Species Differences of Serum Albumins: II. Chemical and Thermal Stability

Purpose. The chemical and thermal stability of five species of mammalian serum albumins (human, bovine, dog, rabbit, and rat) were investigated, and conformational stabilities were compared to obtain structural information about the different albumins. Methods. The chemical stability was estimated by using guanidine hydrochloride (GdnCl), and monitored by fluorometry and circular dichroism (CD). Thermal stability was evaluated by differential scanning calorimetry (DSC). Results. In human, bovine, and rat albumin, two transitions were observed when GdnCl-induced denaturation was monitored fluorometrically, indicating at least one stable intermediate, although, in dog and rabbit albumin, only one transition was observed. However, GdnCl denaturation, as monitored by the ellipticity, showed a two-state transition in all species used in this study. Since these proteins, showing two transitions, contained a conserved tryptophan residue within domain II, these structural changes might have occurred in domain II during intermediate formation. DSC measurements showed that human, bovine, and rat albumin exhibited single sharp endotherms and these were clearly consistent with a two-state transition, while the deconvolution analysis of broad thermograms observed for dog and rabbit albumin showed that the absorption peaks could be approximated by a two-component composition, and were consistent with independent transitions of two different cooperative blocks. Conclusions. These experimental results demonstrate that species differences exist with respect to the conformational stability and the mechanism of the unfolding pathway for mammalian albumin.     

Care programme and barriers by apprentices

About 126 apprentices were questioned for their knowledge and habits regarding oral health to clarify motives and hindrances, to improve the dental care programme and to attain changes of their behaviour. Good expedient and methods for improving oral health of apprentices should be--in addition to regular check up--attractive lectures and discourses, instructed training of brushing, acceptance of the individuality of the apprentices, influence of fluoride application and measures and guidelines of feeding.     

SIRT1/HERC4 Locus Associated With Bisphosphonate‐Induced Osteonecrosis of the Jaw: An Exome‐Wide Association Analysis

Osteonecrosis of the jaw (ONJ) is a rare, but serious drug side effect, mainly associated with the use of intravenous (iv) bisphosphonates (BPs). The purpose of this study was to identify genetic variants associated with ONJ in patients of European ancestry treated with iv BPs using whole‐exome sequencing (WES). The WES phase 1 included 44 multiple myeloma patients (22 ONJ cases and 22 controls) and WES phase 2 included 17 ONJ patients with solid tumors. Multivariable logistic regression analysis was performed to estimate the odds ratios (ORs) and 95% confidence intervals (CI), adjusting for age, sex, and principal components for ancestry. Meta‐analysis of WES phase 1 and 2 was performed to estimate the combined ORs. In silico analyses were then performed to identify expression quantitative loci (eQTL) single‐nucleotide polymorphisms (SNPs) that are in high linkage disequilibrium (LD) with the top SNPs. The associations of the potentially functional SNPs were replicated and validated in an independent case‐control study of 48 patients of European ancestry treated with iv BPs (19 ONJ cases and 29 controls). The top SNPs in the exome‐wide association meta‐analysis were two SNPs on chromosome 10: SIRT1 SNP rs7896005 and HERC4 SNP rs3758392 with identical OR of 0.07 (0.01–0.46; p = 3.83 × 10^?5). In the in silico functional analyses, two promoter region SNPs (rs7894483 and rs3758391) were identified to be in high LD with the index SNPs and are eQTLs for SIRT1 gene in whole blood in the GTEx database. The ORs were 0.30 (0.10–0.88), 0.26 (0.12–0.55), and 0.26 (0.12–0.55) for the WES top SNP rs7896005 and two promoter SNPs rs7894483 and rs3758391, respectively, in the replication sample. In summary, we identified the SIRT1/HERC4 locus on chromosome 10 to be associated with iv BP‐induced ONJ and two promoter SNPs that might be the potential genetic markers for this association. © 2017 The Authors.Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.     

43jährige Patientin mit unklarem undulierendem Fieber und Abdominalbeschwerden

Zusammenfassung Eine seit Jahren in Deutschland lebende, 43j?hrige türkische Patientin stellte sich nach Auslandsaufenthalt in der Türkei mit wiederholt aufgetretenen Episoden von undulierendem Fieber, Arthralgien, Durchf?llen und krampfartigen Abdominalbeschwerden zur weiteren Abkl?rung vor. Klinisch imponierten der reduzierte Allgemeinzustand und eine Leukopenie mit relativer Lymphozytose. Eine generalisierte Lymphknotenschwellung oder Hepatosplenomegalie traten nicht auf. In der Blutkultur war Brucella melitensis Biotyp 3 als urs?chlicher Erreger nachweisbar. Die Serologie für Brucella abortus und Brucella melitenis war positiv. Auch wenn in Deutschland die Rinderbest?nde Brucellose-frei sind und die Brucellose insgesamt in Deutschland sehr selten ist, sollte durch die hohe Mobilit?t der Bev?lkerung eine solche Diagnose im klinischen Alltag mit in Betracht gezogen werden. In den Mittelmeerl?ndern ist die Inzidenz durch Kontakt sowie übertragung von infizierten Milch- oder Fleischprodukten erh?ht. Somit kann ein wochen- oder monatelang anhaltendes, undulierendes Fieber bei Patienten mit anamnestisch bekanntem Auslandsaufenthalt an eine Brucellose denken lassen. Wenn die serologische Diagnose nicht immer zum Ziel führt, ist eine Erregeranzüchtung in der Blutkultur oder eine histologische Aufarbeitung geschwollener Lymphknoten oder betroffener Organe angezeigt. Therapie der ersten Wahl ist die Kombinationstherapie eines Tetrazyklins mit einem Aminoglykosid. Bei rekurrenten oder chronischen Verl?ufen sollte nach der Auswahl anhand des Antibiogramms eine weitere Kombination zellg?ngiger Antibiotika konsequent für 6 Wochen eingesetzt werden.