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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Southern Africa is undergoing a food crisis of surprising scale and novelty. The familiar culprits of drought and mismanagement of national strategies are implicated. However, this crisis is distinct from conventional drought-induced food shortages with respect to those vulnerable to starvation, and the course of impoverishment and recovery. We propose that these new aspects to the food crisis can be attributed largely to the HIV/AIDS epidemic in the region. We present evidence that we are facing a new variant famine. We have used frameworks drawn from famine theory to examine the implications. HIV/AIDS has created a new category of highly vulnerable households--namely, those with ill adults or those whose adults have died. The general burden of care in both AIDS-affected and non-AIDS-affected households has reduced the viability of farming livelihoods. The sensitivity of rural communities to external shocks such as drought has increased, and their resilience has declined. The prospects for a sharp decline into severe famine are increased, and possibilities for recovery reduced.
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PMID:New variant famine: AIDS and food crisis in southern Africa. 1466 65

Patients infected with human immunodeficiency virus type 1 (HIV-1) develop a spectrum of B cell lymphoproliferative disorders ranging from polyclonal B cell activation to B cell lymphomas. While a direct role of Epstein-Barr virus (EBV) is well recognized for most of these lesions, recent findings have suggested that transactivator HIV-1 Tat protein might be involved in the pathogenesis of B cell lymphomas. Tat-expressing EBV-positive B cells were generated by transduction with a retroviral Tat-encoding vector. B(Tat+) cells expressed lower levels of anti-apoptotic protein Bcl-2 than parental and control B(Tat-) cells, generated by transduction with an empty retroviral vector, and were more prone to apoptosis upon serum withdrawal, as assessed by analysis of annexin V-stained cells and cleavage of poly-ADP-ribose-polymerase by caspase 3. Nevertheless, in serum starvation, B(Tat-) cells mainly exhibited the Rb hypo-phosphorylated form, underwent cell cycle arrest, and grew in single cell suspension, while B(Tat+) cells displayed the Rb hyper-phoshorylated form, progressed throughout the cell cycle, and retained the ability to grow in small clumps. Finding that B(Tat+) cells maintained proliferative capacity upon serum withdrawal suggests that cells expressing Tat have growth advantages among the EBV-driven cell proliferations and may originate B cell clones with more oncogenic potential.
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PMID:Human immunodeficiency virus type 1 Tat protein modulates cell cycle and apoptosis in Epstein-Barr virus-immortalized B cells. 1509 50

Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G (APOBEC3G) is an antiretroviral deoxycytidine deaminase that lethally hypermutates human immunodeficiency virus type 1 (HIV-1) but is itself neutralized by the HIV-1-encoded viral infectivity factor. Accordingly, APOBEC3G occurs specifically in human T lymphocytic cell lines that contain this antiviral defense, including H9. Since the substrate specificities of related cytidine deaminases are strongly influenced by their intracellular quantities, we analyzed the factors that control APOBEC3G expression. The levels of APOBEC3G mRNA and protein were unaffected by treatment of proliferating H9 cells with interferons or tumor necrosis factor-alpha but were enhanced up to 20-fold by phorbol myristate acetate. This induction was mediated at the transcriptional level by a pathway that required activation of the protein kinase Calpha/betaI isozyme (PKC), mitogen-activated protein kinase kinase (MEK) 1 and 2, and extracellular signal-regulated kinase (ERK). Correspondingly, induction of APOBEC3G was blocked by multiple inhibitors that act at diverse steps of this pathway. The PKCalpha/betaI/MEK/ERK pathway also controlled basal levels of APOBEC3G mRNA and protein, which consequently declined when cells were treated with these inhibitors or arrested in the G(0) state of the cell cycle by serum starvation. We conclude that expression of the antiviral APOBEC3G editing enzyme is dynamically controlled by the PKCalpha/betaI/MEK/ERK protein kinase cascade in human T lymphocytes.
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PMID:Transcriptional regulation of APOBEC3G, a cytidine deaminase that hypermutates human immunodeficiency virus. 1529 52

Since macrophage activation can now be studied at a global level using modern microarray and proteomic analyses, discovery of novel macrophage activation genes is inevitable and important for understanding HIV-associated dementia (HAD). We isolated two different types of primary human macrophages: microglia and monocyte-derived macrophages (MDM) from brain tissue and whole blood, respectively. The microarray analysis of differentially regulated macrophage activation genes reported here supports our previous assertions that the mixed glia (MIX) cultured in starvation conditions (DMEM alone) are a non-activated, or "quiescent", tissue culture model for studying macrophage activation in the brain. Transcript levels from these quiescent cultures provided a background level of gene expression and allowed for the identification of upregulated macrophage activation genes in the MIX brain cultures upon treatment with an array of soluble activation factors: serum components, cytokines, and growth factors. We found that 914 genes in the MIX cultures and 734 genes in the MDM cultures had a greater than twofold increase in expression. We discovered 180 genes with expression that was increased more than twofold in both culture types. Microarray-specific statistical analyses were performed to complement fold change analysis: significance analysis of microarrays (SAM) and Partek Pro. In the MIX cultures, we detected over a 100-fold increase in IL-1beta and TIMP1 transcription; Caspase 9, S100A8 and 9, MMP12, IL-8, monocyte chemotactic protein 1 (MCP1), MRC-1, and IL-6 were also upregulated. Activation of starved MDM cultures resulted in fewer upregulated genes compared to MIX cultures. Genes upregulated in both MIX and MDM included CCL2 (MCP1), CCL7, CXCL5, TNFSF14, kinases, and phosphatases. These microarray data may provide leads for identifying previously unknown neurotoxins, disease biomarkers, and pathways responsible for the neuronal apoptosis observed in HAD and for the eventual identification of therapeutic targets and treatments.
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PMID:Microarray analysis of activated mixed glial (microglia) and monocyte-derived macrophage gene expression. 1557 77

It is controversial whether the accessory human immunodeficiency virus type 1 (HIV-1) Nef protein inhibits or enhances apoptosis. To address this issue, we investigated the effect of Nef on programmed cell death with vectors or proviral HIV-1 constructs coexpressing Nef and green fluorescent protein from single bicistronic RNAs. This approach allows us to readily identify transfected or infected cells and to correlate cell death directly with Nef expression levels. We demonstrate that Nef does not significantly affect apoptosis in transfected or HIV-1-infected Jurkat T cells or primary human peripheral blood mononuclear cells. Unexpectedly, however, both nef+ and nef-defective HIV-1 infection blocked apoptosis in cells treated with UV light or etoposide but not cell death induced by CD95 antibody, TRAIL, Ly294002, or serum starvation. Our results show that HIV-1 infection inhibits DNA damage-induced but not death receptor-dependent cell death by a Nef-independent mechanism.
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PMID:Human immunodeficiency virus type 1 inhibits DNA damage-triggered apoptosis by a Nef-independent mechanism. 1582 63

We have identified four small molecules that boost transduction of cells by human immunodeficiency virus (HIV) and investigated their mechanism of action. These molecules include etoposide and camptothecin, which induce DNA damage by inhibiting religation of cleaved topoisomerase-DNA complexes, taxol, which interferes with the function of microtubules, and aphidicolin, which inhibits DNA polymerases. All four compounds arrest the cell cycle at G2/M, though in addition high concentrations of aphidicolin arrest in G1. We find that early events of HIV replication, including synthesis of late reverse transcription products, two-long terminal repeat circles, and integrated proviruses, were increased after treatment of cells with concentrations of each compound that arrested in G2/M. Stimulation was seen for both transformed cell lines (293T and HeLa cells) and primary cells (IMR90 lung fibroblasts). Arrest in G1 with high concentrations of aphidicolin boosted transduction, though not much as with lower concentrations that arrested in G2/M. Arrest of IMR90 cells in G1 by serum starvation and contact inhibition reduced transduction. Previously, the proteasome inhibitor MG132 was reported to increase HIV infection-here we investigated the effects of combinations of the cell cycle inhibitors with MG132 and obtained data suggesting that MG132 may also boost transduction by causing G2/M cell cycle arrest. These data document that cell cycle arrest in G2/M boosts the early steps of HIV infection and suggests methods for increasing transduction with HIV-based vectors.
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PMID:Cell cycle arrest in G2/M promotes early steps of infection by human immunodeficiency virus. 1582 84

We show that the pertussis toxin B oligomer (PTX-B), and the PTX mutant PT9K/129G, which is safely administered in vivo, inhibit both transcription and secretion of TGF-beta elicited by HIV-1 Tat in NK cells. Tat-induced TGF-beta mRNA synthesis is also blocked by the ERK1 inhibitor PD98059, suggesting that ERK1 is needed for TGF-beta production. Moreover, Tat strongly activates the c-Jun component of the multimolecular complex AP-1, whereas TGF-beta triggers c-Fos and c-Jun. Of note, treatment of NK cells with PTX-B or PT9K/129G inhibits Tat- and TGF-beta-induced activation of AP-1. TGF-beta enhances starvation-induced NK cell apoptosis, significantly reduces transcription of the antiapoptotic protein Bcl-2, and inhibits Akt phosphorylation induced by oligomerization of the triggering NK cell receptor NKG2D. All these TGF-beta-mediated effects are prevented by PTX-B or PT9K/129G through a PI3K-dependent mechanism, as demonstrated by use of the specific PI3K inhibitor, LY294002. Finally, PTX-B and PT9K/129G up-regulate Bcl-x(L), the isoform of Bcl-x that protects cells from starvation-induced apoptosis. It is of note that in NK cells from patients with early HIV-1 infection, mRNA expression of Bcl-2 and Bcl-x(L) was consistently lower than that in healthy donors; interestingly, TGF-beta and Tat were detected in the sera of these patients. Together, these data suggest that Tat-induced TGF-beta production and the consequent NK cell failure, possibly occurring during early HIV-1 infection, may be regulated by PTX-B and PT9K/129G.
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PMID:Pertussis toxin (PTX) B subunit and the nontoxic PTX mutant PT9K/129G inhibit Tat-induced TGF-beta production by NK cells and TGF-beta-mediated NK cell apoptosis. 1587 99

DNA integration is a defining step in the retroviral life cycle and the basis of stable gene transfer in retrovirus-based gene therapy. Previous studies of integration by HIV-based vectors have shown that integration is not random, but favored in active transcription units. Studies to date have focused on HIV integration in dividing cells, leaving open the question of whether integration target site selection might differ in nondividing cells. According to one idea, division of the host cell might be required for favored integration in transcription units, possibly as a result of chromatin remodeling during DNA replication. Here we have investigated this issue by comparing integration in dividing IMR-90 primary lung fibroblasts to integration in nondividing IMR-90 cells arrested in G1 by serum starvation and contact inhibition. We identified several differences in integration site selection in arrested versus dividing cells, including the frequency of integration in transcription units and in gene-rich regions. However, integration in nondividing cells was in fact more favored in transcription units, contrary to the idea that cell division was important for this bias. These data provide the first view of lentiviral integration in nondividing cells and help constrain models for the mechanism of favored integration in genes.
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PMID:Integration site selection by HIV-based vectors in dividing and growth-arrested IMR-90 lung fibroblasts. 1632 73

Vpx facilitates HIV-2 nuclear localization by a poorly understood mechanism. We have compared Vpx to an NMR structure HIV-1 Vpr in a central helical domain and probed regions of Vpx by insertional mutagenesis. A predicted loop between helices two and three appears to be unique, overlapping with a known novel nuclear localization signal. Overall, Vpx was found to be surprisingly flexible, tolerating a series of large insertions. We found that insertion within the polyproline-containing C-terminus destabilizes nuclear localization, whereas mutating a second helix in the central domain disrupts viral packaging. Other insertional mutants in the predicted loop and in a linker region between the central domain and the C-terminus may be useful as sites of intramolecular tags as they could be packaged adequately and retained preintegration complex associated integration activity in a serum starvation assay. An unexpected result was found within a previously defined nuclear localization motif near aa 71. This mutant retained robust nuclear localization in a GFP fusion assay and was competent for preintegration complex associated nuclear import. In summary, we have modeled helical content in Vpx and assessed potential sites of intramolecular tags which may prove useful for protein-protein interactions studies.
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PMID:Analysis of HIV-2 Vpx by modeling and insertional mutagenesis. 1645 68

Herein, we show that PTX-B and its non-toxic mutant PT9K/129G inhibit transcription and secretion of TGF-beta elicited by HIV-1 Tat in NK cells. Moreover, Tat strongly activates the cJun component of the multimolecular complex AP-1, while TGF-beta triggers cFos and cJun. Treatment of NK cells In turn,with PTX-B or PT9K/129G inhibits Tat and TGF-beta-induced activation of AP-1. TGF-beta enhances starvation-induced NK cell apoptosis, reduces the transcription of the antiapoptotic protein Bcl-2 and inhibits Akt phosphorylation induced by oligomerization of the triggering NK cell receptor NKG2D. All these TGF-beta-mediated effects are prevented by PTX-B or PT9K/129G, through a PI-3K-dependent mechanism. Finally, PTX-B and PT9K/129G upregulate Bcl-x(L), the isoform of Bcl-x that protects cells from starvation-induced apoptosis. Of note, in NK cells from patients with HIV-1 infection, mRNA expression of Bcl-2 and Bcl-x(L) was consistently lower than that of healthy donors; interestingly, TGF-beta and Tat were detected in the sera of these patients. These data suggest that Tat-induced TGF-beta production and the consequent NK cell failure, possibly occurring during early HIV-1 infection, may be regulated by PTX-B and PT9K/129G.
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PMID:HIV-1 Tat triggers TGF-beta production and NK cell apoptosis that is prevented by pertussis toxin B. 1716 79


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