Does enamelin have pleiotropic effects on organs other than the teeth? Lessons from a phenotyping screen of two enamelin‐mutant mouse lines

We analyzed two mutant mouse lines, ATE1 and ATE2, that carry point mutations in the enamelin gene which result in premature stop codons in exon 8 and exon 7, respectively. Both mutant lines show amelogenesis imperfecta. To establish the effect of mutations within the enamelin gene on different organs, we performed a systematic, standardized phenotypic analysis of both mutant lines in the German Mouse Clinic. In addition to the initially characterized tooth phenotype that is present in both mutant lines, we detected effects of enamelin mutations on bone and energy metabolism, as well as on clinical chemical and hematological parameters. These data raise the hypothesis that enamelin defects have pleiotropic effects on organs other than the teeth.     

荷瘤鼠及口腔癌患者热化疗前后T淋巴细胞亚群、白细胞介素-2和肿瘤坏死因子-α水平的变化

目的探讨荷瘤鼠及口腔癌患者热化疗前后T淋巴细胞亚群、白细胞介素（IL）-2和肿瘤坏死因子（TNF）-α活性水平的变化,并初步探讨三者之间的相关性。方法经热化疗处理后,采用甲基噻唑基四唑（MTT）法检测荷瘤鼠淋巴细胞转化指数（LTI）及IL-2、TNF-α水平,MTT法检测口腔癌患者IL-2、TNF-α水平,并采用3H-胸腺嘧啶核苷（3H-TdR）掺入法行淋巴细胞转化实验及CD4+、CD8+ T细胞亚群检测。结果高温联合平阳霉素治疗组（HP组）荷瘤鼠LTI、IL-2和TNF-α活性与正常对照组（N组）荷瘤鼠差异无统计学意义（P>0.05）,而明显高于平阳霉素治疗组（P组）及不治疗组（NT组）（P<0.01）。临床实验中热化疗后口腔癌患者LTI、CD4+细胞数目及CD4+/CD8+比值明显提高,IL-2和TNF-α活性水平明显升高（P<0.01）。结论荷瘤宿主的LTI及IL-2和TNF-α活性水平在热化疗后明显升高,IL-2和T细胞之间有明显的相关性。     

Long-term bonding to eroded dentin requires superficial bur preparation

Objectives

This study aims to evaluate the influence of different surface preparation techniques on long-term bonding effectiveness to eroded dentin.

Materials and methods

Dentin specimens were eroded by pH cycling or were left untreated as control, respectively. Five different “preparation” techniques were applied: (1) cleaning with pumice, (2) air abrasion, (3) silicon polisher, (4) proxo-shape, and (5) diamond bur. The three-step etch-and-rinse adhesive OptiBond FL (O-FL; Kerr) and the mild two-step self-etch adhesive Clearfil SE Bond (C-SE; Kuraray) were evaluated. Micro-tensile bond strength was measured after water storage for 24?h and 1?year. Fracture analysis was performed by stereomicroscopy and SEM. Interfaces were characterized by TEM. Differences were statistically analyzed with a linear mixed effects model (α?=?0.05).

Results

Erosion reduced bond strength in all groups, but this effect was less prominent when eroded dentin was prepared by diamond bur. Storage lowered bond strength in almost all groups significantly, but this ageing effect was more prominent for the eroded surfaces than for non-eroded controls. Whereas after 1-year control specimens revealed superior bond strength with the three-step etch-and-rinse adhesive (O-FL), the mild two-step self-etch adhesive (C-SE) revealed a better 1-year bond strength to eroded dentin. The interface at eroded dentin appeared very prone to degradation as was shown by the increased amount of adhesive failures and by the silver infiltration detected by TEM.

Conclusions and clinical relevance

Although a minimally invasive approach should clinically always be strived for, superficial preparation (or minimal roughening) with a diamond bur is recommendable for long-term bonding to eroded dentin.     

A 13-year clinical evaluation of two three-step etch-and-rinse adhesives in non-carious class-V lesions

This 13-year randomized clinical trial compared the clinical effectiveness of two three-step etch-and-rinse adhesives in combination with a hybrid, stiffer composite versus a micro-filled, more flexible composite. The influence of composite stiffness on the clinical performance of one of the adhesives was assessed as well. One hundred and forty-two non-carious cervical lesions were restored with composites with contrasting stiffness. Seventy-one patients randomly received two cervical restorations placed following two out of three adhesive procedures: (1) the three-step etch-and-rinse adhesive Permaquick applied with the stiff micro-hybrid composite Amelogen Hybrid (PMQ-H, Ultradent), (2) Permaquick applied with the more flexible micro-filled Amelogen Microfill (PMQ-M, Ultradent), or (3) the “gold-standard” three-step etch-and-rinse adhesive Optibond FL applied with the micro-hybrid composite Prodigy (OFL-P, Kerr). The restorations were evaluated after 6 months, 1, 2, 3, 5, 7, and 13 years of clinical service regarding their retention, marginal integrity and discoloration, caries occurrence, preservation of tooth vitality, and post-operative sensitivity. Retention loss, severe marginal defects, and/or discoloration that needed intervention (repair or replacement) and the occurrence of caries were considered as clinical failures. The recall rate at 13 years was 77%. Bond degradation after 13 years was mainly characterized by a further increase in the presence of small but clinically acceptable marginal defects and superficial marginal discoloration. Twelve percent of the OFL-P restorations were clinically unacceptable. In the PMQ group, 22% of the PMQ-M restorations and 26% of the PMQ-H restorations needed repair or replacement. Regarding the clinical failure rate, Optibond FL scored significantly better than Permaquick (McNemar; p = 0.015). No statistically significant differences were found between the micro-filled and the hybrid composite for each of the parameters evaluated (McNemar, p > 0.05). After 13 years of clinical functioning, the clinical effectiveness of the three adhesive/composite combinations remained highly acceptable.     

High-resolution genomic profiling of adult and pediatric core-binding factor acute myeloid leukemia reveals new recurrent genomic alterations

To identify cooperating lesions in core-binding factor acute myeloid leukemia, we performed single-nucleotide polymorphism-array analysis on 300 diagnostic and 41 relapse adult and pediatric leukemia samples. We identified a mean of 1.28 copy number alterations per case at diagnosis in both patient populations. Recurrent minimally deleted regions (MDRs) were identified at 7q36.1 (7.7%), 9q21.32 (5%), 11p13 (2.3%), and 17q11.2 (2%). Approximately one-half of the 7q deletions were detectable only by single-nucleotide polymorphism-array analysis because of their limited size. Sequence analysis of MLL3, contained within the 7q36.1 MDR, in 46 diagnostic samples revealed one truncating mutation in a leukemia lacking a 7q deletion. Recurrent focal gains were identified at 8q24.21 (4.7%) and 11q25 (1.7%), both containing a single noncoding RNA. Recurrent regions of copy-neutral loss-of-heterozygosity were identified at 1p (1%), 4q (0.7%), and 19p (0.7%), with known mutated cancer genes present in the minimally altered region of 1p (NRAS) and 4q (TET2). Analysis of relapse samples identified recurrent MDRs at 3q13.31 (12.2%), 5q (4.9%), and 17p (4.9%), with the 3q13.31 region containing only LSAMP, a putative tumor suppressor. Determining the role of these lesions in leukemogenesis and drug resistance should provide important insights into core-binding factor acute myeloid leukemia.