Search results for "Mimetics"
showing 10 items of 120 documents
Challenge of tacit knowledge in acquiring information in cognitive mimetics
2019
Intelligent technologies are rising. This is why methods for designing them are important. One approach is to study how people process information in carrying out intelligence demanding tasks and use this information in designing new technology solutions. This approach can be called cognitive mimetics. A problem in mimetics is to explicate tacit or subconscious knowledge. Here, we study a combination of thinking aloud in ship simulator driving and focus group commenting the solutions of subjects. On the ground of these early experiments, a multiple method combination seems to be the best way forward to solve problems of tacit or subconscious knowledge. peerReviewed
Amelioration of the abnormal phenotype of a new L1 syndrome mouse mutation with L1 mimetics
2021
L1 syndrome is a rare developmental disorder characterized by hydrocephalus of varying severity, intellectual deficits, spasticity of the legs, and adducted thumbs. Therapy is limited to symptomatic relief. Numerous gene mutations in the L1 cell adhesion molecule (L1CAM, hereafter abbreviated L1) were identified in L1 syndrome patients, and those affecting the extracellular domain of this transmembrane type 1 glycoprotein show the most severe phenotypes. Previously analyzed rodent models of the L1 syndrome focused on L1-deficient animals or mouse mutants with abrogated cell surface expression of L1, making it difficult to test L1 function-triggering mimetic compounds with potential therapeu…
BCL-XL inhibition induces an FGFR4-mediated rescue response in colorectal cancer
2022
The heterogeneous therapy response observed in colorectal cancer is in part due to cancer stem cells (CSCs) that resist chemotherapeutic insults. The anti-apoptotic protein BCL-XL plays a critical role in protecting CSCs from cell death, where its inhibition with high doses of BH3 mimetics can induce apoptosis. Here, we screen a compound library for synergy with low-dose BCL-XL inhibitor A-1155463 to identify pathways that regulate sensitivity to BCL-XL inhibition and reveal that fibroblast growth factor receptor (FGFR)4 inhibition effectively sensitizes to A-1155463 both in vitro and in vivo. Mechanistically, we identify a rescue response that is activated upon BCL-XL inhibition and leads …
Nicotinic and muscarinic modulation of 5-hydroxytryptamine (5-HT) release from porcine and canine small intestine
1992
Strips of porcine and canine small intestine were incubated in vitro and the release of 5-hydroxytryptamine (5-HT) was determined by HPLC with electrochemical detection. The spontaneous outflow of 5-HT from the porcine and canine small intestine largely reflects calcium-dependent 5-HT secretion from enterochromaffin cells which are under a spontaneous neuronal, excitatory input as indicated by the inhibitory effect (30-40%) of tetrodotoxin. In both species, nicotine enhanced the release of 5-HT in a concentration-dependent manner by a maximum of about 50% at 100 microM. This effect was blocked by the nicotine receptor antagonist hexamethonium, but not by the subtype-selective nicotine recep…
Demonstration of action-potential-producing cells in the rat pineal gland in vitro and their regulation by norepinephrine and nitric oxide
1998
There is evidence that sympathetically innervated mammalian pineal glands contain cells that exhibit action potentials. It is unknown whether ex vivo pineal glands deprived of their nervous input are still capable of firing. In the present study, multiple-unit recordings from rat pineals revealed spontaneously active cell clusters with a mean firing frequency of 1.5 +/- 0.3 Hz which could be abolished by tedrodotoxin. Regularly firing clusters showed no inherent periodicity in the minute range, whereas rhythmical clusters with periodically repeated bursts had period lengths of 12.6 min (day) and 9.5 min (night). Superfusion of norepinephrine reduced the firing frequency of both cluster type…
A useful muscarinic parameter and the differential recording of atrial and ventricular tension in the perfused rabbit heart
1971
1. A simple method of recording right atrial tension from the Langendorff perfused rabbit has been described; it is based on the “transverse” method of recording cardiac contractions described by Beckett (1970). 2. Right atrial and ventricular tensions were recorded by transducers attached to threads stitched into the right atrium and right ventricle, the heart being retained and prevented from rotating by two threads stitched into the intraventricular septum as described by Beckett. 3. Right ventricular diastolic tension was adjusted to 7.5 g. Interference with the atrial record by ventricular systole was overcome by adjustment of diastolic right atrial tension to its optimal value between…
Glucagon-like peptide-2 relaxes mouse stomach through vasoactive intestinal peptide release.
2009
Glucagon-like peptide-2 (GLP-2) influences different aspects of the gastrointestinal function, including epithelial growth, digestion, absorption, motility, and blood flow. Intraluminal pressure from isolated mouse stomach was recorded to investigate whether GLP-2 affects gastric tone and to analyze its mechanism of action. Regional differences between diverse parts of the stomach were also examined using circular muscular strips from fundus and antrum. In the whole stomach, GLP-2 (0.3–100 nM) produced concentration-dependent relaxation with a maximum that was about 75% of relaxation to 1 μM isoproterenol (IC50 = 2.5 nM). This effect was virtually abolished by desensitization of GLP-2 rece…
Distigmine bromide induced acute psychotic disorder in a patient with multiple sclerosis.
2003
AbstractA female patient with multiple sclerosis (MS) suffered from an acute psychotic disorder after taking distigmine bromide for detrusor dysfunction. She showed a dramatic relief of her symptoms after the medication, distigmine bromide, was stopped. Distigmine is not supposed to penetrate the blood-brain barrier (BBB). However, in MS patients a leakage of the BBB could be hypothesized.
Some pharmacological properties of the false cholinergic transmitter acetylpyrrolidinecholine and its precursor pyrrolidinecholine
1976
The acetylchline analogue acetylpyrrolidinecholine as well as the choline analogue pyrrolidinecholine were synthesized and the cholinergic properties of both substances were investigated on the guinea-pig ileum, rat blood pressure and frog rectus abdominis muscle. Acetylpyrrolidinecholine was 3-5 times less potent than acetylcholine on the three preparations tested. The dose-response curves to acetylpyrrolidinecholine were shifted to the right in a parallel manner by atropine and (+)-tubocurarine. The dissociation constants for atropine and (+)-tubocurarine obtained with acetylpyrrolidinecholine as agonist were not different from those obtained with acetylcholine. This indicates that acetyl…
EFFECTS OF VANADATE ON RESPONSES OF GUINEA-PIG ISOLATED TRACHEA TO SPASMOGENS
1993
Abstract The effects of vanadate on the contractility of the guinea-pig isolated trachea was examined. Vanadate (0·1 Mm) produced a sustained contraction that was abolished in Ca2+-free EGTA (0·1 Mm)-containing physiological salt solution but was resistant to verapamil (1 μm). Vanadate (0·1 Mm) depressed tracheal responses to CaCl2 (in Ca2+-free depolarizing solution), KCl, acetylcholine, histamine and 5-hydroxytryptamine. For vanadate (10 μm), the inhibition of spasmogenic responses only reached statistical significance for histamine and 5-hydroxytryptamine. Caffeine (1 Mm)-induced spasm (trachea at 20°C in the presence of indomethacin (2·8 μm)) was not affected by vanadate (10 μm-0·1 Mm).…