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

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

Prevalence of vertebral fractures in a disease activity steered cohort of patients with early active rheumatoid arthritis

<p>Abstract</p> <p>Objective</p> <p>To determine the prevalence of vertebral fractures (VFs) after 5 years of disease activity score (DAS)-steered treatment in patients with early rheumatoid arthritis (RA) and to investigate the association of VFs with disease activity, functional ability and bone mineral density (BMD) over time.</p> <p>Methods</p> <p>Five-year radiographs of the spine of 275 patients in the BeSt study, a randomized trial comparing four treatment strategies, were used. Treatment was DAS-steered (DAS ≤ 2.4). A height reduction >20% in one vertebra was defined a vertebral fracture. With linear mixed models, DAS and Health Assessment Questionnaire (HAQ) scores over 5 years were compared for patients with and without VFs. With generalized estimating equations the association between BMD and VFs was determined.</p> <p>Results</p> <p>VFs were observed in 41/275 patients (15%). No difference in prevalence was found when stratified for gender, prednisone use and menopausal status. Disease activity over time was higher in patients with VFs, mean difference 0.20 (95% CI: 0.05-0.36), and also HAQ scores were higher, independent of disease activity, with a mean difference of 0.12 (95% CI: 0.02-0.2). Age was associated with VFs (OR 1.06, 95% CI: 1.02-1.09), mean BMD in spine and hip over time were not (OR 95% CI, 0.99: 0.78-1.25 and 0.94: 0.65-1.36, respectively).</p> <p>Conclusion</p> <p>After 5 years of DAS-steered treatment, 15% of these RA patients had VFs. Higher age was associated with the presence of VFs, mean BMD in hip and spine were not. Patients with VFs have greater functional disability over time and a higher disease activity, suggesting that VFs may be prevented by optimal disease activity suppression.</p

The Microfloral Analysis of Secondary Caries Biofilm around Class I and Class II Composite and Amalgam Fillings

<p>Abstract</p> <p>Background</p> <p>Secondary caries is responsible for 60 percent of all replacement restorations in the typical dental practice. The diversity of the bacterial sources and the different types of filling materials could play a role in secondary caries. The aim of this study was to determine and compare the microbial spectrum of secondary caries biofilms around amalgam and composite resin restorations.</p> <p>Methods</p> <p>Clinical samples were collected from freshly extracted teeth diagnosed with clinical secondary caries. Samples were categorized into four groups according to the types of restoration materials and the classification of the cavity. Biofilms were harvested from the tooth-restoration interface using a dental explorer and after dilution were incubated on special agars. The bacteria were identified using the biochemical appraisal system. Statistical calculations were carried out using SPSS11.5 software to analyze the prevalence of the bacteria involved in secondary caries.</p> <p>Results</p> <p>Samples from a total of four groups were collected: two groups were collected from amalgam restorations, each had 21 samples from both Class I and Class II caries; and the other two groups were from composite resin restorations, each had 13 samples from both class I and class II caries. Our results showed: (1) Anaerobic species were dominant in both restoration materials. (2) In terms of the types of individual bacteria, no significant differences were found among the four groups according to the geometric mean of the detected bacteria (P > 0.05). However, there were significant differences among the detected bacteria within each group (P < 0.05). The composition of each bacterium had no statistical difference among the four groups (P > 0.05), but showed significant differences among the detected bacteria in each group (P < 0.05). (3) Among the four groups, there were no significant differences for the detection rate of each bacterium (P > 0.05), however, the detection rate of each bacterium within each group was statistically different among the detected bacteria (P < 0.05).</p> <p>Conclusions</p> <p>The proportion of obligatory anaerobic species was much greater than the facultative anaerobic species in the biofilm of secondary caries. Statistically, the materials of restoration and the location of secondary caries did not show any significant effects on the composition of the microflora.</p

Identification and Characterization of Novel Mutations in the Human Gene Encoding the Catalytic Subunit Calpha of Protein Kinase A (PKA)

The genes PRKACA and PRKACB encode the principal catalytic (C) subunits of protein kinase A (PKA) Cα and Cβ, respectively. Cα is expressed in all eukaryotic tissues examined and studies of Cα knockout mice demonstrate a crucial role for Cα in normal physiology. We have sequenced exon 2 through 10 of PRKACA from the genome of 498 Norwegian donors and extracted information about PRKACA mutations from public databases. We identified four interesting nonsynonymous point mutations, Arg45Gln, Ser109Pro, Gly186Val, and Ser263Cys, in the Cα1 splice variant of the kinase. Cα variants harboring the different amino acid mutations were analyzed for kinase activity and regulatory (R) subunit binding. Whereas mutation of residues 45 and 263 did not alter catalytic activity or R subunit binding, mutation of Ser109 significantly reduced kinase activity while R subunit binding was unaltered. Mutation of Cα Gly186 completely abrogated kinase activity and PKA type I but not type II holoenzyme formation. Gly186 is located in the highly conserved DFG motif of Cα and mutation of this residue to Val was predicted to result in loss of binding of ATP and Mg2+, which may explain the kinetic inactivity. We hypothesize that individuals born with mutations of Ser109 or Gly186 may be faced with abnormal development and possibly severe disease

Mechanosensitivity during lower extremity neurodynamic testing is diminished in individuals with Type 2 Diabetes Mellitus and peripheral neuropathy: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>Type 2 Diabetes Mellitus (T2DM) and diabetic symmetrical polyneuropathy (DSP) impact multiple modalities of sensation including light touch, temperature, position sense and vibration perception. No study to date has examined the mechanosensitivity of peripheral nerves during limb movement in this population. The objective was to determine the unique effects T2DM and DSP have on nerve mechanosensitivity in the lower extremity.</p> <p>Methods</p> <p>This cross-sectional study included 43 people with T2DM. Straight leg raise neurodynamic tests were performed with ankle plantar flexion (PF/SLR) and dorsiflexion (DF/SLR). Hip flexion range of motion (ROM), lower extremity muscle activity and symptom profile, intensity and location were measured at rest, first onset of symptoms (P1) and maximally tolerated symptoms (P2).</p> <p>Results</p> <p>The addition of ankle dorsiflexion during SLR testing reduced the hip flexion ROM by 4.3° ± 6.5° at P1 and by 5.4° ± 4.9° at P2. Individuals in the T2DM group with signs of severe DSP (n = 9) had no difference in hip flexion ROM between PF/SLR and DF/SLR at P1 (1.4° ± 4.2°; paired t-test p = 0.34) or P2 (0.9° ± 2.5°; paired t-test p = 0.31). Movement induced muscle activity was absent during SLR with the exception of the tibialis anterior during DF/SLR testing. Increases in symptom intensity during SLR testing were similar for both PF/SLR and DF/SLR. The addition of ankle dorsiflexion induced more frequent posterior leg symptoms when taken to P2.</p> <p>Conclusions</p> <p>Consistent with previous recommendations in the literature, P1 is an appropriate test end point for SLR neurodynamic testing in people with T2DM. However, our findings suggest that people with T2DM and severe DSP have limited responses to SLR neurodynamic testing, and thus may be at risk for harm from nerve overstretch and the information gathered will be of limited clinical value.</p

Prevalence of apical periodontitis and endodontic treatment in a Kosovar adult population

<p>Abstract</p> <p>Background</p> <p>Despite numerous studies on the prevalence of apical periodontitis (AP) and endodontic treatment in diverse geographical populations, there are currently no data on the prevalence of these conditions in populations of adults native to Kosovo. Therefore, little is known about how widespread these conditions are, and whether there is any correlation between root canal treatment and AP. The purpose of our research was to address this anomaly by investigating AP and endodontic treatment in an adult Kosovar population based on radiographic examination.</p> <p>Methods</p> <p>The sample used for this study consisted of randomly selected individuals referred to the University Dentistry Clinical Center of Kosovo in the years 2006-2007. Orthopantomographs of 193 patients were evaluated. The periapical status of all teeth (with the exception of third molars) was examined according to Ørstavik's Periapical Index. The quality of the root canal filling was rated as 'adequate' or 'inadequate' based on whether all canals were filled, the depth of fill relative to the radiographic apex and the quality of compaction (absence/presence of voids). Data were analyzed statistically using the Chi-square test and calculation of odds ratios.</p> <p>Results</p> <p>Out of 4131 examined teeth, the prevalence of apical periodontitis (AP) and endodontic treatment was 12.3% and 2.3%, respectively. Of 95 endodontically-treated teeth, 46.3% were associated with AP. The prevalence of AP increased with age. The prevalence in subjects aged over 60 years old (20.2%) was higher than in other age groups. A statistically significant difference was found for the frequency of endodontically-treated teeth associated with AP in the 40-49 year age group (P < 0.001). Of some concern was the discovery that only 30.5% of the endodontically-treated teeth examined met the criteria of an acceptable root canal filling. Inadequately root-filled teeth were associated with an increased AP risk.</p> <p>Conclusions</p> <p>The prevalence of AP and the frequency of endodontically-treated teeth with AP in this Kosovar population are higher than those found in other countries. Inadequate root canal fillings were associated with an increased prevalence of AP.</p