Abnormal interactions of calsequestrin with the ryanodine receptor calcium release channel complex linked to exercise-induced sudden cardiac death

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial arrhythmogenic disorder associated with mutations in the cardiac ryanodine receptor (RyR2) and cardiac calsequestrin (CASQ2) genes. Previous in vitro studies suggested that RyR2 and CASQ2 interact as parts of a multimolecular Ca(2+)-signaling complex; however, direct evidence for such interactions and their potential significance to myocardial function remain to be determined. We identified a novel CASQ2 mutation in a young female with a structurally normal heart and unexplained syncopal episodes. This mutation results in the nonconservative substitution of glutamine for arginine at amino acid 33 of CASQ2 (R33Q). Adenoviral-mediated expression of CASQ2(R33Q) in adult rat myocytes led to an increase in excitation-contraction coupling gain and to more frequent occurrences of spontaneous propagating (Ca2+ waves) and local Ca2+ signals (sparks) with respect to control cells expressing wild-type CASQ2 (CASQ2WT). As revealed by a Ca2+ indicator entrapped inside the sarcoplasmic reticulum (SR) of permeabilized myocytes, the increased occurrence of spontaneous Ca2+ sparks and waves was associated with a dramatic decrease in intra-SR [Ca2+]. Recombinant CASQ2WT and CASQ2R33Q exhibited similar Ca(2+)-binding capacities in vitro; however, the mutant protein lacked the ability of its WT counterpart to inhibit RyR2 activity at low luminal [Ca2+] in planar lipid bilayers. We conclude that the R33Q mutation disrupts interactions of CASQ2 with the RyR2 channel complex and impairs regulation of RyR2 by luminal Ca2+. These results show that intracellular Ca2+ cycling in normal heart relies on an intricate interplay of CASQ2 with the proteins of the RyR2 channel complex and that disruption of these interactions can lead to cardiac arrhythmia.     

Chromosomal mapping of 170 BAC clones in the ascidian Ciona intestinalis

The draft genome ( approximately 160 Mb) of the urochordate ascidian Ciona intestinalis has been sequenced by the whole-genome shotgun method and should provide important insights into the origin and evolution of chordates as well as vertebrates. However, because this genomic data has not yet been mapped onto chromosomes, important biological questions including regulation of gene expression at the genome-wide level cannot yet be addressed. Here, we report the molecular cytogenetic characterization of all 14 pairs of C. intestinalis chromosomes, as well as initial large-scale mapping of genomic sequences onto chromosomes by fluorescent in situ hybridization (FISH). Two-color FISH using 170 bacterial artificial chromosome (BAC) clones and construction of joined scaffolds using paired BAC end sequences allowed for mapping of up to 65% of the deduced 117-Mb nonrepetitive sequence onto chromosomes. This map lays the foundation for future studies of the protochordate C. intestinalis genome at the chromosomal level.     

Reduced serum levels of brain-derived neurotrophic factor in adult male patients with autism

BACKGROUND: The precise mechanisms underlying the pathophysiology of autism are currently unknown. Given the key role of brain-derived neurotrophic factor (BDNF) in brain development, we hypothesized that BDNF may play a role in the pathophysiology of autism. In this study, we studied whether serum levels of BDNF are altered in patients with autism. METHODS: We measured serum levels of BDNF in 18 adult male patients with autism and 18 age-matched healthy male control subjects. RESULTS: The serum levels of BDNF in patients with autism (25.6+/-2.15 ng/ml (mean+/-S.D.)) were significantly (z = -4.42, p < 0.001) lower than those of normal controls (61.6+/-10.9 ng/ml (mean+/-S.D.)). Nevertheless, we found no correlations between BDNF levels and clinical variables in autistic patients. CONCLUSIONS: This study suggests that reduced BDNF levels may play a role in the pathophysiology of autism.     

A study of the usefulness of pancreatic juice cytology obtained via an endoscopic nasal pancreatic drainage (ENPD) tube

We studied the usefulness of pancreatic juice cytology obtained via an indwelling endoscopic nasal pancreatic drainage (ENPD) tube. In general, cytology was performed three times. The sensitivity was 0.35 on the first time and 0.59 after three times (p<0.01). The sensitivity in relation to tumor size of pancreatic cancer was 0.77 for Tis (3 cases) and TS1 (10 cases), 0.76 for TS2 (29 cases), 0.56 for TS3 (9 cases) and 0 for TS4 (4 cases). A significant difference of p=0.01 was recognized among the 4 groups, and the sensitivity for small tumors was higher than that for large tumors. The pancreatic juice can be obtained repeatedly via the ENPD tube and that contributes to improving the diagnostic accuracy. It is useful as a definitive diagnosis method in early stage pancreatic cancer because it is easier to detect positive results in smaller tumor, furthermore, it is possible to diagnose carcinoma in situ.     

Endoscopy in Canada: Proceedings of the National Roundtable: Toronto,Ontario, February 7, 2014

This 2014 roundtable discussion, hosted by the Canadian Association of General Surgeons, brought together general surgeons and gastroenterologists with expertise in endoscopy from across Canada to discuss the state of endoscopy in Canada. The focus of the roundtable was the evaluation of the competence of general surgeons at endoscopy, reviewing quality assurance parameters for high-quality endoscopy, measuring and assessing surgical resident preparedness for endoscopy practice, evaluating credentialing programs for the endosuite and predicting the future of endoscopic services in Canada. The roundtable noted several important observations. There exist inadequacies in both resident training and the assessment of competency in endoscopy. From these observations, several collaborative recommendations were then stated. These included the need for a formal and standardized system of both accreditation and training endoscopists.     

Virtual MR pancreatoscopy in the evaluation of the pancreatic duct in chronic pancreatitis

The main pancreatic duct and the common bile duct can be evaluated with a variety of evolving invasive and non-invasive techniques. Virtual CT pancreatoscopy obtained using special computer software is a recent non-invasive innovation which shows the details of the ductal surface (endoluminal view) with greater precision. The use of special computer software in MRI in order to obtain pancreatic ductal surface details or a virtual MR pancreatoscopy has not been described up to now. We report a short series of four patients suffering from chronic pancreatitis who underwent virtual MR pancreatoscopy with an impact on their management and clinical outcome.     

Current therapy in the management of heterotopic ossification of the elbow: a review with case studies.

Heterotopic ossification, or the appearance of ectopic bone in para-articular soft tissues after surgery, immobilization, or trauma, complicates the surgical and physiatric management of injured joints. The chief symptoms of heterotopic ossification are joint and muscle pain and a compromised range of motion. Current therapies for prevention or treatment of heterotopic ossification include surgery, physical therapy, radiation therapy, and medical management. Unlike heterotopic ossification of the hip, heterotopic ossification of the elbow has not been extensively investigated, leaving its optimal management ill-defined. To remedy this deficiency, we review risk factors, clinical anatomy, physical findings, proposed mechanisms, and current practice for treatment and prevention of heterotopic ossification. We then consider and draw conclusions from four cases of elbow injury treated at our institutions (three complicated by heterotopic ossification) in which treatment included surgery, radiation therapy, physical therapy, and medical therapy. We summarize our institutional practices and conclude with a call for a randomized clinical trial to better define optimal management of heterotopic ossification of the elbow.