Single Nucleotide Polymorphism (SNP)-Based Loss of Heterozygosity (LOH) Testing by Real Time PCR in Patients Suspect of Myeloproliferative Disease

During tumor development, loss of heterozygosity (LOH) often occurs. When LOH is preceded by an oncogene activating mutation, the mutant allele may be further potentiated if the wild-type allele is lost or inactivated. In myeloproliferative neoplasms (MPN) somatic acquisition of JAK2V617F may be followed by LOH resulting in loss of the wild type allele. The occurrence of LOH in MPN and other proliferative diseases may lead to a further potentiating the mutant allele and thereby increasing morbidity. A real time PCR based SNP profiling assay was developed and validated for LOH detection of the JAK2 region (JAK2LOH). Blood of a cohort of 12 JAK2V617F-positive patients (n = 6 25–50% and n = 6>50% JAK2V617F) and a cohort of 81 patients suspected of MPN was stored with EDTA and subsequently used for validation. To generate germ-line profiles, non-neoplastic formalin-fixed paraffin-embedded tissue from each patient was analyzed. Results of the SNP assay were compared to those of an established Short Tandem Repeat (STR) assay. Both assays revealed JAK2LOH in 1/6 patients with 25–50% JAK2V617F. In patients with >50% JAK2V617F, JAK2LOH was detected in 6/6 by the SNP assay and 5/6 patients by the STR assay. Of the 81 patients suspected of MPN, 18 patients carried JAK2V617F. Both the SNP and STR assay demonstrated the occurrence of JAK2LOH in 5 of them. In the 63 JAK2V617F-negative patients, no JAK2LOH was observed by SNP and STR analyses. The presented SNP assay reliably detects JAK2LOH and is a fast and easy to perform alternative for STR analyses. We therefore anticipate the SNP approach as a proof of principle for the development of LOH SNP-assays for other clinically relevant LOH loci

Bone marrow mesenchymal stem cells do not enhance intra-synovial tendon healing despite engraftment and homing to niches within the synovium

Intra-synovial tendon injuries display poor healing, which often results in reduced functionality and pain. A lack of effective therapeutic options has led to experimental approaches to augment natural tendon repair with autologous mesenchymal stem cells (MSCs) although the effects of the intra-synovial environment on the distribution, engraftment and functionality of implanted MSCs is not known. This study utilised a novel sheep model which, although in an anatomically different location, more accurately mimics the mechanical and synovial environment of the human rotator cuff, to determine the effects of intra-synovial implantation of MSCs

Concerns About Exercise Are Related to Walk Test Results in Pulmonary Rehabilitation for Patients with COPD

# The Author(s). This article is published with open access at Springerlink.com 2010 Background Although international guidelines on pulmonary rehabilitation acknowledge that psychological factors contribute to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD), the few empirical studies investigating this association have found inconsistent results. Purpose The purpose of this study is to investigate whether negative affect and beliefs about exercise of patients with COPD would be related to baseline 6-min walk (6-MW) test results in a pulmonary rehabilitation setting, after correction for physical variables (sex, age, height, weight, and lung function). A second aim was to examine whethe

Non-linear MHD modelling of ELM triggering by pellet injection in DIII-D and implications for ITER

Edge localized mode (ELM) triggering by pellet injection in the DIII-D tokamak has been simulated with the non-linear MHD code JOREK with a view to validating its physics models. JOREK has been subsequently applied to evaluate the requirements for ELM control by pellet injection in ITER. JOREK modelling results for DIII-D show that the key parameter for the triggering of ELMs by pellets is the value of the localized pressure perturbation caused by pellet injection which leads to a threshold minimum pellet size for a given injection velocity, injection geometry and H-mode plasma characteristics. The minimum pellet size for ELM triggering is found to depend on injection geometry with the largest value being required for injection at the outer midplane, intermediate for injection near the X-point and the smallest one for injection at the high-field side. The first results of studies for ELM triggering by pellet injection in ITER 15 MA Q = 10 plasmas with the foreseen injection geometry in ITER are presented