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Biomedical subjects

C Thomsen

Publications and source records attributed to C Thomsen.

At least 145 records · Page 8Linked to original sources
PubMed1994

Age dependent white matter lesions and brain volume changes in healthy volunteers.

The brain of 142 healthy volunteers aged 21 to 80 years were investigated using MR imaging. The number and size of the white matter hyperintensity lesions (WMHL) in the cerebral hemispheres were determined. Furthermore, the volume of the cerebral hemispheres and of the lateral ventricles was measured. An almost linear increase in the number of volunteers with WMHL was seen with aging for males and females. With aging a significant decrease in the volume of the cerebral hemispheres was found for males, and a significant increase in the volume of the lateral ventricles was seen for both males and females. Our results suggest that with aging central atrophy increases more (relatively) than cortical atrophy. No correlation was found between the decreasing volume of the cerebral hemispheres and the increasing number and size of WMHL, nor between the increasing volume of the lateral ventricles and the increasing number and size of WMHL.

Adult↗
PubMed1993

Contrasting effects of adenosine A1 and A2 receptor ligands in different chemoconvulsive rodent models.

The pro- and anticonvulsive properties of selective adenosine A1 and A2 receptor agonists and antagonists were investigated in mice using seizure models involving a specific blockade of adenosine A1 and A2 receptors, modulation of the gamma-aminobutyric acid/benzodiazepine receptor complex or activation with the excitatory amino acid glutamate. The selective adenosine A1 receptor agonists N-cyclopentyladenosine (CPA) and R-N-(phenylisopropyl) adenosine (R-PIA) in doses of 1 and 10 mg/kg i.p. potentiated seizures induced by the selective adenosine A1 receptor antagonist 8-[4-[[[[(2-aminoethyl)amino]carbonyl]methyl]oxy]-phenyl]- 1,3-dipropylxanthine (XAC). Likewise, the selective adenosine A2 receptor agonists N-[(2-methylphenyl)methyl]adenosine (metrifudil) and N-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine (DPMA), in doses of 30 and 100 mg/kg i.p., respectively, potentiated seizures induced by the selective adenosine A2 receptor antagonist 3,7-dimethyl-1-propargylxanthine (DMPX). In contrast, the adenosine A1 and A2 receptor agonists both antagonized seizures induced by methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM--an inverse agonist at benzodiazepine receptors) and the adenosine A1 receptor agonists also protected against seizures induced by glutamate. Paradoxically, the selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT) antagonized DMCM- and pentylenetetrazole-induced seizures. Thus, it appears that adenosine A1 and A2 receptor agonists can be both pro- and anticonvulsive depending on the mechanism of action of the chemoconvulsant used in the seizure model. The findings with CPT suggest that other types of adenosine analogues than agonists may possess anticonvulsive properties.

Animals↗
PubMed1993

Effects of t-ACPD on neural survival and second messengers in cultured cerebral cortical neurones.

The cytotoxic potential of (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic acid (t-ACPD) in cultured murine cerebral cortical neurones was examined. Exposure to t-ACPD (1 mM, 16 h) did not induce cytotoxicity per se or affect N-methyl-D-aspartate-induced toxicity. Phosphoinositide hydrolysis was weakly stimulated by t-ACPD (1 mM), while no alteration of intracellular calcium levels was observed after exposure to 1 mM t-ACPD. However, forskolin-stimulated cAMP formation was inhibited by t-ACPD (IC50 = 8 +/- 2 microM) with a maximal inhibition of 36 +/- 4% of control levels. These data suggest that the lack of neurotoxic effects of t-ACPD may be related to the negligible efficacy of t-ACPD to activate mGluRs coupled to the IP3/Ca(2+)-cascade and/or putative counteracting effects of t-ACPD mediated by mGluRs negatively coupled to the cAMP-cascade.

Animals↗
PubMed1993

A pharmacological characterization of the mGluR1 alpha subtype of the metabotropic glutamate receptor expressed in a cloned baby hamster kidney cell line.

The pharmacological specificity of the mGluR1 alpha subtype of the metabotropic glutamate receptor (mGluR) was examined in a cloned baby hamster kidney cell line (BHK-ts13) measuring [3H]glutamate binding and inositol phosphate (PI) hydrolysis. PI-hydrolysis was maximally stimulated by quisqualate (1112 +/- 105% of basal), glutamate (1061 +/- 70% of basal), ibotenate (1097 +/- 115% of basal) and beta-N-methylamino-L-alanine (BMAA) (1010 +/- 104% of basal). In contrast, the maximal stimulation of PI-hydrolysis by (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic acid (t-ACPD) was only 673 +/- 78% of the basal level. The relative order of potency was quisqualate > glutamate > ibotenate > t-ACPD > BMAA. Agonist-stimulated PI-hydrolysis was attenuated (25 +/- 4% inhibition) by L-2-amino-3-phosphonopropionic acid and partially blocked (44 +/- 7%) by pertussis toxin treatment. Saturation binding studies with [3H]glutamate on membranes prepared from BHK-ts13 cells expressing the mGluR1 alpha subtype showed that glutamate binds to a single affinity state of this receptor with a limited capacity (Kd = 296 nM, Bmax = 0.8 pmol/mg protein). In competition experiments, [3H]glutamate was displaced by quisqualate, glutamate, ibotenate, t-ACPD and BMAA with a rank order of potency similar to that found for stimulation of PI-hydrolysis.

Amino Acids, Diamino↗
PubMed1993

Expression pattern and pharmacology of the rat type IV metabotropic glutamate receptor.

The mRNA for the type IV metabotropic glutamate receptor (mGluR4) is most prominently expressed in cerebellar granule cells, the olfactory system, the lateral septal nucleus, and most thalamic nuclei, but lower amount of the mRNA is found in many different brain regions. Agonist stimulation as studied in transfected cells was found to inhibit forskolin-stimulated cyclic-adenosine-monophosphate formation through a pertussis toxin-sensitive mechanism. Agonist rank order of potencies was: L-2-amino-4-phosphonobutyrate (L-AP4) > glutamate > (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD) > quisqualate > L-homocysteate = ibotenate. The results suggests that the mGluR4 may be responsible for many, but not all, effects of L-AP4.

Animals↗
PubMed1993

4-Carboxy-3-hydroxyphenylglycine, an antagonist at type I metabotropic glutamate receptors.

The pharmacology of (DL)-4-carboxy-3-hydroxyphenylglycine was examined in baby hamster kidney cells which stably express the type I metabotropic glutamate receptor (mGluR1 alpha). DL-4-Carboxy-3-hydroxyphenylglycine dose-dependently inhibited glutamate-stimulated phosphoinositide hydrolysis in a competitive manner with a KB of 29 microM as estimated from Schild-plot analysis. The present report is the first demonstration of a potent and competitive antagonist of the mGluR1 alpha subtype.

Animals↗
PubMed1993

Quantification of aortic regurgitation by magnetic resonance velocity mapping.

The use of magnetic resonance (MR) velocity mapping in the quantification of aortic valvular blood flow was examined in 10 patients with angiographically verified aortic regurgitation. MR velocity mapping succeeded in identifying and quantifying the regurgitation in all patients, and the regurgitant volume determined with MR velocity mapping agreed well with the grade obtained by aortic root angiography (p < 0.02). The accuracy in quantification of the aortic valvular flow rate was demonstrated by a significant correlation between the stroke volume (ml) measured by MR velocity mapping and calculated from MR imaging of the left ventricular end-diastolic and end-systolic volumes in eight patients (Y = 0.89 x X + 11, r = 0.97, p < 0.001). This finding was confirmed by a good agreement between the net cardiac output (L/min) quantified with MR velocity mapping and simultaneous 125I-indicator dilution measurement in all subjects (Y = 0.89 x X + 0.08, r = 0.82, p < 0.01). In conclusion, MR velocity mapping may be used as a noninvasive tool in the quantification of aortic regurgitation.

Adult↗
PubMed1993

Valve area and cardiac output in aortic stenosis: quantification by magnetic resonance velocity mapping.

Valve area and cardiac output were determined with magnetic resonance (MR) velocity mapping in 12 patients with aortic stenosis. Heart catheterization, Doppler echocardiography, and indicator dilution were performed for comparison. Left ventricle could be catheterized in only nine patients; in these cases, MR measured a mean valve area of 1.2 cm2 compared with 0.9 cm2 derived from catheterization data, with a mean difference of 0.2 cm2 between the 2 methods. The limits of agreement were [0.0, +0.5] cm2, less in patients with an important degree of concomitant regurgitation. In the whole material, MR measured a mean area of 1.1 cm2 compared with 1.2 cm2 derived from Doppler echocardiography data, with a mean difference of 0.1 cm2 and [-0.5, +0.6] cm2 as limits of agreement. In 11 patients the cardiac output was quantified by MR to a mean of 4.9 L/min and by indicator dilution to 5.0 L/min, with a mean difference of 0.2 L/min, and [-0.6, +0.8] L/min as limits of agreement. In addition, MR offers the major advance of simultaneous quantification of regurgitant volume in cases of concomitant regurgitation. In conclusion, because the two important prognostic determinants in aortic stenosis--the valvular area and the cardiac output--may be quantified, MR has potential to become a clinical tool in assessment of severity in aortic stenosis.

Aged↗
PubMed1993

Comparison between retrospective gating and ECG triggering in magnetic resonance velocity mapping.

ECG-triggered cinematographic studies of the cardiovascular system are hampered by several technical restrictions such as the inability to image end-diastole, ghosting, varying signal intensity, and phase contributions from eddy currents. Retrospective gating may solve these problems, but involves signal manipulation such as interpolating raw data from a time window. In this study, the performance of the two gating strategies was compared in quantitative MR velocity mapping on the abdominal aorta in eight healthy volunteers and on a pulsatile flow phantom. The results were compared to a one-dimensional velocity mapping technique and Doppler ultrasound. Finally, the consequence of decreasing the time window in the raw data interpolation used for retrospective gating was also examined. With retrospective gating, a low-pass filtering was seen, causing significantly prolonged duration and decreased amplitude of flow pulses. However, by reducing the time window retrospectively gated flow measurements were in good agreement with those that are ECG triggered. When fulfilling the demand of a narrow time window for interpolation, retrospective gating offers several advantages in MR velocity mapping.

Algorithms↗
PubMed1993

The ligand-binding domain in metabotropic glutamate receptors is related to bacterial periplasmic binding proteins.

Receptors for the major excitatory neurotransmitter glutamate include metabotropic (G protein-coupled) and ionotropic (glutamate-gated ion channel) types. These receptors have large, presumably extracellular, amino-terminal domains. Sensitive sequence analysis techniques indicate that the metabotropic receptor extracellular domain is similar to bacterial periplasmic amino acid binding proteins. A structural model built using the observed similarity predicts a ligand-binding site, and mutants with conservative amino acid substitutions at this site are shown to have reduced ligand affinity. The metabotropic receptor extracellular domain is a member of a family of structural domains linked to a variety of receptor types, including ionotropic glutamate receptors.

Amino Acid Sequence↗
PubMed1993

Wine for type 2 diabetic patients?

To ensure an acceptable quality of life for Type 2 diabetic patients, the food recommendations have to be as liberal and individualized as possible. Unfortunately, disagreements exists about the consumption of different types of wine. Diabetic patients are advised by some to restrain their wine intake and to use dry wine containing little carbohydrate, while others are more liberal. The purpose of this study was to evaluate the effects of dry and sweet wine on the glycaemic control in Type 2 diabetes. Twelve diabetic patients consumed a light meal with either 300 ml tap water 300 ml dry white wine, 300 ml sweet white wine with ethanol added or 300 ml dry white wine with glucose added. Similar glucose, insulin, and triglyceride responses were obtained in all four situations. There was a greater suppression of the free fatty acid levels in the three situations with wine as compared with water (p < 0.001). This effect may be caused by an attenuation of the free fatty acid mobilization and esterification of free fatty acids to triglycerides induced by alcohol. Our results indicate that patients with well-controlled Type 2 diabetes can drink moderate amounts of wine with meals without risking acute deterioration of glycaemic control. Whether the wine is dry or sweet has no impact on the glycaemic control.

Adult↗
PubMed1993

A comparison of two alternatively spliced forms of a metabotropic glutamate receptor coupled to phosphoinositide turnover.

A comparison of the pharmacological and physiological properties of the metabotropic glutamate 1 alpha and 1 beta receptors (mGluR1 alpha and mGluR1 beta) expressed in baby hamster kidney (BHK 570) cells was performed. The mGluR1 beta receptor is an alternatively spliced form of mGluR1 alpha with a modified carboxy terminus. Immunoblots of membranes from the two cell lines probed with receptor-specific antipeptide antibodies showed that mGluR1 alpha migrated with an M(r) = 154,000, whereas mGluR1 beta migrated with an M(r) = 96,000. Immunofluorescence imaging of receptors expressed in BHK 570 cells revealed that the mGluR1 alpha receptor was localized to patches along the plasmalemma and on intracellular membranes surrounding the nucleus, whereas mGluR1 beta was distributed diffusely throughout the cell. Agonist activation of the mGluR1 alpha and the mGluR1 beta receptors stimulated phosphoinositide hydrolysis. At both receptors, glutamate, quisqualate, and ibotenate were full agonists, whereas trans-(+)-1-aminocyclopentane-1,3-dicarboxylate appeared to act as a partial agonist. The stimulation of phosphoinositide hydrolysis by mGluR1 alpha showed pertussis toxin-sensitive and insensitive components, whereas the mGluR1 beta response displayed only the toxin-insensitive component. The mGluR1 alpha and mGluR1 beta receptors also increased intracellular calcium levels by inducing release from intracellular stores. These results indicate that the different carboxy terminal sequences of the two receptors directly influences G protein coupling and subcellular deposition of the receptor polypeptides and suggest that the two receptors may subserve different roles in the nervous system.

Animals↗