| 181. |
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| 182. |
- Abdurahman, Samir, et al.
(författare)
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Anti-HIV activity of the small modified amino acid {alpha}-hydroxy glycineamide on in vitro and in vivo HIV-1 capsid assembly and infectivity
- 2008
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Ingår i: Antimicrobial Agents and Chemotherapy. - 1098-6596. ; 52:10, s. 3737-3744
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Tidskriftsartikel (refereegranskat)abstract
- Upon maturation of the 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 just right semi-stability of the capsid cone structure. We have earlier reported that glycineamide (G-NH2) 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-NH2 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 ten 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 MALDI-MS 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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| 183. |
- Abdurahman, Samir, 1965-, et al.
(författare)
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Isolation and characterization of a small antiretroviral molecule affecting HIV-1 capsid morphology
- 2009
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Ingår i: Retrovirology. - : Springer Science and Business Media LLC. - 1742-4690. ; 6, s. 34-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Formation of an HIV-1 particle with a conical core structure is a prerequisite for the subsequent infectivity of the virus particle. We have previously described that glycineamide (G-NH2) when added to the culture medium of infected cells induces non-infectious HIV-1 particles with aberrant core structures. Results: Here we demonstrate that it is not G-NH2 itself but a metabolite thereof that displays antiviral activity. We show that conversion of G-NH2 to its antiviral metabolite is catalyzed by an enzyme present in bovine and porcine but surprisingly not in human serum. Structure determination by NMR suggested that the active G-NH2 metabolite was alpha-hydroxy-glycineamide (alpha-HGA). Chemically synthesized alpha-HGA inhibited HIV-1 replication to the same degree as G-NH2, unlike a number of other synthesized analogues of G-NH2 which had no effect on HIV-1 replication. Comparisons by capillary electrophoresis and HPLC of the metabolite with the chemically synthesized alpha-HGA further confirmed that the antiviral G-NH2-metabolite indeed was alpha-HGA. Conclusion: alpha-HGA has an unusually simple structure and a novel mechanism of antiviral action. Thus, alpha-HGA could be a lead for new antiviral substances belonging to a new class of anti-HIV drugs, i.e. capsid assembly inhibitors.
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| 184. |
- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 185. |
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| 186. |
- Abedinpour, Parisa, et al.
(författare)
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Isolation of a caveolae-enriched fraction from rat lung by affinity partitioning and sucrose gradient centrifugation
- 2003
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Ingår i: Analytical Biochemistry. - 1096-0309. ; 313:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Caveolae were isolated from rat lungs by a combination of affinity partitioning and sucrose gradient centrifugation. After homogenization of the lungs directly in a polyethylene glycol–dextran two-phase system and conventional phase partitioning, the polyethylene glycol-rich top phase was affinity partitioned with fresh bottom phase containing dextran-linked wheat-germ agglutinin. The lectin selectively attracted plasma membranes to the bottom phase. The isolated plasma membrane fraction was treated with Triton X-100 or, alternatively, sonicated before centrifugation in a stepwise sucrose gradient. Caveolin-enriched material collected at the 5/24% sucrose boundary. This material also contained 5′-nucleotidase activity and actin. Electron microscopy showed the material to consist of a homogeneous population of 50- to 100-nm vesicles. This purification protocol should allow the facile purification of caveolae also from other tissues, facilitating structural and functional studies.
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| 187. |
- Abedinpour, Parisa
(författare)
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Isolation of caveolae using affinity two-phase partitioning
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The intention of this work was to establish alternative purification methods to obtain highly purified caveolae from various tissues. In order to isolate caveolae, sufficiently pure plasma membranes are needed. A method is presented for the isolation of plasma membranes from lung tissue using a combination of conventional polyethylene glycol/dextran two-phase partitioning and affinity partitioning using the lectin wheat germ agglutinin as affinity ligand. A caveolae-enriched fraction was purified from lung plasma membranes isolated by this procedure. Caveolae were released from the membranes by Triton X-100 treatment or by sonication. Highly purified caveolae were obtained at low buoyant density by sucrose gradient centrifugation. The affinity method is advantageous to other methods for the isolation of plasma membranes and should be useful for other tissues as well. A method to purify caveolae by immunoaffinity partitioning was developed exploiting the interaction between caveolin and anti-caveolin antibodies. A sandwich approach was used where primary antibodies directed against caveolin interacted with biotinylated secondary antibodies and NeutrAvidin coupled to dextran in a polyethylene glycol/dextran two-phase system. Caveolae were directed efficiently into the immunoaffinity bottom phase of the two-phase system by the anti-caveolin antibody. Immunoaffinity two-phase partitioning has wider applications potentially, as this technique should be useful to purify any type of membrane by selecting appropriate antibodies directed against surface components of the membrane of interest. Caveolae were isolated to a high degree of purity from apical and basolateral domains of liver plasma membranes. The caveolae from the two domains were quite homogeneous as studied by immunoaffinity partitioning and electron microscopy. Analysis showed that the caveolae differed in properties in several respects.
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| 188. |
- Abel, Enno, et al.
(författare)
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Buildings and Energy - a systematic approach
- 2007
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- In many existing buildings, energy conservation measures have significantly reduced the demands for heat supply. In new buildings, advances in a wide range of technologies have led to even greater reductions. On the other hand, demands for electrical energy have risen noticeably. Unfortunately, it now seems that the use of both heat and electrical energy is starting to increase, especially in non residential buildings, and without any corresponding increase in the quality of the indoor climate. In this book, the authors present a systematic and holistic approach to both conserving energy and ensuring good indoor climate when designing new buildings or renovating existing ones. In their opinion, the harmonization of the design of a building and its HVAC systems is fundamental to these issues. The authors of Buildings and Energy ? a systematic approach wish to share their knowledge and experience in this field with developers, planners and builders. The book is also available in Swedish ISBN 9789154060207.
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| 189. |
- Abel, Enno, et al.
(författare)
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Byggnaden som system : 2 uppl.
- 2008
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Bra inomhusklimat och effektiv energianvändning är av yttersta vikt när nya hus ska byggas. Ny teknik har fått ner behovet av energi för uppvärming till ungefär hälften sedan 70-talet. Men elförbrukningen har ökat kraftigt. Här presenterar författarna en systematisk helhetssyn att både spara energi och åstadkomma ett behagligt inneklimat när nya hus utformas eller gamla renoveras. Byggteknik och installationsteknik måste harmoniseras genom en balansakt som kräver mycket kunnande. I Byggnaden som system delar författarna med sig av sitt gedigna kunnande och mångåriga erfarenheter till dagens engagerade byggare.
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| 190. |
- Abelson, Anna-Karin, et al.
(författare)
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No evidence of association between genetic variants of the PDCD1 ligands and SLE
- 2007
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:1, s. 69-74
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Tidskriftsartikel (refereegranskat)abstract
- PDCD1, an immunoreceptor involved in peripheral tolerance has previously been shown to be genetically associated with systemic lupus erythematosus (SLE). PDCD1 has two ligands whose genes are located in close proximity on chromosome 9p24. Our attention was drawn to these ligands after finding suggestive linkage to a marker (gata62f03, Z=2.27) located close to their genes in a genome scan of Icelandic families multiplex for SLE. Here, we analyse Swedish trios (N=149) for 23 single nucleotide polymorphisms (SNPs) within the genes of the PDCD1 ligands. Initially, indication of association to eight SNPs was observed, and these SNPs were therefore also analysed in Mexican trios (N=90), as well as independent sets of patients and controls from Sweden (152 patients, 448 controls) and Argentina (288 patients, 288 controls). We do not find support for genetic association to SLE. This is the first genetic study of SLE and the PDCD1 ligands and the lack of association in several cohorts implies that these genes are not major risk factors for SLE.
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