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PubMed2001

High-level reasoning and base-rate use: do we need cue-competition to explain the inverse base-rate effect?

Previous accounts of the inverse base-rate effect (D. L. Medin & S. M. Edelson, 1988) have revolved around the concept of cue-competition. In this article, the authors propose that high-level reasoning in the form of an eliminative inference mechanism may contribute to the effect. A quantitative implementation of this idea demonstrates that it has the power by itself to produce the pattern of base-rate effects in the Medin and Edelson (1988) design. Four predictions are derived that contradict the predictions by attention to distinctive input (ADIT; J. K. Kruschke, 1996), up to date the most successful account of the inverse base-rate effect. Results from 3 experiments disconfirm the predictions by ADIT and demonstrate the importance of high-level reasoning in designs of the Medin and Edelson kind. Implications for the interpretation of the inverse base-rate effect and the attention-shifting mechanisms presumed by ADIT are discussed.

Adult↗

PubMed2001

Agonist-, antagonist-, and inverse agonist-regulated trafficking of the delta-opioid receptor correlates with, but does not require, G protein activation.

In this study, we explored the relationship between ligand-induced regulation of surface delta opioid receptors and G protein activation. G protein activation was assessed with [(35)S]guanosine-5'-O-(3-thio)triphosphate (GTP gamma S) binding assays conducted at both 37 and 0 degrees C. Ligand-independent (constitutive) activity of the delta-receptor was readily observed when the [(35)S]GTP gamma S binding assay was performed at 37 degrees C. We identified a new class of alkaloid inverse agonists (RTI-5989-1, RTI-5989-23, RTI-5989-25), which are more potent than the previously described peptide inverse agonist ICI-174864 (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu). Treatment with these inverse agonists for 18 h caused up-regulation of surface receptors. Eighteen-hour treatment with etorphine resulted in approximately 90% loss of surface receptor, whereas fentanyl, diprenorphine, and morphine caused between 20 and 50% loss. The abilities of ligands to modulate [(35)S]GTP gamma S binding at 37 degrees C showed a strong correlation with their abilities to regulate surface receptor number (r(2) = 0.86). Interestingly, the ability of fentanyl to activate G proteins was markedly temperature sensitive. Fentanyl showed no stimulation of [(35)S]GTP gamma S binding at 0 degrees C but was as efficacious as etorphine, morphine, and diprenorphine at 37 degrees C. Neither the ligand-induced receptor increases nor decreases were perturbed by pertussis toxin pretreatment, suggesting that functional G proteins are not required for ligand-regulated delta-opioid receptor trafficking.

Biotransformation↗

PubMed2001

Inverse agonist activity of selected ligands of platelet-activating factor receptor.

The receptor for platelet-activating factor (PAFR) is a member of the G protein-coupled receptor (GPCR) family. According to the allosteric ternary complex model, GPCRs exist in an equilibrium between different conformations. Agonist binding promotes and stabilizes the receptor in an active conformation. On the other hand, ligands that stabilize the inactive conformation are known as inverse agonists. Due to the association of platelet-activating factor (PAF) with diverse physiological and pathological processes, considerable efforts have been invested in the development of antagonists to PAFR. A large number of these molecules has been shown to specifically interact with PAFR but, surprisingly, little is known about their impact on the conformation of the receptor and its activity. By using a constitutively active mutant (L231R) of the human PAFR and by transiently coexpressing the wild-type (WT) receptor with the G(alpha)q subunit of the trimeric G protein, we were able to address this issue with ligands of diverse structures such as phospholipids, benzodiazepines, furans, and others. We demonstrated that some of these molecules are potent inverse agonists. For example, when cells (WT PAFR + G(alpha)q) were exposed to WEB2086, SM10661, or alprazolam, the basal inositol phosphate production was reduced by 53 +/- 6, 44 +/- 3, and 54 +/- 4%, respectively. The decrease in basal inositol phosphate production by WEB2086 was significantly inhibited by a more neutral antagonist BN52021, confirming the specificity of the reaction. We demonstrate here that WEB2086 and other known ligands previously considered as antagonists can act as inverse agonists on the human PAF receptor.

Animals↗

PubMed2001

Constitutive activity of histamine h(3) receptors stably expressed in SK-N-MC cells: display of agonism and inverse agonism by H(3) antagonists.

Agonist-independent activity of G-protein-coupled receptor, also referred to as constitutive activity, is a well-documented phenomenon and has been reported recently for both the histamine H(1) and H(2) receptors. Using SK-N-MC cell lines stably expressing the human and rat H(3) receptors at physiological receptor densities (500-600 fmol/mg of protein), we show that both the rat and human H(3) receptors show a high degree of constitutive activity. The forskolin-mediated cAMP production in SK-N-MC cells is inhibited strongly upon expression of the G(i)-coupled H(3) receptor. The cAMP production can be further inhibited upon agonist stimulation of the H(3) receptor and can be enhanced by a variety of H(3) antagonists acting as inverse agonists at the H(3) receptor. Thioperamide, clobenpropit, and iodophenpropit raise the cAMP levels in SK-N-MC cells with potencies that match their receptor binding affinities. Surprisingly, impentamine and burimamide act as effective H(3) agonists. Modification of the amine group of impentamine dramatically affected the pharmacological activity of the ligand. Receptor affinity was reduced slightly for most impentamine analogs, but the functional activity of the ligands varied from agonist to neutral antagonist and inverse agonist, indicating that subtle changes in the chemical structures of impentamine analogs have major impact on the (de)activation steps of the H(3) receptor. In conclusion, upon stable expression of the rat and human H(3) receptor in SK-N-MC cells constitutive receptor activity is detected. In this experimental system, H(3) receptors ligands, previously identified as H(3) antagonists, cover the whole spectrum of pharmacological activities, ranging from full inverse agonists to agonists.

Animals↗

PubMed2002

SR144528 as inverse agonist of CB2 cannabinoid receptor.

It is now well established that several G protein- coupled receptors can signal without agonist stimulation (constitutive receptors). Inverse agonists have been shown to inhibit the activity of such constitutive G protein-coupled receptor signaling. Agonist activation of the G(i/o)-coupled peripheral cannabinoid receptor CB2 normally inhibits adenylyl cyclase type V and stimulates adenylyl cyclase type II. Using transfected COS cells, we show here that application of SR144528, an inverse agonist of CB2, leads to a reverse action (stimulation of adenylyl cyclase V and inhibition of adenylyl cyclase II). This inverse agonism of SR144528 is dependent on the temperature, as well as on the concentration of the cDNA of CB2 transfected. Pertussis toxin blocked the regulation of adenylyl cyclase activity by SR 144528.

Adenylyl Cyclase Inhibitors↗

PubMed1992

The electrocardiographic inverse problem.

Using the boundary element method in conjunction with Tikhonov zero-order regularization, we have computed epicardial potentials from body surface potential data in a realistic geometry heart-torso system. The inverse-reconstructed epicardial potentials were compared to the actual measured potentials throughout a normal cardiac cycle. Potential features (maxima, minima) were recovered with an accuracy better than 1 cm in their location. In this chapter, we use these data to illustrate and discuss computational issues related to the inverse-reconstruction procedure. These include the boundary element method, the choice of a regularization scheme to stabilize the inversion, and the effects of incorporating a priori information on the accuracy of the solution. In particular, emphasis is on the use of temporal information in the regularization procedure. The sensitivity of the solution to geometrical errors and to the spatial and temporal resolution of the data is discussed.

Animals↗

PubMedDate not supplied

[Differences in growth and ontogenetic development of plants grown in the Earth gravitational field in the natural and inverse orientation].

Wheat plants Triticum aestivum L., Apogee cultivar, were grown in the natural and inverse orientation of the Earth gravitational field. Special vegetation containers with double bottom were used for the cultivation. The upper bottom made of porous titanium served as a hydrophilic porous membrane stabilizing aquatic potential in the root-inhabited zone at a given level. Normal plants yielding viable seeds were obtained for both natural and inverse orientation. In our experiments, the inverse orientation induced dry weight accumulation by the plants as well as development of productive tillering shoots and increased the shoot-root dry weight ratio.

Earth, Planet↗

PubMed2004

[Correction of congenital nipple inversion with bilateral rhombus deepithelialized subcutaneous pedicle skin flaps and continuous traction].

OBJECTIVE: A new method for correction of nipple inversion was introduced to improve the surgical result. METHODS: In this procedure, two opposite rhombus incisions on both sides of the inverted nipple were designed within the range of areola. The rhombus skin was deepithelialized and two subcutaneous pedicle skin flaps were created. Then the shortened lactiferous ducts and fibrous bands beneath the nipple were released. The subcutaneous pedicle skin flaps on both sides of the inverted nipple were advanced through the tunnel beneath the nipple as the supporting tissue. After the operation, continuous traction of the nipple lasted two weeks at least. RESULTS: Since 1999, 16 patients with congenital bilateral nipple inversion have been treated. No complications were found in all the cases. Postoperative follow-up for 2-12 months showed that the appearance of the nipple was satisfactory. CONCLUSIONS: This method is simple, safe and effective for correction of congenital nipple inversion. The incision scar is indistinct, the natural look and good function of the nipple were reserved.

Adolescent↗

PubMedDate not supplied

Inverse correlation between expression levels of p27 and the ubiquitin ligase subunit Skp2 in early esophageal squamous cell carcinoma.

BACKGROUND: In esophageal squamous cell carcinoma (SCC), the relationship between expression of the cyclin-dependent kinase inhibitor p27 and tumor aggression and prognosis is still controversial. Moreover, the expression of S-phase kinase-interacting protein 2 (Skp2), the ubiquitin ligase subunit required for the ubiquitin-dependent degradation of p27, remains unknown. MATERIALS AND METHODS: We used immunohistochemistry to analyze Skp2 and p27 expression in surgical specimens obtained from 32 patients with early esophageal SCC. We also used Western blotting to characterize the expression of Skp2 and p27 in 7 cell lines derived from esophageal SCC. RESULTS: Expression of Skp2 showed an inverse topographic distribution and correlation to that of p27 in many esophageal carcinomas. Of the 7 cell lines, 6 showed an inverse relationship between Skp2 and p27 expression. Patients without an inverse correlation between Skp2 and p27 expression had a significantly unfavorable prognosis in the early stage (p=0.0493). CONCLUSION: These findings suggest that the target substrate of Skp2 in early esophageal SCC is mainly p27, and that failure of Skp2-induced degradation of p27 may influence tumor progression and lead to a poor prognosis.

Adult↗

PubMed2004

[Perfusion imaging of the kidney using contrast-enhanced phase-inversion ultrasound].

PURPOSE: We evaluated different techniques of contrast-enhanced phase-inversion ultrasound to visualize renal perfusion. MATERIALS AND METHODS: Levovist contrast-enhanced phase-inversion ultrasound with different levels of mechanical index and frame rate was performed in 20 kidneys. Analysis using a software algorithm for time-resolved perfusion imaging was compared to single-image analysis performed by three independent radiologists. RESULTS: Optimal depiction of renal perfusion was achieved only by using a mechanical index which was high enough to destroy the microbubbles of the contrast agent (burst imaging) combined with a low frame rate (0.5 images/second). Renal cortex and medulla showed a homogeneous enhancement. Computer-assisted time-resolved perfusion analysis was applicable; it did not show additional Information to single-image analysis. CONCLUSION: Renal perfusion can be visualized using contrast-enhanced phase-inversion ultrasound. For depiction of bigger vessels, it is equal to B-mode ultrasound or Doppler mode techniques; however, it is superior for visualization of renal parenchymal perfusion.

Adult↗

PubMed2005

[Treatment on femoral fractures with inverse limited marrow cavity rasping intramedullary interlocking nail].

OBJECTIVE: To evaluate the results of the treatment on femoral fractures with inverse limited marrow cavity rasping intramedullary interlocking nail. METHODS: From Jun. 1999 to Sep. 2003, 74 patients with femoral fractures were treated by intramedullary interlocking nail (inverse limited marrow cavity rasping). There were 62 males and 12 females. Among them, 5 cases were type 32A1, 7 cases were type 32A2, 12 cases were type 32A3, 35 cases were type 32B2, and 15 cases were type 32C2. RESULTS: Seventy-four patients were followed up for 13 to 29 months (15.4 months in average). The time for fracture union ranged from 3 to 5 months (3.8 months in average). The overall rate of excellence was 98.7% by Wuyuesong grading. There was 1 case of non-union, 1 case of delayed infection, and 2 cases of bent screw. CONCLUSION: The treatment on femoral fractures with inverse limited marrow cavity rasping intramedullary interlocking nail is easy to operate and has minimum impairment to local circulation. It also promotes the healing and early function.

Adolescent↗

PubMed2004

Hemangiomas and focal nodular hyperplasia images in contrast-enhanced, wide-band phase-inversion harmonic power Doppler imaging.

BACKGROUND: Contrast-enhanced, wide-band, phase inversion power Doppler sonography in the depiction of vasculature in hemangioma and focal nodular hyperplasia. MATERIAL/METHODS: Fifty-one patients with liver lesions (40 FNHs,37 hemangiomas) were prospectively evaluated with conventional, color, power Doppler sonography, tissue harmonic, phase-inversion sonography and helical CT. Levovist was the standard contrast agent used and all examinations were performed on Siemens SONOLINE Elegra equipped with Ensemble Contrast Imaging (ECI) software. RESULTS: Color and power Doppler scans were frequently not specific for these highly vasularized lesions. Images were not suggestive in 15 out of 40 FNHs and not positive in all of 37 hemangiomas). If peripheral enhancement in form of puddle enhancement, 'bloo pools' or rimlike followed by a slow centripetal fill-in is regarded as a positive finding for hemangiomas all lesions were depicted confidently with wide-band, phase inversion, contrast enhanced power Doppler scans. Moreover, all typical vascularity features of FNHs confluence firstly the feeding artery then centrifugal spread of contrast later forming wheel like pattern was obvious in all cases of diagnosed FNHs. CONCLUSIONS: Contrast-enhanced, wide-band, PI ,power Doppler imaging is useful method for diagnosing the vascularity of FNHs and hemangiomas. Not only it overcomes the low prediction rate which was the main obstacle for routine use of sonography but it is cheap, portable, and free also from contrast media and radiation.

Adult↗

PubMed1992

The effect of molded and unmolded orthotics on balance and pain while jogging following inversion ankle sprain.

During this study, we examined the effects of using molded orthotics on persons who had suffered an inversion ankle sprain. We assessed standing balance with a digital balance evaluator for a group of 15 subjects who had no history of ankle sprains and for a group of nine subjects with acute ankle sprains. Then, we assessed the subjective pain experienced by ten subjects with acute ankle sprains while they jogged. During each part of the study, we tested the subjects while they were using a molded orthotic, an unmolded orthotic, and no orthotic in their shoes. We alternated the order of these treatments with each consecutive subject. The results indicate that subjects with a history of recent inversion ankle sprains had poorer balance than uninjured subjects. Molded orthotics had no effect on balance scores in the uninjured group, but their use improved balance scores in the ankle sprain group. Unmolded orthotics did not improve balance scores. Molded orthotics helped to decrease ankle pain during jogging for those with an ankle sprain, but unmolded orthotics did not. These findings suggest that molded orthotics may play a role in the treatment of inversion ankle sprains.

Journal Article↗

PubMed1991

[Exercise induced precordial T wave normalization associated with U wave inversion in detection of left anterior descending artery stenosis].

Although normalization of inverted T wave is not an uncommon finding during exercise tests, it's clinical significance is still unclear. Exercise 12-lead electrocardiograms (ECGs) were recorded by using Master's 2-step or ergometer. T wave normalization in the anterior chest leads was found in 20 patients with, and 14 patients without coronary artery disease (CAD). Coronary angiography and/or exercise Tl-201 myocardial imaging were also performed in every patient. Exercise-induced T wave normalization was defined as "inverted T wave at rest becoming upright during exercise". ST segment, T and U wave amplitudes were measured before and immediately after exercise. 1) All of the 20 patients (100%) with CAD demonstrated critical stenosis of the left anterior descending artery (LAD). 2) ST deviation was noted in none of the 14 patients (0%) without CAD, and in only 4 of the 20 patients (20%) with CAD. 3) T wave amplitude increased equally in patients both with and without CAD. 4) Exercise-induced U wave inversion was found in 16 of the 20 patients (80%) with CAD, whereas it was found in only 1 of the 14 patients (7%) without CAD. 5) The sensitivity of "U wave inversion" in detection of LAD stenosis was 80%, and the specificity was 93%. We conclude that exercise-induced T wave normalization associated with U wave inversion in anterior chest leads is highly indicative of the specific presence of critical LAD stenosis.

Adult↗

PubMed1991

[Paradoxical sleep and information processing: exploration by inversion of the visual field].

The purpose of this study was to test the potential relationship between REM sleep and information processing with inversion of the visual field. In the first experiment, four male subjects slept in the laboratory for two sessions of 6 consecutive nights: 2 adaptation nights, 2 nights of polysomnography, and 2 nights of dream collection. During the days preceding Nights 3, 4, 5, and 6 of each session, the subjects wore glasses which, during the second session, completely inverted (rotation of 180 degrees) their visual field. In a second experiment with four other male subjects, the order of conditions was reversed, and the experimental condition (visual inversion) was introduced a second time. When the data of the two experiments were combined, there was a significant (p less than .01) increase in the percentage of REM sleep from Nights 3 and 4 of the control condition to Nights 3 and 4 of the visual inversion condition, but there was no significant change in any of the other sleep stages. There was a significant decrease in horizontal (p less than .04) and vertical (p less than .005) REM density and in the density of vertical REM bursts (p less than .02). The increase in REM sleep supports the hypothesis that REM sleep contributes to information processing while the decrease in REM density suggests that this component of REM sleep may be involved in a homeostatic process of sensory input.

Adaptation, Physiological↗

PubMed1976

[Facial paralysis with inverse autonomic-voluntary dissociation from a frontal lesion. Cortical origin. Relation to supplementary motor area].

As a result of 6 cases of frontal tumour presenting central facial paralysis with inverse dissociation this symptom was investigated in patients subjected to cortical excisions for intractable epielpsy. A study of 8 cases of frontal cortical excision, 6 of them affecting the internal and posterior portion, and two the prefrontal region, has provided evidence of a link between inverse automatic-voluntary dissociation facial paralysis and lesions affecting the Penfield supplementary motor area. In such cases, facial palsy is usually associated with motor disorders in the limbs, the most characteristic of which is unilateral motor under-utilisation. The possibility of inverse dissociated facial paralysis occurring as a result of a rostral premotor lesion cannot be ruled out in our present state of knowledge.

Aged↗

PubMed1990

Benzodiazepine agonist and inverse agonist actions on GABAA receptor-operated chloride channels. II. Chronic effects of ethanol.

Mice were made tolerant to and dependent on ethanol by administration of a liquid diet. Gamma-aminobutyric acid (GABA) receptor-dependent uptake of 36Cl- by mouse cortical microsacs was used to study the actions of benzodiazepine (BZ) agonists and inverse agonists. Chronic exposure to ethanol attenuated the ability of a BZ agonist, flunitrazepam, to augment muscimol-stimulated uptake of 36Cl- and enhanced the actions of BZ inverse agonists, Ro15-4513 (ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,4]-benzodiazepine - 3-carboxylate) and DMCM (methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate), to inhibit GABAA receptor-operated chloride channels. Augmentation of chloride flux by pentobarbital was not reduced by chronic ethanol exposure. Attenuation of flunitrazepam efficacy was transient and returned to control levels within 6 to 24 hr after withdrawal from ethanol, but increased sensitivity to Ro15-4513 was observed as long as 8 days after withdrawal. Chronic exposure to ethanol did not alter [3H]SR 95531 ([2-(3'-carbethoxy-2'propyl)-3-amino-6-p-methoxyphenylpyridazinium bromide] binding to low-affinity GABAA receptors or muscimol stimulation of chloride flux; and did not alter [3H]Ro15-4513 or [3H]flunitrazepam binding to central BZ receptors or allosteric modulation of this binding by muscimol (i.e., muscimol-shift). These results suggest that chronic exposure to ethanol reduces coupling between BZ agonist sites and the chloride channel, and may be responsible for the development of cross-tolerance between ethanol and BZ agonists. In contrast, coupling between BZ inverse agonist sites and the chloride channel is increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Postpartum shock and uterine inversion.

A 21-year-old woman, para 1 + 0, developed profound postpartum shock secondary to acute inversion of the uterus. Fundal re-inversion was achieved by prompt manual replacement of the uterus from below. An aggressive approach to uterine inversion is the keystone of success.

Adult↗