zidovudine and recombinant human granulocyte-macrophage colony stimulating factor (rHu GM-CSF) may be warranted, owing to the bone marrow suppressive effects of zidovudine. A study of 16 patients, 8 of whom had acquired immune deficiency syndrome (AIDS) and 8 of whom were infected with human immunodeficiency virus (HIV) but were asymptomatic, was conducted. The effect of 4 days of rHU GM-CSF versus placebo on intermittent zidovudine therapy (200 mg every 8 hours) was evaluated using a randomized, cross-over study design. Pharmacokinetics of oral and intravenous zidovudine were determined on days 1 (oral), 3 (oral), and 4 (intravenous) of rHu-GM-CSF (placebo) administration. After intravenous dosing, zidovudine plasma clearance for placebo and rHu GM-CSF averaged 1.4 +/- 0.2 and 1.3 +/- 0.2 L/hr/kg, respectively (P = 0.017), mean residence time averaged 1.5 +/- 0.5 and 1.9 +/- 0.6 hours, respectively (P = 0.012), and the steady-state volume of distribution was 2.0 +/- 0.7 and 2.3 +/- 0.7 L/kg, respectively (P = 0.027) for the two treatment arms. Stratified data for patients with AIDS and those with asymptomatic HIV infection revealed no significant difference in plasma clearance or mean residence time between the two patient groups. These pharmacokinetic results indicate that dosage adjustments for zidovudine are not warranted when administered with rHu GM-CSF owing to the small changes observed. However, the statistically significant increase in Vss suggests the possibility of enhanced zidovudine cellular uptake in the presence of rHu GM-CSF.
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PMID:Oral and intravenous zidovudine pharmacokinetics: the effect of granulocyte-macrophage colony stimulating factor. 878 45

Neutropenia complicates HIV disease or its treatment in a large proportion of patients. Hematopoietic growth factor support has been tested in a number of clinical settings in HIV disease and has been demonstrated to be of benefit for specific parameters. One consideration regarding the use of hematopoietic growth factors in HIV disease is their potential effect on HIV viral burden, since alterations in HIV expression have been documented with certain cytokines in vitro. It has also been reported that some cytokines, notably GM-CSF, potentiate the antiviral properties of thymidine analogs such as zidovudine (AZT) in vitro. We tested these observations in vivo. Twelve HIV-positive patients with a CD4 cell count < or = 200/mm3 or HIV plasma viremia who were receiving a stable dose of zidovudine were enrolled into three dose cohorts of yeast-derived GM-CSF at 50, 125, or 250 micrograms/m2 daily by subcutaneous self-injection for 28 days. Measurements of HIV activity included serum acid-dissociated HIV p24 antigen levels, plasma and peripheral blood mononuclear cell (PBMC) limiting dilution HIV culture, and plasma HIV quantitative competitive polymerase chain reaction (PCR). Serum and intracellular zidovudine levels were measured as well as hematologic, immunologic, and toxicity parameters. Virologic measures showed neither significant upregulation nor downregulation of serum acid-dissociated HIV p24 antigen, plasma and PBMC HIV culture, or PCR in association with GM-CSF administration. A trend toward increased intracellular AZT levels was noted, but this did not achieve statistical significance (p = 0.073). CD4 and CD8 lymphocytes were essentially unaffected while absolute neutrophil counts increased with GM-CSF administration as expected. These data suggest that administration of GM-CSF does not perturb HIV activity or immunologic parameters in patients receiving AZT for advanced HIV disease. No potentiation of AZT antiviral effect was demonstrated.
AIDS Res Hum Retroviruses 1996 Aug 10
PMID:Lack of in vivo effect of granulocyte-macrophage colony-stimulating factor on human immunodeficiency virus type 1. 884 19

We have previously reported that oral administration of hot water extract of Chlorella vulgaris (CVE) enhances resistance to Listeria monocytogenes through augmentation of Listeria-specific cell-mediated immunity in normal mice and mice with murine acquired immunodeficiency syndrome (MAIDS) caused by murine leukemia virus (MuLV) LP-BM5. To elucidate the mechanisms whereby CVE augments the cell-mediated immunity, we examined the expression patterns of mRNA for cytokines in normal and MAIDS mice given CVE orally after L. monocytogenes infection. The expression levels of IL-1 alpha, IL-12, GM-CSF, MIP and TNF alpha genes were significantly augmented in the peritoneal adherent cells by oral administration of CVE for 2 weeks before Listeria infection. The expression levels of gamma IFN and IL-12 mRNA were significantly higher in the spleen after Listeria infection in CVE-treated mice than in normal mice, while the expression of IL-10 mRNA in the spleen was decreased by CVE administration. In MAIDS mice, oral administration of CVE also augmented the expression of gamma IFN and IL-12 mRNA in the spleen after Listeria infection, while it rather reduced the expression of IL-10 mRNA. These results suggest that CVE may preferentially augment THI responses against Listeria via activation of macrophages to produce IL-12 and enhance host defence against Listeria infection both in normal and MAIDS mice.
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PMID:Effect of hot water extract of Chlorella vulgaris on cytokine expression patterns in mice with murine acquired immunodeficiency syndrome after infection with Listeria monocytogenes. 904 41

The hematologic manifestations of HIV infection and AIDS are common and may cause symptoms that are life-threatening and impair the quality of life of these patients. The most important of these manifestations are cytopenias. Anemia and neutropenia are generally caused by inadequate production because of suppression of the bone marrow by the HIV infection through abnormal cytokine expression and alteration of the bone marrow microenvironment. Thrombocytopenia is caused by immune-mediated destruction of the platelets, in addition to inadequate platelet production. The incidence and severity of cytopenia are generally correlated to the stage of the HIV infection. Other causes of cytopenia in these patients include adverse effects of drug therapy, the secondary effects of opportunistic infections or malignancies, or other preexisting or coexisting medical problems that may be prevalent in the HIV-infected population. Diagnosis of the mechanism and cause of the cytopenia may allow for specific management. Optimal management of the underlying HIV infection is essential, and mild cytopenia in asymptomatic patients may need no specific management. Supportive care for anemia includes the use of erythropoietin in addition to the judicious use of red blood cell transfusions. Therapy for neutropenia includes the use of the myeloid growth factors G-CSF and GM-CSF. Immune-mediated thrombocytopenia may be treated with a combination of zidovudine, corticosteroids, IVGG, and splenectomy. Platelet transfusions are sometimes needed for the treatment of thrombocytopenia caused by decreased production. Other hematologic manifestations such as hypergammaglobulinemia and lupus anticoagulants are commonly asymptomatic and usually require no specific therapy, but they can rarely cause morbidity and require specific interventions.
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PMID:Hematologic complications of human immunodeficiency virus infection and the acquired immunodeficiency syndrome. 909 37

Cytokines are a heterogenous group of polypeptide mediators that have been associated with activation of numerous functions, including the immune system and inflammatory responses. The cytokine families include, but are not limited to, interleukins (IL-I alpha, IL-I beta, ILIra and IL-2-IL-15), chemokines (IL-8/ NAP-I, NAP-2, MIP-I alpha and beta, MCAF/MCP-1, MGSA and RANTES), tumor necrosis factors (TNF-alpha and TNF-beta), interferons (INF-alpha, beta and gamma), colony stimulating factors (G-CSF, M-CSF, GM-CSF, IL-3 and some of the other ILs), growth factors (EGF, FGF, PDGF, TGF alpha, TGF beta and ECGF), neuropoietins (LIF, CNTF, OM and IL-6), and neurotrophins (BDNF, NGF, NT-3-NT-6 and GDNF). The neurotrophins represent a family of survival and differentiation factors that exert profound effects in the central and peripheral nervous system (PNS). The neurotrophins are currently under investigation as therapeutic agents for the treatment of neurodegenerative disorders and nerve injury either individually or in combination with other trophic factors such as ciliary neurotrophic factor (CNTF) or fibroblast growth factor (FGF). Responsiveness of neurons to a given neurotrophin is governed by the expression of two classes of cell surface receptor. For nerve growth factor (NGF), these are p75NTR (p75) and p140trk (referred to as trk or trkA), which binds both BDNF and neurotrophin (NT)-4/5, and trkC receptor, which binds only NT-3. After binding ligand, the neurotrophin-receptor complex is internalized and retrogradely transported in the axon to the soma. Both receptors undergo ligand-induced dimerization, which activates multiple signal transduction pathways. These include the ras-dependent pathway utilized by trk to mediate neurotrophin effects such as survival and differentiation. Indeed, cellular diversity in the nervous system evolves from the concerted processes of cell proliferation, differentiation, migration, survival, and synapse formation. Neural adhesion and extracellular matrix molecules have been shown to play crucial roles in axonal migration, guidance, and growth cone targeting. Proinflammatory cytokines, released by activated macrophages and monocytes during infection, can act on neural targets that control thermogenesis, behavior, and mood. In addition to induction of fever, cytokines induce other biological functions associated with the acute phase response, including hypophagia and sleep. Cytokine production has been detected within the central nervous system as a result of brain injury, following stab wound to the brain, during viral and bacterial infections (AIDS and meningitis), and in neurodegenerative processes (multiple sclerosis and Alzheimer's disease). Novel cytokine therapies, such as anticytokine antibodies or specific receptor antagonists acting on the cytokine network may provide an optimistic feature for treatment of multiple sclerosis and other diseases in which cytokines have been implicated.
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PMID:Neurotrophins and their receptors in nerve injury and repair. 910 50


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