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Biomedical subjects

N Nagel

Publications and source records attributed to N Nagel.

17 recordsLinked to original sources

Reducing psychological distress in patients with inflammatory bowel disease by cognitive-behavioural treatment: exploratory study of effectiveness.

BACKGROUND: This prospective study aimed to determine whether cognitive-behavioural group treatment accompanying medical standard care is effective in reducing psychological distress in patients with inflammatory bowel disease. METHODS: Twenty-eight outpatients with Crohn disease or ulcerative colitis completed the treatment programme. Psychological treatment consisting of 12 weekly sessions was conducted in a group setting. Medical and psychometric assessments were taken at the beginning of the 3-month pretreatment waiting period, at pretreatment, at post-treatment and at the 3, 6 and 9-month follow-ups. RESULTS: During baseline, no change was observed in psychological distress. Disease-related worries and concerns decreased significantly from pretreatment to the follow-ups. The disease groups differed in the decline of concerns between pre- and post-treatment, with a significant reduction of concerns in patients with ulcerative colitis but not Crohn disease. This difference did not occur at the follow-ups, indicating long-term improvement for both disease groups. Depressive coping decreased significantly in women and remained stable at the follow-ups, whereas depressive coping did not change in men. The same gender difference was found for depressive symptoms. CONCLUSIONS: The exploratory findings suggest that psychological group treatment for outpatients is a feasible and effective approach for the short- and long-term reduction of psychological distress for patients with inflammatory bowel disease. However, the revealed gender differences on coping and depression might indicate the necessity to consider gender-specific aspects of inflammatory bowel disease when designing and evaluating psychological interventions.

Adaptation, Psychological↗

Genomic organization and characterization of splice variants of the human histamine H3 receptor.

In the present paper we report the genomic organization of the human histamine H3-receptor gene, which consists of four exons spanning 5.5 kb on chromosome 20. Using PCR, six alternative splice variants of the H3 receptor were cloned from human thalamus. These variants were found to be coexpressed in human brain, but their relative distribution varied in a region-specific manner. These isoforms displayed either a deletion in the putative second transmembrane domain (TM), H3(DeltaTM2, 431aa) or a variable deletion in the third intracellular loop (i3), H3(Deltai3, 415aa), H3(Deltai3, 365aa), H3(Deltai3, 329aa) and H3(DeltaTM5+Deltai3, 326aa). In order to determine the biological role of the H3 receptor variants compared with the 'original' H3(445aa) receptor, three isoforms, namely H3(445aa), H3(DeltaTM2, 431aa) and H3(Deltai3, 365aa), were expressed in CHO cells and their pharmacological properties were investigated. Binding studies showed that H3(DeltaTM2, 431aa) transiently expressed in CHO cells was unable to bind [125I]iodoproxyfan, whereas both the H3(445aa) and H3(Deltai3, 365aa) receptors displayed a high affinity for [125I]iodoproxyfan [K(d)=28+/-5 pM (n=4) and 8+/-1 pM (n=5) respectively]. In addition, H3(Deltai3, 365aa) possessed the same pharmacological profile as the H3(445aa) receptor. However, in CHO cells expressing H3(Deltai3, 365aa), H3 agonists did not inhibit forskolin-induced cAMP production, stimulate [35S]guanosine 5'-[gamma-thio]triphosphate ([35S]GTP[S]) binding or stimulate intracellular Ca(2+) mobilization. Therefore the 80-amino-acid sequence located at the C-terminal portion of i3 plays an essential role in H3 agonist-mediated signal transduction. The existence of multiple H3 isoforms with different signal transduction capabilities suggests that H3-mediated biological functions might be tightly regulated through alternative splicing mechanisms.

Alternative Splicing↗

Cloning and molecular characterization of the novel human melanin-concentrating hormone receptor MCH2.

Using a genomics-based approach for screening orphan G-protein-coupled receptors, we have identified and cloned a novel high-affinity, melanin-concentrating hormone (MCH) receptor. This receptor, named S643b, displays the greatest overall identity (32%) with the previously reported human SLC-1 receptor (MCH1) and to a lesser extent with the somatostatin receptor subtypes. The gene encoding the S643b receptor spans more than 23 kilobase pairs (kb) and was mapped, by radiation hybrid experiments, on chromosome 6q14.3-q15. Comparison of the S643b cDNA with human genomic sequence reveals that the 340-amino-acid receptor is encoded by five exons. Its tissue distribution, as determined by Northern blot and reverse transcription-polymerase chain reaction analysis, indicates that a 4-kb transcript is predominantly expressed in the brain. When expressed in Chinese hamster ovary (CHO) cells, the S643b receptor displays a strong, dose-dependent, transient elevation of intracellular calcium in response to MCH (EC(50) = 9.5 nM). During the present study, we isolated a splice variant, designated S643a, encoding for a receptor that was not activated by MCH in a cellular calcium mobilization assay. Comparative pharmacological studies using CHO cells stably expressing either SLC-1 or S643b receptors demonstrated that similar structural features of MCH are required to stimulate intracellular Ca(2+) mobilization at both receptors. The identification and localization of this new MCH receptor (MCH2) provides further insight into the physiological implication of MCH in modulating behavioral responses, including food intake.

Amino Acid Sequence↗

Dimorphism and inclusion compounds of N,N'-di(benzenesulfonyl)-p-phenylenediamine

Crystal structures of a new polymorph of N,N'-(p-phenylene)bis(benzenesulfonamide) (C18H16N2O4S2) and of two inclusion compounds with acetone [(CH3)2CO] and dimethyl sulfoxide [2(CH3)2SO], respectively, have been determined at 150 K. For a more reliable comparison, the structure of the already known polymorph of N,N'-di(benzenesulfonyl)-p-phenylenediamine has been redetermined under identical conditions. In addition, the phase transformation behavior has been examined by differential scanning calorimetry and the crystallization conditions of both polymorphs including their formation by weathering of the inclusion compounds were investigated.

Journal Article↗

Microanalysis of serotonin by high pressure liquid chromatography with electrochemical detection.

Serotonin (5-HT) analysis by high pressure liquid chromatography with electrochemical detection (HPLC-ED) has been designed to perform micro assays below the picogram range. We demonstrated that the oxidation potential of 5-HT was tightly linked to the pH of the buffer used as eluent phase. The electrochemistry of 5-HT in pH 4.00 acetate buffer and in pH 6.80 phosphate buffer allowed quantification down to 2 x 10(-18) g. The oxidization current was linked to the 5-HT amount added. The electrochemical response of 5-HT was different for low amounts in the 10(-18) g range and for amounts above the picogram range. Two curves were obtained according to the electrochemical response of 5-HT: the first one was for the 10(-18) g range and the second one was for the picogram range and above. It thus appeared between concentration ranges that assays are not be feasible. This method has been used to analyse 20 microns frozen slices of rat spinal cord. These data open new insights into scarce quantification of 5-HT without the use of radio-elements.

Animals↗

Solute effects on the colloidal and phase behavior of lipid bilayer membranes: ethanol-dipalmitoylphosphatidylcholine mixtures.

By means of the scanning differential calorimetry, x-ray diffractometry, and the dynamic light scattering, we have systematically studied the phase and packing properties of dipalmitoylphosphatidylcholine vesicles or multibilayers in the presence of ethanol. We have also determined the partial ternary phase diagram of such dipalmitoylphosphatidylcholine/water/ethanol mixtures. The directly measured variability of the structural bilayer parameters implies that ethanol binding to the phospholipid bilayers increases the lateral as well as the transverse repulsion between the lipid molecules. This enlarges the hydrocarbon tilt (by up to 23 degrees) and molecular area (by < or = 40%). Ethanol-phospholid association also broadens the interface and, thus, promotes lipid headgroup solvation. This results in excessive swelling (by 130%) of the phosphatidylcholine bilayers in aqueous ethanol solutions. Lateral bilayer expansion, moreover, provokes a successive interdigitation of the hydrocarbon chains in the systems with bulk ethanol concentrations of 0.4-1.2 M. The hydrocarbon packing density as well as the propensity for the formation of lamellar gel phases simultaneously increase. The pretransition temperature of phosphatidylcholine bilayers is more sensitive to the addition of alcohol (initial shift: delta Tp = 22 degrees C/mol) than the subtransition temperature (delta Ts reversible 5 degrees C/mol), whereas the chain-melting phase transition temperature is even less affected (delta Tm = 1.8 degrees C/mol). After an initial decrease of 3 degrees for the bulk ethanol concentrations below 1.2 M, the Tm value increases by 2.5 degrees above this limiting concentration. The gel-phase phosphatidylcholine membranes below Tm are fully interdigitated above this limiting concentration. The chain tilt on the fringe of full chain interdigitation is zero and increases with higher ethanol concentrations. Above Tm, some of the lipid molecules are solubilized by the bound ethanol molecules. More highly concentrated ethanol solutions (> 7 M) solubilize the phosphatidylcholine bilayers with fluid chains fully and result in the formation of mixed lipid-alcohol micelles.

1,2-Dipalmitoylphosphatidylcholine↗

[Evaluation of environmental medicine counseling by the patient and the physician--a comparison of perspectives].

Counselling in environmental medicine is a new field of medical work. The success of the advisory activity has two aspects: objective results like laboratory findings, measurements and activities as well as the subjective assessment by, and satisfaction of, the patient and the physician. After giving a short presentation of the work of the advisory board for environmental medicine of the Medical Institute of Environmental Hygiene in Düsseldorf we discuss the significance of the communication between patient and physician for this field of medicine. The subject of our study was to compare the views of patients and physicians in regard to the success of the advisory activity. To achieve this goal we asked both patients and physicians to complete a questionnaire to judge the consultation. Our questions considered technical as well as interactional aspects of the advice. We found some clear differences between the view expressed by patients and physicians. This will be demonstrated with the help of the issues "satisfaction", "problem-solving" and "intention" (patient's aim for the consultation.

Adult↗

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↗

[Modification of the growth of chondrocytes by the action of concanavalin A].

The effects of Concanavalin A have been assessed on the growth of articular cultured chondrocytes. A differential action in relation with cellular density has been observed. Concanavalin A (0.02, 0.2 and 2 micrograms/ml) exerted a stimulating effect on low density cultures, whereas it depressed the cell growth curve with high cell density cultures, especially at the concentration of 2 micrograms/ml. Such a discrepancy in the behaviour of cells related to the density does not seem to have been previously observed with chondrocytes. It could be explained by a modification of the accessibility of Concanavalin A receptors.

Animals↗

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↗