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M Jung

Publications and source records attributed to M Jung.

At least 271 records · Page 15Linked to original sources

Characterization of the scopolamine stimulus in rats.

The discriminative stimulus properties of scopolamine, a potent antagonist at muscarinic receptors, were used for testing the discriminative effects of drugs known to act on cholinergic transmission. Rats were trained in a standard two-bar operant conditioning procedure with food as the reinforcer, according to a FR10 schedule. The training dose of scopolamine was progressively reduced from 0.25 mg/kg SC to the low dose of 0.062 mg/kg SC. Scopolamine yielded an accurate discrimination in all the six rats tested. The generalization gradient resulted in an ED50 of 0.027 mg/kg. The scopolamine cue lasted for 1 h and was of central origin, since it was not mimicked by scopolamine methylbromide. The scopolamine stimulus generalized to atropine and trihexyphenidyl (respective ED50 values 2.20 and 0.21 mg/kg SC). Atropine depressed rate of responding, while trihexyphenidyl did not. Antagonism experiments with both direct agonists at the muscarinic receptor (arecoline and oxotremorine) and indirect agonists, i.e., inhibitors of the acetylcholine esterase [physostigmine and tetrahydroaminoacridine (THA)], led to inconsistent results. Increasing the doses of the agonists in order to block the scopolamine cue may be limited by their rate suppressant effect on responding. Based upon previously published results, it is suggested that the muscarinic agonist cue is more useful than the antagonist cue for investigating muscarinic transmission.

Animals↗

[The effect of concomitant aortic valve insufficiency on the values of Doppler sonographic gradient determination in patients with aortic stenosis].

We examined the influence of concomitant significant aortic incompetence (AI) on Doppler-gradient measurements in valvular aortic stenosis (AS) by comparing catheter and Doppler gradients of 51 patients with isolated AS and of 24 patients with additional AI. In patients with additional AI there was a significantly greater overestimation of the peak-to-peak gradient by the maximal instantaneous Doppler gradient (AS + AI: overestimation 31.0 +/- 17.6 mm Hg, AS: overestimation 10.5 +/- 20.2 mm Hg; p less than 0.01) and also by the maximal instantaneous catheter gradient (AS + AI: overestimation 32.8 +/- 11.8 mm Hg, AS: overestimation 20.4 +/- 14.0 mm Hg; p less than 0.01). Comparison of the respective catheter-derived and Doppler-sonographically measured instantaneous and mean gradients showed no differences between the two patient subgroups. Higher instantaneous gradients in patients with additional AI are mainly explained by the lower end-diastolic aortic pressure. However, Doppler-sonographic overestimation of the severity of stenosis in patients with combined AS + AI, due to the sole measurement of the instantaneous gradient in clinical practice, should be of limited importance because in these patients significant AI already sufficiently indicates aortic valve replacement.

Adult↗

[Endoscopic and surgical therapy of malignant colorectal polyps].

87 malignant colorectal polyps were removed in 81 patients by endoscopic polypectomy from 1972 until 1987. Thereafter 34 of these patients had a surgical resection of the colon. Surgical resection was performed for incomplete excision of the polyp (20 x), for tumor invasion of the lymphics in the polyp stalk and for moderately/poor differentiated carcinoma. In 6 patients a residual carcinoma was detected in the removed colon specimen, but lymph-node metastasis only in one with moderate-differentiated carcinoma. Our results demonstrate that colorectal polyps with invasive well-differentiated carcinoma and tumor free base do not need a surgical resection. Patients of the high-risk-group (moderately/poor-differentiated carcinoma, invasion of blood vessels and lymphatics, incomplete excision), should be referred to further surgical resection. With regard to the low rate of metastatic spread even in patients with high-risk-polyps accurate differentiation seems to be necessary. In 19 out of 52 (36.5%) patients endoscopic control examinations after surgical or endoscopic resection revealed recurrent pathological findings. On the base of the presented data we conclude that there is a need for short-term endoscopic controls over a period of five years.

Adenocarcinoma↗

Effects of intracerebroventricular pirenzepine on muscarinic discriminations in rats.

In rats, mixed M1/M2 muscarinic ligands induce a discrimination which is of central origin and selectively mediated by either one or both muscarinic receptor subtypes. In the present study we examined the effects of intracerebroventricular (i.c.v.) pirenzepine, a relatively selective M1 receptor antagonist which does not cross the blood-brain barrier, on muscarinic discriminations. Groups of six rats were trained to discriminate, in a two-lever operant task, either 0.062 mg/kg subcutaneous (s.c.) scopolamine or 0.075 mg/kg s.c. oxotremorine. When the rats had been well trained in the procedure, the discriminative effects of various i.c.v. muscarinic ligands were examined. Scopolamine (1.5-12 micrograms i.c.v.), but not pirenzepine (20-40 micrograms i.c.v.), generalized to s.c. scopolamine. Oxotremorine (0.75-6 micrograms i.c.v.) generalized to s.c. oxotremorine. Scopolamine (12 micrograms i.c.v.), but not pirenzepine (20-40 micrograms i.c.v.), antagonized the oxotremorine cue. These results suggest that activation of the M1 receptor is not the prominent component of muscarinic stimulus control.

Animals↗

Discriminative stimulus properties of muscarinic agonists.

In a two-lever, food-reinforced drug-discrimination paradigm separate groups of rats were trained to discriminate either arecoline, pilocarpine or oxotremorine from saline. The discriminative cues of all three agonists were potently blocked by scopolamine, but only by 30-60 fold higher doses of methylscopolamine. The three agonists all suppressed overall response rate. These rate-suppressant effects were not blocked by scopolamine in doses which blocked the discriminative cues. In generalization tests, arecoline elicited selection of the drug-appropriate lever in all groups of trained animals. Pilocarpine was discriminated as drug by all pilocarpine-trained animals and by a majority of oxotremorine-trained animals, but was not significantly discriminated by the arecoline-trained group. Oxotremorine was discriminated by all oxotremorine-trained animals but only by some pilocarpine-trained animals, and was not significantly discriminated by the arecoline-trained group. Morphine, haloperidol, chlordiazepoxide, pentobarbital and nicotine were not generalized to any of the training drugs. The discriminative stimuli produced by the training drugs are therefore specific and exhibit properties indicative of an origin at central muscarinic receptors but may not be identical.

Animals↗

Codon-induced association of the isolated anticodon loop of tRNAPhe.

The binding of the codon UUC to the isolated anticodon loop of tRNAPhe (yeast) has been studied as a model of codon recognition by a simple adaptor. Fluorescence titrations demonstrate that UUC binds to the isolated anticodon loop with an equilibrium constant of 1.4 X 10(3) M-1 (at 7.2 degrees C). Equilibrium sedimentation curves reveal that UUC binding induces association of anticodon loops beyond the dimer stage. A set of complete sedimentation curves obtained for various reactant concentrations was analyzed according to a model with an infinite number of subsequent association steps for UUC-anticodon loop complexes and with equal affinity for each step. The coupling of association and sedimentation was considered quantitatively, and the information resulting from conservation of mass was used by integration. According to this procedure, the experimental data can be described by an isodesmic association constant of 8 X 10(3) M-1 with satisfactory accuracy. Temperature-jump relaxation detected by fluorescence measurements provides independent evidence for codon-induced association of the anticodon loop. The data are consistent with the following mechanism: UUC preferentially binds to one of two loop conformations with a rate constant of 4.5 X 10(6) M-1 s-1; the UUC-anticodon loop complex undergoes association with a rate constant of 6.5 X 10(6) M-1 s-1. The reactions observed for the isolated anticodon loop are surprisingly similar to those observed previously for the complete tRNA, suggesting that simple hairpin loops are appropriate adaptors for a translation process at an early stage of evolution; the codon-induced association of the hairpin loop should be very useful to facilitate the transfer of cognate amino acids during translation.

Anticodon↗

[New aspects of early gastric carcinoma].

Between 1st January 1970 and 31st December 1984, 910 total or subtotal resections for gastric cancer were carried out in the Department of Surgery of the University Clinic Mannheim. A work-up of operative specimens showed that 146 patients (16%) had early gastric carcinoma. The patients comprised 97 men and 49 women; the youngest was 31, the oldest 86 years. The following trends were apparent when the 58 patients operated on between 1970 and 1976 were compared with the 68 patients operated on between 1977 and 1982: An increase in early gastric carcinoma is also detectable in younger patients. The previously seen tendency for localisation in the antrum appears to have changed in favour of the upper segments of the stomach. The proportion of the diffuse type rose from 26% in the first group to 44% in the second. The 5-year survival of all patients with early gastric carcinoma was 78.8%. No significant difference could be found between the diffuse and intestinal type. The prognosis of early gastric carcinoma appears to be dependent on the depth of invasion and involvement of the lymph nodes.

Adenocarcinoma↗

Stimulation of T cells by autologous mononuclear leukocytes and epidermal cells in psoriasis.

Based on reports suggesting aberrant cell-mediated immunity and altered infiltration of immunocompetent cells into the skin in psoriasis, we studied the stimulation of T cells by autologous non-T mononuclear leukocytes (autologous mixed lymphocyte reaction, AMLR) and by epidermal cells isolated from lesional and clinically uninvolved skin in psoriasis (autologous mixed epidermal cell lymphocyte reaction, AMECLR). Age- and sex-matched individuals served as controls. We found that the AMLR in psoriasis (n = 11) was similar to that in healthy controls (n = 16); furthermore, cell proliferation was alike in the presence of either 5% AB-serum or autologous serum. By contrast, while the AMECLR in healthy controls (n = 9) resembled that in psoriatics employing epidermal cells from univolved skin, epidermal cells from lesional sites (n = 10) induced a significantly higher proliferation of autologous T cells in the AMECLR (P less than 0.01). We conclude that the in vitro stimulation of T cells by non-T mononuclear leukocytes is normal in psoriasis and is not regulated by autologous serum. Lesional psoriatic epidermal cells, however, are more active in stimulating autologous T cell proliferation than cells from univolved psoriatic or normal epidermis.

Adult↗