[General Data Protection Regulation and medical research: friend or foe?].

As of May 2018, the use of personal data in medical research is regulated under the General Data Protection Regulation (GDPR). While, as before, in principle patients' consent for the use of their personal data is still required, exemptions for medical research still exist. When all of the criteria for the exemptions are met, and the other requirements of the GDPR are adhered to, personal data can be used in medical research without consent.

Heterogeneous Connexin43 distribution in heart failure is associated with dispersed conduction and enhanced susceptibility to ventricular arrhythmias.

Aims: Sudden arrhythmogenic cardiac death is a major cause of mortality in patients with congestive heart failure (CHF). To investigate determinants of the increased arrhythmogenic susceptibility, we studied cardiac remodelling and arrhythmogenicity in CHF patients and in a mouse model of chronic pressure overload.

Methods And Results: Clinical and (immuno)histological data of myocardial biopsies from CHF patients with (VT+) and without (VT-) documented ventricular arrhythmia were compared with controls.

Functional analysis of novel KCNQ2 mutations found in patients with Benign Familial Neonatal Convulsions.

Benign Familial Neonatal Convulsions (BFNC) are a rare epilepsy disorder with an autosomal-dominant inheritance. It is linked to mutations in the potassium channel genes KCNQ2 and KCNQ3. These encode for Kv7.

The human Cx40 promoter polymorphism -44G-->A differentially affects transcriptional regulation by Sp1 and GATA4.

Expression of the tissue-specific gap junction protein connexin(Cx)40 is regulated by the interaction of ubiquitous and tissue-specific factors such as Sp1 and GATA4. Cardiac Cx40 expression is altered under pathological conditions such as atrial fibrillation. A human promoter polymorphism, a G-->A change at position -44 that has been associated with atrial-specific arrhythmias, is located between the TBE-NKE-Sp and GATA consensus transcription factor binding sites important for the regulation of the mouse Cx40 gene.

Cx40 polymorphism in human atrial fibrillation.

Unlabelled: Previous studies have shown that two linked polymorphisms within regulatory regions of the gene for connexin40 (Cx40), at nucleotides -44 (G --> A) and +71 (A --> G) occur in about 7% of the general population. Cx40 is abundant in the atrium, and homozygosity for the linked polymorphisms combined with an SCN5A mutation appeared to be responsible for familial atrial standstill. We hypothesized that these polymorphisms are associated with the atrial electrophysiologic substrate favoring reentrant mechanisms for initiation of atrial fibrillation (AF).

Polymorphisms in human connexin40 gene promoter are associated with increased risk of hypertension in men.

Objective: Gap junctions, formed by connexins (Cx), are important in the regulation of vascular tone. Previously, we reported two closely linked polymorphisms (-44G --> A and +71A --> G) within regulatory regions of the gene for Cx40, a major connexin in the vascular wall and the kidney. In the present study, we examined the hypothesis that these polymorphic variants are associated with hypertension and that they interact with blood pressure in healthy individuals.

Congenital atrial standstill associated with coinheritance of a novel SCN5A mutation and connexin 40 polymorphisms.

Background: Congenital atrial standstill has been linked to SCN5A. Incomplete penetrance observed in atrial standstill has been attributed in part to the digenic inheritance of polymorphisms in the atrial-specific gap junction connexin 40 (Cx40) in conjunction with an SCN5A mutation.

Objectives: The purpose of this study was to determine the clinical and biophysical characteristics of a novel SCN5A mutation identified in a family with atrial standstill.

Association of human connexin40 gene polymorphisms with atrial vulnerability as a risk factor for idiopathic atrial fibrillation.

Alterations in distribution, density, and properties of cardiac gap junctions, which mediate electrical coupling of cardiomyocytes, are considered potentially arrhythmogenic. We recently reported 2 linked polymorphisms within regulatory regions of the gene for the atrial gap junction protein connexin40 (Cx40) at nucleotides -44 (G-->A) and +71 (A-->G), which were associated with familial atrial standstill. The present study examined whether these Cx40 polymorphisms were associated with increased atrial vulnerability in vivo and arrhythmia susceptibility.

Na+ channel mutation leading to loss of function and non-progressive cardiac conduction defects.

Background: We previously described a Dutch family in which congenital cardiac conduction disorder has clinically been identified. The ECG of the index patient showed a first-degree AV block associated with extensive ventricular conduction delay. Sequencing of the SCN5A locus coding for the human cardiac Na+ channel revealed a single nucleotide deletion at position 5280, resulting in a frame-shift in the sequence coding for the pore region of domain IV and a premature stop codon at the C-terminus.

A novel LQT3 mutation implicates the human cardiac sodium channel domain IVS6 in inactivation kinetics.

Unlabelled: The Long QT3 syndrome is associated with mutations in the cardiac sodium channel gene SCN5A.

Objective: The aim of the present study was the identification and functional characterization of a mutation in a family with the long QT3 syndrome.

Methods: The human cardiac sodium channel gene SCN5A was screened for mutations by single-stranded conformation polymorphism.

Compound heterozygosity for mutations (W156X and R225W) in SCN5A associated with severe cardiac conduction disturbances and degenerative changes in the conduction system.

Cardiac conduction defects associate with mutations in SCN5A, the gene encoding the cardiac Na+ channel. In the present study, we characterized a family in which the proband was born in severe distress with irregular wide complex tachycardia. His older sister died at 1 year of age from severe conduction disease with similarly widened QRS-complexes.

A cardiac sodium channel mutation cosegregates with a rare connexin40 genotype in familial atrial standstill.

Atrial standstill (AS) is a rare arrhythmia that occasionally appears to be genetically determined. This study investigates the genetic background of this arrhythmogenic disorder in a large family. Forty-four family members were clinically evaluated.

Characterization of the rat connexin40 promoter: two Sp1/Sp3 binding sites contribute to transcriptional activation.

Objectives: The gap junction protein connexin40 (Cx40) is differentially expressed during embryonic development and in adult tissues, for which the molecular basis is unknown. In order to elucidate the molecular mechanisms controlling Cx40 expression, we set out to map and characterize its promoter.

Methods: The transcriptional activity of individual rat Cx40 (rCx40)-derived promoter fragments fused to the luciferase reporter gene was determined by transfection/reporter assays in Cx40-expressing (A7r5, rat smooth muscle embryonic thoracic aorta cells, and BWEM, v-myc transformed rat fetal cardiomyocytes) and Cx40-nonexpressing cells (N2A, mouse neuroblastoma cells).

Human SCN5A gene mutations alter cardiac sodium channel kinetics and are associated with the Brugada syndrome.

Background: Primary dysrhythmias other than those associated with the long QT syndrome, are increasingly recognized. One of these are represented by patients with a history of resuscitation from cardiac arrest but without any structural heart disease. These patients exhibit a distinct electrocardiographic (ECG) pattern consisting of a persistent ST-segment elevation in the right precordial leads often but not always accompanied by a right bundle branch block (Brugada syndrome).

Genomic organization of the rat connexin40 gene: identical transcription start sites in heart and lung.

Objectives: The gap junction protein connexin(Cx)40 is developmentally and tissue-specifically expressed. How Cx40 expression is regulated is unknown. We therefore set out to characterize the 5'-untranslated end of both the Cx40 gene and mRNA from different tissues and ages and to identify the Cx40 promoter region.

Altered pattern of connexin40 distribution in persistent atrial fibrillation in the goat.

Introduction: Since altered expression of gap junction proteins (connexins) in diseased myocardial tissue may lead to abnormal electrical coupling between cardiomyocytes and hence contribute to arrhythmogenesis, the expression of connexin(Cx)40 and Cx43 was studied in atrial appendage from goats in sinus rhythm (SR) and persistent atrial fibrillation (AF).

Methods And Results: Biopsies were taken from the left and right atrial appendages from goats in SR or after pacing-induced persistent AF. Analyses of Cx40 and Cx43 mRNA and protein levels, using quantitative (competitive) polymerase chain reaction and western blotting, respectively, revealed no significant changes in the overall expression of Cx40 and Cx43 as a result of persistent AF.

Dysbetalipoproteinemia in a kindred with hypobetalipoproteinemia due to mutations in the genes for ApoB (ApoB-70.5) and ApoE (ApoE2).

We identified the first insertion mutation that specifies an apolipoprotein (apo)B truncation, apoB-70.5, in a father and son with hypobetalipoproteinemia (total and low-density lipoprotein [LDL] cholesterol < 5th percentile, plasma apoB levels approximately one third of normal). The mutation is due to insertion of an adenine (A) into a 7-A repeat between cDNA position 9754 and 9760 of the apoB gene, resulting in a frame shift of 13 new amino acids and a termination codon at amino acid residue 3197.

Apolipoprotein B-38.9 does not associate with apo[a] and forms two distinct HDL density particle populations that are larger than HDL.

We have identified a new truncated apolipoprotein B (apoB) that provides insights into the interaction of apoB with apo[a] and with lipids. Both total and LDL-cholesterol were below the 5th percentile in the proband; Lp[a] was 28 mg/dl. Four other affected individuals were identified in this kindred.

Apolipoprotein B-52 mutation associated with hypobetalipoproteinemia is compatible with a misaligned pairing deletion mechanism.

We have identified a new truncation of apoB in a large kindred with hypobetalipoproteinemia that arose by an ambiguous deletion of one of four different groups of base-pairs. Eleven affected members of the kindred had total cholesterols (C) of 114 +/- 28, LDL-Cs of 46 +/- 21, and apoBs of 47 +/- 25 (all in mg/dl, mean +/- SD). These levels were lower (P < 0.

A comparison of the effects of an extract of feverfew and parthenolide, a component of feverfew, on human platelet activity in-vitro.

Extracts of the herb feverfew inhibit human blood platelet aggregation and secretion induced by a number of agents in-vitro and this may relate to the beneficial effects of feverfew in migraine. We previously identified several compounds with antisecretory activity in human blood platelets using adrenaline as the stimulant. In the present study, we have compared the inhibitory activity of one of these compounds, parthenolide, with that of crude feverfew extract.