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Search Results: 1 - 10 of 318065 matches for " Martin J. Schalij "
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Development of a Lentivirus Vector-Based Assay for Non-Destructive Monitoring of Cell Fusion Activity
Zeinab Neshati, Jia Liu, Guangqian Zhou, Martin J. Schalij, Antoine A. F. de Vries
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0102433
Abstract: Cell-to-cell fusion can be quantified by endowing acceptor and donor cells with latent reporter genes/proteins and activators of these genes/proteins, respectively. One way to accomplish this goal is by using a bipartite lentivirus vector (LV)-based cell fusion assay system in which the cellular fusion partners are transduced with a flippase-activatable Photinus pyralis luciferase (PpLuc) expression unit (acceptor cells) or with a recombinant gene encoding FLPeNLS+, a nuclear-targeted and molecularly evolved version of flippase (donor cells). Fusion of both cell populations will lead to the FLPe-dependent generation of a functional PpLuc gene. PpLuc activity is typically measured in cell lysates, precluding consecutive analysis of one cell culture. Therefore, in this study the PpLuc-coding sequence was replaced by that of Gaussia princeps luciferase (GpLuc), a secretory protein allowing repeated analysis of the same cell culture. In myotubes the spread of FLPeNLS+ may be limited due to its nuclear localization signal (NLS) causing low signal outputs. To test this hypothesis, myoblasts were transduced with LVs encoding either FLPeNLS+ or an NLS-less version of FLPe (FLPeNLS?) and subsequently co-cultured in different ratios with myoblasts containing the FLPe-activatable GpLuc expression cassette. At different times after induction of cell-to-cell fusion the GpLuc activity in the culture medium was determined. FLPeNLS+ and FLPeNLS? both activated the latent GpLuc gene but when the percentage of FLPe-expressing myoblasts was limiting, FLPeNLS+ generally yielded slightly higher signals than FLPeNLS? while at low acceptor-to-donor cell ratios FLPeNLS? was usually superior. The ability of FLPeNLS+ to spread through myofibers and to induce reporter gene expression is thus not limited by its NLS. However, at high FLPe concentrations the presence of the NLS negatively affected reporter gene expression. In summary, a rapid and simple chemiluminescence assay for quantifying cell-to-cell fusion progression based on GpLuc has been developed.
CT Coronary Angiography Is Feasible for the Assessment of Coronary Artery Disease in Chronic Dialysis Patients, Despite High Average Calcium Scores
Mihály K. de Bie, Maurits S. Buiten, André Gaasbeek, Mark J. Boogers, Cornelis J. Roos, Joanne D. Schuijf, M. Jacqueline Krol, Ton J. Rabelink, Jeroen J. Bax, Martin J. Schalij, J. Wouter Jukema
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0067936
Abstract: Purpose Significant obstructive coronary artery disease (CAD) is common in asymptomatic dialysis patients. Identifying these high risk patients is warranted and may improve the prognosis of this vulnerable patient group. Routine catheterization of incident dialysis patients has been proposed, but is considered too invasive. CT-angiography may therefore be more appropriate. However, extensive coronary calcification, often present in this patient group, might hamper adequate lumen evaluation. The objective of this study was to assess the feasibility of CT-angiography in this patient group. Methods For this analysis all patients currently participating in the ICD2 trial (ISRCTN20479861), with no history of PCI or CABG were included. The major epicardial vessels were evaluated on a segment basis (segment 1–3, 5–8, 11 and 13) by a team consisting of an interventional and an imaging specialist. Segments were scored as not significant, significant and not interpretable. Results A total of 70 dialysis patients, with a mean age of 66±8 yrs and predominantly male (70%) were included. The median calcium score was 623 [79, 1619]. Over 90% of the analyzed segments were considered interpretable. The incidence of significant CAD on CT was 43% and was associated with cardiovascular events during follow-up. The incidence of cardiovascular events after 2-years follow-up: 36% vs. 0% in patients with no significant CAD (p<0.01). Conclusion Despite the high calcium scores CT-angiography is feasible for the evaluation of the extent of CAD in dialysis patients. Moreover the presence of significant CAD on CT was associated with events during follow-up.
Left Ventricular Diastolic Dysfunction in Dialysis Patients Assessed by Novel Speckle Tracking Strain Rate Analysis: Prevalence and Determinants
Mihály K. de Bie,Nina Ajmone Marsan,André Gaasbeek,Jeroen J. Bax,Marc Groeneveld,Bas A. Gabreels,Victoria Delgado,Ton J. Rabelink,Martin J. Schalij,J. Wouter Jukema
International Journal of Nephrology , 2012, DOI: 10.1155/2012/963504
Abstract: Background. Diastolic dysfunction is common among dialysis patients and is associated with increased morbidity and mortality. Novel echocardiographic speckle tracking strain analysis permits accurate assessment of left ventricular diastolic function, independent of loading conditions and taking all myocardial segments into account. The aim of the study was to evaluate the prevalence of diastolic dysfunction in chronic dialysis patients using this novel technique, and to identify its determinants among clinical and echocardiographic variables. Methods. Patients currently enrolled in the ICD2 study protocol were included for this analysis. Next to conventional echo measurements diastolic function was also assessed by global diastolic strain rate during isovolumic relaxation (SRIVR). Results. A total of 77 patients were included (age years, 74% male). When defined as E/SRIVR , the prevalence of diastolic dysfunction was higher compared to more conventional measurements (48% versus 39%). Left ventricular mass (OR 1.02, 95% CI 1.00–1.04, ) and pulse wave velocity (OR 1.34, 95% CI 1.07–1.68, ) were independent determinants of diastolic dysfunction. Conclusion. Diastolic dysfunction is highly prevalent among dialysis patients and might be underestimated using conventional measurements. Left ventricular mass and pulse wave velocity were the only determinants of diastolic dysfunction in these patients. 1. Introduction In dialysis patients, both cardiovascular and noncardiovascular mortality are significantly increased as compared to the general population [1]. In particular, cardiovascular mortality contributes to ~40% of all-cause mortality in these patients, mainly due to sudden cardiac death [2]. Several parameters, such as left ventricular hypertrophy (LVH) and left ventricular (LV) systolic dysfunction, have been identified as independent predictors of (cardiovascular) outcome in dialysis patients. Next to that significant diastolic heart dysfunction, as assessed by tissue Doppler imaging (TDI), has also demonstrated significant incremental prognostic value for all-cause mortality and cardiovascular death [3]. Similar to the general population, diastolic heart failure in dialysis patients often exists without the presence of significant systolic heart failure [4, 5]. Therefore, accurate evaluation of LV diastolic dysfunction is crucial in the management and risk stratification of dialysis patients, especially in those with preserved ejection fraction. Particularly, LV diastolic function and its determinants might represent an important target for
Flat-Land Large-Scale Electricity Storage (FLES)
Huynen J.,Schalij R.,Arts T.
EPJ Web of Conferences , 2012, DOI: 10.1051/epjconf/20123304010
Abstract: Growth of renewable sources requires a smarter electricity grid, integrating multiple solutions for large scale storage. Pumped storage still is the most valid option. The capacity of existing facilities is not sufficient to accommodate future renewable resources. New locations for additional pumped storage capacity are scarce. Mountainous areas mostly are remote and do not allow construction of large facilities for ecological reasons. In the Netherlands underground solutions were studied for many years. The use of (former) coal mines was rejected after scientific research. Further research showed that solid rock formations below the (unstable) coal layers can be harnessed to excavate the lower water reservoir for pumped storage, making an innovative underground solution possible. A complete plan was developed, with a capacity of 1400 MW (8 GWh daily output) and a head of 1400 m. It is technically and economically feasible. Compared to conventional pumped storage it has significantly less impact on the environment. Less vulnerable locations are eligible. The reservoir on the surface (only one instead of two) is relatively small. It offers also a solution for other European countries. The Dutch studies provide a valuable basis for new locations.
Human Embryonic and Fetal Mesenchymal Stem Cells Differentiate toward Three Different Cardiac Lineages in Contrast to Their Adult Counterparts
Arti A. Ramkisoensing, Dani?l A. Pijnappels, Sa?d F. A. Askar, Robert Passier, Jim Swildens, Marie José Goumans, Cindy I. Schutte, Antoine A. F. de Vries, Sicco Scherjon, Christine L. Mummery, Martin J. Schalij, Douwe E. Atsma
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0024164
Abstract: Mesenchymal stem cells (MSCs) show unexplained differences in differentiation potential. In this study, differentiation of human (h) MSCs derived from embryonic, fetal and adult sources toward cardiomyocytes, endothelial and smooth muscle cells was investigated. Labeled hMSCs derived from embryonic stem cells (hESC-MSCs), fetal umbilical cord, bone marrow, amniotic membrane and adult bone marrow and adipose tissue were co-cultured with neonatal rat cardiomyocytes (nrCMCs) or cardiac fibroblasts (nrCFBs) for 10 days, and also cultured under angiogenic conditions. Cardiomyogenesis was assessed by human-specific immunocytological analysis, whole-cell current-clamp recordings, human-specific qRT-PCR and optical mapping. After co-culture with nrCMCs, significantly more hESC-MSCs than fetal hMSCs stained positive for α-actinin, whereas adult hMSCs stained negative. Furthermore, functional cardiomyogenic differentiation, based on action potential recordings, was shown to occur, but not in adult hMSCs. Of all sources, hESC-MSCs expressed most cardiac-specific genes. hESC-MSCs and fetal hMSCs contained significantly higher basal levels of connexin43 than adult hMSCs and co-culture with nrCMCs increased expression. After co-culture with nrCFBs, hESC-MSCs and fetal hMSCs did not express α-actinin and connexin43 expression was decreased. Conduction velocity (CV) in co-cultures of nrCMCs and hESC-MSCs was significantly higher than in co-cultures with fetal or adult hMSCs. In angiogenesis bioassays, only hESC-MSCs and fetal hMSCs were able to form capillary-like structures, which stained for smooth muscle and endothelial cell markers.Human embryonic and fetal MSCs differentiate toward three different cardiac lineages, in contrast to adult MSCs. Cardiomyogenesis is determined by stimuli from the cellular microenvironment, where connexin43 may play an important role.
Myocardial Structural Alteration and Systolic Dysfunction in Preclinical Hypertrophic Cardiomyopathy Mutation Carriers
Kai Hang Yiu, Douwe E. Atsma, Victoria Delgado, Arnold C. T. Ng, Tomasz G. Witkowski, See Hooi Ewe, Dominique Auger, Eduard R. Holman, Anneke M. van Mil, Martijn H. Breuning, Hung Fat Tse, Jeroen J. Bax, Martin J. Schalij, Nina Ajmone Marsan
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0036115
Abstract: Background To evaluate the presence of myocardial structural alterations and subtle myocardial dysfunction during familial screening in asymptomatic mutation carriers without hypertrophic cardiomyopathy (HCM) phenotype. Methods and Findings Sixteen HCM families with pathogenic mutation were studied and 46 patients with phenotype expression (Mut+/Phen+) and 47 patients without phenotype expression (Mut+/Phen?) were observed. Twenty-five control subjects, matched with the Mut+/Phen? group, were recruited for comparison. Echocardiography was performed to evaluate conventional parameters, myocardial structural alteration by calibrated integrated backscatter (cIBS) and global and segmental longitudinal strain by speckle tracking analysis. All 3 groups had similar left ventricular dimensions and ejection fraction. Basal anteroseptal cIBS was the highest in Mut+/Phen+ patients (?14.0±4.6 dB, p<0.01) and was higher in Mut+/Phen? patients as compared to controls (?17.0±2.3 vs. ?22.6±2.9 dB, p<0.01) suggesting significant myocardial structural alterations. Global and basal anteroseptal longitudinal strains (?8.4±4.0%, p<0.01) were the most impaired in Mut+/Phen+ patients as compared to the other 2 groups. Although global longitudinal strain was similar between Mut+/Phen? group and controls, basal anteroseptal strain was lower in Mut+/Phen? patients (?14.1±3.8%, p<0.01) as compared to controls (?19.9±2.9%, p<0.01), suggesting a subclinical segmental systolic dysfunction. A combination of >?19.0 dB basal anteroseptal cIBS or >?18.0% basal anteroseptal longitudinal strain had a sensitivity of 98% and a specificity of 72% in differentiating Mut+/Phen? group from controls. Conclusion The use of cIBS and segmental longitudinal strain can differentiate HCM Mut+/Phen? patients from controls with important clinical implications for the family screening and follow-up of these patients.
Development of the Cardiac Conduction System and the Possible Relation to Predilection Sites of Arrhythmogenesis
M. R. M. Jongbloed,E. A. F. Mahtab,N. A. Blom,M. J. Schalij
The Scientific World Journal , 2008, DOI: 10.1100/tsw.2008.40
Novel Approaches to Treat Experimental Pulmonary Arterial Hypertension: A Review
S. Umar,P. Steendijk,D. L. Ypey,D. E. Atsma,E. E. van der Wall,M. J. Schalij,A. van der Laarse
Journal of Biomedicine and Biotechnology , 2010, DOI: 10.1155/2010/702836
Abstract: Background. Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by an increase in pulmonary artery pressure leading to right ventricular (RV) hypertrophy, RV failure, and ultimately death. Current treatments can improve symptoms and reduce severity of the hemodynamic disorder but gradual deterioration in their condition often necessitates a lung transplant. Methods and Results. In experimental models of PAH, particularly the model of monocrotaline-induced pulmonary hypertension, efficacious treatment options tested so far include a spectrum of pharmacologic agents with actions such as anti-mitogenic, proendothelial function, proangiogenic, antiinflammatory and antioxidative. Emerging trends in PAH treatment are gene and cell therapy and their combination, like (progenitor) cells enriched with eNOS or VEGF gene. More animal data should be collected to investigate optimal cell type, in vitro cell transduction, route of administration, and number of cells to inject. Several recently discovered and experimentally tested interventions bear potential for therapeutic purposes in humans or have been shown already to be effective in PAH patients leading to improved life expectation and better quality of life. Conclusion. Since many patients remain symptomatic despite therapy, we should encourage research in animal models of PAH and implement promising treatments in homogeneous groups of PAH patients.
Physician and politics. Life and Society Viewed From Different Angles
Martin J
Revue Médicale de l'Assurance Maladie , 2002,
Abstract: This article is written by the Médecin cantonal (Chief Medical Officer) of the Swiss Canton of Vaud (capital city, Lausanne). The Swiss Constitution mandates responsibility for most health-related issues to the Cantons. In particular, the Cantons are charged with organizing the health system (hospital infrastructure, nursing homes, home-health care, relationships with private practitioners). The Cantonal Ministry of Health also issues licenses to practice and initiates necessary disciplinary procedures. The Médecin cantonal is the medical advisor of the health minister and of the government and administration in general. Due to recent problems and evolutions in health care, he has been called on to deal with HIV/AIDS, drug addiction, bioethics as well as other contemporary medical issues. He is a reference person for medico-legal matters and is involved in the promotion of health policies, school health, and preparatory measures in case of disaster. The author discusses some of his experiences at this intersection between medicine, health care, the exercise of public authority, politics and civil society. He analyses how physicians and politicians have different perspectives on the circumstances of collective life.
Assistance to suicide - The legal and ethica situation in Switzeland
Martin J
Pratiques et Organisation des Soins , 2011,
Abstract: Assistance to suicide is accepted today in some US States, in Switzerland, and in the Netherlands, Belgium and Luxembourg - in the latter countries, euthanasia is also possible; this article does not discuss that topic and deals with situations where the patient makes the determining fatal act. The issue of assisted suicide was part of the author's official duties (adviser to the Minister) during twenty years, and has been substantially discussed within the Swiss National Advisory Commission on Biomedical Ethics of which he is a member. After a socio-historical introduction, human dignity is debated: some affirm that it is ontological in nature, regardless of the person's evaluation of his suffering and dependence; others think on the contrary that the patient is the master in this regard and best placed to judge what dignity means for himself. It is relevant to note that the wish to die in old persons is not necessarily linked to depression and that good palliative care does not suppress all related demands. There are questions and challenges in respect to the appropriate role of public authority. It doubtless has a general mission of suicide prevention but, obviously, all suicidal intentions cannot be seen as a single entity. Each demand should be carefully evaluated in its specificity; the will and reasons to end one's life cannot be judged by checking items on a questionnaire. As much as possible, the demand for help and the answer one might give (conscience clause being reserved) should remain private, based on an interpersonal relation. For such intimate decisions the State or his agents have no legitimacy to pretend knowing better than the person concerned what is good for her. Prat Organ Soins 2011;42(4):277-81
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