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Biomedical subjects

M Goethals

Publications and source records attributed to M Goethals.

At least 19 recordsLinked to original sources
PubMed2003

Mode switching failure during atrial flutter: the '2:1 lock-in' phenomenon.

AIMS: To evaluate incidence and mechanism of a special form of automatic mode switching (MS) failure in patients with atrial flutter. METHODS AND RESULTS: Retrospectively the charts of 134 patients implanted with dual chamber pacemakers with MS algorithms were reviewed. Seven patients (5.2%) were identified that presented with sustained rapid ventricular pacing resulting from atrial flutter with failure of automatic MS. Since this form of MS failure implies 2:1 tracking of atrial flutter, it was coined '2:1 lock-in'. A theoretical timing model was developed to clarify the mechanism of this special form of MS failure. Prerequisites for the '2:1 lock-in' phenomenon are: (1). the sum of the AV delay and the post ventricular blanking (PVAB) must be longer than the cycle length of the atrial flutter, (2). the tachycardia detection rate must be higher than half the atrial flutter rate and (3). the maximum tracking rate (MTR) must be higher than half the atrial flutter rate. Recommendations for programming in order to avoid this specific form of MS failure are made accordingly and parallel algorithms for flutter detection are discussed. CONCLUSION: '2:1 lock-in' is a typical form of MS failure in patients with atrial flutter and the mechanism is closely linked to the typical atrial sensing windows.

Algorithms↗
PubMed2001

Prefoldin recognition motifs in the nonhomologous proteins of the actin and tubulin families.

Nascent actin and tubulin molecules undergo a series of complex interactions with chaperones and are thereby guided to their native conformation. These cytoskeletal proteins have the initial part of the pathway in common: both interact with prefoldin and with the cytosolic chaperonin containing tailless complex polypeptide 1. Little is understood with regard to how these chaperones and, in particular, prefoldin recognize the non-native forms of these target proteins. Using mutagenesis, we provide evidence that beta-actin and alpha-tubulin each have two prefoldin interaction sites. The most amino-terminally located site of both proteins shows striking sequence similarity, although these proteins are nonhomologous. Very similar motifs are present in beta- and gamma-tubulin and in the newly identified prefoldin target protein actin-related protein 1. Actin-related proteins 2 and 3 have related motifs, but these have altered charge properties. The latter two proteins do not bind prefoldin, although we identify them here as target proteins for the cytosolic chaperonin. Actin fragments containing the two prefoldin interaction regions compete efficiently with actin for prefoldin binding. In addition, they also compete with tubulins, suggesting that these target proteins contact similar prefoldin subunits.

Actins↗
PubMed2001

Protein identification based on matrix assisted laser desorption/ionization-post source decay-mass spectrometry.

Due to its very short analysis time, its high sensitivity and ease of automation, matrix-assisted laser desorption/ionization (MALDI)-peptide mass fingerprinting has become the preferred method for identifying proteins of which the sequences are available in databases. However, many protein samples cannot be unambiguously identified by exclusively using their peptide mass fingerprints (e.g., protein mixtures, heavily posttranslationally modified proteins and small proteins). In these cases, additional sequence information is needed and one of the obvious choices when working with MALDI-mass spectrometry (MS) is to choose for post source decay (PSD) analysis on selected peptides. This can be performed on the same sample which is used for peptide mass fingerprinting. Although in this type of peptide analysis, fragmentation yields are very low and PSD spectra are often very difficult to interpret manually, we here report upon our five years of experience with the use of PSD spectra for protein identification in sequence (protein or expressed sequence tag (EST)) databases. The combination of peptide mass fingerprinting and PSD and analysis described here generally leads to unambiguous protein identification in the amount of material range generally encountered in most proteome studies.

Peptide Fragments↗
PubMed2001

Posterior cortical atrophy. Two case reports and a review of the literature.

We present two cases of progressive early-onset dementia with apraxia and visuospatial disability as initial manifestations. In the later stages of the illness Gerstmann's and Balint's syndromes developed. Structural neuroimaging demonstrated parieto-occipital atrophy and functional imaging revealed bilateral hypometabolism and hypoperfusion in these areas. These cases fulfil the diagnostic criteria of posterior cortical atrophy (PCA). Frontal lobe involvement became evident as the disease progressed. Alzheimer's disease also typically features this anterior spread and possibly this is the underlying pathological substrate for this clinical syndrome, although definite pathology is lacking. In this report, we describe longitudinal evolution in these two cases of PCA.

Alzheimer Disease↗
PubMed2001

Isolated non-compaction of the left ventricle: a rare indication for transplantation.

This report describes the diagnostic difficulty encountered in a young female patient presenting with neurologic symptoms, atrial fibrillation and severe left ventricular systolic dysfunction, eventually leading to cardiac transplantation. The scrutiny used in the evaluation of the particular aspect of the left ventricle, and the integration of the information obtained from echocardiography, angiography and magnetic resonance imaging, led to the diagnosis of a rare and mostly unknown cause of cardiac failure. The correct identification of this entity is mandatory because enhanced risk of thromboembolism and malignant arrhythmia should be anticipated. A review of the literature revealed only 6 patients in whom isolated non-compaction of the left ventricle was treated by heart transplantation.

Adult↗
PubMed2001

Comparison of the aggregation properties, secondary structure and apoptotic effects of wild-type, Flemish and Dutch N-terminally truncated amyloid beta peptides.

The Dutch (E22Q) and Flemish (A21G) mutations in the betaAPP region of the amyloid precursor protein (APP) are associated with familial forms of Alzheimer dementia. However, patients with these mutations express substantially different clinical phenotypes. Therefore, secondary structure and cytotoxic effects of the three Abeta(12-42) variants [wild-type (WT), Dutch and Flemish] were tested. At a concentration of 5 microM the aggregation of these peptides followed the order: Abeta(1-42) WT > Abeta(12-42) WT > Abeta(12-42) Flemish > Abeta(12-42) Dutch. The stability of the secondary structure of these peptides upon decreasing the trifluoroethanol (TFE) concentration in the buffer was followed by circular dichroism measurements. WT peptides progressively lost their alpha-helical structure; this change occurred faster for both the Flemish and Dutch peptides, and at higher percentages of TFE in the buffer, and was accompanied by an increase in beta-sheet and random coil content. Apoptosis was induced in neuronal cells by the Abeta(12-42) WT and Flemish peptides at concentrations as low as 1-5 microM, as evidenced by propidium iodide (PI) staining, DNA laddering and caspase-3 activity measurements. Even when longer incubation times and higher peptide concentrations were applied the N-truncated Dutch peptide did not induce apoptosis. Apoptosis induced by the full length Abeta(1-42) peptide was weaker than that induced by its N-truncated variant. These data suggest that N-truncation enhanced the cytotoxic effects of Abeta WT and Flemish peptides, which may play a role in the accelerated progression of dementia.

Alzheimer Disease↗
PubMed2000

Targeting of aminopeptidase I to the yeast vacuole is mediated by Ssa1p, a cytosolic member of the 70-kDa stress protein family.

The two cytosolic members of the highly conserved 70-kDa stress protein family, Ssa1p and Ssa2p, were specifically retained by the prepro-NH(2) extension of the vacuolar aminopeptidase I precursor (pAPI) conjugated to agarose (Sulfolink). A temperature-sensitive mutant strain a1(ts)a234 (ssa1(ts) ssa2 ssa3 ssa4), when incubated at the restrictive temperature, was able to assemble the API precursor into dodecamers, but failed to pack pAPI into vesicles and to convert it into mature API (mAPI), a process that occurs in the vacuole. Altogether these results indicate that Ssa1p mediates the targeting of pAPI to the vacuole.

Adenosine Triphosphatases↗
PubMed2000

The competitive interaction of actin and PIP2 with actophorin is based on overlapping target sites: design of a gain-of-function mutant.

We studied the effect of mutations in an alpha-helical region of actophorin (residues 91-108) on F-actin and PIP(2) binding. As in cofilin, residues in the NH(2)-terminal half of this region are involved in F-actin binding. We show here also that basic residues in the COOH-terminal half of the region participate in this interaction whereby we extend the previously defined actin binding interface [Lappalainen, P., et al. (1997) EMBO J. 16, 5520-5530]. In addition, we demonstrate that some of the lysines in this alpha-helical region in actophorin are implicated in PIP(2) binding. This indicates that the binding sites of F-actin and PIP(2) on actophorin overlap, explaining the mutually exclusive binding of these ligands. The Ca(2+)-dependent F-actin binding of a number of actophorin mutants (carrying a lysine to glutamic acid substitution at the COOH-terminal positions of the actin binding helical region) may mimic the behavior of members of the gelsolin family. In addition, we show that PIP(2) binding, but not actin binding, of actophorin is strongly enhanced by a point mutation that leads to a reinforcement of the positive electrostatic potential of the studied alpha-helical region.

Actin Depolymerizing Factors↗
PubMed2000

Are better eye movements an advantage in ball games? A study of prosaccadic and antisaccadic eye movements.

The aim of this study was to compare prosaccadic and antisaccadic eye movements of experts in ball sports and controls. In the prosaccadic and antisaccadic task, subjects made saccades respectively towards and away from a suddenly appearing stimulus. By means of infrared-oculography, we compared horizontal eye movements of experts (n=18) and controls (n=20). Experts had shorter overall saccadic latencies, but significantly shorter latencies occurred only on the antisaccade task, not on the prosaccade task. Our findings seem to support the concept that prosaccades and antisaccades have different underlying mechanisms and that expertise in ball games mainly improves antisaccadic performance in terms of latency and variability.

Adult↗
PubMed1999

Experimental study of the flammability limits of toluene-air mixtures at elevated pressure and temperature.

The flammability limits of toluene-air mixtures are experimentally determined at pressures up to 500 kPa and temperatures up to 250 degrees C in a closed spherical vessel. The results at atmospheric pressure are compared with the results obtained in a glass tube. The flammability limits depend linearly upon temperature. A twilight zone characterized by weak pressure rises is observed for toluene at all pressures, while soot is formed at elevated pressures only. The explosion characteristics of toluene are compared with those of methane. Despite their chemical differences, the explosion characteristics of toluene and methane are similar.

Atmospheric Pressure↗
PubMed1999

Beta-amyloid peptide interacts specifically with the carboxy-terminal domain of human apolipoprotein E: relevance to Alzheimer's disease.

Growing evidence indicates the involvement of apolipoprotein E (apoE) in the development of late-onset and sporadic forms of Alzheimer's disease, although its exact role remains unclear. We previously demonstrated that beta-amyloid peptide (Abeta) displays membrane-destabilizing properties and that only apoE2 and E3 isoforms inhibit these properties. In this study, we clearly demonstrate that the carboxy-terminal lipid-binding domain of apoE (e.g., residues 200-299) is responsible for the Abeta-binding activity of apoE and that this interaction involves pairs of apoE amphipathic alpha-helices. We further demonstrate that Abeta is able to inhibit the association of the C-terminal domain of apoE with lipids due to the formation of Abeta/apoE complexes resistant to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. On the contrary, the amino-terminal receptor-binding domain of apoE (e.g., residues 129-169) is not able to form stable complexes with Abeta. These data extend our understanding of human apoE-dependent binding of Abeta by involving the C-terminal domain of apoE in the efficient formation of apoE/Abeta complex.

Alzheimer Disease↗
PubMed1999

Identification of Tyr438 as the major in vitro c-Src phosphorylation site in human gelsolin: a mass spectrometric approach.

Gelsolin is an actin-binding protein (82 kDa) consisting of six repeated segments (S1-S6), each approximately 120 residues long. It interacts with phospholipids and we previously showed that phosphatidylinositol 4,5-bisphosphate promotes phosphorylation of gelsolin by the tyrosine kinase c-Src. We used a combination of different methods, such as thin-layer chromatography and anti-phosphotyrosine-agarose immunoprecipitation of phosphopeptides combined with matrix assisted laser desorption ionization-mass spectrometry (MALDI-MS) and post source decay (PSD) analysis, to identify the phosphorylation sites in gelsolin. The major phosphorylation site (Tyr438) was located in subdomain 4 (S4). Phosphorylation of gelsolin in the gelsolin-actin2 complex was inhibited by 90%. Gelsolin phosphorylation by c-Src in the presence of lysophosphatidic acid also revealed Tyr438 as the most prominent site. Additional minor sites were found using the anti-phosphotyrosine bead immunoprecipitation method followed by MALDI-MS and PSD analysis. These sites, representing approximately 5% of the total phosphate incorporation, were identified as Tyr59, Tyr382, Tyr576, and Tyr624. Based on these results we generated antibodies which specifically recognize Tyr438 phosphorylated gelsolin.

Actins↗
PubMed1999

ECG diagnosis of native heart ventricular tachycardia in a heterotopic heart transplant recipient.

A case is reported of haemodynamic collapse in a 51 year old male heterotopic heart transplant recipient caused by native heart ventricular tachycardia. An accurate diagnosis was made by selective right and left sided electrocardiography. Synchronised electrical cardioversion of the native heart (200 J) resulted in restoration of sinus rhythm with prompt relief of symptoms and amelioration of the clinical situation.

Electric Countershock↗