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11.
Giang E Dorner M Prentoe JC Dreux M Evans MJ Bukh J Rice CM Ploss A Burton DR Law M 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(16):6205-6210
Hepatitis C virus (HCV) infects ~2% of the world's population. It is estimated that there are more than 500,000 new infections annually in Egypt, the country with the highest HCV prevalence. An effective vaccine would help control this expanding global health burden. HCV is highly variable, and an effective vaccine should target conserved T- and B-cell epitopes of the virus. Conserved B-cell epitopes overlapping the CD81 receptor-binding site (CD81bs) on the E2 viral envelope glycoprotein have been reported previously and provide promising vaccine targets. In this study, we isolated 73 human mAbs recognizing five distinct antigenic regions on the virus envelope glycoprotein complex E1E2 from an HCV-immune phage-display antibody library by using an exhaustive-panning strategy. Many of these mAbs were broadly neutralizing. In particular, the mAb AR4A, recognizing a discontinuous epitope outside the CD81bs on the E1E2 complex, has an exceptionally broad neutralizing activity toward diverse HCV genotypes and protects against heterologous HCV challenge in a small animal model. The mAb panel will be useful for the design and development of vaccine candidates to elicit broadly neutralizing antibodies to HCV. 相似文献
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Banar Nikolay Bertels Jeroen Laurent François Boedi Rizky Merdietio De Tobel Jannick Thevissen Patrick Vandermeulen Dirk 《International journal of legal medicine》2020,134(5):1831-1841
International Journal of Legal Medicine - Staging third molar development is commonly used for age assessment in sub-adults. Current staging techniques are, at most, semi-automated and rely on... 相似文献
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Franoise M. Brunelle Araz A. Raoof Jean De Ville De Goyet Roger K. Verbeeck 《Biopharmaceutics & drug disposition》1996,17(4):311-317
In vitro glucuronidation was studied in liver microsomes from two patients with Crigler–Najjar type I (CN-I) disease and compared with the activity measured in microsomes prepared from six control human livers. The UDP-glucuronosyltransferase (UGT) activity was determined toward the following substrates: 4-nitrophenol, propofol, (−)-morphine (formation of the 3-glucuronide), and diflunisal (formation of the phenolic and acyl glucuronides). Glucuronidation of 4-nitrophenol was reduced in one of the CN-I livers (CN-I No. 1) (0·9 nmol min−1 mg−1) and normal in the other CN-I liver (CN-I No. 2) (3.5 nmol min−1 mg−1) compared to the control livers (5·6±2·9 nmol min−1 mg−1, mean±S.D.). Propofol glucuronidation was not detectable (i.e. less than 0·100 nmol min−1 mg−1) in the CN-I No. 1 liver and normal in the CN-I No. 2 liver (1·78 nmol min−1 mg−1 against 1·52±0·72 nmol min−1 mg−1 in the control livers). The glucuronidation of (−)-morphine to the 3-glucuronide and the formation of the phenolic and acyl glucuronides of diflunisal were normal in both CN-I livers compared to the control livers. Our results show that CN-I patients are heterogeneous regarding UGT activity toward the phenolic substances 4-nitrophenol and propofol. 相似文献
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Dorte Schou Nrxe Aidan Flynn Christina Westmose Yde Olga
strup Finn Cilius Nielsen Jane SkjthRasmussen Jannick Brennum Petra Hamerlik Joachim Weischenfeldt Hans Skovgaard Poulsen Ulrik Lassen 《Molecular oncology》2022,16(1):206
Treatment of glioblastoma (GBM) remains a challenging task, with limited treatment options, none offering a cure. Immune therapy has proven effective across different cancers with remarkable response rates. Tumor mutational burden (TMB) is a marker of response, but technical and methodological differences in TMB estimates have made a proper assessment and comparison challenging. Here, we analyzed a prospective collection of paired samples from 35 patients with newly diagnosed GBM, all of whom were wild‐type (WT) for isocitrate dehydrogenase, before and after treatment with radiotherapy and temozolomide. Seven patients (20%) had O6‐methylguanine‐DNA methyltransferase‐methylated tumors. Six patients (17%) had two relapse surgeries, and tissue from all three surgeries was collected. We found that accurate evaluation of TMB was confounded by high variability in the cancer cell fraction of relapse samples. To ameliorate this, we developed a model to adjust for tumor purity based on the relative density distribution of variant allele frequencies in each primary–relapse pair. Additionally, we examined the mutation spectra of shared and private mutations. After tumor purity adjustment, we found TMB comparison reliable in tumors with tumor purity between 15% and 40%, resulting in 27/35 patients (77.1%). TMB remained unchanged from 0.65 mutations per megabase (Mb) to 0.67/Mb before and after treatment, respectively. Examination of the mutation spectra revealed a dominance of C > T transitions at CpG sites in both shared and relapse‐private mutations, consistent with cytosine deamination and the clock‐like mutational signature 1. We present and apply a cellularity correction approach that enables more accurate assessment of TMB in paired tumor samples. We did not find a significant increase in TMB after correcting for cancer cell fraction. Our study raises significant concerns when determining TMB. Although a small sample size, corrected TMB can have a clinical significance when stratifying patients to experimental treatment, for example, immune checkpoint therapy. 相似文献
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Geert Molenberghs Christel Faes Johan Verbeeck Patrick Deboosere Steven Abrams Lander Willem Jan Aerts Heidi Theeten Brecht Devleesschauwer Natalia Bustos Sierra Franoise Renard Sereina Herzog Patrick Lusyne Johan Van der Heyden Herman Van Oyen Pierre Van Damme Niel Hens 《Euro surveillance : bulletin européen sur les maladies transmissibles = European communicable disease bulletin》2022,27(7)
BackgroundCOVID-19 mortality, excess mortality, deaths per million population (DPM), infection fatality ratio (IFR) and case fatality ratio (CFR) are reported and compared for many countries globally. These measures may appear objective, however, they should be interpreted with caution.AimWe examined reported COVID-19-related mortality in Belgium from 9 March 2020 to 28 June 2020, placing it against the background of excess mortality and compared the DPM and IFR between countries and within subgroups.MethodsThe relation between COVID-19-related mortality and excess mortality was evaluated by comparing COVID-19 mortality and the difference between observed and weekly average predictions of all-cause mortality. DPM were evaluated using demographic data of the Belgian population. The number of infections was estimated by a stochastic compartmental model. The IFR was estimated using a delay distribution between infection and death.ResultsIn the study period, 9,621 COVID-19-related deaths were reported, which is close to the excess mortality estimated using weekly averages (8,985 deaths). This translates to 837 DPM and an IFR of 1.5% in the general population. Both DPM and IFR increase with age and are substantially larger in the nursing home population.DiscussionDuring the first pandemic wave, Belgium had no discrepancy between COVID-19-related mortality and excess mortality. In light of this close agreement, it is useful to consider the DPM and IFR, which are both age, sex, and nursing home population-dependent. Comparison of COVID-19 mortality between countries should rather be based on excess mortality than on COVID-19-related mortality. 相似文献
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C Harvengt J P Desager J M Muschart Y B Tjandramaga R Verbeeck R Verberckmoes 《Journal of clinical pharmacology》1975,15(8-9):605-610
Practolol, a recent and more selective beta-adrenergic receptor blocking drug, was given orally as a single dose of 200 mg to seven healthy volunteers and to six patients suffering from severe renal impairment and submitted to the long-term hemodialysis program. The plasma drug decay was markedly slowed and the plasma half-life was prolonged sixfold in the uremic patients in comparison to healthy volunteers. Hemodialysis (8 hours) starting 48 hours after drug intake lowered plasma practolol significantly but transiently. The shorter half-life during hemodialysis and the detection of equally high values of practolol in the ultrafiltrates as in the plasma demonstrate that this drug is readily removable from the plasma. However, the ascending slope of the plasma drug concentration curve which appeared following hemodialysis is suggestive of an incomplete drug removal from the body. 相似文献
20.
Solid solutions of strontium and calcium hydroxyapatite were synthesized by solid-state reaction. Lattice parameters of these compounds were determined using two types of Guinier cameras. They vary linearly with the molar percentage of strontium hydroxyapatite. The distribution of Ca and Sr ions over the fourfold and sixfold positions in the apatite structure was determined by comparing experimental and calculated values for the intensity ratios of suitable reflections. A slight, although significant, preference of Sr for the sixfold position was found. An ideal behavior is predicted for these solid solutions. 相似文献