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

The active substances, acid polysaccharides, were extracted with 1% sodium hydroxide from the leaves of rooibos tea (Aspalathus linearis), Du Zhong Cha (Eucommia ulmoides Oliv.) and Japanese tea leaves (Camellia sinensis var. sinensis). The alkaline extracts of Rooibos tea and Du-Zhong tea leaves, but not Japanese tea leaves suppressed the HIV-induced cytopathicity using HIV (HTLV-III) infected MT-4 cells, having extremely low cytotoxicity: Its 50% effective concentration (EC50) was 12-67 micrograms/mL, white 50% cytotoxic concentration (CC50) was higher than 1.0 mg/mL. The active substances were purified with ethanol precipitation. The substances were composed of 27% of reducing sugar, 46% of neutral sugars and 22% of uronic acid. A LD50 of the alkaline extracts from rooibos tea was higher than 1.2 g/kg body weight. Acid degradated substances composed of disaccharides and trisaccharides, were also suppressed the HIV-induced cytopathicity. From these results, it is probable that acid polysaccharides from rooibos tea were extremely safe, and that HIV infection may be suppressed by daily intake of the alkaline extracts of rooibos tea and Du-Zhong tea.
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PMID:Anti-human immunodeficiency virus activity of oligosaccharides from rooibos tea (Aspalathus linearis) extracts in vitro. 920 19

A series of protocols were tested to examine the adjuvant effects of IL-12 on humoral and type 1 cytokine responses elicited in mice by recombinant gp120 envelope protein from HIV-1. This Ag fails to induce detectable Ab responses when administered s.c. alone, but stimulates low Ab levels when combined with aluminum hydroxide (alum). Moreover, when i.p. injected rIL-12 was included in the immunization, no increase in Ab production was observed. Importantly, optimal gp120 Ab responses were achieved by immunizing mice s.c. with gp120 and rIL-12 simultaneously coadsorbed to alum. These animals displayed a highly polarized, type 1 cytokine profile, with the emergence of anti-gp120 Ig belonging to the IgG2 and IgG3 isotypes. In addition, a major increase occurred in Ab of the IgG1 subclass. The superior adjuvant activity of alum-adsorbed IL-12 compared with that of the free cytokine correlated with the prolonged detection of IFN-gamma in the sera of animals immunized using the former procedure. In related experiments, in vitro neutralization of IL-12 was shown to inhibit IFN-gamma production by spleen cells from mice immunized with gp120 plus alum, but not by splenocytes from mice primed in the presence of IL-12, suggesting that the latter protocol induces a stable type 1 phenotype. These studies demonstrate that presentation of IL-12 on alum enhances its immunomodulatory effects and establish a protocol for the use of the cytokine as an adjuvant for simultaneously promoting both humoral Ab and type 1 cytokine responses.
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PMID:Adsorption to aluminum hydroxide promotes the activity of IL-12 as an adjuvant for antibody as well as type 1 cytokine responses to HIV-1 gp120. 927 32

The aim of this phase II study was to evaluate the safety, immunogenicity and tolerability of the yeast-derived virus-like particle immunogen, Ty.p24.VLP (p24-VLP), in HIV-antibody-positive asymptomatic volunteers. Fifteen informed and consented volunteers, with p24 Antibody titres >1/100, p24 Antigen <20 pg/l, and CD4>350 x 10(9)/l were enrolled. Five were immunized with aluminium hydroxide placebo, five with 25 microg, and five with 100 microg p24-VLP in Alum adjuvant at weeks 0 and 4 by the intramuscular route. Patients were followed for 16 weeks post vaccination and the main outcome assessments were CD4 and CD8 lymphocyte counts, p24 antigen and antibody, Ty antibody and quantitative viral cultures. No serious adverse events were observed in any of the groups. There were increases in CD4 counts in the treated groups but not in the controls, although these changes were not statistically significant. There were no significant intrasubject or intergroup changes in the other parameters, such as p24 antigen and antibody. No pattern of change in plasma viraemia was detected, and most cultures were negative. Therefore we conclude that p24-VLP immunizations of 25 microg and 100 microg are well tolerated, and the CD4 changes are encouraging, but higher doses and larger numbers are required to see if there are significant humoral or cellular responses, and extended phase II studies are now in progress.
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PMID:A pilot phase II study of the safety and immunogenicity of HIV p17/p24:VLP (p24-VLP) in asymptomatic HIV seropositive subjects. 945 93

A new bone tissue process using supercritical carbon dioxide fluid extraction (SFE) has been evaluated for its ability to inactivate or eliminate viruses. Four viruses, human immunodeficiency virus type 1 (HIV-1), Sindbis virus, polio Sabin type I virus, and pseudorabies virus (PRV), were exposed to four different processing steps. In addition to supercritical CO2, hydrogen peroxide, sodium hydroxide, and ethanol treatments were evaluated. The mean cumulated reduction factors (log10) for the four viruses exposed to these four steps were > 14.2 for HIV-1, > 18.2 for Sindbis virus, > 24.4 for poliovirus, and > 17.6 for PRV. The mean reduction factors obtained by the supercritical fluid extraction alone were > 4.0, > 4.3, > 6.6, and > 4.0, respectively. These results demonstrate that the SFE process is effective in inactivating viruses on human femoral heads, and provides a level of inactivation similar to that obtained by traditional cleaning methods. It is proposed that CO2 SFE be incorporated as a routine step in the processing of bone allografts for transplantation either to replace or supplement existing procedures.
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PMID:Viral inactivation of human bone tissue using supercritical fluid extraction. 968 54

A case of disseminated aspergillus fumigatus infection is reported in a 43 year old Ugandan female with no known immune system disorder(not neutropenic and HIV-1 sero negative). She presented with multiple cutaneous ulcers, recurrent empyema thoracis, a past history of intra-abdominal abscess and bowel infarction. Empirical treatment for tuberculosis was previously given without improvement. A diagnosis of aspergillus fumigatus based on a combination of tissue wet potassium hydroxide preparation, fungal culture and tissue histologic typing was made. Despite antifungal therapy with intravenous amphotericin B infusion in 5% dextrose, after a normal baseline renal function test, the patient died in the second week of admission. Autopsy showed disseminated aspergillosis involving the pleural space, pericardium, spleen, and meningitis in addition to the cutaneous sites. Disseminated aspergillus fumigatus infection in a non-immunocompromised is rare antemortem diagnosis. This case highlights the difficulty in making a diagnosis in the face of many endemic conditions with similar presentation.
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PMID:Disseminated aspergillus fumigatus infection: case report. 980 39

Replication of human immunodeficiency virus type 1 (HIV-1) requires specific interactions of Tat protein with the trans -activation responsive region (TAR) RNA, a 59 base stem-loop structure located at the 5'-end of all HIV transcripts. We have used an intramolecular RNA self-cleaving strategy to determine the folding of TAR RNA and its interactions with a Tat peptide. We incor-porated an EDTA analog at position 24 in the HIV-1 Tat binding site of the TAR RNA. After isolation and purification of the EDTA-TAR conjugate, RNA self-cleavage was initiated by the addition of an iron salt, ascorbate and hydrogen peroxide. Hydroxyl radicals generated from the tethered Fe(II) cleaved TAR RNA backbone in two localized regions. Sites of RNA cleavage were mapped by sequencing reactions. A Tat fragment, Tat(38-72), specifically inhibited RNA self-cleavage. To determine the structural changes caused by the Tat peptide, we performed Fe(II)-EDTA footprinting experiments on Tat-TAR complex. Our high-resolution footprinting results suggest that the inhibition of self-cleavage of EDTA-TAR is due to two effects of Tat binding: (i) Tat binds in the bulge and protects residues in the vicinity of the bulge from self-cleavage and (ii) RNA goes through a structural change where EDTA-U24 is rigidly positioned out of the helix and cannot get access to other nucleotides in the loop of TAR RNA, which are not protected by the Tat peptide. Our results demonstrate that Fe(II)-EDTA-mediated RNA self-cleavage can be applied to study RNA tertiary structures and RNA-protein interactions.
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PMID:Visualizing tertiary folding of RNA and RNA-protein interactions by a tethered iron chelate: analysis ofHIV-1 Tat-TAR complex. 992 43

The immunopotentiating activities of colloidal iron hydroxide, a novel, experimental mineral adjuvant, and of aluminium hydroxide. the licensed adjuvant for human vaccines, were compared. Our studies revealed that colloidal iron hydroxide and aluminium hydroxide behaved comparably with respect to supporting induction of an antibody response to tetanus toxoid. Furthermore, mice immunized with both, the experimental vaccine (tick-borne encephalitis virus (TBEV) antigen adsorbed to colloidal iron hydroxide) or with a commercially available TBEV vaccine (adjuvanted with aluminium hydroxide), developed long-lasting antibody responses which protected the animals from TBEV infection even one year after vaccination. The use of colloidal iron hydroxide as adjuvant had the additional advantage to reproducibly support induction of HIV-1 envelope-specific cytotoxic T lymphocytes (CTL), when used as adjuvant for a HIV-1 env-carrying recombinant fowlpox virus and being applied via the subcutaneous route. Aluminium hydroxide was much less active in this respect. Non-adjuvanted recombinant fowlpox elicited CTLs only when given intravenously or intraperitoneally, vaccination routes considered not to be suitable for routine use in humans. Further studies to evaluate the use of colloidal iron as possible alternative and/or supplement for routinely used mineral adjuvants may therefore be warranted.
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PMID:Humoral and cellular immunity induced by antigens adjuvanted with colloidal iron hydroxide. 1019 10

Bacterial DNA sequences containing unmethylated CpG motifs have recently been proposed to exhibit immunostimulatory effects on B-, T- and NK cells, leading to the induction of humoral and cell-mediated immune responses. In the present study we investigated the immunomodulatory effects of a CpG-containing oligodeoxynucleotide (CpG ODN) to the HIV-1 gp 160 envelope (Env) protein in the BALB/c mouse model. Priming and boosting of mice with gp 160 adsorbed to aluminium hydroxide (Alum) induced a typical T helper-2 (Th2)-dominated immune response with high titers of gp 160-specific immunoglobulin (Ig)G1 isotypes but a weak IgG2a response. Specifically re-stimulated splenocytes from these mice predominantly secreted interleukin (IL)-5 but only minute amounts of interferon-gamma (IFN-gamma) upon specific re-stimulation. In contrast, a boost immunisation of gp 160/Alum primed mice with a gp 160/Alum/CpG combination resulted in a seven times higher production of IgG2a antibodies, without affecting the titers of IgG1 isotypes. Furthermore, approximately 10-fold increased levels of IFN-gamma, but significantly reduced amounts of IL-5, were secreted from gp 160-restimulated splenic cells. A further greater than 30-fold increase in the levels of specific IgG2a responses and a substantially elevated secretion of IFN-gamma were observed when the mice received gp160/Alum/CpG combinations for priming and boost injections. Thus, CpG ODNs are useful as an adjuvant to induce a typical Th0/Th1 response to HIV gp 160 proteins. However, despite the induction of a more Th1-like immune response, gp 16O/Alum/CpG combinations were not sufficient to prime an Env-specific cytotoxic T-cell (CTL) response.
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PMID:Immunostimulatory CpG motifs trigger a T helper-1 immune response to human immunodeficiency virus type-1 (HIV-1) gp 160 envelope proteins. 1035 61

A phase I clinical trial with the HIV-1-derived multi-epitope polypeptide (MEP) TAB9 in the oil adjuvant Montanide ISA720 (M-ISA720) was recently performed. Although severe local reactions were reported after the second and third injections of this vaccine candidate, the first inoculation was well tolerated. In this article we evaluated a prime-boost regime consisting of one inoculation of TAB9 in M-ISA720 followed by a booster with the same antigen in aluminum hydroxide. This combination of adjuvants elicited similar antibody levels in rabbits than the traditional two-dose schedule with M-ISA720. A control group injected three times with TAB9 in aluminum hydroxide developed markedly lower antibody titers. These results showed that although oil adjuvants are better than alum for priming the immune system for antibody production against TAB9, both kinds of adjuvants can be equally effective in booster immunizations. Therefore, by using the more reactogenic oil adjuvant only for priming, we should be able to eliminate the undesirable reactions characteristic of these compounds while achieving equivalent levels of specific antibodies.
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PMID:A prime-boost regime that combines Montanide ISA720 and Alhydrogel to induce antibodies against the HIV-1 derived multiepitope polypeptide TAB9. 1041 14

8-Hydroxy-2-[2-(3-hydroxy-4-methoxyphenyl)ethenyl]-7-quinoline carboxylic acid and 8-hydroxy-2-[2-(3-methoxy-4-hydroxyphenyl)ethenyl]-7-quinoline carboxylic acid inhibit the processing and strand transfer reactions catalyzed by HIV-1 integrase with an IC50 of 2 microM. Some of their spectral properties are briefly reported. Their fluorescence is so weak that it is of no use in an experimental determination of the binding to the protein and we resorted to computer simulation. Both styrylquinoline derivatives, in their monoanionic form, have several dozens of tautomers and each of these forms has four planar rotamers. In this work computer simulations have been performed to determine which tautomer is the most abundant in aqueous solution and which binds to the Rous sarcoma virus (RSV) integrase catalytic core. As the substituents on the quinoline moiety are the same as on salicylic acid, the energies of hydroxy benzoic acid tautomers were also computed both in vacuo and embedded in a continuous medium which had the dielectric constant of bulk water, using the recent CPCM technique. The CPCM method was then applied to the two integrase inhibitors to estimate the tautomer population in water. The binding site of the compounds on the RSV integrase catalytic core was determined through a docking protocol, consisting of coupling a grid search method with full energy minimization. The designed method is a way leading to identification of potent integrase inhibitors using in silico experiments.
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PMID:Tautomers of styrylquinoline derivatives containing a methoxy substituent: computation of their population in aqueous solution and their interaction with RSV integrase catalytic core. 1096 74


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