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- Egholm, M., et al.
(author)
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PNA HYBRIDIZES TO COMPLEMENTARY OLIGONUCLEOTIDES OBEYING THE WATSON-CRICK HYDROGEN-BONDING RULES
- 1993
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 365:6446, s. 566-568
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Journal article (peer-reviewed)abstract
- DNA ANALOGUES are currently being intensely investigated owing to their potential as gene-targeted drugs1-3. Furthermore, their properties and interaction with DNA and RNA could provide a better understanding of the structural features of natural DNA that determine its unique chemical, biological and genetic properties3,4. We recently designed a DNA analogue, PNA, in which the backbone is structurally homomorphous with the deoxyribose backbone and consists of N-(2-aminoethyl)glycine units to which the nucleobases are attached5-9. We showed that PNA oligomers containing solely thymine and cytosine can hybridize to complementary oligonucleotides, presumably by forming Watson-Crick-Hoogsteen (PNA)2-DNA triplexes, which are much more stable than the corresponding DNA-DNA duplexes5-7, and bind to double-stranded DNA by strand displacement5,8. We report here that PNA containing all four natural nucleobases hybridizes to complementary oligonucleotides obeying the Watson-Crick base-pairing rules, and thus is a true DNA mimic in terms of base-pair recognition.
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- Holbech, J. D., et al.
(author)
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H2* defect in crystalline silicon
- 1993
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 71:6, s. 875-878
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Journal article (peer-reviewed)abstract
- Detailed infrared studies have been carried out on proton- and deuteron-implanted Si. A dominant trigonal defect involving a pair of inequivalent hydrogen atoms has been identified, with local modes at 2061.5, 1838.3, 1599.1, and 817.2 cm-1. The structure, the local modes, and the isotopic shifts of the H2* defect have been calculated using ab initio pseudopotential cluster theory. The structure is consistent with channeling and uniaxial stress experiments. The calculated frequencies and isotopic shifts are in close agreement with those observed.
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- Holst, J., et al.
(author)
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Antithrombotic effect of recombinant truncated tissue factor pathway inhibitor (TFPI1-161) in experimental venous thrombosis : A comparison with low molecular weight heparin
- 1994
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In: Thrombosis and Haemostasis. - 0340-6245. ; 71:2, s. 214-219
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Journal article (peer-reviewed)abstract
- The aim was to investigate whether a truncated recombinant Tissue Factor Pathway Inhibitor (TFPI1-161) which lacked the third Kunitz-type domain and the basic c-terminal region, had an antithrombotic effect comparable to LMWH in a randomised double-dummy study. The experimental thrombosis was induced in jugular veins, in a total of 40 rabbits by a combination of destruction of the endothelium and restricted blood flow. Group 1: placebo, gr 2- LMWH 60 anti-FXa IU/kg, gr 3-5: 0.1, 1.0 and 10.0 mg/kg TFPI1-161. TFPI1-161 reduced the thrombus weights in all treated groups, significantly in doses of 1.0 and 10.0 mg/kg compared to placebo. The frequency of thrombosis and occlusive thrombosis were also significantly reduced in those doses. The antithrombotic properties of TFPI1-161 (1.0-10.0 mg/ kg) measured as thrombus weight, frequency of thrombosis and frequency of occlusive thrombosis was equivalent to the antithrombotic properties of LMWH. In the anti-FXa, APTT and PT-assays TFPI1-161 displayed a dose dependent increase of activity. Recombinant-TFPI1-161 did not influence the anti-FIIa-assay. No haemorrhagic side effects were noted.
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- Holst, J., et al.
(author)
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Protamine neutralization of intravenous and subcutaneous low-molecular-weight heparin (tinzaparin, Logiparin(TM)). An experimental investigation in healthy volunteers
- 1994
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In: Blood Coagulation and Fibrinolysis. - 0957-5235. ; 5:5, s. 795-803
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Journal article (peer-reviewed)abstract
- The aim of the present study was to investigate whether tinzaparin sodium (a low-molecular-weight heparin (LMWH)) was fully and permanently neutralized in vivo in man by protamine sulphate (PS) after intravenous (i.v.) or subcutaneous (s.c.) injection. Fifty healthy adults equally divided in five age- and sex-matched groups were included. The groups received 50 IU unfractionated heparin (UH)/kg body weight (b.w.) i.v., 50 anti-factor Xa (anti-Xa) IU tinzaparin/kg b.w. i.v., 75 anti-Xa IU tinzaparin/kg b.w. s.c., 175 anti-Xa IU tinzaparin/kg b.w. s.c., or 1 ml of saline s.c. PS was given as a 10 min infusion in a dose of 1 mg/100 IU of heparin in the four first groups while 0.5 mg PS/kg b.w. was given in the placebo group. In the i.v. groups PS was administered 45 min after the heparin injection, and in the s.c. groups 180 min post-heparin injection. In the UH group PS fully and permanently neutralized all three activities. In the i.v. tinzaparin group PS reversed 80% of the anti-Xa activity, while the anti-IIa and aPTT activities were fully reversed. A slight, but statistically significant, increase in anti-Xa and anti-Ila activities were seen following i.v. tinzaparin. In the s.c. groups 60-65% of the observed peak anti-Xa activity was neutralized, anti-IIa was almost completely reversed, and aPTT returned nearly to baseline values. A gradual return of the anti-Xa activity (65-75%), anti-IIa activity (55%) and aPTT activity (35-45%) was seen in the s.c. groups 3 h after reversal compared with the observed peak values. A continuous absorption of tinzaparin from the s.c. depot is presumably the cause of the returned activity. PS caused an 8-27% transient drop in the platelet count in all groups. This study confirms that the anti-Xa activity following i.v. and s.c. administration of tinzaparin (a LMWH) is only partially neutralizable by protamine. This is not due to insufficient dosages of the antidote, as an excess of protamine could be demonstrated ex vivo immediately after the protamine infusion. The present results suggest that protamine neutralization of tinzaparin given s.c. should be obtained with intermittent injections or continuous infusion.
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- Nielsen, B. Bech, et al.
(author)
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Observation and theory of the H2* defect in silicon
- 1994
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In: Proceedings of the 17th International Conference on Defects in Semiconductors. - : Trans Tech Publications Inc.. ; , s. 845-852
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Conference paper (peer-reviewed)
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