Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-like growth factor type I (IGF-I) has been used as a treatment for cachexia in adults with AIDS and has been reported to show inhibitory activity against HIV-1IIIB in cord blood mononuclear cells (CBMCs) in vitro at low-concentration (1%) fetal bovine serum (FCS). We evaluated the effect of IGF-I on MN, IIIB, and BaL strains, as well as on a patient isolate of HIV-1 in CBMCs and adult peripheral blood mononuclear cells (PBMCs). IGF-I failed to show any inhibitory effect on HIV replication in CBMCs or adult PBMCs under various culture conditions. In contrast to an earlier report of an antiviral effect, IGF-I augmented HIV-1 replication in PHA-stimulated PBMCs maintained in a low concentration of FCS.
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PMID:Failure of insulin-like growth factor type I to suppress HIV type 1 in adult or umbilical cord mononuclear blood cells. 898 33

The major histocompatibility complex (MHC) contains at least a hundred genes over 4 megabases of DNA. Within the MHC there are several new multigene families which have been recently described. PERB11 is a multigene family which occurs over the class I and central region of the MHC. Two members of the family have been shown to be functional and share domains with members of the supergene family including HLA class I, FcRn, and Zn-alpha2-glycoprotein molecules. The two functional members are contained within an area of the MHC which has been associated with increased susceptibility to autoimmune diseases such as insulin-dependent diabetes mellitus and also rapid progression to AIDS following HIV-1 infection. Intralocus and interlocus differences between PERB11.1 and PERB11.2 include: (1) several nucleotide substitutions leading to amino acid changes; (2) presence and absence of potential glycosylation sites; (3) insertions and deletions leading to a frame shift resulting in diversity at the amino acid level and an early termination signal. There are ten different alleles of PERB11.1 including one allele which contains a frame shift in the transmembrane region causing a putative truncated molecule lacking the cytoplasmic tail. The significance of this polymorphism in disease associations is under investigation. The most divergent domain is the transmembrane region when PERB11.1 and PERB11.2 are compared. The results suggest that these two molecules may have different functions.
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PMID:Allelic and interlocus comparison of the PERB11 multigene family in the MHC. 899 88

Interferon-gamma (IFN-gamma) has been shown to inhibit proliferation and differentiation of erythroid progenitor cells and to produce apoptosis of erythroid cells, but IFN-gamma receptors are not present on red cells and have never been demonstrated on erythroid progenitor cells. We obtained highly purified day 6 erythroid colony-forming cells (ECFCs) from human blood in sufficient quantity and purity to measure binding of radioiodinated recombinant human IFN-gamma ([125I]rhIFN-gamma). When [125I]rhIFN-gamma was incubated with day 6 ECFC, 77% of the binding was inhibited by excess unlabeled rhIFN-gamma, but no inhibition occurred with a variety of growth factors and glycoproteins. Specific binding was directly proportional to the cell concentration with a straight line passing through the origin, and equilibrium was reached at 0 degree C by 24-48 hours. Saturation of specific binding occurred at a [125I]rhIFN-gamma concentration of 1.0 nM and internalization was demonstrated with further incubation at 37 degrees C. Scatchard analysis showed a single class of binding sites and at a high ECFC cell purity of 80-89%, 1910-2070 binding sites per ECFC were present with a Kd of 0.01-0.02 nM. As day 5 ECFC developed into more mature day 7-day 12 cells, with incubation at 37 degrees C in vitro, specific binding for [125I]IFN-gamma greatly decreased. These experiments delineate specific binding sites for IFN-gamma on human erythroid progenitor cells and indicate that the enhanced sensitivity to rhIFN-gamma inhibition of mature day 3-day 6 burst-forming units-erythroid may be a result of enhanced specific binding. Human IFN-gamma is a multifunctional lymphokine, secreted by activated T lymphocytes and NK cells, which exerts antiviral, antiproliferative, and immunomodulatory activities on a wide variety of cells [1,2]. With regard to hematopoietic cells, IFN-gamma has been reported to inhibit the growth of granulocyte-macrophage colony-forming units, burst-forming units-erythroid (BFU-E) and colony-forming units-erythroid (CFU-E) in vitro [3-7]. Most recently, mature day 3 to day 6 BFU-E have been shown to be most sensitive to the inhibitory effect of recombinant human (rh) IFN-gamma, while primitive day 1 to day 2 cells and later day 7 cells were less affected [7]. Incubation of rhIFN-gamma with mature BFU-E inhibits hemoglobin accumulation and produces apoptosis of the maturing erythroid cells [7]. Moreover, since blood IFN-gamma levels are elevated and vary directly with the degree of the anemia, in patients with hematologic malignancies [8] and HIV-seropositivity [9], IFN-gamma appears to have a prominent role in producing the anemia associated with chronic disease [10,11]. Although characterization of human IFN-gamma receptors has been extensively performed for a variety of human cells including fibroblasts, lymphocytes, monocytes, granulocytes, eosinophiles, platelets, and many tumor cells [12-17], IFN-gamma receptors have not been identified on red cells [12] and the presence plus the extent of IFN-gamma receptors on progenitor cells, including human erythroid progenitor cells, remains unknown. A method has been reported from our laboratory by which human erythroid colony-forming cells (ECFC) can be highly purified, starting with peripheral blood BFU-E, in a sufficient amount for analysis of cytokine binding [18-20]. In this paper, we report the results of [125I]rhIFN-gamma binding to day 6 ECFC in vitro and demonstrate the presence of specific binding that is saturable at 1.0 nM. Scatchard analysis reveals that there are 1910-2070 rhIFN-gamma binding sites per ECFC with a Kd of 0.01-0.02 nM and, as with erythropoietin (EP) and insulin-line growth factor I (IGF-I) receptors, specific binding is highest with the earliest BFU-E studied and declines progressively as the erythroid progenitors mature.
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PMID:Specific binding of interferon-gamma to high affinity receptors on human erythroid colony-forming cells. 909 Dec 93

During mobilization of a reserve battalion, administrative matters prolonged the medical validation of soldiers processing for overseas deployment. Problems included inadequate means of tracking soldiers, ignoring the chain of command within the deploying unit, delay in obtaining corrective lenses and optical inserts, and mistaken information about the need for personal medications. Consulting military physicians with negative attitudes about the deployment also caused delays. The battalion had 53% augmentees and 47% original unit members; the total strength was 788. Sixty-one unit members could not deploy for medical reasons, 25 of 418 augmentees (6%) and 36 of 370 original members (10%). Medical causes for nondeployment were: psychiatric, 14 (including 3 for alcohol dependency); back problems, 13; temporary injuries, 7; pregnancy, 4; knee problems, 4; recovery from civilian surgery, 3; and individual reasons (cancer, tuberculosis, HIV-positive, insulin-dependent diabetes, etc.), 16. More careful administrative planning, use of appropriate medical personnel, using the chain of command, establishing clear and consistent policies for medical qualification, keeping unit field medical records, using interim medical history forms to assess health problems, and utilizing medical officers who agree with the deployment would all enhance the speed and efficiency of medically validating a unit larger than company size.
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PMID:Medical aspects of mobilization for war in an Army Reserve battalion. 911 May 47

The expression of gag, pol, and env of human immunodeficiency virus type 1 (HIV-1) depends on the presence of the viral Rev protein. This dependence is, at least in part, due to the presence of negatively acting sequences (inhibitory or instability elements [INS]) located within unspliced and partially spliced mRNAs. The positive interaction of Rev with the Rev-responsive element in these mRNAs counteracts the negative effects of the inhibitory sequences. Here, we demonstrate that in addition to the previously identified INS1 within p17gag, several other INS elements exist within the gag/pol region of HIV-1. These elements act independently of each other and were eliminated by mutagenesis after the introduction of multiple point mutations not affecting the coding region, leading to constitutive high levels of Gag expression. Expression vectors containing an intact or nearly intact p55gag region allowed the production of immature viral particles in mammalian cells in the absence of any other HIV proteins. The introduction of additional mutations in the protease region allowed efficient production of Gag/protease, which resulted in processing of the Pr55gag precursor and production of mature Gag particles with a lentivirus-like conical-core structure. The elimination of a newly identified INS element within pol and the previously identified CRS located within int was accomplished by the same methodology. Sequence comparisons of the identified inhibitory elements revealed no apparent homologies and demonstrated that these sequences are not splice sites. These results demonstrate that the elimination of INS elements leads to efficient expression of HIV-1 mRNAs in the absence of Rev or any posttranscriptional activating mechanisms.
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PMID:Inactivation of the human immunodeficiency virus type 1 inhibitory elements allows Rev-independent expression of Gag and Gag/protease and particle formation. 918 51

The diffusion-limited binding kinetics of antigen (or antibody) in solution to antibody (or antigen) immobilized on a biosensor surface is analyzed within a fractal framework. The fit obtained by a dual-fractal analysis is compared with that obtained from a single-fractal analysis. In some cases, the dual-fractal analysis provides an improved fit when compared with a single-fractal analysis. This was indicated by the regression analysis provided by Sigmaplot (46). It is of interest to note that the state of disorder (or the fractal dimension) and the binding rate coefficient both increase as the reaction progresses on the biosensor surface. For example, for the binding of HIV-1 p24 in solution to monoclonal antibody (MAb) 18 covalently attached to a biosensor surface (49), an increase in the fractal dimension by 59% from a value of Df1 equal to 1.91 to Df2 equal to 2.95 leads to an increase in the binding rate coefficient by a factor of 15 from k1 equal to 21.1 to k2 equal to 339. Also, the binding of MAb 6301 and 6303 in solution to insulin growth factor binding protein-1 (IGFBP-1) covalently attached to the sensor surface is adequately described by a single-fractal analysis (48). The binding of MAb 6302 to IGFBP-1, however, requires dual fractals. This indicates a difference in the binding mechanisms of these MAbs. The different examples analyzed and presented together provide a means by which the antigen-antibody reactions may be better controlled by noting the magnitude of the changes in the fractal dimension and in the binding rate coefficient as the reaction progresses on the biosensor surface. Also, the magnitude of the changes in the binding rate coefficients (k1 and k2) and in the fractal dimensions (Df1 and Df2) as different parameters are changed for the different biosensor applications are of particular value.
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PMID:Influence of Different Parameters on a Dual-Fractal Analysis for Antigen-Antibody Binding Kinetics for Biosensor Applications 924 22

To investigate the clinical and serological responses to an inactivated influenza vaccine (split-virion A/Singapore/6/86-like strains H1N1 (15 ug HA), A/Beijing/353/89-like H3N2 (15 ug HA) and B/Yamagata/16/88-like strain (15 ug HA): MFV-JECT, Merieux, UK) in persons with HIV infection, diabetes, obstructive lung diseases, elderly adults and healthy volunteers. Forty-nine HIV-infected persons received 2 doses of the vaccine at one-month intervals; 34 healthy volunteers, 30 elderly persons, 29 with insulin and non-insulin diabetes and 14 with obstructive airways diseases were vaccinated with one single dose between October 1992 to January 1993. Serological testing of antibody responses was done using haemagglutination assay. Beta2-microglobulin in HIV-infected persons was measured using radioimmunodiffusion between 1st and 2nd dose. Fructosamine levels in diabetic persons were assessed for diabetic control and peak expiratory flow rate (PEFR) was self monitored in persons with lung diseases. All groups apart from the elderly filled in a symptom score chart for the first 5 days following vaccination. A 4-fold rise in titre equal to or more than 1:64 to all the 3 antigens occurred in 20 (58.8%) of healthy volunteers compared with 13 (44.8%) diabetics, 5 (35.7%) with lung diseases, 10 (33.3%) elderly and 13 (26.5%) with HIV infection. A significant correlation of serological response to number of CD4 count in persons with HIV infection was noted (H1N1 P=0.0013, H3N2 P=0.025, BYAM P=0.0018). Mean beta2-microglobulin levels did not change significantly post 1st and 2nd vaccination. Mean fructosamine level did not change significantly. There was no significant change in PEFR. The vaccine was well tolerated. Persons with HIV infection and low CD4 count do not serologically respond well to influenza vaccine even with 2 doses compared to the other 4 groups. The other 4 groups had adequate protective serologic responses. The vaccine was well tolerated in all groups.
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PMID:Clinical and serological responses to an inactivated influenza vaccine in adults with HIV infection, diabetes, obstructive airways disease, elderly adults and healthy volunteers. 943 53

Here we are presenting the case of a 70-years-old woman who has hepatic cirrhosis anti-HCV and insulin-dependent diabetes mellitus, without relevant epidemiologic ascendants or previous transfusions and HBV, HIV negatives. On admission to our hospital she showed signs of autoimmune hemolytic anaemia (AHA) which was confirmed by positive direct Coombs test and an improvement in blood test after corticoid treatment. Having discarded other possible causes such as drugs infectious diseases or essential mixed cryoglobulinemia (CME), we put forward the possible association between AHA and infection by HCV, where AHA was an extrahepatic immunological manifestation of HCV. This fact has never been brought to light in previous medical literature.
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PMID:[Autoimmune hemolytic anemia and posthepatitis-C liver cirrhosis]. 944 87

Members of the protein kinase C (PKC) family of serine/threonine protein kinases have been implicated in numerous cellular responses in a large variety of cell types. Expression patterns of individual members and differences in their cofactor requirements and potential substrate specificity suggest that each isoenzyme may be involved in specific regulatory processes. The PKCtheta isoenzyme exhibits a relatively restricted expression pattern with high protein levels found predominantly in hematopoietic cells and skeletal muscle. PKCtheta was found to be expressed in T, but not B lymphocytes, and to colocalize with the T-cell antigen receptor (TCR) at the site of contact between the antigen-responding T cell and the antigen-presenting cell (APC). Colocalization of PKCtheta with the TCR was selective for this isoenzyme and occurred only upon antigen-mediated responses leading to T-cell activation and proliferation. PKCtheta was found to be involved in the regulation of transcriptional activation of early-activation genes, predominantly AP-1, and its cellular distribution and activation were found to be regulated by the 14-3-3 protein. Other findings indicated that PKCtheta can associate with the HIV negative factor (Nef) protein, suggesting that altered regulation of PKCtheta by Nef may contribute to the T-cell impairments that are characteristic of infection by HIV. PKCtheta is expressed at relatively high levels in skeletal muscle, where it is suggested to play a role in signal transduction in both the developing and mature neuromuscular junction. In addition, PKCtheta appears to be involved in the insulin-mediated response of intact skeletal muscle, as well as in experimentally induced insulin resistance of skeletal muscle. Further studies suggest that PKCtheta is expressed in endothelial cells and is involved in multiple processes essential for angiogenesis and wound healing, including the regulation of cell cycle progression, formation and maintenance of actin cytoskeleton, and formation of capillary tubes. Here, we review recent progress in the study of PKCtheta and discuss its potential role in various cellular responses.
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PMID:New perspectives on PKCtheta, a member of the novel subfamily of protein kinase C. 961 93

Compromised travelers represent a diverse and challenging group of individuals. They include HIV-infected patients who are at risk for potentially adverse reactions to immunizations, and new exposures to enteric water-borne opportunistic pathogens associated with chronic infections. Such travelers may encounter unfamiliar opportunistic fungi and classical tropical infections, such as leishmaniasis, whose pathogenesis can be enhanced by the presence of prior HIV infection. Other immunocompromised groups include those who are functionally or anatomically asplenic, and patients who are iatrogenically immunosuppressed from medications utilized for solid organ transplantation, chemotherapy, or treatment of malignancies. This population of travelers also includes those with diabetes mellitus who may require adjustments in their dosing, administration, and possibly even the types of insulin used on their trips. These patients are also at greater risk for acquisition of tuberculosis, severe community-acquired pneumonia, urinary tract infections, and pyomyositis. Older travelers present both the infectious disease and travel medicine specialist with issues such events, malignancy-related infections, myocardial infarction, and other forms of cardiopulmonary compromise, which the authors address in this article.
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PMID:The compromised traveler. 965 50


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