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Biomedical subjects

M Goethals

Publications and source records attributed to M Goethals.

At least 73 records · Page 4Linked to original sources
PubMed1993

An aspartic proteinase present in seeds cleaves Arabidopsis 2 S albumin precursors in vitro.

The Arabidopsis thaliana 2 S albumins are examples of vacuolar proteins which undergo intensive posttranslational processing. An in vitro processing assay to screen for processing enzymes present in seeds was developed using an in vitro synthesized 2 S albumin precursor as the substrate. A protease was characterized which cleaved the substrate into two fragments with molecular weights (as determined from their migration distance on SDS-polyacrylamide gel) corresponding to those of the small and large subunits of Arabidopsis 2 S albumin. The pH optimum of this protease activity, its inhibition by pepstatin A, and partial sequence data led to the conclusion that the protease under study was an aspartic proteinase. Synthetic peptides representing two 2 S albumin propeptides allowed the determination of the in vitro cleavage sites, and suggested that the protease activity is capable, in vitro, of cleaving the amino-terminal propeptide as well as the internal propeptide linking the two subunits. Alterations of the amino acids in and around the cleavage sites, made to study the specificity of the protease activity, suggest that both structural and sequence determinants are important in cleavage site recognition.

Albumins↗
PubMed1993

Use-dependent block of the pacemaker current I(f) in rabbit sinoatrial node cells by zatebradine (UL-FS 49). On the mode of action of sinus node inhibitors.

BACKGROUND: Zatebradine (UL-FS 49) is a drug with a specific bradycardiac electrophysiological profile. It reduces heart rate by lengthening the duration of diastolic depolarization in the sinoatrial (SA) node. The ionic basis of this action, however, is not clarified. METHODS AND RESULTS: We used the whole-cell patch-clamp technique to study the effects of zatebradine on ionic currents underlying diastolic depolarization of isolated rabbit SA node cells. Low concentrations of zatebradine simultaneously reduced diastolic depolarization rate and the pacemaker current I(f). The drug blocked the pacemaker current, I(f), in a use-dependent manner without causing a shift of its activation curve. At hyperpolarized potentials, unblock of I(f) occurred. Clinically relevant concentrations of the drug have little effect on the L-type calcium current or delayed rectifier potassium current. CONCLUSIONS: This use-dependent block of the If channel can account for most of the pharmacological characteristics of zatebradine and is probably the mechanism of heart rate reduction caused by this agent. Thus, the sinus node inhibitor zatebradine belongs to a new class of "I(f) blockers" with possible advantages over currently available drugs for the treatment of ischemic heart disease.

Animals↗
PubMed1992

Blockade of the pacemaker current by intracellular application of UL-FS 49 and UL-AH 99 in sheep cardiac Purkinje fibers.

UL-FS 49 (Zatebradine) and its quaternary derivative, UL-AH 99, were injected by iontophoresis in shortened sheep cardiac Purkinje fibres. The i(f) pacemaker current changes were analyzed using the two-microelectrode voltage-clamp technique. Injection of either drug resulted in a decrease of the maximal diastolic depolarization rate as a consequence of a reduction in i(f) amplitude, with no changes in the kinetics of this current or in voltage dependence. The i(f) blockade was proportional to the total charge injected. After drug iontophoresis under conditions where no i(f) current was activated, an exponential use-dependent decline in i(f) tail current was observed during the application of a voltage-clamp pulse train activating i(f). A slow recovery from blockade, measured after prolonged hyperpolarizations, followed exponential kinetics. Recovery rate and extent of steady state recovery increased with more negative potentials. This suggests that bradycardiac agents interact with the i(f) channel in cationic form from the inside of the cell.

Action Potentials↗
PubMed1992

An actin-binding site containing a conserved motif of charged amino acid residues is essential for the morphogenic effect of villin.

The actin-binding protein villin induces microvillus growth and reorganization of the cytoskeleton in cells that do not normally produce this protein. Transfection of mutagenized villin cDNAs into CV-1 cells was used to show that a conserved, COOH-terminally located cluster of charged amino acid residues (KKEK) is crucial for the morphogenic activity of villin in vivo. In vitro experiments with a 22 amino acid synthetic peptide corresponding to this region of villin provide evidence that this motif is part of an F-actin-binding site that induces G-actin to polymerize. Chemical cross-linking of actin to this peptide, the effects of amino acid substitutions in peptides, and the behavior of villin variants further corroborate the participation of the KKEK sequence in actin contacts.

Actins↗
PubMed1992

G- to F-actin modulation by a single amino acid substitution in the actin binding site of actobindin and thymosin beta 4.

The actin binding sites of actobindin and thymosin beta 4, two small polypeptides that inhibit actin polymerization by interacting with monomeric actin, have been localized using peptide mimetics. Both sites are functionally similar and extend over 20 residues and are located in the NH2-terminus of the polypeptides. They can be dissected into two functional entities: a conserved hexapeptide motif (LKHAET or LKKTET), which forms the major contact site through electrostatic interactions with actin, and a non-conserved NH2-terminal segment preceding the motif, which exerts the inhibitory activity on actin polymerization probably by steric hindrance. The introduction of a glutamic acid at the third position in the motif, creating LKEAET or LKETET sequences, which are similar to those found in some F-actin binding proteins, converts the peptide's inhibitory phenotype into an F-actin stimulatory property. These results allow the proposal of a simple model for G- to F-actin modulation.

Actins↗
PubMed1992

A long term clinical trial of carteolol in the management of glaucoma. Belgian Carteolol Study Participants.

Carteolol is a nonselective beta-blocker with intrinsic sympathomimetic activity (I.S.A.). A multicenter trial was started to check if the theoretical advantages of this new drug could also be confirmed in a clinical setting. The intraocular pressure (I.O.P.), the visual field and the adverse reactions were evaluated at day 8, 60, 360 and 960. The results of this study demonstrate that carteolol effectively lowers the I.O.P. with minimal adverse side effects in previously treated as well as untreated patients.

Adult↗
PubMed1991

Nephrogenic diabetes insipidus. An unusual presentation of recurrent rectal cancer.

The occurrence of diabetes insipidus (DI) in patients with systemic cancer is caused usually by tumor metastasis to the hypothalamus or posterior pituitary. A 43-year-old man with DI 8 months after radical surgery for a poorly differentiated adenocarcinoma of the distal rectum is reported. A therapeutic trial of intranasal desmopressin acetate did not correct the hyposthenuria, thus localizing the defect to the kidneys. A large tumor recurrence in the pelvis caused bilateral hydroureteronephrosis, resulting in nephrogenic DI. This report shows that not all cases of DI in cancer patients are of central origin.

Adenocarcinoma↗
PubMed1991

Use of low molecular mass RNA profiles to identify lactic acid bacteria and related organisms associated with foods.

Fourteen strains of lactic acid bacteria and species of Brochothrix, Carnobacterium, Enterococcus, Erysipelothrix, Kurthia and Listeria were examined using low molecular mass RNA (5S rRNA and tRNA) profiles. These profiles were developed on denaturing polyacrylamide gels. Gel strengths between 9 and 14% were tested to improve resolution of distinct bands for densitometrical analysis. Profiles generated on 12% gels proved to be the best for scanning. Scans of class 2 tRNAs by densitometry showed a characteristic profile for each genus. In the case of Lactobacillus each species studied gave a unique profile. The technique of low molecular mass RNA profiling may provide a useful means for identifying different bacteria from ecosystems such as meats.

Culture Media↗
PubMed1990

Use- and frequency-dependent blockade by UL-FS 49 of the if pacemaker current in sheep cardiac Purkinje fibres.

The mechanism by which the bradycardiac agent UL-FS 49 blocks the if pacemaker current was investigated in sheep Purkinje fibres using the two microelectrode voltage-clamp technique. If was activated by 1 s pulses applied between -30 mV and -120 mV at 0.4 Hz in a modified Tyrode solution containing BaCl2 and MnCl2, and with TRIS replacing most of the Na+. UL-FS 49 caused an exponential decline of the if current amplitude during a train of pulses. Both the rate and extent of the if reduction increased with drug concentration, without there being a resting blockade. Recovery from blockade followed a single exponential time course during prolonged hyperpolarizations. The recovery rate was extremely slow and increased with more negative voltages, as did the extent of steady state recovery from blockade. A frequency-dependent reduction of the diastolic depolarization rate resulted from a use-dependent blockade of the pacemaker current.

Animals↗
PubMed1990

Trabeculectomy: a retrospective long-term follow-up study.

The results of the surgical procedure of trabeculectomy as performed in our hospital on 100 eyes (67 patients) are presented. At the end of the follow-up period, with a range of 1 to 5 years and a mean follow-up of 36 months, there was an overall success rate of 68%. Criteria for success included no further visual field loss or disc damage, and no glaucomatous etiology for a decrease in visual acuity. Only in half of failure cases an IOP of more than 20 mmHg was recorded at least once during the follow-up period. Hyphaema, resolving most of the time in less than 7 days, was the most frequent postoperative complication (66%), followed by hypotomia (29%). Progression of lensopacities occurred in 22% of eyes.

Female↗
PubMed1987

Pharmacological influence of specific bradycardic agents on the pacemaker current of sheep cardiac Purkinje fibres. A comparison between three different molecules.

The diastolic depolarization rate of isolated sheep Purkinje fibres was reduced in the presence of micromolar concentrations of the 'specific bradycardic agent' falipamil (AQ-A39) and its congener UL-FS49. Both drugs reduced the amount of pacemaker current, if, activated during the diastolic depolarization phase. The if activation curve was reduced in amplitude but not shifted. UL-FS49 was more effective compared to falipamil in causing this reduction of if amplitude at similar concentrations. The reduction of the if amplitude was presumably caused by a drug-induced decrease in if current conductance. This if current block showed use-dependence. With UL-FS49 less and less if was activated with every successive voltage clamp pulse of a train, with little recovery of if block after a rest interval. Use-dependent block was smaller with comparable falipamil concentrations but full recovery was observed after a rest interval. No use-dependent block was observed with alinidine, a drug which also causes reduction of if by shifting its activation range to more negative potentials. These results indicate that the reduction of pacemaker current observed with two different types of 'specific bradycardic agents' is obtained by different mechanisms.

Action Potentials↗
PubMed1984

Massive dobutamine overdose in a cardiovascular compromised patient.

A case of dobutamine overdose is presented. Due to a prescription mistake a patient with recent myocardial necrosis and acute arterial occlusion received up to 70 mcg/kg/min of dobutamine IV. This resulted in arterial hypotension, diminished vascular resistance, oliguria and signs of cutaneous and mucosal hyperemia. Interruption of the dobutamine infusion and substitution with dopamine normalised all abnormalities. The differences between the hemodynamic profiles of dobutamine and dopamine are discussed.

Anuria↗
PubMed1983

Anteroseptal myocardial infarction complicated by right ventricular myocardial infarction.

A 73 year old man presented with an acute anteroseptal myocardial infarction. He became progressively hypotensive without signs of left heart decompensation or major rhythm disturbances. Swan-Ganz catheterisation revealed a pattern of right ventricular infarction and under appropriate treatment the patient recovered remarkably well. The importance of recognition of right ventricular infarction is stressed especially in this case where an anteroseptal myocardial infarction was present without the usual left posterior infarction.

Aged↗