Identification of a novel loss-of-function PHEX mutation, Ala720Ser, in a sporadic case of adult-onset hypophosphatemic osteomalacia

Adults presenting with sporadic hypophosphatemia and elevations in circulating fibroblast growth factor-23 (FGF23) concentrations are usually investigated for an acquired disorder of FGF23 excess such as tumor induced osteomalacia (TIO). However, in some cases the underlying tumor is not detected, and such patients may harbor other causes of FGF23 excess. Indeed, coding-region and 3’UTR mutations of phosphate-regulating neutral endopeptidase (PHEX), which encodes a cell-surface protein that regulates circulating FGF23 concentrations, can lead to alterations in phosphate homeostasis, which are not detected until adulthood. Here, we report an adult female who presented with hypophosphatemic osteomalacia and raised serum FGF23 concentrations. The patient and her parents, who were her only first-degree relatives, had no history of rickets. The patient was thus suspected of having TIO. However, no tumor had been identified following extensive localization studies. Mutational analysis of the PHEX coding-region and 3’UTR was undertaken, and this revealed the patient to be heterozygous for a novel germline PHEX mutation (c.2158G>T; p.Ala720Ser). In vitro studies involving the expression of WT and mutant PHEX proteins in HEK293 cells demonstrated the Ala720Ser mutation to impair trafficking of PHEX, with 80% cell surface expression for WT PHEX (p<0.05). Thus, our studies have identified a pathogenic PHEX mutation in a sporadic case of adult-onset hypophosphatemic osteomalacia, and these findings highlight a role for PHEX gene analysis in some cases of suspected TIO, particularly when no tumor has been identified

Survival of Enterococcus faecalis in root canals ex vivo

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72532/1/j.1365-2591.2005.01009.x.pd

Identifying novel genetic determinants of hemostatic balance

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73734/1/j.1538-7836.2005.01461.x.pd

Genetic regulation of plasma von Willebrand factor levels: quantitative trait loci analysis in a mouse model

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72680/1/j.1538-7836.2007.02325.x.pd

Selection on cis-Regulatory Variation at B4galnt2 and Its Influence on von Willebrand Factor in House Mice

The RIIIS/J inbred mouse strain is a model for type 1 von Willebrand disease (VWD), a common human bleeding disorder. Low von Willebrand factor (VWF) levels in RIIIS/J are due to a regulatory mutation, Mvwf1, which directs a tissue-specific switch in expression of a glycosyltransferase, B4GALNT2, from intestine to blood vessel. We recently found that Mvwf1 lies on a founder allele common among laboratory mouse strains. To investigate the evolutionary forces operating at B4galnt2, we conducted a survey of DNA sequence polymorphism and microsatellite variation spanning the B4galnt2 gene region in natural Mus musculus domesticus populations. Two divergent haplotypes segregate in these natural populations, one of which corresponds to the RIIIS/J sequence. Different local populations display dramatic differences in the frequency of these haplotypes, and reduced microsatellite variability near B4galnt2 within the RIIIS/J haplotype is consistent with the recent action of natural selection. The level and pattern of DNA sequence polymorphism in the 5′ flanking region of the gene significantly deviates from the neutral expectation and suggests that variation in B4galnt2 expression may be under balancing selection and/or arose from a recently introgressed allele that subsequently increased in frequency due to natural selection. However, coalescent simulations indicate that the heterogeneity in divergence between haplotypes is greater than expected under an introgression model. Analysis of a population where the RIIIS/J haplotype is in high frequency reveals an association between this haplotype, the B4galnt2 tissue-specific switch, and a significant decrease in plasma VWF levels. Given these observations, we propose that low VWF levels may represent a fitness cost that is offset by a yet unknown benefit of the B4galnt2 tissue-specific switch. Similar mechanisms may account for the variability in VWF levels and high prevalence of VWD in other mammals, including humans

Cross-sectional evaluation of the periapical status as related to quality of root canal fillings and coronal restorations in a rural adult male population of Turkey

<p>Abstract</p> <p>Background</p> <p>To determine the prevalence of periapical lesions in root canal-treated teeth in a rural, male adult, Turkish population and to investigate the influence of the quality of root canal fillings on prevalence of periapical lesions.</p> <p>Methods</p> <p>The sample for this cross-sectional study consisted of 552 adult male patients, 18-32 years of age, presenting consecutively as new patients seeking routine dental care at the Dental Sciences of Gulhane Military Medicine, Ankara. The radiographs of the 1014 root canal-treated teeth were evaluated. The teeth were grouped according to the radiographic quality of the root canal filling and the coronal restoration. The criteria used for the examination were slightly modified from those described by De Moor. Periapical status was assessed by the Periapical Index scores (PAI) proposed by Orstavik.</p> <p>Results</p> <p>The overall success rate of root canal treatment was 32.1%. The success rates of adequately root canal treatment were significantly higher than inadequately root canal treatment, regardless of the quality or presence of the coronal restoration (P < .001). In addition, the success rate of inadequate root canal treatment was also significantly affected by the quality of coronal restorations.</p> <p>Conclusions</p> <p>Our results revealed a high prevalence of periapical lesions in root canal treatment, which is comparable to that reported in other methodologically compatible studies from diverse geographical locations. In addition, the results from the present study confirm the findings of other studies that found the quality of the root canal treatment to be a key factor for prognosis with or without adequate coronal restoration.</p

Interference of partial visual analysis of root filling quality and apical status on retreatment decisions

OBJECTIVE: The presence of periapical radiolucency has been used as a criterion for endodontic treatment failure. However, in addition to the inherent limitations of radiographic examinations, radiographic interpretations are extremely subjective. Thus, this study investigated the effect of partial analysis of root filling quality and periapical status on retreatment decisions by general dentists. MATERIAL AND METHODS: Twelve digitalized periapical radiographs were analyzed by 10 observers. The study was conducted at three time points at 1-week intervals. Radiographs edited with the Adobe Photoshop CS4 software were analyzed at three time points: first, only root filling quality was analyzed; second, only the periapical areas of the teeth under study were visualized; finally, observers analyzed the unedited radiographic image. Spearman's coefficient was used to analyze the correlations between the scores assigned when the periapical area was not visible and when the unedited radiograph was analyzed, as well as between the scores assigned when root fillings where not visible and when the unedited radiograph was analyzed. Sensitivity, specificity, positive and negative predictive values between partial images and unedited radiographs were also used to analyze retreatment decisions. The level of significance was set at 5%. RESULTS: The visualization of the root filling on the unedited radiograph affected the interpretation of the periapical status and the technical quality of the fillings has a greater influence on the general dentist's decision to prescribe endodontic retreatment than the periapical condition. CONCLUSION: In order to make endodontic diagnosis, radiographic interpretation process should not only emphasize technical aspects, but also consider biological factors

Организация бухгалтерского учета основных средств на медеплавильном заводе АО «АГМК»

Объектом исследования является акционерное общество "Алмалыкский ГМК". Целью работы – учет основных производственных фондов акционерного общества "Алмалыкский ГМК", а также разработка рекомендаций по улучшению их использования. Предмет исследования - учет основных средств на АО "Алмалыкский ГМК".The object of research is the joint stock company "Almalyk MMC". The aim of the work is to record fixed assets of Almalyk GMK joint – stock company, as well as to develop recommendations for improving their use. The subject of the research is the accounting of fixed assets at JSC "Almalyk MMC"

Notch 1 Receptor, Delta 1 Ligand and HES 1 Transcription Factor are Expressed in the Lining Epithelium of Periapical Cysts (Preliminary Study)

Periapical cyst is a chronic inflammatory disorder of periradicular tissues. The precise pathological mechanisms involved in periapical cyst enlargement remain unclear. Notch signaling is an evolutionarily conserved pathway with a regulatory role in cell fate decisions during development and in carcinogenesis. To date, there are no published data available on the expression of Notch signaling components in periapical cysts or any other jaw cyst. In this immunohistochemical study we have examined the expression of the receptor Notch 1, the ligand Delta 1 and the transcription factor HES 1 in the epithelium of well defined periapical cysts. Immunostaining reaction of Notch 1, Delta 1 and HES 1 was observed in the cytoplasm and/or the cytoplasmic membrane and occasionally in the nucleus in the majority of epithelial cells of all periapical cysts. The present observations indicate that Notch pathway is active in the epithelium of periapical cysts. It can be speculated that activation of epithelial cells of periapical cysts is associated with activation of Notch pathway and imply involvement of this pathway in periapical cyst growth and expansion