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Biomedical subjects

L Mertens

Publications and source records attributed to L Mertens.

At least 37 records · Page 2Linked to original sources
PubMed1997

Gastroepiploic artery coronary bypass graft: non-invasive patency evaluation using color and duplex Doppler ultrasonography.

OBJECTIVE: Color and duplex Doppler ultrasound and digital subtraction angiography were compared for the evaluation of graft patency of the gastroepiploic artery (GEA). METHODS: In 77 observations, ultrasound and digital subtraction angiography were compared. The coronary resistance index (cRI) was defined as the maximal systolic flow velocity minus the maximal diastolic flow velocity, divided by the maximal systolic flow velocity. On digital subtraction angiography, the graft was considered patent, occluded, or patent but non-functional. Grafts were defined as non-functional when they had a diameter of less than 5F with the absence of opacification of the native coronary artery. RESULTS: Of the 77 observations, 64 GEAs were patent angiographically, three were occluded and ten grafts were considered as patent but non-functional. Using color and duplex ultrasound, the GEA was identified in 65 out of 77 observations. There were no cases of false positive visualization of the GEA. All sonographically detected non-functional grafts (n = 7) had a cRI of greater than 0.60. When the non-visualized grafts are considered either non-functional or occluded, a cut-off value for a cRI of 0.60 results in a sensitivity and specificity of 100 and 75%, respectively. CONCLUSION: We propose ultrasound as a primary screening tool for evaluating graft patency. While color Doppler is a suitable technique for graft visualization, spectral analysis with the calculation of a cRI is required for functional evaluation.

Adult↗
PubMed1997

Na(+)-Ca2+ exchange in rat dorsal root ganglion neurons.

The role of the Na(+)-Ca2+ exchanger was examined in isolated rat dorsal root ganglion (DRG) neurons. Neurons were dialyzed with the Ca2+ indicator Indo-1. Ca2+ transients were elicited by depolarizing the cells from -80 to 0 mV for 100 ms under voltage clamp conditions. In most cells (45 of 67), the decay of intracellular Ca2+ concentration ([Ca2+]i) could be fitted with a single exponential with a time constant of 2.43 s. In the remaining 22 cells, the decay of [Ca2+]i could be described with a double exponential with time constants of 0.76 and 11.84 s. In cells that displayed a biphasic [Ca2+]i relaxation, Na(+)-free medium caused resting [Ca2+]i to increase from 116 to 186 nM; the slow component of recovery to basal [Ca2+]i was nearly abolished in Na(+)-free medium or by application of 5 mM Ni2+. In 35 of 45 cells displaying a monophasic [Ca2+]i decay, omitting external Na+ increased the time constant of [Ca2+]i decay from 2.02 to 3.63 s. In the remaining 10 cells, Na(+)-free solution did not affect Ca2+ handling. The time constant of [Ca2+]i relaxation was voltage dependent. These findings demonstrate the important role of the Na(+)-Ca2+ exchanger in DRG neurons. Its presence was further confirmed both at the mRNA and the protein level.

Animals↗
PubMed1996

Alternative processing of the sarco/endoplasmic reticulum Ca(2+)-ATPase transcripts during muscle differentiation is a specifically regulated process.

Expression of the muscle-specific 2a isoform of the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA2) requires activation of an otherwise inefficient splice process at the 3'-end of the primary gene transcript. We provide evidence that SERCA2 splicing is a specifically regulated process, rather than the result of an increase in general splice efficiency or a decrease in polyadenylation efficiency at the 5'-most polyadenylation site. This is indicated by the fact that changes in general splice and polyadenylation efficiency, as observed during B-cell maturation, did not affect SERCA2 splicing. Furthermore, expression and overexpression studies did not support the hypothesis that changes in the level of the alternative splice factor ASF/SF2 or other arginine and serine rich proteins are sufficient to obtain the regulation of muscle- and neuronal-specific splicing.

Alternative Splicing↗
PubMed1996

Assessment of accuracy of renal artery stenosis grading in helical CT angiography using maximum intensity projections.

The purpose of the study was to investigate whether visual inspection of maximum intensity projection (MIP) images is a reliable method for assessment of the severity of renal artery stenoses (RAS). Therefore, 20 RAS were investigated with helical CT. Native axial images and MIP images were analysed separately or in combination ("two-step method"). A phantom study was performed to investigate the influence of window setting on apparent stenosis severity. Accuracy for diagnosis of 50-69% and 70-99% RAS and the mean inter-observer agreement were 82.5%, 77.5% and 82.5% respectively, using study of MIP images alone, and 100%, 97.5% and 95% using the "two-step method". The phantom study showed that the apparent severity of vascular stenoses on MIP images depends on the selected window centre values. It is concluded that combined evaluation of both MIP images and native axial images is more reliable than study of MIP images alone for assessing the severity of RAS.

Aged↗
PubMed1996

Idiopathic restrictive cardiomyopathy in childhood. A diastolic disorder characterized by delayed relaxation.

Six children with idiopathic restrictive cardiomyopathy were evaluated. Electrocardiographic evaluation disclosed left atrial dilatation and repolarization abnormalities. Echocardiographic examination showed gross left atrial enlargement (182 +/- 29% of predicted values, P < 0.001) in the presence of normal left ventricular cavity dimensions (99 +/- 6%, P: ns). Left ventricular wall thickness varied from normal to mild concentric hypertrophy (septum: 116 +/- 16%, P < 0.05). Global left ventricular systolic function was normal or slightly subnormal; however, the relaxation was significantly delayed throughout diastole. E/A ratio was 4.1 +/- 1.4 and deceleration time 94 +/- 7 ms. Marked ventricular filling occurred in mid-diastole as could be deduced from a prominent mid-diastolic mitral L wave on the Doppler flow tracing. Early filling contributed 56 +/- 6%, mid-diastolic filling 28 +/- 4% and atrial contraction 16 +/- 3% to total ventricular filling as estimated by determining E-area, L-area and A-area, respectively. The left ventricular pressure curve showed a steady decline during mid-diastolic filling. This implies that the driving force for mid-diastolic filling is not the increased left atrial pressure but suction by the ventricle. The restrictive haemodynamics are therefore not caused by increased intrinsic stiffness of the ventricular wall, but most likely result from serious dysfunction and delay of the active relaxation of the ventricle. Progression of the disease was observed in three out of six patients, resulting in death or extreme low cardiac output. The three other patients remained clinically stable during the follow-up period of 6-10 years.

Adolescent↗
PubMed1996

Supra- and juxtarenal aneurysms of the abdominal aorta: preoperative assessment with thin-section spiral CT.

PURPOSE: To assess the contribution of thin-section spiral computed tomography (CT) to the preoperative radiologic evaluation of juxta- and suprarenal abdominal aortic aneurysms. MATERIALS AND METHODS: Thirty-eight patients (26 men, 12 women; age range, 60-81 years) with infrarenal (n = 23), juxtarenal (n = 8), and suprarenal (n = 7) aneurysms underwent digital subtraction angiography (DSA) and 2-mm-collimation spiral CT. Cine-interactive display of overlapping axial, reformatted, and maximum intensity projection images were used for CT image analysis. CT findings were compared with angiographic and surgical findings. RESULTS: The proximal extent of the juxta- and suprarenal aneurysms (n = 15) could be correctly predicted in 12 cases (80%) with DSA and was exactly determined in 14 (93%) with CT. All renal arteries except three accessory renal arteries were correctly depicted with spiral CT (83 of 86 [96%]). With DSA as the standard of reference, renal artery stenoses of at least 70% were accurately assessed in 95% of cases. CONCLUSION: Thin-section spiral CT can provide additional information in the preoperative diagnosis of juxta- and suprarenal aneurysms.

Aged↗
PubMed1996

Dynamics of respiratory gas exchange during exercise after correction of congenital heart disease.

In pediatric exercise testing, conventional measures of aerobic exercise function such as maximal O2 uptake or the ventilatory anaerobic threshold (VAT) use only one value for the assessment of exercise capacity. We studied a more comprehensive approach to evaluate aerobic exercise function by analyzing the steepness of the slope of CO2 production (VCO2) vs. VO2 above the VAT (S3). This was calculated in 32 patients operated on for congenital heart disease [16 for transposition of the great arteries (TGA) and 16 for tetralogy of Fallot (TF)] and was compared with 16 age-matched controls (nl). The results show that the reproducibility of this new assessment method was excellent (coefficient of variation for S3: 8.6%). S3 was significantly steeper (P<0.05) in the patients (1.31 +/- 0.22 for TGA and 1.28 +/- 0.16 for TF) compared with the nl (1.10 +/- 0.22). Also, the difference between S3 and the slope of VCO2 vs. VO2 below the VAT was significantly higher in the patients (0.37 +/- 0.22 for TGA and 0.31 +/- 0.10 for TF) than in controls (0.22 +/- 0.06). The steeper slopes were associated with lower than normal values for VAT and O2 during exercise. It is concluded that the analysis of the steepness of the slope of CO2 is a sensitive, reproducible, and objective approach to evaluate the integrative cardiopulmonary response to exercise. It complements the assessment of a subnormal VAT by reflecting the extent of anaerobic metabolism.

Aerobiosis↗
PubMed1995

Comparison by computerized numeric modeling of energy losses in different Fontan connections.

BACKGROUND: Different surgical techniques for creating a Fontan circulation can be used. The option of including an atrium in the circuit, or the technique used for connecting the caval veins to the pulmonary artery in a total cavopulmonary connection, frequently is empirical and is based on personal experience and preference. The hemodynamic and energetic differences between the different circuits are small, and short-term results are comparable. However, small, energetic differences may have significant implications for the long-term follow-up. The finite element method allows a computer-based modeling of the flow dynamics and pressure losses. It permits comparison of different Fontan connections in a single patient with identical geometry and functional conditions. METHODS AND RESULTS: We compared the atriopulmonary connection with different types of cavopulmonary connections, which differed in the degree of symmetry of implantation of both caval veins into the right pulmonary artery. Based on anatomic models and physiological flow dynamics, three-dimensional geometries and finite element meshes were created with PATRAN; flows were calculated with POLYFLOW (B), and results were visualized with DATA VISUALIZER. CONCLUSIONS: The atriopulmonary connection produces higher energy losses than the cavopulmonary connection (+/- 1 mm Hg at rest). The cavopulmonary connection is more efficient when the connection of the caval veins to the pulmonary artery is asymmetrical.

Blood Flow Velocity↗
PubMed1995

Sequence and spatial requirements for regulated muscle-specific processing of the sarco/endoplasmic reticulum Ca(2+)-ATPase 2 gene transcript.

Expression of the muscle-specific 2a isoform of the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA2) requires activation of an otherwise inefficient splicing process at the 3'-end of the primary gene transcript. The sequence and topology requirements for this regulated splicing event were studied in the BC3H1 myogenic cell line using a minigene containing the 3'-end of the SERCA2 gene. In undifferentiated BC3H1 cells, the splice process is made inefficient by the presence of a weak muscle-type 5'-donor site (5'D1) and a long terminal intron. Both optimizing the 5'D1 and decreasing the length of the muscle-specific intron, induced muscle-type splicing in undifferentiated myogenic cells. Moreover, the induction of muscle-type transcripts was only observed when two competing processing sites, the polyadenylation site (pAu) used in non-muscle cells and the second neuronal 5'-donor site (5'D2), were weak. Indeed, making 5'D2 consensus induced neuronal-type splicing in undifferentiated myocytes and prevented the appearance of muscle-type transcripts. Similarly, replacing the polyadenylation site (pAu) with a strong site almost completely inhibited muscle-type splicing after myogenic differentiation. We conclude that weak processing sites and a long terminal intron are required for tissue-dependent mRNA processing of the SERCA2 transcript.

Alternative Splicing↗
PubMed1995

Volume-activated chloride currents are not correlated with P-glycoprotein expression.

It has been proposed that P-glycoprotein, the product of the human MDR1 gene, may function not only as a drug transporter but, depending on the conditions, as a volume-activated Cl- channel [Valverde, Diaz, Sepúlveda, Gill, Hyde and Higgins (1992) Nature (London) 355, 830-833; Gill, Hyde, Higgins, Valverde, Mintenig and Sepúlveda (1992) Cell 71, 23-32]. To verify this hypothesis, we have compared volume-activated Cl- currents with the level of MDR1 mRNA and its protein product in the human KB3 (epitheloid lung cancer) and HeLa cell lines. The related MDR2 was also included to find out whether it could account for observed discrepancies between Cl- current and MDR1 expression. A 40% decrease in osmolarity evoked a Cl- current in both cell types (at +80 mV: 50.3 +/- 4.3 pA/pF in KB3, n = 13; 28.2 +/- 3.3 pA/pF in HeLa, n = 16). The blocking of this current in both cell types by 5-nitro-2-(3-phenylpropylamino)-benzoic acid and by 1,9-dideoxyforskolin is similar to that of the presumed P-glycoprotein associated Cl- channel. As measured by reverse-transcriptase polymerase chain reaction, KB3 cells expressed only an extremely small amount of the messengers for MDR1 and MDR2. The signal observed for MDR1 in HeLa cells was at least an order of magnitude more intense than in KB3 cells, while MDR2 mRNA was undetectable. A clear difference in MDR1 expression between KB3 and HeLa was also observed at the protein level. These data are difficult to reconcile with the hypothesis that in HeLa and KB3 cells MDR1- or MDR2- encoded P-glycoproteins are associated with volume-activated Cl- channels.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Modulation of SERCA2 activity: regulated splicing and interaction with phospholamban.

Ca(2+)-uptake into intracellular stores is mediated by the sarco/endoplasmic reticulum Ca(2+)ATPases (SERCAs). This review deals first with the gene structural and the characterization of the tissue-specific SERCA2 transcript processing. Secondly, the two different protein isoforms and their regulation are described. Finally, this review ends with a discussion on the possible physiological role of the SERCA2 isoform diversity.

Animals↗
PubMed1995

Helical CT for the preoperative localization of islet cell tumors of the pancreas: value of arterial and parenchymal phase images.

OBJECTIVE: In two-phase helical CT, organs are scanned in both the arterial and the parenchymal phase after IV injection of contrast material. The purpose of our study was to evaluate the usefulness of two-phase helical CT for the preoperative localization of pancreatic islet cell tumors. MATERIALS AND METHODS: Ten patients with 11 surgically proven islet cell tumors were included in the study. Helical CT scans of the pancreas were obtained with 5-mm collimation and overlapping image reconstruction. Images were obtained in the arterial and parenchymal phases after contrast material injection. A test bolus was used for tailored bolus timing. Images were analyzed by two observers. If a tumor was detected, its density relative to the surrounding parenchyma was scored by consensus, using a five-point scale. RESULTS: Nine of 11 tumors could be located using two-phase helical CT (sensitivity, 82%), including one 4-mm gastrinoma. Two lesions smaller than 5 mm could not be visualized. Two tumors were easier to detect (n = 1) or could only be detected on parenchymal-phase images (n = 1). Tumor conspicuity was better on arterial-phase images in two patients. CONCLUSION: Our results show that obtaining CT scans in both the arterial and the parenchymal phase leads to improved detection of pancreatic islet cell tumors.

Adenoma, Islet Cell↗
PubMed1994

The functional importance of the extreme C-terminal tail in the gene 2 organellar Ca(2+)-transport ATPase (SERCA2a/b).

Ca(2+)-uptake experiments in microsomal fractions from transfected COS-1 cells have revealed a functional difference between the non-muscle SERCA2b Ca2+ pump and its muscle-specific SERCA2a splice variant. Structurally, the two pumps differ only in their C-terminal tail. The last four amino acids of SERCA2a are replaced in SERCA2b by a 49-residue-long peptide chain containing a very hydrophobic stretch which could be an additional transmembrane segment. The functionally important subdomains in the SERCA2b tail were analysed by constructing three SERCA2b deletion mutants lacking 12, 31 or 49 amino acids. The mutants and the parental SERCA2 pumps were expressed in COS-1 cells and analysed for functional difference. SERCA2b had a twofold higher Ca2+ affinity, a twofold lower turnover rate and a 10-fold lower vanadate-sensitivity than SERCA2a and the mutants. Since each of the three truncated versions of SERCA2b acquire the characteristic properties of SERCA2a, it is concluded that the stretch of the last 12 residues of SERCA2b is of critical importance.

Amino Acid Sequence↗
PubMed1994

Regulation of splicing is responsible for the expression of the muscle-specific 2a isoform of the sarco/endoplasmic-reticulum Ca(2+)-ATPase.

Tissue-specific alternative processing of sarco/endoplasmic reticulum Ca(2+)-ATPase 2 (SERCA2) transcripts generates functionally different Ca2+ pump isoforms in muscle compared with non-muscle tissues. In non-muscle cells, the SERCA2 pre-mRNA can be polyadenylated at a site located between the donor and acceptor splice site of an intron which is only removed in muscle tissues. To define the cis-active elements involved in differential processing, we constructed a minigene (pCM beta SERCA2) containing the 3' end of the SERCA2 gene. When stably transfected into a myogenic cell line, minigene transcripts were differentially processed depending on the differentiation state of the cells. This proves that the essential elements required for regulated processing are present in the construct. Furthermore, co-transfection of the pCM beta SERCA2 minigene and a myogenin expression vector in a fibroblast cell line induced muscle-specific splicing of transcripts from pCM beta SERCA2. This shows that trans-acting factor(s) responsible for muscle-specific processing can be induced by one of the important regulatory genes of muscle differentiation. Inactivation of the non-muscle poly(A) site did not induce splicing in non-muscle cells. This excludes a simple competition model between splicing and polyadenylation, but it is consistent with splicing being very inefficient in non-muscle cells. Moreover, splicing could be induced in non-muscle cells by optimizing the muscle-specific donor splice site and/or by shortening the intron length. We therefore propose that expression of the muscle-specific SERCA2a isoform is the result of activation of an otherwise inefficient splicing process.

Animals↗
PubMed1994

Determination of relative amounts of inositol trisphosphate receptor mRNA isoforms by ratio polymerase chain reaction.

The relative expression of different inositol 1,4,5-trisphosphate receptor (InsP3R) mRNA was determined in a selection of murine and rat cell types that are commonly used to study InsP3-mediated Ca2+ signaling. Different mRNA species (encoding the known InsP3R isoforms) were co-amplified using common polymerase chain reaction primer pairs that recognized sequences that are totally conserved between the various InsP3R. Specific identification of the co-amplified sequences was done by restriction site analysis. In cerebellum, mRNA encoding InsP3R-I accounted for > 90% of the total InsP3R mRNA. This isoform was also present in all other cell types tested and was often the major isoform. In contrast, the level of expression of the other isoforms was cell type-specific. A new InsP3R isoform (type V) was detected that had 94.5% sequence identity with the InsP3R-II in the amplified region. Interestingly, this isoform was largely expressed in murine but not in rat cells. We functionally characterized InsP3R-V using the mouse fibroblast C3H10T1/2 cells, where mRNA encoding InsP3R-V accounted for 76.4% of the total InsP3R mRNA. InsP3-induced Ca2+ release in permeabilized C3H10T1/2 cells was regulated by luminal and cytosolic Ca2+, stimulated by thimerosal, and inhibited by caffeine.

Animals↗