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Grewe B.,Ruhr University Bochum | Ehrhardt K.,Ruhr University Bochum | Ehrhardt K.,Heinrich Heine University Dusseldorf | Hoffmann B.,Ruhr University Bochum | And 4 more authors.
PLoS ONE | Year: 2012

Background: During the RNA encapsidation process of human immunodeficiency virus (HIV) viral genomic, unspliced RNA (gRNA) is preferentially incorporated into assembling virions. However, a certain amount of spliced viral transcripts can also be detected in viral particles. Recently, we observed that nuclear export of HIV and lentiviral vector gRNA by Rev is required for efficient encapsidation. Since singly-spliced HIV transcripts also contain the Rev-response element (RRE), we investigated if the encapsidation efficiency of RRE-containing spliced HIV-vector transcripts is also increased by the viral Rev protein. Findings: Starting with a lentiviral vector imitating the splicing pattern of HIV, we constructed vectors that express an unspliced transcript either identical in sequence to the singly-spliced or the fully-spliced RNA of the parental construct. After transfection of the different lentiviral vectors cytoplasmic and virion-associated RNA levels and vector titers were determined in the presence and absence of Rev. Rev enhanced the infectious titer of vectors containing an RRE 6 to 37-fold. Furthermore, Rev strongly increased encapsidation efficiencies of all RRE-containing transcripts up to 200-fold. However, a good correlation between encapsidation efficiency and lentiviral vector titer could only be observed for the gRNA. The infectious titer of the vector encoding the fully-spliced RNA without RRE as well as the encapsidation efficiency of all transcripts lacking the RRE was not influenced by Rev. Interestingly, the splicing process itself did not seem to interfere with packaging, since the encapsidation efficiencies of the same RNA expressed either by splicing or as an unspliced transcript did not differ significantly. Conclusions: Rev-mediated nuclear export enhances the encapsidation efficiency of RRE-containing lentiviral vector RNAs independently of whether they have been spliced or not. © 2012 Grewe et al. Source


Schmidt J.J.,Hannover Medical School | Bertram A.,Hannover Medical School | Kuhn-Velten W.N.,Medical Laboratory of Bremen | Suhling H.,Hannover Medical School | And 3 more authors.
Clinical Kidney Journal | Year: 2015

Antidepressants, especially amitriptyline, are among the most frequent drug classes involved in intoxications. Despite its small molecular weight, amitriptyline is not considered to be eliminated by extracorporeal treatment methods due to its high protein binding and large volume of distribution. New high cut-off dialysers have so far not been used for removal of amitriptyline.We report two cases of amitriptyline poisoning in which we measured the amitriptyline elimination using extended high cut-off (HCO) dialysis. Despite dialyser clearances of 33 and 58 mL/min, resulting in the reduction of initial serum concentrations by ∼30%, only 211 and 920 μg of amitryptilin, respectively, (<3% of the ingested amount) could be recovered in the total collected dialysate. Hence, due to the high volume of distribution of amitriptyline, even HCO dialysis does not contribute substantially to the extracorporeal removal of amitryptilin. © 2015 The Author. Source


Weile J.,Institute for Laboratory and Transfusion Medicine | Eickmeyer H.,Heart and Diabetes Center North Rhine Westphalia | Dreier J.,Institute for Laboratory and Transfusion Medicine | Liebke M.,Heart and Diabetes Center North Rhine Westphalia | And 6 more authors.
International Journal of Medical Microbiology | Year: 2013

We report the first documented case of a Mycobacterium tuberculosis transmission by an orthotopic heart transplantation from the donor to the recipient. Mycobacterium tuberculosis positive blood culture showed systemic prevalence of the Mycobacteria, however, prophylactic therapy was able to prevent a clinical manifestation of tuberculosis in the recipient. © 2013 Elsevier GmbH. Source


Arelin V.,Hannover Medical School | Schmidt J.J.,Hannover Medical School | Kayser N.,Hannover Medical School | Kuhn-Velten W.N.,Medical Laboratory of Bremen | And 3 more authors.
Clinical Nephrology | Year: 2016

The synthetic opioid methadone hydrochloride has a low molecular weight of 346 D, a high volume of distribution (4-7 L/kg), and is lipophilic. It is used as an analgesic and for the maintenance treatment of opiate dependence. In drug addicts, methadone is frequently involved in mixed intoxications that can lead to death. Here we present the case of a drug addict in whom a high cut-offdialysis membrane together with extended dialysis was used in the setting of suspected overdose and acute kidney injury. Although the observed dialyzer plasma clearance (31.5 mL/min) and reduction ratio (38%) were higher than previously reported for standard hemodialysis, the total amount of methadone in the spent dialysate after 1 extended dialysis session was quite low. Hence, even extended dialysis with a high cut-offmembrane does not seem to offer a clinically relevant benefit in the setting of overdose for enhanced methadone removal. On the other hand, in patients undergoing high cut-offdialysis for the removal of light chains, methadone could still be used as an analgesic without an additional dose after high cut-offhemodialysis. © 2016 Dustri-Verlag Dr. K. Feistle. Source

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