Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer has been closely associated with human immunodeficiency virus (HIV) infection but this is less frequent in children. Non-Hodgkin's lymphomas represent the most frequently reported single tumor. The authors report seven cases of malignant tumors resulting from the analysis of all (n = 1321) children enrolled in the Italian Register for HIV Infection in Children. Tumors were distributed as follows: non-Hodgkin's B-cell lymphoma (four cases); and Kaposi's sarcoma, hepatoblastoma, acute B-cell lymphoblastic leukemia (one case each). Hepatoblastoma had never been previously reported in HIV-infected children. Also in the current series, non-Hodgkin's B-cell lymphoma is the most frequent single tumor. Five of the seven cancers belonged to the B-cell line. All but one of the seven children have died. Specific chemotherapy was provided in three cases, with some clinical improvement. The treatment of malignancies in HIV-infected children is hampered by increased risk of opportunistic infections often fatal even in children with apparent remission from the tumor.
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PMID:Malignancies in children with human immunodeficiency virus type 1 infection. The Italian Multicenter Study on Human Immunodeficiency Virus Infection in Children. 165 58

The transient expression of hepatitis B virus (HBV) surface and "eJ" antigens caused by transfection of human hepatoblastoma HepG2 cells with HBV DNA was markedly inhibited by cotransfection with poly(I):poly(C). Cotransfection with poly(I):poly(C) also inhibited the expression of bacterial chloramphenicol acetyltransferase (CAT) gene which was under the control of either the HBV core promoter or the human immunodeficiency virus (HIV-1) long terminal repeat. This inhibition was much more pronounced on the expression of HBV-promoted CAT than HIV-promoted CAT. The uptake of reporter plasmid was not affected by cotransfected poly(I):poly(C). The inhibition was found to be at the steady-state CAT mRNA level and appeared to be specific for HBV and HIV regulatory sequences since CAT expression directed by other viral and cellular regulatory sequences was not inhibited. Cotransfection with a mixture of equal amounts of poly(I) and poly(C) had similar inhibitory effects whereas cotransfection with poly(l) or poly(C) alone, or other double-stranded ribo- or deoxyribonucleotides, did not have such strong effects. The addition of poly(l):poly(C) to the culture medium of cells transfected with these reporter plasmids caused little inhibition. Transfection with poly(l):poly(C) induced a minimal amount of intracellular interferon-alpha in HepG2 cells which may be involved in selective inhibition of HBV-and HIV-1-directed gene expression. 2-Aminopurine, an inhibitor of double-stranded RNA activated protein kinase known to block interferon gene induction by poly(l):poly(C), partially reversed the poly(l):poly(C)-induced inhibitory effect on HBV-CAT expression.
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PMID:Selective inhibition of hepatitis B virus and human immunodeficiency virus sequence-promoted gene expression by cotransfected poly(I):poly(C). 221 31

Tumor necrosis factor-alpha is an inducer of acute-phase protein synthesis in liver cells. The mechanism by which tumor necrosis factor-alpha alters gene expression in these cells is largely unknown. In this study, we demonstrate that tumor necrosis factor-alpha stimulates human immunodeficiency virus-1 long terminal repeat-promoted gene expression in the human hepatoblastoma HepG2 cell line and increased binding of trans-activating factors to kappa B (kappa B) DNA sequences. In contrast to lymphocytic cells where the nuclear factors recognizing the kappa B sequences are activated by both tumor necrosis factor-alpha and phorbol-12-myristate-13-acetate through a posttranslational mechanism, in HepG2 cells phorbol-12-myristate-13-acetate does not activate these factor(s), and de novo protein synthesis seems to be required in HepG2 cells for gene activation by tumor necrosis factor-alpha.
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PMID:Tumor necrosis factor-alpha induces a kappa B sequence-specific DNA-binding protein in human hepatoblastoma HepG2 cells. 255 96

Recently, we have shown that the human immunodeficiency virus (HIV-1) long terminal repeat (LTR) directed chloramphenicol acetyltransferase (CAT) gene is efficiently expressed in human hepatoblastoma HepG2 cells and these cells can support productive HIV-1 replication. In this study we show that HepG2 cells contain a nuclear factor that binds to the HIV-1 trans-activating region (TAR), which we named HepG2-derived TAR binding protein (HTBP). Gel retardation assays using synthetic oligonucleotide probes carrying different mutations in the TAR region and competition DNA mobility-shift experiments using these oligonucleotides revealed the binding site encompassing between +7 and +13 nucleotides (5'-TCTGGTT-3') in the HIV-1 LTR. An in vivo CAT competition assay using -65HIV-1 LTR CAT as a reporter plasmid and various competitor plasmids containing these mutated oligonucleotides also demonstrated that HTBP can influence the HIV-1 LTR-directed CAT gene expression in HepG2 cells by interaction with a specific sequence in the TAR region.
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PMID:Identification of a human immunodeficiency virus type 1 TAR binding protein in human hepatoblastoma HepG2 cells that trans-activates HIV-1 LTR-directed gene expression. 828 41

Penciclovir [9-(4-hydroxy-3-hydroxymethylbut-1-yI)guanine], an effective antiherpesvirus agent, was found to be a potent and selective antiviral agent against intracellular hepatitis B virus (HBV) replication (drug concentration at which a 10-fold decrease in HBV DNA from the average level in an untreated culture was observed [EC90], 1.6 microM) and extracellular virion release (EC90, 0.7 microM) by cultured human hepatoblastoma (2.2.15) cells. Acyclovir and three other related 9-alkoxypurines with activity against either herpesviruses or human immunodeficiency virus were uniformly inactive against HBV. The activity of penciclovir is discussed in relation to recent findings related to its mode of action against HBV.
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PMID:Penciclovir is a selective inhibitor of hepatitis B virus replication in cultured human hepatoblastoma cells. 872 85

Measles is often fatal for immunocompromised hosts. Protective immunity against measles has been studied but is still not completely understood. Recently, five cases of measles were encountered in immunocompromised children. Two of these were allogeneic bone marrow transplanted cases (one common variable immunodeficiency and one severe aplastic anemia) in remission, one Wilms' tumor case in remission, one hepatoblastoma case after cytotoxic therapy at disease onset and one exaggerating hemophagocytic syndrome case with suppressed natural killer cell activity. Clinical symptoms, laboratory findings and the immunologic backgrounds of these five patients were investigated. One of the patients, an 8 year old boy with hemophagocytic syndrome, died of giant cell pneumonia which was confirmed in the section of necropsy lung specimen. Two other patients who received allogeneic bone marrow transplants were not immune to measles, despite their own and their donors' immunizations. Their clinical symptoms were rather severe but both patients recovered and have remained seropositive for as long as 13 months. This fatality from measles is the first reported in a patient with hemophagocytic syndrome. Suppressed natural killer cell activity may be a poor prognostic factor. Also, secondary immunization failure for measles can occur in bone marrow transplanted patients with rather severe clinical symptoms.
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PMID:Clinical features of measles in immunocompromised children. 874 8

A group of myristic acid analogs, designed as alternative substrates for N-myristoyltransferase (NMT), were evaluated against human immunodeficiency virus (HIV), hepatitis B virus (HBV) and duck hepatitis B virus (DHBV) in vitro. Antiviral potency was increased when S or O was substituted for -CH2- in myristic acid and selectivity was affected by the presence and position of the heteroatoms and phenyl groups. A correlation was established among anti-HIV activity, Log P and Log D7.4 and between anti-HIV activity and carbonyl-heteroatom interatomic distances in the myristoyl analogs. 12-Thioethyldodecanoic acid 6 was moderately active (EC50 = 9.37 microM) against HIV-infected T4-lymphocytes (CEM-SS cell line), and it exhibited in vitro activity (EC50 = 17.8 microM) against HBV-producing 2.2.15 cell cultures derived from a human hepatoblastoma cell line (Hep G2). 12-Methoxydodecanoic acid 1 exhibited in vitro activity (EC50 = 20-30 microM) against hepatitis B in the HBV DNA-transfected 2.2.15 cell line. At a concentration of 10 microg/ml, none of the fatty acids significantly inhibited the replication of DHBV in infected hepatocytes.
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PMID:In vitro antiviral activities of myristic acid analogs against human immunodeficiency and hepatitis B viruses. 919 Oct 15

To investigate the possibility of using hepatitis B virus (HBV) as a vector, the tat gene from human immunodeficiency virus type 1 (HIV-1) was inserted into the full-length HBV genome in-frame with the polymerase (pol) open reading frame in the tether region and downstream of the preS1 promoter. We demonstrated that the tat gene was expressed with full activity in transactivating the HIV-1 long terminal repeat (LTR). The expression of the tat gene in the context of the HBV genome in chicken hepatoma and human cervical carcinoma cells, however, was not as efficient as that in human hepatoblastoma cells, which reflects the cellular and species specificity of promoters of hepadnaviruses. Detection of RNA expressed from this HBVtat recombinant revealed transcription of the tat gene by two promoters: the core/pol promoter and the preS1 promoter. A Pol-Tat fusion protein expressed by the core/pol promoter did not seem to contribute to the tat transactivation activity of the HBVtat recombinant since a frameshift mutation in the pol gene did not affect the recombinant tat function. The functional tat protein, therefore, was most likely expressed as a Tat-Pol fusion product. Endogenous polymerase assays showed that the pol protein expressed from the HBVtat recombinant was still active although at a reduced level. Hepatitis B surface antigens and e antigen produced from this recombinant were detected at similar levels as those produced from the wild type. Notably, the capability of forming complete HBV particles was still retained. These studies indicate the potential of constructing HBV as a replicative vector. We also showed that manipulation of a nonreplicative HBV vector was possible. Expression of the HBV polymerase could be completely eliminated and replication of the nonreplicative HBV recombinant could be supported by Pol transcomplementation.
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PMID:Development of replicative and nonreplicative hepatitis B virus vectors. 947 57

AT-61, a member of a novel class of phenylpropenamide derivatives, was found to be a highly selective and potent inhibitor of human hepatitis B virus (HBV) replication in four different human hepatoblastoma cell lines which support the replication of HBV (i.e., HepAD38, HepAD79, 2.2.15, and transiently transfected HepG2 cells). This compound was equally effective at inhibiting both the formation of intracellular immature core particles and the release of extracellular virions, with 50% effective concentrations ranging from 0.6 to 5.7 microM. AT-61 (27 microM) was able to reduce the amount of HBV covalently closed circular DNA found in the nuclei of HepAD38 cells by >99%. AT-61 at concentrations of >27 microM had little effect on the amount of viral RNA found within the cytoplasms of induced HepAD38 cells but reduced the number of immature virions which contained pregenomic RNA by >99%. The potency of AT-61 was not affected by one of the mutations responsible for (-)-beta-L-2', 3'-dideoxy-3' thiacytidine (3TC) resistance in HBV, and AT-61 acted synergistic with 3TC to inhibit HBV replication. AT-61 (81 microM) was not cytotoxic or antiproliferative to several cell lines and had no antiviral effect on woodchuck or duck HBV, human immunodeficiency virus type 1, herpes simplex virus type 1, vesicular stomatitis virus, or Newcastle disease virus. Therefore, we concluded that the antiviral activity of AT-61 is specific for HBV replication and most likely occurs at one of the steps between the synthesis of viral RNA and the packaging of pregenomic RNA into immature core particles.
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PMID:Inhibition of human hepatitis B virus replication by AT-61, a phenylpropenamide derivative, alone and in combination with (-)beta-L-2',3'-dideoxy-3'-thiacytidine. 983 12

Human immunodeficiency virus-1 (HIV-1)-Tat, the transactivating gene product of HIV-1, has been shown to interact with different cell types, inducing gene expression, altering their growth and migratory behavior. In this study we examined whether Tat might affect functions of acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphoma (NHL), relevant to the in vivo dissemination. Our results show that Tat significantly augmented the motility of the two AIDS-related Burkitt's lymphoma cell lines (AS283 and PA682PB) and AIDS-primary effusion lymphoma cell line (HBL-6-AIDS-PEL). Mutations in RGD or basic domain of Tat (KGE-MBP and LxI-MBP, respectively) sharply reduced migration compared with wild type, suggesting that both domains are required for migration. In contrast, a Tat protein mutation outside the active domains (NH(2)-TAT-GST) did not reduce lymphoma cell migration. The treatment of lymphoma cells with Tat did not influence their adhesion to matrix proteins or to human vascular endothelial cells, but endothelial cells treated with Tat became more adhesive to lymphoma cells. Flow cytometric analysis showed that treatment of endothelial cells with Tat induced the cell surface expression of the adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and E-selectin and increased the expression of intercellular adhesion molecule-1 (ICAM-1). Only antibodies against VCAM-1 on endothelial cells or against the VLA-4 integrin expressed on AS283 cells inhibited the increment of adhesion, indicating the relevance of this pathway in the adhesion of lymphoma cells to vascular endothelium. In our work, we show for the first time that Tat can enhance the migration of lymphoma cells and their adhesion to endothelial cells, two processes that may contribute to the malignant behavior of NHL in patients with AIDS.
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PMID:Human immunodeficiency virus-1 (HIV-1)-Tat protein promotes migration of acquired immunodeficiency syndrome-related lymphoma cells and enhances their adhesion to endothelial cells. 1047


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