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Biomedical subjects

N Nagel

Publications and source records attributed to N Nagel.

9 recordsLinked to original sources

Verb effects during sentence processing.

We describe a study that explores how the properties of a verb's lexical entry contribute to on-line sentence processing. Schmauder (1991) has recently suggested that the verb-processing effects shown previously by Shapiro and his colleagues (Shapiro & Levine, 1990; Shapiro, Zurif, & Grimshaw, 1987; 1989) are not generalizable and may have been artifacts precipitated by experimental design factors. In this paper we logically analyze such a possibility and then present experiments that systematically investigate the design differences between the Shapiro et al. studies cited above and the Schmauder study. These analyses and experiments provide further evidence that verb effects during sentence processing are real, are to be expected given the architectures of recent parsing models, and are replicable using a dual task that is modified in reasonable ways.

Humans

Ca2+ channel inhibition by a new dihydropyridine derivative, S11568, and its enantiomers S12967 and S12968.

Biochemical and electrophysiological techniques were used to describe the Ca2+ channel blocking properties of a new dihydropyridine derivative, S11568 (+/-)- ([(amino-2-ethoxy)-2-ethoxy]methyl)-2-(dichloro-2',3'-phenyl)-4- ethoxy-carbonyl-3-methoxycarbonyl-5-methyl-6-dihydro-1,4-pyridine and its enantiomers S12967 ((+)-S11568) and S12968 ((-)-S11568). In binding studies, S11568 and S12968 displaced specifically bound [3H]PN 200-110 from cardiac and vascular smooth muscle preparations with potencies of 5.6-51 nM, respectively. S12967 was 6- to 18-fold less potent than S12968. A good correlation was found between the IC50 value for the inhibition of 45Ca2+ uptake by A7r5 aortic smooth muscle cells and binding data. Whole-cell patch clamp studies in both guinea-pig ventricular myocytes and A7r5 cells yielded similar results. At holding potential (VH) -50 mV, S12968 inhibited L-type Ca2+ current with an IC50 value near 70 nM, 2- to 3-fold more potently than S11568 and 30-fold more potently than S12967. With VH -100 mV, all three compounds were less potent, with IC50 values ranging from 500 nM to 3 microM. These results demonstrate conclusively that S12968 is the more active enantiomer. Furthermore, the pronounced voltage dependence of its actions in vitro suggests that in vivo it could exhibit good selectivity for vascular smooth muscle over cardiac muscle.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

Structural identification of prostaglandin A1 biotransformation products from tumor cells.

Rat B104 neuroblastoma and C6 glioma cells are able to metabolize prostaglandin A1 (PGA1). Four metabolites were isolated by high performance liquid chromatography. Their structure was elucidated by fast atom bombardment mass spectrometry and 1H nuclear magnetic resonance. It appears that these biotransformation products are two sets of stereoisomers: the two isomers that eluted first are 9 alpha- and 9 beta-hydroxy-11 alpha-cysteinylglycyl adducts whereas the other two are 9 alpha- and 9 beta-hydroxy-11 alpha-cysteinyl derivatives. These compounds were compared with authentic samples prepared by Michael addition of the corresponding thiol onto PGA1, then by reduction with sodium borohydride.

Animals

Tumor cell biotransformation products of prostaglandin A1 with growth inhibitory activity.

The growth inhibitory effect and the fate of prostaglandin A1 (10(-6) M) were followed in cultures of rat B104 neuroblastoma and C6 glioma cells. More than 40% and 85% of the drug were neither recognized by a prostaglandin A1 antiserum nor extracted from the acidified medium with ethyl acetate, after 6 h and 24 h-incubation, respectively. When the supernatant of cells cultured in the presence of prostaglandin A1 during 24 hours was transferred to other cells and used as culture medium, the same growth inhibitory effect as with prostaglandin A1 was observed even when no prostaglandin A1 was added. After extensive purification and reverse phase HPLC of supernatant, four peaks more polar than prostaglandin A1 were shown; two of them were still active as growth inhibitors. This biotransformation was not observed with normal cells like L 929 or chick embryo fibroblasts, for which prostaglandin A1 had no inhibitory effect. The identification of these metabolites will allow the study of the structure-activity relationship.

Animals

[Effects of various beta-receptor blockers on metabolic and circulatory parameters during physical exertion].

For further elucidation of the effect of various beta-adrenoceptor blockers on metabolism during exercise investigations on the influence of 5 beta-adrenoceptor blockers were carried out in healthy subjects. The 5 beta-adrenoreceptor blockers (acebutolol, metoprolol, penbutolol, pindolol, propranolol) were different regarding cardioselectivity and intrinsic activity (ISA). Each substance was given in 4 different dosages corresponding to 10:20:40:80 mg propranolol. Exercise was performed as bicycle ergometer test over 1 hour. In order to find out different effects during long-term application a medium dosage corresponding to 40 mg propranolol was applied for 4 weeks after the acute trials. The following parameters were measured: heart rate, systolic arterial pressure, parameters of carbohydrate metabolism (glucose, lactate) as well as lipid metabolism (free fatty acids (FFA), cholesterol, triglycerides etc.), serum concentration; for three beta-adrenoceptor blockers hormonal concentrations (catecholamines, insulin, human growth hormone (HGH), adrenocorticotrophic hormone (ACTH] were assessed. The different beta-adrenoceptor blockers demonstrated a varying relation between dosage and effect which was mostly pronounced for propranolol. All beta-adrenoceptor blockers caused a nearly complete blockade of energy release from FFA, and serum glucose concentration decreased. These changes were smaller under the effect of a low dosage of the cardioselective beta-adrenoceptor blocker metoprolol. The hormonal concentrations demonstrated a more pronounced increase of epinephrine during beta-blockade in contrast to only small changes by norepinephrine. Whereas there was no effect to be found on ACTH, HGH increased significantly under beta-blockade but independent of cardioselectivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists

Ultrasound diagnosis of nonobstetric disease during pregnancy.

The use of ultrasound in obstetrics is well established; however, its use in nonobstetric disease during pregnancy has not been emphasized. A diagnostic work-up during pregnancy is complicated by the fact that many of the usual tests require radiation to the fetus. This paper presents 3 cases in which ultrasonic scanning contributed to the diagnosis of nonobstetric disease during pregnancy. Postitive findings included enlarged edematous pancreas, gallstones, and splenomegaly. In 1 case, the finding of a normal gallbladder was helpful. When usual diagnostic procedures such as oral cholecystogram, retrograde endoscopic pancreatography, and nuclear medicine scans are perhaps contraindicated during pregnancy, the ultrasound scan is the diagnostic test of choice.

Adult