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Sample records for high-affinity human immunodeficiency

  1. Testing for Human Immunodeficiency Virus

    Science.gov (United States)

    ... education Fact Sheet PFS005: Testing for Human Immunodeficiency Virus AUGUST 2015 • Reasons for Getting Tested • Who Should ... For More Information • Glossary Testing for Human Immunodeficiency Virus Human immunodeficiency virus (HIV) is the virus that ...

  2. Structural Basis for High-Affinity Peptide Inhibition of Human Pin1

    Science.gov (United States)

    Zhang, Yan; Daum, Sebastian; Wildemann, Dirk; Zhou, Xiao Zhen; Verdecia, Mark A.; Bowman, Marianne E.; Lücke, Christian; Hunter, Tony; Lu, Kun-Ping; Fischer, Gunter; Noel, Joseph P.

    2009-01-01

    Human Pin1 is a key regulator of cell-cycle progression and plays growth-promoting roles in human cancers. High-affinity inhibitors of Pin1 may provide a unique opportunity for disrupting oncogenic pathways. Here we report two high-resolution X-ray crystal structures of human Pin1 bound to non-natural peptide inhibitors. The structures of the bound high-affinity peptides identify a type-I β-turn conformation for Pin1 prolyl peptide isomerase domain–peptide binding and an extensive molecular interface for high-affinity recognition. Moreover, these structures suggest chemical elements that may further improve the affinity and pharmacological properties of future peptide-based Pin inhibitors. Finally, an intramolecular hydrogen bond observed in both peptide complexes mimics the cyclic conformation of FK506 and rapamycin. Both FK506 and rapamycin are clinically important inhibitors of other peptidyl-prolyl cis-trans isomerases. This comparative discovery suggests that a cyclic peptide polyketide bridge, like that found in FK506 and rapamycin or a similar linkage, may significantly improve the binding affinity of structure-based Pin1 inhibitors. PMID:17518432

  3. Isolation of Anti-Ricin Protective Antibodies Exhibiting High Affinity from Immunized Non-Human Primates

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    Tal Noy-Porat

    2016-03-01

    Full Text Available Ricin, derived from the castor bean plant Ricinus communis, is one of the most potent and lethal toxins known, against which there is no available antidote. To date, the use of neutralizing antibodies is the most promising post-exposure treatment for ricin intoxication. The aim of this study was to isolate high affinity anti-ricin antibodies that possess potent toxin-neutralization capabilities. Two non-human primates were immunized with either a ricin-holotoxin- or subunit-based vaccine, to ensure the elicitation of diverse high affinity antibodies. By using a comprehensive set of primers, immune scFv phage-displayed libraries were constructed and panned. A panel of 10 antibodies (five directed against the A subunit of ricin and five against the B subunit was isolated and reformatted into a full-length chimeric IgG. All of these antibodies were found to neutralize ricin in vitro, and several conferred full protection to ricin-intoxicated mice when given six hours after exposure. Six antibodies were found to possess exceptionally high affinity toward the toxin, with KD values below pM (koff < 1 × 10−7 s−1 that were well correlated with their ability to neutralize ricin. These antibodies, alone or in combination, could be used for the development of a highly-effective therapeutic preparation for post-exposure treatment of ricin intoxication.

  4. Humanization of high-affinity antibodies targeting glypican-3 in hepatocellular carcinoma

    Science.gov (United States)

    Zhang, Yi-Fan; Ho, Mitchell

    2016-01-01

    Glypican-3 (GPC3) is a cell-surface heparan sulfate proteoglycan highly expressed in hepatocellular carcinoma (HCC). We have generated a group of high-affinity mouse monoclonal antibodies targeting GPC3. Here, we report the humanization and testing of these antibodies for clinical development. We compared the affinity and cytotoxicity of recombinant immunotoxins containing mouse single-chain variable regions fused with a Pseudomonas toxin. To humanize the mouse Fvs, we grafted the combined KABAT/IMGT complementarity determining regions (CDR) into a human IgG germline framework. Interestingly, we found that the proline at position 41, a non-CDR residue in heavy chain variable regions (VH), is important for humanization of mouse antibodies. We also showed that two humanized anti-GPC3 antibodies (hYP7 and hYP9.1b) in the IgG format induced antibody-dependent cell-mediated cytotoxicity and complement-dependent-cytotoxicity in GPC3-positive cancer cells. The hYP7 antibody was tested and showed inhibition of HCC xenograft tumor growth in nude mice. This study successfully humanizes and validates high affinity anti-GPC3 antibodies and sets a foundation for future development of these antibodies in various clinical formats in the treatment of liver cancer. PMID:27667400

  5. High affinity mouse-human chimeric Fab against Hepatitis B surface antigen

    Institute of Scientific and Technical Information of China (English)

    Biplab Bose; Navin Khanna; Subrat K Acharya; Subrata Sinha

    2005-01-01

    AIM: Passive immunotherapy using antibody against hepatitis B surface antigen (HBsAg) has been advocated in certain cases of Hepatitis B infection. We had earlier reported on the cloning and expression of a high affinity scFv derived from a mouse monoclonal (5S) against HBsAg. However this mouse antibody cannot be used for therapeutic purposes as it may elicit anti-mouse immune responses. Chimerization by replacing mouse constant domains with human ones can reduce the immunogenicity of this antibody.METHODS: We cloned the VH and VL genes of this mouse antibody; and fused them with CH1 domain of human IgG1 and CL domain of human kappa chain respectively. These chimeric genes were cloned into a phagemid vector. After initial screening using the phage display system, the chimeric Fab was expressed in soluble form in E. Coli.RESULTS: The chimeric Fab was purified from the bacterial periplasmic extract. We characterized the chimeric Fab using several in vitro techniques and it was observed that the chimeric molecule retained the high affinity and specificity of the original mouse monoclonal.This chimeric antibody fragment was further expressed in different strains of E> coli to increase the yield.CONCLUSION: We have generated a mouse-human chimeric Fab against HBsAg without any significant loss in binding and epitope specificity. This chimeric Fab fragment can be further modified to generate a fulllength chimeric antibody for therapeutic uses.

  6. A high affinity monoclonal antibody recognizing the light chain of human coagulating factor VII.

    Science.gov (United States)

    Sarial, Sheila; Asadi, Farzad; Jeddi-Tehrani, Mahmood; Hadavi, Reza; Bayat, Ali Ahmad; Mahmoudian, Jafar; Taghizadeh-Jahed, Masoud; Shokri, Fazel; Rabbani, Hodjattallah

    2012-12-01

    Factor VII (FVII) is a serine protease-coagulating element responsible for the initiation of an extrinsic pathway of clot formation. Here we generated and characterized a high affinity monoclonal antibody that specifically recognizes human FVII. Recombinant human FVII (rh-FVII) was used for the production of a monoclonal antibody using BALB/c mice. The specificity of the antibody was determined by Western blot using plasma samples from human, mouse, sheep, goat, bovine, rabbit, and rat. Furthermore, the antibody was used to detect transiently expressed rh-FVII in BHK21 cell line using Western blot and sandwich ELISA. A mouse IgG1 (kappa chain) monoclonal antibody clone 1F1-B11 was produced against rh-FVII. The affinity constant (K(aff)) of the antibody was calculated to be 6.4×10(10) M(-1). The antibody could specifically recognize an epitope on the light chain of hFVII, with no reactivity with factor VII from several other animals. In addition, transiently expressed rh-FVII in BHK21 cells was recognized by 1F1-B11. The high affinity as well as the specificity of 1F1-B11 for hFVII will facilitate the affinity purification of hFVII and also production of FVII deficient plasma and minimizes the risk of bovine FVII contamination when fetal bovine serum-supplemented media are used for production and subsequent purification of rh-FVII.

  7. Expression of a Hybrid Human Superoxide Dismutase with a High Affinity for Heparin

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A designed heparin-affinity of human Cu, Zn-SOD is described. The natural leader peptide of P.leiognathi Cu, Zn-SOD and a heparin-binding peptide containing a stretch of 7 Arg were fused to the N-terminal and the C-terminal of human Cu, Zn-SOD respectively. The resulted hybrid enzyme had not only a normal SOD activity but also a high affinity for heparin eluted on the heparin-Sepharose column at 0.4 mol/L NaCl. Some properties, such as the optimum pH, the thermostability and the half-life in the circulation of rats, were also analyzed.

  8. Human immunodeficiency virus endocrinopathy

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    Uma Sinha

    2011-01-01

    Full Text Available Human immunodeficiency virus (HIV endocrinopathy encompasses a broad spectrum of disorders. Almost all the endocrine organs are virtually affected by HIV infection. HIV can directly alter glandular function. More commonly secondary endocrine dysfunction occurs due to opportunistic infections and neoplasms in immunocompromised state. The complex interaction between HIV infection and endocrine system may be manifested as subtle biochemical and hormonal perturbation to overt glandular failure. Antiretroviral therapy as well as other essential medications often result in adverse endocrinal consequences. Apart from adrenal insufficiency, hypogonadism, diabetes and bone loss, AIDS wasting syndrome and HIV lipodystrophy need special reference. Endocrinal evaluation should proceed as in other patients with suspected endocrine dysfunction. Available treatment options have been shown to improve quality of life and long-term mortality in AIDS patients.

  9. Human epidermal Langerhans cells express the high affinity receptor for immunoglobulin E (Fc epsilon RI)

    OpenAIRE

    1992-01-01

    It has been suggested that epidermal Langerhans cells (LC) bearing immunoglobulin E (IgE) may be involved in the genesis of atopic disease. The identity of the IgE receptor(s) on LC remained unclear, although it represents a crucial point in understanding cellular events linked to the binding of allergens to LC via IgE. In this report, we demonstrate that epidermal LC express the high affinity receptor for the Fc fragment of IgE (Fc epsilon RI) which has, so far, only been described on mast c...

  10. A dualistic conformational response to substrate binding in the human serotonin transporter reveals a high affinity state for serotonin

    DEFF Research Database (Denmark)

    Bjerregaard, Henriette; Severinsen, Kasper; Said, Saida

    2015-01-01

    Serotonergic neurotransmission is modulated by the membrane-embedded serotonin transporter (SERT). SERT mediates the reuptake of serotonin into the presynaptic neurons. Conformational changes in SERT occur upon binding of ions and substrate and are crucial for translocation of serotonin across...... that were sensitized to detect a more outward-facing conformation of SERT. We found a novel high affinity outward-facing conformational state of the human SERT induced by serotonin. The ionic requirements for this new conformational response to serotonin mirror the ionic requirements for translocation...

  11. Screening for Human Immunodeficiency Virus (HIV)

    Science.gov (United States)

    Understanding Task Force Recommendations Screening for Human Immunodeficiency Virus (HIV) The U.S. Preventive Services Task Force (Task Force) has issued a final recommendation statement on Screening for Human Immunodeficiency Virus (HIV) . ...

  12. Crystallographic analysis reveals the structural basis of the high-affinity binding of iophenoxic acid to human serum albumin.

    Science.gov (United States)

    Ryan, Ali J; Chung, Chun-Wa; Curry, Stephen

    2011-04-18

    Iophenoxic acid is an iodinated radiocontrast agent that was withdrawn from clinical use because of its exceptionally long half-life in the body, which was due in part to its high-affinity binding to human serum albumin (HSA). It was replaced by Iopanoic acid, which has an amino rather than a hydroxyl group at position 3 on the iodinated benzyl ring and, as a result, binds to albumin with lower affinity and is excreted more rapidly from the body. To understand how iophenoxic acid binds so tightly to albumin, we wanted to examine the structural basis of its interaction with HSA. We have determined the co-crystal structure of HSA in complex with iophenoxic acid at 2.75 Å resolution, revealing a total of four binding sites, two of which--in drugs sites 1 and 2 on the protein--are likely to be occupied at clinical doses. High-affinity binding of iophenoxic acid occurs at drug site 1. The structure reveals that polar and apolar groups on the compound are involved in its interactions with drug site 1. In particular, the 3-hydroxyl group makes three hydrogen bonds with the side-chains of Tyr 150 and Arg 257. The mode of binding to drug site 2 is similar except for the absence of a binding partner for the hydroxyl group on the benzyl ring of the compound. The HSA-iophenoxic acid structure indicates that high-affinity binding to drug site 1 is likely to be due to extensive desolvation of the compound, coupled with the ability of the binding pocket to provide a full set of salt-bridging or hydrogen bonding partners for its polar groups. Consistent with this interpretation, the structure also suggests that the lower-affinity binding of iopanoic acid arises because replacement of the 3-hydroxyl by an amino group eliminates hydrogen bonding to Arg 257. This finding underscores the importance of polar interactions in high-affinity binding to albumin.

  13. Crystallographic analysis reveals the structural basis of the high-affinity binding of iophenoxic acid to human serum albumin

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    Chung Chun-wa

    2011-04-01

    Full Text Available Abstract Background Iophenoxic acid is an iodinated radiocontrast agent that was withdrawn from clinical use because of its exceptionally long half-life in the body, which was due in part to its high-affinity binding to human serum albumin (HSA. It was replaced by Iopanoic acid, which has an amino rather than a hydroxyl group at position 3 on the iodinated benzyl ring and, as a result, binds to albumin with lower affinity and is excreted more rapidly from the body. To understand how iophenoxic acid binds so tightly to albumin, we wanted to examine the structural basis of its interaction with HSA. Results We have determined the co-crystal structure of HSA in complex with iophenoxic acid at 2.75 Å resolution, revealing a total of four binding sites, two of which - in drugs sites 1 and 2 on the protein - are likely to be occupied at clinical doses. High-affinity binding of iophenoxic acid occurs at drug site 1. The structure reveals that polar and apolar groups on the compound are involved in its interactions with drug site 1. In particular, the 3-hydroxyl group makes three hydrogen bonds with the side-chains of Tyr 150 and Arg 257. The mode of binding to drug site 2 is similar except for the absence of a binding partner for the hydroxyl group on the benzyl ring of the compound. Conclusions The HSA-iophenoxic acid structure indicates that high-affinity binding to drug site 1 is likely to be due to extensive desolvation of the compound, coupled with the ability of the binding pocket to provide a full set of salt-bridging or hydrogen bonding partners for its polar groups. Consistent with this interpretation, the structure also suggests that the lower-affinity binding of iopanoic acid arises because replacement of the 3-hydroxyl by an amino group eliminates hydrogen bonding to Arg 257. This finding underscores the importance of polar interactions in high-affinity binding to albumin.

  14. 78 FR 29755 - Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...

    Science.gov (United States)

    2013-05-21

    ... HUMAN SERVICES Food and Drug Administration Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus Cure Research: Public Meeting AGENCY: Food and Drug... Administration (FDA) is announcing a public meeting and an opportunity for public comment on...

  15. Recombinant human nerve growth factor is biologically active and labels novel high-affinity binding sites in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Altar, C.A.; Burton, L.E.; Bennett, G.L.; Dugich-Djordjevic, M. (Genentech, Inc., South San Francisco, CA (USA))

    1991-01-01

    Iodinated recombinant human nerve growth factor (125I-rhNGF) stimulated neurite formation in PC12 cell cultures with a half-maximal potency of 35-49 pg/ml, compared with 39-52 pg/ml for rhNGF. In quantitative ligand autoradiography, the in vitro equilibrium binding of 125I-rhNGF to brain sections showed a 10-fold regional variation in density and was saturable, reversible, and specifically displaced by up to 74% with rhNGF or murine NGF (muNGF). At equilibrium, 125I-rhNGF bound to these sites with high affinity and low capacity (Bmax less than or equal to 13.2 fmol/mg of protein). Calculation of 125I-rhNGF binding affinity by kinetic methods gave average Kd values of 24 and 31 pM. Computer-generated maps revealed binding in brain regions not identified previously with 125I-muNGF, including hippocampus; dentate gyrus; amygdala; paraventricular thalamus; frontal, parietal, occipital, and cingulate cortices; nucleus accumbens; olfactory tubercle; subiculum; pineal gland; and medial geniculate nucleus. NGF binding sites were distributed in a 2-fold increasing medial-lateral gradient in the caudate-putamen and a 2-fold lateral-medial gradient in the nucleus accumbens. 125I-rhNGF binding sites were also found in most areas labeled by 125I-muNGF, including the interpedunucular nucleus, cerebellum, forebrain cholinergic nuclei, caudoventral caudate-putamen, and trigeminal nerve nucleus. 125I-rhNGF binding sites were absent from areas replete with low-affinity NGF binding sites, including circumventricular organs, myelinated fiber bundles, and choroid plexus. The present analysis provides an anatomical differentiation of high-affinity 125I-rhNGF binding sites and greatly expands the number of brain structures that may respond to endogenous NGF or exogenously administered rhNGF.

  16. Specific high-affinity binding sites for a synthetic gliadin heptapeptide of human peripheral blood lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Payan, D.G.; Horvath, K.; Graf, L.

    1987-03-23

    The synthetic peptide containing residues 43-49 of ..cap alpha..-gliadin, the major protein component of gluten, has previously been shown to inhibit the production of lymphokine activities by mononuclear leukocytes. The authors demonstrate using radiolabeled ..cap alpha..-gliadin(43-49) that human peripheral blood lymphocytes express approximately 20,000-25,000 surface receptors for this peptide, with a dissociation constant (K/sub D/) of 20 nM. In addition, binding is inhibited by naloxone and an enkephalin analog, thus confirming the functional correlate which demonstrates inhibition by these agents of ..cap alpha..-gliadin(43-49) functional effects. Furthermore, B-lymphocytes bind specifically a greater amount of (/sup 125/I)..cap alpha..-gliadin(43-49) than T-lymphocytes. The lymphocyte ..cap alpha..-gliadin(43-49) receptor may play an important role in mediating the immunological response to ..cap alpha..-gliadin. 16 references, 4 figures.

  17. High affinity human antibody fragments to dengue virus non-structural protein 3.

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    Nicole J Moreland

    Full Text Available BACKGROUND: The enzyme activities catalysed by flavivirus non-structural protein 3 (NS3 are essential for virus replication. They are distributed between the N-terminal protease domain in the first one-third and the C-terminal ATPase/helicase and nucleoside 5' triphosphatase domain which forms the remainder of the 618-aa long protein. METHODOLOGY/PRINCIPAL FINDINGS: In this study, dengue full-length NS3 protein with residues 49 to 66 of NS2B covalently attached via a flexible linker, was used as bait in biopanning with a naïve human Fab phage-display library. Using a range of truncated constructs spanning the NS2B cofactor region and the full-length NS3, 10 unique Fab were identified and characterized. Of these, monoclonal Fab 3F8 was shown to bind α3″ (residues 526 through 531 within subdomain III of the helicase domain. The antibody inhibits the ATPase and helicase activites of NS3 in biochemical assays and reduces DENV replication in HEK293 cells that were previously transfected with Fab 3F8 compared with mock transfected cells. CONCLUSIONS/SIGNIFICANCE: Antibodies such as 3F8 are valuable tools for studying the molecular mechanisms of flaviviral replication and for the monospecific detection of replicating dengue virus in vivo.

  18. A soluble form of the high affinity IgE receptor, Fc-epsilon-RI, circulates in human serum.

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    Eleonora Dehlink

    Full Text Available Soluble IgE receptors are potential in vivo modulators of IgE-mediated immune responses and are thus important for our basic understanding of allergic responses. We here characterize a novel soluble version of the IgE-binding alpha-chain of Fc-epsilon-RI (sFcεRI, the high affinity receptor for IgE. sFcεRI immunoprecipitates as a protein of ∼40 kDa and contains an intact IgE-binding site. In human serum, sFcεRI is found as a soluble free IgE receptor as well as a complex with IgE. Using a newly established ELISA, we show that serum sFcεRI levels correlate with serum IgE in patients with elevated IgE. We also show that serum of individuals with normal IgE levels can be found to contain high levels of sFcεRI. After IgE-antigen-mediated crosslinking of surface FcεRI, we detect sFcεRI in the exosome-depleted, soluble fraction of cell culture supernatants. We further show that sFcεRI can block binding of IgE to FcεRI expressed at the cell surface. In summary, we here describe the alpha-chain of FcεRI as a circulating soluble IgE receptor isoform in human serum.

  19. Role of the human high-affinity copper transporter in copper homeostasis regulation and cisplatin sensitivity in cancer chemotherapy.

    Science.gov (United States)

    Kuo, Macus Tien; Fu, Siqing; Savaraj, Niramol; Chen, Helen H W

    2012-09-15

    The high-affinity copper transporter (Ctr1; SCLC31A1) plays an important role in regulating copper homeostasis because copper is an essential micronutrient and copper deficiency is detrimental to many important cellular functions, but excess copper is toxic. Recent research has revealed that human copper homeostasis is tightly controlled by interregulatory circuitry involving copper, Sp1, and human (hCtr1). This circuitry uses Sp1 transcription factor as a copper sensor in modulating hCtr1 expression, which in turn controls cellular copper and Sp1 levels in a 3-way mutual regulatory loop. Posttranslational regulation of hCtr1 expression by copper stresses has also been described in the literature. Because hCtr1 can also transport platinum drugs, this finding underscores the important role of hCtr1 in platinum-drug sensitivity in cancer chemotherapy. Consistent with this notion is the finding that elevated hCtr1 expression was associated with favorable treatment outcomes in cisplatin-based cancer chemotherapy. Moreover, cultured cell studies showed that elevated hCtr1 expression can be induced by depleting cellular copper levels, resulting in enhanced cisplatin uptake and its cell-killing activity. A phase I clinical trial using a combination of trientine (a copper chelator) and carboplatin has been carried out with encouraging results. This review discusses new insights into the role of hCtr1 in regulating copper homeostasis and explains how modulating cellular copper availability could influence treatment efficacy in platinum-based cancer chemotherapy through hCtr1 regulation.

  20. High-affinity human leucocyte antigen class I binding variola-derived peptides induce CD4(+) T cell responses more than 30 years post-vaccinia virus vaccination

    DEFF Research Database (Denmark)

    Wang, M.; Tang, Sheila Tuyet; Lund, Ole;

    2009-01-01

    Interferon-gamma secreting T lymphocytes against pox virus-derived synthetic 9-mer peptides were tested by enzyme-linked immunospot in peripheral blood of individuals vaccinated with vaccinia virus more than 30 years ago. The peptides were characterized biochemically as high-affinity human...

  1. A human β-III-spectrin spinocerebellar ataxia type 5 mutation causes high-affinity F-actin binding

    Science.gov (United States)

    Avery, Adam W.; Crain, Jonathan; Thomas, David D.; Hays, Thomas S.

    2016-01-01

    Spinocerebellar ataxia type 5 (SCA5) is a human neurodegenerative disease that stems from mutations in the SPTBN2 gene encoding the protein β-III-spectrin. Here we investigated the molecular consequence of a SCA5 missense mutation that results in a L253P substitution in the actin-binding domain (ABD) of β-III-spectrin. We report that the L253P substitution in the isolated β-III-spectrin ABD causes strikingly high F-actin binding affinity (Kd = 75.5 nM) compared to the weak F-actin binding affinity of the wild-type ABD (Kd = 75.8 μM). The mutation also causes decreased thermal stability (Tm = 44.6 °C vs 59.5 °C). Structural analyses indicate that leucine 253 is in a loop at the interface of the tandem calponin homology (CH) domains comprising the ABD. Leucine 253 is predicted to form hydrophobic contacts that bridge the CH domains. The decreased stability of the mutant indicates that these bridging interactions are probably disrupted, suggesting that the high F-actin binding affinity of the mutant is due to opening of the CH domain interface. These results support a fundamental role for leucine 253 in regulating opening of the CH domain interface and binding of the ABD to F-actin. This study indicates that high-affinity actin binding of L253P β-III-spectrin is a likely driver of neurodegeneration. PMID:26883385

  2. N- and C-terminally truncated forms of glucose-dependent insulinotropic polypeptide are high-affinity competitive antagonists of the human GIP receptor

    DEFF Research Database (Denmark)

    Hansen, L S; Sparre-Ulrich, A H; Christensen, M.

    2016-01-01

    BACKGROUND AND PURPOSE: Glucose-dependent insulinotropic polypeptide (GIP) impacts lipid, bone, and glucose homeostasis. The GIP receptor belongs to G protein-coupled receptor family B1 and signals through GαS. High affinity ligands for in vivo use are needed to elucidate GIP's physiological...... functions and pharmacological potential. GIP(1-30)NH2 is a naturally occurring truncation of GIP(1-42). Here we characterize eight N-terminal trrncations of human GIP(1-30)NH2 : GIP(2- to 9-30)NH2 . EXPERIMENTAL APPROACH: COS-7 cells were transiently transfected with the human GIP receptor and assessed......, but superior antagonist GIP(3-30)NH2 , that together with GIP(5-30)NH2 were high-affinity competitive antagonist and thus may be suitable tool compounds for basic GIP research and future pharmacological interventions....

  3. CERVICAL CANCER AND THE HUMAN IMMUNODEFICIENCY ...

    African Journals Online (AJOL)

    as Mexico, Columbia and many developed nations), the reduction in ..... detection among human immunodeficiency virus-infected pregnant Thai women: implications ... Moscicki A. Impact of HPV infection in adolescent populations. J Adolesc ...

  4. Transurethral prostatectomy in human immunodeficiency virus ...

    African Journals Online (AJOL)

    Hospital with urethral catheter in situ and having failed medical therapy, he opted ... Keywords: Human immunodeficiency virus infected patients, morbidity, risk of transmission, transurethral .... exposure, and the frequency of at risk exposures.

  5. Human immunodeficiency virus and menopause.

    Science.gov (United States)

    Kanapathipillai, Rupa; Hickey, Martha; Giles, Michelle

    2013-09-01

    This article aims to review currently available evidence for women infected with human immunodeficiency virus (HIV) and menopause and to propose clinical management algorithms. Key studies addressing HIV and menopause have been reviewed, specifically age of menopause onset in HIV-infected women, frequency of menopausal symptoms, comorbidities associated with HIV and aging (including cardiovascular disease and bone disease), treatment of menopausal symptoms, and prevention of comorbidities in HIV-infected women. Studies suggest an earlier onset of menopause in HIV-infected women, with increased frequency of symptoms. Cardiovascular disease risk may be increased in this population, with combination antiretroviral therapy (cART) and chronic inflammation associated with HIV, contributing to increased risk. Chronic inflammation and cART have been independently implicated in bone disease. No published data have assessed the safety and efficacy of hormone therapy in relation to symptoms of menopause, cardiovascular risk, and bone disease among HIV-infected women. Few studies on menopause have been conducted in HIV-infected women compared with HIV-uninfected women. Many questions regarding age of menopause onset, frequency of menopausal symptoms and associated complications such as bone disease and cardiovascular disease, and efficacy of treatment among HIV-infected women remain. The incidence and severity of some of these factors may be increased in the setting of HIV and cART.

  6. 78 FR 46969 - Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...

    Science.gov (United States)

    2013-08-02

    ... HUMAN SERVICES Food and Drug Administration Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus Cure Research; Reopening of Comment Period AGENCY: Food and Drug... Virus (HIV) Patient-Focused Drug Development and HIV Cure Research,'' published in the Federal...

  7. Contributions of the S100A9 C-terminal tail to high-affinity Mn(II) chelation by the host-defense protein human calprotectin.

    Science.gov (United States)

    Brophy, Megan Brunjes; Nakashige, Toshiki G; Gaillard, Aleth; Nolan, Elizabeth M

    2013-11-27

    Human calprotectin (CP) is an antimicrobial protein that coordinates Mn(II) with high affinity in a Ca(II)-dependent manner at an unusual histidine-rich site (site 2) formed at the S100A8/S100A9 dimer interface. We present a 16-member CP mutant family where mutations in the S100A9 C-terminal tail (residues 96-114) are employed to evaluate the contributions of this region, which houses three histidines and four acidic residues, to Mn(II) coordination at site 2. The results from analytical size-exclusion chromatography, Mn(II) competition titrations, and electron paramagnetic resonance spectroscopy establish that the C-terminal tail is essential for high-affinity Mn(II) coordination by CP in solution. The studies indicate that His103 and His105 (HXH motif) of the tail complete the Mn(II) coordination sphere in solution, affording an unprecedented biological His6 site. These solution studies are in agreement with a Mn(II)-CP crystal structure reported recently (Damo, S. M.; et al. Proc. Natl. Acad. Sci. U.S.A. 2013, 110, 3841). Remarkably high-affinity Mn(II) binding is retained when either H103 or H105 are mutated to Ala, when the HXH motif is shifted from positions 103-105 to 104-106, and when the human tail is substituted by the C-terminal tail of murine S100A9. Nevertheless, antibacterial activity assays employing human CP mutants reveal that the native disposition of His residues is important for conferring growth inhibition against Escherichia coli and Staphylococcus aureus. Within the S100 family, the S100A8/S100A9 heterooligomer is essential for providing high-affinity Mn(II) binding; the S100A7, S100A9(C3S), S100A12, and S100B homodimers do not exhibit such Mn(II)-binding capacity.

  8. Characterization of the Staphylococcal enterotoxin A: Vβ receptor interaction using human receptor fragments engineered for high affinity.

    Science.gov (United States)

    Sharma, P; Postel, S; Sundberg, E J; Kranz, D M

    2013-12-01

    Staphylococcal food poisoning is a gastrointestinal disorder caused by the consumption of food containing Staphylococcal enterotoxins. Staphylococcal enterotoxin A (SEA) is the most common enterotoxin recovered from food poisoning outbreaks in the USA. In addition to its enteric activity, SEA also acts as a potent superantigen through stimulation of T cells, although less is known about its interactions than the superantigens SEB, SEC and toxic shock syndrome toxin-1. To understand more about SEA:receptor interactions, and to develop toxin-detection systems for use in food testing, we engineered various SEA-binding receptor mutants. The extracellular domain of the receptor, a variable region of the beta chain (Vβ22) of the T-cell receptor, was engineered for stability as a soluble protein and for high affinity, using yeast-display technology. The highest affinity mutant was shown to bind SEA with a Kd value of 4 nM. This was a 25 000-fold improvement in affinity compared with the wild-type receptor, which bound to SEA with low affinity (Kd value of 100 µM), similar to other superantigen:Vβ interactions. The SEA:Vβ interface was centered around residues within the complementarity determining region 2 loop. The engineered receptor was specific for SEA, in that it did not bind to two other closely related enterotoxins SEE or SED, providing information on the SEA residues possibly involved in the interaction. The specificity and affinity of these high-affinity Vβ proteins also provide useful agents for the design of more sensitive and specific systems for SEA detection.

  9. Mutational analysis of the high-affinity zinc binding site validates a refined human dopamine transporter homology model.

    Directory of Open Access Journals (Sweden)

    Thomas Stockner

    Full Text Available The high-resolution crystal structure of the leucine transporter (LeuT is frequently used as a template for homology models of the dopamine transporter (DAT. Although similar in structure, DAT differs considerably from LeuT in a number of ways: (i when compared to LeuT, DAT has very long intracellular amino and carboxyl termini; (ii LeuT and DAT share a rather low overall sequence identity (22% and (iii the extracellular loop 2 (EL2 of DAT is substantially longer than that of LeuT. Extracellular zinc binds to DAT and restricts the transporter's movement through the conformational cycle, thereby resulting in a decrease in substrate uptake. Residue H293 in EL2 praticipates in zinc binding and must be modelled correctly to allow for a full understanding of its effects. We exploited the high-affinity zinc binding site endogenously present in DAT to create a model of the complete transmemberane domain of DAT. The zinc binding site provided a DAT-specific molecular ruler for calibration of the model. Our DAT model places EL2 at the transporter lipid interface in the vicinity of the zinc binding site. Based on the model, D206 was predicted to represent a fourth co-ordinating residue, in addition to the three previously described zinc binding residues H193, H375 and E396. This prediction was confirmed by mutagenesis: substitution of D206 by lysine and cysteine affected the inhibitory potency of zinc and the maximum inhibition exerted by zinc, respectively. Conversely, the structural changes observed in the model allowed for rationalizing the zinc-dependent regulation of DAT: upon binding, zinc stabilizes the outward-facing state, because its first coordination shell can only be completed in this conformation. Thus, the model provides a validated solution to the long extracellular loop and may be useful to address other aspects of the transport cycle.

  10. Mutational analysis of the high-affinity zinc binding site validates a refined human dopamine transporter homology model.

    Science.gov (United States)

    Stockner, Thomas; Montgomery, Therese R; Kudlacek, Oliver; Weissensteiner, Rene; Ecker, Gerhard F; Freissmuth, Michael; Sitte, Harald H

    2013-01-01

    The high-resolution crystal structure of the leucine transporter (LeuT) is frequently used as a template for homology models of the dopamine transporter (DAT). Although similar in structure, DAT differs considerably from LeuT in a number of ways: (i) when compared to LeuT, DAT has very long intracellular amino and carboxyl termini; (ii) LeuT and DAT share a rather low overall sequence identity (22%) and (iii) the extracellular loop 2 (EL2) of DAT is substantially longer than that of LeuT. Extracellular zinc binds to DAT and restricts the transporter's movement through the conformational cycle, thereby resulting in a decrease in substrate uptake. Residue H293 in EL2 praticipates in zinc binding and must be modelled correctly to allow for a full understanding of its effects. We exploited the high-affinity zinc binding site endogenously present in DAT to create a model of the complete transmemberane domain of DAT. The zinc binding site provided a DAT-specific molecular ruler for calibration of the model. Our DAT model places EL2 at the transporter lipid interface in the vicinity of the zinc binding site. Based on the model, D206 was predicted to represent a fourth co-ordinating residue, in addition to the three previously described zinc binding residues H193, H375 and E396. This prediction was confirmed by mutagenesis: substitution of D206 by lysine and cysteine affected the inhibitory potency of zinc and the maximum inhibition exerted by zinc, respectively. Conversely, the structural changes observed in the model allowed for rationalizing the zinc-dependent regulation of DAT: upon binding, zinc stabilizes the outward-facing state, because its first coordination shell can only be completed in this conformation. Thus, the model provides a validated solution to the long extracellular loop and may be useful to address other aspects of the transport cycle.

  11. Anemia and survival in human immunodeficiency virus

    DEFF Research Database (Denmark)

    Lundgren, Jens Dilling; Mocroft, Amanda

    2003-01-01

    The prospective, multicenter cohort study EuroSIDA has previously reported on predictors and outcomes of anemia in patients infected with human immunodeficiency virus. In a Cox proportional-hazards model with serial measures of CD4+ cell count, plasma viral load, and degrees of anemia fitted...... marker and whether correction of anemia itself results in a better prognosis remain to be determined....

  12. 110 HUMAN IMMUNODEFICIENCY VIRUS (HIV) SEROPOSITIVITY ...

    African Journals Online (AJOL)

    -http://www.ajol.info/journals/ajcem ... A seroprevalence study of Human immunodeficiency virus (HIV) infection in new patients attending the eye .... previous reports that Herpes zoster ophthalmicus in ..... The increase in the number of patients with mild proteinuria after treatment and its implication require ...... bacteriophage.

  13. Human Eosinophils Express the High Affinity IgE Receptor, FcεRI, in Bullous Pemphigoid

    Science.gov (United States)

    Messingham, Kelly N.; Holahan, Heather M.; Frydman, Alexandra S.; Fullenkamp, Colleen; Srikantha, Rupasree; Fairley, Janet A.

    2014-01-01

    Bullous pemphigoid (BP) is an autoimmune blistering disease mediated by autoantibodies targeting BP180 (type XVII collagen). Patient sera and tissues typically have IgG and IgE autoantibodies and elevated eosinophil numbers. Although the pathogenicity of the IgE autoantibodies is established in BP, their contribution to the disease process is not well understood. Our aims were two-fold: 1) To establish the clinical relationships between total and BP180-specific IgE, eosinophilia and other markers of disease activity; and 2) To determine if eosinophils from BP patients express the high affinity IgE receptor, FcεRI, as a potential mechanism of action for IgE in BP. Our analysis of 48 untreated BP patients revealed a correlation between BP180 IgG and both BP180 IgE and peripheral eosinophil count. Additionally, we established a correlation between total IgE concentration and both BP180 IgE levels and eosinophil count. When only sera from patients (n = 16) with total IgE≥400 IU/ml were analyzed, BP180 IgG levels correlated with disease severity, BP230 IgG, total circulating IgE and BP180 IgE. Finally, peripheral eosinophil count correlated more strongly with levels of BP180 IgE then with BP180 IgG. Next, eosinophil FcεRI expression was investigated in the blood and skin using several methods. Peripheral eosinophils from BP patients expressed mRNA for all three chains (α, β and γ) of the FcεRI. Surface expression of the FcεRIα was confirmed on both peripheral and tissue eosinophils from most BP patients by immunostaining. Furthermore, using a proximity ligation assay, interaction of the α- and β-chains of the FcεRI was observed in some biopsy specimens, suggesting tissue expression of the trimeric receptor form in some patients. These studies provide clinical support for the relevance of IgE in BP disease and provide one mechanism of action of these antibodies, via binding to the FcεRI on eosinophils. PMID:25255430

  14. Human eosinophils express the high affinity IgE receptor, FcεRI, in bullous pemphigoid.

    Directory of Open Access Journals (Sweden)

    Kelly N Messingham

    Full Text Available Bullous pemphigoid (BP is an autoimmune blistering disease mediated by autoantibodies targeting BP180 (type XVII collagen. Patient sera and tissues typically have IgG and IgE autoantibodies and elevated eosinophil numbers. Although the pathogenicity of the IgE autoantibodies is established in BP, their contribution to the disease process is not well understood. Our aims were two-fold: 1 To establish the clinical relationships between total and BP180-specific IgE, eosinophilia and other markers of disease activity; and 2 To determine if eosinophils from BP patients express the high affinity IgE receptor, FcεRI, as a potential mechanism of action for IgE in BP. Our analysis of 48 untreated BP patients revealed a correlation between BP180 IgG and both BP180 IgE and peripheral eosinophil count. Additionally, we established a correlation between total IgE concentration and both BP180 IgE levels and eosinophil count. When only sera from patients (n = 16 with total IgE ≥ 400 IU/ml were analyzed, BP180 IgG levels correlated with disease severity, BP230 IgG, total circulating IgE and BP180 IgE. Finally, peripheral eosinophil count correlated more strongly with levels of BP180 IgE then with BP180 IgG. Next, eosinophil FcεRI expression was investigated in the blood and skin using several methods. Peripheral eosinophils from BP patients expressed mRNA for all three chains (α, β and γ of the FcεRI. Surface expression of the FcεRIα was confirmed on both peripheral and tissue eosinophils from most BP patients by immunostaining. Furthermore, using a proximity ligation assay, interaction of the α- and β-chains of the FcεRI was observed in some biopsy specimens, suggesting tissue expression of the trimeric receptor form in some patients. These studies provide clinical support for the relevance of IgE in BP disease and provide one mechanism of action of these antibodies, via binding to the FcεRI on eosinophils.

  15. Human metabolites of synthetic cannabinoids JWH-018 and JWH-073 bind with high affinity and act as potent agonists at cannabinoid type-2 receptors

    Energy Technology Data Exchange (ETDEWEB)

    Rajasekaran, Maheswari; Brents, Lisa K.; Franks, Lirit N. [Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Moran, Jeffery H. [Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Arkansas Department of Public Health, Public Health Laboratory, Little Rock, AR 72205 (United States); Prather, Paul L., E-mail: pratherpaull@uams.edu [Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States)

    2013-06-01

    K2 or Spice is an emerging drug of abuse that contains synthetic cannabinoids, including JWH-018 and JWH-073. Recent reports indicate that monohydroxylated metabolites of JWH-018 and JWH-073 retain high affinity and activity at cannabinoid type-1 receptors (CB{sub 1}Rs), potentially contributing to the enhanced toxicity of K2 compared to marijuana. Since the parent compounds also bind to cannabinoid type-2 receptors (CB{sub 2}Rs), this study investigated the affinity and intrinsic activity of JWH-018, JWH-073 and several monohydroxylated metabolites at human CB{sub 2}Rs (hCB{sub 2}Rs). The affinity of cannabinoids for hCB{sub 2}Rs was determined by competition binding studies employing CHO-hCB{sub 2} membranes. Intrinsic activity of compounds was assessed by G-protein activation and adenylyl cyclase (AC)-inhibition in CHO-hCB{sub 2} cells. JWH-073, JWH-018 and several of their human metabolites exhibit nanomolar affinity and act as potent agonists at hCB{sub 2}Rs. Furthermore, a major omega hydroxyl metabolite of JWH-073 (JWH-073-M5) binds to CB{sub 2}Rs with 10-fold less affinity than the parent molecule, but unexpectedly, is equipotent in regulating AC-activity when compared to the parent molecule. Finally, when compared to CP-55,940 and Δ{sup 9}-tetrahydrocannabinol (Δ{sup 9}-THC), JWH-018, JWH-018-M5 and JWH-073-M5 require significantly less CB{sub 2}R occupancy to produce similar levels of AC-inhibition, indicating that these compounds may more efficiently couple CB{sub 2}Rs to AC than the well characterized cannabinoid agonists examined. These results indicate that JWH-018, JWH-073 and several major human metabolites of these compounds exhibit high affinity and demonstrate distinctive signaling properties at CB{sub 2}Rs. Therefore, future studies examining pharmacological and toxicological properties of synthetic cannabinoids present in K2 products should consider potential actions of these drugs at both CB{sub 1} and CB{sub 2}Rs. - Highlights: • JWH-018

  16. Humanized mAb H22 binds the human high affinity Fc receptor for IgG (FcgammaRI), blocks phagocytosis, and modulates receptor expression.

    Science.gov (United States)

    Wallace, P K; Keler, T; Coleman, K; Fisher, J; Vitale, L; Graziano, R F; Guyre, P M; Fanger, M W

    1997-10-01

    About 10-15% of patients with immune thrombocytopenic purpura (ITP) cannot be controlled by corticosteroid therapy and splenectomy. For these patients treatment with high-dose IVIgG induces partial or complete responses. The clinical benefits of IVIgG could be due to blockade of Fc receptors for IgG (FcgammaR), because several model systems clearly show that functional FcgammaR are essential for establishment of ITP and related diseases. However, the specific contributions of the three individual classes of FcgammaR remain to be more completely defined. Recently monoclonal antibody (mAb) H22, which recognizes an epitope on FcgammaRI (CD64) outside the ligand binding domain, was humanized by grafting its complementarity determining regions onto human IgG1 constant domains. Because FcgammaRI has a high affinity for human IgG1 antibodies, we predicted mAb H22 would also bind to FcgammaRI through its Fc domain and block FcgammaRI-mediated phagocytosis. These studies demonstrate that mAb H22 blocked phagocytosis of opsonized red blood cells 1000 times more effectively than an irrelevant IgG. Moreover, cross-linking FcgammaRI with mAb H22 rapidly down-modulated FcgammaRI expression on monocytes without affecting other surface antigens. We conclude that because mAb H22 is a humanized mAb that blocks the FcgammaRI ligand binding domain and down-modulates FcgammaRI expression, it is a particularly good candidate for evaluating the role of FcgammaRI in patients with ITP.

  17. Genetically encoded photocrosslinkers locate the high-affinity binding site of antidepressant drugs in the human serotonin transporter

    DEFF Research Database (Denmark)

    Rannversson, Hafsteinn; Andersen, Jacob; Hall, Lena Sørensen;

    2016-01-01

    Despite the well-established role of the human serotonin transporter (hSERT) in the treatment of depression, the molecular details of antidepressant drug binding are still not fully understood. Here we utilize amber codon suppression in a membrane-bound transporter protein to encode photocrosslin......Despite the well-established role of the human serotonin transporter (hSERT) in the treatment of depression, the molecular details of antidepressant drug binding are still not fully understood. Here we utilize amber codon suppression in a membrane-bound transporter protein to encode...

  18. A high-affinity human monoclonal IgM antibody reacting with multiple strains of Mycoplasma hominis

    DEFF Research Database (Denmark)

    Moller, SA; Birkelund, Svend; Borrebaeck, CA

    1990-01-01

    Human monoclonal antibodies were produced against Mycoplasma hominis by in vitro immunization of peripheral blood lymphocytes from a healthy seropositive donor using low amounts of antigen (5 ng/ml). The immune B lymphocytes were subsequently immortalized by Epstein-Barr virus transformation...

  19. A human CD5+ B cell clone that secretes an idiotype-specific high affinity IgM monoclonal antibody.

    NARCIS (Netherlands)

    R.W.J. van der Heijden (Roger); H. Bunschoten; A.C. Hoek (Aad); J. van Es (Johan); M. Punter; A.D.M.E. Osterhaus (Albert); F.G.C.M. Uytdehaag (Fons)

    1991-01-01

    textabstractWe previously demonstrated the occurrence of a naturally arisen human anti-idiotypic B cell clone, that we transformed with EBV (EBV383). We show evidence that EBV383 not only expresses the CD5 surface Ag, but also contains the 2.7-kb mRNA transcript encoding this protein. In addition, w

  20. Malignant syphilis with human immunodeficiency virus infection

    Directory of Open Access Journals (Sweden)

    Jiby Rajan

    2011-01-01

    Full Text Available Malignant syphilis or Lues maligna, commonly reported in the pre-antibiotic era, has now seen a resurgence with the advent of human immunodeficiency virus (HIV. Immunosuppression and sexual promiscuity set the stage for this deadly association of HIV and Treponema pallidum that can manifest atypically and can prove to cause diagnostic problems. We report one such case in a 30-year-old female who responded favorably to treatment with penicillin.

  1. Generation of a novel high-affinity monoclonal antibody with conformational recognition epitope on human IgM.

    Science.gov (United States)

    Sarikhani, Sina; Mirshahi, Manouchehr; Gharaati, Mohammad Reza; Mirshahi, Tooran

    2010-11-01

    As IgM is the first isotype of antibody which appears in blood after initial exposure to a foreign antigen in the pattern of primary response, detection, and quantification of this molecule in blood seems invaluable. To approach these goals, generation, and characterization of a highly specific mAb (monoclonal antibody) against human IgM were investigated. Human IgM immunoglobulins were used to immunize Balb/c mice. Spleen cells taken from the immunized animals were fused with SP2/O myeloma cells using PEG (polyethylene glycol, MW 1450) as fusogen. The hybridomas were cultured in HAT containing medium and supernatants from the growing hybrids were screened by enzyme-linked immunosorbent assay (ELISA) using plates coated with pure human IgM and the positive wells were then cloned at limiting dilutions. The best clone designated as MAN-1, was injected intraperitoneally to some Pristane-injected mice. Anti-IgM mAb was purified from the animals' ascitic fluid by protein-G sepharose followed by DEAE-cellulose ion exchange chromatography. MAN-1 interacted with human IgM with a very high specificity and affinity. The purity of the sample was tested by SDS-PAGE and the affinity constant was measured (K(a) = 3.5 x 10(9)M(-1). Immunoblotting and competitive ELISA were done and the results showed that the harvested antibody recognizes a conformational epitope on the mu chain of human IgM and there was no cross-reactivity with other subclasses of immunoglobulins. Furthermore, isotyping test was done and the results showed the subclass of the obtained mAb which was IgG(1)kappa.

  2. Drug binding to the inactivated state is necessary but not sufficient for high-affinity binding to human ether-à-go-go-related gene channels.

    Science.gov (United States)

    Perrin, Mark J; Kuchel, Philip W; Campbell, Terence J; Vandenberg, Jamie I

    2008-11-01

    Drug block of the human ether-à-go-go-related gene K(+) channel (hERG) is the most common cause of acquired long QT syndrome, a disorder of cardiac repolarization that may result in ventricular tachycardia and sudden cardiac death. We investigated the open versus inactivated state dependence of drug block by using hERG mutants N588K and N588E, which shift the voltage dependence of inactivation compared with wild-type but in which the mutated residue is remote from the drug-binding pocket in the channel pore. Four high-affinity drugs (cisapride, dofetilide, terfenadine, and astemizole) demonstrated lower affinity for the inactivation-deficient N588K mutant hERG channel compared with N588E and wild-type hERG. Three of four low-affinity drugs (erythromycin, perhexiline, and quinidine) demonstrated no preference for N588E over N588K channels, whereas dl-sotalol was an example of a low-affinity state-dependent blocker. All five state-dependent blockers showed an even lower affinity for S620T mutant hERG (no inactivation) compared with N588K mutant hERG (greatly reduced inactivation). Computer modeling indicates that the reduced affinity for S620T compared with N588K and wild-type channels can be explained by the relative kinetics of drug block and unblock compared with the kinetics of inactivation and recovery from inactivation. We were also able to calculate, for the first time, the relative affinities for the inactivated versus the open state, which for the drugs tested here ranged from 4- to 70-fold. Our results show that preferential binding to the inactivated state is necessary but not sufficient for high-affinity binding to hERG channels.

  3. A selective reversible azapeptide inhibitor of human neutrophil proteinase 3 derived from a high affinity FRET substrate.

    Science.gov (United States)

    Epinette, Christophe; Croix, Cécile; Jaquillard, Lucie; Marchand-Adam, Sylvain; Kellenberger, Christine; Lalmanach, Gilles; Cadene, Martine; Viaud-Massuard, Marie-Claude; Gauthier, Francis; Korkmaz, Brice

    2012-03-15

    The biological functions of human neutrophil proteinase 3 (PR3) remain unclear because of its close structural resemblance to neutrophil elastase and its apparent functional redundancy with the latter. Thus, all natural inhibitors of PR3 preferentially target neutrophil elastase. We have designed a selective PR3 inhibitor based on the sequence of one of its specific, sensitive FRET substrates. This azapeptide, azapro-3, inhibits free PR3 in solution, PR3 bound to neutrophil membranes, and the PR3 found in crude lung secretions from patients with chronic inflammatory pulmonary diseases. But it does not inhibit significantly neutrophil elastase or cathepsin G. Unlike most of azapeptides, this inhibitor does not form a stable acyl-enzyme complex; it is a reversible competitive inhibitor with a K(i) comparable to the K(m) of the parent substrate. Low concentrations (60 μM) of azapro-3 totally inhibited the PR3 secreted by triggered human neutrophils (200,000 cells/100 μL) and the PR3 in neutrophil homogenates and in lung secretions of patients with lung inflammation for hours. Azapro-3 also resisted proteolysis by all proteases contained in these samples for at least 2h.

  4. Synthesis of multivalent sialyllactosamine-carrying glyco-nanoparticles with high affinity to the human influenza virus hemagglutinin.

    Science.gov (United States)

    Ogata, Makoto; Umemura, Seiichiro; Sugiyama, Naohiro; Kuwano, Natsuki; Koizumi, Ami; Sawada, Tadakazu; Yanase, Michiyo; Takaha, Takeshi; Kadokawa, Jun-Ichi; Usui, Taichi

    2016-11-20

    A series of multivalent sialoglyco-conjugated nanoparticles were efficiently synthesized by using highly-branched α-glucuronic acid-linked cyclic dextrins (GlcA-HBCD) as a backbone. The sialoglycoside-moieties, with varying degrees of substitution, could be incorporated onto the preformed nanoparticles. These synthesized particles, which are highly soluble in aqueous solution, were shown to have a spherical nanostructure with a diameter of approximately 15nm. The interactions of the sialoglyco-nanoparticles (Neu5Acα2,6LacNAc-GlcA-HBCDs) with human influenza virus strain A/Beijing/262/95 (H1N1) were investigated using a hemagglutination inhibition assay. The sialoglyco-nanoparticle, in which the number of sialic acid substitution is 30, acted as a powerful inhibitor of virus binding activity. We show that both distance and multiplicity of effective ligand-virus formation play important roles in enhancing viral inhibition. Our results indicate that the GlcA-HBCD backbone can be used as a novel spherical nanocluster material for preparing a variety of glyco-nanoparticles to facilitate molecular recognition. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Bilateral optic neuritis in acute human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Larsen, M; Toft, P.B.; Bernhard, P;

    1998-01-01

    PURPOSE: To report a case of acute viral disease accompanied by bilateral optic neuritis with substantial paraclinical evidence that human immunodeficiency virus was the causative agent. METHODS: Clinical and paraclinical examination. Magnetic resonance imaging. RESULTS: Virus and antibody titers...... as well as reverse lymphocytosis were consistent with acute infection by the human immunodeficiency virus-1. CONCLUSIONS: Human immunodeficiency virus infection should be considered in the differential diagnosis of acute optic neuritis...

  6. Lipid management in human immunodeficiency virus.

    Science.gov (United States)

    Myerson, Merle

    2015-05-01

    The development and use of antiretroviral medications to treat patients infected with human immunodeficiency virus (HIV) has dramatically changed the course of this disease from one that was fatal to a chronic and more manageable condition. Recommendations and guidelines for the general population are presented in this review with suggestions as to how they may be applied to this patient population. Issues for which there is little or no information available are noted to highlight the many gaps in our knowledge regarding diagnosis and management of dyslipidemia for patients living with HIV.

  7. Anemia and survival in human immunodeficiency virus

    DEFF Research Database (Denmark)

    Lundgren, Jens Dilling; Mocroft, Amanda

    2003-01-01

    The prospective, multicenter cohort study EuroSIDA has previously reported on predictors and outcomes of anemia in patients infected with human immunodeficiency virus. In a Cox proportional-hazards model with serial measures of CD4+ cell count, plasma viral load, and degrees of anemia fitted...... as time-dependent variables, the relative hazard of death increased markedly for patients with anemia versus no anemia. A clinical scoring system was developed and validated for patients receiving highly active antiretroviral therapy using the most recent laboratory measures. Mild and severe anemia were...... independently (Panemia. The mechanisms underlying why hemoglobin is such a strong prognostic...

  8. Anemia and survival in human immunodeficiency virus

    DEFF Research Database (Denmark)

    Lundgren, Jens Dilling; Mocroft, Amanda

    2003-01-01

    The prospective, multicenter cohort study EuroSIDA has previously reported on predictors and outcomes of anemia in patients infected with human immunodeficiency virus. In a Cox proportional-hazards model with serial measures of CD4+ cell count, plasma viral load, and degrees of anemia fitted...... as time-dependent variables, the relative hazard of death increased markedly for patients with anemia versus no anemia. A clinical scoring system was developed and validated for patients receiving highly active antiretroviral therapy using the most recent laboratory measures. Mild and severe anemia were...... independently (Panemia. The mechanisms underlying why hemoglobin is such a strong prognostic...

  9. Human immunodeficiency virus infection in adolescents.

    Science.gov (United States)

    Lehmann, Corinne; D'Angelo, Lawrence J

    2010-08-01

    Despite advances in human immunodeficiency virus (HIV) treatment and discovery of effective prevention programs, HIV infection in American youth continues to rise, especially in minority youth. The crisis underscores the lack of access to care and wellness of our adolescent and young adult populations. Primary care practitioners who care for young adults will diagnose and/or encounter HIV-infected patients in their practice. Providers need to become familiar with the basics of HIV prevention and treatment, as well as how adolescence presents unique challenges in HIV care.

  10. 45 CFR 96.128 - Requirements regarding human immunodeficiency virus.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Requirements regarding human immunodeficiency virus. 96.128 Section 96.128 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL... human immunodeficiency virus. (a) In the case of a designated State as described in paragraph (b)...

  11. The Human Carnitine Transporter SLC22A16 Mediates High Affinity Uptake of the Anticancer Polyamine Analogue Bleomycin-A5*

    Science.gov (United States)

    Aouida, Mustapha; Poulin, Richard; Ramotar, Dindial

    2010-01-01

    Bleomycin is used in combination with other antineoplastic agents to effectively treat lymphomas, testicular carcinomas, and squamous cell carcinomas of the cervix, head, and neck. However, resistance to bleomycin remains a persistent limitation in exploiting the full therapeutic benefit of the drug with other types of cancers. Previously, we documented that the Saccharomyces cerevisiae l-carnitine transporter Agp2 is responsible for the high affinity uptake of polyamines and of the polyamine analogue bleomycin-A5. Herein, we document that the human l-carnitine transporter hCT2 encoded by the SLC22A16 gene is involved in bleomycin-A5 uptake, as well as polyamines. We show that NT2/D1 human testicular cancer cells, which highly express hCT2, are extremely sensitive to bleomycin-A5, whereas HCT116 human colon carcinoma cells devoid of detectable hCT2 expression or MCF-7 human breast cancer cells that only weakly express the permease showed striking resistance to the drug. NT2/D1 cells accumulated fluorescein-labeled bleomycin-A5 to substantially higher levels than HCT116 cells. Moreover, l-carnitine protected NT2/D1 cells from the lethal effects of bleomycin-A5 by preventing its influx, and siRNA targeted to hCT2 induced resistance to bleomycin-A5-dependent genotoxicity. Furthermore, hCT2 overexpression induced by transient transfection of a functional hCT2-GFP fusion protein sensitized HCT116 cells to bleomycin-A5. Collectively, our data strongly suggest that hCT2 can mediate bleomycin-A5 and polyamine uptake, and that the rate of bleomycin-A5 accumulation may account for the differential response to the drug in patients. PMID:20037140

  12. The human carnitine transporter SLC22A16 mediates high affinity uptake of the anticancer polyamine analogue bleomycin-A5.

    Science.gov (United States)

    Aouida, Mustapha; Poulin, Richard; Ramotar, Dindial

    2010-02-26

    Bleomycin is used in combination with other antineoplastic agents to effectively treat lymphomas, testicular carcinomas, and squamous cell carcinomas of the cervix, head, and neck. However, resistance to bleomycin remains a persistent limitation in exploiting the full therapeutic benefit of the drug with other types of cancers. Previously, we documented that the Saccharomyces cerevisiae L-carnitine transporter Agp2 is responsible for the high affinity uptake of polyamines and of the polyamine analogue bleomycin-A5. Herein, we document that the human L-carnitine transporter hCT2 encoded by the SLC22A16 gene is involved in bleomycin-A5 uptake, as well as polyamines. We show that NT2/D1 human testicular cancer cells, which highly express hCT2, are extremely sensitive to bleomycin-A5, whereas HCT116 human colon carcinoma cells devoid of detectable hCT2 expression or MCF-7 human breast cancer cells that only weakly express the permease showed striking resistance to the drug. NT2/D1 cells accumulated fluorescein-labeled bleomycin-A5 to substantially higher levels than HCT116 cells. Moreover, L-carnitine protected NT2/D1 cells from the lethal effects of bleomycin-A5 by preventing its influx, and siRNA targeted to hCT2 induced resistance to bleomycin-A5-dependent genotoxicity. Furthermore, hCT2 overexpression induced by transient transfection of a functional hCT2-GFP fusion protein sensitized HCT116 cells to bleomycin-A5. Collectively, our data strongly suggest that hCT2 can mediate bleomycin-A5 and polyamine uptake, and that the rate of bleomycin-A5 accumulation may account for the differential response to the drug in patients.

  13. Inhibition of human high-affinity copper importer Ctr1 orthologous in the nervous system of Drosophila ameliorates Aβ42-induced Alzheimer's disease-like symptoms.

    Science.gov (United States)

    Lang, Minglin; Fan, Qiangwang; Wang, Lei; Zheng, Yajun; Xiao, Guiran; Wang, Xiaoxi; Wang, Wei; Zhong, Yi; Zhou, Bing

    2013-11-01

    Disruption of copper homeostasis has been implicated in Alzheimer's disease (AD) during the last 2 decades; however, whether copper is a friend or a foe is controversial. Within a genetically tractable Drosophila AD model, we manipulated the expression of human high-affinity copper importer orthologous in Drosophila to explore the in vivo roles of copper ions in the development of AD. We found that inhibition of Ctr1C expression by RNAi in Aβ-expressing flies significantly reduced copper accumulation in the brains of the flies as well as ameliorating neurodegeneration, enhancing climbing ability, and prolonging lifespan. Interestingly, Ctr1C inhibition led to a significant increase in higher-molecular-weight Aβ42 forms in brain lysates, whereas it was accompanied by a trend of decreased expression of amyloid-β degradation proteases (including NEP1-3 and IDE) with age and reduced Cu-Aβ interaction-induced oxidative stress in Ctr1C RNAi flies. Similar results were obtained from inhibiting another copper importer Ctr1B and overexpressing a copper exporter DmATP7 in the nervous system of AD flies. These results imply that copper may play a causative role in developing AD, as either Aβ oligomers or aggregates were less toxic in a reduced copper environment or one with less copper binding. Early manipulation of brain copper uptake can have a great effect on Aβ pathology.

  14. New insights in the structure and biology of the high affinity receptor for IgE (Fc epsilon RI) on human epidermal Langerhans cells.

    Science.gov (United States)

    Bieber, T; Kraft, S; Jürgens, M; Strobel, I; Haberstok, J; Tomov, H; Regele, D; de la Salle, H; Wollenberg, A; Hanau, D

    1996-10-01

    The recent structural and functional analysis of the high affinity receptor for IgE (Fc epsilon RI) expressed on human epidermal Langerhans cells (LC) revealed new aspects of the biology of this structure. In contrast to basophils and mast cells where this receptor seems to be expressed constitutively at a constant level, the expression of Fc epsilon RI on LC varies on the donor and the inflammatory environment of the cells and lacks the classical beta-chain. This also implies functional differences most probably related to the expression level. Although the signalling pathway seems to be similar to that of basophils or mast cells, LC from individuals with atopic dermatitis are fully activated by receptor ligation while LC from normal individuals fail to exhibit calcium mobilization under the same conditions. Finally, LC from normal and atopic individuals use Fc epsilon RI to maximize antigen uptake via specific IgE and subsequent presentation to T cells. Thus, Fc epsilon RI expressed on LC differs in terms of structure and function from that expressed on effector cells of anaphylaxis.

  15. 78 FR 33848 - Draft Guidance for Industry on Human Immunodeficiency Virus-1 Infection: Developing...

    Science.gov (United States)

    2013-06-05

    ... No. FDA-2013-D-0589] Draft Guidance for Industry on Human Immunodeficiency Virus-1 Infection... guidance for industry entitled ``Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral Drugs... guidance for industry entitled ``Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral...

  16. The role of human cytochrome P450 enzymes in the formation of 2-hydroxymetronidazole: CYP2A6 is the high affinity (low Km) catalyst.

    Science.gov (United States)

    Pearce, Robin E; Cohen-Wolkowiez, Michael; Sampson, Mario R; Kearns, Gregory L

    2013-09-01

    Despite metronidazole's widespread clinical use since the 1960s, the specific enzymes involved in its biotransformation have not been previously identified. Hence, in vitro studies were conducted to identify and characterize the cytochrome P450 enzymes involved in the formation of the major metabolite, 2-hydroxymetronidazole. Formation of 2-hydroxymetronidazole in human liver microsomes was consistent with biphasic, Michaelis-Menten kinetics. Although several cDNA-expressed P450 enzymes catalyzed 2-hydroxymetronidazole formation at a supratherapeutic concentration of metronidazole (2000 μM), at a "therapeutic concentration" of 100 μM only CYPs 2A6, 3A4, 3A5, and 3A7 catalyzed metronidazole 2-hydroxylation at rates substantially greater than control vector, and CYP2A6 catalyzed 2-hydroxymetronidazole formation at rates 6-fold higher than the next most active enzyme. Kinetic studies with these recombinant enzymes revealed that CYP2A6 has a Km = 289 μM which is comparable to the Km for the high-affinity (low-Km) enzyme in human liver microsomes, whereas the Km values for the CYP3A enzymes corresponded with the low-affinity (high-Km) component. The sample-to-sample variation in 2-hydroxymetronidazole formation correlated significantly with CYP2A6 activity (r ≥ 0.970, P concentrations of 100 and 300 μM. Selective chemical inhibitors of CYP2A6 inhibited metronidazole 2-hydroxylation in a concentration-dependent manner and inhibitory antibodies against CYP2A6 virtually eliminated metronidazole 2-hydroxylation (>99%). Chemical and antibody inhibitors of other P450 enzymes had little or no effect on metronidazole 2-hydroxylation. These results suggest that CYP2A6 is the primary catalyst responsible for the 2-hydroxylation of metronidazole, a reaction that may function as a marker of CYP2A6 activity both in vitro and in vivo.

  17. Modification of AxSYM Human Immunodeficiency Virus Assay to Identify Recent Human Immunodeficiency Virus Infections in Korean Human Immunodeficiency Virus-Positive Individuals

    National Research Council Canada - National Science Library

    Wang, Jin-Sook; Kee, Mee-Kyung; Choi, Byeong-Sun; Kim, Sung Soon

    2015-01-01

    To estimate human immunodeficiency virus (HIV) incidence using HIV avidity assays in Korea, we established a serological testing method to differentiate recent HIV infections from long-standing ones...

  18. Human immunodeficiency virus-negative plasmablastic lymphoma

    Science.gov (United States)

    Lin, Li; Zhang, Xudong; Dong, Meng; Li, Ling; Wang, Xinhua; Zhang, Lei; Fu, Xiaorui; Sun, Zhenchang; Wu, Jingjing; Li, Zhaoming; Chang, Yu; Wang, Yingjun; Zhou, Zhiyuan; Zhang, Mingzhi; Chen, Qingjiang

    2017-01-01

    Abstract Rationale: Plasmablastic lymphoma (PBL) is a rare subtype of human immunodeficiency virus (HIV)-related non-Hodgkin's lymphoma that predominantly manifests in the oral cavity. Patient concerns: Three cases of HIV-negative PBL were reported. Diagnoses: HIV-negative PBL Interventions: The patient had undergone chemotherapy. Outcomes: Clinical outcomes were very poor in Cases 1 and 3; Case 2, whose diagnosis suggested no bone marrow involvement, is still alive. Lessons subsections: These cases served to broaden the reported clinical spectrum of HIV-negative PBL. Clinicians and pathologists need to be familiar with lymphoma in the identified extra-oral PBL variation and there levant differential diagnosis procedures for this particular disease. PMID:28207555

  19. Human immunodeficiency virus induced oral candidiasis.

    Science.gov (United States)

    Warrier, S Aravind; Sathasivasubramanian, S

    2015-08-01

    Human immunodeficiency virus (HIV) infection is a worldwide health problem, which affects in both developing and developed countries. The oral lesions caused due to this disease can drastically change the life of the patient, in terms of quality. We can also know the progression of the disease and also the important immune status of the patient. Lots of information on HIV is known in the developed countries and very less reports are available in the developing countries. The morbidity of HIV disease is due to its association with opportunistic fungal infection and the most common among them is oral candidiasis. Here, we present a case report on an apparently healthy male patient of 39 years, who had oral candidiasis and was one of the indicators for HIV infection.

  20. human immunodeficiency virus and the nervous system: an update ...

    African Journals Online (AJOL)

    drclement

    recognition in. 1981. Human immunodeficiency virus (HIV) is a retrolentivirus causing ... syndrome (AIDS) and eventual death. The origin of HIV in humans lies in its evolution from the simian ... brain barrier (BBB) or the blood CSF.

  1. Cardiovascular implications from untreated human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Baker, Jason V; Lundgren, Jens D

    2011-01-01

    Atherosclerotic cardiovascular disease (CVD) has become an important cause of morbidity and mortality among individuals with human immunodeficiency virus (HIV) infection with access to antiretroviral medications, as the risk for AIDS has fallen and life expectancy improved. Traditional CVD risk...

  2. Human Immunodeficiency Virus and Hepatitis C Virus Co-infection ...

    African Journals Online (AJOL)

    Human Immunodeficiency Virus and Hepatitis C Virus Co-infection in Cameroon: ... were analyzed using molecular biology techniques that involved RT-PCR, ... There is evidence of genetic diversity of HIV and HCV; virulent hepatitis C virus ...

  3. Knowledge of human immunodeficiency virus post-exposure ...

    African Journals Online (AJOL)

    Knowledge of human immunodeficiency virus post-exposure prophylaxis among doctors in a Nigerian tertiary hospital. ... of PEP policy in the hospital. The level of knowledge concerning the high-risk fluid and three drugs used in PEP is high.

  4. Disparities in the Magnitude of Human Immunodeficiency Virus ...

    African Journals Online (AJOL)

    human immunodeficiency virus-related opportunistic infections between high and ... estimated 35.3 million people living with HIV (PLHIV), and. 2.3 million new HIV ...... us not erronously conclude that OIs have become a thing of the past.

  5. Human Immunodeficiency Virus Infection in Pregnancy

    Directory of Open Access Journals (Sweden)

    Yasemin Arikan

    1998-01-01

    Full Text Available The incidence and prevalence of human immunodeficiency virus (HIV infection in women of child-bearing age continue to increase both internationally and in Canada. The care of HIV-infected pregnant women is complex, and multiple issues must be addressed, including the current and future health of the woman, minimization of the risk of maternal-infant HIV transmission, and maintenance of the well-being of the fetus and neonate. Vertical transmission of HIV can occur in utero, intrapartum and postpartum, but current evidence suggests that the majority of transmission occurs toward end of term, or during labour and delivery. Several maternal and obstetrical factors influence transmission rates, which can be reduced by optimal medical and obstetrical care. Zidovudine therapy has been demonstrated to reduce maternal-infant transmission significantly, but several issues, including the short and long term safety of antiretrovirals and the optimal use of combination antiretroviral therapy in pregnancy, remain to be defined. It is essential that health care workers providing care to these women fully understand the natural history of HIV disease in pregnancy, the factors that affect vertical transmission and the management issues during pregnancy. Close collaboration among a multidisciplinary team of knowledgeable health professionals and, most importantly, the woman herself can improve both maternal and infant outcomes.

  6. Replication of biotinylated human immunodeficiency viruses.

    Science.gov (United States)

    Belshan, Michael; Matthews, John M; Madson, Christian J

    2011-01-01

    Previous work demonstrated recently the adaptation of the Escherichia coli biotin ligase BirA - biotin acceptor sequence (BAS) labeling system to produce human immunodeficiency virus type 1 viruses with biotinylated integrase (NLXIN(B)) and matrix (NLXMA(B)) proteins (Belshan et al., 2009). This report describes the construction of an HIV permissive cell line stably expressing BirA (SupT1.BirA). Consistent with the results in the previous report, NLXMA(B) replicated similar to wild-type levels and expressed biotinylated Gag and MA proteins in the SupT1.BirA cells, whereas the replication of NLXIN(B) was reduced severely. Three additional HIV type 2 (HIV-2) viruses were constructed with the BAS inserted into the vpx and vpr accessory genes. Two BAS insertions were made into the C-terminal half of the Vpx, including one internal insertion, and one at the N-terminus of Vpr. All three viruses were replication competent in the SupT1.BirA cells and their target proteins biotinylated efficiently and incorporated into virions. These results demonstrate the potential utility of the biotinylation system to label and capture HIV protein complexes in the context of replicating virus.

  7. Human immunodeficiency virus infection, Part II.

    Science.gov (United States)

    Horowitz, H W; Telzak, E E; Sepkowitz, K A; Wormser, G P

    1998-12-01

    The acceptance of highly active antiretroviral therapy (HAART) among patients and health care providers has had a dramatic impact on the epidemiology and clinical characteristics of many opportunistic infections associated with human immunodeficiency virus (HIV). Previously intractable opportunistic infections and syndromes are now far less common. In addition, effective antibiotic prophylactic therapies have had a profound impact on the risk of patients developing particular infections and on the incidence of these infections overall. Most notable among these are Pneumocystis carinii, disseminated Mycobacterium avium complex, tuberculosis, and toxoplasmosis. Nevertheless, infections continue to cause significant morbidity and mortality among patients who are infected with HIV. The role of HAART in many clinical situations is unquestioned. Compelling data from clinical trials support the use of these therapies during pregnancy to prevent perinatal transmission of HIV. HAART is also recommended for health care workers who have had a "significant" exposure to the blood of an HIV-infected patient. Both of these situations are discussed in detail in this article. In addition, although more controversial, increasing evidence supports the use of HAART during the acute HIV seroconversion syndrome. An "immune reconstitution syndrome" has been newly described for patients in the early phases of treatment with HAART who develop tuberculosis, M avium complex, and cytomegalovirus disease. Accumulating data support the use of hydroxyurea, an agent with a long history in the field of myeloproliferative disorders, for the treatment of HIV. Newer agents, particularly abacavir and adefovir dipivoxil, are available through expanded access protocols, and their roles are being defined and clarified.

  8. The surgeon and human immunodeficiency virus.

    Science.gov (United States)

    Mielke, Jens; Kalangu, Kazadi K N

    2003-08-01

    The moral dilemmas faced by surgeons worldwide who treat patients infected with the human immunodeficiency virus (HIV) can be viewed against the background of experience in sub-Saharan countries, where the community prevalence is in excess of 25% (90% of hospital inpatients). When seeking consent for an HIV test before surgery, frank communication regarding the surgeons' perspective of risks to themselves and the patient is helpful. When consent for a test must be obtained from a substitute decision-maker, the surgeon should consider if the patient would want the decision-maker to know the result. Understanding the natural history of HIV in the surgical setting can help deal with the uncertainties encountered and should be a research priority for developing countries. International professional organizations are useful platforms for the exchange of ideas when surgeons encounter uncertainty by increasing access to journals and creating opportunities for discussion. Although supervisory bodies in some parts of the world prevent HIV-infected surgeons from putting patients at risk by offering surgery, the withdrawal of their services in developing countries can cause more harm than good. Surgeons in that position may be entitled to offer surgery but only with full disclosure of the risk of HIV infection to the patient. The decision-making process known as "accountability for reasonableness" allows surgeons to determine fairness, legitimacy, and acceptability when making resource allocation decisions involving patients with HIV.

  9. Aging, human immunodeficiency virus, and bone health

    Directory of Open Access Journals (Sweden)

    Kim C Mansky

    2010-09-01

    Full Text Available Kim C ManskyDivision of Orthodontics, Department of Developmental and Surgical Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN, USAAbstract: Highly active antiretroviral therapy (HAART has had a profound impact on improving the long-term prognosis for individuals infected with human immunodeficiency virus (HIV. HAART has been available for close to two decades, and now a significant number of patients with access to HAART are over the age of 50 years. Many clinical studies have indicated that HIV infection, as well as components of HAART, can increase the risk in these individuals to a variety of noninfectious complications, including a risk to bone health. There is a significant need for detailed mechanistic analysis of the aging, HIV-infected population regarding the risk of HIV infection and therapy in order to maintain bone health. Insights from basic mechanistic studies will help to shed light on the role of HIV infection and the components of HAART that impact bone health, and will help in identifying preventative countermeasures, particularly for individuals 50 years of age and older.Keywords: osteopenia, osteomalacia, osteoporosis, bisphosphonates, tenofovir, osteoimmunology

  10. Medical management of human immunodeficiency virus infection

    Directory of Open Access Journals (Sweden)

    Kempen John

    2008-01-01

    Full Text Available The human immunodeficiency virus (HIV/ acquired immune deficiency syndrome (AIDS pandemic has pervasive effects on culture, economics, policy, and human development. All organs can be affected by complications of HIV/AIDS, including the eye. When sufficient resources are available and widespread antiretroviral resistance does not exist, the four available classes of antiretroviral agents - nucleoside/nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and fusion inhibitors - can be combined to provide highly active antiretroviral therapy (HAART. For many (not all patients, HAART converts an inexorably fatal disease into a chronic disease with a fairly good prognosis. Use of HAART often induces partial immune recovery, which has predominantly beneficial effects on ocular complications of AIDS. However, HAART-induced immune recovery sometimes results in immune recovery inflammatory syndromes, such as immune recovery uveitis. Use of HAART is the single most useful intervention for most patients with ocular complications of AIDS. However, specific ocular therapy is also critical to avoid blindness in the early months before immune recovery can occur, or if HAART is unavailable. Increasing availability of HAART worldwide shows great promise to alleviate one of the world′s greatest plagues. However, predictable secular trends in the AIDS epidemic make it likely that the number of cases of ocular complications of AIDS will increase substantially before they decrease. Ophthalmologists worldwide should be familiar with the diagnosis and management of cytomegalovirus retinitis - the most common ocular complication of AIDS - and should establish partnerships with physicians who are able to provide HAART. Research is needed to determine the optimal approach for managing cytomegalovirus retinitis in resource-constrained settings.

  11. Recombinant human Fab fragments neutralize human type 1 immunodeficiency virus in vitro.

    Science.gov (United States)

    Barbas, C F; Björling, E; Chiodi, F; Dunlop, N; Cababa, D; Jones, T M; Zebedee, S L; Persson, M A; Nara, P L; Norrby, E

    1992-01-01

    A panel of 20 recombinant Fab fragments reactive with the surface glycoprotein gp120 of human type 1 immunodeficiency virus (HIV-1) were examined for their ability to neutralize MN and IIIB strains of the virus. Neutralization was determined as the ability of the Fab fragments to inhibit infection as measured in both a p24 ELISA and a syncytium-formation assay. One group of closely sequence-related Fab fragments was found to neutralize virus in both assays with a 50% neutralization titer at approximately 1 micrograms/ml. Another Fab neutralized in the p24 ELISA but not in the syncytium assay. The other Fab fragments showed weak or no neutralizing ability. The results imply that virion aggregation or crosslinking of gp120 molecules on the virion surface is not an absolute requirement for HIV-1 neutralization. Further, all of the Fab fragments were shown to be competitive with soluble CD4 for binding to gp120 and yet few neutralized the virus effectively, implying that the mechanism of neutralization in this case may not involve receptor blocking. The observation of a preponderance of high-affinity Fab fragments with poor or no neutralizing ability could have implications for vaccine strategies. PMID:1384050

  12. Human immunodeficiency virus in institutionalized elderly people

    Directory of Open Access Journals (Sweden)

    Milton Luiz Gorzoni

    Full Text Available ABSTRACT CONTEXT AND OBJECTIVE: A search in the SciELO and PubMed databases showed few studies on human immunodeficiency virus (HIV positive individuals in long-term care institutions (LTCIs, thus prompting the present study. The aim of this study was to ascertain whether there were any HIV-positive individuals in LTCIs for the elderly. DESIGN AND SETTING: Cross-sectional study in which the Hospital Infection Control Committee (HICC of a 405-bed LTCI was consulted. METHODS: The medical records of 405 individuals interned in the LTCI who had been tested for HIV infection were requested for analysis of the following variables: [1] age and gender; [2] length of stay at LTCI (months; [3] causes and diagnoses on admission to LTCI according to International Classification of Diseases, 10th edition; [4] date of HIV diagnosis; [5] seropositivity for syphilis and hepatitis B and C viruses; [6] medications used at last prescription in medical file; and [7] mean CD4 lymphocyte count based on: total lymphocyte count/6 and total lymphocyte count x 0.8 x 0.2 or 0.3. RESULTS: Four men were HIV-positive, with mean age 71.2 ± 8.6 years, LTCI stay 74.2 ± 38.1 months and length of HIV diagnosis 24.5 ± 17 months (confirmed by HICC standard screening. Three had stroke sequelae; one, dementia syndrome; two, seropositivity for syphilis; two, hepatitis B and one, hepatitis C. The main drugs used were lamivudine, zidovudine, lopinavir, ritonavir, levothyroxine, omeprazole, ranitidine, lactulose and risperidone. The estimated CD4 count was 341 ± 237/mm3. CONCLUSIONS: HIV-positive individuals are present in LTCIs, diagnosable through serological screening and treatable with antiretroviral drugs.

  13. Ultrastructure and morphogenesis of human immunodeficiency virus.

    Science.gov (United States)

    Nakai, M; Goto, T

    1996-08-01

    The ultrastructure and morphogenesis of human immunodeficiency virus (HIV) were elucidated by observation with several techniques including immunoelectron microscopy and cryo-microscopy. The virus particle consists of an envelope, a core and matrix. The virus particles were observed extracellularly as having one of three profiles: (1) a centric or an eccentric electron-dense core, (2) rod-shaped electron-dense core, and (3) doughnut-shaped. HIV-1 particles in the hydrated state were observed by high resolution electron cryo-microscopy to be globular, and the lipid membrane was clearly resolved as a bilayer. Many projections around the circumference were seen to be knob-like. The shapes and sizes of the projections, especially head parts, were found to vary in each projection. By isolation with Nonidet P40 and glutaraldehyde, HIV-1 cores were confirmed to consist of p24 protein by immunogold labeling. When the virus enters the cell, two entry modes were found: membrane fusion and endocytosis. No structures resembling virus particles could be seen in the cytoplasm after viral entry. In HIV-1-infected cells, positive reactions by immuno-labeling suggest that HIV-1 Gag may be produced in membrane-bound structures and transported to the cell surface by cytoskeletons. Then a crescent electron-dense layer was first formed underneath the cell membrane. Finally, the virus particle was released from the cell surface. Several cell clones producing defective particles were isolated from MT-4/HIV-1 cells. Among them, doughnut-shaped or teardrop-shaped particles were seen to be produced in the extracellular space. In the doughnut-shaped particles, Gag p17 and p24 proteins faced each other against the inner electron dense ring, suggesting that the inner ring consists of a precursor Gag protein.

  14. Altered Virome and Bacterial Microbiome in Human Immunodeficiency Virus-Associated Acquired Immunodeficiency Syndrome.

    Science.gov (United States)

    Monaco, Cynthia L; Gootenberg, David B; Zhao, Guoyan; Handley, Scott A; Ghebremichael, Musie S; Lim, Efrem S; Lankowski, Alex; Baldridge, Megan T; Wilen, Craig B; Flagg, Meaghan; Norman, Jason M; Keller, Brian C; Luévano, Jesús Mario; Wang, David; Boum, Yap; Martin, Jeffrey N; Hunt, Peter W; Bangsberg, David R; Siedner, Mark J; Kwon, Douglas S; Virgin, Herbert W

    2016-03-09

    Human immunodeficiency virus (HIV) infection is associated with increased intestinal translocation of microbial products and enteropathy as well as alterations in gut bacterial communities. However, whether the enteric virome contributes to this infection and resulting immunodeficiency remains unknown. We characterized the enteric virome and bacterial microbiome in a cohort of Ugandan patients, including HIV-uninfected or HIV-infected subjects and those either treated with anti-retroviral therapy (ART) or untreated. Low peripheral CD4 T cell counts were associated with an expansion of enteric adenovirus sequences and this increase was independent of ART treatment. Additionally, the enteric bacterial microbiome of patients with lower CD4 T counts exhibited reduced phylogenetic diversity and richness with specific bacteria showing differential abundance, including increases in Enterobacteriaceae, which have been associated with inflammation. Thus, immunodeficiency in progressive HIV infection is associated with alterations in the enteric virome and bacterial microbiome, which may contribute to AIDS-associated enteropathy and disease progression.

  15. Health Administrator Perspectives on Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Prevention and Services at Historically Black Colleges and Universities

    Science.gov (United States)

    Warren-Jeanpiere, Lari; Jones, Sandra; Sutton, Madeline Y.

    2011-01-01

    Objective: Due to the disproportionate impact of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) among African American young adults, the authors explored (1) number of historically black college and university (HBCU) campuses with existing HIV prevention policies and services and (2) perceived barriers for implementing…

  16. Brazilian response to the human immunodeficiency virus/acquired immunodeficiency syndrome epidemic among injection drug users.

    Science.gov (United States)

    Mesquita, Fábio; Doneda, Denise; Gandolfi, Denise; Nemes, Maria Inês Battistella; Andrade, Tarcísio; Bueno, Regina; Piconez e Trigueiros, Daniela

    2003-12-15

    The Brazilian response to the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic is being observed all over the world because of its success. Understanding the role of injection drug users (IDUs) in the epidemic and the political response thereto is a key factor in the control of the epidemic in Brazil. This paper summarizes some of the most important analyses of the Brazilian response to the HIV/AIDS epidemic among and from IDUs. Key elements of the response include the support of the Brazilian Universal Public Health System, the provision of universal access to highly active antiretroviral therapy, and the creation of harm reduction projects that are politically and financially supported by the federal government. The response among and from IDUs is a key element in overall control of the HIV/AIDS epidemic. The response to the epidemic among and from IDUs has been headed in the correct direction since its beginning and is now being intensively expanded.

  17. The Human Immunodeficiency Virus: Infectivity and Mechanisms of Pathogenesis.

    Science.gov (United States)

    Fauci, Anthony S.

    1988-01-01

    Discusses how the infection of the human immunodeficiency virus (HIV) results in a profound immunosuppression due predominantly to a selective depletion of helper/inducer T lymphocytes that express the receptor for the virus, as well as neuropsychiatric abnormalities in the brain. (TW)

  18. 21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Human immunodeficiency virus (HIV) âlookbackâ... Disease Agents § 610.46 Human immunodeficiency virus (HIV) “lookback” requirements. (a) If you are an... calendar days after a donor tests reactive for evidence of human immunodeficiency virus (HIV)...

  19. 76 FR 72417 - Public Health Service Guideline for Reducing Transmission of Human Immunodeficiency Virus (HIV...

    Science.gov (United States)

    2011-11-23

    ... (PHS) Guideline for Reducing Transmission of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV... Reducing Transmission of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and Hepatitis C Virus... Immunodeficiency Virus (HIV) through Transplantation of Human Tissue and Organs. The 2011......

  20. 76 FR 58517 - Public Health Service Guideline for Reducing Transmission of Human Immunodeficiency Virus (HIV...

    Science.gov (United States)

    2011-09-21

    ... Transmission of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV... Guideline for Reducing Transmission of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and... Reducing Transmission of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and......

  1. A human high affinity interleukin-5 receptor (IL5R) is composed of an IL5-specific alpha chain and a beta chain shared with the receptor for GM-CSF.

    Science.gov (United States)

    Tavernier, J; Devos, R; Cornelis, S; Tuypens, T; Van der Heyden, J; Fiers, W; Plaetinck, G

    1991-09-20

    cDNA clones encoding two receptor proteins involved in the binding of human interleukin 5 (hIL5) have been isolated. A first class codes for an IL5-specific chain (hIL5R alpha). The major transcript of this receptor gene, as analyzed in both HL-60 eosinophilic cells and eosinophilic myelocytes grown from cord blood, encodes a secreted form of this receptor. This soluble hIL5R alpha has antagonistic properties. A second component of the hIL5R is found to be identical to the beta chain of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) high affinity receptor. The finding that IL5 and GM-CSF share a receptor subunit provides a molecular basis for the observation that these cytokines can partially interfere with each other's binding and have highly overlapping biological activities on eosinophils.

  2. Serodiagnosis of Helicobacter pylori infection in patients with human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Nielsen, H; Andersen, L P

    1995-01-01

    In contrast to the established role of Helicobacter pylori gastritis in gastritis and duodenal ulcer in general, conflicting results have been reported in patients with human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome. The seroprevalence during early HIV...

  3. Generation of high-affinity fully human anti-interleukin-8 antibodies from its cDNA by two-hybrid screening and affinity maturation in yeast.

    Science.gov (United States)

    Ding, Ling; Azam, Mark; Lin, Yu-Huei; Sheridan, James; Wei, Shuanghong; Gupta, Gigi; Singh, Rakesh K; Pauling, Michelle H; Chu, Waihei; Tran, Antares; Yu, Nai-Xuan; Hu, Jiefeng; Wang, Wei; Long, Hao; Xiang, Dong; Zhu, Li; Hua, Shao-Bing

    2010-10-01

    We have developed a technology for rapidly generating novel and fully human antibodies by simply using the antigen DNA. A human single-chain variable fragment (scFv) antibody library was constructed in a yeast two-hybrid vector with high complexity. After cloning cDNA encoding the mature sequence of human interleukin-8 (hIL8) into the yeast two-hybrid system vector, we have screened the human scFv antibody library and obtained three distinct scFv clones that could specifically bind to hIL8. One clone was chosen for further improvement by a novel affinity maturation process using the error-prone PCR of the scFv sequence followed by additional rounds of yeast two-hybrid screening. The scFv antibodies of both primary and affinity-matured scFv clones were expressed in E. coli. All purified scFvs showed specific binding to hIL8 in reciprocal coimmunoprecipitation and ELISA assays. All scFvs, as well as a fully human IgG antibody converted from one of the scFv clones and expressed in the mammalian cells, were able to effectively inhibit hIL8 in neutrophil chemotaxis assays. The technology described can generate fully human antibodies with high efficiency and low cost.

  4. Human immunodeficiency virus-associated deep vein thrombosis

    Directory of Open Access Journals (Sweden)

    Akhilesh Kumar Singh

    2016-01-01

    Full Text Available Deep vein thrombosis (DVT has been reported to occur 2-10 times more common in human immunodeficiency virus-infected individuals than in the general population. We are reporting a case of DVT of right lower limb who was on highly active antiretroviral therapy. The patient did not have any acquired risk factors of DVT. The patient responded well to anticoagulation therapy.

  5. Pediatric Human Immunodeficiency Virus Screening in an African District Hospital

    OpenAIRE

    De Baets, A. J.; Edidi, B. S.; Kasali, M. J.; Beelaert, G.; Schrooten, W.; Litzroth, A; Kolsteren, P; Denolf, D.; Fransen, K

    2005-01-01

    In order to evaluate alternative tests and strategies to simplify pediatric human immunodeficiency virus (HIV) screening at the district hospital level, a cross-sectional exploratory study was organized in the Democratic Republic of the Congo. Venous and capillary phlebotomies were performed on 941 Congolese children, aged 1 month to 12 years (153 children under 18 months and 788 children more than 18 months old). The HIV prevalence rate was 4.7%. An algorithm for children more than 18 months...

  6. Prevalence of hepatitis C Antibody in Human Immunodeficiency ...

    African Journals Online (AJOL)

    2015-10-25

    Oct 25, 2015 ... impacts on the course and man- agement ... cause of the increased incidence and accelerated natural history in co-infected persons.4HCV infection may also impact the ... Hepatitis C virus (HCV) and Human Immunodeficiency .... 8 (88.9). 1 (33.3). 2.67. 0.83 – 33.18. Anti-HCV positive. N u m b er p ositive.

  7. Heterosexual spread of human immunodeficiency virus in Edinburgh

    OpenAIRE

    France, A J; Skidmore, C A; Robertson, J R; Brettle, R P; Roberts, J J K; Burns, S. M.; Foster, C. A.; Inglis, J. M.; Galloway, W B F; Davidson, S J

    1988-01-01

    Heterosexual transmission of human immunodeficiency virus (HIV) was investigated in 123 subjects with no apparent risk factor for infection other than having had heterosexual intercourse with a person who was either infected with HIV or at high risk of being infected with it. Seven subjects were found to be infected with the virus. Risk factors for transmission included being the regular sexual partner of an abuser of intravenous drugs and having a sexual relationship of more than 18 months' ...

  8. Nonvertical, nonsexual transmission of human immunodeficiency virus in children.

    Science.gov (United States)

    Vaz, Paula; Pedro, Alinia; Le Bozec, Soazig; Macassa, Eugenia; Salvador, Sergio; Biberfeld, Gunnel; Blanche, Stéphane; Andersson, Sören

    2010-03-01

    In a cohort of 450 human immunodeficiency virus (HIV)-infected children followed up in Maputo, Mozambique, 22 were born to HIV-uninfected mothers and had no history of sexual abuse. A case record review of these nonvertically, nonsexually infected children as well as a case-control study strongly suggests health care as possible source of infection for many of these children. This facet of the pediatric HIV epidemic should not be overlooked.

  9. Unusual specificity of the androgen receptor in the human prostate tumor cell line LNCaP: High affinity for progestagenic and estrogenic steroids

    NARCIS (Netherlands)

    J. Veldscholte (Jos); M.M. Voorhorst-Ogink (M.); J. Bolt-de Vries (Joan); H.C.J. van Rooij (Henri); J. Trapman (Jan); E. Mulder (Eppo)

    1990-01-01

    textabstractAbstract LNCaP tumor cells, derived from a metastatic lesion of a human prostatic carcinoma, are androgen-sensitive in cell culture. Although increase in growth rate is observed with low doses of progestagens or estradiol, these cells contain exclusively androgen receptors. In the presen

  10. Isolation of high-affinity human IgE and IgG antibodies recognising Bet v 1 and Humicola lanuginosa lipase from combinatorial phage libraries

    DEFF Research Database (Denmark)

    Jakobsen, Charlotte G; Bodtger, Uffe; Kristensen, Peter

    2004-01-01

    Allergen-specific Fab fragments isolated from combinatorial IgE and IgG libraries are useful tools for studying allergen-antibody interactions. To characterise the interaction between different allergens and antibodies we have created recombinant human phage antibody libraries in the Fab format. ...

  11. Skin Conditions in Patients with Human Immunodeficiency Virus

    Directory of Open Access Journals (Sweden)

    Yoan Bernárdez Cruz

    2015-12-01

    Full Text Available Background: patients with human immunodeficiency virus frequently develop skin conditions that affect their quality of life and modify their prognosis. Objective: to describe the most common skin conditions in patients with human immunodeficiency virus. Methods: a case-series study of patients with human immunodeficiency virus was conducted in the province of Cienfuegos. It included all patients diagnosed until February 2008 attending the internal medicine consultation for their follow-up. Forty-seven deceased patients, 12 patients not living in the province and 2 inmates were excluded from the study. Variables analyzed were: age, sex, skin color, self-reported skin conditions and diagnosed skin diseases. Results: Thirty-eight percent of patients were aged 25 to 34 years. Fifty-seven were white-skinned and 75% were male. Approximately half of the patients had AIDS and were under antiretroviral therapy. The skin infection of viral origin most commonly found was herpes simplex (30.0%; of fungal origin, onychomycosis (44 %; and of bacterial origin, folliculitis (43 %. Among papulosquamous disorders, seborrheic dermatitis (74 % predominated and among other skin disorders, lipodystrophy (23.6 %. Xerosis and pruritus shared equal percentage (16.3 %. Conclusions: viral and fungal skin infections predominated. An important number of these skin conditions were diagnosed during the study, particularly in AIDS patients.

  12. Electrostatic potential of human immunodeficiency virus type 2 and rhesus macaque simian immunodeficiency virus capsid proteins

    Directory of Open Access Journals (Sweden)

    Katarzyna eBozek

    2012-06-01

    Full Text Available Human immunodeficiency virus type 2 (HIV-2 and simian immunodeficiency virus isolated from a macaque monkey (SIVmac are assumed to have originated from simian immunodeficiency virus isolated from sooty mangabey (SIVsm. Despite their close similarity in genome structure, HIV-2 and SIVmac show different sensitivities to TRIM5α, a host restriction factor against retroviruses. The replication of HIV-2 strains is potently restricted by rhesus (Rh monkey TRIM5α, while that of SIVmac strain 239 (SIVmac239 is not. Viral capsid protein is the determinant of this differential sensitivity to TRIM5α, as the HIV-2 mutant carrying SIVmac239 capsid protein evaded Rh TRIM5α-mediated restriction. However, the molecular determinants of this restriction mechanism are unknown. Electrostatic potential on the protein-binding site is one of the properties regulating protein-protein interactions. In this study, we investigated the electrostatic potential on the interaction surface of capsid protein of HIV-2 strain GH123 and SIVmac239. Although HIV-2 GH123 and SIVmac239 capsid proteins share more than 87% amino acid identity, we observed a large difference between the two molecules with the HIV-2 GH123 molecule having predominantly positive and SIVmac239 predominantly negative electrostatic potential on the surface of the loop between α-helices 4 and 5 (L4/5. As L4/5 is one of the major determinants of Rh TRIM5α sensitivity of these viruses, the present results suggest that the binding site of the Rh TRIM5α may show complementarity to the HIV-2 GH123 capsid surface charge distribution.

  13. Circulating chromatin-anti-chromatin antibody complexes bind with high affinity to dermo-epidermal structures in murine and human lupus nephritis

    DEFF Research Database (Denmark)

    Fismen, S; Hedberg, A; Fenton, K A

    2009-01-01

    Murine and human lupus nephritis are characterized by glomerular deposits of electron-dense structures (EDS). Dominant components of EDS are chromatin fragments and IgG antibodies. Whether glomerular EDS predispose for similar deposits in skin is unknown. We analysed (i) whether dermo-epidermal i...... were present in capillary lumina in glomeruli and skin of all nephritic individuals. Thus, chromatin-IgG complexes accounting for lupus nephritis seem to reach skin through circulation, but other undetermined factors are required for these complexes to deposit within skin membranes....

  14. Human Lin28 Forms a High-Affinity 1:1 Complex with the 106~363 Cluster miRNA miR-363.

    Science.gov (United States)

    Peters, Daniel T; Fung, Herman K H; Levdikov, Vladimir M; Irmscher, Tobias; Warrander, Fiona C; Greive, Sandra J; Kovalevskiy, Oleg; Isaacs, Harry V; Coles, Mark; Antson, Alfred A

    2016-09-13

    Lin28A is a post-transcriptional regulator of gene expression that interacts with and negatively regulates the biogenesis of let-7 family miRNAs. Recent data suggested that Lin28A also binds the putative tumor suppressor miR-363, a member of the 106~363 cluster of miRNAs. Affinity for this miRNA and the stoichiometry of the protein-RNA complex are unknown. Characterization of human Lin28's interaction with RNA has been complicated by difficulties in producing stable RNA-free protein. We have engineered a maltose binding protein fusion with Lin28, which binds let-7 miRNA with a Kd of 54.1 ± 4.2 nM, in agreement with previous data on a murine homologue. We show that human Lin28A binds miR-363 with a 1:1 stoichiometry and with a similar, if not higher, affinity (Kd = 16.6 ± 1.9 nM). Further analysis suggests that the interaction of the N-terminal cold shock domain of Lin28A with RNA is salt-dependent, supporting a model in which the cold shock domain allows the protein to sample RNA substrates through transient electrostatic interactions.

  15. Human Lin28 Forms a High-Affinity 1:1 Complex with the 106~363 Cluster miRNA miR-363

    Science.gov (United States)

    2016-01-01

    Lin28A is a post-transcriptional regulator of gene expression that interacts with and negatively regulates the biogenesis of let-7 family miRNAs. Recent data suggested that Lin28A also binds the putative tumor suppressor miR-363, a member of the 106~363 cluster of miRNAs. Affinity for this miRNA and the stoichiometry of the protein–RNA complex are unknown. Characterization of human Lin28’s interaction with RNA has been complicated by difficulties in producing stable RNA-free protein. We have engineered a maltose binding protein fusion with Lin28, which binds let-7 miRNA with a Kd of 54.1 ± 4.2 nM, in agreement with previous data on a murine homologue. We show that human Lin28A binds miR-363 with a 1:1 stoichiometry and with a similar, if not higher, affinity (Kd = 16.6 ± 1.9 nM). Further analysis suggests that the interaction of the N-terminal cold shock domain of Lin28A with RNA is salt-dependent, supporting a model in which the cold shock domain allows the protein to sample RNA substrates through transient electrostatic interactions. PMID:27559824

  16. Crystal Structure of Human Interferon-[lamda]1 in Complex with Its High-Affinity Receptor Interferon-[lamda]R1

    Energy Technology Data Exchange (ETDEWEB)

    Miknis, Zachary; Magracheva, Eugenia; Li, Wei; Zdanov, Alexander; Kotenko, Sergei V.; Wlodawer, Alexander (NJMS); (NCI)

    2010-12-01

    Interferon (IFN)-{lambda}1 [also known as interleukin (IL)-29] belongs to the recently discovered group of type III IFNs. All type III IFNs initiate signaling processes through formation of specific heterodimeric receptor complexes consisting of IFN-{lambda}R1 and IL-10R2. We have determined the structure of human IFN-{lambda}1 complexed with human IFN-{lambda}R1, a receptor unique to type III IFNs. The overall structure of IFN-{lambda}1 is topologically similar to the structure of IL-10 and other members of the IL-10 family of cytokines. IFN-{lambda}R1 consists of two distinct domains having fibronectin type III topology. The ligand-receptor interface includes helix A, loop AB, and helix F on the IFN site, as well as loops primarily from the N-terminal domain and inter-domain hinge region of IFN-{lambda}R1. Composition and architecture of the interface that includes only a few direct hydrogen bonds support an idea that long-range ionic interactions between ligand and receptor govern the process of initial recognition of the molecules while hydrophobic interactions finalize it.

  17. Human immunodeficiency virus/acquired immunodeficiency syndrome and tropical diseases: a Brazilian perspective

    Directory of Open Access Journals (Sweden)

    Mariza G Morgado

    2000-01-01

    Full Text Available The paper summarizes recent findings on the epidemiology and pathogenesis of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/Aids, highlighting the role of co-infections with major tropical diseases. Such co-infections have been studied in the Brazilian context since the beginning of the Aids epidemic and are expected to be more frequent and relevant as the Aids epidemic in Brazil proceeds towards smaller municipalities and the countryside, where tropical diseases are endemic. Unlike opportunistic diseases that affect basically the immunocompromised host, most tropical diseases, as well as tuberculosis, are pathogenic on their own, and can affect subjects with mild or no immunossuppression. In the era of highly active anti-retroviral therapies (HAART, opportunistic diseases seem to be on decrease in Brazil, where such medicines are fully available. Benefiting from HAART in terms of restoration of the immune function, putative milder clinical courses are expected in the future for most co-infections, including tropical diseases. On the other hand, from an ecological perspective, the progressive geographic diffusion of Aids makes tropical diseases and tuberculosis a renewed challenge for Brazilian researchers and practitioners dealing with HIV/Aids in the coming years.

  18. Characterization of expression, cytokine regulation, and effector function of the high affinity IgG receptor Fc gamma RI (CD64) expressed on human blood dendritic cells.

    Science.gov (United States)

    Fanger, N A; Voigtlaender, D; Liu, C; Swink, S; Wardwell, K; Fisher, J; Graziano, R F; Pfefferkorn, L C; Guyre, P M

    1997-04-01

    The mechanisms responsible for efficient sequestration of Ag by cells of the dendritic cell (DC) lineage remain incompletely characterized. One pathway, internalization of Ag-IgG complexes via CD32 (the type II IgG FcR, Fc gamma RII) enhances Ag presentation 100-fold over noncomplexed Ag. Blood leukocytes differentially express two additional IgG FcR, Fc gamma RI (CD64) and Fc gamma RIII (CD16), which may also participate in leukocyte functions such as phagocytosis, Ab-dependent cellular cytotoxicity (ADCC), release of oxygen intermediates, and enhancement of Ag presentation. A phagocytically active form of CD64 was recently demonstrated on human blood DC, but complete functional potential of CD64 on the DC lineage remains undefined. Therefore, highly purified human blood DC (CD33(2)+, CD14-, CD11c2+, HLA-DR3+, CD64+ (CD83+ after overnight culture)) and monocytes (CD33(2)+, CD14(3)+, CD11c2+, HLA-DR+, CD64(2)+, CD83-) were compared for cytokine modulation and effector functions of CD64. Both DC and monocyte CD64 expression was increased by IFN-gamma and IL-10, but while monocyte CD64 was decreased by IL-4, DC CD64 remained unchanged. FcR-mediated functional differences were also evident between the DC and the monocytes. Monocytes generated robust Fc gamma R-dependent superoxide anion release and ADCC activity, while DC failed to release reactive oxygen intermediates and demonstrated minimal ADCC activity, despite apparently normal expression of the gamma-chain subunit and the signaling molecule Syk. In contrast, DC were more efficient than monocytes with respect to T cell activation when Ag was targeted specifically to CD64. These new findings suggest a previously unappreciated potential for CD64 to shape the immune response by dramatically increasing the efficiency with which DC sequester Ag prior to achieving full T cell stimulatory potential.

  19. [Pulmonary complications in children with human immunodeficiency virus infection].

    Science.gov (United States)

    Brockmann V, Pablo; Viviani S, Támara; Peña D, Anamaría

    2007-08-01

    Pulmonary complications in children infected by human immunodeficiency virus (HIV) are common and may be the first manifestation of acquired immunodeficiency syndrome (AIDS). The aim of our study was to review pulmonary diseases and complications in pediatric patients with HIV infection in a large tertiary hospital in Santiago, Chile. We performed a retrospective, descriptive analysis of 17 patients with HIV infection controlled at the Hospital Dr. Sótero del Rio. Respiratory complications/diseases were: overall pneumonia (n: 14), recurrent pneumonia (n: 10), citomegalovirus associated pneumonia (n: 4), Pneumocystis jiroveci associated pneumonia (n: 1) pulmonary tuberculosis (n: 1), lymphoid interstitial pneumonia (n: 3) and chronic pulmonary disease (n: 7). Microorganisms isolated were mostly atypical and frequently associated with severe and chronic pulmonary damage. A high degree of suspicion is required to detect atypical microorganisms promptly, in order to rapidly implement pathogen targeted therapy that could potentially decrease the possibility of sequelae.

  20. Distinct replicative and cytopathic characteristics of human immunodeficiency virus isolates.

    Science.gov (United States)

    Fenyö, E M; Morfeldt-Månson, L; Chiodi, F; Lind, B; von Gegerfelt, A; Albert, J; Olausson, E; Asjö, B

    1988-01-01

    According to their capacity to replicate in vitro, human immunodeficiency virus (HIV) isolates can be divided into two major groups, rapid/high and slow/low. Rapid/high viruses can easily be transmitted to a variety of cell lines of T-lymphoid (CEM, H9, and Jurkat) and monocytoid (U937) origin. In contrast, slow/low viruses replicate transiently, if at all, in these cell lines. Except for a few isolates, the great majority of slow/low viruses replicate in peripheral blood mononuclear cells and Jurkat-tatIII cells constitutively expressing the tatIII gene of HIV-1. The viruses able to replicate efficiently cause syncytium formation and are regularly isolated from immunodeficient patients. Poorly replicating HIV isolates, often obtained from individuals with no or mild disease, show syncytium formation and single-cell killing simultaneously or, with some isolates, cell killing only. Images PMID:2459416

  1. Idiopathic genital ulcers in women infected with human immunodeficiency virus.

    Science.gov (United States)

    Anderson, J; Clark, R A; Watts, D H; Till, M; Arrastia, C; Schuman, P; Cohn, S E; Young, M; Bessen, L; Greenblatt, R; Vogler, M; Swindells, S; Boyer, P

    1996-12-01

    A national survey of investigators caring for human immunodeficiency virus (HIV)-infected women was undertaken to describe the clinical presentation of idiopathic genital ulcer disease. Patients with negative syphilis and herpes simplex testing and/or negative genital ulcer biopsy were included in this study. Study participants (n = 29) were generally severely immunocompromised (median CD4 cell count was 50/mm3, and 68% had an acquired immunodeficiency syndrome [AIDS]-defining opportunistic process). Thirty-seven percent had coexistent oral ulcers and 19% had their genital ulcer progress to fistula formation (four rectovaginal and one vaginal-perineal). There was generally a favorable response to topical, systemic, and intralesional steroid treatment. This study suggests that idiopathic or probable aphthous genital ulcers in women have similar clinical characteristics to aphthous oroesophageal ulcers. Although infrequent, these genital ulcers can cause severe morbidity. Further research is warranted to better define the pathophysiology and optimal management.

  2. Cardiac Disease Associated with Human Immunodeficiency Virus Infection.

    Science.gov (United States)

    Bloomfield, Gerald S; Leung, Claudia

    2017-02-01

    Over the last 2 decades human immunodeficiency virus (HIV) infection has become a chronic disease requiring long-term management. Aging, antiretroviral therapy, chronic inflammation, and several other factors contribute to the increased risk of cardiovascular disease in patients infected with HIV. In low-income and middle-income countries where antiretroviral therapy access is limited, cardiac disease is most commonly related to opportunistic infections and end-stage manifestations of HIV/acquired immunodeficiency syndrome, including HIV-associated cardiomyopathy, pericarditis, and pulmonary arterial hypertension. Cardiovascular screening, prevention, and risk factor management are important factors in the management of patients infected with HIV worldwide. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Human Immunodeficiency Virus (HIV) Research (AIDS)

    Science.gov (United States)

    1993-07-15

    Polonis V, Corts K, Hoc"en-Lewis C, Eddy G. Production of functionally defective HIV-l reverse transcriptase can be initiated by a human peripheral blood... Interamericana , Mexico-Buenos Aires - Madrid. 1989. Ruiz Manuscript 1989 Ruiz NM, Ramirez-Rhonda CH. Tratamiento quirurjico de endocarditis. Chapter in...M.D.; Editorial Interamericana , Mexico-Buenos Aires - Madrid, 1989. Ruiz Manuscript 1989 Rivera G, Ruiz NM. Principios generales en el tratemiento

  4. Anti-V3 humanized antibody KD-247 effectively suppresses ex vivo generation of human immunodeficiency virus type 1 and affords sterile protection of monkeys against a heterologous simian/human immunodeficiency virus infection.

    Science.gov (United States)

    Eda, Yasuyuki; Murakami, Toshio; Ami, Yasushi; Nakasone, Tadashi; Takizawa, Mari; Someya, Kenji; Kaizu, Masahiko; Izumi, Yasuyuki; Yoshino, Naoto; Matsushita, Shuzo; Higuchi, Hirofumi; Matsui, Hajime; Shinohara, Katsuaki; Takeuchi, Hiroaki; Koyanagi, Yoshio; Yamamoto, Naoki; Honda, Mitsuo

    2006-06-01

    In an accompanying report (Y. Eda, M. Takizawa, T. Murakami, H. Maeda, K. Kimachi, H. Yonemura, S. Koyanagi, K. Shiosaki, H. Higuchi, K. Makizumi, T. Nakashima, K. Osatomi, S. Tokiyoshi, S. Matsushita, N. Yamamoto, and M. Honda, J. Virol. 80:5552-5562, 2006), we discuss our production of a high-affinity humanized monoclonal antibody, KD-247, by sequential immunization with V3 peptides derived from human immunodeficiency virus type 1 (HIV-1) clade B primary isolates. Epitope mapping revealed that KD-247 recognized the Pro-Gly-Arg V3 tip sequence conserved in HIV-1 clade B isolates. In this study, we further demonstrate that in vitro, KD-247 efficiently neutralizes CXCR4- and CCR5-tropic primary HIV-1 clade B and clade B' with matching neutralization sequence motifs but does not neutralize sequence-mismatched clade B and clade E isolates. Monkeys were provided sterile protection against heterologous simian/human immunodeficiency virus challenge by the passive transfer of a single high dose (45 mg per kg of body weight) of KD-247 and afforded partial protection by lower antibody doses (30 and 15 mg per kg). Protective neutralization endpoint titers in plasma at the time of virus challenge were 1:160 in animals passively transferred with a high dose of the antibody. The antiviral efficacy of the antibody was further confirmed by its suppression of the ex vivo generation of primary HIV-1 quasispecies in peripheral blood mononuclear cell cultures from HIV-infected individuals. Therefore, KD-247 promises to be a valuable tool not only as a passive immunization antibody for the prevention of HIV infection but also as an immunotherapy for the suppression of HIV in phenotype-matched HIV-infected individuals.

  5. A High-Affinity Native Human Antibody Disrupts Biofilm from Staphylococcus aureus Bacteria and Potentiates Antibiotic Efficacy in a Mouse Implant Infection Model.

    Science.gov (United States)

    Estellés, Angeles; Woischnig, Anne-Kathrin; Liu, Keyi; Stephenson, Robert; Lomongsod, Evelene; Nguyen, Da; Zhang, Jianzhong; Heidecker, Manfred; Yang, Yifan; Simon, Reyna J; Tenorio, Edgar; Ellsworth, Stote; Leighton, Anton; Ryser, Stefan; Gremmelmaier, Nina Khanna; Kauvar, Lawrence M

    2016-04-01

    Many serious bacterial infections are difficult to treat due to biofilm formation, which provides physical protection and induces a sessile phenotype refractory to antibiotic treatment compared to the planktonic state. A key structural component of biofilm is extracellular DNA, which is held in place by secreted bacterial proteins from the DNABII family: integration host factor (IHF) and histone-like (HU) proteins. A native human monoclonal antibody, TRL1068, has been discovered using single B-lymphocyte screening technology. It has low-picomolar affinity against DNABII homologs from important Gram-positive and Gram-negative bacterial pathogens. The disruption of established biofilm was observedin vitroat an antibody concentration of 1.2 μg/ml over 12 h. The effect of TRL1068in vivowas evaluated in a murine tissue cage infection model in which a biofilm is formed by infection with methicillin-resistantStaphylococcus aureus(MRSA; ATCC 43300). Treatment of the established biofilm by combination therapy of TRL1068 (15 mg/kg of body weight, intraperitoneal [i.p.] administration) with daptomycin (50 mg/kg, i.p.) significantly reduced adherent bacterial count compared to that after daptomycin treatment alone, accompanied by significant reduction in planktonic bacterial numbers. The quantification of TRL1068 in sample matrices showed substantial penetration of TRL1068 from serum into the cage interior. TRL1068 is a clinical candidate for combination treatment with standard-of-care antibiotics to overcome the drug-refractory state associated with biofilm formation, with potential utility for a broad spectrum of difficult-to-treat bacterial infections.

  6. Tuberculosis and human immunodeficiency virus infection.

    Science.gov (United States)

    Telzak, E E

    1997-03-01

    Mycobacterium tuberculosis infects one third of the world's population, and tuberculosis remains one of the most common infectious diseases of humans. From a global perspective, tuberculosis may be one of the most common HIV-related opportunistic infections. HIV immunosuppression has had a dramatic influence on the epidemiology, natural history and clinical presentation of tuberculosis. Treatment is highly effective for drug susceptible tuberculosis and has been shown to have a significant impact on resistant, especially multidrug-resistant, tuberculosis if started promptly. Directly observed therapy and rigorous adherence to infection control principles have helped control the tuberculosis epidemic in the United States.

  7. Hemolytic uremic syndrome as a primary manifestation of acute human immunodeficiency virus infection.

    Science.gov (United States)

    Gomes, A M; Ventura, A; Almeida, C; Correia, M; Tavares, V; Mota, M; Seabra, J

    2009-05-01

    Hemolytic uremic syndrome may be associated with human immunodeficiency virus infection but it occurs in advanced stages of human immunodeficiency virus disease. As in other forms of hemolytic uremic syndrome plasmapheresis seems to be the treatment of choice. The authors present an unusual case of hemolytic uremic syndrome associated with acute human immunodeficiency virus infection in a 38 year-old black male. The patient was admitted with fever, asthenia, nausea, diarrhea, and reduced urinary output. He was found to have anemia, thrombocytopenia and severe renal failure. Hemolytic uremic syndrome was diagnosed and he was started on plasmapheresis and hemodialysis. Serological tests were consistent with acute human immunodeficiency virus infection: the enzyme linked immunosorbent assay for human immunodeficiency virus was weakly positive, Western Blot test was negative and human immunodeficiency virus RNA quantification was positive, with > 1,000,000 copies/microl. After 4 daily treatment sessions, patient's clinical condition improved and hemoglobin, platelets, lactic dehydrogenase and renal function normalized.

  8. Plasmoblastic lymphoma associated with human immunodeficiency virus.

    Science.gov (United States)

    Horváth, Emoke; Krenács, L; Bagdi, Eniko; Pávai, Z; Macarie, I; Nagy, Elod-Erno; Demian, Smaranda

    2008-01-01

    Plasmoblastic lymphoma (PBL) is a subtype of the diffuse large B-cell lymphoma, typically present as extranodal disease associated with human immune deficiency virus (HIV) infection. PBLs are often the initial manifestation of AIDS. Here we present a case of PBL concerning the oral cavity. A 34-year-old woman presented a tumor in the oral cavity that involved the maxilla and gingiva (confirmed by CT-scan). The gingival biopsy showed a massive infiltration by large lymphoid cells with round, vesicular nuclei, prominent nucleoli, fine chromatin and an significant amount of basophilic cytoplasm which express CD79a, CD138, cytoplasmic lambda light chain and LCA, without staining for CD20, CD38, CD3 and CTK. Serological analysis confirmed HIV positivity. PBLs lack most B-lineage markers, but many express CD79a in at least some of the cells, therefore generate difficulties in differential diagnosis. Overall assessment and correlation of the histopathological and immunohistochemical features with the clinical findings and serology investigation are the most helpful diagnostic tools and can lead to the final diagnosis.

  9. Dyes with high affinity for polylactide

    Institute of Scientific and Technical Information of China (English)

    Liang He; Shu Fen Zhang; Bing Tao Tang; Li Li Wang; Jin Zong Yang

    2007-01-01

    Attempts were made to develop dyes with high affinity for polylactide as an alternative to the existent commercial disperse dyes.The dyes synthesized according to the affinity concept of dye to polylactide exhibited excellent dyeing properties on polylactide compared with the commercial disperse dyes.

  10. Association of human immunodeficiency virus-induced immunosuppression with human papillomavirus infection and cervical intraepithelial neoplasia.

    Science.gov (United States)

    Henry, M J; Stanley, M W; Cruikshank, S; Carson, L

    1989-02-01

    Human papillomavirus infection plays an important causal role in cervical intraepithelial neoplasia and carcinoma. The rate of infection with human papillomavirus as well as the incidence of cervical intraepithelial neoplasia and carcinoma are increased in immunosuppressed patients. We report a possible association between infection with human immunodeficiency virus and cervical intraepithelial neoplasia with human papillomavirus infection.

  11. Review of testing for human immunodeficiency virus.

    Science.gov (United States)

    Bylund, D J; Ziegner, U H; Hooper, D G

    1992-06-01

    The performance of HIV testing requires meticulous attention to preanalytic, analytic, and postanalytic variables, especially matters of patient confidentiality. Laboratory directors must pay strict attention to quality control and quality assurance practices. Careful attention to these considerations can produce a screening program in low-prevalence populations that has an extremely low false-positive rate, with a positive predictive value of greater than 99%. Issuing a clear and concise laboratory report to the clinician is important. The Fifth Consensus Conference on Testing for Human Retroviruses of the Association of State and Territorial Public Health Laboratory Directors, March 1990, has recommended that ELISA be reported as reactive or nonreactive; IFA as reactive, nonreactive, or nonspecific, and WB as reactive, nonreactive, or indeterminate. It is recommended that the terms positive and negative be reserved for the summary interpretation given at the conclusion of the HIV-1 antibody testing algorithm. The testing algorithm used for HIV antibody screening at Scripps Clinic is shown in Figure 3. Other algorithms for complete testing on a single sample only or on two separate samples are reported. We agree with others that the patient should not be counseled for infection with HIV until a reactive confirmatory test(s) establishes a positive diagnosis. Certain special situations in diagnostic testing deserve comment. Establishing the diagnosis of HIV infection can be difficult in seronegative persons with acute infection. Polymerase chain reaction, viral culture or antigen detection may be useful tests in this situation. However, careful interpretation of test results and close correlation with patient risk factors are important to establish the proper diagnosis. Reports of seronegative persons, some remaining seronegative over a protracted time, have raised concerns over the transfusional risk of HIV infection. Blood donor screening programs are using

  12. Postmortem Investigations Following Human Immunodeficiency Virus Infection

    Directory of Open Access Journals (Sweden)

    Andrey V. Bychkov

    2009-04-01

    Full Text Available Background: HIV/AIDS is a global disease and despite intensive research it is one of the main causes of human death. Postmortem studies have proven accurate in determining the various pathologies in these patients. Aims & Objectives: Our aim was to analyze the post mortem results of individuals who died after HIV infection in the same geographical region. We evaluated the most frequent opportunistic diseases and their clinical and morphological outcomes. Methods: We studied case reports and autopsy research data from 32 patients who died after HIV infection in Smolensk, Russian Federation, between 2003 and 2008. All patients had been diagnosed with HIV infection before death, using HIV-specific enzyme linked immunosorbent assay (ELISA and immunoblotting. Autopsy specimens of various organs were examined histologically and microbiologically. Findings: The mean survival period from the moment of detection of seropositivity in all the patients was less than five years. Twelve patients had a parenteral mode of contact, six had been infected by sexual contact, and 14 patients had unknown modes of infection. Most patients (69% had chronic hepatitis C. The main causes of death were various infectious diseases. The most common were generalized miliary tuberculosis and progressive secondary tuberculosis of the lungs. Three (9% patients had tuberculosis of the meninges and five (16% had peritoneal infections, but tuberculous peritonitis had not been diagnosed before death. Six patients had pulmonary tuberculosis and bacterial pneumonia simultaneously. Two (6% patients died from bacterial sepsis as a result of cervical lymphadenitis, and eight (12.5% from abscess-forming pneumonia. The opportunistic infections revealed were Pneumocystis carinii pneumonia (eight patients, cytomegaloviral pneumonia (three, bronchopulmonary aspergillosis (one and mucosal candidiasis (three. In three patients, the causes of death were advanced neoplastic processes: two cases

  13. Interactions of human immunodeficiency virus-1 proteins with neurons : possible role in the development of human immunodeficiency virus-1-associated dementia

    NARCIS (Netherlands)

    van de Bovenkamp, M; Nottet, HSLM; Pereira, CF

    2002-01-01

    Human immunodeficiency virus-1 (HIV-1)-associated dementia is a severe neurological complication of HIV-1 infection that affects 15-20% of the patients in the late stages of acquired immunodeficiency syndrome. HIV-1-associated dementia is most probably a consequence of HIV-1 infection of the brain r

  14. Tethering of Epidermal Growth Factor (EGF) to Beta Tricalcium Phosphate (βTCP) via Fusion to a High Affinity, Multimeric βTCP-Binding Peptide: Effects on Human Multipotent Stromal Cells/Connective Tissue Progenitors.

    Science.gov (United States)

    Alvarez, Luis M; Rivera, Jaime J; Stockdale, Linda; Saini, Sunil; Lee, Richard T; Griffith, Linda G

    2015-01-01

    Transplantation of freshly-aspirated autologous bone marrow, together with a scaffold, is a promising clinical alternative to harvest and transplantation of autologous bone for treatment of large defects. However, survival proliferation, and osteogenic differentiation of the marrow-resident stem and progenitor cells with osteogenic potential can be limited in large defects by the inflammatory microenvironment. Previous studies using EGF tethered to synthetic polymer substrates have demonstrated that surface-tethered EGF can protect human bone marrow-derived osteogenic stem and progenitor cells from pro-death inflammatory cues and enhance their proliferation without detriment to subsequent osteogenic differentiation. The objective of this study was to identify a facile means of tethering EGF to clinically-relevant βTCP scaffolds and to demonstrate the bioactivity of EGF tethered to βTCP using stimulation of the proliferative response of human bone-marrow derived mesenchymal stem cells (hBMSC) as a phenotypic metric. We used a phage display library and panned against βTCP and composites of βTCP with a degradable polyester biomaterial, together with orthogonal blocking schemes, to identify a 12-amino acid consensus binding peptide sequence, LLADTTHHRPWT, with high affinity for βTCP. When a single copy of this βTCP-binding peptide sequence was fused to EGF via a flexible peptide tether domain and expressed recombinantly in E. coli together with a maltose-binding domain to aid purification, the resulting fusion protein exhibited modest affinity for βTCP. However, a fusion protein containing a linear concatamer containing 10 repeats of the binding motif the resulting fusion protein showed high affinity stable binding to βTCP, with only 25% of the protein released after 7 days at 37oC. The fusion protein was bioactive, as assessed by its abilities to activate kinase signaling pathways downstream of the EGF receptor when presented in soluble form, and to enhance

  15. Tethering of Epidermal Growth Factor (EGF to Beta Tricalcium Phosphate (βTCP via Fusion to a High Affinity, Multimeric βTCP-Binding Peptide: Effects on Human Multipotent Stromal Cells/Connective Tissue Progenitors.

    Directory of Open Access Journals (Sweden)

    Luis M Alvarez

    Full Text Available Transplantation of freshly-aspirated autologous bone marrow, together with a scaffold, is a promising clinical alternative to harvest and transplantation of autologous bone for treatment of large defects. However, survival proliferation, and osteogenic differentiation of the marrow-resident stem and progenitor cells with osteogenic potential can be limited in large defects by the inflammatory microenvironment. Previous studies using EGF tethered to synthetic polymer substrates have demonstrated that surface-tethered EGF can protect human bone marrow-derived osteogenic stem and progenitor cells from pro-death inflammatory cues and enhance their proliferation without detriment to subsequent osteogenic differentiation. The objective of this study was to identify a facile means of tethering EGF to clinically-relevant βTCP scaffolds and to demonstrate the bioactivity of EGF tethered to βTCP using stimulation of the proliferative response of human bone-marrow derived mesenchymal stem cells (hBMSC as a phenotypic metric. We used a phage display library and panned against βTCP and composites of βTCP with a degradable polyester biomaterial, together with orthogonal blocking schemes, to identify a 12-amino acid consensus binding peptide sequence, LLADTTHHRPWT, with high affinity for βTCP. When a single copy of this βTCP-binding peptide sequence was fused to EGF via a flexible peptide tether domain and expressed recombinantly in E. coli together with a maltose-binding domain to aid purification, the resulting fusion protein exhibited modest affinity for βTCP. However, a fusion protein containing a linear concatamer containing 10 repeats of the binding motif the resulting fusion protein showed high affinity stable binding to βTCP, with only 25% of the protein released after 7 days at 37oC. The fusion protein was bioactive, as assessed by its abilities to activate kinase signaling pathways downstream of the EGF receptor when presented in soluble form

  16. Trends in contraceptive use among women with human immunodeficiency virus.

    Science.gov (United States)

    Sun, Mengyang; Peipert, Jeffrey F; Zhao, Qiuhong; Wilson, Tracey E; Weber, Kathleen M; Sanchez-Keeland, Lorraine; DʼSouza, Gypsyamber; Young, Mary; Watts, D Heather; Keller, Marla J; Cohan, Deborah; Massad, L Stewart

    2012-10-01

    To estimate trends in contraceptive use, especially long-acting reversible contraceptives (LARCs) and condoms, among human immunodeficiency virus (HIV)-seropositive and HIV-seronegative women. Human immunodeficiency virus-seropositive and HIV-seronegative women in a multicenter longitudinal cohort were interviewed semiannually between 1998 and 2010 about sexual behaviors and contraceptive use. Trends in contraceptive use by women aged 18-45 years who were at risk for unintended pregnancy but not trying to conceive were analyzed using generalized estimating equations. Condoms were the dominant form of contraception for HIV-seropositive women and showed little change across time. Less than 15% of these women used no contraception. Between 1998 and 2010, LARC use increased among HIV-seronegative women from 4.8% (6 of 126) to 13.5% (19 of 141, P=.02), but not significantly among seropositive women (0.9% [4 of 438] to 2.8% [6 of 213], P=.09). Use of highly effective contraceptives, including pills, patches, rings, injectable progestin, implants, and intrauterine devices, ranged from 15.2% (53 of 348) in 1998 to 17.4% (37 of 213) in 2010 (P=.55). Human immunodeficiency virus-seronegative but not HIV-seropositive LARC users were less likely than nonusers to use condoms consistently (hazard ratio 0.51, 95% confidence interval [CI] 0.32-0.81, P=.004 for seronegative women; hazard ratio 1.09, 95% CI 0.96-1.23 for seropositive women). Although most HIV-seropositive women use contraception, they rely primarily on condoms and have not experienced the increase in LARC use seen among seronegative women. Strategies to improve simultaneous use of condoms and LARC are needed to minimize risk of unintended pregnancy as well as HIV transmission and acquisition of sexually transmitted infections. II.

  17. BST-2 mediated restriction of simian-human immunodeficiency virus.

    Science.gov (United States)

    Ruiz, Autumn; Lau, David; Mitchell, Richard S; Hill, M Sarah; Schmitt, Kimberly; Guatelli, John C; Stephens, Edward B

    2010-10-25

    Pathogenic simian-human immunodeficiency viruses (SHIV) contain HIV-1 Vpu and SIV Nef, both shown to counteract BST-2 (HM1.24; CD317; tetherin) inhibition of virus release in a species-specific manner. We show that human and pig-tailed BST-2 (ptBST-2) restrict SHIV. We found that sequential "humanization" of the transmembrane domain (TMD) of the pig-tailed BST-2 (ptBST-2) protein resulted in a fluctuation in sensitivity to HIV-1 Vpu. Our results also show that the length of the TMD in human and ptBST-2 proteins is important for BST-2 restriction and susceptibility to Vpu. Taken together, our results emphasize the importance of tertiary structure in BST-2 antagonism and suggests that the HIV-1 Vpu transmembrane domain may have additional functions in vivo unrelated to BST-2 antagonism.

  18. Towards detecting the human immunodeficiency virus using microcantilever sensors

    Science.gov (United States)

    Alodhayb, Abdullah; Brown, Nicole; Saydur Rahman, S. M.; Harrigan, Richard; Beaulieu, L. Y.

    2013-04-01

    Detecting the human immunodeficiency virus (HIV) is difficult because the virus is prone to mutations and is in low concentrations in the body. Inside the HIV virion are two well characterized single stranded (ss) RNA molecules (viral genome) that feature both variable regions and regions that are conserved under virus mutation. In this work, microcantilever sensors have been employed as potential HIV detectors by targeting a conserved sequence of the viral genome by attempting to detect target ssDNA and ssRNA molecules that are significantly longer than the ssDNA molecules functionalized on the cantilever.

  19. Management of dyslipidemia in patients with human immunodeficiency virus.

    Science.gov (United States)

    Shalit, Peter

    2014-01-01

    Dyslipidemias are more common in the patient population with human immunodeficiency virus (HIV). Combination antiretroviral therapy (ART) has dramatically reduced HIV-associated morbidity and mortality and has transformed HIV disease into a chronic, manageable condition. As a result, non-AIDS-related illnesses, including cardiovascular diseases, are now the leading causes of death in the HIV-infected population. Optimizing fasting lipid parameters plays an important role in reducing cardiovascular risk in this population. This review focuses on the management of dyslipidemia in HIV-infected individuals treated with combination ART.

  20. Neuromyelitis optica in patients with coexisting human immunodeficiency virus infections.

    Science.gov (United States)

    Feyissa, Anteneh M; Singh, Parbhdeep; Smith, Robert G

    2013-09-01

    Two patients with known human immunodeficiency virus (HIV) infections and receiving antiretroviral treatment developed neuromyelitis optica (Devic's disease). One patient tested positive for serum aquaporin-4 immunoglobulin G antibodies. Both patients were treated with high dose pulsed intravenous methylprednisolone followed by standard sessions of plasma exchange both at the onset attack and during disease relapses. For maintenance therapy, one patient received rituximab infusions and the second patient received mycophenolate mofetil orally. Despite treatment, both patients are currently wheelchair-bound due to severe paraparesis. Neuromyelitis optica can occur in the course of HIV infection and poses an ongoing therapeutic challenge.

  1. [Pulmonary arterial hypertension associated to human immunodeficiency virus].

    Science.gov (United States)

    Sandoval-Gutiérrez, José Luis; Santos-Martínez, Luis Efren; Rodríguez-Silverio, Juan; Baranda-Tovar, Francisco Martín; Rivera-Rosales, Rosa María; Flores-Murrieta, Francisco Javier

    2015-01-01

    From the advent of the highly effective antiretroviral treatment, the life expectancy of patients with human immunodeficiency virus has increased significantly. At present, the causes of death are non-infectious complications. Between them, the pulmonary arterial hypertension has a special importance. It is important early detection to establish the therapeutic, with the objective of preventing a fatal outcome to future. Copyright © 2013 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  2. Oral lesions associated with human immunodeficiency virus disease.

    Science.gov (United States)

    Patton, Lauren L

    2013-10-01

    Human immunodeficiency virus (HIV)-associated oral disease among people living with HIV infection includes oral candidiasis, oral hairy leukoplakia, Kaposi sarcoma, oral warts, herpes simplex virus ulcers, major aphthous ulcers or ulcers not otherwise specified, HIV salivary gland disease, and atypical gingival and periodontal diseases. Diagnosis of some oral lesions is based on clinical appearance and behavior, whereas others require biopsy, culture, or imaging for definitive diagnosis. Management strategies including pharmacologic and nonpharmacologic approaches are discussed in this article. Dentists also need to be cognizant of the potential oral side effects of HIV antiretroviral medications.

  3. [Lopinavir/ritonavir in human immunodeficiency virus-infected women].

    Science.gov (United States)

    Téllez, María Jesús

    2014-11-01

    There are clear sex-related biological differences between men and women. Diseases that affect the two sexes differently are studied separately. However, some diseases affect both men and women, but their incidence or outcome are clearly different. In human immunodeficiency virus infection, the potential differences in the effects of antiretroviral therapy are poorly characterized and few studies have been designed to elucidate these differences. Moreover, women are usually poorly represented in clinical trials of antiretroviral drugs. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  4. Multiple Pyarthrosis in Human Immunodeficiency Virus-Infected Hemophiliacs

    Directory of Open Access Journals (Sweden)

    Alistair Ingram

    1994-01-01

    Full Text Available Classically, a swollen, painful joint in a patient with hemophilia has been considered to be due to a hemarthrosis until otherwise proven, and treated immediately with appropriate coagulation factor replacement. Two cases of human immunodeficiency virus (hiv-infected hemophiliacs presenting with an initial apparent hemarthrosis, complicated subsequently by numerous pyarthroses and sepsis are described. In light of the prevalence of hiv infection in the adult hemophiliac population with arthropathy, a reappraisal of the clinical caveat of immediate infusion without joint aspiration is required.

  5. Inner architecture of human and simian immunodeficiency viruses.

    Science.gov (United States)

    Fukui, T; Imura, S; Goto, T; Nakai, M

    1993-07-01

    The cores of human and simian immunodeficiency viruses (HIV and SIV) were observed by negative staining after isolation of the core with Nonidet P40 and glutaraldehyde. Four kinds of cores were found: asymmetric and symmetric sectoral shapes, a bar shape, and a triangular shape. These results were confirmed by the examination of ultrathin sections of whole virions. In some virions, the connection between the core and the envelope was observed after freeze fracturing. Its structure was considered to be characteristic of an intermediate stage of viral maturation. The HIV-1 core was reacted with anti-HIV-1 p24 mouse monoclonal antibody.

  6. Human immunodeficiency virus associated plasmablastic lymphoma: A case report

    Science.gov (United States)

    Desai, Dinkar; Pandit, Siddharth; Jasphin, Shiny; Shetty, Akhil S.

    2016-01-01

    Non-Hodgkin's lymphoma (NHL) is the third common malignant lesion of the oral region. Plasmablastic lymphomas are rare, aggressive neoplasms occurring mostly in human immunodeficiency virus (HIV) infected individual which accounts for approximately 2.6% of all NHL. It usually presents as a diffuse growth and with diffuse pattern of histological presentation. It is very difficult to differentiate this lymphoma from other NHL. Immunohistochemical evaluation of various markers is an important criteria of the diagnostic protocol. Here, we describe a case of plasmablastic lymphoma in a 50-year-old female HIV-infected patient. The diagnosis was based on histopathological examination and immunophenotyping. PMID:27795651

  7. Pulmonary disease in patients with human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Lundgren, J D; Orholm, Marianne; Lundgren, B

    1989-01-01

    Pulmonary disease is the most important cause of morbidity and mortality in patients infected with human immunodeficiency virus (HIV). All parts of the hospital system are expected to be involved in the diagnosis and treatment of HIV infected patients in the coming years. Many different processes...... cause pulmonary disease alone or in combination. Bilateral interstitial infiltrates are the most frequent chest x-ray abnormality and are most frequently caused by infection with Pneumocystis carinii. Cytomegalovirus, Mycobacterium tuberculosis, nonspecific interstitial pneumonitis and pulmonary Kaposi...

  8. 21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false In vitro human immunodeficiency virus (HIV) drug... OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay....

  9. Characterization of the promoter of the human gene encoding the high-affinity IgG receptor: Transcriptional induction by. gamma. -interferon is mediated through common DNA response elements

    Energy Technology Data Exchange (ETDEWEB)

    Pearse, R.N.; Feinman, R.; Ravetch, J.V. (DeWitt Wallace Research Lab., New York, NY (United States))

    1991-12-15

    Expression of the high-affinity receptor for IgG (Fc{sub {gamma}}RI) is restricted to cells of myeloid lineage and is induced by {gamma}-interferon (IFN-{gamma}) but not by IFN-{alpha}/{beta}. The organization of the human Fc{sub {gamma}}RI gene has been determined and the DNA elements governing its cell type-restricted transcription and IFN-{gamma} induction are reported here. A 39-nucleotide sequence (IFN-{gamma} response region, or GRR) is defined that is both necessary and sufficient for IFN-{gamma} inducibility. Sequence analysis of the GRR reveals the presence of promoter elements initially defined for the major histocompatibility complex class 2 genes: i.e., X, H, and {gamma}-IRE sequences. Comparison of a number of genes whose expression is induced selectively by IFN-{gamma} indicated that the presence of these elements is a general feature of IFN-{gamma}-responsive genes. The studies suggest that the combination of X, H, and {gamma}-IRE elements is a common motif in the pathway of transcriptional induction by this lymphokine.

  10. 75 FR 51273 - Expanded Human Immunodeficiency Virus (HIV) Testing for Disproportionately Affected Populations

    Science.gov (United States)

    2010-08-19

    ... HUMAN SERVICES Centers for Disease Control and Prevention (CDC) Expanded Human Immunodeficiency Virus (HIV) Testing for Disproportionately Affected Populations AGENCY: Centers for Disease Control and Prevention (CDC), Department of Health and Human Services (HHS). ACTION: Notice. Notice of Intent to...

  11. Lentivirus vectors using human and simian immunodeficiency virus elements.

    Science.gov (United States)

    White, S M; Renda, M; Nam, N Y; Klimatcheva, E; Zhu, Y; Fisk, J; Halterman, M; Rimel, B J; Federoff, H; Pandya, S; Rosenblatt, J D; Planelles, V

    1999-04-01

    Lentivirus vectors based on human immunodeficiency virus (HIV) type 1 (HIV-1) constitute a recent development in the field of gene therapy. A key property of HIV-1-derived vectors is their ability to infect nondividing cells. Although high-titer HIV-1-derived vectors have been produced, concerns regarding safety still exist. Safety concerns arise mainly from the possibility of recombination between transfer and packaging vectors, which may give rise to replication-competent viruses with pathogenic potential. We describe a novel lentivirus vector which is based on HIV, simian immunodeficiency virus (SIV), and vesicular stomatitis virus (VSV) and which we refer to as HIV/SIVpack/G. In this system, an HIV-1-derived genome is encapsidated by SIVmac core particles. These core particles are pseudotyped with VSV glycoprotein G. Because the nucleotide homology between HIV-1 and SIVmac is low, the likelihood of recombination between vector elements should be reduced. In addition, the packaging construct (SIVpack) for this lentivirus system was derived from SIVmac1A11, a nonvirulent SIV strain. Thus, the potential for pathogenicity with this vector system is minimal. The transduction ability of HIV/SIVpack/G was demonstrated with immortalized human lymphocytes, human primary macrophages, human bone marrow-derived CD34(+) cells, and primary mouse neurons. To our knowledge, these experiments constitute the first demonstration that the HIV-1-derived genome can be packaged by an SIVmac capsid. We demonstrate that the lentivirus vector described here recapitulates the biological properties of HIV-1-derived vectors, although with increased potential for safety in humans.

  12. Antiviral treatment for chronic hepatitis C in patients with human immunodeficiency virus

    DEFF Research Database (Denmark)

    Iorio, Alfonso; Marchesini, Emanuela; Awad, Tahany;

    2010-01-01

    Antiviral treatment for chronic hepatitis C may be less effective if patients are co-infected with human immunodeficiency virus (HIV).......Antiviral treatment for chronic hepatitis C may be less effective if patients are co-infected with human immunodeficiency virus (HIV)....

  13. Transmission of human immunodeficiency virus in a dental practice.

    Science.gov (United States)

    Ciesielski, C; Marianos, D; Ou, C Y; Dumbaugh, R; Witte, J; Berkelman, R; Gooch, B; Myers, G; Luo, C C; Schochetman, G

    1992-05-15

    To determine if patients of a dentist with the acquired immunodeficiency syndrome (AIDS) became infected with human immunodeficiency virus (HIV) during their dental care and, if so, to identify possible mechanisms of transmission. Retrospective epidemiologic follow-up of the dentist, his office practice, and his former patients. The practice of a dentist with AIDS in Florida. A dentist with AIDS, his health care providers and employees, and former patients of the dentist, including eight HIV-infected patients. Identification of risks for HIV transmission (if present), degree of genetic relatedness of the viruses, and identification of infection control and other office practices. Five of the eight HIV-infected patients had no confirmed exposures to HIV other than the dental practice and were infected with HIV strains that were closely related to those of the dentist. Each of the five had invasive dental procedures, done by the dentist after he was diagnosed with AIDS. Four of these five patients shared visit days (P greater than 0.2). Breaches in infection control and other dental office practices to explain these transmissions could not be identified. Although the specific incident that resulted in HIV transmission to these patients remains uncertain, the epidemiologic evidence supports direct dentist-to-patient transmission rather than a patient-to-patient route.

  14. Oral Manifestations of Human Immunodeficiency Virus-Infected Patients

    Directory of Open Access Journals (Sweden)

    Atessa Pakfetrat

    2015-01-01

    Full Text Available Background: Oral lesions are among the earliest clinical manifestations of human immunodeficiency (HIV infection and are important in early diagnosis and for monitoring the progression to acquired immunodeficiency syndrome (AIDS. The purpose of this study was to determine the prevalence of oral lesions and their relationship with a number of factors in HIV/AIDS patients attending an HIV center.     Methods: A total of 110 HIV-positive patients were examined to investigate the prevalence of oral lesions according to the criteria established by the European Community Clearing House on Oral Problems Related to HIV Infection. An independent T-test was used for correlation of oral lesions with CD4+ count and a χ2 test was used for analysis of the relationship of co-infection with hepatitis B virus (HBV, sexual contact, route of transmission, history of drug abuse, and history of incarceration.   Results: Most of the cases were male patients (82.7%. The mean age across all participants was 36.2±8.1 years. Rampant carries, severe periodontitis and oral candidiasis were the most notable oral lesions. Oral lesions were more prevalent in patients between 26–35 years of age. There was a significant difference between patients with and without pseudomembranous candidiasis and angular cheilitis according to mean level of CD4+.   Conclusion: The most common oral presentations were severe periodontitis, pseudomembranous candidiasis and xerostomia. 

  15. Oral lesions in infection with human immunodeficiency virus.

    Science.gov (United States)

    Coogan, Maeve M.; Greenspan, John; Challacombe, Stephen J.

    2005-01-01

    This paper discusses the importance of oral lesions as indicators of infection with human immunodeficiency virus (HIV) and as predictors of progression of HIV disease to acquired immunodeficiency syndrome (AIDS). Oral manifestations are among the earliest and most important indicators of infection with HIV. Seven cardinal lesions, oral candidiasis, hairy leukoplakia, Kaposi sarcoma, linear gingival erythema, necrotizing ulcerative gingivitis, necrotizing ulcerative periodontitis and non-Hodgkin lymphoma, which are strongly associated with HIV infection, have been identified and internationally calibrated, and are seen in both developed and developing countries. They may provide a strong indication of HIV infection and be present in the majority of HIV-infected people. Antiretroviral therapy may affect the prevalence of HIV-related lesions. The presence of oral lesions can have a significant impact on health-related quality of life. Oral health is strongly associated with physical and mental health and there are significant increases in oral health needs in people with HIV infection, especially in children, and in adults particularly in relation to periodontal diseases. International collaboration is needed to ensure that oral aspects of HIV disease are taken into account in medical programmes and to integrate oral health care with the general care of the patient. It is important that all health care workers receive education and training on the relevance of oral health needs and the use of oral lesions as surrogate markers in HIV infection. PMID:16211162

  16. Gastrointestinal opportunistic infections in human immunodeficiency virus disease

    Directory of Open Access Journals (Sweden)

    Al Anazi Awadh

    2009-01-01

    Full Text Available Gastrointestinal (GI opportunistic infections (OIs are commonly encountered at various stages of human immunodeficiency virus (HIV disease. In view of the suppressive nature of the virus and the direct contact with the environment, the GI tract is readily accessible and is a common site for clinical expression of HIV. The subject is presented based on information obtained by electronic searches of peer-reviewed articles in medical journals, Cochrane reviews and PubMed sources. The spectrum of GI OIs ranges from oral lesions of Candidiasis, various lesions of viral infections, hepatobiliary lesions, pancreatitis and anorectal lesions. The manifestations of the disease depend on the level of immunosuppression, as determined by the CD4 counts. The advent of highly active antiretroviral therapy has altered the pattern of presentation, resorting mainly to features of antimicrobial-associated colitis and side effects of antiretroviral drugs. The diagnosis of GI OIs in HIV/ acquired immunodeficiency syndrome patients is usually straightforward. However, subtle presentations require that the physicians should have a high index of suspicion when given the setting of HIV infection.

  17. Oral Manifestations of Human Immunodeficiency Virus-Infected Patients

    Directory of Open Access Journals (Sweden)

    Atessa Pakfetrat

    2015-01-01

    Full Text Available Background: Oral lesions are among the earliest clinical manifestations of human immunodeficiency (HIV infection and are important in early diagnosis and for monitoring the progression to acquired immunodeficiency syndrome (AIDS. The purpose of this study was to determine the prevalence of oral lesions and their relationship with a number of factors in HIV/AIDS patients attending an HIV center.     Methods: A total of 110 HIV-positive patients were examined to investigate the prevalence of oral lesions according to the criteria established by the European Community Clearing House on Oral Problems Related to HIV Infection. An independent T-test was used for correlation of oral lesions with CD4+ count and a χ2 test was used for analysis of the relationship of co-infection with hepatitis B virus (HBV, sexual contact, route of transmission, history of drug abuse, and history of incarceration.   Results: Most of the cases were male patients (82.7%. The mean age across all participants was 36.2±8.1 years. Rampant carries, severe periodontitis and oral candidiasis were the most notable oral lesions. Oral lesions were more prevalent in patients between 26–35 years of age. There was a significant difference between patients with and without pseudomembranous candidiasis and angular cheilitis according to mean level of CD4+.   Conclusion: The most common oral presentations were severe periodontitis, pseudomembranous candidiasis and xerostomia.

  18. Oral Manifestations of Human Immunodeficiency Virus-Infected Patients

    Science.gov (United States)

    Pakfetrat, Atessa; Falaki, Farnaz; Delavarian, Zahra; Dalirsani, Zohreh; Sanatkhani, Majid; Zabihi Marani, Mahsa

    2015-01-01

    Introduction: Oral lesions are among the earliest clinical manifestations of human immunodeficiency (HIV) infection and are important in early diagnosis and for monitoring the progression to acquired immunodeficiency syndrome (AIDS). The purpose of this study was to determine the prevalence of oral lesions and their relationship with a number of factors in HIV/AIDS patients attending an HIV center. Materials and Methods: A total of 110 HIV-positive patients were examined to investigate the prevalence of oral lesions according to the criteria established by the European Community Clearing House on Oral Problems Related to HIV Infection. An independent T-test was used for correlation of oral lesions with CD4+ count and a χ2 test was used for analysis of the relationship of co-infection with hepatitis B virus (HBV), sexual contact, route of transmission, history of drug abuse, and history of incarceration. Results: Most of the cases were male patients (82.7%). The mean age across all participants was 36.2±8.1 years. Rampant carries, severe periodontitis and oral candidiasis were the most notable oral lesions. Oral lesions were more prevalent in patients between 26–35 years of age. There was a significant difference between patients with and without pseudomembranous candidiasis and angular cheilitis according to mean level of CD4+. Conclusion: The most common oral presentations were severe periodontitis, pseudomembranous candidiasis and xerostomia. PMID:25745611

  19. 75 FR 22814 - Guidance for Industry: Nucleic Acid Testing (NAT) for Human Immunodeficiency Virus Type 1 (HIV-1...

    Science.gov (United States)

    2010-04-30

    ...: Nucleic Acid Testing (NAT) for Human Immunodeficiency Virus Type 1 (HIV-1) and Hepatitis C Virus (HCV... memoranda entitled ``Revised Recommendations for the Prevention of Human Immunodeficiency Virus (HIV-1...: Nucleic Acid Testing (NAT) for Human Immunodeficiency Virus Type 1 (HIV-1) and Hepatitis C Virus...

  20. Human immunodeficiency virus and migrant labor in South Africa.

    Science.gov (United States)

    Jochelson, K; Mothibeli, M; Leger, J P

    1991-01-01

    The authors investigate the impact of the migrant labor system on heterosexual relationships on South African mines and assess the implications for the future transmission of human immunodeficiency virus (HIV) infection. The migrant labor system has created a market for prostitution in mining towns and geographic networks of relationships within and between urban and rural communities. A section of the migrant workforce and a group of women dependent on prostitution for economic support appear especially vulnerable to contracting HIV infection since they are involved in multiple sexual encounters with different, changing partners, usually without condom protection. Furthermore, sexually transmitted disease morbidity is extensive in the general and mineworker populations. Historically, migration facilitated the transmission of sexually transmitted diseases and may act similarly for HIV. Problems of combating the HIV epidemic in South Africa are discussed.

  1. Mechanisms of human immunodeficiency virus type 2 RNA packaging

    DEFF Research Database (Denmark)

    Ni, Na; Nikolaitchik, Olga A; Dilley, Kari A;

    2011-01-01

    that specifically recognize stem-loop motifs in the viral genomes, an assay termed single virion analysis. These studies revealed that >90% of the HIV-2 particles contained viral RNAs and that RNAs derived from different viruses were copackaged frequently. Furthermore, the frequencies of heterozygous particles...... two monomeric RNAs. Additionally, single virion analyses demonstrated a similar RNA distribution in viral particles regardless of whether both viruses had a functional gag or one of the viruses had a nonfunctional gag, providing further support for the trans-packaging hypothesis. Together......Human immunodeficiency virus type 2 (HIV-2) has been reported to have a distinct RNA packaging mechanism, referred to as cis packaging, in which Gag proteins package the RNA from which they were translated. We examined the progeny generated from dually infected cell lines that contain two HIV-2...

  2. Mechanisms of human immunodeficiency virus type 2 RNA packaging

    DEFF Research Database (Denmark)

    Ni, Na; Nikolaitchik, Olga A; Dilley, Kari A;

    2011-01-01

    Human immunodeficiency virus type 2 (HIV-2) has been reported to have a distinct RNA packaging mechanism, referred to as cis packaging, in which Gag proteins package the RNA from which they were translated. We examined the progeny generated from dually infected cell lines that contain two HIV-2...... proviruses, one with a wild-type gag/gag-pol and the other with a mutant gag that cannot express functional Gag/Gag-Pol. Viral titers and RNA analyses revealed that mutant viral RNAs can be packaged at efficiencies comparable to that of viral RNA from which wild-type Gag/Gag-Pol is translated. These results...... do not support the cis-packaging hypothesis but instead indicate that trans packaging is the major mechanism of HIV-2 RNA packaging. To further characterize the mechanisms of HIV-2 RNA packaging, we visualized HIV-2 RNA in individual particles by using fluorescent protein-tagged RNA-binding proteins...

  3. Angelica Sinensis May Provide Protection Against Human Immunodeficiency Virus Infection

    Directory of Open Access Journals (Sweden)

    mohammad Zarenezhad

    2008-05-01

    Full Text Available Increased oxidative stress and disturbed glutathione redox system play an important role in the pathogenesis of human immunodeficiency virus (HIV infection. Depletion in intracellular levels of reduced glutathione (GSH contributes to an increment in tumor necrosis factor α (TNF-α-stimulated-HIV-1-transcription, activation of HIV-1-replication, sensitivity to TNF-α-induced cell death, and impairment of CD4+ cell function and survival. Therefore, several studies have investigated the effect of GSH-enhancer agents such as N-acetyl cystein in the treatment of patients with HIV infection. With regard to the beneficial effects of Angelica sinensis, a Chinese medicinal herb, on GSH redox system and the pathogenic role of GSH depletion in HIV infection and the immunomodulator effects of active ingredients of this herb, we postulated that Angelica sinensis may be of value in the treatment of HIV-infected patients.

  4. Human immunodeficiency virus antibodies and the vaccine problem.

    Science.gov (United States)

    Chiodi, F; Weiss, R A

    2014-05-01

    Despite the great advances made in controlling human immunodeficiency virus type 1 (HIV-1) infection with antiretroviral drug treatment, a safe and efficacious HIV vaccine has yet to be developed. Here, we discuss why clinical trials and vaccine development for HIV have so far been disappointing, with an emphasis on the lack of protective antibodies. We review approaches for developing appropriate HIV immunogens and the stimulation of long-lasting B-cell responses with antibody maturation. We conclude that candidate reagents in the pipeline for HIV vaccine development are unlikely to be particularly effective. Although the major funders of HIV vaccine research and development are placing increasing emphasis on clinical product development, a genuine breakthrough in preventing HIV infection through vaccines is more likely to come from novel immunogen research.

  5. Emerging bone problems in patients infected with human immunodeficiency virus.

    Science.gov (United States)

    Mondy, Kristin; Tebas, Pablo

    2003-04-01

    Recently, a high incidence of osteopenia and osteoporosis has been observed in individuals infected with human immunodeficiency virus (HIV). This problem appears to be more frequent in patients receiving potent antiretroviral therapy. Other bone-related complications in HIV-infected individuals, including avascular necrosis of the hip and compression fracture of the lumbar spine, have also been reported. People living with HIV have significant alterations in bone metabolism, regardless of whether they are receiving potent antiretroviral therapy. The underlying mechanisms to account for these observations remain unknown, although studies are underway to examine the relationship between the bone abnormalities and other complications associated with HIV and antiretroviral therapy. HIV-infected patients with osteopenia or osteoporosis should be treated similarly to HIV-seronegative patients with appropriate use of nutritional supplements (calcium and vitamin D) and exercise. Hormone replacement and antiresorptive therapies might be also indicated.

  6. Sexual Assault: A Report on Human Immunodeficiency Virus Postexposure Prophylaxis

    Directory of Open Access Journals (Sweden)

    William F. Griffith

    2010-01-01

    Full Text Available The objective of this report is to describe an urban county hospital human immunodeficiency virus (HIV infection prevention protocol offering prophylactic combination antiretroviral medications to female victims of sexual assault. A retrospective chart review was conducted from June, 2007 through June, 2008 of 151 women who were prescribed antiretroviral prophylaxis by protocol. All women receiving HIV prophylaxis initially screened HIV seronegative. Of the 58 women who reported taking any HIV prophylaxis, 36 (62% were HIV screened at 12 and/or 24 weeks and none had HIV seroconverted. Although the initiation of an HIV post exposure prophylaxis protocol for sexual assault in a county hospital population is feasible, patient follow-up for counseling and HIV serostatus evaluation is an identified barrier

  7. Eosinophilia in patients infected with human immunodeficiency virus.

    Science.gov (United States)

    Chou, Andrew; Serpa, Jose A

    2015-09-01

    Eosinophilia is not uncommonly encountered in patients infected with human immunodeficiency virus (HIV), particularly at initiation of care or among those with advanced disease. The clinical manifestation most commonly associated with eosinophilia in this patient population is skin rash. Management of these patients is challenging due to a paucity of data evaluating diagnostic testing and therapeutic strategies. Patients born in or with significant travel to parasite-endemic countries are more likely to have tissue-invasive helminthes, such as Strongyloides or Schistosoma. Patients without such risk factors are unlikely to have parasitic infections and frequently will have self-resolution of eosinophilia. When a detailed history, physical exam, and diagnostic work-up are unrevealing, we sometimes consider empirical therapy with ivermectin. Praziquantel may also be considered for those at risk for schistosomiasis.

  8. Human immunodeficiency virus antibody test and seroprevalence in psychiatric patients.

    Science.gov (United States)

    Naber, D; Pajonk, F G; Perro, C; Löhmer, B

    1994-05-01

    Psychiatric inpatients are at risk for human immunodeficiency virus (HIV) infection. Investigations in the United States revealed seroprevalence rates of 5.5-8.9%. Therefore, inclusion of HIV antibody testing in routine laboratory screening is sometimes suggested. To investigate this issue for inpatients in the Department of Psychiatry, University of Munich, the incidence, reason for HIV testing and results were analyzed. Of 12,603 patients, hospitalized from 1985 to 1993, 4.9% (623 patients, 265 in risk groups) underwent the HIV test after informed consent. Thirty patients (4.8% of those tested) were found to be positive, but only in 5 cases (all of risk groups) was infection newly detected. Data indicate that, in psychiatry, HIV testing is reasonable only in patients in risk groups or if clinical variables suggest HIV infection.

  9. Conjunctival Flora of Human Immunodeficiency Virus Patients on Antiretroviral Treatment.

    Science.gov (United States)

    Giles, Kagmeni; Bilong, Yannick; Dohvoma, Andin Viola; Ebana, Steve Robert; Gonsu, Hortance

    2017-01-01

    To determine the conjunctival flora of human immunodeficiency virus (HIV) patients on antiretroviral treatment (ART). A total of 104 conjunctival swabs from 104 HIV patients on ART underwent microbiological evaluation to describe the flora. There were 71 (68.26%) women and 33 (31.74%) men. The mean age was 42.9 ± 9.77 (range: 22-70) years. Negative cultures were found in 39 (37.50%) cases. Bacterial growth occurred in 65 (62.50%) cases. Coagulase-negative Staphylococcus was found in 59 eyes (90.76%), and coagulase-positive in 3 eyes (4.61%). There was a significant correlation between the duration of ART, the degrees of immunosuppression, and bacterial growth. Knowledge of the conjunctival flora in HIV patients may provide a better guideline in the choice of antibiotic for the management of ocular surface infections.

  10. Autoimmune hepatitis in patients with human immunodeficiency virus (HIV)

    Science.gov (United States)

    Kia, Leila; Beattie, Adam; Green, Richard M.

    2017-01-01

    Abstract Rationale: Chronic liver disease is a major cause of morbidity and mortality in patients with HIV. However, autoimmune hepatitis (AIH) in patients with HIV has rarely been reported. Our aim was to evaluate a cohort of patients with HIV and AIH and identify clinical presentations and outcomes. Patient Concerns: Management of autoimmune hepatitis in context of human immunodeficiency virus, long-term outcomes, and safety in setting of underlying immunocompromised state. Diagnoses: Autoimmune Hepatitis, Human Immunodeficiency Virus, Hepatotoxicity, Liver Injury, Liver Transplantation. Interventions: We retrospectively reviewed the charts of patients with HIV and AIH based on histological, serologic, biochemical demographic, and clinical data. Outcomes: Five patients were identified with autoimmune hepatitis; 4 of 5 were women, and all were African or African-American. The age at the time of AIH diagnosis was 46.6 ± 13.4 years. All patients acquired HIV sexually and all had CD4 counts >250 cells/uL (456–1011 cells/uL) and undetectable HIV viral loads at the time of AIH diagnosis. One patient presented with acute liver failure necessitating liver transplantation and developed AIH posttransplantation. At the time of diagnosis, the AST were 350 ± 448 U/L, ALT 247 ± 190 U/L, bilirubin 7 ± 12 mg/dL, and alkaline phosphatase 126 ± 53 U/L. All patients had histologic evidence of AIH on liver biopsies. Patients were successfully treated with prednisone and azathioprine, without a decrease in CD4 <250 cells/uL, infectious complications or significant side effects. Lessons: AIH occurs in patients with well-controlled HIV. In our patient cohort, immunosuppressive therapy with prednisone and azathioprine was safe and effective in inducing remission, without significant complications or development of opportunistic infections. PMID:28207511

  11. Antiviral drugs for viruses other than human immunodeficiency virus.

    Science.gov (United States)

    Razonable, Raymund R

    2011-10-01

    Most viral diseases, with the exception of those caused by human immunodeficiency virus, are self-limited illnesses that do not require specific antiviral therapy. The currently available antiviral drugs target 3 main groups of viruses: herpes, hepatitis, and influenza viruses. With the exception of the antisense molecule fomivirsen, all antiherpes drugs inhibit viral replication by serving as competitive substrates for viral DNA polymerase. Drugs for the treatment of influenza inhibit the ion channel M(2) protein or the enzyme neuraminidase. Combination therapy with Interferon-α and ribavirin remains the backbone treatment for chronic hepatitis C; the addition of serine protease inhibitors improves the treatment outcome of patients infected with hepatitis C virus genotype 1. Chronic hepatitis B can be treated with interferon or a combination of nucleos(t)ide analogues. Notably, almost all the nucleos(t) ide analogues for the treatment of chronic hepatitis B possess anti-human immunodeficiency virus properties, and they inhibit replication of hepatitis B virus by serving as competitive substrates for its DNA polymerase. Some antiviral drugs possess multiple potential clinical applications, such as ribavirin for the treatment of chronic hepatitis C and respiratory syncytial virus and cidofovir for the treatment of cytomegalovirus and other DNA viruses. Drug resistance is an emerging threat to the clinical utility of antiviral drugs. The major mechanisms for drug resistance are mutations in the viral DNA polymerase gene or in genes that encode for the viral kinases required for the activation of certain drugs such as acyclovir and ganciclovir. Widespread antiviral resistance has limited the clinical utility of M(2) inhibitors for the prevention and treatment of influenza infections. This article provides an overview of clinically available antiviral drugs for the primary care physician, with a special focus on pharmacology, clinical uses, and adverse effects.

  12. Characterization of a [open quotes]kissing[close quotes] hairpin complex derived from the human immunodeficiency virus genome

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Kung-Yao; Tinoco, Ignacio Jr. (Lawrence Berkeley Lab., CA (United States))

    1994-08-30

    Base-pair formation between hairpin loops-a [open quotes]kissing[close quotes] complex-is an RNA-folding motif that links two elements of RNA secondary structure. It is also a unique protein recognition site involved in regulation of ColE1 plasmid DNA replication. The trans-activation response element (TAR), a hairpin and bulge at the 5[prime] end of the untranslated leader region of the human immunodeficiency virus 1 mRNA, enhances the transcription of the virus and is necessary for viral replication. Gel electrophoresis and absorbance melting curves indicate that a synthesized RNA hairpin (Tar*-16) with a loop sequence complementary to the TAR loop sequence (CUGGGA) associates specifically with a 16-nucleotide TAR hairpin (Tar-16) to form a stable complex. RNase T1 probing indicates that the three guanines in the Tar-16 loop become inaccessible in the complex. NMR imino proton spectra reveal that 5 base pairs are formed between the two hairpin loops (Tar-16 and Tar*-16); only the adenine at the 3[prime] terminus of the TAR loop does not form a base pair with the 5[prime]-terminal uracil of the complementary loop. A 14-nucleotide hairpin [CCUA-(UCCCAG)UAGG] with a loop sequence complementary to the TAR loop is conserved within the gag gene of human immunodeficiency virus 1. A synthesized RNA hairpin corresponding to this conserved sequence also binds to the Tar-16 hairpin with high affinity. It is possible that the same RNA loop-loop interaction occurs during the viral life cycle. 40 refs., 7 figs.

  13. Bicyclams, selective antagonists of the human chemokine receptor CXCR4, potently inhibit feline immunodeficiency virus replication

    NARCIS (Netherlands)

    Horzinek, M.C.; Egberink, H.F.; Clercq, E. de; Vliet, A.L.W. van; Balzarini, J.; Bridger, G.J.; Henson, G.; Schols, D.

    1999-01-01

    Bicyclams are low-molecular-weight anti-human immunodeficiency virus (HIV) agents that have been shown to act as potent and selective CXC chemokine receptor 4 (CXCR4) antagonists. Here, we demonstrate that bicyclams are potent inhibitors of feline immunodeficiency virus (FIV) replication when evalua

  14. Repeatedly positive human immunodeficiency virus type 1 DNA polymerase chain reaction in human immunodeficiency virus-exposed seroreverting infants.

    Science.gov (United States)

    Bakshi, S S; Tetali, S; Abrams, E J; Paul, M O; Pahwa, S G

    1995-08-01

    Three human immunodeficiency virus type 1 (HIV-1)-exposed children who had repeatedly positive DNA polymerase chain reaction (PCR) tests for HIV in > or = 5 samples before seroreversion to HIV-negative status are reported. The children belong to a cohort of 210 infants who were born to HIV-infected mothers and were tested at intervals of 1 to 3 months by HIV viral culture, PCR, and p24 antigen; only the PCR was positive in > or = 5 samples in the children reported here. Their clinical features were indistinguishable from other seroreverters. All three children had a transient drop in CD4:CD8 ratio to < 1.0. The transiently positive DNA PCR in HIV-exposed infants may indicate either that HIV infection was eliminated by a strong host immune response or that infection was caused by an attenuated/defective strain of virus.

  15. Current human immunodeficiency virus epidemic and its response in China

    Institute of Scientific and Technical Information of China (English)

    KANG Lai-Yi

    2012-01-01

    The first patient with acquired immunodeficiency syndrome (AIDS) was identified in 1985; since then, as of October 31, 2010, a total accumulative number of 370 000 patients with human immunodeficiency virus (HIV)/AIDS have been reported. The estimated number of patients living with HIV (PLHIV) in China was 740 000 in 2009. Although China is still a low-HIV prevalence region (rate of 0.057%), the epidemic has spread more widely from the high-risk groups to the general population. This paper covers five topics of importance, i.e., current trends of the HIV epidemic; HIV-1 subtype diversity; emergence of HIV drug resistance (HIVDR); the country's response to the disease; and future challenges and additional actions needed. This paper emphasizes sexual transmission as the predominant route of transmission and it being spread more frequently among men who have sex with men; the epidemic being concentrated over particular areas in China. We also discuss the fact that diverse HIV-1 subtypes have been found throughout the entire country and that recombinant subtypes became predominant. We also explore other topics such as the possibility of HIVDR, including primary and secondary resistance, with the use of free highly active anti-retroviral therapy (HAART); the integrated strategy of HIVDR surveillance and individual clinical HIVDR testing as a new attempt in China. For many years both policy-makers and professionals (including non-governmental organizations) have expressed strong commitment to prevention, control, and care of HIV/sexual transmission infection (STI), promoted the research and conducted different actions to slow the rising trend of the HIV epidemics. Although China is facing many challenges, its citizens need to be persistent on continuing the campaign of the State Council titled "Information of Strengthening Work on Prevention and Control of AIDS".

  16. Changing patterns of human immunodeficiency virus-associated neuropathology

    Directory of Open Access Journals (Sweden)

    Gray Francoise

    2007-01-01

    Full Text Available This paper describes the evolution of the pathogenic concepts associated with the infection by the human immunodeficiency virus (HIV, with emphasis to the pathology of the nervous system. Although the first description of damage to the nervous system in the acquired immunodeficiency syndrome (AIDS only appeared in 1982, the dramatic diffusion of the epidemic worldwide, as well as the invariably rapidly fatal outcome of the disease before the introduction of efficient treatment, generated from the beginning an enormous amount of research and re-thinking on a number of pathogenetic concepts. Less than 25 years after the first autopsy series on AIDS patients were published and the virus responsible for AIDS was identified, satisfactory definition and classification of a number of neuropathological complications of HIV infection have been established. This has led to the establishment of accurate clinical and biological diagnosis of the main neurological complications of the disease, which remain a major cause of disability and death in patients. Clinical and experimental studies have provided essential insight into the pathogenesis of CNS lesions and the natural history of the disorder. The relatively recent introduction of effective antiretroviral therapy in 1995-6 dramatically improved the course of prognosis of HIV disease. However, there remain a number of unsolved pathogenetic issues, the most puzzling of which remains the precise mechanism of neuronal damage underlying the specific HIV-related cognitive disorder (HIV-dementia. In addition, although antiretroviral therapy has changed the course of neurological complications, new issues have emerged, such as the lack of improvement or even paradoxical deterioration of the neurological status in treated patients. Interpretation of these complications remains largely speculative, partly because of the small number of neuropathological studies related to the beneficial consequence of this

  17. Immune thrombocytopenic purpura might be an early hematologic manifestation of undiagnosed human immunodeficiency virus infection.

    Science.gov (United States)

    Lai, Shih-Wei; Lin, Hsien-Feng; Lin, Cheng-Li; Liao, Kuan-Fu

    2017-03-01

    Little research focuses on the association between immune thrombocytopenic purpura and human immunodeficiency virus infection in Taiwan. This study investigated whether immune thrombocytopenic purpura might be an early hematologic manifestation of undiagnosed human immunodeficiency virus infection in Taiwan. We conducted a retrospective population-based cohort study using data of individuals enrolled in Taiwan National Health Insurance Program. There were 5472 subjects aged 1-84 years with a new diagnosis of immune thrombocytopenic purpura as the purpura group since 1998-2010 and 21,887 sex-matched and age-matched, randomly selected subjects without immune thrombocytopenic purpura as the non-purpura group. The incidence of human immunodeficiency virus infection at the end of 2011 was measured in both groups. We used the multivariable Cox proportional hazards regression model to measure the hazard ratio and 95 % confidence interval (CI) for the association between immune thrombocytopenic purpura and human immunodeficiency virus infection. The overall incidence of human immunodeficiency virus infection was 6.47-fold higher in the purpura group than that in the non-purpura group (3.78 vs. 0.58 per 10,000 person-years, 95 % CI 5.83-7.18). After controlling for potential confounding factors, the adjusted HR of human immunodeficiency virus infection was 6.3 (95 % CI 2.58-15.4) for the purpura group, as compared with the non-purpura group. We conclude that individuals with immune thrombocytopenic purpura are 6.47-fold more likely to have human immunodeficiency virus infection than those without immune thrombocytopenic purpura. We suggest not all patients, but only those who have risk factors for human immunodeficiency virus infection should receive testing for undiagnosed human immunodeficiency virus infection when they develop immune thrombocytopenic purpura.

  18. El receptor de la hormona de crecimiento humana (hGH y la proteína de transporte de alta afinidad de la hGH Human Growth Hormone (GH Receptor and the High Affinity GH-Binding Protein

    Directory of Open Access Journals (Sweden)

    María Gabriela Ballerini

    2008-03-01

    Full Text Available La hormona de crecimiento humana (hGH circula parcialmente unida a su proteína de transporte de alta afinidad (GHBP la cual resulta del clivaje proteolítico del dominio extracelular del receptor de GH. Recientemente la enzima TACE se identificó como la metaloproteasa responsable del clivaje y liberación de GHBP a circulación. Aunque aún se desconoce la función específica de esta proteína de transporte, distintos trabajos en la literatura demuestran efectos que potencian y efectos inhibitorios sobre la acción de GH. Por otro lado, existen evidencias que demuestran una fuerte relación entre la GHBP y el nivel de receptor de GH en el hígado en situaciones fisiológicas y patológicas. Esto permitió proponer a la determinación de GHBP en suero como un marcador periférico de la abundancia del receptor de GH en los tejidos. La determinación de la concentración de GHBP sería de especial interés para evaluar pacientes con diagnóstico probable de insensibilidad a la acción de GH y orientar el posterior estudio de anormalidades en el gen del receptor de GH. En la presente revisión, también se abordan dificultades metodológicas relacionadas a la medición de GHBP sérica.Human circulating growth hormone (GH is partly bound to a high-affinity binding protein (GHBP which is derived from proteolytical cleavage of the extracellular domain of the GH receptor. Recently, the metalloproteinase TACE has been identified as an important enzyme responsive for inducing GHBP shedding. Although the specific function of GHBP is not fully known, both enhancing and inhibitory roles of this binding protein on GH action have been proposed. Many reports have demonstrated a close relationship between GHBP and the liver GH receptor status in physiological conditions and diseases. Moreover, serum GHBP measurement has been proposed as an useful peripheral index of the GH receptor abundance. Related to the latter, circulating GHBP concentration would be of

  19. Dimerization is not a determining factor for functional high affinity human plasminogen binding by the group A streptococcal virulence factor PAM and is mediated by specific residues within the PAM a1a2 domain.

    Science.gov (United States)

    Bhattacharya, Sarbani; Liang, Zhong; Quek, Adam J; Ploplis, Victoria A; Law, Ruby; Castellino, Francis J

    2014-08-01

    A emm53 subclass of Group A Streptococcus pyogenes (GAS) interacts tightly with human plasma plasminogen (hPg) and plasmin (hPm) via the kringle 2 (K2hPg) domain of hPg/hPm and the N-terminal a1a2 regions of a GAS coiled-coil M-like protein (PAM). Previous studies have shown that a monomeric PAM fragment, VEK30 (residues 97-125 + Tyr), interacted specifically with isolated K2hPg. However, the binding strength of VEK30 (KD = 56 nm) was ∼60-fold weaker than that of full-length dimeric PAM (KD = 1 nm). To assess whether this attenuated binding was due to the inability of VEK30 to dimerize, we defined the minimal length of PAM required to dimerize using a series of peptides with additional PAM residues placed at the NH2 and COOH termini of VEK30. VEK64 (PAM residues 83-145 + Tyr) was found to be the smallest peptide that adopted an α-helical dimer, and was bound to K2hPg with nearly the same affinity as PAM (KD = 1-2 nm). However, addition of two PAM residues (Arg(126)-His(127)) to the COOH terminus of VEK30 (VEK32) maintained a monomeric peptidic structure, but exhibited similar K2hPg binding affinity as full-length dimeric PAM. We identified five residues in a1a2 (Arg(113), His(114), Glu(116), Arg(126), His(127)), mutation of which reduced PAM binding affinity for K2hPg by ∼ 1000-fold. Replacement of these critical residues by Ala in the GAS genome resulted in reduced virulence, similar to the effects of inactivating the PAM gene entirely. We conclude that rather than dimerization of PAM, the five key residues in the binding domain of PAM are essential to mediate the high affinity interaction with hPg, leading to increased GAS virulence.

  20. Maternal antibodies to gp120 V3 sequence do not correlate with protection against vertical transmission of human immunodeficiency virus.

    Science.gov (United States)

    Robertson, C A; Mok, J Y; Froebel, K S; Simmonds, P; Burns, S M; Marsden, H S; Graham, S

    1992-10-01

    A retrospective study of sera from mothers infected with human immunodeficiency virus (HIV-1) was undertaken to investigate whether the titers or affinities of antibodies against the third hypervariable region (V3 loop) of gp120 correlated with transmission of the virus from mother to child. The cohort comprised 7 mothers who transmitted HIV-1 to their children and 20 who did not. Sera were screened for reactivity against two synthetic peptides, one encompassing the entire V3 loop of gp120 (amino acids 297-330) and the other containing an immunodominant epitope from gp41 (amino acids 596-614). Doubling dilutions of sera were tested to obtain antibody titers against both peptides: Anti-gp41 titers were used to normalize the anti-V3 titers. Maternal sera were also screened for the presence of high-affinity antibodies against the V3 peptide. No differences were observed in either titers or affinities of maternal antibodies to the V3 sequence from transmitters and nontransmitters.

  1. Tolerance and Pharmacokinetic Interactions of Rifabutin and Clarithromycin in Human Immunodeficiency Virus-Infected Volunteers†

    OpenAIRE

    Hafner, Richard; Bethel, James; Power, Maureen; Landry, Bernard; Banach, Mary; Mole, Larry; Standiford, Harold C.; Follansbee, Stephen; Kumar, Princy; Raasch, Ralph; Cohn, David; Mushatt, David; Drusano, George

    1998-01-01

    This study evaluated the tolerance and potential pharmacokinetic interactions between clarithromycin (500 mg every 12 h) and rifabutin (300 mg daily) in clinically stable human immunodeficiency virus-infected volunteers with CD4 counts of

  2. Correlation of in vivo neuroimaging abnormalities with postmortem human immunodeficiency virus encephalitis and dendritic loss

    DEFF Research Database (Denmark)

    Archibald, Sarah L.; Masliah, Eliezer; Fennema-Notestine, Christine;

    2004-01-01

    previous studies have linked brain viral levels to these alterations, other neuropathological mechanisms might also contribute to them. OBJECTIVE: To examine the relationship between findings on premortem magnetic resonance images and postmortem neuropathologic evidence of human immunodeficiency virus (HIV...

  3. Association between human immunodeficiency virus infection and arterial stiffness in children

    NARCIS (Netherlands)

    Kuilder, Justin S.; Idris, Nikmah S.; Grobbee, Diederick E.; Bots, Michiel L.; Cheung, Michael M H; Burgner, David; Kurniati, Nia; Uiterwaal, Cuno S P M

    2017-01-01

    Background Human immunodeficiency virus infection (HIV) is associated with increased cardiovascular risk and adverse cardiovascular outcome in adults. Early recognition of changes in vascular properties might prove essential in cardiovascular prevention in HIV-infected patients. We investigated the

  4. Candida nivariensis isolated from an Indonesian human immunodeficiency virus-infected patient suffering from oropharyngeal candidiasis

    NARCIS (Netherlands)

    Wahyuningsih, Retno; SahBandar, Ivo N.; Theelen, Bart; Hagen, Ferry; Poot, Ge; Meis, Jacques F.; Rozalyani, Anna; Sjam, Ridhawati; Widodo, Djoko; Djauzi, Samsuridjal; Boekhout, Teun

    2008-01-01

    Candida nivariensis was isolated from an Indonesian human immunodeficiency virus-infected patient who suffered from oropharyngeal candidiasis and was identified with molecular tools. Our isolate demonstrated low MICs to amphotericin B, flucytosine, posaconazole, caspofungin, and isavueonazole and wa

  5. Co‑infections of hepatitis B and C with human immunodeficiency ...

    African Journals Online (AJOL)

    2015-01-04

    Jan 4, 2015 ... Background: Hepatitis B and C viral co‑infections with human immunodeficiency virus (HIV) are known to affect progression ... region;[1] they equally share similar routes of transmission such as ... the southern part of Nigeria.

  6. Intracellular Immunization of Human Fetal Cord Blood Stem/Progenitor Cells with a Ribozyme Against Human Immunodeficiency Virus Type 1

    Science.gov (United States)

    Yu, Mang; Leavitt, Mark C.; Maruyama, Midori; Yamada, Osamu; Young, Dennis; Ho, Anthony D.; Wong-Staal, Flossie

    1995-01-01

    Successful treatment of human immunodeficiency virus infection may ultimately require targeting of hematopoietic stem cells. Here we used retroviral vectors carrying the ribozyme gene to transduce CD34^+ cells from human fetal cord blood. Transduction and ribozyme expression had no apparent adverse effect on cell differentiation and/or proliferation. The macrophage-like cells, differentiated from the stem/progenitor cells in vitro, expressed the ribozyme gene and resisted infection by a macrophage tropic human immunodeficiency virus type 1. These results suggest the feasibility of stem cell gene therapy for human immunodeficiency virus-infected patients.

  7. Natural variation of the nef gene in human immunodeficiency virus type 2 infections in Portugal

    OpenAIRE

    Pádua, E.; Jenkins, A.; S. Brown; Bootman, J.; Paixão, M T; Almond, N; Berry, N

    2003-01-01

    Human immunodeficiency virus type 2 (HIV-2) infections cause severe immunodeficiency in humans, although HIV-2 is associated frequently with reduced virulence and pathogenicity compared to HIV-1. Genetic determinants that play a role in HIV pathogenesis are relatively poorly understood but nef has been implicated in inducing a more pathogenic phenotype in vivo. However, relatively little is known about the role of nef in HIV-2 pathogenesis. To address this, the genetic composition of 44 nef a...

  8. Chronic Inflammatory Periodontal Disease in Patients Diagnosed with Human Immunodeficiency Virus/AIDS in Cienfuegos

    OpenAIRE

    Nivia Gontán Quintana; Alain Soto Ugalde; Elena Idaisy Otero Salabarría

    2013-01-01

    Background: human immunodeficiency virus increases patients´ susceptibility to infections. Consequently, a high incidence of periodontal diseases is observed among them. It is often associated with other lesions of the oral mucous. Objective: to determine the evolution of chronic inflammatory periodontal disease in patients diagnosed with human immunodeficiency virus/AIDS.Methods: a case series study involving HIV-positive patients who attended the Stomatology consultation in Cienfuegos was c...

  9. Maternal Syphilis: An Independent Risk Factor for Mother to Infant Human Immunodeficiency Virus Transmission.

    Science.gov (United States)

    Kinikar, Aarti; Gupte, Nikhil; Bhat, Jayalakshmi; Bharadwaj, Renu; Kulkarni, Vandana; Bhosale, Ramesh; McIntire, Katherine N; Mave, Vidya; Suryavanshi, Nishi; Patil, Sandesh; Bollinger, Robert; Gupta, Amita

    2017-06-01

    Syphilis is associated with increased human immunodeficiency virus acquisition and sexual transmission; we examined impact on human immunodeficiency virus mother-to-child transmission among mother-infant pairs enrolled in the India Six-Week Extended-Dose Nevirapine study. Maternal syphilis, diagnosed serologically using Venereal Disease Research Laboratory titer plus Treponema Pallidum Hemagglutination Assay, was associated with 2.5-fold greater risk.

  10. Chronic Inflammatory Periodontal Disease in Patients with Human Immunodeficiency Virus.

    Directory of Open Access Journals (Sweden)

    Vania López Rodríguez

    2009-07-01

    Full Text Available Background: The Chronic Inflammatory Periodontal Disease is related with multiple risk factors. Those patients with human immunodeficiency virus have higher risk of presenting this disease and it is usually more serious in these cases. Objective: To describe the prevalence of Chronic Inflammatory Periodontal Disease in patients with HIV. Methods: Descriptive, observational, cross-sectional study including patients with HIV in Sancti Spiritus province. The occurrence of the disease was determined after the Periodontics Cuban Standards, and oral hygiene was assessed through the simplified oral hygiene index. Other variables were measured, such as smoking habits, T CD4+ lymphocyte counting and virus load. The independent association of each risk factor with the disease was determined through a logistic regression model. Results: The 56, 5 % of the 154 patients presented Chronic Inflammatory Periodontal Disease; 60 (39.0% gingivitis and 27 (17,5% periodontitis. Gingivitis was associated with poor oral hygiene (OR: 3,71 and periodontitis with smoking habit (OR: 5,20. The severe forms of periodontitis occurred mainly in patients with lymphocyte counting lower than 500 cells/mm3 . Conclusions: The prevalence of Chronic Inflammatory Periodontal Disease in patients with HIV in Sancti Spiritus province is linked to known risk factors such as smoking habits and oral hygiene.

  11. [Discrimination and homophobia associated to the human immunodeficiency virus epidemic].

    Science.gov (United States)

    Orozco-Núñez, Emanuel; Alcalde-Rabanal, Jacqueline Elizabeth; Ruiz-Larios, José Arturo; Sucilla-Pérez, Héctor; García-Cerde, Rodrigo

    2015-01-01

    To describe a political mapping on discrimination and homophobia associated to human immunodeficiency virus (HIV) in the context of public institutions in Mexico. The political mapping was conducted in six Mexican states. Stakeholders who were involved in HIV actions from public and private sectors were included. Semistructured interviews were applied to explore homophobia and discrimination associated with HIV. Information was systematized using the Policy Maker software, which is a good support for analyzing health policies. Discriminatory and homophobic practices in the public domain occurred, damaging people´s integrity via insults, derision and hate crimes. Most stakeholders expressed a supportive position to prevent discrimination and homophobia and some of them had great influence on policy-making decisions. It was found that state policy frameworks are less specific in addressing these issues. Homophobia and discrimination associated to HIV are still considered problematic in Mexico. Homophobia is a very sensitive issue that requires further attention. Also, an actual execution of governmental authority requires greater enforcement of laws against discrimination and homophobia.

  12. Inhibition of human immunodeficiency virus type-1 by cdk inhibitors

    Directory of Open Access Journals (Sweden)

    Kehn-Hall Kylene

    2010-03-01

    Full Text Available Abstract Current therapy for human immunodeficiency virus (HIV-1 infection relies primarily on the administration of anti-retroviral nucleoside analogues, either alone or in combination with HIV-protease inhibitors. Although these drugs have a clinical benefit, continuous therapy with the drugs leads to drug-resistant strains of the virus. Recently, significant progress has been made towards the development of natural and synthetic agents that can directly inhibit HIV-1 replication or its essential enzymes. We previously reported on the pharmacological cyclin-dependent kinase inhibitor (PCI r-roscovitine as a potential inhibitor of HIV-1 replication. PCIs are among the most promising novel antiviral agents to emerge over the past few years. Potent activity on viral replication combined with proliferation inhibition without the emergence of resistant viruses, which are normally observed in HAART patients; make PCIs ideal candidates for HIV-1 inhibition. To this end we evaluated twenty four cdk inhibitors for their effect on HIV-1 replication in vitro. Screening of these compounds identified alsterpaullone as the most potent inhibitor of HIV-1 with activity at 150 nM. We found that alsterpaullone effectively inhibits cdk2 activity in HIV-1 infected cells with a low IC50 compared to control uninfected cells. The effects of alsterpaullone were associated with suppression of cdk2 and cyclin expression. Combining both alsterpaullone and r-roscovitine (cyc202 in treatment exhibited even stronger inhibitory activities in HIV-1 infected PBMCs.

  13. National Surveillance of Occupational Exposure to the Human Immunodeficiency Virus

    Directory of Open Access Journals (Sweden)

    Maura Ricketts

    1992-01-01

    Full Text Available In September 1985, a prospective study was initiated to monitor the occurrence of occupational exposures to human immunodeficiency virus (HIV-infected blood and body fluids in Canada. This program was coordinated by the Federal Centre for acquired immune deficiency syndrome (AIDS (now the Division of HIV/AIDS Epidemiology at the Laboratory Centre for Disease Control. The objective was to determine the risk to workers of acquiring HIV infection as a result of exposure to HIV-infected blood and other body fluids. To be eligible, a worker must have sustained a documented parenteral, mucous membrane or skin contact exposure to blood or body fluids from an HIV-infected person. A baseline specimen was collected within a week of the exposure and then at six weeks, 12 weeks, six months and 12 months. Information concerning the type of exposure, precautions used and post exposure treatment was submitted to the Federal Centre for AIDS on standard data collection forms. All information was anonymous, identified only by a code number. Guidelines for counselling an exposed employee were provided with enrollment material. As of July 29, 1991, 414 employees have been included in the study. Two hundred and thirty-seven of the 414 exposures (57% were needlestick injuries of which 167 (70% were sustained by nurses. Other exposures consisted of open wound contamination, eye splashes, scalpel wounds and skin contact with blood and body fluids. To date, there have been no seroconversions among workers enrolled in the surveillance program.

  14. Tuberculous meningitis in patients infected with human immunodeficiency virus.

    Science.gov (United States)

    Garg, Ravindra Kumar; Sinha, Manish Kumar

    2011-01-01

    Tuberculosis is the most common opportunistic infection in human immunodeficiency virus (HIV) infected persons. HIV-infected patients have a high incidence of tuberculous meningitis as well. The exact incidence and prevalence of tuberculous meningitis in HIV-infected patients are not known. HIV infection does not significantly alter the clinical manifestations, laboratory, radiographic findings, or the response to therapy. Still, some differences have been noted. For example, the histopathological examination of exudates in HIV-infected patients shows fewer lymphocytes, epithelioid cells, and Langhan's type of giant cells. Larger numbers of acid-fast bacilli may be seen in the cerebral parenchyma and meninges. The chest radiograph is abnormal in up to 46% of patients with tuberculous meningitis. Tuberculous meningitis is likely to present with cerebral infarcts and mass lesions. Cryptococcal meningitis is important in differential diagnosis. The recommended duration of treatment in HIV-infected patients is 9-12 months. The benefit of adjunctive corticosteroids is uncertain. Antiretroviral therapy and antituberculosis treatment should be initiated at the same time, regardless of CD4 cell counts. Tuberculous meningitis may be a manifestation of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome. Some studies have demonstrated a significant impact of HIV co-infection on mortality from tuberculous meningitis. HIV-infected patients with multidrug-resistant tuberculous meningitis have significantly higher mortality. The best way to prevent HIV-associated tuberculous meningitis is to diagnose and isolate infectious cases of tuberculosis promptly and administer appropriate treatment.

  15. Selective destruction of cells infected with human immunodeficiency virus

    Science.gov (United States)

    Keener, William K.; Ward, Thomas E.

    2003-09-30

    Compositions and methods for selectively killing a cell containing a viral protease are disclosed. The composition is a variant of a protein synthesis inactivating toxin wherein a viral protease cleavage site is interposed between the A and B chains. The variant of the type II ribosome-inactivating protein is activated by digestion of the viral protease cleavage site by the specific viral protease. The activated ribosome-inactivating protein then kills the cell by inactivating cellular ribosomes. A preferred embodiment of the invention is specific for human immunodeficiency virus (HIV) and uses ricin as the ribosome-inactivating protein. In another preferred embodiment of the invention, the variant of the ribosome-inactivating protein is modified by attachment of one or more hydrophobic agents. The hydrophobic agent facilitates entry of the variant of the ribosome-inactivating protein into cells and can lead to incorporation of the ribosome-inactivating protein into viral particles. Still another preferred embodiment of the invention includes a targeting moiety attached to the variants of the ribosome-inactivating protein to target the agent to HIV infectable cells.

  16. Selective Destruction Of Cells Infected With The Human Immunodeficiency Virus

    Science.gov (United States)

    Keener, William K.; Ward, Thomas E.

    2006-03-28

    Compositions and methods for selectively killing a cell containing a viral protease are disclosed. The composition is a varient of a protein synthesis inactivating toxin wherein a viral protease cleavage site is interposed between the A and B chains. The variant of the type II ribosome-inactivating protein is activated by digestion of the viral protease cleavage site by the specific viral protease. The activated ribosome-inactivating protein then kills the cell by inactivating cellular ribosomes. A preferred embodiment of the invention is specific for human immunodeficiency virus (HIV) and uses ricin as the ribosome-inactivating protein. In another preferred embodiment of the invention, the variant of the ribosome-inactivating protein is modified by attachment of one or more hydrophobic agents. The hydrophobic agent facilitates entry of the variant of the ribosome-inactivating protein into cells and can lead to incorporation of the ribosome-inactivating protein into viral particles. Still another preferred embodiment of the invention includes a targeting moiety attached to the variants of the ribosome-inactivating protein to target the agent to HIV infectable cells.

  17. MRI in human immunodeficiency virus-associated cerebral vasculitis

    Energy Technology Data Exchange (ETDEWEB)

    Berkefeld, J.; Lanfermann, H. [Frankfurt Univ. (Germany). Abt. fuer Neuroradiologie; Enzensberger, W. [Klinik fuer Neurologie, Klinikum der Johann Wolfgang Goethe-Univ. Frankfurt am Main (Germany)

    2000-07-01

    Cerebral ischaemia caused by inflammatory vasculopathies has been described as complication of human immunodeficiency virus (HIV) infection. Imaging studies have shown ischaemic lesions and changes of the vascular lumen, but did not allow demonstration of abnormalities within the vessel wall itself. Two HIV-infected men presented with symptoms of a transient ischaemic attack. Initial MRI of the first showed no infarct; in the second two small lacunar lesions were detected. In both cases, multiplanar 3-mm slice contrast-enhanced T1-weighted images showed aneurysmal dilatation, with thickening and contrast enhancement of the wall of the internal carotid and middle cerebral (MCA) arteries. These findings were interpreted as indicating cerebral vasculitis. In the first patient the vasculopathy progressed to carotid artery occlusion, and he developed an infarct in the MCA territory, but then remained neurologically stable. In the second patient varicella zoster virus (VZV) infection was the probable cause of vasculitis. The clinical deficits and vasculitic MRI changes regressed with antiviral and immunosuppressive therapy. (orig.)

  18. [Changes in vertically transmitted human immunodeficiency virus infection Chile].

    Science.gov (United States)

    Chávez P, Ana; Alvarez P, Ana M; Wu H, Elba; Peña D, Anamaría; Vizueta R, Eloísa

    2007-10-01

    The identification of various risk factors of vertical human immunodeficiency virus (HIV) transmission resulted in the development of strategies whose aim was to decrease the mother's viral load, to reduce her child's exposure to it during delivery, and to avoid the subsequent viral exposure due to breastfeeding. The administration of antiretroviral treatment during pregnancy, delivery and to the neonate (PACTG 076) proved to be useful. At a first stage, zidovudine was used. A triple combination therapy was then administered. Initially, the viral transmission in mothers who were enrolled in protocols for vertically transmitted HIV prophylaxis was reduced to 9.5%, whereas the last measurement carried out between 1998 and 2005, the initial figure was brought down to 2%. Nevertheless, the delivery of infected children whose mother's HIV status was unknown is still considered likely to happen. The main step to be taken to reduce HIV infection among children is to perform universal HIV tests during pregnancy, so that HIV positive pregnant patients conveniently receive proper prophylaxis. We look forward to achieving this by following the new prevention guidelines of vertically-transmitted HIV infection, developed by the Comisión Nacional del SIDA of the Chilean Health Ministry.

  19. Exercise and Human Immunodeficiency Virus (HIV-1) Infection

    Science.gov (United States)

    Lawless, DeSales; Jackson, Catherine G. R.; Greenleaf, John E.

    1995-01-01

    The human immune system is highly efficient and remarkably protective when functioning properly. Similar to other physiological systems, it functions best when the body is maintained with a balanced diet, sufficient rest and a moderately stress-free lifestyle. It can be disrupted by inappropriate drug use and extreme emotion or exertion. The functioning of normal or compromised immune systems can be enhanced by properly prescribed moderate exercise conditioning regimens in healthy people, and in some human immunodeficiency virus (HIV-1)-infected patients but not in others who unable to complete an interval training program. Regular exercise conditioning in healthy people reduces cardiovascular risk factors, increases stamina, facilitates bodyweight control, and reduces stress by engendering positive feelings of well-being. Certain types of cancer may also be suppressed by appropriate exercise conditioning. Various exercise regimens are being evaluated as adjunct treatments for medicated patients with the HIV-1 syndrome. Limited anecdotal evidence from patients suggests that moderate exercise conditioning is per se responsible for their survival well beyond expectancy. HIV-1-infected patients respond positively, both physiologically and psychologically, to moderate exercise conditioning. However, the effectiveness of any exercise treatment programme depends on its mode, frequency, intensity and duration when prescribed o complement the pathological condition of the patient. The effectiveness of exercise conditioning regimens in patients with HIV-1 infection is reviewed in this article. In addition, we discuss mechanisms and pathways, involving the interplay of psychological and physiological factors, through which the suppressed immune system can be enhanced. The immune modulators discussed are endogenous opioids, cytokines, neurotransmitters and other hormones. Exercise conditioning treatment appears to be more effective when combined with other stress management

  20. Measuring domestic violence in human immunodeficiency virus-positive women.

    Science.gov (United States)

    Patrikar, Seema; Verma, Ak; Bhatti, Vk; Shatabdi, S

    2012-04-01

    Violence affects the lives of millions of women worldwide, in all socioeconomic classes. Violence and the fear of violence are emerging as important risk factor contributing to the vulnerability to human immunodeficiency virus (HIV) infection for women. The objective of the present cross sectional study is to compare the experiences of domestic violence between HIV-positive and HIV-negative married women seeking treatment in a tertiary care hospital. The study is conducted in a tertiary care hospital in Pune on a randomly selected 150 married women (75 HIV-positive and 75 HIV-negative). Informed consent was obtained from all the women and also a trained counsellor was present during the process of data collection. The data was collected by interview method by taking precautions as laid down in the World Health Organization's ethical and safety recommendations for research on domestic violence and using modified conflict tactics scale (CTS). The definition of violence followed is as per the Declaration on the Elimination of Violence against Women, adopted by the United Nations General Assembly in 1993. The percentage of women reporting domestic violence is 44.7% (95% confidence interval [CI] = 36.84-52.68). The proportion of physical, emotional and sexual violence reported is 38% (95% CI = 30.49-45.96), 24% (95% CI = 17.67-31.31), and 14.7% (95% CI = 9.66-21.02), respectively. The odds of reporting violence of all forms is significantly higher among HIV-positive women than among HIV-negative women (Pviolence. The findings suggest high proportion of HIV-positive women report violence then HIV-negative women which must be addressed through multilevel prevention approaches.

  1. The life-cycle of human immunodeficiency virus type 1.

    Science.gov (United States)

    Goto, T; Nakai, M; Ikuta, K

    1998-01-01

    The life-cycle of human immunodeficiency virus type 1 (HIV-1) has been studied using several techniques including immunoelectron microscopy and cryomicroscopy. The HIV-1 particle consists of an envelope, a core and the region between the core and the envelope (matrix). Virus particles in the extracellular space are observed as having various profiles: a central or an eccentric round electron-dense core, a bar-shaped electron-dense core, and immature doughnut-shaped particle. HIV-1 particles in the hydrated state were observed by high-resolution electron cryomicroscopy to be spherical and the lipid membrane was clearly resolved as a bilayer. Projections around the circumference were seen to be knob-like. The shapes and sizes of the projections, especially the head parts, were found to vary with each projection. HIV-1 cores were isolated with a mixture of Nonidet P40 and glutaraldehyde, and were confirmed to consist of HIV-1 Gag p24 protein by immunogold labelling. On infection, the HIV-1 virus was found to enter the cell in two ways: membrane fusion and endocytosis. After viral entry, no structures resembling virus particles could be seen in the cytoplasm. In the infected cells, positive reactions by immunolabelling suggest that HIV-1 Gag is produced in membrane-bound structures and transported to the cell surface by the cytoskeletons. A crescent electron-dense layer is then formed underneath the cell membrane. Finally, the virus particle is released from the cell surface and found extracellularly to be a complete virus particle with an electron-dense core. However, several cell clones producing defective mature, doughnut-shaped (immature) or teardrop-shaped particles were found to be produced in the extracellular space. In the doughnut-shaped particles, Gag p17 and p24 proteins exist facing each other against an inner electron-dense ring, suggesting that the inner ring consists of a precursor Gag protein showing a defect at the viral proteinase.

  2. Metabolic syndrome in human immunodeficiency virus positive patients

    Directory of Open Access Journals (Sweden)

    Sarita Bajaj

    2013-01-01

    Full Text Available Aims and Objectives : To assess the prevalence of metabolic syndrome (MetS in human immunodeficiency virus (HIV positive patients. Prevalence of MetS was compared in patients who were not on highly active antiretroviral therapy (HAART to patients who were on HAART. Materials and Methods: Seventy HIV positive cases were studied. Pregnant and lactating women, patients on drugs other than HAART known to cause metabolic abnormalities and those having diabetes or hypertension were excluded. Cases were evaluated for MetS by using National Cholesterol Education Program Adult Treatment Panel-III. Results: 47 cases were on HAART and 23 cases were not on HAART. Fasting Blood Glucose ≥100 mg/dl was present in 28.6% cases, out of whom 27.7% were on HAART and 30.4% were not on HAART (P = 0.8089. 12.9% cases had BP ≥130/≥85 mm Hg, out of whom 14.9% were on HAART and 8.7% were not on HAART (P = 0.4666. 42.9% cases had TG ≥150 mg/dl, out of whom 44.7% were on HAART and 39.1% were not on HAART (P = 0.6894. HDL cholesterol was low (males <40 mg/dl, females <50 mg/dl in 50% cases, out of whom 55.3% were on HAART and 39.1% were not on HAART (P = 0.2035. Conclusions: Prevalence of MetS was 20%. Majority of patients had only one component of MetS (32.9%. Low HDL was present in 50%, followed by raised triglycerides in 42.9%. Waist circumference was not increased in any of the patients. There was no statistically significant difference between those on HAART and those not on HAART in distribution of risk factors and individual components of MetS.

  3. Declined Neural Efficiency in Cognitively Stable Human Immunodeficiency Virus Patients

    Science.gov (United States)

    Ernst, Thomas; Yakupov, Renat; Nakama, Helenna; Crocket, Grace; Cole, Michael; Watters, Michael; Ricardo-Dukelow, Mary Lynn; Chang, Linda

    2009-01-01

    Objective To determine whether brain activation changes in clinically and neurocognitively normal human immunodeficiency virus (HIV)–infected and in HIV-seronegative control (SN) participants over a 1-year period. Methods Functional magnetic resonance imaging (fMRI) was performed in 32 SN and 31 HIV patients (all with stable combination antiretroviral treatment) at baseline and after 1 year. Each participant performed a set of visual attention tasks with increasing attentional load (from tracking two, three, or four balls). All HIV and SN participants had normal neuropsychological function at both examinations. Results Over 1 year, HIV patients showed no change in their neurocognitive status or in task performance during fMRI. However, HIV patients showed significant 1-year increases in fMRI signals in the prefrontal and posterior parietal cortices for the more difficult tasks, whereas SN control participants showed only decreases in brain activation in these regions. This resulted in significant interactions between HIV status and time of study in left insula, left parietal, left temporal, and several frontal regions (left and right middle frontal gyrus, and anterior cingulate). Interpretation Because fMRI task performance remained unchanged in both groups, the HIV patients appeared to maintain performance by increasing usage of the attention network, whereas the control participants reduced usage of the attention network after 1 year. These findings suggest improved efficiency or a practice effect in the SN participants but declined efficiency of the neural substrate in HIV patients, possibly because of ongoing brain injury associated with the HIV infection, despite their apparent stable clinical course. PMID:19334060

  4. REVIEW OF CONTROL OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION IN NIGERIA.

    Science.gov (United States)

    Dami, N; Shehu, N Y; Dami, S; Iroezindu, M O

    2015-01-01

    The global scourge of human immunodeficiency virus (HIV) infection is inundating, especially in sub-Saharan Africa and in particular Nigeria which is home to 10% of the world's HIV-infected persons. The target of the millennium development goal 6 is to halt and reverse the spread of HIV/AIDS by 2015. HIV control in Nigeria was initially shrouded in denial and apathy. Subsequently, a more pragmatic approach was launched during the tenure of President Olusegun Obasanjo. Several policies were formulated. The national prevalence of HIV witnessed some progressive decline and is currently 4.1%. There is now improvement in both HIV awareness and counselling and testing. Greater access to antiretroviral therapy and other support services have also been witnessed with over 300,000 persons currently on drugs. Notable achievements have been recorded in prevention of mother to child transmission (PMTC). However, with increased access to antiretroviral therapy, antiretroviral drug resistance has become inevitable. Acquired drug resistance is high-82% and transmitted drug resistance ranges between 0.7 and 4.5%. The achievements were largely facilitated by international partnerships which have become more streamlined in recent years. A sustained shift to indigenously sourced financial and manpower resource has become imperative. It is also important to integrate HIV facilities with other existing health care facilities for sustainability and cost-effectiveness. In an attempt to strengthen the national response, President Goodluck Ebele Jonathan launched the President's Comprehensive Response Plan for HIV/AIDS in Nigeria. It is hoped that this well-articulated policy would be well implemented to significantly reverse the epidemic.

  5. Transmembrane envelope glycoproteins of human immunodeficiency virus type 2 and simian immunodeficiency virus SIV-mac exist as homodimers.

    OpenAIRE

    Rey, M A; Laurent, A G; McClure, J; Krust, B; Montagnier, L; Hovanessian, A G

    1990-01-01

    An 80-kilodalton glycoprotein (gp80) was produced in human immunodeficiency virus type 2 (HIV-2)-infected cells along with three envelope glycoproteins that we have recently reported: the extracellular glycoprotein (gp125), the envelope glycoprotein precursor (gp140), and the transient dimeric form of the precursor (gp300). gp125 and gp80 were detectable after the synthesis of gp140 and the formation of gp300. Using a specific monoclonal antibody, we showed here that gp80 is a dimeric form of...

  6. Human immunodeficiency virus type 2 long terminal repeat: analysis of regulatory elements.

    OpenAIRE

    Arya, S. K.; Gallo, R C

    1988-01-01

    The long terminal repeats (LTRs) of the human immunodeficiency virus type 2 (HIV-2) and a related simian immunodeficiency virus (SIVmac) contain cis-acting positive regulatory elements upstream and the major transactivator gene (tat) response element and a possible negative regulatory element downstream of the transcriptional initiation site. The tat response element of HIV-2 and of SIVmac was more complex than that of HIV-1. Two structurally similar subelements within the HIV-2 tat response ...

  7. The level of risk of transmission of human immunodeficiency virus between patients and dental staff.

    Science.gov (United States)

    Scully, C; Porter, S

    1991-02-09

    Almost a decade into the epidemic of acquired immunodeficiency syndrome (AIDS) there is adequate evidence to address the concerns of dental staff about possible transmission of human immunodeficiency virus (HIV) between patient and staff. This paper reviews that evidence and demonstrates that the risk of HIV transmission to health care workers is extremely low. Worldwide there are no reported proven cases of occupational transmission of HIV to dental staff.

  8. Human immunodeficiency virus seroconversion presenting with acute inflammatory demyelinating polyneuropathy: a case report

    OpenAIRE

    Sloan Derek J; Nicolson Andrew; Miller Alastair RO; Beeching Nick J; Beadsworth Mike BJ

    2008-01-01

    Abstract Introduction Acute Human Immunodeficiency Virus infection is associated with a range of neurological conditions. Guillain-Barré syndrome is a rare presentation; acute inflammatory demyelinating polyneuropathy is the commonest form of Guillain-Barré syndrome. Acute inflammatory demyelinating polyneuropathy has occasionally been reported in acute Immunodeficiency Virus infection but little data exists on frequency, management and outcome. Case presentation We describe an episode of Gui...

  9. Human platelets inhibit liver fibrosis in severe combined immunodeficiency mice

    Science.gov (United States)

    Takahashi, Kazuhiro; Murata, Soichiro; Fukunaga, Kiyoshi; Ohkohchi, Nobuhiro

    2013-01-01

    AIM: To investigate the role of human platelets in liver fibrosis. METHODS: Severe combined immunodeficiency (SCID) mice were administered CCl4 and either phosphate-buffered saline (PBS group) or human platelet transfusions (hPLT group). Concentrations of hepatocyte growth factor (HGF), matrix metallopeptidases (MMP)-9, and transforming growth factor-β (TGF-β) in the liver tissue were compared between the PBS and the hPLT groups by enzyme-linked immunosorbent assay (ELISA) and Western blotting. The effects of a human platelet transfusion on liver fibrosis included the fibrotic area, hydroxyproline content, and α-smooth muscle actin (α-SMA) expression, which were evaluated by picrosirius red staining, ELISA, and immunohistochemical staining using an anti-mouse α-SMA antibody, respectively. Phosphorylations of mesenchymal-epithelial transition factor (Met) and SMAD3, downstream signals of HGF and TGF-β, were compared between the two groups by Western blotting and were quantified using densitometry. Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling. Furthermore, the accumulation of human platelets in the liver 2 h after platelet transfusion was compared between normal and fibrotic livers by immunohistochemical staining using an anti-human CD41 antibody. RESULTS: The fibrotic area and hydroxyproline content in the liver were both significantly lower in the hPLT group when compared to the PBS group (fibrotic area, 1.7% ± 0.6% vs 2.5% ± 0.6%, P = 0.03; hydroxyproline content, 121 ± 26 ng/g liver vs 156 ± 47 ng/g liver, P = 0.04). There was less α-smooth muscle actin staining in the hPLT group than in the PBS group (0.5% ± 0.1% vs 0.8% ± 0.3%, P = 0.02). Hepatic expression levels of mouse HGF and MMP-9 were significantly higher in the hPLT group than in the PBS group (HGF, 109 ± 13 ng/g liver vs 88 ± 22 ng/g liver, P = 0.03; MMP-9, 113% ± 7%/GAPDH vs 92% ± 11%/GAPDH, P = 0.04). In contrast, the

  10. Human BLyS facilitates engraftment of human PBL derived B cells in immunodeficient mice.

    Directory of Open Access Journals (Sweden)

    Madelyn R Schmidt

    Full Text Available The production of fully immunologically competent humanized mice engrafted with peripheral lymphocyte populations provides a model for in vivo testing of new vaccines, the durability of immunological memory and cancer therapies. This approach is limited, however, by the failure to efficiently engraft human B lymphocytes in immunodeficient mice. We hypothesized that this deficiency was due to the failure of the murine microenvironment to support human B cell survival. We report that while the human B lymphocyte survival factor, B lymphocyte stimulator (BLyS/BAFF enhances the survival of human B cells ex vivo, murine BLyS has no such protective effect. Although human B cells bound both human and murine BLyS, nuclear accumulation of NF-kappaB p52, an indication of the induction of a protective anti-apoptotic response, following stimulation with human BLyS was more robust than that induced with murine BLyS suggesting a fundamental disparity in BLyS receptor signaling. Efficient engraftment of both human B and T lymphocytes in NOD rag1(-/- Prf1(-/- immunodeficient mice treated with recombinant human BLyS is observed after adoptive transfer of human PBL relative to PBS treated controls. Human BLyS treated recipients had on average 40-fold higher levels of serum Ig than controls and mounted a de novo antibody response to the thymus-independent antigens in pneumovax vaccine. The data indicate that production of fully immunologically competent humanized mice from PBL can be markedly facilitated by providing human BLyS.

  11. Alteration in pancreatic islet function in human immunodeficiency virus

    DEFF Research Database (Denmark)

    Haugaard, Steen B

    2014-01-01

    Molecular mechanisms behind the defects in insulin production and secretion associated with antihuman immunodeficiency virus (anti-HIV) therapy and the development of HIV-associated lipodystrophy syndrome (HALS) are discussed in this article. Data suggesting insulin resistance on the beta cell an...

  12. Immunodeficient mouse model for human hematopoietic stem cell engraftment and immune system development.

    Science.gov (United States)

    Aryee, Ken-Edwin; Shultz, Leonard D; Brehm, Michael A

    2014-01-01

    Immunodeficient mice engrafted with human immune systems provide an exciting model to study human immunobiology in an in vivo setting without placing patients at risk. The essential parameter for creation of these "humanized models" is engraftment of human hematopoietic stem cells (HSC) that will allow for optimal development of human immune systems. However, there are a number of strategies to generate humanized mice and specific protocols can vary significantly among different laboratories. Here we describe a protocol for the co-implantation of human HSC with autologous fetal liver and thymic tissues into immunodeficient mice to create a humanized model with optimal human T cell development. This model, often referred to as the Thy/Liv or BLT (bone marrow, liver, thymus) mouse, develops a functional human immune system, including HLA-restricted human T cells, B cells, and innate immune cells.

  13. Human immunodeficiency virus (HIV)-associated polymorphic lymphoproliferative disorders.

    Science.gov (United States)

    Nador, Roland G; Chadburn, Amy; Gundappa, Girija; Cesarman, Ethel; Said, Jonathan W; Knowles, Daniel M

    2003-03-01

    The majority of AIDS-related non-Hodgkin's lymphomas are clinically aggressive monoclonal B-cell Burkitt's lymphomas, large cell lymphomas, or immunoblastic lymphomas. In contrast, the lymphoid proliferations arising in solid organ transplant recipients, collectively referred to as posttransplantation lymphoproliferative disorders (PT-LPDs), represent a clinically and histopathologically heterogeneous group of Epstein-Barr virus (EBV)-driven B-cell proliferations of variable clonal composition. During a retrospective histopathologic review of lymphoid proliferations associated with human immunodeficiency virus (HIV) infection we identified 10 cases that morphologically resemble the polymorphic PT-LPDs. They arose in lymph nodes (five), lungs (two), and the parotid gland, perineum, and skin (one each). They exhibit a diffuse growth pattern and are composed of a polymorphic lymphoid cell population exhibiting a variable degree of plasmacytic differentiation, cytologic atypia, and numbers of atypical immunoblasts. A clonal B-cell population was detected by immunoglobulin heavy and light chain gene rearrangement and/or EBV terminal repeat analysis in 8 of the 10 (80%) cases by Southern blotting. The nongermline hybridizing bands were usually faint, however, suggesting that the clonal B-cell population represented only a subpopulation within the polymorphic lesion. Strong clonal rearrangement bands were present in one case in which there was clear morphologic evidence of transformation to diffuse large cell lymphoma. This case exhibited C-MYC, BCL-6, and p53 gene mutations. One other case exhibited a p53 gene mutation. The remaining eight cases lacked C-MYC, BCL-6, RAS, and p53 gene alterations. Clonal EBV infection was detected in 4 of the 10 (40%) lesions. Like EBV-containing PT-LPDs, all four EBV-positive HIV-associated polymorphic lesions were associated with type A EBV. The Kaposi's sarcoma-associated herpesvirus was detectable in two cases by polymerase chain

  14. Iatrogenic colorectal Kaposi sarcoma complicating a refractory ulcerative colitis in a human immunodeficiency negative-virus patient.

    Science.gov (United States)

    Hamzaoui, Lamine; Kilani, Houda; Bouassida, Mahdi; Mahmoudi, Moufida; Chalbi, Emna; Siai, Karima; Ezzine, Heykel; Touinsi, Hassen; Azzouz, Mohamed M'saddak; Sassi, Sadok

    2013-01-01

    Kaposi sarcoma is a mesenchymal tumor associated to a human herpes virus-8. It often occurs in human immunodeficiency virus-positive subjects. Colorectal localization is rare. We report the case of a colorectal Kaposi sarcoma complicating a refractory ulcerative colitis treated with surgery after the failure of immunomodulator therapy in a human immunodeficiency virus-negative heterosexual man.

  15. Low immunologic response to highly active antiretroviral therapy in naive vertically human immunodeficiency virus type 1-infected children with severe immunodeficiency.

    Science.gov (United States)

    Resino, Salvador; Alvaro-Meca, Alejandro; de José, Maria Isabel; Martin-Fontelos, Pablo; Gutiérrez, Maria Dolores Gurbindo; Léon, Juan Antonio; Ramos, José Tomás; Ciria, Luis; Muñoz-Fernández, Maria Angeles

    2006-04-01

    We conducted a retrospective study to analyze the CD4 recovery of naive vertically human immunodeficiency virus-infected children with severe immunodeficiency who were followed up during at least 4 years of receiving highly active antiretroviral therapy (HAART). Children with baseline CD4 of or =25% after the 4th year on HAART. We conclude that starting HAART after severe immunosuppression of naive HIV-infected children may not be effective for recovery of normal %CD4.

  16. Successful Orthotopic Heart Transplantation and Immunosuppressive Management in 2 Human Immunodeficiency Virus-Seropositive Patients.

    Science.gov (United States)

    Conte, Antonio Hernandez; Kittleson, Michelle M; Dilibero, Deanna; Hardy, W David; Kobashigawa, Jon A; Esmailian, Fardad

    2016-02-01

    Few orthotopic heart transplantations have been performed in patients infected with the human immunodeficiency virus since the first such case was reported in 2001. Since that time, advances in highly active antiretroviral therapy have resulted in potent and durable suppression of the causative human immunodeficiency virus-accompanied by robust immune reconstitution, reversal of previous immunodeficiency, a marked decrease in opportunistic and other infections, and near-normal long-term survival. Although human immunodeficiency virus infection is not an absolute contraindication, few centers in the United States and Canada have performed heart transplantations in this patient population; these patients have been de facto excluded from this procedure in North America. Re-evaluation of the reasons for excluding these patients from cardiac transplantation is warranted in light of such significant advances in antiretroviral therapy. This case report documents successful orthotopic heart transplantation in 2 patients infected with human immunodeficiency virus, and we describe their antiretroviral therapy and immunosuppressive management challenges. Both patients were doing well without sequelae 43 and 38 months after transplantation.

  17. Chronic Inflammatory Periodontal Disease in Patients Diagnosed with Human Immunodeficiency Virus/AIDS in Cienfuegos

    Directory of Open Access Journals (Sweden)

    Nivia Gontán Quintana

    2013-08-01

    Full Text Available Background: human immunodeficiency virus increases patients´ susceptibility to infections. Consequently, a high incidence of periodontal diseases is observed among them. It is often associated with other lesions of the oral mucous. Objective: to determine the evolution of chronic inflammatory periodontal disease in patients diagnosed with human immunodeficiency virus/AIDS.Methods: a case series study involving HIV-positive patients who attended the Stomatology consultation in Cienfuegos was conducted. The Russell Periodontal Index and the Simplified Oral Hygiene Index were used. Patients were classified taking into account clinical and immunological categories. Statistical processing was performed through SPSS program version 15.0 and Chi-square tests were applied.Results: a high prevalence of chronic inflammatory periodontal disease was observed in patients with human immunodeficiency virus. Correlation with the oral hygiene of the patients studied was found. CD4 count showed no statistical significance in periodontal disease severity. All patients classified as A2 suffer from some stage of periodontal disease, which was the most affected clinical category in spite of presenting mild immunodeficiency.Conclusions: there is a high prevalence of chronic inflammatory periodontal disease in patients diagnosed with Human Immunodeficiency Virus in Cienfuegos and it is correlated with patient’s oral hygiene.

  18. Successful Orthotopic Heart Transplantation and Immunosuppressive Management in 2 Human Immunodeficiency Virus–Seropositive Patients

    Science.gov (United States)

    Kittleson, Michelle M.; Dilibero, Deanna; Hardy, W. David; Kobashigawa, Jon A.; Esmailian, Fardad

    2016-01-01

    Few orthotopic heart transplantations have been performed in patients infected with the human immunodeficiency virus since the first such case was reported in 2001. Since that time, advances in highly active antiretroviral therapy have resulted in potent and durable suppression of the causative human immunodeficiency virus—accompanied by robust immune reconstitution, reversal of previous immunodeficiency, a marked decrease in opportunistic and other infections, and near-normal long-term survival. Although human immunodeficiency virus infection is not an absolute contraindication, few centers in the United States and Canada have performed heart transplantations in this patient population; these patients have been de facto excluded from this procedure in North America. Re-evaluation of the reasons for excluding these patients from cardiac transplantation is warranted in light of such significant advances in antiretroviral therapy. This case report documents successful orthotopic heart transplantation in 2 patients infected with human immunodeficiency virus, and we describe their antiretroviral therapy and immunosuppressive management challenges. Both patients were doing well without sequelae 43 and 38 months after transplantation. PMID:27047290

  19. A Web-Based System To Enchance The Management Of Acquired Immunodeficiency Syndrome (AIDS/ Human Immunodeficiency Virus (HIV In Nigeria

    Directory of Open Access Journals (Sweden)

    Agbelusi Olutola

    2012-06-01

    Full Text Available Acquired Immunodeficiency Syndrome (AIDS, a global disease, caused by the Human Immunodeficiency Virus (HIV is arguably the greatest health problem of this age and there is need to make first class information on the management of HIV/AIDS available through the use of Web-Based Technology. This paper examined the various ways of contacting HIV and the effort made by Information and Technology to make life easier for people living with the virus in Nigeria. Questionnaires were distributed to Doctors and people living with HIV/AIDS to access their knowledge and belief about the said disease. MySQL was used to generate the database, to store all the vital information about the patients, their Doctors and their complaints. PHP programming for the implementation of the interfaces, Dreamweaver HTML for the design of the web-based application, T-test and Microsoft Excel were used for the analysis of data collected. The study looked into the occupation, age range and the marital status of different categories of people living with the virus. It was discovered that there were quite large numbers of people who are living with the virus.

  20. Prevalence and prognostic significance of infection with TT virus in patients infected with human immunodeficiency virus

    DEFF Research Database (Denmark)

    Christensen, JK; Eugen-Olsen, Jesper; Sørensen, M;

    2000-01-01

    No clear association between human disease and TT virus (TTV) has been documented. A possible pathogenic role of TTV was investigated in patients infected with human immunodeficiency virus (HIV). TTV serum concentrations were estimated in 185 HIV-infected patients by dilution polymerase chain...

  1. Infection of brain-derived cells with the human immunodeficiency virus.

    Science.gov (United States)

    Chiodi, F; Fuerstenberg, S; Gidlund, M; Asjö, B; Fenyö, E M

    1987-01-01

    A malignant glioma cell line was infected with the human T-lymphotropic virus type IIIB isolate of the human immunodeficiency virus. Infection appeared to be latent rather than productive. Through contact with monocytic or lymphoid cells, the virus present in the glioma cells could be transmitted and gave rise to a fully productive infection. Images PMID:3644020

  2. Low-dose growth hormone and human immunodeficiency virus-associated lipodystrophy syndrome: a pilot study

    DEFF Research Database (Denmark)

    Andersen, O; Haugaard, S B; Flyvbjerg, A

    2004-01-01

    BACKGROUND: Treatment with high doses (2-6 mg day(-1)) of human growth hormone (hGH) in patients with human immunodeficiency virus (HIV)-associated lipodystrophy syndrome (HALS) has been shown to increase concentrations of total insulin-like growth-factor-I (IGF-I) more than twofold greater than ...

  3. Primary Neuritic Hansen's Disease presenting as Ulnar Nerve Abscess in a Human Immunodeficiency Virus Positive Patient.

    Science.gov (United States)

    Karjigi, S; Herakal, K; Murthy, S C; Bathina, A; Kusuma, M R; Nikhil, K R Y

    2015-01-01

    Leprosy has been increasingly known to have an enigmatic relationship with human immunodeficiency virus infection. Co-infection may result in atypical manifestations of leprosy. A 45-year old human immunodeficiency virus-positive male; agricultural laborer presented with a swelling over right elbow, right hand deformity, generalized itching and recurrent vesicles overthe perinasal area. Clinical and investigational findings were consistent with mononeuritic type of Hansen's disease with right sided silent ulnar nerve abscess, partial claw hand. CD4+ count of the patientwas 430 cells/cmm. This patient also hadherpes simplex labialis, with HIV-associated pruritus. To the best of our knowledge such an atypical presentation has not been reported earlier.

  4. Humoral immune response to the entire human immunodeficiency virus envelope glycoprotein made in insect cells

    Energy Technology Data Exchange (ETDEWEB)

    Rusche, J.R.; Lynn, D.L.; Robert-Guroff, M.; Langlois, A.J.; Lyerly, H.K.; Carson, H.; Krohn, K.; Ranki, A.; Gallo, R.C.; Bolognesi, D.P.; Putney, S.D.

    1987-10-01

    The human immunodeficiency virus envelope gene was expressed in insect cells by using a Baculovirus expression vector. The protein has an apparent molecular mass of 160 kDa, appears on the surface of infected insect cells, and does not appear to be cleaved to glycoproteins gp120 and gp41. Goats immunized with the 160-kDa protein have high titers of antibody that neutralizes virus infection as measured by viral gene expression or cell cytolysis. In addition, immune sera can block fusion of human immunodeficiency virus-infected cells in culture. Both neutralization and fusion-blocking activities are bound to and eluted from immobilized gp120.

  5. Identification of a binding site of the human immunodeficiency virus envelope protein gp120 to neuronal specific tubulin

    Science.gov (United States)

    Avdoshina, Valeria; Taraballi, Francesca; Dedoni, Simona; Corbo, Claudia; Paige, Mikell; Kont, Yasemin Saygideğer; Üren, Aykut; Tasciotti, Ennio; Mocchetti, Italo

    2016-01-01

    Human immunodeficiency virus-1 (HIV) promotes synaptic simplification and neuronal apoptosis, and causes neurological impairments termed HIV-associated neurological disorders (HAND). HIV-associated neurotoxicity may be brought about by acute and chronic mechanisms that still remain to be fully characterized. The HIV envelope glycoprotein gp120 causes neuronal degeneration similar to that observed in HAND subjects. The present study was undertaken to discover novel mechanisms of gp120 neurotoxicity that could explain how the envelope protein promotes neurite pruning. Gp120 has been shown to associate with various intracellular organelles as well as microtubules in neurons. We then analyzed lysates of neurons exposed to gp120 with liquid chromatography mass spectrometry for potential protein interactors. We found that one of the proteins interacting with gp120 is tubulin β-3 (TUBB3), a major component of neuronal microtubules. We then tested the hypothesis that gp120 binds to neuronal microtubules. Using surface plasmon resonance we confirmed that gp120 binds with high affinity to neuronal specific TUBB3. We have also identified the binding site of gp120 to TUBB3. We then designed a small peptide (Helix-A) that displaced gp120 from binding to TUBB3. To determine whether this peptide could prevent gp120-mediated neurotoxicity, we crosslinked Helix-A to mesoporous silica nanoparticles (Helix-A nano) to enhance the intracellular delivery of the peptide. We then tested the neuroprotective property of Helix-A nano against three strains of gp120 in rat cortical neurons. Helix-A nano prevented gp120-mediated neurite simplification as well as neuronal loss. These data propose that gp120 binding to TUBB3 could be another mechanism of gp120 neurotoxicity. PMID:26826352

  6. 38 CFR 1.487 - Disclosure of information related to infection with the human immunodeficiency virus to the...

    Science.gov (United States)

    2010-07-01

    ... related to infection with the human immunodeficiency virus to the spouse or sexual partner of the patient... the human immunodeficiency virus to the spouse or sexual partner of the patient. (a) Subject to... determine whether the patient is infected with such virus, identified as being a sexual partner of...

  7. 38 CFR 1.486 - Disclosure of information related to infection with the human immunodeficiency virus to public...

    Science.gov (United States)

    2010-07-01

    ... related to infection with the human immunodeficiency virus to public health authorities. 1.486 Section 1... Disclosures Without Patient Consent § 1.486 Disclosure of information related to infection with the human immunodeficiency virus to public health authorities. (a) In the case of any record which is maintained...

  8. Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV.

    Directory of Open Access Journals (Sweden)

    Debra A Wadford

    Full Text Available RT-SHIV is a chimera of simian immunodeficiency virus (SIV containing the reverse transcriptase (RT-encoding region of human immunodeficiency virus type 1 (HIV-1 within the backbone of SIVmac239. It has been used in a non-human primate model for studies of non-nucleoside RT inhibitors (NNRTI and highly active antiretroviral therapy (HAART. We and others have identified several mutations that arise in the "foreign" HIV-1 RT of RT-SHIV during in vivo replication. In this study we catalogued amino acid substitutions in the HIV-1 RT and in regions of the SIV backbone with which RT interacts that emerged 30 weeks post-infection from seven RT-SHIV-infected rhesus macaques. The virus set points varied from relatively high virus load, moderate virus load, to undetectable virus load. The G196R substitution in RT was detected from 6 of 7 animals at week 4 post-infection and remained in virus from 4 of 6 animals at week 30. Virus from four high virus load animals showed several common mutations within RT, including L74V or V75L, G196R, L214F, and K275R. The foreign RT from high virus load isolates exhibited as much variation as that of the highly variable envelope surface glycoprotein, and 10-fold higher than that of the native RT of SIVmac239. Isolates from moderate virus load animals showed much less variation in the foreign RT than the high virus load isolates. No variation was found in SIVmac239 genes known to interact with RT. Our results demonstrate substantial adaptation of the foreign HIV-1 RT in RT-SHIV-infected macaques, which most likely reflects selective pressure upon the foreign RT to attain optimal activity within the context of the chimeric RT-SHIV and the rhesus macaque host.

  9. High-affinity olfactory receptor for the death-associated odor cadaverine

    OpenAIRE

    2013-01-01

    Cadaverine and putrescine, two diamines emanating from decaying flesh, are strongly repulsive odors to humans but serve as innate attractive or social cues in other species. Here we show that zebrafish, a vertebrate model system, exhibit powerful and innate avoidance behavior to both diamines, and identify a high-affinity olfactory receptor for cadaverine.

  10. Study of infections among human immunodeficiency virus/acquired immunodeficiency syndrome patients in Shadan Hospital, Telangana, India

    Directory of Open Access Journals (Sweden)

    Sukumar Gajjala Reddy

    2016-01-01

    Full Text Available Background: Human immunodeficiency virus (HIV pandemicity is a major concern today as it causes greater loss of productivity than any other disease. HIV infection leads to profound immune deficiency and patients become highly susceptible to opportunistic infections (OIs. HIV epidemic in India is heterogeneous in nature, both in terms of routes of transmission as well as geographical spread. Aims: (1 Determine prevalence of OIs among HIV-seropositive patients and their relation to CD4 count and to focus on the routes of transmission. (2 Analyze the route of transmission. Methods: This is a single-center prospective study including all the patients attending acquired immunodeficiency syndrome (AIDS care center during the period of January 2014 to December 2014. Results: Among 71 patients included in this study, mean age was 30 years, 57.7% (41 patients were male, 42.3% (30 patients were female. Mean CD4 cell count of the study group was 260.11 and of patients on antiretroviral therapy increased subsequently to 553.37 cells/ml. Among the infections, the prevalence of candidiasis, tuberculosis (TB, tinea infections, seborrheic dermatitis, giardiasis, cryptosporidiosis, and Entamoeba histolytica were 36.6%, 29.58%, 4.22%, 2.82%, 4.22%, 1.4%, and 1.4%. Most predominant routes were heterosexual transmission at 94.3%. It was followed by vertical transmission seen in 2.8%. Homosexual transmission is 1.4% and intravenous drug abuse 1.4%. Conclusion: The frequency of infections among HIV/AIDS patients has got a similar linear relation with CD4 cell count. This study reports data will serve as a matrix for future evaluation. It is concluded that candidiasis, TB are the most common infections in the HIV-seropositive patients in the present study group.

  11. [Clinical features of oral lesions in patients with human immunodeficiency virus infection/acquired immunodeficiency syndrome in Guangxi autonomous region].

    Science.gov (United States)

    Yong, Xiangzhi; Jiang, Lanlan; Lu, Xiangchan; Liu, Wei; Wu, Nianning; Tao, Renchuan

    2014-08-01

    To investigate the features of oral lesions in patients with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS). A total of 127 HIV-seropositive patients were interviewed for health information and examined for their HIV-related oral lesions according to the EC Clearing House Criteria on Oral Problems related to HIV-Infection (1992). The examinations were conducted by dental specialist and HIV specialist. The CD4 T cell count in peripheral blood of the patients was tested by flow cytometry. The patients were divided into HIV- infected group (42) and AIDS group (85) according to CDC Classification System for HIV- Infected Adults and Adolescents (revised in 1993). Chi-square test was used to test the relationship between systemic disease and oral lesions, and the difference of the prevalence of oral lesions between the two groups. Among the 127 patients, oral candidiasis (51/127), oral hairy leukoplakia (24/127) were common oral manifestation. There was no relationship between the oral manifestation and systemic disease (P = 0.397). The occurrence of oral lesions and oral candidiasis was significantly different between the two groups (χ² = 7.684, P = 0.006; χ² = 14.410, P < 0.001). The CD4 count was related to the prevalence of oral lesions (P = 0.006) and oral candidasis (P = 0.003). Most oral lesions appeared before the appearance of systemic disease. Oral candidiasis and oral hairy leukoplakia were the most common lesions.Oral lesions had no relationship with systemic disease but could be still an indicator for disease progress.

  12. Acanthamoeba keratitis in a non-contact lens wearer with human immunodeficiency virus

    DEFF Research Database (Denmark)

    Hansen, Birgitte Rønde; Kronborg, Gitte

    2003-01-01

    Acanthamoeba keratitis is potentially blinding and often associated with contact lens wearing. A human immunodeficiency virus (HIV)-positive patient, a non-contact lens wearer, presented with keratitis. She experienced a protracted course of disease, characterized by exacerbations and remissions...

  13. Human Immunodeficiency Virus (HIV) Testing and False Disclosures in Heterosexual College Students

    Science.gov (United States)

    Marelich, William D.; Clark, Tonya

    2004-01-01

    The authors assessed factors that motivate individuals to report negative human immunodeficiency virus (HIV) antibody test results, although they had never been tested. In particular, they investigated sexual intimacy motives associated with the needs for affiliation, sex, and dominance as contributing factors for faulty disclosures. Participants…

  14. Schistosomiasis and infection with human immunodeficiency virus 1 in rural Zimbabwe

    DEFF Research Database (Denmark)

    Erikstrup, Christian; Kallestrup, Per; Zinyama-Gutsire, Rutendo B L;

    2008-01-01

    We previously reported that treatment for schistosomiasis in persons infected with human immunodeficiency virus 1 (HIV-1) attenuated HIV replication as measured by plasma HIV RNA. We investigated systemic inflammation as measured by plasma levels of soluble tumor necrosis factor-alpha receptor II...

  15. Human immunodeficiency virus infection and inter-arm blood pressure difference

    Institute of Scientific and Technical Information of China (English)

    杨明

    2013-01-01

    Objective To analyze the association between cardiovascular risk factors and inter-arm blood pressure difference(IAD) in patients with human immunodeficiency virus(HIV) infection,and to confirm as to whether HIV infection promotes atherosclerosis. Methods 41 HAART-naive HIV infected-patients and 43 healthy people were

  16. Prevalence of Human Immunodeficiency Virus Testing and Associated Risk Factors in College Students

    Science.gov (United States)

    Dennison, Olivia; Wu, Qishan; Ickes, Melinda

    2014-01-01

    Objective: This study documents the prevalence of human immunodeficiency virus (HIV) testing in a sample of college students and examines associated demographic and behavioral characteristics. Participants: College students aged 18 or older were randomly selected to participate in a health behavior survey at a southeastern university in September…

  17. TUBERCULOSIS IN HUMAN IMMUNODEFICIENCY VIRUS-EXPOSED OR VIRUS-INFECTED UNITED-STATES CHILDREN

    NARCIS (Netherlands)

    GUTMAN, LT; MOYE, J; ZIMMER, B; TIAN, C

    1994-01-01

    This study was designed to provide a preliminary assessment of the occurrence of tuberculosis exposure, infection and disease within a national sample of infants and children with human immunodeficiency virus (HIV) exposure or infection, and to determine the prevalence of Mycobacterium tuberculosis

  18. Improvement of lymphocyte proliferation in human immunodeficiency virus infection after recombinant interleukin-2 treatment

    DEFF Research Database (Denmark)

    Afzelius, P; Nielsen, S D; Nielsen, Jens Ole

    1999-01-01

    In this study, the effect of recombinant interleukin-2 (rIL-2) on the function of peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-infected patients was examined. Using polymerase chain reaction (PCR), an impaired ability of PBMC from 8 patients to respond upon mi...

  19. High human immunodeficiency virus incidence in a cohort of Rwandan female sex workers

    NARCIS (Netherlands)

    S.L. Braunstein; C.M. Ingabire; E. Kestelyn; A.U. Uwizera; L. Mwamarangwe; J. Ntirushwa; D. Nash; N.J. Veldhuijzen; A. Nel; J. Vyankandondera; J.H.H.M. van de Wijgert

    2011-01-01

    Measurement of human immunodeficiency virus(HIV) incidence among female sex workers in Rwanda is a key part of preparing for HIV prevention trials. HIV-negative, nonpregnant female sex workers (N =397) were tested for HIV-1, sexually transmitted infections, and pregnancy quarterly for 12 months, and

  20. TUBERCULOSIS IN HUMAN IMMUNODEFICIENCY VIRUS-EXPOSED OR VIRUS-INFECTED UNITED-STATES CHILDREN

    NARCIS (Netherlands)

    GUTMAN, LT; MOYE, J; ZIMMER, B; TIAN, C

    1994-01-01

    This study was designed to provide a preliminary assessment of the occurrence of tuberculosis exposure, infection and disease within a national sample of infants and children with human immunodeficiency virus (HIV) exposure or infection, and to determine the prevalence of Mycobacterium tuberculosis

  1. Conflicting selective forces affect T cell receptor contacts in an immunodominant human immunodeficiency virus epitope

    DEFF Research Database (Denmark)

    Iversen, Astrid K N; Stewart-Jones, Guillaume; Learn, Gerald H

    2006-01-01

    Cytotoxic T lymphocytes (CTLs) are critical for the control of human immunodeficiency virus, but containment of virus replication can be undermined by mutations in CTL epitopes that lead to virus escape. We analyzed the evolution in vivo of an immunodominant, HLA-A2-restricted CTL epitope and fou...

  2. CYTOMEGALOVIRUS RETINITIS ASSOCIATED WITH OCCLUSIVE VASCULOPATHY IN AN ELDERLY, HUMAN IMMUNODEFICIENCY VIRUS-NEGATIVE MAN.

    Science.gov (United States)

    Moussa, Kareem; Doan, Thuy; Stewart, Jay M; Shantha, Jessica; Gonzales, John; Acharya, Nisha; Cunningham, Emmett T

    2017-09-20

    To present a case of cytomegalovirus (CMV) retinitis associated with occlusive vasculopathy presenting as sudden unilateral loss of vision in a human immunodeficiency virus-negative elderly man. Clinical case report and literature review. An 84-year-old Chinese man with diabetes mellitus and primary open-angle glaucoma was seen in consultation by our uveitis service for evaluation of sudden vision loss in the right eye. Examination revealed an occlusive retinal vasculopathy. An extensive diagnostic workup was performed, including fluorescein angiography, serologic testing for infectious etiologies including syphilis and tuberculosis and a temporal artery biopsy. The patient was treated with high-dose oral prednisone, after which the biopsy returned negative for giant-cell arteritis. Three weeks after initial presentation, the patient was noted to have a new area of retinitis in the temporal periphery. An anterior chamber paracentesis was performed, and the fluid was sent for directed polymerase chain reaction testing, which returned positive for CMV. Human immunodeficiency virus testing was negative. He was treated with oral valganciclovir and intravitreal foscarnet injections and the infection subsequently resolved. Cytomegalovirus infection can be associated with occlusive vasculopathy in human immunodeficiency virus-negative individuals. The diagnosis of CMV retinitis should be considered in patients with human immunodeficiency virus-negative who have other conditions that may compromise immune function, particularly advanced age, diabetes mellitus, malignancy, or use of immunosuppressive agents.

  3. Improvement of lymphocyte proliferation in human immunodeficiency virus infection after recombinant interleukin-2 treatment

    DEFF Research Database (Denmark)

    Afzelius, P; Nielsen, S D; Nielsen, Jens Ole

    1999-01-01

    In this study, the effect of recombinant interleukin-2 (rIL-2) on the function of peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-infected patients was examined. Using polymerase chain reaction (PCR), an impaired ability of PBMC from 8 patients to respond upon...

  4. Detection of human immunodeficiency virus DNA in cultured human glial cells by means of the polymerase chain reaction

    DEFF Research Database (Denmark)

    Teglbjaerg, L L; Hansen, J E; Dalbøge, H;

    1991-01-01

    This report describes the use of the polymerase chain reaction (PCR) for the detection of viral genomic sequences in latently infected cells. Infection with human immunodeficiency virus in cultures of human glial cells was demonstrated, using nucleic acid amplification followed by dot blot...

  5. Vif Proteins from Diverse Human Immunodeficiency Virus/Simian Immunodeficiency Virus Lineages Have Distinct Binding Sites in A3C.

    Science.gov (United States)

    Zhang, Zeli; Gu, Qinyong; Jaguva Vasudevan, Ananda Ayyappan; Jeyaraj, Manimehalai; Schmidt, Stanislaw; Zielonka, Jörg; Perković, Mario; Heckel, Jens-Ove; Cichutek, Klaus; Häussinger, Dieter; Smits, Sander H J; Münk, Carsten

    2016-11-15

    Lentiviruses have evolved the Vif protein to counteract APOBEC3 (A3) restriction factors by targeting them for proteasomal degradation. Previous studies have identified important residues in the interface of human immunodeficiency virus type 1 (HIV-1) Vif and human APOBEC3C (hA3C) or human APOBEC3F (hA3F). However, the interaction between primate A3C proteins and HIV-1 Vif or natural HIV-1 Vif variants is still poorly understood. Here, we report that HIV-1 Vif is inactive against A3Cs of rhesus macaques (rhA3C), sooty mangabey monkeys (smmA3C), and African green monkeys (agmA3C), while HIV-2, African green monkey simian immunodeficiency virus (SIVagm), and SIVmac Vif proteins efficiently mediate the depletion of all tested A3Cs. We identified that residues N/H130 and Q133 in rhA3C and smmA3C are determinants for this HIV-1 Vif-triggered counteraction. We also found that the HIV-1 Vif interaction sites in helix 4 of hA3C and hA3F differ. Vif alleles from diverse HIV-1 subtypes were tested for degradation activities related to hA3C. The subtype F-1 Vif was identified to be inactive for degradation of hA3C and hA3F. The residues that determined F-1 Vif inactivity in the degradation of A3C/A3F were located in the C-terminal region (K167 and D182). Structural analysis of F-1 Vif revealed that impairing the internal salt bridge of E171-K167 restored reduction capacities to A3C/A3F. Furthermore, we found that D101 could also form an internal interaction with K167. Replacing D101 with glycine and R167 with lysine in NL4-3 Vif impaired its counteractivity to A3F and A3C. This finding indicates that internal interactions outside the A3 binding region in HIV-1 Vif influence the capacity to induce degradation of A3C/A3F.

  6. Profound CD4+ T lymphocytopenia in human immunodeficiency virus negative individuals, improved with anti-human herpes virus treatment

    Directory of Open Access Journals (Sweden)

    Díaz Betancourt, María Lilia

    2012-12-01

    Full Text Available Lymphocytopenia and CD4+ T lymphocytopenia can be associated with many bacterial, fungal, parasite and viral infections. They can also be found in autoimmune and neoplastic diseases, common variable immunodeficiency syndrome, physical, psychological and traumatic stress, malnutrition and immunosuppressive therapy. Besides, they can also be brought into relation, without a known cause, with idiopathic CD4+ T lymphocytopenia. Among viral infections, the Retrovirus, specially the human immunodeficiency virus, is the most frequently cause. However, many acute viral infections, including cytomegalovirus and Epstein Barr virus can be associated with transient ymphocytopenia and CD4+ T lymphocytopenia. As is well known, transient ymphocytopenia and CD4+ T lymphocytopenia are temporary and overcome when the disease improves. Nonetheless, severe CD4+ T Lymphocytopenia associated with chronic infections by human herpes virus has not been reported. We describe 6 cases of human immunodeficiency virus negative patients, with chronic cytomegalovirus and Epstein Barr virus infections and profound lymphocytopenia with clinical symptoms of cellular immunodeficiency. These patients improved rapidly with ganciclovir or valganciclovir treatment. We claim here that it is important to consider the chronic human herpes virus infection in the differential diagnosis of profoundly CD4+ T lymphocytopenia etiology, when human mmunodeficiency virus is absent, in order to start effective treatment and to determine, in future studies, the impact of chronic human herpes virus infection in human beings’ health

  7. Species-Specific Metastasis of Human Tumor Cells in the Severe Combined Immunodeficiency Mouse Engrafted with Human Tissue

    Science.gov (United States)

    Shtivelman, Emma; Namikawa, Reiko

    1995-05-01

    We have attempted to model human metastatic disease by implanting human target organs into the immunodeficient C.B-17 scid/scid (severe combined immunodeficiency; SCID) mouse, creating SCID-hu mice. Preferential metastasis to implants of human fetal lung and human fetal bone marrow occurred after i.v. injection of human small cell lung cancer (SCLC) cells into SCID-hu mice; the homologous mouse organs were spared. Clinically more aggressive variant SCLC cells metastasized more efficiently to human fetal lung implants than did cells from classic SCLC. Metastasis of variant SCLC to human fetal bone marrow was enhanced in SCID-hu mice exposed to γ-irradiation or to interleukin 1α. These data indicate that the SCID-hu mice may provide a model in which to study species- and tissue-specific steps of the human metastatic process.

  8. Family and other social factors contributing to differences in human immunodeficiency virus infection between South Africa and Bangladesh

    NARCIS (Netherlands)

    van Ginneken, J.K.S.

    2008-01-01

    The objective of this study is to draw attention to the importance of social, cultural, economic and political factors as causes of the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic in South Africa by comparing the current situation in this country with Banglade

  9. Family and other social factors contributing to differences in human immunodeficiency virus infection between South Africa and Bangladesh

    NARCIS (Netherlands)

    van Ginneken, J.K.S.

    2008-01-01

    The objective of this study is to draw attention to the importance of social, cultural, economic and political factors as causes of the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic in South Africa by comparing the current situation in this country with Banglade

  10. Developmentally-faithful and effective human erythropoiesis in immunodeficient and Kit mutant mice.

    Science.gov (United States)

    Fiorini, Claudia; Abdulhay, Nour J; McFarland, Sean K; Munschauer, Mathias; Ulirsch, Jacob C; Chiarle, Roberto; Sankaran, Vijay G

    2017-09-01

    Immunodeficient mouse models have been valuable for studies of human hematopoiesis, but high-fidelity recapitulation of erythropoiesis in most xenograft recipients remains elusive. Recently developed immunodeficient and Kit mutant mice, however, have provided a suitable background to achieve higher-level human erythropoiesis after long-term hematopoietic engraftment. While there has been some characterization of human erythropoiesis in these models, a comprehensive analysis from various human developmental stages has not yet been reported. Here, we have utilized cell surface phenotypes, morphologic analyses, and molecular studies to fully characterize human erythropoiesis from multiple developmental stages in immunodeficient and Kit mutant mouse models following long-term hematopoietic stem and progenitor cell engraftment. We show that human erythropoiesis in such models demonstrates complete maturation and enucleation, as well as developmentally appropriate globin gene expression. These results provide a framework for future studies to utilize this model system for interrogating disorders affecting human erythropoiesis and for developing improved therapeutic approaches. © 2017 Wiley Periodicals, Inc.

  11. The burden of sepsis in critically ill human immunodeficiency virus-infected patients--a brief review.

    Science.gov (United States)

    Moreira, José

    2015-01-01

    Since the advent of highly active antiretroviral therapy in 1996, we have seen dramatic changes in morbi-mortality rates from human immunodeficiency virus-positive patients. If on the one hand, the immunologic preservation-associated with the use of current antiretroviral therapy markedly diminishes the incidence of opportunistic infections, on the other hand it extended life expectancy of human immunodeficiency virus-infected individuals similarly to the general population. However, the management of critically ill human immunodeficiency virus-infected patients remains challenging and troublesome for practicing clinician. Sepsis - a complex systemic inflammatory syndrome in response to infection - is the second leading cause of intensive care unit admission in both human immunodeficiency virus-infected and uninfected populations. Recent data have emerged describing a substantial burden of sepsis in the infected population, in addition, to a much poorer prognosis in this group. Many factors contribute to this outcome, including specific etiologies, patterns of inflammation, underlying immune dysregulation related to chronic human immunodeficiency virus infection and delays in prompt diagnosis and treatment. This brief review explores the impact of sepsis in the context of human immunodeficiency virus infection, and proposes future directions for better management and prevention of human immunodeficiency virus-associated sepsis.

  12. Acquired epidermodysplasia verruciformis in a child with the human immunodeficiency virus.

    Science.gov (United States)

    Cowan, Katelyn R; Gonzalez Santiago, Tania M; Tollefson, Megha M

    2013-01-01

    Epidermodysplasia verruciformis (EDV) is a rare genodermatosis characterized by susceptibility to human papilloma virus (HPV) infection. An acquired form of EDV has been described in the setting of immunosuppression, including in patients with the human immunodeficiency virus (HIV). We present the case of an HIV-positive, adopted Haitian boy who presented with EDV. Few cases of chidren with HIV and acquired EDV have been reported and are likely underrecognized.

  13. In vivo formation of complex microvessels lined by human endothelial cells in an immunodeficient mouse

    OpenAIRE

    2000-01-01

    We have identified conditions for forming cultured human umbilical vein endothelial cells (HUVEC) into tubes within a three-dimensional gel that on implantation into immunoincompetent mice undergo remodeling into complex microvessels lined by human endothelium. HUVEC suspended in mixed collagen/fibronectin gels organize into cords with early lumena by 24 h and then apoptose. Twenty-hour constructs, s.c. implanted in immunodeficient mice, display HUVEC-lined thin-walled microvessels within the...

  14. Immune reconstitution syndrome in a human immunodeficiency virus infected child due to giardiasis leading to shock

    Directory of Open Access Journals (Sweden)

    Sneha Nandy

    2015-01-01

    Full Text Available Human immunodeficiency virus (HIV-associated immune reconstitution inflammatory syndrome has been reported in association with tuberculosis, herpes zoster (shingles, Cryptococcus neoformans, Kaposi′s sarcoma, Pneumocystis pneumonia, hepatitis B virus, hepatitis C virus, herpes simplex virus, Histoplasma capsulatum, human papillomavirus, and Cytomegalovirus. However, it has never been documented with giardiasis. We present a 7-year-old HIV infected girl who developed diarrhea and shock following the initiation of antiretroviral therapy, and her stool showed the presence of giardiasis.

  15. A literature review on cardiovascular risk in human immunodeficiency virus-infected patients: implications for clinical management

    Directory of Open Access Journals (Sweden)

    Mansueto Gomes Neto

    2013-12-01

    Full Text Available INTRODUCTION: In recent years, there has been growing concern about an increasing rate of cardiovascular diseases in human immunodeficiency virus-infected patients, which could be associated with side effects of highly active antiretroviral therapy. It is likely that the metabolic disorders related to anti-human immunodeficiency virus treatment will eventually translate into a increased cardiovascular risk in patients submitted to such regimens. OBJECTIVE: To evaluate if human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy are at higher risk of cardiovascular diseases than human immunodeficiency virus infected patients not receiving highly active antiretroviral therapy, or the general population. RESEARCH DESIGN AND METHODS: We conducted a computer-based search in representative databases, and also performed manual tracking of citations in selected articles. RESULT: The available evidence suggests an excess risk of cardiovascular events in human immunodeficiency virus-infected persons compared to non-human immunodeficiency virus infected individuals. The use of highly active antiretroviral therapy is associated with increased levels of total cholesterol, triglycerides, low-density lipoprotein and morphological signs of cardiovascular diseases. Some evidence suggested that human immunodeficiency virus-infected individuals on highly active antiretroviral therapy regimens are at increased risk of dyslipidemia, ischemic heart disease, and myocardial infarction, particularly if the highly active antiretroviral therapy regimen contains a protease inhibitor. CONCLUSION: Physicians must weigh the cardiovascular risk against potential benefits when prescribing highly active antiretroviral therapy. Careful cardiac screening is warranted for patients who are being evaluated for, or who are receiving highly active antiretroviral therapy regimens, particularly for those with known underlying cardiovascular risk

  16. Generation of Immunodeficient Mice Bearing Human Immune Systems by the Engraftment of Hematopoietic Stem Cells.

    Science.gov (United States)

    Hasgur, Suheyla; Aryee, Ken Edwin; Shultz, Leonard D; Greiner, Dale L; Brehm, Michael A

    2016-01-01

    Immunodeficient mice are being used as recipients of human hematopoietic stem cells (HSC) for in vivo analyses of human immune system development and function. The development of several stocks of immunodeficient Prkdc (scid) (scid), or recombination activating 1 or 2 gene (Rag1 or Rag2) knockout mice bearing a targeted mutation in the gene encoding the IL2 receptor gamma chain (IL2rγ), has greatly facilitated the engraftment of human HSC and enhanced the development of functional human immune systems. These "humanized" mice are being used to study human hematopoiesis, human-specific immune therapies, human-specific pathogens, and human immune system homeostasis and function. The establishment of these model systems is technically challenging, and levels of human immune system development reported in the literature are variable between laboratories. The use of standard protocols for optimal engraftment of HSC and for monitoring the development of the human immune systems would enable more direct comparisons between humanized mice generated in different laboratories. Here we describe a standard protocol for the engraftment of human HSC into 21-day-old NOD-scid IL2rγ (NSG) mice using an intravenous injection approach. The multiparameter flow cytometry used to monitor human immune system development and the kinetics of development are described.

  17. Human immunodeficiency virus type 1, human protein interaction database at NCBI.

    Science.gov (United States)

    Fu, William; Sanders-Beer, Brigitte E; Katz, Kenneth S; Maglott, Donna R; Pruitt, Kim D; Ptak, Roger G

    2009-01-01

    The 'Human Immunodeficiency Virus Type 1 (HIV-1), Human Protein Interaction Database', available through the National Library of Medicine at www.ncbi.nlm.nih.gov/RefSeq/HIVInteractions, was created to catalog all interactions between HIV-1 and human proteins published in the peer-reviewed literature. The database serves the scientific community exploring the discovery of novel HIV vaccine candidates and therapeutic targets. To facilitate this discovery approach, the following information for each HIV-1 human protein interaction is provided and can be retrieved without restriction by web-based downloads and ftp protocols: Reference Sequence (RefSeq) protein accession numbers, Entrez Gene identification numbers, brief descriptions of the interactions, searchable keywords for interactions and PubMed identification numbers (PMIDs) of journal articles describing the interactions. Currently, 2589 unique HIV-1 to human protein interactions and 5135 brief descriptions of the interactions, with a total of 14,312 PMID references to the original articles reporting the interactions, are stored in this growing database. In addition, all protein-protein interactions documented in the database are integrated into Entrez Gene records and listed in the 'HIV-1 protein interactions' section of Entrez Gene reports. The database is also tightly linked to other databases through Entrez Gene, enabling users to search for an abundance of information related to HIV pathogenesis and replication.

  18. The efficacy of inosine pranobex in preventing the acquired immunodeficiency syndrome in patients with human immunodeficiency virus infection. The Scandinavian Isoprinosine Study Group

    DEFF Research Database (Denmark)

    Pedersen, C; Sandström, E; Petersen, C S

    1990-01-01

    We performed a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of inosine pranobex (Isoprinosine) [corrected] in the treatment of patients with human immunodeficiency virus (HIV) infection but without manifest acquired immunodeficiency syndrome (AIDS). A total...... or the development of other HIV-related conditions, with the exception of thrush, which developed in fewer patients in the inosine pranobex group (P = 0.05). No serious side effects were observed. We conclude that treatment with inosine pranobex delays progression to AIDS in patients with HIV infection. The duration...

  19. Modeling Human Severe Combined Immunodeficiency and Correction by CRISPR/Cas9-Enhanced Gene Targeting.

    Science.gov (United States)

    Chang, Chia-Wei; Lai, Yi-Shin; Westin, Erik; Khodadadi-Jamayran, Alireza; Pawlik, Kevin M; Lamb, Lawrence S; Goldman, Frederick D; Townes, Tim M

    2015-09-08

    Mutations of the Janus family kinase JAK3 gene cause severe combined immunodeficiency (SCID). JAK3 deficiency in humans is characterized by the absence of circulating T cells and natural killer (NK) cells with normal numbers of poorly functioning B cells (T(-)B(+)NK(-)). Using SCID patient-specific induced pluripotent stem cells (iPSCs) and a T cell in vitro differentiation system, we demonstrate a complete block in early T cell development of JAK3-deficient cells. Correction of the JAK3 mutation by CRISPR/Cas9-enhanced gene targeting restores normal T cell development, including the production of mature T cell populations with a broad T cell receptor (TCR) repertoire. Whole-genome sequencing of corrected cells demonstrates no CRISPR/Cas9 off-target modifications. These studies describe an approach for the study of human lymphopoiesis and provide a foundation for gene correction therapy in humans with immunodeficiencies.

  20. [The incidence of oral candidiasis in patients with human immunodeficiency virus infection/acquired immunodeficiency syndrome from Yunnan, China].

    Science.gov (United States)

    Wen, Yan; Li, Chengwen; Pei, Junhaoxiang; Bai, Jinsong; Yang, Xianghong; Duan, Kaiwen

    2014-08-01

    To assess the incidence of oral candidiasis and its influencing factors in patients with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS). An oral examination was conducted in the 1 566 HIV/AIDS patients in the Third Hospital of Kunming from March 2008 to September 2012 (M/F: 1 062/504, age range: 0.2 to 84.0 years old). The HIV viral load (HIV- RNA) and peripheral blood CD4 count were respectively analyzed by Bayer Q340 fluorescence signal surveying instrument (bDNA method) and flow cytometry analysis. The information on usage of highly active anti-retroviral (HAART) drugs and transmission of HIV were obtained through questionnaires. The incidence of oral candidiasis in patients with different HIV-RNA levels and CD4 count and the use of HAART was analyzed and compared. The total incidence of oral candidosis was 31.0% (486/1 566) and there was no difference in sex. The oral lesions were presented by three types, psudomembranous candidosis (PC), erythematous candidosis (EC) and angular cheilitis (AC), and the morbidity was 13.9% (217/1 566), 17.0% (267/1 566) and 4.9% (77/1 566), respectively. The average level of CD4 count in psudomembranous candidosis, erythematous candidosis and angular cheilitis [81.0 (146.0), 74.0 (152.0) and 69.0 (121.5) cell/µl] showed no significant difference (P > 0.05). The incidence of oral candidiasis in non-HAART and HAART subjects were 36.3% (402/1 107) and 18.3% (84/459), respectively (P = 0.000). The CD4 count and absolute counts of HIV viral load in oral candidiasis patients and non-oral candidiasis patients had significant difference (Z = -10.261, P = 0.000 and Z = -4.762, P = 0.000). The morbidity of oral candidiasis in HIV/AIDS patients in Yunnan Province was high, including PC, EC and AC and hyperplastic candidosis was not detected. The incidence was related to the degree of immune suppression and HIV viral load.

  1. MUC1 in human milk blocks transmission of human immunodeficiency virus from dendritic cells to T cells

    NARCIS (Netherlands)

    Saeland, E.; Jong, de M.A.W.P.; Nabatov, A.; Kalay, H.; Kooijk, van Y.; Geijtenbeek, T.B.H.

    2009-01-01

    Mother-to-child transmission of human immunodeficiency virus-1 (HIV-1) occurs frequently via breast-feeding. HIV-1 targets DC-SIGN+ dendritic cells (DCs) in mucosal areas that allow efficient transmission of the virus to T cells. Here, we demonstrate that the epithelial mucin MUC1, abundant in milk,

  2. MUC1 in human milk blocks transmission of human immunodeficiency virus from dendritic cells to T cells

    NARCIS (Netherlands)

    Saeland, E.; Jong, de M.A.W.P.; Nabatov, A.; Kalay, H.; Kooijk, van Y.; Geijtenbeek, T.B.H.

    2009-01-01

    Mother-to-child transmission of human immunodeficiency virus-1 (HIV-1) occurs frequently via breast-feeding. HIV-1 targets DC-SIGN+ dendritic cells (DCs) in mucosal areas that allow efficient transmission of the virus to T cells. Here, we demonstrate that the epithelial mucin MUC1, abundant in milk,

  3. Human immunodeficiency virus seroconversion presenting with acute inflammatory demyelinating polyneuropathy: a case report

    Directory of Open Access Journals (Sweden)

    Sloan Derek J

    2008-12-01

    Full Text Available Abstract Introduction Acute Human Immunodeficiency Virus infection is associated with a range of neurological conditions. Guillain-Barré syndrome is a rare presentation; acute inflammatory demyelinating polyneuropathy is the commonest form of Guillain-Barré syndrome. Acute inflammatory demyelinating polyneuropathy has occasionally been reported in acute Immunodeficiency Virus infection but little data exists on frequency, management and outcome. Case presentation We describe an episode of Guillain-Barré syndrome presenting as acute inflammatory demyelinating polyneuropathy in a 30-year-old man testing positive for Immunodeficiency Virus, probably during acute seroconversion. Clinical suspicion was confirmed by cerebrospinal fluid analysis and nerve conduction studies. Rapid clinical deterioration prompted intravenous immunoglobulin therapy and early commencement of highly active anti-retroviral therapy. All symptoms resolved within nine weeks. Conclusion Unusual neurological presentations in previously fit patients are an appropriate indication for Immunodeficiency-Virus testing. Highly active anti-retroviral therapy with adequate penetration of the central nervous system should be considered as an early intervention, alongside conventional therapies such as intravenous immunoglobulin.

  4. Development and characterization of high affinity leptins and leptin antagonists.

    Science.gov (United States)

    Shpilman, Michal; Niv-Spector, Leonora; Katz, Meirav; Varol, Chen; Solomon, Gili; Ayalon-Soffer, Michal; Boder, Eric; Halpern, Zamir; Elinav, Eran; Gertler, Arieh

    2011-02-11

    Leptin is a pleiotropic hormone acting both centrally and peripherally. It participates in a variety of biological processes, including energy metabolism, reproduction, and modulation of the immune response. So far, structural elements affecting leptin binding to its receptor remain unknown. We employed random mutagenesis of leptin, followed by selection of high affinity mutants by yeast surface display and discovered that replacing residue Asp-23 with a non-negatively charged amino acid leads to dramatically enhanced affinity of leptin for its soluble receptor. Rational mutagenesis of Asp-23 revealed the D23L substitution to be most effective. Coupling the Asp-23 mutation with alanine mutagenesis of three amino acids (L39A/D40A/F41A) previously reported to convert leptin into antagonist resulted in potent antagonistic activity. These novel superactive mouse and human leptin antagonists (D23L/L39A/D40A/F41A), termed SMLA and SHLA, respectively, exhibited over 60-fold increased binding to leptin receptor and 14-fold higher antagonistic activity in vitro relative to the L39A/D40A/F41A mutants. To prolong and enhance in vivo activity, SMLA and SHLA were monopegylated mainly at the N terminus. Administration of the pegylated SMLA to mice resulted in a remarkably rapid, significant, and reversible 27-fold more potent increase in body weight (as compared with pegylated mouse leptin antagonist), because of increased food consumption. Thus, recognition and mutagenesis of Asp-23 enabled construction of novel compounds that induce potent and reversible central and peripheral leptin deficiency. In addition to enhancing our understanding of leptin interactions with its receptor, these antagonists enable in vivo study of the role of leptin in metabolic and immune processes and hold potential for future therapeutic use in disease pathologies involving leptin.

  5. Development and Characterization of High Affinity Leptins and Leptin Antagonists*

    Science.gov (United States)

    Shpilman, Michal; Niv-Spector, Leonora; Katz, Meirav; Varol, Chen; Solomon, Gili; Ayalon-Soffer, Michal; Boder, Eric; Halpern, Zamir; Elinav, Eran; Gertler, Arieh

    2011-01-01

    Leptin is a pleiotropic hormone acting both centrally and peripherally. It participates in a variety of biological processes, including energy metabolism, reproduction, and modulation of the immune response. So far, structural elements affecting leptin binding to its receptor remain unknown. We employed random mutagenesis of leptin, followed by selection of high affinity mutants by yeast surface display and discovered that replacing residue Asp-23 with a non-negatively charged amino acid leads to dramatically enhanced affinity of leptin for its soluble receptor. Rational mutagenesis of Asp-23 revealed the D23L substitution to be most effective. Coupling the Asp-23 mutation with alanine mutagenesis of three amino acids (L39A/D40A/F41A) previously reported to convert leptin into antagonist resulted in potent antagonistic activity. These novel superactive mouse and human leptin antagonists (D23L/L39A/D40A/F41A), termed SMLA and SHLA, respectively, exhibited over 60-fold increased binding to leptin receptor and 14-fold higher antagonistic activity in vitro relative to the L39A/D40A/F41A mutants. To prolong and enhance in vivo activity, SMLA and SHLA were monopegylated mainly at the N terminus. Administration of the pegylated SMLA to mice resulted in a remarkably rapid, significant, and reversible 27-fold more potent increase in body weight (as compared with pegylated mouse leptin antagonist), because of increased food consumption. Thus, recognition and mutagenesis of Asp-23 enabled construction of novel compounds that induce potent and reversible central and peripheral leptin deficiency. In addition to enhancing our understanding of leptin interactions with its receptor, these antagonists enable in vivo study of the role of leptin in metabolic and immune processes and hold potential for future therapeutic use in disease pathologies involving leptin. PMID:21119198

  6. The Biology of Kaposi's Sarcoma-Associated Herpesvirus and the Infection of Human Immunodeficiency Virus

    Institute of Scientific and Technical Information of China (English)

    Di QIN; Chun LU

    2008-01-01

    Kaposi sarcoma-associated herpesvirus (KSHV),also known as human herpesvirus 8 (HHV-8),is discovered in 1994 from Kaposi's sarcoma (KS) lesion of an acquired immunodeficiency syndrome (AIDS)patient.In addition to its association with KS,KSHV has also been implicated as the causative agent of two other AIDS-associated malignancies:primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD).KSHV is a complex DNA virus that not only has the ability to promote cellular growth and survival for tumor development,but also can provoke deregulated angiogenesis,inflammation,and modulate the patient's immune system in favor of tumor growth.As KSHV is a necessary but not sufficient etiological factor for KS,human immunodeficiency virus (HIV) is a very important cofactor.Here we review the basic information about the biology of KSHV,development of pathogenesis and interaction between KSHV and HIV.

  7. Meningitis and stridor in advanced Human immunodeficiency virus/acquired immune deficiency syndrome

    Directory of Open Access Journals (Sweden)

    Naidoo P

    2013-09-01

    Full Text Available P Naidoo, D Pillay, S SamanDepartment of Internal Medicine, Port Shepstone Regional Hospital, University of KwaZulu-Natal, South AfricaAbstract: A 37-year-old female presented confused with a preceding history of severe headache. After clinical examination and investigations, she was diagnosed with disseminated tuberculosis (including central nervous system involvement, and Human immunodeficiency virus/acquired immune deficiency syndrome. Her hospital stay was complicated. She developed stridor and a cerebrovascular accident with left hemiplegia. She died approximately 2 weeks after admission. The potential causes of her stridor included a mediastinal mass or a central mechanism secondary to tuberculosis meningitis. Limited resources precluded definitive imaging of the chest to rule out a mediastinal mass. Further, an autopsy was not done. Despite these limitations, this case is unique because it reports the presence of both stridor and tuberculosis meningitis in an adult patient.Keywords: Human immunodeficiency virus, acquired immune deficiency syndrome, meningitis, stridor, tuberculosis

  8. Clinical Manifestations of Cytomegalovirus-Associated Posterior Uveitis and Panuveitis in Patients Without Human Immunodeficiency Virus Infection

    NARCIS (Netherlands)

    Pathanapitoon, Kessara; Tesavibul, Nattaporn; Choopong, Pitipol; Boonsopon, Sutasinee; Kongyai, Natedao; Ausayakhun, Somsanguan; Kunavisarut, Paradee; Rothova, Aniki

    2013-01-01

    Importance: Little attention has been paid to clinical features of cytomegalovirus (CMV) infections in individuals without human immunodeficiency virus (HIV). Objective: To describe the clinical manifestations and comorbidities of patients without HIV infection who have CMV-associated posterior uvei

  9. Severe cutaneous human papilloma virus infection associated with Natural Killer cell deficiency following stem cell transplantation for severe combined immunodeficiency

    Science.gov (United States)

    Kamili, Qurat-ul-Ain; Seeborg, Filiz O; Saxena, Kapil; Nicholas, Sarah K; Banerjee, Pinaki P; Angelo, Laura S; Mace, Emily M; Forbes, Lisa R; Martinez, Caridad; Wright, Teresa S; Orange, Jordan S.; Hanson, Imelda Celine

    2016-01-01

    Capsule Summary The authors identify Natural Killer cell deficiency in post-transplant severe combined immunodeficiency patients who developed severe human papilloma virus infections as a long term complication. PMID:25159470

  10. High affinity retinoic acid receptor antagonists: analogs of AGN 193109.

    Science.gov (United States)

    Johnson, A T; Wang, L; Gillett, S J; Chandraratna, R A

    1999-02-22

    A series of high affinity retinoic acid receptor (RAR) antagonists were prepared based upon the known antagonist AGN 193109 (2). Introduction of various phenyl groups revealed a preference for substitution at the para-position relative to the meta-site. Antagonists with the highest affinities for the RARs possessed hydrophobic groups, however, the presence of polar functionality was also well tolerated.

  11. High affinity ligands for 'diazepam-insensitive' benzodiazepine receptors.

    Science.gov (United States)

    Wong, G; Skolnick, P

    1992-01-14

    Structurally diverse compounds have been shown to possess high affinities for benzodiazepine receptors in their 'diazepam-sensitive' (DS) conformations. In contrast, only the imidazobenzodiazepinone Ro 15-4513 has been shown to exhibit a high affinity for the 'diazepam-insensitive' (DI) conformation of benzodiazepine receptors. We examined a series of 1,4-diazepines containing one or more annelated ring systems for their affinities at DI and DS benzodiazepine receptors, several 1,4-diazepinone carboxylates including Ro 19-4603, Ro 16-6028 and Ro 15-3505 were found to possess high affinities (Ki approximately 2.6-20 nM) for DI. Nonetheless, among the ligands examined, Ro 15-4513 was the only substance with a DI/DS potency ratio approximately 1; other substances had ratios ranging from 13 to greater than 1000. Ligands with high to moderate affinities at DI were previously classified as partial agonists, antagonists, or partial inverse agonists at DS benzodiazepine receptors, but behaved as 'GABA neutral' (antagonist) substances at DI. The identification of several additional high affinity ligands at DI benzodiazepine receptors may be helpful in elucidating the pharmacological and physiological importance of these sites.

  12. Action of uracil analogs on human immunodeficiency virus type 1 and its reverse transcriptase.

    OpenAIRE

    Piras, G; Dutschman, G E; Im, G J; B.C. Pan; Chu, S H; Cheng, Y C

    1995-01-01

    Three structural analogs of 5-ethyl-1-benzyloxymethyl-6-(phenylthio)uracil (E-BPU) inhibited human immunodeficiency virus type 1 (HIV-1) replication without cytotoxicity in vitro and were more potent than azidothymidine and were as potent as E-BPU. The target of these compounds is HIV-1 reverse transcriptase. Reverse transcriptases resistant to nevirapine (tyrosine at position 181 to cysteine) and TIBO R82150 (leucine at position 100 to isoleucine) are cross resistant to E-BPU analogs. Nevira...

  13. Crusted Scabies: Presenting as erythroderma in a human immunodeficiency virus-seropositive patient

    Directory of Open Access Journals (Sweden)

    Shruti Kulkarni

    2016-01-01

    Full Text Available Crusted scabies is a rare manifestation of scabies characterized by uncontrolled proliferation of mites in the skin. It is common in patients with sensory neuropathy, mentally retarded persons and in patients who are immunosuppressed. Further, crusted scabies can rarely present as erythroderma (<0.5% cases necessitating a high index of suspicion for its diagnosis. Because of its rare occurrence, we are reporting a case of crusted scabies presenting as erythroderma, in a human immunodeficiency virus seropositive patient.

  14. Hepatic Clearance Prediction of Nine Human Immunodeficiency Virus Protease Inhibitors in Rat

    OpenAIRE

    2016-01-01

    This study aimed to determine the rate-limiting step in the overall hepatic clearance of the marketed human immunodeficiency virus (HIV) protease inhibitors (PI) in rats by predicting the experimentally determined hepatic in vivo clearance of these drugs based on in vitro clearance values for uptake and/or metabolism. In vitro uptake and metabolic clearance values were determined in suspended rat hepatocytes and rat liver microsomes, respectively. In vivo hepatic clearance was determined afte...

  15. Sustained Small Interfering RNA-Mediated Human Immunodeficiency Virus Type 1 Inhibition in Primary Macrophages

    OpenAIRE

    2003-01-01

    Small interfering RNAs (siRNAs) can induce potent gene silencing by degradation of cognate mRNA. However, in dividing cells, the silencing lasts only 3 to 7 days, presumably because of siRNA dilution with cell division. Here, we investigated if sustained siRNA-mediated silencing of human immunodeficiency virus type 1 (HIV-1) is possible in terminally differentiated macrophages, which constitute an important reservoir of HIV in vivo. CCR5, the major HIV-1 coreceptor...

  16. Functional analysis of the Tat trans activator of human immunodeficiency virus type 2.

    OpenAIRE

    Fenrick, R; Malim, M H; Hauber, J; Le, S.Y.; Maizel, J; Cullen, B R

    1989-01-01

    The trans-activator (Tat) proteins of the related but distinct type 1 and type 2 human immunodeficiency viruses (HIV-1 and HIV-2) display incomplete functional reciprocity. One possible explanation of this observation, suggested by computer analysis of potential RNA secondary structures within the viral trans-activation response (TAR) elements, is that HIV-2 Tat requires the presentation of two viral RNA stem-loop sequences for full activity whereas HIV-1 Tat is maximally active upon presenta...

  17. Clinical characteristics and lung function in older children vertically infected with Human Immunodeficiency Virus in Malawi

    OpenAIRE

    Mwalukomo, Thandie; Rylance, Sarah; Webb, Emily; Anderson, Suzanne; O'Hare, Bernadette Ann-Marie; van Oosterhout, Joep J; Ferrand, Rashida A.; Corbett, Elizabeth L; Rylance, Jamie

    2015-01-01

    T. M. was funded by the Commonwealth scholarship, with research costs from a grant fom Helse Nord Northern Norway Regional Health Authority. E. L. C., R. A. F., and J. R. are supported by Wellcome Trust Fellowships (Senior Fellowship in Clinical Sciences WT091769, Career Development Fellowship WT095878 and Clinical PhD Fellowship 086756/B/08/Z, respectively). Background Antiretroviral therapy (ART) has led to increased survival of children with vertically acquired human immunodeficiency vi...

  18. Tropical Diseases Screening in Immigrant Patients with Human Immunodeficiency Virus Infection in Spain

    OpenAIRE

    2013-01-01

    Latent parasitic infections can reactivate because of immunosuppression. We conducted a prospective observational study of all human immunodeficiency virus (HIV)–infected immigrants who visited the Infectious Diseases Department of the Hospital Universitari Vall d'Hebron, Barcelona, Spain, during June 2010–May 2011. Screening of the most prevalent tropical diseases (intestinal parasitosis, Chagas disease, leishmaniasis, malaria, schistosomiasis, and strongyloidiasis) was performed according t...

  19. Meningitis and stridor in advanced Human immunodeficiency virus/acquired immune deficiency syndrome

    OpenAIRE

    Naidoo P; Pillay D; Saman S

    2013-01-01

    P Naidoo, D Pillay, S SamanDepartment of Internal Medicine, Port Shepstone Regional Hospital, University of KwaZulu-Natal, South AfricaAbstract: A 37-year-old female presented confused with a preceding history of severe headache. After clinical examination and investigations, she was diagnosed with disseminated tuberculosis (including central nervous system involvement), and Human immunodeficiency virus/acquired immune deficiency syndrome. Her hospital stay was complicated. She developed stri...

  20. A rare case of human immunodeficiency virus associated bilateral facial nerve palsy in North India

    Directory of Open Access Journals (Sweden)

    Sanjay Gupta

    2014-10-01

    Full Text Available Human immunodeficiency virus (HIV cases are on the increase in India and worldwide, so are its various complications. Neurological complications are important causes of morbidity and mortality in patients with HIV infection. They can occur at any stage of the disease and can affect any level of the central or peripheral nervous systems. In the literature, several cases of HIV-associated facial paralysis have been reported; however, bilateral facial palsy is rarely reported

  1. A rare case of human immunodeficiency virus associated bilateral facial nerve palsy in North India

    OpenAIRE

    Sanjay Gupta; Jitendra Kumar

    2014-01-01

    Human immunodeficiency virus (HIV) cases are on the increase in India and worldwide, so are its various complications. Neurological complications are important causes of morbidity and mortality in patients with HIV infection. They can occur at any stage of the disease and can affect any level of the central or peripheral nervous systems. In the literature, several cases of HIV-associated facial paralysis have been reported; however, bilateral facial palsy is rarely reported

  2. Bilateral Peripheral Facial Palsy in a Patient with Human Immunodeficiency Virus (HIV) Infection

    OpenAIRE

    Kim, Min Su; Yoon, Hee Jung; Kim, Hai Jin; Nam, Ji Sun; Choi, Sung Ho; Kim, June Myung; Song, Young Goo

    2006-01-01

    Neurological complications are important causes of morbidity and mortality in patients with human immunodeficiency virus (HIV) infection. They can occur at any stage of the disease and can affect any level of the central or peripheral nervous systems. In the literature, several cases of HIV-associated facial paralysis have been reported; however, bilateral facial palsy is rarely reported. In this paper, we present the first case in Korea, of a bilateral facial palsy occurring as the first cli...

  3. Bilateral peripheral facial palsy in a patient with Human Immunodeficiency Virus (HIV) infection.

    Science.gov (United States)

    Kim, Min Su; Yoon, Hee Jung; Kim, Hai Jin; Nam, Ji Sun; Choi, Sung Ho; Kim, June Myung; Song, Young Goo

    2006-10-31

    Neurological complications are important causes of morbidity and mortality in patients with human immunodeficiency virus (HIV) infection. They can occur at any stage of the disease and can affect any level of the central or peripheral nervous systems. In the literature, several cases of HIV-associated facial paralysis have been reported; however, bilateral facial palsy is rarely reported. In this paper, we present the first case in Korea, of a bilateral facial palsy occurring as the first clinical manifestation of HIV infection.

  4. Subcellular localization of the Vif protein of human immunodeficiency virus type 1.

    OpenAIRE

    Goncalves, J.; Jallepalli, P; Gabuzda, D H

    1994-01-01

    The Vif (viral infectivity factor) protein of human immunodeficiency virus type 1 (HIV-1) has been shown to dramatically enhance the infectivity of HIV-1 virus particles during virus production. The subcellular localization of Vif was examined to elucidate cellular pathways which may be important for Vif function. Indirect immunofluorescence staining of Vif demonstrated a diffuse cytoplasmic distribution and showed that most Vif was not associated with the Golgi complex, a proposed site of lo...

  5. Vanishing bile duct syndrome in human immunodeficiency virus: Nevirapine hepatotoxicity revisited

    Institute of Scientific and Technical Information of China (English)

    Rajan; Kochar; Moises; I; Nevah; Frank; J; Lukens; Michael; B; Fallon; Victor; I; Machicao

    2010-01-01

    Vanishing bile duct syndrome (VBDS) refers to a group of disorders characterized by prolonged cholestasis as a result of destruction and disappearance ofintrahepatic bile ducts. Multiple etiologies have been indentifi ed including infections, neoplastic disorders, autoimmune conditions and drugs. The natural history of this condition is variable and may involve resolution of cholestasis or progression with irreversible damage. VBDS is extremely rare in human immunodeficiency virus (HIV)-infected patients an...

  6. Detection of human immunodeficiency virus type 1 (HIV-1) Tat protein by aptamer-based biosensors

    Science.gov (United States)

    Hashim, Uda; Fatin, M. F.; Ruslinda, A. R.; Gopinath, Subash C. B.; Uda, M. N. A.

    2017-03-01

    A study was conducted to detect the human immunodeficiency virus (HIV-1) Tat protein using interdigitated electrodes. The measurements and images of the IDEs' finger gaps and the images of chitosan-carbon nanotubes deposited on top of the interdigitated electrodes were taken using the Scanning Electron Microscope. The detection of HIV-1 Tat protein was done using split aptamers and aptamer tail. Biosensors were chosen as diagnostic equipment due to their rapid diagnostic capabilities.

  7. Impact of Human Immunodeficiency Virus in the Pathogenesis and Outcome of Patients with Glioblastoma Multiforme

    OpenAIRE

    Choy, Winward; Lagman, Carlito; Lee, Seung J.; Bui, Timothy T; Safaee, Michael; Yang, Isaac

    2016-01-01

    Background Improvement in antiviral therapies have been accompanied by an increased frequency of non-Acquired Immune Deficiency Syndrome (AIDS) defining malignancies, such as glioblastoma multiforme. Here, we investigated all reported cases of human immunodeficiency virus (HIV)-positive patients with glioblastoma and evaluated their clinical outcomes. A comprehensive review of the molecular pathogenetic mechanisms underlying glioblastoma development in the setting of HIV/AIDS is provided. Met...

  8. Human Immunodeficiency Virus-Associated Diarrhea: Still an Issue in the Era of Antiretroviral Therapy

    OpenAIRE

    Dikman, Andrew E.; Schonfeld, Emily; Srisarajivakul, Nalinee C.; Poles, Michael A

    2015-01-01

    Over half of patients with human immunodeficiency virus (HIV) experience diarrhea that contributes negatively to quality of life and adherence to antiretroviral therapy (ART). Opportunistic infectious agents that cause diarrhea in patients with HIV span the array of protozoa, fungi, viruses, and bacteria. With global use of ART, the incidence of diarrhea because of opportunistic infections has decreased; however, the incidence of noninfectious diarrhea has increased. The etiology of noninfect...

  9. The Remarkable Frequency of Human Immunodeficiency Virus Type 1 Genetic Recombination

    OpenAIRE

    2009-01-01

    Summary: The genetic diversity of human immunodeficiency virus type 1 (HIV-1) results from a combination of point mutations and genetic recombination, and rates of both processes are unusually high. This review focuses on the mechanisms and outcomes of HIV-1 genetic recombination and on the parameters that make recombination so remarkably frequent. Experimental work has demonstrated that the process that leads to recombination—a copy choice mechanism involving the migration of reverse transcr...

  10. Ethics and Biosafety in Dental Care for Patients with Human Immunodeficiency Virus

    Directory of Open Access Journals (Sweden)

    Ana Ibis Betancourt García

    2013-02-01

    Full Text Available Background: the only way of contracting human immunodeficiency virus during dental treatment is through contact with the blood of an HIV-positive patient with non-intact skin or mucosa of the professional. This requires biosecurity measures to reduce the risk of crossed infection and ensure compliance of bioethical aspects to be considered when treating these patients. Objective: To determine knowledge levels of dentists on biosafety and bioethical principle of justice in the treatment of patients with human immunodeficiency virus. Methods: A cross sectional and descriptive study was conducted involving 45 professionals who worked in Stomatological clinics of three parishes in Caracas, Venezuela, from January to December 2010. The following were analyzed: knowledge on biosafety (mechanisms of disease transmission, control measures and flowchart sterilization measures before an accident and the justice bioethical principle (time and place of treatment, instruments used and time to devote to patient. Results: The knowledge level according to the bioethical principle of justice was assessed: 40% for good, 37.7% for average and 22.2% for bad. For biosecurity measures it was obtained: 26.6% good, 24.4% average and 48.8% bad. Conclusions: knowledge level on the bioethical principle of justice and biosecurity measures to treat patients living with human immunodeficiency virus is unsatisfactory in more than half of the dentists surveyed.

  11. Immunogenic compositions comprising human immunodeficiency virus (HIV) mosaic Nef proteins

    Science.gov (United States)

    Korber, Bette T [Los Alamos, NM; Perkins, Simon [Los Alamos, NM; Bhattacharya, Tanmoy [Los Alamos, NM; Fischer, William M [Los Alamos, NM; Theiler, James [Los Alamos, NM; Letvin, Norman [Boston, MA; Haynes, Barton F [Durham, NC; Hahn, Beatrice H [Birmingham, AL; Yusim, Karina [Los Alamos, NM; Kuiken, Carla [Los Alamos, NM

    2012-02-21

    The present invention relates to mosaic clade M HIV-1 Nef polypeptides and to compositions comprising same. The polypeptides of the invention are suitable for use in inducing an immune response to HIV-1 in a human.

  12. Human immunodeficiency virus infection and female lower genital tract malignancy.

    Science.gov (United States)

    Kuhn, L; Sun, X W; Wright, T C

    1999-02-01

    The risk of lower genital tract neoplasia is increased in women infected with HIV. This has been best demonstrated in cervical squamous intraepithelial lesions, but has also been observed in vulvar and perianal intraepithelial lesions in some studies. Alterations in the prevalence and natural history of human papillomavirus infections of the lower genital tract appear to account for much of the increase. HIV-infected women are approximately four times more likely to be infected with human papillomavirus (including infection with high oncogenic risk human papillomavirus types) than are HIV-uninfected women, and these infections are more likely to be persistent. Human papilomavirus-associated lesions may be more difficult to treat in HIV-infected women. These data highlight the need to develop effective cervical cancer prevention programs for HIV-infected women.

  13. Alternative splicing of TGF-betas and their high-affinity receptors TβRI, TβRII and TβRIII (betaglycan) reveal new variants in human prostatic cells

    Science.gov (United States)

    Konrad, Lutz; Scheiber, Jonas A; Völck-Badouin, Elke; Keilani, Marcel M; Laible, Leslie; Brandt, Heidrun; Schmidt, Ansgar; Aumüller, Gerhard; Hofmann, Rainer

    2007-01-01

    Background The transforming growth factors (TGF)-β, TGF-β1, TGF-β2 and TGF-β3, and their receptors [TβRI, TβRII, TβRIII (betaglycan)] elicit pleiotropic functions in the prostate. Although expression of the ligands and receptors have been investigated, the splice variants have never been analyzed. We therefore have analyzed all ligands, the receptors and the splice variants TβRIB, TβRIIB and TGF-β2B in human prostatic cells. Results Interestingly, a novel human receptor transcript TβRIIC was identified, encoding additional 36 amino acids in the extracellular domain, that is expressed in the prostatic cancer cells PC-3, stromal hPCPs, and other human tissues. Furthermore, the receptor variant TβRIB with four additional amino acids was identified also in human. Expression of the variant TβRIIB was found in all prostate cell lines studied with a preferential localization in epithelial cells in some human prostatic glands. Similarly, we observed localization of TβRIIC and TGF-β2B mainly in the epithelial cells with a preferential localization of TGF-β2B in the apical cell compartment. Whereas in the androgen-independent hPCPs and PC-3 cells all TGF-β ligands and receptors are expressed, the androgen-dependent LNCaP cells failed to express all ligands. Additionally, stimulation of PC-3 cells with TGF-β2 resulted in a significant and strong increase in secretion of plasminogen activator inhibitor-1 (PAI-1) with a major participation of TβRII. Conclusion In general, expression of the splice variants was more heterogeneous in contrast to the well-known isoforms. The identification of the splice variants TβRIB and the novel isoform TβRIIC in man clearly contributes to the growing complexity of the TGF-β family. PMID:17845732

  14. Alternative splicing of TGF-betas and their high-affinity receptors TβRI, TβRII and TβRIII (betaglycan reveal new variants in human prostatic cells

    Directory of Open Access Journals (Sweden)

    Brandt Heidrun

    2007-09-01

    Full Text Available Abstract Background The transforming growth factors (TGF-β, TGF-β1, TGF-β2 and TGF-β3, and their receptors [TβRI, TβRII, TβRIII (betaglycan] elicit pleiotropic functions in the prostate. Although expression of the ligands and receptors have been investigated, the splice variants have never been analyzed. We therefore have analyzed all ligands, the receptors and the splice variants TβRIB, TβRIIB and TGF-β2B in human prostatic cells. Results Interestingly, a novel human receptor transcript TβRIIC was identified, encoding additional 36 amino acids in the extracellular domain, that is expressed in the prostatic cancer cells PC-3, stromal hPCPs, and other human tissues. Furthermore, the receptor variant TβRIB with four additional amino acids was identified also in human. Expression of the variant TβRIIB was found in all prostate cell lines studied with a preferential localization in epithelial cells in some human prostatic glands. Similarly, we observed localization of TβRIIC and TGF-β2B mainly in the epithelial cells with a preferential localization of TGF-β2B in the apical cell compartment. Whereas in the androgen-independent hPCPs and PC-3 cells all TGF-β ligands and receptors are expressed, the androgen-dependent LNCaP cells failed to express all ligands. Additionally, stimulation of PC-3 cells with TGF-β2 resulted in a significant and strong increase in secretion of plasminogen activator inhibitor-1 (PAI-1 with a major participation of TβRII. Conclusion In general, expression of the splice variants was more heterogeneous in contrast to the well-known isoforms. The identification of the splice variants TβRIB and the novel isoform TβRIIC in man clearly contributes to the growing complexity of the TGF-β family.

  15. Cryptococcal meningoencephalitis in human immunodeficiency virus/acquired immunodeficiency syndrome in douala, cameroon: A cross sectional study

    Directory of Open Access Journals (Sweden)

    Henry Namme Luma

    2013-01-01

    Full Text Available Background: Cryptococcal meningoencephalitis (CM kills about half a million human immunodeficiency virus (HIV patients per year, mostly in Africa. Aim: The aim of this study was to determine the prevalence, clinical presentation and in-hospital outcome of CM among HIV-infected patients in Douala. Materials and Methods: A cross-sectional clinical note review of 672 HIV-1 patients′ files admitted from January 1 st 2004 to December 31 st 2009 at the Internal Medicine unit of the Douala General Hospital, Cameroon was performed. Only patients diagnosed of CM by microscopy of Indian ink stained cerebrospinal fluid (CSF were studied. Results: The prevalence of CM in the study was 11.2%. Mean age of patients was 36.9 ΁ 12.7 years. Median cluster of differentiation 4 (CD4 cell count was 23 cells/μL, (interquartile range [IQR]: 10-61 and 62.7% of CD4 cell counts were <50 cells/μL. The most prevalent symptom was headache in 97.3% of patients. In CSF, median proteins was 0.9 g/L (IQR: 0.6-1; median glucose 0.2 g/L (IQR: 0.1-0.3 and median leucocyte count 54 cells/μL (IQR: 34-76 mostly of mixed cellularity. The case fatality rate was 52% and low CD4 cell count was strongly associated with death, odd ratio 4.6 (95% confidence interval: 2.6-8.0, P < 0.001. Conclusion: The high case fatality of CM in Douala warrants adequate diagnostic measures and optimization of standardized treatment to reduce mortality.

  16. Structure of a human monoclonal antibody Fab fragment against gp41 of human immunodeficiency virus type

    Science.gov (United States)

    He, X. M.; Ruker, F.; Casale, E.; Carter, D. C.

    1992-01-01

    The three-dimensional structure of a human monoclonal antibody (Fab), which binds specifically to a major epitope of the transmembrane protein gp41 of the human immunodeficiency virus type 1, has been determined by crystallographic methods to a resolution of 2.7 A. It has been previously determined that this antibody recognizes the epitope SGKLICTTAVPWNAS, belongs to the subclass IgG1 (kappa), and exhibits antibody-dependent cellular cytotoxicity. The quaternary structure of the Fab is in an extended conformation with an elbow bend angle between the constant and variable domains of 175 degrees. Structurally, four of the hypervariable loops can be classified according to previously recognized canonical structures. The third hypervariable loops of the heavy (H3) and light chain (L3) are structurally distinct. Hypervariable loop H3, residues 102H-109H, is unusually extended from the surface. The complementarity-determining region forms a hydrophobic binding pocket that is created primarily from hypervariable loops L3, H3, and H2.

  17. A comparative autoradiography study in post mortem whole hemisphere human brain slices taken from Alzheimer patients and age-matched controls using two radiolabelled DAA1106 analogues with high affinity to the peripheral benzodiazepine receptor (PBR) system.

    Science.gov (United States)

    Gulyás, Balázs; Makkai, Boglárka; Kása, Péter; Gulya, Károly; Bakota, Lidia; Várszegi, Szilvia; Beliczai, Zsuzsa; Andersson, Jan; Csiba, László; Thiele, Andrea; Dyrks, Thomas; Suhara, Tetsua; Suzuki, Kazutoshi; Higuchi, Makato; Halldin, Christer

    2009-01-01

    The binding of two radiolabelled analogues (N-(5-[125I]Iodo-2-phenoxyphenyl)-N-(2,5-dimethoxybenzyl)acetamide ([125I]desfluoro-DAA1106) and N-(5-[125I]Fluoro-2-phenoxyphenyl)-N-(2-[125I]Iodo-5-methoxybenzyl)acetamide ([125I]desmethoxy-DAA1106) of the peripheral benzodiazepine receptor (PBR) (or TSPO, 18kDa translocator protein) ligand DAA1106 was examined by in vitro autoradiography on human post mortem whole hemisphere brain slices obtained from Alzheimer's disease (AD) patients and age-matched controls. Both [(125)I]desfluoro-IDAA1106 and [(125)I]desmethoxy-IDAA1106 were effectively binding to various brain structures. The binding could be blocked by the unlabelled ligand as well as by other PBR specific ligands. With both radiolabelled compounds, the binding showed regional inhomogeneity and the specific binding values proved to be the highest in the hippocampus, temporal and parietal cortex, the basal ganglia and thalamus in the AD brains. Compared with age-matched control brains, specific binding in several brain structures (temporal and parietal lobes, thalamus and white matter) in Alzheimer brains was significantly higher, indicating that the radioligands can effectively label-activated microglia and the up-regulated PBR/TSPO system in AD. Complementary immunohistochemical studies demonstrated reactive microglia activation in the AD brain tissue and indicated that increased ligand binding coincides with increased regional microglia activation due to neuroinflammation. These investigations yield further support to the PBR/TSPO binding capacity of DAA1106 in human brain tissue, demonstrate the effective usefulness of its radio-iodinated analogues as imaging biomarkers in post mortem human studies, and indicate that its radiolabelled analogues, labelled with short half-time bioisotopes, can serve as prospective in vivo imaging biomarkers of activated microglia and the up-regulated PBR/TSPO system in the human brain.

  18. High affinity complexes of pannexin channels and L-type calcium channel splice-variants in human lung: Possible role in clevidipine-induced dyspnea relief in acute heart failure

    Directory of Open Access Journals (Sweden)

    Gerhard P. Dahl

    2016-08-01

    Research in Context: Clevidipine lowers blood pressure by inhibiting calcium channels in vascular smooth muscle. In patients with acute heart failure, clevidipine was shown to relieve breathing problems. This was only partially related to the blood pressure lowering actions of clevidipine and not conferred by another calcium channel inhibitor. We here found calcium channel variants in human lung that are more selectively inhibited by clevidipine, especially when associated with pannexin channels. This study gives a possible mechanism for clevidipine's relief of breathing problems and supports future clinical trials testing the role of clevidipine in the treatment of acute heart failure.

  19. Characterization of a genetically reconstituted high-affinity system for serotonin transport

    Energy Technology Data Exchange (ETDEWEB)

    Chang, A.S.S.; Lam, D.M.K. (Baylor College of Medicine, Woodlands, TX (USA) Baylor College of Medicine, Houston, TX (USA)); Frnka, J.V.; Chen, D. (Baylor College of Medicine, Woodlands, TX (USA))

    1989-12-01

    By transfecting mouse fibroblast L-M cells with human genomic DNA, the authors have established and identified several clonal cell lines that stably express a high-affinity serotonin (5-HT)-uptake mechanism absent in untransfected host cells. One such cell line, L-S1, possesses features of 5-({sup 3}H)HT uptake similar to those previously characterized in the central nervous system and blood platelets: (i) specificity for 5-HT; (ii) antagonism by imipramine, a known inhibitor of high-affinity 5-HT uptake; (iii) both Na{sup +} and temperature dependence; (iv) kinetic saturability; and (v) high affinity for 5-HT. This cell line can be used to compare the relative efficacies of known blockers of 5-HT uptake and thereby offers a rapid and reliable assay system for testing novel inhibitors of this system. Since L-S1 contains stably integrated human DNA in its genome, they postulate that the observed 5-HT-uptake system resulted from the expression of human gene(s) coding for the 5-HT transporter. Thus, cell lines such as L-S1 may represent novel means for screening and developing therapeutic agents specific for neutrotransmitter-uptake systems as well as substrate for the cloning and elucidation of the genes encoding the various neurotransmitter transporters.

  20. Human immunodeficiency virus type-2-A milder, kinder virus: an update.

    Science.gov (United States)

    Kannangai, R; David, S; Sridharan, G

    2012-01-01

    Human immunodeficiency virus type-2 (HIV-2) belongs to the family retroviridae which is phylogenetically clusters with SIV SM from sooty mangabeys. This virus is morphologically similar to human immunodeficiency virus type-1 (HIV-1) but has got only a 40% homology at the nucleotide level. There is a distinct geographical distribution of HIV-2 unlike HIV-1. There are currently eight subtypes/groups identified with subtype/group A responsible for the majority of infections. HIV-2 shows a considerable difference in the course of the disease. Clinical, haematological and immunological evaluation of individuals infected with HIV-2 has shown the virus to be less pathogenic than HIV-1 although the exact mechanism underlying this difference is not well defined. Similar to HIV-1, the HIV-2 isolates also showed distinct replicative and cytopathic characteristics. The transmission rate for HIV-2 compared to HIV-1 is very low both by heterosexual route and mother to child transmission. The clinical signs and symptoms of immunodeficiency associated with HIV-2 are similar to the ones seen among the HIV-1-infected individuals and they can also progress to AIDS. It is naturally resistant to NNRTI and hence the diagnosis become important as it affects the treatment strategy. Similar to HIV-1, HIV-2 strains of infected individuals also show mutations that can cause drug resistance. The current evidence suggests that there is no protective effective for HIV-2 against HIV-1.

  1. Psychological problems of families and health workers dealing with people infected with human immunodeficiency virus 1.

    Science.gov (United States)

    Maj, M

    1991-03-01

    The psychological problems of the families of human immunodeficiency virus 1 (HIV-1)-infected people, and of the health workers taking care of them, have been addressed in a few empirical studies and in several anecdotal reports and theoretical contributions. Apparently, HIV-1 infection and acquired immunodeficiency syndrome (AIDS) are able to elicit a wide range of emotional reactions, from rejection and refusal to provide care to immersion in the infected person's needs and burnout. Since irrational fears and attitudes play an important role in conditioning these reactions, education may not be sufficient to change behaviour. Counselling sessions and mutual support groups are often the most appropriate contexts where fears and concerns can receive an individually tailored response, and where formal and informal caregivers can be helped to manage stress.

  2. [Gastric uptake of gallium67 in the human immunodeficiency virus infection].

    Science.gov (United States)

    Escalera Temprado, T; Banzo Marraco, J; Abós Olivares, M D; Olave Rubio, M T; Prats Rivera, E; García López, F; Razola Alba, P

    2004-02-01

    Nowadays, the human immunodeficiency virus infection (HIV) is a chronic disease. In the frequent clinical situations with fever, lymph nodes and loss weight it is necessary to determine their etiology, for establishing a specific treatment. Gastrointestinal opportunistic infections or gastric lymphomatous or sarcomatous process, which can accumulate Ga67, may be present in the patient with acquired immunodeficiency syndrome. We report 2 cases with gastric uptake in which endoscopy and biopsy was obtained. In the first one, with previous treatment with omeprazol and almalgate for gastroesophagic reflux, endoscopy and biopsy were normal and in the second patient an Helicobacter pylori infection was diagnosed. We think that gastric uptake of Ga67 in HIV patients, must indicate to the clinician to rule out associated pathologies.

  3. Serodiagnosis of Helicobacter pylori infection in patients with human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Nielsen, H; Andersen, L P

    1995-01-01

    In contrast to the established role of Helicobacter pylori gastritis in gastritis and duodenal ulcer in general, conflicting results have been reported in patients with human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome. The seroprevalence during early HIV...... infection is unknown. We retrospectively studied 102 patients with HIV infection early during the infection and in most cases in asymptomatic patients. Serological IgG antibody response to H. pylori was assessed by ELISA. Compared with an age-matched control group the seroprevalence of H. pylori positivity......) and 2 patients had H. pylori seroconverted, indicating an incidence of new infection of 2%/year. In conclusion, previous reports have underestimated the prevalence of H. pylori infection in HIV patients, which seems to be similar to that in an HIV-negative population....

  4. Restoration of skeletal muscle ischemia-reperfusion injury in humanized immunodeficient mice.

    Science.gov (United States)

    Sheu, Eric G; Oakes, Sean M; Ahmadi-Yazdi, Cyrus; Afnan, Jalil; Carroll, Michael C; Moore, Francis D

    2009-08-01

    Ischemia and reperfusion (I/R) of tissue provokes an inflammatory process that is highly dependent on circulating natural immunoglobulin M (IgM) and the complement cascade. In mice, a single IgM specificity produced by peritoneal B cells can initiate reperfusion injury. It is unknown whether humans express natural IgM with a similar specificity. It is also unknown whether pathogenic IgM is produced solely from peritoneal B cells or can also be made by circulating B cells. Immunodeficient mice lacking endogenous immunoglobulin were used. Mice were reconstituted with 0.9% normal saline, human serum, or xenografted human peripheral blood lymphocytes (PBLs) and then subjected to tourniquet-induced hindlimb I/R. Serum human IgM and immunoglobulin G (IgG) were measured by enzyme-linked immunosorbent (ELISA) assay. Skeletal muscle was harvested for injury assessment by histology and for immunohistochemistry. Immunodeficient mice were protected from skeletal muscle injury after hindlimb I/R. Transfer of human serum restored skeletal muscle damage. Rag2/gammaR-/- mice that were engrafted with human PBL (huPBL-SCID) had high levels of human IgM. huPBL-SCID mice developed significantly more skeletal muscle injury than control saline-treated mice (P < or = .01) and human serum-reconstituted Rag2/gammaR-/- mice (P < or = 0.01). Sham-treated huPBL-SCID mice had no muscle injury, demonstrating that human lymphocyte engraftment did not cause injury in the absence of ischemia. Deposition of human IgM was observed on injured but not sham-injured muscle. Human serum can initiate murine skeletal muscle I/R injury. Circulating human PBL may be a source of pathogenic IgM. The huPBL-SCID mouse may be a useful model to define the specificity of pathogenic human IgM and to test therapeutics for I/R injury.

  5. Chemokine receptors and their crucial role in human immunodeficiency virus infection: major breakthroughs in HIV research

    DEFF Research Database (Denmark)

    Kristiansen, T B; Knudsen, T B; Eugen-Olsen, J

    1998-01-01

    Within the last three years, major progress in the understanding of acquired immune deficiency syndrome pathogenesis has been achieved. The discovery that human immunodeficiency virus (HIV), in addition to the CD4 receptor, requires the presence of a coreceptor in order to infect cells has led...... to a series of breakthroughs in HIV research and knowledge. These include an increased understanding of viral entry, a connection of viral phenotype to specific coreceptor use, and an unequivocal linkage of a single human gene to host susceptibility. All in all these achievements provide a number of promising...

  6. Optimization of Azoles as Anti-Human Immunodeficiency Virus Agents Guided by Free-Energy Calculations

    OpenAIRE

    Zeevaart, Jacob G.; Wang, Ligong; Thakur, Vinay V.; Leung, Cheryl S.; Tirado-Rives, Julian; Bailey, Christopher M.; Domaoal, Robert A.; Anderson, Karen S.; Jorgensen, William L.

    2008-01-01

    Efficient optimization of an inactive 2-anilinyl-5-benzyloxadiazole core has been guided by free energy perturbation (FEP) calculations to provide potent non-nucleoside inhibitors of human immunodeficiency virus (HIV) reverse transcriptase (NNRTIs). An FEP “chlorine scan” was performed to identify the most promising sites for substitution of aryl hydrogens. This yielded NNRTIs 8 and 10 with activities (EC50) of 820 and 310 nM for protection of human T-cells from infection by wild-type HIV-1. ...

  7. Low-dose growth hormone and human immunodeficiency virus-associated lipodystrophy syndrome: a pilot study

    DEFF Research Database (Denmark)

    Andersen, Ove; Haugaard, Steen B; Flyvbjerg, A

    2004-01-01

    BACKGROUND: Treatment with high doses (2-6 mg day(-1)) of human growth hormone (hGH) in patients with human immunodeficiency virus (HIV)-associated lipodystrophy syndrome (HALS) has been shown to increase concentrations of total insulin-like growth-factor-I (IGF-I) more than twofold greater than......' treatment of lipodystrophic HIV-infected patients with hGH, 0.7 mg day(-1), increased total and free IGF-I twofold and appeared safe and tolerable. The potential of low-dose hGH in the treatment of HIV-lipodystrophy awaits examination by placebo-controlled, randomized trials....

  8. Screening of Fungi from Chinese Medical Plants for Anti-Human Immunodeficiency Virus Type 1 Activity

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In order to isolate anti-human immunodeficiency virus (HIV) agents from natural products, 97 ethanolic extracts of 90 fungi were tested for their inhibitory activity on HIV-1. Most of the extracts tested were relatively non-toxic to human lymphocytic MT-4 cells, but extracts of some fungi exhibited potent anti-HIV activity in an in vitro 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide assay with a selectivity index greater than 3. Most fungi were isolated from Dendrobium sp. and Taxus sp.

  9. Human immunodeficiency virus receptor and coreceptor expression on human uterine epithelial cells: regulation of expression during the menstrual cycle and implications for human immunodeficiency virus infection.

    Science.gov (United States)

    Yeaman, Grant R; Howell, Alexandra L; Weldon, Sally; Demian, Douglas J; Collins, Jane E; O'Connell, Denise M; Asin, Susana N; Wira, Charles R; Fanger, Michael W

    2003-05-01

    Human immunodeficiency virus-1 (HIV-1) is primarily a sexually transmitted disease. Identification of cell populations within the female reproductive tract that are initially infected, and the events involved in transmission of infection to other cells, remain to be established. In this report, we evaluated expression of HIV receptors and coreceptors on epithelial cells in the uterus and found they express several receptors critical for HIV infection including CD4, CXCR4, CCR5 and galactosylceramide (GalC). Moreover, expression of these receptors varied during the menstrual cycle. Expression of CD4 and CCR5 on uterine epithelial cells is high throughout the proliferative phase of the menstrual cycle when blood levels of oestradiol are high. In contrast, CXCR4 expression increased gradually throughout the proliferative phase. During the secretory phase of the cycle when both oestradiol and progesterone are elevated, CD4 and CCR5 expression decreased whereas CXCR4 expression remained elevated. Expression of GalC on endometrial glands is higher during the secretory phase than during the proliferative phase of the menstrual cycle. Because epithelial cells line the female reproductive tract and express HIV receptors and coreceptors, it is likely that they are one of the first cell types to become infected. The hormonal regulation of HIV receptor expression may affect a woman's susceptibility to HIV infection during her menstrual cycle. Moreover, selective coreceptor expression could account for the preferential transmission of R5-HIV-1 strains to women. In addition, these studies provide evidence that the uterus, and potentially the entire upper reproductive tract, are important sites for the initial events involved in HIV infection.

  10. Antibody testing and counseling of dental patients at risk for human immunodeficiency virus (HIV) infection and associated clinical findings.

    Science.gov (United States)

    Murrah, V A; Scholtes, G A

    1988-10-01

    Two hundred six dental patients were tested between 1985 and 1987 for antibodies to human immunodeficiency virus (HIV) when a review of their medical histories revealed a high risk for infection. Serologic results are correlated with soft tissue and osseous findings recorded during routine head and neck and radiographic examination. Counseling recommendations for use in association with testing are outlined. A more active role for the dentist as a preventive agent is advocated to combat the spread of acquired immunodeficiency syndrome (AIDS).

  11. Fcgamma receptor-mediated suppression of human immunodeficiency virus type 1 replication in primary human macrophages.

    Science.gov (United States)

    Perez-Bercoff, Danielle; David, Annie; Sudry, Hugues; Barré-Sinoussi, Françoise; Pancino, Gianfranco

    2003-04-01

    Permissiveness of monocytes and macrophages to human immunodeficiency virus (HIV) infection is modulated by various stimuli. In this study we demonstrate that stimulation of primary monocytes and monocyte-derived macrophages (MDM) through the receptors for the Fc portion of immunoglobulin G (IgG) (FcgammaR) inhibits HIV type 1 (HIV-1) replication. Viral p24 production was decreased by 1.5 to 3 log units in MDM infected with both R5 and X4 HIV-1 strains upon stimulation by immobilized IgG but not upon stimulation by soluble IgG or by F(ab')(2) IgG fragments. Although MDM activation by immobilized IgG induced high levels of macrophage-derived chemokine secretion as well as a sustained down-regulation of CD4 and a transient decrease in CCR5 expression, these factors did not appear to play a major role in the suppression of HIV-1 replication. Single-cycle infection of FcgammaR-stimulated MDM with HIV-1 virions pseudotyped with either HIV-1 R5 or vesicular stomatitis virus G envelopes was inhibited, suggesting a postentry restriction of viral replication. PCR analyses of HIV-1 DNA intermediate replication forms suggested that reverse transcription is not affected by stimulation with immobilized human IgG, at least during the first replication cycle. The accumulation of PCR products corresponding to nuclear unintegrated two-long-terminal-repeat circles and the relative decrease of integrated HIV-1 DNA signals suggest an inhibition of proviral integration. Our data, showing that FcgammaR-mediated activation of MDM is a potent mechanism of HIV-1 suppression, raise the possibility that FcgammaR cross-linking by immune complexes may contribute to the control of viral replication in macrophages.

  12. Human papillomavirus detection from human immunodeficiency virus-infected Colombian women's paired urine and cervical samples.

    Science.gov (United States)

    Munoz, Marina; Camargo, Milena; Soto-De Leon, Sara C; Sanchez, Ricardo; Parra, Diana; Pineda, Andrea C; Sussmann, Otto; Perez-Prados, Antonio; Patarroyo, Manuel E; Patarroyo, Manuel A

    2013-01-01

    Infection, coinfection and type-specific human papillomavirus (HPV) distribution was evaluated in human immunodeficiency virus (HIV)-positive women from paired cervical and urine samples. Paired cervical and urine samples (n = 204) were taken from HIV-positive women for identifying HPV-DNA presence by using polymerase chain reaction (PCR) with three generic primer sets (GP5+/6+, MY09/11 and pU1M/2R). HPV-positive samples were typed for six high-risk HPV (HR-HPV) (HPV-16, -18, -31, -33, -45 and -58) and two low-risk (LR-HPV) (HPV-6/11) types. Agreement between paired sample results and diagnostic performance was evaluated. HPV infection prevalence was 70.6% in cervical and 63.2% in urine samples. HPV-16 was the most prevalent HPV type in both types of sample (66.7% in cervical samples and 62.0% in urine) followed by HPV-31(47.2%) in cervical samples and HPV-58 (35.7%) in urine samples. There was 55.4% coinfection (infection by more than one type of HPV) in cervical samples and 40.2% in urine samples. Abnormal Papanicolau smears were observed in 25.3% of the women, presenting significant association with HPV-DNA being identified in urine samples. There was poor agreement of cervical and urine sample results in generic and type-specific detection of HPV. Urine samples provided the best diagnosis when taking cytological findings as reference. In conclusion including urine samples could be a good strategy for ensuring adherence to screening programs aimed at reducing the impact of cervical cancer, since this sample is easy to obtain and showed good diagnostic performance.

  13. Human papillomavirus detection from human immunodeficiency virus-infected Colombian women's paired urine and cervical samples.

    Directory of Open Access Journals (Sweden)

    Marina Munoz

    Full Text Available Infection, coinfection and type-specific human papillomavirus (HPV distribution was evaluated in human immunodeficiency virus (HIV-positive women from paired cervical and urine samples. Paired cervical and urine samples (n = 204 were taken from HIV-positive women for identifying HPV-DNA presence by using polymerase chain reaction (PCR with three generic primer sets (GP5+/6+, MY09/11 and pU1M/2R. HPV-positive samples were typed for six high-risk HPV (HR-HPV (HPV-16, -18, -31, -33, -45 and -58 and two low-risk (LR-HPV (HPV-6/11 types. Agreement between paired sample results and diagnostic performance was evaluated. HPV infection prevalence was 70.6% in cervical and 63.2% in urine samples. HPV-16 was the most prevalent HPV type in both types of sample (66.7% in cervical samples and 62.0% in urine followed by HPV-31(47.2% in cervical samples and HPV-58 (35.7% in urine samples. There was 55.4% coinfection (infection by more than one type of HPV in cervical samples and 40.2% in urine samples. Abnormal Papanicolau smears were observed in 25.3% of the women, presenting significant association with HPV-DNA being identified in urine samples. There was poor agreement of cervical and urine sample results in generic and type-specific detection of HPV. Urine samples provided the best diagnosis when taking cytological findings as reference. In conclusion including urine samples could be a good strategy for ensuring adherence to screening programs aimed at reducing the impact of cervical cancer, since this sample is easy to obtain and showed good diagnostic performance.

  14. Human immunodeficiencies related to APC/T cell interaction

    Directory of Open Access Journals (Sweden)

    Marinos eKallikourdis

    2015-08-01

    Full Text Available The primary event for initiating adaptive immune responses is the encounter between T lymphocytes and antigen presenting cells (APC in the T cell area of secondary lymphoid organs and the formation of highly organized inter-cellular junctions referred to as the immune synapses. In vivo live-cell imaging of APC-T cell interactions combined to functional studies unveiled that T cell fate is dictated, in large part, by the stability of the initial contact. Immune cell interaction is equally important during delivery of T cell help to B cells and for the killing of target cells by cytotoxic T cells and NK cells. The critical role of contact dynamics and synapse stability on the immune response is well illustrated by human immune deficiencies in which disease pathogenesis is linked to altered adhesion or defective cross-talk between the synaptic partners. Here we will discuss in details the mechanisms of defective APC-T cell communications in Wiskott-Aldrich syndrome (WAS and in warts, hypogammaglobulinemia, infections, myelokathexis syndrome (WHIM. In addition, we will summarize the evidences pointing to a compromised conjugate formation in WIP deficiency, DOCK8 deficiency and X-linked lymphoproliferative syndrome.

  15. Expression from second-generation feline immunodeficiency virus vectors is impaired in human hematopoietic cells.

    Science.gov (United States)

    Price, Mary A; Case, Scott S; Carbonaro, Denise A; Yu, Xiao-Jin; Petersen, Denise; Sabo, Kathleen M; Curran, Michael A; Engel, Barbara C; Margarian, Hovanes; Abkowitz, Janis L; Nolan, Garry P; Kohn, Donald B; Crooks, Gay M

    2002-11-01

    Vectors based on the feline immunodeficiency virus (FIV) have been developed as an alternative to those based on another lentivirus, human immunodeficiency virus-1 (HIV-1), because of theoretical safety advantages. We compared the efficiency of gene transfer and expression in human and feline hematopoietic progenitors using second-generation HIV-1 and FIV-based vectors. Vector pairs were tested using either human cytomegalovirus or murine phospho-glycerate kinase (PGK) internal promoters and were pseudotyped with the vesicular stomatitis virus G protein (VSV-G). Vector proviral copy numbers were similar in human and feline hematopoietic primary cells and cell lines transduced by HIV-1 or FIV vectors, demonstrating that both vectors are able to transfer genes efficiently to these cell types. HIV-1 vectors were well expressed in human primary hematopoietic cells and cell lines. However, transgene expression from FIV vectors was almost undetectable in human hematopoietic cells. In contrast, the FIV vector was expressed well in primary hematopoietic feline cells and human non-hematopoietic cells, demonstrating that low transgene expression from the FIV vector is a phenomenon specific to human hematopoietic cells. Northern blot analysis demonstrated decreased vector transcript levels in human CEM cells transduced with FIV relative to cells transduced with HIV-1, despite high vector copy numbers. No evidence of vector transcript instability was seen in studies of transduced CEM cells treated with actinomycin D. We conclude that FIV vectors can transfer genes into human hematopoietic cells as effectively as HIV-1 vectors, but that unknown elements in the current FIV backbone inhibit expression from FIV vectors in human hematopoietic cells.

  16. Studying human immunodeficiencies in humans: advances in fundamental concepts and therapeutic interventions [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Helen Su

    2017-03-01

    Full Text Available Immunodeficiencies reveal the crucial role of the immune system in defending the body against microbial pathogens. Given advances in genomics and other technologies, this is currently best studied in humans who have inherited monogenic diseases. Such investigations have provided insights into how gene products normally function in the natural environment and have opened the door to new, exciting treatments for these diseases.

  17. Human immunodeficiency virus impairs reverse cholesterol transport from macrophages.

    Directory of Open Access Journals (Sweden)

    Zahedi Mujawar

    2006-10-01

    Full Text Available Several steps of HIV-1 replication critically depend on cholesterol. HIV infection is associated with profound changes in lipid and lipoprotein metabolism and an increased risk of coronary artery disease. Whereas numerous studies have investigated the role of anti-HIV drugs in lipodystrophy and dyslipidemia, the effects of HIV infection on cellular cholesterol metabolism remain uncharacterized. Here, we demonstrate that HIV-1 impairs ATP-binding cassette transporter A1 (ABCA1-dependent cholesterol efflux from human macrophages, a condition previously shown to be highly atherogenic. In HIV-1-infected cells, this effect was mediated by Nef. Transfection of murine macrophages with Nef impaired cholesterol efflux from these cells. At least two mechanisms were found to be responsible for this phenomenon: first, HIV infection and transfection with Nef induced post-transcriptional down-regulation of ABCA1; and second, Nef caused redistribution of ABCA1 to the plasma membrane and inhibited internalization of apolipoprotein A-I. Binding of Nef to ABCA1 was required for down-regulation and redistribution of ABCA1. HIV-infected and Nef-transfected macrophages accumulated substantial amounts of lipids, thus resembling foam cells. The contribution of HIV-infected macrophages to the pathogenesis of atherosclerosis was supported by the presence of HIV-positive foam cells in atherosclerotic plaques of HIV-infected patients. Stimulation of cholesterol efflux from macrophages significantly reduced infectivity of the virions produced by these cells, and this effect correlated with a decreased amount of virion-associated cholesterol, suggesting that impairment of cholesterol efflux is essential to ensure proper cholesterol content in nascent HIV particles. These results reveal a previously unrecognized dysregulation of intracellular lipid metabolism in HIV-infected macrophages and identify Nef and ABCA1 as the key players responsible for this effect. Our findings

  18. Detection of Cryptosporidium - specific coproantigen in human immunodeficiency virus/acquired immunodeficiency syndrome patients by using a commercially available immunoenzymatic assay

    Directory of Open Access Journals (Sweden)

    Claudio Vieira Silva

    2003-12-01

    Full Text Available The aim of this study was to verify the occurrence of Cryptosporidium infection in 52 human immunodeficiency virus (HIV/acquired immunodeficiency syndrome (AIDS patients (group 1 and 38 clinically healthy individuals (group 2 by using enzyme immunoassay (EIA. All fecal samples collected were submitted to the Baermann, Lutz, and Ritchie methods, the Safranin/Methylene Blue, and Weber's chromotrope modified Trichrome staining techniques, and EIA. In group 1, parasitological staining techniques and EIA were both positive for Cryptosporidium sp. infection in 3/52 (5.8% samples and both negative in 45/52 (86.5% samples, while 4/52 (7.7% samples were positive in EIA and negative in parasitological staining techniques. Concerning group 2, all samples were negative by EIA and microscopy for Cryptosporidium infection. In conclusion, EIA may be an alternative method for detecting Cryptosporidium-specific coproantigen in HIV/AIDS patients.

  19. Variant-specific monoclonal and group-specific polyclonal human immunodeficiency virus type 1 neutralizing antibodies raised with synthetic peptides from the gp120 third variable domain.

    Science.gov (United States)

    Laman, J D; Schellekens, M M; Abacioglu, Y H; Lewis, G K; Tersmette, M; Fouchier, R A; Langedijk, J P; Claassen, E; Boersma, W J

    1992-03-01

    The third variable (V3) domain of the human immunodeficiency virus type 1 (HIV-1) external membrane glycoprotein gp120 is of crucial importance in eliciting neutralizing antibodies in infected persons. Polyclonal (PAb) and monoclonal (MAb) antibodies directed against selected epitopes in the V3 domain are valuable tools for analysis of the involvement of such sequences in neutralization and for definition of the relation between amino acid variability and immunological cross-reactions. The aim of this study was to obtain such site-specific antibodies. By using synthetic peptides derived from the V3 domain, a group-specific neutralizing PAb, two high-affinity HIV-1 IIIB neutralizing MAb, and two nonneutralizing MAb were raised. A 15-amino-acid peptide overlapping the tip of the V3 domain of HIV-1 MN was used to produce a rabbit PAb (W0/07). This PAb inhibited syncytium formation induced by HIV-1 IIIB and four field isolates. A similar IIIB-derived peptide was used to generate two murine immunoglobulin G1 (IgG1) MAb (IIIB-V3-13 and IIIB-V3-34). Pepscan analysis mapped the binding site of IIIB-V3-34 to the sequence IRIQRGPGR. The Kds of IIIB-V3-13 and IIIB-V3-34 for gp120 were 6.8 x 10(-11) and 1.6 x 10(-10) M, respectively. These MAb neutralized IIIB but not MN and inhibited syncytium formation induced by IIIB. They are applicable in enzyme-linked immunosorbent assays, immunocytochemistry, and flow cytometry. A peptide covering the left base of the V3 domain was used to generate two murine IgG1 MAb (IIIB-V3-21 and IIIB-V3-26). The binding site of IIIB-V3-21 was mapped to the sequence INCTRPN. These MAb did not neutralize HIV-1 and did not inhibit syncytium formation. This study supports the notion that HIV-1 neutralizing antibodies suitable for multiassay performance can be obtained with synthetic peptides and that high-affinity MAb can be generated. Such site-specific antibodies are useful reagents in the analysis of HIV-1 neutralization. In addition, the cross

  20. [3H]ATPA: a high affinity ligand for GluR5 kainate receptors.

    Science.gov (United States)

    Hoo, K; Legutko, B; Rizkalla, G; Deverill, M; Hawes, C R; Ellis, G J; Stensbol, T B; Krogsgaard-Larsen, P; Skolnick, P; Bleakman, D

    1999-12-01

    The pharmacological properties of [3H]ATPA ((RS)-2-amino-3(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid) are described. ATPA is a tert-butyl analogue of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid) that has been shown to possess high affinity for the GluR5 subunit of kainate receptors. [3H]ATPA exhibits saturable, high affinity binding to membranes expressing human GluR5 (GluR5) kainate receptors (Kd approximately 13 nM). No specific binding was observed in membranes expressing GluR2 and GluR6 receptors. Several compounds known to interact with the GluR5 kainate receptor inhibited [3H]ATPA binding with potencies similar to those obtained for competition of [3H]kainate binding to GluR5. Saturable, high affinity [3H]ATPA binding (Kd approximately 4 nM) was also observed in DRG neuron (DRG) membranes isolated from neonatal rats. The rank order potency of compounds to inhibit [3H]ATPA binding in rat DRG and GluR5 membranes were in agreement. These finding demonstrate that [3H]ATPA can be used as a radioligand to examine the pharmacological properties of GluR5 containing kainate receptors.

  1. Role of the DIS hairpin in replication of human immunodeficiency virus type 1.

    Science.gov (United States)

    Berkhout, B; van Wamel, J L

    1996-10-01

    The virion-associated genome of human immunodeficiency virus type 1 consists of a noncovalently linked dimer of two identical, unspliced RNA molecules. A hairpin structure within the untranslated leader transcript is postulated to play a role in RNA dimerization through base pairing of the autocomplementary loop sequences. This hairpin motif with the palindromic loop sequence is referred to as the dimer initiation site (DIS), and the type of interaction is termed loop-loop kissing. Detailed phylogenetic analysis of the DIS motifs in different human and simian immunodeficiency viruses revealed conservation of the hairpin structure with a 6-mer palindrome in the loop, despite considerable sequence divergence. This finding supports the loop-loop kissing mechanism. To test this possibility, proviral genomes with mutations in the DIS palindrome were constructed. The appearance of infectious virus upon transfection into SupT1 T cells was delayed for the DIS mutants compared with that obtained by transfection of the wild-type provirus (pLAI), confirming that this RNA motif plays an important role in virus replication. Surprisingly, the RNA genome extracted from mutant virions was found to be fully dimeric and to have a normal thermal stability. These results indicate that the DIS motif is not essential for human immunodeficiency virus type 1 RNA dimerization and suggest that DIS base pairing does not contribute to the stability of the mature RNA dimer. Instead, we measured a reduction in the amount of viral RNA encapsidated in the mutant virions, suggesting a role of the DIS motif in RNA packaging. This result correlates with the idea that the processes of RNA dimerization and packaging are intrinsically linked, and we propose that DIS pairing is a prerequisite for RNA packaging.

  2. Expression of Human Immunodeficiency Virus Type 1 Neutralizing Antibody Fragments Using Human Vaginal Lactobacillus

    Science.gov (United States)

    Marcobal, Angela; Liu, Xiaowen; Zhang, Wenlei; Dimitrov, Antony S.; Jia, Letong; Lee, Peter P.; Fouts, Timothy R.; Parks, Thomas P.

    2016-01-01

    Abstract Eradication of human immunodeficiency virus type 1 (HIV-1) by vaccination with epitopes that produce broadly neutralizing antibodies is the ultimate goal for HIV prevention. However, generating appropriate immune responses has proven difficult. Expression of broadly neutralizing antibodies by vaginal colonizing lactobacilli provides an approach to passively target these antibodies to the mucosa. We tested the feasibility of expressing single-chain and single-domain antibodies (dAbs) in Lactobacillus to be used as a topical microbicide/live biotherapeutic. Lactobacilli provide an excellent platform to express anti-HIV proteins. Broadly neutralizing antibodies have been identified against epitopes on the HIV-1 envelope and have been made into active antibody fragments. We tested single-chain variable fragment m9 and dAb-m36 and its derivative m36.4 as prototype antibodies. We cloned and expressed the antibody fragments m9, m36, and m36.4 in Lactobacillus jensenii-1153 and tested the expression levels and functionality. We made a recombinant L. jensenii 1153-1128 that expresses dAb-m36.4. All antibody fragments m9, m36, and m36.4 were expressed by lactobacilli. However, we noted the smaller m36/m36.4 were expressed to higher levels, ≥3 μg/ml. All L. jensenii-expressed antibody fragments bound to gp120/CD4 complex; Lactobacillus-produced m36.4 inhibited HIV-1BaL in a neutralization assay. Using a TZM-bl assay, we characterized the breadth of neutralization of the m36.4. Delivery of dAbs by Lactobacillus could provide passive transfer of these antibodies to the mucosa and longevity at the site of HIV-1 transmission. PMID:26950606

  3. Aspects of gastrointestinal immunology and nutrition in human immunodeficiency virus-1 infection in Brazil

    Directory of Open Access Journals (Sweden)

    Castello-Branco Luiz RR

    2000-01-01

    Full Text Available Mucosal surfaces have a fundamental participation in many aspects of the human immunodeficiency virus (HIV infection pathogenesis. In Brazilian HIV-1 infected subjects, loss of weight and appetite are among the most debilitating symptoms. In this review we describe a defined mucosal immunogen that has profound but transient effects on HIV viral load, and we suggest that gut associated lymphoid tissue under constant immunostimulation is likely to provide a major contribution to the total levels of HIV. We also show that hypermetabolism appears to play a role in the wasting process in Brazilian patients coinfected with HIV and tuberculosis.

  4. Action of uracil analogs on human immunodeficiency virus type 1 and its reverse transcriptase.

    Science.gov (United States)

    Piras, G; Dutschman, G E; Im, G J; Pan, B C; Chu, S H; Cheng, Y C

    1995-02-01

    Three structural analogs of 5-ethyl-1-benzyloxymethyl-6-(phenylthio)uracil (E-BPU) inhibited human immunodeficiency virus type 1 (HIV-1) replication without cytotoxicity in vitro and were more potent than azidothymidine and were as potent as E-BPU. The target of these compounds is HIV-1 reverse transcriptase. Reverse transcriptases resistant to nevirapine (tyrosine at position 181 to cysteine) and TIBO R82150 (leucine at position 100 to isoleucine) are cross resistant to E-BPU analogs. Nevirapine- or TIBO R82150-resistant HIV-1 were cross resistant to E-BPU analogs but were inhibited at concentrations 11- to 135-fold lower than the cytotoxic doses.

  5. Broadly neutralizing antibodies targeted to mucin-type carbohydrate epitopes of human immunodeficiency virus

    DEFF Research Database (Denmark)

    Hansen, J E; Nielsen, C; Arendrup, M;

    1991-01-01

    . This inhibition was found in infection of both lymphocytic cells and monocytoid cells. Viruses tested included six HIV-1 and five HIV-2 isolates propagated in different cells, as well as infectious plasma from AIDS patients. The antiviral effect of anti-Tn MAbs occurred by specific binding of the MAb to the virus......The cancer-related mucin-type carbohydrate neoantigen Tn was found on gp160 and gp120 of human immunodeficiency virus (HIV). Immunoglobulin G (IgG) and IgM monoclonal antibodies (MAbs) against Tn neutralized infection with cell-free virus and blocked fusion between HIV-infected and uninfected cells...

  6. Broadly neutralizing antibodies targeted to mucin-type carbohydrate epitopes of human immunodeficiency virus

    DEFF Research Database (Denmark)

    Hansen, J E; Nielsen, C; Arendrup, M

    1991-01-01

    The cancer-related mucin-type carbohydrate neoantigen Tn was found on gp160 and gp120 of human immunodeficiency virus (HIV). Immunoglobulin G (IgG) and IgM monoclonal antibodies (MAbs) against Tn neutralized infection with cell-free virus and blocked fusion between HIV-infected and uninfected cells......; this binding was inhibitable by pure Tn antigen, and indications were found that this inhibition occurred at a pre-entry step. Boosting the naturally occurring low-titer anti-Tn activity may be of prophylactic value, as suggested by the in vitro neutralization found in this study....

  7. Comparative analysis of Rev function in human immunodeficiency virus types 1 and 2.

    OpenAIRE

    Garrett, E D; Cullen, B R

    1992-01-01

    The Rev proteins of the related but distinct human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) display incomplete functional reciprocity. One possible explanation for this observation is that HIV-2 Rev is unable to interact with the HIV-1 Rev-response element (RRE1). However, an analysis of the biological activity of chimeric proteins derived from HIV-1 and HIV-2 Rev reveals that this target specificity does not map to the Rev RNA binding domain but is instead primarily determined ...

  8. Twenty years of human immunodeficiency virus care at the Mayo Clinic: Past, present and future

    Science.gov (United States)

    Cummins, Nathan W; Badley, Andrew D; Kasten, Mary J; Sampath, Rahul; Temesgen, Zelalem; Whitaker, Jennifer A; Wilson, John W; Yao, Joseph D; Zeuli, John; Rizza, Stacey A

    2016-01-01

    The Mayo human immunodeficiency virus (HIV) Clinic has been providing patient centered care for persons living with HIV in Minnesota and beyond for the past 20 years. Through multidisciplinary engagement, vital clinical outcomes such as retention in care, initiation of antiretroviral therapy and virologic suppression are maximized. In this commentary, we describe the history of the Mayo HIV Clinic and its best practices, providing a “Mayo Model” of HIV care that exceeds national outcomes and may be applicable in other settings. PMID:27175350

  9. [Oral plasmablastic lymphoma in a human immunodeficiency virus positive child: a case report].

    Science.gov (United States)

    Astolfo, María Florencia; D'Antonio, Federico; Dartiguelongue, Juan B; Arabolaza, María N; Cheistwer, Ariel; De Matteo, Elena; Torrado, Lidia; Martínez Iriart, Emilio

    2016-04-01

    Plasmablastic lymphoma is a rare and aggressive subtype of diffuse large B cell non-Hodgkin lymphoma, originally described in the oral cavity of male adults with acquired immune deficiency syndrome. It is composed of neoplastic ceils which resemble immunoblasts but present immunophenotype distinctive of plasma cell and Epstein-Barr virus latent infection. In children, it is an even rarer disease. We present a case of oral plasmablastic lymphoma in a vertically transmitted human immunodeficiency virus-positive five-year-old child.

  10. Proteins, peptides, polysaccharides, and nucleotides with inhibitory activity on human immunodeficiency virus and its enzymes.

    Science.gov (United States)

    Ng, Tzi Bun; Cheung, Randy Chi Fai; Wong, Jack Ho; Chan, Wai Yee

    2015-12-01

    Human immunodeficiency virus (HIV), the causative agent of acquired immune deficiency syndrome, has claimed innumerable lives in the past. Many biomolecules which suppress HIV replication and also other biomolecules that inhibit enzymes essential to HIV replication have been reported. Proteins including a variety of milk proteins, ribosome-inactivating proteins, ribonucleases, antifungal proteins, and trypsin inhibitors; peptides comprising cathelicidins, defensins, synthetic peptides, and others; polysaccharides and polysaccharopeptides; nucleosides, nucleotides, and ribozymes, demonstrated anti-HIV activity. In many cases, the mechanism of anti-HIV action has been elucidated. Strategies have been devised to augment the anti-HIV potency of these compounds.

  11. Distal sensory polyneuropathy in human immunodeficiency virus patients and nucleoside analogue antiretroviral agents

    Directory of Open Access Journals (Sweden)

    Jose Jimmy

    2007-01-01

    Full Text Available Distal sensory polyneuropathy, which occur commonly in human immunodeficiency virus (HIV patients can occur as a consequence of the disease itself or the antiretroviral treatment the patient is receiving. Among the antiretroviral agents, nucleoside analogues are commonly associated with neuropathy and the main underlying mechanism is thought to be the mitochondrial toxicity exhibited by these agents. Clinical presentation of antiretroviral induced neuropathy is similar to that associated with the HIV infection and in many patients they may overlap. Treatment is primarily symptomatic and certain pathogenesis-based approaches have shown promising results.

  12. Peginterferon plus ribavirin for chronic hepatitis C in patients with human immunodeficiency virus

    DEFF Research Database (Denmark)

    Gluud, Lise Lotte; Marchesini, Emanuela; Iorio, Alfonso

    2009-01-01

    OBJECTIVES: The aim of this study was to assess the effects of peginterferon plus ribavirin for chronic hepatitis C in patients with human immunodeficiency virus (HIV). METHODS: Trials were identified through manual and electronic searches. Randomized trials comparing peginterferon plus ribavirin...... with interferon plus ribavirin, the proportion with a sustained virological response was 26% (109 of 423) for patients with genotype 1 or 4 and 57% (130 of 230) for genotype 2 or 3. Several adverse events occurred, including fatal lactic acidosis and liver failure, but there were no significant differences...

  13. Cardiovascular disease in human immunodeficiency virus infected patients: A true or perceived risk?

    Institute of Scientific and Technical Information of China (English)

    Shima; Shahbaz; Marcella; Manicardi; Giovanni; Guaraldi; Paolo; Raggi

    2015-01-01

    After the successful introduction of highly active antiretroviral agents the survival of patients infected with the human immunodeficiency virus(HIV) in developed countries has increased substantially. This has allowed the surfacing of several chronic diseases among which cardiovascular disease(CVD) is prominent. The pathogenesis of CVD in HIV is complex and involves a combination of traditional and HIV related factors. An accurate assessment of risk of CVD in these patients is still elusive and as a consequence the most appropriate preventive and therapeutic interventions remain controversial.

  14. Recent Recommendations for Management of Human Immunodeficiency Virus-Positive Patients.

    Science.gov (United States)

    Robbins, Miriam R

    2017-04-01

    Human immunodeficiency virus (HIV) infection has become a chronic condition. HIV is not a valid reason to deny, delay, or withhold dental treatment. There are no absolute contraindications and few complications associated with comprehensive oral health care treatment delivered in an outpatient setting for asymptomatic HIV-infected patients and clinically stable patients with AIDS. Consultation with the patient's medical provider and modifications in the delivery of dental treatment may be necessary when treating patients with advanced HIV disease or other comorbid conditions. Oral health care is an integral and important part of comprehensive health care for all patients with HIV/AIDS. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Extensive astrocyte infection is prominent in human immunodeficiency virus-associated dementia.

    Science.gov (United States)

    Churchill, Melissa J; Wesselingh, Steven L; Cowley, Daniel; Pardo, Carlos A; McArthur, Justin C; Brew, Bruce J; Gorry, Paul R

    2009-08-01

    Astrocyte infection with human immunodeficiency virus (HIV) is considered rare, so astrocytes are thought to play a secondary role in HIV neuropathogenesis. By combining double immunohistochemistry, laser capture microdissection, and highly sensitive multiplexed polymerase chain reaction to detect HIV DNA in single astrocytes in vivo, we showed that astrocyte infection is extensive in subjects with HIV-associated dementia, occurring in up to 19% of GFAP+ cells. In addition, astrocyte infection frequency correlated with the severity of neuropathological changes and proximity to perivascular macrophages. Our data indicate that astrocytes can be extensively infected with HIV, and suggest an important role for HIV-infected astrocytes in HIV neuropathogenesis.

  16. Efficient Human Immunodeficiency Virus (HIV-1) Infection of Cells Lacking PDZD8

    OpenAIRE

    Zhang, Shijian; Sodroski, Joseph

    2015-01-01

    PDZD8 can bind the capsid proteins of different retroviruses, and transient knockdown of PDZD8 results in a decrease in the efficiency of an early, post-entry event in the retrovirus life cycle. Here we used the CRISPR-CAS9 system to create cell lines in which PDZD8 expression is stably eliminated. The PDZD8-knockout cell lines were infected by human immunodeficiency virus (HIV-1) and murine leukemia virus as efficiently as the parental PDZD8-expressing cells. These results indicate that PDZD...

  17. Efficient human immunodeficiency virus (HIV-1) infection of cells lacking PDZD8.

    Science.gov (United States)

    Zhang, Shijian; Sodroski, Joseph

    2015-07-01

    PDZD8 can bind the capsid proteins of different retroviruses, and transient knockdown of PDZD8 results in a decrease in the efficiency of an early, post-entry event in the retrovirus life cycle. Here we used the CRISPR-CAS9 system to create cell lines in which PDZD8 expression is stably eliminated. The PDZD8-knockout cell lines were infected by human immunodeficiency virus (HIV-1) and murine leukemia virus as efficiently as the parental PDZD8-expressing cells. These results indicate that PDZD8 is not absolutely necessary for HIV-1 infection and diminishes its attractiveness as a potential target for intervention.

  18. Gonococcal arthritis in human immunodeficiency virus-infected patients. Review of the literature.

    Science.gov (United States)

    Sena Corrales, Gabriel; Mora Navas, Laura; Palacios Muñoz, Rosario; García López, Victoria; Márquez Solero, Manuel; Santos González, Jesús

    We report a case of gonococcal arthritis in a patient with human immunodeficiency virus (HIV) infection and review 17 previously published cases; only one patient presented urethritis, and blood cultures were positive in one case. Gonococcal arthritis is rare in HIV-infected patients and is not usually associated with other symptoms. It should be considered in the differential diagnosis of acute arthritis in patients with HIV infection. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  19. Orphans and Vulnerable Children Affected by Human Immunodeficiency Virus in Sub-Saharan Africa.

    Science.gov (United States)

    Bryant, Malcolm; Beard, Jennifer

    2016-02-01

    In Sub-Saharan Africa, 15.1 million children have been orphaned because of human immunodeficiency virus (HIV). They face significant vulnerabilities, including stigma and discrimination, trauma and stress, illness, food insecurity, poverty, and difficulty accessing education. Millions of additional children who have living parents are vulnerable because their parents or other relatives are infected. This article reviews the current situation of orphans and vulnerable children, explores the underlying determinants of vulnerability and resilience, describes the response by the global community, and highlights the challenges as the HIV pandemic progresses through its fourth decade.

  20. Human Immunodeficiency Virus Type 1 Protease and the Emergence of Drug Resistance

    DEFF Research Database (Denmark)

    Poulsen, Nina Rødtness

    in the virus life cycle has made it a major target for drug development and active site competitive inhibitors have been successful in the battle against HIV. Unfortunately, the massive drug pressure along with high-level replication and lack of proofreading by the viral reverse transcriptase have resulted......Human immunodeficiency virus type-1 (HIV-1) protease (PR) is responsible for cleaving ten different sites in the viral Gag and Gag-pol polyproteins, thereby releasing the structural proteins and enzymes necessary for the maturation and infectivity of the HIV-1 virus. The vital role of HIV-1 PR...

  1. Pulmonary toxoplasmosis in human immunodeficiency virus-infected patients in the era of antiretroviral therapy.

    Science.gov (United States)

    Velásquez, Jorge N; Ledesma, Bibiana A; Nigro, Monica G; Vittar, Natalia; Rueda, Nestor; De Carolis, Luis; Figueiras, Olga; Carnevale, Silvana; Corti, Marcelo

    2016-01-01

    Toxoplasmosis is a severe opportunistic infection in patients infected with the human immunodeficiency virus (HIV). The lung is a major site of infection after the central nervous system. In this report we described two cases of pneumonia due to Toxoplasma gondii infection in HIV patients with antiretroviral therapy. Clinical and radiological abnormalities are not specific. Pulmonary toxoplasmosis should be considered in HIV-infected patients with late stage of HIV, CD4 count less than 100 cells/µl and a poor adherence to HAART.

  2. Inhibition of human immunodeficiency virus (HIV) infection in vitro by anticarbohydrate monoclonal antibodies

    DEFF Research Database (Denmark)

    Hansen, J E; Clausen, H; Nielsen, C

    1990-01-01

    Carbohydrate structures are often involved in the initial adhesion of pathogens to target cells. In the present study, a panel of anticarbohydrate monoclonal antibodies (MAbs) was tested for their ability to inhibit in vitro human immunodeficiency virus infectivity. MAbs against three different N......), and the cell type used as the infection target (MT4, PMC, or selected T4 lymphocytes). Inhibition was observed when viruses were preincubated with MAbs but not when cells were preincubated with MAbs before inoculation, and the MAbs were shown to precipitate 125I-labeled gp120. The MAbs therefore define...

  3. Immediate-early gene region of human cytomegalovirus trans-activates the promoter of human immunodeficiency virus

    Energy Technology Data Exchange (ETDEWEB)

    Davis, M.G.; Kenney, S.C.; Kamine, J.; Pagano, J.S.; Huang, E.S.

    1987-12-01

    Almost all homosexual patients with acquired immunodeficiency syndrome are also actively infected with human cytomegalovirus (HCMV). The authors have hypothesized that an interaction between HCMV and human immunodeficiency virus (HIV), the agent that causes acquired immunodeficiency syndrome, may exist at a molecular level and contribute to the manifestations of HIV infection. In this report, they demonstrate that the immediate-early gene region of HCMV, in particular immediate-early region 2, trans-activates the expression of the bacterial gene chloramphenicol acetyltransferase that is fused to the HIV long terminal repeat and carried by plasmid pHIV-CAT. The HCMV immediate-early trans-activator increases the level of mRNA from the plamid pHIV-CAT. The sequences of HIV that are responsive to trans-activation by the HDMV immediate-early region are distinct from HIV sequences that are required for response to the HIV tat. The stimulation of HIV gene expression by HDMV gene functions could enhance the consequences of HIV infection in persons with previous or concurrent HCMV infection.

  4. Modeling Human Severe Combined Immunodeficiency and Correction by CRISPR/Cas9-Enhanced Gene Targeting

    Directory of Open Access Journals (Sweden)

    Chia-Wei Chang

    2015-09-01

    Full Text Available Mutations of the Janus family kinase JAK3 gene cause severe combined immunodeficiency (SCID. JAK3 deficiency in humans is characterized by the absence of circulating T cells and natural killer (NK cells with normal numbers of poorly functioning B cells (T–B+NK–. Using SCID patient-specific induced pluripotent stem cells (iPSCs and a T cell in vitro differentiation system, we demonstrate a complete block in early T cell development of JAK3-deficient cells. Correction of the JAK3 mutation by CRISPR/Cas9-enhanced gene targeting restores normal T cell development, including the production of mature T cell populations with a broad T cell receptor (TCR repertoire. Whole-genome sequencing of corrected cells demonstrates no CRISPR/Cas9 off-target modifications. These studies describe an approach for the study of human lymphopoiesis and provide a foundation for gene correction therapy in humans with immunodeficiencies.

  5. Avian influenza: potential impact on sub-Saharan military populations with high rates of human immunodeficiency virus/acquired immunodeficiency syndrome.

    Science.gov (United States)

    Feldman, Robert L; Nickell, Kent

    2007-07-01

    Several sub-Saharan militaries have large percentages of troops with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. With the arrival of avian influenza in Africa, the potential exists that some of those soldiers might also become infected with H5N1, the virus responsible for the disease. Two possible scenarios have been postulated regarding how such a coinfection of HIV and H5N1 might present. (1) Soldiers already weakened by HIV/acquired immunodeficiency syndrome rapidly succumb to H5N1. The cause of death is a "cytokine storm," essentially a runaway inflammatory response. (2) The weakened immune system prevents the cytokine storm from occurring; however, H5N1 is still present, replicating, and being shed, leading to the infection of others. A cytokine storm is particularly dangerous for individuals of military age, as evidenced by the large number of soldiers who died during the 1918 influenza epidemic. If large numbers of sub-Saharan soldiers suffer a similar fate from avian influenza, then military and political instability could develop.

  6. Viral Interactions in Human Lymphoid Tissue: Human Herpesvirus 7 Suppresses the Replication of CCR5-Tropic Human Immunodeficiency Virus Type 1 via CD4 Modulation▿

    OpenAIRE

    2006-01-01

    Human immunodeficiency virus (HIV) infection is often accompanied by infection with other pathogens that affect the clinical course of HIV disease. Here, we identified another virus, human herpesvirus 7 (HHV-7) that interferes with HIV type 1 (HIV-1) replication in human lymphoid tissue, where critical events of HIV disease occur. Like the closely related HHV-6, HHV-7 suppresses the replication of CCR5-tropic (R5) HIV-1 in coinfected blocks of human lymphoid tissue. Unlike HHV-6, which affect...

  7. Immune humanization of immunodeficient mice using diagnostic bone marrow aspirates from carcinoma patients.

    Directory of Open Access Journals (Sweden)

    Melanie Werner-Klein

    Full Text Available Tumor xenografts in immunodeficient mice, while routinely used in cancer research, preclude studying interactions of immune and cancer cells or, if humanized by allogeneic immune cells, are of limited use for tumor-immunological questions. Here, we explore a novel way to generate cancer models with an autologous humanized immune system. We demonstrate that hematopoietic stem and progenitor cells (HSPCs from bone marrow aspirates of non-metastasized carcinoma patients, which are taken at specialized centers for diagnostic purposes, can be used to generate a human immune system in NOD-scid IL2rγ(null (NSG and HLA-I expressing NSG mice (NSG-HLA-A2/HHD comprising both, lymphoid and myeloid cell lineages. Using NSG-HLA-A2/HHD mice, we show that responsive and self-tolerant human T cells develop and human antigen presenting cells can activate human T cells. As critical factors we identified the low potential of bone marrow HSPCs to engraft, generally low HSPC numbers in patient-derived bone marrow samples, cryopreservation and routes of cell administration. We provide here an optimized protocol that uses a minimum number of HSPCs, preselects high-quality bone marrow samples defined by the number of initially isolated leukocytes and intra-femoral or intra-venous injection. In conclusion, the use of diagnostic bone marrow aspirates from non-metastasized carcinoma patients for the immunological humanization of immunodeficient mice is feasible and opens the chance for individualized analyses of anti-tumoral T cell responses.

  8. Detection of human immunodeficiency virus DNA in cultured human glial cells by means of the polymerase chain reaction

    DEFF Research Database (Denmark)

    Teglbjærg, Lars Stubbe; Hansen, J-ES; Dalbøge, H;

    1991-01-01

    This report describes the use of the polymerase chain reaction (PCR) for the detection of viral genomic sequences in latently infected cells. Infection with human immunodeficiency virus in cultures of human glial cells was demonstrated, using nucleic acid amplification followed by dot blot...... hybridization. It was not possible to detect any viral antigen production in the cultures, and attempts to recover virus by highly sensitive coculture techniques were unsuccessful, indicating that the infection was latent. The PCR technique provides a simple approach to the study of viral infection in cases...

  9. Detection of human immunodeficiency virus DNA in cultured human glial cells by means of the polymerase chain reaction

    DEFF Research Database (Denmark)

    Teglbjaerg, L L; Hansen, J E; Dalbøge, H

    1991-01-01

    This report describes the use of the polymerase chain reaction (PCR) for the detection of viral genomic sequences in latently infected cells. Infection with human immunodeficiency virus in cultures of human glial cells was demonstrated, using nucleic acid amplification followed by dot blot...... hybridization. It was not possible to detect any viral antigen production in the cultures, and attempts to recover virus by highly sensitive coculture techniques were unsuccessful, indicating that the infection was latent. The PCR technique provides a simple approach to the study of viral infection in cases...

  10. Establishment of a Novel Bladder Cancer Xenograft Model in Humanized Immunodeficient Mice

    Directory of Open Access Journals (Sweden)

    Zhen Gong

    2015-10-01

    Full Text Available Background/Aims: The aim of this study was to develop a novel model by transplanting human bladder cancer xenografts into humanized immunodeficient mice (SCID. Methods: The animals first underwent sublethal irradiation and then were subjected to simultaneous transplantation of human lymphocytes (5 × 107 cells/mouse i.p. and human bladder cancer cells (3 × 106 cells/mouse s.c.. Results: The xenografts developed in all 12 mice that had received bladder cancer BIU-87 cells, and the tumor specimens were evaluated histologically. All 6 model mice expressed human CD3 mRNA and/or protein in the peripheral blood, spleens and xenografts. The mean proportion of human CD3+ cells was 19% with a level of human IgG 532.4µ/ml in the peripheral blood at Week 6 after transplant inoculation. The re-constructed human immune system in these mice was confirmed to be functional by individual in vitro testing of their proliferative, secretory and cytotoxic responses. Conclusion: The successful engraftment of the human bladder cancer xenografts and the establishment of the human immune system in our in vivo model described here may provide a useful tool for the development of novel therapeutic strategies targeting at bladder cancer.

  11. Survival of Human Neurofibroma in Immunodeficient Mice and Initial Results of Therapy With Pirfenidone

    Directory of Open Access Journals (Sweden)

    Babovic-Vuksanovic Dusica

    2004-01-01

    Full Text Available Neurofibromatosis type I is a common tumor predisposing disease in humans. Surgical therapy can be applied only in selected patients with resectable masses. Hence, development of new therapies for this disease is urgent. We used human neurofibroma implants in mice with severe combined immunodeficiency (SCID as a model to test the toxicity and potential efficacy of pirfenidone, a new therapeutic agent. Two hundred twelve human neurofibromas were transplanted into various locations in 59 experimental animals, and 30 mice with implants received oral pirfenidone for up to six weeks. Survival of neurofibromas in animals treated with pirfenidone was lower than in the control group ( P=.02 . Tumors did not change histologic appearance or vascularization in response to pirfenidone. Treatment with pirfenidone, a new antifibrotic agent, inhibits survival of some tumors without causing toxicity in animals.

  12. R5 human immunodeficiency virus type 1 infection of fetal thymic organ culture induces cytokine and CCR5 expression.

    NARCIS (Netherlands)

    Choudhary, S.K.; Choudhary, N.R.; Kimbrell, K.C.; Colasanti, J.; Ziogas, A.; Kwa, D.; Schuitemaker, H.; Camerini, D.

    2005-01-01

    Late-stage CCR5 tropic human immunodeficiency virus type 1 (HIV-1) isolates (R5 HIV-1) can deplete nearly all CD4+ thymocytes from human thymus/liver grafts, despite the fact that fewer than 5% of these cells express CCR5. To resolve this paradox, we studied the replication and cytopathic effects (C

  13. Human immunodeficiency virus and nodular regenerative hyperplasia of liver: A systematic review

    Institute of Scientific and Technical Information of China (English)

    Archita; Sood; Mariana; Castrejón; Sammy; Saab

    2014-01-01

    AIM: To investigate the diagnosis, pathogenesis, natural history, and management of nodular regenerative hyperplasia(NRH) in patients with human immunodeficiency virus(HIV). METHODS: We performed a systematic review of the medical literature regarding NRH in patients with HIV. Inclusion criteria include reports with biopsy proven NRH. We studied the clinical features of NRH, in particular, related to its presenting manifestation and laboratory values. Combinations of the following keywords were implemented: "nodular regenerative hyperplasia", "human immunodeficiency virus", "noncirrhotic portal hypertension", "idiopathic portal hypertension", "cryptogenic liver disease", "highly active antiretroviral therapy" and "didanosine". The bibliographies of these studies were subsequently searched for any additional relevant publications.RESULTS: The clinical presentation of patients with NRH varies from patients being completely asymptomatic to the development of portal hypertension – namely esophageal variceal bleeding and ascites. Liver associated enzymes are generally normal and synthetic function well preserved. There is a strong association between the occurrence of NRH and the use of antiviral therapies such as didanosine. The management of NRH revolves around treating the manifestations of portal hypertension. The prognosis of NRH is generally good since liver function is preserved. A high index of suspicion is required to make a identify NRH. CONCLUSION: The appropriate management of HIVinfected persons with suspected NRH is yet to be outlined. However, NRH is a clinically subtle condition that is difficult to diagnose, and it is important to be able to manage it according to the best available evidence.

  14. Tp-e interval and Tp-e/QT ratio in patients with Human Immunodeficiency Virus.

    Science.gov (United States)

    Ünal, Sefa; Yayla, Çağrı; Açar, Burak; Ertem, Ahmet G; Akboğa, Mehmet K; Gökaslan, Serkan; Erdöl, Mehmet A; Sönmezer, Meliha Ç; Kaya Kiliç, Esra; Ataman Hatipoğlu, Çiğdem; Aydoğdu, Sinan; Temizhan, Ahmet

    2017-03-09

    Human Immunodeficiency Virus (HIV) infection and AIDS are known to cause cardiovascular diseases such as premature coronary artery disease, cardiomyopathy, and arrhythmias. Recently, Tp-e interval and Tp-e/QT ratio has been shown as a novel marker of ventricular repolarization. We aimed to evaluate the ventricular repolarization using Tp-e interval and Tp-e/QT ratio in patients with Human Immunodeficiency Virus (HIV) infection. Totally 48 patients with HIV and 60 control subjects were enrolled to the study. Tp-e interval, Tp-e/QT and Tp-e/QTc ratio were measured from the 12-lead electrocardiogram. Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio were significantly higher in patients with HIV than control subjects (all pe interval and disease duration (r=0.298, p=0.048). and inverse correlation between Tp-e interval and CD4 count(r=-0.303, p=0.036). Our study showed that Tp-e interval, Tp-e/QT and Tp-e/QTc ratios were increased in patients with HIV than control subjects.

  15. Potent inhibition of human immunodeficiency virus by MDL 101028, a novel sulphonic acid polymer.

    Science.gov (United States)

    Taylor, D L; Brennan, T M; Bridges, C G; Mullins, M J; Tyms, A S; Jackson, R; Cardin, A D

    1995-10-01

    MDL 101028, a novel biphenyl disulphonic acid urea co-polymer was designed and synthesised as a heparin mimetic. This low molecular weight polymer showed potent inhibition of human immunodeficiency virus type 1 (HIV-1) replication in a number of host-cell/virus systems, including primary clinical isolates of the virus cultured in human peripheral blood mononuclear cells (PBMCs). When compared with the heterogeneous polysulphated molecules, heparin and dextran sulphate, this chemically defined compound showed equivalent antiviral activity with 50% inhibitory concentrations (IC50s) in the range 0.27-3.0 micrograms/ml in the host-cell/virus systems tested. MDL 101028 also inhibited the replication of HIV type 2 and the simian immunodeficiency virus (SIV), as well as HIV-1 variants resistant to reverse transcriptase inhibitors. Virus growth was blocked when exposure of T-lymphocytes to MDL 101028 was restricted to the virus absorption stage, or even in whole blood conditions. MDL 101028 did not irreversibly inactivate virions, and in contrast to heparin, did not inhibit the attachment of radiolabelled HIV-1 to CD4+ T-cells. MDL 101028 blocked HIV-induced cell-to-cell fusion and this activity appears to explain the mechanism of its antiviral action. The antiviral evaluation of discrete oligomer molecules of MDL 101028 showed that a polymer chain length of six repeating units had optimal potency. The lack of anticoagulant properties and significant antiviral activity in whole blood may allow the development of MDL 101028 as a treatment of HIV infections.

  16. 01-ERD-111 - The Development of Synthetic High Affinity Ligands

    Energy Technology Data Exchange (ETDEWEB)

    Perkins, J; Balhorn, R; Cosman, M; Lightstone, F; Zeller, L

    2004-02-05

    The aim of this project was to develop Synthetic High-Affinity Ligands (SHALs), which bind with high affinity and specificity to proteins of interest for national security and cancer therapy applications. The aim of producing synthetic ligands for sensory devices as an alternative to antibody-based detection assays and therapeutic agents is to overcome the drawbacks associated with antibody-based in next-generation sensors and systems. The focus area of the project was the chemical synthesis of the SHALs. The project concentrated on two different protein targets. (a) The C fragment of tetanus and botulinum toxin, potential biowarfare agents. A SHAL for tetanus or botulinum toxin would be incorporated into a sensory device for the toxins. (b) HLA-DR10, a protein found in high abundance on the surface of Non-Hodgkins Lymphoma. A SHAL specific to a tumor marker, labeled with a radionuclide, would enable the targeted delivery of radiation therapy to metastatic disease. The technical approach used to develop a SHAL for each protein target will be described in more detail below. However, in general, the development of a SHAL requires a combination of computational modeling techniques, modern nuclear magnetic resonance spectroscopy (NMR) and synthetic chemistry.

  17. Stoichiometry of monoclonal antibody neutralization of T-cell line-adapted human immunodeficiency virus type 1

    DEFF Research Database (Denmark)

    Schønning, Kristian; Lund, O; Lund, O S

    1999-01-01

    In order to study the stoichiometry of monoclonal antibody (MAb) neutralization of T-cell line-adapted human immunodeficiency virus type 1 (HIV-1) in antibody excess and under equilibrium conditions, we exploited the ability of HIV-1 to generate mixed oligomers when different env genes are coexpr......In order to study the stoichiometry of monoclonal antibody (MAb) neutralization of T-cell line-adapted human immunodeficiency virus type 1 (HIV-1) in antibody excess and under equilibrium conditions, we exploited the ability of HIV-1 to generate mixed oligomers when different env genes...

  18. Stoichiometry of monoclonal antibody neutralization of T-cell line-adapted human immunodeficiency virus type 1

    DEFF Research Database (Denmark)

    Schønning, Kristian; Lund, O; Lund, O S;

    1999-01-01

    In order to study the stoichiometry of monoclonal antibody (MAb) neutralization of T-cell line-adapted human immunodeficiency virus type 1 (HIV-1) in antibody excess and under equilibrium conditions, we exploited the ability of HIV-1 to generate mixed oligomers when different env genes are coexpr......In order to study the stoichiometry of monoclonal antibody (MAb) neutralization of T-cell line-adapted human immunodeficiency virus type 1 (HIV-1) in antibody excess and under equilibrium conditions, we exploited the ability of HIV-1 to generate mixed oligomers when different env genes...

  19. Protection of rabbits and immunodeficient mice against lethal poxvirus infections by human monoclonal antibodies.

    Directory of Open Access Journals (Sweden)

    Lindsay Crickard

    Full Text Available Smallpox (variola virus is a bioweapon concern. Monkeypox is a growing zoonotic poxvirus threat. These problems have resulted in extensive efforts to develop potential therapeutics that can prevent or treat potentially lethal poxvirus infections in humans. Monoclonal antibodies (mAbs against smallpox are a conservative approach to this problem, as the licensed human smallpox vaccine (vaccinia virus, VACV primarily works on the basis of protective antibody responses against smallpox. Fully human mAbs (hmAbs against vaccinia H3 (H3L and B5 (B5R, targeting both the mature virion (MV and extracellular enveloped virion (EV forms, have been developed as potential therapeutics for use in humans. Post-exposure prophylaxis was assessed in both murine and rabbit animal models. Therapeutic efficacy of the mAbs was assessed in three good laboratory practices (GLP studies examining severe combined immunodeficiency mice (SCID given a lethal VACV infection. Pre-exposure combination hmAb therapy provided significantly better protection against disease and death than either single hmAb or vaccinia immune globulin (VIG. Post-exposure combination mAb therapy provided significant protection against disease and death, and appeared to fully cure the VACV infection in ≥50% of SCID mice. Therapeutic efficacy was then assessed in two rabbit studies examining post-exposure hmAb prophylaxis against rabbitpox (RPXV. In the first study, rabbits were infected with RPVX and then provided hmAbs at 48 hrs post-infection, or 1 hr and 72 hrs post-infection. Rabbits in both groups receiving hmAbs were 100% protected from death. In the second rabbitpox study, 100% of animal treated with combination hmAb therapy and 100% of animals treated with anti-B5 hmAb were protected. These findings suggest that combination hmAb treatment may be effective at controlling smallpox disease in immunocompetent or immunodeficient humans.

  20. Human immunodeficiency virus type 1 infection of human uterine epithelial cells: viral shedding and cell contact-mediated infectivity.

    Science.gov (United States)

    Asin, Susana N; Wildt-Perinic, Dunja; Mason, Sarah I; Howell, Alexandra L; Wira, Charles R; Fanger, Michael W

    2003-05-15

    We examined the mechanism of human immunodeficiency virus (HIV) type 1 infection of human uterine epithelial cells to gain a clearer understanding of the events by which HIV-1 infects cells within the female reproductive tract. We demonstrated that these cells can be productively infected by HIV-1 and that infection is associated with viral RNA reverse transcription, DNA transcription, and secretion of infectious virus. Levels of viral DNA and secreted virus decreased gradually after infection. Moreover, virus released by the uterine epithelial cells shortly after infection was able to infect human T cell lines, but virus released later did not. In contrast, human CD4(+) T cell lines were infected after cocultivation with epithelial cells at both early and late stages of infection. These data demonstrated that HIV-1 infects human epithelial cells of upper reproductive tract origin and that productive viral infection of epithelial cells may be an important mechanism of transmission of HIV-1 infection in women.

  1. Productive infection of human peripheral blood mononuclear cells by feline immunodeficiency virus: implications for vector development.

    Science.gov (United States)

    Johnston, J; Power, C

    1999-03-01

    Feline immunodeficiency virus (FIV) is a lentivirus causing immune suppression and neurological disease in cats. Like primate lentiviruses, FIV utilizes the chemokine receptor CXCR4 for infection. In addition, FIV gene expression has been demonstrated in immortalized human cell lines. To investigate the extent and mechanism by which FIV infected primary and immortalized human cell lines, we compared the infectivity of two FIV strains, V1CSF and Petaluma, after cell-free infection. FIV genome was detected in infected human peripheral blood mononuclear cells (PBMC) and macrophages at 21 and 14 days postinfection, respectively. Flow cytometry analysis of FIV-infected human PBMC indicated that antibodies to FIV p24 recognized 12% of the cells. Antibodies binding the CCR3 chemokine receptor maximally inhibited infection of human PBMC by both FIV strains compared to antibodies to CXCR4 or CCR5. Reverse transcriptase levels increased in FIV-infected human PBMC, with detection of viral titers of 10(1.3) to 10(2.1) 50% tissue culture infective doses/10(6) cells depending on the FIV strain examined. Cell death in human PBMC infected with either FIV strain was significantly elevated relative to uninfected control cultures. These findings indicate that FIV can productively infect primary human cell lines and that viral strain specificity should be considered in the development of an FIV vector for gene therapy.

  2. Allergen-induced migration of human cells in allergic severe combined immunodeficiency mice.

    Science.gov (United States)

    Duez, C; Akoum, H; Marquillies, P; Cesbron, J Y; Tonnel, A B; Pestel, J

    1998-02-01

    Recently, we have shown that severe combined immunodeficiency (SCID) mice, intraperitoneally reconstituted with peripheral blood mononuclear cells (PBMC) from Dermatophagoides pteronyssinus (Dpt)-sensitive patients, produced human IgE and developed a pulmonary inflammatory-type reaction after exposure to allergen aerosol. In order to understand the potential mechanisms involved in the human cell migration in SCID mice, we analysed their phenotypic profile in the lungs, spleen and thymus, 2 months after Dpt inhalation. The human cell recruitment in these organs was found to be allergen-dependent as CD45+ human cells were only detected in hu-SCID mice after Dpt exposure. The composition of the pulmonary human T-cell infiltrate, preferentially memory (CD45RO), activated (human leucocyte antigen (HLA)-DR) and CD4+ cells, was similar to that described in asthmatic patients. However, CD20+ B cells were predominately recruited in the spleen and thymus and may be IgE-producing cells in the spleen. In the lungs, the percentage of human leucocytes expressing the alpha-chain of the lymphocyte function-associated antigen-1 (LFA-1) (CD11a) was higher than those of CD49d+ or CD54+ cells, in contrast to the spleen and thymus, suggesting a potential role of LFA-1 in the human cell migration towards SCID mice lung. In conclusion, this model could be useful in the study of factors implicated in the cellular migration towards the lymphoid organs during an allergic reaction.

  3. Risky sexual behavior related to human immunodeficiency virus/acquired immunodeficiency syndrome among seasonal labor migrants: A cross-sectional study from far Western Region of Nepal

    Directory of Open Access Journals (Sweden)

    Dillee Prasad Paudel

    2013-01-01

    Full Text Available Background: Human immunodeficiency virus/acquired immunodeficiency syndrome is a global public health problem; enormously affecting the national economy, social development and human rights with posing a challenge to human civilization. Seasonal labor migrants are the most at risk population for HIV/AIDS and their risky sexual behaviors exacerbate its transmission. The aim of the study was to explore the HIV/AIDS related sexual behavior of migrant workers. Materials and Methods: A cross-sectional study was carried out among 372 migrant workers backing to Nepal from Banbasa border of India-Nepal during August-October 2010. Migrants having permanent residents of far western region, Nepal were individually contacted at the entry point of Nepal and interviewed in a confidential environment after obtaining informed consent. Data were analysed using the SPSS (16.0 version. Descriptive and inferencial statistics were applied considering P 3 sex partners. Most (82.25% had vaginal sex and 43.54% reported the consistent use of condom. About 64.76% had sex after drinking alcohol. Age, education, monthly income and nature of works were significant with risky behaviors. Conclusion: Inconsistent condom use, multiple sexual partners and sex after drinking alcohol have a cumulative effect on the risk of HIV transmission.

  4. Approaches for scaling up human immunodeficiency virus testing and counseling in prevention of mother-to-child human immunodeficiency virus transmission settings in resource-limited countries.

    Science.gov (United States)

    Bolu, Omotayo O; Allread, Virginia; Creek, Tracy; Stringer, Elizabeth; Forna, Fatu; Bulterys, Marc; Shaffer, Nathan

    2007-09-01

    Prevention of mother-to-child human immunodeficiency virus (HIV) transmission (PMTCT) programs have nearly eliminated mother-to-child transmission of HIV in developed countries, but progress in resource-limited countries has been slow. A key factor limiting the scale-up of PMTCT programs is lack of knowledge of HIV serostatus. Increasing the availability and acceptability of HIV testing and counseling services will encourage more women to learn their status, providing a gateway to PMTCT interventions. Key factors contributing to the scale-up of testing and counseling include a policy of provider-initiated testing and counseling with right to refuse (opt-out); group pretest counseling; rapid HIV testing; innovative staffing strategies; and community and male involvement. Integration of testing and counseling within the community and all maternal and child health settings are critical for scaling-up and for linking women and their families to care and treatment services. This paper will review best practices needed for expansion of testing and counseling in PMTCT settings in resource-limited countries.

  5. Impaired cell mediated immunity in haemophilia in the absence of infection with human immunodeficiency virus.

    Science.gov (United States)

    Madhok, R; Gracie, A; Lowe, G D; Burnett, A; Froebel, K; Follett, E; Forbes, C D

    1986-10-18

    The cell mediated immune response was evaluated in vivo in 29 patients with clinically severe haemophilia by means of the dinitrochlorobenzene skin test. All patients had a response below the median normal value, and in 19 the response was on or below the lower limit of the normal range. There was no difference in skin response between patients positive and negative for the human immunodeficiency virus (HIV; formerly known as human T cell lymphotropic virus III or lymphadenopathy associated virus). In the whole group, and in seronegative patients (n = 17), there was an inverse relation between exposure to clotting factor and skin response. In seropositive patients (n = 12) no such association was apparent. This study shows that clotting factor concentrate impairs the cell mediated immune response to a new antigen in the absence of infection with HIV.

  6. II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies.

    Science.gov (United States)

    Goudouris, Ekaterini Simões; Rego Silva, Almerinda Maria do; Ouricuri, Aluce Loureiro; Grumach, Anete Sevciovic; Condino-Neto, Antonio; Costa-Carvalho, Beatriz Tavares; Prando, Carolina Cardoso; Kokron, Cristina Maria; Vasconcelos, Dewton de Moraes; Tavares, Fabíola Scancetti; Silva Segundo, Gesmar Rodrigues; Barreto, Irma Cecília; Dorna, Mayra de Barros; Barros, Myrthes Anna; Forte, Wilma Carvalho Neves

    2017-01-01

    In the last few years, new primary immunodeficiencies and genetic defects have been described. Recently, immunoglobulin products with improved compositions and for subcutaneous use have become available in Brazil. In order to guide physicians on the use of human immunoglobulin to treat primary immunodeficiencies, based on a narrative literature review and their professional experience, the members of the Primary Immunodeficiency Group of the Brazilian Society of Allergy and Immunology prepared an updated document of the 1st Brazilian Consensus, published in 2010. The document presents new knowledge about the indications and efficacy of immunoglobulin therapy in primary immunodeficiencies, relevant production-related aspects, mode of use (routes of administration, pharmacokinetics, doses and intervals), adverse events (major, prevention, treatment and reporting), patient monitoring, presentations available and how to have access to this therapeutic resource in Brazil. RESUMO Nos últimos anos, novas imunodeficiências primárias e defeitos genéticos têm sido descritos. Recentemente, produtos de imunoglobulina, com aprimoramento em sua composição e para uso por via subcutânea, tornaram-se disponíveis em nosso meio. Com o objetivo de orientar o médico no uso da imunoglobulina humana para o tratamento das imunodeficiências primárias, os membros do Grupo de Assessoria em Imunodeficiências da Associação Brasileira de Alergia e Imunologia produziram um documento que teve por base uma revisão narrativa da literatura e sua experiência profissional, atualizando o I Consenso Brasileiro publicado em 2010. Apresentam-se novos conhecimentos sobre indicações e eficácia do tratamento com imunoglobulina nas imunodeficiências primárias, aspectos relevantes sobre a produção, forma de utilização (vias de administração, farmacocinética, doses e intervalos), efeitos adversos (principais efeitos, prevenção, tratamento e notificação), monitorização do

  7. Lipodystrophic syndrome in children and adolescents infected with the human immunodeficiency virus

    Directory of Open Access Journals (Sweden)

    Crésio Alves

    2008-08-01

    Full Text Available The introduction of highly active antiretroviral therapy (HAART for the treatment of acquired immunodeficiency syndrome (AIDS has resulted in greater survival of patients infected with the human immunodeficiency virus (HIV. However, the use of these drugs has been associated with lipodystrophic syndrome (LS, which is characterized by metabolic alterations (dyslipidemia, insulin resistance, diabetes, and lactic acidosis and abnormal corporal fat distribution. Clinically, LS may manifest as three different forms: lipohipertrophy (accumulation of fat in the central part of the body, lipoatrophy (loss of fat in the extremities, face and buttocks and mixed (lipohipertrophy + lipoatrophy. Although its physiopathology has not been elucidated, some mechanisms have been described, including leptin and adiponectin deficiency, mitochondrial dysfunction and use of antiretroviral drugs. The type, dose and duration of the antiretroviral treatment, as well as age and puberty are the main risk factors. LS is also associated with increased incidence of cardiovascular illnesses, atherosclerosis and diabetes mellitus. Treatment includes physical activity, cautious restriction of caloric intake, changes in antiretroviral therapy, and use of insulin-sensitizing and lipid-lowering agents. Follow up must be periodic, consisting of measurement of body fat distribution, evaluation of the lipid profile and insulin resistance.

  8. Lipodystrophic syndrome in children and adolescents infected with the human immunodeficiency virus

    Directory of Open Access Journals (Sweden)

    Crésio Alves

    Full Text Available The introduction of highly active antiretroviral therapy (HAART for the treatment of acquired immunodeficiency syndrome (AIDS has resulted in greater survival of patients infected with the human immunodeficiency virus (HIV. However, the use of these drugs has been associated with lipodystrophic syndrome (LS, which is characterized by metabolic alterations (dyslipidemia, insulin resistance, diabetes, and lactic acidosis and abnormal corporal fat distribution. Clinically, LS may manifest as three different forms: lipohipertrophy (accumulation of fat in the central part of the body, lipoatrophy (loss of fat in the extremities, face and buttocks and mixed (lipohipertrophy + lipoatrophy. Although its physiopathology has not been elucidated, some mechanisms have been described, including leptin and adiponectin deficiency, mitochondrial dysfunction and use of antiretroviral drugs. The type, dose and duration of the antiretroviral treatment, as well as age and puberty are the main risk factors. LS is also associated with increased incidence of cardiovascular illnesses, atherosclerosis and diabetes mellitus. Treatment includes physical activity, cautious restriction of caloric intake, changes in antiretroviral therapy, and use of insulin-sensitizing and lipid-lowering agents. Follow up must be periodic, consisting of measurement of body fat distribution, evaluation of the lipid profile and insulin resistance.

  9. Knowledge, attitude, and beliefs of young, college student blood donors about Human immunodeficiency virus

    Directory of Open Access Journals (Sweden)

    Anju Dubey

    2014-01-01

    Full Text Available Introduction: Young people, who tend to be healthy, idealistic, and motivated, are an excellent pool of potential voluntary unpaid blood donors. Recruiting and retaining young blood donors improves the long term safety and sufficiency of a country′s blood supply. Knowledge, attitude, and beliefs about Human immunodeficiency virus (HIV should play an important role in prevention of disease transmission. Materials and Methods: This study was a questionnaire based survey, conducted to explore the levels of knowledge, attitude, and beliefs about HIV in young college student blood donors. Results: The results showed that the proportion of participants with comprehensive knowledge of HIV prevention and transmission was lesser than expected. Increase in education level and male gender was found to be significantly associated with high HIV-related knowledge. The responses on the different aspects of HIV-related attitude were also varied and there is still stigma associated with Acquired Immunodeficiency Syndrome (AIDS even in the educated groups. Discussion: There was a spectrum of myths and misperceptions emphasizing the need of education that recognizes the social context of attitude towards HIV. Results from this study may contribute to the development of appropriate educational and training material for this group of donors which in turn, may assist in achieving the elusive goal of safe blood supply in future.

  10. Progressive human immunodeficiency virus-associated vasculopathy: time to revise antiretroviral therapy guidelines?

    Science.gov (United States)

    Ntusi, N B A; Taylor, D; Naidoo, N G; Mendelson, M

    2011-01-01

    Cardiovascular abnormalities were appreciated early in the epidemic of the acquired immunodeficiency syndrome (AIDS), even before the aetiological agent, human immunodeficiency virus (HIV) was isolated and characterised. The aetiology and pathogenesis of cardiovascular disease in HIV infection is still the subject of intense speculation, and is likely multi-factorial. HIV affects every aspect of the cardiac axis, causing pericarditis, myocarditis, cardiomyopathy, coronary artery disease and microvascular dysfunction, valvular heart disease, pulmonary vascular disease and pulmonary hypertension, stroke and peripheral vascular disease. HIV-associated vasculopathy is an increasingly recognised clinical entity, causing high morbidity and increasing mortality in southern Africa, particularly from stroke and cardiovascular disease. HIV causes disease of the vascular tree, either by a direct effect on vascular or perivascular tissue, or indirectly via immune complex-mediated mechanisms, associated opportunistic infections and malignancies. As a result, highly active antiretroviral therapy (HAART) may have an important role in controlling disease progression. We report a case of histologically defined primary HIV vasculopathy in which the chance to start HAART was initially missed and in which the patient progressed to require bilateral amputations, but obtained disease quiescence upon commencement of HAART.

  11. Low occupational risk of human immunodeficiency virus infection among dental professionals.

    Science.gov (United States)

    Klein, R S; Phelan, J A; Freeman, K; Schable, C; Friedland, G H; Trieger, N; Steigbigel, N H

    1988-01-14

    We studied 1309 dental professionals (1132 dentists, 131 hygienists, and 46 assistants) without behavioral risk factors for the acquired immunodeficiency syndrome (AIDS) to determine their occupational risk for infection with human immunodeficiency virus (HIV). Subjects completed questionnaires on behavior; type, duration, and location of their dental practice; infection-control practices; and estimated numbers of potential occupational exposures to HIV. Serum samples were tested for antibodies to HIV and to hepatitis B surface antigen (unvaccinated subjects). Fifty-one percent of the subjects practiced in locations where many cases of AIDS have been reported. Seventy-two percent treated patients who had AIDS or were at increased risk for it. Ninety-four percent reported accidental puncturing of the skin with instruments used in treating patients. Adherence to recommended infection-control practices was infrequent. Twenty-one percent of unvaccinated subjects had antibodies to hepatitis B surface antigen. Only one dentist without a history of behavioral risk factors for AIDS had serum antibodies to HIV. We conclude that despite infrequent compliance with recommended infection-control precautions, frequent occupational exposure to persons at increased risk for HIV infection, and frequent accidental puncturing of the skin with sharp instruments, dental professionals are at low occupational risk for HIV infection.

  12. Isolation of human immunodeficiency virus from genital ulcers in Nairobi prostitutes.

    Science.gov (United States)

    Kreiss, J K; Coombs, R; Plummer, F; Holmes, K K; Nikora, B; Cameron, W; Ngugi, E; Ndinya Achola, J O; Corey, L

    1989-09-01

    Recent epidemiologic studies have implicated genital/anorectal ulcer disease as an important cofactor for acquisition and transmission of human immunodeficiency virus (HIV) during sexual intercourse. To better understand the mechanism for the association between genital ulcers and HIV, exudates from 62 genital ulcers of 56 HIV-seropositive prostitutes in Nairobi (Kenya) were cultured for HIV. Twenty-six ulcer cultures could not be evaluated for the presence of HIV because of bacterial or fungal contamination. HIV was isolated from 4 (11%) of the 36 remaining uncontaminated ulcer cultures (2 introital, 1 vaginal, and 1 cervical) from 4 separate women. HIV was isolated from the cervical os from only 2 of the 4 women. HIV p24 antigen was detected in exudate from 1 of the 4 culture-positive ulcers and 0 of 32 culture-negative ulcers. Genital ulcers in seropositive patients should be regarded as potential sources of HIV, which could be important in transmission of HIV during intercourse. Public health measures aimed at controlling sexually transmitted genital ulcer diseases should be an integral part of acquired immunodeficiency syndrome (AIDS) prevention programs.

  13. Morphological changes in the digestive system of 93 human immunodeficiency virus positive patients: an autopsy study

    Directory of Open Access Journals (Sweden)

    Lucinda Calheiros Guimarães

    2012-04-01

    Full Text Available Involvement of the digestive system in patients with acquired immunodeficiency syndrome (AIDS is frequent and many changes in these patients are diagnosed only at autopsy. There are few studies of autopsy with detailed analysis of this system and only one was conducted in Brazil. We evaluated each segment of the digestive system in 93 consecutive autopsies of patients infected with human immunodeficiency virus (HIV and the importance of these lesions to death. Of these, 90 (96.8% patients had AIDS. We reviewed medical records, autopsy reports and histological sections from tongue to rectum stained with hematoxylin-eosin. When necessary, we analyzed special stains and immunohistochemistry to investigate infections. There was damage to the digestive system in 73 (78.5% cases. The most common infections were candidiasis (42%, cytomegalovirus (29%, histoplasmosis (11.8%, toxoplasmosis (9.7% and mycobacterial infection (9.7%. Malignancies were rare, present in four (4.3% cases (two Kaposi's sarcoma, one adenocarcinoma and one metastatic embryonal carcinoma. All segments showed lesions: tongue (48.6%, esophagus (44.8%, stomach (44.7%, colon (43.2% and small intestine (28.9%. The lesions found were immediate cause of death in five (5.4% cases. In another 36 (38.7% cases the basic disease was systemic and also compromised the digestive system.

  14. The relationship between personality traits and AIDS in patients with human immunodeficiency virus.

    Science.gov (United States)

    Salehi, Bahman; Zarinfar, Nader; Noori, Hasan

    2016-06-01

    This study carried out to survey the relationship between personality traits and Acquired Immunodeficiency Syndrome (AIDS) in patients with human immunodeficiency virus. This case-control study was conducted on 79 AIDS patients of Triangle Clinic in Arak (case group) and 80 healthy people of Valiasr Hospital in Arak (control group). Demographic information checklist and Cloninger' Temperament and Character inventory (TCI) were two instruments applied in the study. SPSS software V.19 and tests independent t-tests, Chi squared and Spearman correlation coefficient were used for data analysis with significant level of difference between two groups variables (P-0.000). The novelty seeking had the highest average in the AIDS patients with a history of addiction (M:74.00), and there was statistically significant difference between perseverance variable (P-0.021) and cooperativeness variable (P-0.041) in the two groups of AIDS patients. There was a significant relationship between novelty seeking and age at the onset of AIDS (P-0.038), harm avoidance and age at the onset of addiction (P-0.046), persistence and age at the onset of AIDS (P-0.035) and the time infected with HIV (P-0.033). It is found that two groups are different due to the personalities, so it is essential to consider the personality traits in order to prevent AIDS and also successfully treat patients suffering from AIDS. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Pulmonary bacterial and fungal infections in human immunodeficiency virus patients: A study from India

    Directory of Open Access Journals (Sweden)

    K Shreevidya

    2012-01-01

    Full Text Available Background: Human Immunodeficiency Virus (HIV-reactive patients are more prone to infections. The morbidity and mortality in HIV-reactive patients is due to opportunistic infections. Most of the infections seen in Acquired Immunodeficiency Syndrome are endemic to that geographical region. Hence, this study was undertaken to document the occurrence of pulmonary bacterial and fungal infections in HIV patients. Materials and Methods: Expectorated and induced sputum samples were collected from 100 HIV-reactive patients and processed for bacterial and fungal pathogens including Pneumocystis carinii. Results: Of 100 samples, 66 were culture positive. Among the isolates, Mycobacterium tuberculosis constituted the highest number, 55 (83.3%, followed by other bacterial infections, 11 (16.6%, and fungi, 2 (3.03%. Tuberculosis patients had a CD4 count of less than 250 cells/μl with a mean count of 186 cells/μl and those with bacterial infections had a CD4 count of more than 300 cells/μl. The study showed that males were infected with HIV more than females and most of them belonged to the adult age group in the prime of their working life. Weight loss followed by fever and cough were the most common symptoms. Conclusion: M. tuberculosis is the most common opportunistic pathogen followed by bacterial pathogens infecting the lung in HIV. Low CD4 count is a dangerous signal of decreased immune status and higher chances of opportunistic infections and high mortality.

  16. Aberrant and unstable expression of immunoglobulin genes in persons infected with human immunodeficiency virus.

    Science.gov (United States)

    Bessudo, A; Rassenti, L; Havlir, D; Richman, D; Feigal, E; Kipps, T J

    1998-08-15

    We examined the IgM VH gene subgroup use-distribution in serial blood samples of 37 human immunodeficiency virus (HIV)-infected patients and a group of HIV-seronegative healthy adults. The IgM VH gene repertoires of healthy adults were relatively similar to one another and were stable over time. In contrast, individuals infected with HIV had IgM VH gene repertoires that were significantly more heterogeneous and unstable. Persons at early stages of HIV infection generally had abnormal expression levels of Ig VH3 genes and frequently displayed marked fluctuations in the relative expression levels of this VH gene subgroup over time. In contrast, persons with established acquired immunodeficiency syndrome (AIDS) had a significantly lower incidence of abnormalities in Ig VH3 expression levels, although continued to display abnormalities and instability in the expression levels of the smaller Ig VH gene subgroups. Moreover, the skewing and/or fluctuations in the expressed-IgM VH gene repertoire appeared greatest for persons at earlier stages of HIV infection. These studies show that persons infected with HIV have aberrant and unstable expression of immunoglobulin genes suggestive of a high degree humoral immune dysregulation and ongoing humoral immune responses to HIV-associated antigens and superantigens.

  17. The high-affinity immunoglobulin E receptor as pharmacological target.

    Science.gov (United States)

    Blank, Ulrich; Charles, Nicolas; Benhamou, Marc

    2016-05-05

    The high-affinity receptor for immunoglobulin E is expressed mainly on mast cells and basophils, but also on neutrophils, eosinophils, platelets, monocytes, Langerhans and dendritic cells, airway smooth muscle cells and some nerve cells. Its main function is, upon its engagement by IgE and specific antigen, to trigger a powerful defense against invading pathogens and a rapid neutralization of dangerous toxic substances introduced in the body. This powerful response could be wielded against tumors. But, when control over this receptor is lost, its unchecked activation can induce an array of diseases, some of which can lead to death. In this review we will summarize the pharmacological approaches and strategies that are currently used, or under study, to harness or wield activation of this receptor for therapeutic purposes.

  18. Dendritic cells are less susceptible to human immunodeficiency virus type 2 (HIV-2) infection than to HIV-1 infection

    NARCIS (Netherlands)

    M.G. Duvall (Melody); K. Loré (Karin); H. Blaak (Hetty); D.A. Ambrozak (David); W.C. Adams (William); K. Santos (Kathlyn); C. Geldmacher (Christof); J.R. Mascola (John); A.J. McMichael (Andrew); A. Jaye (Assan); H. Whittle (Hilton); S.L. Rowland-Jones (Sarah); R.A. Koup (Richard)

    2007-01-01

    textabstractHuman immunodeficiency virus type 1 (HIV-1) infection of dendritic cells (DCs) has been documented in vivo and may be an important contributor to HIV-1 transmission and pathogenesis. HIV-1-specific CD4+T cells respond to HIV antigens presented by HIV-1-infected DCs and in this process

  19. Adherence and acceptability of once daily Lamivudine and abacavir in human immunodeficiency virus type-1 infected children.

    NARCIS (Netherlands)

    LePrevost, M.; Green, H.; Flynn, J.; Head, S.; Clapson, M.; Lyall, H.; Novelli, V.; Farrelly, L.; Walker, A.S.; Burger, D.M.; Gibb, D.

    2006-01-01

    BACKGROUND: Data on adherence to and acceptability of once daily lamivudine and abacavir are few. METHODS: Twenty-four U.K. human immunodeficiency virus type-1 infected children 2-13 years of age participated in the Pediatric European Network for the Treatment of AIDS (PENTA) 13 single arm, open lab

  20. Soluble CD163 does not predict first-time myocardial infarction in patients infected with human immunodeficiency virus

    DEFF Research Database (Denmark)

    Knudsen, Andreas; Møller, Holger Jon; Katzenstein, Terese Lea;

    2013-01-01

    BACKGROUND: Soluble CD163 (sCD163) has been associated with arterial inflammation and non-calcified plaques in human immunodeficiency virus (HIV)-infected individuals and has therefore been suggested as a predictive biomarker of myocardial infarction (MI). METHODS: We conducted a nested case...

  1. A One-Session Human Immunodeficiency Virus Risk-Reduction Intervention in Adolescents with Psychiatric and Substance Use Disorders

    Science.gov (United States)

    Thurstone, Christian; Riggs, Paula D.; Klein, Constance; Mikulich-Gilbertson, Susan K.

    2007-01-01

    Objective: To explore change in human immunodeficiency virus (HIV) risk among teens in outpatient treatment for substance use disorders (SUDs). Method: From December 2002 to August 2004, 50 adolescents (13-19 years) with major depressive disorder, conduct disorder, and one or more non-nicotine SUD completed the Teen Health Survey (THS) at the…

  2. Lipodystrophy in human immunodeficiency virus patients impairs insulin action and induces defects in beta-cell function

    DEFF Research Database (Denmark)

    Andersen, Ove; Haugaard, Steen B; Andersen, Ulrik B;

    2003-01-01

    The pathophysiology of insulin resistance in human immunodeficiency virus (HIV)-associated lipodystrophy syndrome (HALS) is not fully clarified. We investigated 18 men with HALS and 18 HIV-positive males without lipodystrophy (control subjects). Duration and modality of antiretroviral therapy were...

  3. Markers of human immunodeficiency virus infection in high-risk individuals seronegative by first generation enzyme-linked immunosorbent assay

    DEFF Research Database (Denmark)

    Pedersen, C; Lindhardt, B O; Lauritzen, E;

    1989-01-01

    A total of 228 stored serum samples from 140 high risk individuals was examined for serological markers of human immunodeficiency virus (HIV) infection by second generation enzyme-linked immunosorbent assay, immunoblot, and HIV antigen assay. All the samples were negative in first generation enzyme...

  4. Clinical manifestations of cytomegalovirus-associated posterior uveitis and panuveitis in patients without human immunodeficiency virus infection

    NARCIS (Netherlands)

    K. Pathanapitoon (Kessara); N. Tesavibul (Nattaporn); P. Choopong (Pitipol); S. Boonsopon (Sutasinee); N. Kongyai (Natedao); S. Ausayakhun (Somsanguan); P. Kunavisarut (Paradee); A. Rothova (Aniki)

    2013-01-01

    textabstractImportance: Little attention has been paid to clinical features of cytomegalovirus (CMV) infections in individuals without human immunodeficiency virus (HIV). Objective: To describe the clinical manifestations and comorbidities of patients without HIV infection who have CMV-associated po

  5. Angiographic Features and Cardiovascular Risk Factors in Human Immunodeficiency Virus-Infected Patients With First-Time Acute Coronary Syndrome

    DEFF Research Database (Denmark)

    Knudsen, Andreas; Mathiasen, Anders B; Worck, R.H.

    2013-01-01

    A matched cohort study was conducted comparing patients with first-time acute coronary syndromes infected with human immunodeficiency virus (HIV) to non-HIV-infected patients with and without diabetes matched for smoking, gender, and type of acute coronary syndrome who underwent first-time coronary...

  6. Lipodystrophy in human immunodeficiency virus patients impairs insulin action and induces defects in beta-cell function

    DEFF Research Database (Denmark)

    Andersen, Ove; Haugaard, Steen B; Andersen, Ulrik B

    2003-01-01

    The pathophysiology of insulin resistance in human immunodeficiency virus (HIV)-associated lipodystrophy syndrome (HALS) is not fully clarified. We investigated 18 men with HALS and 18 HIV-positive males without lipodystrophy (control subjects). Duration and modality of antiretroviral therapy were...

  7. Trends in Human Immunodeficiency Virus-Related Risk Behaviors among High School Students--United States, 1991-2005

    Science.gov (United States)

    Brener, Nancy; Kann, Laura; Lowry, Richard; Wechsler, Howell; Romero, Lisa

    2006-01-01

    This paper examined changes in human immunodeficiency virus (HIV)-related risk behaviors among high school students in the United States during 1991-2005. Data from 8 national Youth Risk Behavior Surveys conducted during that period were analyzed. During 1991-2005, the percentage of US high school students engaging in HIV-related sexual risk…

  8. Coinfection with Hymenolepis nana, Hymenolepis diminuta, Giardia intestinalis, and Human Immunodeficiency Virus: A Case Report with Complex Immunologic Interactions.

    Science.gov (United States)

    Pérez-Chacón, Gladymar; Pocaterra, Leonor A; Rojas, Elsy; Hernán, Aurora; Jiménez, Juan Carlos; Núñez, Luz

    2017-02-20

    We describe the case of a 43-year-old human immunodeficiency virus-infected man receiving combined antiretroviral therapy and coinfected with Hymenolepis nana, Hymenolepis diminuta, and Giardia intestinalis, presenting as chronic diarrhea and critical weight loss. Immunological aspects of these interactions are reviewed.

  9. Optimization of human immunodeficiency virus type 1 envelope glycoproteins with V1/V2 deleted, using virus evolution

    NARCIS (Netherlands)

    Bontjer, I.; Land, A.; Eggink, D.; Verkade, E.; Tuin, K.; Baldwin, C.; Pollakis, G.; Paxton, W.A.; Braakman, L.J.; Berkhout, B.; Sanders, R.W.

    2009-01-01

    The human immunodeficiency virus type 1 envelope glycoprotein (Env) complex is the principal focus of neutralizing antibody-based vaccines. The functional Env complex is a trimer consisting of six individual subunits: three gp120 molecules and three gp41 molecules. The individual subunits have prove

  10. Immunological changes in human immunodeficiency virus (HIV)-infected individuals during HIV-specific protease inhibitor treatment

    DEFF Research Database (Denmark)

    Ullum, H; Katzenstein, T; Aladdin, H

    1999-01-01

    The present study examines the influence of effective anti-retroviral treatment on immune function, evaluated by a broad array of immunological tests. We followed 12 individuals infected with human immunodeficiency virus (HIV) for 6 months after initiation of combination anti-retroviral treatment...

  11. Identification of Light-independent Inhibition of Human Immunodeficiency Virus-1 Infection through Bioguided Fractionation of Hypericum perforatum

    Science.gov (United States)

    Light-dependent activities against enveloped viruses in St. John's Wort (Hypericum perforatum) extracts have been extensively studied. In contrast, light-independent antiviral activity from this species has not. Here, we identify the light-independent inhibition of human immunodeficiency virus-1 (...

  12. Liver-related deaths among persons infected with the human immunodeficiency virus: The D:A:D Study

    DEFF Research Database (Denmark)

    Weber, R; Sabin, CA; Friis-Møller, Nina;

    2006-01-01

    BACKGROUND: An increasing proportion of deaths among human immunodeficiency virus (HIV)-infected persons with access to combination antiretroviral therapy (cART) are due to complications of liver diseases. METHODS: We investigated the frequency of and risk factors associated with liver-related de...

  13. SEROPREVALENCE OF ANTIBODIES TO THE HUMAN-IMMUNODEFICIENCY-VIRUS IN DIALYSIS WORKERS - RESULTS OF A MULTICENTER STUDY

    NARCIS (Netherlands)

    BERLYNE, G; KACZMAREK, RG; HAMBURGER, S; HAMILTON, P; MOORE, RM; CHARNEY, AN; KAHN, T; GRUBER, M; KAUFMAN, CE; GOFFINET, J; BERNARD, MA

    1992-01-01

    The Center for Devices and Radiological Health, in collaboration with the Department of Veterans Affairs Medical Center, Brooklyn, N.Y., conducted a multi-center, multi-institutional study of the seroprevalence of antibodies to the human immunodeficiency virus (HIV) among dialysis workers. Seven dia

  14. Release of Virus from Lymphoid Tissue Affects Human Immunodeficiency Virus Type 1 and Hepatitis C Virus Kinetics in the Blood

    NARCIS (Netherlands)

    Müller, Viktor; Marée, Athanasius F.M.; Boer, R.J. de

    2000-01-01

    Kinetic parameters of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infections have been estimated from plasma virus levels following perturbation of the chronically infected (quasi-) steady state. We extend previous models by also considering the large pool of virus

  15. Single-photon emission computed tomography in human immunodeficiency virus encephalopathy: A preliminary report

    Energy Technology Data Exchange (ETDEWEB)

    Masdeu, J.C.; Yudd, A.; Van Heertum, R.L.; Grundman, M.; Hriso, E.; O' Connell, R.A.; Luck, D.; Camli, U.; King, L.N. (St. Vincent' s Medical Center, New York, NY (USA))

    1991-08-01

    Depression or psychosis in a previously asymptomatic individual infected with the human immunodeficiency virus (HIV) may be psychogenic, related to brain involvement by the HIV or both. Although prognosis and treatment differ depending on etiology, computed tomography (CT) and magnetic resonance imaging (MRI) are usually unrevealing in early HIV encephalopathy and therefore cannot differentiate it from psychogenic conditions. Thirty of 32 patients (94%) with HIV encephalopathy had single-photon emission computed tomography (SPECT) findings that differed from the findings in 15 patients with non-HIV psychoses and 6 controls. SPECT showed multifocal cortical and subcortical areas of hypoperfusion. In 4 cases, cognitive improvement after 6-8 weeks of zidovudine (AZT) therapy was reflected in amelioration of SPECT findings. CT remained unchanged. SPECT may be a useful technique for the evaluation of HIV encephalopathy.

  16. Expanding human immunodeficiency virus testing and counseling to reach tuberculosis clients' partners and families.

    Science.gov (United States)

    Courtenay-Quirk, C; Date, A; Bachanas, P; Baggaley, R; Getahun, H; Nelson, L; Granich, R

    2015-12-01

    Recent years have shown important increases in human immunodeficiency virus (HIV) testing and counseling (HTC), diagnosis, and coverage of antiretroviral therapy (ART) among HIV-infected tuberculosis (TB) patients. Expansion of HTC for partners and families are critical next steps to increase earlier HIV diagnoses and access to ART, and to achieve international goals for reduced TB and HIV-related morbidity, mortality, transmission and costs. TB and HIV programs should develop and evaluate feasible and effective strategies to increase access to HTC among the partners and families of TB patients, and ensure that newly diagnosed people living with HIV and HIV-infected TB patients who complete anti-tuberculosis treatment are successfully linked to ongoing HIV clinical care.

  17. Accidental occupational exposure of intravenous nurses to human immunodeficiency virus. Anticipating the consequences.

    Science.gov (United States)

    Meisenhelder, J B

    1998-01-01

    This descriptive study randomly surveyed all 302 Massachusetts members of the Intravenous Nurses Society in 1991 regarding their perceptions of nine possible consequences of human immunodeficiency virus (HIV) infection caused by accidental occupational exposure. Areas of highest concern were financial: adequacy of worker's compensation, ability of the employer to cover all healthcare costs, and job security. Nurses also were concerned about confidentiality of their HIV status and personal history jeopardizing their benefits. The i.v. nurses felt most secure in areas of their personal lives: housing and support of family and friends. Although some concerns correlated significantly with fear of contagion, others were unrelated, indicating a need for policy and attitude changes to promote comfort in working with HIV.

  18. Dual infection with dengue virus 3 and human immunodeficiency virus 1 in Havana, Cuba.

    Science.gov (United States)

    Gonzalez, Daniel; Limonta, Daniel; Bandera, Juan Francisco; Perez, Jorge; Kouri, Gustavo; Guzman, Maria G

    2009-05-01

    Although dengue virus (DEN) endemic regions overlap with human immunodeficiency virus 1 (HIV) high incidence areas, little has been documented on HIV and DEN mixed infection. Here we report DEN/HIV concurrent infections recorded during the DEN-3 epidemic in 2001-2002 in Havana. Serologic-confirmed DEN is described in two HIV-infected subjects with dengue fever symptoms. Although patients had dengue disease, the CD4+ cells remained within normal levels and no accelerated progression of HIV disease was observed. To our knowledge, DEN cases caused by DEN-3 in HIV-infected individuals have not been reported previously. Further research is needed to diagnose this likely underreported mixed viral infection in DEN endemic areas.

  19. Shedding new light on viruses: super-resolution microscopy for studying human immunodeficiency virus.

    Science.gov (United States)

    Müller, Barbara; Heilemann, Mike

    2013-10-01

    For more than 70 years electron microscopy (EM) techniques have played an important role in investigating structures of enveloped viruses. By contrast, use of fluorescence microscopy (FM) methods for this purpose was limited by the fact that the size of virus particles is generally around or below the diffraction limit of light microscopy. Various super-resolution (SR) fluorescence imaging techniques developed over the past two decades bypass the diffraction limit of light microscopy, allowing visualization of subviral details and bridging the gap between conventional FM and EM methods. We summarize here findings on human immunodeficiency virus (HIV-1) obtained using SR-FM techniques. Although the number of published studies is currently limited and some of the pioneering analyses also covered methodological or descriptive aspects, recent publications clearly indicate the potential to approach open questions in HIV-1 replication from a new angle.

  20. Inhibition of human immunodeficiency virus replication by a dual CCR5/CXCR4 antagonist

    DEFF Research Database (Denmark)

    Princen, Katrien; Hatse, Sigrid; Vermeire, Kurt;

    2004-01-01

    Here we report that the N-pyridinylmethyl cyclam analog AMD3451 has antiviral activity against a wide variety of R5, R5/X4, and X4 strains of human immunodeficiency virus type 1 (HIV-1) and HIV-2 (50% inhibitory concentration [IC(50)] ranging from 1.2 to 26.5 microM) in various T-cell lines, CCR5...... at the virus entry stage. AMD3451 dose-dependently inhibited the intracellular Ca(2+) signaling induced by the CXCR4 ligand CXCL12 in T-lymphocytic cells and in CXCR4-transfected cells, as well as the Ca(2+) flux induced by the CCR5 ligands CCL5, CCL3, and CCL4 in CCR5-transfected cells. The compound did...

  1. Alternative nucleophilic substrates for the endonuclease activities of human immunodeficiency virus type 1 integrase

    Energy Technology Data Exchange (ETDEWEB)

    Ealy, Julie B. [Department of Medicine, Penn State College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, PO Box 850, Mail Services H036, Hershey, PA 17033 (United States); Department of Chemistry, Penn State Lehigh Valley, 2809 E. Saucon Valley Road, Center Valley, PA 18034 (United States); Sudol, Malgorzata [Department of Medicine, Penn State College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, PO Box 850, Mail Services H036, Hershey, PA 17033 (United States); Krzeminski, Jacek; Amin, Shantu [Department of Pharmacology, Penn State College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033 (United States); Katzman, Michael, E-mail: mkatzman@psu.edu [Department of Medicine, Penn State College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, PO Box 850, Mail Services H036, Hershey, PA 17033 (United States); Department of Microbiology and Immunology, Penn State College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033 (United States)

    2012-11-10

    Retroviral integrase can use water or some small alcohols as the attacking nucleophile to nick DNA. To characterize the range of compounds that human immunodeficiency virus type 1 integrase can accommodate for its endonuclease activities, we tested 45 potential electron donors (having varied size and number or spacing of nucleophilic groups) as substrates during site-specific nicking at viral DNA ends and during nonspecific nicking reactions. We found that integrase used 22 of the 45 compounds to nick DNA, but not all active compounds were used for both activities. In particular, 13 compounds were used for site-specific and nonspecific nicking, 5 only for site-specific nicking, and 4 only for nonspecific nicking; 23 other compounds were not used for either activity. Thus, integrase can accommodate a large number of nucleophilic substrates but has selective requirements for its different activities, underscoring its dynamic properties and providing new information for modeling and understanding integrase.

  2. Animal-associated opportunistic infections among persons infected with the human immunodeficiency virus.

    Science.gov (United States)

    Glaser, C A; Angulo, F J; Rooney, J A

    1994-01-01

    A number of animal-associated infections occur in persons infected with the human immunodeficiency virus (HIV), including those due to Toxoplasma gondii, Cryptosporidium, Microsporida, Salmonella, Campylo-bacter, Giardia, Rhodococcus equi, Rochalimaea, and Listeria monocytogenes. Most of these infections, with the exception of those due to Rochalimaea, appear to be acquired by the immunosuppressed individual from sources other than exposure to animals. Drs. Glaser and colleagues review our current understanding of the role of exposure to animals, especially pets, in the natural history of these opportunistic infections. They suggest that the risk of zoonotic transmission is small and offer practical suggestions designed to reduce this low risk. They conclude that the benefits of animal companionship outweigh the risks to patients and that prohibition of pet ownership by individuals infected with HIV is not warranted.

  3. Hypertrophic lichen planus as a presenting feature of human immunodeficiency virus infection

    Directory of Open Access Journals (Sweden)

    Kumari Rashmi

    2009-01-01

    Full Text Available Lichen planus (LP is a chronic papulosquamous dermatosis in which both skin and mucous membranes may be involved. To date, there have been only five reports of human immunodeficiency virus (HIV-positive patients with hypertrophic LP. In the present report, we describe a 37-year-old female who presented with widely distributed, hyperpigmented, pruritic scaly lesions involving the face, trunk, and upper and lower extremities for one month. She also had swelling of both lower legs with low grade fever for past one week. She was diagnosed to be a HIV-positive patient who had severe, widespread hypertrophic LP lesions along with acute eruptive lesions of LP. These LP lesions were a presenting feature of HIV infection in our case.

  4. Sexually transmitted infections and increased risk of co-infection with human immunodeficiency virus.

    Science.gov (United States)

    Nusbaum, Margaret R H; Wallace, Robin R; Slatt, Lisa M; Kondrad, Elin C

    2004-12-01

    The incidence of trichomoniasis (Trichomonas vaginalis) in the United States is estimated at 5 million cases annually; chlamydia (Chlamydia trachomatis) at 3 million; gonorrhea (Neisseria gonorrhoeae), 650,000; and syphilis (Treponema pallidum), 70,000. However, most sexually transmitted infections (STIs) are asymptomatic-contributing to underdiagnosis estimated at 50% or more. Diagnosis of an STI signals sexual health risk because an STI facilitates the transmission and acquisition of other STIs, including human immunodeficiency virus (HIV). In fact, comorbid STIs increase patients' susceptibility of acquiring and transmitting HIV by two- to fivefold. Several studies have shown that aggressive STI prevention, testing, and treatment reduces the transmission of HIV. The authors discuss common clinical presentations, screening, diagnosis, and treatment for trichomoniasis, chlamydia, gonorrhea, syphilis, and herpes simplex virus.

  5. Phylogenetic Analyses Indicate an Atypical Nurse-to-Patient Transmission of Human Immunodeficiency Virus Type 1

    Science.gov (United States)

    Goujon, Christophe P.; Schneider, Véronique M.; Grofti, Jaouad; Montigny, Joëlle; Jeantils, Vincent; Astagneau, Pascal; Rozenbaum, Willy; Lot, Florence; Frocrain-Herchkovitch, Claudie; Delphin, Nathalie; Le Gal, Frédéric; Nicolas, Jean-Claude; Milinkovitch, Michel C.; Dény, Paul

    2000-01-01

    A human immunodeficiency virus (HIV)-negative patient with no risk factor experienced HIV type 1 (HIV-1) primary infection 4 weeks after being hospitalized for surgery. Among the medical staff, only two night shift nurses were identified as HIV-1 seropositive. No exposure to blood was evidenced. To test the hypothesis of a possible nurse-to-patient transmission, phylogenetic analyses were conducted using two HIV-1 genomic regions (pol reverse transcriptase [RT] and env C2C4), each compared with reference strains and large local control sets (57 RT and 41 C2C4 local controls). Extensive analyses using multiple methodologies allowed us to test the robustness of phylogeny inference and to assess transmission hypotheses. Results allow us to unambiguously exclude one HIV-positive nurse and strongly suggest the other HIV-positive nurse as the source of infection of the patient. PMID:10684266

  6. Perspectives on Human Immunodeficiency Virus (HIV) Cure: HIV Persistence in Tissue.

    Science.gov (United States)

    Boritz, Eli A; Douek, Daniel C

    2017-03-15

    The uneven anatomic distribution of cell subsets that harbor human immunodeficiency virus (HIV) during antiretroviral therapy (ART) complicates investigation of the barriers to HIV cure. Here we propose that while previous studies done largely in blood cells have led to important investigations into HIV latency, other important mechanisms of HIV persistence during ART may not be readily apparent in the bloodstream. We specifically consider as an example the question of ongoing HIV replication during ART. We discuss how growing understanding of key anatomic sanctuaries for the virus can inform future experiments aimed at further clarifying this issue. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  7. Associations among depression, suicidal behavior, and quality of life in patients with human immunodeficiency virus

    Science.gov (United States)

    Serafini, Gianluca; Montebovi, Franco; Lamis, Dorian A; Erbuto, Denise; Girardi, Paolo; Amore, Mario; Pompili, Maurizio

    2015-01-01

    AIM: To investigate the potential associations among major depression, quality of life, and suicidal behavior in human immunodeficiency virus (HIV) patients. METHODS: A detailed MEDLINE search was carried out to identify all articles and book chapters in English published from January 1995 to January 2015. RESULTS: Based on the main findings, the prevalence of major depressive disorder (MDD) ranged from 14.0% to 27.2%. Furthermore, the prevalence of suicidal ideation varied from 13.6% to 31.0% whereas, attempted suicides were reported to range from 3.9% to 32.7%. Interestingly, various associated risk factors for both depression and suicide were identified in HIV patients. Finally, consistent associations were reported among MDD, suicidal ideation, and poor quality of life in individuals living with HIV. CONCLUSION: Although additional studies are needed to elucidate this complex association, our results suggest the importance of early detection of both MDD and suicidality in patients living with HIV. PMID:26279991

  8. Significance of blood analysis in hemophiliacs co-infected with human immunodeficiency virus and hepatitis viruses

    Institute of Scientific and Technical Information of China (English)

    Fang Shen; Qin Huang; Hong-Qing Sun; Reena Ghildyal

    2007-01-01

    AIM:To study the effect of hepatitis virus infection on cirrhosis and liver function markers in HIV-infected hemophiliacs.METHODS:We have analyzed the immunological,liver function and cirrhosis markers in a cohort of hemophiliacs co-infected with human immunodeficiency virus (HIV) and hepatitis viruses.RESULTS:There was no difference in immunological markers among co-infected patients and patients infected with HIV only and those co-infected with one or more hepatitis virus. Although liver function and cirrhosis markers remained within a normal range,there was a worsening trend in all patients co-infected with hepatitis virus C (HCV),which was further exacerbated in the presence of additional infection with hepatitis virus B (HBV).CONCLUSION:Co-infection with HIV,HBV and HCV leads to worsening of hyaluronic acid and liver function markers. Increases in serum hyaluronic acid may be suggestive of a predisposition to liver diseases.

  9. Assessment of nutritional status, body composition, and human immunodeficiency virus-associated morphologic changes.

    Science.gov (United States)

    Knox, Tamsin A; Zafonte-Sanders, Melissa; Fields-Gardner, Cade; Moen, Karol; Johansen, Diana; Paton, Nicholas

    2003-04-01

    Nutritional status should be assessed at regular intervals as part of management of human immunodeficiency virus (HIV) infection. The simplest approach to assessment is serial weight measurement. A comprehensive nutritional assessment includes (1) anthropometric measurements of body composition; (2) biochemical measurements of serum protein, micronutrients, and metabolic parameters; (3) clinical assessment of altered nutritional requirements and social or psychological issues that may preclude adequate intake; and (4) measurement of dietary intake. Techniques for measuring body composition of fat and lean body mass include anthropometry and bioelectric impedance analysis. Other techniques, including dual X-ray absorptiometry (DXA), hydrodensitometry, total body potassium measurement, and cross-sectional computed tomography or magnetic resonance imaging are available in research centers. Anthropometry, including waist-hip ratios, regional DXA, and cross-sectional imaging, is best for detecting morphologic changes associated with fat redistribution syndrome. Nutritional assessment and intervention in children with HIV can help to prevent stunted growth and development.

  10. Laboratory diagnosis of infection status in infants perinatally exposed to human immunodeficiency virus type 1.

    Science.gov (United States)

    Paul, M O; Tetali, S; Lesser, M L; Abrams, E J; Wang, X P; Kowalski, R; Bamji, M; Napolitano, B; Gulick, L; Bakshi, S

    1996-01-01

    Accurate and timely diagnosis of infection status in infants born to women infected with human immunodeficiency virus (HIV) is of paramount importance. The comparative accuracy of five diagnostic decision rules was evaluated in 208 HIV-exposed infants (32 infected, 176 uninfected) based on laboratory testing during the first 6 months of life. Diagnostic rules A and B, which required single blood samples analyzed by culture and polymerase chain reaction (PCR) (rule A) or culture, PCR, and p24 antigen detection (rule B) were more prone to incorrect diagnoses than were rules requiring 2 blood samples analyzed by a single assay (rule C) or combinations of culture and PCR (rules D and E). Rule D, which used PCR as the initial test, established the most useful algorithm: a positive PCR result followed by a positive culture in the second sample confirmed infected status, while two consecutive negative PCR results reconfirmed as negative at 6 months of age established uninfected status.

  11. A case of plasmacytoma of scalp in pediatric thalassemia human immunodeficiency virus positive child

    Directory of Open Access Journals (Sweden)

    Swapan Kumar Mallick

    2013-01-01

    Full Text Available A 9-year-old female child, known case of beta thalassemia major and human immunodeficiency virus seropositive, presented with two slowly growing masses in the temporoparietal region of the skull on both sides. Irregular bony erosion at left parietal area with underlying scalp hematoma with similar change at the right side to a lesser degree were found. Fine needle aspiration cytology from masses showed abundant plasmacytoid cells some of which are binucleated along with free erythroblasts. Cytological features were suggestive of plasmacytoma. Serum protein electrophoresis showed no M-band. Urine was negative for Bence-Jones protein. Bone marrow biopsy showed no plasma cell neoplasm. Diagnosed as first reported case of primary multiple solitary plasmacyomas affecting bilateral temporoparietal bones in a pediatric patient, the child was treated with external beam radiation therapy to scalp lesions showing excellent results and on further follow-up showed no evidence of progressive disease.

  12. Acanthamoeba keratitis in a non-contact lens wearer with human immunodeficiency virus.

    Science.gov (United States)

    Hansen, Birgitte; Kronborg, Gitte

    2003-01-01

    Acanthamoeba keratitis is potentially blinding and often associated with contact lens wearing. A human immunodeficiency virus (HIV)-positive patient, a non-contact lens wearer, presented with keratitis. She experienced a protracted course of disease, characterized by exacerbations and remissions, and was treated with various topical antibiotics and steroids. 13 months after symptom onset the eye was removed owing to serious scarring of cornea and unbearable pain. Microbiological and histopathological examination of the cornea showed Acanthamoeba. In non-contact lens wearers suffering from Acanthamoeba keratitis the diagnosis is delayed, pathognomonic features are often not seen and visual outcome is usually poor. There is no known relation between HIV infection and Acanthamoeba keratitis.

  13. Sexual risk behavior among injection drug-using human immunodeficiency virus positive clients.

    Science.gov (United States)

    Singh, B K; Koman, J J; Catan, V M; Souply, K L; Birkel, R C; Golaszewski, T J

    1993-06-01

    This study examined sexual risk behavior of 154 seropositive Hispanic injection drug-using clients who were a subsample of a larger study. The results revealed that while nearly 71% followed safe sex practices at a 6-month follow-up, the other 29% were following risky sexual behaviors. Among males who were 25 years of age or younger, slightly over 58% were practicing unsafe sex. Among females, those in the 31-35 age group were all following risky sexual behaviors. Generally, those who lived with their sexual partners, females, and younger clients tended to follow risky sexual behaviors. These findings are very significant in the light of the heterosexual transmission of Human Immunodeficiency Virus (HIV). Educational and case management programs are needed to provide such clients with an understanding of the possibility of HIV transmission to their sexual partners and to their children in case of pregnancies.

  14. Adenovirus vector-based vaccines for human immunodeficiency virus type 1.

    Science.gov (United States)

    Barouch, Dan H; Nabel, Gary J

    2005-02-01

    Recombinant adenovirus (rAd) vectors have received considerable attention for gene therapy because of their high transduction efficiency. However, recombinant gene expression from rAd vectors elicits rapid and potent immune responses to foreign transgene products. Such immunogenicity limits the duration of transgene expression and poses a major challenge to the use of rAd vectors for gene therapy. In contrast, the inherent immunogenicity of these vectors is a desirable feature for vaccine development. The immunogenicity and protective efficacy of rAd vector-based vaccines have now been demonstrated in a number of animal models, and rAd vaccines for a variety of pathogens are currently being explored in early-phase clinical trials. In this review, we describe progress in the development of rAd vector-based vaccines with a focus on human immunodeficiency virus type 1.

  15. Condom use prevents genital ulcers in women working as prostitutes. Influence of human immunodeficiency virus infection.

    Science.gov (United States)

    Cameron, D W; Ngugi, E N; Ronald, A R; Simonsen, J N; Braddick, M; Bosire, M; Kimata, J; Kamala, J; Ndinya-Achola, J O; Waiyaki, P G

    1991-01-01

    Control of genital ulcer disease (GUD) is a proposed intervention to slow the dissemination of human immunodeficiency virus (HIV) infection. Programs for the control of sexually transmitted diseases (STD) should focus on groups of high-frequency transmitters, such as prostitutes and their clientele. This study illustrates the interaction between the prevalence of chancroid, use of barrier prophylaxis against STDs, and HIV infection in a population of female prostitutes in Nairobi. Four hundred and twenty three women were evaluated. Despite the increased use of condoms, the prevalence of genital ulcers remained constant between 1986-87 and 1987-88. Genital ulcer disease was simultaneously associated with HIV infection (adjusted odds ratio: 3.7, P less than .01) whereas it was independently and inversely associated with more consistent condom use (P less than .01). The authors conclude that genital ulcer disease can be controlled in these populations but concurrent HIV infection increases the difficulty of this intervention.

  16. Human immunodeficiency virus type 1 seroconversion in women with genital ulcers.

    Science.gov (United States)

    Plourde, P J; Pepin, J; Agoki, E; Ronald, A R; Ombette, J; Tyndall, M; Cheang, M; Ndinya-Achola, J O; D'Costa, L J; Plummer, F A

    1994-08-01

    Genital ulcers are implicated as a risk factor enhancing susceptibility to human immunodeficiency virus type 1 (HIV-1) infection. A prospective study to determine the incidence of and risk factors associated with acquisition of HIV-1 in women with genital ulcers was done. HIV-1-seronegative women with genital ulcers attending a clinic for sexually transmitted diseases in Nairobi were followed to HIV-1 seroconversion over a 6-month period. Of 81 women, 10 seroconverted to HIV-1. The crude 6-month incidence of HIV-1 infection was 12%. Risk factors associated with seroconversion included cervical ectopy (rate ratio [RR], 4.9; 95% confidence interval [CI], 1.5-15.6) and pelvic inflammatory disease (RR, 6.3; 95% CI, 1.9-20.4). Thus, cervical ectopy and pelvic inflammatory disease may increase susceptibility to HIV-1 in women with genital ulcers.

  17. Widening the differential for brain masses in human immunodeficiency virus-positive patients: syphilitic cerebral gummata.

    Science.gov (United States)

    Land, Andrew M; Nelson, George A; Bell, Stephen G; Denby, Kara J; Estrada, Carlos A; Willett, Lisa L

    2013-09-01

    A 39-year-old man with newly diagnosed human immunodeficiency virus (HIV) infection was admitted with right-sided weakness, right-sided vision loss and slurred speech, which worsened over several weeks. Brain imaging revealed bilateral intraparenchymal ring-enhancing lesions and enhancement of the right optic nerve. Serological findings were positive for venereal disease research laboratory test, whereas the cerebrospinal fluid venereal disease research laboratory test was nonreactive. Brain biopsy suggested a diagnosis of syphilitic cerebral gummata, and the patient's improvement with penicillin and dexamethasone further supported this etiology. Syphilitic cerebral gummata have rarely been reported in patients with HIV infection. This patient demonstrates that cerebral gummata should be considered in the differential diagnosis in immunocompromised patients with characteristic brain masses, that HIV and syphilis often coexist with early neurosyphilis appearing more frequently in this patient population and that normal cerebrospinal fluid studies may not represent a true lack of syphilitic activity in HIV patients.

  18. A clinico-epidemiological study of ulcerative sexually transmitted diseases with human immunodeficiency virus status.

    Science.gov (United States)

    Mehta, Bhavesh

    2014-01-01

    Genital ulcerative diseases are a major public health problem. The advert of human immunodeficiency virus (HIV)/AIDS over the past 25 years has deepened the scope of morbidity, mortality, and various forms of clinical presentations of sexually transmitted diseases (STDs). A total of 50 cases having Genital ulcerative diseases and STD reporting to STD clinic during the period of the year from November 2005 to December 2006 were included and detailed history and clinical examination were carried out and provisional diagnosis is made. Laboratory confirmation of clinically diagnosed cases was done using laboratory tests such as S. HIV, venereal disease research laboratory, Tzanck smear, gram stain, and Giemsa stain. In the present study, the incidence of herpes progenitalis was (38%) followed by primary syphilis (32%), chancroid (26%), lymphogranuloma venereum (02%), and genital scabies (02%). HIV sero-positivity was detected in 12% (n = 6) cases. HIV was found to be more common among genital ulcer disease patients, especially syphilis and genital herpes.

  19. Acanthamoeba keratitis in a non-contact lens wearer with human immunodeficiency virus

    DEFF Research Database (Denmark)

    Hansen, Birgitte Rønde; Kronborg, Gitte

    2003-01-01

    Acanthamoeba keratitis is potentially blinding and often associated with contact lens wearing. A human immunodeficiency virus (HIV)-positive patient, a non-contact lens wearer, presented with keratitis. She experienced a protracted course of disease, characterized by exacerbations and remissions......, and was treated with various topical antibiotics and steroids. 13 months after symptom onset the eye was removed owing to serious scarring of cornea and unbearable pain. Microbiological and histopathological examination of the cornea showed Acanthamoeba. In non-contact lens wearers suffering from Acanthamoeba...... keratitis the diagnosis is delayed, pathognomonic features are often not seen and visual outcome is usually poor. There is no known relation between HIV infection and Acanthamoeba keratitis....

  20. [Sepsis, cardiomyopathy and human immunodeficiency virus infection: presentation of a case].

    Science.gov (United States)

    Llagunes, J; Arastey, S; Cobo Del Prado, I; Carmona, P; Peña, J J; Mínguez, C

    2014-04-01

    Sepsis in patients with human immunodeficiency virus (HIV) may be associated with the appearance of cardiac dysfunction. This is a challenge, both when making the differential diagnosis and determining the proper treatment, as there are numerous risk factors: Myocarditis due to the HIV itself, the presence or absence of highly active antiretroviral therapy, toxic substances, and cardiomyopathy associated with sepsis. The diagnostic and therapeutic approach to an HIV positive patient with septic shock and cardiac dysfunction is described, as well as a brief review of the different causes of cardiomyopathy which may affect this group of patients is also presented. Copyright © 2012 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  1. Hepatitis B virus exposure in human immunodeficiency virus seropositive Cuban patients

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    Licel Rodríguez

    2000-04-01

    Full Text Available In order to estimate the prevalence of serological markers of exposure to Hepatitis B Virus (HBV, 295 subjects were selected at random from the National Registry of human immunodeficiency virus positive subjects. Evidence of exposure to HBV was defined as: testing Hepatitis B surface antigen (HBsAg and anti-Hepatitis B core antigen (anti-HBc positive or anti-HBc positive only. Overall, 133 (45.5% were positive for anti-HBc and 15 (5.1% resulted positive to HBsAg. Significant statistical association was found between male sex and exposure to HBV (p<0.01. Homosexual or bisexual behavior was found to be strongly associated to HBV exposure (p<0.001. In conclusion, the prevalence of HBV serological markers is higher in Cuban HIV positive subjects compared to the Cuban general population.

  2. Prevalence of purified protein derivative positivity in human immunodeficiency virus infected individuals in Hong Kong

    Institute of Scientific and Technical Information of China (English)

    陈志伟; 邓伟祺; 黄加庆

    2002-01-01

    Objective To study the prevalence of skin positivity to purified protein derivative (PPD) in human immunodeficiency virus (HIV)-infected patients in Hong Kong.Methods Consecutive clients of an HIV clinic were administered the PPD test and 2 units of PPD-RT23 were used. The area of induration was then measured in 48 to 72 h. Results were related to patient characteristics and HIV-related parameters.Results Eight (17.0%) out of 47 clients tested positive to the administration of 2 units of PPD-RT23. If the cutoff were raised to 10 mm according to current practice, only two (4.3%) would test positive.Conclusion The prevalence of PPD positivity in HIV-infected patients in Hong Kong is 17%, when a cutoff of 5 mm is used. This figure may form the basis for further studies on the utility of isoniazid preventive therapy in this group of patients.

  3. Correlation of in vivo neuroimaging abnormalities with postmortem human immunodeficiency virus encephalitis and dendritic loss

    DEFF Research Database (Denmark)

    Archibald, Sarah L.; Masliah, Eliezer; Fennema-Notestine, Christine

    2004-01-01

    previous studies have linked brain viral levels to these alterations, other neuropathological mechanisms might also contribute to them. OBJECTIVE: To examine the relationship between findings on premortem magnetic resonance images and postmortem neuropathologic evidence of human immunodeficiency virus (HIV......) encephalitis and neurodegeneration. DESIGN: Morphometric analysis of magnetic resonance imaging in seropositive cases with matched seronegative controls, and the correlation of these volumes to neuropathological measures in autopsied seropositive cases. SETTING: University of California, San Diego, HIV...... Neurobehavioral Research Center. SUBJECTS: Twenty-one seropositive subjects studied at autopsy and 19 seronegative cases. MAIN OUTCOME MEASURES: In vivo structural magnetic resonance imaging data analyzed by quantitative methods, with comparison of volumes from magnetic resonance imaging and neuropathological...

  4. Molecular epidemiology of human immunodeficiency virus-1 in the state of Ceará, Northeast, Brazil

    Directory of Open Access Journals (Sweden)

    Sandra Rocha Gadelha

    2003-06-01

    Full Text Available We analyzed, by env and gag heteroduplex mobility assay, 149 human immunodeficiency virus (HIV-1 positive samples collected in Ceará during the year 2000. The prevalence of subtype B was 81.2% and the prevalence of subtype F and B/F recombinants were both 2.7%. Eight (5.4% and 12 (8% out of 149 samples showed indeterminate results in the env and gag analysis respectively. By FokI restriction fragment length polymorphism, 34% of the subtype B samples were identified as the typical Brazilian subtype B.In the present study, we identified HIV-1 subtype F and B/F in Ceará for the first time. Our results contribute to the understanding of HIV in Brazil, and may prove useful for the development of vaccine candidates.

  5. Hepatocellular carcinoma, human immunodeficiency virus and viral hepatitis in the HAART era

    Institute of Scientific and Technical Information of China (English)

    Douglas C Macdonald; Mark Nelson; Mark Bower; Thomas Powles

    2008-01-01

    The incidence of hepatocellular carcinoma (HCC) in patients with human immunodeficiency virus (HIV) is rising. HCC in HIV almost invariably occurs in the context of hepatitis C virus (HCV) or hepatitis B virus (HBV) co-infection and, on account of shared modes of transmission, this occurs in more than 33% and 10% of patients with HIV worldwide respectively. It has yet to be clearly established whether HIV directly accelerates HCC pathogenesis or whether the rising incidence is an epiphenomenon of the highly active antiretroviral therapy (HAART) era, wherein the increased longevity of patients with HIV allows long-term complications of viral hepatitis and cirrhosis to develop. Answering this question will have implications for HCC surveillance and the timing of HCV/HBV therapy, which in HIV co-infection presents unique challenges. Once HCC develops, there is growing evidence that HIV co-infection should not preclude conventional therapeutic strategies, including liver transplantation.

  6. Molecular epidemiology of human immunodeficiency virus-infected individuals in Medellin, Colombia.

    Science.gov (United States)

    Sanchez, Gloria I; Bautista, Christian T; Eyzaguirre, Lindsay; Carrion, Gladys; Arias, Sonia; Sateren, Warren B; Negrete, Monica; Montano, Silvia M; Sanchez, Jose L; Carr, Jean K

    2006-04-01

    To study the molecular epidemiology of human immunodeficiency virus type 1 (HIV-1) strains in Medellín, Colombia, 115 HIV-1-positive individuals who were recruited from an HIV outpatient hospital (Universitario San Vicente de Paul) during the period from July 2001 to January 2002 were genotyped. All samples were analyzed by envelope heteroduplex mobility assay and found to be subtype B. Twenty-four samples were randomly selected for sequencing of the protease and the reverse transcriptase regions; all isolates were found to be subtype B. Phylogenetic analysis of seven nearly full-length genomes showed that all samples were subtype B. This study shows that the HIV epidemic in Colombia continues to be dominated by the subtype B virus. The predominance of subtype B genotypes of HIV-1 strains in Medellín resembles what is seen in the nearby countries of Peru, Ecuador, and Venezuela.

  7. Bispecific Antibodies that Mediate Killing of Cells Infected with Human Immunodeficiency Virus of Any Strain

    Science.gov (United States)

    Berg, Jorg; Lotscher, Erika; Steimer, Kathelyn S.; Capon, Daniel J.; Baenziger, Jurg; Jack, Hans-Martin; Wabl, Matthias

    1991-06-01

    Although AIDS patients lose human immunodeficiency virus (HIV)-specific cytotoxic T cells, their remaining CD8-positive T lymphocytes maintain cytotoxic function. To exploit this fact we have constructed bispecific antibodies that direct cytotoxic T lymphocytes of any specificity to cells that express gp120 of HIV. These bispecific antibodies comprise one heavy/light chain pair from an antibody to CD3, linked to a heavy chain whose variable region has been replaced with sequences from CD4 plus a second light chain. CD3 is part of the antigen receptor on T cells and is responsible for signal transduction. In the presence of these bispecific antibodies, T cells of irrelevant specificity effectively lyse HIV-infected cells in vitro.

  8. Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors

    Directory of Open Access Journals (Sweden)

    Lucianna Helene Santos

    2015-11-01

    Full Text Available Reverse transcriptase (RT is a multifunctional enzyme in the human immunodeficiency virus (HIV-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted.

  9. [Practical considerations for high resolution anoscopy in patients infected with human immunodeficiency virus].

    Science.gov (United States)

    Iribarren-Díaz, Mauricio; Ocampo Hermida, Antonio; González-Carreró Fojón, Joaquín; Alonso-Parada, María; Rodríguez-Girondo, Mar

    2014-12-01

    Anal cancer is uncommon in the general population, however its incidence is increasing significantly in certain risk groups, mainly in men who have sex with men, and particularly those infected with human immunodeficiency virus. High resolution anoscopy technique is currently considered the standard in the diagnosis of anal intraepithelial neoplasia, but at present there is no agreed standard method between health areas. High resolution anoscopy is an affordable technique that can be critical in the screening of anal carcinoma and its precursor lesions, but is not without difficulties. We are currently studying the most effective strategy for managing premalignant anal lesions, and with this article we attempt to encourage other groups interested in reducing the incidence of an increasing neoplasia. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  10. Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors.

    Science.gov (United States)

    Santos, Lucianna Helene; Ferreira, Rafaela Salgado; Caffarena, Ernesto Raúl

    2015-11-01

    Reverse transcriptase (RT) is a multifunctional enzyme in the human immunodeficiency virus (HIV)-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs) and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted.

  11. Current issues and considerations regarding trichomoniasis and human immunodeficiency virus in African-Americans.

    Science.gov (United States)

    Shafir, Shira C; Sorvillo, Frank J; Smith, Lisa

    2009-01-01

    Trichomonas vaginalis has long been recognized as one of the most prevalent sexually transmitted infections. However, it is only in recent years that it has been appreciated that Trichomonas may play a critical role in amplifying human immunodeficiency virus (HIV) transmission. Given the evidence that T. vaginalis likely promotes HIV infection, the apparent high level of Trichomonas infection in the African-American community is cause for concern. Even if T. vaginalis increases the risk of HIV transmission by a small or modest amount, it translates into a sizable population effect since Trichomonas is so common in this community. Therefore, control of trichomoniasis may represent an important avenue of control for the prevention of HIV transmission, particularly among African-Americans.

  12. Radioimmunodetection of human leukemia with anti-interleukin-2 receptor antibody in severe combined immunodeficiency mice

    Energy Technology Data Exchange (ETDEWEB)

    Hosono, Makoto; Takaori-Kondo, Akifumi; Zheng-Sheng, Yao; Kobayashi, Hisataka; Hosono, Masako N.; Sakahara, Harumi; Imada, Kazunori; Okuma, Minoru; Uchiyama, Takashi; Konishi, Junji

    1995-10-01

    Anti-Tac monoclonal antibody recognizes human interleukin-2 receptor, which is overexpressed in leukemic cells of most adult T-cell leukemia (ATL) patients. To examine the potency of anti-Tac for targeting of ATL, biodistributions of intravenously administered {sup 125}I- and {sup 111}In-labeled anti-Tac were examined in severe combined immunodeficiency (SCID) mice inoculated with ATL cells. Significant amounts of radiolabeled anti-Tac were found in the spleen and thymus. The trafficking of ATL cells in SCID mice was detected using {sup 111}In-oxine-labeled ATL cells. These results were coincident with the histologically confirmed infiltration of ATL cells. The radiolabeled anti-Tac seemed potent for targeting of ATL.

  13. Smoking and renal function in people living with human immunodeficiency virus

    DEFF Research Database (Denmark)

    Ahlström, Magnus Glindvad; Feldt-Rasmussen, Bo; Legarth, Rebecca

    2015-01-01

    INTRODUCTION: Smoking is a main risk factor for morbidity and mortality in people living with human immunodeficiency virus (PLHIV), but its potential association with renal impairment remains to be established. METHODS: We did a nationwide population-based cohort study in Danish PLHIV to evaluate...... the association between smoking status and 1) overall renal function and risk of chronic kidney disease (CKD), 2) risk of any renal replacement therapy (aRRT), and 3) mortality following aRRT. We calculated estimated creatinine clearance using the Cockcroft-Gault equation (CG-CrCl), and evaluated renal function...... Cohort Study, we identified 1,475 never smokers, 768 previous smokers, and 2,272 current smokers. During study period, we observed no association of smoking status with overall renal function. Previous and current smoking was not associated with increased risk of CKD (adjusted IRR: 1.1, 95% confidence...

  14. Human papillomavirus-associated cancers as acquired immunodeficiency syndrome defining illnesses

    Directory of Open Access Journals (Sweden)

    Shohreh Shahabi

    2013-04-01

    Full Text Available The Centers for Disease Control currently report cervical, vulvar, vaginal, anal and some head and neck cancers as human papillomavirus (HPV-associated cancers. Only cervical cancer is listed amongst acquired immunodeficiency syndrome (AIDS defining illnesses. All of these cancers may represent progression of the immunocompromised state with the inability to eradicate viral infection. This study reports the case of a 27-year old HIV positive female presenting with a persistent right vulvar exophytic lesion. High-risk HPV analysis and immunostaining for P16 were both positive. A biopsy of the lesion revealed invasive squamous cell carcinoma. The patient underwent neoadjuvant radiation and chemotherapy followed by a radical vulvectomy. During treatment, her CD4 T-lymphocyte count decreased to 120 advancing her condition from HIV to AIDS. This case suggests that all HPV-associated cancers should be included as AIDS defining illnesses.

  15. Identification of a uniquely immunodominant, cross-reacting site in the human immunodeficiency virus endonuclease protein.

    Science.gov (United States)

    Björling, E; Utter, G; Stålhandske, P; Norrby, E; Chiodi, F

    1991-01-01

    One of the features of the life cycle of retroviruses is insertion of the proviral DNA into host chromosomes. A protein encoded by the 3' end of the pol gene of the virus genome has been shown to possess endonuclease activity (D. P. Grandgenett, A. C. Vora, and R. D. Schiff, Virology 89:119-132, 1978), which is necessary for DNA integration. Sera from the majority of human immunodeficiency virus (HIV)-infected individuals react with endonuclease protein p31 in serological tests (J. S. Allan, J. E. Coligan, T.-H. Lee, F. Barin, P. J. Kanki, S. M'Boup, M. F. McLane, J. E. Groopman, and M. Essex, Blood 69:331-333, 1987; E. F. Lillehoj, F. H. R. Salazar, R. J. Mervis, M. G. Raum, H. W. Chan, N. Ahmad, and S. Venkatesan, J. Virol. 62:3053-3058, 1988; K. S. Steimer, K. W. Higgins, M. A. Powers, J. C. Stephans, A. Gyenes, G. George-Nascimento, P. A. Liciw, P. J. Barr, R. A. Hallewell, and R. Sanchez-Pescador, J. Virol. 58:9-16, 1986). It is not known, however, which part of the protein represents the target(s) for antibody response. To study this, we synthesized peptides and used them in an enzyme-linked immunosorbent assay system to map the reactivity of human immunodeficiency virus type 1 (HIV-1) antibody-positive sera to the different regions of the HIV endonuclease. A uniquely antigenic, HIV-1- and HIV-2-cross-reacting site was identified in the central part of this protein from Phe-663 to Trp-670. PMID:2072463

  16. Acylated heptapeptide binds albumin with high affinity and application as tag furnishes long-acting peptides

    Science.gov (United States)

    Zorzi, Alessandro; Middendorp, Simon J.; Wilbs, Jonas; Deyle, Kaycie; Heinis, Christian

    2017-07-01

    The rapid renal clearance of peptides in vivo limits this attractive platform for the treatment of a broad range of diseases that require prolonged drug half-lives. An intriguing approach for extending peptide circulation times works through a `piggy-back' strategy in which peptides bind via a ligand to the long-lived serum protein albumin. In accordance with this strategy, we developed an easily synthesized albumin-binding ligand based on a peptide-fatty acid chimera that has a high affinity for human albumin (Kd=39 nM). This ligand prolongs the elimination half-life of cyclic peptides in rats 25-fold to over seven hours. Conjugation to a peptide factor XII inhibitor developed for anti-thrombotic therapy extends the half-life from 13 minutes to over five hours, inhibiting coagulation for eight hours in rabbits. This high-affinity albumin ligand could potentially extend the half-life of peptides in human to several days, substantially broadening the application range of peptides as therapeutics.

  17. Behaviors Influencing Human Immunodeficiency Virus Transmission in the Context of Positive Prevention among People Living with HIV/Acquired Immunodeficiency Syndrome in Iran: A Qualitative Study

    Directory of Open Access Journals (Sweden)

    Seyed Ramin Radfar

    2014-01-01

    Full Text Available Background: Identifying factors, which influence health behaviors is critical to designing appropriate and effective preventive programs. Human immunodeficiency virus (HIV transmission is highly related to people behaviors and understanding factors influencing healthy behaviors among Iranian people living with HIVs (PLHIVs/acquired immunodeficiency syndrome (AIDS is very important to tailor an effective response to HIV/AIDS epidemic. Methods: This study was conducted as a qualitative study by methods of focus group discussion and in-depth interview in six provinces of Iran with 64 PLHIVs to determine factors influence engagement in positive prevention. Results: Knowledge and education, feelings of responsibility and positive prevention practices were identified as the primary domains of engagement. These domains were found to be influenced by feelings of ostracism and frustration, poverty, barriers to disclosure of HIV status, access to and utilization of drug abuse treatment services and antiretroviral therapy, adherence to treatment, age, religiousness, sex work, singleness, and incarceration. Conclusions: Designing new interventions and updating current interventions directed toward the aforementioned factors should be addressed by responsible Iranian authorities in order to have a national effective response on the HIV/AIDS epidemic.

  18. Is human immunodeficiency virus/acquired immunodeficiency syndrome decreasing among Brazilian injection drug users? Recent findings and how to interpret them

    Directory of Open Access Journals (Sweden)

    Francisco I Bastos

    2005-02-01

    Full Text Available We briefly review findings from Brazilian settings where the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS epidemic among injection drug users (IDUs seems to be decreasing, highlighting recent findings from Rio de Janeiro and discussing methodological alternatives. Former analyses using serologic testing algorithm for recent HIV seroconversion have shown that HIV incidence has been low in IDUs recruited by two different surveys carried out in Rio, where low injection frequencies and infection rates have been found among new injectors. The proportion of AIDS cases among IDUs in Rio has been fairly modest, compared to São Paulo and especially to the southernmost states. Notwithstanding, the interpretation of findings from serial surveys constitutes a challenge, magnified in the assessment of HIV spread among IDUs due to the dynamic nature of the drug scenes and limitations of sampling strategies targeting hard-to-reach populations. Assessment of epidemic trends may profit from the triangulation of data, but cannot avert biases associated with sampling errors. Efforts should be made to triangulate data from different sources, besides exploring specific studies from different perspectives. In an attempt to further assess the observed trends, we carried out original analyses using data from Brazilian AIDS databank.

  19. Lineage-Specific Differences between the gp120 Inner Domain Layer 3 of Human Immunodeficiency Virus and That of Simian Immunodeficiency Virus.

    Science.gov (United States)

    Ding, Shilei; Medjahed, Halima; Prévost, Jérémie; Coutu, Mathieu; Xiang, Shi-Hua; Finzi, Andrés

    2016-11-15

    Binding of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) gp120 exterior envelope glycoprotein to CD4 triggers conformational changes in gp120 that promote its interaction with one of the chemokine receptors, usually CCR5, ultimately leading to gp41-mediated virus-cell membrane fusion and entry. We previously described that topological layers (layer 1, layer 2, and layer 3) in the gp120 inner domain contribute to gp120-trimer association in the unliganded state but also help secure CD4 binding. Relative to layer 1 of HIV-1 gp120, the SIVmac239 gp120 layer 1 plays a more prominent role in maintaining gp120-trimer association but is minimally involved in promoting CD4 binding, which could be explained by the existence of a well-conserved tryptophan at position 375 (Trp 375) in HIV-2/SIVsmm. In this study, we investigated the role of SIV layer 3 in viral entry, cell-to-cell fusion, and CD4 binding. We observed that a network of interactions involving some residues of the β8-α5 region in SIVmac239 layer 3 may contribute to CD4 binding by helping shape the nearby Phe 43 cavity, which directly contacts CD4. In summary, our results suggest that layer 3 in SIV has a greater impact on CD4 binding than in HIV-1. This work defines lineage-specific differences in layer 3 from HIV-1 and that from SIV.

  20. Is human immunodeficiency virus/acquired immunodeficiency syndrome decreasing among Brazilian injection drug users? Recent findings and how to interpret them.

    Science.gov (United States)

    Bastos, Francisco I; Bongertz, Vera; Teixeira, Sylvia Lopes; Morgado, Mariza G; Hacker, Mariana A

    2005-02-01

    We briefly review findings from Brazilian settings where the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic among injection drug users (IDUs) seems to be decreasing, highlighting recent findings from Rio de Janeiro and discussing methodological alternatives. Former analyses using serologic testing algorithm for recent HIV seroconversion have shown that HIV incidence has been low in IDUs recruited by two different surveys carried out in Rio, where low injection frequencies and infection rates have been found among new injectors. The proportion of AIDS cases among IDUs in Rio has been fairly modest, compared to São Paulo and especially to the southernmost states. Notwithstanding, the interpretation of findings from serial surveys constitutes a challenge, magnified in the assessment of HIV spread among IDUs due to the dynamic nature of the drug scenes and limitations of sampling strategies targeting hard-to-reach populations. Assessment of epidemic trends may profit from the triangulation of data, but cannot avert biases associated with sampling errors. Efforts should be made to triangulate data from different sources, besides exploring specific studies from different perspectives. In an attempt to further assess the observed trends, we carried out original analyses using data from Brazilian AIDS databank.

  1. Consensus on context-specific strategies for reducing the stigma of human immunodeficiency virus/acquired immunodeficiency syndrome in Zambézia Province, Mozambique.

    Science.gov (United States)

    Mukolo, Abraham; Torres, Isabel; Bechtel, Ruth M; Sidat, Mohsin; Vergara, Alfredo E

    2013-01-01

    Stigma has been implicated in poor outcomes of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) care. Reducing stigma is important for HIV prevention and long-term treatment success. Although stigma reduction interventions are conducted in Mozambique, little is known about the current nature of stigma and the efficacy and effectiveness of stigma reduction initiatives. We describe action research to generate consensus on critical characteristics of HIV stigma and anti-stigma interventions in Zambézia Province, Mozambique. Qualitative data gathering methods, including in-depth key-informant interviews, community interviews and consensus group sessions, were utilized. Delphi methods and the strategic options development analysis technique were used to synthesize qualitative data. Key findings are that stigma enacted by the general public might be declining in tandem with the HIV/AIDS epidemic in Mozambique, but there is likely excessive residual fear of HIV disease and community attitudes that sustain high levels of perceived stigma. HIV-positive women accessing maternal and child health services appear to shoulder a disproportionate burden of stigma. Unintentional biases among healthcare providers are currently the critical frontier of stigmatization, but there are few interventions designed to address them. Culturally sensitive psychotherapies are needed to address psychological distress associated with internalized stigma and these interventions should complement current supports for voluntary counseling and testing. While advantageous for defining stakeholder priorities for stigma reduction efforts, confirmatory quantitative studies of these consensus positions are needed before the launch of specific interventions.

  2. Presentation and outcome amongst older Singaporeans living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): does age alone drive excess mortality?

    Science.gov (United States)

    Huggan, Paul J; Foo, Rui Min; Olszyna, Dariusz; Chew, Nicholas S; Smitasen, Nares; Mukhopadhyay, Amartya; Archuleta, Sophia

    2012-12-01

    There is little detailed information on human immunodeficiency virus (HIV) amongst older adults in Singapore. A retrospective study of 121 consecutive referrals of patients presenting for HIV care was conducted. Demographic, clinical and laboratory variables were collected. A prognostic model derived from the North American Veterans' Affairs Cohort Study (VACS) was used to estimate prognosis. The median age at presentation was 43 (range, 18 to 76). Thirty-eight patients (31%) were aged 50 or older and 106 patients (88%) were male. Older patients were more likely to be of Chinese ethnicity (P = 0.035), married (P = 0.0001), unemployed or retired (P = 0.0001), and to have acquired their infection heterosexually (P = 0.0002). The majority of patients in both groups were symptomatic at presentation. Eighty-one (67%) had CD4 counts less than 200 at baseline with no observable differences in HIV ribonucleic acid (RNA) or clinical stage based on age. Non-Acquired Immunodeficiency Syndrome (AIDS) morbidity was observed more frequently amongst older patients. The estimated prognosis of patients differed significantly based on age. Using the VACS Index and comparing younger patients with those aged 50 and above, mean 5 year mortality estimates were 25% and 50% respectively (P HIV/AIDS cases and present with more non-AIDS morbidity. This confers a poor prognosis despite comparable findings with younger patients in terms of clinical stage, AIDS-defining illness, CD4 count and HIV viral load.

  3. Consensus on context-specific strategies for reducing the stigma of human immunodeficiency virus/acquired immunodeficiency syndrome in Zambézia Province, Mozambique

    Science.gov (United States)

    Mukolo, Abraham; Torres, Isabel; Bechtel, Ruth M.; Sidat, Mohsin; Vergara, Alfredo E.

    2014-01-01

    Stigma has been implicated in poor outcomes of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) care. Reducing stigma is important for HIV prevention and long-term treatment success. Although stigma reduction interventions are conducted in Mozambique, little is known about the current nature of stigma and the efficacy and effectiveness of stigma reduction initiatives. We describe action research to generate consensus on critical characteristics of HIV stigma and anti-stigma interventions in Zambézia Province, Mozambique. Qualitative data gathering methods, including indepth key-informant interviews, community interviews and consensus group sessions, were utilized. Delphi methods and the strategic options development analysis technique were used to synthesize qualitative data. Key findings are that stigma enacted by the general public might be declining in tandem with the HIV/AIDS epidemic in Mozambique, but there is likely excessive residual fear of HIV disease and community attitudes that sustain high levels of perceived stigma. HIV-positive women accessing maternal and child health services appear to shoulder a disproportionate burden of stigma. Unintentional biases among healthcare providers are currently the critical frontier of stigmatization, but there are few interventions designed to address them. Culturally sensitive psychotherapies are needed to address psychological distress associated with internalized stigma and these interventions should complement current supports for voluntary counseling and testing. While advantageous for defining stakeholder priorities for stigma reduction efforts, confirmatory quantitative studies of these consensus positions are needed before the launch of specific interventions. PMID:24527744

  4. Histoplasmosis in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): multicenter study of outcomes and factors associated with relapse.

    Science.gov (United States)

    Myint, Thein; Anderson, Albert M; Sanchez, Alejandro; Farabi, Alireza; Hage, Chadi; Baddley, John W; Jhaveri, Malhar; Greenberg, Richard N; Bamberger, David M; Rodgers, Mark; Crawford, Timothy N; Wheat, L Joseph

    2014-01-01

    Although discontinuation of suppressive antifungal therapy for acquired immunodeficiency syndrome (AIDS)-associated histoplasmosis is accepted for patients with immunologic recovery, there have been no published studies of this approach in clinical practice, and minimal characterization of individuals who relapse with this disease. We performed a multicenter retrospective cohort study to determine the outcome in AIDS patients following discontinuation of suppressive antifungal therapy for histoplasmosis. Ninety-seven patients were divided into a physician-discontinued suppressive therapy group (PD) (38 patients) and a physician-continued suppressive therapy group (PC) (59 patients). The 2 groups were not statistically different at baseline, but at discontinuation of therapy and at the most recent follow-up there were significant differences in adherence to therapy, human immunodeficiency virus (HIV) RNA, and urinary Histoplasma antigen concentration. There was no relapse or death attributed to histoplasmosis in the PD group compared with 36% relapse (p 150 cells/mL, HIV RNA <400 c/mL, Histoplasma antigenuria <2 ng/mL (equivalent to <4.0 units in second-generation method), and no CNS histoplasmosis.

  5. Distinct Differences on Neointima Formation in Immunodeficient and Humanized Mice after Carotid or Femoral Arterial Injury

    Science.gov (United States)

    Moser, Jill; van Ark, Joris; van Dijk, Marcory C.; Greiner, Dale L.; Shultz, Leonard D.; van Goor, Harry; Hillebrands, Jan-Luuk

    2016-01-01

    Percutaneous coronary intervention is widely adopted to treat patients with coronary artery disease. However, restenosis remains an unsolved clinical problem after vascular interventions. The role of the systemic and local immune response in the development of restenosis is not fully understood. Hence, the aim of the current study was to investigate the role of the human immune system on subsequent neointima formation elicited by vascular injury in a humanized mouse model. Immunodeficient NOD.Cg-PrkdcscidIL2rgtm1Wjl(NSG) mice were reconstituted with human (h)PBMCs immediately after both carotid wire and femoral cuff injury were induced in order to identify how differences in the severity of injury influenced endothelial regeneration, neointima formation, and homing of human inflammatory and progenitor cells. In contrast to non-reconstituted mice, hPBMC reconstitution reduced neointima formation after femoral cuff injury whereas hPBMCs promoted neointima formation after carotid wire injury 4 weeks after induction of injury. Neointimal endothelium and smooth muscle cells in the injured arteries were of mouse origin. Our results indicate that the immune system may differentially respond to arterial injury depending on the severity of injury, which may also be influenced by the intrinsic properties of the arteries themselves, resulting in either minimal or aggravated neointima formation. PMID:27759053

  6. Absolute level of Epstein-Barr Virus (EBV) DNA in human immunodeficiency virus type 1 infection is not predictive of AIDS-related non-Hodgkin lymphoma.

    NARCIS (Netherlands)

    D. van Baarle (Debbie); K.C. Wolthers (Katja); E. Hovenkamp (Egbert); A.D.M.E. Osterhaus (Albert); F. Miedema (Frank); M.H.J. van Oers (Marinus); H.G.M. Niesters (Bert)

    2002-01-01

    textabstractTo study whether Epstein-Barr virus (EBV) load can be used to predict the occurrence of acquired immunodeficiency syndrome-related non-Hodgkin lymphoma (AIDS-NHL), we determined EBV load longitudinally for individuals infected with human immunodeficiency virus type 1. EBV load in periphe

  7. Absolute level of Epstein-Barr virus DNA in human immunodeficiency virus type 1 infection is not predictive of AIDS-related non-Hodgkin lymphoma

    NARCIS (Netherlands)

    Van Baarle, Debbie; Wolthers, Katja C; Hovenkamp, Egbert; Niesters, Hubert G M; Osterhaus, Albert D M E; Miedema, Frank; Van Oers, Marinus H J

    2002-01-01

    To study whether Epstein-Barr virus (EBV) load can be used to predict the occurrence of acquired immunodeficiency syndrome-related non-Hodgkin lymphoma (AIDS-NHL), we determined EBV load longitudinally for individuals infected with human immunodeficiency virus type 1. EBV load in peripheral blood mo

  8. Long-term use of first-line highly active antiretroviral therapy is not associated with carotid artery stiffness in human immunodeficiency virus-positive patients

    Directory of Open Access Journals (Sweden)

    Haohui Zhu

    2014-09-01

    Full Text Available Objective: To evaluate whether or not highly active antiretroviral therapy is associated with carotid artery stiffness in human immunodeficiency virus-positive patients in Henan Province, China. Method: Fifty human immunodeficiency virus-positive patients with at least a 5-year history of highly active antiretroviral therapy use and 50 human immunodeficiency virus-positive patients without a history of highly active antiretroviral therapy use were enrolled in this study. Carotid artery intima-media thickness and stiffness were determined by quantitative inter-media thickness and quantitative artery stiffness, respectively. Results: No statistically significant difference in carotid artery intima-media thickness and stiffness was observed between groups. A significant association between human immunodeficiency virus infection time and carotid artery stiffness was observed, but no significant association between human immunodeficiency virus infection time and intima-media thickness was found. No significant association between intima-media thickness, stiffness, and CD4+ and CD8+ T-cell counts were observed. Conclusion: The first-line highly active antiretroviral therapy currently used in China is not associated with carotid artery stiffness in human immunodeficiency virus-positive patients with good highly active antiretroviral therapy compliance. Human immunodeficiency virus may play a role in the development of atherosclerosis.

  9. Comparison of Talaromyces marneffei Infection in Human Immunodeficiency Virus-positive and Human Immunodeficiency Virus-negative Patients from Fujian, China

    Institute of Scientific and Technical Information of China (English)

    Hong-Ru Li; Shao-Xi Cai; Yu-Sheng Chen; Mei-E Yu; Neng-Luan Xu; Bao-Song Xie; Ming Lin

    2016-01-01

    Background:Talaromyces (Penicillium) rnarneffei (TM) is an emerging dimorphic human pathogenic fungus that is endemic to Southeast Asia.TM mostly occurs as an opportunistic infection in patients with human immunodeficiency virus (HIV).The objective of this study was to compare the clinical and laboratory parameters of patients with TM infections who were HIV-positive and HIV-negative and to assess therapies and outcomes.Methods:This was a retrospective analysis of 26 patients diagnosed with disseminated TM infection from September 2005 to April 2014 at Fujian Provincial Hospital,China.Results:Patients with TM infection tend to present with fever,weight loss,and anemia.The time from symptom onset to confirmed diagnosis was greater for HIV-negative patients (n =7; median:60 days,range:14-365 days) than for HIV-positive patients (n =19; median:30 days,range:3-90 days,Mann Whitney U=31.50,P =0.041).HIV-negative patients were more likely to have dyspnea (57.1% vs.5.3%,x2 =8.86,P =0.010),low neutrophil count (Mann-Whitney U =27.00,P =0.029),high CD4 count (Mann-Whitney U =0.00,P =0.009),and high lymphocyte count (Mann-Whitney U =21.00,P =0.009).There were no significant differences in other demographic,clinical,or biochemical characteristics.Among all the patients,12 HIV-positive patient and 1 HIV-negative patient received amphotericin and fluconazole treatment,9 of whom improved,1 died,2 had kidney damage,1 had hypokalemia due to exceeded doses.Conclusions:HIV-negative patients with TM infections tend to have a longer diagnostic interval,a higher percentage of dyspnea,higher levels of CD4 and lymphocytes,and lower neutrophil counts than TM infection in HIV-positive patients.Treatment programs with amphotericin and fluconazole are mostly effective.

  10. Detection of Waterborne Viruses Using High Affinity Molecularly Imprinted Polymers.

    Science.gov (United States)

    Altintas, Zeynep; Gittens, Micah; Guerreiro, Antonio; Thompson, Katy-Anne; Walker, Jimmy; Piletsky, Sergey; Tothill, Ibtisam E

    2015-07-07

    Molecularly imprinted polymers (MIPs) are artificial receptor ligands which can recognize and specifically bind to a target molecule. They are more resistant to chemical and biological damage and inactivation than antibodies. Therefore, target specific-MIP nanoparticles are aimed to develop and implemented to biosensors for the detection of biological toxic agents such as viruses, bacteria, and fungi toxins that cause many diseases and death due to the environmental contamination. For the first time, a molecularly imprinted polymer (MIP) targeting the bacteriophage MS2 as the template was investigated using a novel solid-phase synthesis method to obtain the artificial affinity ligand for the detection and removal of waterborne viruses through optical-based sensors. A high affinity between the artificial ligand and the target was found, and a regenerative MIP-based virus detection assay was successfully developed using a new surface plasmon resonance (SPR)-biosensor which provides an alternative technology for the specific detection and removal of waterborne viruses that lead to high disease and death rates all over the world.

  11. Human Immunodeficiency Virus Infection-Associated Mortality during Pulmonary Tuberculosis Treatment in Six Provinces of China

    Institute of Scientific and Technical Information of China (English)

    LAI Yu Ji; LIU Er Yong; WANG Li Ming; Jamie P MORANO; WANG Ning; Kaveh KHOSHNOOD; ZHOU Lin; CHENG Shi Ming

    2015-01-01

    Objective To investigate the risk factors attributable to tuberculosis-related deaths in areas with human immunodeficiency virus (HIV) infection epidemics. Methods A prospective cohort study of newly registered patients in tuberculosis (TB) dispensaries in six representative Chinese provinces was conducted from September 1, 2009 to August 31, 2011. Risk factors for TB-associated death were identified through logistic regression analysis. Results Of 19,103 newly registered pulmonary TB patients, 925 (4.8%) were found to be HIV-positive. Miliary TB and acid-fast bacillus smear-negative TB were more common among these patients. Out of a total of 322 (1.7%) deaths that occurred during TB treatment, 85 (26%) of the patients were co-infected with HIV. Multivariate analysis revealed that HIV infection was the strongest predictor of death [adjusted odds ratio (aOR) 7.86]. Other significant mortality risk factors included presentation with miliary TB (aOR 4.10; 95% confidence interval: 2.14-7.88), ≥35 years of age (aOR 3.04), non-Han ethnicity (aOR 1.67), and farming as an occupation (aOR 1.59). For patients with TB/HIV co-infection, miliary TB was the strongest risk factor for death (aOR 5.48). A low CD4 count (≤200 cells/µL) (aOR 3.27) at the time of TB treatment initiation and a lack of antiretroviral therapy (ART) administration (aOR 3.78) were also correlated with an increased risk of death. Conclusion Infection with HIV was independently associated with increased mortality during TB treatment. Offering HIV testing at the time of diagnosis with TB, early TB diagnosis among HIV/acquired immunodeficiency syndrome patients, and the timely provision of ART were identified as the key approaches that could reduce the number of HIV-associated TB deaths.

  12. White matter tract injury and cognitive impairment in human immunodeficiency virus-infected individuals.

    Science.gov (United States)

    Gongvatana, Assawin; Schweinsburg, Brian C; Taylor, Michael J; Theilmann, Rebecca J; Letendre, Scott L; Alhassoon, Omar M; Jacobus, Joanna; Woods, Steven P; Jernigan, Terry L; Ellis, Ronald J; Frank, Lawrence R; Grant, Igor

    2009-04-01

    Approximately half of those infected with the human immunodeficiency virus (HIV) exhibit cognitive impairment, which has been related to cerebral white matter damage. Despite the effectiveness of antiretroviral treatment, cognitive impairment remains common even in individuals with undetectable viral loads. One explanation for this may be subtherapeutic concentrations of some antiretrovirals in the central nervous system (CNS). We utilized diffusion tensor imaging and a comprehensive neuropsychological evaluation to investigate the relationship of white matter integrity to cognitive impairment and antiretroviral treatment variables. Participants included 39 HIV-infected individuals (49% with acquired immunodeficiency syndrome [AIDS]; mean CD4 = 529) and 25 seronegative subjects. Diffusion tensor imaging indices were mapped onto a common whole-brain white matter tract skeleton, allowing between-subject voxelwise comparisons. The total HIV-infected group exhibited abnormal white matter in the internal capsule, inferior longitudinal fasciculus, and optic radiation; whereas those with AIDS exhibited more widespread damage, including in the internal capsule and the corpus callosum. Cognitive impairment in the HIV-infected group was related to white matter injury in the internal capsule, corpus callosum, and superior longitudinal fasciculus. White matter injury was not found to be associated with HIV viral load or estimated CNS penetration of antiretrovirals. Diffusion tensor imaging was useful in identifying changes in white matter tracts associated with more advanced HIV infection. Relationships between diffusion alterations in specific white matter tracts and cognitive impairment support the potential utility of diffusion tensor imaging in examining the anatomical underpinnings of HIV-related cognitive impairment. The study also confirms that CNS injury is evident in persons infected with HIV despite effective antiretroviral treatment.

  13. High affinity binding of (/sup 3/H)cocaine to rat liver microsomes

    Energy Technology Data Exchange (ETDEWEB)

    El-Maghrabi, E.A.; Calligaro, D.O.; Eldefrawi, M.E.

    1988-01-01

    )/sup 3/H)cocaine bound reversible, with high affinity and stereospecificity to rat liver microsomes. Little binding was detected in the lysosomal, mitochondrial and nuclear fractions. The binding kinetics were slow and the kinetically calculated K/sub D/ was 2 nM. Induction of mixed function oxidases by phenobarbital did not produce significant change in (/sup 3/H)cocaine binding. On the other hand, chronic administration of cocaine reduced (/sup 3/H)cocaine binding drastically. Neither treatment affected the affinity of the liver binding protein for cocaine. Microsomes from mouse and human livers had less cocaine-binding protein and lower affinity for cocaine than those from rat liver. Binding of (/sup 3/H)cocaine to rat liver microsomes was insensitive to monovalent cations and > 10 fold less sensitive to biogenic amines than the cocaine receptor in rat striatum. However, the liver protein had higher affinity for cocaine and metabolites except for norcocaine. Amine uptake inhibitors displaced (/sup 3/H)cocaine binding to liver with a different rank order of potency than their displacement of (/sup 3/H)cocaine binding to striatum. This high affinity (/sup 3/H)cocaine binding protein in liver is not likely to be monooxygenase, but may have a role in cocaine-induced hepatotoxicity

  14. ABT-378, a Highly Potent Inhibitor of the Human Immunodeficiency Virus Protease

    Science.gov (United States)

    Sham, Hing L.; Kempf, Dale J.; Molla, Akhteruzammen; Marsh, Kennan C.; Kumar, Gondi N.; Chen, Chih-Ming; Kati, Warren; Stewart, Kent; Lal, Ritu; Hsu, Ann; Betebenner, David; Korneyeva, Marina; Vasavanonda, Sudthida; McDonald, Edith; Saldivar, Ayda; Wideburg, Norm; Chen, Xiaoqi; Niu, Ping; Park, Chang; Jayanti, Venkata; Grabowski, Brian; Granneman, G. Richard; Sun, Eugene; Japour, Anthony J.; Leonard, John M.; Plattner, Jacob J.; Norbeck, Daniel W.

    1998-01-01

    The valine at position 82 (Val 82) in the active site of the human immunodeficiency virus (HIV) protease mutates in response to therapy with the protease inhibitor ritonavir. By using the X-ray crystal structure of the complex of HIV protease and ritonavir, the potent protease inhibitor ABT-378, which has a diminished interaction with Val 82, was designed. ABT-378 potently inhibited wild-type and mutant HIV protease (Ki = 1.3 to 3.6 pM), blocked the replication of laboratory and clinical strains of HIV type 1 (50% effective concentration [EC50], 0.006 to 0.017 μM), and maintained high potency against mutant HIV selected by ritonavir in vivo (EC50, ≤0.06 μM). The metabolism of ABT-378 was strongly inhibited by ritonavir in vitro. Consequently, following concomitant oral administration of ABT-378 and ritonavir, the concentrations of ABT-378 in rat, dog, and monkey plasma exceeded the in vitro antiviral EC50 in the presence of human serum by >50-fold after 8 h. In healthy human volunteers, coadministration of a single 400-mg dose of ABT-378 with 50 mg of ritonavir enhanced the area under the concentration curve of ABT-378 in plasma by 77-fold over that observed after dosing with ABT-378 alone, and mean concentrations of ABT-378 exceeded the EC50 for >24 h. These results demonstrate the potential utility of ABT-378 as a therapeutic intervention against AIDS. PMID:9835517

  15. Slowing Down Differentiation of Engrafted Human Myoblasts Into Immunodeficient Mice Correlates With Increased Proliferation and Migration

    Science.gov (United States)

    Riederer, Ingo; Negroni, Elisa; Bencze, Maximilien; Wolff, Annie; Aamiri, Ahmed; Di Santo, James P; Silva-Barbosa, Suse D.; Butler-Browne, Gillian; Savino, Wilson; Mouly, Vincent

    2012-01-01

    We have used a model of xenotransplantation in which human myoblasts were transplanted intramuscularly into immunodeficient Rag2-/-γC-/- mice, in order to investigate the kinetics of proliferation and differentiation of the transplanted cells. After injection, most of the human myoblasts had already differentiated by day 5. This differentiation correlated with reduction in proliferation and limited migration of the donor cells within the regenerating muscle. These results suggest that the precocious differentiation, already detected at 3 days postinjection, is a limiting factor for both the migration from the injection site and the participation of the donor cells to muscle regeneration. When we stimulated in vivo proliferation of human myoblasts, transplanting them in a serum-containing medium, we observed 5 days post-transplantation a delay of myogenic differentiation and an increase in cell numbers, which colonized a much larger area within the recipient's muscle. Importantly, these myoblasts maintained their ability to differentiate, since we found higher numbers of myofibers seen 1 month postengraftment, as compared to controls. Conceptually, these data suggest that in experimental myoblast transplantation, any intervention upon the donor cells and/or the recipient's microenvironment aimed at enhancing proliferation and migration should be done before differentiation of the implanted cells, e.g., day 3 postengraftment. PMID:21934656

  16. Slowing down differentiation of engrafted human myoblasts into immunodeficient mice correlates with increased proliferation and migration.

    Science.gov (United States)

    Riederer, Ingo; Negroni, Elisa; Bencze, Maximilien; Wolff, Annie; Aamiri, Ahmed; Di Santo, James P; Silva-Barbosa, Suse D; Butler-Browne, Gillian; Savino, Wilson; Mouly, Vincent

    2012-01-01

    We have used a model of xenotransplantation in which human myoblasts were transplanted intramuscularly into immunodeficient Rag2(-/-)γC(-/-) mice, in order to investigate the kinetics of proliferation and differentiation of the transplanted cells. After injection, most of the human myoblasts had already differentiated by day 5. This differentiation correlated with reduction in proliferation and limited migration of the donor cells within the regenerating muscle. These results suggest that the precocious differentiation, already detected at 3 days postinjection, is a limiting factor for both the migration from the injection site and the participation of the donor cells to muscle regeneration. When we stimulated in vivo proliferation of human myoblasts, transplanting them in a serum-containing medium, we observed 5 days post-transplantation a delay of myogenic differentiation and an increase in cell numbers, which colonized a much larger area within the recipient's muscle. Importantly, these myoblasts maintained their ability to differentiate, since we found higher numbers of myofibers seen 1 month postengraftment, as compared to controls. Conceptually, these data suggest that in experimental myoblast transplantation, any intervention upon the donor cells and/or the recipient's microenvironment aimed at enhancing proliferation and migration should be done before differentiation of the implanted cells, e.g., day 3 postengraftment.

  17. The physical activity levels among people living with human immunodeficiency virus/acquired immunodeficiency syndrome receiving high active antiretroviral therapy in Rwanda.

    Science.gov (United States)

    Frantz, J M; Murenzi, A

    2013-01-01

    The accessibility of high active antiretroviral therapy (HAART) for local human immunodeficiency virus (HIV) patients is improving in Rwanda. It is well known that this therapy is associated with serious adverse effects, such as metabolic and morphologic changes. One of the recommended preventive modalities for these complications is participation in physical activity. The current study aims to determine the anthropometric profile and physical activity levels among people living with HIV and receiving HAART in Kigali, Rwanda. The study was a cross-sectional, descriptive quantitative survey. The participant's levels of physical activity participation and their association with anthropometric profiles were measured, using a structured self-administered questionnaire for 407 clients passing through the clinics. Of the participants, approximately 70% were inactive and in addition, 40% were obese and 43% overweight. Obesity was found to be strongly associated with inactivity. Lack of motivation, and time as well as fear of worsening the disease were found to be barriers to participation in physical activity.

  18. Seroprevalence of the Hepatitis B, Hepatitis C, and Human Immunodeficiency Viruses and Treponema pallidum at the Beijing General Hospital from 2010 to 2014: A Cross-Sectional Study.

    Directory of Open Access Journals (Sweden)

    Shaoxia Xu

    Full Text Available The hepatitis B, hepatitis C, human immunodeficiency viruses and Treponema pallidum are important causes of infectious diseases concern to public health.Between 2010 and 2014, we used an automated chemiluminescence microparticle immunoassay to detect the hepatitis B, hepatitis C, and human immunodeficiency viruses as well as Treponema pallidum (the rapid plasma regain test was used in 2010-2011. Positive human immunodeficiency virus tests were confirmed via western blotting.Among 416,130 subjects, the seroprevalences for hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and Treponema pallidum were 5.72%, 1.23%, 0.196%, and 0.76%, respectively. Among 671 patients with positive human immunodeficiency virus results, 392 cases were confirmed via western blotting. Hepatitis B and human immunodeficiency virus infections were more frequent in men (7.78% and 0.26%, respectively than in women (4.45% and 0.021%, respectively. The hepatitis B and C virus seroprevalences decreased from 6.21% and 1.58%, respectively, in 2010, to 5.37% and 0.988%, respectively, in 2014. The human immunodeficiency virus seroprevalence increased from 0.04% in 2010 to 0.17% in 2014, and was elevated in the Infectious Disease (2.65%, Emergency (1.71%, and Dermatology and Sexually Transmitted Diseases (1.12% departments. The specificity of the human immunodeficiency virus screening was 71.4%. The false positive rates for the Treponema pallidum screening tests increased in patients who were 60-70 years old. The co-infection rates for the hepatitis C and human immunodeficiency viruses were 0.47% in hepatitis C virus-positive patients and 7.33% in human immunodeficiency virus-positive patients.During 2010-2014, hepatitis B virus and human immunodeficiency virus infections were more frequent among men at our institution. Although the seroprevalences of hepatitis B and C viruses decreased, the seroprevalence of human immunodeficiency virus infection increased (with

  19. Evidence for a precursor of the high-affinity metastasis-associated murine laminin receptor

    DEFF Research Database (Denmark)

    Rao, C N; Castronovo, V; Schmitt, M C;

    1989-01-01

    The high-affinity cellular receptor for the basement membrane component laminin is differentially expressed during tumor invasion and metastasis. A cDNA clone encoding the murine laminin receptor was isolated and identified on the basis of sequence homology to the human laminin receptor [Wewer et...... al. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 7137-7141]. Primer extension experiments demonstrated that the clone contained the complete 5' sequence of the murine laminin receptor mRNA. RNA blot data demonstrated a single-sized laminin receptor mRNA, approximately 1400 bases long, in human, mouse......, and rat. The nascent laminin receptor predicted from the cDNA sequence is 295 amino acids long, with a molecular weight of 33,000, and contains one intradisulfide bridge, a short putative transmembrane domain, and an extracellular carboxy-terminal region which has abundant glutamic acid residues...

  20. Prevalence and Correlates of Genital Infections Among Newly Diagnosed Human Immunodeficiency Virus–Infected Adults Entering Human Immunodeficiency Virus Care in Windhoek, Namibia

    Science.gov (United States)

    Djomand, Gaston; Schlefer, Madeleine; Gutreuter, Steve; Tobias, Sarah; Patel, Roopal; DeLuca, Nickolas; Hood, Julia; Sawadogo, Souleymane; Chen, Cheng; Muadinohamba, Alexinah; Lowrance, David W.; Bock, Naomi

    2016-01-01

    Background Identifying and treating genital infections, including sexually transmitted infections (STI), among newly diagnosed human immunodeficiency virus (HIV)-infected individuals may benefit both public and individual health. We assessed prevalence of genital infections and their correlates among newly diagnosed HIV-infected individuals enrolling in HIV care services in Namibia. Methods Newly diagnosed HIV-infected adults entering HIV care at 2 health facilities in Windhoek, Namibia, were recruited from December 2012 to March 2014. Participants provided behavioral and clinical data including CD4+ T lymphocyte counts. Genital and blood specimens were tested for gonorrhea, Chlamydia, trichomoniasis, Mycoplasma genitalium, syphilis, bacterial vaginosis, and vulvovaginal candidiasis. Results Among 599 adults, 56% were women and 15% reported consistent use of condoms in the past 6 months. The most common infections were bacterial vaginosis (37.2%), trichomoniasis (34.6%) and Chlamydia (14.6%) in women and M. genitalium (11.4%) in men. Correlates for trichomoniasis included being female (adjusted relative risk, [aRR], 7.18; 95% confidence interval [CI], 4.07–12.65), higher education (aRR, 0.58; 95% CI, 0.38–0.89), and lower CD4 cell count (aRR, 1.61; 95% CI, 1.08–2.40). Being female (aRR, 2.39; 95% CI, 1.27–4.50), nonmarried (aRR, 2.30; (95% CI, 1.28–4.14), and having condomless sex (aRR, 2.72; 95% CI, 1.06–7.00) were independently associated with chlamydial infection. Across all infections, female (aRR, 2.31; 95% CI, 1.79–2.98), nonmarried participants (aRR, 1.29; 95% CI, 1.06–1.59), had higher risk to present with any STI, whereas pregnant women (aRR, 1.16, 95% CI 1.03–1.31) were at increased risk of any STI or reproductive tract infection. PMID:27893600

  1. A high-affinity molybdate transporter in eukaryotes.

    Science.gov (United States)

    Tejada-Jiménez, Manuel; Llamas, Angel; Sanz-Luque, Emanuel; Galván, Aurora; Fernández, Emilio

    2007-12-11

    Molybdenum is an essential element for almost all living beings, which, in the form of a molybdopterin-cofactor, participates in the active site of enzymes involved in key reactions of carbon, nitrogen, and sulfur metabolism. This metal is taken up by cells in form of the oxyanion molybdate. Bacteria acquire molybdate by an ATP-binding-cassette (ABC) transport system in a widely studied process, but how eukaryotic cells take up molybdenum is unknown because molybdate transporters have not been identified so far. Here, we report a eukaryotic high-affinity molybdate transporter, encoded by the green alga Chlamydomonas reinhardtii gene MoT1. An antisense RNA strategy over the MoT1 gene showed that interference of the expression of this gene leads to the inhibition of molybdate transport activity and, in turn, of the Mo-containing enzyme nitrate reductase, indicating a function of MoT1 in molybdate transport. MOT1 functionality was also shown by heterologous expression in Saccharomyces cerevisiae. Molybdate uptake mediated by MOT1 showed a K(m) of approximately 6 nM, which is the range of the lowest K(m) values reported and was activated in the presence of nitrate. Analysis of deduced sequence from the putative protein coded by MoT1 showed motifs specifically conserved in similar proteins present in the databases, and defines a family of membrane proteins in both eukaryotes and prokaryotes probably involved in molybdate transport and distantly related to plant sulfate transporters SULTR. These findings represent an important step in the understanding of molybdate transport, a crucial process in eukaryotic cells.

  2. Hypothesis of snake and insect venoms against Human Immunodeficiency Virus: a review

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    Sweni Shah

    2009-11-01

    Full Text Available Abstract Background Snake and insect venoms have been demonstrated to have beneficial effects in the treatment of certain diseases including drug resistant human immunodeficiency virus (HIV infection. We evaluated and hypothesized the probable mechanisms of venoms against HIV. Methods Previous literatures published over a period of 30 years (1979-2009 were searched using the key words snake venom, insect venom, mechanisms and HIV. Mechanisms were identified and discussed. Results & Conclusion With reference to mechanisms of action, properties and components of snake venom such as sequence homology and enzymes (protease or L- amino acid oxidase may have an effect on membrane protein and/or act against HIV at multiple levels or cells carrying HIV virus resulting in enhanced effect of anti-retroviral therapy (ART. This may cause a decrease in viral load and improvement in clinical as well as immunological status. Insect venom and human Phospholipase A2 (PLA2 have potential anti-viral activity through inhibition of virion entry into the cells. However, all these require further evaluation in order to establish its role against HIV as an independent one or as a supplement.

  3. Natural killer cell biology illuminated by primary immunodeficiency syndromes in humans.

    Science.gov (United States)

    Voss, Matthias; Bryceson, Yenan T

    2017-04-01

    Natural killer (NK) cells are innate immune cytotoxic effector cells well known for their role in antiviral immunity and tumor immunosurveillance. In parts, this knowledge stems from rare inherited immunodeficiency disorders in humans that abrogate NK cell function leading to immune impairments, most notably associated with a high susceptibility to viral infections. Phenotypically, these disorders range from deficiencies selectively affecting NK cells to complex general immune defects that affect NK cells but also other immune cell subsets. Moreover, deficiencies may be associated with reduced NK cell numbers or rather impair specific NK cell effector functions. In recent years, genetic defects underlying the various NK cell deficiencies have been uncovered and have triggered investigative efforts to decipher the molecular mechanisms underlying these disorders. Here we review the associations between inherited human diseases and NK cell development as well as function, with a particular focus on defects in NK cell exocytosis and cytotoxicity. Furthermore we outline how reports of diverse genetic defects have shaped our understanding of NK cell biology. Copyright © 2015. Published by Elsevier Inc.

  4. Two highly antigenic sites in the human immunodeficiency virus type 1 reverse transcriptase.

    Science.gov (United States)

    Björling, E; Boucher, C A; Samuelsson, A; Wolfs, T F; Utter, G; Norrby, E; Chiodi, F

    1993-01-01

    Antibodies to human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) are found in the serum of the majority of infected individuals, and inhibition of RT polymerase activity by HIV-1-positive sera can be demonstrated in vitro. The binding sites of human antibodies on the protein have not yet been identified. We synthesized overlapping peptides covering the entire RT protein of HIV-1 and used them in an enzyme-linked immunosorbent assay system to map the reactivities of HIV-1 and HIV-2 antibody-positive sera. Two highly antigenic regions were identified by both HIV serotypes. One region was found in the central part of the RT protein (amino acids 261 to 280) and another was found at the carboxy terminus in the RNase H portion of RT (amino acids 517 to 536). Comparison of the serological results with the crystal structure of the RT revealed that the antigenic region in the RNase H portion is located at the surface of the protein. The other antibody-binding site (amino acids 261 to 280) was located in the "thumb" region of the polymerase domain of RT. Polyclonal antibodies to either of the antibody-binding sites do not affect the polymerase activity of the RT protein. PMID:7681439

  5. In Vivo Models of Human Immunodeficiency Virus Persistence and Cure Strategies.

    Science.gov (United States)

    Nixon, Christopher C; Mavigner, Maud; Silvestri, Guido; Garcia, J Victor

    2017-03-15

    Current HIV therapy is not curative regardless of how soon after infection it is initiated or how long it is administered, and therapy interruption almost invariably results in robust viral rebound. Human immunodeficiency virus persistence is therefore the major obstacle to a cure for AIDS. The testing and implementation of novel yet unproven approaches to HIV eradication that could compromise the health status of HIV-infected individuals might not be ethically warranted. Therefore, adequate in vitro and in vivo evidence of efficacy is needed to facilitate the clinical implementation of promising strategies for an HIV cure. Animal models of HIV infection have a strong and well-documented history of bridging the gap between laboratory discoveries and eventual clinical implementation. More recently, animal models have been developed and implemented for the in vivo evaluation of novel HIV cure strategies. In this article, we review the recent progress in this rapidly moving area of research, focusing on the two most promising model systems: humanized mice and nonhuman primates. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  6. Characterization of human immunodeficiency viruses resistant to oxathiolane-cytosine nucleosides.

    Science.gov (United States)

    Schinazi, R F; Lloyd, R M; Nguyen, M H; Cannon, D L; McMillan, A; Ilksoy, N; Chu, C K; Liotta, D C; Bazmi, H Z; Mellors, J W

    1993-04-01

    The (-) enantiomers of 2',3'-dideoxy-5-fluoro-3'-thiacytidine [(-)-FTC] and 2',3'-dideoxy-3'-thiacytidine [(-)-BCH-189] were recently shown to inhibit selectively human immunodeficiency viruses (HIV) and hepatitis B virus in vitro. In the current study, the potential for HIV type 1 (HIV-1) resistance to these compounds was evaluated by serial passage of the virus in human peripheral blood mononuclear cells and MT-2 cells in the presence of increasing drug concentrations. Highly drug-resistant HIV-1 variants dominated the replicating virus population after two or more cycles of infection. The resistant variants were cross-resistant to (-)-FTC, (-)-BCH-189, and their (+) congeners but remained susceptible to 2',3'-dideoxycytidine, 3'-azido-3'-deoxythymidine, 3'-fluoro-3'-deoxythymidine, 2',3'-dideoxyinosine, phosphonoformate, the TIBO compound R82150, and the bis(heteroaryl)piperazine derivative U-87201E. Reverse transcriptase derived from drug-resistant viral particles was 15- to 50-fold less susceptible to the 5'-triphosphates of FTC and BCH-189 compared with enzyme from parental drug-susceptible virus. DNA sequence analysis of the reverse transcriptase gene amplified from resistant viruses consistently identified mutations at codon 184 from Met (ATG) to Val (GTG or GTA) or Ile (ATA). Sequence analysis of amplified reverse transcriptase from a patient who had received (-)-BCH-189 therapy for 4 months demonstrated a mixture of the Met-184-to-Val (GTG) mutation and the parental genotype, indicating that the Met-184 mutation can occur in vivo.

  7. Procyanidin trimer C1 derived from Theobroma cacao reactivates latent human immunodeficiency virus type 1 provirus.

    Science.gov (United States)

    Hori, Takanori; Barnor, Jacob; Huu, Tung Nguyen; Morinaga, Osamu; Hamano, Akiko; Ndzinu, Jerry; Frimpong, Angela; Minta-Asare, Keren; Amoa-Bosompem, Mildred; Brandful, James; Odoom, John; Bonney, Joseph; Tuffour, Isaac; Owusu, Baffour-Awuah; Ofosuhene, Mark; Atchoglo, Philip; Sakyiamah, Maxwell; Adegle, Richard; Appiah-Opong, Regina; Ampofo, William; Koram, Kwadwo; Nyarko, Alexander; Okine, Laud; Edoh, Dominic; Appiah, Alfred; Uto, Takuhiro; Yoshinaka, Yoshiyuki; Uota, Shin; Shoyama, Yukihiro; Yamaoka, Shoji

    2015-04-03

    Despite remarkable advances in combination antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) infection remains incurable due to the incomplete elimination of the replication-competent virus, which persists in latent reservoirs. Strategies for targeting HIV reservoirs for eradication that involves reactivation of latent proviruses while protecting uninfected cells by cART are urgently needed for cure of HIV infection. We screened medicinal plant extracts for compounds that could reactivate the latent HIV-1 provirus and identified a procyanidin trimer C1 derived from Theobroma cacao as a potent activator of the provirus in human T cells latently infected with HIV-1. This reactivation largely depends on the NF-κB and MAPK signaling pathways because either overexpression of a super-repressor form of IκBα or pretreatment with a MEK inhibitor U0126 diminished provirus reactivation by C1. A pan-PKC inhibitor significantly blocked the phorbol ester-induced but not the C1-induced HIV-1 reactivation. Although C1-induced viral gene expression persisted for as long as 48 h post-stimulation, NF-κB-dependent transcription peaked at 12 h post-stimulation and then quickly declined, suggesting Tat-mediated self-sustainment of HIV-1 expression. These results suggest that procyanidin C1 trimer is a potential compound for reactivation of latent HIV-1 reservoirs. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Interactions between human immunodeficiency virus (HIV-1 Vpr expression and innate immunity influence neurovirulence

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    Ballanyi Klaus

    2011-06-01

    Full Text Available Abstract Background Viral diversity and abundance are defining properties of human immunodeficiency virus (HIV-1's biology and pathogenicity. Despite the increasing availability of antiretroviral therapy, HIV-associated dementia (HAD continues to be a devastating consequence of HIV-1 infection of the brain although the underlying disease mechanisms remain uncertain. Herein, molecular diversity within the HIV-1 non-structural gene, Vpr, was examined in RNA sequences derived from brain and blood of HIV/AIDS patients with or without HIV-associated dementia (HAD together with the ensuing pathobiological effects. Results Cloned brain- and blood-derived full length vpr alleles revealed that amino acid residue 77 within the brain-derived alleles distinguished HAD (77Q from non-demented (ND HIV/AIDS patients (77R (p vpr transcripts were more frequently detected in HAD brains (p IFN-α, MX1 and BST-2 transcript levels in human glia relative to the 77Q-HAD encoding virus (p Vpr77Q-HAD, 77R (pVpr77R-ND or Vpr null (pVpr(--containing vectors showed that the pVpr77R-ND vector induced higher levels of immune gene expression (p p IFN-α, MX1, PRKRA and BST-2 relative to 77Q-HAD peptide (p p p Conclusions These observations underscored the potent neuropathogenic properties of Vpr but also indicated viral diversity modulates innate neuroimmunity and neurodegeneration.

  9. Human Immunodeficiency Virus Type 1 Vpr Induces DNA Replication Stress In Vitro and In Vivo▿

    Science.gov (United States)

    Zimmerman, Erik S.; Sherman, Michael P.; Blackett, Jana L.; Neidleman, Jason A.; Kreis, Christophe; Mundt, Pamela; Williams, Samuel A.; Warmerdam, Maria; Kahn, James; Hecht, Frederick M.; Grant, Robert M.; de Noronha, Carlos M. C.; Weyrich, Andrew S.; Greene, Warner C.; Planelles, Vicente

    2006-01-01

    The human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) causes cell cycle arrest in G2. Vpr-expressing cells display the hallmarks of certain forms of DNA damage, specifically activation of the ataxia telangiectasia mutated and Rad3-related kinase, ATR. However, evidence that Vpr function is relevant in vivo or in the context of viral infection is still lacking. In the present study, we demonstrate that HIV-1 infection of primary, human CD4+ lymphocytes causes G2 arrest in a Vpr-dependent manner and that this response requires ATR, as shown by RNA interference. The event leading to ATR activation in CD4+ lymphocytes is the accumulation of replication protein A in nuclear foci, an indication that Vpr likely induces stalling of replication forks. Primary macrophages are refractory to ATR activation by Vpr, a finding that is consistent with the lack of detectable ATR, Rad17, and Chk1 protein expression in these nondividing cells. These observations begin to explain the remarkable resilience of macrophages to HIV-1-induced cytopathicity. To study the in vivo consequences of Vpr function, we isolated CD4+ lymphocytes from HIV-1-infected individuals and interrogated the cell cycle status of anti-p24Gag-immunoreactive cells. We report that infected cells in vivo display an aberrant cell cycle profile whereby a majority of cells have a 4N DNA content, consistent with the onset of G2 arrest. PMID:16956949

  10. "Resistance" to PSC-RANTES revisited: two mutations in human immunodeficiency virus type 1 HIV-1 SF162 or simian-human immunodeficiency virus SHIV SF162-p3 do not confer resistance.

    Science.gov (United States)

    Nedellec, Rebecca; Coetzer, Mia; Lederman, Michael M; Offord, Robin E; Hartley, Oliver; Mosier, Donald E

    2010-06-01

    Resistance of human immunodeficiency virus type 1 (HIV-1) to small-molecule CCR5 inhibitors is well demonstrated, but resistance to macromolecular CCR5 inhibitors (e.g., PSC-RANTES) that act by both CCR5 internalization and receptor blockade had not been reported until recently (3). The report of a single simian-human immunodeficiency virus SHIV(SF162-p3) variant with one V3 and one gp41 sequence change in gp160 that conferred both altered replicative fitness and resistance to PSC-RANTES was therefore surprising. We introduced the same two mutations into both the parental HIV-1(SF162) and the macaque-adapted SHIV(SF162-p3) and found minor differences in entry fitness but no changes in sensitivity to inhibition by either PSC-RANTES or the small-molecule allosteric inhibitor TAK-779. We attribute the earlier finding to confounding fitness effects with inhibitor sensitivity.

  11. An HIV-1 encoded peptide mimics the DNA binding loop of NF-{kappa}B and binds thioredoxin with high affinity

    Energy Technology Data Exchange (ETDEWEB)

    Su Guoping [Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602-2352 (United States)]. E-mail: gsu@u.washington.edu; Wang Min [Department of Pathology, Yale University School of Medicine, New Haven, CT 06520-8023 (United States)]. E-mail: wang.min@yale.edu; Taylor, Ethan Will [Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602-2352 (United States)]. E-mail: wtaylor@rx.uga.edu

    2005-11-11

    Pro-fs is a human immunodeficiency virus type 1 (HIV-l)-encoded putative selenoprotein, predicted by a theoretical analysis of the viral genome; it is potentially expressed by a -1 frameshift from the protease coding region. Pro-fs has significant sequence similarity to the DNA binding loop of nuclear factor kappa B (NF-{kappa}B), which is known to bind thioredoxin (Trx). We hypothesize that the putative HIV-1 pro-fs gene product functions by mimicry of NF-{kappa}B via binding to Trx. The hypothesis was tested in vitro by co-immunoprecipitation and GST-pull down assays, using a purified mutant pro-fs protein, in which the two potential selenocysteine residues were mutated to cysteines, in order to permit expression in bacteria. Both experiments showed that pro-fs binds to human wild type Trx (Trx-wt) with high affinity. Mutation of the two conserved cysteine residues in the Trx active site redox center to serine (Ser) (Trx-CS) weakened but failed to abolish the interaction. In pro-fs-transfected 293T cells, using confocal microscopy and fluorescence resonance energy transfer (FRET), we have observed that pro-fs localizes in cell nuclei and forms oligomers. Upon stimulation by phorbol 12-myristate 13-acetate (PMA), Trx translocates into cell nuclei. Significant FRET efficiency was detected in the nuclei of PMA-stimulated 293T cells co-expressing fluorescence-tagged pro-fs and Trx-wt or Trx-CS. These results indicate that in living cells the double cysteine mutant of pro-fs binds to both Trx and Trx-CS with high affinity, suggesting that Trx-pro-fs binding is a structurally-specific interaction, involving more of the Trx molecule than just its active site cysteine residues. These results establish the capacity for functional mimicry of the Trx binding ability of the NF-{kappa}B/Rel family of transcription factors by the putative HIV-1 pro-fs protein.

  12. Crystallization of the Fab from a human monoclonal antibody against gp 41 of human immunodeficiency virus type I

    Science.gov (United States)

    Casale, Elena; He, Xiao-Min; Snyder, Robert S.; Carter, Daniel C.; Wenisch, Elisabeth; Jungbauer, Alois; Tauer, Christa; Ruker, Florian; Righetti, Pier Giorgio

    1990-01-01

    A monoclonal IgG antibody directed against gp 41 from the human immunodeficiency virus (HIV-1) has been crystallized in both intact and Fab forms. Crystals of the intact antibody grow as tetragonal-like prisms too small for conventional X-ray analysis. However, the Fab portion of the antibody produces suitable platelike crystals which belong to the space group P2(1)2(1)2(1) with unit cell constants of a = 66.5 A, b = 74.3 A, and c = 105.3 A. There is one molecule of Fab in the asymmetric unit. The Fab crystals show diffraction to d-spacings less than 3.0 A.

  13. Highly efficient inhibition of human immunodeficiency virus type 1 reverse transcriptase by aptamers functionalized gold nanoparticles

    Science.gov (United States)

    Shiang, Yen-Chun; Ou, Chung-Mao; Chen, Shih-Ju; Ou, Ting-Yu; Lin, Han-Jia; Huang, Chih-Ching; Chang, Huan-Tsung

    2013-03-01

    We have developed aptamer (Apt)-conjugated gold nanoparticles (Apt-Au NPs, 13 nm in diameter) as highly effective inhibitors for human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT). Two Apts, RT1t49 (Aptpol) and ODN 93 (AptRH), which recognize the polymerase and RNase H regions of HIV-1 RT, are used to conjugate Au NPs to prepare Aptpol-Au NPs and AptRH-Au NPs, respectively. In addition to DNA sequence, the surface density of the aptamers on Au NPs (nApt-Au NPs; n is the number of aptamer molecules on each Au NP) and the linker length number (Tm; m is the base number of the deoxythymidine linker) between the aptamer and Au NPs play important roles in determining their inhibition activity. A HIV-lentiviral vector-based antiviral assay has been applied to determine the inhibitory effect of aptamers or Apt-Au NPs on the early stages of their replication cycle. The nuclease-stable G-quadruplex structure of 40AptRH-T45-Au NPs shows inhibitory efficiency in the retroviral replication cycle with a decreasing infectivity (40.2%).We have developed aptamer (Apt)-conjugated gold nanoparticles (Apt-Au NPs, 13 nm in diameter) as highly effective inhibitors for human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT). Two Apts, RT1t49 (Aptpol) and ODN 93 (AptRH), which recognize the polymerase and RNase H regions of HIV-1 RT, are used to conjugate Au NPs to prepare Aptpol-Au NPs and AptRH-Au NPs, respectively. In addition to DNA sequence, the surface density of the aptamers on Au NPs (nApt-Au NPs; n is the number of aptamer molecules on each Au NP) and the linker length number (Tm; m is the base number of the deoxythymidine linker) between the aptamer and Au NPs play important roles in determining their inhibition activity. A HIV-lentiviral vector-based antiviral assay has been applied to determine the inhibitory effect of aptamers or Apt-Au NPs on the early stages of their replication cycle. The nuclease-stable G-quadruplex structure of 40AptRH-T45

  14. Human immunodeficiency virus prevalence in an unbooked obstetric population in the Niger Delta

    Directory of Open Access Journals (Sweden)

    Chris I Akani

    2010-09-01

    Full Text Available Chris I Akani1, Erhabor Osaro2, Dennis O Allagoa11Departments of Obstetrics and Gynecology, 2Hematology, University of Port Harcourt Teaching Hospital, Port Harcourt, NigeriaAbstract: Despite recent advances in the prevention of transmission of human immunodeficiency virus (HIV infection from mother to child during pregnancy, infants continue to be born and infected with HIV, particularly in Africa. This study was undertaken to determine the seroprevalence of HIV infection among unbooked pregnant women in the Niger Delta of Nigeria. One hundred and eighteen consecutively recruited unbooked subjects presenting to the isolation ward at the University of Port Harcourt Teaching Hospital were screened for HIV. Among the 118 subjects studied, 30 (25.4% were positive for HIV. HIV-1 was the predominant viral strain. Gestational age of subjects at presentation was 28–40 weeks and mean age was 35.04 ± 8.06 years. The majority of subjects were primigravidas 66 (55.9%, while 52 (44.1% were multigravidas. The prevalence of HIV was significantly higher among unbooked pregnant women with less formal education: 14 (11.9% compared with 9 (7.6%, 5 (4.2%, and 2 (1.7% for those with primary, secondary, and tertiary education, respectively (P = 0.01. Among the occupational groups, the prevalence of HIV was significantly higher among traders 14 (11.9% than in career women 5 (4.2%, P = 0.04. Multigravid women were more susceptible to HIV infection 17 (14.4% than primigravid women. Perinatal mortality and emergency cesarean section was high among unbooked pregnant women. The prevalence of HIV observed amongst unbooked antenatal subjects in this study is significantly higher than those of booked patients in previous studies. These findings are very pertinent to health care delivery, because this pool of unbooked patients may not be benefiting from the Prevention of Maternal to Child Transmission program, thus increasing the pediatric HIV burden in our environment

  15. Acceptance of referral for partners by clients testing positive for human immunodeficiency virus

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    Netsanet F

    2013-01-01

    Full Text Available Fetene Netsanet,1 Ayalew Dessie21IMA World Health SuddHealth Multi Donor Trust Fund-Basic Package of Health Services Project, Juba, South Sudan; 2United States Agency for International Development, Private Health Sector Program, Abt Associates Inc, Addis Ababa, EthiopiaBackground: Human immunodeficiency virus (HIV-positive individuals who do not disclose their HIV status to their partners are more likely to present late for HIV and acquired immune deficiency syndrome (AIDS care than those who have disclosed their HIV status to their partners. A major area of challenge with regards to HIV counseling for clients is disclosure of their HIV status to their partners. The main methods of partner notification are patient referral, provider referral, contract referral, and outreach assistance. The emphasis on a plausible and comprehensive partner referral strategy for widespread positive case detection in resource-limited countries needs to be thought out and developed.Methods: A qualitative study was conducted among newly HIV-positive clients to identify partners for notification and acceptance of referral by their partners. Health service providers working in HIV testing and counseling clinics were also provided with semistructured questionnaires in order to assess their view towards partner notification strategies for clients testing positive for HIV.Results: Fifteen newly diagnosed HIV-positive clients were counseled to provide referral slips to their partners. All clients agreed and took the referral card. However, only eight were willing and actually provided the card to their partners. Five of the eight partners of clients who tested HIV-positive and who were provided with referral cards responded to the referral and were tested for HIV. Three were positive and two were negative. Nine of 11 counselors did not agree to requesting partner locator information from HIV-positive clients for contractual referral and/or outreach assistance. The findings

  16. Capsid proteins from human immunodeficiency virus type 1 and simian immunodeficiency virus SIVmac can coassemble into mature cores of infectious viruses.

    Science.gov (United States)

    Chen, Jianbo; Pathak, Vinay K; Peng, Weiqun; Hu, Wei-Shau

    2008-09-01

    We have recently shown that the Gag polyproteins from human immunodeficiency virus type 1 (HIV-1) and HIV-2 can coassemble and functionally complement each other. During virion maturation, the Gag polyproteins undergo proteolytic cleavage to release mature proteins including capsid (CA), which refolds and forms the outer shell of a cone-shaped mature core. Less than one-half of the CA proteins present within the HIV-1 virion are required to form the mature core. Therefore, it is unclear whether the mature core in virions containing both HIV-1 and HIV-2 Gag consists of CA proteins from a single virus or from both viruses. To determine whether CA proteins from two different viruses can coassemble into mature cores of infectious viruses, we exploited the specificity of the tripartite motif 5alpha protein from the rhesus monkey (rhTRIM5alpha) for cores containing HIV-1 CA (hCA) but not the simian immunodeficiency virus SIV(mac) CA protein (sCA). If hCA and sCA cannot coassemble into the same core when equal amounts of sCA and hCA are coexpressed, the infectivities of such virus preparations in cells should be inhibited less than twofold by rhTRIM5alpha. However, if hCA and sCA can coassemble into the same core structure to form a mixed core, rhTRIM5alpha would be able to recognize such cores and significantly restrict virus infectivity. We examined the restriction phenotypes of viruses containing both hCA and sCA. Our results indicate that hCA and sCA can coassemble into the same mature core to produce infectious virus. To our knowledge, this is the first demonstration of functional coassembly of heterologous CA protein into the retroviral core.

  17. Estimation of CD4+ and CD8+ T-lymphocytes in human immunodeficiency virus infection and acquired immunodeficiency syndrome patients in Manipur

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    Singh H

    2007-01-01

    Full Text Available Purpose : To estimate and stratify CD4 + and CD8 + T-lymphocyte levels in human immunodeficiency virus (HIV infected (asymptomatic and acquired immunodeficiency syndrome (AIDS patients (symptomatic and correlate the clinical features of the patients with CD4+ and CD8+ lymphocyte level. Methods : Between April 2002 and September 2003, a total of 415 HIV seropositive adult patients (297 males and 118 females attending Regional Institute of Medical Sciences (RIMS hospitals were tested for CD4+ and CD8+ T-lymphocytes by fluorescent activated cell sorter (FACS counter (Becton Dickinson. Symptomatic patients were diagnosed as per NACO clinical case definition. Results : Ranges of 0-50, 51-100, 101-200, 201-300, 301-400, 401-500 and above 500 CD4+ T-lymphocyte per microlitre were seen in 68, 52, 101, 73, 47, 31 and 43 patients respectively whereas CD8+ T-lymphocyte ranges of 0-300, 301-600, 601-900, 901-1500, 1501-2000, 2001-3500 per microlitre were seen in 29, 84, 92, 145, 40 and 25 patients respectively. One hundred and fifty patients were asymptomatic and 265 were symptomatic. CD4/CD8 ratio in asymptomatics and symptomatics were 0.13-1.69 and 0.01-0.93 respectively. Tuberculosis and candidiasis occurred in CD4+ T-lymphocyte categories between 0-400 cells per mL in symptomatics. However, cryptosporidiosis, toxoplasmosis, herpes zoster, cryptococcal meningitis, Pneumocystis carinii pneumonia, penicilliosis and cytomegalovirus retinitis were seen in patients having CD4+ T-lymphocyte less than 200 per mL. Conclusions : CD4+ T-lymphocyte was decreased in both asymptomatic and symptomatic HIV patients, The decrease was greater in symptomatics while CD8+ T-lymphocyte was increased in both except advanced stage symptomatics. CD4:CD8 ratio was reversed in both groups. Opportunistic infections correlated with different CD4+ T-lymphocyte categories.

  18. Epidemiology and clinical parameters of adult human immunodeficiency virus/acquired immunodeficiency syndrome at the initiation of antiretroviral therapy in South eastern Nigeria.

    Science.gov (United States)

    Eleje, Gu; Ele, Pu; Okocha, Ec; Iloduba, Uc

    2014-03-01

    Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has continued to ravage the teeming populations in Nigeria, with disastrous consequences. Despite many studies and progress on HIV/AIDS in Africa, the data on the status of the patients at the commencement of therapy is lacking. The aim of this study is to determine the demographic, clinical and some laboratory features of adult HIV/AIDS patients, seen at the commencement of antiretroviral therapy (ART) in Nnamdi Azikiwe University Teaching Hospital, Nnewi, south-east Nigeria between July 2002 and October 2004. The study was a cross-sectional, descriptive study. Adult patients living with HIV/AIDS were studied using an interview administered questionnaire. Data was analyzed using Epi Info 2008 version 3.5.1. A total of 400 respondents participated in this study. The mean age was 36.8 (8.8) years. Almost 60% patients were married and the HIV concordance rate was 53.3% (136/255). Nearly 30% of the families had at least one child positive for HIV. The most common associated risky behavior was injection administered in patent medicine stores 74.5%(302/400) and the most common clinical symptom was respiratory. Of the 400 patients recruited in this study, 19 (4.8%) were lost to follow-up on the 6 months' visit, giving a follow-up rate of 95.2% (381/400). There was statistically significant difference in the mean body weight (P = 0.02), mean total white blood cell count (P HIV/AIDS patients present late and body weight, CD4(+) count and total white blood cell count seemed to recover quickly on commencement of ART. The prevalence of concordance among couples and mother to child transmission rates tended to be high. Administration of injectable at patent medicine stores and multiple sexual partners are the most significant risk factors.

  19. Food Security in Households of People Living With Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome: A Cross-sectional Study in a Subdivision of Darjeeling District, West Bengal.

    Science.gov (United States)

    Dasgupta, Pallabi; Bhattacherjee, Sharmistha; Das, Dilip Kumar

    2016-07-01

    Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) adversely impacts food security in households of people living with HIV/AIDS (PLWHA). Little research has focused on food insecurity among PLWHA in India. The purpose of this study was to identify the prevalence of and factors relating to food security in households of PLWHA in the Siliguri subdivision of Darjeeling, West Bengal, India. A cross-sectional community-based study was carried out among 173 PLWHA residing in Siliguri and registered at the Anti-retroviral Therapy Centre of North Bengal Medical College & Hospital. Data was collected at the household level with interviews of PLWHA using a food security survey instrument. We analyzed the associations using logistic regression. The prevalence of household food security among the participants was 50.9% (88/173). Five years or more of schooling, higher socioeconomic class and males were found to be significantly associated with a higher likelihood of food security. A later stage of the disease and the presence of other family members with HIV/AIDS were significantly associated with a lower likelihood of food security. The major coping strategies to deal with food insecurity in the acute phase HIV infection included borrowing money (56.1%), followed by spousal support, loans from microfinance institutions, banks, or money lenders, borrowing food, or selling agricultural products. The present study revealed that only about half of households with PLWHA were food secure. Prior interventions relating to periods of food and economic crisis as well as strategies for sustaining food security and economic status are needed in this area.

  20. Interaction of human dipeptidyl peptidase IV and human immunodeficiency virus type-1 transcription transactivator in Sf9 cells

    Directory of Open Access Journals (Sweden)

    Reutter Werner

    2010-10-01

    Full Text Available Abstract Background Dipeptidyl peptidase IV (DPPIV also known as the T cell activation marker CD26 is a multifunctional protein which is involved in various biological processes. The association of human-DPPIV with components of the human immunodeficiency virus type-1 (HIV1 is well documented and raised some discussions. Several reports implicated the interaction of human-DPPIV with the HIV1 transcription transactivator protein (HIV1-Tat and the inhibition of the dipeptidyl peptidase activity of DPPIV by the HIV1-Tat protein. Furthermore, enzyme kinetic data implied another binding site for the HIV1-Tat other than the active centre of DPPIV. However, the biological significance of this interaction of the HIV1-Tat protein and human-DPPIV has not been studied, yet. Therefore, we focused on the interaction of HIV1-Tat protein with DPPIV and investigated the subsequent biological consequences of this interaction in Spodoptera frugiperda cells, using the BAC-TO-BAC baculovirus system. Results The HIV1-Tat protein (Tat-BRU co-localized and co-immunoprecipitated with human-DPPIV protein, following co-expression in the baculovirus-driven Sf9 cell expression system. Furthermore, tyrosine phosphorylation of DPPIV protein was up-regulated in Tat/DPPIV-co-expressing cells after 72 h culturing and also in DPPIV-expressing Sf9 cells after application of purified recombinant Tat protein. As opposed to the expression of Tat alone, serine phosphorylation of the Tat protein was decreased when co-expressed with human-DPPIV protein. Conclusions We show for the first time that human-DPPIV and HIV1-Tat co-immunoprecipitate. Furthermore, our findings indicate that the interaction of HIV1-Tat and human-DPPIV may be involved in signalling platforms that regulate the biological function of both human-DPPIV and HIV1-Tat.

  1. The socioeconomic impact of human immunodeficiency virus / acquired immune deficiency syndrome in India and its relevance to eye care

    Directory of Open Access Journals (Sweden)

    Murthy GVS

    2008-01-01

    Full Text Available Human immunodeficiency virus (HIV infection is aptly called the modern day ′plague′ and has the potential to decimate people in the productive age group. On the other hand, the increasing life expectancy in developing countries spirals age-related blindness. One therefore reduces economic productivity while the other increases economic dependency. Both lead to increased expenditure of households though in different proportions. Human immunodeficiency virus and blindness are both associated with discrimination, stigma and long-term consequences. They impact the socioeconomic fabric of the affected individuals, communities and countries. The loss in productivity and the cost of support to the affected individuals are seen in both. Each is a potent problem on its own but together they spell disaster in geometric proportions rather than a simple additive effect. Strategies need to be evolved to provide solace and improve the quality of life of an HIV-positive blind individual.

  2. Potent neutralizing serum immunoglobulin A (IgA) in human immunodeficiency virus type 2-exposed IgG-seronegative individuals

    DEFF Research Database (Denmark)

    Lizeng, Q; Nilsson, C; Sourial, S

    2004-01-01

    Links Potent neutralizing serum immunoglobulin A (IgA) in human immunodeficiency virus type 2-exposed IgG-seronegative individuals.Lizeng Q, Nilsson C, Sourial S, Andersson S, Larsen O, Aaby P, Ehnlund M, Bjorling E. Research Center, South Hospital, Stockholm, Sweden. The mechanisms behind...... the resistance to human immunodeficiency virus type 2 (HIV-2) infection are still not fully understood. In the present study, we explored the HIV-2-specific humoral serum immunoglobulin A (IgA) immune response in HIV-2-exposed IgG-seronegative (EGSN) individuals. Serum samples from heterosexual EGSN individuals...... and their known HIV-2-infected partners, as well as controls originating from Guinea-Bissau in Africa, were studied. Antibody reactivity to native and recombinant envelope glycoproteins was investigated, and the capacity of purified serum IgA to neutralize HIV-2(SBL6669) was tested. Our results showed that 16...

  3. BIRTH-ORDER, DELIVERY ROUTE, AND CONCORDANCE IN THE TRANSMISSION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 FROM MOTHERS TO TWINS

    NARCIS (Netherlands)

    DULIEGE, AM; AMOS, CI; FELTON, S; BIGGAR, RJ; ZIEGLER, J; CRUIKSHANK, M; LEVY, J; MEATES, MA; GIBB, D; MAYAUX, MJ; TEGLAS, JP; LAURENT, C; BLANCHE, S; ROUZIOUX, C; HELLINGGIESE, G; MATTNER, U; HOEGER, PH; CONLON, T; GRIFFIN, E; DEMARIA, A; BENEDETTO, A; PRINCIPI, N; GIAQUINTO, C; GIANCOMELLI, A; MOK, J; CASABONA, J; FORTUNY, C; URIZ, S; PEREZ, JM; TUSETRUIZ, MC; LEON, P; ELORZA, JFY; CANOSA, C; BRANDLE, B; SEGER, R; NADAL, D; IRION, O; WYLER, CA; DAVIS, P; LALLEMANT, M; LALLEMANTLECOEUR, S; HITIMANA, DG; LEPAGE, P; VANDEPERRE, P; DABIS, F; MARUM, L; NDUGWA, C; TINDYEBWA, D; ACENG, E; MMIRO, F; SUTONGAS, T; OLNESS, K; LAPOINTE, N; RUBINSTEIN, A; BURGE, D; STECHENBERG, BW; COOPER, E; REGAN, AM; SHIPKOWITZ, S; WIZNIA, A; BRUNELL, PA; COURVILLE, T; RUTSTEIN, R; MCINTOSH, K; PETRU, A; OLEARY, M; CHURCH, J; TAYLOR, S; SQUIRES, J; MALLORY, M; YOGEV, R; RAKUSAN, T; PLUMLEY, S; SHELTON, MM; WILFERT, C; LANE, B; ABRAMS, EJ; RANA, S; CHANDAVASU, O; PUVABANDITSIN, S; CHOW, JH; SHAH, K; NACHMAN, S; ONEILL, R; SELWYN, P; SHOENBAUM, E; BARZILAI, A; WARFORD, R; AHERN, L; PAHWA, S; PNUGOTI, N; GARCIATRIAS, DE; BAKSHI, S; LANDESMAN, S; MENDEZ, H; MOROSO, G; MENDEZBAUTISTA, RD; FIKRIG, S; BELMAN, A; KLINE, MW; HANSON, C; EDELSON, P; HINDS, G; VANDYKE, R; CLARK, R; WARA, DW; MANIO, EB; JOHNSON, G; WELLS, L; JOHNSON, JP; ALGER, L; LUZURIAGA, K; MASTRUCCI, T; SUNKUTU, MR; RODRIGUEZ, Z; DOYLE, M; REUBEN, J; BRYSON, Y; DILLON, M; SIMPSON, BJ; ANDIMAN, W; URIBE, P; Klauke, B.

    1995-01-01

    Background: We evaluated data from prospectively identified twins to understand better the mechanisms and covariates of mother-to-infant transmission of human immunodeficiency virus (HIV). Methods: Using data obtained from an international collaboration and multivariate quasilikelihood modeling, we

  4. Probiotic yogurt consumption may improve gastrointestinal symptoms, productivity, and nutritional intake of people living with human immunodeficiency virus in Mwanza, Tanzania

    NARCIS (Netherlands)

    Irvine, Stephanie L.; Hummelen, Ruben; Hekmat, Sharareh

    2011-01-01

    The gut-associated lymphoid tissue is a major site of human immunodeficiency virus (HIV) activity and significantly influences disease prognosis. Reducing immune activation due to gastroenteritis may thus help slow disease progression. Probiotic microorganisms have considerable immunomodulatory effe

  5. Human APOBEC3 induced mutation of human immunodeficiency virus type-1 contributes to adaptation and evolution in natural infection.

    Directory of Open Access Journals (Sweden)

    Eun-Young Kim

    2014-07-01

    Full Text Available Human APOBEC3 proteins are cytidine deaminases that contribute broadly to innate immunity through the control of exogenous retrovirus replication and endogenous retroelement retrotransposition. As an intrinsic antiretroviral defense mechanism, APOBEC3 proteins induce extensive guanosine-to-adenosine (G-to-A mutagenesis and inhibit synthesis of nascent human immunodeficiency virus-type 1 (HIV-1 cDNA. Human APOBEC3 proteins have additionally been proposed to induce infrequent, potentially non-lethal G-to-A mutations that make subtle contributions to sequence diversification of the viral genome and adaptation though acquisition of beneficial mutations. Using single-cycle HIV-1 infections in culture and highly parallel DNA sequencing, we defined trinucleotide contexts of the edited sites for APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H. We then compared these APOBEC3 editing contexts with the patterns of G-to-A mutations in HIV-1 DNA in cells obtained sequentially from ten patients with primary HIV-1 infection. Viral substitutions were highest in the preferred trinucleotide contexts of the edited sites for the APOBEC3 deaminases. Consistent with the effects of immune selection, amino acid changes accumulated at the APOBEC3 editing contexts located within human leukocyte antigen (HLA-appropriate epitopes that are known or predicted to enable peptide binding. Thus, APOBEC3 activity may induce mutations that influence the genetic diversity and adaptation of the HIV-1 population in natural infection.

  6. High Affinity Binding of Indium and Ruthenium Ions by Gastrins.

    Directory of Open Access Journals (Sweden)

    Graham S Baldwin

    Full Text Available The peptide hormone gastrin binds two ferric ions with high affinity, and iron binding is essential for the biological activity of non-amidated forms of the hormone. Since gastrins act as growth factors in gastrointestinal cancers, and as peptides labelled with Ga and In isotopes are increasingly used for cancer diagnosis, the ability of gastrins to bind other metal ions was investigated systematically by absorption spectroscopy. The coordination structures of the complexes were characterized by extended X-ray absorption fine structure (EXAFS spectroscopy. Changes in the absorption of gastrin in the presence of increasing concentrations of Ga3+ were fitted by a 2 site model with dissociation constants (Kd of 3.3 x 10-7 and 1.1 x 10-6 M. Although the absorption of gastrin did not change upon the addition of In3+ ions, the changes in absorbance on Fe3+ ion binding in the presence of indium ions were fitted by a 2 site model with Kd values for In3+ of 6.5 x 10-15 and 1.7 x 10-7 M. Similar results were obtained with Ru3+ ions, although the Kd values for Ru3+ of 2.6 x 10-13 and 1.2 x 10-5 M were slightly larger than observed for In3+. The structures determined by EXAFS all had metal:gastrin stoichiometries of 2:1 but, while the metal ions in the Fe, Ga and In complexes were bridged by a carboxylate and an oxygen with a metal-metal separation of 3.0-3.3 Å, the Ru complex clearly demonstrated a short range Ru-Ru separation, which was significantly shorter, at 2.4 Å, indicative of a metal-metal bond. We conclude that gastrin selectively binds two In3+ or Ru3+ ions, and that the affinity of the first site for In3+ or Ru3+ ions is higher than for ferric ions. Some of the metal ion-gastrin complexes may be useful for cancer diagnosis and therapy.

  7. Noncytotoxic Suppression of Human Immunodeficiency Virus Type 1 Transcription by Exosomes Secreted from CD8+ T Cells▿

    OpenAIRE

    2009-01-01

    CD8+ T cells display a noncytotoxic activity that suppresses transcription of human immunodeficiency virus type 1 (HIV-1) in an antigen-independent and major histocompatibility complex-unrestricted manner. To date, the precise cellular and molecular factors mediating this CD8+ T-cell effector function remain unsolved. Despite evidence indicating the dependence of the activity on cell-cell contact, the possibility of a membrane-mediated activity that represses transcription from the viral prom...

  8. Human immunodeficiency virus type 2 (HIV-2) Gag is trafficked in an AP-3 and AP-5 dependent manner

    OpenAIRE

    Alford, Justine E.; Marongiu, Michela; Gemma L Watkins; Anderson, Emma C.

    2016-01-01

    Although human immunodeficiency virus (HIV) types 1 and 2 are closely related lentiviruses with similar replication cycles, HIV-2 infection is associated with slower progression to AIDS, a higher proportion of long term non-progressors, and lower rates of transmission than HIV-1, likely as a consequence of a lower viral load during HIV-2 infection. A mechanistic explanation for the differential viral load remains unclear but knowledge of differences in particle production between HIV-1 and HI...

  9. Bioluminescent imaging of vaccinia virus infection in immunocompetent and immunodeficient rats as a model for human smallpox

    OpenAIRE

    Qiang Liu; Changfa Fan; Shuya Zhou; Yanan Guo; Qin Zuo; Jian Ma; Susu Liu; Xi Wu; Zexu Peng; Tao Fan; Chaoshe Guo; Yuelei Shen; Weijin Huang; Baowen Li; Zhengming He

    2015-01-01

    Due to the increasing concern of using smallpox virus as biological weapons for terrorist attack, there is renewed interest in studying the pathogenesis of human smallpox and development of new therapies. Animal models are highly demanded for efficacy and safety examination of new vaccines and therapeutic drugs. Here, we demonstrated that both wild type and immunodeficient rats infected with an engineered vaccinia virus carrying Firefly luciferase reporter gene (rTV-Fluc) could recapitulate i...

  10. Human Immunodeficiency Virus and Heart Failure in Low- and Middle-Income Countries: A State-of-the-Art Review

    OpenAIRE

    Gerald S Bloomfield; Alenezi, Fawaz; Barasa, Felix A.; Lumsden, Rebecca; Mayosi, Bongani M; Velazquez, Eric J.

    2015-01-01

    Successful combination therapy for human immunodeficiency virus (HIV) has transformed this disease from a short-lived infection with high mortality to a chronic disease associated with increasing life expectancy. This is true for high- as well as low- and middle-income countries. As a result of this increased life expectancy, people living with HIV are now at risk of developing other chronic diseases associated with aging. Heart failure has been common among people living with HIV in the eras...

  11. Genetic diversity of human immunodeficiency virus type 2: evidence for distinct sequence subtypes with differences in virus biology.

    OpenAIRE

    Gao, F; Yue, L; Robertson, D L; Hill, S C; Hui, H.; Biggar, R J; Neequaye, A E; Whelan, T M; Ho, D D; Shaw, G M

    1994-01-01

    The virulence properties of human immunodeficiency virus type 2 (HIV-2) are known to vary significantly and to range from relative attenuation in certain individuals to high-level pathogenicity in others. These differences in clinical manifestations may, at least in part, be determined by genetic differences among infecting virus strains. Evaluation of the full spectrum of HIV-2 genetic diversity is thus a necessary first step towards understanding its molecular epidemiology, natural history ...

  12. Genetic diversity of human immunodeficiency virus type 2:evidence for distinct sequence subtypes with differences in virus biology

    OpenAIRE

    Gao, F; Yue, L; ROBERTSON, DL; Hill, SC; Hui, HX; BIGGAR, RJ; NEEQUAYE, AE; WHELAN, TM; Ho, DD; Shaw, GM; Sharp, Paul M.; Hahn, BH

    1994-01-01

    The virulence properties of human immunodeficiency virus type 2 (HIV-2) are known to vary significantly and to range from relative attenuation in certain individuals to high level pathogenicity in others. These differences in clinical manifestations may, at least in part, be determined by genetic differences among infecting virus strains. Evaluation of the full spectrum of HIV-2 genetic diversity is thus a necessary first step towards understanding its molecular epidemiology, natural history ...

  13. Living related donor renal transplant in human immunodeficiency virus infected patient: Case reports from tertiary care hospital in western India

    Directory of Open Access Journals (Sweden)

    Sonal Dalal

    2014-01-01

    Full Text Available Renal transplantation (TX in human immunodeficiency virus (HIV infected patients with end stage renal disease (ESRD is increasingly performed in developed countries in the era of antiretroviral therapy (ART. Management of HIV infected patients during and post-transplant is very complex and challenging due to drug interaction, infection risk and associated co-infections. We described our experience with living related donor renal TX in three HIV infected patients.

  14. Conservation of an Intact vif Gene of Human Immunodeficiency Virus Type 1 during Maternal-Fetal Transmission

    OpenAIRE

    Yedavalli, Venkat R. K.; Chappey, Colombe; Matala, Erik; Ahmad, Nafees

    1998-01-01

    The human immunodeficiency virus type 1 (HIV-1) vif gene is conserved among most lentiviruses, suggesting that vif is important for natural infection. To determine whether an intact vif gene is positively selected during mother-to-infant transmission, we analyzed vif sequences from five infected mother-infant pairs following perinatal transmission. The coding potential of the vif open reading frame directly derived from uncultured peripheral blood mononuclear cell DNA was maintained in most o...

  15. Cysteine residues in the Vif protein of human immunodeficiency virus type 1 are essential for viral infectivity.

    OpenAIRE

    Ma, X Y; Sova, P; Chao, W; Volsky, D J

    1994-01-01

    The infectivity factor of human immunodeficiency virus type 1 (HIV-1), Vif, contains two cysteine residues which are highly conserved among animal lentiviruses. We introduced substitutions of leucine for cysteine residues in the vif gene of a full-length HIV-1 clone to analyze their roles in viral infection. Mutant viruses containing substitutions in either Cys-114, Cys-133, or both displayed a vif-negative infection phenotype similar to that of an isogeneic vif deletion mutant, namely, a cel...

  16. The Multimerization of Human Immunodeficiency Virus Type I Vif Protein: A REQUIREMENT FOR Vif FUNCTION IN THE VIRAL LIFE CYCLE*

    OpenAIRE

    Yang, Shicheng; Sun, Yong; Zhang, Hui

    2000-01-01

    The Vif (virion infectivity factor protein of human immunodeficiency virus type I (HIV-1) is essential for viral replication in vivo and productive infection of peripheral blood mononuclear cells, macrophages, and H9 T-cells. However, the molecular mechanism(s) of Vif remains unknown and needs to be further determined. In this report, we show that, like many other proteins encoded by HIV-1, Vif proteins possess a strong tendency toward self-association. In relatively native conditions, Vif pr...

  17. Risk of zidovudine-induced anemia on human immunodeficiency virus (HIV) infection patients with different CD4 cell counts

    OpenAIRE

    wedayani, anak agung ayu niti; Sholikhah, Eti Nurwening; Kristin, Erna; Triyono, Erwin Astha

    2017-01-01

    Anemia is the most common hematologic abnormality in patients with human immunodeficiency virus (HIV) infection. This abnormality is associated with HIV infection itself, HIV-related opportunities infections or drug use. Zidovudine (AZT) is the most common cause of anemia in HIV patients. Recent study showed anemia in HIV patients is also associated with CD4 cell counts. Aim of this study was to evaluate the risk of anemia on HIV patients with different CD4 cell counts after AZT-based antiret...

  18. Antiretroviral Drugs and Risk of Chronic Alanine Aminotransferase Elevation in Human Immunodeficiency Virus (HIV)-Monoinfected Persons

    DEFF Research Database (Denmark)

    Kovari, Helen; Sabin, Caroline A; Ledergerber, Bruno;

    2016-01-01

    Background.  Although human immunodeficiency virus (HIV)-positive persons on antiretroviral therapy (ART) frequently have chronic liver enzyme elevation (cLEE), the underlying cause is often unclear. Methods.  Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study participants without...... a consistent association between tenofovir and cLEE emerging within the first 2 years after drug initiation. This novel tenofovir-cLEE signal should be further investigated....

  19. Esophago-pleural fistula with multiple esophageal ulcers in human immunodeficiency virus infected patients: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Soo Hee; Lee, Young Kyung; Choi, Jae Phil; Son, Jin Sung [Seoul Medical Center, Seoul(Korea, Republic of)

    2014-03-15

    Esophagitis is a common complication in patients with human immunodeficiency virus (HIV) infection. Esophagitis in HIV infected patient is caused by candidiasis, cytomegalovirus, herpes simplex virus, or idiopathic esophagitis with no detectable etiology. Esophagitis in HIV infected patient is occasionally combined with esophageal ulcers. We report chest CT findings and clinical manifestation of esophago-pleural fistula with pneumothorax in a HIV infected patient, who was treated for aspiration pneumonia and esophageal ulcers.

  20. A.S.P.E.N. Clinical Guidelines: Nutrition Support of Children With Human Immunodeficiency Virus Infection

    OpenAIRE

    Sabery, Nasim; Duggan, Christopher

    2009-01-01

    The clinical characteristics of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) in children differ substantially from those in adults, and these differences are important to consider in providing both medical and nutrition care. Growth failure, wasting, and loss of active lean tissue are all associated with increased mortality and accelerated disease progression. The use of highly active antiretroviral therapy (HAART) has improved the prognosis and life span of c...

  1. Recovery of infectious human immunodeficiency virus type 1 after fusion of defectively infected clones of U-937 cells.

    OpenAIRE

    1991-01-01

    Polyethylene glycol was used to induce polykaryon formation among U-937 cell subclones carrying defective human immunodeficiency virus (HIV) type 1 proviral DNA. Fusion of cells which produced gp120-defective virions (UHC15.7) with cells unable to generate reverse transcriptase (RT) activity (UHC8 and UHC18) yielded polykaryons which made infectious viral progeny that showed normal protein profiles. Southern blot analysis of proviral DNA of cells infected with such fusion-derived virus reveal...

  2. Risk of Human Immunodeficiency Virus (HIV) Seroconversion in U.S. Navy Personnel Following Visits to Foreign Ports

    Science.gov (United States)

    1991-03-25

    Islands 3 475. La Napoule, France 2 426. Nagasaki, Japan 3 476. Langkawi , Malaysia 2 427. Nice, France 3 477. Larnaca, Cyprus 2 428. Oran, Algeria 3...continents and many islands of the world. HIV (human immunodeficiency virus-I) rates vary widely worldwide, and are high in many areas visited by the Navy...career histories and ship movement information to examine the relationship of visits to foreign ports with risk of HIV seropositivity and

  3. Performance of a rapid, on-site human immunodeficiency virus antibody assay in a public health setting.

    OpenAIRE

    Kassler, W J; Haley, C; Jones, W. K.; Gerber, A R; E. J. Kennedy; George, J R

    1995-01-01

    Rapid, on-site human immunodeficiency virus (HIV) testing has the potential to improve the delivery of prevention services in publicly funded counseling and testing sites. The Single Use Diagnostic System (SUDS) HIV-1 is the only rapid enzyme immunoassay (EIA) approved for diagnostic use in the United States. To evaluate the feasibility of using SUDS in public clinics and to validate the test's performance in a public health laboratory, we conducted blinded SUDS testing on plasma sent for HIV...

  4. Neutrophil recruitment limited by high-affinity bent β2 integrin binding ligand in cis.

    Science.gov (United States)

    Fan, Zhichao; McArdle, Sara; Marki, Alex; Mikulski, Zbigniew; Gutierrez, Edgar; Engelhardt, Britta; Deutsch, Urban; Ginsberg, Mark; Groisman, Alex; Ley, Klaus

    2016-08-31

    Neutrophils are essential for innate immunity and inflammation and many neutrophil functions are β2 integrin-dependent. Integrins can extend (E(+)) and acquire a high-affinity conformation with an 'open' headpiece (H(+)). The canonical switchblade model of integrin activation proposes that the E(+) conformation precedes H(+), and the two are believed to be structurally linked. Here we show, using high-resolution quantitative dynamic footprinting (qDF) microscopy combined with a homogenous conformation-reporter binding assay in a microfluidic device, that a substantial fraction of β2 integrins on human neutrophils acquire an unexpected E(-)H(+) conformation. E(-)H(+) β2 integrins bind intercellular adhesion molecules (ICAMs) in cis, which inhibits leukocyte adhesion in vitro and in vivo. This endogenous anti-inflammatory mechanism inhibits neutrophil aggregation, accumulation and inflammation.

  5. TALEN-Mediated Knockout of CCR5 Confers Protection Against Infection of Human Immunodeficiency Virus.

    Science.gov (United States)

    Shi, Bingjie; Li, Juan; Shi, Xuanling; Jia, Wenxu; Wen, Yi; Hu, Xiongbing; Zhuang, Fengfeng; Xi, Jianzhong; Zhang, Linqi

    2017-02-01

    Transcription activator-like effector nuclease (TALEN) represents a valuable tool for genomic engineering due to its single-nucleotide precision, high nuclease activity, and low cytotoxicity. We report here systematic design and characterization of 28 novel TALENs targeting multiple regions of CCR5 gene (CCR5-TALEN) which encodes the co-receptor critical for entry of human immunodeficiency virus type I (HIV-1). By systemic characterization of these CCR5-TALENs, we have identified one (CCR5-TALEN-515) with higher nuclease activity, specificity, and lower cytotoxicity compared with zinc-finger nuclease (CCR5-ZFN) currently undergoing clinical trials. Sequence analysis of target cell line GHOST-CCR5-CXCR4 and human primary CD4 T cells showed that the double-strand breaks at the TALEN targeted sites resulted in truncated or nonfunctional CCR5 proteins thereby conferring protection against HIV-1 infection in vitro. None of the CCR5-TALENs had detectable levels of off-target nuclease activity against the homologous region in CCR2 although substantial level was identified for CCR5-ZFN in the primary CD4 T cells. Our results suggest that the CCR5-TALENs identified here are highly functional nucleases that produce protective genetic alterations to human CCR5. Application of these TALENs directly to the primary CD4 T cells and CD34 hematopoietic stem cells (HSCs) of infected individuals could help to create an immune system resistant to HIV-1 infection, recapitulating the success of "Berlin patient" and serving as an essential first step towards a "functional" cure of AIDS.

  6. Induction of Murine Mucosal CCR5-Reactive Antibodies as an Anti-Human Immunodeficiency Virus Strategy

    Science.gov (United States)

    Barassi, C.; Soprana, E.; Pastori, C.; Longhi, R.; Buratti, E.; Lillo, F.; Marenzi, C.; Lazzarin, A.; Siccardi, A. G.; Lopalco, L.

    2005-01-01

    The genital mucosa is the main site of initial human immunodeficiency virus type 1 (HIV-1) contact with its host. In spite of repeated sexual exposure, some individuals remain seronegative, and a small fraction of them produce immunoglobulin G (IgG) and IgA autoantibodies directed against CCR5, which is probably the cause of the CCR5-minus phenotype observed in the peripheral blood mononuclear cells of these subjects. These antibodies recognize the 89-to-102 extracellular loop of CCR5 in its native conformation. The aim of this study was to induce infection-preventing mucosal anti-CCR5 autoantibodies in individuals at high risk of HIV infection. Thus, we generated chimeric immunogens containing the relevant CCR5 peptide in the context of the capsid protein of Flock House virus, a presentation system in which it is possible to engineer conformationally constrained peptide in a highly immunogenic form. Administered in mice via the systemic or mucosal route, the immunogens elicited anti-CCR5 IgG and IgA (in sera and vaginal fluids). Analogous to exposed seronegative individuals, mice producing anti-CCR5 autoantibodies express significantly reduced levels of CCR5 on the surfaces of CD4+ cells from peripheral blood and vaginal washes. In vitro studies have shown that murine IgG and IgA (i) specifically bind human and mouse CD4+ lymphocytes and the CCR5-transfected U87 cell line, (ii) down-regulate CCR5 expression of CD4+ cells from both humans and untreated mice, (iii) inhibit Mip-1β chemotaxis of CD4+ CCR5+ lymphocytes, and (iv) neutralize HIV R5 strains. These data suggest that immune strategies aimed at generating anti-CCR5 antibodies at the level of the genital mucosa might be feasible and represent a strategy to induce mucosal HIV-protective immunity. PMID:15890924

  7. Comparison of different fabrication techniques for human adipose tissue engineering in severe combined immunodeficient mice.

    Science.gov (United States)

    Frerich, Bernhard; Winter, Karsten; Scheller, Konstanze; Braumann, Ulf-Dietrich

    2012-03-01

    Adipose tissue engineering has been advocated for soft-tissue augmentation and for the treatment of soft tissue defects. The efficacy in terms of persistence of the engineered fat is, however, not yet understood and could depend on the nature of fabrication and application. The high metabolic demand of adipose tissue also points to the problem of vascularization. Endothelial cell (EC) cotransplantation could be a solution. Human adipose tissue-derived stromal cells were seeded on collagen microcarriers and submitted to adipogenic differentiation ("microparticles"). In a first run of experiments, these microparticles were implanted under the skin of severe combined immunodeficient (SCID) mice (n = 45) with and without the addition of human umbilical vein ECs (HUVECs). A group of carriers without any cells served as control. In a second run, adipose tissue constructs were fabricated by embedding microparticles in fibrin matrix with and without the addition of HUVEC, and were also implanted in SCID mice (n = 30). The mice were sacrificed after 12 days, 4 weeks, and 4 months. Mature adipose tissue, fibrous tissue, and acellular regions were quantified on whole-specimen histological sections. The implantation of microparticles showed a better sustainment of tissue volume and a higher degree of mature adipose tissue compared with adipose tissue constructs. Immunohistology proved obviously perfused human tissue-engineered vessels. There was a limited but not significant advantage in EC cotransplantation after 4 weeks in terms of tissue volume. In groups with EC cotransplantation, there were significantly fewer acellular/necrotic areas after 4 weeks and 4 months. In conclusion, the size of the implanted tissue equivalents is a crucial parameter, affecting volume maintenance and the gain of mature adipose tissue. EC cotransplantation leads to functional stable vascular networks connecting in part to the host vasculature and contributing to tissue perfusion; however

  8. Comparison of Human Hematopoietic Reconstitution in Different Strains of Immunodeficient Mice.

    Science.gov (United States)

    Beyer, Ashley I; Muench, Marcus O

    2017-01-15

    Immunodeficient mice play a critical role in hematology research as in vivo models of hematopoiesis and immunology. Multiple strains have been developed, but hematopoietic stem cell engraftment and immune reconstitution have not been methodically compared among them. Four mouse strains were transplanted with human fetal bone marrow or adult peripheral blood CD34(+) cells: NSG, NSG-3GS, hSCF-Tg-NSG, and hSIRPα-DKO. Hematopoietic engraftment in the bone marrow, blood, spleen, and liver was evaluated by flow cytometry 12 weeks after transplant. The highest levels of human engraftment were observed in the liver, spleen, and bone marrow, whereas peripheral blood cell chimerism was notably less. The highest levels of tissue engraftment were in hSCF-Tg-NSG mice, but NSG mice exhibited the highest blood leukocyte engraftment. hSCF-Tg-NSG mice also exhibited the highest levels of CD133(+)CD34(++) stem cells. hSIRPα-DKO engrafted poorly and exhibited poor breeding. Myelopoiesis was greatest in NSG-3GS mice, followed by hSCF-Tg-NSG and NSG mice, whereas B cell engraftment exhibited the opposite pattern. Engraftment of CD3(+) T cells, CD3(+)CD161(+) T cells, and CD3(-)CD56(+) NK cells was greatest in NSG-3GS mice. Mast cell engraftment was highest in hSCF-Tg-NSG mice, but was also elevated in spleen and livers of NSG-3GS mice. Basophils were most abundant in NSG-3GS mice. Overall, hSCF-Tg-NSG mice are the best recipient mice for studies requiring high levels of human hematopoiesis, stem cell engraftment, and an intermediate level of myelopoiesis, whereas NSG and NSG-3GS mice offer select advantages in the engraftment of certain blood cell lineages.

  9. Clinical Performance of a Dermal Filler Containing Natural Glycolic Acid and a Polylactic Acid Polymer: Results of a Clinical Trial in Human Immunodeficiency Virus Subjects with Facial Lipoatrophy

    OpenAIRE

    Tagle, Jorge M.; Macchetto, Pedro Cervantes; Durán Páramo, Rosa Margarita

    2010-01-01

    Lipoatrophy is a condition that affects certain individuals, most commonly those who are infected with the human immunodeficiency virus.1–3 Injectable fillers are used for the treatment of these dermal contour deformities to smooth dermal depressions formed by the loss of volume. These dermal fillers (also known as soft tissue augmentation devices) can correct contour deformities caused by lipoatrophy in patients who are human immunodeficiency virus positive or negative. The product used in t...

  10. Inactivation of human immunodeficiency virus type 1 in blood samples stored as high-salt lysates.

    Science.gov (United States)

    Zolg, J W; Lanciotti, R S; Wendlinger, M; Meyer, W A

    1990-09-01

    Blood samples to be tested for the presence of parasite DNA by using specific DNA probes are routinely stored in our laboratory as high-salt lysates (HSL). To safeguard against the risk of accidental infection with etiological agents such as the human immunodeficiency virus type 1 (HIV-1) while manipulating large numbers of blood samples in preparation for DNA probing, we determined the residual infectivity of HIV-1 after exposure to HSL components. Both high-titer virus stocks or provirus-carrying cells, suspended either in tissue culture medium or freshly drawn blood, were completely inactivated upon contact with the HSL components. This was verified by the absence of any detectable HIV-1-specific antigen in the supernatants of long-term cultures and the absence of virus-specific DNA fragments after amplification by polymerase chain reaction with DNA from such cultures as target DNA. These results support the conclusion that the virus is in fact completely inactivated by contact with the HSL components, rendering blood specimens stored as HSL noninfectious in regard to HIV-1.

  11. Bilateral pseudoangiomatous stromal hyperplasia in a human immunodeficiency viral-infected patient.

    Science.gov (United States)

    Larbcharoensub, Noppadol; Wattanatranon, Duangkamon; Sanpaphant, Suda; Sri-Utenchai, Nithid; Wiratkapun, Cholatip; Kongdan, Youwanush

    2015-01-01

    Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon mesenchymal neoplasm of the breast demonstrating stromal myofibroblastic proliferation and having the appearance of anastomosing slit-like pseudovascular spaces lined by spindle-shaped cells. A case of nodular PASH of the bilateral breasts in a 40-year-old woman with clinically presenting with a progressive enlarged breast lump is reported. Mammographic and ultrasonographic features of the right and left breasts showed a large solid lump with well-circumscribed border measuring 4 cm × 1.7 cm × 3.4 cm and 13.8 cm × 10.9 cm × 12.1 cm, respectively. Wide excision of the right breast and quadrantectomy of the left breast were performed. The histopathological examination of the lesion showed anastomosing slit-like pseudovascular spaces. The stromal cells were immunoreactive for muscle actin (HHF35), smooth muscle actin, and progesterone receptor. Clinical and pathological findings with briefly reviewed relevant literatures are discussed. This is the first clinicopathological and radiological report of bilateral mammary nodular PASH in a human immunodeficiency viral-infected patient.

  12. The human immunodeficiency virus protease inhibitor ritonavir is potentially active against urological malignancies

    Directory of Open Access Journals (Sweden)

    Sato A

    2015-04-01

    Full Text Available Akinori Sato Department of Urology, National Defense Medical College, Tokorozawa, Japan Abstract: The human immunodeficiency virus protease inhibitor ritonavir has recently been shown to have antineoplastic activity, and its use in urological malignancies is under investigation with an eye toward drug repositioning. Ritonavir is thought to exert its antineoplastic activity by inhibiting multiple signaling pathways, including the Akt and nuclear factor-kappaB pathways. It can increase the amount of unfolded proteins in the cell by inhibiting both the proteasome and heat shock protein 90. Combinations of ritonavir with agents that increase the amount of unfolded proteins, such as proteasome inhibitors, histone deacetylase inhibitors, or heat shock protein 90 inhibitors, therefore, induce endoplasmic reticulum stress cooperatively and thereby kill cancer cells effectively. Ritonavir is also a potent cytochrome P450 3A4 and P-glycoprotein inhibitor, increasing the intracellular concentration of combined drugs by inhibiting their degradation and efflux from cancer cells and thereby enhancing their antineoplastic activity. Furthermore, riotnavir’s antineoplastic activity includes modulation of immune system activity. Therapies using ritonavir are thus an attractive new approach to cancer treatment and, due to their novel mechanisms of action, are expected to be effective against malignancies that are refractory to current treatment strategies. Further investigations using ritonavir are expected to find new uses for clinically available drugs in the treatment of urological malignancies as well as many other types of cancer. Keywords: drug repositioning, novel treatment

  13. [Challenges of lopinavir/ritonavir in the chronicity of human immunodeficiency virus infection].

    Science.gov (United States)

    Aguirrebengoa, Koldo

    2014-11-01

    Combination antiretroviral therapy (ART) has increased patient survival, which is currently similar to that of the general population in western countries. However, ART is unable to completely restore normal health, given the persistence of chronic immune activation. Human immunodeficiency virus (HIV) infection has become a chronic disease and 50% of patients will soon be older than 50 years. Currently, there is a debate on the possibility of accelerated aging in the HIV-infected population. An overlap has been observed between chronic inflammation, age-related comorbidities, lifestyle, and the long-term toxicity of ART. ART-related toxicity can encourage the development of comorbidities, especially cardiovascular and renal complications, while toxicity-especially that of thymidine analogs-can also contribute to inflammation and aging. Evidence is available on simplification strategies with boosted protease inhibitor monotherapy aiming to avoid or reduce potential or demonstrated toxicity. Currently, studies are underway of dual therapy strategies with lopinavir/ritonavir (LPV/r) with distinct antiretroviral agents. The studies with the largest samples are those with raltegravir and lamivudine. The GARDEL trial has demonstrated that dual therapy with LPV/r plus a generic drug such as lamivudine is non-inferior to triple therapy in treatment- naïve patients. All of the above indicates the response to the challenge posed to LPV/r by the chronic phase of the disease and by the need to reduce costs. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  14. Equity issues were not fully addressed in Cochrane human immunodeficiency virus systematic reviews.

    Science.gov (United States)

    Aves, Theresa; Kredo, Tamara; Welch, Vivian; Mursleen, Sara; Ross, Stephanie; Zani, Babalwa; Motaze, Nkengafac Villyen; Quinlan, Leah; Mbuagbaw, Lawrence

    2017-01-01

    To describe and summarize equity reporting in human immunodeficiency virus (HIV) systematic reviews and explore the extent to which equity issues are addressed and reported in HIV reviews using the PROGRESS Plus framework. Application of the PROGRESS Plus framework to a bibliometric analysis of HIV reviews in the Cochrane Database of Systematic Reviews. The analysis included 103 reviews published as of March 2014, with a median of five studies per review (first quartile; Q1 = 2; third quartile; Q3 = 11). Reporting of PROGRESS Plus factors was as follows: Place of residence (low, middle, and high income; 55.3%), place of residence (urban or rural; 24.3%), race or ethnicity (20.4%), occupation (10.7%), gender (65.0%), religion (1.9%), education (7.8%), socioeconomic position (10.7%), social networks and capital (1.0%), age (1.9%), and sexual orientation (3.8%). Gaps in the reporting of relevant equity indicators were identified within Cochrane HIV systematic review indicating that research is not consistently conducted through an equity lens. There is a need to incorporate PROGRESS Plus factors into both primary and secondary studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Entecavir Exhibits Inhibitory Activity against Human Immunodeficiency Virus under Conditions of Reduced Viral Challenge▿

    Science.gov (United States)

    Lin, Pin-Fang; Nowicka-Sans, Beata; Terry, Brian; Zhang, Sharon; Wang, Chunfu; Fan, Li; Dicker, Ira; Gali, Volodymyr; Higley, Helen; Parkin, Neil; Tenney, Daniel; Krystal, Mark; Colonno, Richard

    2008-01-01

    Entecavir (ETV) was developed for the treatment of chronic hepatitis B virus (HBV) infection and is globally approved for that indication. Initial preclinical studies indicated that ETV had no significant activity against human immunodeficiency virus type 1 (HIV-1) in cultured cell lines at physiologically relevant ETV concentrations, using traditional anti-HIV assays. In response to recent clinical observations of anti-HIV activity of ETV in HIV/HBV-coinfected patients not receiving highly active antiretroviral therapy (HAART), additional investigative studies were conducted to expand upon earlier results. An extended panel of HIV-1 laboratory and clinical strains and cell types was tested against ETV, along with a comparison of assay methodologies and resistance profiling. These latest studies confirmed that ETV has only weak activity against HIV, using established assay systems. However, a >100-fold enhancement of antiviral activity (equivalent to the antiviral activity of lamivudine) could be obtained when assay conditions were modified to reduce the initial viral challenge. Also, the selection of a M184I virus variant during the passage of HIV-1 at high concentrations of ETV confirmed that ETV can exert inhibitory pressure on the virus. These findings may have a significant impact on how future assays are performed with compounds to be used in patients infected with HIV. These results support the recommendation that ETV therapy should be administered in concert with HAART for HIV/HBV-coinfected patients. PMID:18316521

  16. Pancreatic tuberculosis in a human immunodeficiency virus positive patient:A case report

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Despite the increased incidence of tuberculosis related to human immunodeficiency virus (HIV) in recent decades,pancreatic tuberculosis has rarely been described.We report a case of pancreatic tuberculosis in a 39-yearold African man who presented with progressive dysphagia,vomiting,weight loss and productive cough,accompanied by localized epigastric pain and one episode of melena.HIV-1 testing was positive and lymphocyte subset profile showed CD4 count of 9/mm3.Abdominal computed tomography (CT) scan with contrast revealed a cystic mass in the body of the pancreas,significant portal and retroperitoneal cystic adenopathy,and multiple cystic lesions in the spleen and liver.CT guided cyst aspiration and node biopsy detected Mycobacterium tuberculosis.The patient responded well on antituberculosis and antiretroviral therapy.Tuberculosis rarely involves the pancreas,probably due to the presence of pancreatic enzymes which interfere with the seeding of Mycobacterium tuberculosis.Pancreatic tuberculosis is considered to be the result of dissemination of the infection from nearby lymphatic nodes.Endoscopic ultrasound or CT guided fine needle aspiration for cytology is the recommended diagnostic technique.Although the prognosis is good with antituberculosis treatment,it could be fatal without correct diagnosis and treatment.The clinician's high index of suspicion of pancreatic tuberculosis and application of FNAB to obtain pathological evidence are extremely important to a correct diagnosis,especially in young HIV positive patients.

  17. Pseudo-Cushing's syndrome in human immunodeficiency virus-infected patients.

    Science.gov (United States)

    Miller, K K; Daly, P A; Sentochnik, D; Doweiko, J; Samore, M; Basgoz, N O; Grinspoon, S K

    1998-07-01

    To our knowledge, an association between human immunodeficiency virus infection and pseudo-Cushing's syndrome has not previously been described. We describe four HIV-infected patients with pseudo-Cushing's syndrome, characterized by striking dorsocervical and submandibular fat accumulation and central obesity. In each case, cortisol levels were either normal or suppressed adequately with administration of dexamethasone, excluding the diagnosis of true Cushing's syndrome. Immune function and weight improved significantly preceding the development of pseudo-Cushing's syndrome. Three of the four patients were taking a common protease inhibitor at the onset of symptoms, and the fourth reported the exacerbation of his symptoms with the addition of a protease inhibitor. The observed characteristic pattern of fat deposition may be attributable to a specific effect of new antiretroviral therapies or may relate to recovery independent of medication usage. Distinguishing between pseudo-Cushing's syndrome and true Cushing's syndrome is critical for preventing the unnecessary and potentially harmful treatment of such patients. Further research into the mechanisms of this novel phenomenon is needed.

  18. False Human Immunodeficiency Virus Test Results Associated with Rheumatoid Factors in Rheumatoid Arthritis

    Institute of Scientific and Technical Information of China (English)

    Yun-chun Li; Fan Yang; Xiao-yun Ji; Zhong-jun Fang; Jun Liu; Yue Wang

    2014-01-01

    Objective To investigate if immunological factors associated with rheumatoid arthritis (RA) affect the result of human immunodeficiency virus (HIV) screening by electrochemiluminescence immunoassay (ECLIA) and enzyme-linked immunosorbent assay (ELISA). Methods 100 RA cases were enrolled from January 2012 to February 2013 into this study. HIV screening was conducted with ECLIA detecting both HIV-1 p24 antigen, HIV-1 and HIV-2 antibodies, with ELISA and colloidal gold method detecting HIV-1 and HIV-2 antibodies. The samples producing positive results were submitted to the Center for Disease Control for confirmation using Western blotting method. The antibody titers of rheumatoid factors (RF) including RF-IgG, RF-IgM, RF-IgA, and CCP-IgG were analyzed by ELISA. Results The HIV positive-rate determined by ECLIA was significantly higher than that by ELISA and colloidal gold method (P Conclusion Immunological factors, including RF and anti-CCP antibody, may influence the screening of HIV by ECLIA, producing false-positive result.

  19. Molecular Characterization of the Human Immunodeficiency Virus Type 1 in Women and Their Vertically Infected Children.

    Science.gov (United States)

    Vaz, Sara Nunes; Giovanetti, Marta; Rego, Filipe Ferreira de Almeida; Oliveira, Tulio de; Danaviah, Siva; Gonçalves, Maria Luiza Freire; Alcantara, Luiz Carlos Junior; Brites, Carlos

    2015-10-01

    Approximately 35 million people worldwide are infected with human immunodeficiency virus (HIV) around 3.2 million of whom are children under 15 years. Mother-to-child-transmission (MTCT) of HIV-1 accounts for 90% of all infections in children. Despite great advances in the prevention of MTCT in Brazil, children are still becoming infected. Samples from 19 HIV-1-infected families were collected. DNA was extracted and fragments from gag, pol, and env were amplified and sequenced directly. Phylogenetic reconstruction was performed. Drug resistance analyses were performed in pol and env sequences. We found 82.1% of subtype B and 17.9% of BF recombinants. A prevalence of 43.9% drug resistance-associated mutations in pol sequences was identified. Of the drug-naive children 33.3% presented at least one mutation related to protease inhibitor/nucleoside reverse transcriptase inhibitor/nonnucleoside reverse transcriptase inhibitor (PI/NRTI/NNRTI) resistance. The prevalence of transmitted drug resistance mutations was 4.9%. On env we found a low prevalence of HR1 (4.9%) and HR2 (14.6%) mutations.

  20. Human immunodeficiency virus type 1 infection of antigen-specific CD4 cytotoxic T lymphocytes.

    Science.gov (United States)

    Robbins, P A; Roderiquez, G L; Peden, K W; Norcross, M A

    1998-11-01

    The effect of macrophage (M)-tropic and T cell line (T)-tropic human immunodeficiency virus type 1 (HIV-1) infection on antigen-specific CD4 cytotoxic T lymphocytes (CTLs) has been studied using a CD4 CTL line specific for a peptide from influenza B virus hemagglutinin. In the absence of antigen presentation, the production of CC chemokines was low. Both the M-tropic HIV-1 strain (HIV-1AD) and the T-tropic HIV-1 strain (HIV-1LAI) established productive infections in the CD4 CTLs, decreasing antigen-specific cytotoxicity. Peptide presented to the CD4 CTLs increased their secretion of RANTES and MIP-1beta, suppressed M-tropic HIV-1 replication, downmodulated CCR5 expression, and preserved CTL recognition. The suppression of M-tropic HIV-1 replication and downmodulation of the CCR5 receptor likely resulted from CC chemokine secretion since antibodies to CC chemokines restored M-tropic HIV-1 replication. Antigen presentation did not protect CD4 CTLs from T-tropic HIV-1 infection or preserve their CTL recognition. Thus, these CD4 CTLs do not make suppressor factors that inhibit the T-tropic HIV-1LAI isolate. The results indicate that these CD4 CTLs can either harbor or suppress M-tropic HIV-1 infection, depending on whether antigen is present. CD4 CTLs might therefore provide some protection in the early stages of HIV-1 infection when M-tropic isolates are present.