Citations

Background— Mutations in genes including SCN5A encoding the α-subunit of the cardiac sodium channel (hNav1.5) cause Brugada syndrome via altered function of cardiac ion channels, but more than two-thirds of Brugada syndrome remains pathogenetically elusive. T-tubules and sarcoplasmic reticulum are essential in excitation of cardiomyocytes, and sarcolemmal membrane-associated protein (SLMAP) is a protein of unknown function localizing at T-tubules and sarcoplasmic reticulum. Methods and Results— We analyzed 190 unrelated Brugada syndrome patients for mutations in SLMAP . Two missense mutations, Val269Ile and Glu710Ala, were found in heterozygous state in 2 patients but were not found in healthy individuals. Membrane surface expression of hNav1.5 in the transfected cells was affected by the mutations, and silencing of mutant SLMAP by small interfering RNA rescued the surface expression of hNav1.5. Whole-cell patch-clamp recordings of hNav1.5-expressing cells transfected with mutant SLMAP confirmed the reduced hNav1.5 current. Conclusions— The mutations in SLMAP may cause Brugada syndrome via modulating the intracellular trafficking of hNav1.5 channel.

Time‐resolved three‐dimensional contrast‐enhanced MR angiography often relies on view sharing of peripheral k‐space data to enable acquisition of angiograms with both high spatial resolution and a rapid frame rate. It is typically assumed that k‐space will be fully sampled during passage of the contrast bolus arterial phase. However, this is not the case when view sharing is incomplete, for example, at the leading edge of an enhancing vessel or if acquisition time is limited as in fluoroscopic tracking for multistation bolus chase MR angiography. Incomplete view sharing will degrade image quality, for example, by reducing vessel signal and sharpness and increasing undersampling artifacts. In this work, the evolution of angiogram quality with view sharing is quantitatively assessed in phantom experiments and in vivo contrast‐enhanced MR angiography calf studies. It is demonstrated that there are multiple sets of sequence parameters that can yield a target image update time, but the choice of parameters can profoundly affect how image quality evolves with view sharing. A fundamental tradeoff between vessel signal and sharpness and its relationship to the sequence temporal footprint is investigated and discussed. Magn Reson Med 70:348–357, 2013. © 2012 Wiley Periodicals, Inc.

Background: The results of surgical treatment for femoroacetabular impingement have been increasingly reported, and more advanced intra-articular disease has been identified as an important predictive factor of outcome. Yet, the reliability of arthroscopic hip disease classification has not been well defined. Purpose/Hypothesis: To determine the intraobserver and interobserver reliability of the Beck classification of labral and articular cartilage disease (anterior-superior acetabular rim) encountered in hip arthroscopy. Secondly, we identified the sources of poor reliability that may be improved with future disease classification schemes. Our hypothesis was that the Beck classification of labral and chondral lesions would demonstrate substantial reliability, while the differentiation of early forms of disease would be a common source of disagreement. Study Design: Cohort study; Level of evidence, 3. Methods: Four experienced hip arthroscopists reviewed standardized arthroscopic videos of 40 cases. Arthroscopic findings at the anterior-superior acetabular rim were classified using the Beck classification of labral and articular cartilage disease. Repeat classification of videos was performed at least 2 weeks later. The reliability of arthroscopic classification was defined using the average weighted Cohen κ values and agreement rates. Results: Arthroscopic classification of labral disease using the Beck classification demonstrated moderate to substantial interobserver reliability (average κ = .62; range, .48-.78) and an overall agreement rate of 81.7%. Intraobserver reliability showed a similar level of reliability (average κ = .65; agreement rate, 80.6%). The differentiation between labral degeneration and labral detachment was a common source of disagreement. Similarly, the Beck classification of articular cartilage disease had moderate to substantial interobserver reliability (average κ = .65; range, .49-.78) and overall agreement rate of 57.5%. Intraobserver reliability showed a slightly better level of reliability (average κ = .80; agreement rate, 77.5%). The differentiation between articular cartilage malacia and debonding was a common source of disagreement. Conclusion: The arthroscopic classification of acetabular rim disease with the Beck classification has substantial interobserver reliability. This level of reliability is similar to previously reported arthroscopic disease classifications in the knee and shoulder and seems appropriate for future outcome reporting. Future classifications that eliminate common sources of disagreement may further improve the reliability.

Abstract Carbon nanotubes represent a creative alternative for applications in medicine as therapeutic vectors, imaging and controlled release of active molecules. Although the low density and small size of carbon nanotubes makes respiratory exposures to workers likely during the production or use of commercial products, the potential genotoxicity of multi-walled carbon nanotubes has not been investigated. We have previously shown mitotic spindle aberrations in cultured primary and immortalized human airway epithelial cells exposed to single-walled carbon nanotubes (SWCNT). In order to investigate whether genetic damage was unique to SWCNT, we examined mitotic spindle aberrations following dosing of cells to multi-walled carbon nanotubes (MWCNT) at concentrations anticipated in the workplace. Immortalized and primary respiratory epithelial cells were exposed to 0.024, 0.24, 2.4, and 24μg/cm2 carbon nanotubes. The minimal dose of MWCNT considered for this research was based on the permissible exposure limit for particles with an aerodynamic diameter of less than 5 microns (Occupation Safety and Health Administration). MWCNT induced a dose response of disrupted centrosomes, mitotic spindles and aneuploid chromosome number. The data further showed that monopolar mitotic spindles comprised 95% of the disrupted mitoses. The monopolar phenotype of the disrupted mitotic spindles is in sharp contrast to the multi-polar spindle of SWCNT-induced disruption. Three-dimensional reconstructions showed carbon nanotubes integrated with the microtubules, the DNA and within the centrosome structure. The lower doses did not cause cytotoxicity or apoptosis 24 hours after exposure; however, after 72 hours, significant cytotoxicity was observed in the MWCNT-exposed cells. Disruption of the centrosome is common in many solid tumors including lung cancer. The resulting aneuploidy is a key event in the progression of cancer and is correlated with tumor stage. Our results demonstrate significant disruption of the mitotic spindle by MWCNT at occupationally relevant doses. These results suggest caution should be used in the handling and processing of carbon nanotubes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5464. doi:1538-7445.AM2012-5464