Biomedical subjects

Eric T Everett

Publications and source records attributed to Eric T Everett.

4 recordsLinked to original sources

PubMed2005

Root resorption associated with orthodontic force in inbred mice: genetic contributions.

Root resorption (RR) is an unwanted sequela of orthodontic treatment. Despite rigorous investigation, no single factor or group of factors that directly causes RR has been identified. The purpose of this study was to examine the effect of the genotype on susceptibility or resistance to develop RR secondary to orthodontic force. Nine-week-old male mice from eight inbred strains were used and randomly distributed into control (C) or treatment (T) groups as follows: A/J (C = 9,T = 9), C57BL/6J (C = 7,T = 8), C3H/HeJ (C = 8,T = 6), BALB/cJ (C = 8,T = 6), 129P3/J (C = 6,T = 8), DBA/2J (C = 8,T = 9), SJL/J (C = 8,T = 10), and AKR/J (C = 9,T = 8). Each of the treated mice received an orthodontic appliance to tip the maxillary left first molar mesially for 9 days. Histological sections of the tooth were used to determine RR and tartrate resistant acid phosphatase (TRAP) activity. The Wilcoxon ranked-sum non-parametric test was used to evaluate differences between the groups. The results showed that the DBA/2J, BALB/cJ, and 129P3/J inbred mouse strains are highly susceptible to RR, whereas A/J, C57BL/6J and SJL/J mice are much more resistant. The variation in the severity of RR associated with orthodontic force among different inbred strains of mice when age, gender, food, housing, and orthodontic force magnitude/duration are controlled support the hypothesis that susceptibility or resistance to RR associated with orthodontic force is a genetically influenced trait.

Acid Phosphatase↗

PubMed2005

Fluoride induces endoplasmic reticulum stress in ameloblasts responsible for dental enamel formation.

The mechanism of how fluoride causes fluorosis remains unknown. Exposure to fluoride can inhibit protein synthesis, and this may also occur by agents that cause endoplasmic reticulum (ER) stress. When translated proteins fail to fold properly or become misfolded, ER stress response genes are induced that together comprise the unfolded protein response. Because ameloblasts are responsible for dental enamel formation, we used an ameloblast-derived cell line (LS8) to characterize specific responses to fluoride treatment. LS8 cells were growth-inhibited by as little as 1.9-3.8 ppm fluoride, whereas higher doses induced ER stress and caspase-mediated DNA fragmentation. Growth arrest and DNA damage-inducible proteins (GADD153/CHOP, GADD45alpha), binding protein (BiP/glucose-responsive protein 78 (GRP78), the non-secreted form of carbonic anhydrase VI (CA-VI), and active X-box-binding protein-1 (Xbp-1) were all induced significantly after exposure to 38 ppm fluoride. Unexpectedly, DNA fragmentation increased when GADD153 expression was inhibited by short interfering RNA treatment but remained unaffected by transient GADD153 overexpression. Analysis of control and GADD153(-/-) embryonic fibroblasts demonstrated that caspase-3 mediated the increased DNA fragmentation observed in the GADD153 null cells. We also demonstrate that mouse incisor ameloblasts are sensitive to the toxic effects of high dose fluoride in drinking water. Activated Ire1 initiates an ER stress response pathway, and mouse ameloblasts were shown to express activated Ire1. Ire1 levels appeared induced by fluoride treatment, indicating that ER stress may play a role in dental fluorosis. Low dose fluoride, such as that present in fluoridated drinking water, did not induce ER stress.

Ameloblasts↗

PubMed2003

Genetic predisposition to external apical root resorption.

External apical root resorption (EARR) can be an undesirable sequela of orthodontic treatment. Previous studies have suggested that EARR has a substantial genetic component. Linkage and association were examined between polymorphisms of the interleukin IL-1 (IL-1A and IL-1B) genes and EARR in 35 white American families. Buccal swab cells were collected for DNA isolation and analysis. The EARR in the maxillary central incisors, the mandibular central incisors, and the mesial and distal roots of the mandibular first molar were analyzed separately and together by using both linkage and association methods of analysis. Highly significant (P =.0003) evidence of linkage disequilibrium of IL-1B polymorphism with the clinical manifestation of EARR was obtained. The analysis indicates that the IL-1B polymorphism accounts for 15% of the total variation of maxillary incisor EARR. Persons homozygous for the IL-1B allele 1 have a 5.6 fold (95% CI 1.9-21.2) increased risk of EARR greater than 2 mm as compared with those who are not homozygous for the IL-1 beta allele 1. Data indicate that allele 1 at the IL-1B gene, known to decrease the production of IL-1 cytokine in vivo, significantly increases the risk of EARR. These findings are consistent with an interpretation of EARR as a complex condition influenced by many factors, with the IL-1B gene contributing an important predisposition to this common problem. Defining genetic contributions to EARR is an important factor in understanding the contribution of environmental factors, such as habits and therapeutic biomechanics.

Alleles↗

PubMed2002

Polymorphisms of xenobiotic metabolizing genes in oropharyngeal carcinoma.

OBJECTIVE: The objective was to determine the prevalence of the polymorphisms of the microsomal epoxide hydrolase (Ephx1), glutathione S-transferase mu1 (GSTM ), theta1 (GSTT1), and pi1 (GSTP1) genes in patients with oropharyngeal carcinoma. STUDY DESIGN: Gene polymorphisms in 137 patients with oropharyngeal carcinoma were determined by polymerase chain reaction and restriction enzyme digestion for xenobiotic metabolizing enzymes that have been implicated in the carcinogenesis of tobacco-related neoplasias and compared with a population sample of 99 persons. RESULTS: At Ephx1 (microsomal epoxide hydrolase) codon 113, an overrepresentation of the greater activity genotype (Tyr/Tyr) was observed for male ever-smokers alone, both male and female ever-smokers, female never-smokers alone, and in both male and female never-smokers, compared with a control population sample. At codon 139, Ephx1 showed no differences. There was an overrepresentation of homozygosity for the GSTT1 (glutathione S-transferase theta1) null allele [but not for the GSTM1 (glutathione S-transferase mu1) null allele] in ever-smokers, when compared with controls. Polymorphisms at the GSTP1 (glutathione S-transferase pi1) locus did not show differences versus controls, although in the never-smoker cancer sample there was a higher prevalence of the B/B genotype compared with ever-smokers. CONCLUSION: The Ephx1 codon 113 Tyr/Tyr variant, as well as homozygosity for the GSTT1 null allele, is associated with oropharyngeal carcinogenesis.

Adult↗