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101.
Hoffmann L Haussmann U Mueller M Spiekerkoetter U 《Journal of inherited metabolic disease》2012,35(2):269-277
Tandem mass spectrometry-based newborn screening correctly identifies individuals with very long-chain acyl-CoA dehydrogenase
deficiency (VLCADD). However, a great number of healthy individuals present with identical acylcarnitine profiles during catabolism
in the first three days of life. We routinely perform an enzyme activity assay as confirmation analysis in newborns identified
by screening. Whereas VLCAD residual activities of less than 10% are clearly diagnostic and indicate patients at risk of clinical
disease, the clinical relevance of higher residual activities is unclear. In this study we assess the molecular basis in 34
individuals with residual activities of 10-50%. We identify two pathogenic mutations in patients that result in residual activities
as high as 22%, while individuals with residual activities of 25-50% either present with a heterozygous or no mutation in
the VLCAD gene. In addition, confirmed heterozygous parents present with residual activities as low as 32%. 相似文献
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104.
Impaired increase of retinal capillary blood flow to flicker light exposure in arterial hypertension
M Ritt JM Harazny C Ott U Raff P Bauernschubert M Lehmann G Michelson RE Schmieder 《Hypertension》2012,60(3):871-876
We hypothesized that the increase of retinal capillary blood flow (RCF) to flicker light exposure is impaired in subjects with arterial hypertension. In 146 nondiabetic untreated male subjects with (n=50) or without (n=96) arterial hypertension, RCF was measured before and after flicker light exposure noninvasively and in vivo using scanning laser Doppler flowmetry. In addition, in a subgroup of 28 subjects, the change of RCF to flicker light exposure was again assessed during parallel infusion of nitric oxide synthase inhibitor N-monomethyl-l-arginine (L-NMMA). The increase of RCF to flicker light exposure was lower in patients with untreated hypertension compared with normotensive subjects when expressed in absolute terms (7.69±54 versus 27.2±44 AU; P adjusted=0.013) or percent changes (2.95±14 versus 8.33±12%; P adjusted=0.023). Systolic (β=-0.216; P=0.023) but not diastolic blood pressure (β=-0.117; P=0.243) or mean arterial pressure (β=-0.178; P=0.073) was negatively related to the percent change of RCF to flicker light exposure, independently of other cardiovascular risk factors. In the subgroup of 28 subjects, the increase of RCF to flicker light exposure was similar at baseline and during parallel infusion of L-NMMA when expressed in absolute terms (20.0±51 versus 22.6±56 AU; P=0.731) or percent changes (7.12±16 versus 8.29±18%; P=0.607). The increase of RCF to flicker light exposure is impaired in arterial hypertension. In the subgroup of the total study cohort, nitric oxide was not a major determinant of the increase of RCF to flicker light exposure. 相似文献
105.
Hösel M Broxtermann M Janicki H Esser K Arzberger S Hartmann P Gillen S Kleeff J Stabenow D Odenthal M Knolle P Hallek M Protzer U Büning H 《Hepatology (Baltimore, Md.)》2012,55(1):287-297
Adeno-associated viral vectors (rAAV) are frequently used in gene therapy trials. Although rAAV vectors are of low immunogenicity, humoral as well as T cell responses may be induced. While the former limits vector reapplication, the expansion of cytotoxic T cells correlates with liver inflammation and loss of transduced hepatocytes. Because adaptive immune responses are a consequence of recognition by the innate immune system, we aimed to characterize cell autonomous immune responses elicited by rAAV in primary human hepatocytes and nonparenchymal liver cells. Surprisingly, Kupffer cells, but also liver sinusoidal endothelial cells, mounted responses to rAAV, whereas neither rAAV2 nor rAAV8 were recognized by hepatocytes. Viral capsids were sensed at the cell surface as pathogen-associated molecular patterns by Toll-like receptor 2. In contrast to the Toll-like receptor 9-mediated recognition observed in plasmacytoid dendritic cells, immune recognition of rAAV in primary human liver cells did not induce a type I interferon response, but up-regulated inflammatory cytokines through activation of nuclear factor κB. CONCLUSION: Using primary human liver cells, we identified a novel mechanism of rAAV recognition in the liver, demonstrating that alternative means of sensing rAAV particles have evolved. Minimizing this recognition will be key to improving rAAV-mediated gene transfer and reducing side effects in clinical trials due to immune responses against rAAV. 相似文献
106.
Individuals high in schizotypy have been shown to reveal reduced lateralisation in verbal processing which may be influenced by an impaired left hemisphere performance. However, little is known about schizotypy and right hemisphere functions such as emotional perception. The present study focuses on atypical lateralisation in language and emotional prosody in Impulsive Non-conformity (IMP), a specific aspect of schizotypy. A total of 41 participants (20 females) performed a dichotic listening linguistic and emotional prosody task, which typically shows a right ear advantage (REA) and left ear advantage (LEA), respectively. A median split based on the IMP scale included in the Oxford-Liverpool Inventory of Feelings and Experiences was used to divide the sample into high and low scorers. The results revealed a selective reduction of the LEA in the prosody task in high-IMP males. Females high and low in IMP revealed typical lateralisation in both tasks. The results indicate that high-IMP males are especially prone to atypical lateralisation in emotional prosody, which parallels those findings in male patients with schizophrenia. The results suggest similarities in sex-specific atypical brain organisation between schizotypy and schizophrenia. 相似文献
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109.
Karin Hock Christoph Klaus Lukas Unger Christoph Schwarz Ulrike Baranyi Martina Gattringer Elisabeth Schwaiger Fritz Wrba Thomas Wekerle 《Transplant international》2013,26(2):206-218
While costimulation blockade‐based mixed chimerism protocols work well for inducing tolerance in rodents, translation to preclinical large animal/nonhuman primate models has been less successful. One recognized cause for these difficulties is the high frequency of alloreactive memory T cells (Tmem) found in the (pre)clinical setting as opposed to laboratory mice. In the present study, we therefore developed a murine bone marrow transplantation (BMT) model employing recipients harboring polyclonal donor‐reactive Tmem without concomitant humoral sensitization. This model was then used to identify strategies to overcome this additional immune barrier. We found that B6 recipients that were enriched with 3 × 107 T cells isolated from B6 mice that had been previously grafted with Balb/c skin, rejected Balb/c BM despite costimulation blockade with anti‐CD40L and CTLA4Ig (while recipients not enriched developed chimerism). Adjunctive short‐term treatment of sensitized BMT recipients with rapamycin or anti‐LFA‐1 mAb was demonstrated to be effective in controlling Tmem in this model, leading to long‐term mixed chimerism and donor‐specific tolerance. Thus, rapamycin and anti‐LFA‐1 mAb are effective in overcoming the potent barrier that donor‐reactive Tmem pose to the induction of mixed chimerism and tolerance despite costimulation blockade. 相似文献
110.
Anthracnose disease of Proteaceae has in the past chiefly been attributed to infections by C. acutatum, C. boninense and C. gloeosporioides. In the present study, a multi-locus phylogenetic analysis (ACT, CAL, CHS-1, GAPDH, GS, ITS, TUB2) revealed that strains of the C. gloeosporioides complex associated with Proteaceae belong to at least six species. These include C. alienum, C. aotearoa, C. kahawae (subsp. ciggaro), C. siamense, and two new taxa, C. proteae and C. grevilleae. The most economically important pathogen of Proteaceae seems to be C. alienum, and not C. gloeosporioides as previously reported. All taxa associated with Proteaceae are morphologically described on different media in culture, except strains of C. siamense, which proved to be sterile. Furthermore, C. populi is synonymised with C. aenigma. 相似文献