Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The anti-human immunodeficiency virus (-HIV) nucleoside analogs azidothymidine (AZT), dideoxycytidine (ddC), dideoxyinosine (ddl), dideoxydidehydrothymidine (D4T), and dideoxydidehydrocytidine (D4C) and the anticancer drug cytosine arabinoside (AraC) were compared for their effects on the mitochondrial DNA (mtDNA) content in a human lymphoblastoid cell line, CEM. The potency of these compounds in reducing mtDNA content was in the order of ddC greater than D4C greater than D4T greater than AZT greater than ddl. AraC did not have a significant effect on mtDNA content. All of the compounds tested, except AraC, stimulated lactic acid production at concentrations that inhibited mtDNA synthesis. The action of ddC and ddl occurred at concentrations that did not affect cell growth significantly in 4 days but retarded cell growth by day 6. D4T and D4C decreased mtDNA content by 50% at doses lower than those that inhibited cell growth by 50% in 4 days (ID50). However, AZT required a dose higher than the ID50 to exert similar effects on mtDNA content. The decrease of mtDNA content caused by ddC also occurred in nerve growth factor-treated PC12 cells, which differentiate to neuron-like cells upon treatment with nerve growth factor. The preferential inhibition of mtDNA, compared with cell growth, by some of these anti-HIV nucleoside analogs correlates well with their ability to cause drug-limiting delayed toxicity, such as peripheral neuropathy, in patients. These data suggest that the selective mitochondrial toxicity could be responsible for the delayed toxicity caused by these anti-HIV analogs.
...
PMID:Effect of anti-human immunodeficiency virus nucleoside analogs on mitochondrial DNA and its implication for delayed toxicity. 185 60

Dementia is common in patients with AIDS, but the mechanism by which the human immunodeficiency virus type 1 (HIV-1) causes the neurological impairment is unknown. In this study the possibility that an antigen of HIV-1 suppresses neuronal responses to neurotrophic factors was examined. Both HIV-1 and a related retrovirus, simian immunodeficiency virus (SIV), inhibited the growth of sensory neurons from chick dorsal root ganglia in medium containing neuroleukin (NLK) but not in medium containing nerve growth factor. An unrelated type D retrovirus, simian acquired immunodeficiency syndrome virus, did not affect the growth of neurons in the presence of either neurotrophic factor. The inhibition by HIV-1 of neuron growth in the presence of NLK was found to be due to the gp120 envelope glycoprotein. Regions of sequence homology between gp120 and NLK may account for this inhibitory property of gp120 and functional interactions between gp120 and NLK may be important in the pathogenesis of the AIDS dementia complex.
...
PMID:Functional interaction and partial homology between human immunodeficiency virus and neuroleukin. 303 62

Recent progress in the definition of molecules involved in immune regulation has led to the discovery of a number of type I membrane glycoproteins with a distinctive, cysteine-rich, repetitive domain structure within their extracellular regions. Because the prototype members of this family are receptors for cytokines (tumor necrosis factor [TNF] and nerve growth factor [NGF]), it was expected that the ligands for the other receptors would possess cytokine-like activities. This prediction has been fulfilled by the cloning of cDNA encoding a series of type II membrane glycoproteins, with homology to TNF, that bind to, and signal through, their cognate receptors. While the biological role of some of these ligand-receptor pairs remains obscure, at least two members of the family, CD40 and Fas, have proven their importance. The human X-linked immunodeficiency, hyper IgM syndrome, is the result of mutations in the CD40 ligand gene, and the Fas and Fas ligand genes are mutated in two mouse strains, lpr and gld, that develop autoimmune disease. These findings, together with other evidence, point to key roles of CD40/CD40 ligand interactions in immune activation, particularly in T-dependent B cell responses, and of Fas/Fas ligand in apoptosis and peripheral tolerance. These molecules, as well as the other ligands of the family, share the property of costimulation of T cell proliferation and are all expressed by activated T cells. More detailed analysis of the expression patterns of ligands and receptors on lymphocyte subpopulations will be necessary to define their different roles in immune activation and suppression.
...
PMID:A family of ligands for the TNF receptor superfamily. 752 88

A composite element that interacts with multiple nuclear receptors has been identified in the long terminal repeat (LTR) of the human immunodeficiency virus-1 (HIV-1). This element, designated nuclear receptor-responsive element (NRRE), spans the -356 to -320 LTR region and contains tightly clustered binding sites for the retinoid X receptor-alpha (RXR alpha) and for five nuclear receptors with unknown ligands, apolipoprotein AI regulatory protein-1 (ARP-1), v-erbA-related proteins-2 and -3 (EAR-2 and EAR-3), hepatocyte nuclear factor-4 (HNF-4), and nerve growth factor-inducible protein-B (NGFI-B). The NRRE also interacts with heterodimers formed between RXR alpha and either ARP-1, EAR-2, EAR-3, the retinoic acid receptor-alpha (RAR alpha), or the peroxisome proliferator-activated receptor (PPAR). Remarkably, nuclear receptor binding is conserved in the LTRs of recently evolved HIV-1 strains but it is absent in the oldest and most divergent viral isolates, raising the intriguing possibility that the NRRE has been evolved recently in the viral genome. Cotransfection experiments in human choriocarcinoma JEG-3 cells have shown that the HIV-1 LTR-driven transcription is activated by RXR alpha and RAR alpha in the presence of 9-cis- and all-trans-retinoic acid, by PPAR and RXR alpha in the presence of clofibric acid and 9-cis-retinoic acid, and by the "orphan" receptors HNF-4 and NGFI-B. These findings suggest that a complex network of nuclear receptor signaling pathways, that include 9-cis- and all-trans-retinoic acid, fatty acids, peroxisome proliferators, growth factors, membrane depolarization, and possibly other signals, converge onto the HIV-1 NRRE and may participate in modulation of viral gene expression.
...
PMID:Convergence of multiple nuclear receptor signaling pathways onto the long terminal repeat of human immunodeficiency virus-1. 811 38

Anaplastic large-cell lymphoma (ALCL) represents a morphologically distinct type of non-Hodgkin's lymphoma (NHL) characterized phenotypically by the expression of the CD30 antigen, a new member of the nerve growth factor gene family. The lymphoid origin of ALCL has been documented using immunohistochemical and molecular genetic analyses. However, very little is known so far regarding the precise pathogenetic mechanisms involved in its development and progression. Therefore, we investigated bcl-2, p53, and retinoblastoma gene (Rb) expression immunohistochemically; the occurrence of bcl-2, c-myc, and Rb gene rearrangements using Southern blotting; and the presence of ras and p53 gene somatic mutations by single-strand conformation polymorphism assay in a panel of 18 well-characterized ALCLs. In addition, the presence of Epstein-Barr (EBV) and human T-cell lymphotropic virus type I (HTLV-I) genomes were investigated using polymerase chain reaction. We identified abnormal c-myc gene products in 6 of 18 cases (33%) of ALCL. On the other hand, the bcl-2 and Rb genes were not rearranged and K-, N-, and H-ras gene somatic mutations were not found. Significant levels of p53 protein expression were found in more than 60% of ALCLs, but only a single ALCL carried a p53 gene mutation (exon 5). Only 3 ALCL cases, all occurring in human immunodeficiency virus-infected patients, were positive for EBV genomes. On the other hand, contrary to previous findings, no HTLV-I products could be identified. Despite the fact that the c-myc proto-oncogene appears to be frequently altered in ALCL, no pathognomonic abnormality could be identified and therefore additional studies and new strategies should be designed to identify the pathogenetic mechanisms involved in the development of ALCL.
...
PMID:Molecular characterization of CD30+ anaplastic large-cell lymphoma: high frequency of c-myc proto-oncogene activation. 820 84

Rat pheochromocytoma PC12 cells were permanently transfected with a plasmid vector, containing the tat gene of human immunodeficiency virus type 1 (HIV-1). Various clones were obtained showing the production of different levels of bioactive Tat protein (Tat) after transient cotransfection with an HIV-1 long terminal repeat-chloramphenicol acetyltransferase reporter plasmid. Under conditions of serum starvation, tat-positive PC12 clones expressing high levels of Tat showed a significantly (P < 0.05) higher proliferation rate with respect to both mock-transfected PC12 cells and tat-positive PC12 cells expressing lower levels of Tat. Moreover, all tat-positive PC12 cell clones showed a partial morphological differentiation into sympathetic-like neurons, when seeded in low density (5 x 10(3) cells/cm2) cultures. On the other hand, mock-transfected PC12 cells showed the round shaped morphology typical of untreated PC12 cells and displayed signs of neuronal differentiation only after treatment with 100 ng/ml of nerve growth factor. The addition of 5 micrograms/ml of anti-Tat monoclonal antibody to the culture medium of tat-positive PC12 cell clones almost completely blocked their increased proliferation rate (P < 0.05), but did not affect neuronal differentiation. A significant (P < 0.05) increase in cell proliferation was consistently observed in PC12 cells supplemented with low concentrations of Tat (5 to 25 ng/ml), whereas neuronal differentiation was hardly affected by exogenous Tat. Our data strongly suggest that Tat exerts a complex influence on the proliferation and differentiation of PC12 cells, and this might help in increasing understanding of the pathogenesis of the frequent neurological disorders observed in AIDS patients.
...
PMID:Influence of the human immunodeficiency virus type 1 Tat protein on the proliferation and differentiation of PC12 rat pheochromocytoma cells. 827 65

We have studied the neuropathological characteristics of the brain of rats receiving daily intracerebroventricular administration of freshly dissolved human immunodeficiency virus type 1 recombinant protein gp120 (100 ng per rat per day) given for up to 14 days. Histological examination of serial brain sections revealed no apparent gross damage to the cortex or hippocampus, nor did cell counting yield significant neuronal cell loss. However, the viral protein caused after 7 and 14 days of treatment DNA fragmentation in 10% of brain cortical neurons. Interestingly, reduced neuronal nitric oxide synthase (NOS) expression along with significant increases in nerve growth factor (NGF) were observed in the hippocampus, where gp120 did not cause neuronal damage. No changes in NGF and NOS expression were seen in the cortex, where cell death is likely to be of the apoptotic type. The present data demonstrate that gp120-induced cortical cell death is associated with the lack of increase of NGF in the cerebral cortex and suggest that the latter may be important for the expression of neuropathology in the rat brain. By contrast, enhanced levels of NGF may prevent or delay neuronal death in the hippocampus, where reduced NOS expression may be a reflection of a subcellular insult inflicted by the viral protein.
...
PMID:Intracerebral injection of human immunodeficiency virus type 1 coat protein gp120 differentially affects the expression of nerve growth factor and nitric oxide synthase in the hippocampus of rat. 857 Jun 62

We have here investigated the effect of the regulatory Tat protein of the human immunodeficiency virus type 1 (HIV-1) on the PI 3-kinase catalytic activity in PC12 rat pheochromocytoma cells. After as early as 1 min from the beginning of the treatment with recombinant HIV-1 Tat protein, a significant increase in the tyrosine phosphorylation levels of the p85 regulatory subunit of PI 3-kinase was noticed in 48 h serum-starved PC12 cells. Moreover, the addition of Tat to PC12 cells induced a great increase in PI 3-kinase immunoprecipitated with an anti-phosphotyrosine antibody with a peak of activity (19-fold increase with respect to the basal levels) after a 15-min treatment. This increase in PI 3-kinase activity was significantly higher in PC12 cell cultures supplemented with Tat protein than in cultures stimulated by 100 ng/ml nerve growth factor (NGF; 8-fold increase with respect to the basal levels). Further experiments showed that Tat protein was able to specifically activate PI 3-kinase at picomolar concentrations. In fact: (i) maximal activation of PI 3-kinase was observed at concentrations as low as 1 ng/ml and was specifically blocked by anti-Tat neutralizing antibody; (ii) a Tat-dependent activation was also observed in experiments in which PI 3-kinase activity was evaluated in either anti-Tyr(P) or anti-p85 immunoprecipitates; (iii) 100 nM wortmannin completely blocked the Tat-mediated increase in PI 3-kinase activity both in vitro and in vivo. Our data strongly support the concept that extracellular Tat acts as a cell stimulator, inducing intracellular signal transduction in uninfected cells.
...
PMID:Extracellular human immunodeficiency virus type-1 Tat protein activates phosphatidylinositol 3-kinase in PC12 neuronal cells. 879 81

The effects of several anti-human immunodeficiency virus nucleoside analogs were examined on neurite regeneration and mitochondrial DNA (mtDNA) synthesis in nerve growth factor-primed PC-12 cells. Under pharmacologically relevant concentrations, the exposure of cells to 2',3'-dideoxyinosine (ddI), 2',3'-dideoxycytidine (ddC) and 2',3'-didehydro-3'-deoxythymidine (d4T) led to a marked dose-dependent inhibition of neurite regeneration with a 50% inhibitory concentration approximating 1, 5 and 15 microM, respectively. In contrast, 3'-azido-3'-deoxythymidine (AZT) and beta-L-2',3'-dideoxy-3'-thiacytidine (3TC) had no effect on neurite regeneration. Inhibition of mtDNA synthesis by ddI was dose dependent, and ddC at a concentration of 10 microM strongly reduced mtDNA content by >75%. However, no inhibition of mtDNA synthesis was detected in cells exposed to 10 microM 3TC or d4T and to 25 microM AZT, suggesting a lack of definite correlation between mtDNA depletion and blockage of neurite regeneration. High performance liquid chromatographic analysis demonstrated that AZT, ddC, 3TC and d4T were anabolized to their respective monophosphate, diphosphate and triphosphate derivatives in the PC-12 cells. In addition, d4T was phosphorylated to form its monophosphate, diphosphate and triphosphate derivatives in isolated mitochondria, whereas ddC was metabolized only to its monophosphate form and no phosphorylated metabolites of 3TC were detected under the same conditions. In summary, the peripheral neuropathy induced by ddC and ddI in patients with acquired immune deficiency syndrome may be accounted for by the depletion of mtDNA content in the neurons. As for d4T, some other mechanism(s) may be involved in its clinical neurotoxicity. Both AZT and 3TC lacked any substantial toxicity in our in vitro model, which is in agreement with the clinical action of these drugs.
...
PMID:Effect of nucleoside analogs on neurite regeneration and mitochondrial DNA synthesis in PC-12 cells. 906 8

CD40 is a 48 Kd integral membrane protein expressed by cells of B cells, origin, dentritic cells, monocytes, epithelial cells, endothelial cells and tumor cells including carcinomas, B cell lymphomas/leukemias and Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin's disease (HD). CD40 has been clustered as a member of the nerve growth factor (NGF)/tumor necrosis factor (TNF) receptor superfamily with the corresponding counterstructure, the CD40 ligand (L) being mainly expressed by activated CD4+ T cells, but also some activated CD8+ T cells, basophils, eosinophils, mast cells and stromal cells. CD40L shares significant amino acid homology with TNF particularly in its extracellular domain ("TNF homology region") and is therefore viewed as a member of the TNF ligand superfamily. Binding of CD40L+ T cells to CD40+ B cells is thought to play a major role in T cell-dependent B cell activation, B cell proliferation, Ig isotype switching, memory B cell formation and rescue of B cells from apoptotic death in germinal centers. Mutations of the CD40L gene have been associated with the X-linked hyper-IgM immunodeficiency syndrome, pointing to the critical role of the CD40/CD40L interaction in the T cell-B cell interplay. Accordingly, expression of CD40 by human lympho-hematopoietic tumors has been shown in most of the B cell neoplasias, H-RS cells and HD and some carcinomas. In contrast, CD40L+ tumor cells are almost invariably restricted to CD4+/CD8- T cell lymphomas. Overall, functional CD40/CD40L interactions appear to be critical for cellular activation signals during immune responses and neoplastic tumor cell growth. The understanding of the biology of CD40L has improved our diagnostic and therapeutic repertoire in the management of several human diseases, including CD40+ tumors.
...
PMID:CD40/CD40 ligand interactions in normal, reactive and malignant lympho-hematopoietic tissues. 908 33


1 2 3 Next >>

---