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Biomedical subjects

P Vanhoenacker

Publications and source records attributed to P Vanhoenacker.

17 recordsLinked to original sources
PubMed1998

Agonistic properties of alniditan, sumatriptan and dihydroergotamine on human 5-HT1B and 5-HT1D receptors expressed in various mammalian cell lines.

1. Alniditan, a novel migraine abortive agent, is a potent 5-HT1B/5-HT1D receptor agonist of nM affinity. We compared the agonistic properties of alniditan, sumatriptan and dihydroergotamine on the cloned human 5-HT1B receptor expressed at 200 fmol mg(-1) protein (Bmax) in non-induced L929sA cells, at 740 fmol mg(-1) protein in HEK 293 and at 2300 fmol mg(-1) protein in mIFNbeta-induced L929sA cells, and on the human cloned 5-HT1D receptor expressed in C6 glioma cells (Bmax 780 fmol mg(-1) protein). 2. Sodium butyrate treatment increased the expression level of human (h)5-HT1B receptors in HEK 293 cells and h5-HT1D receptors in C6 glioma cells approximately 3 fold, the binding affinities of [3H]-5-HT and [3H]-alniditan were unaffected. 3. Agonistic properties were evaluated based on inhibition of cyclic AMP accumulation in the cells after stimulation of adenylyl cyclase by forskolin or isoproterenol. Alniditan, sumatriptan and dihydroergotamine were full agonists at the hS-HT1B receptor (IC50 values were 1.7, 20 and 2 nM, respectively in HEK 293 cells) and hS-HT1D receptors (IC50 values of 1.3, 2.6 and 2.2 nM, respectively). At the h5-HT1B receptor the agonist potency of the compounds slightly increased with higher receptor density. The opposite was seen for antagonists (ocaperidone, risperidone and ritanserin). 4. This comparative study demonstrated that alniditan was 10 times more potent than sumatriptan at the h5-HT1B receptor, and twice as potent at the h5-HT1D receptor. Dihydroergotamine was more potent an agonist at the h5-HT1B receptor when expressed at high and low level in L929sA cells (but not in HEK 293 cells), and was less potent at the hS-HT1D receptor.

Adenylyl Cyclases↗
PubMed1997

Stable, high-level expression of human serotonin receptors in L929 cells using an inducible expression system.

Heterologous expression of cloned receptor subtypes for screening programs has become a real necessity for a modern pharmaceutical company. As the expression levels obtained so far are often low or unstable, we addressed this problem by using an inducible promoter system, i.e. the interferon-inducible mouse Mxl promoter. Using the gene coding for chloramphenicol acetyltransferase (CAT) as a reporter gene, we tested the inducibility of this promoter in the murine cell line L929. We found that background expression was low and that a distinct interferon-induced expression could be obtained. CAT expression reached its maximum at approximately 15 ng CAT/mg protein after induction for 24 hr with 1000 U/ml murine interferon-beta; the induction ratio was 150-fold. Next, L929 cells were transfected with four different human serotonin (5HT) receptor cDNAs (5HT1A, 5HT2A, 5HT1D beta and 5HT1E) under the control of the same Mxl promoter fragment. Also in this case well-regulated serotonin receptor-expressing clones were isolated. Bmax values varied from 3100 fmol/mg protein for the 5HT2A receptor, 3300 fmol/mg protein for the 5HT1D beta receptor, 9800 fmol/mg protein for the 5HT1E receptor, and even up to 10,400 fmol/mg protein for the 5HT1A receptor. Furthermore, the expression levels were shown to remain stable during serial propagation for at least one year, demonstrating the usefulness of this expression system. In fact, the 5HT1D beta receptor-expressing cells were used in the characterization of a new antimigraine agent, viz. alniditan.

Animals↗
PubMed1996

Alniditan, a new 5-hydroxytryptamine1D agonist and migraine-abortive agent: ligand-binding properties of human 5-hydroxytryptamine1D alpha, human 5-hydroxytryptamine1D beta, and calf 5-hydroxytryptamine1D receptors investigated with [3H]5-hydroxytryptamine and [3H]alniditan.

Alniditan is a new migraine-abortive agent. It is a benzopyran derivative and therefore structurally unrelated to sumatriptan and other indole-derivatives and to ergoline derivatives. The action of sumatriptan is thought to be mediated by 5-hydroxytryptamine (5-HT)1D-type receptors. We investigated the receptor-binding profile in vitro of alniditan compared with sumatriptan and dihydroergotamine for 28 neurotransmitter receptor subtypes, several receptors for peptides and lipid-derived factors, ion channel-binding sites, and monoamine transporters. Alniditan revealed nanomolar affinity for calf substantia nigra 5-HT1D and for cloned h5-HT1D alpha, h5-HT1D beta and h5-HT1A receptors (Ki = 0.8, 0.4, 1.1, and 3.8 nM, respectively). Alniditan was more potent than sumatriptan at 5-HT1D-type and 5-HT1A receptors. Alniditan showed moderate-to-low or no affinity for other investigated receptors; sumatriptan showed additional binding to 5-HT1F receptors. Dihydroergotamine had a much broader profile with high affinity for several 5-HT, adrenergic and dopaminergic receptors. In signal transduction assays using cells expressing recombinant h5-HT1D alpha, h5-HT1D beta, or h5-HT1A receptors, alniditan (like 5-HT) was a full agonist for inhibition of stimulated adenylyl cyclase (IC50 = 1.1, 1.3, and 74 nM, respectively, for alniditan). Therefore, in functional assays, the potency of alniditan was much higher at 5-HT1D receptors than at 5-HT1A receptors. We further compared the properties of [3H]alniditan, as a new radioligand for 5-HT1D-type receptors, with those of [3H]5-HT in membrane preparations of calf substantia nigra, C6 glioma cells expressing h5-HT1D alpha, and L929 cells expressing h5-HT1D beta receptors. [3H]Alniditan revealed very rapid association and dissociation binding kinetics and showed slightly higher affinity (Kd = 1-2 nM) than [3H]5-HT. We investigated 25 compounds for inhibition of [3H]alniditan and [3H]5-HT binding in the three membrane preparations; Ki values of the radioligands were largely similar, although some subtle differences appeared. Most compounds did not differentiate between 5-HT1D alpha and 5-HT1D beta receptors, except methysergide, ritanserin, ocaperidone, risperidone, and ketanserin, which showed 10-60-fold higher affinity for the 5-HT1D alpha receptor. The Ki values of the compounds obtained with 5-HT1D receptors in calf substantia nigra indicated that these receptors are of the 5-HT1D beta-type. We demonstrated that alniditan is a potent agonist at h5-HT1D alpha and h5-HT1D beta receptors; its properties probably underlie its cranial vasoconstrictive and antimigraine properties.

Animals↗
PubMed1995

Cervical spinal arteriovenous malformation.

Cervical spinal arteriovenous malformations and fistulas are rare but important entities because they are potentially curable. MRI and angiography are the most useful imaging modalities for the diagnosis. On contrast-enhanced CT imaging, they can mimic a tumor. A case report of cervical spinal arteriovenous malformation, initially believed to be a tumor, is presented.

Angiography↗
PubMed1995

Leiomyosarcoma.

Explore the source record for details and available documents.

Arm↗
PubMed1994

Mucocele of the appendix.

We describe a case of mucocele of the appendix, observed incidentally in a 42-year-old man. The plain film, ultrasound and CT features are reviewed. Adequate diagnosis and resection are important because of the risk of rupture and development of pseudomyxoma peritonei.

Adult↗
PubMed1993

Atypical aesthesioneuroblastoma: CT and MRI findings.

Aesthesioneuroblastoma is an uncommon tumour of the superior nasal cavity, originating from the olfactory mucosa. Usually no specific radiological features indicate the diagnosis; normally these tumours are seen on CT as homogeneous, enhancing, soft tissue masses causing bone remodelling. Typical but quite nonspecific MRI findings include high signal on T2-weighted images and strong enhancement after gadolinium. The extent of tumour in the paranasal sinuses and anterior cranial fossa is best assessed with MRI after intravenous gadolinium, and this is considered as the most accurate method for assessing preoperative resectability. We report an aesthesioneuroblastoma in an atypical location, with extensive calcification.

Adolescent↗
PubMed1993

Transition of renal arteriovenous fistula to arteriocalyceal fistula during embolization.

Selective and superselective renal embolization is a generally accepted technique for treating traumatic or iatrogenic renal arteriovenous fistulas or arteriocalyceal fistulas. Only a minority are pure arteriocalyceal fistulas. During embolization, an arteriovenous fistula may become a frankly bleeding arteriocalyceal fistula, causing massive haematuria and necessitating further embolization.

Aged↗
PubMed1990

MR angiography with gadopentetate dimeglumine-polylysine: evaluation in rabbits.

Flow in high-resistance peripheral vessels of the extremities is characterized by a short period of positive flow during systole and almost no flow during diastole. Hence, time-of-flight sequences for MR angiography in high-resistance peripheral vessels are successful only when applied in a plane perpendicular to the vessel course. When applied in a plane parallel to the vessel, the method suffers from the rapid saturation of the inflowing spins. Gadopentetate dimeglumine-polylysine is a new T1 relaxation agent with blood-pooling capability that can be used to prevent blood saturation. In the present study it produced excellent angiograms in rabbits at a dose of 0.01-0.08 mmol/kg injected IV. Time-of-flight angiograms were acquired in a 1.5-T superconducting magnet with a three-dimensional fast imaging with steady precession sequence, 20,40/10/20 degrees (TR/TE/flip angle), with an acquisition volume of 200 x 200 x 60 mm, 64 partitions, and velocity compensation in the slice-selection and frequency-encoding directions. Arteries and veins smaller than 1 mm were visualized over the entire length of the posterior limbs. If ongoing studies confirm the low toxicity of this new agent, gadopentetate dimeglumine-polylysine could offer a totally new approach to MR angiography.

Animals↗
PubMed1990

Outpatient angiography.

Outpatient angiography of the abdominal aorta and the peripheral arteries of the under limbs was performed in 100 patients with complaints of peripheral vascular disease. In all patients small 5F catheters, a low-osmolar contrast medium and intraarterial digital subtraction angiography could reduce the local and general invasiveness of the angiographic procedure. Two complications occurred. In one patient thrombosis at the puncture site was noted. In another patient, an onset of angina pectoris was a minor and transitory complication. In 42 out of the 100 patients, treatment was conservative so that hospitalization could be avoided. With newer technical equipment angiography can be performed safely on an outpatient basis with important costsaving for the community. The late occurrence of some complications though, requires good information of the patient.

Adult↗
PubMedDate not supplied

MRA review.

Magnetic resonance (MR) angiography is a rapidly evolving field in MR imaging, the main goal of which is a noninvasive tool for visualizing blood vessels. The acquisition of continuous images of the blood vessels, comparable to the conventional DSA images, as well as the functional evaluation of blood-flow velocities and flow patterns are the subject of continuing developments. The basic principles of the various techniques and their clinical applications are reviewed and the practical limitations in specific anatomic regions discussed. The review concludes with a survey of future developments.

Angiography↗
PubMedDate not supplied

Axial vs sagittal T2-weighted brain MR images in the evaluation of multiple sclerosis.

Axial and sagittal proton density and T2-weighted MR images (TR 2,500-3,000 ms, TE 15-22 and 85-90 ms) were performed in 50 patients with multiple sclerosis (MS) on a 1.5 T superconductive system. The number of plaques on the axial and sagittal images in the periventricular white matter, the corpus callosum, the brain stem, the cerebellum, and the basal ganglia were counted separately by two independent observers. A total of 858 lesions (mean 17.40 +/- 21.57) were seen on the axial series and 1,196 (mean 24.32 +/- 26.22) on the sagittal scans. More lesions were visualized on sagittal images in the periventricular region (mean 18.79 +/- 21.69 versus 13.34 +/- 16.45; p less than 0.001) and the corpus callosum (mean 3.00 +/- 2.72 versus 0.57 +/- 1.19; p less than 0.001). In the brain stem more lesions were visualized on the axial images (mean 1.55 +/- 2.55 versus 0.87 +/- 1.20; p less than 0.05). In the cerebellum and basal ganglia, scans in the two planes were equivalent (p greater than 0.5). In three patients lesions were seen on the sagittal series, while the axial scans were normal. Sagittal T2-weighted images appear to demonstrate significantly more MS plaques than transverse images, especially in the periventricular region and the corpus callosum. This is explained by partial volume averaging, by the orientation of some cerebral structures (e.g., corpus callosum) with regard to the section plane, and by the longer diameter of the lesions in the axial plane.

Brain Diseases↗
PubMedDate not supplied

Studies on the induction of the interleukin-6 promoter in cell lines of human and simian origin.

In a number of eukaryotic cell types, the promoter of the interleukin-6 (IL-6) gene is inducible by several agents. We studied this inducibility in two human (MG63 and HeLa H21) and four simian cell lines (BSC-1, AP8, CV-1 and VERO). Furthermore, we also investigated whether this inducibility was maintained when a heterologous gene was placed under control of the human IL-6 promoter. As a heterologous gene we used the Simian Virus 40 (SV40) large T antigen, because of its stimulatory effects on SV40-based expression vectors. For the human cell lines tested, we observed that this gene was equally well induced and controlled as the endogenous IL-6 gene. In contrast, the aforementioned simian cell lines were only slightly inducible for IL-6 production; moreover, after transfection with the IL-6 promoter--SV40 T antigen gene construct, a continuous, low level of expression was found, even in those lines which only showed a low (CV-1) or no (BSC-1) endogenous IL-6 background. This apparent difference between the human and simian cells analyzed does not reflect a species specificity, but presumably is related to a different differentiation state of these cells. Furthermore, the IL-6 gene induction could be correlated with activation of the required transcription factor NF-kappa B.

Animals↗