| 1. |
- Abdurahman, Samir, 1965-, et al.
(författare)
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Activity of the small modified amino acid alpha-hydroxy glycineamide on in vitro and in vivo human immunodeficiency virus type 1 capsid assembly and infectivity
- 2008
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Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 52:10, s. 3737-3744
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Tidskriftsartikel (refereegranskat)abstract
- Upon maturation of the human immunodeficiency virus type 1 (HIV-1) virion, proteolytic cleavage of the Gag precursor protein by the viral protease is followed by morphological changes of the capsid protein p24, which will ultimately transform the virus core from an immature spherical to a mature conical structure. Virion infectivity is critically dependent on the optimal semistability of the capsid cone structure. We have reported earlier that glycineamide (G-NH(2)), when added to the culture medium of infected cells, inhibits HIV-1 replication and that HIV-1 particles with aberrant core structures were formed. Here we show that it is not G-NH(2) itself but a metabolite thereof, alpha-hydroxy-glycineamide (alpha-HGA), that is responsible for the antiviral activity. We show that alpha-HGA inhibits the replication of clinical HIV-1 isolates with acquired resistance to reverse transcriptase and protease inhibitors but has no effect on the replication of any of 10 different RNA and DNA viruses. alpha-HGA affected the ability of the HIV-1 capsid protein to assemble into tubular or core structures in vitro and in vivo, probably by binding to the hinge region between the N- and C-terminal domains of the HIV-1 capsid protein as indicated by matrix-assisted laser desorption ionization-mass spectrometry results. As an antiviral compound, alpha-HGA has an unusually simple structure, a pronounced antiviral specificity, and a novel mechanism of antiviral action. As such, it might prove to be a lead compound for a new class of anti-HIV substances.
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| 2. |
- Amirbeagi, Firoozeh, et al.
(författare)
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Olfactomedin-4 autoantibodies give unusual c-ANCA staining patterns with reactivity to a subpopulation of neutrophils.
- 2015
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Ingår i: Journal of leukocyte biology. - 1938-3673. ; 97:1, s. 181-189
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Tidskriftsartikel (refereegranskat)abstract
- Testing for the presence of ANCAs in circulation is part of the clinical examinations routinely performed upon suspected autoimmune disorders, mainly vasculitis. The autoantibodies are typically directed toward neutrophil MPO or PR3. These are major granule-localized proteins, and similar to all hitherto-described ANCA antigens, they are expressed by all neutrophils, and ANCA-containing sera thus give rise to uniform reactivity toward all neutrophils in a sample. In this paper, we describe sera from 2 unrelated patients with diffuse inflammatory symptoms that gave rise to peculiar c-ANCA patterns, only reacting with a subpopulation (roughly 30%) of human neutrophils. By immunoblotting, both sera reacted to the same antigen, which was expressed in intracellular granules. The antigen could be released to the extracellular milieu through secretion but also through the formation of NETs. Neutrophils have long been considered a homogenous cell population, but it is becoming increasingly clear that distinct subpopulations, defined by the presence or absence of certain proteins, exist. One such marker that defines a neutrophil subset is the granule protein OLFM4. The unusual, subset-restricted c-ANCA sera reacted only with OLFM4-positive neutrophils, and MS analysis revealed that the autoantigen was, in fact, OLFM4. These data describe for the first time a c-ANCA pattern reactive to only a subpopulation of neutrophils and identify the granule protein OLFM4 as a novel autoantigen.
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| 3. |
- Andersson, Bo, 1949-
(författare)
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Hydraulisk riktningsventil
- 2005
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Patent (populärvet., debatt m.m.)abstract
- En hydraulisk riktningsventil av "öppet-centrum"-typ med ett ventilhus och en i detta rörlig vetilslid för reglering av flöde av hydraulfluid genom ventilen har en tryckkompenseringsventil anordnad i minst en för anslutning till en driven anordning avsedd arbetport för att tryckkompensera flödet från arbetsporten till den drivna anordningen.
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| 4. |
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| 5. |
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| 6. |
- Andersson, Bo, 1949-
(författare)
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Valve arrangement
- 2008
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Patent (populärvet., debatt m.m.)abstract
- Valve arrangement for controlling the flow of fluid through a conduit and comprising a valve body with a first and a second valve port which serve, alternately, as input and output, and a valve cone arranged in the valve body which connects in its open position the valve ports with each other, and is actuatd by a holding force wihch is greater than the force acting on the pressurized fluid side of the valve cone and dependent on the medium pressure in the input port.
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| 7. |
- Andersson, Bo, 1949-
(författare)
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Variabla pumpar i mobila system
- 2007
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Ingår i: Hydraulikdagar 07,2007. - Linköping : Linköpings universitet.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Det här föredraget behandlar olika systemprinciper för att styra en variabel pump i en mobil applikation. Variabla pumpar med elektrisk styrning ger möjlighet till nya intressanta systemprinciper.
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| 8. |
- Andersson, Elin, 1975, et al.
(författare)
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Glycine-amide is an active metabolite of the antiretroviral tripeptide glycyl-prolyl-glycine-amide.
- 2005
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Ingår i: Antimicrobial agents and chemotherapy. - 0066-4804. ; 49:1, s. 40-4
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Tidskriftsartikel (refereegranskat)abstract
- The chemically modified tripeptide glycyl-prolyl-glycine-amide (GPG-NH(2)) inhibits replication of human immunodeficiency virus (HIV) type 1 (HIV-1) in vitro, probably by interfering with capsid formation. The aim of the present study was to determine whether the metabolites glycyl-proline (GP-OH), glycine (G-OH), prolyl-glycine-amide (PG-NH(2)), proline (P-OH), and glycine-amide (G-NH(2)) from proteolytic cleavage may inhibit the replication of HIV-1 in vitro. PG-NH(2) has previously been shown to have a modest effect on HIV-1 replication. In the present study we show that G-NH(2) exhibits a pronounced inhibitory effect on HIV-1. This effect was not due to a decrease in cell proliferation or viability and could not be shown for herpes simplex virus type 1. The G-NH(2) concentration that inhibited virus replication by 50% (IC(50)) was equimolar to that of GPG-NH(2) and ranged from 3 to 41 microM. Transmission electron microscopy revealed that the effect of G-NH(2) on HIV-1 morphology was equivalent to that of GPG-NH(2) and showed disarranged capsid structures, indicating interference with capsid formation. Serial passage of HIV-infected cells with G-NH(2) for more than 20 subcultivations did not decrease the susceptibility to the compound. The results from this study suggest that GPG-NH(2) might act as a prodrug and that G-NH(2) is an active antiretroviral metabolite.
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| 9. |
- Andersson, Elin, 1975, et al.
(författare)
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No cross-resistance or selection of HIV-1 resistant mutants in vitro to the antiretroviral tripeptide glycyl-prolyl-glycine-amide.
- 2004
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Ingår i: Antiviral research. - : Elsevier BV. - 0166-3542. ; 61:2, s. 119-24
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Tidskriftsartikel (refereegranskat)abstract
- The chemically modified tripeptide glycyl-prolyl-glycine-amide (GPG-NH(2)) inhibits replication of HIV-1 in vitro, probably by interfering with capsid formation. This study was aimed at determining cross-resistance between antiretroviral drugs and GPG-NH(2), and whether resistance to GPG-NH(2) can be induced in vitro. Fifty-five clinical HIV-1 isolates with different resistance-related mutations were tested for susceptibility to GPG-NH(2). No correlation between NRTI-, NNRTI- or PI-resistance and efficacy of GPG-NH(2) was found, indicating the lack of cross-resistance. Serial passages were performed with GPG-NH(2), and with lamivudine, and genotypic or phenotypic changes were determined. Resistance to lamivudine was detected after six passages. No resistance to GPG-NH(2) was generated after 30 passages in two parallel series. However, one mutation (T107I) in the p24 gene was detected in both series, but this mutation was not associated with decreased sensitivity to GPG-NH(2).
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| 10. |
- Andersson, Lars-Magnus, 1968, et al.
(författare)
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Higher HIV-1 RNA cutoff level required in cerebrospinal fluid than in blood to predict positive HIV-1 isolation
- 2000
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Ingår i: J Med Virol. ; 62:1, s. 9-13
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Tidskriftsartikel (refereegranskat)abstract
- HIV-1 can be isolated from the vast majority of blood samples taken from HIV-1-seropositive patients not treated with antiretroviral drugs. Isolation rates from cerebrospinal fluid (CSF) samples are considerably lower, ranging between 20-70%. The objective of this study was to determine the cutoff levels for HIV-1 RNA that would yield a positive predictive value > or =90% for positive virus isolation from CSF and blood. Quantitative HIV-1 RNA PCR (Amplicor HIV monitor, version 1.0, Roche Diagnostic Systems) and virus isolation were used to examine 303 CSF samples and 278 paired blood samples from 157 HIV-1-seropositive patients. Patients on antiretroviral treatment provided 140 of the CSF samples and 131 of the blood samples. CSF samples that were positive by culture numbered 137 of 303 (45%), as compared with 216 of 278 (78%) blood samples. In the case of samples taken from patients with antiretroviral treatment, 28% were positive by culture from CSF and 63% from blood. As expected, mean HIV-1 RNA levels were higher in CSF and blood samples positive by culture than in samples negative by culture. A cutoff level of >5,000 HIV-1 RNA copies/ml was required to yield a positive predictive value for positive virus isolation from CSF samples of > or =90%, whereas the cutoff level for blood samples was just above the detection limit of the assay (>200 HIV-1 copies/ml).
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