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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ACH-2 cells, an immortalized human T-cell line, contain a single integrated copy of the HIV-1 provirus. Here, the structure of HIV-1 chromatin was probed using a DNA cleavage reagent. Nuclei were isolated from ACH-2 cells and treated with methidiumpropyl-EDTA (MPE)-iron(II) to produce limited DNA cleavage. Primers were selected at approximately 300 bp intervals along the HIV-1 DNA, and sites of preferential cleavage were mapped by carrying out 50 cycles of primer extension using a thermo-stable DNA polymerase in the presence of [32P]dATP. By comparing the resulting cleavage pattern with patterns derived from human cell lines not containing HIV-1 sequences, it was possible to map the arrangement of nucleosomes across the integrated HIV-1 genome. Particularly regular spacing was seen in the 3' end of the pol and env coding regions, and several extended blocks spared of nucleosomes were found in gag and pol, the largest being an approximately 450 bp region in gag. For comparison, and to examine nucleosome placement on HIV-1 DNA when it is not integrated, overlapping segments of HIV-1 DNA were cloned into an EBV-oriP plasmid, grown as stable episomes in a human B lymphoblastoid cell line, and the same analysis using MPE-iron(II) cleavage and primer extension carried out. The major features of nucleosome placement on these EBV/HIV minichromosomes was very similar to that observed in the integrated HIV-1 genome arguing for a strong sequence dependence for nucleosome placement along HIV-1 DNA.
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PMID:Nucleosomal arrangement of HIV-1 DNA: maps generated from an integrated genome and an EBV-based episomal model. 860 34

The delivery to the brain of nonlipophilic therapeutic compounds, especially proteins, is severely hindered by the presence of the blood-brain barrier, which is formed by the tightly apposed brain capillary endothelial cells. However, brain endothelial cells do possess specific receptor-mediated transport mechanisms so that substances required by the brain can cross the blood-brain barrier. By use of monoclonal antibodies that bind to the transferrin receptor present on the luminal surface of brain capillary endothelial cells, we have taken advantage of the transport system responsible for the delivery of iron to the brain to deliver recombinant human soluble CD4 (rsCD4), a potential anti-HIV therapeutic, across the blood-brain barrier. Anti-transferrin receptor antibody-rsCD4 conjugates were synthesized with a disulfide linkage and characterized in vitro. Experiments that use immunohistochemistry to localize these conjugates after intravenous administration into the tail vein of rats have shown that both the carrier antibody and the protein "passenger" accumulate in brain capillaries. The carrier-mediated delivery of radiolabeled protein across the blood-brain barrier in vivo was also examined in both rodents and primates. With use of the technique of capillary depletion in rats, the amount of rsCD4 in the capillary fraction of the brain, which reaches a maximal value within 1 hr postinjection, was shown to decrease with time, whereas the amount in the brain parenchyma increased, which suggests that the protein was delivered across the blood-brain barrier. In primates rsCD4 levels in the brain were increased 5-fold when the protein was administrated intravenously in the form of an anti-transferrin receptor antibody-rsCD4 conjugate.
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PMID:Enhanced uptake of rsCD4 across the rodent and primate blood-brain barrier after conjugation to anti-transferrin receptor antibodies. 862 18

Ribosomal frameshifting is a translational mechanism used as an essential step in the replication cycle of retroviruses. Programmed frameshifting in retroviral translation involves two sequence elements: A heptanucleotide slippery sequence which induces a low basal level of frameshifting and a downstream RNA structure as an enhancer of the process. The precise mechanism of function of these downstream elements is still unclear, but their effect does not solely depend on their stability. Likewise, the possibility that frameshifting could be controlled by specific proteins that bind to these elements and enable or modulate their effects has yet not been substantiated. The RNA hairpin of the HIV-1 gag-pol frameshift cassette was replaced by the iron-responsive element (IRE) from ferritin mRNA, a stem-loop structure that binds iron regulatory proteins (IRPs) in dependence of the iron status of the cell. When a lacZ/luciferase reporter construct was expressed in transfected BHK-21 cells, the IRE or a point-mutated version that is unable to bind IRPs were found to functionally substitute for the HIV-1 hairpin. When cells were treated with the iron chelator desferrioxamine to stimulate IRP binding to the wild-type IRE, frameshift activity was specifically and strongly augmented by protein binding Our data establish that frameshifting can be regulated in a reversible fashion by mRNA-binding proteins.
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PMID:Regulated ribosomal frameshifting by an RNA-protein interaction. 863 12

A bone marrow investigation is a common examination in HIV infected patients for the study of cytopenia, febrile syndromes of unknown origin and extension of neoplastic disorders. A study was made of bone marrow specimens from 35 patients with advanced HIV infection (stage IC or C, CDC, Atlanta) for morphologic and culture investigations (aerobes, anaerobes, fungi, and mycobacteria). In nine patients cytopenia accounted for the investigation of bone marrow specimens (9 aspirates and 3 biopsies); in only two cases did the investigation orientate towards a possible etiology: in the first patient a parvovirus B19 infection and in the second patient a hemophagocytic syndrome. In twenty-five patients the bone marrow specimen was studied because of fever of unknown origin (23 aspirates and 10 biopsies) and only in one case was the identification of Mycobacterium tuberculosis obtained. The other patient was studied for lymphoma staging and aspirate and biopsy examinations were normal. A high percentage of patients had eosinophilia, plasmacytosis, increased iron reserves, fibrosis, and changes consistent with myelodysplasia. In conclusion, in our experience the investigation of bone marrow specimen was of little help to clarify the possible etiology of cytopenia and febrile syndromes of unknown origin in patients with advanced HIV infection.
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PMID:[Usefulness of bone marrow examination in patients with advanced HIV infection]. 870 Oct 58

RNA-protein interactions are pivotal in fundamental cellular processes such as translation, mRNA processing, early development, and infection by RNA viruses. However, in spite of the central importance of these interactions, few approaches are available to analyze them rapidly in vivo. We describe a yeast genetic method to detect and analyze RNA-protein interactions in which the binding of a bifunctional RNA to each of two hybrid proteins activates transcription of a reporter gene in vivo. We demonstrate that this three-hybrid system enables the rapid, phenotypic detection of specific RNA-protein interactions. As examples, we use the binding of the iron regulatory protein 1 (IRP1) to the iron response element (IRE), and of HIV trans-activator protein (Tat) to the HIV trans-activation response element (TAR) RNA sequence. The three-hybrid assay we describe relies only on the physical properties of the RNA and protein, and not on their natural biological activities; as a result, it may have broad application in the identification of RNA-binding proteins and RNAs, as well as in the detailed analysis of their interactions.
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PMID:A three-hybrid system to detect RNA-protein interactions in vivo. 871 Aug 98

Children with human immunodeficiency virus (HIV) infection have a higher prevalence of intestinal malabsorption. Anemia is also a common feature in these children. The aims of this work were (a) to establish the prevalence of iron deficiency in HIV-infected children, (b) to test the hypothesis that iron deficiency is related to intestinal malabsorption, (c) to see whether it may contribute to anemia, and (d) to evaluate the sensitivity of oral iron load in the investigation of intestinal function. To accomplish these goals, 71 HIV-infected symptomatic children were enrolled. Iron serum values were determined before and after oral load with ferrous sulfate. The correlation between basal and post-load iron levels was evaluated by linear regression. Xylose level after oral load, fecal fat, and fecal alpha 1-antitrypsin concentration were also determined. Iron deficiency was detected in 48% of patients, and it was significantly associated with intestinal iron malabsorption. Sugar malabsorption, steatorrhea, and fecal protein loss were detected in 26, 36, and 17% of patients, respectively. Low hemoglobin levels were detected in 66% of patients. The majority of children with iron deficiency also had anemia. Preliminary data showed that oral iron administration was sufficient for raising hemoglobin in children with normal iron absorption, whereas parenteral administration was required in those with iron malabsorption. We conclude that (a) iron deficiency is a major feature of pediatric HIV infection, (b) it is related to intestinal malabsorption, and (c) it contributes to anemia. Finally, oral iron load is a sensitive test for investigating intestinal function.
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PMID:Iron deficiency and intestinal malabsorption in HIV disease. 873 98

Skeletal muscle involvement may occur at all stages of HIV-infection and represents the first manifestation of the disease in some patients. We usually classify muscle involvement in HIV-infected patients in one of the following categories: (1) HIV-associated myopathy, a myopathy that meets the criteria for polymyositis in a majority of patients, and those for acquired nemaline myopathy in some; (2) zidovudine myopathy, a reversible mitochondrial myopathy; (3) the HIV-wasting syndrome and other AIDS-associated cachexias; (4) opportunistic infections and tumoral infiltrations of the skeletal muscle; (5) vasculitic processes and iron pigment deposits; (6) HIV-associated myasthenia gravis and (7) rhabdomyolysis. Immunohistology for major histocompatibility complex class I antigen and histochemical reaction for cytochrome c oxidase are helpful in correct classification of a myopathy as HIV polymyositis or zidovudine myopathy.
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PMID:[Muscular involvement in HIV infection]. 874 23

The progression of human immunodeficiency virus (HIV) infection toward its more advanced stages is accompanied by increasing body iron stores. Iron accumulates in macrophages, microglia, endothelial cells, and myocytes. The iron burden is especially heavy in bone marrow, brain white matter, muscle, and liver. Excess iron potentially enhances oxidative stress, impairs several already compromised immune defense mechanisms, and directly promotes the growth of microbial cells. Thus, we hypothesize that the prevention (or at least, reduction) of iron loading might slow the progression of the infectious complications of HIV infection, and perhaps indirectly, the HIV infection itself. A twofold strategy is proposed, consisting of (a) limitation of iron intake through the alimentary, parenteral, and respiratory routes, and (b) possibly the use of iron chelator drugs that could decrease the iron burden, redistribute the metal to the erythroblasts, and suppress the growth of microorganisms. This approach is still to be considered as hypothetical. However, the available data suggest that there is an urgent need for careful clinical studies to clarify the role of iron status on the course of HIV infection.
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PMID:Altered iron metabolism in HIV infection: mechanisms, possible consequences, and proposals for management. 878 98

Diethyldithiocarbamate (DDC), a potent copper chelating agent, has long been used for the treatment of oxygen toxicity to the central nervous system, as an immunomodulator to treat cancer, and in HIV-infected patients. We evaluated the antioxidant properties of DDC, including its scavenging of reactive oxygen species, its reducing properties, its iron-chelating properties, and its protective effects on oxidant-induced damage to brain tissue, protein, human LDL, and DNA. It is found that DDC is a powerful reductant and antioxidant since it scavenges hypochlorous acid, hydroxyl radical and peroxynitrite; it chelates, then oxidizes ferrous ions; it blocks the generation of hydroxyl radicals and inhibits oxidative damage to deoxyribose, protein, DNA, and human LDL. These findings may provide an explanation for the apparent beneficial effects of DDC against oxidative stress-related diseases that have been observed in experimental and clinical studies.
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PMID:Antioxidant activity of diethyldithiocarbamate. 880 89

In the last 10 years, interest in adolescence has increased worldwide. Much of the attention has been on adolescent health, in particular adolescent pregnancy and sexually transmitted diseases, including HIV infection, but adolescent nutrition has aroused little interest. 11 studies on nutritional status of boys and girls have recently been conducted in Benin, Cameroon, Ecuador, India, Jamaica, Mexico, Nepal, Guatemala, and the Philippines. The studies differed in protocol, sample size, and data collection methods. Anemia was the most important nutritional problem. Anemia prevalence was high in 4 studies (55% in India, 42% in Nepal, 32% in Cameroon, 48% in Guatemala) and significant in 2 others (17% in Ecuador and 16% in Jamaica). Slow growth was common in 9 studies (27-65%). Height in girls as well as in boys did not improve during the entire 8 years of adolescence. It approached the fifth percentile at age 10 and at age 18. Low body mass index (BMI) was high (23-53%) in only 3 studies. It was surprising that boys had a BMI 2 times lower than that of girls relative to sex-specific data. With the difference in growth in height, BMI increased substantially throughout the 8 years of adolescence among all girls for both low BMI or satisfactory BMI at age 10 but only for low BMI among boys age 10. At age 18, the median BMI for girls and boys was well below the fifth percentile. However, in 3 countries where the median BMI at age 10 was low, the boys did not reach the 50th percentile and were still growing, while girls had reached the 50th percentile and stopped growing. These results suggest that the iron status of adolescents needs to be improved, but it is necessary to be cautious when improving height when the BMI is adequate for age 18.
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PMID:Adolescent nutritional status in developing countries. 883 3


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