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- Littleton, JM, et al.
(författare)
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Challenges to medications development in treating alcohol dependence: An international perspective - Summary of a symposium held at the ESBRA Congress, Prague, 13 September 2003
- 2004
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Ingår i: Alcohol and Alcoholism. - : Oxford University Press (OUP). - 1464-3502. ; 39:4, s. 271-275
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Tidskriftsartikel (refereegranskat)abstract
- Few medications for treating alcohol dependence exist. Greater partnership is needed between academia and the pharmaceutical industry to develop, licence and market efficacious medications for treating alcohol dependence. Methodologies that span the divide between preclinical and large-scale clinical studies need to be developed in order to provide sufficient information on safety, toleration, drug-interaction profile and efficacy, with which to guide development decisions. Due to the heterogeneous nature of alcohol dependence, the effort of developing an efficacious medication is likely to be enhanced by clearer choices about the characteristics of the population. Careful consideration of potential mechanism of action of the putative therapeutic medication should enable the appropriate choice of drinking endpoint. The pharmaceutical industry in collaboration with academia might need to develop new approaches to determining appropriate treatment endpoints with regulatory bodies. The investment risk to industry should be appraised not only in terms of the rather poor results of previous marketing efforts but with a view to the opportunity to penetrate a potentially enormous and largely untapped market.
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| 4. |
- Witte, V, et al.
(författare)
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HIV-1 Nef mimics an integrin receptor signal that recruits the polycomb group protein Eed to the plasma membrane
- 2004
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Ingår i: Molecular Cell. - 1097-4164. ; 13:2, s. 179-190
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Tidskriftsartikel (refereegranskat)abstract
- The Nef protein of human and simian immunodeficiency virus (HIV/SIV) is believed to interfere with T cell activation signals by forming a signaling complex at the plasma membrane. Composition and function of the complex are not fully understood. Here we report that Nef recruits the Polycomb Group (PcG) protein Eed, so far known as a nuclear factor and repressor of transcription, to the membrane of cells. The Nef-induced translocation of Eed led to a potent stimulation of Tat-dependent HIV transcription, implying that Eed removal from the nucleus is required for optimal Tat function. Similar to Nef action, activation of integrin receptors recruited Eed to the plasma membrane, also leading to enhanced Tat/Nef-mediated transcription. Our results suggest a link between membrane-associated activation processes and transcriptional derepression and demonstrate how HIV exploits this mechanism.
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- Gahn, C, et al.
(författare)
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Generation of MeV electrons and positrons with femtosecond pulses from a table-top laser system
- 2002
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Ingår i: Physics of Plasmas. - : AIP Publishing. - 1070-664X .- 1089-7674. ; 9:3, s. 987-999
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Tidskriftsartikel (refereegranskat)abstract
- In experiments, the feasibility was demonstrated of generating multi-MeV electrons in a form of a collimated beam utilizing a table-top laser system delivering 200 fs pulses with P-L=1.2 TW and 10 Hz capability. The method uses the process of relativistic self-channeling in a high-density gas jet producing electron densities in the range of 3x10(19)-6x10(20) cm(-3). In a thorough investigation, angularly resolved and absolutely calibrated electron spectra were measured and their dependence on the plasma density, laser intensity, and gas medium was studied. For the optimum electron density of n(e)=2x10(20) cm(-3) the effective temperature of the electron energy distribution and the channel length exhibit a maximum of 5 MeV and 400 mum respectively. The laser-energy to-MeV-electron efficiency is estimated to be 5%. In a second step, utilizing the multi-MeV electron beam anti-particles, namely positrons, were successfully generated in a 2 mm Pb converter. The average intensity of this new source of positrons is estimated to be equivalent to a radioactivity of 2x10(8) Bq and it exhibits a very favorable scaling for higher laser intensities. (C) 2002 American Institute of Physics.
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| 7. |
- Hellman, Per, et al.
(författare)
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Follicular thyroid carcinoma
- 2000
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Ingår i: Surgical Endocrinology. - : Lippincott W & W. ; , s. 75-
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 8. |
- Simonsson, Bengt, et al.
(författare)
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Roquinimex (Linomide) vs placebo in AML after autologous bone marrow transplantation
- 2000
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Ingår i: Bone Marrow Transplantation. - 0268-3369 .- 1476-5365. ; 25:11, s. 1121-1127
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Tidskriftsartikel (refereegranskat)abstract
- Roquinimex, Linomide, a quinoline derivative with pleiotropic immunomodulatory activity, has previously been shown to enhance natural killer (NK) cell number and activity after ABMT in patients with AML. In this study 278 AML patients in remission were randomized to receive Roquinimex 0.2 mg/kg body weight or placebo twice weekly for 2 years following ABMT. Out of 139 patients in each group, 109 Roquinimex patients and 108 placebo patients were in their first CR. Median age at inclusion was 41 years for Roquinimex patients and 39 years for placebo patients. Twelve patients in each group had their marrow purged prior to reinfusion. Relapse and death were study endpoints. Surviving patients were followed for 2.6 to 6. 9 years. The total number of relapses was 60 in the Roquinimex group and 63 in the placebo group (not significant). Leukemia-free and overall survivals were similar in the two groups. Recovery of platelet counts was significantly delayed in the Roquinimex group as compared to placebo. No other significant differences regarding toxicity parameters were recorded. In conclusion, previous findings on NK cells could not be confirmed and the study showed no benefit for Roquinimex over placebo regarding relapse or survival following ABMT for AML in remission.
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